WorldWideScience

Sample records for paranodal myelin splitting

  1. Myelination and myelin disorders

    International Nuclear Information System (INIS)

    The first part of this thesis contains the results of a study into the capabilities of MR in the assessment of normal cerebral development. The process of normal myelination under the age of 1 year is divided into stages with specific MRI characteristics. An indication of normal age limits for each stage is given. The relationships between changes in signal intensities and biochemical background, and between progress of myelination and psychomotor development are discussed. The latter in the light of a study performed in hydrocephalic children, prior to and repeatedly after shunt implantation. Normal changes in 1H and 31P spectra of the brain in infants and children are described. The relationship between observed spectral changes and cerebral maturational processes is discussed. The second part deals with assessment of myelin disorders with MRI. Basic information about demyelinating disorders and biochemical background are reviewed. A new classification of myelin disorders, underlying the development of an MRI pattern recognition scheme, is proposed based on the most recent scientific developments. Common histological characteristics are described for all main categories of myelin disorders. Extensive information is presented about MRI patterns of abnormalities in patients in whom the disease is predominantly or exclusively located in the white matter. On the basis of the data of these patients a global MRI pattern recognition scheme has been developed covering all white matter disorders that were encountered. Also an example of an in-depth pattern recognition in a circumscribed category of disorders is presented. Finally a study of MRS in demyelinating disorders as opposed to neuronal disorders is described. While MRI provides information about the extent of the process of demyelination and about the disease category, MRS turns out to provide information about the severity of the demyelination and of the concomitant neuronal damage. (H.W.). 725 refs.; 53 figs.; 16 tabs

  2. Neutron scattering from myelin revisited: bilayer asymmetry and water-exchange kinetics

    Energy Technology Data Exchange (ETDEWEB)

    Denninger, Andrew R. [Boston College, Chestnut Hill, MA 02467 (United States); Demé, Bruno; Cristiglio, Viviana [Institut Laue–Langevin (ILL), CS 20156, F-38042 Grenoble CEDEX 9 (France); LeDuc, Géraldine [European Synchrotron Radiation Facility (ESRF), CS 40220, F-38043 Grenoble CEDEX 9 (France); Feller, W. Bruce [NOVA Scientific Inc., Sturbridge, MA 01566 (United States); Kirschner, Daniel A., E-mail: kirschnd@bc.edu [Boston College, Chestnut Hill, MA 02467 (United States)

    2014-12-01

    The structure of internodal myelin in the rodent central and peripheral nervous systems has been determined using neutron diffraction. The kinetics of water exchange in these tissues is also described. Rapid nerve conduction in the central and peripheral nervous systems (CNS and PNS, respectively) of higher vertebrates is brought about by the ensheathment of axons with myelin, a lipid-rich, multilamellar assembly of membranes. The ability of myelin to electrically insulate depends on the regular stacking of these plasma membranes and on the presence of a number of specialized membrane-protein assemblies in the sheath, including the radial component, Schmidt–Lanterman incisures and the axo–glial junctions of the paranodal loops. The disruption of this fine-structure is the basis for many demyelinating neuropathies in the CNS and PNS. Understanding the processes that govern myelin biogenesis, maintenance and destabilization requires knowledge of myelin structure; however, the tight packing of internodal myelin and the complexity of its junctional specializations make myelin a challenging target for comprehensive structural analysis. This paper describes an examination of myelin from the CNS and PNS using neutron diffraction. This investigation revealed the dimensions of the bilayers and aqueous spaces of myelin, asymmetry between the cytoplasmic and extracellular leaflets of the membrane, and the distribution of water and exchangeable hydrogen in internodal multilamellar myelin. It also uncovered differences between CNS and PNS myelin in their water-exchange kinetics.

  3. The myelin sheath aqueous layers improve the membrane properties of simulated chronic demyelinating neuropathies.

    Science.gov (United States)

    Stephanova, D I; Krustev, S M; Negrev, N; Daskalova, M

    2011-03-01

    Recently, patients with chronic demyelinating neuropathies have demonstrated significant abnormalities in their multiple nerve excitability properties measured by a non-invasive threshold tracking technique. In order to expand our studies on the possible mechanisms underlying these abnormalities, which are not yet well understood, we investigate the contributions of the aqueous layers within the myelin sheath on multiple membrane properties of simulated fibre demyelinations. Four degrees of systematic paranodal demyelinations (two mild demyelinations termed PSD1 and PSD2, without/with aqueous layers respectively, and two severe demyelinations termed PSD3 and PSD4, with/without aqueous layers, respectively) are simulated using our previous multi-layered model of human motor nerve fibre. We studied the following parameters of myelinated axonal function: potentials (intracellular action, electrotonic-reflecting the propagating and accommodative fibre processes, respectively) and strength-duration time constants, rheobases, recovery cycles (reflecting the adaptive fibre processes). The results show that each excitability parameter is markedly potentiated when the aqueous layers within their paranodally demyelinated sheaths are taken into account. The effect of the aqueous layers is significantly higher on the propagating processes than on the accommodative and adaptive processes in the fibres. The aqueous layers restore the action potential propagation, which is initially blocked when they are not taken into account. The study provides new and important information on the mechanisms of chronic demyelinating neuropathies, such as chronic inflammatory demyelinating polyneuropathy (CIDP). PMID:21425485

  4. CSF myelin basic protein

    Science.gov (United States)

    CSF myelin basic protein is a test to measure the level of myelin basic protein (MBP) in the cerebrospinal fluid (CSF). The CSF ... less than 4 ng/mL of myelin basic protein in the CSF. Note: ng/mL = nanogram per ...

  5. Uncompacted Myelin Lamellae and Nodal Ion Channel Disruption in POEMS Syndrome.

    Science.gov (United States)

    Hashimoto, Rina; Koike, Haruki; Takahashi, Mie; Ohyama, Ken; Kawagashira, Yuichi; Iijima, Masahiro; Sobue, Gen

    2015-12-01

    To elucidate the significance of uncompacted myelin lamellae (UML) and ion channel disruption at the nodes of Ranvier in the polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, we evaluated sural nerve biopsy specimens from 33 patients with POEMS syndrome and from 7 control patients. Uncompacted myelin lamellae distribution was assessed by electron microscopy and immunofluorescence microscopy. In the POEMS patient biopsies, UML were seen more frequently in small versus large myelinated fibers. Paranodes and Schmidt-Lanterman incisures, where normal physiologic UM is located, were frequently associated with UM. Widening of the nodes of Ranvier (i.e. segmental demyelination) was not associated with UML. There was axonal hollowing with neurofilament condensation at Schmidt-Lanterman incisures with abnormal UML, suggesting axonal damage at those sites in the POEMS patient biopsies. Myelin sheath irregularity was conspicuous in large myelinated fibers and was associated with abnormally widened bizarrely shaped Schmidt-Lanterman incisures. Indirect immunofluorescent studies revealed abnormalities of sodium (pan sodium) and potassium (KCNQ2) channels, even at nonwidened nodes of Ranvier. Thus, UML was not apparently associated with segmental demyelination but seemed to be associated with axonal damage. These observations suggest that nodal ion channel disruption may be associated with functional deficits in POEMS syndrome patient nerves. PMID:26574667

  6. Myelin protein composition is altered in mice lacking either sulfated or both sulfated and non-sulfated galactolipids.

    Science.gov (United States)

    Fewou, Simon Ngamli; Fernandes, Alda; Stockdale, Katie; Francone, Victor P; Dupree, Jeffrey L; Rosenbluth, Jack; Pfeiffer, Steven E; Bansal, Rashmi

    2010-02-01

    Myelin is highly enriched in galactocerebroside (GalCer) and its sulfated form sulfatide. Mice, unable to synthesize GalCer and sulfatide (CGT(null)) or sulfatide alone (CST(null)), exhibit disorganized paranodal structures and progressive dysmyelination. To obtain insights into the molecular mechanisms underlying these defects, we examined myelin composition of these mutants by two-dimensional differential fluorescence intensity gel electrophoresis proteomic approach and immunoblotting. We identified several proteins whose expressions were significantly altered in these mutants. These proteins are known to regulate cytoskeletal dynamics, energy metabolism, vesicular trafficking or adhesion, suggesting a disruption in these physiological processes in the absence of myelin galactolipids. Further analysis of one of these proteins, nucleotide diphosphate kinase (NDK)/Nm23, showed that it was reduced in myelin of CGT(null) and increased in CST(null), but not in whole brain homogenate. Immunostaining showed an increase in its expression in the cell bodies of CGT(null)- and a decrease in CST(null)-oligodenrocytes, together leading to the hypothesis that transport of NDK/Nm23 from oligodenrocyte cell bodies into myelin may be differentially dysregulated in the absence of these galactolipids. This study provides new insights into the changes that occur in the composition/distribution of myelin proteins in mice lacking either unsulfated and/or sulfated galactolipids and reinforces the role of these lipids in intracellular trafficking. PMID:19878436

  7. Myelin, myelin-related disorders, and psychosis.

    Science.gov (United States)

    Mighdoll, Michelle I; Tao, Ran; Kleinman, Joel E; Hyde, Thomas M

    2015-01-01

    The neuropathological basis of schizophrenia and related psychoses remains elusive despite intensive scientific investigation. Symptoms of psychosis have been reported in a number of conditions where normal myelin development is interrupted. The nature, location, and timing of white matter pathology seem to be key factors in the development of psychosis, especially during the critical adolescent period of association area myelination. Numerous lines of evidence implicate myelin and oligodendrocyte function as critical processes that could affect neuronal connectivity, which has been implicated as a central abnormality in schizophrenia. Phenocopies of schizophrenia with a known pathological basis involving demyelination or dysmyelination may offer insights into the biology of schizophrenia itself. This article reviews the pathological changes in white matter of patients with schizophrenia, as well as demyelinating diseases associated with psychosis. In an attempt to understand the potential role of dysmyelination in schizophrenia, we outline the evidence from a number of both clinically-based and post-mortem studies that provide evidence that OMR genes are genetically associated with increased risk for schizophrenia. To further understand the implication of white matter dysfunction and dysmyelination in schizophrenia, we examine diffusion tensor imaging (DTI), which has shown volumetric and microstructural white matter differences in patients with schizophrenia. While classical clinical-neuropathological correlations have established that disruption in myelination can produce a high fidelity phenocopy of psychosis similar to schizophrenia, the role of dysmyelination in schizophrenia remains controversial. PMID:25449713

  8. GM1 improves neurofascin155 association with lipid rafts and prevents rat brain myelin injury after hypoxia-ischemia

    Scientific Electronic Library Online (English)

    Y.P., Zhang; Q.L., Huang; C.M., Zhao; J.L., Tang; Y.L., Wang.

    2011-06-01

    Full Text Available White matter injury characterized by damage to myelin is an important process in hypoxic-ischemic brain damage (HIBD). Because the oligodendrocyte-specific isoform of neurofascin, neurofascin 155 (NF155), and its association with lipid rafts are essential for the establishment and stabilization of t [...] he paranodal junction, which is required for tight interaction between myelin and axons, we analyzed the effect of monosialotetrahexosyl ganglioside (GM1) on NF155 expression and its association with lipid rafts after HIBD in Sprague-Dawley rats, weighing 12-15 g, on day 7 post-partum (P7; N = 20 per group). HIBD was induced on P7 and the rats were divided into two groups: one group received an intraperitoneal injection of 50 mg/kg GM1 three times and the other group an injection of saline. There was also a group of 20 sham-operated rats. After sacrifice, the brains of the rats were removed on P30 and studied by immunochemistry, SDS-PAGE, Western blot analysis, and electron microscopy. Staining showed that the saline group had definite rarefaction and fragmentation of brain myelin sheaths, whereas the GM1 group had no obvious structural changes. The GM1 group had 1.9-2.9-fold more GM1 in lipid rafts than the saline group (fraction 3-6; all P

  9. Magnetic resonance imaging and myelin

    International Nuclear Information System (INIS)

    Postnatal development of the brain is characterized by growth and by myelination. Myelination of the brain normally extends from birth until about two years of age. MRI changes corresponding to the various myelination stages are due mainly to changes in the water content of the cerebral parenchyma. Myelination kinetics follow a fairly precise timetable, with variations across areas of the brain. Abnormalities of white matter are responsible for relatively stereotyped, nonspecific manifestations, which are mainly due to an increase in the amount of water contained in diseased white matter, whatever the cause of the disorder. Interpretation is based on the location, distribution, and progression of lesions. (authors). 7 refs., 5 figs

  10. Rituximab in treatment-resistant CIDP with antibodies against paranodal proteins

    Science.gov (United States)

    Querol, Luis; Rojas-García, Ricard; Diaz-Manera, Jordi; Barcena, Joseba; Pardo, Julio; Ortega-Moreno, Angel; Sedano, Maria Jose; Seró-Ballesteros, Laia; Carvajal, Alejandra; Ortiz, Nicolau; Gallardo, Eduard

    2015-01-01

    Objective: To describe the response to rituximab in patients with treatment-resistant chronic inflammatory demyelinating polyneuropathy (CIDP) with antibodies against paranodal proteins and correlate the response with autoantibody titers. Methods: Patients with CIDP and IgG4 anti–contactin-1 (CNTN1) or anti–neurofascin-155 (NF155) antibodies who were resistant to IV immunoglobulin and corticosteroids were treated with rituximab and followed prospectively. Immunocytochemistry was used to detect anti-CNTN1 and anti-NF155 antibodies and ELISA with human recombinant CNTN1 and NF155 proteins was used to determine antibody titers. Results: Two patients had a marked improvement; another patient improved slightly after 10 years of stable, severe disease; and the fourth patient had an ischemic stroke unrelated to treatment and was lost to follow-up. Autoantibodies decreased in all patients after rituximab treatment. Conclusions: Rituximab treatment is an option for patients with CIDP with IgG4 anti-CNTN1/NF155 antibodies who are resistant to conventional therapies. Classification of evidence: This study provides Class IV evidence that rituximab is effective for patients with treatment-resistant CIDP with IgG4 anti-CNTN1 or anti-NF155 antibodies. PMID:26401517

  11. Genetic dissection of myelinated axons in zebrafish

    OpenAIRE

    Monk, Kelly R; Talbot, William S

    2009-01-01

    In the vertebrate nervous system, the myelin sheath allows for rapid and efficient conduction of action potentials along axons. Despite the essential function of myelin, many questions remain unanswered about the mechanisms that govern the development of myelinated axons. The fundamental properties of myelin are widely shared among vertebrates, and the zebrafish has emerged as a powerful system to study myelination in vivo. This review will highlight recent advances from genetic screens in ze...

  12. Reactivity to myelin antigens in multiple sclerosis. Peripheral blood lymphocytes respond predominantly to myelin oligodendrocyte glycoprotein.

    OpenAIRE

    Kerlero de Rosbo, N; Milo, R.; Lees, M B; Burger, D; Bernard, C C; Ben-Nun, A (Avraham)

    1993-01-01

    Although T cell responses to the quantitatively major myelin proteins, myelin basic protein (MBP) and proteolipid protein (PLP), are likely to be of importance in the course of multiple sclerosis (MS), cell-mediated autoimmune responses to other myelin antigens, in particular quantitatively minor myelin antigens, such as myelin-associated glycoprotein (MAG) and the central nervous system-specific myelin oligodendrocyte glycoprotein (MOG), could also play a prevalent role in disease initiation...

  13. Computerized image recognition for morphometry of nerve attribute of shape of sampled transverse sections of myelinated fibers which best estimates their average diameter.

    Science.gov (United States)

    Karnes, J; Robb, R; O'Brien, P C; Lambert, E H; Dyck, P J

    1977-10-01

    A computerized image recognition method was used to measure various attributes of shape of cross-sections of myelinated nerve fibers. Measurements were made at intervals over 1/2 internode of each fiber on 20 fibers from each of 4 sural nerves from rats. Diameters were computed in 6 different ways from the computer measurements and compared for bias, precision, and accuracy between sections and to the diameter of an idealized cylinder reconstructed for each fiber from multiple actual cross sections. The diameter computed from cross-sectional areas of transversely sectioned myelinated fibers, converted into a circle, showed the highest precision, greatest accuracy and least bias. Fibers were classified by shape and the frequency was determined in defined regions (I1 = paranodal, I3= nuclear and I2=region between I1 and I3) of the 1/2 internode. A crenated shape is highly characteristic of the I1 region. The boomerang shape was found most frequently in I3 whereas the circular shape was found most frequently in I2. Epileptical and boomerang shapes of myelinated fibers within fascicles which have been orientated carefully to obtain transverse sections, are not due to obliquity of section. Therefore, using the minor axis to determine the diameter of such profiles, as we had done previously in our laboratory, is in error. We conclude from these studies, that in carefully orientated transverse sections of nerve trucks, the diameter calculated from measurement of area converted to a circular shape is the best among the various estimates of myelinated fiber diameter and is the most suitable one for use in computerized image recognition systems for nerve morphometry. It seems reasonable to extrapolate this general conclusion to myelinated fibers of man. PMID:915537

  14. Myelination in very low birth weight infants

    International Nuclear Information System (INIS)

    The prognostic significance of cerebral myelination was evaluated with magnetic resonance imaging (MRI) in very low birth weight infants. Myelination was graded in two specified sites, optic radiation and corpus callosum, based on the stages of normal term babies and healthy premature infants. The subjects were 30 preterm infants weighing less than 1,500 gm at birth. MRI was performed at 4 to 7 months (corrected age). The normal myelination stage was seen in 18 cases, while a delayed stage was noticed in 12 cases. In the normal myelination group, only 1 case (6%) had handicaps. In the delayed myelination group, 8 cases (67%) had handicaps. Our results showed that delayed myelination was closely related to a poor prognosis. We believe that MRI would be a very good imaging modality for predicting the outcome of very low birth weight infants, particularly in terms of evaluation of myelination. (author)

  15. Morphometric studies of myelination in the spinal cord of mice exposed developmentally to aluminum.

    Science.gov (United States)

    Golub, M S; Tarara, R P

    1999-12-01

    Swiss-Webster mice were exposed to diets containing 7 or 1000 microg aluminum (Al)/g as Al lactate from conception through maturity (45 days of age). This exposure has previously been shown to cause changes in CNS myelin composition and peroxidizability; in this study myelin sheath widths were measured. Initially, samples of epon embedded, toluidine blue stained cervical spinal cord sectioned at 0.5 mm were examined light microscopically. Qualitatively, Al-treated mice appeared to have a diffuse paleness in nerve tracts. No indication of myelin structural damage (splitting, degeneration) was noted. Quantitative microscopy was performed using images captured with Scion Image Dage 1.59 at 1000x with oil. Axon perimeters and sheaths were measured with NIH image using a standardized sampling pattern in the right medial dorsal and ventral regions of the cervical spinal cord in 6 mice (3 male, 3 female) per group. Mean myelin sheath widths were 16% smaller in the Al-treated group compared to controls (p=.03). There was no effect of sex or region (dorsal/ventral). Axon perimeters were also smaller on the average in the Al treated group but this difference was not significant (p=.16). The relationship between sheath width and axon diameter was similar in the two groups. The density of myelinated axons was greater in some areas for the Al-treated group. The data indicate that dietary aluminum exposure can interfere with myelination in the spinal cord. PMID:10693976

  16. Detection of Myelination Using a Novel Histological Probe

    OpenAIRE

    Xiang, Zhongmin; Nesterov, Evgueni E.; Skoch, Jesse; Lin, Tong; Hyman, Bradley T; Swager, Timothy M.; Bacskai, Brian J; Reeves, Steven A

    2005-01-01

    Current methods for myelin staining in tissue sections include both histological and immunohistochemical techniques. Fluorescence immunohistochemistry, which uses antibodies against myelin components such as myelin basic protein, is often used because of the convenience for multiple labeling. To facilitate studies on myelin, this paper describes a quick and easy method for direct myelin staining in rodent and human tissues using novel near-infrared myelin (NIM) dyes that are comparable to oth...

  17. Assessing intracortical myelin in the living human brain using myelinated cortical thickness

    Science.gov (United States)

    Rowley, Christopher D.; Bazin, Pierre-Louis; Tardif, Christine L.; Sehmbi, Manpreet; Hashim, Eyesha; Zaharieva, Nadejda; Minuzzi, Luciano; Frey, Benicio N.; Bock, Nicholas A.

    2015-01-01

    Alterations in the myelination of the cerebral cortex may underlie abnormal cortical function in a variety of brain diseases. Here, we describe a technique for investigating changes in intracortical myelin in clinical populations on the basis of cortical thickness measurements with magnetic resonance imaging (MRI) at 3 Tesla. For this, we separately compute the thickness of the shallower, lightly myelinated portion of the cortex and its deeper, heavily myelinated portion (referred to herein as unmyelinated and myelinated cortex, respectively). Our expectation is that the thickness of the myelinated cortex will be a specific biomarker for disruptions in myeloarchitecture. We show representative atlases of total cortical thickness, T, unmyelinated cortical thickness, G, and myelinated cortical thickness, M, for a healthy group of 20 female subjects. We further demonstrate myelinated cortical thickness measurements in a preliminary clinical study of 10 bipolar disorder type-I subjects and 10 healthy controls, and report significant decreases in the middle frontal gyrus in T, G, and M in the disorder, with the largest percentage change occurring in M. This study highlights the potential of myelinated cortical thickness measurements for investigating intracortical myelin involvement in brain disease at clinically relevant field strengths and resolutions. PMID:26557052

  18. Stimulation of adult oligodendrogenesis by myelin-specific T cells

    DEFF Research Database (Denmark)

    Hvilsted Nielsen, Helle; Toft-Hansen, Henrik; Lambertsen, Kate Lykke; Owens, Trevor; Finsen, Bente

    2011-01-01

    In multiple sclerosis (MS), myelin-specific T cells are normally associated with destruction of myelin and axonal damage. However, in acute MS plaque, remyelination occurs concurrent with T-cell infiltration, which raises the question of whether T cells might stimulate myelin repair. We investigated the effect of myelin-specific T cells on oligodendrocyte formation at sites of axonal damage in the mouse hippocampal dentate gyrus. Infiltrating T cells specific for myelin proteolipid protein stimu...

  19. Astrocytic TIMP-1 Promotes Oligodendrocyte Differentiation and Enhances CNS Myelination

    OpenAIRE

    Craig S. Moore; Milner, Richard; Nishiyama, Akiko; Frausto, Ricardo F.; Serwanski, David R; Pagarigan, Roberto R.; WHITTON, J. LINDSAY; Miller, Robert H; Crocker, Stephen J

    2011-01-01

    Tissue inhibitor of metalloproteinase-1 (TIMP-1) is an extracellular protein and endogenous regulator of matrix metalloproteinases (MMPs) secreted by astrocytes in response to CNS myelin injury. We have previously reported that adult TIMP-1KO mice exhibit poor myelin repair following demyelinating injury. This observation led us to hypothesize a role for TIMP-1 in oligodendrogenesis and CNS myelination. Herein, we demonstrate that compact myelin formation is significantly delayed in TIMP-1KO ...

  20. Axon-glia interaction and membrane traffic in myelin formation

    Directory of Open Access Journals (Sweden)

    Robin White

    2014-01-01

    Full Text Available In vertebrate nervous systems myelination of neuronal axons has evolved to increase conduction velocity of electrical impulses with minimal space and energy requirements. Myelin is formed by specialised glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarisation followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is established. Continuous communication between neurons and glial cells is essential for myelin maintenance and axonal integrity. A diverse group of diseases, from multiple sclerosis to schizophrenia, have been linked to malfunction of myelinating cells reflecting the physiological importance of the axon-glial unit. This review describes the mechanisms of axonal signal integration by oligodendrocytes emphasising the central role of the Src-family kinase Fyn during CNS myelination. Furthermore, we discuss myelin membrane trafficking with particular focus on endocytic recycling and the control of PLP (proteolipid protein transport by SNARE proteins. Finally, PLP mistrafficking is considered in the context of myelin diseases.

  1. On the stability and growth of single myelin figures

    CERN Document Server

    Zou, L N; Zou, Ling-Nan; Nagel, Sidney R.

    2006-01-01

    Myelin figures are long thin cylindrical structures that typically grow into a dense tangled mass when water is added to the concentrated lamellar phase of certain surfactants. We show that, if one starts from a well-ordered initial state, single myelin figures can be produced in isolation thus allowing a detailed study of their growth and stability. These structures grow with their base at the exposed edges of bilayer stacks as material is transported from the base into the myelin. Furthermore, myelins are non-equilibrium structures which require a driving force to form and grow; when the driving force is removed, they do not persist but retract into their parent structure.

  2. Cortical maturation and myelination in healthy toddlers and young children.

    Science.gov (United States)

    Deoni, Sean C L; Dean, Douglas C; Remer, Justin; Dirks, Holly; O'Muircheartaigh, Jonathan

    2015-07-15

    The maturation of cortical structures, and the establishment of their connectivity, are critical neurodevelopmental processes that support and enable cognitive and behavioral functioning. Measures of cortical development, including thickness, curvature, and gyrification have been extensively studied in older children, adolescents, and adults, revealing regional associations with cognitive performance, and alterations with disease or pathology. In addition to these gross morphometric measures, increased attention has recently focused on quantifying more specific indices of cortical structure, in particular intracortical myelination, and their relationship to cognitive skills, including IQ, executive functioning, and language performance. Here we analyze the progression of cortical myelination across early childhood, from 1 to 6 years of age, in vivo for the first time. Using two quantitative imaging techniques, namely T1 relaxation time and myelin water fraction (MWF) imaging, we characterize myelination throughout the cortex, examine developmental trends, and investigate hemispheric and gender-based differences. We present a pattern of cortical myelination that broadly mirrors established histological timelines, with somatosensory, motor and visual cortices myelinating by 1 year of age; and frontal and temporal cortices exhibiting more protracted myelination. Developmental trajectories, defined by logarithmic functions (increasing for MWF, decreasing for T1), were characterized for each of 68 cortical regions. Comparisons of trajectories between hemispheres and gender revealed no significant differences. Results illustrate the ability to quantitatively map cortical myelination throughout early neurodevelopment, and may provide an important new tool for investigating typical and atypical development. PMID:25944614

  3. Proposed evolutionary changes in the role of myelin

    Science.gov (United States)

    Stiefel, Klaus M.; Torben-Nielsen, Benjamin; Coggan, Jay S.

    2013-01-01

    Myelin is the multi-layered lipid sheet periodically wrapped around neuronal axons. It is most frequently found in vertebrates. Myelin allows for saltatory action potential (AP) conduction along axons. During this form of conduction, the AP travels passively along the myelin-covered part of the axon, and is recharged at the intermittent nodes of Ranvier. Thus, myelin can reduce the energy load needed and/or increase the speed of AP conduction. Myelin first evolved during the Ordovician period. We hypothesize that myelin's first role was mainly energy conservation. During the later “Mesozoic marine revolution,” marine ecosystems changed toward an increase in marine predation pressure. We hypothesize that the main purpose of myelin changed from energy conservation to conduction speed increase during this Mesozoic marine revolution. To test this hypothesis, we optimized models of myelinated axons for a combination of AP conduction velocity and energy efficiency. We demonstrate that there is a trade-off between these objectives. We then compared the simulation results to empirical data and conclude that while the data are consistent with the theory, additional measurements are necessary for a complete evaluation of the proposed hypothesis. PMID:24265603

  4. Proposed Evolutionary Changes In The Role Of Myelin

    Directory of Open Access Journals (Sweden)

    JaySCoggan

    2013-11-01

    Full Text Available Myelin is the multi-layered lipid sheet periodically wrapped around neuronal axons. It is most frequently found in vertebrates. Myelin allows for saltatory action potential (AP conduction along axons. During this form of conduction, the AP travels passively along the myelin-covered part of the axon, and is recharged at the intermittent nodes of Ranvier. Thus, myelin can reduce the energy load needed and/or increase the speed of AP conduction. Myelin first evolved during the Ordovician period. We hypothesize that myelin's first role was mainly energy conservation. During the later “Mesozoic marine revolution”, marine ecosystems changed towards an increase in marine predation pressure. We hypothesize that the main purpose of myelin changed from energy conservation to conduction speed increase during this Mesozoic marine revolution. To test this hypothesis, we optimized models of myelinated axons for a combination of AP conduction velocity and energy efficiency. We demonstrate that there is a trade-off between these objectives. We then compared the simulation results to empirical data and conclude that while the data are consistent with the theory, additional measurements are necessary for a complete evaluation of the proposed hypothesis.

  5. Targeted overexpression of a golli–myelin basic protein isoform to oligodendrocytes results in aberrant oligodendrocyte maturation and myelination

    Directory of Open Access Journals (Sweden)

    Erin C Jacobs

    2009-09-01

    Full Text Available Recently, several in vitro studies have shown that the golli–myelin basic proteins regulate Ca2+ homoeostasis in OPCs (oligodendrocyte precursor cells and immature OLs (oligodendrocytes, and that a number of the functions of these cells are affected by cellular levels of the golli proteins. To determine the influence of golli in vivo on OL development and myelination, a transgenic mouse was generated in which the golli isoform J37 was overexpressed specifically within OLs and OPCs. The mouse, called JOE (J37-overexpressing, is severely hypomyelinated between birth and postnatal day 50. During this time, it exhibits severe intention tremors that gradually abate at later ages. After postnatal day 50, ultrastructural studies and Northern and Western blot analyses indicate that myelin accumulates in the brain, but never reaches normal levels. Several factors appear to underlie the extensive hypomyelination. In vitro and in vivo experiments indicate that golli overexpression causes a significant delay in OL maturation, with accumulation of significantly greater numbers of pre-myelinating OLs that fail to myelinate axons during the normal myelinating period. Immunohistochemical studies with cell death and myelin markers indicate that JOE OLs undergo a heightened and extended period of cell death and are unable to effectively myelinate until 2 months after birth. The results indicate that increased levels of golli in OPC/OLs delays myelination, causing significant cell death of OLs particularly in white matter tracts. The results provide in vivo evidence for a significant role of the golli proteins in the regulation of maturation of OLs and normal myelination.

  6. Split symmetries

    Science.gov (United States)

    Buchmuller, Wilfried; Dierigl, Markus; Ruehle, Fabian; Schweizer, Julian

    2015-11-01

    We consider six-dimensional supergravity with gauge group SO (10) × U(1)A, compactified on the orbifold T2 /Z2. Three quark-lepton generations arise as zero modes of a bulk 16-plet due to magnetic flux of the anomalous U(1)A. Boundary conditions at the four fixed points break SO (10) to subgroups whose intersection is the Standard Model gauge group. The gauge and Higgs sector consist of "split" SO (10) multiplets. As a consequence of the U(1)A flux, squarks and sleptons are much heavier than gauge bosons, Higgs bosons, gauginos and higgsinos. We thus obtain a picture similar to "split supersymmetry". The flavor structure of the quark and lepton mass matrices is determined by the symmetry breaking at the orbifold fixed points.

  7. Split symmetries

    Directory of Open Access Journals (Sweden)

    Wilfried Buchmuller

    2015-11-01

    Full Text Available We consider six-dimensional supergravity with gauge group SO(10×U(1A, compactified on the orbifold T2/Z2. Three quark–lepton generations arise as zero modes of a bulk 16-plet due to magnetic flux of the anomalous U(1A. Boundary conditions at the four fixed points break SO(10 to subgroups whose intersection is the Standard Model gauge group. The gauge and Higgs sector consist of “split” SO(10 multiplets. As a consequence of the U(1A flux, squarks and sleptons are much heavier than gauge bosons, Higgs bosons, gauginos and higgsinos. We thus obtain a picture similar to “split supersymmetry”. The flavor structure of the quark and lepton mass matrices is determined by the symmetry breaking at the orbifold fixed points.

  8. Stimulation of adult oligodendrogenesis by myelin-specific T cells

    DEFF Research Database (Denmark)

    Hvilsted Nielsen, Helle; Toft-Hansen, Henrik

    2011-01-01

    In multiple sclerosis (MS), myelin-specific T cells are normally associated with destruction of myelin and axonal damage. However, in acute MS plaque, remyelination occurs concurrent with T-cell infiltration, which raises the question of whether T cells might stimulate myelin repair. We investigated the effect of myelin-specific T cells on oligodendrocyte formation at sites of axonal damage in the mouse hippocampal dentate gyrus. Infiltrating T cells specific for myelin proteolipid protein stimulated proliferation of chondroitin sulfate NG2-expressing oligodendrocyte precursor cells early after induction via axonal transection, resulting in a 25% increase in the numbers of oligodendrocytes. In contrast, T cells specific for ovalbumin did not stimulate the formation of new oligodendrocytes. In addition, infiltration of myelin-specific T cells enhanced the sprouting response of calretinergic associational/commissural fibers within the dentate gyrus. These results have implications for the perception of MS pathogenesis because they show that infiltrating myelin-specific T cells can stimulate oligodendrogenesis in the adult central nervous system.

  9. Splitting Descartes

    DEFF Research Database (Denmark)

    Schilhab, Theresa

    2007-01-01

    Kognition og Pædagogik vol. 48:10-18. 2003 Short description : The cognitivistic paradigm and Descartes' view of embodied knowledge. Abstract: That the philosopher Descartes separated the mind from the body is hardly news: He did it so effectively that his name is forever tied to that division. But what exactly is Descartes' point? How does the Kartesian split hold up to recent biologically based learning theories?

  10. Low-density lipoprotein receptor-related protein 1 is an essential receptor for myelin phagocytosis

    OpenAIRE

    Gaultier, Alban; Wu, Xiaohua; Le Moan, Natacha; Takimoto, Shinako; Mukandala, Gatambwa; Akassoglou, Katerina; Campana, W. Marie; Gonias, Steven L.

    2009-01-01

    Multiple sclerosis (MS) is an autoimmune disease in which myelin is progressively degraded. Because degraded myelin may both initiate and accelerate disease progression, clearing degraded myelin from extracellular spaces may be critical. In this study, we prepared myelin vesicles (MV) from rat brains as a model of degraded myelin. Murine embryonic fibroblasts (MEFs) rapidly internalized MVs, which accumulated in lysosomes only when these cells expressed low-density lip...

  11. Mapping early stage of myelin degradation at nanoscale resolution

    CERN Document Server

    Poccia, Nicola; Ricci, Alessandro; Caporale, Alessandra S; Di Cola, Emanuela; Hawkins, Thomas A; Bianconi, Antonio

    2013-01-01

    To provide insight into the early process of degradation often occurring in severely debilitating diseases with myelin pathology an increased level of spatial structural resolution is needed to bear in the biological realm. Although many observations have connected changes in the periodicity of myelin with illness, few information exist about the microscopic process in the early period of damage of the nerve and how these changes time percolate in space. Here we fill this gap by using first, a short time scale for data collection of scanning micro X-ray diffraction microscopy and second, methods of statistical physics for the analysis of time evolution of this non-invasive local structure experimental approach. We have mapped the time evolution of the fluctuations in myelin period in the degradation nerve process in a freshly extracted sciatic nerve of Xenopus laevis with a spatial resolution of 1 micron. We identify the first stage of myelin degradation with the period evolving through a bimodal distribution...

  12. Evaluation of white matter myelin water fraction in chronic stroke?

    OpenAIRE

    Borich, M.R.; Mackay, A. L.; Vavasour, I.M.; Rauscher, A.; Boyd, L.A.

    2013-01-01

    Multi-component T2 relaxation imaging (MCRI) provides specific in vivo measurement of myelin water content and tissue water environments through myelin water fraction (MWF), intra/extra-cellular water fraction (I/EWF) and intra/extracellular and global geometric mean T2 (GMT2) times. Quantitative MCRI assessment of tissue water environments has provided new insights into the progression and underlying white matter pathology in neural disorders such as multiple sclerosis. It has not previously...

  13. Structural insights into the antigenicity of myelin oligodendrocyte glycoprotein

    OpenAIRE

    Breithaupt, Constanze; Schubart, Anna; Zander, Hilke; Skerra, Arne; Huber, Robert; Linington, Christopher; Jacob, Uwe

    2003-01-01

    Multiple sclerosis is a chronic disease of the central nervous system (CNS) characterized by inflammation, demyelination, and axonal loss. The immunopathogenesis of demyelination in multiple sclerosis involves an autoantibody response to myelin oligodendrocyte glycoprotein (MOG), a type I transmembrane protein located at the surface of CNS myelin. Here we present the crystal structures of the extracellular domain of MOG (MOGIgd) at 1.45-Å resolution and the complex of ...

  14. Axonal protective effects of the myelin associated glycoprotein

    OpenAIRE

    Nguyen, Thien; Mehta, Niraj R.; Conant, Katherine; Kim, Kee-Jun; Jones, Melina; Calabresi, Peter A; Melli, Giorgia; Hoke, Ahmet; Schnaar, Ronald L; MING, Guo-li; SONG, Hongjun; Keswani, Sanjay C; Griffin, John W.

    2009-01-01

    Progressive axonal degeneration follows demyelination in many neurological diseases, including multiple sclerosis and inherited demyelinating neuropathies, such as Charcot-Marie-Tooth disease. One glial molecule, the myelin-associated glycoprotein (MAG), located in the adaxonal plasmalemma of myelin-producing cells, is known to signal to the axon and to modulate axonal caliber through phosphorylation of axonal neurofilament proteins. This report establishes for the first time that MAG also pr...

  15. Feasibility of Imaging Myelin Lesions in Multiple Sclerosis

    OpenAIRE

    Zavodszky, Maria I.; Graf, John F.; Tan Hehir, Cristina A.

    2011-01-01

    The goal of this study was to provide a feasibility assessment for PET imaging of multiple sclerosis (MS) lesions based on their decreased myelin content relative to the surrounding normal-appearing brain tissue. The imaging agent evaluated for this purpose is a molecule that binds strongly and specifically to myelin basic protein. Physiology-based pharmacokinetic modeling combined with PET image simulation applied to a brain model was used to examine whether such an agent would allow the dif...

  16. Myelin-associated Glycoprotein gene and brain morphometry in schizophrenia

    OpenAIRE

    JamesKennedy; JasonPLerch; ArashNazeri

    2012-01-01

    Myelin and oligodendrocyte disruption may be a core feature of schizophrenia pathophysiology. The purpose of the present study was to localize the effects of previously identified risk variants in the myelin associated glycoprotein gene on brain morphometry in schizophrenia patients and healthy controls. 45 schizophrenia patients and 47 matched healthy controls underwent clinical, structural magnetic resonance imaging, and genetics procedures. Gray and white matter cortical lobe volumes alon...

  17. Novel signals controlling embryonic Schwann cell development, myelination and dedifferentiation.

    Science.gov (United States)

    Mirsky, Rhona; Woodhoo, Ashwin; Parkinson, David B; Arthur-Farraj, Peter; Bhaskaran, Ambily; Jessen, Kristján R

    2008-06-01

    Immature Schwann cells found in perinatal rodent nerves are generated from Schwann cell precursors (SCPs) that originate from the neural crest. Immature Schwann cells generate the myelinating and non-myelinating Schwann cells of adult nerves. When axons degenerate following injury, Schwann cells demyelinate, proliferate and dedifferentiate to assume a molecular phenotype similar to that of immature cells, a process essential for successful nerve regeneration. Increasing evidence indicates that Schwann cell dedifferentiation involves activation of specific receptors, intracellular signalling pathways and transcription factors in a manner analogous to myelination. We have investigated the roles of Notch and the transcription factor c-Jun in development and after nerve transection. In vivo, Notch signalling regulates the transition from SCP to Schwann cell, times Schwann cell generation, controls Schwann cell proliferation and acts as a brake on myelination. Notch is elevated in injured nerves where it accelerates the rate of dedifferentiation. Likewise, the transcription factor c-Jun is required for Schwann cell proliferation and death and is down-regulated by Krox-20 on myelination. Forced expression of c-Jun in Schwann cells prevents myelination, and in injured nerves, c-Jun is required for appropriate dedifferentiation, the re-emergence of the immature Schwann cell state and nerve regeneration. Thus, both Notch and c-Jun are negative regulators of myelination. The growing realisation that myelination is subject to negative as well as positive controls and progress in molecular identification of negative regulators is likely to impact on our understanding of demyelinating disease and mechanisms that control nerve repair. PMID:18601657

  18. Rapid myelin water content mapping on clinical MR systems

    International Nuclear Information System (INIS)

    We present an algorithm for the fast mapping of myelin water content using standard multiecho gradient echo acquisitions of the human brain. The method extents a previously published approach for the simultaneous measurement of brain T1, T*2 and total water content. Employing the multiexponential T*2 decay signal of myelinated tissue, myelin water content was measured based on the quantification of two water pools ('myelin water' and 'rest') with different relaxation times. As the existing protocol was focussed on the fast mapping of quantitative MR parameters with whole brain coverage in clinically relevant measurement times, the sampling density of the T*2 curve was compromised to 10 echo times with a T Emax of approx. 40 ms. Therefore, pool amplitudes were determined using a quadratic optimisation approach. The optimisation was constrained by including a priori knowledge about brain water pools. All constraints were optimised in a simulation study to minimise systematic error sources given the incomplete knowledge about the real pool-specific relaxation properties. Based on the simulation results, whole brain in vivo myelin water content maps were acquired in 10 healthy controls and one subject with multiple sclerosis. The in vivo results obtained were consistent with previous reports which demonstrates that a simultaneous whole brain mapping of T1, T*2, total and myelin water content is feasible on almost any modern MR scanner in less than 10 minutes. (orig.)

  19. Brittle Splitting Nails (Onychoschizia)

    Science.gov (United States)

    ... Category: Share: Yes No, Keep Private Brittle Splitting Nails Share | Onychoschizia or splitting of the fingernails is ... term onychoschizia includes splitting, brittle, soft or thin nails. Onychoschizia is more common in women. Only very ...

  20. Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I.

    Science.gov (United States)

    Provenzale, James M; Nestrasil, Igor; Chen, Steven; Kan, Shih-Hsin; Le, Steven Q; Jens, Jacqueline K; Snella, Elizabeth M; Vondrak, Kristen N; Yee, Jennifer K; Vite, Charles H; Elashoff, David; Duan, Lewei; Wang, Raymond Y; Ellinwood, N Matthew; Guzman, Miguel A; Shapiro, Elsa G; Dickson, Patricia I

    2015-11-01

    Children with mucopolysaccharidosis I (MPS I) develop hyperintense white matter foci on T2-weighted brain magnetic resonance (MR) imaging that are associated clinically with cognitive impairment. We report here a diffusion tensor imaging (DTI) and tissue evaluation of white matter in a canine model of MPS I. We found that two DTI parameters, fractional anisotropy (a measure of white matter integrity) and radial diffusivity (which reflects degree of myelination) were abnormal in the corpus callosum of MPS I dogs compared to carrier controls. Tissue studies of the corpus callosum showed reduced expression of myelin-related genes and an abnormal composition of myelin in MPS I dogs. We treated MPS I dogs with recombinant alpha-l-iduronidase, which is the enzyme that is deficient in MPS I disease. The recombinant alpha-l-iduronidase was administered by intrathecal injection into the cisterna magna. Treated dogs showed partial correction of corpus callosum myelination. Our findings suggest that abnormal myelination occurs in the canine MPS I brain, that it may underlie clinically-relevant brain imaging findings in human MPS I patients, and that it may respond to treatment. PMID:26222335

  1. Rapid myelin water content mapping on clinical MR systems

    Energy Technology Data Exchange (ETDEWEB)

    Tonkova, Vyara; Arhelger, Volker [Fachhochschule Koblenz, RheinAhrCampus Remagen (Germany); Schenk, Jochen [Radiologisches Institut, Koblenz (Germany); Neeb, Heiko [Fachhochschule Koblenz, RheinAhrCampus Remagen (Germany); Koblenz Univ. (Germany). Inst. for Medical Engineering and Information Processing - MTI Mittelrhein

    2012-07-01

    We present an algorithm for the fast mapping of myelin water content using standard multiecho gradient echo acquisitions of the human brain. The method extents a previously published approach for the simultaneous measurement of brain T{sub 1}, T{sup *}{sub 2} and total water content. Employing the multiexponential T{sup *}{sub 2} decay signal of myelinated tissue, myelin water content was measured based on the quantification of two water pools ('myelin water' and 'rest') with different relaxation times. As the existing protocol was focussed on the fast mapping of quantitative MR parameters with whole brain coverage in clinically relevant measurement times, the sampling density of the T{sup *}{sub 2} curve was compromised to 10 echo times with a T {sub Emax} of approx. 40 ms. Therefore, pool amplitudes were determined using a quadratic optimisation approach. The optimisation was constrained by including a priori knowledge about brain water pools. All constraints were optimised in a simulation study to minimise systematic error sources given the incomplete knowledge about the real pool-specific relaxation properties. Based on the simulation results, whole brain in vivo myelin water content maps were acquired in 10 healthy controls and one subject with multiple sclerosis. The in vivo results obtained were consistent with previous reports which demonstrates that a simultaneous whole brain mapping of T{sub 1}, T{sup *}{sub 2}, total and myelin water content is feasible on almost any modern MR scanner in less than 10 minutes. (orig.)

  2. Altered lipid levels provide evidence for myelin dysfunction in multiple system atrophy

    OpenAIRE

    Don, Anthony S.; Hsiao, Jen-Hsiang T.; Bleasel, Jonathan M; Couttas, Timothy A; Halliday, Glenda M; Kim, Woojin Scott

    2014-01-01

    Multiple system atrophy (MSA) is a rapidly-progressive neurodegenerative disease characterized by parkinsonism, cerebellar ataxia and autonomic failure. A pathological hallmark of MSA is the presence of ?-synuclein deposits in oligodendrocytes, the myelin-producing support cells of the brain. Brain pathology and in vitro studies indicate that myelin instability may be an early event in the pathogenesis of MSA. Lipid is a major constituent (78% w/w) of myelin and has been implicated in myelin ...

  3. Clozapine promotes glycolysis and myelin lipid synthesis in cultured oligodendrocytes

    Directory of Open Access Journals (Sweden)

    Johann Steiner

    2014-11-01

    Our findings support the superior impact of clozapine on white matter integrity in schizophrenia as previously observed, suggesting that this drug improves the energy supply and myelin lipid synthesis in oligodendrocytes. Characterizing the underlying signal transduction pathways may pave the way for novel oligodendrocyte-directed schizophrenia therapies.

  4. Lymphocyte adherence to myelinated tissue in multiple sclerosis.

    OpenAIRE

    Dore-Duffy, P.; Goertz, V; Rothman, B L

    1980-01-01

    A small subpopulation of human peripheral blood T lymphocytes has the capacity to adhere selectively to myelinated sections of human and nonhuman brain tissue. Adherence of lymphocytes from patients with multiple sclerosis is significantly greater than adherence of control lymphocytes. Monocytes inhibit binding in controls. This function appears to be lost by multiple sclerosis monocytes.

  5. Expression of myelin proteins in the opossum optic nerve: late appearance of inhibitors implicates an earlier non-myelin factor in preventing ganglion cell regeneration.

    OpenAIRE

    Maclaren, RE

    1996-01-01

    The pattern of appearance of myelin-associated proteins in the visual system of the Brazilian opossum Monodelphis domestica is described. Whole mounts of optic nerve, chiasm, and optic tract were sectioned horizontally and incubated with antibodies to myelin basic protein (MBP), proteolipid protein (PLP), myelin-associated glycoprotein (MAG), "Rip," and the neurite inhibitory protein (IN-1), followed by visualization with diaminobenzidine and a peroxidase-conjugated secondary antibody. PLP is...

  6. Myelin management by the 18.5–kDa and 21.5–kDa classic myelin basic protein isoforms

    OpenAIRE

    Harauz, George; Boggs, Joan M.

    2013-01-01

    The classic myelin basic protein (MBP) splice isoforms range in nominal molecular mass from 14 to 21.5 kDa, and arise from the gene in the oligodendrocyte lineage (Golli) in maturing oligodendrocytes. The 18.5-kDa isoform that predominates in adult myelin adheres the cytosolic surfaces of oligodendrocyte membranes together, and forms a two-dimensional molecular sieve restricting protein diffusion into compact myelin. However, this protein has additional roles including cytoskeletal assembly a...

  7. Tibetan medical interpretation of myelin lipids and multiple sclerosis.

    Science.gov (United States)

    Husted, Cynthia; Dhondup, Lobsang

    2009-08-01

    Tibetan medicine integrates diet, lifestyle, herbs, and accessory therapies to increase health and longevity. A comparison of the three humor theory of Tibetan medicine and the three thermodynamic phase properties of myelin lipids exemplifies how integrating medical systems can increase understanding of complex chronic disabling conditions. As a correlative study to microscopically better understand multiple sclerosis (MS) from the view of Tibetan medicine, the physical disruption of central nervous system myelin membranes in MS is interpreted from the theory of the three humors (vital energies) of Tibetan medicine: rLung (Wind), MKhris pa (Bile), and Bad gen (Phlegm). The three classes of myelin lipids--phospholipids, sphingolipids, and cholesterol--are interpreted as one of three humors based on Langmuir isotherm thermodynamic measurements. The nature of rLung is movement or change. Myelin sphingolipids have rLung properties based on thermodynamic observations of changes in phase organization. MKhris pa is fire, energetic. Phospholipids have MKhris pa properties based on thermodynamic observations of being energetic membrane lipids with fast molecular motions and fluid-like properties. The nature of Bad gen is substance and form; it dominates body structure. Cholesterol relates to Bad gen because it dominates membrane structure. We propose a theoretical relationship whereby demyelination in MS is viewed as a continuum of imbalance of the three humors as understood in Tibetan medicine. Myelin lipid data is presented to support this theoretical relationship. Clinically, MS is, in general, a rLung-MKhrispa disorder in women and a Bad gen-MKhrispa disorder in men, with rLung-MKhrispa excess in both genders during exacerbation, inflammation, and demyelination. Studying Tibetan medicine in its traditional context will create an integrative model for the treatment of MS and other chronic conditions. PMID:19743559

  8. Axonal plasticity elicits long-term changes in oligodendroglia and myelinated fibers

    DEFF Research Database (Denmark)

    DrØjdahl, Nina; Nielsen, Helle Hvilsted

    2010-01-01

    Axons are linked to induction of myelination during development and to the maintenance of myelin and myelinated tracts in the adult CNS. Currently, it is unknown whether and how axonal plasticity in adult CNS impacts the myelinating cells and their precursors. In this article, we report that newly formed axonal sprouts are able to induce a protracted myelination response in adult CNS. We show that newly formed axonal sprouts, induced by lesion of the entorhino-hippocampal perforant pathway, have the ability to induce a myelination response in stratum radiatum and lucidum CA3. The lesion resulted in significant recruitment of newly formed myelinating cells, documented by incorporation of the proliferation marker bromodeoxyuridine into chondroitin sulphate NG2 expressing cells in stratum radiatum and lucidum CA3 early after lesion, and the occurrence of a 28% increase in the number of oligodendrocytes, of which some had incorporated bromodeoxyuridine, 9 weeks post-lesion. Additionally, a marked increase (41%) in myelinated fibres was detected in silver stained sections. Interestingly, these apparently new fibres achieved the same axon diameter as unlesioned mice but myelin thickness remained thinner than normal, suggesting that the sprouting axons in stratum radiatum and lucidum CA3 were not fully myelinated 9 weeks after lesion. Our combined results show that sprouting axons provide a strong stimulus to oligodendrocyte lineage cells to engage actively in the myelination processes in the adult CNS.

  9. Involvement of the Tyro3 receptor and its intracellular partner Fyn signaling in Schwann cell myelination.

    Science.gov (United States)

    Miyamoto, Yuki; Torii, Tomohiro; Takada, Shuji; Ohno, Nobuhiko; Saitoh, Yurika; Nakamura, Kazuaki; Ito, Akihito; Ogata, Toru; Terada, Nobuo; Tanoue, Akito; Yamauchi, Junji

    2015-10-01

    During early development of the peripheral nervous system, Schwann cell precursors proliferate, migrate, and differentiate into premyelinating Schwann cells. After birth, Schwann cells envelop neuronal axons with myelin sheaths. Although some molecular mechanisms underlying myelination by Schwann cells have been identified, the whole picture remains unclear. Here we show that signaling through Tyro3 receptor tyrosine kinase and its binding partner, Fyn nonreceptor cytoplasmic tyrosine kinase, is involved in myelination by Schwann cells. Impaired formation of myelin segments is observed in Schwann cell neuronal cultures established from Tyro3-knockout mouse dorsal root ganglia (DRG). Indeed, Tyro3-knockout mice exhibit reduced myelin thickness. By affinity chromatography, Fyn was identified as the binding partner of the Tyro3 intracellular domain, and activity of Fyn is down-regulated in Tyro3-knockout mice, suggesting that Tyro3, acting through Fyn, regulates myelination. Ablating Fyn in mice results in reduced myelin thickness. Decreased myelin formation is observed in cultures established from Fyn-knockout mouse DRG. Furthermore, decreased kinase activity levels and altered expression of myelination-associated transcription factors are observed in these knockout mice. These results suggest the involvement of Tyro3 receptor and its binding partner Fyn in Schwann cell myelination. This constitutes a newly recognized receptor-linked signaling mechanism that can control Schwann cell myelination. PMID:26224309

  10. Neuronal Regulation of Schwann Cell Mitochondrial Ca2+ Signaling during Myelination

    Directory of Open Access Journals (Sweden)

    Daisuke Ino

    2015-09-01

    Full Text Available Schwann cells (SCs myelinate peripheral neurons to promote the rapid conduction of action potentials, and the process of myelination is known to be regulated by signals from axons to SCs. Given that SC mitochondria are one of the potential regulators of myelination, we investigated whether SC mitochondria are regulated by axonal signaling. Here, we show a purinergic mechanism that sends information from neurons to SC mitochondria during myelination. Our results show that electrical stimulation of rat sciatic nerve increases extracellular ATP levels enough to activate purinergic receptors. Indeed, electrical stimulation of sciatic nerves induces Ca2+ increases in the cytosol and the mitochondrial matrix of surrounding SCs via purinergic receptor activation. Chronic suppression of this pathway during active myelination suppressed the longitudinal and radial development of myelinating SCs and caused hypomyelination. These results demonstrate a neuron-to-SC mitochondria signaling, which is likely to have an important role in proper myelination.

  11. Regulation of myelin genes implicated in psychiatric disorders by functional activity in axons

    Directory of Open Access Journals (Sweden)

    Douglas Fields

    2009-06-01

    Full Text Available Myelination is a highly dynamic process that continues well into adulthood in humans. Several recent gene expression studies have found abnormal expression of genes involved in myelination in the prefrontal cortex of brains from patients with schizophrenia and other psychiatric illnesses. Defects in myelination could contribute to the pathophysiology of psychiatric illness by impairing information processing as a consequence of altered impulse conduction velocity and synchrony between cortical regions carrying out higher level cognitive functions. Myelination can be altered by impulse activity in axons and by environmental experience. Psychiatric illness is treated by psychotherapy, behavioral modification, and drugs affecting neurotransmission, raising the possibility that myelinating glia may not only contribute to such disorders, but that activity-dependent effects on myelinating glia could provide one of the cellular mechanisms contributing to the therapeutic effects of these treatments. This review examines evidence showing that genes and gene networks important for myelination can be regulated by functional activity in axons.

  12. Frog muscle spindles with unbranched myelinated afferent axons: the response to stretch and the length of the first myelinated segment.

    Science.gov (United States)

    Ito, F; Komatsu, Y

    1977-01-01

    1. Twenty-five muscle spindles innervated by unbranched myelinated axons in the capsule were isolated from sartorius muscle in young frogs (2-2--9-5 g in weight, 28-47 mm in rostro-caudal length). 2. The lengths and the diameters of the first myelinated segments varied from 30 to 170 mum and from 9 to 20 mum respectively. There was no relationship between the lengths and the diameters. 3. Dynamic and static components were analysed from discharge rates of the muscle spindles during ramp-and-hold stretches of 0-8 mm from different initial lengths. The values of the dynamic components to a certain stretch stimulation increased with shortening in the length of the first myelinated segment. The values of the static components were independent in length. 4. The amplitudes of action potentials recorded from the spindle terminal decreased during the dynamic phase of the stretch. The ratio of amplitude decrease at the end of the dynamic phase versus the initial length depended upon the length of the first myelinated segment. 5. These results suggest that the discharges during stretch may arise at the first node, though the spontaneous discharges may be generated at the terminal. PMID:139468

  13. Of mothers and myelin: Aberrant myelination phenotypes in mouse model of Angelman syndrome are dependent on maternal and dietary influences.

    Science.gov (United States)

    Grier, Mark D; Carson, Robert P; Lagrange, Andre H

    2015-09-15

    Angelman syndrome (AS) is a neurodevelopmental disorder characterized by a number of neurological problems, including developmental delay, movement disorders, and epilepsy. AS results from the loss of UBE3A (an imprinted gene) expressed from the maternal chromosome in neurons. Given the ubiquitous expression of Ube3a and the devastating nature of AS, the role of environmental and maternal effects has been largely ignored. Severe ataxia, anxiety-like behaviors and learning deficits are well-documented in patients and AS mice. More recently, clinical imaging studies of AS patients suggest myelination may be delayed or reduced. Utilizing a mouse model of AS, we found disrupted expression of cortical myelin proteins, the magnitude of which is influenced by maternal status, in that the aberrant myelination in the AS pups of AS affected mothers were more pronounced than those seen in AS pups raised by unaffected (Ube3a (m+/p-)) Carrier mothers. Furthermore, feeding the breeding mothers a higher fat (11% vs 5%) diet normalizes these myelin defects. These effects are not limited to myelin proteins. Since AS mice have abnormal stress responses, including altered glucocorticoid receptor (GR) expression, we measured GR expression in pups from Carrier and affected AS mothers. AS pups had higher GR expression than their WT littermates. However, we also found an effect of maternal status, with reduced GR levels in pups from affected mothers compared to genotypically identical pups raised by unaffected Carrier mothers. Taken together, our findings suggest that the phenotypes observed in AS mice may be modulated by factors independent of Ube3a genotype. PMID:26028516

  14. Nail Splitting (Onychoschizia)

    Science.gov (United States)

    ... reaction in the skin. When to Seek Medical Care Nail splitting is generally considered a cosmetic problem, but ... nail splitting is biotin supplementation. Trusted Links MedlinePlus: ... Symptoms Self-Care Guidelines When to Seek Medical Care Treatments Your ...

  15. The Dyadic Splitting Scale.

    Science.gov (United States)

    Siegel, J.; Spellman, M. E.

    2002-01-01

    Article describes how defensive splitting, a theory used to understand the interpersonal dynamics of individuals who were traumatized in childhood, can affect a couple's relationship. A scale was developed to measure splitting in couples. Results appear to confirm the instrument's ability to identify splitting and to distinguish healthy couples…

  16. Liver X receptors alpha and beta promote myelination and remyelination in the cerebellum.

    Science.gov (United States)

    Meffre, Delphine; Shackleford, Ghjuvan'Ghjacumu; Hichor, Mehdi; Gorgievski, Victor; Tzavara, Eleni T; Trousson, Amalia; Ghoumari, Abdel M; Deboux, Cyrille; Nait Oumesmar, Brahim; Liere, Philippe; Schumacher, Michael; Baulieu, Etienne-Emile; Charbonnier, Frédéric; Grenier, Julien; Massaad, Charbel

    2015-06-16

    The identification of new pathways governing myelination provides innovative avenues for remyelination. Liver X receptors (LXRs) ? and ? are nuclear receptors activated by oxysterols that originated from the oxidation of cholesterol. They are crucial for cholesterol homeostasis, a major lipid constituent of myelin sheaths that are formed by oligodendrocytes. However, the role of LXRs in myelin generation and maintenance is poorly understood. Here, we show that LXRs are involved in myelination and remyelination processes. LXRs and their ligands are present in oligodendrocytes. We found that mice invalidated for LXRs exhibit altered motor coordination and spatial learning, thinner myelin sheaths, and reduced myelin gene expression. Conversely, activation of LXRs by either 25-hydroxycholesterol or synthetic TO901317 stimulates myelin gene expression at the promoter, mRNA, and protein levels, directly implicating LXR?/? in the transcriptional control of myelin gene expression. Interestingly, activation of LXRs also promotes oligodendroglial cell maturation and remyelination after lysolecithin-induced demyelination of organotypic cerebellar slice cultures. Together, our findings represent a conceptual advance in the transcriptional control of myelin gene expression and strongly support a new role of LXRs as positive modulators in central (re)myelination processes. PMID:26023184

  17. Voltage clamp calculations for myelinated and demyelinated axons.

    Science.gov (United States)

    Tuckwell, H C

    1993-01-01

    Exact cable theory is used to calculate voltage distributions along fully myelinated axons and those with various patterns of demyelination. The model employed uses an R-C circuit for the soma, an equivalent cable for the dendrites, a myelinated axon with n internodes and a cable representing telodendria. For the case of a voltage clamp at the soma, a system of 2n + 1 equations must be solved to obtain the potential distribution and this is done for arbitrary n. An explicit calculation is performed for one internode whereas computer-generated solutions are obtained for several internodes. The relative importance of the position of a single demyelinated internode is determined. An approximate expression is given for the critical internodal length necessary for action potential generation. PMID:8390352

  18. Glycolytic oligodendrocytes maintain myelin and long-term axonal integrity

    OpenAIRE

    Funfschilling, Ursula; Supplie, Lotti M.; Mahad, Don; Boretius, Susann; Saab, Aiman S; Edgar, Julia; Brinkmann, Bastian G.; Kassmann, Celia M.; Tzvetanova, Iva D.; Mobius, Wiebke; Diaz, Francisca; Meijer, Dies; Suter, Ueli; Hamprecht, Bernd; Sereda, Michael W.

    2012-01-01

    Oligodendrocytes, the myelin-forming glial cells of the central nervous system, maintain long-term axonal integrity1–3. However, the underlying support mechanisms are not understood4. Here we identify ametabolic component of axon–glia interactions by generating conditional Cox10 (protoheme IX farnesyltransferase) mutant mice, in which oligodendrocytes and Schwann cells fail to assemble stable mitochondrial cytochrome c oxidase (COX, also known as mitochondrial complex IV). In the peripheral n...

  19. Cross-Reactive Myelin Antibody Induces Renal Disease

    OpenAIRE

    PETERSON, LISA K.; Masaki, Takahisa; Wheelwright, Steven R.; TSUNODA, IKUO; Fujinami, Robert S

    2008-01-01

    Experimental autoimmune encephalomyelitis (EAE) is an autoimmune model for multiple sclerosis (MS). Previously, we reported renal immunoglobulin (Ig) deposition in mice with myelin oligodendrocyte glycoprotein (MOG92-106) induced progressive-EAE and naïve mice injected with MOG92-106 hybridoma cells producing antibody that cross-reacts with various autoantigens including double-stranded DNA. To assess whether MOG92-106 antibodies actually induce kidney changes, the extent of renal Ig depositi...

  20. Peripheral nervous system plasmalogens regulate Schwann cell differentiation and myelination

    OpenAIRE

    da Silva, Tiago Ferreira; Eira, Jessica; Lopes, André T.; Malheiro, Ana R.; Sousa, Vera; Luoma, Adrienne; Avila, Robin L; Wanders, Ronald J. A.; Just, Wilhelm W.; Kirschner, Daniel A; Sousa, Mónica M.; Brites, Pedro

    2014-01-01

    Rhizomelic chondrodysplasia punctata (RCDP) is a developmental disorder characterized by hypotonia, cataracts, abnormal ossification, impaired motor development, and intellectual disability. The underlying etiology of RCDP is a deficiency in the biosynthesis of ether phospholipids, of which plasmalogens are the most abundant form in nervous tissue and myelin; however, the role of plasmalogens in the peripheral nervous system is poorly defined. Here, we used mouse models of RCDP...

  1. The peripheral myelin protein 22 and epithelial membrane protein family.

    Science.gov (United States)

    Jetten, A M; Suter, U

    2000-01-01

    The peripheral myelin protein 22 (PMP22) and the epithelial membrane proteins (EMP-1, -2, and -3) comprise a subfamily of small hydrophobic membrane proteins. The putative four-transmembrane domain structure as well as the genomic structure are highly conserved among family members. PMP22 and EMPs are expressed in many tissues, and functions in cell growth, differentiation, and apoptosis have been reported. EMP-1 is highly up-regulated during squamous differentiation and in certain tumors, and a role in tumorigenesis has been proposed. PMP22 is most highly expressed in peripheral nerves, where it is localized in the compact portion of myelin. It plays a crucial role in normal physiological and pathological processes in the peripheral nervous system. Progress in molecular genetics has revealed that genetic alterations in the PMP22 gene, including duplications, deletions, and point mutations, are responsible for several forms of hereditary peripheral neuropathies, including Charcot-Marie-Tooth disease type 1A (CMT1A), Dejerine-Sottas syndrome (DDS), and hereditary neuropathy with liability to pressure palsies (HNPP). The natural mouse mutants Trembler and Trembler-J contain a missense mutation in different hydrophobic domains of PMP22, resulting in demyelination and Schwann cell proliferation. Transgenic mice carrying many copies of the PMP22 gene and PMP22-null mice display a variety of defects in the initial steps of myelination and/or maintenance of myelination, whereas no pathological alterations are detected in other tissues normally expressing PMP22. Further characterization of the interactions of PMP22 and EMPs with other proteins as well as their regulation will provide additional insight into their normal physiological function and their roles in disease and possibly will result in the development of therapeutic tools. PMID:10697408

  2. Neurotoxocarosis alters myelin protein gene transcription and expression.

    Science.gov (United States)

    Heuer, Lea; Beyerbach, Martin; Lühder, Fred; Beineke, Andreas; Strube, Christina

    2015-06-01

    Neurotoxocarosis is an infection of the central nervous system caused by migrating larvae of the common dog and cat roundworms (Toxocara canis and Toxocara cati), which are zoonotic agents. As these parasites are prevalent worldwide and neuropathological and molecular investigations on neurotoxocarosis are scare, this study aims to characterise nerve fibre demyelination associated with neurotoxocarosis on a molecular level. Transcription of eight myelin-associated genes (Cnp, Mag, Mbp, Mog, Mrf-1, Nogo-A, Plp1, Olig2) was determined in the mouse model during six time points of the chronic phase of infection using qRT-PCR. Expression of selected proteins was analysed by Western blotting or immunohistochemistry. Additionally, demyelination and neuronal damage were investigated histologically. Significant differences (p???0.05) between transcription rates of T. canis-infected and uninfected control mice were detected for all analysed genes while T. cati affected five of eight investigated genes. Interestingly, 2', 3 ´-cyclic nucleotide 3'-phosphodiesterase (Cnp) and myelin oligodendrocyte glycoprotein (Mog) were upregulated in both T. canis- and T. cati-infected mice preceding demyelination. Later, CNPase expression was additionally enhanced. As expected, myelin basic protein (Mbp) was downregulated in cerebra and cerebella of T. canis-infected mice when severe demyelination was present 120 days post infectionem (dpi). The transcriptional pattern observed in the present study appears to reflect direct traumatic and hypoxic effects of larval migration as well as secondary processes including host immune reactions, demyelination and attempts to remyelinate damaged areas. PMID:25773181

  3. Antibodies to native myelin oligodendrocyte glycoprotein are serologic markers of early inflammation in multiple sclerosis

    OpenAIRE

    Lalive, Patrice H; Menge, Til; Delarasse, Cecile; Della Gaspera, Bruno; Pham-Dinh, Danielle; Villoslada, Pablo; von Büdingen, H.-C.; Genain , Claude P

    2006-01-01

    Myelin oligodendrocyte glycoprotein (MOG) is an integral membrane protein expressed in CNS oligodendrocytes and outermost myelin lamellae. Anti-MOG Abs cause myelin destruction (demyelination) in animal models of multiple sclerosis (MS); however, such pathogenic Abs have not yet been characterized in humans. Here, a method that specifically detects IgG binding to human MOG in its native, membrane-embedded conformation on MOG-transfected mammalian cells was used to evaluate the significance of...

  4. Identification of a pathogenic antibody response to native myelin oligodendrocyte glycoprotein in multiple sclerosis

    OpenAIRE

    Zhou, Dun; Srivastava, Rajneesh; Nessler, Stefan; Grummel, Verena; Sommer, Norbert; Brück, Wolfgang; Hartung, Hans-Peter; Stadelmann, Christine; Hemmer, Bernhard

    2006-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system. Although the cause of MS is still uncertain, many findings point toward an ongoing autoimmune response to myelin antigens. Because of its location on the outer surface of the myelin sheath and its pathogenicity in the experimental autoimmune encephalomyelitis model, myelin oligodendrocyte glycoprotein (MOG) is one of the potential disease-causing self antigens in MS. However, the role of MOG in the pathog...

  5. Guanine nucleotides stimulate hydrolysis of phosphatidyl inositol bis phosphate in human myelin membranes

    Energy Technology Data Exchange (ETDEWEB)

    Boulias, C.; Moscarello, M.A. (Hospital for Sick Children, Toronto, Ontario (Canada))

    1989-07-14

    Phosphodiesterase activity was stimulated in myelin membranes in the presence of guanine nucleotide analogues. This activity was reduced in myelin membranes which had been adenosine diphosphate ribosylated in the presence of cholera toxin which ADP-ribosylated three proteins of Mr 46,000, 43,000 and 18,500. Aluminum fluoride treatment of myelin had the same stimulatory effects on phosphodiesterase activity as did the guanine nucleotides.

  6. Quaking I controls a unique cytoplasmic pathway that regulates alternative splicing of myelin-associated glycoprotein

    OpenAIRE

    Zhao, Lixia; Mandler, Mariana D.; YI, HONG; Feng, Yue

    2010-01-01

    Precise control of alternative splicing governs oligodendrocyte (OL) differentiation and myelination in the central nervous system (CNS). A well-known example is the developmentally regulated expression of splice variants encoding myelin-associated glycoprotein (MAG), which generates two protein isoforms that associate with distinct cellular components crucial for axon-glial recognition during myelinogenesis and axon-myelin stability. In the quakingviable (qkv) hypomyelination mutant mouse, d...

  7. Sorting and trafficking of proteins in oligodendrocytes during myelin membrane biogenesis

    OpenAIRE

    Klunder, Lammert,

    2007-01-01

    During myelin formation OLGs may utilize basic mechanisms of epithelial membrane trafficking, as described and summarized in the introductory chapter (Chapter 1). However, whether specific transport pathways, unique to myelin biogenesis are involved and how such pathways might be regulated in biogenesis and maintenance of the myelin sheath, is largely unexplored. Such insight is of major relevance for devising strategies for exogenous manipulation to stimulate and/or promote de novo biogen...

  8. Central myelin gene expression during postnatal development in rats exposed to nicotine gestationally

    OpenAIRE

    Cao, Junran; Dwyer, Jennifer B.; Gautier, Nicole M.; LESLIE, FRANCES M.; Li, Ming D

    2013-01-01

    Abnormal myelin gene expression in the central nervous system (CNS) is associated with many mental illnesses, including psychiatric disorders and drug addiction. We have previously shown that prenatal exposure to nicotine, the major psychoactive component in cigarette smoke, alters myelin gene expression in the CNS of adolescent rats. To examine whether this effect is specific for adolescents, we examined myelin gene expression in the CNS of juveniles and adults. Pregnant Sprague-Dawley rats ...

  9. Functional organization of an Mbp enhancer exposes striking transcriptional regulatory diversity within myelinating glia

    DEFF Research Database (Denmark)

    Dionne, Nancy; Dib, Samar; Finsen, Bente; Denarier, Eric; Kuhlmann, Tanja; Drouin, Régen; Kokoeva, Maia; Hudson, Thomas J; Siminovitch, Kathy; Friedman, Hana C; Peterson, Alan C

    2016-01-01

    In mammals, large caliber axons are ensheathed by myelin, a glial specialization supporting axon integrity and conferring accelerated and energy-efficient action potential conduction. Myelin basic protein (MBP) is required for normal myelin elaboration with maximal mbp transcription in oligodendrocytes requiring the upstream M3 enhancer. To further characterize the mechanism regulating mbp transcription, we defined M3 structure/function relationships by evaluating its evolutionary conservation, ...

  10. X-ray studies on the bilayer structure of trypsin-treated rat brain myelin

    International Nuclear Information System (INIS)

    Trypsin-treated rat brain myelin was subjected to biochemical and x-ray studies. Untreated myelin gave rise to a pattern of three rings with a fundamental repeat period of 155 A consisting of two bilayers per repeat period, whereas myelin treated with trypsin showed a fundamental repeat period of 75 A with one bilayer per repeat period. The integrated raw intensity of the h = 4 reflection with respect to the h = 2 reflection is 0.38 for untreated myelin. The corresponding value reduced to 0.23, 0.18, 0.17 for myelin treated with 5, 10, 40 units of trypsin per mg of myelin, respectively, for 30 min at 30 degC. The decrease in relative raw intensity of the higher-order reflection relative to the lower-order reflection is suggestive of a disordering of the phosphate groups upon trypsin treatment or an increased mosaicity of the membrane or a combination of both these effects. However, trypsin treatment does not lead to a complete breakdown of the membrane. The integrated intensity of the h = 1 reflection, though weak, is above the measurable threshold for untreated myelin, whereas the corresponding intensity is below the measurable threshold for trypsin-treated myelin, indicating a possible asymmetric to symmetric transition of the myelin bilayer structure about its centre after trypsin treatment. (author). 24 refs., 4 figs., 1 tab

  11. Coded Splitting Tree Protocols

    DEFF Research Database (Denmark)

    Sørensen, Jesper Hemming; Stefanovic, Cedomir; Popovski, Petar

    2013-01-01

    This paper presents a novel approach to multiple access control called coded splitting tree protocol. The approach builds on the known tree splitting protocols, code structure and successive interference cancellation (SIC). Several instances of the tree splitting protocol are initiated, each instance is terminated prematurely and subsequently iterated. The combined set of leaves from all the tree instances can then be viewed as a graph code, which is decodable using belief propagation. The main ...

  12. Split-target neutronics

    International Nuclear Information System (INIS)

    Monte Carlo simulations show that, for the LANSCE split-target of machineable tungsten, about 60% of the low-energy (20 MeV) particles are also forward directed. Consequently, the neutronic performance of the LANSCE Target-Moderator-Reflector-Shield (TMRS) system is not adversely impacted by employing a split-target. Implementing a split-target allows us to use flux-trap moderators around the void zone between the targets to simultaneously service twelve neutron flight paths. (author)

  13. Axo-Glia Interaction Preceding CNS Myelination Is Regulated by Bidirectional Eph-Ephrin Signaling

    Science.gov (United States)

    Linneberg, Cecilie; Harboe, Mette

    2015-01-01

    In the central nervous system, myelination of axons is required to ensure fast saltatory conduction and for survival of neurons. However, not all axons are myelinated, and the molecular mechanisms involved in guiding the oligodendrocyte processes toward the axons to be myelinated are not well understood. Only a few negative or positive guidance clues that are involved in regulating axo-glia interaction prior to myelination have been identified. One example is laminin, known to be required for early axo-glia interaction, which functions through ?6?1 integrin. Here, we identify the Eph-ephrin family of guidance receptors as novel regulators of the initial axo-glia interaction, preceding myelination. We demonstrate that so-called forward and reverse signaling, mediated by members of both Eph and ephrin subfamilies, has distinct and opposing effects on processes extension and myelin sheet formation. EphA forward signaling inhibits oligodendrocyte process extension and myelin sheet formation, and blocking of bidirectional signaling through this receptor enhances myelination. Similarly, EphB forward signaling also reduces myelin membrane formation, but in contrast to EphA forward signaling, this occurs in an integrin-dependent manner, which can be reversed by overexpression of a constitutive active ?1-integrin. Furthermore, ephrin-B reverse signaling induced by EphA4 or EphB1 enhances myelin sheet formation. Combined, this suggests that the Eph-ephrin receptors are important mediators of bidirectional signaling between axons and oligodendrocytes. It further implies that balancing Eph-ephrin forward and reverse signaling is important in the selection process of axons to be myelinated. PMID:26354550

  14. Cleavage of Myelin Associated Glycoprotein by Matrix Metalloproteinases

    OpenAIRE

    Milward, Elizabeth; Kim, Kee Jun; Szklarczyk, Arek; Nguyen, Thien; Melli, Giorgia; Nayak, Mamatha; Deshpande, Deepa; Fitzsimmons, Chantel; Hoke, Ahmet; Kerr, Douglas; Griffin, John W.; Calabresi, Peter A; Conant, Katherine

    2007-01-01

    Derivative myelin associated glycoprotein (dMAG) results from proteolysis of transmembrane MAG and can inhibit axonal growth. We have tested the ability of certain matrix metalloproteinases (MMPs) elevated with inflammatory and demyelinating diseases to cleave MAG. We show MMP-2, MMP-7 and MMP-9, but not MMP-1, cleave recombinant human MAG. Cleavage by MMP-7 occurs at Leu 509, just distal to the transmembrane domain and, to a lesser extent, at Met 234. We also show that MMP-7 cleaves MAG expr...

  15. Syndrome of myelinated retinal nerve fibres, myopia, amblyopia and strabismus in a Nigerian

    OpenAIRE

    Osaguona, Vivian B.; Uhumwangho, Odarosa M.

    2014-01-01

    Myelinated retinal nerve fibres (MRNF) are rare congenital anomalies. They may present in a syndrome characterised by ipsilateral myelinated retinal nerve fibres, myopia and amblyopia. We report a case of this rare condition with unilateral extensive MRNF, axial myopia, amblyopia and strabismus in a Nigerian girl.

  16. Myelin/oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex.

    OpenAIRE

    Pham-Dinh, D.; MATTEI, M. G.; Nussbaum, J L; Roussel, G.; Pontarotti, P.; Roeckel, N; Mather, I H; Artzt, K; Lindahl, K F; Dautigny, A.

    1993-01-01

    Myelin/oligodendrocyte glycoprotein (MOG) is found on the surface of myelinating oligodendrocytes and external lamellae of myelin sheaths in the central nervous system, and it is a target antigen in experimental autoimmune encephalomyelitis and multiple sclerosis. We have isolated bovine, mouse, and rat MOG cDNA clones and shown that the developmental pattern of MOG expression in the rat central nervous system coincides with the late stages of myelination. The amino-terminal, extracellular do...

  17. Severe hypomyelination of the murine CNS in the absence of myelin-associated glycoprotein and fyn tyrosine kinase.

    OpenAIRE

    Biffiger, K; Bartsch, S.; Montag, D; Aguzzi, A.; Schachner, M.; Bartsch, U

    2000-01-01

    The analysis of mice deficient in the myelin-associated glycoprotein (MAG) or Fyn, a nonreceptor-type tyrosine kinase proposed to act as a signaling molecule downstream of MAG, has revealed that both molecules are involved in the initiation of myelination. To obtain more insights into the role of the MAG-Fyn signaling pathway during initiation of myelination and formation of morphologically intact myelin sheaths, we have analyzed optic nerves of MAG-, Fyn- and MAG/Fyn-deficient mice. We obser...

  18. Ultrastructural Alterations of Myelinated Fibers and Oligodendrocytes in the Prefrontal Cortex in Schizophrenia: A Postmortem Morphometric Study

    OpenAIRE

    Diana D. Orlovskaya; Rachmanova, Valentina I.; Vikhreva, Olga V.; Uranova, Natalya A.

    2011-01-01

    Schizophrenia is believed to result from altered neuronal connectivity and impaired myelination. However, there are few direct evidence for myelin abnormalities in schizophrenia. We performed electron microscopic study of myelinated fibers and oligodendrocytes and morphometric study of myelinated fibers in the prefrontal cortex in gray and white matters in schizophrenia and normal controls. Six types of abnormal fibers and ultrastructural alterations of oligodendrocytes were found in schizoph...

  19. Contribution of axonal transport to the renewal of myelin phospholipids in peripheral nerves. I

    International Nuclear Information System (INIS)

    Kinetics of phospholipid constituents transferred from the axon to the myelin sheath were studied in the oculomotor nerve (OMN) and the ciliary ganglion (CG) of chicken. Axons of the OMN were loaded with transported phospholipids after an intracerebral injection of [2-3H]glycerol or [3H]labeled choline. Quantitative electron microscope radioautography revealed that labeled lipids were transported in the axons mainly associated with the smooth endoplasmic reticulum. Simultaneously, the labeling of the myelin sheath was found in the Schmidt-Lanterman clefts and the inner myelin layers. The outer Schwann cell cytoplasm and the outer myelin layers contained some label with [methyl-3H]choline, but virtually none with [2-3H]glycerol. With time the radioactive lipids were redistributed throughout and along the whole myelin sheath. (Auth.)

  20. Functional organization of an Mbp enhancer exposes striking transcriptional regulatory diversity within myelinating glia

    DEFF Research Database (Denmark)

    Dionne, Nancy; Dib, Samar

    2015-01-01

    In mammals, large caliber axons are ensheathed by myelin, a glial specialization supporting axon integrity and conferring accelerated and energy-efficient action potential conduction. Myelin basic protein (MBP) is required for normal myelin elaboration with maximal mbp transcription in oligodendrocytes requiring the upstream M3 enhancer. To further characterize the mechanism regulating mbp transcription, we defined M3 structure/function relationships by evaluating its evolutionary conservation, DNA footprints and the developmental programing conferred in mice by M3 derivatives. Multiple M3 regulatory element combinations were found to drive expression in oligodendrocytes and Schwann cells with a minimal 129 bp sequence conferring expression in oligodendrocytes throughout myelin elaboration, maintenance and repair. Unexpectedly, M3 derivatives conferred markedly different spatial and temporal expression programs thus illuminating striking transcriptional heterogeneity within post-mitotic oligodendrocytes. Finally, one M3 derivative engaged only during primary myelination, not during adult remyelination, demonstrating that transcriptional regulation in the two states is not equivalent. GLIA 2015.

  1. A quantitative measure of myelination development in infants, using MR images

    International Nuclear Information System (INIS)

    The objective of this study was to measure myelination of frontal lobe changes in infants and young children. Twenty-four cases of infants and children (age range 12-121 months) were evaluated by a quantitative assessment of T2-weighted MR image features. Reliable quantitative changes between white and gray matter correlated with developmental age in a group of children with no neurological findings. Myelination appears to be an increasing exponential function with the greatest rate of change occurring over the first 3 years of life. The quantitative changes observed were in accordance with previous qualitative judgments of myelination development. Children with periventricular leukomalacia (PVL) showed delays in achieving levels of myelination when compared to normal children and adjusted for chronological age. The quantitative measure of myelination development may prove to be useful in assessing the stages of development and helpful in the quantitative descriptions of white matter disorders such as PVL. (orig.)

  2. Myelin-associated Glycoprotein gene and brain morphometry in schizophrenia

    Directory of Open Access Journals (Sweden)

    JamesKennedy

    2012-05-01

    Full Text Available Myelin and oligodendrocyte disruption may be a core feature of schizophrenia pathophysiology. The purpose of the present study was to localize the effects of previously identified risk variants in the myelin associated glycoprotein gene on brain morphometry in schizophrenia patients and healthy controls. 45 schizophrenia patients and 47 matched healthy controls underwent clinical, structural magnetic resonance imaging, and genetics procedures. Gray and white matter cortical lobe volumes along with subcortical structure volumes were calculated from T1-weighted MRI scans. Each subject was also genotyped for the two disease-associated MAG single nucleotide polymorphisms (rs720308 and rs720309. Repeated measures general linear model analysis found significant region by genotype and region by diagnosis interactions for the effects of MAG risk variants on lobar gray matter volumes. No significant associations were found with lobar white matter volumes or subcortical structure volumes. Follow-up univariate general linear models found the AA genotype of rs720308 predisposed schizophrenia patients to left temporal and parietal gray matter volume deficits. These results suggest that the effects of the MAG gene on cortical gray matter volume in schizophrenia patients can be localized to temporal and parietal cortices. Our results support a role for MAG gene variation in brain morphometry in schizophrenia, align with other lines of evidence implicating MAG in schizophrenia, and provide genetically-based insight into the heterogeneity of brain imaging findings in this disorder.

  3. Concentric Split Flow Filter

    Science.gov (United States)

    Stapleton, Thomas J. (Inventor)

    2015-01-01

    A concentric split flow filter may be configured to remove odor and/or bacteria from pumped air used to collect urine and fecal waste products. For instance, filter may be designed to effectively fill the volume that was previously considered wasted surrounding the transport tube of a waste management system. The concentric split flow filter may be configured to split the air flow, with substantially half of the air flow to be treated traveling through a first bed of filter media and substantially the other half of the air flow to be treated traveling through the second bed of filter media. This split flow design reduces the air velocity by 50%. In this way, the pressure drop of filter may be reduced by as much as a factor of 4 as compare to the conventional design.

  4. STEREOLOGY OF NEURONAL CONNECTIONS (MYELINATED FIBERS OF WHITE MATTER AND SYNAPSES OF NEOCORTEX IN HUMAN BRAIN

    Directory of Open Access Journals (Sweden)

    Yong Tang

    2011-05-01

    Full Text Available Unbiased stereological sampling and counting techniques for estimating the total length, total volume and diameter distribution of myelinated nerve fibers in white matter and the total number of synapses in neocortex of human autopsy brains were described. Uniform random sampling of tissues from entire hemisphere was performed. The total volume and total length of myelinated fibers in white matter were estimated from the product of the volume of white matter obtained with the Cavalieri principle and the volume density and length density of myelinated fibers in white matter, respectively. The volume density of myelinated nerve fibers in white a matter was estimated with a point counting method. The length density of myelinated fibers in white matter was estimated from the isotropic, uniform random sections that were ensured by the sector. The diameter of myelinated fibers was derived by measuring the profile diameterperpendicular to its longest axis. The ethanolic phosphotungstic acid staining technique was modified for staining synapses in human autopsy brains. The total number of synapses in each neocortical region was estimated as the product of the volume of each neocortical region and the numerical density of synapses in each region. The numerical density of synapses in each neocortical region was obtained with the disector at the electron microscopical level. The presented methods will be useful for quantitative studies of the changes of myelinated nerve fibers and synapses in various distinct regions of the central nervous system due to development, aging and diseases.

  5. Single myelin fiber imaging in living rodents without labeling by deep optical coherence microscopy.

    Science.gov (United States)

    Ben Arous, Juliette; Binding, Jonas; Léger, Jean-François; Casado, Mariano; Topilko, Piotr; Gigan, Sylvain; Boccara, A Claude; Bourdieu, Laurent

    2011-11-01

    Myelin sheath disruption is responsible for multiple neuropathies in the central and peripheral nervous system. Myelin imaging has thus become an important diagnosis tool. However, in vivo imaging has been limited to either low-resolution techniques unable to resolve individual fibers or to low-penetration imaging of single fibers, which cannot provide quantitative information about large volumes of tissue, as required for diagnostic purposes. Here, we perform myelin imaging without labeling and at micron-scale resolution with >300-?m penetration depth on living rodents. This was achieved with a prototype [termed deep optical coherence microscopy (deep-OCM)] of a high-numerical aperture infrared full-field optical coherence microscope, which includes aberration correction for the compensation of refractive index mismatch and high-frame-rate interferometric measurements. We were able to measure the density of individual myelinated fibers in the rat cortex over a large volume of gray matter. In the peripheral nervous system, deep-OCM allows, after minor surgery, in situ imaging of single myelinated fibers over a large fraction of the sciatic nerve. This allows quantitative comparison of normal and Krox20 mutant mice, in which myelination in the peripheral nervous system is impaired. This opens promising perspectives for myelin chronic imaging in demyelinating diseases and for minimally invasive medical diagnosis. PMID:22112117

  6. Memory cells specific for myelin oligodendrocyte glycoprotein (MOG) transfer experimental autoimmune encephalomyelitis1

    OpenAIRE

    Williams, Jessica L.; Kithcart, Aaron P; Smith, Kristen M.; Shawler, Todd; Cox, Gina M.; Caroline C. Whitacre

    2011-01-01

    Multiple sclerosis (MS) is an inflammatory disease of the CNS mediated by CD4+ T cells directed against myelin antigens. Experimental autoimmune encephalomyelitis (EAE) is induced by immunization with myelin antigens like myelin oligodendrocyte glycoprotein (MOG). We have explored transfer of EAE using MOG35-55-specific TCR transgenic (2D2) T cells. Unsorted 2D2 Th1 cells reliably transferred EAE. Further, we found that CD44hiCD62Llo effector/memory CD4+ T cells are likely responsible for dis...

  7. Whole brain myelin mapping using T1- and T2-weighted MR imaging data

    OpenAIRE

    Dante Mantini; Nicole Wenderoth

    2014-01-01

    Despite recent advancements in MR imaging, non-invasive mapping of myelin in the brain still remains an open issue. Here we attempted to provide a potential solution. Specifically, we developed a processing workflow based on T1-w and T2-w MR data to generate an optimized myelin enhanced contrast image. The workflow allows whole brain mapping using the T1-w/T2-w technique, which was originally introduced as a non-invasive method for assessing cortical myelin content. The hallmark of our approa...

  8. Charge Isomers of Myelin Basic Protein: Structure and Interactions with Membranes, Nucleotide Analogues, and Calmodulin

    OpenAIRE

    Wang, Chaozhan; Neugebauer, Ute; Bürck, Jochen; Myllykoski, Matti; Baumgärtel, Peter; Popp, Jürgen; Kursula, Petri

    2011-01-01

    As an essential structural protein required for tight compaction of the central nervous system myelin sheath, myelin basic protein (MBP) is one of the candidate autoantigens of the human inflammatory demyelinating disease multiple sclerosis, which is characterized by the active degradation of the myelin sheath. In this work, recombinant murine analogues of the natural C1 and C8 charge components (rmC1 and rmC8), two isoforms of the classic 18.5-kDa MBP, were used as model proteins to get insi...

  9. Delayed myelination in a rhizomelic chondrodysplasia punctata case: MR spectroscopy findings.

    Science.gov (United States)

    Alkan, Alpay; Kutlu, Ramazan; Yakinci, Cengiz; Sigirci, Ahmet; Aslan, Mehmet; Sarac, Kaya

    2003-01-01

    Rhizomelic chondrodysplasia punctata is a member of genetic peroxisomal disorders. Delayed myelination, which is probably related to the inadequacy of plasmalogens biosynthesis, is an important feature of this disorder. Direct assessment of neuropathologic aspects of RCDP syndrome such as neuronal degeneration and delayed myelination is possible with MR spectroscopy. In this report, MR spectroscopy findings (decreased Cho/Cr and increased Ins-Gly/Cr ratios and increased levels of mobile lipids) of a rhizomelic chondrodysplasia punctata case supporting delayed myelination are presented. This is the second report of MR spectroscopy examination of the specific brain metabolic changes associated with rhizomelic chondrodysplasia punctata. PMID:12620550

  10. (O)Mega Split

    CERN Document Server

    Benakli, Karim; Goodsell, Mark

    2015-01-01

    We study two realisations of the Fake Split Supersymmetry Model (FSSM), the simplest model that can easily reproduce the experimental value of the Higgs mass for an arbitrarily high supersymmetry scale, as a consequence of swapping higgsinos for equivalent states, fake higgsinos, with suppressed Yukawa couplings. If the LSP is identified as the main Dark matter component, then a standard thermal history of the Universe implies upper bounds on the supersymmetry scale, which we derive. On the other hand, we show that renormalisation group running of soft masses above the supersymmetry scale barely constrains the model - in stark contrast to Split Supersymmetry - and hence we can have a "Mega Split" spectrum even with all of these assumptions and constraints, which include the requirements of a correct relic abundance, a gluino life-time compatible with Big Bang Nucleosynthesis and absence of signals in present direct detection experiments of inelastic dark matter. In an appendix we describe a related scenario, ...

  11. Aspects of Split Supersymmetry

    CERN Document Server

    Arkani-Hamed, N; Giudice, Gian Francesco; Romanino, A

    2005-01-01

    We explore some fundamental differences in the phenomenology, cosmology and model building of Split Supersymmetry compared with traditional low-scale supersymmetry. We show how the mass spectrum of Split Supersymmetry naturally emerges from theories where the dominant source of supersymmetry breaking preserves an $R$ symmetry, characterize the class of theories where the unavoidable $R$-breaking by gravity can be neglected, and point out a new possibility, where supersymmetry breaking is directly communicated at tree level to the visible sector via renormalizable interactions. Next, we discuss possible low-energy signals for Split Supersymmetry. The absence of new light scalars removes all the phenomenological difficulties of low-energy supersymmetry, associated with one-loop flavor and CP violating effects. However, the electric dipole moments of leptons and quarks do arise at two loops, and are automatically at the level of present limits with no need for small phases, making them accessible to several ongo...

  12. The MR evaluation of normal children and disorders of neuronal migration and myelination

    International Nuclear Information System (INIS)

    Magnetic resonance imaging (MRI) scans were available for review in 10 healthy children (aged one month-4 years) and 5 pediatric patients with disorders of neuronal migration and myelination during the developing process (aged 2-10 years). Such disorders in the 5 patients were megalencephaly, pachygyria, heterotopia, delayed myelination, and dysmyelinating disease. In the heathy group, myelination was matured during the first two years on MRI. This was depicted earlier on T1-weighted images than T2-weighted images (7 months vs one year and 9 months after birth). Abnormality in myelination was clearly visualized on T2-weighted images. Furthermore, MRI had the ability to detect morphologically the associated brain malformations. Thus, MRI may be a promising diagnostic procedure of choice in pediatric brain abnormality. (N.K.)

  13. Structure and stability of internodal myelin in mouse models of hereditary neuropathy.

    Science.gov (United States)

    Avila, Robin L; Inouye, Hideyo; Baek, Rena C; Yin, Xinghua; Trapp, Bruce D; Feltri, M Laura; Wrabetz, Lawrence; Kirschner, Daniel A

    2005-11-01

    Peripheral neuropathies often result in abnormalities in the structure of internodal myelin, including changes in period and membrane packing, as observed by electron microscopy (EM). Mutations in the gene that encodes the major adhesive structural protein of internodal myelin in the peripheral nervous system of humans and mice--P0 glycoprotein--correlate with these defects. The mechanisms by which P0 mutations interfere with myelin packing and stability are not well understood and cannot be provided by EM studies that give static and qualitative information on fixed material. To gain insights into the pathogenesis of mutant P0, we used x-ray diffraction, which can detect more subtle and dynamic changes in native myelin, to investigate myelin structure in sciatic nerves from murine models of hereditary neuropathies. We used mice with disruption of one or both copies of the P0 gene (models of Charcot-Marie-Tooth-like neuropathy [CMT1B] or Dejerine-Sottas-like neuropathy) and mice with a CMT1B resulting from a transgene encoding P0 with an amino terminal myc-tag. To directly test the structural role of P0, we also examined a mouse that expresses P0 instead of proteolipid protein in central nervous system myelin. To link our findings on unfixed nerves with EM results, we analyzed x-ray patterns from unembedded, aldehyde-fixed nerves and from plastic-embedded nerves. From the x-ray patterns recorded from whole nerves, we assessed the amount of myelin and its quality (i.e. relative thickness and regularity). Among sciatic nerves having different levels of P0, we found that unfixed nerves and, to a lesser extent, fixed but unembedded nerves gave diffraction patterns of sufficient quality to distinguish periods, sometimes differing by a few Angstroms. Certain packing abnormalities were preserved qualitatively by aldehyde fixation, and the relative amount and structural integrity of myelin among nerves could be distinguished. Measurements from the same nerve over time showed that the amount of P0 affected myelin's stability against swelling, thus directly supporting the hypothesis that packing defects underlie instability in "live" or intact myelin. Our findings demonstrate that diffraction can provide a quantitative basis for understanding, at a molecular level, the membrane packing defects that occur in internodal myelin in demyelinating peripheral neuropathies. PMID:16254492

  14. Quantitative Magnetization Transfer Measured Pool Size Ratio Reflects Optic Nerve Myelin Content in ex vivo Mice

    OpenAIRE

    Ou, Xiawei; Sun, Shu-Wei; Liang, Hsiao-Fang; Song, Sheng-Kwei; Gochberg, Daniel F.

    2009-01-01

    Optic nerves from mice that have undergone retinal ischemia were examined using a newly implemented quantitative magnetization transfer (qMT) technique. Previously published results indicate that the optic nerve from retinal ischemia mice suffered significant axon degeneration without detectable myelin injury at three days after reperfusion. At this time point, we acquired ex vivo qMT parameters from both shiverer mice (which have nearly no myelin) and control mice that have undergone retinal...

  15. Damage to Myelin and Oligodendrocytes: A Role in Chronic Outcomes Following Traumatic Brain Injury?

    OpenAIRE

    William L. Maxwell

    2013-01-01

    There is increasing evidence in the experimental and clinical traumatic brain injury (TBI) literature that loss of central myelinated nerve fibers continues over the chronic post-traumatic phase after injury. However, the biomechanism(s) of continued loss of axons is obscure. Stretch-injury to optic nerve fibers in adult guinea-pigs was used to test the hypothesis that damage to the myelin sheath and oligodendrocytes of the optic nerve fibers may contribute to, or facilitate, the continuance ...

  16. Gpr126 Functions in Schwann Cells to Control Differentiation and Myelination via G-Protein Activation

    OpenAIRE

    Mogha, Amit; Benesh, Andrew E.; Patra, Chinmoy; Engel, Felix B.; Schöneberg, Torsten; Liebscher, Ines; Monk, Kelly R

    2013-01-01

    The myelin sheath surrounding axons ensures that nerve impulses travel quickly and efficiently, allowing for the proper function of the vertebrate nervous system. We previously showed that the adhesion G-protein-coupled receptor (aGPCR) Gpr126 is essential for peripheral nervous system myelination, although the molecular mechanisms by which Gpr126 functions were incompletely understood. aGPCRs are a significantly understudied protein class, and it was unknown whether Gpr126 couples to G-prote...

  17. Progesterone Synthesized by Schwann Cells during Myelin Formation Regulates Neuronal Gene Expression

    OpenAIRE

    Chan, Jonah R; Rodriguez-Waitkus, Paul M.; Ng, Benjamin K.; Liang, Peng; Glaser, Michael

    2000-01-01

    Previously, progesterone was found to regulate the initiation and biosynthetic rate of myelin synthesis in Schwann cell/neuronal cocultures. The mRNA for cytochrome P450scc (converts cholesterol to pregnenolone), 3?-hydroxysteroid dehydrogenase (3?-HSD, converts pregnenolone to progesterone), and the progesterone receptor were found to be markedly induced during active myelin synthesis. However, the cells in the cocultures responsible for these changes were not identified. In this study, in s...

  18. Molecular characterization of antibody specificities against myelin/oligodendrocyte glycoprotein in autoimmune demyelination

    OpenAIRE

    von Büdingen, Hans-Christian; Hauser, Stephen L.; Fuhrmann, Antje; Nabavi, Cameron B.; Lee, Joy I.; Genain , Claude P

    2002-01-01

    Myelin/oligodendrocyte glycoprotein (MOG) is a target antigen for myelin-destructive Abs in autoimmune central nervous system demyelinating disorders. Little is known about the molecular and structural basis of these pathogenic Ab responses. Here, we have characterized anti-MOG Ab specificities in the marmoset model of experimental allergic encephalomyelitis, by means of a combinatorial IgG-Fab library. We found that a diverse population of Ig genes encodes for auto-Abs that exclusively recog...

  19. Immunologische Kreuzreaktivität zwischen dem Myelin-Oligodendrozyten-Glykoprotein (MOG) und Butyrophilin (BTN) bei Multipler Sklerose

    OpenAIRE

    Guggenmos, Johannes

    2003-01-01

    The aetiology of multiple sclerosis (MS) is believed to involve environmental factors that disrupt self-tolerance to myelin autoantigens but their identity and mode of action are unknown. This study reports that the epitope specificity of autoantibodies to the myelin oligodendrocyte glycoprotein (MOG), an important candidate autoantigen in MS, is heterogeneous and that MOG exhibits extensive immunological cross-reactivity with the bovine milk protein butyrophilin (BTN), an ubiquitous dietary ...

  20. CD4+ T cell responses to myelin autoantigens: activation, memory and tolerance

    OpenAIRE

    Chung, Chen-Yen

    2009-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a CD4+ T cell mediated autoimmune disease of the central nervous system and shares many characteristics with multiple sclerosis (MS). Induction of EAE is mediated by myelin reactive CD4+ T helper (Th) cells, particularly Th1 and Th17 cells, which can be provoked by the immunization with myelin derived protein (or peptide) and Toll-like receptor (TLR) stimulus (eg, complete Freund¡s adjuvant, CFA). If given an injection of solub...

  1. Pathogenic myelin oligodendrocyte glycoprotein antibodies recognize glycosylated epitopes and perturb oligodendrocyte physiology

    OpenAIRE

    Marta, Cecilia B.; Oliver, Alfred R.; Sweet, Rebecca A.; Pfeiffer, Steven E.; Ruddle, Nancy H.

    2005-01-01

    Antibodies to myelin components are routinely detected in multiple sclerosis patients. However, their presence in some control subjects has made it difficult to determine their contribution to disease pathogenesis. Immunization of C57BL/6 mice with either rat or human myelin oligodendrocyte glycoprotein (MOG) leads to experimental autoimmune encephalomyelitis (EAE) and comparable titers of anti-MOG antibodies as detected by ELISA. However, only immunization with human (but not rat) MOG result...

  2. Membrane interactions in nerve myelin: II. Determination of surface charge from biochemical data.

    OpenAIRE

    Inouye, H.; Kirschner, D. A.

    1988-01-01

    In our accompanying paper (Inouye and Kirschner, 1988) we calculated the surface charge density at the extracellular surfaces in peripheral and central nervous system (PNS; CNS) myelins from observations on the dependency of the width of the extracellular space on pH and ionic strength. Here, we have determined the surface charge density of the membrane surfaces in myelin from its chemical composition and the localization of some of its molecular components. We then analyzed the attractive an...

  3. Complement receptor-3 negatively regulates the phagocytosis of degenerated myelin through tyrosine kinase Syk and cofilin

    Directory of Open Access Journals (Sweden)

    Hadas Smadar

    2012-07-01

    Full Text Available Abstract Background Intact myelin, which normally surrounds axons, breaks down in Wallerian degeneration following axonal injury and during neurodegenerative diseases such as multiple sclerosis. Clearance of degenerated myelin by phagocytosis is essential since myelin impedes repair and exacerbates damage. CR3 (complement receptor-3 is a principal phagocytic receptor in myelin phagocytosis. We studied how tyrosine kinase Syk (spleen tyrosine kinase and cofilin control phagocytosis of degenerated myelin by CR3 in microglia and macrophages. Syk is a non-receptor tyrosine kinase that CR3 recruits to convey cellular functions. Cofilin is an actin-depolymerizing protein that controls F-actin (filamentous actin remodeling (i.e., disassembly and reassembly by shifting between active unphosphorylated and inactive phosphorylated states. Results Syk was continuously activated during prolonged phagocytosis. Phagocytosis increased when Syk activity and expression were reduced, suggesting that normally Syk down regulates CR3-mediated myelin phagocytosis. Levels of inactive p-cofilin (phosphorylated cofilin decreased transiently during prolonged phagocytosis. In contrast, p-cofilin levels decreased continuously when Syk activity and expression were continuously reduced, suggesting that normally Syk advances the inactive state of cofilin. Observations also revealed inverse relationships between levels of phagocytosis and levels of inactive p-cofilin, suggesting that active unphosphorylated cofilin advances phagocytosis. Active cofilin could advance phagocytosis by promoting F-actin remodeling, which supports the production of membrane protrusions (e.g., filopodia, which, as we also revealed, are instrumental in myelin phagocytosis. Conclusions CR3 both activates and downregulates myelin phagocytosis at the same time. Activation was previously documented. We presently demonstrate that downregulation is mediated through Syk, which advances the inactive phosphorylated state of cofilin. Self-negative control of phagocytosis by the phagocytic receptor can be useful in protecting phagocytes from excessive phagocytosis (i.e., “overeating” during extended exposure to particles that are destined for ingestion.

  4. The ectopic expression of myelin basic protein isoforms in Shiverer oligodendrocytes: implications for myelinogenesis

    OpenAIRE

    1991-01-01

    The myelin basic proteins (MBPs) are a set of peripheral membrane polypeptides that are required for the compaction of the major dense line of central nervous system myelin. We have used primary cultures of oligodendrocytes from MBP-deficient shiverer mice as host cells for the expression by cDNA transfection of each of the four major MBP isoforms. The distributions of the encoded polypeptides were studied by immunofluorescence and confocal microscopy and compared with patterns of MBP express...

  5. Damage to Myelin and Oligodendrocytes: A Role in Chronic Outcomes Following Traumatic Brain Injury?

    Directory of Open Access Journals (Sweden)

    William L. Maxwell

    2013-09-01

    Full Text Available There is increasing evidence in the experimental and clinical traumatic brain injury (TBI literature that loss of central myelinated nerve fibers continues over the chronic post-traumatic phase after injury. However, the biomechanism(s of continued loss of axons is obscure. Stretch-injury to optic nerve fibers in adult guinea-pigs was used to test the hypothesis that damage to the myelin sheath and oligodendrocytes of the optic nerve fibers may contribute to, or facilitate, the continuance of axonal loss. Myelin dislocations occur within internodal myelin of larger axons within 1–2 h of TBI. The myelin dislocations contain elevated levels of free calcium. The volume of myelin dislocations increase with greater survival and are associated with disruption of the axonal cytoskeleton leading to secondary axotomy. Waves of Ca2+ depolarization or spreading depression extend from the initial locus injury for perhaps hundreds of microns after TBI. As astrocytes and oligodendrocytes are connected via gap junctions, it is hypothesized that spreading depression results in depolarization of central glia, disrupt axonal ionic homeostasis, injure axonal mitochondria and allow the onset of axonal degeneration throughout an increasing volume of brain tissue; and contribute toward post-traumatic continued loss of white matter.

  6. Erythropoietin treatment alleviates ultrastructural myelin changes induced by murine cerebral malaria

    DEFF Research Database (Denmark)

    Hempel, Casper; Hyttel, Poul

    2012-01-01

    BACKGROUND: Cerebral malaria (CM) is a severe complication of malaria with considerable mortality. In addition to acute encephalopathy, survivors frequently suffer from neurological sequelae. The pathogenesis is incompletely understood, hampering the development of an effective, adjunctive therapy, which is not available at present. Previously, erythropoietin (EPO) was reported to significantly improve the survival and outcome in a murine CM model. The study objectives were to assess myelin thickness and ultrastructural morphology in the corpus callosum in murine CM and to adress the effects of EPO treatment in this context. METHODS: The study consisted of two groups of Plasmodium berghei-infected mice and two groups of uninfected controls that were either treated with EPO or placebo (n?=?4 mice/group). In the terminal phase of murine CM the brains were removed and processed for electron microscopy. Myelin sheaths in the corpus callosum were analysed with transmission electron microscopy and stereology. RESULTS: The infection caused clinical CM, which was counteracted by EPO. The total number of myelinated axons was identical in the four groups and mice with CM did not have reduced mean thickness of the myelin sheaths. Instead, CM mice had significantly increased numbers of abnormal myelin sheaths, whereas EPO-treated mice were indistinguishable from uninfected mice. Furthermore, mice with CM had frequent and severe axonal injury, pseudopodic endothelial cells, perivascular oedemas and intracerebral haemorrhages. CONCLUSIONS: EPO treatment reduced clinical signs of CM and reduced cerebral pathology. Murine CM does not reduce the general thickness of myelin sheaths in the corpus callosum.

  7. Phosphorylation of LKB1/Par-4 establishes Schwann cell polarity to initiate and control myelin extent.

    Science.gov (United States)

    Shen, Yun-An A; Chen, Yan; Dao, Dang Q; Mayoral, Sonia R; Wu, Laiman; Meijer, Dies; Ullian, Erik M; Chan, Jonah R; Lu, Q Richard

    2014-01-01

    The Schwann cell (SC)-axon interface represents a membrane specialization that integrates axonal signals to coordinate cytoskeletal dynamics resulting in myelination. Here we show that LKB1/Par-4 is asymmetrically localized to the SC-axon interface and co-localizes with the polarity protein Par-3. Using purified SCs and myelinating cocultures, we demonstrate that localization is dependent on the phosphorylation of LKB1 at serine-431. SC-specific deletion of LKB1 significantly attenuates developmental myelination, delaying the initiation and altering the myelin extent into adulthood, resulting in a 30% reduction in the conduction velocity along the adult sciatic nerves. Phosphorylation of LKB1 by protein kinase A is essential to establish the asymmetric localization of LKB1 and Par-3 and rescues the delay in myelination observed in the SC-specific knockout of LKB1. Our findings suggest that SC polarity may coordinate multiple signalling complexes that couple SC-axon contact to the redistribution of specific membrane components necessary to initiate and control myelin extent. PMID:25255972

  8. The Splitting Loope

    Science.gov (United States)

    Wilkins, Jesse L. M.; Norton, Anderson

    2011-01-01

    Teaching experiments have generated several hypotheses concerning the construction of fraction schemes and operations and relationships among them. In particular, researchers have hypothesized that children's construction of splitting operations is crucial to their construction of more advanced fractions concepts (Steffe, 2002). The authors…

  9. Split image optical display

    Science.gov (United States)

    Veligdan, James T. (Manorville, NY)

    2007-05-29

    A video image is displayed from an optical panel by splitting the image into a plurality of image components, and then projecting the image components through corresponding portions of the panel to collectively form the image. Depth of the display is correspondingly reduced.

  10. Impossibility of obtaining split links from split links via twistings

    OpenAIRE

    Ozawa, Makoto

    2001-01-01

    We show that if a split link is obtained from a split link $L$ in $S^3$ by $1/n$-Dehn surgery along a trivial knot $C$, then the link $L\\cup C$ is splittable. That is to say, it is impossible to obtain a split link from a split link via a non-trivial twisting. As its corollary, we completely determine when a trivial link is obtained from a trivial link via a twisting.

  11. Crystal structure of the extracellular domain of human myelin protein zero

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Zhigang; Wang, Yong; Yedidi, Ravikiran S.; Brunzelle, Joseph S.; Kovari, Iulia A.; Sohi, Jasloveleen; Kamholz, John; Kovari, Ladislau C. (WSU-MED); (NWU)

    2012-03-27

    Charcot-Marie-Tooth disease (CMT), a hereditary motor and sensory neuropathy, is the most common genetic neuropathy with an incidence of 1 in 2600. Several forms of CMT have been identified arising from different genomic abnormalities such as CMT1 including CMT1A, CMT1B, and CMTX. CMT1 with associated peripheral nervous system (PNS) demyelination, the most frequent diagnosis, demonstrates slowed nerve conduction velocities and segmental demyelination upon nerve biopsy. One of its subtypes, CMT1A, presents a 1.5-Mb duplication in the p11-p12 region of the human chromosome 17 which encodes peripheral myelin protein 22 (PMP22). CMT1B, a less common form, arises from the mutations in the myelin protein zero (MPZ) gene on chromosome 1, region q22-q23, which encodes the major structural component of the peripheral myelin. A rare type of CMT1 has been found recently and is caused by point mutations in early growth response gene 2 (EGR2), encoding a zinc finger transcription factor in Schwann cells. In addition, CMTX, an X-linked form of CMT, arises from a mutation in the connexin-32 gene. Myelin protein zero, associated with CMT1B, is a transmembrane protein of 219 amino acid residues. Human MPZ consists of three domains: 125 residues constitute the glycosylated immunoglobulin-like extracellular domain; 27 residues span the membrane; and 67 residues comprise the highly basic intracellular domain. MPZ makes up approximately 50% of the protein content of myelin, and is expressed predominantly in Schwann cells, the myelinating cell of the PNS. Myelin protein zero, a homophilic adhesion molecule, is a member of the immunoglobulin super-family and is essential for normal myelin structure and function. In addition, MPZ knockout mice displayed abnormal myelin that severely affects the myelination pathway, and overexpression of MPZ causes congenital hypomyelination of peripheral nerves. Myelin protein zero mutations account for {approx}5% of patients with CMT. To date, over 125 different mutations in the MPZ gene leading to peripheral neuropathy in patients have been reported worldwide (http://www.molgen. ua.ac.be/CMTMutations). All identified mutations resulting in a change or deletion of amino acid residues in MPZ give rise to neuropathy with the exception of R215L, which instead causes a benign polymorphism. Furthermore, more detailed analysis has classified the MPZ mutations into two major groups. In the first group, the mutations disrupt the intracellular processing of MPZ and are primarily associated with early onset neuropathy. It has been proposed that the mutated MPZ is trapped inside the cell rather than being transported to the plasma membrane. However, other evidence suggests that the mutated MPZ protein is expressed on the plasma membrane, but dominant-negatively disrupts the structure of myelin. In the second group, the MPZ mutations are associated with late onset neuropathy as these mutations cause only mild demyelination. The underlying mechanism is elusive with the hypothesis being that the second group of mutations cause minor abnormalities in the myelin sheath that over time may lead to aberrant Schwann cell-axon interactions and subsequently to axonal degeneration. The crystal structure of the extracellular domain of human MPZ (hP0ex) fused with maltose binding protein (MBP) is reported at 2.1 {angstrom} resolution. While the crystal structure of rat MPZ extracellular domain (rP0ex) is available, the crystal structure of the human counterpart is useful for the analysis of the two homologs as well as a comparison between the two species. The hP0ex molecule reveals subtle structural variations between two homologs allowing comparison of the human myelin protein zero to that of the rat protein. The alignment of these homologs is shown in Figure 1(a).

  12. Influence of myelin proteins on the structure and dynamics of a model membrane with emphasis on the low temperature regime

    International Nuclear Information System (INIS)

    Myelin is an insulating, multi-lamellar membrane structure wrapped around selected nerve axons. Increasing the speed of nerve impulses, it is crucial for the proper functioning of the vertebrate nervous system. Human neurodegenerative diseases, such as multiple sclerosis, are linked to damage to the myelin sheath through demyelination. Myelin exhibits a well defined subset of myelin-specific proteins, whose influence on membrane dynamics, i.e., myelin flexibility and stability, has not yet been explored in detail. In a first paper [W. Knoll, J. Peters, P. Kursula, Y. Gerelli, J. Ollivier, B. Demé, M. Telling, E. Kemner, and F. Natali, Soft Matter 10, 519 (2014)] we were able to spotlight, through neutron scattering experiments, the role of peripheral nervous system myelin proteins on membrane stability at room temperature. In particular, the myelin basic protein and peripheral myelin protein 2 were found to synergistically influence the membrane structure while keeping almost unchanged the membrane mobility. Further insight is provided by this work, in which we particularly address the investigation of the membrane flexibility in the low temperature regime. We evidence a different behavior suggesting that the proton dynamics is reduced by the addition of the myelin basic protein accompanied by negligible membrane structural changes. Moreover, we address the importance of correct sample preparation and characterization for the success of the experiment and for the reliability of the obtained results

  13. Environmental tobacco smoke in the early postnatal period induces impairment in brain myelination.

    Science.gov (United States)

    Torres, Larissa H; Annoni, Raquel; Balestrin, Natalia T; Coleto, Priscila L; Duro, Stephanie O; Garcia, Raphael C T; Pacheco-Neto, Maurílio; Mauad, Thais; Camarini, Rosana; Britto, Luiz R G; Marcourakis, Tania

    2015-11-01

    Environmental tobacco smoke (ETS) is associated with high morbidity and mortality, mainly in children. However, few studies focus on the brain development effects of ETS exposure. Myelination mainly occurs in the early years of life in humans and the first three postnatal weeks in rodents and is sensitive to xenobiotics exposure. This study investigated the effects of early postnatal ETS exposure on myelination. BALB/c mice were exposed to ETS generated from 3R4F reference research cigarettes from the third to the fourteenth days of life. The myelination of nerve fibers in the optic nerve by morphometric analysis and the levels of Olig1 and myelin basic protein (MBP) were evaluated in the cerebellum, diencephalon, telencephalon, and brainstem in infancy, adolescence, and adulthood. Infant mice exposed to ETS showed a decrease in the percentage of myelinated fibers in the optic nerve, compared with controls. ETS induced a decrease in Olig1 protein levels in the cerebellum and brainstem and an increase in MBP levels in the cerebellum at infant. It was also found a decrease in MBP levels in the telencephalon and brainstem at adolescence and in the cerebellum and diencephalon at adulthood. The present study demonstrates that exposure to ETS, in a critical phase of development, affects the percentage of myelinated fibers and myelin-specific proteins in infant mice. Although we did not observe differences in the morphological analysis in adolescence and adulthood, there was a decrease in MBP levels in distinctive brain regions suggesting a delayed effect in adolescence and adulthood. PMID:25182420

  14. Split Malcev Algebras

    Indian Academy of Sciences (India)

    Antonio J Calderón Martín; Manuel Forero Piulestán; José M Sánchez Delgado

    2012-05-01

    We study the structure of split Malcev algebras of arbitrary dimension over an algebraically closed field of characteristic zero. We show that any such algebras is of the form $M=\\mathcal{U}+\\sum_jI_j$ with $\\mathcal{U}$ a subspace of the abelian Malcev subalgebra and any $I_j$ a well described ideal of satisfying $[I_j, I_k]=0$ if $j\

  15. Syntax for Split Preorders

    CERN Document Server

    Dosen, K

    2009-01-01

    A split preorder is a preordering relation on the disjoint union of two sets, which function as source and target when one composes split preorders. The paper presents by generators and equations the category SplPre, whose arrows are the split preorders on the disjoint union of two finite ordinals. The same is done for the subcategory Gen of SplPre, whose arrows are equivalence relations, and for the category Rel, whose arrows are the binary relations between finite ordinals, and which has an isomorphic image within SplPre by a map that preserves composition, but not identity arrows. It was shown previously that SplPre and Gen have an isomorphic representation in Rel in the style of Brauer. The syntactical presentation of Gen and Rel in this paper exhibits the particular Frobenius algebra structure of Gen and the particular bialgebraic structure of Rel, the latter structure being built upon the former structure in SplPre. This points towards algebraic modelling of various categories motivated by logic, and re...

  16. Mini-Split

    CERN Document Server

    Arvanitaki, Asimina; Dimopoulos, Savas; Villadoro, Giovanni

    2012-01-01

    The lack of evidence for new physics beyond the standard model at the LHC points to a paucity of new particles near the weak scale. This suggests that the weak scale is tuned and that supersymmetry, if present at all, is realized at higher energies. The measured Higgs mass constrains the scalar sparticles to be below 10^5 TeV, while gauge coupling unification favors Higgsinos below 100 TeV. Nevertheless, in many models gaugino masses are suppressed and remain within reach of the LHC. Tuning the weak scale and the renormalization group evolution of the scalar masses constrain Split model building. Due to the small gaugino masses, either the squarks or the up-higgs often run tachyonic; in the latter case, successful electroweak breaking requires heavy higgsinos near the scalar sparticles. We discuss the consequences of tuning the weak scale and the phenomenology of several models of Split supersymmetry including anomaly mediation, U(1)_(B-L) mediation, and Split gauge mediation.

  17. Mini-Split

    Science.gov (United States)

    Arvanitaki, Asimina; Craig, Nathaniel; Dimopoulos, Savas; Villadoro, Giovanni

    2013-02-01

    The lack of evidence for new physics beyond the standard model at the LHC points to a paucity of new particles near the weak scale. This suggests that the weak scale is tuned and that supersymmetry, if present at all, is realized at higher energies. The measured Higgs mass constrains the scalar sparticles to be below 105 TeV, while gauge coupling unification favors Higgsinos below 100 TeV. Nevertheless, in many models gaugino masses are suppressed and remain within reach of the LHC. Tuning the weak scale and the renormalization group evolution of the scalar masses constrain Split model building. Due to the small gaugino masses, either the squarks or the up-higgs often run tachyonic; in the latter case, successful electroweak breaking requires heavy higgsinos near the scalar sparticles. We discuss the consequences of tuning the weak scale and the phenomenology of several models of Split supersymmetry including anomaly mediation, U(1) B-L mediation, and Split gauge mediation.

  18. Exposure to serotonin adversely affects oligodendrocyte development and myelination in vitro.

    Science.gov (United States)

    Fan, Lir-Wan; Bhatt, Abhay; Tien, Lu-Tai; Zheng, Baoying; Simpson, Kimberly L; Lin, Rick C S; Cai, Zhengwei; Kumar, Praveen; Pang, Yi

    2015-05-01

    Serotonin (5-hydroxytryptamine, 5-HT) has been implicated to play critical roles in early neural development. Recent reports have suggested that perinatal exposure to selective serotonin reuptake inhibitors (SSRIs) resulted in cortical network miswiring, abnormal social behavior, callosal myelin malformation, as well as oligodendrocyte (OL) pathology in rats. To gain further insight into the cellular and molecular mechanisms underlying SSRIs-induced OL and myelin abnormalities, we investigated the effect of 5-HT exposure on OL development, cell death, and myelination in cell culture models. First, we showed that 5-HT receptor 1A and 2A subtypes were expressed in OL lineages, using immunocytochemistry, Western blot, as well as intracellular Ca(2+) measurement. We then assessed the effect of serotonin exposure on the lineage development, expression of myelin proteins, cell death, and myelination, in purified OL and neuron-OL myelination cultures. For pure OL cultures, our results showed that 5-HT exposure led to disturbance of OL development, as indicated by aberrant process outgrowth and reduced myelin proteins expression. At higher doses, such exposure triggered a development-dependent cell death, as immature OLs exhibited increasing susceptibility to 5-HT treatment compared to OL progenitor cells (OPC). We showed further that 5-HT-induced immature OL death was mediated at least partially via 5-HT2A receptor, since cell death could be mimicked by 5-HT2A receptor agonist 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride, (±)-2,5-dimethoxy-4-iodoamphetamine hydrochloride, but atten-uated by pre-treatment with 5-HT2A receptor antagonist ritanserin. Utilizing a neuron-OL myelination co-culture model, our data showed that 5-HT exposure significantly reduced the number of myelinated internodes. In contrast to cell injury observed in pure OL cultures, 5-HT exposure did not lead to OL death or reduced OL density in neuron-OL co-cultures. However, abnormal patterns of contactin-associated protein (Caspr) clustering were observed at the sites of Node of Ranvier, suggesting that 5-HT exposure may affect other axon-derived factors for myelination. In summary, this is the first study to demonstrate that manipulation of serotonin levels affects OL development and myelination, which may contribute to altered neural connectivity noted in SSRIs-treated animals. The current in vitro study demonstrated that exposure to high level of serotonin (5-HT) led to aberrant oligodendrocyte (OL) development, cell injury, and myelination deficit. We propose that elevated extracellular serotonin levels in the fetal brain, such as upon the use of selective serotonin reuptake inhibitors (SSRIs) during pregnancy, may adversely affect OL development and/or myelination, thus contributing to altered neural connectivity seen in Autism Spectrum Disorders. OPC = oligodendrocyte progenitor cell. PMID:25382136

  19. CNS myelin structural modification induced in vitro by phospholipases A2.

    Science.gov (United States)

    Yunes Quartino, Pablo J; Pusterla, Julio M; Galván Josa, Victor M; Fidelio, Gerardo D; Oliveira, Rafael G

    2016-01-01

    Myelin is the self-stacked membrane surrounding axons; it is also the target of several pathological and/or neurodegenerative processes like multiple sclerosis. These processes involve, among others, the hydrolytic attack by phospholipases. In this work we describe the changes in isolated myelin structure after treatment with several secreted PLA2 (sPLA2), by using small angle x-ray scattering (SAXS) measurements. It was observed that myelin treated with all the tested sPLA2s (from cobra and bee venoms and from pig pancreas) preserved the lamellar structure but displayed an enlarged separation between membranes in certain zones. Additionally, the peak due to membrane asymmetry was clearly enhanced. The coherence length was also lower than the non-treated myelin, indicating increased disorder. These SAXS results were complemented by Langmuir film experiments to follow myelin monolayer hydrolysis at the air/water interface by a decrease in electric surface potential at different surface pressures. All enzymes produced hydrolysis with no major qualitative difference between the isoforms tested. PMID:26514604

  20. Myelin Abnormalities in the Optic and Sciatic Nerves in Mice With GM1-Gangliosidosis

    Science.gov (United States)

    Heinecke, Karie A.; Luoma, Adrienne; d’Azzo, Alessandra; Kirschner, Daniel A.

    2015-01-01

    GM1-gangliosidosis is a glycosphingolipid lysosomal storage disease involving accumulation of GM1 and its asialo form (GA1) primarily in the brain. Thin-layer chromatography and X-ray diffraction were used to analyze the lipid content/composition and the myelin structure of the optic and sciatic nerves from 7- and 10-month old ?-galactosidase (?-gal) +/? and ?-gal ?/? mice, a model of GM1gangliosidosis. Optic nerve weight was lower in the ?-gal ?/? mice than in unaffected ?-gal +/? mice, but no difference was seen in sciatic nerve weight. The levels of GM1 and GA1 were significantly increased in both the optic nerve and sciatic nerve of the ?-gal ?/? mice. The content of myelin-enriched cerebrosides, sulfatides, and plasmalogen ethanolamines was significantly lower in optic nerve of ?-gal ?/? mice than in ?-gal +/? mice; however, cholesteryl esters were enriched in the ?-gal ?/? mice. No major abnormalities in these lipids were detected in the sciatic nerve of the ?-gal ?/? mice. The abnormalities in GM1 and myelin lipids in optic nerve of ?-gal ?/? mice correlated with a reduction in the relative amount of myelin and periodicity in fresh nerve. By contrast, the relative amount of myelin and periodicity in the sciatic nerves from control and ?-gal ?/? mice were indistinguishable, suggesting minimal pathological involvement in sciatic nerve. Our results indicate that the greater neurochemical pathology observed in the optic nerve than in the sciatic nerve of ?-gal ?/? mice is likely due to the greater glycolipid storage in optic nerve. PMID:25694553

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

    International Nuclear Information System (INIS)

    The simultaneous incorporation of [3H]fucose and [1-14C]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

  2. MR imaging evaluation of early myelination patterns in normal and developmentally delayed infants

    International Nuclear Information System (INIS)

    The gray-white matter differentiation of myelination patterns in 64 normal and developmentally delayed children (aged 4 days to 36 months) was evaluated using either 0.3-T or 0.35-T imaging systems and T2-weighted pulse sequences (spin echo 2,000/80-84). Progression of myelination was correlated with mapping of myelination using stained pathologic sections. Gray-white matter patterns observed were defined as (1) infantile, (2) isointense, and (3) early adult. In children scanned sequentially, progression through these patterns was demonstrated. In developmentally delayed children, the infantile and isointense patterns persisted in the age distribution of the normal and developmentally delayed children (P values: infantiles, <.025; isointense, <.01; early adult, <.05)

  3. Myelin-associated glycoprotein (MAG) protects neurons from acute toxicity using a ganglioside-dependent mechanism.

    Science.gov (United States)

    Mehta, Niraj R; Nguyen, Thien; Bullen, John W; Griffin, John W; Schnaar, Ronald L

    2010-03-17

    Myelin-associated glycoprotein (MAG), a protein expressed on the innermost wrap of myelin, contributes to long-term axon stability as evidenced by progressive axon degeneration in Mag-null mice. Recently, MAG was also found to protect axons from acute toxic insults. In the current study, rat dorsal root ganglion neurons were cultured on control substrata and substrata adsorbed with myelin proteins. Neurons on myelin-adsorbed surfaces were resistant to acute degeneration of neurites induced by vincristine, a cancer chemotherapeutic agent with neuropathic side effects. Myelin-mediated protection was reversed by anti-MAG antibody and was absent when cells were cultured on extracts from Mag-null mouse myelin, confirming the protective role of MAG. Gangliosides (sialylated glycosphingolipids) are one functional class of axonal receptors for MAG. In the current studies, a direct role for gangliosides in mediating the acute protective effects of MAG was established. Treatment of neurons with sialidase, an enzyme that cleaves the terminal sialic acids required for MAG binding, reversed MAG's protective effect, as did treatment with (1R,2R)-1-phenyl-2-hexadecanoylamino-3-pyrrolidino-1-propanol, an inhibitor of glycosphingolipid biosynthesis. In contrast, treatment with phosphatidylinositol-specific phospholipase C, an enzyme that cleaves Nogo receptors (NgR, another class of MAG receptor), or with a peptide inhibitor of an NgR-associated signaling molecule p75(NTR), failed to diminish MAG-mediated protection. Inhibiting the Rho-associated protein kinase ROCK reversed protection. We conclude that MAG protects neurites from acute toxic insult via a ganglioside-mediated signaling pathway that involves activation of RhoA. Understanding MAG-mediated protection may provide opportunities to reduce axonal damage and loss. PMID:20436925

  4. Two novel missense mutations in the myelin protein zero gene causes Charcot-Marie-Tooth type 2 and Déjérine-Sottas syndrome

    OpenAIRE

    Sand Jette C; Braathen Geir J; Russell Michael B

    2010-01-01

    Abstract Background The Charcot-Marie-Tooth (CMT) phenotype caused by mutation in the myelin protein zero (MPZ) gene varies considerably, from early onset and severe forms to late onset and milder forms. The mechanism is not well understood. The myelin protein zero (P0) mediates adhesion in the spiral wraps of the Schwann cell's myelin sheath. The crystalline structure of the extracellular domain of the myelin protein zero (P0ex) is known, while the transmembrane and intracellular structure i...

  5. Malnutrition and myelin structure: an X-ray scattering study of rat sciatic and optic nerves

    International Nuclear Information System (INIS)

    Taking advantage of the fast and accurate X-ray scattering techniques recently developed in our laboratory, we tackled the study of the structural alterations induced in myelin by malnutrition. Our work was performed on sciatic and optic nerves dissected from rats fed with either a normal or a low-protein caloric diet, as a function of age (from birth to 60 days). By way of electrophysiological controls we also measured (on the sciatic nerves) the height and velocity of the compound action potential. Malnutrition was found to decrease the amount of myelin and to impair the packing order of the membranes in the sheaths. (orig.)

  6. Splitting (Complicated) Surfaces is Hard

    OpenAIRE

    Chambers, Erin,; Colin De Verdière, Eric; Erickson, Jeff; Lazarus, Francis; Whittlesey, Kim

    2006-01-01

    Let $\\MM$ be an orientable combinatorial surface without boundary. A cycle on $\\MM$ is \\emph{splitting} if it has no self-intersections and it partitions $\\MM$ into two components, neither of which is homeomorphic to a disk. In other words, splitting cycles are simple, separating, and non-contractible. We prove that finding the shortest splitting cycle on a combinatorial surface is NP-hard but fixed-parameter tractable with respect to the surface genus. Specifically, we describe an algorithm ...

  7. Split families unified

    CERN Document Server

    Craig, Nathaniel; Gherghetta, Tony

    2012-01-01

    We present a simple supersymmetric model of split families consistent with flavor limits that preserves the successful prediction of gauge coupling unification and naturally accounts for the Higgs mass. The model provides an intricate connection between the Standard Model flavor hierarchy, supersymmetric flavor problem, unification and the Higgs mass. In particular unification favors a naturally large Higgs mass from D-term corrections to the quartic couplings in the Higgs potential. The unification scale is lowered with a stable proton that can account for the success of b-tau Yukawa coupling unification. The sparticle spectrum is similar to that of natural supersymmetry, as motivated by the supersymmetric flavor problem and recent LHC bounds, with a heavy scalar particle spectrum except for a moderately light stop required for viable electroweak symmetry breaking. Finally, Higgs production and decays, NLSP decays, and new states associated with extending the Standard Model gauge group above the TeV scale pr...

  8. Fuel pin bundle splitting

    International Nuclear Information System (INIS)

    The patent describes the splitting of a bundle of nuclear fuel pins into smaller bundles, during the dismantling of a fuel element, in preparation for the reprocessing of the spent fuel. The size of the small bundles are such that they are suitable for cropping in an easily maintainable shearing machine. The cropping of fuel pins into short sections exposes the irradiated fuel to be reprocessed. The invention involves feeding a number of blades into the exposed end of a fuel pin bundle. The bundle is forced out of the containing sheath by a ram, and the fuel pins are forced to pass either side of theblades, there by the bundle is sorted into a number of smaller bundles. (U.K.)

  9. LINGO-1 antibody ameliorates myelin impairment and spatial memory deficits in experimental autoimmune encephalomyelitis mice

    Science.gov (United States)

    Sun, Jun-Jun; Ren, Qing-Guo; Xu, Lin; Zhang, Zhi-Jun

    2015-01-01

    More than 50% of multiple sclerosis patients develop cognitive impairment. However, the underlying mechanisms are still unclear, and there is no effective treatment. LINGO-1 (LRR and Ig domain containing NOGO receptor interacting protein 1) has been identified as an inhibitor of oligodendrocyte differentiation and myelination. Using the experimental autoimmune encephalomyelitis (EAE) mouse model, we assessed cognitive function at early and late stages of EAE, determined brain expression of myelin basic protein (MBP) and investigated whether the LINGO-1 antibody could restore deficits in learning and memory and ameliorate any loss of MBP. We found that deficits in learning and memory occurred in late EAE and identified decreased expression of MBP in the parahippocampal cortex (PHC) and fimbria-fornix. Moreover, the LINGO-1 antibody significantly improved learning and memory in EAE and partially restored MBP in PHC. Furthermore, the LINGO-1 antibody activated the AKT/mTOR signaling pathway regulating myelin growth. Our results suggest that demyelination in the PHC and fimbria-fornix might contribute to cognitive deficits and the LINGO-1 antibody could ameliorate these deficits by promoting myelin growth in the PHC. Our research demonstrates that LINGO-1 antagonism may be an effective approach to the treatment of the cognitive impairment of multiple sclerosis patients. PMID:26383267

  10. Detection of Autoantibodies Against Myelin Oligodendrocyte Glycoprotein in Multiple Sclerosis and Related Diseases.

    Science.gov (United States)

    Spadaro, Melania; Meinl, Edgar

    2016-01-01

    Autoantibodies against myelin oligodendrocyte glycoprotein (MOG) occur in a proportion of patients with different inflammatory demyelinating diseases of the central nervous system, such as childhood multiple sclerosis (MS), acute disseminated encephalomyelitis (ADEM), and neuromyelitis optica spectrum disorders (NMOSD). We describe here in detail a sensitive cell-based assay that allows the identification of autoantibodies against MOG in serum. PMID:25814289

  11. Myelination Is Associated with Processing Speed in Early Childhood: Preliminary Insights

    Science.gov (United States)

    Chevalier, Nicolas; Kurth, Salome; Doucette, Margaret Rae; Wiseheart, Melody; Deoni, Sean C. L.; Dean, Douglas C.; O’Muircheartaigh, Jonathan; Blackwell, Katharine A.; Munakata, Yuko; LeBourgeois, Monique K.

    2015-01-01

    Processing speed is an important contributor to working memory performance and fluid intelligence in young children. Myelinated white matter plays a central role in brain messaging, and likely mediates processing speed, but little is known about the relationship between myelination and processing speed in young children. In the present study, processing speed was measured through inspection times, and myelin volume fraction (VFM) was quantified using a multicomponent magnetic resonance imaging (MRI) approach in 2- to 5-years of age. Both inspection times and VFM were found to increase with age. Greater VFM in the right and left occipital lobes, the body of the corpus callosum, and the right cerebellum was significantly associated with shorter inspection times, after controlling for age. A hierarchical regression showed that VFM in the left occipital lobe predicted inspection times over and beyond the effects of age and the VFM in the other brain regions. These findings are consistent with the hypothesis that myelin supports processing speed in early childhood. PMID:26440654

  12. Transfer of axonally transported phospholipids into myelin isolated from the rabbit optic pathway

    International Nuclear Information System (INIS)

    The contribution of the axonal transport to the biosynthesis of myelin phospholipids was investigated in the rabbit optic pathway. A double labeling technique was used. The same animals were injected with one isotope intravitreally and the other intraventricularly. This procedure allows double labeling of the optic nerves, optic tracts, lateral geniculate bodies (LGB), and superior colliculus (SC). The precursors simultaneously injected were: [1-14C]palmitate (15 microCi intravitreally in both eyes or 50 microCi intraventricularly) and [2-3H]glycerol (50 microCi intravitreally in both eyes of 100 microCi intraventricularly). Twenty four hours and 10 days after the injections, myelin was purified from pooled optic nerves and optic tracts as well as from pooled LGBs or SCs. The phospholipids were extracted and then separated by thin-layer chromatography; the specific radioactivity of the various classes of phospholipids was determined. Using both administration routes of C- or 3H-precursors, the distribution of label and specific radioactivity of myelin phospholipids in the retina and in all other optic structures were very similar. Phosphatidylcholine, phosphatidylethanolamine and phosphatidylserine + phosphoinositol were preferentially labeled with both precursors. These results suggest that, in the rabbit optic pathway the phospholipids synthesized in the retinal ganglion cells and transported along the axons, could undergo transaxonal transfer into myelin

  13. Erythropoietin promotes oligodendrogenesis and myelin repair following lysolecithin-induced injury in spinal cord slice culture

    International Nuclear Information System (INIS)

    Highlights: ? Lysolecithin-induced demyelination elevated EpoR expression in OPCs. ? In association with elevated EpoR, EPO increased OPCs proliferation. ? EPO enhanced the oligodendrogenesis via activation of JAK2 pathway. ? EPO promoted myelin repair following lysolecithin-induced demyelination. -- Abstract: Here, we sought to delineate the effect of EPO on the remyelination processes using an in vitro model of demyelination. We report that lysolecithin-induced demyelination elevated EPO receptor (EpoR) expression in oligodendrocyte progenitor cells (OPCs), facilitating the beneficial effect of EPO on the formation of oligodendrocytes (oligodendrogenesis). In the absence of EPO, the resultant remyelination was insufficient, possibly due to a limiting number of oligodendrocytes rather than their progenitors, which proliferate in response to lysolecithin-induced injury. By EPO treatment, lysolecithin-induced proliferation of OPCs was accelerated and the number of myelinating oligodendrocytes and myelin recovery was increased. EPO also enhanced the differentiation of neural progenitor cells expressing EpoR at high level toward the oligodendrocyte-lineage cells through activation of cyclin E and Janus kinase 2 pathways. Induction of myelin-forming oligodendrocytes by high dose of EPO implies that EPO might be the key factor influencing the final differentiation of OPCs. Taken together, our data suggest that EPO treatment could be an effective way to enhance remyelination by promoting oligodendrogenesis in association with elevated EpoR expression in spinal cord slice culture after lysolecithin-induced demyelination.

  14. Myelination Is Associated with Processing Speed in Early Childhood: Preliminary Insights.

    Science.gov (United States)

    Chevalier, Nicolas; Kurth, Salome; Doucette, Margaret Rae; Wiseheart, Melody; Deoni, Sean C L; Dean, Douglas C; O'Muircheartaigh, Jonathan; Blackwell, Katharine A; Munakata, Yuko; LeBourgeois, Monique K

    2015-01-01

    Processing speed is an important contributor to working memory performance and fluid intelligence in young children. Myelinated white matter plays a central role in brain messaging, and likely mediates processing speed, but little is known about the relationship between myelination and processing speed in young children. In the present study, processing speed was measured through inspection times, and myelin volume fraction (VFM) was quantified using a multicomponent magnetic resonance imaging (MRI) approach in 2- to 5-years of age. Both inspection times and VFM were found to increase with age. Greater VFM in the right and left occipital lobes, the body of the corpus callosum, and the right cerebellum was significantly associated with shorter inspection times, after controlling for age. A hierarchical regression showed that VFM in the left occipital lobe predicted inspection times over and beyond the effects of age and the VFM in the other brain regions. These findings are consistent with the hypothesis that myelin supports processing speed in early childhood. PMID:26440654

  15. Role of myelin plasticity in oscillations and synchrony of neuronal activity.

    Science.gov (United States)

    Pajevic, S; Basser, P J; Fields, R D

    2014-09-12

    Conduction time is typically ignored in computational models of neural network function. Here we consider the effects of conduction delays on the synchrony of neuronal activity and neural oscillators, and evaluate the consequences of allowing conduction velocity (CV) to be regulated adaptively. We propose that CV variation, mediated by myelin, could provide an important mechanism of activity-dependent nervous system plasticity. Even small changes in CV, resulting from small changes in myelin thickness or nodal structure, could have profound effects on neuronal network function in terms of spike-time arrival, oscillation frequency, oscillator coupling, and propagation of brain waves. For example, a conduction delay of 5ms could change interactions of two coupled oscillators at the upper end of the gamma frequency range (?100Hz) from constructive to destructive interference; delays smaller than 1ms could change the phase by 30°, significantly affecting signal amplitude. Myelin plasticity, as another form of activity-dependent plasticity, is relevant not only to nervous system development but also to complex information processing tasks that involve coupling and synchrony among different brain rhythms. We use coupled oscillator models with time delays to explore the importance of adaptive time delays and adaptive synaptic strengths. The impairment of activity-dependent myelination and the loss of adaptive time delays may contribute to disorders where hyper- and hypo-synchrony of neuronal firing leads to dysfunction (e.g., dyslexia, schizophrenia, epilepsy). PMID:24291730

  16. Chondroitin sulfate proteoglycans impede myelination by oligodendrocytes after perinatal white matter injury.

    Science.gov (United States)

    Deng, Ying-Ping; Sun, Yi; Hu, Lan; Li, Zhi-Hua; Xu, Quan-Mei; Pei, Yi-Ling; Huang, Zhi-Heng; Yang, Zhen-Gang; Chen, Chao

    2015-07-01

    Hypomyelination is the major cause of neurodevelopmental deficits that are associated with perinatal white matter injury. Chondroitin sulfate proteoglycans (CSPGs) are known to exert inhibitory effects on the migration and differentiation of oligodendrocytes (OLs). However, few studies describe the roles of CSPGs in myelination by OLs and the cognitive dysfunction that follows perinatal white matter injury. Here, we examined the alterations in the expression of CSPGs and their functional impact on the maturation of OLs and myelination in a neonatal rat model of hypoxic-ischemic (HI) brain injury. Three-day-old Sprague-Dawley rats underwent a right common carotid artery ligation and were exposed to hypoxia (6% oxygen for 2.5h). Rats were given chondroitinase ABC (cABC) via an intracerebroventricular injection to digest CSPGs. Animals were sacrificed at 7, 14, 28 and 56days after HI injury and the accompanying surgical procedure. We found that the expression of CSPGs was significantly up-regulated in the cortical regions surrounding the white matter after HI injury. cABC successfully degraded CSPGs in the rats that received cABC. Immunostaining showed decreased expression of the pre-oligodendrocyte marker O4 in the cingulum, external capsule and corpus callosum in HI+cABC rats compared to HI rats. However HI+cABC rats exhibited greater maturation of OLs than did HI rats, with increased expression of O1 and myelin basic protein in the white matter. Furthermore, using electron microscopy, we demonstrated that myelin formation was enhanced in HI+cABC rats, which had an increased number of myelinated axons and decreased G-ratios of myelin compared to HI rats. Finally, HI+cABC rats performed better in the Morris water maze task than HI rats, which indicates an improvement in cognitive ability. Our results suggest that CSPGs inhibit both the maturation of OLs and the process of myelination after neonatal HI brain injury. The data also raise the possibility that modifying CSPGs may repair this type of lesion associated with demyelination. PMID:25862289

  17. Depleting endogenous neurotrophin-3 enhances myelin formation in the Trembler-J mouse, a model of a peripheral neuropathy.

    Science.gov (United States)

    Liu, Ning; Varma, Sushama; Tsao, David; Shooter, Eric M; Tolwani, Ravi J

    2007-10-01

    The heterozygous Trembler-J (TrJ/+) mouse, containing a point mutation in the peripheral myelin protein 22 (Pmp22) gene, is characterized by severe hypomyelination and is a representative model of Charcot-Marie-Tooth 1A (CMT1A) disease/Dejerine-Sottas syndrome (DSS). Given that the neurotrophin-3 (NT3)-TrkC signaling pathway is inhibitory to myelination during development, we investigated the role of the NT3-TrkC pathway in myelination and manipulated this pathway to improve myelin formation in the CMT1A/DSS mouse model. Injection of NT3 to the TrJ/+ mice decreased the myelin protein P(0) level in the sciatic nerves. Suppressing the NT3-TrkC pathway with TrkC-Fc, an NT3 scavenger, enhanced myelination in vitro and in vivo in the TrJ/+ mouse. Furthermore, we found that full-length TrkC was expressed in adult TrJ/+ mouse sciatic nerves but was not detected in the wild-type adults, suggesting that the full-length TrkC is a potential target of treatment to enhance myelination in the TrJ/+ mouse. PMID:17628499

  18. Ribosomal trafficking is reduced in Schwann cells following induction of myelination

    Directory of Open Access Journals (Sweden)

    James M. Love

    2015-08-01

    Full Text Available Local synthesis of proteins within the Schwann cell periphery is extremely important for efficient process extension and myelination, when cells undergo dramatic changes in polarity and geometry. Still, it is unclear how ribosomal distributions are developed and maintained within Schwann cell projections to sustain local translation. In this multi-disciplinary study, we expressed a plasmid encoding a fluorescently labeled ribosomal subunit (L4-GFP in cultured primary rat Schwann cells. This enabled the generation of high-resolution, quantitative data on ribosomal distributions and trafficking dynamics within Schwann cells during early stages of myelination, induced by ascorbic acid treatment. Ribosomes were distributed throughout Schwann cell projections, with ~2-3 bright clusters along each projection. Clusters emerged within 1 day of culture and were maintained throughout early stages of myelination. Three days after induction of myelination, net ribosomal movement remained anterograde (directed away from the Schwann cell body, but ribosomal velocity decreased to about half the levels of the untreated group. Statistical and modeling analysis provided additional insight into key factors underlying ribosomal trafficking. Multiple regression analysis indicated that net transport at early time points was dependent on anterograde velocity, but shifted to dependence on anterograde duration at later time points. A simple, data-driven rate kinetics model suggested that the observed decrease in net ribosomal movement was primarily dictated by an increased conversion of anterograde particles to stationary particles, rather than changes in other directional parameters. These results reveal the strength of a combined experimental and theoretical approach in examining protein localization and transport, and provide evidence of an early establishment of ribosomal populations within Schwann cell projections with a reduction in trafficking following initiation of myelination.

  19. Peripheral nervous system manifestations in a Sandhoff disease mouse model: nerve conduction, myelin structure, lipid analysis

    Directory of Open Access Journals (Sweden)

    Strichartz Gary R

    2007-07-01

    Full Text Available Abstract Background Sandhoff disease is an inherited lysosomal storage disease caused by a mutation in the gene for the ?-subunit (Hexb gene of ?-hexosaminidase A (?? and B (??. The ?-subunit together with the GM2 activator protein catabolize ganglioside GM2. This enzyme deficiency results in GM2 accumulation primarily in the central nervous system. To investigate how abnormal GM2 catabolism affects the peripheral nervous system in a mouse model of Sandhoff disease (Hexb-/-, we examined the electrophysiology of dissected sciatic nerves, structure of central and peripheral myelin, and lipid composition of the peripheral nervous system. Results We detected no significant difference in signal impulse conduction velocity or any consistent change in the frequency-dependent conduction slowing and failure between freshly dissected sciatic nerves from the Hexb+/- and Hexb-/- mice. The low-angle x-ray diffraction patterns from freshly dissected sciatic and optic nerves of Hexb+/- and Hexb-/- mice showed normal myelin periods; however, Hexb-/- mice displayed a ~10% decrease in the relative amount of compact optic nerve myelin, which is consistent with the previously established reduction in myelin-enriched lipids (cerebrosides and sulfatides in brains of Hexb-/- mice. Finally, analysis of lipid composition revealed that GM2 content was present in the sciatic nerve of the Hexb-/- mice (undetectable in Hexb+/-. Conclusion Our findings demonstrate the absence of significant functional, structural, or compositional abnormalities in the peripheral nervous system of the murine model for Sandhoff disease, but do show the potential value of integrating multiple techniques to evaluate myelin structure and function in nervous system disorders.

  20. Enhancement of Schwann cell myelin formation by K252a in the Trembler-J mouse dorsal root ganglion explant culture.

    Science.gov (United States)

    Liu, Ning; Varma, Sushama; Shooter, Eric M; Tolwani, Ravi J

    2005-02-01

    The Trembler-J (TrJ) mouse, containing a point mutation in the peripheral myelin protein 22 gene, is characterized by severe hypomyelination and is a representative model of Charcot-Marie-Tooth 1A disease/Dejerine-Sottas Syndrome. Previous studies have shown that protein kinase inhibitor K252a enhances wild-type Schwann cell myelination in culture. We used a dorsal root ganglion (DRG) explant culture system from the heterozygous TrJ/+ mouse to investigate if myelination could be enhanced by K252a. The TrJ/+ DRG explant cultures replicated some important features of the TrJ/+ mouse, showing reduced myelin protein accumulation, thinner myelin sheaths, and shortened myelin internodes. K252a increased myelin protein accumulation and myelin sheath thickness but did not substantially increase myelin internode length. Furthermore, the TrJ/+ DRG explant culture and sciatic nerves continued to respond to K252a during the stage when myelination is complete in the wild type. A general tyrosine kinase inhibitor, genistein, but not inhibitors of serine/threonine protein kinase inhibitors, had a similar effect to K252a. K252a is therefore able to partially overcome hypomyelination by enhancing mutant Schwann cell myelin formation in the TrJ/+ mouse. PMID:15605381

  1. Myelination delay in the cerebral white matter of immature rats with kaolin-induced hydrocephalus is reversible.

    Science.gov (United States)

    Del Bigio, M R; Kanfer, J N; Zhang, Y W

    1997-09-01

    We hypothesized that hydrocephalus in young animals could cause a delay in myelination. Hydrocephalus was induced in 3-week-old rats by injecting kaolin into the cisterna magna. Ventricular size was assessed by magnetic resonance imaging. After 1 to 4 weeks, rats were either sacrificed, or treated by diversionary shunting of cerebrospinal fluid and then sacrificed 3 to 4 weeks later. Samples of corpus callosum/supraventricular white matter, fimbria, medulla, and spinal cord were assayed for myelin-related enzyme activities including p-nitrophenylphosphorylcholine phosphocholine phosphodiesterase (PNPCP), glycerophosphocholine phosphocholine phosphodiesterase (GPCP), and 2',3'-cyclic neucleotide 3'-phosphodiesterase (CNPase), and the oligodendrocyte enzyme UDP-galactose, ceramide galactosyltransferase (CGa1T). Myelin basic protein (MBP) and proteolipid protein (PLP) were assayed in cerebrum by immunoblots and Northern blot. The corpus callosum was processed for electron microscopy and myelin thickness to axon diameter ratios were quantified. One week after induction of hydrocephalus, CGa1T and GPCP activity were reduced in the corpus callosum there was less MBP and PLP in the cerebrum, and myelin sheaths around axons greater than 0.4 micron in diameter were abnormally thin. With persistent hydrocephalus, the corpus callosum became thinned, axons were lost, and myelin-related enzyme activities and proteins were decreased. Treatment of hydrocephalus at 1 week largely prevented the damage while shunting at 4 weeks failed to restore the injured white matter. Early reduction in CGa1T activity in the medulla and spinal cord suggest that oligodendrocyte production of myelin was reduced, even before irreversible damage occurred in the corticospinal tracts. We conclude that hydrocephalus in the immature rat brain delays myelination, but compensatory myelination is possible if treatment is instituted prior to the development of axonal injury. Possible mechanisms of oligodendrocyte impairment are discussed. PMID:9291946

  2. Myelin oligodendrocyte glycoprotein-35-55 peptide induces severe chronic experimental autoimmune encephalomyelitis in HLA-DR2-transgenic mice.

    OpenAIRE

    Rich, C; Link, JM; Zamora, A.; Jacobsen, H; Meza-Romero, R; OFFNER, H.; JONES, R.; Burrows, GG; Fugger, L; Vandenbark, AA

    2004-01-01

    The use of HLA class II-transgenic (Tg) mice has facilitated identification of antigenic T cell epitopes that may contribute to inflammation in T cell-mediated diseases such as rheumatoid arthritis and multiple sclerosis (MS). In this study, we compared the encephalitogenic activity of three DR2-restricted myelin determinants [mouse (m) myelin oligodendrocyte glycoprotein (MOG)-35-55, human (h)MOG-35-55 and myelin basic protein (MBP)-87-99] in Tg mice expressing the MS-associated DR2 allele, ...

  3. Quantitative analysis of the myelin g-ratio from electron microscopy images of the macaque corpus callosum

    Science.gov (United States)

    Stikov, Nikola; Campbell, Jennifer S.W.; Stroh, Thomas; Lavelée, Mariette; Frey, Stephen; Novek, Jennifer; Nuara, Stephen; Ho, Ming-Kai; Bedell, Barry J.; Dougherty, Robert F.; Leppert, Ilana R.; Boudreau, Mathieu; Narayanan, Sridar; Duval, Tanguy; Cohen-Adad, Julien; Picard, Paul-Alexandre; Gasecka, Alicja; Côté, Daniel; Pike, G. Bruce

    2015-01-01

    We provide a detailed morphometric analysis of eight transmission electron micrographs (TEMs) obtained from the corpus callosum of one cynomolgus macaque. The raw TEM images are included in the article, along with the distributions of the axon caliber and the myelin g-ratio in each image. The distributions are analyzed to determine the relationship between axon caliber and g-ratio, and compared against the aggregate metrics (myelin volume fraction, fiber volume fraction, and the aggregate g-ratio), as defined in the accompanying research article entitled ‘In vivo histology of the myelin g-ratio with magnetic resonance imaging’ (Stikov et al., NeuroImage, 2015). PMID:26217818

  4. Quantitative analysis of the myelin g-ratio from electron microscopy images of the macaque corpus callosum

    Directory of Open Access Journals (Sweden)

    Nikola Stikov

    2015-09-01

    Full Text Available We provide a detailed morphometric analysis of eight transmission electron micrographs (TEMs obtained from the corpus callosum of one cynomolgus macaque. The raw TEM images are included in the article, along with the distributions of the axon caliber and the myelin g-ratio in each image. The distributions are analyzed to determine the relationship between axon caliber and g-ratio, and compared against the aggregate metrics (myelin volume fraction, fiber volume fraction, and the aggregate g-ratio, as defined in the accompanying research article entitled ‘In vivo histology of the myelin g-ratio with magnetic resonance imaging’ (Stikov et al., NeuroImage, 2015.

  5. Split-ball resonator

    CERN Document Server

    Kuznetsov, Arseniy I; Fu, Yuan Hsing; Viswanathan, Vignesh; Rahmani, Mohsen; Valuckas, Vytautas; Kivshar, Yuri; Pickard, Daniel S; Lukiyanchuk, Boris

    2014-01-01

    We introduce a new concept of split-ball resonator and demonstrate a strong omnidirectional magnetic dipole response for both gold and silver spherical plasmonic nanoparticles with nanometer-scale cuts. Tunability of the magnetic dipole resonance throughout the visible spectral range is demonstrated by a change of the depth and width of the nanoscale cut. We realize this novel concept experimentally by employing the laser-induced transfer method to produce near-perfect spheres and helium ion beam milling to make cuts with the nanometer resolution. Due to high quality of the spherical particle shape, governed by strong surface tension forces during the laser transfer process, and the clean, straight side walls of the cut made by helium ion milling, magnetic resonance is observed at 600 nm in gold and at 565 nm in silver nanoparticles. Structuring arbitrary features on the surface of ideal spherical resonators with nanoscale dimensions provides new ways of engineering hybrid resonant modes and ultra-high near-f...

  6. Global Locator, Local Locator, and Identifier Split (GLI-Split

    Directory of Open Access Journals (Sweden)

    Michael Menth

    2013-03-01

    Full Text Available The locator/identifier split is an approach for a new addressing and routing architecture to make routing in the core of the Internet more scalable. Based on this principle, we developed the GLI-Split framework, which separates the functionality of current IP addresses into a stable identifier and two independent locators, one for routing in the Internet core and one for edge networks. This makes routing in the Internet more stable and provides more flexibility for edge networks. GLI-Split can be incrementally deployed and it is backward-compatible with the IPv6 Internet. We describe its architecture, compare it to other approaches, present its benefits, and finally present a proof-of-concept implementation of GLI-Split.

  7. LDL receptor-related protein-1 is a sialic-acid-independent receptor for myelin-associated glycoprotein that functions in neurite outgrowth inhibition by MAG and CNS myelin

    OpenAIRE

    Stiles, Travis L.; Dickendesher, Travis L.; Gaultier, Alban; Fernandez-Castaneda, Anthony; Mantuano, Elisabetta; Giger, Roman J.; Gonias, Steven L.

    2013-01-01

    In the injured adult mammalian central nervous system (CNS), products are generated that inhibit neuronal sprouting and regeneration. In recent years, most attention has focused on the myelin-associated inhibitory proteins (MAIs) Nogo-A, OMgp, and myelin-associated glycoprotein (MAG). Binding of MAIs to neuronal cell-surface receptors leads to activation of RhoA, growth cone collapse, and neurite outgrowth inhibition. In the present study, we identify low-density lipoprotein (LDL) receptor-re...

  8. ISR split-field magnet

    CERN Multimedia

    1974-01-01

    The Split-Field-Magnet at the ISR with arrays of multiwire proportional chambers installed in its large aperture. The detection system is now in full action for experiments and the first results have been reported.

  9. ISR split-field magnet

    CERN Multimedia

    1975-01-01

    The experimental apparatus used at intersection 4 around the Split-Field Magnet by the CERN-Bologna Collaboration (experiment R406). The plastic scintillator telescopes are used for precise pulse-height and time-of-flight measurements.

  10. A Study of Molecular Mimicry and Immunological Cross-reactivity between Hepatitis B Surface Antigen and Myelin Mimics

    OpenAIRE

    Diego Vergani; Giorgina Mieli-Vergani; Harold Baum; Yun Ma; Heather Smith; Dimitrios-Petrou Bogdanos

    2005-01-01

    On the basis of the reported association between hepatitis B vaccination (HBvacc) and autoimmune demyelinating complications such as multiple sclerosis (MS), we have looked for aminoacid similarities between the small hepatitis B virus surface antigen (SHBsAg), and the MS-autoantigens myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) that could serve as targets of immunological cross-reactivity. Twenty-mer...

  11. Myelin repair in vivo is increased by targeting oligodendrocyte precursor cells with nanoparticles encapsulating leukaemia inhibitory factor (LIF)

    Science.gov (United States)

    Rittchen, Sonja; Boyd, Amanda; Burns, Alasdair; Park, Jason; Fahmy, Tarek M.; Metcalfe, Su; Williams, Anna

    2015-01-01

    Multiple sclerosis (MS) is a progressive demyelinating disease of the central nervous system (CNS). Many nerve axons are insulated by a myelin sheath and their demyelination not only prevents saltatory electrical signal conduction along the axons but also removes their metabolic support leading to irreversible neurodegeneration, which currently is untreatable. There is much interest in potential therapeutics that promote remyelination and here we explore use of leukaemia inhibitory factor (LIF), a cytokine known to play a key regulatory role in self-tolerant immunity and recently identified as a pro-myelination factor. In this study, we tested a nanoparticle-based strategy for targeted delivery of LIF to oligodendrocyte precursor cells (OPC) to promote their differentiation into mature oligodendrocytes able to repair myelin. Poly(lactic-co-glycolic acid)-based nanoparticles of ?120 nm diameter were constructed with LIF as cargo (LIF-NP) with surface antibodies against NG-2 chondroitin sulfate proteoglycan, expressed on OPC. In vitro, NG2-targeted LIF-NP bound to OPCs, activated pSTAT-3 signalling and induced OPC differentiation into mature oligodendrocytes. In vivo, using a model of focal CNS demyelination, we show that NG2-targeted LIF-NP increased myelin repair, both at the level of increased number of myelinated axons, and increased thickness of myelin per axon. Potency was high: a single NP dose delivering picomolar quantities of LIF is sufficient to increase remyelination. Impact statement Nanotherapy-based delivery of leukaemia inhibitory factor (LIF) directly to OPCs proved to be highly potent in promoting myelin repair in vivo: this delivery strategy introduces a novel approach to delivering drugs or biologics targeted to myelin repair in diseases such as MS. PMID:25934281

  12. Loss of lysophosphatidic acid receptor LPA1 alters oligodendrocyte differentiation and myelination in the mouse cerebral cortex.

    Science.gov (United States)

    García-Díaz, Beatriz; Riquelme, Raquel; Varela-Nieto, Isabel; Jiménez, Antonio Jesús; de Diego, Isabel; Gómez-Conde, Ana Lsabel; Matas-Rico, Elisa; Aguirre, José Ángel; Chun, Jerold; Pedraza, Carmen; Santín, Luis Javier; Fernández, Oscar; Rodríguez de Fonseca, Fernando; Estivill-Torrús, Guillermo

    2015-11-01

    Lysophosphatidic acid (LPA) is an intercellular signaling lipid that regulates multiple cellular functions, acting through specific G-protein coupled receptors (LPA1-6). Our previous studies using viable Malaga variant maLPA1-null mice demonstrated the requirement of the LPA1 receptor for normal proliferation, differentiation, and survival of the neuronal precursors. In the cerebral cortex LPA1 is expressed extensively in differentiating oligodendrocytes, in parallel with myelination. Although exogenous LPA-induced effects have been investigated in myelinating cells, the in vivo contribution of LPA1 to normal myelination remains to be demonstrated. This study identified a relevant in vivo role for LPA1 as a regulator of cortical myelination. Immunochemical analysis in adult maLPA1-null mice demonstrated a reduction in the steady-state levels of the myelin proteins MBP, PLP/DM20, and CNPase in the cerebral cortex. The myelin defects were confirmed using magnetic resonance spectroscopy and electron microscopy. Stereological analysis limited the defects to adult differentiating oligodendrocytes, without variation in the NG2(+) precursor cells. Finally, a possible mechanism involving oligodendrocyte survival was demonstrated by the impaired intracellular transport of the PLP/DM20 myelin protein which was accompanied by cellular loss, suggesting stress-induced apoptosis. These findings describe a previously uncharacterized in vivo functional role for LPA1 in the regulation of oligodendrocyte differentiation and myelination in the CNS, underlining the importance of the maLPA1-null mouse as a model for the study of demyelinating diseases. PMID:25226845

  13. Experimental autoimmune peripheral neuritis induced in BALB/c mice by myelin basic protein-specific T cell clones

    OpenAIRE

    1995-01-01

    In vivo adoptive transfer of CD4+ T helper cell type 1 clones reactive with autologous myelin basic protein (MBP) may initiate an inflammatory demyelinating disease of the central nervous system called experimental autoimmune encephalomyelitis. Although MBP is also a component of peripheral nervous system (PNS) myelin, previous studies have failed to demonstrate inflammation in the PNS induced by MBP-reactive T cells. Here, we report on two MBP-specific T cell clones that preferentially initi...

  14. Long-term consequences of chronic fluoxetine exposure on the expression of myelination-related genes in the rat hippocampus.

    Science.gov (United States)

    Kroeze, Y; Peeters, D; Boulle, F; van den Hove, D L A; van Bokhoven, H; Zhou, H; Homberg, J R

    2015-01-01

    The selective serotonin reuptake inhibitor (SSRI) fluoxetine is widely prescribed for the treatment of symptoms related to a variety of psychiatric disorders. After chronic SSRI treatment, some symptoms remediate on the long term, but the underlying mechanisms are not yet well understood. Here we studied the long-term consequences (40 days after treatment) of chronic fluoxetine exposure on genome-wide gene expression. During the treatment period, we measured body weight; and 1 week after treatment, cessation behavior in an SSRI-sensitive anxiety test was assessed. Gene expression was assessed in hippocampal tissue of adult rats using transcriptome analysis and several differentially expressed genes were validated in independent samples. Gene ontology analysis showed that upregulated genes induced by chronic fluoxetine exposure were significantly enriched for genes involved in myelination. We also investigated the expression of myelination-related genes in adult rats exposed to fluoxetine at early life and found two myelination-related genes (Transferrin (Tf) and Ciliary neurotrophic factor (Cntf)) that were downregulated by chronic fluoxetine exposure. Cntf, a neurotrophic factor involved in myelination, showed regulation in opposite direction in the adult versus neonatally fluoxetine-exposed groups. Expression of myelination-related genes correlated negatively with anxiety-like behavior in both adult and neonatally fluoxetine-exposed rats. In conclusion, our data reveal that chronic fluoxetine exposure causes on the long-term changes in expression of genes involved in myelination, a process that shapes brain connectivity and contributes to symptoms of psychiatric disorders. PMID:26393488

  15. Electron microscopic study of the myelinated nerve fibres and the perineurial cell basement membrane in the diabetic human peripheral nerves

    International Nuclear Information System (INIS)

    To study the quantitative and ultrastructural changes in myelinated nerve fibers and the basement membranes of the perineurial cells in diabetic nerves. The study was performed at the Department of Anatomy, Faculty of Medicine, King Abdul-Aziz University, Jeddah, Saudi Arabia from 2003 to 2005. Human sural nerves were obtained from 15 lower limbs and 5 diabetic nerve biopsies. The total mean and density of myelinated nerve fibers per fascicle were calculated, with density of microtubules and mitochondria in the axoplasm. The number of the perineurial cell basement membrane layers was counted, and thickness of the basement membrane was measured. Among the 15 diabetic and 5 normal human sural nerves, the average diameters, number and surface area of myelinated nerve fibers and axonal microtubules density were found to be less in diabetic nerves. Mitochondrial density was higher in diabetic axons. Thickness of the perineurial cell basement membrane had a greater mean, but the number of perineurial cell layers was less than that of the diabetic group. The inner cellular layer of the perineurium of the diabetic nerves contained large vacuoles containing electron-dense degenerated myelin. A few specimens showed degenerated myelinated nerve fibers, while others showed recovering ones. Retracted axoplasms were encountered with albumin extravasation. Diabetes caused an increase in perineurial permeability. The diabetic sural nerve showed marked decrease in the myelinated nerve fibres, increase degenerated mitochondria, and decreased microtubules. (author)

  16. Immunoscintigraphy of experimental transplantable tumours using monoclonal antibody against myelin basic protein

    Energy Technology Data Exchange (ETDEWEB)

    Koevesi, G.; Mohari, K.; Kocsar, L.; Fekete, B.; Szilvasi, I.; Szabo, G. (Semmelweis Univ. of Medicine, Budapest (Hungary). Dept. of Maxillofacial Surgery National Frederic Joliot Curie Radiology Radiohygiene Inst., Budapest (Hungary) Biological Centre of Hungary, Szeged (Hungary) Central State Hospital, Budapest (Hungary) Postgraduate Univ. of Medicine, Budapest (Hungary). 3. Physiological Clinic)

    1991-07-01

    Monoclonal antibody was prepared against myelin basic protein a so called pancarcinoma antigen. After labelling with {sup 131}I the monoclonal antibody was injected into Lewis-lung cancer mice and rats with Walker breast cancer. Two, 24, 48, 72 and 96 hours after the labelled monoclonal antibody injection, radioimmunoimaging studies were carried out. After each gamma-camera study, organ distribution of the labelled monoclonal antibody was determined with radiobioassay technique which showed signficantly higher activity in the tumour tissue than in healthy ones. Significant sample radioactivity could be recovered in the tumour masses 48 hours after injection, which persisted even after 96 hours. The later finding might enable diagnosing types of malignancy with isotope-labelled monoclonal antibody against myelin basic protein. (orig.).

  17. Myelin- and microbe-specific antibodies in Guillain-Barré syndrome.

    Science.gov (United States)

    Terryberry, J; Sutjita, M; Shoenfeld, Y; Gilburd, B; Tanne, D; Lorber, M; Alosachie, I; Barka, N; Lin, H C; Youinou, P

    1995-01-01

    We surveyed the frequency of reported infections and target autoantigens in 56 Guillain Barré syndrome (GBS) patients by detecting antibodies to myelin and microbes. Sulfatide (43%), cardiolipin (48%), GD1a (15%), SGPG (11%), and GM3 (11%) antibodies were the most frequently detected heterogenous autoantibodies. A wide spectrum of antimicrobial IgG and IgM antibodies were also detected; mumps-specific IgG (66%), adenovirus-specific IgG (52%), varicella-zoster virus-specific IgG (46%), and S. pneumoniae serotype 7-specific IgG (45%) were the most prevalent. Our results indicate that polyclonal expansion of physiologic and pathologic antibodies and/or molecular mimicry likely occurs following infection and is related to other autoimmune factors in the etiology of GBS. Although no single definitive myelin-specific autoantibody was identified, our results suggest a unique pattern of reactivity against autoantigens. PMID:8531012

  18. Proteolysis of multiple myelin basic protein isoforms after neurotrauma: characterization by mass spectrometry

    OpenAIRE

    Ottens, Andrew K.; Golden, Erin C.; Bustamante, Liliana; Hayes, Ronald L.; Denslow, Nancy D; Wang, Kevin K. W.

    2007-01-01

    Neurotrauma, as in the case of traumatic brain injury, promotes protease over-activation characterized by the select fragmentation of brain proteins. The resulting polypeptides are indicators of biochemical processes, which can be used to study post-injury dynamics and may also be developed into biomarkers. To this end, we devised a novel mass spectrometry approach to characterize post-injury calpain proteolytic processing of myelin basic protein (MBP), a biomarker of brain injury that denote...

  19. Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders

    OpenAIRE

    Mader Simone; Gredler Viktoria; Schanda Kathrin; Rostasy Kevin; Dujmovic Irena; Pfaller Kristian; Lutterotti Andreas; Jarius Sven; Di Pauli Franziska; Kuenz Bettina; Ehling Rainer; Hegen Harald; Deisenhammer Florian; Aboul-Enein Fahmy; Storch Maria K

    2011-01-01

    Abstract Background Serum autoantibodies against the water channel aquaporin-4 (AQP4) are important diagnostic biomarkers and pathogenic factors for neuromyelitis optica (NMO). However, AQP4-IgG are absent in 5-40% of all NMO patients and the target of the autoimmune response in these patients is unknown. Since recent studies indicate that autoimmune responses to myelin oligodendrocyte glycoprotein (MOG) can induce an NMO-like disease in experimental animal models, we speculate that MOG might...

  20. Multiple sclerosis patients show sexual dimorphism in cytokine responses to myelin antigens

    OpenAIRE

    Moldovan, Ioana R.; Cotleur, Anne C.; Zamor, Natacha; Butler, Robert S.; Pelfrey, Clara M.

    2007-01-01

    Multiple sclerosis affects more women than men. The reasons for this are unknown. Previously, we have shown significant differences in women versus men in inflammatory cytokine responses to the major protein component of myelin, proteolipid protein (PLP), which is thought to be a target in MS patients. Here, using the ELISPOT assay, we examined sex differences in single-cell secretion of Th1 and Th2 cytokines from freshly isolated PBMC between relapsing remitting (RR) MS patients and healthy ...

  1. Self-antigen tetramers discriminate between myelin autoantibodies to native or denatured protein

    OpenAIRE

    O’Connor, Kevin C; McLaughlin, Katherine A; De Jager, Philip L.; Chitnis, Tanuja; Bettelli, Estelle; Xu, Chenqi; Robinson, William H; Cherry, Sunil V; Bar-Or, Amit; Banwell, Brenda; Fukaura, Hikoaki; Fukazawa, Toshiyuki; Tenembaum, Silvia; Wong, Susan J.; Tavakoli, Norma P

    2007-01-01

    The role of autoantibodies in the pathogenesis of multiple sclerosis (MS) and other demyelinating diseases is controversial, in part because widely used western blotting and ELISA methods either do not permit the detection of conformation-sensitive antibodies or do not distinguish them from conformation-independent antibodies. We developed a sensitive assay based on self-assembling radiolabeled tetramers that allows discrimination of antibodies against folded or denatured myelin oligodendrocy...

  2. Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis

    OpenAIRE

    Menge Til; Lalive Patrice H; von Büdingen H -Christian; Genain Claude P

    2011-01-01

    Abstract Background Myelin/oligodendrocyte glycoprotein (MOG) is a putative autoantigen in multiple sclerosis (MS). Establishing the pathological relevance and validity of anti-MOG antibodies as biomarkers has yielded conflicting reports mainly due to different MOG isoforms used in different studies. Because epitope specificity may be a key factor determining anti-MOG reactivity we aimed at identifying a priori immunodominant MOG epitopes by monoclonal antibodies (mAbs) and at assessing clini...

  3. Myelin Oligodendrocyte Glycoprotein–specific T Cell Receptor Transgenic Mice Develop Spontaneous Autoimmune Optic Neuritis

    OpenAIRE

    Bettelli, Estelle; Pagany, Maria; Weiner, Howard L.; Linington, Christopher; Sobel, Raymond A.; Kuchroo, Vijay K

    2003-01-01

    Multiple sclerosis (MS) is considered to be an autoimmune disease of the central nervous system (CNS) that in many patients first presents clinically as optic neuritis. The relationship of optic neuritis to MS is not well understood. We have generated novel T cell receptor (TCR) transgenic mice specific for myelin oligodendrocyte glycoprotein (MOG). MOG-specific transgenic T cells are not deleted nor tolerized and are functionally competent. A large proportion (>30%) of MOG-specific TCR trans...

  4. The crystal structure of myelin oligodendrocyte glycoprotein, a key autoantigen in multiple sclerosis

    OpenAIRE

    Clements, Craig S.; Reid, Hugh H.; Beddoe, Travis; Tynan, Fleur E.; Perugini, Matthew A; Johns, Terrance G.; Bernard, Claude C A; Rossjohn, Jamie

    2003-01-01

    Myelin oligodendrocyte glycoprotein (MOG) is a key CNS-specific autoantigen for primary demyelination in multiple sclerosis. Although the disease-inducing role of MOG has been established, its precise function in the CNS remains obscure. To gain new insights into the physiological and immunopathological role of MOG, we determined the 1.8-Å crystal structure of the MOG extracellular domain (MOGED). MOGED adopts a classical Ig (Ig variable domain) fold that was observed to form an antiparallel ...

  5. Vaccination with DNA encoding a myelin autoantigen exacerbates experimental autoimmune encephalitis

    OpenAIRE

    Bourquin, Carole

    2000-01-01

    The ultimate goal in the treatment of autoimmune diseases is to reestablish tolerance to self antigens. One strategy to induce tolerance is to express the target autoantigen by DNA vaccination. In this work, the potential of vaccination with a DNA construct encoding the myelin oligodendrocyte glycoprotein (MOG), an important candidate autoantigen in multiple sclerosis, to induce tolerance and protect against experimental autoimmune encephalomyelitis (EAE) was assessed. Unexpectedly, mice vac...

  6. Age-dependent B cell Autoimmunity to a Myelin Surface Antigen in Pediatric Multiple Sclerosis

    OpenAIRE

    McLaughlin, Katherine A; Chitnis, Tanuja; Newcombe, Jia; Franz, Bettina; Kennedy, Julia; McArdel, Shannon; Kuhle, Jens; Kappos, Ludwig; Rostasy, Kevin; Pohl, Daniela; Gagne, Donald; Ness, Jayne M.; Tenembaum, Silvia; O'Connor, Kevin C.; Viglietta, Vissia

    2009-01-01

    Multiple sclerosis (MS) typically manifests in early to mid adulthood, but there is increasing recognition of pediatric-onset MS, aided by improvements in imaging techniques. The immunological mechanisms of disease are largely unexplored in pediatric-onset MS, in part because studies have historically focused on adult-onset disease. We investigated autoantibodies to myelin surface antigens in a large cohort of pediatric MS cases by flow cytometric labeling of transfectants that expressed diff...

  7. Polyreactive Myelin Oligodendrocyte Glycoprotein Antibodies: Implications for Systemic Autoimmunity in Progressive Experimental Autoimmune Encephalomyelitis

    OpenAIRE

    PETERSON, LISA K.; TSUNODA, IKUO; Masaki, Takahisa; Fujinami, Robert S

    2007-01-01

    Two myelin oligodendrocyte glycoprotein (MOG92–106) monoclonal antibodies (mAbs) were produced from an A.SW mouse with progressive experimental autoimmune encephalomyelitis. Polyreactivity/specificity of the mAbs was demonstrated by ELISA. Functionality and a potential role in pathogenesis of systemic autoimmunity were demonstrated in vitro in a lymphocytotoxicity assay and in vivo upon injection into naïve mice. Injection of MOG mAb producing hybridomas into naïve mice resulted in immunoglob...

  8. Myelin-oligodendrocyte glycoprotein antibodies in adults with a neuromyelitis optica phenotype.

    OpenAIRE

    Kitley, J; WOODHALL, M; Waters, P.; Leite, MI; Devenney, E; Craig, J; Palace, J.; Vincent, A

    2012-01-01

    OBJECTIVES: To report an association of myelin-oligodendrocyte glycoprotein (MOG) antibodies with aquaporin-4 (AQP4) antibody-seronegative neuromyelitis optica (NMO) and neuromyelitis optica spectrum disorder (NMOSD) in adults. METHODS: We describe the clinical and serologic features of 4 adult patients with an NMO/NMOSD phenotype who had antibodies to MOG. RESULTS: Twenty-seven adult AQP4-seronegative NMO/NMOSD patients were tested for MOG antibodies. Four patients (3 male, 1 female) with se...

  9. Redox regulation of cytokine-mediated inhibition of myelin gene expression in human primary oligodendrocytes

    OpenAIRE

    JANA, Malabendu; Pahan, Kalipada

    2005-01-01

    Multiple sclerosis (MS) is a chronic autoimmune demyelinating disorder of the central nervous system (CNS) of unknown etiology. Several studies have shown that demyelination in MS is caused by proinflammatory mediators which are released by perivascular infiltrates and/or activated glial cells. To understand if proinflammatory mediators such as IL (interleukin)-1? and TNF (tumor necrosis factor)-? are capable of modulating the expression of myelin-specific genes, we investigated the effect of...

  10. Microglial Fc Receptors Mediate Physiological Changes Resulting From Antibody Cross-Linking of Myelin Oligodendrocyte Glycoprotein

    OpenAIRE

    Marta, Cecilia B.; Bansal, Rashmi; Pfeiffer, Steven E.

    2008-01-01

    Antibodies to myelin oligodendrocyte glycoprotein (MOG) have been implicated in Multiple Sclerosis demyelination through activation of complement and/or macrophage-effector processes. We presented a novel mechanism, whereby MOG on oligodendrocytes, when cross-linked with anti-MOG and secondary antibody resulted in its repartitioning into lipid rafts, and changes in protein phosphorylation and morphology. Here, we show that similar events occur when anti-MOG is cross-linked with Fc receptors (...

  11. Circulating antibody to myelin basic protein in relapsing-remitting multiple sclerosis

    International Nuclear Information System (INIS)

    Sera from multiple sclerosis patients with relapsing-remitting disease and normal subjects were tested for antibody to myelin basic protein by a sensitive radioimmunoassay. The results showed a marginally decreased titre in multiple sclerosis superimposed on a seasonal variation. There was no correlation with the clinical state of the patients. Results are discussed briefly in relation to humoral antibody function in multiple sclerosis and experimental autoimmune encephalitis. (author)

  12. T(2)-relaxometry for myelin water fraction extraction using wald distribution and extended phase graph.

    Science.gov (United States)

    Akhondi-Asl, Alireza; Afacan, Onur; Mulkern, Robert V; Warfield, Simon K

    2014-01-01

    Quantitative assessment of myelin density in the white matter is an emerging tool for neurodegenerative disease related studies such as multiple sclerosis and Schizophrenia. For the last two decades, T2 relaxometry based on multi-exponential fitting to a single slice multi-echo sequence has been the most common MRI technique for myelin water fraction (MWF) mapping, where the short T2 is associated with myelin water. However, modeling the spectrum of the relaxations as the sum of large number of impulse functions with unknown amplitudes makes the accuracy and robustness of the estimated MWF's questionable. In this paper, we introduce a novel model with small number of parameters to simultaneously characterize transverse relaxation rate spectrum and B1 inhomogeneity at each voxel. We use mixture of three Wald distributions with unknown mixture weights, mean and shape parameters to represent the distribution of the relative amount of water in between myelin sheets, tissue water, and cerebrospinal fluid. The parameters of the model are estimated using the variable projection method and are used to extract the MWF at each voxel. In addition, we use Extended Phase Graph (EPG) method to compensate for the stimulated echoes caused by B1 inhomogeneity. To validate our model, synthetic and real brain experiments were conducted where we have compared our novel algorithm with the non-negative least squares (NNLS) as the state-of-the-art technique in the literature. Our results indicate that we can estimate MWF map with substantially higher accuracy as compared to the NNLS method. PMID:25320793

  13. An autometallographic technique for myelin staining in formaldehyde-fixed tissue

    OpenAIRE

    Larsen, M.; Bjarkam, C.R.; M Stoltenberg; Sorensen, J.C.; Danscher, G.

    2003-01-01

    A new autometallographic (AMG) technique for staining myelin in formaldehyde- or paraformaldehyde- (PFA) fixed tissue is presented. The tissue sections were exposed to AMG development without prior treatment with silver salts. The method was examined on PFA-fixed tissue from mouse, rat, pig, and formaldehyde-fixed human autopsy material. Samples from brain, spinal cord, cranial, and spinal nerves were either cut on a vibratome, frozen and cryostat sectioned...

  14. Steroid responsive polyneuropathy in a family with a novel myelin protein zero mutation

    OpenAIRE

    Donaghy, M; Sisodiya, S; Kennett, R.; McDonald, B.; Haites, N.; Bell, C

    2000-01-01

    OBJECTIVE—To report a novel hereditary motor and sensory neuropathy (HMSN) phenotype, with partial steroid responsiveness, caused by a novel dominant mutation in the myelin protein zero (MPZ) gene. Most MPZ mutations lead to the HMSN type I phenotype, with recent reports of Déjérine-Sottas, congenital hypomyelination, and HMSN II also ascribed to MPZ mutations. Differing phenotypes may reflect the effect of particular mutations on MPZ structure and adhesivity.?METHO...

  15. Induction of Oligodendrocyte Differentiation and In Vitro Myelination by Inhibition of Rho-Associated Kinase

    OpenAIRE

    Pedraza, Carlos E.; Taylor, Christopher, Lama; Pereira, Albertina; Seng, Michelle; Tham, Chui-Se; Izrael, Michal; Webb, Michael

    2014-01-01

    In inflammatory demyelinating diseases such as multiple sclerosis (MS), myelin degradation results in loss of axonal function and eventual axonal degeneration. Differentiation of resident oligodendrocyte precursor cells (OPCs) leading to remyelination of denuded axons occurs regularly in early stages of MS but halts as the pathology transitions into progressive MS. Pharmacological potentiation of endogenous OPC maturation and remyelination is now recognized as a promising th...

  16. Skin-derived neural precursors competitively generate functional myelin in adult demyelinated mice.

    Science.gov (United States)

    Mozafari, Sabah; Laterza, Cecilia; Roussel, Delphine; Bachelin, Corinne; Marteyn, Antoine; Deboux, Cyrille; Martino, Gianvito; Baron-Van Evercooren, Anne

    2015-09-01

    Induced pluripotent stem cell-derived (iPS-derived) neural precursor cells may represent the ideal autologous cell source for cell-based therapy to promote remyelination and neuroprotection in myelin diseases. So far, the therapeutic potential of reprogrammed cells has been evaluated in neonatal demyelinating models. However, the repair efficacy and safety of these cells has not been well addressed in the demyelinated adult CNS, which has decreased cell plasticity and scarring. Moreover, it is not clear if these induced pluripotent-derived cells have the same reparative capacity as physiologically committed CNS-derived precursors. Here, we performed a side-by-side comparison of CNS-derived and skin-derived neural precursors in culture and following engraftment in murine models of adult spinal cord demyelination. Grafted induced neural precursors exhibited a high capacity for survival, safe integration, migration, and timely differentiation into mature bona fide oligodendrocytes. Moreover, grafted skin-derived neural precursors generated compact myelin around host axons and restored nodes of Ranvier and conduction velocity as efficiently as CNS-derived precursors while outcompeting endogenous cells. Together, these results provide important insights into the biology of reprogrammed cells in adult demyelinating conditions and support use of these cells for regenerative biomedicine of myelin diseases that affect the adult CNS. PMID:26301815

  17. Vitamin D3 potentiates myelination and recovery after facial nerve injury.

    Science.gov (United States)

    Montava, Marion; Garcia, Stéphane; Mancini, Julien; Jammes, Yves; Courageot, Joël; Lavieille, Jean-Pierre; Feron, François

    2015-10-01

    Roles of vitamin D on the immune and nervous systems are increasingly recognized. Two previous studies demonstrated that ergocalciferol (vitamin D2) or cholecalciferol (vitamin D3) induced functional recovery and increased myelination in a rat model of peroneal nerve transection. The current report assessed whether cholecalciferol was efficient in repairing transected rabbit facial nerves. Animals were randomized into two groups of rabbits with an unilateral facial nerve surgery: the vitamin D group included animals receiving a weekly oral bolus of vitamin D3 (200 IU/kg/day), from day 1 post-surgery; the control group included animals receiving a weekly oral bolus of vehicle (triglycerides). Contralateral unsectioned facial nerves from all experimental animals were used as controls for the histological study. The facial functional index was measured every week while the inner diameter of myelin sheath and the G ratio were quantified at the end of the 3 month experiment. The current report indicates that cholecalciferol significantly increases functional recovery and myelination, after 12 weeks of treatment. To the best of our knowledge, this is the first study investigating the therapeutic benefit of vitamin D supplementation in an animal model of facial paralysis. It paves further the way for clinical trials based on the administration of this steroid in individuals with injured facial nerves. PMID:25261104

  18. Determinação de Anticorpos Anti-Mielina na Esclerose Múltipla / Anti-Myelin Autoantibodies in Multiple Sclerosis

    Scientific Electronic Library Online (English)

    Eduardo, Lima; Joana, Guimarães; Ana, Pereira; Abília, Bodas; Luís, Delgado; Maria José, Sá.

    Full Text Available Introdução: A Esclerose Múltipla é uma doença desmielinizante primária de carácter autoimune, envolvendo diferentes mecanismos imunopatológicos. Pensa-se que anticorpos dirigidos contra antigénios da mielina podem estar associados aos danos na mielina ou surgirem devido a estes, pelo que, o seu dose [...] amento poderá constituir um marcador de evolução da doença. No entanto, a positividade desta pesquisa pode levantar dúvidas em termos de valorização clínica dada a descrição destes auto-anticorpos também em indivíduos sem doença. O objectivo deste trabalho foi a avaliação da presença de auto-anticorpos para a mielina em pacientes com o diagnóstico de Esclerose Múltipla, comparativamente a amostras de controlo, avaliando a sua associação com sintomas clínicos em pacientes com diferentes formas clínicas da Esclerose Múltipla. Métodos: A pesquisa de anticorpos para a mielina foi realizada por uma técnica de imuno?uorescência indirecta usando como substrato, nervo periférico de primata (EUROIMMUN®). Foram estudados 34 doentes (14M/11H), observados no serviço de Neurologia do Hospital de São João: 8 com forma monosintomática em surto, 11 com forma Surto/Remissão (SR) em remissão, 11 com forma SR em surto e 4 com forma Primária Progressiva (PP) em remissão. A população de controlo foi constituída por 25 amostras de indivíduos saudáveis (26M/8H). Resultados: Encontraram-se diferenças signi?cativas nas duas populações em relação à presença de anticorpos para a mielina (p Abstract in english Introduction: Multiple Sclerosis (MS) is a primary demyelinating disease of autoimmune ethiology with different immunopathologic mechanisms. Anti-myelin autoantibodies may be associated with myelin damage and a possible marker of the disease evolution. However, the clinical usefulness of these autoa [...] ntibodies is questionable as they may be present in healthy individuals. The aim of this work was the evaluation of autoantibodies against myelin in patients with MS comparatively with control samples, and their association with differents clinical types. Methology: For the search of anti-myelin antibodies we used indirect immunofluorescence in primate peripheral nerves (EUROIMMUN®). Thirty four patients (14 female/11 male) followed in the Neurology department were studied: 8 with the Clinically Isolated Syndrome (CIS) with relapse, 11 with Relapsing/Remitting (RR) in remission, 11 with RR with relapse and 4 with Primary Progressive (PP); 25 samples of healthy individuals (26 female/8 male) were studied as controls. Results: The presence of autoantibodies to myelin was signifiantly different in the two studied populations (p

  19. Efficient presentation of myelin oligodendrocyte glycoprotein peptides but not protein by astrocytes from HLA-DR2 and HLA-DR4 transgenic mice.

    OpenAIRE

    Kort, JJ; Kawamura, K.; Fugger, L; Weissert, R.; Forsthuber, TG

    2006-01-01

    The role of astrocytes in the pathogenesis of multiple sclerosis (MS) is not well understood. Astrocytes may modulate the activity of pathogenic T cells by presenting myelin antigens in combination with pro- or anti-inflammatory signals. Astrocytes have been shown to present myelin basic protein (MBP) and proteolipid protein (PLP) to T cells, but it has remained unresolved whether astrocytes present myelin oligodendrocyte glycoprotein (MOG), which has been implicated as an important autoantig...

  20. Split liver transplantation: What's unique?

    Science.gov (United States)

    Dalal, Aparna R

    2015-09-24

    The intraoperative management of split liver transplantation (SLT) has some unique features as compared to routine whole liver transplantations. Only the liver has this special ability to regenerate that confers benefits in survival and quality of life for two instead of one by splitting livers. Primary graft dysfunction may result from small for size syndrome. Graft weight to recipient body weight ratio is significant for both trisegmental and hemiliver grafts. Intraoperative surgical techniques aim to reduce portal hyperperfusion and decrease venous portal pressure. Ischemic preconditioning can be instituted to protect against ischemic reperfusion injury which impacts graft regeneration. Advancement of the technique of SLT is essential as use of split cadaveric grafts expands the donor pool and potentially has an excellent future. PMID:26421261

  1. Mass splitting induced by gravitation

    International Nuclear Information System (INIS)

    The exact combination of internal and geometrical symmetries and the associated mass splitting problem is discussed. A 10-parameter geometrical symmetry is defined in a curved space-time in such a way that it is a combination of de Sitter groups. In the flat limit it reproduces the Poincare-group and its Lie algebra has a nilpotent action on the combined symmetry only in that limit. An explicit mass splitting expression is derived and an estimation of the order of magnitude for spin-zero mesons is made. (author)

  2. Splitting strings on integrable backgrounds

    International Nuclear Information System (INIS)

    We use integrability to construct the general classical splitting string solution on R x S3. Namely, given any incoming string solution satisfying a necessary self-intersection property at some given instant in time, we use the integrability of the worldsheet ?-model to construct the pair of outgoing strings resulting from a split. The solution for each outgoing string is expressed recursively through a sequence of dressing transformations, the parameters of which are determined by the solutions to Birkhoff factorization problems in an appropriate real form of the loop group of SL2(C). (orig.)

  3. Geometrical Applications of Split Octonions

    CERN Document Server

    Gogberashvili, Merab

    2015-01-01

    Physical signals and space-time intervals are described in terms of split octonions. Geometrical symmetries are represented by the automorphism group of the algebra - the real non-compact form of Cartan's smallest exceptional group G2. This group generates specific rotations of (3+4)-vector parts of split octonions with three extra time-like coordinates and in certain limits reduces to standard Lorentz group. In this picture several physical characteristics of ordinary (3+1)-dimensional theory (such as: number of spatial dimensions, existence of maximal velocities, the uncertainty principle, some quantum numbers) are naturally emerge from the properties of the algebra.

  4. Split supersymmetry in brane models

    Indian Academy of Sciences (India)

    Ignatios Antoniadis

    2006-11-01

    Type-I string theory in the presence of internal magnetic fields provides a concrete realization of split supersymmetry. To lowest order, gauginos are massless while squarks and sleptons are superheavy. For weak magnetic fields, the correct Standard Model spectrum guarantees gauge coupling unification with $\\sin^{2} \\theta_{W} = 3/8$ at the com-pactification scale of $M_{GUT} \\simeq 2 \\times 10^{16}$ GeV. I discuss mechanisms for generating gaugino and higgsino masses at the TeV scale, as well as generalizations to models with split extended supersymmetry in the gauge sector.

  5. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

    Energy Technology Data Exchange (ETDEWEB)

    Rai, Nagendra Kumar; Ashok, Anushruti [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Rai, Asit; Tripathi, Sachin [Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India); Nagar, Geet Kumar [Endocrinology, CSIR-Central Drug Research Institute (CSIR-CDRI) (India); Mitra, Kalyan [Electron Microscopy Unit, CSIR-CDRI, Lucknow 226001 (India); Bandyopadhyay, Sanghamitra, E-mail: sanghmitra@iitr.res.in [Academy of Scientific and Innovative Research (India); Developmental Toxicology, Council of Scientific and Industrial Research-Indian Institute of Toxicology Research (CSIR-IITR) (India)

    2013-12-01

    Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2?-, 3?-cyclic-nucleotide-3?-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase. • The retina exhibits diminished neurotrophin levels and cellular differentiation. • The toxic effect is apoptotic.

  6. Exposure to As, Cd and Pb-mixture impairs myelin and axon development in rat brain, optic nerve and retina

    International Nuclear Information System (INIS)

    Arsenic (As), lead (Pb) and cadmium (Cd) are the major metal contaminants of ground water in India. We have reported the toxic effect of their mixture (metal mixture, MM), at human relevant doses, on developing rat astrocytes. Astrocyte damage has been shown to be associated with myelin disintegration in CNS. We, therefore, hypothesized that the MM would perturb myelinating white matter in cerebral cortex, optic nerve (O.N.) and retina. We observed modulation in the levels of myelin and axon proteins, such as myelin basic protein (MBP), proteolipid protein, 2?-, 3?-cyclic-nucleotide-3?-phosphodiesterase, myelin-associated glycoprotein and neurofilament (NF) in the brain of developing rats. Dose and time-dependent synergistic toxic effect was noted. The MBP- and NF-immunolabeling, as well as luxol-fast blue (LFB) staining demonstrated a reduction in the area of intact myelin-fiber, and an increase in vacuolated axons, especially in the corpus-callosum. Transmission electron microscopy (TEM) of O.N. revealed a reduction in myelin thickness and axon-density. The immunolabeling with MBP, NF, and LFB staining in O.N. supported the TEM data. The hematoxylin and eosin staining of retina displayed a decrease in the thickness of nerve-fiber, plexiform-layer, and retinal ganglion cell (RGC) count. Investigating the mechanism revealed a loss in glutamine synthetase activity in the cerebral cortex and O.N., and a fall in the brain derived neurotrophic factor in retina. An enhanced apoptosis in MBP, NF and Brn3b-containing cells justified the diminution in myelinating axons in CNS. Our findings for the first time indicate white matter damage by MM, which may have significance in neurodevelopmental-pediatrics, neurotoxicology and retinal-cell biology. - Highlights: • As, Cd and Pb-mixture, at human relevant dose, demyelinate developing rat CNS. • The attenuation in myelin and axon is synergistic. • The optic nerve and brain demonstrate reduced glutamine synthetase. • The retina exhibits diminished neurotrophin levels and cellular differentiation. • The toxic effect is apoptotic

  7. Development and applications of a solid-phase radioimmunoassay for the P0 protein of peripheral myelin

    International Nuclear Information System (INIS)

    The assay uses antigen-coated plastic microwells, with antibody binding detected by 125I-labelled protein A. Either peripheral myelin proteins or purified P0 may be used as the antigen. This method allows the detection of 0.8 ng of P0 (20 ng/ml). Results showed little or no immunoreactivity in extracts of brain, central myelin, liver, purified myelin basic proteins, cultured, purified secondary Schwann cells, or membrane preparations from these cells. P0 was clearly detectable in Schwann cell cultures from 3- 4-day-old rats at 12-18 h after dissociation (4% of the level in adult sciatic nerve) and in extracts of one-day-old rat sciatic nerve (2% of the level in adult nerve). Myelin basic protein radioimmunoassays showed that the ratio of P0 to myelin basic protein is essentially constant in extracts of sciatic nerve from one-day-old, four-day-old, and young adult rats. Another results was that P0 levels are reduced in the trembler mouse sciatic nerve. (author)

  8. The Myelin and Lymphocyte Protein MAL Is Required for Binding and Activity of Clostridium perfringens ?-Toxin

    Science.gov (United States)

    Oo, Myat Lin; Anrather, Josef; Schaeren-Wiemers, Nicole; Alonso, Miguel A.; Fischetti, Vincent A.; McClain, Mark S.; Vartanian, Timothy

    2015-01-01

    Clostridium perfringens ?-toxin (ETX) is a potent pore-forming toxin responsible for a central nervous system (CNS) disease in ruminant animals with characteristics of blood-brain barrier (BBB) dysfunction and white matter injury. ETX has been proposed as a potential causative agent for Multiple Sclerosis (MS), a human disease that begins with BBB breakdown and injury to myelin forming cells of the CNS. The receptor for ETX is unknown. Here we show that both binding of ETX to mammalian cells and cytotoxicity requires the tetraspan proteolipid Myelin and Lymphocyte protein (MAL). While native Chinese Hamster Ovary (CHO) cells are resistant to ETX, exogenous expression of MAL in CHO cells confers both ETX binding and susceptibility to ETX-mediated cell death. Cells expressing rat MAL are ~100 times more sensitive to ETX than cells expressing similar levels of human MAL. Insertion of the FLAG sequence into the second extracellular loop of MAL abolishes ETX binding and cytotoxicity. ETX is known to bind specifically and with high affinity to intestinal epithelium, renal tubules, brain endothelial cells and myelin. We identify specific binding of ETX to these structures and additionally show binding to retinal microvasculature and the squamous epithelial cells of the sclera in wild-type mice. In contrast, there is a complete absence of ETX binding to tissues from MAL knockout (MAL-/-) mice. Furthermore, MAL-/- mice exhibit complete resistance to ETX at doses in excess of 1000 times the symptomatic dose for wild-type mice. We conclude that MAL is required for both ETX binding and cytotoxicity. PMID:25993478

  9. Systemic 5-fluorouracil treatment causes a syndrome of delayed myelin destruction in the central nervous system

    Directory of Open Access Journals (Sweden)

    Han Ruolan

    2008-04-01

    Full Text Available Abstract Background Cancer treatment with a variety of chemotherapeutic agents often is associated with delayed adverse neurological consequences. Despite their clinical importance, almost nothing is known about the basis for such effects. It is not even known whether the occurrence of delayed adverse effects requires exposure to multiple chemotherapeutic agents, the presence of both chemotherapeutic agents and the body's own response to cancer, prolonged damage to the blood-brain barrier, inflammation or other such changes. Nor are there any animal models that could enable the study of this important problem. Results We found that clinically relevant concentrations of 5-fluorouracil (5-FU; a widely used chemotherapeutic agent were toxic for both central nervous system (CNS progenitor cells and non-dividing oligodendrocytes in vitro and in vivo. Short-term systemic administration of 5-FU caused both acute CNS damage and a syndrome of progressively worsening delayed damage to myelinated tracts of the CNS associated with altered transcriptional regulation in oligodendrocytes and extensive myelin pathology. Functional analysis also provided the first demonstration of delayed effects of chemotherapy on the latency of impulse conduction in the auditory system, offering the possibility of non-invasive analysis of myelin damage associated with cancer treatment. Conclusions Our studies demonstrate that systemic treatment with a single chemotherapeutic agent, 5-FU, is sufficient to cause a syndrome of delayed CNS damage and provide the first animal model of delayed damage to white-matter tracts of individuals treated with systemic chemotherapy. Unlike that caused by local irradiation, the degeneration caused by 5-FU treatment did not correlate with either chronic inflammation or extensive vascular damage and appears to represent a new class of delayed degenerative damage in the CNS.

  10. Cool covered sky-splitting spectrum-splitting FK

    Energy Technology Data Exchange (ETDEWEB)

    Mohedano, Rubén; Chaves, Julio; Falicoff, Waqidi; Hernandez, Maikel; Sorgato, Simone [LPI, Altadena, CA, USA and Madrid (Spain); Miñano, Juan C.; Benitez, Pablo [LPI, Altadena, CA, USA and Madrid, Spain and Universidad Politécnica de Madrid (UPM), Madrid (Spain); Buljan, Marina [Universidad Politécnica de Madrid (UPM), Madrid (Spain)

    2014-09-26

    Placing a plane mirror between the primary lens and the receiver in a Fresnel Köhler (FK) concentrator gives birth to a quite different CPV system where all the high-tech components sit on a common plane, that of the primary lens panels. The idea enables not only a thinner device (a half of the original) but also a low cost 1-step manufacturing process for the optics, automatic alignment of primary and secondary lenses, and cell/wiring protection. The concept is also compatible with two different techniques to increase the module efficiency: spectrum splitting between a 3J and a BPC Silicon cell for better usage of Direct Normal Irradiance DNI, and sky splitting to harvest the energy of the diffuse radiation and higher energy production throughout the year. Simple calculations forecast the module would convert 45% of the DNI into electricity.

  11. Myelin-specific regulatory T cells accumulate in the CNS but fail to control autoimmune inflammation

    OpenAIRE

    Korn, Thomas; Reddy, Jayagopala; GAO, WENDA; Bettelli, Estelle; Awasthi, Amit; Petersen, Troels R.; Bäckström, B. Thomas; Sobel, Raymond A.; Wucherpfennig, Kai W.; Strom, Terry B.; Oukka, Mohamed; Kuchroo, Vijay K

    2007-01-01

    Treatment with ex vivo–generated regulatory T cells (T-reg) has been regarded as a potentially attractive therapeutic approach for autoimmune diseases. However, the dynamics and function of T-reg in autoimmunity are not well understood. Thus, we developed Foxp3gfp knock-in (Foxp3gfp.KI) mice and myelin oligodendrocyte glycoprotein (MOG)35–55/IAb (MHC class II) tetramers to track autoantigen-specific effector T cells (T-eff) and T-reg in vivo during experimental autoimmune encephalomyelitis (E...

  12. Tracing Myelin Protein Zero (P0) in vivo by construction of P0-GFP fusion proteins

    OpenAIRE

    Van Broeckhoven Christine; Nelis Eva; Fuchs Christina; Oezbey Sevinc; Ekici Arif B; Schachner Melitta; Rautenstrauss Bernd

    2002-01-01

    Abstract Background Mutations in P0, the major protein of the myelin sheath in peripheral nerves, cause the inherited peripheral neuropathies Charcot-Marie-Tooth disease type 1B (CMT1B), Dejerine-Sottas syndrome (DSS) and congenital hypomyelination (CH). We reported earlier a de novo insertional mutation c.662_663GC (Ala221fs) in a DSS patient. The c.662_663GC insertion results in a frame shift mutation Ala221fs altering the C-terminal amino acid sequence. The adhesion-relevant intracellular ...

  13. Myelination disturbance in a patient with hyperuricemia and hyperserotoninemia combined with 18q deletion syndrome.

    Science.gov (United States)

    László, Aranka; Vörös, Erika; Buga, Klára; Horváth, Katalin; Mayer, Péter; Osztovics, Magda; Pávics, László; Svekus, András; Patterson, Marc C

    2009-11-30

    We previously reported a male patient with an 18q21.3 deletion, hyperuricemia and typical symptoms of the Lesch-Nyhan syndrome who lacked hypoxanthine-guanine-phosphoribosyl-transferase (HGPRT) deficiency. The patient developed progressive peripheral neuropathy in additon to his profound mental retardation and self-injurious behavior. At the age of 23 years MR imaging revealed globally delayed myelination with relative sparing of the corpus callosum and frontal lobes. They were focal hyperintensities suggestive of gliosis. Multimodality evoked potentials found evidence of impaired central and peripheral conduction. Single photon emission computed tomographic (SPECT) imaging demonstrated left frontal hyperperfusion and under it a temporoparietal hypoperfusion. PMID:20025132

  14. 7 CFR 51.2958 - Splits.

    Science.gov (United States)

    2010-01-01

    ...United States Standards for Grades of Walnuts in the Shell Definitions § 51.2958 Splits. Splits...walnuts with the seam opened completely around the nut so that the two halves of the shell are held together only by the...

  15. Rapid Simultaneous Mapping of Total and Myelin Water Content, T1 and T2* in Multiple Sclerosis

    CERN Document Server

    Arhelger, Volker; Gliedstein, Detlef; Lafontaine, Marie-Sofie; Tonkova, Vyara; Holz, Dietrich; Böer, Andreas; Schenk, Jochen; Neeb, Heiko; (,; Koblenz, University of Applied Sciences; Koblenz, Radiologisches Institut Hohenzollernstrasse; Engineering, Institute for Medical; Koblenz, Information Processing; Boeer, Neurologie Dr; Koblenz,

    2010-01-01

    Quantitative magnetic resonance imaging might provide a more specific insight into disease process, progression and therapeutic response of multiple sclerosis. We present an extension of a previously published approach for the simultaneous mapping of brain T1, T2* and total water content. In addition to those three parameters, the method presented in the current work allows for the measurement of myelin bound water content, a surrogate marker of tissue myelination. Myelin water was measured based on its distinct relaxation with reduced T2*, resulting in a multiexponential decay signal. However, only 10 points could be acquired on the relaxation curve within a maximum echo time of <40ms as the quantitative protocol has been adapted previously for fast acquisitions with whole brain coverage. The sparse sampling required an adaption of the optimisation approach with additional constraints necessary in order to obtain reliable results. Therefore, the corresponding pool fractions were determined using linear op...

  16. Evaluation of Optimal Split-Plot Designs

    OpenAIRE

    Julian Mbegbu; Ogege Ikhata Francis

    2012-01-01

    The study introduced an algorithm for generating optimal split-plot designs. The designs were considered as optimal because they were capable and ecient in estimating the xed e ects of the statistical model that is appropriate given the split-plot design structure. Here, we introduced I-optimal design of split-plot experiments. The algorithm used in this research does not require the prior speci cation of a candidate set. Therefore, making the design of split-plot experiments computationally ...

  17. Unmyelinated nerve fibers in the human dental pulp express markers for myelinated fibers and show sodium channel accumulations

    Directory of Open Access Journals (Sweden)

    Henry Michael A

    2012-03-01

    Full Text Available Abstract Background The dental pulp is a common source of pain and is used to study peripheral inflammatory pain mechanisms. Results show most fibers are unmyelinated, yet recent findings in experimental animals suggest many pulpal afferents originate from fibers that are myelinated at more proximal locations. Here we use the human dental pulp and confocal microscopy to examine the staining relationships of neurofilament heavy (NFH, a protein commonly expressed in myelinated afferents, with other markers to test the possibility that unmyelinated pulpal afferents originate from myelinated axons. Other staining relationships studied included myelin basic protein (MBP, protein gene product (PGP 9.5 to identify all nerve fibers, tyrosine hydroxylase (TH to identify sympathetic fibers, contactin-associated protein (caspr to identify nodal sites, S-100 to identify Schwann cells and sodium channels (NaChs. Results Results show NFH expression in most PGP9.5 fibers except those with TH and include the broad expression of NFH in axons lacking MBP. Fibers with NFH and MBP show NaCh clusters at nodal sites as expected, but surprisingly, NaCh accumulations are also seen in unmyelinated fibers with NFH, and in fibers with NFH that lack Schwann cell associations. Conclusions The expression of NFH in most axons suggests a myelinated origin for many pulpal afferents, while the presence of NaCh clusters in unmyelinated fibers suggests an inherent capacity for the unmyelinated segments of myelinated fibers to form NaCh accumulations. These findings have broad implications on the use of dental pulp to study pain mechanisms and suggest possible novel mechanisms responsible for NaCh cluster formation and neuronal excitability.

  18. Myelin structure is a key difference in the x-ray scattering signature between meningioma, schwannoma and glioblastoma multiforme

    International Nuclear Information System (INIS)

    Small angle x-ray scattering (SAXS) patterns of benign and malignant brain tumour tissue were examined. Independent component analysis was used to find a feature set representing the images collected. A set of coefficients was then used to describe each image, which allowed the use of the statistical technique of flexible discriminant analysis to discover a hidden order in the data set. The key difference was found to be in the intensity and spectral content of the second and fourth order myelin scattering peaks. This has clearly demonstrated that significant differences in the structure of myelin exist in the highly malignant glioblastoma multiforme as opposed to the benign: meningioma and schwannoma

  19. P0 (Protein Zero) Mutation S34C Underlies Instability of Internodal Myelin in S63C Mice*

    OpenAIRE

    Avila, Robin L; D'Antonio, Maurizio; Bachi, Angela; Inouye, Hideyo; Feltri, M. Laura; Wrabetz, Lawrence; Kirschner, Daniel A

    2010-01-01

    P0 constitutes 50–60% of protein in peripheral nerve myelin and is essential for its structure and stability. Mutations within the P0 gene (MPZ) underlie a variety of hereditary neuropathies. MpzS63C transgenic mice encode a P0 with a serine to cysteine substitution at position 34 in the extracellular domain of mature P0 (P0S34C), associated with the hypomyelinating Déjérine-Sottas syndrome in human. S63C mice develop a dysmyelinating neuropathy, with packing defects in peripheral myelin. Her...

  20. Increases in size and myelination of the rat corpus callosum during adulthood are maintained into old age

    OpenAIRE

    Yates, M.A.; Juraska, J.M.

    2007-01-01

    Although there are indications of growth in the size and myelination of the rat corpus callosum during adulthood, it is not known how long this growth continues. In addition, the potential for age-related changes in these measures to affect the sex differences seen in adulthood has not been examined. Here the size of callosal subregions and area occupied by myelin were examined in the genu and splenium of male and female rats in adulthood, middle-age, and old age. Our findings revealed increa...

  1. Myelin structure is a key difference in the x-ray scattering signature between meningioma, schwannoma and glioblastoma multiforme

    Science.gov (United States)

    Falzon, G.; Pearson, S.; Murison, R.; Hall, C.; Siu, K.; Round, A.; Schültke, E.; Kaye, A. H.; Lewis, R.

    2007-11-01

    Small angle x-ray scattering (SAXS) patterns of benign and malignant brain tumour tissue were examined. Independent component analysis was used to find a feature set representing the images collected. A set of coefficients was then used to describe each image, which allowed the use of the statistical technique of flexible discriminant analysis to discover a hidden order in the data set. The key difference was found to be in the intensity and spectral content of the second and fourth order myelin scattering peaks. This has clearly demonstrated that significant differences in the structure of myelin exist in the highly malignant glioblastoma multiforme as opposed to the benign: meningioma and schwannoma.

  2. On Split Lie Triple Systems

    Indian Academy of Sciences (India)

    Antonio J Calderón Martín

    2009-04-01

    We begin the study of arbitrary split Lie triple systems by focussing on those with a coherent 0-root space. We show that any such triple systems with a symmetric root system is of the form $T=\\mathcal{U}+\\sum_j I_j$ with $\\mathcal{U}$ a subspace of the 0-root space $T_0$ and any $I_j$ a well described ideal of , satisfying $[I_j,T,I_k]=0$ if $j\

  3. Empirical Methods for Compound Splitting

    CERN Document Server

    Koehn, P; Koehn, Philipp; Knight, Kevin

    2003-01-01

    Compounded words are a challenge for NLP applications such as machine translation (MT). We introduce methods to learn splitting rules from monolingual and parallel corpora. We evaluate them against a gold standard and measure their impact on performance of statistical MT systems. Results show accuracy of 99.1% and performance gains for MT of 0.039 BLEU on a German-English noun phrase translation task.

  4. Quantum Teleportation and Beam Splitting

    OpenAIRE

    Fichtner, Karl-Heinz; Ohya, Masanori

    2000-01-01

    Following the previous paper in which quantum teleportation is rig orously discussed with coherent entangled states given by beam splittings, we further discuss two types of models, perfect teleportation model and non-perfect teleportation model, in general scheme. Then the difference among several models, i.e., the perfect models and the non-perfect models, is studied. Our teleportation models are constructed by means of coherent states in some Fock space with counting meas...

  5. The ketogenic diet compensates for AGC1 deficiency and improves myelination.

    Science.gov (United States)

    Dahlin, Maria; Martin, Daniel A; Hedlund, Zandra; Jonsson, Monica; von Döbeln, Ulrika; Wedell, Anna

    2015-11-01

    The brain aspartate-glutamate carrier (AGC1) is specifically expressed in neurons, where it transports aspartate from the mitochondria to the cytosol, and plays a role in transfer of nicotinamide adenine dinucleotide (NADH)-reducing equivalents into the mitochondria as a part of the malate-aspartate shuttle. Deficient function of AGC1 underlies an inborn error of metabolism that presents with severe hypotonia, arrested psychomotor development, and seizures from a few months of age. In AGC1 deficiency, there is secondary hypomyelination due to lack of N-acetylaspartate (NAA), which is normally generated by acetylation of aspartate in the neuron and required for fatty acid synthesis by the adjacent oligodendrocyte. Based on experiences from AGC2 deficiency, we predicted that reduced glycolysis should compensate for the metabolic defect and allow resumed myelination in AGC1 deficiency. Carbohydrate restriction was therefore initiated in a patient with AGC1 deficiency at 6 years of age by introducing a ketogenic diet. The response was dramatic, clinically as well as radiologically. Psychomotor development showed clear improvement, and magnetic resonance imaging (MRI) indicated resumed myelination. This is the first successful treatment of secondary hypomyelination reported. Because AGC1 is driven by the proton gradient generated by the neuronal mitochondrial respiratory chain, the results have potential relevance for secondary hypomyelination in general. PMID:26401995

  6. Adult mesenchymal stem cell therapy for myelin repair in Multiple Sclerosis

    Scientific Electronic Library Online (English)

    Francisco J, Rivera; Ludwig, Aigner.

    Full Text Available Multiple sclerosis (MS) is a demyelinating immune-mediated disease of the central nervous system (CNS). It is the most frequent neurological disease in young adults and affects over 2 million people worldwide. Current treatments reduce the relapse rate and the formation of inflammatory lesions in th [...] e CNS, but with only temporary and limited success. Despite the presence of endogenous oligodendroglial progenitors (OPCs) and of spontaneous remyelination, at least in early MS its levels and its qualities are apparently insufficient for a sustained endogenous functional repair. Therefore, novel MS therapies should consider not only immunemodulatory but also myelin repair activities. Mesenchymal stem cells (MSCs) represent an attractive alternative to develop a cell-based therapy for MS. MSCs display stromal features and exert bystander immunemodulatory and neuroprotective activities. Importantly, MSCs induce oligodendrocyte fate decision and differentiation/maturation of adult neural progenitors, suggesting the existence of MSC-derived remyelination activity. Moreover, transplanted MSCs promote functional recovery and myelin repair in different MS animal models. Here, we summarize the current knowledge on endogenous mechanisms for remyelination and proposed autologous MSC therapy as a promising strategy for MS treatment.

  7. Gabapentin attenuates neuropathic pain and improves nerve myelination after chronic sciatic constriction in rats.

    Science.gov (United States)

    Câmara, Carlos C; Araújo, Celina V; de Sousa, Kalina Kelma Oliveira; Brito, Gerly A C; Vale, Mariana L; Raposo, Ramon da Silva; Mendonça, Fabiana Evaristo; Mietto, Bruno S; Martinez, Ana Maria B; Oriá, Reinaldo B

    2015-10-21

    Gabapentin (GBP) is an anti-convulsive drug often used as analgesic to control neuropathic pain. This study aimed at evaluating oral GBP treatment (30, 60, 120mg/kg, 60min prior to chronic constriction of the sciatic nerve (CCSN) along 15-day treatment post-injury, 12h/12h) by monitoring spontaneous and induced-pain behaviors in Wistar rats on 5th and 15th days post-injury during early neuropathic events. CCSN animals receiving saline were used as controls. Another aim of this study was to evaluate GBP effects on myelin basic protein (MBP) on the 5th and 15th days post-injury and nerve morphology by transmission electron microscopy to address nerve regeneration. On the 5th and 15th days, GBP (60mg/kg) reduced neuropathic pain behaviors (scratching and biting) in the ipsilateral paw and alleviated mechanical allodynia in comparison with the neuropathic saline group. GBP significantly increased climbing and rearing behaviors in CCSN and CCSN-free animals suggesting increased motor activity rather than sedation. We found three-fold significant increase in MBP expression by western blots on the 15th day when compared to controls. In addition, GPB (60mg/kg) improved nerve axonal, fiber and myelin area 15 days post-surgery. In conclusion, GBP alleviated mechanical and thermal allodynia and spontaneous pain-related behaviors and improved later nerve morphology. Our findings suggest that GBP improve nerve remyelination after chronic constriction of the sciatic nerve. PMID:26391746

  8. Clinical implications of peripheral myelin protein 22 for nerve compression and neural regeneration: a review.

    Science.gov (United States)

    Hui-Chou, Helen G; Hashemi, Sharyhar S; Hoke, Ahmet; Dellon, A Lee

    2011-01-01

    Peripheral myelin protein 22 (PMP22) is a major component of the peripheral myelin sheath. The PMP22 gene is located on chromosome 17p11.2, and defects in PMP22 gene have been implicated in several common inherited peripheral neuropathies. Hereditary neuropathy with liability to pressure palsies (HNPP), Charcot-Marie Tooth disease type 1A (CMT1A), Dejerine-Sottas syndrome, and congenital hypomyelinating neuropathy are all associated with defects in PMP22 gene. The disease phenotypes mirror the range of expression of PMP22 due to the corresponding genetic defect. HNPP, characterized by a milder recurrent episodic focal demyelinating neuropathy, is attributed to a deletion leading to PMP22 underexpression. On the other end of the spectrum, CMT1A leads to a more uniform demyelination and axonal loss, resulting in severe progressive distal weakness and paresthesias; it is due to a duplication at 17p11.2 leading to PMP22 overexpression. Additional point mutations result in varying phenotypes due to dysfunction of the resultant PMP22 protein. All inherited neuropathies are diagnosed with a combination of physical findings on examination, electromyography, sural nerve biopsies, and genetic testing. Treatment and management of these disorders differ depending on the underlying genetic defect, nerves involved, and resulting functional impairments. A review of current literature elucidates clinical, microsurgical implications, and management of patients with PMP22-related neuropathy. PMID:20976668

  9. Marked phenotypic variation in a family with a new myelin protein zero mutation.

    Science.gov (United States)

    Szabo, A; Züchner, S; Siska, E; Mechler, F; Molnar, M J

    2005-11-01

    Myelin protein zero (MPZ) is a member of the immunoglobulin gene superfamily, which has a role in myelin compaction. MPZ gene mutations cause mostly demyelinating neuropathies of the Charcot-Marie-Tooth 1B type (CMT1B), but axonal CMT have been described as well. There is a broad spectrum of phenotypic manifestation of neuropathies caused by MPZ mutations. Some mutations of MPZ cause severe early-onset neuropathies such as Dejerine-Sottas disease, while others cause the classical CMT phenotype with normal early milestones but development of disability during the first two decades of life. We describe a family in which five members of three consecutive generations had a heterozygous mutation in nucleotide position 143 with a T-C transition in exon 2 of the MPZ gene. The resulting substitution of Leu48 with proline has not been previously described. The age of onset of symptoms varied from 8 months to 41 years. The marked variation of the age of disease onset and clinical phenotype in this one family, related to the same MPZ mutation, suggests that in addition to the type and intragenic location of the mutation, other putative modifying gene(s) are regulating MPZ gene expression, mRNA stability and posttranslational protein modification and may have an important effect on the ultimate clinical phenotype. PMID:16198109

  10. A heme binding site on myelin basic protein: characterization, location, and significance.

    Science.gov (United States)

    Vacher, M; Nicot, C; Pflumm, M; Luchins, J; Beychok, S; Waks, M

    1984-05-15

    Myelin basic protein (MBP), an extrinsic membrane protein from the myelin sheath, binds dicyanohemin. The binding generates absorption bands in the Soret region and quenches the fluorescence emitted by the sole tryptophan residue. The absorption titration curves in the Soret demonstrate that the binding is stoichiometric, one heme per protein, with a large value of the extinction coefficient (8 X 10(4) M-1 cm-1 at 420 nm). Fluorescence quenching titration curves indicate an identical stoichiometry and a low quenching efficiency of 20%. From the heme titration curve the association constant between dicyanohemin and MBP is estimated to be greater than or equal to 10 nM-1 in 50 mM 4-morpholinepropanesulfonic acid buffer, pH 7.0, at 20 degrees C. Digestion of MBP by Staphylococcus aureus V8 protease yields a peptide (38-118) whose heme binding properties are identical to those of MBP. In contrast, peptides obtained by digestion of MBP with cathepsin D do not exhibit any specific binding of dicyanohemin. The cleavage of the Phe-Phe (42-43) bond appears to be critical in this respect. A comparison of the sequence immediately preceding, including these residues with a probable heme binding site of a mitochondrial cytochrome b, reveals a high degree of homology. The possible significance of heme binding is discussed. PMID:6202238

  11. Contribution of axonal transport to the renewal of myelin phospholipids in peripheral nerves. II

    International Nuclear Information System (INIS)

    The classes of radioactive phospholipids appearing in the ciliary ganglion (CG) and especially in the myelin sheath of the intraorbital part of the oculomotor nerve (OMN) were determined after the intracerebral injection of [2-3H]glycerol and [methyl-14C]choline to chickens. Analysis of the radioactive compounds in water-soluble fractions and chloroform-methanol extracts was performed by thin-layer chromatography (TLC). The water-soluble content of the OMN and CG was much poorer in [2-3H]glycerol and metabolites than in [methyl-14C]choline and derivatives. All classes of glycerophospholipids were found to be axonally transported along the OMN and into the CG, but choline-phosphoglycerides (CPG) were largely predominant. In myelin fractions from the OMN, the specific radioactivity (SRA) of CPG labeled with [2-3H]glycerol reached a maximum earlier (40 h) than the SRA of CPG labeled with [methyl-14C]choline. A 25-fold enhancement of the [14C]SRA of sphingomyelin (SM) was observed between 12 h and 7 days. (Auth.)

  12. Supplementation with complex milk lipids during brain development promotes neuroplasticity without altering myelination or vascular density

    Directory of Open Access Journals (Sweden)

    Rosamond B. Guillermo

    2015-03-01

    Full Text Available Background: Supplementation with complex milk lipids (CML during postnatal brain development has been shown to improve spatial reference learning in rats. Objective: The current study examined histo-biological changes in the brain following CML supplementation and their relationship to the observed improvements in memory. Design: The study used the brain tissues from the rats (male Wistar, 80 days of age after supplementing with either CML or vehicle during postnatal day 10–80. Immunohistochemical staining of synaptophysin, glutamate receptor-1, myelin basic protein, isolectin B-4, and glial fibrillary acidic protein was performed. The average area and the density of the staining and the numbers of astrocytes and capillaries were assessed and analysed. Results: Compared with control rats, CML supplementation increased the average area of synaptophysin staining and the number of GFAP astrocytes in the CA3 sub-region of the hippocampus (p<0.01, but not in the CA4 sub-region. The supplementation also led to an increase in dopamine output in the striatum that was related to nigral dopamine expression (p<0.05, but did not alter glutamate receptors, myelination or vascular density. Conclusion: CML supplementation may enhance neuroplasticity in the CA3 sub-regions of the hippocampus. The brain regions-specific increase of astrocyte may indicate a supporting role for GFAP in synaptic plasticity. CML supplementation did not associate with postnatal white matter development or vascular remodelling.

  13. Interaction between the C-terminal region of human myelin basic protein and calmodulin: analysis of complex formation and solution structure

    Directory of Open Access Journals (Sweden)

    Hayashi Nobuhiro

    2008-02-01

    Full Text Available Abstract Background The myelin sheath is a multilamellar membrane structure wrapped around the axon, enabling the saltatory conduction of nerve impulses in vertebrates. Myelin basic protein, one of the most abundant myelin-specific proteins, is an intrinsically disordered protein that has been shown to bind calmodulin. In this study, we focus on a 19-mer synthetic peptide from the predicted calmodulin-binding segment near the C-terminus of human myelin basic protein. Results The interaction of native human myelin basic protein with calmodulin was confirmed by affinity chromatography. The binding of the myelin basic protein peptide to calmodulin was tested with isothermal titration calorimetry (ITC in different temperatures, and Kd was observed to be in the low ?M range, as previously observed for full-length myelin basic protein. Surface plasmon resonance showed that the peptide bound to calmodulin, and binding was accompanied by a conformational change; furthermore, gel filtration chromatography indicated a decrease in the hydrodynamic radius of calmodulin in the presence of the peptide. NMR spectroscopy was used to map the binding area to reside mainly within the hydrophobic pocket of the C-terminal lobe of calmodulin. The solution structure obtained by small-angle X-ray scattering indicates binding of the myelin basic protein peptide into the interlobal groove of calmodulin, while calmodulin remains in an extended conformation. Conclusion Taken together, our results give a detailed structural insight into the interaction of calmodulin with a C-terminal segment of a major myelin protein, the myelin basic protein. The used 19-mer peptide interacts mainly with the C-terminal lobe of calmodulin, and a conformational change accompanies binding, suggesting a novel mode of calmodulin-target protein interaction. Calmodulin does not collapse and wrap around the peptide tightly; instead, it remains in an extended conformation in the solution structure. The observed affinity can be physiologically relevant, given the high abundance of both binding partners in the nervous system.

  14. Myelin-oligodendrocyte glycoprotein is a member of a subset of the immunoglobulin superfamily encoded within the major histocompatibility complex

    Energy Technology Data Exchange (ETDEWEB)

    Pham-Dinh, D.; Dautigny, A. (Institut des Neurosciences, Paris (France)); Mattei, M.G.; Roeckel, N. (Institut National de la Sante et de la Recherche Medicale Unite, Marseille (France)); Nussbaum, J.H.; Roussel, G. (Centre National de la Recherche Scientifique Unite, Strasbourg (France)); Pontarotti, P. (Centre Natinal de la Recherche Scientifique Unite, Toulouse (France)); Mather, I.H. (Univ. of Maryland, College Park, MD (United States)); Artzt, K. (Univ. of Texas, Austin, TX (United States)); Lindahl, K.F. (Univ. of Texas Southwestern Medical Center, Dallas, TX (United States))

    1993-09-01

    Myelin/oligodendrocyte glycoprotein (MOG) is found on the surface of myelinating oligodendrocytes and external lamellae of myelin sheaths in the central nervous system, and it is target antigen in experimental autoimmune encephalomyelitis and multiple sclerosis. The authors have isolated bovine, mouse, and rat MOG cDNA clones and shown that the developmental pattern of MOG expression in the rat central nervous system coincides with the late stages of myelination. The amino-terminal, extracellular domain of MOG has characteristics of an immunoglobulin variable domain and is 46% and 41% identical with the amino terminus of bovine butyrophilin (expressed in the lactating mammary gland) and B-G antigens of the chicken major histocompatibility complex (MHC), respectively; these proteins thus form a subset of the immunoglobulin superfamily. The homology between MOG and B-G extends beyond their structure and genetic mapping to their ability to induce strong antibody responses and has implications for the role of MOG in pathological, autoimmune conditions. The authors colocalized the MOG and BT genes to the human MHC on chromosome 6p21.3-p22. The mouse MOG gene was mapped to the homologous band C of chromosome 17, within the M region of the mouse MHC. 38 refs., 6 figs.

  15. Split-by-edges trees

    OpenAIRE

    Brændeland, Asbjørn

    2015-01-01

    A split-by-edges tree of a graph G on n vertices is a binary tree T where the root = V(G), every leaf is an independent set in G, and for every other node N in T with children L and R there is a pair of vertices {u, v} in N such that L = N - v, R = N - u, and uv is an edge in G. It follows from the definition that every maximal independent set in G is a leaf in T, and the maximum independent sets of G are the leaves closest to the root of T.

  16. Quantum teleportation and beam splitting

    International Nuclear Information System (INIS)

    Following the previous paper in which quantum teleportation is rigorously discussed with coherent entangled states given by beam splittings, we further discuss two types of models, the perfect teleportation model and non-perfect teleportation model, in a general scheme. Then the difference among several models, i.e., the perfect models and the non-perfect models, is studied. Our teleportation models are constructed by means of coherent states in some Fock space with counting measures, so that our model can be treated in the frame of usual optical communication. (orig.)

  17. Split quaternion nonlinear adaptive filtering.

    Science.gov (United States)

    Ujang, Bukhari Che; Took, Clive Cheong; Mandic, Danilo P

    2010-04-01

    A split quaternion learning algorithm for the training of nonlinear finite impulse response adaptive filters for the processing of three- and four-dimensional signals is proposed. The derivation takes into account the non-commutativity of the quaternion product, an aspect neglected in the derivation of the existing learning algorithms. It is shown that the additional information taken into account by a rigorous treatment of quaternion algebra provides improved performance on hypercomplex processes. A rigorous analysis of the convergence of the proposed algorithms is also provided. Simulations on both benchmark and real-world signals support the approach. PMID:19926443

  18. Molecular characterization of myelin protein zero in Xenopus laevis peripheral nerve

    Science.gov (United States)

    Xie, Bo; Luo, Xiaoyang; Zhao, Cheng; Priest, Christina Marie; Chan, Shiu-Yung; O'Connor, Peter B.; Kirschner, Daniel A.; Costello, Catherine E.

    2007-12-01

    Myelin protein zero (P0), a glycosylated single-pass transmembrane protein, is essential in the formation and maintenance of peripheral nervous system (PNS) compact myelin. P0 in Xenopus (xP0) exists primarily as a dimeric form that remains stable after various physical and chemical treatments. In exploring the nature of the interactions underlying the dimer stability, we found that xP0 dimer dissociated into monomer during continuous elution gel electrophoresis and conventional SDS-PAGE, indicating that the dimer is stabilized by non-covalent interactions. Furthermore, as some of the gel-purified monomer re-associated into dimer on SDS-PAGE gels, there is likely a dynamic equilibrium between xP0 dimer and monomer in vivo. Because the carbohydrate and fatty acyl moieties may be crucial for the adhesion role of P0, we used sensitive mass spectrometry approaches to elucidate the detailed N-glycosylation and S-acylation profiles of xP0. Asn92 was determined to be the single, fully-occupied glycosylation site of xP0, and a total of 12 glycans was detected that exhibited new structural features compared with those observed from P0 in other species: (1) the neutral glycans were composed mainly of high mannose and hybrid types; (2) 5 of 12 were acidic glycans, among which three were sialylated and the other two were sulfated; (3) none of the glycans had core fucosylation; and (4) no glucuronic acid, hence no HNK-1 epitope, was detected. The drastically different carbohydrate structures observed here support the concept of the species-specific variation in N-glycosylation of P0. Cys152 was found to be acylated with stearoyl (C18:0), whereas palmitoyl (C16:0) is the corresponding predominant fatty acyl group on P0 from higher vertebrates. We propose that the unique glycosylation and acylation patterns of Xenopus P0 may underlie its unusual dimerization behavior. Our results should shed light on the understanding of the phylogenetic development of P0's adhesion role in PNS compact myelin.

  19. Gender effect on neurodegeneration and myelin markers in an animal model for multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Massella Alessandro

    2012-01-01

    Full Text Available Abstract Background Multiple sclerosis (MS varies considerably in its incidence and progression in females and males. In spite of clinical evidence, relatively few studies have explored molecular mechanisms possibly involved in gender-related differences. The present study describes possible cellular- and molecular-involved markers which are differentially regulated in male and female rats and result in gender-dependent EAE evolution and progression. Attention was focused on markers of myelination (MBP and PDGF?R and neuronal distress and/or damage (GABA synthesis enzymes, GAD65 and GAD67, NGF, BDNF and related receptors, in two CNS areas, i.e. spinal cord and cerebellum, which are respectively severely and mildly affected by inflammation and demyelination. Tissues were sampled during acute, relapse/remission and chronic phases and results were analysed by two-way ANOVA. Results 1. A strong gender-dependent difference in myelin (MBP and myelin precursor (PDGF?R marker mRNA expression levels is observed in control animals in the spinal cord, but not in the cerebellum. This is the only gender-dependent difference in the expression level of the indicated markers in healthy animals; 2. both PDGF?R and MBP mRNAs in the spinal cord and MBP in the cerebellum are down-regulated during EAE in gender-dependent manner; 3. in the cerebellum, the expression profile of neuron-associated markers (GAD65, GAD67 is characterized by a substantial down-regulation during the inflammatory phase of the disease, which does not differ between male and female rats (two-way ANOVA; 4. there is an up-regulation of NGF, trkA and p75 mRNA expression in the early phases of the disease (14 and 21 days post-immunization, which is not different between male and female. Conclusions It is reported herein that the regulation of markers involved in demyelination and neuroprotection processes occurring during EAE, a well-established MS animal model, is gender- and time-dependent. These findings might contribute to gender- and phase disease-based therapy strategies.

  20. Magnetization transfer ratio does not correlate to myelin content in the brain in the MOG-EAE mouse model.

    Science.gov (United States)

    Fjær, Sveinung; Bø, Lars; Myhr, Kjell-Morten; Torkildsen, Øivind; Wergeland, Stig

    2015-01-01

    Magnetization transfer ratio (MTR) is a magnetic resonance imaging (MRI) method which may detect demyelination not detected by conventional MRI in the central nervous system of patients with multiple sclerosis (MS). A decrease in MTR value has previously been shown to correlate to myelin loss in the mouse cuprizone model for demyelination. In this study, we investigated the sensitivity of MTR for demyelination in the myelin oligodendrocyte (MOG) 1-125 induced experimental autoimmune encephalomyelitis (EAE) mouse model. A total of 24 female c57Bl/6 mice were randomized to a control group (N?=?6) or EAE (N?=?18). MTR images were obtained at a preclinical 7 Tesla Bruker MR-scanner before EAE induction (baseline), 17-19 days (midpoint) and 31-32 days (endpoint) after EAE induction. Mean MTR values were calculated in five regions of the brain and compared to weight, EAE severity score and myelin content assessed by immunostaining for proteolipid protein and luxol fast blue, lymphocyte and monocyte infiltration and iron deposition. Contrary to what was expected, MTR values in the EAE mice were higher than in the control mice at the midpoint and endpoint. No significant difference in myelin content was found according to histo- or immunohistochemistry. Changes in MTR values did not correlate to myelin content, iron content, lymphocyte or monocyte infiltration, weight or EAE severity scores. This suggest that MTR measures of brain tissue can give significant differences between control mice and EAE mice not caused by demyelination, inflammation or iron deposition, and may not be useful surrogate markers for demyelination in the MOG1-125 mouse model. PMID:25744931

  1. Impact of Morphometry, Myelinization and Synaptic Current Strength on Spike Conduction in Human and Cat Spiral Ganglion Neurons

    Science.gov (United States)

    Rattay, Frank; Potrusil, Thomas; Wenger, Cornelia; Wise, Andrew K.; Glueckert, Rudolf; Schrott-Fischer, Anneliese

    2013-01-01

    Background Our knowledge about the neural code in the auditory nerve is based to a large extent on experiments on cats. Several anatomical differences between auditory neurons in human and cat are expected to lead to functional differences in speed and safety of spike conduction. Methodology/Principal Findings Confocal microscopy was used to systematically evaluate peripheral and central process diameters, commonness of myelination and morphology of spiral ganglion neurons (SGNs) along the cochlea of three human and three cats. Based on these morphometric data, model analysis reveales that spike conduction in SGNs is characterized by four phases: a postsynaptic delay, constant velocity in the peripheral process, a presomatic delay and constant velocity in the central process. The majority of SGNs are type I, connecting the inner hair cells with the brainstem. In contrast to those of humans, type I neurons of the cat are entirely myelinated. Biophysical model evaluation showed delayed and weak spikes in the human soma region as a consequence of a lack of myelin. The simulated spike conduction times are in accordance with normal interwave latencies from auditory brainstem response recordings from man and cat. Simulated 400 pA postsynaptic currents from inner hair cell ribbon synapses were 15 times above threshold. They enforced quick and synchronous spiking. Both of these properties were not present in type II cells as they receive fewer and much weaker (?26 pA) synaptic stimuli. Conclusions/Significance Wasting synaptic energy boosts spike initiation, which guarantees the rapid transmission of temporal fine structure of auditory signals. However, a lack of myelin in the soma regions of human type I neurons causes a large delay in spike conduction in comparison with cat neurons. The absent myelin, in combination with a longer peripheral process, causes quantitative differences of temporal parameters in the electrically stimulated human cochlea compared to the cat cochlea. PMID:24260179

  2. Algebraic techniques for diagonalization of a split quaternion matrix in split quaternionic mechanics

    Science.gov (United States)

    Jiang, Tongsong; Jiang, Ziwu; Zhang, Zhaozhong

    2015-08-01

    In the study of the relation between complexified classical and non-Hermitian quantum mechanics, physicists found that there are links to quaternionic and split quaternionic mechanics, and this leads to the possibility of employing algebraic techniques of split quaternions to tackle some problems in complexified classical and quantum mechanics. This paper, by means of real representation of a split quaternion matrix, studies the problem of diagonalization of a split quaternion matrix and gives algebraic techniques for diagonalization of split quaternion matrices in split quaternionic mechanics.

  3. Telugu Bigram Splitting using Consonant-based and Phrase-based Splitting

    Directory of Open Access Journals (Sweden)

    T. Kameswara Rao

    2014-06-01

    Full Text Available Splitting is a conventional process in most of Indian languages according to their grammar rules. It is called ‘pada vicchEdanam’ (a Sanskrit term for word splitting and is widely used by most of the Indian languages. Splitting plays a key role in Machine Translation (MT particularly when the source language (SL is an Indian language. Though this splitting may not succeed completely in extracting the root words of which the compound is formed, but it shows considerable impact in Natural Language Processing (NLP as an important phase. Though there are many types of splitting, this paper considers only consonant based and phrase based splitting.

  4. Gluon splitting in a shockwave

    Energy Technology Data Exchange (ETDEWEB)

    Iancu, E., E-mail: edmond.iancu@cea.fr; Laidet, J., E-mail: julien.laidet@cea.fr

    2013-10-23

    The study of azimuthal correlations in particle production at forward rapidities in proton–nucleus collisions provides direct information about high gluon density effects, like gluon saturation, in the nuclear wavefunction. In the kinematical conditions for proton–lead collisions at the LHC, the forward di-hadron production is dominated by partonic processes in which a gluon from the proton splits into a pair of gluons, while undergoing multiple scattering off the dense gluon system in the nucleus. We compute the corresponding cross-section using the Colour Glass Condensate effective theory, which enables us to include the effects of multiple scattering and gluon saturation in the leading logarithmic approximation at high energy. This opens the way towards systematic studies of angular correlations in two-gluon production, similar to previous studies for quark–gluon production in the literature. We consider in more detail two special kinematical limits: the “back-to-back correlation limit”, where the transverse momenta of the produced gluons are much larger than the nuclear saturation momentum, and the “double parton scattering limit”, where the two gluons are produced by a nearly collinear splitting occurring prior to the collision. We argue that saturation effects remain important even for relatively high transverse momenta (i.e. for nearly back-to-back configurations), leading to geometric scaling in the azimuthal distribution.

  5. Instability of Myelin Tubes under Dehydration deswelling of layered cylindrical structures

    CERN Document Server

    Chen, C M; Olmsted, P D; MacKintosh, F C

    2001-01-01

    We report experimental observations of an undulational instability of myelin figures. Motivated by this, we examine theoretically the deformation and possible instability of concentric, cylindrical, multi-lamellar membrane structures. Under conditions of osmotic stress (swelling or dehydration), we find a stable, deformed state in which the layer deformation is given by \\delta R ~ r^{\\sqrt{B_A/(hB)}}, where B_A is the area compression modulus, B is the inter-layer compression modulus, and h is the repeat distance of layers. Also, above a finite threshold of dehydration (or osmotic stress), we find that the system becomes unstable to undulations, first with a characteristic wavelength of order \\sqrt{xi d_0}, where xi is the standard smectic penetration depth and d_0 is the thickness of dehydrated region.

  6. Robust myelin quantitative imaging from multi-echo T2 MRI using edge preserving spatial priors.

    Science.gov (United States)

    Shen, Xiaobo; Nguyen, Thanh D; Gauthier, Susan A; Raj, Ashish

    2013-01-01

    Demyelinating diseases such as multiple sclerosis cause changes in the brain white matter microstructure. Multi-exponential T2 relaxometry is a powerful technology for detecting these changes by generating a myelin water fraction (MWF) map. However, conventional approaches are subject to noise and spatial in-consistence. We proposed a novel approach by imposing spatial consistency and smoothness constraints. We first introduce a two-Gaussian model to approximate the T2 distribution. Then an expectation-maximization framework is introduced with an edge-preserving prior incorporated. Three-dimensional multi-echo MRI data sets were collected from three patients and three healthy volunteers. MWF maps obtained using the conventional, Spatially Regularized Non-negative Least Squares (srNNLS) algorithm as well as the proposed algorithm are compared. The proposed method provides MWF maps with improved depiction of brain structures and significantly lower coefficients of variance in various brain regions, PMID:24505719

  7. Quasiperiodic Tip Splitting in Directional Solidification

    OpenAIRE

    Utter, B.; Ragnarsson, R; Bodenschatz, E

    2001-01-01

    We report experimental results on the tip splitting dynamics of seaweed growth in directional solidification of succinonitrile alloys with poly(ethylene oxide) or acetone as solutes. The seaweed or dense branching morphology was selected by solidifying grains which are oriented close to the {111} plane. Despite the random appearance of the growth, a quasiperiodic tip splitting morphology was observed in which the tip alternately splits to the left and to the right. The tip s...

  8. Muonic hydrogen ground state hyperfine splitting

    OpenAIRE

    Faustov, R. N.; Martynenko, A. P.

    2003-01-01

    Corrections of orders alpha^5, alpha^6 are calculated in the hyperfine splitting of the muonic hydrogen ground state. The nuclear structure effects are taken into account in the one- and two-loop Feynman amplitudes by means of the proton electromagnetic form factors. The modification of the hyperfine splitting part of the Breit potential due to the electron vacuum polarization is considered. Total numerical value of the 1S state hyperfine splitting 182.638 meV in the (mu p) ...

  9. Brain microsomal fatty acid elongation is increased in abcd1-deficient mouse during active myelination phase.

    Science.gov (United States)

    Morita, Masashi; Kawamichi, Misato; Shimura, Yusuke; Kawaguchi, Kosuke; Watanabe, Shiro; Imanaka, Tsuneo

    2015-12-01

    The dysfunction of ABCD1, a peroxisomal ABC protein, leads to the perturbation of very long chain fatty acid (VLCFA) metabolism and is the cause of X-linked adrenoleukodystrophy. Abcd1-deficient mice exhibit an accumulation of saturated VLCFAs, such as C26:0, in all tissues, especially the brain. The present study sought to measure microsomal fatty acid elongation activity in the brain of wild-type (WT) and abcd1-deficient mice during the course of development. The fatty acid elongation activity in the microsomal fraction was measured by the incorporation of [2-(14)C]malonyl-CoA into fatty acids in the presence of C16:0-CoA or C20:0-CoA. Cytosolic fatty acid synthesis activity was completely inhibited by the addition of N-ethylmaleimide (NEM). The microsomal fatty acid elongation activity in the brain was significantly high at 3 weeks after birth and decreased substantially at 3 months after birth. Furthermore, we detected two different types of microsomal fatty acid elongation activity by using C16:0-CoA or C20:0-CoA as the substrate and found the activity toward C20:0-CoA in abcd1-deficient mice was higher than the WT 3-week-old animals. These results suggest that during the active myelination phase the microsomal fatty acid elongation activity is stimulated in abcd1-deficient mice, which in turn perturbs the lipid composition in myelin. PMID:26108493

  10. Telugu Bigram Splitting using Consonant-based and Phrase-based Splitting

    OpenAIRE

    T. Kameswara Rao; Dr. T. V. Prasa

    2014-01-01

    Splitting is a conventional process in most of Indian languages according to their grammar rules. It is called ‘pada vicchEdanam’ (a Sanskrit term for word splitting) and is widely used by most of the Indian languages. Splitting plays a key role in Machine Translation (MT) particularly when the source language (SL) is an Indian language. Though this splitting may not succeed completely in extracting the root words of which the compound is formed, but it shows considerable impact in Natural La...

  11. Gluon splitting in a shockwave

    CERN Document Server

    Iancu, Edmond

    2013-01-01

    The study of azimuthal correlations in particle production at forward rapidities in proton-nucleus collisions provides direct information about high gluon density effects, like gluon saturation, in the nuclear wavefunction. In the kinematical conditions for proton-lead collisions at the LHC, the forward di-hadron production is dominated by partonic processes in which a gluon from the proton splits into a pair of gluons, while undergoing multiple scattering off the dense gluon system in the nucleus. We compute the corresponding cross-section using the Colour Glass Condensate effective theory, which enables us to include the effects of multiple scattering and gluon saturation in the leading logarithmic approximation at high energy. This opens the way towards systematic studies of angular correlations in two-gluon production, similar to previous studies for quark-gluon production in the literature. We consider in more detail two special kinematical limits: the "back-to-back correlation limit", where the transver...

  12. Salt splitting with ceramic membranes

    International Nuclear Information System (INIS)

    The purpose of this task is to develop ceramic membrane technologies for salt splitting of radioactively contaminated sodium salt solutions. This technology has the potential to reduce the low-level waste (LLW) disposal volume, the pH and sodium hydroxide content for subsequent processing steps, the sodium content of interstitial liquid in high-level waste (HLW) sludges, and provide sodium hydroxide free of aluminum for recycle within processing plants at the DOE complex. Potential deployment sites include Hanford, Savannah River, and Idaho National Engineering Laboratory (INEL). The technical approach consists of electrochemical separation of sodium ions from the salt solution using sodium (Na) Super Ion Conductors (NaSICON). As the name implies, sodium ions are transported rapidly through these ceramic crystals even at room temperatures

  13. Salt splitting with ceramic membranes

    Energy Technology Data Exchange (ETDEWEB)

    Kurath, D. [Pacific Northwest National Lab., Richland, WA (United States)

    1996-10-01

    The purpose of this task is to develop ceramic membrane technologies for salt splitting of radioactively contaminated sodium salt solutions. This technology has the potential to reduce the low-level waste (LLW) disposal volume, the pH and sodium hydroxide content for subsequent processing steps, the sodium content of interstitial liquid in high-level waste (HLW) sludges, and provide sodium hydroxide free of aluminum for recycle within processing plants at the DOE complex. Potential deployment sites include Hanford, Savannah River, and Idaho National Engineering Laboratory (INEL). The technical approach consists of electrochemical separation of sodium ions from the salt solution using sodium (Na) Super Ion Conductors (NaSICON). As the name implies, sodium ions are transported rapidly through these ceramic crystals even at room temperatures.

  14. Gauge Mediated Mini-Split

    CERN Document Server

    Cohen, Timothy; Knapen, Simon

    2015-01-01

    We propose a simple model of split supersymmetry from gauge mediation. This model features gauginos that are parametrically a loop factor lighter than scalars, accommodates a Higgs boson mass of 125 GeV, and incorporates a simple solution to the $\\mu-b_\\mu$ problem. The gaugino mass suppression can be understood as resulting from collective symmetry breaking. Imposing collider bounds on $\\mu$ and requiring viable electroweak symmetry breaking implies small $a$-terms and small $\\tan \\beta$ -- the stop mass ranges from $10^5$ to $10^8 \\mbox{ GeV}$. In contrast with models with anomaly + gravity mediation (which also predict a one-loop loop suppression for gaugino masses), our gauge mediated scenario predicts aligned squark masses and a gravitino LSP. Gluinos, electroweakinos and Higgsinos can be accessible at the LHC and/or future colliders for a wide region of the allowed parameter space.

  15. Salt splitting using ceramic membranes

    Energy Technology Data Exchange (ETDEWEB)

    Kurath, D.E. [Pacific Northwest National Lab., Richland, WA (United States)

    1997-10-01

    Many radioactive aqueous wastes in the DOE complex have high concentrations of sodium that can negatively affect waste treatment and disposal operations. Sodium can decrease the durability of waste forms such as glass and is the primary contributor to large disposal volumes. Waste treatment processes such as cesium ion exchange, sludge washing, and calcination are made less efficient and more expensive because of the high sodium concentrations. Pacific Northwest National Laboratory (PNNL) and Ceramatec Inc. (Salt Lake City UT) are developing an electrochemical salt splitting process based on inorganic ceramic sodium (Na), super-ionic conductor (NaSICON) membranes that shows promise for mitigating the impact of sodium. In this process, the waste is added to the anode compartment, and an electrical potential is applied to the cell. This drives sodium ions through the membrane, but the membrane rejects most other cations (e.g., Sr{sup +2}, Cs{sup +}). The charge balance in the anode compartment is maintained by generating H{sup +} from the electrolysis of water. The charge balance in the cathode is maintained by generating OH{sup {minus}}, either from the electrolysis of water or from oxygen and water using an oxygen cathode. The normal gaseous products of the electrolysis of water are oxygen at the anode and hydrogen at the cathode. Potentially flammable gas mixtures can be prevented by providing adequate volumes of a sweep gas, using an alternative reductant or destruction of the hydrogen as it is generated. As H{sup +} is generated in the anode compartment, the pH drops. The process may be operated with either an alkaline (pH>12) or an acidic anolyte (pH <1). The benefits of salt splitting using ceramic membranes are (1) waste volume reduction and reduced chemical procurement costs by recycling of NaOH; and (2) direct reduction of sodium in process streams, which enhances subsequent operations such as cesium ion exchange, calcination, and vitrification.

  16. Quintessence and phantom emerging from the split-complex field, split-quaternion field and split-complex DBI field

    CERN Document Server

    Gao, Changjun; Shen, You-Gen

    2015-01-01

    Motivated by the mathematic theory of split-complex numbers (or hyperbolic numbers, also perplex numbers) and the split-quaternion numbers (or coquaternion numbers), we define the notion of split-complex scalar field and the split-quaternion scalar field. Then we explore the cosmic evolution of these scalar fields in the background of spatially flat Friedmann-Robertson-Walker Universe. We find that both the quintessence field and the phantom field could naturally emerge in these scalar fields. Introducing the metric of field space, these theories fall into a subclass of the multi-field theories which have been extensively studied in inflationary cosmology. Using the brane world model, the split-complex Dirac-Born-Infeld Lagrangian is constructed and analyzed.

  17. Operator splitting for dissipative delay equations

    OpenAIRE

    Bátkai, András; Csomós, Petra; Farkas, Bálint

    2010-01-01

    We investigate operator splitting methods for a special class of nonlinear partial differential equations with delay. Using results from the theory of nonlinear contraction semigroups in Hilbert spaces, we explain the convergence of the splitting procedure. The order of the convergence is also investigated in detail along with numerical comparisons.

  18. The mystery of the split earlobe.

    Science.gov (United States)

    Raveendran, Sherine Subodhini; Amarasinghe, Lalantha

    2004-12-01

    The ancient art of body piercing has rejuvenated in the recent years as part of the fashion process. The ear is the most frequent body part to be pierced to wear jewelry. Split earlobes are commonly presented to plastic surgeons and the recurrence rate is high. The etiology of the acquired split earlobe was thought to be attributable to either trauma or heavy earrings. In this study, the authors explored the cause of the split earlobe and recurrence after surgical repair. Twenty-five patients who were using gold earrings presented with split earlobe and were studied, and the etiology of the condition was analyzed. A questionnaire was completed and the tissue obtained during surgical repair of the split earlobes was submitted for histopathological studies. This group of patients was compared with 17 subjects having stretched earlobe who were using heavy gold earrings. The control group consists of 50 subjects using gold earrings with normal earlobes. Clinical presentation and the histological studies suggest that allergy to metals used in the earring could lead to split earlobe. There is a difference between the split earlobe and stretched earlobe; the latter results from constant pull by heavy earrings. The authors present a new theory regarding the etiology of split earlobe and recommend that avoiding the offending metal in the earring is indispensable to prevent recurrence. PMID:15577366

  19. Transferring Goods or Splitting a Resource Pool

    Science.gov (United States)

    Dijkstra, Jacob; Van Assen, Marcel A. L. M.

    2008-01-01

    We investigated the consequences for exchange outcomes of the violation of an assumption underlying most social psychological research on exchange. This assumption is that the negotiated direct exchange of commodities between two actors (pure exchange) can be validly represented as two actors splitting a fixed pool of resources (split pool…

  20. Standard Model Particles from Split Octonions

    CERN Document Server

    Gogberashvili, Merab

    2015-01-01

    We model physical signals using elements of the algebra of split octonions over the field of real numbers. Elementary particles are corresponded to the special elements of the algebra that nullify octonionic norms (zero divisors). It is shown that the standard model particle spectrum naturally follows from the classification of the independent primitive zero divisors of split octonions.

  1. Countering the Creative Misbehavior of "Staff Splitting."

    Science.gov (United States)

    Hewitt, Mary Beth

    1995-01-01

    Discusses five variations of staff splitting, a psychological process that starts with seemingly innocent comments that fester in the subconscious of others, leading members of the staff to seek evidence of inconsistencies and individual differences. Provides explicit guidelines and insights about how to turn staff splitting into an opportunity…

  2. Quasiperiodic Tip Splitting in Directional Solidification

    CERN Document Server

    Utter, B C; Bodenschatz, E

    2001-01-01

    We report experimental results on the tip splitting dynamics of seaweed growth in directional solidification of succinonitrile alloys with poly(ethylene oxide) or acetone as solutes. The seaweed or dense branching morphology was selected by solidifying grains which are oriented close to the {111} plane. Despite the random appearance of the growth, a quasiperiodic tip splitting morphology was observed in which the tip alternately splits to the left and to the right. The tip splitting frequency f was found to be related to the growth velocity V as a power law f V^{1.5}. This finding is consistent with the predictions of a tip splitting model that is also presented. Small anisotropies are shown to lead to different kinds of seaweed morphologies.

  3. Two-loop splitting functions in QCD

    International Nuclear Information System (INIS)

    We present the universal two-loop splitting functions that describe the limits of two-loop n-point amplitudes of massless particles when two of the momenta are collinear. To derive the splitting amplitudes, we take the collinear limits of explicit two-loop four-point helicity amplitudes computed in the 't Hooft-Veltman scheme. The g?gg splitting amplitude has recently been computed using the unitarity sewing method and we find complete agreement with the results presented elsewhere. The two-loop q?qg and g?qq-bar splitting functions are new results. We also provide an expression for the two-loop soft splitting function. (author)

  4. Two-loop splitting functions in QCD

    CERN Document Server

    Badger, S D

    2004-01-01

    We present the universal two-loop splitting functions that describe the limits of two-loop $n$-point amplitudes of massless particles when two of the momenta are collinear. To derive the splitting amplitudes, we take the collinear limits of explicit two-loop four-point helicity amplitudes computed in the 't Hooft-Veltman scheme. The $g \\to gg$ splitting amplitude has recently been computed using the unitarity sewing method and we find complete agreement with the results of Ref. \\cite{Bern:2lsplit}. The two-loop $q \\to qg$ and $g \\to q\\bar q$ splitting functions are new results. We also provide an expression for the two-loop soft splitting function.

  5. Rational Design and Synthesis of Altered Peptide Ligands based on Human Myelin Oligodendrocyte Glycoprotein 35–55 Epitope: Inhibition of Chronic Experimental Autoimmune Encephalomyelitis in Mice

    OpenAIRE

    Theodore Tselios; Mihalis Aggelidakis; Anthi Tapeinou; Vivian Tseveleki; Ioannis Kanistras; Dimitrios Gatos; John Matsoukas

    2014-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS). Although the etiology of MS remains unclear, there is evidence T-cell recognition of immunodominant epitopes of myelin proteins, such as the 35–55 epitope of myelin oligodendrocyte glycoprotein (MOG), plays a pathogenic role in the induction of chronic EAE. Cyclization of peptides is of great interest since the limited stability of linear ...

  6. Serum Levels of Anti-Myelin Antibodies in Relapsing-Remitting Multiple Sclerosis Patients during Different Phases of Disease Activity and Immunomodulatory Therapy

    OpenAIRE

    Francesco Angelucci; Massimiliano Mirabella; Giovanni Frisullo; Marcella Caggiula; Pietro Attilio Tonali; Anna Paola Batocchi

    2005-01-01

    Antibodies against myelin oligodendrocyte antigens have been found in the immunoreactive brain lesions of Multiple Sclerosis (MS) patients. Recently it has been proposed that these antibodies can be used as a prognostic marker in the course of disease. However, the serum levels of these autoantibodies during different phases of disease activity or after an immunomodulatory therapy have been poorly investigated. In this study the serum levels of anti-myelin oligodendrocyte glycoprotein (MOG) (...

  7. Schwann-cell differentiation in clonal cultures of the neural crest, as evidenced by the anti-Schwann cell myelin protein monoclonal antibody.

    OpenAIRE

    Dupin, E; Baroffio, A; Dulac, C; Cameron-Curry, P; Le Douarin, N. M.

    1990-01-01

    In the vertebrate embryo, Schwann cells lining the peripheral nerves originate from the neural crest (NC), a structure that also gives rise to ganglion satellite cells, most of the neurons of the peripheral nervous system, melanocytes, and part of the cranial mesenchyme. We have studied the emergence of the Schwann cell lineage in vitro in clonal cultures of quail mesencephalic NC cells by using the Schwann cell myelin protein antigen as an early and specific marker for myelinating and nonmye...

  8. Curcumin Treatment Abrogates Endoplasmic Reticulum Retention and Aggregation-Induced Apoptosis Associated with Neuropathy-Causing Myelin Protein Zero–Truncating Mutants

    OpenAIRE

    Khajavi, Mehrdad ; Inoue, Ken ; Wiszniewski, Wojciech ; Ohyama, Tomoko ; Snipes, G. Jackson ; Lupski, James R. 

    2005-01-01

    Mutations in MPZ, the gene encoding myelin protein zero (MPZ), the major protein constituent of peripheral myelin, can cause the adult-onset, inherited neuropathy Charcot-Marie-Tooth disease, as well as the more severe, childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Most MPZ-truncating mutations associated with severe forms of peripheral neuropathy result in premature termination codons within the terminal or penultimate exons that are not subject to non...

  9. Multimodal coherent anti-Stokes Raman scattering microscopy reveals microglia-associated myelin and axonal dysfunction in multiple sclerosis-like lesions in mice

    OpenAIRE

    Imitola, Jaime; Côté, Daniel; Rasmussen, Stine; Xie, X. Sunney; Liu, Yingru; Chitnis, Tanuja; Sidman, Richard L.; Lin, Charles P; Khoury, Samia J.

    2011-01-01

    Myelin loss and axonal degeneration predominate in many neurological disorders; however, methods to visualize them simultaneously in live tissue are unavailable. We describe a new imaging strategy combining video rate reflectance and fluorescence confocal imaging with coherent anti-Stokes Raman scattering (CARS) microscopy tuned to CH2 vibration of myelin lipids, applied in live tissue of animals with chronic experimental autoimmune encephalomyelitis (EAE). Our method allows monitoring over t...

  10. Severe demyelination but no astrocytopathy in clinically definite neuromyelitis optica with anti-myelin-oligodendrocyte glycoprotein antibody.

    Science.gov (United States)

    Ikeda, Kensuke; Kiyota, Naoki; Kuroda, Hiroshi; Sato, Douglas Kazutoshi; Nishiyama, Shuhei; Takahashi, Toshiyuki; Misu, Tatsuro; Nakashima, Ichiro; Fujihara, Kazuo; Aoki, Masashi

    2015-04-01

    We report a patient with neuromyelitis optica (NMO) presenting anti-myelin-oligodendrocyte glycoprotein (MOG)-seropositive, in whom biomarkers of demyelination and astrocyte damage were measured during an acute attack. A 31-year-old man developed right optic neuritis followed by longitudinally extensive transverse myelitis, fulfilling the criteria for definite NMO. He was anti-MOG-seropositive and anti-aquaporin-4 seronegative. The myelin basic protein level was markedly elevated whereas glial fibrillary acidic protein was not detectable in cerebrospinal fluid during an acute attack. His symptoms quickly improved after high-dose methylprednisolone therapy. This case suggests that NMO patients with anti-MOG may have severe demyelination in the absence of astrocyte injury. PMID:25257613

  11. Age-related changes in human and non-human primate white matter: from myelination disturbances to cognitive decline

    OpenAIRE

    Kohama, Steven G.; Rosene, Douglas L; Sherman, Larry S

    2011-01-01

    The cognitive decline associated with normal aging was long believed to be due primarily to decreased synaptic density and neuron loss. Recent studies in both humans and non-human primates have challenged this idea, pointing instead to disturbances in white matter (WM) including myelin damage. Here, we review both cross-sectional and longitudinal studies in humans and non-human primates that collectively support the hypothesis that WM disturbances increase with age starting at middle age in h...

  12. Components of Myelin Damage and Repair in the Progression of White Matter Pathology After Mild Traumatic Brain Injury

    OpenAIRE

    Mierzwa, Amanda J.; Marion, Christina M.; Sullivan, Genevieve M.; McDaniel, Dennis P; Armstrong, Regina C

    2015-01-01

    White matter tracts are highly vulnerable to damage from impact-acceleration forces of traumatic brain injury (TBI). Mild TBI is characterized by a low density of traumatic axonal injury, whereas associated myelin pathology is relatively unexplored. We examined the progression of white matter pathology in mice after mild TBI with traumatic axonal injury localized in the corpus callosum. Adult mice received a closed-skull impact and were analyzed from 3 days to 6 weeks post-TBI/sham surgery. A...

  13. Antibodies to myelin oligodendrocyte glycoprotein in HIV-1 associated neurocognitive disorder: a cross-sectional cohort study

    OpenAIRE

    Berger Thomas; Morandell Maria; Reindl Markus; Kuenz Bettina; Lackner Peter; Schmutzhard Erich; Eggers Christian

    2010-01-01

    Abstract Background Neuroinflammation and demyelination have been suggested as mechanisms causing HIV-1 associated neurocognitive disorder (HAND). This cross-sectional cohort study explores the potential role of antibodies to myelin oligodendrocyte glycoprotein (MOG), a putative autoantigen in multiple sclerosis, in the pathogenesis of HAND. Methods IgG antibodies against MOG were measured by ELISA in sera and cerebrospinal fluid (CSF) of 65 HIV-positive patients with HAND (n = 14), cerebral ...

  14. Myelin oligodendrocyte glycoprotein–specific T and B cells cooperate to induce a Devic-like disease in mice

    OpenAIRE

    Bettelli, E.; Baeten, D.; Jager, A.; Sobel, R.A.; Kuchroo, V.K.

    2006-01-01

    Multiple sclerosis (MS) is a clinically and pathologically heterogeneous inflammatory/demyelinating disease of the CNS. In the MS variant Devic disease, lesions are predominantly found in the optic nerves and spinal cord but not the brain. The immunological bases of the different forms of MS are unknown. We previously generated myelin oligodendrocyte glycoprotein–specific (MOG-specific) TCR transgenic mice (TCRMOG mice; also referred to as 2D2 mice) and reported that a large proportion of the...

  15. Early postnatal myelin content estimate of white matter via T1w/T2w ratio

    Science.gov (United States)

    Lee, Kevin; Cherel, Marie; Budin, Francois; Gilmore, John; Zaldarriaga Consing, Kirsten; Rasmussen, Jerod; Wadhwa, Pathik D.; Entringer, Sonja; Glasser, Matthew F.; Van Essen, David C.; Buss, Claudia; Styner, Martin

    2015-03-01

    To develop and evaluate a novel processing framework for the relative quantification of myelin content in cerebral white matter (WM) regions from brain MRI data via a computed ratio of T1 to T2 weighted intensity values. We employed high resolution (1mm3 isotropic) T1 and T2 weighted MRI from 46 (28 male, 18 female) neonate subjects (typically developing controls) scanned on a Siemens Tim Trio 3T at UC Irvine. We developed a novel, yet relatively straightforward image processing framework for WM myelin content estimation based on earlier work by Glasser, et al. We first co-register the structural MRI data to correct for motion. Then, background areas are masked out via a joint T1w and T2 foreground mask computed. Raw T1w/T2w-ratios images are computed next. For purpose of calibration across subjects, we first coarsely segment the fat-rich facial regions via an atlas co-registration. Linear intensity rescaling based on median T1w/T2w-ratio values in those facial regions yields calibrated T1w/T2wratio images. Mean values in lobar regions are evaluated using standard statistical analysis to investigate their interaction with age at scan. Several lobes have strongly positive significant interactions of age at scan with the computed T1w/T2w-ratio. Most regions do not show sex effects. A few regions show no measurable effects of change in myelin content change within the first few weeks of postnatal development, such as cingulate and CC areas, which we attribute to sample size and measurement variability. We developed and evaluated a novel way to estimate white matter myelin content for use in studies of brain white matter development.

  16. Calibration of the stereological estimation of the number of myelinated axons in the rat sciatic nerve: A multicenter study

    OpenAIRE

    Kaplan, S.; S. Geuna; G Ronchi; Ulkay, M.B.; von Bartheld, C.S.

    2010-01-01

    Several sources of variability can affect stereological estimates. Here we measured the impact of potential sources of variability on numerical stereological estimates of myelinated axons in the adult rat sciatic nerve. Besides biological variation, parameters tested included two variations of stereological methods (unbiased counting frame versus 2D-disector), two sampling schemes (few large versus frequent small sampling boxes), and workstations with varying degrees of sophistication. All es...

  17. Normal centrolineal myelination of the callosal splenium reflects the development of the cortical origin and size of its commissural fibers

    Energy Technology Data Exchange (ETDEWEB)

    Whitehead, Matthew T. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States); Children' s National Medical Center, Department of Radiology, Washington, DC (United States); Raju, Anand; Choudhri, Asim F. [University of Tennessee Health Science Center, Department of Radiology, Memphis, TN (United States); Le Bonheur Children' s Hospital, Le Bonheur Neuroscience Institute, Memphis, TN (United States)

    2014-04-15

    Commissural white matter fibers comprising the callosal splenium are diverse. Subsections of the splenium myelinate at different times, in a centrolineal manner. The aims of this study are to depict the normal callosal splenium myelination pattern and to distinguish the transient age-related mid splenium hypointensity from pathology. We reviewed 131 consecutive brain MRIs in patients between ages 3 and 6 months from a single academic children's hospital. Patients that were preterm, hydrocephalic, and/or had volume loss were excluded. Fifty total MR exams that included T1-weighted MR imaging (T1WI), T2-weighted MR imaging (T2WI), and diffusion tensor imaging (DTI) were reviewed. Regions of callosal splenium myelination manifested by T1 and T2 shortening were evaluated. Tractography was performed with seeds placed over the posterior, mid, and anterior splenium to define the origin, destination, and course of traversing fibers. Splenium signal varied significantly from 3 to 6 months, with distinct age-related trends. On T1WI, the splenium was hypointense at 3 months (12/13), centrally hypointense/peripherally hyperintense at 4 months (15/16), and hyperintense at 6 months (10/11). Tractography revealed three distinct white matter tract populations: medial occipital (posterior); precuneus, posterior cingulate, and medial temporal (middle); and postcentral gyri (anterior). Specific commissural fiber components of the splenium myelinate at different times. The transient developmental mid splenium hypointensity on T1WI corresponds to tracts from the associative cortex, principally the precuneus. Heterogeneous splenium signal alteration in patients ages 3-6 months is a normal developmental phenomenon that should not be confused with pathologic lesions. (orig.)

  18. Development of Myelination and Cholinergic Innervation in the Central Auditory System of a Prosimian Primate (Otolemur garnetti)

    OpenAIRE

    Miller, Daniel J.; Lackey, Elizabeth P.; Hackett, Troy A; Kaas, Jon H.

    2013-01-01

    Change in the timeline of neurobiological growth is an important source of biological variation, and thus phenotypic evolution. However, no study has to date investigated sensory system development in any of the prosimian primates that are thought to most closely resemble our earliest primate ancestors. Acetylcholine (ACh) is a neurotransmitter critical to normal brain function by regulating synaptic plasticity associated with attention and learning. Myelination is an important structural com...

  19. Normal centrolineal myelination of the callosal splenium reflects the development of the cortical origin and size of its commissural fibers

    International Nuclear Information System (INIS)

    Commissural white matter fibers comprising the callosal splenium are diverse. Subsections of the splenium myelinate at different times, in a centrolineal manner. The aims of this study are to depict the normal callosal splenium myelination pattern and to distinguish the transient age-related mid splenium hypointensity from pathology. We reviewed 131 consecutive brain MRIs in patients between ages 3 and 6 months from a single academic children's hospital. Patients that were preterm, hydrocephalic, and/or had volume loss were excluded. Fifty total MR exams that included T1-weighted MR imaging (T1WI), T2-weighted MR imaging (T2WI), and diffusion tensor imaging (DTI) were reviewed. Regions of callosal splenium myelination manifested by T1 and T2 shortening were evaluated. Tractography was performed with seeds placed over the posterior, mid, and anterior splenium to define the origin, destination, and course of traversing fibers. Splenium signal varied significantly from 3 to 6 months, with distinct age-related trends. On T1WI, the splenium was hypointense at 3 months (12/13), centrally hypointense/peripherally hyperintense at 4 months (15/16), and hyperintense at 6 months (10/11). Tractography revealed three distinct white matter tract populations: medial occipital (posterior); precuneus, posterior cingulate, and medial temporal (middle); and postcentral gyri (anterior). Specific commissural fiber components of the splenium myelinate at different times. The transient developmental mid splenium hypointensity on T1WI corresponds to tracts from the associative cortex, principally the precuneus. Heterogeneous splenium signal alteration in patients ages 3-6 months is a normal developmental phenomenon that should not be confused with pathologic lesions. (orig.)

  20. Innovative solar thermochemical water splitting.

    Energy Technology Data Exchange (ETDEWEB)

    Hogan, Roy E. Jr.; Siegel, Nathan P.; Evans, Lindsey R.; Moss, Timothy A.; Stuecker, John Nicholas (Robocasting Enterprises, Albuquerque, NM); Diver, Richard B., Jr.; Miller, James Edward; Allendorf, Mark D. (Sandia National Laboratories, Livermore, CA); James, Darryl L. (Texas Tech University, Lubbock, TX)

    2008-02-01

    Sandia National Laboratories (SNL) is evaluating the potential of an innovative approach for splitting water into hydrogen and oxygen using two-step thermochemical cycles. Thermochemical cycles are heat engines that utilize high-temperature heat to produce chemical work. Like their mechanical work-producing counterparts, their efficiency depends on operating temperature and on the irreversibility of their internal processes. With this in mind, we have invented innovative design concepts for two-step solar-driven thermochemical heat engines based on iron oxide and iron oxide mixed with other metal oxides (ferrites). The design concepts utilize two sets of moving beds of ferrite reactant material in close proximity and moving in opposite directions to overcome a major impediment to achieving high efficiency--thermal recuperation between solids in efficient counter-current arrangements. They also provide inherent separation of the product hydrogen and oxygen and are an excellent match with high-concentration solar flux. However, they also impose unique requirements on the ferrite reactants and materials of construction as well as an understanding of the chemical and cycle thermodynamics. In this report the Counter-Rotating-Ring Receiver/Reactor/Recuperator (CR5) solar thermochemical heat engine and its basic operating principals are described. Preliminary thermal efficiency estimates are presented and discussed. Our ferrite reactant material development activities, thermodynamic studies, test results, and prototype hardware development are also presented.

  1. Regulatory role of vitamin D in T-cell reactivity against myelin peptides in relapsing-remitting multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    Grau-López Laia

    2012-09-01

    Full Text Available Abstract Background Low levels of plasma 25-hydroxyvitaminD (25(OHD are associated with a higher incidence of multiple sclerosis (MS due to the immune suppressive properties of vitamin D. The aim of this study was to determine the correlation between plasma 25(OHD concentrations and clinical and immunological variables in a cohort of multiple sclerosis patients. Methods Plasma 25(OHD concentrations were evaluated in summer and winter in 15 primary progressive MS (PPMS patients, 40 relapsing- remitting MS (RRMS patients and 40 controls (HC. Protocol variables included demographic and clinical data, radiological findings and immunological variables (oligoclonal bands, HLADR15 and T-lymphocyte proliferation to a definite mix of 7 myelin peptides. Results During the winter, plasma concentrations were significantly lower in RRMS patients compared to HC, whereas no differences were found in summer. No relationships were found between plasma 25(OHD concentrations and clinical or radiological variables. RRMS patients with a positive T-cell proliferation to a mix of myelin peptides (n?=?31 had lower 25(OHD concentrations. Conclusions 25(OHD is an immunomodulatory molecule that might have a regulatory role in T-cell proliferation to myelin peptides in RRMS patients.

  2. Production and crystallization of a panel of structure-based mutants of the human myelin peripheral membrane protein P2

    International Nuclear Information System (INIS)

    The myelin protein P2 is a peripheral membrane protein functional in lipid bilayer binding and stacking. In order to study the fine details of P2 structure and function, 14 point mutants of human P2 were generated and crystallized; a total of eight different crystal forms were obtained, some of which diffracted to atomic resolution. The myelin sheath is a multilayered membrane that surrounds and insulates axons in the nervous system. One of the proteins specific to the peripheral nerve myelin is P2, a protein that is able to stack lipid bilayers. With the goal of obtaining detailed information on the structure–function relationship of P2, 14 structure-based mutated variants of human P2 were generated and produced. The mutants were designed to potentially affect the binding of lipid bilayers by P2. All mutated variants were also crystallized and preliminary crystallographic data are presented. The structural data from the mutants will be combined with diverse functional assays in order to elucidate the fine details of P2 function at the molecular level

  3. Dejerine-sottas disease with a novel de novo dominant mutation, Ser 149 Arg, of the peripheral myelin protein 22.

    Science.gov (United States)

    Ohnishi, A; Yamamoto, T; Izawa, K; Yamamori, S; Takahashi, K; Mega, H; Jinnai, K

    2000-03-01

    The Ser149Arg mutation of peripheral myelin protein 22 (PMP22) was found in a 19-year-old woman with a sporadic case of Dejerine-Sottas disease. The patient showed delayed motor development. She walked for the first time with support at the age of 2 years. Scoliosis developed at age 4 years. Her walking ability was best at age 11. Thereafter, she showed progressive muscle weakness and sensory disturbances in the distal extremities. At the age of 18 years, the use of a wheelchair became necessary. Motor and sensory nerve conduction studies showed absent motor and sensory responses on electrical stimulation of the limb nerves. A sural nerve biopsy specimen showed marked decreases in the numbers of both large and small myelinated fibers, abundant onion-bulb formation, and hypomyelination. Electron microscopic observation revealed the presence of demyelinated axons and myelin sheaths disproportionately thin relative to axon diameter. That this was a de novo mutation was established by parentage testing and PMP22 gene analysis of the parents. The mutation seems to be novel and dominant. PMID:10663978

  4. Failure of central nervous system myelination in MBP/c-myc transgenic mice: evidence for c-myc cytotoxicity

    DEFF Research Database (Denmark)

    Jensen, N A; Pedersen, Karen-Marie

    1998-01-01

    c-myc is a member of the helix-loop-helix/leucine zipper family of proteins that modulate the transcriptional activity of specific target genes. Although aberrant c-myc expression has been reported to play a role in multistage carcinogenesis in astrocytic gliomas, little is known about the effects of the expression of c-myc on oligodendrocytes. Using transgenic animals expressing a human c-myc oncogene under transcriptional control of the myelin basic protein gene, we investigated the effect of overexpression of this oncogene in oligodendrocytes. The MBP/c-myc transgenic mice developed severe neurological disturbances characterized by action tremors and recurrent seizures, and premature death during postnatal weeks three to five. Affected transgenic mice of various strains had severely hypomyelinated central nervous systems and expressed low levels of c-myc, myelin basic protein (MBP) and proteolipid protein (PLP) mRNAs in the brain. These c-myc transgenic mice also exhibited an increased number of TUNEL positive nuclei, which in most cases were located in cells that expressed c-myc, as judged by double immunohistochemistry. There was no evidence of brain tumors in the c-myc transgenic mice, including heterozygous mice from two strains that had normal lifespans. These observations indicate that the myelin deficiency observed in the MBP/c-myc transgenic animals results from a cytotoxic effect of the c-myc transgene.

  5. Laminar order within Langmuir-Blodgett multilayers from phospholipid and myelin basic protein: a neutron reflectivity study.

    Science.gov (United States)

    Haas, H; Steitz, R; Fasano, A; Liuzzi, G M; Polverini, E; Cavatorta, P; Riccio, P

    2007-07-31

    Multilayers consisting of negatively charged phospholipid DMPA and myelin basic protein (MBP) were assembled by Langmuir-Blodgett deposition of floating Langmuir monolayers from the air/water interface to solid substrates. Protein/lipid samples were obtained by binding MBP from the aqueous subphase to the phospholipid monolayers before deposition. The vertical organization of these model membranes (i.e., with organization perpendicular to the substrate surface) was investigated in detail by neutron reflectivity measurements, and the internal distribution of water molecules was determined from the change of contrast after in-situ H2O/D2O exchange. The multilayers were well ordered, with repeating lipid bilayers as fundamental structural unit. MBP was inserted in between adjacent lipid headgroups, such as in the natural myelin membrane. Water molecules in the multilayers were present mainly in the lipid headgroup and protein slab. On exposition of the pure lipid multilayers to a dry atmosphere, a reduction of the bilayer spacing was determined, whereas the global lamellar order was not affected. In contrast, drying of the protein/lipid multilayers induced degradation of the laminar order. The data demonstrate that ordered Langmuir-Blodgett multilayers are versatile model systems for studying how competing interactions between lipid, protein, water, and ions affect the global organization of such multilamellar lipid/protein assemblies. Here, the water molecules were found to be a necessary mediator to maintain the laminar order in a multilayer from DMPA and myelin basic protein. PMID:17616158

  6. Human umbilical cord Wharton's jelly-derived oligodendrocyte precursor-like cells for axon and myelin sheath regeneration?

    Science.gov (United States)

    Chen, Hong; Zhang, Yan; Yang, Zhijun; Zhang, Hongtian

    2013-01-01

    Human umbilical mesenchymal stem cells from Wharton's jelly of the umbilical cord were induced to differentiate into oligodendrocyte precursor-like cells in vitro. Oligodendrocyte precursor cells were transplanted into contused rat spinal cords. Immunofluorescence double staining indicated that transplanted cells survived in injured spinal cord, and differentiated into mature and immature oligodendrocyte precursor cells. Biotinylated dextran amine tracing results showed that cell transplantation promoted a higher density of the corticospinal tract in the central and caudal parts of the injured spinal cord. Luxol fast blue and toluidine blue staining showed that the volume of residual myelin was significantly increased at 1 and 2 mm rostral and caudal to the lesion epicenter after cell transplantation. Furthermore, immunofluorescence staining verified that the newly regenerated myelin sheath was derived from the central nervous system. Basso, Beattie and Bresnahan testing showed an evident behavioral recovery. These results suggest that human umbilical mesenchymal stem cell-derived oligodendrocyte precursor cells promote the regeneration of spinal axons and myelin sheaths. PMID:25206380

  7. Muonic hydrogen ground state hyperfine splitting

    CERN Document Server

    Faustov, R N

    2003-01-01

    Corrections of order alpha^5, alpha^6 are calculated in the hyperfine splitting of muonic hydrogen ground state. Nuclear structure effects are taken into account in one- and two-loop Feynman amplitudes by means of the proton electromagnetic form factors. The modification of the hyperfine splitting part of the Breit potential due to electron vacuum polarization is considered. Total numerical value of the 1S state hyperfine splitting 182.725 meV in (mu p) can play the role of proper estimation for the corresponding experiment with the accuracy 30 ppm.

  8. Photoinduced water splitting with oxotitanium tetraphenylporphyrin.

    Science.gov (United States)

    Morawski, O; Izdebska, K; Karpiuk, E; Nowacki, J; Suchocki, A; Sobolewski, A L

    2014-08-01

    Photocatalytic splitting of water was investigated in a heterogeneous system consisting of micro-crystallites of oxotitanium tetraphenylporphyrin deposited on fused silica plates, immersed in water and excited within the visible range of their absorption spectra. The water photolysis was evidenced by the spectroscopic detection of hydroxyl radicals generated in the reaction. The experimental results confirm the mechanism of water splitting and generation of OH? radicals proposed theoretically by Sobolewski and Domcke [Phys. Chem. Chem. Phys., 2012, 14, 12807] for the oxotitaniumporphyrin-water complex. It is shown that photocatalytic water splitting occurs in pure water, and neither pH-bias nor external voltage is required to promote the reaction. PMID:24938429

  9. 2S Hyperfine splitting of muonic hydrogen

    CERN Document Server

    Martynenko, A P

    2004-01-01

    Corrections of orders alpha^5, alpha^6 are calculated in the hyperfine splitting of the 2S state in the muonic hydrogen. The nuclear structure effects are taken into account in the one- and two-loop Feynman amplitudes by means of the proton electromagnetic form factors. Total numerical value of the 2S state hyperfine splitting 22.8148 meV in the (\\mu p) can be considered as reliable estimation for the corresponding experiment with the accuracy 10^{-5}. The value of the Sternheim's hyperfine splitting interval [8\\Delta E^{HFS}(2S)-\\Delta E^{HFS}(1S)] is obtained with the accuracy 10^{-6}.

  10. PTPBR7 Binding Proteins in Myelinating Neurons of the Mouse Brain

    Directory of Open Access Journals (Sweden)

    Irene M. Chesini, Griet Debyser, Huib Croes, Gerdy B. ten Dam, Bart Devreese, Andrew W. Stoker, Wiljan J.A.J. Hendriks

    2011-01-01

    Full Text Available Mouse protein tyrosine phosphatase PTPBR7 is a receptor-like, transmembrane protein that is localized on the surface of neuronal cells. Its protein phosphatase activity is reduced upon multimerization, and PTPBR7-deficient mice display motor coordination defects. Extracellular molecules that may influence PTPBR7 activity, however, remain to be determined. We here show that the PTPBR7 extracellular domain binds to highly myelinated regions in mouse brain, in particular the white matter tracks in cerebellum. PTPBR7 deficiency does not alter this binding pattern, as witnessed by RAP in situ staining of Ptprr-/- mouse brain sections. Additional in situ and in vitro experiments also suggest that sugar moieties of heparan sulphate and chondroitin sulphate glycosaminoglycans are not critical for PTPBR7 binding. Candidate binding proteins were affinity-purified exploiting the PTPBR7 extracellular domain and identified by mass spectrometric means. Results support the suggested link between PTPRR isoforms and cerebellar calcium ion homeostasis, and suggest an additional role in the process of cell-cell adhesion.

  11. The role of N-glycan in folding, trafficking and pathogenicity of myelin oligodendrocyte glycoprotein (MOG).

    Science.gov (United States)

    Jung, Joanna; Dudek, Elzbieta; Michalak, Marek

    2015-09-01

    Myelin oligodendrocyte glycoprotein (MOG) is a type I integral membrane protein that is expressed in the central nervous system. MOG has a single N-glycosylation site within its extracellular domain. MOG has been linked with pathogenesis of multiple sclerosis; anti-MOG antibodies have been detected in the sera of multiple sclerosis patients. N-glycosylation is an important post-translational modification of protein that might impact their folding, localization and function. However, the role of sugar in the biology of MOG is not well understood. In this study, we created a mutant MOG lacking N-linked glycan and tested its properties. We concluded that the lack of sugar did not impact on MOG abundance in the absence of endoplasmic reticulum molecular chaperone calnexin. We also show that the absence of N-glycan did not interfere with MOG's subcellular localization and it did not result in activation of endoplasmic reticulum stress. This article is part of a Special Issue entitled: 13th European Symposium on Calcium. PMID:25541284

  12. Missense mutations in TENM4, a regulator of axon guidance and central myelination, cause essential tremor.

    Science.gov (United States)

    Hor, Hyun; Francescatto, Ludmila; Bartesaghi, Luca; Ortega-Cubero, Sara; Kousi, Maria; Lorenzo-Betancor, Oswaldo; Jiménez-Jiménez, Felix J; Gironell, Alexandre; Clarimón, Jordi; Drechsel, Oliver; Agúndez, José A G; Kenzelmann Broz, Daniela; Chiquet-Ehrismann, Ruth; Lleó, Alberto; Coria, Francisco; García-Martin, Elena; Alonso-Navarro, Hortensia; Martí, Maria J; Kulisevsky, Jaume; Hor, Charlotte N; Ossowski, Stephan; Chrast, Roman; Katsanis, Nicholas; Pastor, Pau; Estivill, Xavier

    2015-10-15

    Essential tremor (ET) is a common movement disorder with an estimated prevalence of 5% of the population aged over 65 years. In spite of intensive efforts, the genetic architecture of ET remains unknown. We used a combination of whole-exome sequencing and targeted resequencing in three ET families. In vitro and in vivo experiments in oligodendrocyte precursor cells and zebrafish were performed to test our findings. Whole-exome sequencing revealed a missense mutation in TENM4 segregating in an autosomal-dominant fashion in an ET family. Subsequent targeted resequencing of TENM4 led to the discovery of two novel missense mutations. Not only did these two mutations segregate with ET in two additional families, but we also observed significant over transmission of pathogenic TENM4 alleles across the three families. Consistent with a dominant mode of inheritance, in vitro analysis in oligodendrocyte precursor cells showed that mutant proteins mislocalize. Finally, expression of human mRNA harboring any of three patient mutations in zebrafish embryos induced defects in axon guidance, confirming a dominant-negative mode of action for these mutations. Our genetic and functional data, which is corroborated by the existence of a Tenm4 knockout mouse displaying an ET phenotype, implicates TENM4 in ET. Together with previous studies of TENM4 in model organisms, our studies intimate that processes regulating myelination in the central nervous system and axon guidance might be significant contributors to the genetic burden of this disorder. PMID:26188006

  13. The wheat proteins puroindoline-a and alpha1-purothionin induce nodal swelling in myelinated axons.

    Science.gov (United States)

    Mattei, C; Elmorjani, K; Molgó, J; Marion, D; Benoit, E

    1998-12-01

    The effects of two basic cysteine-rich lipid-binding proteins isolated from wheat seedlings, puroindoline-a and alpha1-purothionin, were studied on single frog myelinated axons stained with the fluorescent dye FM1-43 using confocal laser scanning microscopy. During exposure to either puroindoline-a or alpha1-purothionin (10 and 100 microM) a marked swelling of nodes of Ranvier was observed, provided NaCl was present in the external solution. It is suggested that these proteins increase the internal osmolality by forming pores in the axonal membrane and induce water influx to compensate for such an increase. Moreover, in the presence of alpha1-purothionin (100 microM), the intensity of the axonal staining with FM1-43 was increased. It is the first time, to our knowledge, that basic proteins containing domains of a cysteine-rich repeated motif are reported to produce swelling and water movements across neuronal cell membranes. PMID:9875708

  14. Polyneuropathy syndromes associated with serum antibodies to sulfatide and myelin-associated glycoprotein.

    Science.gov (United States)

    Pestronk, A; Li, F; Griffin, J; Feldman, E L; Cornblath, D; Trotter, J; Zhu, S; Yee, W C; Phillips, D; Peeples, D M

    1991-03-01

    We studied a series of 64 patients with sensory +/- motor peripheral neuropathies by comparing clinical and physiologic features to serum antibody reactivity against compounds containing sulfated carbohydrate moieties. We determined antibody reactivity by an enzyme-linked immunosorbent assay (ELISA) using purified glycolipids and glycoproteins as antigens, and we used high-performance thin-layer chromatography and Western blotting to test the specificity of results. Twelve patients with high titers of IgM antibodies directed against the myelin-associated glycoprotein (MAG) had sensory-motor polyneuropathies with physiologic evidence of demyelination. IgM antibody reactivity to MAG was associated with an IgM serum M protein in five patients. Eight other patients, most with sensory greater than motor polyneuropathies, had high titers of antibody reactivity to sulfatide but not of IgM to MAG. Two had an associated IgM paraprotein. None of the patients with selective serum antisulfatide activity had predominantly demyelinating features on physiologic testing. We conclude that (1) high ELISA titers of antibodies to MAG may be more common than previously suspected in patients with chronic demyelinating sensory-motor neuropathies, and (2) the presence of high titers of antisulfatide antibodies in serum may provide clues to the pathogenesis of otherwise idiopathic, axonal, predominantly sensory neuropathies. PMID:1706491

  15. Poincaré Map Based on Splitting Methods

    International Nuclear Information System (INIS)

    Firstly, by using the Liouville formula, we prove that the Jacobian matrix determinants of splitting methods are equal to that of the exact Sow. However, for the explicit Runge–Kutta methods, there is an error term of order p + 1 for the Jacobian matrix determinants. Then, the volume evolution law of a given region in phase space is discussed for different algorithms. It is proved that splitting methods can exactly preserve the sum of Lyapunov exponents invariable. Finally, a Poincaré map and its energy distribution of the Duffing equation are computed by using the second-order splitting method and the Heun method (a second-order Runge–Kutta method). Computation illustrates that the results by splitting methods can properly represent systems' chaotic phenomena. (general)

  16. Divided Opinions on the Split Fovea

    Science.gov (United States)

    Ellis, Andrew W.; Brysbaert, Marc

    2010-01-01

    We explain once again the distinction between the "split fovea theory" and the "bilateral projection theory", and consider the implications of the two theories for understanding the processing of centrally fixated words and faces.

  17. Evaluation of Optimal Split-Plot Designs

    Directory of Open Access Journals (Sweden)

    Julian Mbegbu

    2012-08-01

    Full Text Available The study introduced an algorithm for generating optimal split-plot designs. The designs were considered as optimal because they were capable and ecient in estimating the xed e ects of the statistical model that is appropriate given the split-plot design structure. Here, we introduced I-optimal design of split-plot experiments. The algorithm used in this research does not require the prior speci cation of a candidate set. Therefore, making the design of split-plot experiments computationally feasible in situations where the candidate set is too large to be tractable. Flexible choice of the sample size, inclusion of both continuous and categorical factors were allowed by this method. We show through an example the substantial bene ts of this method.

  18. Dominated splittings for flows with singularities

    International Nuclear Information System (INIS)

    We obtain sufficient conditions for an invariant splitting over a compact invariant subset of a C1 flow Xt to be dominated. In particular, we reduce the requirements to obtain sectional hyperbolicity and hyperbolicity. (paper)

  19. Irrational beliefs, attitudes about competition, and splitting.

    Science.gov (United States)

    Watson, P J; Morris, R J; Miller, L

    2001-03-01

    Rational-Emotive Behavior Therapy (REBT) theoretically promotes actualization of both individualistic and social-oriented potentials. In a test of this assumption, the Belief Scale and subscales from the Survey of Personal Beliefs served as measures of what REBT presumes to be pathogenic irrationalities. These measures were correlated with the Hypercompetitive Attitude Scale (HCAS), the Personal Development Competitive Attitude Scale (PDCAS), factors from the Splitting Index, and self-esteem. Results for the HCAS and Self-Splitting supported the REBT claim about individualistic self-actualization. Mostly nonsignificant and a few counterintuitive linkages were observed for irrational beliefs with the PDCAS, Family-Splitting, and Other-Splitting, and these data suggested that REBT may be less successful in capturing the "rationality" of a social-oriented self-actualization. PMID:11241364

  20. Structural basis of photosynthetic water-splitting

    International Nuclear Information System (INIS)

    Photosynthetic water-splitting takes place in photosystem II (PSII), a membrane protein complex consisting of 20 subunits with an overall molecular mass of 350 kDa. The light-induced water-splitting reaction catalyzed by PSII not only converts light energy into biologically useful chemical energy, but also provides us with oxygen indispensible for sustaining oxygenic life on the earth. We have solved the structure of PSII at a 1.9 Å resolution, from which, the detailed structure of the Mn4CaO5-cluster, the catalytic center for water-splitting, became clear. Based on the structure of PSII at the atomic resolution, possible mechanism of light-induced water-splitting was discussed

  1. Structural basis of photosynthetic water-splitting

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Jian-Ren [Graduate School of Natural Science and Technology/Faculty of Science, Okayama University, Okayama (Japan); Umena, Yasufumi [The OCU Advanced Research Institute for Natural Science and Technology (OCARINA), Osaka City University, Osaka, Japan and PRESTO, JST (Japan); Kawakami, Keisuke [The OCU Advanced Research Institute for Natural Science and Technology (OCARINA), Osaka City University, Osaka (Japan); Kamiya, Nobuo [The OCU Advanced Research Institute for Natural Science and Technology (OCARINA), Osaka City University, Osaka, Japan and Department of Chemistry, Graduate School of Science, Osaka City University, Osaka (Japan)

    2013-12-10

    Photosynthetic water-splitting takes place in photosystem II (PSII), a membrane protein complex consisting of 20 subunits with an overall molecular mass of 350 kDa. The light-induced water-splitting reaction catalyzed by PSII not only converts light energy into biologically useful chemical energy, but also provides us with oxygen indispensible for sustaining oxygenic life on the earth. We have solved the structure of PSII at a 1.9 Å resolution, from which, the detailed structure of the Mn{sub 4}CaO{sub 5}-cluster, the catalytic center for water-splitting, became clear. Based on the structure of PSII at the atomic resolution, possible mechanism of light-induced water-splitting was discussed.

  2. Split-Quaternions and the Dirac Equation

    CERN Document Server

    Antonuccio, Francesco

    2014-01-01

    We show that Dirac 4-spinors admit an entirely equivalent formulation in terms of 2-spinors defined over the split-quaternions. In this formalism, a Lorentz transformation is represented as a $2 \\times 2$ unitary matrix over the split-quaternions. The corresponding Dirac equation is then derived in terms of these 2-spinors. In this framework the $SO(3,2; {\\bf R})$ symmetry of the Lorentz invariant scalar $\\overline{\\psi}\\psi$ is manifest.

  3. Splitting tensile test for fibre reinforced concrete

    OpenAIRE

    Denneman, Erik; Kearsley, Elsabe P.; Visser, Alex T.

    2011-01-01

    The splitting tensile test is a much used method to determine the tensile strength of concrete. The conventional test procedure is known to have a number of limitations related to size effect and boundary conditions. Furthermore, it has been reported to be impossible to determine the tensile strength of Fibre Reinforced Concrete (FRC) using the standard splitting tensile test method. The objective of this paper is to present a methodology to obtain a close estimate of the true tensile strengt...

  4. Laser beam splitting by polarization encoding.

    Science.gov (United States)

    Wan, Chenhao

    2015-03-20

    A scheme is proposed to design a polarization grating that splits an incident linearly polarized beam to an array of linearly polarized beams of identical intensity distribution and various azimuth angles of linear polarization. The grating is equivalent to a wave plate with space-variant azimuth angle and space-variant phase retardation. The linear polarization states of all split beams make the grating suitable for coherent beam combining architectures based on Dammann gratings. PMID:25968540

  5. Ray splitting in paraxial optical cavities

    OpenAIRE

    Puentes, G.; Aiello, A.; Woerdman, J.P.

    2003-01-01

    We present a numerical investigation of the ray dynamics in a paraxial optical cavity when a ray splitting mechanism is present. The cavity is a conventional two-mirror stable resonator and the ray splitting is achieved by inserting an optical beam splitter perpendicular to the cavity axis. We show that depending on the position of the beam splitter the optical resonator can become unstable and the ray dynamics displays a positive Lyapunov exponent.

  6. Ink Film Splitting Acoustics in Offset Printing

    OpenAIRE

    Voltaire, Joakim

    2006-01-01

    This thesis claims a relationship between the film splitting sound emission from the printing press nip and the dynamic interaction occurring there between ink, fountain solution and substrate in offset lithography. The film splitting sound derives from the cavitation formed by the pressure drop in the second half of the print nip flow passage. As the ink film is strained, the cavities expand and eventually implode into breaking filaments at the nip exit, while emitting a partly audible, broa...

  7. Observers and Splitting Structures in Relativistic Electrodynamics

    OpenAIRE

    Auchmann, Bernhard; Kurz, Stefan

    2014-01-01

    We introduce a relativistic splitting structure as a means to map fields and equations of electromagnetism from curved four-dimensional space-time to three-dimensional observer's space. We focus on a minimal set of mathematical structures that are directly motivated by the language of the physical theory. Space-time, world-lines, time translation, space platforms, and time synchronization all find their mathematical counterparts. The splitting structure is defined without re...

  8. Anomalous magnetic splitting of the Kondo resonance

    OpenAIRE

    Moore, Joel E.; Wen, Xiao-Gang

    1999-01-01

    The splitting of the Kondo resonance in the density of states of an Anderson impurity in finite magnetic field is calculated from the exact Bethe-ansatz solution. The result gives an estimate of the electron spectral function for nonzero magnetic field and Kondo temperature, with consequences for transport experiments on quantum dots in the Kondo regime. The strong correlations of the Kondo ground state cause a significant low-temperature reduction of the peak splitting. Exp...

  9. Kondo spin splitting with slave boson

    Scientific Electronic Library Online (English)

    J. M. Aguiar, Hualde; G., Chiappe; E.V., Anda.

    2006-09-01

    Full Text Available The slave boson (SB) technique is employed to study the Zeeman spin splitting in a quantum dot. Unlike traditional SB method, each spin is renormalized differently. Two geometries are compared: side connected and embedded. In both cases, it's shown a non linear behavior of the splitting as a functio [...] n of the magnetic field applied. The results are in line with the latest experiments.

  10. Determination of structure coefficients from splitting matrices

    OpenAIRE

    Gilbert, F.; Woodhouse, JH

    2000-01-01

    The splitting matrix for a set of coupled multiplets is a linear combination of structure coefficients, first-order Coriolis terms and terms for ellipticity and centrifugal force. These latter terms are calculated for a good 1-D earth model and removed. The first-order Coriolis terms are then uniquely determined. They are linear functionals of the density of the 1-D model. The remaining splitting matrix is an orthogonal transformation of the structure coefficients. The inverse orthogonal tran...

  11. Conformational epitopes of myelin oligodendrocyte glycoprotein are targets of potentially pathogenic antibody responses in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Menge Til

    2011-11-01

    Full Text Available Abstract Background Myelin/oligodendrocyte glycoprotein (MOG is a putative autoantigen in multiple sclerosis (MS. Establishing the pathological relevance and validity of anti-MOG antibodies as biomarkers has yielded conflicting reports mainly due to different MOG isoforms used in different studies. Because epitope specificity may be a key factor determining anti-MOG reactivity we aimed at identifying a priori immunodominant MOG epitopes by monoclonal antibodies (mAbs and at assessing clinical relevance of these epitopes in MS. Methods Sera of 325 MS patients, 69 patients with clinically isolated syndrome and 164 healthy controls were assayed by quantitative, high-throughput ELISA for reactivity to 3 different MOG isoforms, and quantitative titers correlated with clinical characteristics. mAbs defined unique immunodominant epitopes distinct to each of the isoforms. Results In the majority of human samples anti-MOG levels were skewed towards low titers. However, in 8.2% of samples high-titer anti-MOG antibodies were identified. In contrast to anti-MOG reactivity observed in a mouse model of MS, in patients with MS these never reacted with ubiquitously exposed epitopes. Moreover, in patients with relapsing-remitting MS high-titer anti-MOG IgG correlated with disability (EDSS; Spearman r = 0.574; p = 0.025. Conclusions Thus high-titer reactivity likely represents high-affinity antibodies against pathologically relevant MOG epitopes, that are only present in a small proportion of patients with MS. Our study provides valuable information about requirements of anti-MOG reactivity for being regarded as a prognostic biomarker in a subtype of MS.

  12. How big is the myelinating orchestra? Cellular diversity within the oligodendrocyte lineage: facts and hypotheses.

    Directory of Open Access Journals (Sweden)

    Giulio Srubek Tomassy

    2014-07-01

    Full Text Available Since monumental studies from scientists like His, Ramón y Cajal, Lorente de Nó and many others have put down roots for modern neuroscience, the scientific community has spent a considerable amount of time, and money, investigating any aspect of the evolution, development and function of neurons. Today, the complexity and diversity of myriads of neuronal populations is still focus of extensive studies in hundreds of laboratories around the world. However, our prevalent neuron-centric perspective has dampened the efforts in understanding glial cells, even though their active participation in the brain physiology and pathophysiology has been increasingly recognized over the years. Among all glial cells of the central nervous system (CNS, oligodendrocytes (OLs are a particularly specialized type of cells that provide fundamental support to neuronal activity by producing the myelin sheath. Despite their functional relevance, the developmental mechanisms regulating the generation of OLs are still poorly understood. In particular, it is still not known whether these cells share the same degree of heterogeneity of their neuronal companions and whether multiple subtypes exist within the lineage. Here, we will review and discuss current knowledge about OL development and function in the brain and spinal cord. We will try to address some specific questions: do multiple OL subtypes exist in the CNS? What is the evidence for their existence and those against them? What are the functional features that define an oligodendrocyte? We will end our journey by reviewing recent advances in human pluripotent stem cell differentiation towards OLs. This exciting field is still at its earliest days, but it is quickly evolving with improved protocols to generate functional OLs from different spatial origins. As stem cells constitute now an unprecedented source of human OLs, we believe that they will become an increasingly valuable tool for deciphering the complexity of human OL identity.

  13. Uptake and presentation of myelin basic protein by normal human B cells

    DEFF Research Database (Denmark)

    Brimnes, Marie Klinge; Hansen, Bjarke Endel

    2014-01-01

    B cells may play both pathogenic and protective roles in T-cell mediated autoimmune diseases such as multiple sclerosis (MS). These functions relate to the ability of B cells to bind and present antigens. Under serum-free conditions we observed that 3-4% of circulating B cells from healthy donors were capable of binding the MS-associated self-antigen myelin basic protein (MBP) and of presenting the immunodominant peptide MBP85-99, as determined by staining with the mAb MK16 recognising the peptide presented by HLA-DR15-positive cells. In the presence of serum, however, the majority of B cells bound MBP in a complement-dependent manner, and almost half of the B cells became engaged in presentation of MBP85-99. Even though complement receptor 1 (CR1, CD35) and CR2 (CD21) both contributed to binding of MBP to B cells, only CR2 was important for the subsequent presentation of MBP85-99. A high proportion of MBP85-99 presenting B cells expressed CD27, and showed increased expression of CD86 compared to non-presenting B cells. MBP-pulsed B cells induced a low frequency of IL-10-producing CD4+ T cells in 3 out of 6 donors, indicating an immunoregulatory role of B cells presenting MBP-derived peptides. The mechanisms described here refute the general assumption that B-cell presentation of self-antigens requires uptake via specific B-cell receptors, and may be important for maintenance of tolerance as well as for driving T-cell responses in autoimmune diseases.

  14. How big is the myelinating orchestra? Cellular diversity within the oligodendrocyte lineage: facts and hypotheses.

    Science.gov (United States)

    Tomassy, Giulio Srubek; Fossati, Valentina

    2014-01-01

    Since monumental studies from scientists like His, Ramón y Cajal, Lorente de Nó and many others have put down roots for modern neuroscience, the scientific community has spent a considerable amount of time, and money, investigating any possible aspect of the evolution, development and function of neurons. Today, the complexity and diversity of myriads of neuronal populations, and their progenitors, is still focus of extensive studies in hundreds of laboratories around the world. However, our prevalent neuron-centric perspective has dampened the efforts in understanding glial cells, even though their active participation in the brain physiology and pathophysiology has been increasingly recognized over the years. Among all glial cells of the central nervous system (CNS), oligodendrocytes (OLs) are a particularly specialized type of cells that provide fundamental support to neuronal activity by producing the myelin sheath. Despite their functional relevance, the developmental mechanisms regulating the generation of OLs are still poorly understood. In particular, it is still not known whether these cells share the same degree of heterogeneity of their neuronal companions and whether multiple subtypes exist within the lineage. Here, we will review and discuss current knowledge about OL development and function in the brain and spinal cord. We will try to address some specific questions: do multiple OL subtypes exist in the CNS? What is the evidence for their existence and those against them? What are the functional features that define an oligodendrocyte? We will end our journey by reviewing recent advances in human pluripotent stem cell differentiation towards OLs. This exciting field is still at its earliest days, but it is quickly evolving with improved protocols to generate functional OLs from different spatial origins. As stem cells constitute now an unprecedented source of human OLs, we believe that they will become an increasingly valuable tool for deciphering the complexity of human OL identity. PMID:25120430

  15. Myelin protein zero gene sequencing diagnoses Charcot-Marie-Tooth Type 1B disease

    Energy Technology Data Exchange (ETDEWEB)

    Su, Y.; Zhang, H.; Madrid, R. [Univ. of California, San Francisco, CA (United States)] [and others

    1994-09-01

    Charcot-Marie-Tooth disease (CMT), the most common genetic neuropathy, affects about 1 in 2600 people in Norway and is found worldwide. CMT Type 1 (CMT1) has slow nerve conduction with demyelinated Schwann cells. Autosomal dominant CMT Type 1B (CMT1B) results from mutations in the myelin protein zero gene which directs the synthesis of more than half of all Schwann cell protein. This gene was mapped to the chromosome 1q22-1q23.1 borderline by fluorescence in situ hybridization. The first 7 of 7 reported CMT1B mutations are unique. Thus the most effective means to identify CMT1B mutations in at-risk family members and fetuses is to sequence the entire coding sequence in dominant or sporadic CMT patients without the CMT1A duplication. Of the 19 primers used in 16 pars to uniquely amplify the entire MPZ coding sequence, 6 primer pairs were used to amplify and sequence the 6 exons. The DyeDeoxy Terminator cycle sequencing method used with four different color fluorescent lables was superior to manual sequencing because it sequences more bases unambiguously from extracted genomic DNA samples within 24 hours. This protocol was used to test 28 CMT and Dejerine-Sottas patients without CMT1A gene duplication. Sequencing MPZ gene-specific amplified fragments identified 9 polymorphic sites within the 6 exons that encode the 248 amino acid MPZ protein. The large number of major CMT1B mutations identified by single strand sequencing are being verified by reverse strand sequencing and when possible, by restriction enzyme analysis. This protocol can be used to distringuish CMT1B patients from othre CMT phenotypes and to determine the CMT1B status of relatives both presymptomatically and prenatally.

  16. Molecular alterations resulting from frameshift mutations in peripheral myelin protein 22: implications for neuropathy severity.

    Science.gov (United States)

    Johnson, J S; Roux, K J; Fletcher, B S; Fortun, J; Notterpek, L

    2005-12-15

    Alterations in peripheral myelin protein 22 (PMP22) expression are associated with a heterogeneous group of hereditary demyelinating peripheral neuropathies. Two mutations at glycine 94, a single guanine insertion or deletion in PMP22, result in different reading frameshifts and, consequently, an extended G94fsX222 or a truncated G94fsX110 protein, respectively. Both of these autosomal dominant mutations alter the second half of PMP22 and yet are linked to clinical phenotypes with distinct severities. The G94fsX222 is associated with hereditary neuropathy with liability to pressure palsies, whereas G94fsX110 causes severe neuropathy diagnosed as Dejerine-Sottas disease or Charcot-Marie-Tooth disease type IA. To investigate the subcellular changes associated with the G94 frameshift mutations, we expressed epitope-tagged forms in primary rat Schwann cells. Biochemical and immunolabeling studies indicate that, unlike the wild-type protein, which is targeted for the plasma membrane, frameshift PMP22s are retained in the cell, prior to reaching the medial Golgi compartment. Similar to Wt-PMP22, both frameshift mutants are targeted for proteasomal degradation and accumulate in detergent-insoluble, ubiquitin-containing aggregates upon inhibition of this pathway. The extended frameshift PMP22 shows the ability to form spontaneous aggregates in the absence of proteasome inhibition. On the other hand, Schwann cells expressing the truncated protein proliferate at a significantly higher rate than Schwann cells expressing the wild-type or the extended PMP22. In summary, these results suggest that a greater potential for PMP22 aggregation is associated with a less severe phenotype, whereas dysregulation of Schwann cell proliferation is linked to severe neuropathy. PMID:16273544

  17. Tracing Myelin Protein Zero (P0 in vivo by construction of P0-GFP fusion proteins

    Directory of Open Access Journals (Sweden)

    Van Broeckhoven Christine

    2002-11-01

    Full Text Available Abstract Background Mutations in P0, the major protein of the myelin sheath in peripheral nerves, cause the inherited peripheral neuropathies Charcot-Marie-Tooth disease type 1B (CMT1B, Dejerine-Sottas syndrome (DSS and congenital hypomyelination (CH. We reported earlier a de novo insertional mutation c.662_663GC (Ala221fs in a DSS patient. The c.662_663GC insertion results in a frame shift mutation Ala221fs altering the C-terminal amino acid sequence. The adhesion-relevant intracellular RSTK domain is replaced by a sequence similar to Na+/K+ ATPase. To further clarify the molecular disease mechanisms in this sporadic patient we constructed wild type P0 and the c.662_663GC mutant expression cassettes by site-specific mutagenesis and transfected the constructs into insect cells (S2, High5. To trace the effects in live cells, green fluorescent protein (GFP has been added to the carboxyterminus of the wild type and mutated P0 protein. Results In contrast to the membrane-localized wild type P0-GFP the Ala221fs P0-GFP protein was detectable almost only in the cytoplasm of the cells, and a complete loss of adhesion function was observed. Conclusions The present study provides evidence that GFP is a versatile tool to trace in vivo effects of P0 and its mutations. Not only a loss of adhesion function as a result of the loss of the RSTK domain, but also altered intracellular trafficking indicated by a loss of membrane insertion are possible consequences of the Ala221fs mutation.

  18. A critical review of pro-cognitive drug targets in psychosis: Convergence on myelination and inflammation.

    Directory of Open Access Journals (Sweden)

    Rune A.Kroken

    2014-02-01

    Full Text Available Antipsychotic drugs have thus far focused on dopaminergic antagonism at the D2 receptors, as counteracting the hyperdopaminergia in nigrostriatal and mesolimbic projections has been considered mandatory for the antipsychotic action of the drugs. Current drugs effectively target the positive symptoms of psychosis such as hallucinations and delusions in the majority of patients, whereas effect sizes are smaller for negative symptoms and cognitive dysfunctions. With the understanding that neurocognitive dysfunction associated with schizophrenia have a greater impact on functional outcome than the positive symptoms, the focus in pharmacotherapy for schizophrenia has shifted to the potential effect of future drugs on cognitive enhancement. A major obstacle is, however, that the biological underpinnings of cognitive dysfunction remain largely unknown. With the availability of increasingly sophisticated techniques in molecular biology and brain imaging, this situation is about to change, with major advances being made in identifying the neuronal substrates underlying schizophrenia, and putative pro-cognitive drug targets may be revealed. In relation to cognitive effects, this review focuses on evidence from basic neuroscience and clinical studies, taking two separate perspectives. One perspective is the identification of previously under-recognized treatment targets for existing antipsychotic drugs, including myelination and mediators of inflammation. A second perspective is the development of new drugs or novel treatment targets for well-known drugs which act on recently discovered treatment targets for cognitive enhancement, and which may complement the existing drugs. This might pave the way for personalized treatment regimens for patients with schizophrenia aimed at improved functional outcome. The review also aims at identifying major current constraints for pro-cognitive drug development for patients with schizophrenia.

  19. Nimodipine-mediated re-myelination after facial nerve crush injury in rats.

    Science.gov (United States)

    Tang, Yin-da; Zheng, Xue-Sheng; Ying, Ting-Ting; Yuan, Yan; Li, Shi-Ting

    2015-10-01

    This study aimed to investigate the mechanism of nimodipine-mediated neural repair after facial nerve crush injury in rats. Adult Sprague-Dawley rats were divided into three groups: healthy controls, surgery alone, and surgery plus nimodipine. A facial nerve crush injury model was constructed. Immediately after surgery, the rats in the surgery plus nimodipine group were administered nimodipine, 6mg/kg/day, for a variable numbers of days. The animals underwent electromyography (EMG) before surgery and at 3, 10, or 20days after surgery. After sacrifice, nerve samples were stained with hematoxylin and eosin (H&E) and luxol fast blue. The EMG at 20days revealed an apparent recovery of eletroconductivity, with the surgery plus nimodipine group having a higher amplitude and shorter latency time than the surgery only group. H&E staining showed that at 20days, the rats treated with nimodipine had an obvious recovery of myelination and reduction in the number of infiltrating cells, suggesting less inflammation, compared with the rats in the surgery only group. Luxol fast blue staining was relatively even in the surgery plus nimodipine group, indicating a protective effect against injury-induced demyelination. Staining for S100 calcium-binding protein B (S-100?) was not evident in the surgery alone group, but was evident in the surgery plus nimodipine group, indicating that nimodipine reversed the damage of the crush injury. After a facial nerve crush injury, treatment with nimodipine for 20days reduced the nerve injury by mediating remyelination by Schwann cells. The protective effect of nimodipine may include a reduction of inflammation and an increase in calcium-binding S-100? protein. PMID:26169537

  20. Urban pattern: Layout design by hierarchical domain splitting

    KAUST Repository

    Yang, Yongliang

    2013-11-01

    We present a framework for generating street networks and parcel layouts. Our goal is the generation of high-quality layouts that can be used for urban planning and virtual environments. We propose a solution based on hierarchical domain splitting using two splitting types: streamline-based splitting, which splits a region along one or multiple streamlines of a cross field, and template-based splitting, which warps pre-designed templates to a region and uses the interior geometry of the template as the splitting lines. We combine these two splitting approaches into a hierarchical framework, providing automatic and interactive tools to explore the design space.

  1. Functional recovery of regenerating motor axons is delayed in mice heterozygously deficient for the myelin protein P(0) gene

    DEFF Research Database (Denmark)

    Rosberg, Mette Romer; Alvarez, Susana

    2013-01-01

    Mice with a heterozygous knock-out of the myelin protein P0 gene (P0+/-) develop a neuropathy similar to human Charcot-Marie-Tooth disease. They are indistinguishable from wild-types (WT) at birth and develop a slowly progressing demyelinating neuropathy. The aim of this study was to investigate whether the regeneration capacity of early symptomatic P0+/- is impaired as compared to age matched WT. Right sciatic nerves were lesioned at the thigh in 7-8 months old mice. Tibial motor axons at ankle were investigated by conventional motor conduction studies and axon excitability studies using threshold tracking. To evaluate regeneration we monitored the recovery of motor function after crush, and then compared the fiber distribution by histology. The overall motor performance was investigated using Rotor-Rod. P0+/- had reduced compound motor action potential amplitudes and thinner myelinated axons with only a borderline impairment in conduction and Rotor-Rod. Plantar muscle reinnervation occurred within 21 days in all mice. Shortly after reinnervation the conduction of P0+/- regenerated axons was markedly slower than WT, however, this difference decayed with time. Nevertheless, after 1 month, regenerated P0+/- axons had longer strength-duration time constant, larger threshold changes during hyperpolarizing electrotonus and longer relative refractory period. Their performance at Rotor-Rod remained also markedly impaired. In contrast, the number and diameter distribution of regenerating myelinated fibers became similar to regenerated WT. Our data suggest that in the presence of heterozygously P0 deficient Schwann cells, regenerating motor axons retain their ability to reinnervate their targets and remyelinate, though their functional recovery is delayed.

  2. Síndrome de mielinización de fibras nerviosas retinales, miopía y ambliopía / Syndrome of myelinated retinal nerve fibers, myopia and amblyopia

    Scientific Electronic Library Online (English)

    Daniel, López Felipe; Teresita de Jesús, Méndez Sánchez.

    Full Text Available Las fibras de mielina intraoculares se presentan desde el nacimiento y suelen localizarse alrededor de la papila. El síndrome de mielinización de las fibras nerviosas retinales fue descrito por Virchow por primera vez en 1856. Este aparece como parches estriados, blanco o blanco grisáceos con los bo [...] rdes imprecisos y plumosos siguiendo una configuración coincidente con la distribución de las fibras nerviosas retinales. Se presenta una paciente femenina de 4 años que es traída a consulta por desviación del ojo derecho. En el examen oftalmológico se detecta una agudeza visual con corrección de 0,1 y la oftalmoscopia confirma la mielinización de las fibras nerviosas retinales. En estos pacientes se asocia frecuentemente la miopía y ambliopía. A pesar de los pobres resultados visuales y ante la ausencia de otras terapias disponibles existe tendencia a tratamiento agresivo para la ambliopía, aunque en la literatura esto es aún controversial. Abstract in english The intraocular myelin fibers emerge since one's birth and it is usually located around the papilla. The syndrome of myelinated retinal nerve fibers was described for the first time by Virchow in 1856. This appears in the form of grooved patches, white or grayish white with imprecise and feathery bo [...] rders following a coincident configuration with the distribution of the retinal nerve fibers. A four years-old girl who was taken to the doctor's office because she presented with right eye deviation. In the ophthalmologic exam, the best corrected visual acuity was 0.1 and the ophthalmoscopy confirmed myelinated retinal nerve fibers. Myopia and amblyopia were often associated in these patients. In spite of the poor visual results and the lack of other available therapies, specialists tend to apply aggressive treatment for amblyopia, although this procedure is still controversial in the medical literature.

  3. Atomic resolution view into the structure–function relationships of the human myelin peripheral membrane protein P2

    International Nuclear Information System (INIS)

    The structure of the human myelin peripheral membrane protein P2 has been refined at 0.93 Å resolution. In combination with functional experiments in vitro, in vivo and in silico, the fine details of the structure–function relationships in P2 are emerging. P2 is a fatty acid-binding protein expressed in vertebrate peripheral nerve myelin, where it may function in bilayer stacking and lipid transport. P2 binds to phospholipid membranes through its positively charged surface and a hydrophobic tip, and accommodates fatty acids inside its barrel structure. The structure of human P2 refined at the ultrahigh resolution of 0.93 Å allows detailed structural analyses, including the full organization of an internal hydrogen-bonding network. The orientation of the bound fatty-acid carboxyl group is linked to the protonation states of two coordinating arginine residues. An anion-binding site in the portal region is suggested to be relevant for membrane interactions and conformational changes. When bound to membrane multilayers, P2 has a preferred orientation and is stabilized, and the repeat distance indicates a single layer of P2 between membranes. Simulations show the formation of a double bilayer in the presence of P2, and in cultured cells wild-type P2 induces membrane-domain formation. Here, the most accurate structural and functional view to date on P2, a major component of peripheral nerve myelin, is presented, showing how it can interact with two membranes simultaneously while going through conformational changes at its portal region enabling ligand transfer

  4. Mutational analysis of the myelin protein zero (MPZ) gene associated with Charcot-Marie-Tooth neuropathy type 1B

    Energy Technology Data Exchange (ETDEWEB)

    Roa, B.B.; Warner, L.E.; Lupski, J.R. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    The MPZ gene that maps to chromosome 1q22q23 encodes myelin protein zero, which is the most abundant peripheral nerve myelin protein that functions as a homophilic adhesion molecule in myelin compaction. Association of the MPZ gene with the dysmyelinating peripheral neuropathies Charcot-Marie-Tooth disease type 1B (CMT1B) and the more severe Dejerine-Sottas syndrome (DSS) was previously demonstrated by MPZ mutations identified in CMT1B and in rare DSS patients. In this study, the coding region of the MPZ gene was screened for mutations in a cohort of 74 unrelated patients with either CMT type 1 or DSS who do not carry the most common CMT1-associated molecular lesion of a 1.5 Mb DNA duplication on 17p11.2-p12. Heteroduplex analysis detected base mismatches in ten patients that were distributed over three exons of MPZ. Direct sequencing of PCR-amplified genomic DNA identified a de novo MPZ mutation associated with CMT1B that predicts an Ile(135)Thr substitution. This finding further confirms the role of MPZ in the CMT1B disease process. In addition, two polymorphisms were identified within the Gly(200) and Ser(228) codons that do not alter the respective amino acid residues. A fourth base mismatch in MPZ exon 3 detected by heteroduplex analysis is currently being characterized by direct sequence determination. Previously, four unrelated patients in this same cohort were found to have unique point mutations in the coding region of the PMP22 gene. The collective findings on CMT1 point mutations could suggest that regulatory region mutations, and possibly mutations in CMT gene(s) apart from the MPZ, PMP22 and Cx32 genes identified thus far, may prove to be significant for a number of CMT1 cases that do not involve DNA duplication.

  5. Fibroblast Growth Factor-2 Enhanced The Recruitment of Progenitor Cells and Myelin Repair in Experimental Demyelination of Rat Hippocampal Formations

    Directory of Open Access Journals (Sweden)

    Mahdieh Azin

    2015-11-01

    Full Text Available Objective: Hippocampal insults have been observed in multiple sclerosis (MS patients. Fibroblast growth factor-2 (FGF2 induces neurogenesis in the hippocampus and enhances the proliferation, migration and differentiation of oligodendrocyte progenitor cells (OPCs. In the current study, we have investigated the effect of FGF2 on the processes of gliotoxin induced demyelination and subsequent remyelination in the hippocampus. Materials and Methods: In this experimental study adult male Sprague-Dawley rats received either saline or lysolecithin (LPC injections to the right hippocampi. Animals received intraperitoneal (i.p. injections of FGF2 (5 ng/g on days 0, 5, 12 and 26 post-LPC. Expressions of myelin basic protein (Mbp as a marker of myelination, Olig2 as a marker of OPC proliferation, Nestin as a marker of neural progenitor cells, and glial fibrillary acidic protein (Gfap as a marker of reactive astrocytes were investigated in the right hippocampi by reverse transcriptase-polymerase chain reaction (RT-PCR. Results: There was reduced Mbp expression at seven days after LPC injection, increased expressions of Olig2 and Nestin, and the level of Gfap did not change. FGF2 treatment reversed the expression level of Mbp to the control, significantly enhanced the levels of Olig2 and Nestin, but did not change the level of Gfap. At day-28 post- LPC, the expression level of Mbp was higher than the control in LPC-treated animals that received FGF2. The levels of Olig2, Nestin and Gfap were at the control level in the non-treated LPC group but significantly higher in the FGF2-t reated LPC group. Conclusion: FGF2 enhanced hippocampal myelination and potentiated the recruitment of OPCs and neural stem cells (NSCs to the lesion area. Long-term application of FGF2 might also enhance astrogliosis in the lesion site.

  6. Atomic resolution view into the structure–function relationships of the human myelin peripheral membrane protein P2

    Energy Technology Data Exchange (ETDEWEB)

    Ruskamo, Salla [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Yadav, Ravi P. [Banaras Hindu University, Varanasi (India); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); Sharma, Satyan; Lehtimäki, Mari [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Laulumaa, Saara [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); Aggarwal, Shweta; Simons, Mikael [Max Planck Institute for Experimental Medicine, Göttingen (Germany); Bürck, Jochen; Ulrich, Anne S. [Karlsruhe Institute for Technology (KIT), Karlsruhe (Germany); Juffer, André H. [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Kursula, Inari [University of Oulu, Oulu (Finland); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); Kursula, Petri, E-mail: petri.kursula@oulu.fi [University of Oulu, Oulu (Finland); University of Oulu, Oulu (Finland); Helmholtz Centre for Infection Research (CSSB-HZI), German Electron Synchrotron (DESY), Hamburg (Germany); University of Hamburg, Hamburg (Germany)

    2014-01-01

    The structure of the human myelin peripheral membrane protein P2 has been refined at 0.93 Å resolution. In combination with functional experiments in vitro, in vivo and in silico, the fine details of the structure–function relationships in P2 are emerging. P2 is a fatty acid-binding protein expressed in vertebrate peripheral nerve myelin, where it may function in bilayer stacking and lipid transport. P2 binds to phospholipid membranes through its positively charged surface and a hydrophobic tip, and accommodates fatty acids inside its barrel structure. The structure of human P2 refined at the ultrahigh resolution of 0.93 Å allows detailed structural analyses, including the full organization of an internal hydrogen-bonding network. The orientation of the bound fatty-acid carboxyl group is linked to the protonation states of two coordinating arginine residues. An anion-binding site in the portal region is suggested to be relevant for membrane interactions and conformational changes. When bound to membrane multilayers, P2 has a preferred orientation and is stabilized, and the repeat distance indicates a single layer of P2 between membranes. Simulations show the formation of a double bilayer in the presence of P2, and in cultured cells wild-type P2 induces membrane-domain formation. Here, the most accurate structural and functional view to date on P2, a major component of peripheral nerve myelin, is presented, showing how it can interact with two membranes simultaneously while going through conformational changes at its portal region enabling ligand transfer.

  7. Effect of postnatal progesterone therapy following preterm birth on neurosteroid concentrations and cerebellar myelination in guinea pigs.

    Science.gov (United States)

    Palliser, H K; Kelleher, M A; Tolcos, M; Walker, D W; Hirst, J J

    2015-08-01

    Allopregnanolone protects the fetal brain and promotes normal development including myelination. Preterm birth results in the early separation of the infant from the placenta and consequently a decline in blood and brain allopregnanolone concentrations. Progesterone therapy may increase allopregnanolone and lead to improved oligodendrocyte maturation. The objectives of this study were to examine the efficacy of progesterone replacement in augmenting allopregnanolone concentrations during the postnatal period and to assess the effect on cerebellar myelination - a region with significant postnatal development. Preterm guinea pig neonates delivered at 62 days of gestation by caesarean section received daily s.c. injections of vehicle (2-Hydroxypropyl-?-cyclodextrin) or progesterone (16 mg/kg) for 8 days until term-equivalent age (TEA). Term delivered controls (PND1) received vehicle. Neonatal condition/wellbeing was scored, and salivary progesterone was sampled over the postnatal period. Brain and plasma allopregnanolone concentrations were measured by radioimmunoassay; cortisol and progesterone concentrations were determined by enzyme immunoassay; and myelin basic protein (MBP), proteolipid protein (PLP), oligodendroctye transcription factor 2 (OLIG2) and platelet-derived growth factor receptor-? (PDGFR?) were quantified by immunohistochemistry and western blot. Brain allopregnanolone concentrations were increased in progesterone-treated neonates. Plasma progesterone and cortisol concentrations were elevated in progesterone-treated male neonates. Progesterone treatment decreased MBP and PLP in lobule X of the cerebellum and total cerebellar OLIG2 and PDGFR? in males but not females at TEA compared with term animals. We conclude that progesterone treatment increases brain allopregnanolone concentrations, but also increases cortisol levels in males, which may disrupt developmental processes. Consideration should be given to the use of non-metabolizable neurosteroid agonists. PMID:25907069

  8. On the additive splitting procedures and their computer realization

    DEFF Research Database (Denmark)

    Farago, I.; Thomsen, Per Grove; Zlatev, Z.

    2008-01-01

    Two additive splitting procedures are defined and studied in this paper. It is shown that these splitting procedures have good stability properties. Some other splitting procedures, which are traditionally used in mathematical models used in many scientific and engineering fields, are sketched. All splitting procedures are tested by using six different numerical methods for solving differential equations. Many conclusions, which are related both to the comparison of the additive splitting proced...

  9. Compressive Split-Step Fourier Method

    CERN Document Server

    Bayindir, Cihan

    2015-01-01

    In this paper an approach for decreasing the computational effort required for the split-step Fourier method (SSFM) is introduced. It is shown that using the sparsity property of the simulated signals, the compressive sampling algorithm can be used as a very efficient tool for the split-step spectral simulations of various phenomena which can be modeled by using differential equations. The proposed method depends on the idea of using a smaller number of spectral components compared to the classical split-step Fourier method with a high number of components. After performing the time integration with a smaller number of spectral components and using the compressive sampling technique with l1 minimization, it is shown that the sparse signal can be reconstructed with a significantly better efficiency compared to the classical split-step Fourier method. Proposed method can be named as compressive split-step Fourier method (CSSFM). For testing of the proposed method the Nonlinear Schrodinger Equation and its one-s...

  10. The MT pool size ratio and the DTI radial diffusivity may reflect the myelination in shiverer and control mice

    OpenAIRE

    Ou, Xiawei; Sun, Shu-Wei; Liang, Hsiao-Fang; Song, Sheng-Kwei; Gochberg, Daniel F.

    2009-01-01

    A quantitative magnetization transfer (qMT) technique was employed to quantify the ratio of the sizes of the bound and free water proton pools in ex vivo mouse brains. The goal was to determine the pool size ratio sensitivity to myelin. Fixed brains from both shiverer mice and control littermates were imaged. The pool size ratio in the corpus callosum of shiverer mice was substantially lower than that in the control mice, while there was no distinguishable difference in the pool size ratio in...

  11. Myelin basic protein interaction with zinc and phosphate: fluorescence studies on the water-soluble form of the protein.

    OpenAIRE

    Cavatorta, P; Giovanelli, S; BOBBA, A; Riccio, P.; Szabo, A G; Quagliariello, E.

    1994-01-01

    The interaction of myelin basic protein (MBP) with zinc and phosphate ions has been studied by using the emission properties of the single tryptophan residue of the protein (Trp-115). The studies have been carried out by means of both static and time-resolved fluorescence techniques. The addition of either zinc to MBP in the presence of phosphate or phosphate to MBP in the presence of zinc resulted in an increase of fluorescence intensity and a blue shift of the emission maximum wavelength. F...

  12. Functional recovery of regenerating motor axons is delayed in mice heterozygously deficient for the myelin protein P(0) gene

    DEFF Research Database (Denmark)

    Rosberg, Mette Romer; Alvarez, Susana; Krarup, Christian; Moldovan, Mihai

    2013-01-01

    Mice with a heterozygous knock-out of the myelin protein P0 gene (P0+/-) develop a neuropathy similar to human Charcot-Marie-Tooth disease. They are indistinguishable from wild-types (WT) at birth and develop a slowly progressing demyelinating neuropathy. The aim of this study was to investigate whether the regeneration capacity of early symptomatic P0+/- is impaired as compared to age matched WT. Right sciatic nerves were lesioned at the thigh in 7-8 months old mice. Tibial motor axons at ankle...

  13. Multiple Spectral Splits of Supernova Neutrinos

    CERN Document Server

    Dasgupta, Basudeb; Raffelt, Georg G; Smirnov, Alexei Yu

    2009-01-01

    Collective oscillations of supernova neutrinos swap the electron neutrino and antineutrino spectra with those of another flavor in certain energy intervals bounded by sharp spectral splits. This phenomenon is far more general than previously appreciated: typically one finds one or more swaps and accompanying splits in the neutrino and antineutrino channels for both inverted and normal neutrino mass hierarchies. Depending on an instability condition, swaps develop around spectral crossings (energies where the electron neutrino or antineutrino fluxes are equal to that of another flavor, as well as infinite E where all fluxes vanish), and the widths of swaps are determined by the spectra and fluxes. Wash-out by multi-angle decoherence varies across the spectrum and splits can survive as sharp spectral features.

  14. Split liver transplantation: What’s unique?

    Science.gov (United States)

    Dalal, Aparna R

    2015-01-01

    The intraoperative management of split liver transplantation (SLT) has some unique features as compared to routine whole liver transplantations. Only the liver has this special ability to regenerate that confers benefits in survival and quality of life for two instead of one by splitting livers. Primary graft dysfunction may result from small for size syndrome. Graft weight to recipient body weight ratio is significant for both trisegmental and hemiliver grafts. Intraoperative surgical techniques aim to reduce portal hyperperfusion and decrease venous portal pressure. Ischemic preconditioning can be instituted to protect against ischemic reperfusion injury which impacts graft regeneration. Advancement of the technique of SLT is essential as use of split cadaveric grafts expands the donor pool and potentially has an excellent future. PMID:26421261

  15. High efficiency beam splitting for H- accelerators

    International Nuclear Information System (INIS)

    Beam splitting for high energy accelerators has typically involved a significant loss of beam and radiation. This paper reports on a new method of splitting beams for H- accelerators. This technique uses a high intensity flash of light to strip a fraction of the H- beam to H0 which are then easily separated by a small bending magnet. A system using a 900-watt (average electrical power) flashlamp and a highly efficient collector will provide 10-3 to 10-2 splitting of a 50 MeV H- beam. Results on the operation and comparisons with stripping cross sections are presented. Also discussed is the possibility for developing this system to yield a higher stripping fraction

  16. Observers and splitting structures in relativistic electrodynamics

    Science.gov (United States)

    Auchmann, B.; Kurz, S.

    2014-10-01

    We introduce a relativistic splitting structure as a means to map fields and equations of electromagnetism from curved four-dimensional space-time to three-dimensional observer's space. We focus on a minimal set of mathematical structures that are directly motivated by the language of the physical theory. Space-time, world-lines, time translation, space platforms and time synchronization all find their mathematical counterparts. The splitting structure is defined without recourse to coordinates or frames. This is noteworthy since, in much of the prevalent literature, observers are identified with adapted coordinates and frames. Among the benefits of the approach is a concise and insightful classification of splitting structures that is juxtaposed to a classification of observers. The application of the framework to the Ehrenfest paradox and Schiff's ‘Question in General Relativity’ further illustrates the advantages of the framework, enabling a compact, yet profound analysis of the problems at hand.

  17. Observers and splitting structures in relativistic electrodynamics

    International Nuclear Information System (INIS)

    We introduce a relativistic splitting structure as a means to map fields and equations of electromagnetism from curved four-dimensional space–time to three-dimensional observer's space. We focus on a minimal set of mathematical structures that are directly motivated by the language of the physical theory. Space–time, world-lines, time translation, space platforms and time synchronization all find their mathematical counterparts. The splitting structure is defined without recourse to coordinates or frames. This is noteworthy since, in much of the prevalent literature, observers are identified with adapted coordinates and frames. Among the benefits of the approach is a concise and insightful classification of splitting structures that is juxtaposed to a classification of observers. The application of the framework to the Ehrenfest paradox and Schiff's ‘Question in General Relativity’ further illustrates the advantages of the framework, enabling a compact, yet profound analysis of the problems at hand. (paper)

  18. Symmetric splitting of very light systems

    International Nuclear Information System (INIS)

    Fission reactions that produce fragments close to one half the mass of the composite system are traditionally observed in heavy nuclei. In light systems, symmetric splitting is rarely observed and poorly understood. It would be interesting to verify the existence of the symmetric splitting of compound nuclei with A 12C + 40Ca, 141 MeV 9Be + 40Ca and 153 MeV 6Li + 40Ca. The out-of-plane correlation of symmetric products was also measured for the reaction 186 MeV 12C + 40Ca. The coincidence measurements of the 12C + 40Ca system demonstrated that essentially all of the inclusive yield of symmetric products around 400 results from a binary decay. To characterize the dependence of the symmetric splitting process on the excitation energy of the 12C + 40C system, inclusive measurements were made at bombarding energies of 74, 132, 162, and 185 MeV

  19. Splitting neutrino masses and showering into Sky

    OpenAIRE

    Fargion, D.; D'Armiento, D.; Iacobelli, M.; Lanciano, O.; P. Oliva; Lucentini, P. G. De Sanctis; Grossi, M.; de Santis, M.

    2006-01-01

    Neutrino masses might be as light as a few time the atmospheric neutrino mass splitting. High Energy ZeV cosmic neutrinos (in Z-Showering model) might hit relic ones at each mass in different resonance energies in our nearby Universe. This non-degenerated density and energy must split UHE Z-boson secondaries (in Z-Burst model) leading to multi injection of UHECR nucleons within future extreme AUGER energy. Secondaries of Z-Burst as neutral gamma, below a few tens EeV are bet...

  20. 2S Hyperfine splitting of muonic hydrogen

    OpenAIRE

    Martynenko, A. P.

    2004-01-01

    Corrections of orders alpha^5, alpha^6 are calculated in the hyperfine splitting of the 2S state in the muonic hydrogen. The nuclear structure effects are taken into account in the one- and two-loop Feynman amplitudes by means of the proton electromagnetic form factors. Total numerical value of the 2S state hyperfine splitting 22.8148 meV in the (\\mu p) can be considered as reliable estimation for the corresponding experiment with the accuracy 10^{-5}. The value of the Stern...

  1. Membrane interactions in nerve myelin. I. Determination of surface charge from effects of pH and ionic strength on period.

    OpenAIRE

    Inouye, H.; Kirschner, D. A.

    1988-01-01

    We have used x-ray diffraction to study the interactions between myelin membranes in the sciatic nerve (PNS) and optic nerve (CNS) as a function of pH (2-10) and ionic strength (0-0.18). The period of myelin was found to change in a systematic manner with pH and ionic strength. PNS periods ranged from 165 to 250 A or more, while CNS periods ranged from 150 to 230 A. The native periods were observed only near physiological ionic strength at neutral or alkaline pH. The smallest periods were obs...

  2. The effect of beta-interferon therapy on myelin basic protein-elicited CD4+ T cell proliferation and cytokine production in multiple sclerosis

    DEFF Research Database (Denmark)

    Hedegaard, Chris J; Krakauer, Martin

    2008-01-01

    Interferon (IFN)-beta therapy has well-established clinical benefits in multiple sclerosis (MS), but the underlying modulation of cytokine responses to myelin self-antigens remains poorly understood. We analysed the CD4+ T cell proliferation and cytokine responses elicited by myelin basic protein (MBP) and a foreign recall antigen, tetanus toxoid (TT), in mononuclear cell cultures from fourteen MS patients undergoing IFN-beta therapy. The MBP-elicited IFN-gamma-, TNF-alpha- and IL-10 production decreased during therapy (p

  3. Complement activating antibodies to myelin oligodendrocyte glycoprotein in neuromyelitis optica and related disorders

    Directory of Open Access Journals (Sweden)

    Mader Simone

    2011-12-01

    Full Text Available Abstract Background Serum autoantibodies against the water channel aquaporin-4 (AQP4 are important diagnostic biomarkers and pathogenic factors for neuromyelitis optica (NMO. However, AQP4-IgG are absent in 5-40% of all NMO patients and the target of the autoimmune response in these patients is unknown. Since recent studies indicate that autoimmune responses to myelin oligodendrocyte glycoprotein (MOG can induce an NMO-like disease in experimental animal models, we speculate that MOG might be an autoantigen in AQP4-IgG seronegative NMO. Although high-titer autoantibodies to human native MOG were mainly detected in a subgroup of pediatric acute disseminated encephalomyelitis (ADEM and multiple sclerosis (MS patients, their role in NMO and High-risk NMO (HR-NMO; recurrent optic neuritis-rON or longitudinally extensive transverse myelitis-LETM remains unresolved. Results We analyzed patients with definite NMO (n = 45, HR-NMO (n = 53, ADEM (n = 33, clinically isolated syndromes presenting with myelitis or optic neuritis (CIS, n = 32, MS (n = 71 and controls (n = 101; 24 other neurological diseases-OND, 27 systemic lupus erythematosus-SLE and 50 healthy subjects for serum IgG to MOG and AQP4. Furthermore, we investigated whether these antibodies can mediate complement dependent cytotoxicity (CDC. AQP4-IgG was found in patients with NMO (n = 43, 96%, HR-NMO (n = 32, 60% and in one CIS patient (3%, but was absent in ADEM, MS and controls. High-titer MOG-IgG was found in patients with ADEM (n = 14, 42%, NMO (n = 3, 7%, HR-NMO (n = 7, 13%, 5 rON and 2 LETM, CIS (n = 2, 6%, MS (n = 2, 3% and controls (n = 3, 3%, two SLE and one OND. Two of the three MOG-IgG positive NMO patients and all seven MOG-IgG positive HR-NMO patients were negative for AQP4-IgG. Thus, MOG-IgG were found in both AQP4-IgG seronegative NMO patients and seven of 21 (33% AQP4-IgG negative HR-NMO patients. Antibodies to MOG and AQP4 were predominantly of the IgG1 subtype, and were able to mediate CDC at high-titer levels. Conclusions We could show for the first time that a subset of AQP4-IgG seronegative patients with NMO and HR-NMO exhibit a MOG-IgG mediated immune response, whereas MOG is not a target antigen in cases with an AQP4-directed humoral immune response.

  4. Adrenomedullin promotes differentiation of oligodendrocyte precursor cells into myelin-basic-protein expressing oligodendrocytes under pathological conditions in vitro

    Directory of Open Access Journals (Sweden)

    Takakuni Maki

    2015-07-01

    Full Text Available Oligodendrocytes, which are the main cell type in cerebral white matter, are generated from their precursor cells (oligodendrocyte precursor cells: OPCs. However, the differentiation from OPCs to oligodendrocytes is disturbed under stressed conditions. Therefore, drugs that can improve oligodendrocyte regeneration may be effective for white matter-related diseases. Here we show that a vasoactive peptide adrenomedullin (AM promotes the in vitro differentiation of OPCs under pathological conditions. Primary OPCs were prepared from neonatal rat brains, and differentiated into myelin-basic-protein expressing oligodendrocytes over time. This in vitro OPC differentiation was inhibited by prolonged chemical hypoxic stress induced by non-lethal CoCl2 treatment. However, AM promoted the OPC differentiation under the hypoxic stress conditions, and the AM receptor antagonist AM22–52 canceled the AM-induced OPC differentiation. In addition, AM treatment increased the phosphorylation level of Akt in OPC cultures, and correspondingly, the PI3K/Akt inhibitor LY294002 blocked the AM-induced OPC differentiation. Taken together, AM treatment rescued OPC maturation under pathological conditions via an AM-receptor-PI3K/Akt pathway. Oligodendrocytes play critical roles in white matter by forming myelin sheath. Therefore, AM signaling may be a promising therapeutic target to boost oligodendrocyte regeneration in CNS disorders.

  5. High frequency of mutations in codon 98 of the peripheral myelin protein Po gene in 20 French CMT1 patients

    Energy Technology Data Exchange (ETDEWEB)

    Rougher, H.; LeGuern, E. Gouider, R. [and others

    1996-03-01

    Charcot-Marie-Tooth disease, characterized by distal muscle weakness and amyotrophy, decreased or absent tendon reflexes, and high arched feet, is the most common inherited peripheral neuropathy, with a prevalence of 1 in 2,500. Two types of CMT have been distinguished on the basis of nerve conduction velocities. CMT type 1 is the most frequent, with markedly slowed velocities ({<=}40 m/s) associated with hypertrophic onion bulb changes on nerve biopsy. Autosomal dominant CMT1 is genetically heterogeneous: CMT1A is caused by a 1.5-Mb duplication in 17p11.2 and, more rarely, by a point mutation in tha PMP22 (peripheral myelin protein, 22 kD) gene located in the duplicated region; CMT1B results from mutations in the Po (peripheral myelin protein zero) gene in 1q22-23. Forty-five percent (7/16) of the published mutations associated with CMT1 occur in exon 3 of Po. In order to determine the cause of CMT1 in 20 unrelated patients without 17p11.2 duplications, mutations were sought in exon 3 of Po with three techniques: nonradioactive SSCP, automated sequencing, and PCR enzymatic restriction. 18 refs., 2 figs.

  6. On splitting polynomials with noncommutative coefficients

    OpenAIRE

    Maszczyk, Tomasz

    2007-01-01

    It is shown that for every splitting of a polynomial with noncommutative coefficients into linear factors $(X-a_{k})$ with $a_{k}$'s commuting with coefficients, any cyclic permutation of linear factors gives the same result and all $a_{k}$ are roots of that polynomial. Examples are given and analyzed from Galois theory point of view.

  7. Mechanics analysis of molar tooth splitting.

    Science.gov (United States)

    Barani, Amir; Chai, Herzl; Lawn, Brian R; Bush, Mark B

    2015-03-01

    A model for the splitting of teeth from wedge loading of molar cusps from a round indenting object is presented. The model is developed in two parts: first, a simple 2D fracture mechanics configuration with the wedged tooth simulated by a compact tension specimen; second, a full 3D numerical analysis using extended finite element modeling (XFEM) with an embedded crack. The result is an explicit equation for splitting load in terms of indenter radius and key tooth dimensions. Fracture experiments on extracted human molars loaded axially with metal spheres are used to quantify the splitting forces and thence to validate the model. The XFEM calculations enable the complex crack propagation, initially in the enamel coat and subsequently in the interior dentin, to be followed incrementally with increasing load. The fracture evolution is shown to be stable prior to failure, so that dentin toughness, not strength, is the controlling material parameter. Critical conditions under which tooth splitting in biological and dental settings are likely to be met, however rare, are considered. PMID:25584989

  8. Supporting Students' Constructions of the Splitting Operation

    Science.gov (United States)

    Norton, Anderson; Wilkins, Jesse L. M.

    2013-01-01

    Previous research has demonstrated the effectiveness of particular instructional practices that support students' constructions of the partitive unit fraction scheme and measurement concepts for fractions. Another body of research has demonstrated the power of a particular mental operation--the splitting operation--in supporting students'…

  9. Crystal-field splitting in Pr dideuteride

    International Nuclear Information System (INIS)

    From inelastic neutron scattering experiments, it is concluded that the crystal-field splitting in PrD/sub 1.95/ is 41 meV. Because of this high value, the antiferromagnetic ordering below T/sub N/ = 2.3 K is ascribed to a magnetic ground state, probably GAMMA5, of the Pr3+ ions

  10. Helioseismic Solar Cycle Changes and Splitting Coefficients

    Indian Academy of Sciences (India)

    S. C. Tripathy; Kiran Jain; A. Bhatnagar

    2000-09-01

    Using the GONG data for a period over four years, we have studied the variation of frequencies and splitting coefficients with solar cycle. Frequencies and even-order coefficients are found to change significantly with rising phase of the solar cycle. We also find temporal variations in the rotation rate near the solar surface.

  11. Czech, Slovak science ten years after split

    CERN Document Server

    2003-01-01

    Ten years after the split of Czechoslovakia Czech and Slovak science are facing the same difficulties: shortage of money for research, poor salaries, obsolete equipment and brain drain, especially of the young, according to a feature in the Daily Lidove Noviny (1 page).

  12. The geometry of the Hilton splitting

    OpenAIRE

    Wang, Jianhua

    2002-01-01

    One of the important theorems in homotopy theory is the Hilton splitting. In this paper we will construct all the Hilton homomorphisms by geometrical means and prove a family of sharper symmetry relations of linking coefficients which desuspend and generalize the relations of Kervaire, Haefliger and Steer.

  13. Spin splitting in 2D monochalcogenide semiconductors

    CERN Document Server

    Do, Dat T; Lai, Chih-Wei

    2015-01-01

    We report ab initio calculations of the spin splitting of the uppermost valence band (UVB) and the lowermost conduction band (LCB) in bulk and atomically thin GaS, GaSe, GaTe, and InSe. These layered monochalcogenides appear in four major polytypes ($\\epsilon$, $\\beta$, $\\gamma$, and $\\delta$) depending on the stacking order, except for the monoclinic GaTe. Bulk and few-layer $\\epsilon$- and $\\gamma$-type, as well as odd-number few-layer $\\beta$-type GaS, GaSe, and InSe crystals are noncentrosymmetric. The spin splittings of the UVB and the LCB near the $\\Gamma$ point in the Brillouin zone are finite, but still smaller than those in a zinc-blende semiconductor, such as GaAs. On the other hand, the spin splitting is zero in centrosymmetric bulk and even-number few-layer $\\beta$-type GaS, GaSe, and InSe, owing to the constraint of spatial inversion symmetry. By contrast, GaTe exhibits zero spin splitting because it is centrosymmetric down to a single layer. The electron and hole spin relaxation times in these s...

  14. Isospin Splittings of Doubly Heavy Baryons

    Energy Technology Data Exchange (ETDEWEB)

    Brodsky, Stanley J.; /SLAC; Guo, Feng-Kun; /Bonn U., HISKP /Bonn U.; Hanhart, Christoph; /Julich, Forschungszentrum /JCHP, Julich /IAS, Julich; Meissner, Ulf-G.; /Julich, Forschungszentrum /JCHP, Julich /IAS, Julich /Bonn U., HISKP /Bonn U.

    2011-08-18

    The SELEX Collaboration has reported a very large isospin splitting of doubly charmed baryons. We show that this effect would imply that the doubly charmed baryons are very compact. One intriguing possibility is that such baryons have a linear geometry Q-q-Q where the light quark q oscillates between the two heavy quarks Q, analogous to a linear molecule such as carbon dioxide. However, using conventional arguments, the size of a heavy-light hadron is expected to be around 0.5 fm, much larger than the size needed to explain the observed large isospin splitting. Assuming the distance between two heavy quarks is much smaller than that between the light quark and a heavy one, the doubly heavy baryons are related to the heavy mesons via heavy quark-diquark symmetry. Based on this symmetry, we predict the isospin splittings for doubly heavy baryons including {Xi}{sub cc}, {Xi}{sub bb} and {Xi}{sub bc}. The prediction for the {Xi}{sub cc} is much smaller than the SELEX value. On the other hand, the {Xi}{sub bb} baryons are predicted to have an isospin splitting as large as (6.3 {+-} 1.7) MeV. An experimental study of doubly bottomed baryons is therefore very important to better understand the structure of baryons with heavy quarks.

  15. Planar microfluidic drop splitting and merging.

    Science.gov (United States)

    Collignon, Sean; Friend, James; Yeo, Leslie

    2015-04-21

    Open droplet microfluidic platforms offer attractive alternatives to closed microchannel devices, including lower fabrication cost and complexity, significantly smaller sample and reagent volumes, reduced surface contact and adsorption, as well as drop scalability, reconfigurability, and individual addressability. For these platforms to be effective, however, they require efficient schemes for planar drop transport and manipulation. While there are many methods that have been reported for drop transport, it is far more difficult to carry out other drop operations such as dispensing, merging and splitting. In this work, we introduce a novel alternative to merge and, more crucially, split drops using laterally-offset modulated surface acoustic waves (SAWs). The energy delivery into the drop is divided into two components: a small modulation amplitude excitation to initiate weak rotational flow within the drop followed by a short burst in energy to induce it to stretch. Upon removal of the SAW energy, capillary forces at the center of the elongated drop cause the liquid in this capillary bridge region to drain towards both ends of the drop, resulting in its collapse and therefore the splitting of the drop. This however occurs only below a critical Ohnesorge number, which is a balance between the viscous forces that retard the drainage and the sufficiently large capillary forces that cause the liquid bridge to pinch. We show the possibility of reliably splitting drops into two equal sized droplets with an average deviation in their volumes of only around 4% and no greater than 10%, which is comparable to the 7% and below splitting deviation obtained with electrowetting drop splitting techniques. In addition, we also show that it is possible to split the drop asymmetrically to controllably and reliably produce droplets of different volumes. Such potential as well as the flexibility in tuning the device to operate on drops of different sizes without requiring electrode reconfiguration, i.e., the use of different devices, as is required in electrowetting-therefore makes the present method an attractive alternative to electrowetting schemes. PMID:25738425

  16. Benefits of pathway splitting in sensory coding.

    Science.gov (United States)

    Gjorgjieva, Julijana; Sompolinsky, Haim; Meister, Markus

    2014-09-01

    In many sensory systems, the neural signal splits into multiple parallel pathways. For example, in the mammalian retina, ~20 types of retinal ganglion cells transmit information about the visual scene to the brain. The purpose of this profuse and early pathway splitting remains unknown. We examine a common instance of splitting into ON and OFF neurons excited by increments and decrements of light intensity in the visual scene, respectively. We test the hypothesis that pathway splitting enables more efficient encoding of sensory stimuli. Specifically, we compare a model system with an ON and an OFF neuron to one with two ON neurons. Surprisingly, the optimal ON-OFF system transmits the same information as the optimal ON-ON system, if one constrains the maximal firing rate of the neurons. However, the ON-OFF system uses fewer spikes on average to transmit this information. This superiority of the ON-OFF system is also observed when the two systems are optimized while constraining their mean firing rate. The efficiency gain for the ON-OFF split is comparable with that derived from decorrelation, a well known processing strategy of early sensory systems. The gain can be orders of magnitude larger when the ecologically important stimuli are rare but large events of either polarity. The ON-OFF system also provides a better code for extracting information by a linear downstream decoder. The results suggest that the evolution of ON-OFF diversification in sensory systems may be driven by the benefits of lowering average metabolic cost, especially in a world in which the relevant stimuli are sparse. PMID:25186757

  17. Non-Mendelian transmission in a human developmental disorder: split hand/split foot.

    OpenAIRE

    Jarvik, G. P.; Patton, M.A.; Homfray, T.; Evans, J. P.

    1994-01-01

    The study of Mendelian disorders that do not meet some Mendelian expectations has led to an increased understanding of such previously obscure genetic phenomena as anticipation. Split hand/split foot (SHSF), a human developmental malformation, demonstrates such distinctive genetic features as reduced penetrance and variable expressivity. In this study, new pedigrees with defined ascertainment confirm the existence of non-Mendelian transmission characterized by the overtransmission of SHSF fro...

  18. Split mandrel versus split sleeve coldworking: Dual methods for extending the fatigue life of metal structures

    Science.gov (United States)

    Rodman, Geoffrey A.; Creager, Matthew

    1994-01-01

    It is common practice to use split sleeve coldworking of fastener holes as a means of extending the fatigue life of metal structures. In search of lower manufacturing costs, the aerospace industry is examining the split mandrel (sleeveless) coldworking process as an alternative method of coldworking fastener holes in metal structures. The split mandrel process (SpM) significantly extends the fatigue life of metal structures through the introduction of a residual compressive stress in a manner that is very similar to the split sleeve system (SpSl). Since the split mandrel process is significantly less expensive than the split sleeve process and more adaptable to robotic automation, it will have a notable influence upon other new manufacture of metal structures which require coldworking a significant number of holes, provided the aerospace community recognizes that the resulting residual stress distributions and fatigue life improvement are the same for both processes. Considerable testing has validated the correctness of that conclusion. The findings presented in this paper represent the results of an extensive research and development program, comprising data collected from over 400 specimens fabricated from 2024-T3 and 7075-T651 aluminum alloys in varied configurations, which quantify the benefits (fatigue enhancement and cost savings) of automating a sleeveless coldworking system.

  19. Split mandrel versus split sleeve coldworking: Dual methods for extending the fatigue life of metal structures

    Science.gov (United States)

    Rodman, Geoffrey A.; Creager, Matthew

    1994-09-01

    It is common practice to use split sleeve coldworking of fastener holes as a means of extending the fatigue life of metal structures. In search of lower manufacturing costs, the aerospace industry is examining the split mandrel (sleeveless) coldworking process as an alternative method of coldworking fastener holes in metal structures. The split mandrel process (SpM) significantly extends the fatigue life of metal structures through the introduction of a residual compressive stress in a manner that is very similar to the split sleeve system (SpSl). Since the split mandrel process is significantly less expensive than the split sleeve process and more adaptable to robotic automation, it will have a notable influence upon other new manufacture of metal structures which require coldworking a significant number of holes, provided the aerospace community recognizes that the resulting residual stress distributions and fatigue life improvement are the same for both processes. Considerable testing has validated the correctness of that conclusion. The findings presented in this paper represent the results of an extensive research and development program, comprising data collected from over 400 specimens fabricated from 2024-T3 and 7075-T651 aluminum alloys in varied configurations, which quantify the benefits (fatigue enhancement and cost savings) of automating a sleeveless coldworking system.

  20. Cross-recognition of a myelin peptide by CD8+ T cells in the CNS is not sufficient to promote neuronal damage.

    Science.gov (United States)

    Reuter, Eva; Gollan, René; Grohmann, Nadia; Paterka, Magdalena; Salmon, Hélène; Birkenstock, Jérôme; Richers, Sebastian; Leuenberger, Tina; Brandt, Alexander U; Kuhlmann, Tanja; Zipp, Frauke; Siffrin, Volker

    2015-03-25

    Multiple sclerosis (MS) is an inflammatory disease of the CNS thought to be driven by CNS-specific T lymphocytes. Although CD8(+) T cells are frequently found in multiple sclerosis lesions, their distinct role remains controversial because direct signs of cytotoxicity have not been confirmed in vivo. In the present work, we determined that murine ovalbumin-transgenic (OT-1) CD8(+) T cells recognize the myelin peptide myelin oligodendrocyte glycoprotein 40-54 (MOG40-54) both in vitro and in vivo. The aim of this study was to investigate whether such cross-recognizing CD8(+) T cells are capable of inducing CNS damage in vivo. Using intravital two-photon microscopy in the mouse model of multiple sclerosis, we detected antigen recognition motility of the OT-1 CD8(+) T cells within the CNS leading to a selective enrichment in inflammatory lesions. However, this cross-reactivity of OT-1 CD8(+) T cells with MOG peptide in the CNS did not result in clinically or subclinically significant damage, which is different from myelin-specific CD4(+) Th17-mediated autoimmune pathology. Therefore, intravital imaging demonstrates that local myelin recognition by autoreactive CD8(+) T cells in inflammatory CNS lesions alone is not sufficient to induce disability or increase axonal injury. PMID:25810515

  1. Quetiapine attenuates cognitive impairment and decreases seizure susceptibility possibly through promoting myelin development in a rat model of malformations of cortical development.

    Science.gov (United States)

    Ma, Lei; Yang, Feng; Zhao, Rui; Li, Li; Kang, Xiaogang; Xiao, Lan; Jiang, Wen

    2015-10-01

    Developmental delay, cognitive impairment, and refractory epilepsy are the most frequent consequences found in patients suffering from malformations of cortical development (MCD). However, therapeutic options for these psychiatric and neurological comorbidities are currently limited. The development of white matter undergoes dramatic changes during postnatal brain maturation, thus myelination deficits resulting from MCD contribute to its comorbid diseases. Consequently, drugs specifically targeting white matter are a promising therapeutic option for the treatment of MCD. We have used an in utero irradiation rat model of MCD to investigate the effects of postnatal quetiapine treatment on brain myelination as well as neuropsychological and cognitive performances and seizure susceptibility. Fatally irradiated rats were treated with quetiapine (10mg/kg, i.p.) or saline once daily from postnatal day 0 (P0) to P30. We found that postnatal administration of quetiapine attenuated object recognition memory impairment and improved long-term spatial memory in the irradiated rats. Quetiapine treatment also reduced the susceptibility and severity of pentylenetetrazol-induced seizures. Importantly, quetiapine treatment resulted in an inhibition of irradiation-induced myelin breakdown in the cerebral cortex and corpus callosum. These findings suggest that quetiapine may have beneficial, postnatal effects in the irradiated rats, strongly suggesting that improving MCD-derived white matter pathology is a possible underlying mechanism. Collectively, these results indicate that brain myelination represents an encouraging pharmacological target to improve the prognosis of patients with MCD. PMID:26188240

  2. Alterations of p75 neurotrophin receptor and Myelin transcription factor 1 in the hippocampus of perinatal phencyclidine treated rats.

    Science.gov (United States)

    Andrews, Jessica L; Newell, Kelly A; Matosin, Natalie; Huang, Xu-Feng; Fernandez-Enright, Francesca

    2015-12-01

    Postnatal administration of phencyclidine (PCP) in rodents causes major disturbances to neurological processes resulting in severe modifications to normal behavioral traits into adulthood. It is routinely used to model psychiatric disorders such as schizophrenia, producing many of the dysfunctional processes in the brain that are present in this devastating disorder, including elevated levels of apoptosis during neurodevelopment and disruptions to myelin and plasticity processes. Lingo-1 (or Leucine-rich repeat and immunoglobulin domain-containing protein) is responsible for negatively regulating neurite outgrowth and the myelination of axons. Recent findings using a postmortem human brain cohort showed that Lingo-1 signaling partners in the Nogo receptor (NgR)/p75/TNF receptor orphan Y (TROY) signaling complex, and downstream signaling partners With No Lysine (K) (WNK1) and Myelin transcription factor 1 (Myt1), play a significant part in schizophrenia pathophysiology. Here we have examined the implication of Lingo-1 and its signaling partners in a neurodevelopmental model of schizophrenia using PCP to determine if these pathways are altered in the hippocampus throughout different stages of neurodevelopment. Male Sprague-Dawley rats were injected subcutaneously with PCP (10mg/kg) or saline solution on postnatal days (PN) 7, 9, and 11. Rats (n=6/group) were sacrificed at PN12, 5weeks, or 14weeks. Relative expression levels of Lingo-1 signaling proteins were examined in the hippocampus of the treated rats. p75 and Myt1 were decreased (0.001?p?0.011) in the PCP treated rats at PN12. There were no significant changes in any of the tested proteins at 5weeks (p>0.05). At 14weeks, p75, TROY, and Myt1 were increased in the PCP treated rats (0.014?p?0.022). This is the first report of an alteration in Lingo-1 signaling proteins in the rat hippocampus, both directly after PCP treatment in early development and in adulthood. Based on our results, we propose that components of the Lingo-1 signaling pathways may be involved in the acute neurotoxicity induced by perinatal administration of PCP in rats early in development and suggest that this may have implications for the hippocampal deficits seen in schizophrenia. PMID:26071990

  3. $F$ tests for the strip-split plot design

    OpenAIRE

    Díaz-Pachón, Daniel Andrés; Francisco J. P. Zimmermann; López, Luis Alberto

    2015-01-01

    In this article we present the structure of the $F$ tests, the variance components and the approximate degrees of freedom for each of the eight possible mixed models of the strip-split plot design. We present an example to illustrate the model and compare it to more traditional settings like a three-way factorial design and a split-split plot model.

  4. Endogenous Interferon-?-Inducible Gene Expression and Interferon-?-Treatment Are Associated with Reduced T Cell Responses to Myelin Basic Protein in Multiple Sclerosis

    DEFF Research Database (Denmark)

    Börnsen, Lars; Romme Christensen, Jeppe

    2015-01-01

    Autoreactive CD4+ T-cells are considered to play a major role in the pathogenesis of multiple sclerosis. In experimental autoimmune encephalomyelitis, an animal model of multiple sclerosis, exogenous and endogenous type I interferons restrict disease severity. Recombinant interferon-? is used for treatment of multiple sclerosis, and some untreated multiple sclerosis patients have increased expression levels of type I interferon-inducible genes in immune cells. The role of endogenous type I interferons in multiple sclerosis is controversial: some studies found an association of high expression levels of interferon-?-inducible genes with an increased expression of interleukin-10 and a milder disease course in untreated multiple sclerosis patients, whereas other studies reported an association with a poor response to treatment with interferon-?. In the present study, we found that untreated multiple sclerosis patients with an increased expression of interferon-?-inducible genes in peripheral blood mononuclear cells and interferon-?-treated multiple sclerosis patients had decreased CD4+ T-cell reactivity to the autoantigen myelin basic protein ex vivo. Interferon-?-treated multiple sclerosis patients had increased IL10 and IL27 gene expression levels in monocytes in vivo. In vitro, neutralization of interleukin-10 and monocyte depletion increased CD4+ T-cell reactivity to myelin basic protein while interleukin-10, in the presence or absence of monocytes, inhibited CD4+ T-cell reactivity to myelin basic protein. Our findings suggest that spontaneous expression of interferon-?-inducible genes in peripheral blood mononuclear cells from untreated multiple sclerosis patients and treatment with interferon-? are associated with reduced myelin basic protein-induced T-cell responses. Reduced myelin basic protein-induced CD4+ T-cell autoreactivity in interferon-?-treated multiple sclerosis patients may be mediated by monocyte-derived interleukin-10.

  5. Myelin-specific T cells induce interleukin-1beta expression in lesion-reactive microglial-like cells in zones of axonal degeneration

    DEFF Research Database (Denmark)

    Grebing, Manuela; Nielsen, Helle H

    2015-01-01

    Infiltration of myelin-specific T cells into the central nervous system induces the expression of proinflammatory cytokines in patients with multiple sclerosis (MS). We have previously shown that myelin-specific T cells are recruited into zones of axonal degeneration, where they stimulate lesion-reactive microglia. To gain mechanistic insight, we used RNA microarray analysis to compare the transcript profile in hippocampi from perforant pathway axonal-lesioned mice with and without adoptively transferred myelin-specific T cells 2 days postlesion, when microglia are clearly lesion reactive. Pathway analysis revealed that, among the 1,447 differently expressed transcripts, the interleukin (IL)-1 pathway including all IL-1 receptor ligands was upregulated in the presence of myelin-specific T cells. Quantitative polymerase chain reaction showed increased mRNA levels of IL-1?, IL-1?, and IL-1 receptor antagonist in the T-cell-infiltrated hippocampi from axonal-lesioned mice. In situ hybridization and immunohistochemistry showed a T-cell-enhanced lesion-specific expression of IL-1? mRNA and protein, respectively, and induction of the apoptosis-associated speck-like protein, ASC, in CD11b(+) cells. Double in situ hybridization showed colocalization of IL-1? mRNA in a subset of CD11b mRNA(+) cells, of which many were part of cellular doublets or clusters, characteristic of proliferating, lesion-reactive microglia. Double-immunofluorescence showed a T-cell-enhanced colocalization of IL-1? to CD11b(+) cells, including lesion-reactive CD11b(+) ramified microglia. These results suggest that myelin-specific T cells stimulate lesion-reactive microglial-like cells to produce IL-1?. These findings are relevant to understand the consequences of T-cell infiltration in white and gray matter lesions in patients with MS. GLIA 2015.

  6. Solar Water Splitting Using Semiconductor Photocatalyst Powders.

    Science.gov (United States)

    Takanabe, Kazuhiro

    2016-01-01

    Solar energy conversion is essential to address the gap between energy production and increasing demand. Large scale energy generation from solar energy can only be achieved through equally large scale collection of the solar spectrum. Overall water splitting using heterogeneous photocatalysts with a single semiconductor enables the direct generation of H2 from photoreactors and is one of the most economical technologies for large-scale production of solar fuels. Efficient photocatalyst materials are essential to make this process feasible for future technologies. To achieve efficient photocatalysis for overall water splitting, all of the parameters involved at different time scales should be improved because the overall efficiency is obtained by the multiplication of all these fundamental efficiencies. Accumulation of knowledge ranging from solid-state physics to electrochemistry and a multidisciplinary approach to conduct various measurements are inevitable to be able to understand photocatalysis fully and to improve its efficiency. PMID:26134367

  7. Splitting Technique Initialization in Local PCA

    Directory of Open Access Journals (Sweden)

    Alok Sharma

    2006-01-01

    Full Text Available The local Principal Component Analysis (PCA reduces linearly redundant components that may present in higher dimensional space. It deploys an initial guess technique which can be utilized when the distribution of a given multivariate data is known to the user. The problem in initialization arises when the distribution is not known. This study explores a technique that can be easily integrated in the local PCA design and is efficient even when the given statistical distribution is unknown. The initialization using this proposed splitting technique not only splits and reproduces the mean vector but also the orientation of components in the subspace domain. This would ensure that all clusters are used in the design. The proposed integration with the reconstruction distance local PCA design enables easier data processing and more accurate representation of multivariate data. A comparative approach is undertaken to demonstrate the greater effectiveness of the proposed approach in terms of percentage error.

  8. Strong contribution to octet baryon mass splittings

    International Nuclear Information System (INIS)

    We calculate the md?mu contribution to the mass splittings in baryonic isospin multiplets using SU(3) chiral perturbation theory and lattice QCD. Fitting isospin-averaged perturbation theory functions to PACS-CS and QCDSF-UKQCD Collaboration lattice simulations of octet baryon masses, and using the physical light-quark mass ratio mu/md as input, allows Mn?Mp, M???M?+ and M???M?0 to be evaluated from the full SU(3) theory. The resulting values for each mass splitting are consistent with the experimental values after allowing for electromagnetic corrections. In the case of the nucleon, we find Mn?Mp=2.9±0.4 MeV, with the dominant uncertainty arising from the error in mu/md.

  9. Transport properties of isospin effective mass splitting

    CERN Document Server

    Rizzo, J; Di Toro, M; Greco, V

    2004-01-01

    We investigate in detail the momentum dependence ($MD$) of the effective in medium Nucleon-Nucleon ($NN$) interaction in the isovector channel. We focus the discussion on transport properties of the expected neutron-proton ($n/p$) effective mass splitting at high isospin density. We look at observable effects from collective flows in Heavy Ion Collisions ($HIC$) of charge asymmetric nuclei at intermediate energies. Using microscopic kinetic equation simulations nucleon transverse and elliptic collective flows in $Au+Au$ collisions are evaluated. In spite of the reduced charge asymmetry of the interacting system interesting $isospin-MD$ effects are revealed. Good observables, particularly sensitive to the $n/p$-mass splitting, appear to be the differences between neutron and proton flows. The importance of more exclusive measurements, with a selection of different bins of the transverse momenta ($p_t$) of the emitted particles, is stressed. In more inclusive data a compensation can be expected from different $...

  10. Isospin breaking in octet baryon mass splittings

    International Nuclear Information System (INIS)

    Using an SU(3) flavour symmetry breaking expansion in the quark mass, we determine the QCD component of the nucleon, Sigma and Xi mass splittings of the baryon octet due to up-down (and strange) quark mass differences in terms of the kaon mass splitting. Provided the average quark mass is kept constant, the expansion coefficients in our procedure can be determined from computationally cheaper simulations with mass degenerate sea quarks and partially quenched valence quarks. Both the linear and quadratic terms in the SU(3) flavour symmetry breaking expansion are considered; it is found that the quadratic terms only change the result by a few percent, indicating that the expansion is highly convergent.

  11. Meshed split skin graft for extensive vitiligo

    Directory of Open Access Journals (Sweden)

    Srinivas C

    2004-05-01

    Full Text Available A 30 year old female presented with generalized stable vitiligo involving large areas of the body. Since large areas were to be treated it was decided to do meshed split skin graft. A phototoxic blister over recipient site was induced by applying 8 MOP solution followed by exposure to UVA. The split skin graft was harvested from donor area by Padgett dermatome which was meshed by an ampligreffe to increase the size of the graft by 4 times. Significant pigmentation of the depigmented skin was seen after 5 months. This procedure helps to cover large recipient areas, when pigmented donor skin is limited with minimal risk of scarring. Phototoxic blister enables easy separation of epidermis thus saving time required for dermabrasion from recipient site.

  12. Groundstate splitting around rotating mini Blackholes

    OpenAIRE

    Sturm, I.; Witte, F. M. C.

    2007-01-01

    In this letter we present the result of a spin-dependent groundstate-energy calculation for fermionic boundstates in the spacetime around a rotating blackhole. Using a slow rotation approximation and a minimax variational approach we find boundstate energies of 0 to 5 percent of the fermions flatspace restmass. The groundstate displays a spin-dependent splitting with an energy difference of about 10 percent of the binding energy. For a dilute gas of primordial mini blackhole...

  13. Large Bandgap Semiconductors for Solar Water Splitting

    DEFF Research Database (Denmark)

    Malizia, Mauro

    2014-01-01

    Photoelectrochemical water splitting represents an eco-friendly technology that could enable the production of hydrogen using water as reactant and solar energy as primary energy source. The exploitation of solar energy for the production of hydrogen would help modern society to reduce the reliance on fossil fuels as primary feedstock for hydrogen production and diminish the emission of greenhouse gases in the atmosphere, weakening the global warming phenomenon.The dissertation reports the devel...

  14. Design of a Cocoa Pod Splitting Machine

    OpenAIRE

    I.A. Adetunde; S.K. Adzimah and E.K. Asiam

    2010-01-01

    This study outlines the design of a very efficient, highly productive, cost- effective, ergonomic and environmentally friendly cocoa splitting machine that will be used by cocoa Farmers world - wide to increase and boost productivity and enhance the quality of coca products to the highest possible level devoid of any hazards, dangers or perils. This machine can be manufactured from locally available scraps and assembled and maintained at a relatively low cost. The knives which do the splittin...

  15. Phase splitting for periodic Lie systems

    Energy Technology Data Exchange (ETDEWEB)

    Flores-Espinoza, R; Vorobiev, Yu M [Departamento de Matematicas, Universidad de Sonora (Mexico); De Lucas, J, E-mail: rflorese@gauss.mat.uson.m, E-mail: delucas@impan.gov.p, E-mail: yurimv@guaymas.uson.m [Departamento de Fisica Teorica, Universidad de Zaragoza (Spain)

    2010-05-21

    In the context of the Floquet theory, using a variation of parameter argument, we show that the logarithm of the monodromy of a real periodic Lie system with appropriate properties admits a splitting into two parts called dynamic and geometric phases. The dynamic phase is intrinsic and linked to the Hamiltonian of a periodic linear Euler system on the co-algebra. The geometric phase is represented as a surface integral of the symplectic form of a co-adjoint orbit.

  16. Height in Splittings of Hyperbolic Groups

    Indian Academy of Sciences (India)

    Mahan Mitra

    2004-02-01

    Suppose is a hyperbolic subgroup of a hyperbolic group . Assume there exists $n>0$ such that the intersection of essentially distinct conjugates of is always finite. Further assume splits over with hyperbolic vertex and edge groups and the two inclusions of are quasi-isometric embeddings. Then is quasiconvex in . This answers a question of Swarup and provides a partial converse to the main theorem of [23].

  17. Splitting trees with neutral mutations at birth

    OpenAIRE

    Richard, Mathieu

    2014-01-01

    We consider a population model where individuals behave independently from each other and whose genealogy is described by a chronological tree called splitting tree. The individuals have i.i.d. (non-exponential) lifetime durations and give birth at constant rate to clonal or mutant children in an infinitely many alleles model with neutral mutations. First, to study the allelic partition of the population, we are interested in its frequency spectrum, which, at a fixed time, d...

  18. Phenomenology of Dirac Neutrinogenesis in Split Supersymmetry

    OpenAIRE

    Thomas, Brooks; Toharia, Manuel

    2005-01-01

    In Split Supersymmetry scenarios the possibility of having a very heavy gravitino opens the door to alleviate or completely solve the worrisome "gravitino problem'' in the context of supersymmetric baryogenesis models. Here we assume that the gravitino may indeed be heavy and that Majorana masses for neutrinos are forbidden as well as direct Higgs Yukawa couplings between left and right handed neutrinos. We investigate the viability of the mechansim known as Dirac leptogenes...

  19. The Penrose Transform in the Split Signature

    OpenAIRE

    Aryapoor, Masood

    2008-01-01

    A version of the Penrose transform is introduced in the split signature. It relates the cohomological data with supports on the open subsets of the complex 3-projective space and kernel of differential operators on the (real) Grassmannian of 2-planes in the Euclidean 4-space. As an example we derive a cohomological interpretation of the so-called X-ray transform. Furthermore, a cohomological realization of the so-called "minimal" representation of SL(4,R) is given. We also p...

  20. Atom beams split by gentle persuasion

    International Nuclear Information System (INIS)

    Two different research teams have taken a big step toward atom interferometry. They have succeeded in splitting atomic beams by using atoms in spin states that neither absorb nor reemit laser light. By proper adjustment of experimental conditions, atoms are changed from one spin state to another, without passing through the intermediary excited state. The atoms in essence absorb momentum from the laser photons, without absorption or emission of photons. The change in momentum deflects atoms in the proper spin state

  1. Nanostructured hematite for photoelectrochemical water splitting

    Science.gov (United States)

    Ling, Yichuan

    Solar water splitting is an environmentally friendly reaction of producing hydrogen gas. Since Honda and Fujishima first demonstrated solar water splitting in 1972 by using semiconductor titanium dioxide (TiO2) as photoanode in a photoelectrochemical (PEC) cell, extensive efforts have been invested into improving the solar-to-hydrogen (STH) conversion efficiency and lower the production cost of photoelectrochemical devices. In the last few years, hematite (alpha-Fe2O3) nanostructures have been extensively studied as photoanodes for PEC water splitting. Although nanostructured hematite can improve its photoelectrochemical water splitting performance to some extent, by increasing active sites for water oxidation and shortening photogenerated hole path length to semiconductor/electrolyte interface, the photoactivity of pristine hematite nanostructures is still limited by a number of factors, such as poor electrical conductivities and slow oxygen evolution reaction kinetics. Previous studies have shown that tin (Sn) as an n-type dopant can substantially enhance the photoactivity of hematite photoanodes by modifying their optical and electrical properties. In this thesis, I will first demonstrate an unintentional Sn-doping method via high temperature annealing of hematite nanowires grown on fluorine-doped tin oxide (FTO) substrate to enhance the donor density. In addition to introducing extrinsic dopants into semiconductors, the carrier densities of hematite can also be enhanced by creating intrinsic defects. Oxygen vacancies function as shallow donors for a number of hematite. In this regard, I have investigated the influence of oxygen content on thermal decomposition of FeOOH to induce oxygen vacancies in hematite. In the end, I have studied low temperature activation of hematite nanostructures.

  2. Splitting and focusing of neutrino collective states

    OpenAIRE

    Marklund, Mattias; Shukla, Padma K.; Stenflo, Lennart

    2003-01-01

    It is shown that the collective nonlinear interactions between intense neutrino or anti-neutrino fluxes and a dense neutrino plasma are governed by a multi-dimensional coupled cubic Schr\\"odinger equation in which the interaction potential is positive or negative depending on the neutrino type. The cubic Schr\\"odinger equation describes the splitting and focusing of intense neutrino beams due to the nonlinear excitations associated with the modifications of the individual ne...

  3. Limits on split supersymmetry from gluino cosmology

    International Nuclear Information System (INIS)

    An upper limit on the masses of scalar superpartners in split supersymmetry is found by considering cosmological constraints on long-lived gluinos. Over most of parameter space, the most stringent constraint comes from big bang nucleosynthesis. A TeV-mass gluino must have a lifetime of less than 100 seconds to avoid altering the abundances of D and 6Li. This sets an upper limit on the supersymmetry breaking scale mS of 109 GeV

  4. Limits on Split Supersymmetry from Gluino Cosmology

    OpenAIRE

    Arvanitaki, A; Davis, C.; Graham, P. W.; Pierce, A.; Wacker, J G

    2005-01-01

    An upper limit on the masses of scalar superpartners in split supersymmetry is found by considering cosmological constraints on long-lived gluinos. Over most of parameter space, the most stringent constraint comes from big bang nucleosynthesis. A TeV mass gluino must have a lifetime of less than 100 seconds to avoid altering the abundances of D and Li-6. This sets an upper limit on the supersymmetry breaking scale of 10^9 GeV.

  5. Limits on split supersymmetry from gluino cosmology

    Science.gov (United States)

    Arvanitaki, Asimina; Davis, Chad; Graham, Peter W.; Pierce, Aaron; Wacker, Jay G.

    2005-10-01

    An upper limit on the masses of scalar superpartners in split supersymmetry is found by considering cosmological constraints on long-lived gluinos. Over most of parameter space, the most stringent constraint comes from big bang nucleosynthesis. A TeV-mass gluino must have a lifetime of less than 100 seconds to avoid altering the abundances of D and 6Li. This sets an upper limit on the supersymmetry breaking scale mS of 109 GeV.

  6. Limits on Split Supersymmetry from Gluino Cosmology

    Energy Technology Data Exchange (ETDEWEB)

    Arvanitaki, A.

    2005-04-25

    An upper limit on the masses of scalar superpartners in split supersymmetry is found by considering cosmological constraints on long-lived gluinos. Over most of parameter space, the most stringent constraint comes from big bang nucleosynthesis. A TeV mass gluino must have a lifetime of less than 100 seconds to avoid altering the abundances of D and Li-6. This sets an upper limit on the supersymmetry breaking scale of 10{sup 9} GeV.

  7. Multiplet mass splitting in a gravitational field

    International Nuclear Information System (INIS)

    An expression for the mass splitting of particles belonging to the same spin multiplet defined in a space-time of general relativity is derived. The geometrical symmetry is a subgroup of SO(r,s), 9 >=r > 3, 5 >=s >=1, the mass operator being proportional to the second order Casimir operator of that subgroup. A brief analysis of the calculated values as compared to the experimental data is included. (Author)

  8. Almost split sequences for Knorr lattices

    OpenAIRE

    Poulton, Andrew

    2013-01-01

    Let $O$ be a complete d.v.r. and $G$ a finite group. We give two applications of an adjunction in the stable category of $OG$. The first application gives necessary and sufficient conditions for the middle term of an almost split sequence terminating in a Knorr lattice to be indecomposable. The second characterises the stable endomorphism rings of Heller lattices of kG-modules.

  9. A thermodynamically compatible splitting procedure in hyperelasticity

    Energy Technology Data Exchange (ETDEWEB)

    Favrie, N., E-mail: nicolas.favrie@univ-amu.fr; Gavrilyuk, S., E-mail: sergey.gavrilyuk@univ-amu.fr; Ndanou, S., E-mail: serge.ndanou@univ-amu.fr

    2014-08-01

    A material is hyperelastic if the stress tensor is obtained by variation of the stored energy function. The corresponding 3D mathematical model of hyperelasticity written in the Eulerian coordinates represents a system of 14 conservative partial differential equations submitted to stationary differential constraints. A classical approach for numerical solving of such a 3D system is a geometrical splitting: the 3D system is split into three 1D systems along each spatial direction and solved then by using a Godunov type scheme. Each 1D system has 7 independent eigenfields corresponding to contact discontinuity, longitudinal waves and shear waves. The construction of the corresponding Riemann solvers is not an easy task even in the case of isotropic solids. Indeed, for a given specific energy it is extremely difficult, if not impossible, to check its rank-one convexity which is a necessary and sufficient condition for hyperbolicity of the governing equations. In this paper, we consider a particular case where the specific energy is a sum of two terms. The first term is the hydrodynamic energy depending only on the density and the entropy, and the second term is the shear energy which is unaffected by the volume change. In this case a very simple criterion of hyperbolicity can be formulated. We propose then a new splitting procedure which allows us to find a numerical solution of each 1D system by solving successively three 1D sub-systems. Each sub-system is hyperbolic, if the full system is hyperbolic. Moreover, each sub-system has only three waves instead of seven, and the velocities of these waves are given in explicit form. The last property allows us to construct reliable Riemann solvers. Numerical 1D tests confirm the advantage of the new approach. A multi-dimensional extension of the splitting procedure is also proposed.

  10. A Frequency Splitting Method For CFM Imaging

    DEFF Research Database (Denmark)

    Udesen, Jesper; Gran, Fredrik; Jensen, Jørgen Arendt

    2006-01-01

    The performance of conventional CFM imaging will often be degraded due to the relatively low number of pulses (4-10) used for each velocity estimate. To circumvent this problem we propose a new method using frequency splitting (FS). The FS method uses broad band chirps as excitation pulses instead of narrow band pulses as in conventional CFM imaging. By appropriate filtration, the returned signals are divided into a number of narrow band signals which are approximately disjoint. After clutter fi...

  11. Circular Permutation Prediction Reveals a Viable Backbone Disconnection for Split Proteins: An Approach in Identifying a New Functional Split Intein

    OpenAIRE

    Lee, Yun-Tzai; Su, Tz-Hsiang; Lo, Wei-Cheng; Lyu, Ping-Chiang; Sue, Shih-Che

    2012-01-01

    Split-protein systems have emerged as a powerful tool for detecting biomolecular interactions and reporting biological reactions. However, reliable methods for identifying viable split sites are still unavailable. In this study, we demonstrated the feasibility that valid circular permutation (CP) sites in proteins have the potential to act as split sites and that CP prediction can be used to search for internal permissive sites for creating new split proteins. Using a protein ligase, intein, ...

  12. P-wave Cooper pair splitting

    Directory of Open Access Journals (Sweden)

    Henning Soller

    2012-07-01

    Full Text Available Background: Splitting of Cooper pairs has recently been realized experimentally for s-wave Cooper pairs. A split Cooper pair represents an entangled two-electron pair state, which has possible application in on-chip quantum computation. Likewise the spin-activity of interfaces in nanoscale tunnel junctions has been investigated theoretically and experimentally in recent years. However, the possible implications of spin-active interfaces in Cooper pair splitters so far have not been investigated.Results: We analyze the current and the cross correlation of currents in a superconductor–ferromagnet beam splitter, including spin-active scattering. Using the Hamiltonian formalism, we calculate the cumulant-generating function of charge transfer. As a first step, we discuss characteristics of the conductance for crossed Andreev reflection in superconductor–ferromagnet beam splitters with s-wave and p-wave superconductors and no spin-active scattering. In a second step, we consider spin-active scattering and show how to realize p-wave splitting using only an s-wave superconductor, through the process of spin-flipped crossed Andreev reflection. We present results for the conductance and cross correlations.Conclusion: Spin-activity of interfaces in Cooper pair splitters allows for new features in ordinary s-wave Cooper pair splitters, that can otherwise only be realized by using p-wave superconductors. In particular, it provides access to Bell states that are different from the typical spin singlet state.

  13. Consimilarity of Split Quaternion Matrices and a Solution of the Split Quaternion Matrix Equation X-AX_B=C

    OpenAIRE

    Kosal, Hidayet Huda; Akyigit, Mahmut; Tosun, Murat

    2014-01-01

    In this paper, the consimilarity of complex matrices is generalized for the split quaternions. In this regard, coneigenvalue and coneigenvector are de?ned for split quaternion matrices. Also, the existence of solution to the split quaternion matrix equation X-AXB = C is characterized and the solution of the equation in the explicit form are derived via its real representation.

  14. Premyelin synthesis and myelination of the brain in mice after fractionated X-ray treatment in the prenatal state

    International Nuclear Information System (INIS)

    Daily fractionated X-irradiations, during embryonic development induce compensating proliferation reactions during cerebral gliosis, in the course of which cell formation is the more enhanced the more markedly the brains are retarded. In the pursuit of these investigations on age-specific proliferation responses the lipid synthesis during the period of premyelination gliosis was examined on the basis of uptake of tritiated mevalonic acid, tritiated glucose and 32P-sodium-phosphate by means of scintillation - spectrometric and histoautoradiographic methods. During gliosis lipid synthesis and cell formation are linked in a striking manner, independent of the period and the dose of irradiation and of the different degrees, in which mevalonic acid, glucose and phosphate are utilized. An increased accumulation of tritiated mevalonic acid and 32P-sodium-phosphate in the brain could be shown by autoradiographic examinations of frozen sections too. A rise in the activity of incorporation with an advancing degree of retardation is demonstrated especially by the percentage of deviations for the silver grains set free over the brain stem. Microphotometric measurements show that this is parallelled by percentual increase of myelin density in several median and basal regions of the fibers of the brain stem. Moreover it was possible to prove in a direct manner with Rio-Hortega preparations a heightened density of packing of the oligodendrocytes responsible for myelination of the brain. It is inferred from the remarkable coincidence of radiation-induced deviations in the density of oligodendrocytes as well as in the DNA and lipid synthesis that lipogenesis during premyelination is not stimulated directly but in an indirect way through cell-specific proliferation reactions. In the strongly retarded brains probably uncoordinated surplus reactions occur. (orig./MG) 891 MG/orig.- 892 MKO

  15. The second order pole over split quaternions

    Science.gov (United States)

    Libine, Matvei

    2015-04-01

    This is an addition to a series of papers [1, 2, 3, 4], where we develop quaternionic analysis from the point of view of representation theory of the conformal Lie group and its Lie algebra. In this paper we develop split quaternionic analogues of certain results from [4]. Thus we introduce a space of functions Dh ? Da with a natural action of the Lie algebra gl(2, HC) ? sl(4, C), decompose Dh ? Da into irreducible components and find the gl(2, Hc)- equivariant projectors onto each of these irreducible components.

  16. Multiparty hierarchical quantum-information splitting

    Energy Technology Data Exchange (ETDEWEB)

    Wang Xinwen; Zhang Dengyu; Tang Shiqing; Xie Lijun, E-mail: xwwang0826@yahoo.com.cn [Department of Physics and Electronic Information Science, Hengyang Normal University, Hengyang 421008 (China)

    2011-02-14

    We propose a scheme for multiparty hierarchical quantum-information splitting (QIS) with a multipartite entangled state, where a boss distributes a secret quantum state to two grades of agents asymmetrically. The agents who belong to different grades have different authorities for recovering the boss's secret. Except for the boss's Bell-state measurement, no nonlocal operation is involved. The presented scheme is also shown to be secure against eavesdropping. Such a hierarchical QIS is expected to find useful applications in the field of modern multipartite quantum cryptography.

  17. Hyperfine splitting in hydrogen with form factors

    CERN Document Server

    Daza, F Garcia; Nowakowski, M

    2010-01-01

    Proton structure corrections to the hyperfine splittings in hydrogen are evaluated using the Breit potential with electromagnetic form factors. In contrast to other methods, several new features emerge: the Breit potential with $q^2$-dependent form factors is just an extension of the standard Breit equation which gives the hyperfine Hamiltonian. Order $\\alpha^5$ corrections are obtained from a one-photon exchange amplitude and time-independent perturbation theory. Structure corrections to $D_{21} = 8 E^{2S}_{hfs} - E^{1S}_{hfs}$ start at order $\\alpha^6$. QED corrections are comparable to structure corrections which must be evaluated ab initio.

  18. Computational model of photocatalytic water splitting.

    Science.gov (United States)

    Sobolewski, Andrzej L; Domcke, Wolfgang

    2008-08-14

    The photochemistry of a supramolecular system consisting of a (truncated) chlorophyll, benzoquinone and water has been explored with ab initio computational methods. It is shown that this photosynthetic model system can split a water molecule upon the absorption of a visible photon via an electron-driven proton-transfer process. It is suggested that the coupled transfer of an electron and a proton in hydrogen-bonded systems is mechanistically superior to electronic charge separation in covalently bonded donor-bridge-acceptor systems. PMID:18642889

  19. Basic dynamics of split Stirling refrigerators

    Science.gov (United States)

    de Waele, A. T. A. M.; Liang, W.

    2008-09-01

    The basic features of the split Stirling refrigerator, driven by a linear compressor, are described. Friction of the compressor piston and of the regenerator, and the viscous losses due to the gas flow through the regenerator matrix are taken into account. The temperature at the cold end is an input parameter. The general equations are derived which are subsequently treated in the harmonic approximation. Examples are given of application of the relations for describing optimum-performance conditions as well as the interrelationship between cooler and heat-engine operation.

  20. Comparing Electrochemical and Biological Water Splitting

    DEFF Research Database (Denmark)

    Rossmeisl, Jan; Dimitrievski, Kristian

    2007-01-01

    On the basis of density functional theory calculations, we compare the free energies of key intermediates in the water splitting reaction over transition metal oxide surfaces to those of the Mn cluster in photo system II. In spite of the very different environments in the enzyme system and on the inorganic catalyst surface of an acidic electrolysis cell, the thermochemical features of the catalysts can be directly compared. We suggest a simple test for a thermochemically optimal catalyst. We show that, although both the RuO2 surface and the Mn cluster in photo system II are quite close to optimal, the biological catalyst appears to be best.

  1. Photoelectrochemical water splitting materials, processes and architectures

    CERN Document Server

    Lewerenz, Hans-Joachim

    2013-01-01

    There has been a resurgence of interest in light-induced water splitting as the search for storable carbon neutral energy becomes more urgent. Although the history of the basic idea dates back more than four decades, efficient, economical and stable integrated devices have yet to be realized. In the continuing quest for such devices, the field of photoelectrochemistry is entering a new phase where the extraordinary interdisciplinary of the research and development efforts are opening new avenues. This aspect of current research effort is reflected in the chapters of this book, which encompass

  2. Miniaturized Planar Split-Ring Resonator Antenna

    DEFF Research Database (Denmark)

    Kim, Oleksiy S.; Breinbjerg, Olav

    2009-01-01

    A miniaturized planar antenna based on a broadside-coupled split ring resonator excited by an arc-shaped dipole is presented. The excitation dipole acts as a small tuning capacitor in series with a parallel RLC circuit represented by the SRR. The antenna resonance frequency and dimensions a essentially determined by the SRR, while by varying the dipole arm length the input resistance is changed in a wide range, thus matching the antenna to a feed line and compensating for simulation and manufact...

  3. Strong CP, Flavor, and Twisted Split Fermions

    Energy Technology Data Exchange (ETDEWEB)

    Harnik, Roni; Perez, Gilad; Schwartz, Matthew D.; Shirman, Yuri

    2004-11-10

    We present a natural solution to the strong CP problem in the context of split fermions. By assuming CP is spontaneously broken in the bulk, a weak CKM phase is created in the standard model due to a twisting in flavor space of the bulk fermion wavefunctions. But the strong CP phase remains zero, being essentially protected by parity in the bulk and CP on the branes. As always in models of spontaneous CP breaking, radiative corrections to theta bar from the standard model are tiny, but even higher dimension operators are not that dangerous. The twisting phenomenon was recently shown to be generic, and not to interfere with the way that split fermions naturally weaves small numbers into the standard model. It follows that out approach to strong CP is compatible with flavor, and we sketch a comprehensive model. We also look at deconstructed version of this setup which provides a viable 4D model of spontaneous CP breaking which is not in the Nelson-Barr class.

  4. Colorimetry and TV Colour Splitting Systems

    Directory of Open Access Journals (Sweden)

    J. Kaiser

    2001-01-01

    Full Text Available The colorimetric standard of the present-day television system goes back to the American NTSC system from 1953. In this RGB colorimetric system it is not possible, for basic reasons, to produce a scanning device which will provide signals suitable for controlling any displayed unit. From the very beginning of the television system the scanning device has produced inevitable colour deformation. The range of reproductive colours is not fully utilized either by a contemporary Cathode Ray Tube display unit or by a Liquid Crystal Display. In addition, the range is not sufficient for true reproduction of colours. Specific technical and scientific applications in which colour bears a substantial part of the information (cosmic development, medicine demand high fidelity colour reproduction. The colour splitting system, working in the RGB colorimetric system, continues to be universally used. This article submits the results of a design for a colour splitting system working in the XYZ colorimetric system (hereafter referred to as the XYZ prism. A way to obtain theoretical spectral reflectances of partial XYZ prism filters is briefly described. These filters are then approximated by real optical interference filters and the geometry of the XYZ prism is established.

  5. Transport properties of isospin effective mass splitting

    International Nuclear Information System (INIS)

    We investigate in detail the momentum dependence (MD) of the effective in medium nucleon-nucleon (NN) interaction in the isovector channel. We focus the discussion on transport properties of the expected neutron-proton (n/p) effective mass splitting at high isospin density. We look at observable effects from collective flows in heavy ion collisions (HIC) of charge asymmetric nuclei at intermediate energies. Using microscopic kinetic equation simulations nucleon transverse and elliptic collective flows in Au+Au collisions are evaluated. In spite of the reduced charge asymmetry of the interacting system interesting isospin-MD effects are revealed. Good observables, particularly sensitive to the n/p mass splitting, appear to be the differences between neutron and proton flows. The importance of more exclusive measurements, with a selection of different bins of the transverse momenta (pt) of the emitted particles, is stressed. In more inclusive data a compensation can be expected from different pt-contributions, due to the microscopic isospin-MD structure of the nuclear mean field in asymmetric matter

  6. Micro-Miniature Split Stirling Linear Crycooler

    Science.gov (United States)

    Veprik, A.; Zehtzer, S.; Vilenchik, H.; Pundak, N.

    2010-04-01

    Novel tactics for rescue, surveillance, reconnaissance, force protection, perimeter security, navigation and targeting often involve the use of miniature infrared imagers, where the cooled imaging systems are known to be superior to their uncooled rivals in terms of working range, resolution and ability to distinguish/track fast moving objects in dynamic infrared scenes. The latest technological advances in industrial applications of high-temperature infrared detectors have spurred the development of linearly driven, long life, dynamically quiet and aurally undetectable micro-miniature split Stirling linear cryogenic coolers. Recent progress in designing highly efficient "moving magnet" resonant linear actuators and dedicated smart electronics have enabled further improvements to the cooler's size, weight, power consumption, cooldown time and ownership costs. The authors report on the development of a novel micro-miniature split Stirling linear cryogenic cooler, where, by means of increasing the driving frequency up to 90 Hz, it appeared possible to shorten the cold finger to 19 mm. The cooler was specifically designed to cool a new generation of 130 K infrared detectors for portable infrared imagers, where compactness, low steady-state power consumption, fast cool-down time, vibration export and aural stealth are of primary concern.

  7. Artificial photosynthesis: understanding water splitting in nature.

    Science.gov (United States)

    Cox, Nicholas; Pantazis, Dimitrios A; Neese, Frank; Lubitz, Wolfgang

    2015-06-01

    In the context of a global artificial photosynthesis (GAP) project, we review our current work on nature's water splitting catalyst. In a recent report (Cox et al. 2014 Science 345, 804-808 (doi:10.1126/science.1254910)), we showed that the catalyst-a Mn4O5Ca cofactor-converts into an 'activated' form immediately prior to the O-O bond formation step. This activated state, which represents an all Mn(IV) complex, is similar to the structure observed by X-ray crystallography but requires the coordination of an additional water molecule. Such a structure locates two oxygens, both derived from water, in close proximity, which probably come together to form the product O2 molecule. We speculate that formation of the activated catalyst state requires inherent structural flexibility. These features represent new design criteria for the development of biomimetic and bioinspired model systems for water splitting catalysts using first-row transition metals with the aim of delivering globally deployable artificial photosynthesis technologies. PMID:26052426

  8. Severe demyelinating hypertrophic polyneuropathy caused by a de novo frameshift mutation within the intracellular domain of myelin protein zero (MPZ/P0).

    Science.gov (United States)

    Zschüntzsch, Jana; Dibaj, Payam; Pilgram, Sara; Kötting, Judith; Gerding, Wanda M; Neusch, C

    2009-06-15

    Hereditary motor and sensory neuropathy (HMSN), also known as Charcot-Marie-Tooth disease (CMT) is a group of clinically and genetically heterogeneous neuropathies classically divided into demyelinating (CMT1) and axonal forms (CMT2). The most common demyelinating form is CMT1A with an underlying duplication in the gene coding for the peripheral myelin protein 22 (PMP22). Less frequently, mutations in the myelin protein zero gene (MPZ/P(0)) account for demyelinating CMT1B, Dejerine-Sottas syndrome (DSS), or congenital hypomyelinating neuropathy (CHN). Here, we report a patient with a severe, early-onset hypertrophic and dysmyelinating neuropathy. The patient exhibits a novel frameshift mutation with an insertion of a single T-nucleotide on position c.618_619 of the MPZ gene resulting in a premature stop M207fsX38. PMID:19344920

  9. Quantitative analysis on electric dipole energy in Rashba band splitting

    Science.gov (United States)

    Hong, Jisook; Rhim, Jun-Won; Kim, Changyoung; Ryong Park, Seung; Hoon Shim, Ji

    2015-09-01

    We report on quantitative comparison between the electric dipole energy and the Rashba band splitting in model systems of Bi and Sb triangular monolayers under a perpendicular electric field. We used both first-principles and tight binding calculations on p-orbitals with spin-orbit coupling. First-principles calculation shows Rashba band splitting in both systems. It also shows asymmetric charge distributions in the Rashba split bands which are induced by the orbital angular momentum. We calculated the electric dipole energies from coupling of the asymmetric charge distribution and external electric field, and compared it to the Rashba splitting. Remarkably, the total split energy is found to come mostly from the difference in the electric dipole energy for both Bi and Sb systems. A perturbative approach for long wave length limit starting from tight binding calculation also supports that the Rashba band splitting originates mostly from the electric dipole energy difference in the strong atomic spin-orbit coupling regime.

  10. Prolonged high frequency electrical stimulation is lethal to motor axons of mice heterozygously deficient for the myelin protein P0 gene

    DEFF Research Database (Denmark)

    Alvarez, Susana; Moldovan, Mihai; Krarup, Christian

    2013-01-01

    The relationship between dysmyelination and the progression of neuropathy in Charcot-Marie-Tooth (CMT) hereditary polyneuropathy is unclear. Mice heterozygously deficient for the myelin protein P? gene (P?+/-) are indistinguishable from wild-type (WT) at birth and then develop a slowly progressing demyelinating neuropathy reminiscent of CMT Type 1b. Accumulating evidence suggests that impulse conduction can become lethal to acutely demyelinated central and peripheral axons. Here we investigated ...

  11. Recognition of a High Affinity MHC Class I-Restricted Epitope of Myelin Oligodendrocyte Glycoprotein by CD8+ T Cells Derived from Autoantigen-Deficient Mice

    OpenAIRE

    Leech, Melanie D; Carrillo-Vico, Antonio; Liblau, Roland S.; Anderton, Stephen M.

    2011-01-01

    CD4+ T cells have a well-defined pathogenic role in experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS), yet CD8+ T cells are commonly found in MS lesions. To determine whether immunological tolerance might impact differently on CD4+ versus CD8+ T cells, we studied T cell responses in mice genetically deficient for the central nervous system (CNS) autoantigen myelin oligodendrocyte glycoprotein (MOG) versus wild type (WT) C57BL/6 mice. We show that MOG?/? mi...

  12. Effects of endurance exercise on expressions of glial fibrillary acidic protein and myelin basic protein in developing rats with maternal infection-induced cerebral palsy

    OpenAIRE

    Kim, Kijeong; Shin, Mal-Soon; Cho, Han-Sam; Kim, Young-Pyo

    2014-01-01

    Periventricular leukomalacia (PVL) is a common white matter lesion affecting the neonatal brain. PVL is closely associated with cerebral palsy (CP) and characterized by increase in the number of astrocytes, which can be detected by positivity for glial fibrillary acidic protein (GFAP). Change in myelin basic protein (MBP) is an early sign of white matter abnormality. Maternal or placental infection can damage the neonatal brain. In the present study, we investigated the effects of treadmill w...

  13. Splitting of any initial field distribution in GRIN media

    CERN Document Server

    Moya-Cessa, H M; Arrizon, V; Zúñiga-Segundo, A

    2015-01-01

    We show the splitting effect of an electromagnetic field assuming non paraxial propagation in a quadratic GRIN medium. The field distribution at the splitting distance is given by fractional Fourier transforms of the initial field and of a reflected version of it. We apply this result to an initial field given by a Bessel function and show that it splits into two generalized Bessel functions.

  14. Excitonic fine structure splitting in type-II quantum dots

    OpenAIRE

    K?ápek, Vlastimil; Klenovský, Petr; Šikola, Tomáš

    2015-01-01

    Excitonic fine structure splitting in quantum dots is closely related to the lateral shape of the wave functions. We have studied theoretically the fine structure splitting in InAs quantum dots with a type-II confinement imposed by a GaAsSb capping layer. We show that very small values of the fine structure splitting comparable with the natural linewidth of the excitonic transitions are achievable for realistic quantum dot morphologies despite the structural elongation and t...

  15. Instrument for fast and effective splitting of organizations:

    OpenAIRE

    Op 't Land, M.

    2008-01-01

    Organizations increasingly split off parts and start cooperating with those parts, for instance in Shared Service Centers or by using in- or outsourcing. However, what is the right spot and way for finding the organization split? Martin Op 't Land (Capgemini) offers a long-awaited answer to this question, based on both literature and field research. His research resulted in a practical instrument to support organization splitting, allying and post-merger integration - an instrument that i...

  16. One-loop triple collinear splitting amplitudes in QCD

    CERN Document Server

    Badger, Simon; Peraro, Tiziano

    2015-01-01

    We study the factorisation properties of one-loop scattering amplitudes in the triple collinear limit and extract the universal splitting amplitudes for processes initiated by a gluon. The splitting amplitudes are derived from the analytic Higgs plus four partons amplitudes. We present compact results for primitive helicity splitting amplitudes making use of super-symmetric decompositions. The universality of the collinear factorisation is checked numerically against the full colour six parton squared matrix elements.

  17. A Splitting Algorithm for Directional Regularization and Sparsification

    DEFF Research Database (Denmark)

    Rakêt, Lars Lau; Nielsen, Mads

    2012-01-01

    We present a new split-type algorithm for the minimization of a p-harmonic energy with added data fidelity term. The half-quadratic splitting reduces the original problem to two straightforward problems, that can be minimized efficiently. The minimizers to the two sub-problems can typically be computed pointwise and are easily implemented on massively parallel processors. Furthermore the splitting method allows for the computation of solutions to a large number of more advanced directional regul...

  18. Systematic investigation of THz-induced excitonic Rabi splitting

    OpenAIRE

    Teich, M.; Wagner, M.; Stehr, D.; Schneider, H; Van der Helm, M.; Khitrova, G.; Gibbs, H. M.; Klettke, A. C.; Chatterjee, S.; Kira, M.; Koch, S. W.

    2013-01-01

    Weak near-infrared and strong terahertz excitation are applied to study excitonic Rabi splitting in (GaIn)As/GaAs quantum wells. Pronounced anticrossing behavior of the split peaks is observed for different terahertz intensities and detunings relative to the intraexcitonic heavy-hole 1s-2p-transition. At intermediate to high electric fields the splitting becomes highly asymmetric and exhibits significant broadening. A fully microscopic theory is needed to explain the experim...

  19. Resonant peak splitting for ballistic conductance in magnetic superlattices

    OpenAIRE

    Z. Y. Zeng; L. D. Zhang; Yan, X. H.; You, J. Q.

    2001-01-01

    We investigate theoretically the resonant splitting of ballistic conductance peaks in magnetic superlattices. It is found that, for magnetic superlattices with periodically arranged $n$ identical magnetic-barriers, there exists a general $(n-1)$-fold resonant peak splitting rule for ballistic conductance, which is the analogy of the $(n-1)$-fold resonant splitting for transmission in $n$-barrier electric superlattices (R. Tsu and L. Esaki, Appl. Phys. Lett. {\\bf 22}, 562 (19...

  20. Split Architecture for Large Scale Wide Area Networks

    OpenAIRE

    John, Wolfgang; Devlic, Alisa; Ding, Zhemin; Jocha, David; Kern, Andras; Kind, Mario; Köpsel, Andreas; Nordell, Viktor; Sharma, Sachin; Sköldström, Pontus; Staessens, Dimitri; Takacs, Attila; Topp, Steffen; Westphal, F. -Joachim; Woesner, Hagen

    2014-01-01

    This report defines a carrier-grade split architecture based on requirements identified during the SPARC project. It presents the SplitArchitecture proposal, the SPARC concept for Software Defined Networking (SDN) introduced for large-scale wide area networks such as access/aggregation networks, and evaluates technical issues against architectural trade-offs. First we present the control and management architecture of the proposed SplitArchitecture. Here, we discuss a recurs...

  1. Split Cord Malformation Type I And Lipomyelomeningocele: A Case Report

    OpenAIRE

    ?ENEL, A.; ÇOKLUK, C.; AKAN, H.; ÇEL?K, F.

    2010-01-01

    Spina bifida is a term comonly used to refer to myelomeningocele, lumbosacral lipomas, split cord malformation (diastematomyelia), meningoceles and some other neural tube defects. Split cord malformations with a fibrous, cartilaginous or bony band or spicule separating the spinal cord into hemicords, can occur as an isolated defect or either with a myelomeningocele or a lipomyelomeningocele. The occurrence of split cord malformations with lipomyelomeningocele is relatively rare...

  2. A Study of Molecular Mimicry and Immunological Cross-reactivity between Hepatitis B Surface Antigen and Myelin Mimics

    Directory of Open Access Journals (Sweden)

    Diego Vergani

    2005-01-01

    Full Text Available On the basis of the reported association between hepatitis B vaccination (HBvacc and autoimmune demyelinating complications such as multiple sclerosis (MS, we have looked for aminoacid similarities between the small hepatitis B virus surface antigen (SHBsAg, and the MS-autoantigens myelin basic protein (MBP and myelin oligodendrocyte glycoprotein (MOG that could serve as targets of immunological cross-reactivity. Twenty-mer peptides spanning 4 SHBsAg/MOG and 1 SHBsAg/MBP mimicking pairs, were constructed and tested by ELISA as targets of cross-reactive responses. A total of 147 samples from 58 adults were collected before HBvacc (58/58, and post-HBvacc (48/58 before the second and 41/58 before the third boost. Eighty-seven sera from anti-SHBsAg antibody negative patients with various diseases were tested as pathological controls. Reactivity to at least one of the SHBsAg peptides was found in 8 (14% pre-HBvacc subjects; amongst the remaining 50, reactivity to at least one of the SHBsAg peptides appeared in 47 (94% post-HBvacc. Reactivity to at least one of the MOG mimics was present in 4 (8% pre-HBvacc and in 30 (60% post-HBvacc (p < 0.001. Overall 30/50 (60% vaccinees had SHBsAg/MOG double reactivity on at least one occasion compared to none before-vaccination and in 2 (2% of the pathological controls (p < 0.001 for both. SHBsAg/MOG double reactivity was cross-reactive as confirmed by inhibition studies. At 6 months post-vaccination, 3 of the 4 anti-MOG reactive cases before vaccination and 7 of the 24 (29% of the anti-MOG reactive cases at 3 months post-vaccination had lost their reactivity to MOG5-24. There was no reactivity to the SHBsAg/MBP mimics. None of the vaccinees reported symptoms of demyelinating disorders. In view of the observed SHBsAg/MOG cross-reactivity, the vaccine's possible role as an immunomodulator of viral/self cross-reactivity must be further investigated.

  3. Quantification of [(11)C]PIB PET for imaging myelin in the human brain: a test-retest reproducibility study in high-resolution research tomography.

    Science.gov (United States)

    Veronese, Mattia; Bodini, Benedetta; García-Lorenzo, Daniel; Battaglini, Marco; Bongarzone, Salvatore; Comtat, Claude; Bottlaender, Michel; Stankoff, Bruno; Turkheimer, Federico E

    2015-11-01

    An accurate in vivo measure of myelin content is essential to deepen our insight into the mechanisms underlying demyelinating and dysmyelinating neurological disorders, and to evaluate the effects of emerging remyelinating treatments. Recently [(11)C]PIB, a positron emission tomography (PET) tracer originally conceived as a beta-amyloid marker, has been shown to be sensitive to myelin changes in preclinical models and humans. In this work, we propose a reference-region methodology for the voxelwise quantification of brain white-matter (WM) binding for [(11)C]PIB. This methodology consists of a supervised procedure for the automatic extraction of a reference region and the application of the Logan graphical method to generate distribution volume ratio (DVR) maps. This approach was assessed on a test-retest group of 10 healthy volunteers using a high-resolution PET tomograph. The [(11)C]PIB PET tracer binding was shown to be up to 23% higher in WM compared with gray matter, depending on the image reconstruction. The DVR estimates were characterized by high reliability (outliers 0.95). [(11)C]PIB parametric maps were also found to be significantly correlated (R(2)>0.50) to mRNA expressions of the most represented proteins in the myelin sheath. On the contrary, no correlation was found between [(11)C]PIB imaging and nonmyelin-associated proteins. PMID:26058700

  4. Selectively splitting a droplet using superhydrophobic stripes on hydrophilic surfaces.

    Science.gov (United States)

    Song, Dong; Song, Baowei; Hu, Haibao; Du, Xiaosong; Zhou, Feng

    2015-06-01

    Superhydrophobic patterns were fabricated on hydrophilic surfaces by selective painting. The impinging process of water droplets on these hybrid surfaces was investigated. The droplet can be split by impinging on the hydrophilic surface with a single stripe at a high velocity. The time to split the droplet is independent of the impact velocity and it is smaller than the contact time of a droplet impinging on the fully superhydrophobic surface. The volume ratios of the split mini-droplets could be precisely controlled by adjusting the landing position of the original droplet. The droplet could be split uniformly into more mini-marbles by increasing the stripe numbers. PMID:25946666

  5. Splitting Neutrino masses and Showering into Sky

    Energy Technology Data Exchange (ETDEWEB)

    Fargion, D. [Physics Department, Rome University La Sapienza, 00185, Ple.A.Moro 2, Rome (Italy); INFN, Istituto Nazionale di Fisica Nucleare (Italy); D' Armiento, D.; Lanciano, O.; Oliva, P.; Iacobelli, M.; De Sanctis Lucentini, P.G.; Grossi, M.; De Santis, M. [Physics Department, Rome University La Sapienza, 00185, Ple.A.Moro 2, Rome (Italy)

    2007-06-15

    Neutrino masses might be as light as a few time the atmospheric neutrino mass splitting. The relic cosmic neutrinos may cluster in wide Dark Hot Local Group Halo. High Energy ZeV cosmic neutrinos (in Z-Showering model) might hit relic ones at each mass in different resonance energies in our nearby Universe. This non-degenerated density and energy must split UHE Z-boson secondaries (in Z-Burst model) leading to multi injection of UHECR nucleons within future extreme AUGER energy. Secondaries of Z-Burst as neutral gamma, below a few tens EeV are better surviving local GZK cut-off and they might explain recent Hires BL-Lac UHECR correlations at small angles. A different high energy resonance must lead to Glashow's anti-neutrino showers while hitting electrons in matter. In water and ice it leads to isotropic light explosions. In air, Glashow's anti-neutrino showers lead to collimated and directional air-showers offering a new Neutrino Astronomy. Because of neutrino flavor mixing, astrophysical energetic tau neutrino above tens GeV must arise over atmospheric background. At TeV range is difficult to disentangle tau neutrinos from other atmospheric flavors. At greater energy around PeV, Tau escaping mountains and Earth and decaying in flight are effectively showering in air sky. These Horizontal showering is splitting by geomagnetic field in forked shapes. Such air-showers secondaries release amplified and beamed gamma bursts (like observed TGF), made also by muon and electron pair bundles, with their accompanying rich Cherenkov flashes. Also planet's largest (Saturn, Jupiter) atmosphere limbs offer an ideal screen for UHE GZK and Z-burst tau neutrino, because their largest sizes. Titan thick atmosphere and small radius are optimal for discovering up-going resonant Glashow resonant anti-neutrino electron showers. Detection from Earth of Tau, anti-Tau, anti-electron neutrino induced Air-showers by twin Magic Telescopes on top mountains, or space based detection on balloons and satellites arrays facing the atmosphere's limbs are the simplest and cheapest way toward UHE Neutrino Astronomy Horizons.

  6. Splitting Neutrino masses and Showering into Sky

    International Nuclear Information System (INIS)

    Neutrino masses might be as light as a few time the atmospheric neutrino mass splitting. The relic cosmic neutrinos may cluster in wide Dark Hot Local Group Halo. High Energy ZeV cosmic neutrinos (in Z-Showering model) might hit relic ones at each mass in different resonance energies in our nearby Universe. This non-degenerated density and energy must split UHE Z-boson secondaries (in Z-Burst model) leading to multi injection of UHECR nucleons within future extreme AUGER energy. Secondaries of Z-Burst as neutral gamma, below a few tens EeV are better surviving local GZK cut-off and they might explain recent Hires BL-Lac UHECR correlations at small angles. A different high energy resonance must lead to Glashow's anti-neutrino showers while hitting electrons in matter. In water and ice it leads to isotropic light explosions. In air, Glashow's anti-neutrino showers lead to collimated and directional air-showers offering a new Neutrino Astronomy. Because of neutrino flavor mixing, astrophysical energetic tau neutrino above tens GeV must arise over atmospheric background. At TeV range is difficult to disentangle tau neutrinos from other atmospheric flavors. At greater energy around PeV, Tau escaping mountains and Earth and decaying in flight are effectively showering in air sky. These Horizontal showering is splitting by geomagnetic field in forked shapes. Such air-showers secondaries release amplified and beamed gamma bursts (like observed TGF), made also by muon and electron pair bundles, with their accompanying rich Cherenkov flashes. Also planet's largest (Saturn, Jupiter) atmosphere limbs offer an ideal screen for UHE GZK and Z-burst tau neutrino, because their largest sizes. Titan thick atmosphere and small radius are optimal for discovering up-going resonant Glashow resonant anti-neutrino electron showers. Detection from Earth of Tau, anti-Tau, anti-electron neutrino induced Air-showers by twin Magic Telescopes on top mountains, or space based detection on balloons and satellites arrays facing the atmosphere's limbs are the simplest and cheapest way toward UHE Neutrino Astronomy Horizons

  7. All-electrostatic split LEBT test results

    International Nuclear Information System (INIS)

    An all-electrostatic LEBT for an RFQ has been assembled and tested with beam. The LEBT includes two quasi-einzel lenses, allowing a wider range of Twiss parameters to be accommodated, and the lenses are split into quadrants, allowing electrical steering of the beam. Moreover, mechanical steering by moving the entire LEBT with a special low-friction vacuum joint was also demonstrated. The LEBT was tested with unanalyzed protons from an RF-driven bucket source by measuring the beam directly and by measuring the transmission through a subsequent RFQ as a function of LEBT electrode parameters. Agreement between calculated LEBT beam characteristics and actual measured values is excellent. This LEBT offers fully unneutralized beam transport with steering and two-knob control of exit Twiss parameters, and can be applied to negative hydrogen as well as proton beams. (author)

  8. Graduate Program in Astrophysics in Split

    CERN Document Server

    Krajnovic, D

    2006-01-01

    Beginning in autumn 2008 the first generation of astronomy master students will start a 2 year course in Astrophysics offered by the Physics department of the University of Split, Croatia (http://fizika.pmfst.hr/astro/english/index.html). This unique master course in South-Eastern Europe, following the Bologna convention and given by astronomers from international institutions, offers a series of comprehensive lectures designed to greatly enhance students' knowledge and skills in astrophysics, and prepare them for a scientific career. An equally important aim of the course is to recognise the areas in which astronomy and astrophysics can serve as a national asset and to use them to prepare young people for real life challenges, enabling graduates to enter the modern society as a skilled and attractive work-force. In this contribution, I present an example of a successful organisation of international astrophysics studies in a developing country, which aims to become a leading graduate program in astrophysics ...

  9. Niobium-nitrides derived from nitrogen splitting.

    Science.gov (United States)

    Searles, Keith; Carroll, Patrick J; Chen, Chun-Hsing; Pink, Maren; Mindiola, Daniel J

    2015-02-28

    The easy-to-prepare Nb(V) aryloxide complex [(ArO)2Nb(?-Cl)Cl2]2 (OAr = 2,6-bis(diphenylmethyl)-4-tert-butylphenoxide) is a precursor to both Nb(IV), [trans-(ArO)2NbCl2(THF)2], and Nb(III), K3[(ArO)4Nb2(?-Cl)3Cl2], molecules. The Nb(IV) and (V) complexes readily split atmospheric nitrogen at room temperature and 1 atmosphere, under reducing conditions, to produce the low-coordinate nitride dimer [(ArO)2Nb(?-N)]2 and its radical anion, K[(ArO)2Nb(?-N)]2. PMID:25642464

  10. Large Bandgap Semiconductors for Solar Water Splitting

    DEFF Research Database (Denmark)

    Malizia, Mauro

    2014-01-01

    Photoelectrochemical water splitting represents an eco-friendly technology that could enable the production of hydrogen using water as reactant and solar energy as primary energy source. The exploitation of solar energy for the production of hydrogen would help modern society to reduce the reliance on fossil fuels as primary feedstock for hydrogen production and diminish the emission of greenhouse gases in the atmosphere, weakening the global warming phenomenon.The dissertation reports the development of GaP (gallium phosphide) photocathodes as a large bandgap semiconductor for photoelectrochemical water splitting devices having tandem design. The increase of the photovoltage produced by GaP under illumination was the main goal of this work. GaP has a bandgap of 2.25 eV and could in theory produce a photovoltage of approximately 1.7 V. Instead, the photovoltage produced by the semiconductor is limited to ? 0.35 V when utilized to produce hydrogen in acidic electrolyte with Pt catalyst. The formation of an effective p–n heterojunction between p?GaP and sputter deposited n?TiO2 or n?Nb2O5 enables the photocathode to produce a photovoltage of 0.70 V. The large built-in potential formed at the junction and the high donor density of the metal oxides determines the effectiveness of the p–n heterojunction approach. Moreover, TiO2 protects the GaP from corrosion in acidic electrolyte and enables the photocathode to perform continuous hydrogen generation for a time period of 24 hours.The photocurrent density generated by GaP was increased by more than 60% by electrochemical etching of the surface. The etching process produces a rough microstructured surface that increases the optical path length of the incident photons and the collection of photogenerated electrons.Furthermore, the synthesis of BiVO4 (bismuth vanadate) was investigated in view of combining this 2.4 eV large bandgap semiconductor with a Si back-illuminated photocathode. A device obtained by mechanical stacking of BiVO4 photoanode and standard Si photocathode performs non-assisted water splitting under illumination with Solar-to-Hydrogen efficiency lower than 0.5%. In addition, BiVO4 was synthesized on the back-side of a Si back-illuminated photocathode to produce a preliminary monolithic solar water splitting device.The Faradaic efficiency of different types of catalysts for the electrochemical production of hydrogen or oxygen was evaluated with gas chromatography analysis. The gas chromatograph interfaced with the electrochemical cell provided qualitative and quantitative measurements of the reaction products produced during the electrochemical experiments. The results show high efficiencies for Pt as hydrogen evolution catalyst and for IrOx and RuO2 as oxygen evolution catalysts in acidic electrolytes

  11. Studies of thermochemical water-splitting cycles

    Science.gov (United States)

    Remick, R. J.; Foh, S. E.

    1980-01-01

    Higher temperatures and more isothermal heat profiles of solar heat sources are developed. The metal oxide metal sulfate class of cycles were suited for solar heat sources. Electrochemical oxidation of SO2 and thermochemical reactions are presented. Electrolytic oxidation of sulfur dioxide in dilute sulfuric acid solutions were appropriate for metal oxide metal sulfate cycles. The cell voltage at workable current densities required for the oxidation of SO2 was critical to the efficient operation of any metal oxide metal sulfate cycle. A sulfur dioxide depolarized electrolysis cell for the splitting of water via optimization of the anode reaction is discussed. Sulfuric acid concentrations of 30 to 35 weight percent are preferred. Platinized platinum or smooth platinum gave the best anode kinetics at a given potential of the five materials examined.

  12. Molecular concepts of water splitting. Nature's approach

    International Nuclear Information System (INIS)

    Based on studies of natural systems, much has also been learned concerning the design principles required for biomimetic catalysis of water splitting and hydrogen evolution. In summary, these include use of abundant and inexpensive metals, the effective protection of the active sites in functional environments, repair/replacement of active components in case of damage, and the optimization of reaction rates. Biomimetic chemistry aims to mimic all these features; many labs are working toward this goal by developing new approaches in the design and synthesis of such systems, encompassing not only the catalytic center, but also smart matrices and assembly via self-organization. More stable catalysts that do not require self-repair may be obtained from fully artificial (inorganic) catalytic systems that are totally different from the biological ones and only apply some basic principles learned from nature. Metals other than Mn/Ca, Fe, and Ni could be used (e.g. Co) in new ligand spheres and other matrices. For light harvesting, charge separation/stabilization, and the effective coupling of the oxidizing/reducing equivalents to the redox catalysts, different methods have been proposed - for example, covalently linked molecular donor-acceptor systems, photo-voltaic devices, semiconductor-based systems, and photoactive metal complexes. The aim of all these approaches is to develop catalytic systems that split water with sunlight into hydrogen and oxygen while displaying high efficiency and long-term stability. Such a system - either biological, biomimetic, or bioinspired - has the potential to be used on a large scale to produce 'solar fuels' (e.g. hydrogen or secondary products thereof). (orig.)

  13. Deviant white matter structure in adults with attention-deficit/hyperactivity disorder points to aberrant myelination and affects neuropsychological performance.

    Science.gov (United States)

    Onnink, A Marten H; Zwiers, Marcel P; Hoogman, Martine; Mostert, Jeanette C; Dammers, Janneke; Kan, Cornelis C; Vasquez, Alejandro Arias; Schene, Aart H; Buitelaar, Jan; Franke, Barbara

    2015-12-01

    Attention-deficit/hyperactivity disorder (ADHD) in childhood is characterized by gray and white matter abnormalities in several brain areas. Considerably less is known about white matter microstructure in adults with ADHD and its relation with clinical symptoms and cognitive performance. In 107 adult ADHD patients and 109 gender-, age- and IQ-matched controls, we used diffusion tensor imaging (DTI) with tract-based spatial statistics (TBSS) to investigate whole-skeleton changes of fractional anisotropy (FA) and mean, axial, and radial diffusivity (MD, AD, RD). Additionally, we studied the relation of FA and MD values with symptom severity and cognitive performance on tasks measuring working memory, attention, inhibition, and delay discounting. In comparison to controls, participants with ADHD showed reduced FA in corpus callosum, bilateral corona radiata, and thalamic radiation. Higher MD and RD were found in overlapping and even more widespread areas in both hemispheres, also encompassing internal and external capsule, sagittal stratum, fornix, and superior lateral fasciculus. Values of FA and MD were not associated with symptom severity. However, within some white matter clusters that distinguished patients from controls, worse inhibition performance was associated with reduced FA and more impulsive decision making was associated with increased MD. This study shows widespread differences in white matter integrity between adults with persistent ADHD and healthy individuals. Changes in RD suggest aberrant myelination as a pathophysiological factor in persistent ADHD. The microstructural differences in adult ADHD may contribute to poor inhibition and greater impulsivity but appear to be independent of disease severity. PMID:25956761

  14. Análise quantitativa das fibras mielínicas dos nervos laríngeos em humanos de acordo com a idade Quantitative analysis of myelinic fibers in human laryngeal nerves according to age

    Directory of Open Access Journals (Sweden)

    Romualdo Suzano Louzeiro Tiago

    2008-02-01

    Full Text Available INTRODUÇÃO E OBJETIVO: Realizar análise morfométrica das fibras mielínicas dos nervos laríngeos com a finalidade de verificar modificações quantitativas decorrentes do processo de envelhecimento. FORMA DE ESTUDO: Clínico e experimental. Material e Método: Foi coletado fragmento de 1cm dos nervos laríngeos superiores e nervos laríngeos recorrentes de 12 cadáveres do sexo masculino. A amostra foi dividida em dois grupos: idade inferior a 60 anos (Adulto e idade igual ou superior a 60 anos (Idoso. O material foi avaliado em microscópio de luz acoplado a sistema analisador de imagem. RESULTADOS: O número total de fibras mielínicas do nervo laríngeo superior foi semelhante nos dois grupos etários, mas com tendência para o maior número de fibras de 1µm no grupo adulto (p=0,0744. O grupo adulto apresentou maior número total de fibras mielínicas no nervo laríngeo recorrente (p=0,0006, e esta diferença ocorreu nas fibras com diâmetros de 1-3µm (pINTRODUCTION AND AIM: To carry out a morphometric analysis of myelinic fibers in laryngeal nerves aiming to identify quantitative changes as a result of aging. Study design: Clinical and experimental. MATERIAL AND METHOD: A 1cm fragment was collected from the superior laryngeal nerves and recurrent laryngeal nerves taken from twelve male cadavers. The sample was divided into two groups: those aged below 60 years (Adult and those aged 60 years or more (Elderly. The material was evaluated under light microscopy coupled with an image analysis system. RESULTS: The total number of myelinic fibers from the superior laryngeal nerve was similar in both age groups; there was, however, a trend for a higher number of 1?m fibers in the adult group (p=0.0744. The adult group had a higher total number of myelinic fibers in the recurrent laryngeal nerve (p=0.0006, and this difference was seen in fibers with diameters betwee 1-3?m (p<0.007. The adult group had a higher total number of myelinic fibers in the laryngeal nerves (sum of superior laryngeal nerves and recurrent laryngeal nerves fibers compared to the elderly group (p<0.0091. CONCLUSION:The total number of myelinic fibers in laryngeal nerves is higher for the group aged below 60 years.

  15. Splitting of a turbulent puff in pipe flow

    Energy Technology Data Exchange (ETDEWEB)

    Shimizu, Masaki; Kawahara, Genta [Graduate School of Engineering Science, Osaka University, Toyonaka, 560-8531 (Japan); Manneville, Paul [LadHyX, CNRS-UMR 7646, Ecole Polytechnique, F-91128, Palaiseau (France); Duguet, Yohann, E-mail: shimizu@me.es.osaka-u.ac.jp [LIMSI-CNRS, UPR 3251, Université Paris-Sud, F-91403 Orsay (France)

    2014-12-01

    The transition to turbulence of the flow in a pipe of constant radius is numerically studied over a range of Reynolds numbers where turbulence begins to expand by puff splitting. We first focus on the case Re=2300 where splitting occurs as discrete events. Around this value only long-lived pseudo-equilibrium puffs can be observed in practice, as typical splitting times become very long. When Re is further increased, the flow enters a more continuous puff splitting regime where turbulence spreads faster. Puff splitting presents itself as a two-step stochastic process. A splitting puff first emits a chaotic pseudopod made of azimuthally localized streaky structures at the downstream (leading) laminar–turbulent interface. This structure can later expand azimuthally as it detaches from the parent puff. Detachment results from a collapse of turbulence over the whole cross-section of the pipe. Once the process is achieved a new puff is born ahead. Large-deviation consequences of elementary stochastic processes at the scale of the streak are invoked to explain the statistical nature of splitting and the Poisson-like distributions of splitting times reported by Avila et al (2011 Science 333 192–6). (paper)

  16. Photocatalytic Water-Splitting Reaction from Catalytic and Kinetic Perspectives

    KAUST Repository

    Hisatomi, Takashi

    2014-10-16

    Abstract: Some particulate semiconductors loaded with nanoparticulate catalysts exhibit photocatalytic activity for the water-splitting reaction. The photocatalysis is distinct from the thermal catalysis because photocatalysis involves photophysical processes in particulate semiconductors. This review article presents a brief introduction to photocatalysis, followed by kinetic aspects of the photocatalytic water-splitting reaction.Graphical Abstract: [Figure not available: see fulltext.

  17. End-Regularity of the Join of n Split Graphs

    OpenAIRE

    Hailong Hou; Aifen Feng; Rui Gu

    2013-01-01

    A graph X is said to be End-regular if its endomorphism monoid End (X) is a regular semigroup. In this study, End-regular graphs which are the join of n split graphs are characterized. We give the conditions under which the endomorphism monoid of the join of n splits graphs is regular.

  18. Recent advances in semiconductors for photocatalytic and photoelectrochemical water splitting.

    Science.gov (United States)

    Hisatomi, Takashi; Kubota, Jun; Domen, Kazunari

    2014-11-21

    Photocatalytic and photoelectrochemical water splitting under irradiation by sunlight has received much attention for production of renewable hydrogen from water on a large scale. Many challenges still remain in improving energy conversion efficiency, such as utilizing longer-wavelength photons for hydrogen production, enhancing the reaction efficiency at any given wavelength, and increasing the lifetime of the semiconductor materials. This introductory review covers the fundamental aspects of photocatalytic and photoelectrochemical water splitting. Controlling the semiconducting properties of photocatalysts and photoelectrode materials is the primary concern in developing materials for solar water splitting, because they determine how much photoexcitation occurs in a semiconductor under solar illumination and how many photoexcited carriers reach the surface where water splitting takes place. Given a specific semiconductor material, surface modifications are important not only to activate the semiconductor for water splitting but also to facilitate charge separation and to upgrade the stability of the material under photoexcitation. In addition, reducing resistance loss and forming p-n junction have a significant impact on the efficiency of photoelectrochemical water splitting. Correct evaluation of the photocatalytic and photoelectrochemical activity for water splitting is becoming more important in enabling an accurate comparison of a number of studies based on different systems. In the latter part, recent advances in the water splitting reaction under visible light will be presented with a focus on non-oxide semiconductor materials to give an overview of the various problems and solutions. PMID:24413305

  19. Splitting of a Dexamethasone Implant (Ozurdex) following the Injection

    OpenAIRE

    Ali Osman Saatci; Aylin Yaman; Melih Parlak; Oya Donmez

    2013-01-01

    In this brief report, we share our observations on a splitted Dexamethasone implant (Ozurdex) which we discovered a week after the injection. It is likely that implant splitting neither changes the efficacy of the implant nor creates a mishap for the patient.

  20. Splitting of a Dexamethasone Implant (Ozurdex) following the Injection.

    Science.gov (United States)

    Donmez, Oya; Parlak, Melih; Yaman, Aylin; Saatci, Ali Osman

    2013-01-01

    In this brief report, we share our observations on a splitted Dexamethasone implant (Ozurdex) which we discovered a week after the injection. It is likely that implant splitting neither changes the efficacy of the implant nor creates a mishap for the patient. PMID:23984139

  1. Proton polarizability contribution to the hyperfine splitting in muonic hydrogen

    OpenAIRE

    Cherednikova, E. V.; Faustov, R. N.; Martynenko, A. P.

    2001-01-01

    The contribution of the proton polarizability to the ground state hyperfine splitting in muonic hydrogen is evaluated on the basis of modern experimental and theoretical results on the proton polarized structure functions. The value of this correction is equal to 4.6(8)\\cdot 10^{-4} times the Fermi splitting E_F.

  2. Proton polarizability contribution to the hyperfine splitting in muonic hydrogen

    CERN Document Server

    Faustov, R N; Martynenko, A P

    2002-01-01

    The contribution of the proton polarizability to the ground state hyperfine splitting in muonic hydrogen is evaluated on the basis of modern experimental and theoretical results on the proton polarized structure functions. The value of this correction is equal to 3.5(8)\\cdot 10^{-4} times the Fermi splitting E_F.

  3. Touching Syllable Segmentation using Split Profile Algorithm

    Directory of Open Access Journals (Sweden)

    L.Pratap Reddy

    2010-05-01

    Full Text Available The most challenging task of a character recognition system is associated with segmentation of individual components of the script with maximum efficiency. This process is relatively easy with regard to stroke based and standard scripts. Cursive scripts are more complex possessing a large number of overlapping and touching objects, where in the statistical behavior of the topological properties are to be studied extensively for achieving highest accuracy. Certain amount of similarity exists between unconstrained hand written text as well as South Indian scripts in terms of topology, component combinations, overlapping and merging characteristics. The concept of syllables and their formulations is an additive complexity with regard to Indian scripts. In this paper the statistical behavior of the cursive script, Telugu, is presented. The topological properties in terms of zones, component combinations, behavioural aspects of syllables are studied and adopted in the segmentation process. The statistical behaviour of cursive components are evaluated. Split Profile Algorithm is proposed while handling touching components. The proposed algorithm is evaluated on different fonts and sizes. The performance of the proposed algorithm is compared with two approaches methods viz aspect ratio and syllable width approaches.

  4. Field-Split Preconditioned Inexact Newton Algorithms

    KAUST Repository

    Liu, Lulu

    2015-06-02

    The multiplicative Schwarz preconditioned inexact Newton (MSPIN) algorithm is presented as a complement to additive Schwarz preconditioned inexact Newton (ASPIN). At an algebraic level, ASPIN and MSPIN are variants of the same strategy to improve the convergence of systems with unbalanced nonlinearities; however, they have natural complementarity in practice. MSPIN is naturally based on partitioning of degrees of freedom in a nonlinear PDE system by field type rather than by subdomain, where a modest factor of concurrency can be sacrificed for physically motivated convergence robustness. ASPIN, originally introduced for decompositions into subdomains, is natural for high concurrency and reduction of global synchronization. We consider both types of inexact Newton algorithms in the field-split context, and we augment the classical convergence theory of ASPIN for the multiplicative case. Numerical experiments show that MSPIN can be significantly more robust than Newton methods based on global linearizations, and that MSPIN can be more robust than ASPIN and maintain fast convergence even for challenging problems, such as high Reynolds number Navier--Stokes equations.

  5. Image Segmentation Using Two Step Splitting Function

    Directory of Open Access Journals (Sweden)

    Gopal Kumar Jha

    2013-12-01

    Full Text Available Image processing and computer vision is widely using Level Set Method (LSM. In conventional level set formulation, irregularities are developed during evolution of level set function, which cause numerical errors and eventually destroy the stability of the evolution. Therefore a numerical remedy called re-initialization is typically applied periodically to replace the degraded level set function. However re –initialization raises serious problem that is when and how it should be performed and also affects numerical accuracy in an undesirable way. To overcome this drawback of re-initialization process, a new variation level set formulation called Distance regularization level set evolution (DRLSE is introduced in which the regularity of the level set function is internally maintained during the level set evolution. DRLSE allows more general and effective initialization of the level set function. But DRLSE uses relatively large number of steps to ensure efficient numerical accuracy. Here in this thesis we are implementing faster and equally efficient computation technique called two step splitting method (TSSM. TSSM is physio-chemical reaction diffusion equation in which firstly LSE equation get iterated and then regularize the level set function from the first step to ensure the stability and hence re-initialization is completely eliminated from LSE which also satisfy DRLSE.

  6. Descent Assisted Split Habitat Lunar Lander Concept

    Science.gov (United States)

    Mazanek, Daniel D.; Goodliff, Kandyce; Cornelius, David M.

    2008-01-01

    The Descent Assisted Split Habitat (DASH) lunar lander concept utilizes a disposable braking stage for descent and a minimally sized pressurized volume for crew transport to and from the lunar surface. The lander can also be configured to perform autonomous cargo missions. Although a braking-stage approach represents a significantly different operational concept compared with a traditional two-stage lander, the DASH lander offers many important benefits. These benefits include improved crew egress/ingress and large-cargo unloading; excellent surface visibility during landing; elimination of the need for deep-throttling descent engines; potentially reduced plume-surface interactions and lower vertical touchdown velocity; and reduced lander gross mass through efficient mass staging and volume segmentation. This paper documents the conceptual study on various aspects of the design, including development of sortie and outpost lander configurations and a mission concept of operations; the initial descent trajectory design; the initial spacecraft sizing estimates and subsystem design; and the identification of technology needs

  7. Deformation and signature splitting in 74Br

    International Nuclear Information System (INIS)

    The high-spin states of 74Br were studied via the 48Ti(32S,?pn)74Br and the 58Ni(19F,2pn)74Br fusion-evaporation reactions at energies of 105 and 62 MeV, respectively, using the Florida State University Tandem LINAC. ?-? coincidence arrays were produced using four Compton-suppressed Ge detectors. Two independent groups of ? rays were studied--one of positive parity and one of negative parity, both of which appear to be based on an isomeric 4(+) state. Lifetimes were measured using both the Doppler-shift attenuation and recoil-distance methods. A cranking-model analysis of the bands shows that the kinematic and dynamic moments of inertia for the bands are rather similar and fairly constant for high spins with values of (20--23)?2/MeV. A phase reversal occurs in the signature splitting in the yrast band around spin 9 which is related to the quasiparticle alignments. The lifetimes imply an average axial quadrupole deformation of 0.37 in the yrast band and 0.34 in the negative-parity band. These deformations are close to those predicted by Hartree-Fock-Bogolyubov cranking calculations

  8. Split-Field Magnet facility upgraded

    CERN Multimedia

    1977-01-01

    The Split Field Magnet (SFM) was the largest spectrometer for particles from beam-beam collisions in the ISR. It could determine particle momenta in a large solid angle, but was designed mainly for the analysis of forward travelling particles.As the magnet was working on the ISR circulating beams, its magnetic field had to be such as to restore the correct proton orbit.The SFM, therefore, produced zero field at the crossing point and fields of opposite signs upstream and downstream of it and was completed by 2 large and 2 small compensator magnets. The gradient effects were corrected by magnetic channels equipped with movable flaps. The useful magnetic field volume was 28 m3, the induction in the median plane 1.14 T, the gap heigth 1.1 m, the length 10.5 m, the weight about 1000 ton. Concerning the detectors, the SFM was the first massive application of multiwire proportional chambers (about 70000 wires) which filled the main and the large compensator magnets. In 1976 an improved programme was started with tw...

  9. Miniaturized Planar Split-Ring Resonator Antenna

    DEFF Research Database (Denmark)

    Kim, Oleksiy S.; Breinbjerg, Olav

    2009-01-01

    A miniaturized planar antenna based on a broadside-coupled split ring resonator excited by an arc-shaped dipole is presented. The excitation dipole acts as a small tuning capacitor in series with a parallel RLC circuit represented by the SRR. The antenna resonance frequency and dimensions a essentially determined by the SRR, while by varying the dipole arm length the input resistance is changed in a wide range, thus matching the antenna to a feed line and compensating for simulation and manufacturing inaccuracies. No additional matching network is required. Theoretically, there is no limit on how small this antenna can be. In practice, the lower bound is set by losses in utilized materials and manufacturing inaccuracies. As an example, an antenna of ka=0.09 was designed, fabricated and tested. Although the initially fabricated antenna prototype had the input impedance of 43 ohms, it was subsequently tuned to 50 ohms simply by cutting out the excessive arm length. This tuning technique is especially useful inpractical applications, since it allows the antenna to be tuned in-place and thereby compensate for various inaccuracies as well as for an antenna environment.

  10. Antibodies to myelin oligodendrocyte glycoprotein in HIV-1 associated neurocognitive disorder: a cross-sectional cohort study

    Directory of Open Access Journals (Sweden)

    Berger Thomas

    2010-11-01

    Full Text Available Abstract Background Neuroinflammation and demyelination have been suggested as mechanisms causing HIV-1 associated neurocognitive disorder (HAND. This cross-sectional cohort study explores the potential role of antibodies to myelin oligodendrocyte glycoprotein (MOG, a putative autoantigen in multiple sclerosis, in the pathogenesis of HAND. Methods IgG antibodies against MOG were measured by ELISA in sera and cerebrospinal fluid (CSF of 65 HIV-positive patients with HAND (n = 14, cerebral opportunistic infections (HIVOI, n = 25, primary HIV infection (HIVM, n = 5 and asymptomatic patients (HIVasy, n = 21. As control group HIV-negative patients with bacterial or viral CNS infections (OIND, n = 18 and other neurological diseases (OND, n = 22 were included. In a subset of HAND patients MOG antibodies were determined before and during antiviral therapy. Results In serum, significantly higher MOG antibody titers were observed in HAND compared to OND patients. In CSF, significantly higher antibody titers were observed in HAND and HIVOI patients compared to HIVasy and OND patients and in OIND compared to OND patients. CSF anti-MOG antibodies showed a high sensitivity and specificity (85.7% and 76.2% for discriminating patients with active HAND from asymptomatic HIV patients. MOG immunopositive HAND patients performed significantly worse on the HIV dementia scale and showed higher viral load in CSF. In longitudinally studied HAND patients, sustained antibody response was noted despite successful clearance of viral RNA. Conclusions Persistence of MOG antibodies despite viral clearance in a high percentage of HAND patients suggests ongoing neuroinflammation, possibly preventing recovery from HAND.

  11. Cyclosporin A increases recovery after spinal cord injury but does not improve myelination by oligodendrocyte progenitor cell transplantation

    Directory of Open Access Journals (Sweden)

    Wang Feng-Chao

    2010-10-01

    Full Text Available Abstract Background Transplantation of oligodendrocyte precursor cells (OPCs is an attractive therapy for demyelinating diseases. Cyclosporin A (CsA is one of the foremost immunosuppressive agents and has widespread use in tissue and cell transplantation. However, whether CsA affects survival and differentiation of engrafted OPCs in vivo is unknown. In this study, the effect of CsA on morphological, functional and immunological aspects, as well as survival and differentiation of engrafted OPCs in injured spinal cord was explored. Results We transplanted green fluorescent protein (GFP expressed OPCs (GFP-OPCs into injured spinal cords of rats treated with or without CsA (10 mg/kg. Two weeks after cell transplantation, more GFP-positive cells were found in CsA-treated rats than that in vehicle-treated ones. However, the engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes in both groups. In the CsA-treated group, a significant decrease in spinal cord lesion volume along with increase in spared myelin and neurons were found compared to the control group. Such histological improvement correlated well with an increase in behavioral recovery. Further study suggested that CsA treatment could inhibit infiltration of T cells and activation of resident microglia and/or macrophages derived from infiltrating monocytes in injured spinal cords, which contributes to the survival of engrafted OPCs and repair of spinal cord injury (SCI. Conclusions These results collectively indicate that CsA can promote the survival of engrafted OPCs in injured spinal cords, but has no effect on their differentiation. The engrafted cells mostly differentiated into astrocytes, but not oligodendrocytes. The beneficial effect of CsA on SCI and the survival of engrafted cells may be attributed to its neuroprotective effect.

  12. Prolonged high frequency electrical stimulation is lethal to motor axons of mice heterozygously deficient for the myelin protein P? gene

    DEFF Research Database (Denmark)

    Alvarez, Susana; Moldovan, Mihai

    2013-01-01

    The relationship between dysmyelination and the progression of neuropathy in Charcot-Marie-Tooth (CMT) hereditary polyneuropathy is unclear. Mice heterozygously deficient for the myelin protein P? gene (P?+/-) are indistinguishable from wild-type (WT) at birth and then develop a slowly progressing demyelinating neuropathy reminiscent of CMT Type 1b. Accumulating evidence suggests that impulse conduction can become lethal to acutely demyelinated central and peripheral axons. Here we investigated the vulnerability of motor axons to long-lasting, high-frequency repetitive stimulation (RS) in P?+/- mice as compared to WT littermates at 7, 12, and 20 months of age. RS was carried out in interrupted trains of 200 Hz trains for 3h. Tibial nerves were stimulated at the ankle while the evoked compound muscle action potentials (CMAPs) and the ascending compound nerve action potentials (CNAPs) were recorded from plantar muscles and the sciatic nerve, respectively. In 7-month old mice, there was recovery of CMAP and CNAPfollowing RS. When mice were about one year old, electrophysiological recovery following RS was incomplete and in P?+/- also associated with morphological signs of partial Wallerian degeneration. The effect of RS was larger in P?+/- as compared to age-matched WT. When mice were about 2 years old, the effect was stronger and became similar between WT and P?+/-. RS was followed by a transient hyperpolarization, which decreased with age and was smaller in P0+/- than in WT. Our data suggest that both aging and the dysmyelinating disease process may contribute to the susceptibility to activity-induced axonal degeneration. It is possible that in aging mice and in P?+/- there is inadequate energy-dependent Na(+)/K(+) pumping, as indicated by the reduced post-stimulation hyperpolarization, which may lead to a lethal Na(+) overload in some axons.

  13. To Split or Not to Split, That Is the Question in Some Shallow Water Equations

    OpenAIRE

    Martínez, Vicente

    2012-01-01

    In this paper we analyze the use of time splitting techniques for solving shallow water equation. We discuss some properties that these schemes should satisfy so that interactions between the source term and the shock waves are controlled. This paper shows that these schemes must be well balanced in the meaning expressed by Greenberg and Leroux [5]. More speci?cally, we analyze in what cases it is enough to verify an Approximate C-property and in which cases it is required t...

  14. Split-Plot Designs with Mirror Image Pairs as Subplots

    DEFF Research Database (Denmark)

    Tyssedal, John; Kulahci, Murat; Bisgaard, Soren

    2011-01-01

    In this article we investigate two-level split-plot designs where the sub-plots consist of only two mirror image trials. Assuming third and higher order interactions negligible, we show that these designs divide the estimated effects into two orthogonal sub-spaces, separating sub-plot main effects and sub-plot by whole-plot interactions from the rest. Further we show how to construct split-plot designs of projectivity P?3. We also introduce a new class of split-plot designs with mirror image pai...

  15. Split-Plot Designs with Mirror Image Pairs as Subplots

    OpenAIRE

    Tyssedal, John; Kulahci, Murat; Bisgaard, Soren

    2010-01-01

    In this article we investigate two-level split-plot designs where the sub-plots consist of only two mirror image trials. Assuming third and higher order interactions negligible, we show that these designs divide the estimated effects into two orthogonal sub-spaces, separating sub-plot main effects and sub-plot by whole-plot interactions from the rest. Further we show how to construct split-plot designs of projectivity P?3. We also introduce a new class of split-plot designs with mirror image ...

  16. Single and Double Perturbative Splitting Diagrams in Double Parton Scattering

    CERN Document Server

    Gaunt, Jonathan R

    2012-01-01

    We discuss the role of two different types of diagram in the proton-proton double parton scattering (DPS) cross section - single and double perturbative splitting graphs. Using explicit calculations of simple graphs from these classes we show that the treatment of these graphs by the 'double PDF' framework for describing the DPS cross section, introduced a number of years ago by Snigirev and collaborators, is unsatisfactory. We suggest that a contribution from single perturbative splitting graphs should be included in the DPS cross section, albeit with a different geometrical prefactor to the contribution from 'zero perturbative splitting' graphs.

  17. On Splitting Invariants and Sign Conventions in Endoscopic Transfer

    CERN Document Server

    Kottwitz, R

    2012-01-01

    The transfer factors for standard endoscopy involve, among other things, the Langlands-Shelstad splitting invariant. This note introduces a twisted version of that splitting invariant. The twisted splitting invariant is then used to define a better twisted factor $\\Delta_I$. In addition we correct a sign error in the definition of twisted transfers. There are two ways to correct the sign error. One way yields twisted transfer factors $\\Delta'$ that are compatible with the classical Langlands correspondence. The other way yields twisted transfer factors $\\Delta_D$ that are compatible with a renormalized version of the Langlands correspondence.

  18. Higher-order QCD corrections to triple collinear splitting functions

    CERN Document Server

    Sborlini, German F R; Rodrigo, German

    2015-01-01

    We present splitting functions in the triple collinear limit at next-to-leading order in the strong coupling. We performed the computation in the context of massless QCD+QED, and consider first collinear processes which include at least one photon. The IR divergent structure of the multi-partonic splitting functions agrees with the Catani's formula. Consistency checks based on symmetry arguments have been implemented and results for different configurations have been cross-checked. Studying photon-started processes, we obtained very compact results: this allowed us to simplify the expressions for the remaining splitting functions.

  19. Partially secret broadcasting, partially secret splitting with quantum entanglement

    International Nuclear Information System (INIS)

    In this paper, we propose a classical secret broadcasting and splitting joint protocol in a quantum scenario. With those genuinely entangled states, the boss can always broadcast some of his secrets and split some others to multi-receivers at the same time. The efficiency of the joint protocol is also compared with that of two separate ones which realise classical secret broadcasting and classical secret splitting respectively, and based on the comparison we can see the promising advantage of our joint protocol is that it can realise the two tasks more efficiently and more conveniently. (general)

  20. Initial-state splitting kernels in cold nuclear matter

    CERN Document Server

    Ovanesyan, Grigory; Vitev, Ivan

    2015-01-01

    We derive medium-induced splitting kernels for energetic partons that undergo interactions in dense QCD matter before a hard-scattering event at large momentum transfer $Q^2$. Working in the framework of the effective theory ${\\rm SCET}_{\\rm G}\\,$, we compute the splitting kernels beyond the soft gluon approximation. We present numerical studies that compare our new results with previous findings. We expect the full medium-induced splitting kernels to be most relevant for the extension of initial-state cold nuclear matter energy loss phenomenology in both p+A and A+A collisions.

  1. Patchy distributions of myelin and vesicular glutamate transporter 2 align with cytochrome oxidase blobs and interblobs in the superficial layers of the primary visual cortex

    Directory of Open Access Journals (Sweden)

    Rockoff EC

    2014-09-01

    Full Text Available Emily C Rockoff,1 Pooja Balaram,1 Jon H Kaas1,2 1Department of Psychology, 2Department of Cell and Molecular Biology, Vanderbilt University, Nashville, TN, USA Abstract: Blobs are a modular component of the primary visual cortex (area 17 of all primates, but not of other mammals closely related to primates. They are characterized as an even distribution of patches, puffs, or blobs of dense cytochrome oxidase (CO expression in layer III of area 17, and are now known to differ from surrounding, nonblob cortex in thalamic, intrinsic, and extrastriate connections. Previous studies have also recognized a blob-like pattern of myelin-dense patches in layer III of area 17 of primates, and more recently the vesicular glutamate transporter (VGLUT-2 isoform of the VGLUT family has been found to selectively distribute to layer III patches in a similar blob-like pattern. Here, we sought to determine if the blob-like patterns all identify the same modular structures in area 17 of primates by staining alternate brain sections cut parallel to the surface of area 17 of a prosimian primate (Otolemur garnettii for CO, myelin, and VGLUT2. By aligning the sections from the three preparations, we provide clear evidence that the three preparations all identify the same modular blob structures. The results provide a further understanding of the functional nature of the blobs by demonstrating that their higher level of CO activity is related to thalamic inputs from the lateral geniculate nucleus that use VGLUT2 as their main glutamate transporter, and via myelinated axons. Keywords: columns, modules, visual cortex, primates, prosimians

  2. Conduction block and tonic pupils in Charcot-Marie-Tooth disease caused by a myelin protein zero p.Ile112Thr mutation.

    LENUS (Irish Health Repository)

    Murphy, Sinéad M

    2011-03-01

    We report a patient with Charcot-Marie-Tooth disease (CMT) due to the p.Ile112Thr mutation in myelin protein zero (MPZ) who presented with a patchy neuropathy with conduction block and tonic pupils. Conduction block is unusual in inherited neuropathies, while pupil abnormalities are recognised to occur in CMT especially due to MPZ mutations. This case highlights that patchy demyelinating neuropathy with conduction block may occur in p.Ile112Thr MPZ mutations. Involvement of the pupils, as in this case, may be a pointer towards a genetic rather than inflammatory cause of neuropathy.

  3. Studies on water splitting hydrogen production

    International Nuclear Information System (INIS)

    Studies on two kinds of water splitting process for hydrogen production, i.e. thermochemical Iodine-Sulfur(IS) Process and high temperature steam electrolysis, have been conducted at JAERI which utilize high temperature nuclear heat supplied by HTGR. IS process, which is composed of three chemical reactions, works as a chemical engine producing hydrogen driven by HTGR. A laboratory scale experimental study has been conducted to demonstrate the continuous hydrogen production by IS process, using a glass-made apparatus designed to include all the elemental unit operations. So far, stable production of hydrogen and oxygen at the rate of 1.5 liter-H2/hr has been successfully demonstrated for over 8 hours. In parallel with the demonstration study, studies for improving the process thermal efficiency have been conducted focusing on the hydrogen iodide decomposition step. Also, a study on the materials of construction suitable for the corrosive process environments is under way for large scale realization of the process. High temperature steam electrolysis is an advanced electrolysis process using solid oxide electrolytes working at high temperature ranging from 850degC to 1000degC. The electrolysis process features its simple process scheme and lower working electricity than the conventional water electrolysis. Through laboratory-scale experiments, electrolysis cells such as tubular cells and planar cells have been developed to improve hydrogen production performance. Using a planar cell, hydrogen could be produced at a rate of 2.4 liter/hr at steam temperature of 850degC. (J.P.N.)

  4. Baryon mass splittings in chiral perturbation theory

    International Nuclear Information System (INIS)

    Baryon masses are calculated in chiral perturbation theory at the one-loop O(p3) level in chiral expansion and to leading order in the heavy baryon expansion. Ultraviolet divergences occur requiring the introduction of counterterms. Despite this necessity, no knowledge of the counterterms is required to determine the violations of the Gell-Mann--Okubo mass relation for the baryon octet or of the decuplet equal-mass-spacing rule, as all divergences cancel exactly at this order. For the same reason all references to an arbitrary scale ? are absent. Neither of these features continue to higher powers in the chiral expansion. We also discuss critically the absolute necessity of simultaneously going beyond the leading-order heavy baryon expansion, if one goes beyond the one-loop O(p3) level. We point out that these corrections in 1/MB generate new divergences ?m4/M10. These divergences together with the divergences occurring in one-loop O(p4) graphs of chiral perturbation theory are taken care of by the same set of counterterms. Because of these unknown counterterms one cannot predict the baryon mass splittings at the one-loop O(p4) level even if the parameters of all scrL1?N terms are known. We point out another serious problem of going to the one-loop O(p4) level. When the decuplet is off its mass shell there are additional ?N? and ??? interaction terms. These interactions contribute to the divergent terms ?(m4/M10), and also to nonanalytic terms such as ?(m4/M10)ln(m/M10). Without knowledge of the coupling constants appearing in these interactions, one cannot carry out a consistent one-loop O(p4) level calculation

  5. Collider Phenomenology with Split-UED

    Energy Technology Data Exchange (ETDEWEB)

    Kong, Kyoungchul; /SLAC; Park, Seong Chan; /Tokyo U., IPMU; Rizzo, Thomas G.; /SLAC

    2011-12-15

    We investigate the collider implications of Split Universal Extra Dimensions. The non-vanishing fermion mass in the bulk, which is consistent with the KK-parity, largely modifies the phenomenology of Minimal Universal Extra Dimensions. We scrutinize the behavior of couplings and study the discovery reach of the Tevatron and the LHC for level-2 Kaluza-Klein modes in the dilepton channel, which would indicates the presence of the extra dimensions. Observation of large event rates for dilepton resonances can result from a nontrivial fermion mass profile along the extra dimensions, which, in turn, may corroborate extra dimensional explanation for the observation of the positron excess in cosmic rays. The Minimal Universal Extra Dimensions scenario has received great attention. Recently non-vanishing bulk fermion masses have been introduced without spoiling the virtue of KK-parity. The fermion profiles are no longer simple sine/cosine functions and depend upon the specific values of bulk parameters. The profiles of fermions are split along the extra dimensions while the wave functions of the bosons remain the same as in UED. A simple introduction of a KK-parity conserving bulk fermion mass has significant influences on collider aspects as well as astrophysical implications of UED. For instance, the DM annihilation fraction into certain SM fermion pairs is either enhanced or reduced (compared to the MUED case) so that one can perhaps explain the PAMELA positron excess while suppressing the anti-proton flux. In this paper, we have concentrated on collider phenomenology of Split Universal Extra Dimensions. We have revisited the KK decomposition in detail and analyzed wave function overlaps to compute relevant couplings for collider studies. We have discussed general collider implication for level-1 KK modes and level-2 KK with non-zero bulk mass and have computed LHC reach for the EW level-2 KK bosons, {gamma}{sub 2} and Z{sub 2}, in the dilepton channel. The LHC should able to cover the large parameter space (up to M{sub V{sub 2}} {approx} 1.5 TeV for {mu}L {ge} 1) even with early data assuming {approx}100 pb{sup -1} or less. The existence of double resonances is one essential feature arising from extra dimensional models. Whether or not one can see double resonances depends both on how degenerate the two resonances are and on the mass resolution of the detector. The very high P{sub T} from the decay makes resolution in dimuon channel worse than in dielectron final state. This is because one can reconstruct electron from ECAL but muon momentum reconstruction relies on its track, which is barely curved in this case. Further indication for SUED might be the discovery of W'-like signature of mass close to Z{sub 2}. The MUED predicts a somewhat lower event rate due to 1-loop suppressed coupling of level-2 bosons to SM fermion pair, while it exists at tree level in SUED. Therefore in UED, one has to rely on indirect production of level-2 bosons, whose collider study requires complete knowledge of the model: the mass spectrum and all the couplings. On the other hand, in the large {mu} limit of SUED, the dependence on mass spectrum is diminished since level-2 KK bosons decay only into SM fermion pairs. This allows us to estimate the signal rate from their direct production, so that they can be discovered at the early phase of the LHC. The indirect production mechanism only increases production cross sections, improving our results. Once a discovery has been made, one should try to reconstruct events and do further measurements such as spin and coupling determination, with more accumulated data, which might discriminate KK resonances from other Z' models. The coupling measurement is directly related to the determination of the bulk masses. A challenging issue might be the existence of two resonances which are rather close to each other.

  6. A guiding oblique osteotomy cut to prevent bad split in sagittal split ramus osteotomy: a technical note

    Directory of Open Access Journals (Sweden)

    Gururaj Arakeri

    2015-06-01

    Full Text Available Aim: To present a simple technical modification of a medial osteotomy cut which prevents its misdirection and overcomes various anatomical variations as well as technical problems. Methods: The medial osteotomy cut is modified in the posterior half at an angle of 15°-20° following novel landmarks. Results: The proposed cut exclusively directs the splitting forces downwards to create a favorable lingual fracture, preventing the possibility of an upwards split which would cause a coronoid or condylar fracture. Conclusion: This modification has proven to be successful to date without encountering the complications of a bad split or nerve damage.

  7. Evaluation of hadronic vacuum polarization contribution to muonium hyperfine splitting

    CERN Document Server

    Faustov, R N; Martynenko, A P

    1999-01-01

    The contribution of hadronic vacuum polarization (HVP) to the hyperfine splitting of the muonium ground state is evaluated with the account of modern experimental data on the cross section of $e^+e^- \\to$ annihilation into hadrons.

  8. Proton polarizability correction to the hydrogen hyperfine splitting

    CERN Document Server

    Faustov, R N; Saleev, V A

    1999-01-01

    The contribution of \\Delta isobar to the correction on proton polarizability in the hyperfine splitting of hydrogen and muonic hydrogen is calculated with the account of the experimental data on N-\\Delta transition form factors.

  9. Opportunistic splitting for scheduling using a score-based approach

    KAUST Repository

    Rashid, Faraan

    2012-06-01

    We consider the problem of scheduling a user in a multi-user wireless environment in a distributed manner. The opportunistic splitting algorithm is applied to find the best group of users without reporting the channel state information to the centralized scheduler. The users find the best among themselves while requiring just a ternary feedback from the common receiver at the end of each mini-slot. The original splitting algorithm is modified to handle users with asymmetric channel conditions. We use a score-based approach with the splitting algorithm to introduce time and throughput fairness while exploiting the multi-user diversity of the network. Analytical and simulation results are given to show that the modified score-based splitting algorithm works well as a fair scheduling scheme with good spectral efficiency and reduced feedback. © 2012 IEEE.

  10. Split Hopkinson (Kolsky) bar design, testing and applications

    CERN Document Server

    Chen, Weinong W

    2010-01-01

    This book details the general principles of Kolsky bars, or split Hopkinson bars, used for obtaining dynamic material properties. It assists both beginners and professionals in characterizing high-rate material response with high quality and consistency.

  11. Renormgroup origin and analysis of Split Higgsino scenario

    OpenAIRE

    Beylin, V. A.; Kuksa, V. I.; Vereshkov, G. M.; Pasechnik, R. S.

    2007-01-01

    We present a renormalization group motivation of scale hierarchies in SUSY SU(5) model. The Split Higgsino scanrio with a high scale of the SUSY breaking is considered in detail. Its manifestations in experiments are discussed.

  12. Field Monitoring Protocol. Mini-Split Heat Pumps

    Energy Technology Data Exchange (ETDEWEB)

    Christensen, Dane [National Renewable Energy Lab. (NREL), Golden, CO (United States); Fang, Xia [National Renewable Energy Lab. (NREL), Golden, CO (United States); Tomerlin, Jeff [National Renewable Energy Lab. (NREL), Golden, CO (United States); Winkler, Jon [National Renewable Energy Lab. (NREL), Golden, CO (United States); Hancock, E. [Mountain Energy Partnership, Longmont, CO (United States)

    2011-03-01

    This Building America program report provides a detailed method for accurately measuring and monitoring performance of a residential mini-split heat pump, which will be used in high-performance retrofit applications.

  13. Mathematical aspects of laser beam shaping and splitting.

    Energy Technology Data Exchange (ETDEWEB)

    Dickey, Fred McCartney (FMD Consulting, LLC, Springfield MO); Romero, Louis Anthony

    2010-05-01

    We will discuss general mathematical ideas arising in the problems of Laser beam shaping and splitting. We will be particularly concerned with questions concerning the scaling and symmetry of such systems.

  14. Proton structure in the hyperfine splitting of muonic hydrogen

    CERN Document Server

    Hagelstein, Franziska

    2015-01-01

    We present the leading-order prediction of baryon chiral perturbation theory for the proton polarizability contribution to the 2S hyperfine splitting in muonic hydrogen, and compare with the results of dispersive calculations.

  15. Mini-Split Heat Pumps Multifamily Retrofit Feasibility Study

    Energy Technology Data Exchange (ETDEWEB)

    Dentz, J.; Podorson, D.; Varshney, K.

    2014-05-01

    Mini-split heat pumps can provide space heating and cooling in many climates and are relatively affordable. These and other features make them potentially suitable for retrofitting into multifamily buildings in cold climates to replace electric resistance heating or other outmoded heating systems. This report investigates the suitability of mini-split heat pumps for multifamily retrofits. Various technical and regulatory barriers are discussed and modeling was performed to compare long-term costs of substituting mini-splits for a variety of other heating and cooling options. A number of utility programs have retrofit mini-splits in both single family and multifamily residences. Two such multifamily programs are discussed in detail.

  16. 26 CFR 1.482-6 - Profit split method.

    Science.gov (United States)

    2010-04-01

    ...of the residual profit split relies on market benchmarks of profitability. Thus, the comparability considerations that are relevant...of these intangibles, the district director compares the ratios of the capitalized value of expenditures as of 1995 on...

  17. Proton polarizability contribution to the hydrogen hyperfine splitting

    OpenAIRE

    Faustov, R. N.; Martynenko, A. P.

    2000-01-01

    The contribution of the proton polarizability to the hydrogen hyperfine splitting is evaluated on the basis of modern experimental and theoretical results on the proton polarized structure functions. The value of this correction is equal to 1.4 ppm.

  18. Proton polarizability correction to the hydrogen hyperfine splitting

    OpenAIRE

    Faustov, R. N.; Martynenko, A. P.; Saleev, V. A.

    1998-01-01

    The contribution of \\Delta isobar to the correction on proton polarizability in the hyperfine splitting of hydrogen and muonic hydrogen is calculated with the account of the experimental data on N-\\Delta transition form factors.

  19. Evaluation of hadronic vacuum polarization contribution to muonium hyperfine splitting

    OpenAIRE

    Faustov, R. N.; Karimkhodzhaev, A.; Martynenko, A. P.

    1998-01-01

    The contribution of hadronic vacuum polarization (HVP) to the hyperfine splitting of the muonium ground state is evaluated with the account of modern experimental data on the cross section of $e^+e^- \\to$ annihilation into hadrons.

  20. Hadronic vacuum polarization contribution to muonium hyperfine splitting

    International Nuclear Information System (INIS)

    The contribution of hadronic vacuum polarization to the hyperfine splitting of the muonium ground state is evaluated with the account of modern experimental data on the cross section of e+e- annihilation into hadrons

  1. Electrochemical Water-Splitting Based on Hypochlorite Oxidation.

    Czech Academy of Sciences Publication Activity Database

    Minhová Macounová, Kate?ina; Simic, N.; Ahlberg, E.; Krtil, Petr

    2015-01-01

    Ro?. 137, ?. 23 (2015), s. 7262-7265. ISSN 0002-7863 Institutional support: RVO:61388955 Keywords : electrochemistry * hypochlorite oxidation * water-splitting Subject RIV: CG - Electrochemistry Impact factor: 12.113, year: 2014

  2. Visualization of the sequence of a couple splitting outside shop

    DEFF Research Database (Denmark)

    Visualization of tracks of couple walking together before splitting and one goes into shop the other waits outside. The visualization represents the sequence described in figure 7 in the publication 'Taking the temperature of pedestrian movement in public spaces'

  3. Nonlinear Fracture Mechanics and Plasticity of the Split Cylinder Test

    DEFF Research Database (Denmark)

    Olesen, John Forbes; Østergaard, Lennart; Stang, Henrik

    2006-01-01

    The split cylinder testis subjected to an analysis combining nonlinear fracture mechanics and plasticity. The fictitious crack model is applied for the analysis of splitting tensile fracture, and the Mohr-Coulomb yield criterion is adopted for modelling the compressive crushing/sliding failure. Two models are presented, a simple semi-analytical model based on analytical solutions for the crack propagation in a rectangular prismatic body, and a finite element model including plasticity in bulk ma...

  4. Split-plot fractional designs: Is minimum aberration enough?

    DEFF Research Database (Denmark)

    Kulahci, Murat; Ramirez, Jose; Tobias, Randy

    2006-01-01

    Split-plot experiments are commonly used in industry for product and process improvement. Recent articles on designing split-plot experiments concentrate on minimum aberration as the design criterion. Minimum aberration has been criticized as a design criterion for completely randomized fractional factorial design and alternative criteria, such as the maximum number of clear two-factor interactions, are suggested (Wu and Hamada (2000)). The need for alternatives to minimum aberration is even mor...

  5. Designing fractional factorial split-plot experiments using integer programming

    DEFF Research Database (Denmark)

    Capehart, Shay R.; Keha, Ahmet; Kulahci, Murat; Montgomery, Douglas C.

    2011-01-01

    Split-plot designs are commonly used in industrial experiments when there are hard-to-change and easy-to-change factors. Due to the number of factors and resource limitations, it is more practical to run a fractional factorial split-plot (FFSP) design. These designs are variations of the fractional factorial (FF) design, with the restricted randomisation structure to account for the whole plots and subplots. We discuss the formulation of FFSP designs using integer programming (IP) to achieve var...

  6. The Equal Split-Off Set for Cooperative Games

    OpenAIRE

    Brânzei, R.; Dimitrov, D.A.; Tijs, S.H.

    2004-01-01

    In this paper the equal split-o. set is introduced as a new solution concept for cooperative games.This solution is based on egalitarian considerations and it turns out that for superadditive games the equal split-o. set is a subset of the equal division core.Moreover, the proposed solution is single valued on the class of convex games and it coincides with the Dutta-Ray constrained egalitarian solution.

  7. Confidence sets for split points in decision trees

    OpenAIRE

    Banerjee, Moulinath; McKeague, Ian W.

    2007-01-01

    We investigate the problem of finding confidence sets for split points in decision trees (CART). Our main results establish the asymptotic distribution of the least squares estimators and some associated residual sum of squares statistics in a binary decision tree approximation to a smooth regression curve. Cube-root asymptotics with nonnormal limit distributions are involved. We study various confidence sets for the split point, one calibrated using the subsampling bootstra...

  8. Tabu Split and Merge for the Simplification of Polygonal Curves

    OpenAIRE

    Ménier, Gildas; Marteau, Pierre-François

    2009-01-01

    A Tabu Move Merge Split (TMMS) algorithm is proposed for the polygonal approximation problem. TMMS incorporates a tabu principle to avoid premature convergence into local minima. TMMS is compared to optimal, near to optimal top down Multi-Resolution (TDMR) and classical split and merge heuristics solutions. Experiments show that potential improvements for crudest approximations can be obtained. The evaluation is carried out on 2D geographic maps according to effectiveness and efficiency measu...

  9. Endoscopic classification of representations of quasi-split unitary groups

    OpenAIRE

    Mok, Chung Pang

    2012-01-01

    In this paper we establish the endoscopic classification of tempered representations of quasi-split unitary groups over local fields, and the endoscopic classification of the discrete automorphic spectrum of quasi-split unitary groups over global number fields. The method is analogous to the work of Arthur on orthogonal and symplectic groups, based on the theory of endoscopy and the comparison of trace formulas on unitary groups and general linear groups.

  10. Evaluation of pressure beneath a split above elbow plaster cast.

    OpenAIRE

    Walker, R W; Draper, E.; Cable, J.

    2000-01-01

    It has previously been shown that splitting a plaster cast after manipulation of, or surgery on, a limb leads to a decrease in pressure beneath the cast by accommodating the swelling that may occur. However, it is not known whether the axis along which the cast is split influences the amount of swelling that can occur before a critical pressure is reached. We investigated this with reference to above elbow plaster casts.

  11. The Market Reaction To Stock Splits Used as Dividends

    OpenAIRE

    Yang Xiao-Xuan

    2013-01-01

    This paper investigates the market reaction to stock splits based on China’s A share companies between 2007 to 2010. I find significant positive abnormal returns around the announcement date (especially before the announcement date) as well as four to six days before the execution date of China stock splits. I also observe significant negative abnormal returns just around the execution date. The above phenomenon is relatively stable even if the selection of samples and empirical models may va...

  12. Complex split-cord malformation associated with situs inversus totalis

    Directory of Open Access Journals (Sweden)

    Agrawal Deepak

    2007-01-01

    Full Text Available Although meningoceles are known to be associated with split cord malformations, the association of dextrocardia is extremely rare. The authors report a case of a 15 day male child who had an atretic meningocele in the lumbosacral region along with dextrocardia and a split cord malformation with a posterior spur. This importance of preoperative MRI for proper management of such patients is highlighted in this report.

  13. Complex split-cord malformation associated with situs inversus totalis

    OpenAIRE

    Agrawal Deepak; Mahapatra A

    2007-01-01

    Although meningoceles are known to be associated with split cord malformations, the association of dextrocardia is extremely rare. The authors report a case of a 15 day male child who had an atretic meningocele in the lumbosacral region along with dextrocardia and a split cord malformation with a posterior spur. This importance of preoperative MRI for proper management of such patients is highlighted in this report.

  14. Key Issues in Vowel Based Splitting of Telugu Bigrams

    OpenAIRE

    Kameswara Rao; Prasad, Dr. T. V.

    2014-01-01

    Splitting of compound Telugu words into its components or root words is one of the important, tedious and yet inaccurate tasks of Natural Language Processing (NLP). Except in few special cases, at least one vowel is necessarily involved in Telugu conjunctions. In the result, vowels are often repeated as they are or are converted into other vowels or consonants. This paper describes issues involved in vowel based splitting of a Telugu bigram into proper root words using Telugu grammar conjunct...

  15. QED corrections to the Altarelli-Parisi splitting functions

    CERN Document Server

    de Florian, Daniel; Rodrigo, German

    2015-01-01

    We discuss the combined effect of QED and QCD corrections to the evolution of parton distributions. We extend the available knowledge of the Altarelli-Parisi splitting functions to one order higher in QED, and provide explicit expressions for the splitting kernels up to ${\\cal O}(\\alpha \\, \\alpha_{\\mathrm{S}})$. The results provided in this article allow to perform a parton distribution function analysis reaching full NLO QCD-QED combined precision.

  16. Electrochemical water-splitting based on hypochlorite oxidation.

    Science.gov (United States)

    Macounová, Kate?ina Minhová; Simic, Nina; Ahlberg, Elisabet; Krtil, Petr

    2015-06-17

    Effective catalytic water-splitting can be electrochemically triggered in an alkaline solution of sodium hypochlorite. Hypochlorite oxidation on polycrystalline platinum yields ClO· radicals, which initiate a radical-assisted water-splitting, yielding oxygen, hydrogen peroxide, and protons. The efficiency of the O2 production corresponds to about two electrons per molecule of the produced O2 and is controlled primarily by the hypochlorite concentration and pH. PMID:26030185

  17. Split Octonion electrodynamics and unified fields of dyons

    International Nuclear Information System (INIS)

    Split octonion electrodynamics has been developed in terms of Zorn's vector matrix realization by reformulating electromagnetic potential, current, field tensor and other dynamical quantities. Corresponding field equation (Unified Maxwell's equations) and equation of motion have been reformulated by means of split octonion and its Zorn vector realization in unique, simpler and consistent manner. It has been shown that this theory reproduces the dyon field equations in the absence of gravito-dyons and vice versa

  18. Kac-Moody groups split and relative theories. Lattices

    CERN Document Server

    Rémy, B

    2002-01-01

    In this survey article, we recall some facts about split Kac-Moody groups as defined by J. Tits, describe their main properties and then propose an analogue of Borel-Tits theory for a non-split version of them. The main result is a Galois descent theorem, i.e. the persistence of a nice combinatorial structure after passing to rational points. We are also interested in the geometric point of view, namely the production of new buildings admitting (nonuniform) lattices.

  19. Defense on Split-Network Attack in Wireless Sensor Network

    OpenAIRE

    Ma Li; Du Chunlai; hang Jianshun

    2012-01-01

    Wireless Sensor Network is an open self-organized network, which faces serious challenge. Whole network can be split up into many separate subnets which cannot communicate with each other because some vital sensor nodes are attacked. A defense scheme which based on frequency hopping and fast network integration wasproposed to react against split-network attack. Frequency hopping makes the communication frequency of the network escape from attack frequency while fast network integration makes ...

  20. Hydrogen Production from Semiconductor-based Photocatalysis via Water Splitting

    Directory of Open Access Journals (Sweden)

    Jeffrey C. S. Wu

    2012-10-01

    Full Text Available Hydrogen is the ideal fuel for the future because it is clean, energy efficient, and abundant in nature. While various technologies can be used to generate hydrogen, only some of them can be considered environmentally friendly. Recently, solar hydrogen generated via photocatalytic water splitting has attracted tremendous attention and has been extensively studied because of its great potential for low-cost and clean hydrogen production. This paper gives a comprehensive review of the development of photocatalytic water splitting for generating hydrogen, particularly under visible-light irradiation. The topics covered include an introduction of hydrogen production technologies, a review of photocatalytic water splitting over titania and non-titania based photocatalysts, a discussion of the types of photocatalytic water-splitting approaches, and a conclusion for the current challenges and future prospects of photocatalytic water splitting. Based on the literatures reported here, the development of highly stable visible–light-active photocatalytic materials, and the design of efficient, low-cost photoreactor systems are the key for the advancement of solar-hydrogen production via photocatalytic water splitting in the future.

  1. Recent developments in solar H2 generation from water splitting

    Indian Academy of Sciences (India)

    Sivaraman Rajaambal; Kumarsrinivasan Sivaranjani; Chinnakonda S Gopinath

    2015-01-01

    Hydrogen production from water and sunlight through photocatalysis could become one of the channels, in the not-so-distant future, to meet a part of ever growing energy demands. However, accomplishing solar water splitting through semiconductor particulate photocatalysis seems to be the ‘Holy Grail’ problem of science. In the present mini-review, some of the critical strategies of semiconductor photocatalysis are focused with the aim of enumerating underlying critical factors such as visible light harvesting, charge carrier separation, conduction and their utilization that determine the quantum efficiency. We attempted to bring out the essential requirements expected in a material for facile water splitting by explaining important and new designs contributed in the last decade. The newly emerged designs in semiconductor architecture employing nanoscience towards meeting the critical factors of facile photocatalysis are elucidated. The importance of band gap engineering is emphasized to utilize potential wide band gap semiconductors. Assistance of metal nanostructures and quantum dots to semiconductors attains vital importance as they are exuberant visible light harvesters and charge carrier amplifiers. Benevolent use of quantum dots in solar water splitting and photoelectrochemical water splitting provides scope to revolutionize the quantum efficiency by its multiple exciton generation features. A list of drawbacks and issues that hamper the much needed breakthrough in photocatalysis of water splitting is provided to invite attention to address them and move towards sustainable water splitting.

  2. The Glycosylphosphatidyl Inositol-Anchored Adhesion Molecule F3/Contactin Is Required for Surface Transport of Paranodin/Contactin-Associated Protein (Caspr)

    OpenAIRE

    Faivre-Sarrailh, Catherine; Gauthier, France; Denisenko-Nehrbass, Natalia; Le Bivic, André; Rougon, Geneviève; Girault, Jean-Antoine

    2000-01-01

    Paranodin/contactin-associated protein (caspr) is a transmembrane glycoprotein of the neurexin superfamily that is highly enriched in the paranodal regions of myelinated axons. We have investigated the role of its association with F3/contactin, a glycosylphosphatidyl inositol (GPI)-anchored neuronal adhesion molecule of the Ig superfamily. Paranodin was not expressed at the cell surface when transfected alone in CHO or neuroblastoma cells. Cotransfection with F3 resulted in plasma membrane de...

  3. Increased interleukin-6 correlates with myelin oligodendrocyte glycoprotein antibodies in pediatric monophasic demyelinating diseases and multiple sclerosis.

    Science.gov (United States)

    Horellou, Philippe; Wang, Min; Keo, Vixra; Chrétien, Pascale; Serguera, Ché; Waters, Patrick; Deiva, Kumaran

    2015-12-15

    Acquired demyelinating syndromes (ADS) in children evolve either as a monophasic disease diagnosed as acute demyelinating encephalomyelitis (ADEM), transverse myelitis (TM) or optic neuritis (ON), or a multiphasic one with several relapses most often leading to the diagnosis of multiple sclerosis (MS) or neuromyelitis optica (NMO). These neuroinflammatory disorders are increasingly associated with autoantibodies against proteins such as aquaporin-4 in rare instances, and more frequently against myelin oligodendrocyte glycoprotein (MOG). Recently, in adult NMO patients, C5a levels were shown to be elevated in cerebrospinal fluid (CSF) during acute exacerbation. We investigated the CSF levels of anaphylatoxins and pro-inflammatory cytokines, and plasma MOG antibodies in onset samples from children with ADS. Thirty four children presenting with a first episode of ADS, 17 with monophasic ADS (9 with ADEM, 4 with TM and 4 with ON) and 17 with MS, who had paired blood and CSF samples at onset were included and compared to 12 patients with other non-inflammatory neurological disorders (OND). Cytokines and anaphylatoxins in CSF were measured by Cytometric Bead Array immunoassay. MOG antibody titers in plasma were tested by flow cytometry using a stable cell line expressing full-length human MOG. We found a significant increase in C5a levels in the CSF of patients with monophasic ADS (n=17) compared to OND (n=12, p=0.0036) and to MS (n=17, p=0.0371). The C5a levels in MS were higher than in OND without reaching significance (p=0.2). CSF IL-6 levels were significantly increased in monophasic ADS compared to OND (p=0.0027) and to MS (p=0.0046). MOG antibody plasma levels were significantly higher in monophasic ADS (pMOG antibodies and CSF IL-6 levels were significantly correlated (r=0.51, p=0.018). CSF C5a and IL-6 levels are increased in monophasic ADS but not in MS when compared to OND, suggesting that these markers may help to predict monophasic or relapsing fate of ADS at onset. MOG antibody titers, which were higher in monophasic ADS than in MS, correlated with IL-6 levels, but not with C5a, suggesting an association between MOG antibodies and neuroinflammation in pediatric ADS. PMID:26616865

  4. Evidence in chronic fatigue syndrome for severity-dependent upregulation of prefrontal myelination that is independent of anxiety and depression.

    Science.gov (United States)

    Barnden, Leighton R; Crouch, Benjamin; Kwiatek, Richard; Burnet, Richard; Del Fante, Peter

    2015-03-01

    White matter (WM) involvement in chronic fatigue syndrome (CFS) was assessed using voxel-based regressions of brain MRI against CFS severity scores and CFS duration in 25 subjects with CFS and 25 normal controls (NCs). As well as voxel-based morphometry, a novel voxel-based quantitative analysis of T1 - and T2 -weighted spin-echo (T1w and T2w) MRI signal level was performed. Severity scores included the Bell CFS disability scale and scores based on the 10 most common CFS symptoms. Hospital Anxiety and Depression Scale (HADS) depression and anxiety scores were included as nuisance covariates. By relaxing the threshold for cluster formation, we showed that the T1w signal is elevated with increasing CFS severity in the ventrolateral thalamus, internal capsule and prefrontal WM. Earlier reports of WM volume losses and neuroinflammation in the midbrain, together with the upregulated prefrontal myelination suggested here, are consistent with the midbrain changes being associated with impaired nerve conduction which stimulates a plastic response on the cortical side of the thalamic relay in the same circuits. The T2w signal versus CFS duration and comparison of T2w signal in the CFS group with the NC group revealed changes in the right middle temporal lobe WM, where impaired communication can affect cognitive function. Adjustment for depression markedly strengthened cluster statistics and increased cluster size in both T1w severity regressions, but adjustment for anxiety less so. Thus, depression and anxiety are statistical confounders here, meaning that they contribute variance to the T1w signal in prefrontal WM but this does not correlate with the co-located variance from CFS severity. MRI regressions with depression itself only detected associations with WM volume, also located in prefrontal WM. We propose that impaired reciprocal brain-body and brain-brain communication through the midbrain provokes peripheral and central responses which contribute to CFS symptoms. Although anxiety, depression and CFS may share biological features, the present evidence indicates that CFS is a distinct disorder. PMID:25702943

  5. GABA and its B-receptor are present at the node of Ranvier in a small population of sensory fibers, implicating a role in myelination

    DEFF Research Database (Denmark)

    Corell, Mikael; Wicher, Grzegorz

    2015-01-01

    The ?-aminobutyric acid (GABA) type B receptor has been implicated in glial cell development in the peripheral nervous system (PNS), although the exact function of GABA signaling is not known. To investigate GABA and its B receptor in PNS development and degeneration, we studied the expression of the GABAB receptor, GABA, and glutamic acid decarboxylase GAD65/67 in both development and injury in fetal dissociated dorsal root ganglia (DRG) cell cultures and in the rat sciatic nerve. We found that GABA, GAD65/67, and the GABAB receptor were expressed in premyelinating and nonmyelinating Schwann cells throughout development and after injury. A small population of myelinated sensory fibers displayed all of these molecules at the node of Ranvier, indicating a role in axon-glia communication. Functional studies using GABAB receptor agonists and antagonists were performed in fetal DRG primary cultures to study the function of this receptor during development. The results show that GABA, via its B receptor, is involved in the myelination process but not in Schwann cell proliferation. The data from adult nerves suggest additional roles in axon-glia communication after injury.

  6. Rational Design and Synthesis of Altered Peptide Ligands based on Human Myelin Oligodendrocyte Glycoprotein 35–55 Epitope: Inhibition of Chronic Experimental Autoimmune Encephalomyelitis in Mice

    Directory of Open Access Journals (Sweden)

    Theodore Tselios

    2014-11-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is a demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS. Although the etiology of MS remains unclear, there is evidence T-cell recognition of immunodominant epitopes of myelin proteins, such as the 35–55 epitope of myelin oligodendrocyte glycoprotein (MOG, plays a pathogenic role in the induction of chronic EAE. Cyclization of peptides is of great interest since the limited stability of linear peptides restricts their potential use as therapeutic agents. Herein, we have designed and synthesized a number of linear and cyclic peptides by mutating crucial T cell receptor (TCR contact residues of the human MOG35–55 epitope. In particular, we have designed and synthesized cyclic altered peptide ligands (APLs by mutating Arg41 with Ala or Arg41 and Arg46 with Ala. The peptides were synthesized in solid phase on 2-chlorotrityl chloride resin (CLTR-Cl using the Fmoc/t-Bu methodology. The purity of final products was verified by RP-HPLC and their identification was achieved by ESI-MS. It was found that the substitutions of Arg at positions 41 and 46 with Ala results in peptide analogues that reduce the severity of MOG-induced EAE clinical symptoms in C57BL/6 mice when co-administered with mouse MOG35–55 peptide at the time of immunization.

  7. Rational design and synthesis of altered peptide ligands based on human myelin oligodendrocyte glycoprotein 35-55 epitope: inhibition of chronic experimental autoimmune encephalomyelitis in mice.

    Science.gov (United States)

    Tselios, Theodore; Aggelidakis, Mihalis; Tapeinou, Anthi; Tseveleki, Vivian; Kanistras, Ioannis; Gatos, Dimitrios; Matsoukas, John

    2014-01-01

    Experimental autoimmune encephalomyelitis (EAE) is a demyelinating disease of the central nervous system and is an animal model of multiple sclerosis (MS). Although the etiology of MS remains unclear, there is evidence T-cell recognition of immunodominant epitopes of myelin proteins, such as the 35-55 epitope of myelin oligodendrocyte glycoprotein (MOG), plays a pathogenic role in the induction of chronic EAE. Cyclization of peptides is of great interest since the limited stability of linear peptides restricts their potential use as therapeutic agents. Herein, we have designed and synthesized a number of linear and cyclic peptides by mutating crucial T cell receptor (TCR) contact residues of the human MOG35-55 epitope. In particular, we have designed and synthesized cyclic altered peptide ligands (APLs) by mutating Arg41 with Ala or Arg41 and Arg46 with Ala. The peptides were synthesized in solid phase on 2-chlorotrityl chloride resin (CLTR-Cl) using the Fmoc/t-Bu methodology. The purity of final products was verified by RP-HPLC and their identification was achieved by ESI-MS. It was found that the substitutions of Arg at positions 41 and 46 with Ala results in peptide analogues that reduce the severity of MOG-induced EAE clinical symptoms in C57BL/6 mice when co-administered with mouse MOG35-55 peptide at the time of immunization. PMID:25375337

  8. Expression, purification, and initial characterization of different domains of recombinant mouse 2',3'-cyclic nucleotide 3'-phosphodiesterase, an enigmatic enzyme from the myelin sheath

    Directory of Open Access Journals (Sweden)

    Kursula Petri

    2010-01-01

    Full Text Available Abstract Background 2',3'-cyclic nucleotide 3'-phosphodiesterase (CNPase is an enigmatic enzyme specifically expressed at high levels in the vertebrate myelin sheath, whose function and physiological substrates are unknown. The protein consists of two domains: an uncharacterized N-terminal domain with little homology to other proteins, and a C-terminal phosphodiesterase domain. Findings In order to be able to fully characterize CNPase structurally and functionally, we have set up expression systems for different domains of CNPase, using a total of 18 different expression constructs. CNPase was expressed in E. coli with a TEV-cleavable His-tag. Enzymatic activity assays indicated that the purified proteins were active and correctly folded. The folding of both the full-length protein, as well as the N- and C-terminal domains, was also studied by synchrotron CD spectroscopy. A thermal shift assay was used to optimize buffer compositions to be used during purification and storage. The assay also indicated that CNPase was most stable at a pH of 5.5, and could be significantly stabilized by high salt concentrations. Conclusions We have been able to express and purify recombinantly several different domains of CNPase, including the isolated N-terminal domain, which is folded mainly into a ?-sheet structure. The expression system can be used as an efficient tool to elucidate the role of CNPase in the myelin sheath.

  9. Curcumin treatment abrogates endoplasmic reticulum retention and aggregation-induced apoptosis associated with neuropathy-causing myelin protein zero-truncating mutants.

    Science.gov (United States)

    Khajavi, Mehrdad; Inoue, Ken; Wiszniewski, Wojciech; Ohyama, Tomoko; Snipes, G Jackson; Lupski, James R

    2005-11-01

    Mutations in MPZ, the gene encoding myelin protein zero (MPZ), the major protein constituent of peripheral myelin, can cause the adult-onset, inherited neuropathy Charcot-Marie-Tooth disease, as well as the more severe, childhood-onset Dejerine-Sottas neuropathy and congenital hypomyelinating neuropathy. Most MPZ-truncating mutations associated with severe forms of peripheral neuropathy result in premature termination codons within the terminal or penultimate exons that are not subject to nonsense-mediated decay and are stably translated into mutant proteins with potential dominant-negative activity. However, some truncating mutations at the 3' end of MPZ escape the nonsense-mediated decay pathway and cause a mild peripheral neuropathy phenotype. We examined the functional properties of MPZ-truncating proteins that escaped nonsense-mediated decay, and we found that frameshift mutations associated with severe disease cause an intracellular accumulation of mutant proteins, primarily within the endoplasmic reticulum (ER), which induces apoptosis. Curcumin, a chemical compound derived from the curry spice tumeric, releases the ER-retained MPZ mutants into the cytoplasm accompanied by a lower number of apoptotic cells. Our findings suggest that curcumin treatment is sufficient to relieve the toxic effect of mutant aggregation-induced apoptosis and may potentially have a therapeutic role in treating selected forms of inherited peripheral neuropathies. PMID:16252242

  10. Peripheral myelin protein 22 gene duplication with atypical presentations: a new example of the wide spectrum of Charcot-Marie-Tooth 1A disease.

    Science.gov (United States)

    Mathis, Stéphane; Corcia, Philippe; Tazir, Meriem; Camu, William; Magdelaine, Corinne; Latour, Philippe; Biberon, Julien; Guennoc, Anne-Marie; Richard, Laurence; Magy, Laurent; Funalot, Benoît; Vallat, Jean-Michel

    2014-06-01

    Charcot-Marie-Tooth type 1A (CMT1A) and hereditary neuropathy with liability to pressure palsies (HNPP) are both autosomal-dominant disorders linked to peripheral myelin anomalies. CMT1A is associated with a Peripheral Myelin Protein 22 (PMP22) duplication, whereas HNPP is due to a PMP22 deletion on chromosome 17. In spite of this crucial difference, we report three observations of patients with the 1.4 megabase CMT1A duplication and atypical presentation (electrophysiological, clinical or pathological): a 10 year-old girl with tomaculous lesions on nerve biopsy; a 26 year-old woman with recurrent paresthesiae and block conduction on the electrophysiological study; a 46 year-old woman with transient recurrent nerve palsies mimicking HNPP. These observations highlight the wide spectrum of CMT1A and the overlap between CMT1A and HNPP (both linked to the PMP22 gene), and finally illustrate the complexity of the genotype-phenotype correlations in Charcot-Marie-Tooth diseases. PMID:24792522

  11. Split Light Higgsino from Split Supersymmetry as providers of the residual SUSY effects

    CERN Document Server

    Vereshkov, G; Kuksa, V; Pasechnik, R; Vereshkov, Gregory; Beylin, Vitaliy; Kuksa, Vladimir; Pasechnik, Roman

    2005-01-01

    New version of MSSM scales is discussed. In this version mu << M_{SUSY} ~ M_0 \\~ M_{1/2}, where mu is the Higgsino mass, M_0 is the mass scale of sleptons and squarks, M_{1/2} is the mass scale of gaugino. Renormalization group motivation of this MSSM version is proposed. Analysis of Split Supersymmetry ideas in this case together with the Dark Matter arguments results in the statement that the formation of residual neutralino concentration occurs in the high symmetric phase of cosmological plasma. The value of Higgsino mass is estimated. The recharging process for high energy neutralinos in the neutralino-nucleus scattering is considered. There has been reported the possibility to check-up of the model predictions at modern experimental facilities NUSEL and GLAST.

  12. Splitting parameter yield (SPY): A program for semiautomatic analysis of shear-wave splitting

    Science.gov (United States)

    Zaccarelli, Lucia; Bianco, Francesca; Zaccarelli, Riccardo

    2012-03-01

    SPY is a Matlab algorithm that analyzes seismic waveforms in a semiautomatic way, providing estimates of the two observables of the anisotropy: the shear-wave splitting parameters. We chose to exploit those computational processes that require less intervention by the user, gaining objectivity and reliability as a result. The algorithm joins the covariance matrix and the cross-correlation techniques, and all the computation steps are interspersed by several automatic checks intended to verify the reliability of the yields. The resulting semiautomation generates two new advantages in the field of anisotropy studies: handling a huge amount of data at the same time, and comparing different yields. From this perspective, SPY has been developed in the Matlab environment, which is widespread, versatile, and user-friendly. Our intention is to provide the scientific community with a new monitoring tool for tracking the temporal variations of the crustal stress field.

  13. Experimental study on dynamic splitting of recycled concrete using SHPB

    Science.gov (United States)

    Lu, Yubin; Yu, Shuisheng; Cai, Yong

    2015-09-01

    To study the recycled concrete splitting tensile properties and fracture state with various recycled coarse aggregate replacement percentage (i.e. 0%, 25%, 50%, 75% and 100%), the dynamic splitting test of recycled concrete was carried out using large diameter (75 mm) split Hopkinson pressure bar (SHPB). The results show that the recycled concrete splitting tensile strength increases with the increase of loading rate, and the loading rate also affects the recycled concrete fracture state, which indicates that the recycled concrete has obvious rate sensitivity. The damage state of the recycled concrete is not only the destruction of the interface between coarse aggregate and cement mortar, but also associates with the fracture damage of aggregates. Under the same water cement ratio, when the replacement percentage of coarse aggregates is around 50%-75%, the gradation of natural and recycled coarse aggregate is optimal, and thus the splitting tensile strength is the largest. This study offers theoretical basis for the engineering applications of recycled concrete.

  14. Nanoparticle Superlattices as Efficient Bifunctional Electrocatalysts for Water Splitting.

    Science.gov (United States)

    Li, Jun; Wang, Yongcheng; Zhou, Tong; Zhang, Hui; Sun, Xuhui; Tang, Jing; Zhang, Lijuan; Al-Enizi, Abdullah M; Yang, Zhongqin; Zheng, Gengfeng

    2015-11-18

    The solar-driven water splitting process is highly attractive for alternative energy utilization, while developing efficient, earth-abundant, bifunctional catalysts for both oxygen evolution reaction and hydrogen evolution reaction has remained as a major challenge. Herein, we develop an ordered CoMnO@CN superlattice structure as an efficient bifunctional water-splitting electrocatalyst, in which uniform Co-Mn oxide (CoMnO) nanoparticles are coated with a thin, continuous nitrogen-doped carbon (CN) framework. The CoMnO nanoparticles enable optimized OER activity with effective electronic structure configuration, and the CN framework serves as an excellent HER catalyst. Importantly, the ordered superlattice structure is beneficial for enhanced reactive sites, efficient charge transfer, and structural stability. This bifunctional superlattice catalyst manifests optimized current densities and electrochemical stability in overall water splitting, outperforming most of the previously reported single- or bifunctional electrocatalysts. Combining with a silicon photovoltaic cell, this CoMnO@CN superlattice bifunctional catalyst enables unassisted solar water splitting continuously for ?5 days with a solar-to-hydrogen conversion efficiency of ?8.0%. Our discovery suggests that these transition metal oxide-based superlattices may serve as a unique structure modality for efficient bifunctional water splitting electrocatalysts with scale-up potentials. PMID:26496655

  15. Distribution of split DnaE inteins in cyanobacteria.

    Science.gov (United States)

    Caspi, Jonathan; Amitai, Gil; Belenkiy, Olga; Pietrokovski, Shmuel

    2003-12-01

    Inteins are genetic elements found inside the coding regions of different host proteins and are translated in frame with them. The intein-encoded protein region is removed by an autocatalytic protein-splicing reaction that ligates the host protein flanks with a peptide bond. This reaction can also occur in trans with the intein and host protein split in two. After translation of the two genes, the two intein parts ligate their flanking protein parts to each other, producing the mature protein. Naturally split inteins are only known in the DNA polymerase III alpha subunit (polC or dnaE gene) of a few cyanobacteria. Analysing the phylogenetic distribution and probable genetic propagation mode of these split inteins, we conclude that they are genetically fixed in several large cyanobacterial lineages. To test our hypothesis, we sequenced parts of the dnaE genes from five diverse cyanobacteria and found all species to have the same type of split intein. Our results suggest the occurrence of a genetic rearrangement in the ancestor of a large division of cyanobacteria. This event fixed the dnaE gene in a unique two-genes one-protein configuration in the progenitor of many cyanobacteria. Our hypothesis, findings and the cloning procedure that we established allow the identification and acquisition of many naturally split inteins. Having a large and diverse repertoire of these unique inteins will enable studies of their distinct activity and enhance their use in biotechnology. PMID:14651639

  16. Nonlinear split-ring metamaterial slabs for magnetic resonance imaging

    Science.gov (United States)

    Lopez, Marcos A.; Freire, Manuel J.; Algarin, Jose M.; Behr, Volker C.; Jakob, Peter M.; Marqués, Ricardo

    2011-03-01

    This work analyzes the ability of split-ring metamaterial slabs with zero/high permeability to reject/confine the radiofrequency magnetic field in magnetic resonance imaging systems. Split-ring slabs are designed and fabricated to work in a 1.5 T system. Nonlinear elements consisting of pairs of crossed diodes are inserted in the split-rings, so that the slab permeability can be switched between a value close to unity when interacting with the strong field of the transmitting coil, and zero or high values when interacting with the weak field produced by protons in tissue. Experiments are shown where these slabs locally increase the signal-to-noise-ratio.

  17. Active split-ring metamaterial slabs for magnetic resonance imaging

    CERN Document Server

    Lopez, Marcos A; Freire, Manuel J; Behr, Volker C; Jakob, Peter M; Marques, Ricardo

    2011-01-01

    In this work, it is analyzed the ability of split-ring metamaterial slabs with zero/high permeability to reject/confine the radiofrequency magnetic field in magnetic resonance imaging systems. Using an homogenization procedure, split-ring slabs have been designed and fabricated to work in a 1.5T system. Active elements consisting of pairs of crossed diodes are inserted in the split-rings. With these elements, the permeability of the slabs can be automatically switched between a unity value when interacting with the strong excitation field of the transmitting body coil, and zero or high values when interacting with the weak field produced by protons in tissue. Experiments are shown for different configurations where these slabs can help to locally increase the signal-to-noise-ratio.

  18. Enabling unassisted solar water splitting by iron oxide and silicon

    Science.gov (United States)

    Jang, Ji-Wook; Du, Chun; Ye, Yifan; Lin, Yongjing; Yao, Xiahui; Thorne, James; Liu, Erik; McMahon, Gregory; Zhu, Junfa; Javey, Ali; Guo, Jinghua; Wang, Dunwei

    2015-06-01

    Photoelectrochemical (PEC) water splitting promises a solution to the problem of large-scale solar energy storage. However, its development has been impeded by the poor performance of photoanodes, particularly in their capability for photovoltage generation. Many examples employing photovoltaic modules to correct the deficiency for unassisted solar water splitting have been reported to-date. Here we show that, by using the prototypical photoanode material of haematite as a study tool, structural disorders on or near the surfaces are important causes of the low photovoltages. We develop a facile re-growth strategy to reduce surface disorders and as a consequence, a turn-on voltage of 0.45 V (versus reversible hydrogen electrode) is achieved. This result permits us to construct a photoelectrochemical device with a haematite photoanode and Si photocathode to split water at an overall efficiency of 0.91%, with NiFeOx and TiO2/Pt overlayers, respectively.

  19. Confidence sets for split points in decision trees

    CERN Document Server

    Banerjee, Moulinath

    2007-01-01

    We investigate the problem of finding confidence sets for split points in decision trees (CART). Our main results establish the asymptotic distribution of the least squares estimators and some associated residual sum of squares statistics in a binary decision tree approximation to a smooth regression curve. Cube-root asymptotics with nonnormal limit distributions are involved. We study various confidence sets for the split point, one calibrated using the subsampling bootstrap, and others calibrated using plug-in estimates of some nuisance parameters. The performance of the confidence sets is assessed in a simulation study. A motivation for developing such confidence sets comes from the problem of phosphorus pollution in the Everglades. Ecologists have suggested that split points provide a phosphorus threshold at which biological imbalance occurs, and the lower endpoint of the confidence set may be interpreted as a level that is protective of the ecosystem. This is illustrated using data from a Duke University...

  20. Anisotropic merging and splitting of dipolar Bose–Einstein condensates

    International Nuclear Information System (INIS)

    We study the merging and splitting of quasi-two-dimensional Bose–Einstein condensates with strong dipolar interactions. We observe that if the dipoles have a non-zero component in the plane of the condensate, the dynamics of merging or splitting along two orthogonal directions, parallel and perpendicular to the projection of dipoles on the plane of the condensate, are different. The anisotropic merging and splitting of the condensate is a manifestation of the anisotropy of the roton-like mode in the dipolar system. The difference in dynamics disappears if the dipoles are oriented at right angles to the plane of the condensate as in this case the Bogoliubov dispersion, despite having roton-like features, is isotropic. (paper)