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Sample records for aberrant axon pathfinding

  1. Perturbations of microRNA function in mouse dicer mutants produce retinal defects and lead to aberrant axon pathfinding at the optic chiasm.

    Rita Pinter

    Full Text Available BACKGROUND: During development axons encounter a variety of choice points where they have to make appropriate pathfinding decisions. The optic chiasm is a major decision point for retinal ganglion cell (RGC axons en route to their target in order to ensure the correct wiring of the visual system. MicroRNAs (miRNAs belong to the class of small non-coding RNA molecules and have been identified as important regulators of a variety of processes during embryonic development. However, their involvement in axon guidance decisions is less clear. METHODOLOGY/PRINCIPAL FINDINGS: We report here that the early loss of Dicer, an essential protein for the maturation of miRNAs, in all cells of the forming retina and optic chiasm leads to severe phenotypes of RGC axon pathfinding at the midline. Using a conditional deletion approach in mice, we find in homozygous Dicer mutants a marked increase of ipsilateral projections, RGC axons extending outside the optic chiasm, the formation of a secondary optic tract and a substantial number of RGC axons projecting aberrantly into the contralateral eye. In addition, the mutant mice display a microphthalmia phenotype. CONCLUSIONS: Our work demonstrates an important role of Dicer controlling the extension of RGC axons to the brain proper. It indicates that miRNAs are essential regulatory elements for mechanisms that ensure correct axon guidance decisions at the midline and thus have a central function in the establishment of circuitry during the development of the nervous system.

  2. Ascending Midbrain Dopaminergic Axons Require Descending GAD65 Axon Fascicles for Normal Pathfinding

    Claudia Marcela Garcia-Peña

    2014-06-01

    Full Text Available The Nigrostriatal pathway (NSP is formed by dopaminergic axons that project from the ventral midbrain to the dorsolateral striatum as part of the medial forebrain bundle. Previous studies have implicated chemotropic proteins in the formation of the NSP during development but little is known of the role of substrate-anchored signals in this process. We observed in mouse and rat embryos that midbrain dopaminergic axons ascend in close apposition to descending GAD65-positive axon bundles throughout their trajectory to the striatum. To test whether such interaction is important for dopaminergic axon pathfinding, we analyzed transgenic mouse embryos in which the GAD65 axon bundle was reduced by the conditional expression of the diphtheria toxin. In these embryos we observed dopaminergic misprojection into the hypothalamic region and abnormal projection in the striatum. In addition, analysis of Robo1/2 and Slit1/2 knockout embryos revealed that the previously described dopaminergic misprojection in these embryos is accompanied by severe alterations in the GAD65 axon scaffold. Additional studies with cultured dopaminergic neurons and whole embryos suggest that NCAM and Robo proteins are involved in the interaction of GAD65 and dopaminergic axons. These results indicate that the fasciculation between descending GAD65 axon bundles and ascending dopaminergic axons is required for the stereotypical NSP formation during brain development and that known guidance cues may determine this projection indirectly by instructing the pathfinding of the axons that are part of the GAD65 axon scaffold.

  3. Motoneuron axon pathfinding errors in zebrafish: Differential effects related to concentration and timing of nicotine exposure

    Menelaou, Evdokia; Paul, Latoya T. [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Perera, Surangi N. [Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States); Svoboda, Kurt R., E-mail: svobodak@uwm.edu [Department of Biological Sciences, Louisiana State University, Baton Rouge, LA 70803 (United States); Joseph J. Zilber School of Public Health, University of Wisconsin — Milwaukee, Milwaukee, WI 53205 (United States)

    2015-04-01

    Nicotine exposure during embryonic stages of development can affect many neurodevelopmental processes. In the developing zebrafish, exposure to nicotine was reported to cause axonal pathfinding errors in the later born secondary motoneurons (SMNs). These alterations in SMN axon morphology coincided with muscle degeneration at high nicotine concentrations (15–30 μM). Previous work showed that the paralytic mutant zebrafish known as sofa potato exhibited nicotine-induced effects onto SMN axons at these high concentrations but in the absence of any muscle deficits, indicating that pathfinding errors could occur independent of muscle effects. In this study, we used varying concentrations of nicotine at different developmental windows of exposure to specifically isolate its effects onto subpopulations of motoneuron axons. We found that nicotine exposure can affect SMN axon morphology in a dose-dependent manner. At low concentrations of nicotine, SMN axons exhibited pathfinding errors, in the absence of any nicotine-induced muscle abnormalities. Moreover, the nicotine exposure paradigms used affected the 3 subpopulations of SMN axons differently, but the dorsal projecting SMN axons were primarily affected. We then identified morphologically distinct pathfinding errors that best described the nicotine-induced effects on dorsal projecting SMN axons. To test whether SMN pathfinding was potentially influenced by alterations in the early born primary motoneuron (PMN), we performed dual labeling studies, where both PMN and SMN axons were simultaneously labeled with antibodies. We show that only a subset of the SMN axon pathfinding errors coincided with abnormal PMN axonal targeting in nicotine-exposed zebrafish. We conclude that nicotine exposure can exert differential effects depending on the levels of nicotine and developmental exposure window. - Highlights: • Embryonic nicotine exposure can specifically affect secondary motoneuron axons in a dose-dependent manner.

  4. Regenerative Responses and Axon Pathfinding of Retinal Ganglion Cells in Chronically Injured Mice

    Yungher, Benjamin J.; Ribeiro, Márcio; Park, Kevin K.

    2017-01-01

    Purpose Enhanced regeneration of retinal ganglion cell (RGC) axons can be achieved by modification of numerous neuronal-intrinsic factors. However, axon growth initiation and the pathfinding behavior of these axons after traumatic injury remain poorly understood outside of acute injury paradigms, despite the clinical relevance of more chronic settings. We therefore examined RGC axon regeneration following therapeutic delivery that is postponed until 2 months after optic nerve crush injury. Methods Optic nerve regeneration was induced by virally mediated (adeno-associated virus) ciliary neurotrophic factor (AAV-CNTF) administered either immediately or 56 days after optic nerve crush in wild-type or Bax knockout (KO) mice. Retinal ganglion nerve axon regeneration was assessed 21 and 56 days after viral injection. Immunohistochemical analysis of RGC injury signals and extrinsic factors in the optic nerve were also examined at 5 and 56 days post crush. Results In addition to sustained expression of injury response proteins in surviving RGCs, we observe axon regrowth in wild-type and apoptosis-deficient Bax KO mice following AAV-CNTF treatment. Fewer instances of aberrant axon growth are seen, at least in the area near the lesion site, in animals given treatment 56 days after crush injury compared to the animals given treatment immediately after injury. We also find evidence of long distance growth into a visual target in Bax KO mice despite postponed initiation of this regenerative program. Conclusions These studies provide evidence against an intrinsic critical period for RGC axon regeneration or degradation of injury signals. Regeneration results from Bax KO mice imply highly sustained regenerative capacity in RGCs, highlighting the importance of long-lasting neuroprotective strategies as well as of RGC axon guidance research in chronically injured animals. PMID:28324115

  5. Shh signaling guides spatial pathfinding of raphespinal tract axons by multidirectional repulsion

    Lijuan Song; Yuehui Liu; YangYu; Xin Duan; Shening Qi; Yaobo Liu

    2012-01-01

    Relatively little is known about the molecular mechanisms underlying spatial pathfinding in the descending serotonergic raphespinal tract (RST) in the developing spinal cord,one of the most important nerve pathways for pain,sensory and motor functions.We provide evidence that ventral floor plate-secreted Sonic hedgehog (Shh) is responsible for the establishment of decreasing gradients in both the anterior-to-posterior (A-P) and the medialto-lateral (M-L) directions in the ventral spinal cord during serotonergic RST axon projection.Downstream components of the Shh pathway,Patched 1 (Ptch1) and Smoothened (Smo),were expressed in the serotonergic caudal raphe nuclei and enriched in the descending serotonergic RST axons.Diffusible Shh repulsion of serotonergic RST axons was shown to be mediated by Shh-Ptch1 interactions and derepression of Smo.Using a co-culture assay,we showed that A-P graded repulsion mediated by Shh signaling pushed the serotonergic axons caudally through the ventral spinal cord and M-L graded repulsion mediated by Shh signaling simultaneously restricted the serotonergic axons to the ventral and ventral-lateral funiculus.Prominent pathfinding errors of serotonergic RST axons were observed in various Shh,Ptch1 and Smo mutants.We conclude that Shh signaling-mediated multidirectional repulsion is required to push descending serotonergic RST axons in the A-P direction,and to restrict these axons to the ventral and ventral-lateral funiculus in the M-L direction.This is the first demonstration that Shh signalingmediated muitidirectional repulsion of serotonergic RST axons maintains spatial axon pathfinding in the developing spinal cord.

  6. Shh signaling guides spatial pathfinding of raphespinal tract axons by multidirectional repulsion.

    Song, Lijuan; Liu, Yuehui; Yu, Yang; Duan, Xin; Qi, Shening; Liu, Yaobo

    2012-04-01

    Relatively little is known about the molecular mechanisms underlying spatial pathfinding in the descending serotonergic raphespinal tract (RST) in the developing spinal cord, one of the most important nerve pathways for pain, sensory and motor functions. We provide evidence that ventral floor plate-secreted Sonic hedgehog (Shh) is responsible for the establishment of decreasing gradients in both the anterior-to-posterior (A-P) and the medial-to-lateral (M-L) directions in the ventral spinal cord during serotonergic RST axon projection. Downstream components of the Shh pathway, Patched 1 (Ptch1) and Smoothened (Smo), were expressed in the serotonergic caudal raphe nuclei and enriched in the descending serotonergic RST axons. Diffusible Shh repulsion of serotonergic RST axons was shown to be mediated by Shh-Ptch1 interactions and derepression of Smo. Using a co-culture assay, we showed that A-P graded repulsion mediated by Shh signaling pushed the serotonergic axons caudally through the ventral spinal cord and M-L graded repulsion mediated by Shh signaling simultaneously restricted the serotonergic axons to the ventral and ventral-lateral funiculus. Prominent pathfinding errors of serotonergic RST axons were observed in various Shh, Ptch1 and Smo mutants. We conclude that Shh signaling-mediated multidirectional repulsion is required to push descending serotonergic RST axons in the A-P direction, and to restrict these axons to the ventral and ventral-lateral funiculus in the M-L direction. This is the first demonstration that Shh signaling-mediated multidirectional repulsion of serotonergic RST axons maintains spatial axon pathfinding in the developing spinal cord.

  7. Midline governs axon pathfinding by coordinating expression of two major guidance systems.

    Liu, Qing-Xin; Hiramoto, Masaki; Ueda, Hitoshi; Gojobori, Takashi; Hiromi, Yasushi; Hirose, Susumu

    2009-05-15

    Formation of the neural network requires concerted action of multiple axon guidance systems. How neurons orchestrate expression of multiple guidance genes is poorly understood. Here, we show that Drosophila T-box protein Midline controls expression of genes encoding components of two major guidance systems: Frazzled, ROBO, and Slit. In midline mutant, expression of all these molecules are reduced, resulting in severe axon guidance defects, whereas misexpression of Midline induces their expression. Midline is present on the promoter regions of these genes, indicating that Midline controls transcription directly. We propose that Midline controls axon pathfinding through coordinating the two guidance systems.

  8. Characterizing Semaphorin-Mediated Effects on Sensory and Motor Axon Pathfinding and Connectivity During Embryonic Development.

    Huettl, Rosa Eva; Huber, Andrea B

    2017-01-01

    How are precise connectivity to peripheral targets and corresponding sensory-motor networks established during developmental innervation of the vertebrate extremities? The formation of functional sensory-motor circuits requires highly appropriate temporal and spatial regulation of axon growth which is achieved through the combination of different molecular mechanisms such as communication between heterotypic fiber systems, axon-environment, or axon-glia interactions that ensure proper fasciculation and accurate pathfinding to distal targets. Family members of the class 3 semaphorins and their cognate receptors, the neuropilins, were shown to govern various events during wiring of central and peripheral circuits, with mice lacking Sema3-Npn signaling showing deficits in timing of growth, selective fasciculation, guidance fidelity, and coupling of sensory axon growth to motor axons at developmental time points. Given the accuracy with which these processes have to interact in a stepwise manner, deficiency of the smallest cog in the wheel may impact severely on the faithful establishment and functionality of peripheral circuitries, ultimately leading to behavioral impairments or even cause the death of the animal. Reliable quantitative analyses of sensory-motor fasciculation, extension, and guidance of axons to their cognate target muscles and the skin during development, but also assessment of physiological and behavioral consequences at adult age, are therefore a necessity to extend our understanding of the molecular mechanisms of peripheral circuit formation. In this chapter we provide a detailed methodology to characterize class 3 semaphorin-mediated effects on peripheral sensory and motor axon pathfinding and connectivity during embryonic development.

  9. Zebrafish foxP2 zinc finger nuclease mutant has normal axon pathfinding.

    Lingyan Xing

    Full Text Available foxP2, a forkhead-domain transcription factor, is critical for speech and language development in humans, but its role in the establishment of CNS connectivity is unclear. While in vitro studies have identified axon guidance molecules as targets of foxP2 regulation, and cell culture assays suggest a role for foxP2 in neurite outgrowth, in vivo studies have been lacking regarding a role for foxP2 in axon pathfinding. We used a modified zinc finger nuclease methodology to generate mutations in the zebrafish foxP2 gene. Using PCR-based high resolution melt curve analysis (HRMA of G0 founder animals, we screened and identified three mutants carrying nonsense mutations in the 2(nd coding exon: a 17 base-pair (bp deletion, an 8bp deletion, and a 4bp insertion. Sequence analysis of cDNA confirmed that these were frameshift mutations with predicted early protein truncations. Homozygous mutant fish were viable and fertile, with unchanged body morphology, and no apparent differences in CNS apoptosis, proliferation, or patterning at embryonic stages. There was a reduction in expression of the known foxP2 target gene cntnap2 that was rescued by injection of wild-type foxP2 transcript. When we examined axon pathfinding using a pan-axonal marker or transgenic lines, including a foxP2-neuron-specific enhancer, we did not observe any axon guidance errors. Our findings suggest that foxP2 is not necessary for axon pathfinding during development.

  10. The fax-1 nuclear hormone receptor regulates axon pathfinding and neurotransmitter expression.

    Much, J W; Slade, D J; Klampert, K; Garriga, G; Wightman, B

    2000-02-01

    Specification of neuron identity requires the activation of a number of discrete developmental programs. Among these is pathway selection by growth cones: in order for a neuron's growth cone to respond appropriately to guidance cues presented by other cells or the extracellular matrix, the neuron must express genes to mediate the response. The fax-1 gene of C. elegans is required for pathfinding of axons that extend along the ventral nerve cord. We show that fax-1 is also required for pathfinding of axons in the nerve ring, the largest nerve bundle in the nematode, and for normal expression of FMRFamide-like neurotransmitters in the AVK interneurons. The fax-1 gene encodes a member of the superfamily of nuclear hormone receptors and has a DNA-binding domain related to the human PNR and Drosophila Tailless proteins. We observe fax-1 expression in embryonic neurons, including the AVK interneurons, just prior to axon extension, but after neurogenesis. These data suggest that fax-1 coordinately regulates the transcription of genes that function in the selection of axon pathways, neurotransmitter expression and, perhaps, other aspects of the specification of neuron identity.

  11. Influence of brain-derived neurotrophic factor on pathfinding of dentate granule cell axons, the hippocampal mossy fibers.

    Tamura, Makoto; Tamura, Naohiro; Ikeda, Takamitsu; Koyama, Ryuta; Ikegaya, Yuji; Matsuki, Norio; Yamada, Maki K

    2009-01-31

    Mossy fibers, the dentate granule cell axons, are generated throughout an animal's lifetime. Mossy fiber paths and synapses are primarily restricted to the stratum lucidum within the CA3 region. Brain-derived neurotrophic factor (BDNF), a neurotrophin family protein that activates Trk neurotrophin receptors, is highly expressed in the stratum lucidum in an activity-dependent manner. The addition of a Trk neurotrophin receptor inhibitor, K252a, to cultured hippocampal slices induced aberrant extension of mossy fibers into ectopic regions. BDNF overexpression in granule cells ameliorated the mossy fiber pathway abnormalities caused by a submaximal dose of K252a. A similar rescue was observed when BDNF was expressed in CA3 pyramidal cells, most notably in mossy fibers distal to the expression site. These findings are the first to clarify the role of BDNF in mossy fiber pathfinding, not as an attractant cue but as a regulator, possibly acting in a paracrine manner. This effect of BDNF may be as a signal for new fibers to fasciculate and extend further to form synapses with neurons that are far from active BDNF-expressing synapses. This mechanism would ensure the emergence of new independent dentate gyrus-CA3 circuits by the axons of new-born granule cells.

  12. Influence of brain-derived neurotrophic factor on pathfinding of dentate granule cell axons, the hippocampal mossy fibers

    Tamura Makoto

    2009-01-01

    Full Text Available Abstract Mossy fibers, the dentate granule cell axons, are generated throughout an animal's lifetime. Mossy fiber paths and synapses are primarily restricted to the stratum lucidum within the CA3 region. Brain-derived neurotrophic factor (BDNF, a neurotrophin family protein that activates Trk neurotrophin receptors, is highly expressed in the stratum lucidum in an activity-dependent manner. The addition of a Trk neurotrophin receptor inhibitor, K252a, to cultured hippocampal slices induced aberrant extension of mossy fibers into ectopic regions. BDNF overexpression in granule cells ameliorated the mossy fiber pathway abnormalities caused by a submaximal dose of K252a. A similar rescue was observed when BDNF was expressed in CA3 pyramidal cells, most notably in mossy fibers distal to the expression site. These findings are the first to clarify the role of BDNF in mossy fiber pathfinding, not as an attractant cue but as a regulator, possibly acting in a paracrine manner. This effect of BDNF may be as a signal for new fibers to fasciculate and extend further to form synapses with neurons that are far from active BDNF-expressing synapses. This mechanism would ensure the emergence of new independent dentate gyrus-CA3 circuits by the axons of new-born granule cells.

  13. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes.

    Biankin, Andrew V; Waddell, Nicola; Kassahn, Karin S; Gingras, Marie-Claude; Muthuswamy, Lakshmi B; Johns, Amber L; Miller, David K; Wilson, Peter J; Patch, Ann-Marie; Wu, Jianmin; Chang, David K; Cowley, Mark J; Gardiner, Brooke B; Song, Sarah; Harliwong, Ivon; Idrisoglu, Senel; Nourse, Craig; Nourbakhsh, Ehsan; Manning, Suzanne; Wani, Shivangi; Gongora, Milena; Pajic, Marina; Scarlett, Christopher J; Gill, Anthony J; Pinho, Andreia V; Rooman, Ilse; Anderson, Matthew; Holmes, Oliver; Leonard, Conrad; Taylor, Darrin; Wood, Scott; Xu, Qinying; Nones, Katia; Fink, J Lynn; Christ, Angelika; Bruxner, Tim; Cloonan, Nicole; Kolle, Gabriel; Newell, Felicity; Pinese, Mark; Mead, R Scott; Humphris, Jeremy L; Kaplan, Warren; Jones, Marc D; Colvin, Emily K; Nagrial, Adnan M; Humphrey, Emily S; Chou, Angela; Chin, Venessa T; Chantrill, Lorraine A; Mawson, Amanda; Samra, Jaswinder S; Kench, James G; Lovell, Jessica A; Daly, Roger J; Merrett, Neil D; Toon, Christopher; Epari, Krishna; Nguyen, Nam Q; Barbour, Andrew; Zeps, Nikolajs; Kakkar, Nipun; Zhao, Fengmei; Wu, Yuan Qing; Wang, Min; Muzny, Donna M; Fisher, William E; Brunicardi, F Charles; Hodges, Sally E; Reid, Jeffrey G; Drummond, Jennifer; Chang, Kyle; Han, Yi; Lewis, Lora R; Dinh, Huyen; Buhay, Christian J; Beck, Timothy; Timms, Lee; Sam, Michelle; Begley, Kimberly; Brown, Andrew; Pai, Deepa; Panchal, Ami; Buchner, Nicholas; De Borja, Richard; Denroche, Robert E; Yung, Christina K; Serra, Stefano; Onetto, Nicole; Mukhopadhyay, Debabrata; Tsao, Ming-Sound; Shaw, Patricia A; Petersen, Gloria M; Gallinger, Steven; Hruban, Ralph H; Maitra, Anirban; Iacobuzio-Donahue, Christine A; Schulick, Richard D; Wolfgang, Christopher L; Morgan, Richard A; Lawlor, Rita T; Capelli, Paola; Corbo, Vincenzo; Scardoni, Maria; Tortora, Giampaolo; Tempero, Margaret A; Mann, Karen M; Jenkins, Nancy A; Perez-Mancera, Pedro A; Adams, David J; Largaespada, David A; Wessels, Lodewyk F A; Rust, Alistair G; Stein, Lincoln D; Tuveson, David A; Copeland, Neal G; Musgrove, Elizabeth A; Scarpa, Aldo; Eshleman, James R; Hudson, Thomas J; Sutherland, Robert L; Wheeler, David A; Pearson, John V; McPherson, John D; Gibbs, Richard A; Grimmond, Sean M

    2012-11-15

    Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.

  14. Coexpression of high-voltage-activated ion channels Kv3.4 and Cav1.2 in pioneer axons during pathfinding in the developing rat forebrain.

    Huang, Chia-Yi; Chu, Dachen; Hwang, Wei-Chao; Tsaur, Meei-Ling

    2012-11-01

    Precise axon pathfinding is crucial for establishment of the initial neuronal network during development. Pioneer axons navigate without the help of preexisting axons and pave the way for follower axons that project later. Voltage-gated ion channels make up the intrinsic electrical activity of pioneer axons and regulate axon pathfinding. To elucidate which channel molecules are present in pioneer axons, immunohistochemical analysis was performed to examine 14 voltage-gated ion channels (Kv1.1-Kv1.3, Kv3.1-Kv3.4, Kv4.3, Cav1.2, Cav1.3, Cav2.2, Nav1.2, Nav1.6, and Nav1.9) in nine axonal tracts in the developing rat forebrain, including the optic nerve, corpus callosum, corticofugal fibers, thalamocortical axons, lateral olfactory tract, hippocamposeptal projection, anterior commissure, hippocampal commissure, and medial longitudinal fasciculus. We found A-type K⁺ channel Kv3.4 in both pioneer axons and early follower axons and L-type Ca²⁺ channel Cav1.2 in pioneer axons and early and late follower axons. Spatially, Kv3.4 and Cav1.2 were colocalized with markers of pioneer neurons and pioneer axons, such as deleted in colorectal cancer (DCC), in most fiber tracts examined. Temporally, Kv3.4 and Cav1.2 were expressed abundantly in most fiber tracts during axon pathfinding but were downregulated beginning in synaptogenesis. By contrast, delayed rectifier Kv channels (e.g., Kv1.1) and Nav channels (e.g., Nav1.2) were absent from these fiber tracts (except for the corpus callosum) during pathfinding of pioneer axons. These data suggest that Kv3.4 and Cav1.2, two high-voltage-activated ion channels, may act together to control Ca²⁺ -dependent electrical activity of pioneer axons and play important roles during axon pathfinding.

  15. Slit and Netrin-1 guide cranial motor axon pathfinding via Rho-kinase, myosin light chain kinase and myosin II

    Drescher Uwe

    2010-06-01

    Full Text Available Abstract Background In the developing hindbrain, cranial motor axon guidance depends on diffusible repellent factors produced by the floor plate. Our previous studies have suggested that candidate molecules for mediating this effect are Slits, Netrin-1 and Semaphorin3A (Sema3A. It is unknown to what extent these factors contribute to floor plate-derived chemorepulsion of motor axons, and the downstream signalling pathways are largely unclear. Results In this study, we have used a combination of in vitro and in vivo approaches to identify the components of floor plate chemorepulsion and their downstream signalling pathways. Using in vitro motor axon deflection assays, we demonstrate that Slits and Netrin-1, but not Sema3A, contribute to floor plate repulsion. We also find that the axon pathways of dorsally projecting branchiomotor neurons are disrupted in Netrin-1 mutant mice and in chick embryos expressing dominant-negative Unc5a receptors, indicating an in vivo role for Netrin-1. We further demonstrate that Slit and Netrin-1 signalling are mediated by Rho-kinase (ROCK and myosin light chain kinase (MLCK, which regulate myosin II activity, controlling actin retrograde flow in the growth cone. We show that MLCK, ROCK and myosin II are required for Slit and Netrin-1-mediated growth cone collapse of cranial motor axons. Inhibition of these molecules in explant cultures, or genetic manipulation of RhoA or myosin II function in vivo causes characteristic cranial motor axon pathfinding errors, including the inability to exit the midline, and loss of turning towards exit points. Conclusions Our findings suggest that both Slits and Netrin-1 contribute to floor plate-derived chemorepulsion of cranial motor axons. They further indicate that RhoA/ROCK, MLCK and myosin II are components of Slit and Netrin-1 signalling pathways, and suggest that these pathways are of key importance in cranial motor axon navigation.

  16. Slit-Robo signals regulate pioneer axon pathfinding of the tract of the postoptic commissure in the mammalian forebrain.

    Ricaño-Cornejo, Itzel; Altick, Amy L; García-Peña, Claudia M; Nural, Hikmet Feyza; Echevarría, Diego; Miquelajáuregui, Amaya; Mastick, Grant S; Varela-Echavarría, Alfredo

    2011-10-01

    During early vertebrate forebrain development, pioneer axons establish a symmetrical scaffold descending longitudinally through the rostral forebrain, thus forming the tract of the postoptic commissure (TPOC). In mouse embryos, this tract begins to appear at embryonic day 9.5 (E9.5) as a bundle of axons tightly constrained at a specific dorsoventral level. We have characterized the participation of the Slit chemorepellants and their Robo receptors in the control of TPOC axon projection. In E9.5-E11.5 mouse embryos, Robo1 and Robo2 are expressed in the nucleus origin of the TPOC (nTPOC), and Slit expression domains flank the TPOC trajectory. These findings suggested that these proteins are important factors in the dorsoventral positioning of the TPOC axons. Consistently with this role, Slit2 inhibited TPOC axon growth in collagen gel cultures, and interfering with Robo function in cultured embryos induced projection errors in TPOC axons. Moreover, absence of both Slit1 and Slit2 or Robo1 and Robo2 in mutant mouse embryos revealed aberrant TPOC trajectories, resulting in abnormal spreading of the tract and misprojections into both ventral and dorsal tissues. These results reveal that Slit-Robo signaling regulates the dorsoventral position of this pioneer tract in the developing forebrain.

  17. Axonal pathfinding mechanisms at the cortical midline and in the development of the corpus callosum

    Richards L.J.

    2002-01-01

    Full Text Available The corpus callosum is a large fiber tract that connects neurons in the right and left cerebral hemispheres. Agenesis of the corpus callosum (ACC is associated with a large number of human syndromes but little is known about why ACC occurs. In most cases of ACC, callosal axons are able to grow toward the midline but are unable to cross it, continuing to grow into large swirls of axons known as Probst bundles. This phenotype suggests that in some cases ACC may be due to defects in axonal guidance at the midline. General guidance mechanisms that influence the development of axons include chemoattraction and chemorepulsion, presented by either membrane-bound or diffusible molecules. These molecules are not only expressed by the final target but by intermediate targets along the pathway, and by pioneering axons that act as guides for later arriving axons. Midline glial populations are important intermediate targets for commissural axons in the spinal cord and brain, including the corpus callosum. The role of midline glial populations and pioneering axons in the formation of the corpus callosum are discussed. Finally the differential guidance of the ipsilaterally projecting perforating pathway and the contralaterally projecting corpus callosum is addressed. Development of the corpus callosum involves the coordination of a number of different guidance mechanisms and the probable involvement of a large number of molecules.

  18. Stem-loop binding protein is required for retinal cell proliferation, neurogenesis, and intraretinal axon pathfinding in zebrafish.

    Imai, Fumiyasu; Yoshizawa, Asuka; Matsuzaki, Ayako; Oguri, Eri; Araragi, Masato; Nishiwaki, Yuko; Masai, Ichiro

    2014-10-01

    In the developing retina, neurogenesis and cell differentiation are coupled with cell proliferation. However, molecular mechanisms that coordinate cell proliferation and differentiation are not fully understood. In this study, we found that retinal neurogenesis is severely delayed in the zebrafish stem-loop binding protein (slbp) mutant. SLBP binds to a stem-loop structure at the 3'-end of histone mRNAs, and regulates a replication-dependent synthesis and degradation of histone proteins. Retinal cell proliferation becomes slower in the slbp1 mutant, resulting in cessation of retinal stem cell proliferation. Although retinal stem cells cease proliferation by 2 days postfertilization (dpf) in the slbp mutant, retinal progenitor cells in the central retina continue to proliferate and generate neurons until at least 5dpf. We found that this progenitor proliferation depends on Notch signaling, suggesting that Notch signaling maintains retinal progenitor proliferation when faced with reduced SLBP activity. Thus, SLBP is required for retinal stem cell maintenance. SLBP and Notch signaling are required for retinal progenitor cell proliferation and subsequent neurogenesis. We also show that SLBP1 is required for intraretinal axon pathfinding, probably through morphogenesis of the optic stalk, which expresses attractant cues. Taken together, these data indicate important roles of SLBP in retinal development.

  19. Influence of brain-derived neurotrophic factor on pathfinding of dentate granule cell axons, the hippocampal mossy fibers

    Tamura Makoto; Tamura Naohiro; Ikeda Takamitsu; Koyama Ryuta; Ikegaya Yuji; Matsuki Norio; Yamada Maki K

    2009-01-01

    Abstract Mossy fibers, the dentate granule cell axons, are generated throughout an animal's lifetime. Mossy fiber paths and synapses are primarily restricted to the stratum lucidum within the CA3 region. Brain-derived neurotrophic factor (BDNF), a neurotrophin family protein that activates Trk neurotrophin receptors, is highly expressed in the stratum lucidum in an activity-dependent manner. The addition of a Trk neurotrophin receptor inhibitor, K252a, to cultured hippocampal slices induced a...

  20. 4-Hydroxy-2-nonenal induces mitochondrial dysfunction and aberrant axonal outgrowth in adult sensory neurons that mimics features of diabetic neuropathy.

    Akude, Eli; Zherebitskaya, Elena; Roy Chowdhury, Subir K; Girling, Kimberly; Fernyhough, Paul

    2010-01-01

    Modification of proteins by 4-hydroxy-2-nonenal (4-HNE) has been proposed to cause neurotoxicity in a number of neurodegenerative diseases, including distal axonopathy in diabetic sensory neuropathy. We tested the hypothesis that exposure of cultured adult rat sensory neurons to 4-HNE would result in the formation of amino acid adducts on mitochondrial proteins and that this process would be associated with impaired mitochondrial function and axonal regeneration. In addition, we compared 4-HNE-induced axon pathology with that exhibited by neurons isolated from diabetic rats. Cultured adult rat dorsal root ganglion (DRG) sensory neurons were incubated with varying concentrations of 4-HNE. Cell survival, axonal morphology, and level of axon outgrowth were assessed. In addition, video microscopy of live cells, western blot, and immunofluorescent staining were utilized to detect protein adduct formation by 4-HNE and to localize actively respiring mitochondria. 4-HNE induced formation of protein adducts on cytoskeletal and mitochondrial proteins, and impaired axon regeneration by approximately 50% at 3 microM while having no effect on neuronal survival. 4-HNE initiated formation of aberrant axonal structures and caused the accumulation of mitochondria in these dystrophic structures. Neurons treated with 4-HNE exhibited a distal loss of active mitochondria. Finally, the distal axonopathy and the associated aberrant axonal structures generated by 4-HNE treatment mimicked axon pathology observed in DRG sensory neurons isolated from diabetic rats and replicated aspects of neurodegeneration observed in human diabetic sensory neuropathy.

  1. A Drosophila homolog of cyclase-associated proteins collaborates with the Abl tyrosine kinase to control midline axon pathfinding.

    Wills, Zachary; Emerson, Mark; Rusch, Jannette; Bikoff, Jay; Baum, Buzz; Perrimon, Norbert; Van Vactor, David

    2002-11-14

    We demonstrate that Drosophila capulet (capt), a homolog of the adenylyl cyclase-associated protein that binds and regulates actin in yeast, associates with Abl in Drosophila cells, suggesting a functional relationship in vivo. We find a robust and specific genetic interaction between capt and Abl at the midline choice point where the growth cone repellent Slit functions to restrict axon crossing. Genetic interactions between capt and slit support a model where Capt and Abl collaborate as part of the repellent response. Further support for this model is provided by genetic interactions that both capt and Abl display with multiple members of the Roundabout receptor family. These studies identify Capulet as part of an emerging pathway linking guidance signals to regulation of cytoskeletal dynamics and suggest that the Abl pathway mediates signals downstream of multiple Roundabout receptors.

  2. Aberrant Schwann cell lipid metabolism linked to mitochondrial deficits leads to axon degeneration and neuropathy.

    Viader, Andreu; Sasaki, Yo; Kim, Sungsu; Strickland, Amy; Workman, Cayce S; Yang, Kui; Gross, Richard W; Milbrandt, Jeffrey

    2013-03-06

    Mitochondrial dysfunction is a common cause of peripheral neuropathy. Much effort has been devoted to examining the role played by neuronal/axonal mitochondria, but how mitochondrial deficits in peripheral nerve glia (Schwann cells [SCs]) contribute to peripheral nerve diseases remains unclear. Here, we investigate a mouse model of peripheral neuropathy secondary to SC mitochondrial dysfunction (Tfam-SCKOs). We show that disruption of SC mitochondria activates a maladaptive integrated stress response (ISR) through the actions of heme-regulated inhibitor (HRI) kinase, and causes a shift in lipid metabolism away from fatty acid synthesis toward oxidation. These alterations in SC lipid metabolism result in depletion of important myelin lipid components as well as in accumulation of acylcarnitines (ACs), an intermediate of fatty acid β-oxidation. Importantly, we show that ACs are released from SCs and induce axonal degeneration. A maladaptive ISR as well as altered SC lipid metabolism are thus underlying pathological mechanisms in mitochondria-related peripheral neuropathies.

  3. The actin-binding protein Canoe/AF-6 forms a complex with Robo and is required for Slit-Robo signaling during axon pathfinding at the CNS midline.

    Slováková, Jana; Speicher, Stephan; Sánchez-Soriano, Natalia; Prokop, Andreas; Carmena, Ana

    2012-07-18

    Axon guidance is a key process during nervous system development and regeneration. One of the best established paradigms to study the mechanisms underlying this process is the axon decision of whether or not to cross the midline in the Drosophila CNS. An essential regulator of that decision is the well conserved Slit-Robo signaling pathway. Slit guidance cues act through Robo receptors to repel axons from the midline. Despite good progress in our knowledge about these proteins, the intracellular mechanisms associated with Robo function remain poorly defined. In this work, we found that the scaffolding protein Canoe (Cno), the Drosophila orthologue of AF-6/Afadin, is essential for Slit-Robo signaling. Cno is expressed along longitudinal axonal pioneer tracts, and longitudinal Robo/Fasciclin2-positive axons aberrantly cross the midline in cno mutant embryos. cno mutant primary neurons show a significant reduction of Robo localized in growth cone filopodia and Cno forms a complex with Robo in vivo. Moreover, the commissureless (comm) phenotype (i.e., lack of commissures due to constitutive surface presentation of Robo in all neurons) is suppressed in comm, cno double-mutant embryos. Specific genetic interactions between cno, slit, robo, and genes encoding other components of the Robo pathway, such as Neurexin-IV, Syndecan, and Rac GTPases, further confirm that Cno functionally interacts with the Slit-Robo pathway. Our data argue that Cno is a novel regulator of the Slit-Robo signaling pathway, crucial for regulating the subcellular localization of Robo and for transducing its signaling to the actin cytoskeleton during axon guidance at the midline.

  4. Midbrain dopaminergic axons are guided longitudinally through the diencephalon by Slit/Robo signals.

    Dugan, James P; Stratton, Andrea; Riley, Hilary P; Farmer, W Todd; Mastick, Grant S

    2011-01-01

    Dopaminergic neurons from the ventral mesencephalon/diencephalon (mesodiencephalon) form vital pathways constituting the majority of the brain's dopamine systems. Mesodiencephalic dopaminergic (mdDA) neurons extend longitudinal projections anteriorly through the diencephalon, ascending toward forebrain targets. The mechanisms by which mdDA axons initially navigate through the diencephalon are poorly understood. Recently the Slit family of secreted axon guidance proteins, and their Robo receptors, have been identified as important guides for descending longitudinal axons. To test the potential roles of Slit/Robo guidance in ascending trajectories, we examined tyrosine hydroxylase-positive (TH+) projections from mdDA neurons in mutant mouse embryos. We found that mdDA axons grow out of and parallel to Slit-positive ventral regions within the diencephalon, and that subsets of the mdDA axons likely express Robo1 and possibly also Robo2. Slit2 was able to directly inhibit TH axon outgrowth in explant co-culture assays. The mdDA axons made significant pathfinding errors in Slit1/2 and Robo1/2 knockout mice, including spreading out in the diencephalon to form a wider tract. The wider tract resulted from a combination of invasion of the ventral midline, consistent with Slit repulsion, but also axons wandering dorsally, away from the ventral midline. Aberrant dorsal trajectories were prominent in Robo1 and Robo1/2 knockout mice, suggesting that an aspect of Robo receptor function is Slit-independent. These results indicate that Slit/Robo signaling is critical during the initial establishment of dopaminergic pathways, with roles in the dorsoventral positioning and precise pathfinding of these ascending longitudinal axons.

  5. School libraries Pathfinders

    Shideh Taleban

    2009-01-01

    Full Text Available School library represents one of the important locations suited for offering reference services. The skill set necessary in order to use information resources, is called information literacy. When discussing information literacy and means of enhancing it, the first thing that comes to mind is the classroom for it is in schools that the foundation for learning skills is laid. Pathfinders have been used by libraries and librarians for guiding patrons to the required sources and answering their research questions since 1970’s. It is far different from a bibliography in as much as it does not necessarily include a complete list of available resources on a given topic. Nevertheless it provides sufficient basic resources for research for the patrons. Nowadays pathfinders are prepared by teacher-librarian or with the help of teachers at school so as to assist students in searching their prescribed assignments. The present paper offers definition of pathfinder, creation of pathfinders in schools, type of pathfinders, pathfinders characteristics, pathfinder elements as well as how to design pathfinders for children and teenagers.

  6. Aberrant expression of miR-218 and miR-204 in human mesial temporal lobe epilepsy and hippocampal sclerosis-Convergence on axonal guidance

    Kaalund, Sanne Simone; Venø, Morten T; Bak, Mads

    2014-01-01

    R-204 and miR-218 showed strong changes in expression during fetal development of the hippocampus in pigs, and we identified four target genes, involved in axonal guidance and synaptic plasticity, ROBO1, GRM1, SLC1A2, and GNAI2, as bona fide targets of miR-218. GRM1 was also shown to be a direct target...

  7. The LISA Pathfinder mission

    Antonucci, F.; Armano, M.; Audley, H.; Auger, G.; Benedetti, M.; Binetruy, P.; Bogenstahl, J.; Bortoluzzi, D.; Bosetti, P.; Brandt, N.; Caleno, M.; Cañizares, P.; Cavalleri, A.; Cesa, M.; Chmeissani, M.; Conchillo, A.; Congedo, G.; Cristofolini, I.; Cruise, M.; Danzmann, K.; De Marchi, F.; Diaz-Aguilo, M.; Diepholz, I.; Dixon, G.; Dolesi, R.; Dunbar, N.; Fauste, J.; Ferraioli, L.; Ferrone, V.; Fichter, W.; Fitzsimons, E.; Freschi, M.; García Marin, A.; García Marirrodriga, C.; Gerndt, R.; Gesa, L.; Gilbert, F.; Giardini, D.; Grimani, C.; Grynagier, A.; Guillaume, B.; Guzmán, F.; Harrison, I.; Heinzel, G.; Hernández, V.; Hewitson, M.; Hollington, D.; Hough, J.; Hoyland, D.; Hueller, M.; Huesler, J.; Jennrich, O.; Jetzer, P.; Johlander, B.; Karnesis, N.; Killow, C.; Llamas, X.; Lloro, I.; Lobo, A.; Maarschalkerweerd, R.; Madden, S.; Mance, D.; Mateos, I.; McNamara, P. W.; Mendes, J.; Mitchell, E.; Monsky, A.; Nicolini, D.; Nicolodi, D.; Nofrarias, M.; Pedersen, F.; Perreur-Lloyd, M.; Plagnol, E.; Prat, P.; Racca, G. D.; Ramos-Castro, J.; Reiche, J.; Romera Perez, J. A.; Robertson, D.; Rozemeijer, H.; Sanjuan, J.; Schleicher, A.; Schulte, M.; Shaul, D.; Stagnaro, L.; Strandmoe, S.; Steier, F.; Sumner, T. J.; Taylor, A.; Texier, D.; Trenkel, C.; Tu, H.-B.; Vitale, S.; Wanner, G.; Ward, H.; Waschke, S.; Wass, P.; Weber, W. J.; Ziegler, T.; Zweifel, P.

    2012-06-01

    In this paper, we describe the current status of the LISA Pathfinder mission, a precursor mission aimed at demonstrating key technologies for future space-based gravitational wave detectors, like LISA. Since much of the flight hardware has already been constructed and tested, we will show that performance measurements and analysis of these flight components lead to an expected performance of the LISA Pathfinder which is a significant improvement over the mission requirements, and which actually reaches the LISA requirements over the entire LISA Pathfinder measurement band.

  8. Pathfinder Climate Data

    National Oceanic and Atmospheric Administration, Department of Commerce — The NOAA/NASA Pathfinder climate data CD-ROM contains seven data sets: Advanced Very High Resolution Radiometer (AVHRR)Land and Ocean, TIROS Operational Vertical...

  9. Pathfinder Innovation Projects

    The Pathfinder program supports high-risk, high-reward research ideas with funding and staff time. The goal is to feed a culture of innovation in the Agency and integrate innovative ideas in EPA research programs.

  10. Apc1-mediated antagonism of Wnt/beta-catenin signaling is required for retino-tectal pathfinding in the zebrafish.

    Paridaen, J.T.M.; Danesin, C.; Elas, A.T.; van de Water, S.G.P.; Houart, C.; Zivkovic, D.

    2009-01-01

    The tumor suppressor Apc1 is an intracellular antagonist of the Wnt/beta-catenin pathway. We examined the effects of an Apc1 loss-of-function mutation on retino-tectal axon pathfinding in zebrafish. In apc mutants, the retina is disorganized and optic nerves portray pathfinding defects at the optic

  11. JWST Pathfinder Telescope Integration

    Matthews, Gary W.; Kennard, Scott H.; Broccolo, Ronald T.; Ellis, James M.; Daly, Elizabeth A.; Hahn, Walter G.; Amon, John N.; Mt. Pleasant, Stephen M.; Texter, Scott; Atkinson, Charles B.; McKay, Andrew; Levi, Joshua; Keski-Kuha, Ritva; Feinberg, Lee

    2015-01-01

    The James Webb Space Telescope (JWST) is a 6.5m, segmented, IR telescope that will explore the first light of the universe after the big bang. In 2014, a major risk reduction effort related to the Alignment, Integration, and Test (AI&T) of the segmented telescope was completed. The Pathfinder telescope includes two Primary Mirror Segment Assemblies (PMSA's) and the Secondary Mirror Assembly (SMA) onto a flight-like composite telescope backplane. This pathfinder allowed the JWST team to assess the alignment process and to better understand the various error sources that need to be accommodated in the flight build. The successful completion of the Pathfinder Telescope provides a final integration roadmap for the flight operations that will start in August 2015.

  12. The LISA Pathfinder Mission

    McNamara, Paul

    2013-04-01

    LISA Pathfinder, the second of the European Space Agency's Small Missions for Advanced Research in Technology (SMART), is a dedicated technology validation mission for future interferometric spaceborne gravitational wave observatories, for example the proposed eLISA mission. The technologies required for eLISA are many and extremely challenging. This coupled with the fact that some flight hardware cannot be fully tested on ground due to Earth-induced noise, led to the implementation of the LISA Pathfinder mission to test the critical eLISA technologies in a flight environment. LISA Pathfinder essentially mimics one arm of the eLISA constellation by shrinking the 1 million kilometre armlength down to a few tens of centimetres, giving up the sensitivity to gravitational waves, but keeping the measurement technology: the distance between the two test masses is measured using a laser interferometric technique similar to one aspect of the eLISA interferometry system. The scientific objective of the LISA Pathfinder mission consists then of the first in-flight test of low frequency gravitational wave detection metrology. Here I will present an overview of the mission, focusing on scientific and technical goals, followed by the current status of the project.

  13. The Mars Pathfinder Mission

    Golombek, M. P.

    1996-09-01

    The Mars Pathfinder mission is a Discovery class mission that will place a small lander and rover on the surface of Mars on July 4, 1997. The Pathfinder flight system is a single small lander, packaged within an aeroshell and back cover with a back-pack-style cruise stage. The vehicle will be launched, fly independently to Mars, and enter the atmosphere directly on approach behind the aeroshell. The vehicle is slowed by a parachute and 3 small solid rockets before landing on inflated airbags. Petals of a small tetrahedron shaped lander open up, to right the vehicle. The lander is solar powered with batteries and will operate on the surface for up to a year, downlinking data on a high-gain antenna. Pathfinder will be the first mission to use a rover, with 3 imagers and an alpha proton X-ray spectrometer, to characterize the rocks and soils in a landing area over hundreds of square meters on Mars, which will provide a calibration point or "ground truth" for orbital remote sensing observations. The rover (includes a series of technology experiments), the instruments (including a stereo multispectral surface imager on a pop up mast and an atmospheric structure instrument-surface meteorology package) and the telemetry system will allow investigations of: the surface morphology and geology at meter scale, the petrology and geochemistry of rocks and soils, the magnetic properties of dust, soil mechanics and properties, a variety of atmospheric investigations and the rotational and orbital dynamics of Mars. Landing downstream from the mouth of a giant catastrophic outflow channel, Ares Vallis, offers the potential of identifying and analyzing a wide variety of crustal materials, from the ancient heavily cratered terrain, intermediate-aged ridged plains and reworked channel deposits, thus allowing first-order scientific investigations of the early differentiation and evolution of the crust, the development of weathering products and early environments and conditions on Mars.

  14. The planar cell polarity protein Vangl2 is required for retinal axon guidance.

    Leung, Vicki; Iliescu, Alexandra; Jolicoeur, Christine; Gravel, Michel; Apuzzo, Sergio; Torban, Elena; Cayouette, Michel; Gros, Philippe

    2016-02-01

    Vangl2 plays a critical role in the establishment of planar cell polarity (PCP). Previously, we detected expression of Vangl2 in the developing retina during late embryogenesis, which led us to investigate the possible role of Vangl2-mediated PCP signaling in eye development. We have generated a Vangl2(BGeo) knock-in mouse allowing us to evaluate Vangl2 mRNA expression during retinal development, and used an isoform-specific antibody to examine Vangl2 protein expression in cryosections. To investigate the role of Vangl2 in retinal development, we examined eyes taken from embryos homozygous for independent alleles of Looptail (Lp, Lp(m1jus) ) mutant mice. We found that Vangl2 mRNA and protein are dynamically expressed in the developing embryonic and postnatal retina, with Vangl2 expression becoming progressively restricted to the ganglion cell layer and optic nerve as the retina matures. The expression pattern of Vangl2 transcript and protein is most prominent in retinal ganglion cells (RGC), and their axons. Additionally, we show that Vangl2 is required for retinal and optic nerve development as Vangl2 (Lp/Lp) mutant embryos display a significantly reduced eye size, marked thickening of the retina, and striking abnormalities in the morphology of the optic nerve (significant hypoplasia, and aberrant exit trajectory). Notably, we identified a salient intraretinal axon guidance defect in Vangl2 (Lp/Lp) mutant embryos through which axon bundles traverse the entire thickness of the retina and become trapped within the subretinal space. Our observations identify a new and essential role for Vangl2-dependent PCP signaling in the intraretinal path-finding of RGC axons.

  15. LISA Pathfinder: mission and status

    Antonucci, F.; Armano, M.; Audley, H.; Auger, G.; Benedetti, M.; Binetruy, P.; Boatella, C.; Bogenstahl, J.; Bortoluzzi, D.; Bosetti, P.; Caleno, M.; Cavalleri, A.; Cesa, M.; Chmeissani, M.; Ciani, G.; Conchillo, A.; Congedo, G.; Cristofolini, I.; Cruise, M.; Danzmann, K.; De Marchi, F.; Diaz-Aguilo, M.; Diepholz, I.; Dixon, G.; Dolesi, R.; Dunbar, N.; Fauste, J.; Ferraioli, L.; Fertin, D.; Fichter, W.; Fitzsimons, E.; Freschi, M.; García Marin, A.; García Marirrodriga, C.; Gerndt, R.; Gesa, L.; Gilbert, F.; Giardini, D.; Grimani, C.; Grynagier, A.; Guillaume, B.; Guzmán, F.; Harrison, I.; Heinzel, G.; Hewitson, M.; Hollington, D.; Hough, J.; Hoyland, D.; Hueller, M.; Huesler, J.; Jeannin, O.; Jennrich, O.; Jetzer, P.; Johlander, B.; Killow, C.; Llamas, X.; Lloro, I.; Lobo, A.; Maarschalkerweerd, R.; Madden, S.; Mance, D.; Mateos, I.; McNamara, P. W.; Mendes, J.; Mitchell, E.; Monsky, A.; Nicolini, D.; Nicolodi, D.; Nofrarias, M.; Pedersen, F.; Perreur-Lloyd, M.; Perreca, A.; Plagnol, E.; Prat, P.; Racca, G. D.; Rais, B.; Ramos-Castro, J.; Reiche, J.; Romera Perez, J. A.; Robertson, D.; Rozemeijer, H.; Sanjuan, J.; Schleicher, A.; Schulte, M.; Shaul, D.; Stagnaro, L.; Strandmoe, S.; Steier, F.; Sumner, T. J.; Taylor, A.; Texier, D.; Trenkel, C.; Tombolato, D.; Vitale, S.; Wanner, G.; Ward, H.; Waschke, S.; Wass, P.; Weber, W. J.; Zweifel, P.

    2011-05-01

    LISA Pathfinder, the second of the European Space Agency's Small Missions for Advanced Research in Technology (SMART), is a dedicated technology demonstrator for the joint ESA/NASA Laser Interferometer Space Antenna (LISA) mission. The technologies required for LISA are many and extremely challenging. This coupled with the fact that some flight hardware cannot be fully tested on ground due to Earth-induced noise led to the implementation of the LISA Pathfinder mission to test the critical LISA technologies in a flight environment. LISA Pathfinder essentially mimics one arm of the LISA constellation by shrinking the 5 million kilometre armlength down to a few tens of centimetres, giving up the sensitivity to gravitational waves, but keeping the measurement technology: the distance between the two test masses is measured using a laser interferometric technique similar to one aspect of the LISA interferometry system. The scientific objective of the LISA Pathfinder mission consists then of the first in-flight test of low frequency gravitational wave detection metrology. LISA Pathfinder is due to be launched in 2013 on-board a dedicated small launch vehicle (VEGA). After a series of apogee raising manoeuvres using an expendable propulsion module, LISA Pathfinder will enter a transfer orbit towards the first Sun-Earth Lagrange point (L1). After separation from the propulsion module, the LPF spacecraft will be stabilized using the micro-Newton thrusters, entering a 500 000 km by 800 000 km Lissajous orbit around L1. Science results will be available approximately 2 months after launch.

  16. LISA Pathfinder data analysis

    Antonucci, F.; Armano, M.; Audley, H.; Auger, G.; Benedetti, M.; Binetruy, P.; Boatella, C.; Bogenstahl, J.; Bortoluzzi, D.; Bosetti, P.; Caleno, M.; Cavalleri, A.; Cesa, M.; Chmeissani, M.; Ciani, G.; Conchillo, A.; Congedo, G.; Cristofolini, I.; Cruise, M.; Danzmann, K.; De Marchi, F.; Diaz-Aguilo, M.; Diepholz, I.; Dixon, G.; Dolesi, R.; Fauste, J.; Ferraioli, L.; Fertin, D.; Fichter, W.; Fitzsimons, E.; Freschi, M.; García Marin, A.; García Marirrodriga, C.; Gesa, L.; Giardini, D.; Grimani, C.; Grynagier, A.; Guillaume, B.; Guzmán, F.; Harrison, I.; Heinzel, G.; Hewitson, M.; Hollington, D.; Hough, J.; Hoyland, D.; Hueller, M.; Huesler, J.; Jeannin, O.; Jennrich, O.; Jetzer, P.; Johlander, B.; Killow, C.; Llamas, X.; Lloro, I.; Lobo, A.; Maarschalkerweerd, R.; Madden, S.; Mance, D.; Mateos, I.; McNamara, P. W.; Mendes, J.; Mitchell, E.; Monsky, A.; Nicolini, D.; Nicolodi, D.; Nofrarias, M.; Pedersen, F.; Perreur-Lloyd, M.; Perreca, A.; Plagnol, E.; Prat, P.; Racca, G. D.; Rais, B.; Ramos-Castro, J.; Reiche, J.; Romera Perez, J. A.; Robertson, D.; Rozemeijer, H.; Sanjuan, J.; Schulte, M.; Shaul, D.; Stagnaro, L.; Strandmoe, S.; Steier, F.; Sumner, T. J.; Taylor, A.; Texier, D.; Trenkel, C.; Tombolato, D.; Vitale, S.; Wanner, G.; Ward, H.; Waschke, S.; Wass, P.; Weber, W. J.; Zweifel, P.

    2011-05-01

    As the launch of LISA Pathfinder (LPF) draws near, more and more effort is being put in to the preparation of the data analysis activities that will be carried out during the mission operations. The operations phase of the mission will be composed of a series of experiments that will be carried out on the satellite. These experiments will be directed and analysed by the data analysis team, which is part of the operations team. The operations phase will last about 90 days, during which time the data analysis team aims to fully characterize the LPF, and in particular, its core instrument the LISA Technology Package. By analysing the various couplings present in the system, the different noise sources that will disturb the system, and through the identification of the key physical parameters of the system, a detailed noise budget of the instrument will be constructed that will allow the performance of the different subsystems to be assessed and projected towards LISA. This paper describes the various aspects of the full data analysis chain that are needed to successfully characterize the LPF and build up the noise budget during mission operations.

  17. LISA Pathfinder data analysis

    Antonucci, F; Cavalleri, A; Congedo, G [Dipartimento di Fisica, Universita di Trento and INFN, Gruppo Collegato di Trento, 38123 Povo, Trento (Italy); Armano, M [European Space Astronomy Centre, European Space Agency, Villanueva de la Canada, 28692 Madrid (Spain); Audley, H; Bogenstahl, J; Danzmann, K [Albert-Einstein-Institut, Max-Planck-Institut fuer Gravitationsphysik und Universitaet Hannover, 30167 Hannover (Germany); Auger, G; Binetruy, P [APC UMR7164, Universite Paris Diderot, Paris (France); Benedetti, M [Dipartimento di Ingegneria dei Materiali e Tecnologie Industriali, Universita di Trento and INFN, Gruppo Collegato di Trento, Mesiano, Trento (Italy); Boatella, C [CNES, DCT/AQ/EC, 18 Avenue Edouard Belin, 31401 Toulouse, Cedex9 (France); Bortoluzzi, D; Bosetti, P; Cristofolini, I [Dipartimento di Ingegneria Meccanica e Strutturale, Universita di Trento and INFN, Gruppo Collegato di Trento, Mesiano, Trento (Italy); Caleno, M; Cesa, M [European Space Technology Centre, European Space Agency, Keplerlaan 1, 2200 AG Noordwijk (Netherlands); Chmeissani, M [IFAE, Universitat Autonoma de Barcelona, E-08193 Bellaterra (Barcelona) (Spain); Ciani, G [Department of Physics, University of Florida, Gainesville, FL 32611-8440 (United States); Conchillo, A [ICE-CSIC/IEEC, Facultat de Ciencies, E-08193 Bellaterra (Barcelona) (Spain); Cruise, M, E-mail: martin.hewitson@aei.mpg.de [Department of Physics and Astronomy, University of Birmingham, Birmingham (United Kingdom)

    2011-05-07

    As the launch of LISA Pathfinder (LPF) draws near, more and more effort is being put in to the preparation of the data analysis activities that will be carried out during the mission operations. The operations phase of the mission will be composed of a series of experiments that will be carried out on the satellite. These experiments will be directed and analysed by the data analysis team, which is part of the operations team. The operations phase will last about 90 days, during which time the data analysis team aims to fully characterize the LPF, and in particular, its core instrument the LISA Technology Package. By analysing the various couplings present in the system, the different noise sources that will disturb the system, and through the identification of the key physical parameters of the system, a detailed noise budget of the instrument will be constructed that will allow the performance of the different subsystems to be assessed and projected towards LISA. This paper describes the various aspects of the full data analysis chain that are needed to successfully characterize the LPF and build up the noise budget during mission operations.

  18. The LISA Pathfinder Radiation Monitor

    Wass, P. J.; Araújo, H.; Boatella, C.; Chmeissani, M.; Hajdas, W.; Lobo, A.; Puigdengoles, C.; Sumner, T.

    2006-11-01

    We present the concept, design and testing of the radiation monitor for LISA Pathfinder. Galactic cosmic rays (GCRs) and solar energetic particles (SEPs) will cause charging of the LISA Pathfinder test masses producing unwanted disturbances which could be significant during a large solar eruption. A radiation monitor on board LISA Pathfinder, using silicon PIN diodes as particle detectors, will measure the particle flux responsible for charging. It will also be able to record spectral information to identify solar energetic particle events. The design of the monitor was supported by Monte Carlo simulations which allow detailed predictions of the radiation monitor performance. We present these predictions as well as the results of high-energy proton tests carried out at the Paul Scherrer Institute, Switzerland. The tests show good agreement with our simulations and confirm the capability of the radiation monitor to perform well in the space environment, meeting all science requirements.

  19. LISA Pathfinder: mission and status

    Antonucci, F; Cavalleri, A; Congedo, G [Dipartimento di Fisica, Universita di Trento and INFN, Gruppo Collegato di Trento, 38050 Povo, Trento (Italy); Armano, M [European Space Astronomy Centre, European Space Agency, Villanueva de la Canada, 28692 Madrid (Spain); Audley, H; Bogenstahl, J; Danzmann, K [Albert-Einstein-Institut, Max-Planck-Institut fuer Gravitationsphysik und Universitaet Hannover, 30167 Hannover (Germany); Auger, G; Binetruy, P [APC UMR7164, Universite Paris Diderot, Paris (France); Benedetti, M [Dipartimento di Ingegneria dei Materiali e Tecnologie Industriali, Universita di Trento and INFN, Gruppo Collegato di Trento, Mesiano, Trento (Italy); Boatella, C [CNES, DCT/AQ/EC, 18 Avenue Edouard Belin, 31401 Toulouse, Cedex 9 (France); Bortoluzzi, D; Bosetti, P; Cristofolini, I [Dipartimento di Ingegneria Meccanica e Strutturale, Universita di Trento and INFN, Gruppo Collegato di Trento, Mesiano, Trento (Italy); Caleno, M; Cesa, M [European Space Technology Centre, European Space Agency, Keplerlaan 1, 2200 AG Noordwijk (Netherlands); Chmeissani, M [IFAE, Universitat Autonoma de Barcelona, E-08193 Bellaterra, Barcelona (Spain); Ciani, G [Department of Physics, University of Florida, Gainesville, FL 32611-8440 (United States); Conchillo, A [ICE-CSIC/IEEC, Facultat de Ciencies, E-08193 Bellaterra, Barcelona (Spain); Cruise, M, E-mail: Paul.McNamara@esa.int [Department of Physics and Astronomy, University of Birmingham, Birmingham (United Kingdom)

    2011-05-07

    LISA Pathfinder, the second of the European Space Agency's Small Missions for Advanced Research in Technology (SMART), is a dedicated technology demonstrator for the joint ESA/NASA Laser Interferometer Space Antenna (LISA) mission. The technologies required for LISA are many and extremely challenging. This coupled with the fact that some flight hardware cannot be fully tested on ground due to Earth-induced noise led to the implementation of the LISA Pathfinder mission to test the critical LISA technologies in a flight environment. LISA Pathfinder essentially mimics one arm of the LISA constellation by shrinking the 5 million kilometre armlength down to a few tens of centimetres, giving up the sensitivity to gravitational waves, but keeping the measurement technology: the distance between the two test masses is measured using a laser interferometric technique similar to one aspect of the LISA interferometry system. The scientific objective of the LISA Pathfinder mission consists then of the first in-flight test of low frequency gravitational wave detection metrology. LISA Pathfinder is due to be launched in 2013 on-board a dedicated small launch vehicle (VEGA). After a series of apogee raising manoeuvres using an expendable propulsion module, LISA Pathfinder will enter a transfer orbit towards the first Sun-Earth Lagrange point (L1). After separation from the propulsion module, the LPF spacecraft will be stabilized using the micro-Newton thrusters, entering a 500 000 km by 800 000 km Lissajous orbit around L1. Science results will be available approximately 2 months after launch.

  20. Crossing the Border: Molecular Control of Motor Axon Exit

    Arlene Bravo-Ambrosio

    2011-11-01

    Full Text Available Living organisms heavily rely on the function of motor circuits for their survival and for adapting to ever-changing environments. Unique among central nervous system (CNS neurons, motor neurons (MNs project their axons out of the CNS. Once in the periphery, motor axons navigate along highly stereotyped trajectories, often at considerable distances from their cell bodies, to innervate appropriate muscle targets. A key decision made by pathfinding motor axons is whether to exit the CNS through dorsal or ventral motor exit points (MEPs. In contrast to the major advances made in understanding the mechanisms that regulate the specification of MN subtypes and the innervation of limb muscles, remarkably little is known about how MN axons project out of the CNS. Nevertheless, a limited number of studies, mainly in Drosophila, have identified transcription factors, and in some cases candidate downstream effector molecules, that are required for motor axons to exit the spinal cord. Notably, specialized neural crest cell derivatives, referred to as Boundary Cap (BC cells, pre-figure and demarcate MEPs in vertebrates. Surprisingly, however, BC cells are not required for MN axon exit, but rather restrict MN cell bodies from ectopically migrating along their axons out of the CNS. Here, we describe the small set of studies that have addressed motor axon exit in Drosophila and vertebrates, and discuss our fragmentary knowledge of the mechanisms, which guide motor axons out of the CNS.

  1. Long Memory of Pathfinding Aesthetics

    Ron Coleman

    2009-01-01

    Full Text Available This paper investigates a new dynamic (i.e., space-time model to measure aesthetic values in pathfinding for videogames. The results we report are important firstly because the artificial intelligence literature has given relatively little attention to aesthetic considerations in pathfinding. Secondly, those investigators who have studied aesthetics in pathfinding have relied largely on anecdotal arguments rather than metrics. Finally, in those cases where metrics have been used in the past, they show only that aesthetic paths are different. They provide no quantitative means to classify aesthetic outcomes. The model we develop here overcomes these deficiencies using rescaled range (R/S analysis to estimate the Hurst exponent, . It measures long-range dependence (i.e., long memory in stochastic processes and provides a novel well-defined mathematical classification for pathfinding. Indeed, the data indicates that aesthetic and control paths have statistically significantly distinct signatures. Aesthetic paths furthermore have more long memory than controls with an effect size that is large, more than three times that of an alternative approach. These conclusions will be of interest to researchers investigating games as well as other forms of entertainment, simulation, and in general nonshortest path motion planning.

  2. Desert Pathfinder at Work

    2005-09-01

    The Atacama Pathfinder Experiment (APEX) project celebrates the inauguration of its outstanding 12-m telescope, located on the 5100m high Chajnantor plateau in the Atacama Desert (Chile). The APEX telescope, designed to work at sub-millimetre wavelengths, in the 0.2 to 1.5 mm range, passed successfully its Science Verification phase in July, and since then is performing regular science observations. This new front-line facility provides access to the "Cold Universe" with unprecedented sensitivity and image quality. After months of careful efforts to set up the telescope to work at the best possible technical level, those involved in the project are looking with satisfaction at the fruit of their labour: APEX is not only fully operational, it has already provided important scientific results. "The superb sensitivity of our detectors together with the excellence of the site allow fantastic observations that would not be possible with any other telescope in the world," said Karl Menten, Director of the group for Millimeter and Sub-Millimeter Astronomy at the Max-Planck-Institute for Radio Astronomy (MPIfR) and Principal Investigator of the APEX project. ESO PR Photo 30/05 ESO PR Photo 30/05 Sub-Millimetre Image of a Stellar Cradle [Preview - JPEG: 400 x 627 pix - 200k] [Normal - JPEG: 800 x 1254 pix - 503k] [Full Res - JPEG: 1539 x 2413 pix - 1.3M] Caption: ESO PR Photo 30/05 is an image of the giant molecular cloud G327 taken with APEX. More than 5000 spectra were taken in the J=3-2 line of the carbon monoxide molecule (CO), one of the best tracers of molecular clouds, in which star formation takes place. The bright peak in the north of the cloud is an evolved star forming region, where the gas is heated by a cluster of new stars. The most interesting region in the image is totally inconspicuous in CO: the G327 hot core, as seen in methanol contours. It is a truly exceptional source, and is one of the richest sources of emission from complex organic molecules in the

  3. Mission design for LISA Pathfinder

    Landgraf, M; Kemble, S

    2004-01-01

    Here we describe the mission design for SMART-2/LISA Pathfinder. The best trade-off between the requirements of a low-disturbance environment and communications distance is found to be a free-insertion Lissajous orbit around the first co-linear Lagrange point of the Sun-Earth system L1, 1.5x 10^6 km from Earth. In order to transfer SMART-2/LISA Pathfinder from a low Earth orbit, where it will be placed by a small launcher, the spacecraft carries out a number of apogee-raise manoeuvres, which ultimatively place it to a parabolic escape trajectory towards L1. The challenges of the design of a small mission are met, fulfilling the very demanding technology demonstration requirements without creating excessive requirements on the launch system or the ground segment.

  4. Strategic Team AI Path Plans: Probabilistic Pathfinding

    Tng C. H. John

    2008-01-01

    Full Text Available This paper proposes a novel method to generate strategic team AI pathfinding plans for computer games and simulations using probabilistic pathfinding. This method is inspired by genetic algorithms (Russell and Norvig, 2002, in that, a fitness function is used to test the quality of the path plans. The method generates high-quality path plans by eliminating the low-quality ones. The path plans are generated by probabilistic pathfinding, and the elimination is done by a fitness test of the path plans. This path plan generation method has the ability to generate variation or different high-quality paths, which is desired for games to increase replay values. This work is an extension of our earlier work on team AI: probabilistic pathfinding (John et al., 2006. We explore ways to combine probabilistic pathfinding and genetic algorithm to create a new method to generate strategic team AI pathfinding plans.

  5. Expansion of the piriform cortex contributes to corticothalamic pathfinding defects in Gli3 conditional mutants.

    Amaniti, Eleni-Maria; Fu, Chaoying; Lewis, Sean; Saisana, Marina; Magnani, Dario; Mason, John O; Theil, Thomas

    2015-02-01

    The corticothalamic and thalamocortical tracts play essential roles in the communication between the cortex and thalamus. During development, axons forming these tracts have to follow a complex path to reach their target areas. While much attention has been paid to the mechanisms regulating their passage through the ventral telencephalon, very little is known about how the developing cortex contributes to corticothalamic/thalamocortical tract formation. Gli3 encodes a zinc finger transcription factor widely expressed in telencephalic progenitors which has important roles in corticothalamic and thalamocortical pathfinding. Here, we conditionally inactivated Gli3 in dorsal telencephalic progenitors to determine its role in corticothalamic tract formation. In Emx1Cre;Gli3(fl/fl) mutants, only a few corticothalamic axons enter the striatum in a restricted dorsal domain. This restricted entry correlates with a medial expansion of the piriform cortex. Transplantation experiments showed that the expanded piriform cortex repels corticofugal axons. Moreover, expression of Sema5B, a chemorepellent for corticofugal axons produced by the piriform cortex, is similarly expanded. Finally, time course analysis revealed an expansion of the ventral pallial progenitor domain which gives rise to the piriform cortex. Hence, control of lateral cortical development by Gli3 at the progenitor level is crucial for corticothalamic pathfinding.

  6. A forward genetic screen with a thalamocortical axon reporter mouse yields novel neurodevelopment mutants and a distinct emx2 mutant phenotype

    Vock Vita M

    2011-01-01

    Full Text Available Abstract Background The dorsal thalamus acts as a gateway and modulator for information going to and from the cerebral cortex. This activity requires the formation of reciprocal topographic axon connections between thalamus and cortex. The axons grow along a complex multistep pathway, making sharp turns, crossing expression boundaries, and encountering intermediate targets. However, the cellular and molecular components mediating these steps remain poorly understood. Results To further elucidate the development of the thalamocortical system, we first created a thalamocortical axon reporter line to use as a genetic tool for sensitive analysis of mutant mouse phenotypes. The TCA-tau-lacZ reporter mouse shows specific, robust, and reproducible labeling of thalamocortical axons (TCAs, but not the overlapping corticothalamic axons, during development. Moreover, it readily reveals TCA pathfinding abnormalities in known cortical mutants such as reeler. Next, we performed an unbiased screen for genes involved in thalamocortical development using random mutagenesis with the TCA reporter. Six independent mutant lines show aberrant TCA phenotypes at different steps of the pathway. These include ventral misrouting, overfasciculation, stalling at the corticostriatal boundary, and invasion of ectopic cortical cell clusters. An outcross breeding strategy coupled with a genomic panel of single nucleotide polymorphisms facilitated genetic mapping with small numbers of mutant mice. We mapped a ventral misrouting mutant to the Emx2 gene, and discovered that some TCAs extend to the olfactory bulbs in this mutant. Mapping data suggest that other lines carry mutations in genes not previously known for roles in thalamocortical development. Conclusions These data demonstrate the feasibility of a forward genetic approach to understanding mammalian brain morphogenesis and wiring. A robust axonal reporter enabled sensitive analysis of a specific axon tract inside the

  7. Electrostatic disturbances aboard LISA Pathfinder

    Ferroni, Valerio

    Test mass charging and stray electrostatic fields are a potentially important source of force noise for the LISA Pathfinder mission. During the flight we plan to measure the relevant stray electrostatic fields on the surfaces of both the test mass and the electrode housing and compensate them with DC electrode bias voltages. In addition we monitor the charge and reduce it to near zero by UV illumination. We describe the analysis techniques used during the mission and explain the importance of periodic charging/discharging and of long-term charge measurements to limit the force noise at low frequency, which is particularly relevant for the eLISA mission.

  8. Symbolic PathFinder v7

    Luckow, Kasper Søe; Păsăreanu, Corina

    2014-01-01

    We describe Symbolic PathFinder v7 in terms of its updated design addressing the changes of Java PathFinder v7 and of its new optimization when computing path conditions. Furthermore, we describe the Symbolic Execution Tree Extension; a newly added feature that allows for outputting the symbolic ...

  9. Extracellular matrix molecules play diverse roles in the growth and guidance of central nervous system axons

    M.A. Pires-Neto

    1999-05-01

    Full Text Available Axon growth and guidance represent complex biological processes in which probably intervene diverse sets of molecular cues that allow for the appropriate wiring of the central nervous system (CNS. The extracellular matrix (ECM represents a major contributor of molecular signals either diffusible or membrane-bound that may regulate different stages of neural development. Some of the brain ECM molecules form tridimensional structures (tunnels and boundaries that appear during time- and space-regulated events, possibly playing relevant roles in the control of axon elongation and pathfinding. This short review focuses mainly on the recognized roles played by proteoglycans, laminin, fibronectin and tenascin in axonal development during ontogenesis.

  10. Guidance of Drosophila Mushroom Body Axons Depends upon DRL-Wnt Receptor Cleavage in the Brain Dorsomedial Lineage Precursors

    Elodie Reynaud

    2015-05-01

    Full Text Available In vivo axon pathfinding mechanisms in the neuron-dense brain remain relatively poorly characterized. We study the Drosophila mushroom body (MB axons, whose α and β branches connect to different brain areas. We show that the Ryk family WNT5 receptor, DRL (derailed, which is expressed in the dorsomedial lineages, brain structure precursors adjacent to the MBs, is required for MB α branch axon guidance. DRL acts to capture and present WNT5 to MB axons rather than transduce a WNT5 signal. DRL’s ectodomain must be cleaved and shed to guide α axons. DRL-2, another Ryk, is expressed within MB axons and functions as a repulsive WNT5 signaling receptor. Finally, our biochemical data support the existence of a ternary complex composed of the cleaved DRL ectodomain, WNT5, and DRL-2. Thus, the interaction of MB-extrinsic and -intrinsic Ryks via their common ligand acts to guide MB α axons.

  11. Computing along the axon

    Chen Haiming; Tseren-Onolt Ishdorj; Gheorghe Pǎun

    2007-01-01

    A special form of spiking neural P systems, called axon P systems, corresponding to the activity of Ranvier nodes of neuron axon, is considered and a class of SN-like P systems where the computation is done along the axon is introduced and their language generative power is investigated.

  12. Spacetime Metrology with LISA Pathfinder

    Congedo, Giuseppe

    2012-01-01

    LISA is the proposed ESA-NASA gravitational wave detector in the 0.1 mHz - 0.1 Hz band. LISA Pathfinder is the down-scaled version of a single LISA arm. The arm -- named Doppler link -- can be treated as a differential accelerometer, measuring the relative acceleration between test masses. LISA Pathfinder -- the in-flight test of the LISA instrumentation -- is currently in the final implementation and planned to be launched in 2014. It will set stringent constraints on the ability to put test masses in geodesic motion to within the required differential acceleration of 3\\times10^{-14} m s^{-2} Hz^{-1/2} and track their relative motion to within the required differential displacement measurement noise of 9\\times10^{-12} m Hz^{-1/2}, around 1 mHz. Given the scientific objectives, it will carry out -- for the first time with such high accuracy required for gravitational wave detection -- the science of spacetime metrology, in which the Doppler link between two free-falling test masses measures the curvature. Thi...

  13. Optical Aberrations and Wavefront

    Nihat Polat

    2014-08-01

    Full Text Available The deviation of light to create normal retinal image in the optical system is called aberration. Aberrations are divided two subgroup: low-order aberrations (defocus: spherical and cylindrical refractive errors and high-order aberrations (coma, spherical, trefoil, tetrafoil, quadrifoil, pentafoil, secondary astigmatism. Aberrations increase with aging. Spherical aberrations are compensated by positive corneal and negative lenticular spherical aberrations in youth. Total aberrations are elevated by positive corneal and positive lenticular spherical aberrations in elderly. In this study, we aimed to analyze the basic terms regarding optic aberrations which have gained significance recently. (Turk J Ophthalmol 2014; 44: 306-11

  14. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb.

    Rosa-Eva Huettl

    2011-02-01

    Full Text Available The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1 in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG, we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs.

  15. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb.

    Huettl, Rosa-Eva; Soellner, Heidi; Bianchi, Elisa; Novitch, Bennett G; Huber, Andrea B

    2011-02-01

    The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1) in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG), we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs.

  16. Using Map Decomposition to Improve Pathfinding

    Kári Halldórsson 1979

    2015-01-01

    Artificial intelligence in games performs computationally expensive searches in large state spaces, i.e. for pathfinding and strategic decisions. Breaking the state space down into regions, with clear connections, can greatly benefit these algorithms, allowing decision making on a higher level and guiding searches in a more focused way through the search space. We present an improved heuristic for pathfinding search that takes advantage of such decompositions, as well as a fully automated m...

  17. Functional complexity of the axonal growth cone: a proteomic analysis.

    Adriana Estrada-Bernal

    Full Text Available The growth cone, the tip of the emerging neurite, plays a crucial role in establishing the wiring of the developing nervous system. We performed an extensive proteomic analysis of axonal growth cones isolated from the brains of fetal Sprague-Dawley rats. Approximately 2000 proteins were identified at ≥ 99% confidence level. Using informatics, including functional annotation cluster and KEGG pathway analysis, we found great diversity of proteins involved in axonal pathfinding, cytoskeletal remodeling, vesicular traffic and carbohydrate metabolism, as expected. We also found a large and complex array of proteins involved in translation, protein folding, posttranslational processing, and proteasome/ubiquitination-dependent degradation. Immunofluorescence studies performed on hippocampal neurons in culture confirmed the presence in the axonal growth cone of proteins representative of these processes. These analyses also provide evidence for rough endoplasmic reticulum and reveal a reticular structure equipped with Golgi-like functions in the axonal growth cone. Furthermore, Western blot revealed the growth cone enrichment, relative to fetal brain homogenate, of some of the proteins involved in protein synthesis, folding and catabolism. Our study provides a resource for further research and amplifies the relatively recently developed concept that the axonal growth cone is equipped with proteins capable of performing a highly diverse range of functions.

  18. Integrin antagonists affect growth and pathfinding of ventral motor nerves in the trunk of embryonic zebrafish.

    Becker, Thomas; McLane, Mary Ann; Becker, Catherina G

    2003-05-01

    Integrins are thought to be important receptors for extracellular matrix (ECM) components on growing axons. Ventral motor axons in the trunk of embryonic zebrafish grow in a midsegmental pathway through an environment rich in ECM components. To test the role of integrins in this process, integrin antagonists (the disintegrin echistatin in native and recombinant form, as well as the Arg-Gly-Asp-Ser peptide) were injected into embryos just prior to axon outgrowth at 14-16 h postfertilization (hpf). All integrin antagonists affected growth of ventral motor nerves in a similar way and native echistatin was most effective. At 24 hpf, when only the three primary motor axons per trunk hemisegment had grown out, 80% (16 of 20) of the embryos analyzed had abnormal motor nerves after injection of native echistatin, corresponding to 19% (91 of 480) of all nerves. At 33 hpf, when secondary motor axons were present in the pathway, 100% of the embryos were affected (24 of 24), with 20% of all nerves analyzed (196 of 960) being abnormal. Phenotypes comprised abnormal branching (64% of all abnormal nerves) and truncations (36% of all abnormal nerves) of ventral motor nerves at 24 hpf and mostly branching of the nerves at 33 hpf (94% of all abnormal nerves). Caudal branches were at least twice as frequent as rostral branches. Surrounding trunk tissue and a number of other axon fascicles were apparently not affected by the injections. Thus integrin function contributes to both growth and pathfinding of axons in ventral motor nerves in the trunk of zebrafish in vivo.

  19. Axonal GABAA receptors.

    Trigo, Federico F; Marty, Alain; Stell, Brandon M

    2008-09-01

    Type A GABA receptors (GABA(A)Rs) are well established as the main inhibitory receptors in the mature mammalian forebrain. In recent years, evidence has accumulated showing that GABA(A)Rs are prevalent not only in the somatodendritic compartment of CNS neurons, but also in their axonal compartment. Evidence for axonal GABA(A)Rs includes new immunohistochemical and immunogold data: direct recording from single axonal terminals; and effects of local applications of GABA(A)R modulators on action potential generation, on axonal calcium signalling, and on neurotransmitter release. Strikingly, whereas presynaptic GABA(A)Rs have long been considered inhibitory, the new studies in the mammalian brain mostly indicate an excitatory action. Depending on the neuron that is under study, axonal GABA(A)Rs can be activated by ambient GABA, by GABA spillover, or by an autocrine action, to increase either action potential firing and/or transmitter release. In certain neurons, the excitatory effects of axonal GABA(A)Rs persist into adulthood. Altogether, axonal GABA(A)Rs appear as potent neuronal modulators of the mammalian CNS.

  20. Regulation of axon guidance by compartmentalized nonsense-mediated mRNA decay

    Colak, Dilek; Ji, Sheng-Jian; Porse, Bo T

    2013-01-01

    show that Robo3.2, a receptor for the Slit family of guidance cues, is synthesized locally within axons of commissural neurons. Robo3.2 translation is induced by floor-plate-derived signals as axons cross the spinal cord midline. Robo3.2 is also a predicted target of the nonsense-mediated mRNA decay...... (NMD) pathway. We find that NMD regulates Robo3.2 synthesis by inducing the degradation of Robo3.2 transcripts in axons that encounter the floor plate. Commissural neurons deficient in NMD proteins exhibit aberrant axonal trajectories after crossing the midline, consistent with misregulation of Robo3...

  1. Evidence for the Role of MAP1B in Axon Formation

    Gonzalez-Billault, Christian; Avila, Jesus; Cáceres, Alfredo

    2001-01-01

    Cultured neurons obtained from a hypomorphous MAP1B mutant mouse line display a selective and significant inhibition of axon formation that reflects a delay in axon outgrowth and a reduced rate of elongation. This phenomenon is paralleled by decreased microtubule formation and dynamics, which is dramatic at the distal axonal segment, as well as in growth cones, where the more recently assembled microtubule polymer normally predominates. These neurons also have aberrant growth cone formation and increased actin-based protrusive activity. Taken together, this study provides direct evidence showing that by promoting microtubule dynamics and regulating cytoskeletal organization MAP1B has a crucial role in axon formation. PMID:11452005

  2. Axons take a dive

    Tong, Cheuk Ka; Cebrián-Silla, Arantxa; Paredes, Mercedes F; Huang, Eric J; García-Verdugo, Jose Manuel; Alvarez-Buylla, Arturo

    2015-01-01

    In the walls of the lateral ventricles of the adult mammalian brain, neural stem cells (NSCs) and ependymal (E1) cells share the apical surface of the ventricular–subventricular zone (V–SVZ). In a recent article, we show that supraependymal serotonergic (5HT) axons originating from the raphe nuclei in mice form an extensive plexus on the walls of the lateral ventricles where they contact E1 cells and NSCs. Here we further characterize the contacts between 5HT supraependymal axons and E1 cells in mice, and show that suprependymal axons tightly associated to E1 cells are also present in the walls of the human lateral ventricles. These observations raise interesting questions about the function of supraependymal axons in the regulation of E1 cells. PMID:26413556

  3. Axonal bleb recording

    Wenqin Hu; Yousheng Shu

    2012-01-01

    Patch-clamp recording requires direct accessibility of the cell membrane to patch pipettes and allows the investigation of ion channel properties and functions in specific cellular compartments.The cell body and relatively thick dendrites are the most accessible compartments of a neuron,due to their large diameters and therefore great membrane surface areas.However,axons are normally inaccessible to patch pipettes because of their thin structure; thus studies of axon physiology have long been hampered by the lack of axon recording methods.Recently,a new method of patchclamp recording has been developed,enabling direct and tight-seal recording from cortical axons.These recordings are performed at the enlarged structure (axonal bleb) formed at the cut end of an axon after slicing procedures.This method has facilitated studies of the mechanisms underlying the generation and propagation of the main output signal,the action potential,and led to the finding that cortical neurons communicate not only in action potential-mediated digital mode but also in membrane potential-dependent analog mode.

  4. Mechanical design of the Mars Pathfinder mission

    Eisen, Howard Jay; Buck, Carl W.; Gillis-Smith, Greg R.; Umland, Jeffrey W.

    1997-01-01

    The Mars Pathfinder mission and the Sojourner rover is reported on, with emphasis on the various mission steps and the performance of the technologies involved. The mechanical design of mission hardware was critical to the success of the entry sequence and the landing operations. The various mechanisms employed are considered.

  5. Free-flight experiments in LISA Pathfinder

    Armano, M; Auger, G; Baird, J; Binetruy, P; Born, M; Bortoluzzi, D; Brandt, N; Bursi, A; Caleno, M; Cavalleri, A; Cesarini, A; Cruise, M; Cutler, C; Danzmann, K; Diepholz, I; Dolesi, R; Dunbar, N; Ferraioli, L; Ferroni, V; Fitzsimons, E; Freschi, M; Gallegos, J; Marirrodriga, C Garcia; Gerndt, R; Gesa, LI; Gibert, F; Giardini, D; Giusteri, R; Grimani, C; Harrison, I; Heinzel, G; Hewitson, M; Hollington, D; Hueller, M; Huesler, J; Inchauspe, H; Jennrich, O; Jetzer, P; Johlander, B; Karnesis, N; Kaune, B; Korsakova, N; Killow, C; Lloro, I; Maarschalkerweerd, R; Madden, S; Maghami, P; Mance, D; Martin, V; Martin-Porqueras, F; Mateos, I; McNamara, P; Mendes, J; Mendes, L; Moroni, A; Nofrarias, M; Paczkowski, S; Perreur-Lloyd, M; Petiteau, A; Pivato, P; Plagnol, E; Prat, P; Ragnit, U; Ramos-Castro, J; Reiche, J; Perez, J A Romera; Robertson, D; Rozemeijer, H; Russano, G; Sarra, P; Schleicher, A; Slutsky, J; Sopuerta, C F; Sumner, T; Texier, D; Thorpe, J; Trenkel, C; Tu, H B; Vetrugno, D; Vitale, S; Wanner, G; Ward, H; Waschke, S; Wass, P; Wealthy, D; Wen, S; Weber, W; Wittchen, A; Zanoni, C; Ziegler, T; Zweifel, P

    2014-01-01

    The LISA Pathfinder mission will demonstrate the technology of drag-free test masses for use as inertial references in future space-based gravitational wave detectors. To accomplish this, the Pathfinder spacecraft will perform drag-free flight about a test mass while measuring the acceleration of this primary test mass relative to a second reference test mass. Because the reference test mass is contained within the same spacecraft, it is necessary to apply forces on it to maintain its position and attitude relative to the spacecraft. These forces are a potential source of acceleration noise in the LISA Pathfinder system that are not present in the full LISA configuration. While LISA Pathfinder has been designed to meet it's primary mission requirements in the presence of this noise, recent estimates suggest that the on-orbit performance may be limited by this `suspension noise'. The drift-mode or free-flight experiments provide an opportunity to mitigate this noise source and further characterize the underlyi...

  6. EFN-4 functions in LAD-2-mediated axon guidance in Caenorhabditis elegans.

    Dong, Bingyun; Moseley-Alldredge, Melinda; Schwieterman, Alicia A; Donelson, Cory J; McMurry, Jonathan L; Hudson, Martin L; Chen, Lihsia

    2016-04-01

    During development of the nervous system, growing axons rely on guidance molecules to direct axon pathfinding. A well-characterized family of guidance molecules are the membrane-associated ephrins, which together with their cognate Eph receptors, direct axon navigation in a contact-mediated fashion. InC. elegans, the ephrin-Eph signaling system is conserved and is best characterized for their roles in neuroblast migration during early embryogenesis. This study demonstrates a role for the C. elegans ephrin EFN-4 in axon guidance. We provide both genetic and biochemical evidence that is consistent with the C. elegans divergent L1 cell adhesion molecule LAD-2 acting as a non-canonical ephrin receptor to EFN-4 to promote axon guidance. We also show that EFN-4 probably functions as a diffusible factor because EFN-4 engineered to be soluble can promote LAD-2-mediated axon guidance. This study thus reveals a potential additional mechanism for ephrins in regulating axon guidance and expands the repertoire of receptors by which ephrins can signal.

  7. Chicago aberration correction work.

    Beck, V D

    2012-12-01

    The author describes from his personal involvement the many improvements to electron microscopy Albert Crewe and his group brought by minimizing the effects of aberrations. The Butler gun was developed to minimize aperture aberrations in a field emission electron gun. In the 1960s, Crewe anticipated using a spherical aberration corrector based on Scherzer's design. Since the tolerances could not be met mechanically, a method of moving the center of the octopoles electrically was developed by adding lower order multipole fields. Because the corrector was located about 15 cm ahead of the objective lens, combination aberrations would arise with the objective lens. This fifth order aberration would then limit the aperture of the microscope. The transformation of the off axis aberration coefficients of a round lens was developed and a means to cancel anisotropic coma was developed. A new method of generating negative spherical aberration was invented using the combination aberrations of hexapoles. Extensions of this technique to higher order aberrations were developed. An electrostatic electron mirror was invented, which allows the cancellation of primary spherical aberration and first order chromatic aberration. A reduction of chromatic aberration by two orders of magnitude was demonstrated using such a system.

  8. Chicago aberration correction work

    Beck, V.D., E-mail: vnlbeck@earthlink.net [1 Hobby Drive, Ridgefield, CT 06877-01922 (United States)

    2012-12-15

    The author describes from his personal involvement the many improvements to electron microscopy Albert Crewe and his group brought by minimizing the effects of aberrations. The Butler gun was developed to minimize aperture aberrations in a field emission electron gun. In the 1960s, Crewe anticipated using a spherical aberration corrector based on Scherzer's design. Since the tolerances could not be met mechanically, a method of moving the center of the octopoles electrically was developed by adding lower order multipole fields. Because the corrector was located about 15 cm ahead of the objective lens, combination aberrations would arise with the objective lens. This fifth order aberration would then limit the aperture of the microscope. The transformation of the off axis aberration coefficients of a round lens was developed and a means to cancel anisotropic coma was developed. A new method of generating negative spherical aberration was invented using the combination aberrations of hexapoles. Extensions of this technique to higher order aberrations were developed. An electrostatic electron mirror was invented, which allows the cancellation of primary spherical aberration and first order chromatic aberration. A reduction of chromatic aberration by two orders of magnitude was demonstrated using such a system. -- Highlights: Black-Right-Pointing-Pointer Crewe and his group made significant advances in aberration correction and reduction. Black-Right-Pointing-Pointer A deeper understanding of the quadrupole octopole corrector was developed. Black-Right-Pointing-Pointer A scheme to correct spherical aberration using hexapoles was developed. Black-Right-Pointing-Pointer Chromatic aberration was corrected using a uniform field mirror.

  9. Direction Oriented Pathfinding In Video Games

    Xiao Cui

    2011-11-01

    Full Text Available Pathfinding has been one of major research areas in video games for many years. It is a key problem that most video games are confronted with. Search algorithm such as Dijkstra’s algorithm and A* algorithm are representing only half of the picture. The underlying map representations such as regular grid, visibility graph and navigation mesh also have significant impact on the performance. This paper reviews the current widely used solutions for pathfinding and proposes a new method which is expected to generate a higher quality path using less time and memory than other existing solutions. The deployment of methodology and techniques is described in detail. The aim and significance of the proposed method in future video games is addressed and the conclusion is given at the end.

  10. Parameter estimation in LISA Pathfinder operational exercises

    Nofrarias, Miquel; Congedo, Giuseppe; Hueller, Mauro; Armano, M; Diaz-Aguilo, M; Grynagier, A; Hewitson, M

    2011-01-01

    The LISA Pathfinder data analysis team has been developing in the last years the infrastructure and methods required to run the mission during flight operations. These are gathered in the LTPDA toolbox, an object oriented MATLAB toolbox that allows all the data analysis functionalities for the mission, while storing the history of all operations performed to the data, thus easing traceability and reproducibility of the analysis. The parameter estimation methods in the toolbox have been applied recently to data sets generated with the OSE (Off-line Simulations Environment), a detailed LISA Pathfinder non-linear simulator that will serve as a reference simulator during mission operations. These operational exercises aim at testing the on-orbit experiments in a realistic environment in terms of software and time constraints. These simulations, so called operational exercises, are the last verification step before translating these experiments into tele-command sequences for the spacecraft, producing therefore ve...

  11. Testing MOND/TEVES with LISA Pathfinder

    Trenkel, Christian; Bevis, Neil; Magueijo, Joao

    2010-01-01

    We suggest that LISA Pathfinder could be used to subject TEVES, and in particular the non-relativistic MOND phenomenology it incorporates, to a direct, controlled experimental test, in just a few years' time. The basic concept is to fly LISA Pathfinder through the region around the Sun-Earth saddle point, following its nominal mission, in order to look for anomalous gravity gradients. We examine various strategies to reach the saddle point, and conclude that the preferred strategy, resulting in relatively short transfer times of order one year, probably involves a lunar fly-by. We present robust estimates of the MOND gravity gradients that LISA Pathfinder should be exposed to, and conclude that if the gradiometer on-board the spacecraft achieves its nominal performance, these gradients will not just be detected, but measured and characterised in some detail, should they exist. Conversely, given the large predicted signal based on standard assumptions, a null result would most likely spell the end of TEVES/MON...

  12. Glia to axon RNA transfer.

    Sotelo, José Roberto; Canclini, Lucía; Kun, Alejandra; Sotelo-Silveira, José Roberto; Calliari, Aldo; Cal, Karina; Bresque, Mariana; Dipaolo, Andrés; Farias, Joaquina; Mercer, John A

    2014-03-01

    The existence of RNA in axons has been a matter of dispute for decades. Evidence for RNA and ribosomes has now accumulated to a point at which it is difficult to question, much of the disputes turned to the origin of these axonal RNAs. In this review, we focus on studies addressing the origin of axonal RNAs and ribosomes. The neuronal soma as the source of most axonal RNAs has been demonstrated and is indisputable. However, the surrounding glial cells may be a supplemental source of axonal RNAs, a matter scarcely investigated in the literature. Here, we review the few papers that have demonstrated that glial-to-axon RNA transfer is not only feasible, but likely. We describe this process in both invertebrate axons and vertebrate axons. Schwann cell to axon ribosomes transfer was conclusively demonstrated (Court et al. [2008]: J. Neurosci 28:11024-11029; Court et al. [2011]: Glia 59:1529-1539). However, mRNA transfer still remains to be demonstrated in a conclusive way. The intercellular transport of mRNA has interesting implications, particularly with respect to the integration of glial and axonal function. This evolving field is likely to impact our understanding of the cell biology of the axon in both normal and pathological conditions. Most importantly, if the synthesis of proteins in the axon can be controlled by interacting glia, the possibilities for clinical interventions in injury and neurodegeneration are greatly increased.

  13. Transient neuronal populations are required to guide callosal axons: a role for semaphorin 3C.

    Mathieu Niquille

    2009-10-01

    Full Text Available The corpus callosum (CC is the main pathway responsible for interhemispheric communication. CC agenesis is associated with numerous human pathologies, suggesting that a range of developmental defects can result in abnormalities in this structure. Midline glial cells are known to play a role in CC development, but we here show that two transient populations of midline neurons also make major contributions to the formation of this commissure. We report that these two neuronal populations enter the CC midline prior to the arrival of callosal pioneer axons. Using a combination of mutant analysis and in vitro assays, we demonstrate that CC neurons are necessary for normal callosal axon navigation. They exert an attractive influence on callosal axons, in part via Semaphorin 3C and its receptor Neuropilin-1. By revealing a novel and essential role for these neuronal populations in the pathfinding of a major cerebral commissure, our study brings new perspectives to pathophysiological mechanisms altering CC formation.

  14. Dynamics of degeneration and regeneration in developing zebrafish peripheral axons reveals a requirement for extrinsic cell types

    Villegas Rosario

    2012-06-01

    Full Text Available Abstract Background Understanding the cellular mechanisms regulating axon degeneration and regeneration is crucial for developing treatments for nerve injury and neurodegenerative disease. In neurons, axon degeneration is distinct from cell body death and often precedes or is associated with the onset of disease symptoms. In the peripheral nervous system of both vertebrates and invertebrates, after degeneration of detached fragments, axons can often regenerate to restore function. Many studies of axonal degeneration and regeneration have used in vitro approaches, but the influence of extrinsic cell types on these processes can only be fully addressed in live animals. Because of its simplicity and superficial location, the larval zebrafish posterior lateral line (pLL nerve is an ideal model system for live studies of axon degeneration and regeneration. Results We used laser axotomy and time-lapse imaging of pLL axons to characterize the roles of leukocytes, Schwann cells and target sensory hair cells in axon degeneration and regeneration in vivo. Immune cells were essential for efficient removal of axonal debris after axotomy. Schwann cells were required for proper fasciculation and pathfinding of regenerating axons to their target cells. Intact target hair cells were not themselves required for regeneration, but chemical ablation of neuromasts caused axons to transiently deviate from their normal paths. Conclusions Macrophages, Schwann cells, and target sensory organs are required for distinct aspects of pLL axon degeneration or regeneration in the zebrafish larva. Our work introduces a powerful vertebrate model for analyzing axonal degeneration and regeneration in the living animal and elucidating the role of extrinsic cell types in these processes.

  15. A role for myosin VI in the localization of axonal proteins.

    Tommy L Lewis

    2011-03-01

    Full Text Available In neurons polarized trafficking of vesicle-bound membrane proteins gives rise to the distinct molecular composition and functional properties of axons and dendrites. Despite their central role in shaping neuronal form and function, surprisingly little is known about the molecular processes that mediate polarized targeting of neuronal proteins. Recently, the plus-end-directed motor Myosin Va was shown to play a critical role in targeting of transmembrane proteins to dendrites; however, the role of myosin motors in axonal targeting is unknown. Here we show that Myosin VI, a minus-end-directed motor, plays a vital role in the enrichment of proteins on the surface of axons. Engineering non-neuronal proteins to interact with Myosin VI causes them to become highly concentrated at the axonal surface in dissociated rat cortical neurons. Furthermore, disruption of either Myosin VI function or expression leads to aberrant dendritic localization of axonal proteins. Myosin VI mediates the enrichment of proteins on the axonal surface at least in part by stimulating dendrite-specific endocytosis, a mechanism that has been shown to underlie the localization of many axonal proteins. In addition, a version of Channelrhodopsin 2 that was engineered to bind to Myosin VI is concentrated at the surface of the axon of cortical neurons in mice in vivo, suggesting that it could be a useful tool for probing circuit structure and function. Together, our results indicate that myosins help shape the polarized distributions of both axonal and dendritic proteins.

  16. Bergmann glia and the recognition molecule CHL1 organize GABAergic axons and direct innervation of Purkinje cell dendrites.

    Fabrice Ango

    2008-04-01

    Full Text Available The geometric and subcellular organization of axon arbors distributes and regulates electrical signaling in neurons and networks, but the underlying mechanisms have remained elusive. In rodent cerebellar cortex, stellate interneurons elaborate characteristic axon arbors that selectively innervate Purkinje cell dendrites and likely regulate dendritic integration. We used GFP BAC transgenic reporter mice to examine the cellular processes and molecular mechanisms underlying the development of stellate cell axons and their innervation pattern. We show that stellate axons are organized and guided towards Purkinje cell dendrites by an intermediate scaffold of Bergmann glial (BG fibers. The L1 family immunoglobulin protein Close Homologue of L1 (CHL1 is localized to apical BG fibers and stellate cells during the development of stellate axon arbors. In the absence of CHL1, stellate axons deviate from BG fibers and show aberrant branching and orientation. Furthermore, synapse formation between aberrant stellate axons and Purkinje dendrites is reduced and cannot be maintained, leading to progressive atrophy of axon terminals. These results establish BG fibers as a guiding scaffold and CHL1 a molecular signal in the organization of stellate axon arbors and in directing their dendritic innervation.

  17. Scientific results of the Mars Pathfinder mission.

    Golombek, M. P.

    1999-02-01

    The author, project scientist of the Mars Pathfinder mision, presents a summary of the most important scientific results from the space probe, which descended to the Martian surface on July 4, 1997. These results include the strong evidence for catastrophic water floods in the history of the planet; close-up studies of the morphology and mineralogy of Martian rocks; the characteristics, chemistry, and origin of the magnetic dust particles deposited on the Martian surface; and meteorological measurements of temperature fluctuations, pressure variations, and wind velocities.

  18. The LISA Pathfinder DMU and Radiation Monitor

    Canizares, P.; Chmeissani, M.; Conchillo, A.; Diaz–Aguiló, M.; García-Berro, E.; Gesa, L.; Gibert, F.; Grimani, C.; Lloro, I.; Lobo, A.; Mateos, I.; Nofrarias, M.; Ramos-Castro, J.; Sanjuán, J.; Sopuerta, Carlos F.; Araújo, H. M.; Wass, P.

    2011-05-01

    The LISA Pathfinder DMU (Data Management Unit) flight model was formally accepted by ESA and ASD on 11 February 2010, after all hardware and software tests had been successfully completed. The diagnostics items are scheduled to be delivered by the end of 2010. In this paper, we review the requirements and performance of this instrumentation, specially focusing on the Radiation Monitor and the DMU, as well as the status of their programmed use during mission operations, on which work is ongoing at the time of writing.

  19. The LISA Pathfinder DMU and Radiation Monitor

    Canizares, P; Conchillo, A; Gesa, L; Lloro, I; Lobo, A; Mateos, I; Sopuerta, Carlos F [Institut de Ciencies de l' Espai, CSIC, Facultat de Ciencies, Torre C5 parell, 08193 Bellaterra (Spain); Chmeissani, M [Institut de Fisica d' Altes Energies (IFAE), Edifici CN, UAB Campus, 08193 Bellaterra (Spain); Diaz-Aguilo, M; GarcIa-Berro, E; Gibert, F [Institut d' Estudis Espacials de Catalunya (IEEC), Edifici Nexus, Gran Capita 2-4, 08034 Barcelona (Spain); Grimani, C [Universita degli Studi di Urbino, MFI Department, Via Santa Chiara 27, 61029 Urbino, and INFN Florence (Italy); Nofrarias, M [Max-Planck-Institut fuer Gravitationsphysik (Albert-Einstein-Institut), Callinstrasse 38, D-30167 Hannover (Germany); Ramos-Castro, J [Departament d' Enginyeria Electronica, UPC, Campus Nord, Edifici C4, Jordi Girona 1-3, 08034 Barcelona (Spain); Sanjuan, J [Department of Physics, University of Florida, NPB-22258 PO Box 118 440, Gainesville, FL 32611-8440 (United States); Araujo, H M; Wass, P, E-mail: lobo@ieec.fcr.es [High Energy Physics Blackett Laboratory, Prince Consort Road, Imperial College London, London SW7 2BW (United Kingdom)

    2011-05-07

    The LISA Pathfinder DMU (Data Management Unit) flight model was formally accepted by ESA and ASD on 11 February 2010, after all hardware and software tests had been successfully completed. The diagnostics items are scheduled to be delivered by the end of 2010. In this paper, we review the requirements and performance of this instrumentation, specially focusing on the Radiation Monitor and the DMU, as well as the status of their programmed use during mission operations, on which work is ongoing at the time of writing.

  20. Developmental expression of the lipocalin Lazarillo and its role in axonal pathfinding in the grasshopper embryo.

    Sánchez, D; Ganfornina, M D; Bastiani, M J

    1995-01-01

    This article describes the expression pattern and functional analysis of Lazarillo, a novel cell surface glycoprotein expressed in the embryonic grasshopper nervous system, and a member of the lipocalin family. Lazarillo is expressed by a subset of neuroblasts, ganglion mother cells and neurons of the central nervous system, by all sensory neurons of the peripheral nervous system, and by a subset of neurons of the enteric nervous system. It is also present in a few non neuronal cells associated mainly with the excretory system. A monoclonal antibody raised against Lazarillo perturbs the extent and direction of growth of identified commissural pioneer neurons. We propose that Lazarillo is the receptor for a midline morphogen involved in the outgrowth and guidance of these neurons.

  1. SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome.

    Naresh Kumar Hanchate

    2012-08-01

    Full Text Available Kallmann syndrome (KS associates congenital hypogonadism due to gonadotropin-releasing hormone (GnRH deficiency and anosmia. The genetics of KS involves various modes of transmission, including oligogenic inheritance. Here, we report that Nrp1(sema/sema mutant mice that lack a functional semaphorin-binding domain in neuropilin-1, an obligatory coreceptor of semaphorin-3A, have a KS-like phenotype. Pathohistological analysis of these mice indeed showed abnormal development of the peripheral olfactory system and defective embryonic migration of the neuroendocrine GnRH cells to the basal forebrain, which results in increased mortality of newborn mice and reduced fertility in adults. We thus screened 386 KS patients for the presence of mutations in SEMA3A (by Sanger sequencing of all 17 coding exons and flanking splice sites and identified nonsynonymous mutations in 24 patients, specifically, a frameshifting small deletion (D538fsX31 and seven different missense mutations (R66W, N153S, I400V, V435I, T688A, R730Q, R733H. All the mutations were found in heterozygous state. Seven mutations resulted in impaired secretion of semaphorin-3A by transfected COS-7 cells (D538fsX31, R66W, V435I or reduced signaling activity of the secreted protein in the GN11 cell line derived from embryonic GnRH cells (N153S, I400V, T688A, R733H, which strongly suggests that these mutations have a pathogenic effect. Notably, mutations in other KS genes had already been identified, in heterozygous state, in five of these patients. Our findings indicate that semaphorin-3A signaling insufficiency contributes to the pathogenesis of KS and further substantiate the oligogenic pattern of inheritance in this developmental disorder.

  2. SEMA3A, a gene involved in axonal pathfinding, is mutated in patients with Kallmann syndrome.

    Hanchate, Naresh Kumar; Giacobini, Paolo; Lhuillier, Pierre; Parkash, Jyoti; Espy, Cécile; Fouveaut, Corinne; Leroy, Chrystel; Baron, Stéphanie; Campagne, Céline; Vanacker, Charlotte; Collier, Francis; Cruaud, Corinne; Meyer, Vincent; García-Piñero, Alfons; Dewailly, Didier; Cortet-Rudelli, Christine; Gersak, Ksenija; Metz, Chantal; Chabrier, Gérard; Pugeat, Michel; Young, Jacques; Hardelin, Jean-Pierre; Prevot, Vincent; Dodé, Catherine

    2012-08-01

    Kallmann syndrome (KS) associates congenital hypogonadism due to gonadotropin-releasing hormone (GnRH) deficiency and anosmia. The genetics of KS involves various modes of transmission, including oligogenic inheritance. Here, we report that Nrp1(sema/sema) mutant mice that lack a functional semaphorin-binding domain in neuropilin-1, an obligatory coreceptor of semaphorin-3A, have a KS-like phenotype. Pathohistological analysis of these mice indeed showed abnormal development of the peripheral olfactory system and defective embryonic migration of the neuroendocrine GnRH cells to the basal forebrain, which results in increased mortality of newborn mice and reduced fertility in adults. We thus screened 386 KS patients for the presence of mutations in SEMA3A (by Sanger sequencing of all 17 coding exons and flanking splice sites) and identified nonsynonymous mutations in 24 patients, specifically, a frameshifting small deletion (D538fsX31) and seven different missense mutations (R66W, N153S, I400V, V435I, T688A, R730Q, R733H). All the mutations were found in heterozygous state. Seven mutations resulted in impaired secretion of semaphorin-3A by transfected COS-7 cells (D538fsX31, R66W, V435I) or reduced signaling activity of the secreted protein in the GN11 cell line derived from embryonic GnRH cells (N153S, I400V, T688A, R733H), which strongly suggests that these mutations have a pathogenic effect. Notably, mutations in other KS genes had already been identified, in heterozygous state, in five of these patients. Our findings indicate that semaphorin-3A signaling insufficiency contributes to the pathogenesis of KS and further substantiate the oligogenic pattern of inheritance in this developmental disorder.

  3. Aberration Corrected Emittance Exchange

    Nanni, Emilio A

    2015-01-01

    Full exploitation of emittance exchange (EEX) requires aberration-free performance of a complex imaging system including active radio-frequency (RF) elements which can add temporal distortions. We investigate the performance of an EEX line where the exchange occurs between two dimensions with normalized emittances which differ by orders of magnitude. The transverse emittance is exchanged into the longitudinal dimension using a double dog-leg emittance exchange setup with a 5 cell RF deflector cavity. Aberration correction is performed on the four most dominant aberrations. These include temporal aberrations that are corrected with higher order magnetic optical elements located where longitudinal and transverse emittance are coupled. We demonstrate aberration-free performance of emittances differing by 4 orders of magnitude, i.e. an initial transverse emittance of $\\epsilon_x=1$ pm-rad is exchanged with a longitudinal emittance of $\\epsilon_z=10$ nm-rad.

  4. Drosophila as a genetic and cellular model for studies on axonal growth

    Whitington Paul

    2007-05-01

    Full Text Available Abstract One of the most fascinating processes during nervous system development is the establishment of stereotypic neuronal networks. An essential step in this process is the outgrowth and precise navigation (pathfinding of axons and dendrites towards their synaptic partner cells. This phenomenon was first described more than a century ago and, over the past decades, increasing insights have been gained into the cellular and molecular mechanisms regulating neuronal growth and navigation. Progress in this area has been greatly assisted by the use of simple and genetically tractable invertebrate model systems, such as the fruit fly Drosophila melanogaster. This review is dedicated to Drosophila as a genetic and cellular model to study axonal growth and demonstrates how it can and has been used for this research. We describe the various cellular systems of Drosophila used for such studies, insights into axonal growth cones and their cytoskeletal dynamics, and summarise identified molecular signalling pathways required for growth cone navigation, with particular focus on pathfinding decisions in the ventral nerve cord of Drosophila embryos. These Drosophila-specific aspects are viewed in the general context of our current knowledge about neuronal growth.

  5. Detection of Micrometeoroids with LISA Pathfinder

    Thorpe, Ira; Littenberg, Tyson; Janchez, Diego; Baker, John; The LISA Pathfinder Team Team

    2017-01-01

    The LISA Pathfinder mission (LPF), a joint ESA/NASA technology demonstration mission currently operating at the Sun-Earth L1 point, contains the most precise accelerometry system ever flown. Analysis suggests that LPF should have sufficient sensitivity to detect impacts of small micrometeoroids and dust through their transfer of momentum to the spacecraft. Moreover, LPF's ability to fully resolve both the linear and angular momentum transfer in three dimensions allows a magnitude, direction, and location to be estimated for each impact. We present preliminary results from a systematic search of the LISA Pathfinder data for such impacts and discuss the prospects for using these and future results to inform models of the formation and evolution of dust populations in the inner solar system. These models have wide applicability to both pure and applied space science, ranging from the physics of planet formation and dynamics of minor Solar System bodies to estimates of the micrometeorite hazard for future spacecraft. 2017 NASA Science Innovation Fund.

  6. Canadian Hydrogen Intensity Mapping Experiment (CHIME) Pathfinder

    Bandura, Kevin; Amiri, Mandana; Bond, J Richard; Campbell-Wilson, Duncan; Connor, Liam; Cliche, Jean-Francois; Davis, Greg; Deng, Meiling; Denman, Nolan; Dobbs, Matt; Fandino, Mateus; Gibbs, Kenneth; Gilbert, Adam; Halpern, Mark; Hanna, David; Hincks, Adam D; Hinshaw, Gary; Hofer, Carolin; Klages, Peter; Landecker, Tom L; Masui, Kiyoshi; Mena, Juan; Newburgh, Laura B; Pen, Ue-Li; Peterson, Jeffrey B; Recnik, Andre; Shaw, J Richard; Sigurdson, Kris; Sitwell, Michael; Smecher, Graeme; Smegal, Rick; Vanderlinde, Keith; Wiebe, Don

    2014-01-01

    A pathfinder version of CHIME (the Canadian Hydrogen Intensity Mapping Experiment) is currently being commissioned at the Dominion Radio Astrophysical Observatory (DRAO) in Penticton, BC. The instrument is a hybrid cylindrical interferometer designed to measure the large scale neutral hydrogen power spectrum across the redshift range 0.8 to 2.5. The power spectrum will be used to measure the baryon acoustic oscillation (BAO) scale across this poorly probed redshift range where dark energy becomes a significant contributor to the evolution of the Universe. The instrument revives the cylinder design in radio astronomy with a wide field survey as a primary goal. Modern low-noise amplifiers and digital processing remove the necessity for the analog beamforming that characterized previous designs. The Pathfinder consists of two cylinders 37\\,m long by 20\\,m wide oriented north-south for a total collecting area of 1,500 square meters. The cylinders are stationary with no moving parts, and form a transit instrument ...

  7. In-flight Diagnostics in LISA Pathfinder

    Lobo, A.; Nofrarias, M.; Ramos-Castro, J.; Sanjuan, J.; Conchillo, A.; Ortega, J. A.; Xirgu, X.; Araujo, H.; Boatella, C.; Chmeissani, M.; Grimani, C.; Puigdengoles, C.; Wass, P.; García-Berro, E.; García, S.; Martínez, L. M.; Montero, G.

    2006-11-01

    LISA PathFinder (LPF) will be flown with the objective to test in space key technologies for LISA. However its sensitivity goals are, for good reason, one order of magnitude less than those which LISA will have to meet, both in drag-free and optical metrology requirements, and in the observation frequency band. While the expected success of LPF will of course be of itself a major step forward to LISA, one might not forget that a further improvement by an order of magnitude in performance will still be needed. Clues for the last leap are to be derived from proper disentanglement of the various sources of noise which contribute to the total noise, as measured in flight during the PathFinder mission. This paper describes the principles, workings and requirements of one of the key tools to serve the above objective: the diagnostics subsystem. This consists in sets of temperature, magnetic field, and particle counter sensors, together with generators of controlled thermal and magnetic perturbations. At least during the commissioning phase, the latter will be used to identify feed-through coefficients between diagnostics sensor readings and associated actual noise contributions. A brief progress report of the current state of development of the diagnostics subsystem will be given as well.

  8. In-flight Diagnostics in LISA Pathfinder

    Lobo, A; Ramos-Castro, J; Sanjuan, J; Conchillo, A; Ortega, J A; Xirgu, X; Araujo, H; Boatella, C; Chmeissani, M; Grimani, C; Puigdengoles, C; Wass, P; García-Berro, E; García, S; Martínez, L; Montero, G; Lobo, Alberto; Nofrarias, Miquel; Ramos-Castro, Juan; Sanjuan, Josep; Conchillo, Aleix; Ortega, Jose Antonio; Xirgu, Xevi; Araujo, Henrique; Boatella, Cesar; Chmeissani, Mokhtar; Grimani, Catia; Puigdengoles, Carles; Wass, Peter; Garcia-Berro, Enrique; Garcia, Sergi; Martinez, Lluis; Montero, Gustau

    2007-01-01

    LISA PathFinder (LPF) will be flown with the objective to test in space key technologies for LISA. However its sensitivity goals are, for good reason, one order of magnitude less than those which LISA will have to meet, both in drag-free and optical metrology requirements, and in the observation frequency band. While the expected success of LPF will of course be of itself a major step forward to LISA, one might not forget that a further improvement by an order of magnitude in performance will still be needed. Clues for the last leap are to be derived from proper disentanglement of the various sources of noise which contribute to the total noise, as measured in flight during the PathFinder mission. This paper describes the principles, workings and requirements of one of the key tools to serve the above objective: the diagnostics subsystem. This consists in sets of temperature, magnetic field, and particle counter sensors, together with generators of controlled thermal and magnetic perturbations. At least durin...

  9. Pathfinder landing sites at candidate SNC impact ejection sites

    Golombek, Matthew P.

    1994-01-01

    If Mars Pathfinder were able to land at a site on Mars from which the SNC meteorites were ejected by impact, the Pathfinder mission would essentially represent a very inexpensive sample return mission. Geologic units that contain four potential impact craters from which SNC meteorites could have been ejected from Mars are accessible to the Mars Pathfinder lander. Determining that SNC meteorites came from a particular spot on Mars raises the intriguing possibility of using Pathfinder as a sample return mission and providing a radiometric age for the considerably uncertain martian crater-age timescale. Pathfinder instruments are capable of determining if the rock type at the landing site is similar to that of one or more of the SNC meteorites, which would strengthen the hypothesis that the SNC meteorites did, in fact, come from Mars. Unfortunately, instrument observations from Pathfinder are probably not capable of determining if the geologic unit sampled by the lander is definitively the unit from which a SNC meteorite came from as opposed to Mars in general or perhaps a particular region on Mars. This abstract evaluates the possibility of landing at potential SNC ejection sites and the ability of Pathfinder to identify the landing site as the place from which an SNC meteorite came.

  10. Model Checking JAVA Programs Using Java Pathfinder

    Havelund, Klaus; Pressburger, Thomas

    2000-01-01

    This paper describes a translator called JAVA PATHFINDER from JAVA to PROMELA, the "programming language" of the SPIN model checker. The purpose is to establish a framework for verification and debugging of JAVA programs based on model checking. This work should be seen in a broader attempt to make formal methods applicable "in the loop" of programming within NASA's areas such as space, aviation, and robotics. Our main goal is to create automated formal methods such that programmers themselves can apply these in their daily work (in the loop) without the need for specialists to manually reformulate a program into a different notation in order to analyze the program. This work is a continuation of an effort to formally verify, using SPIN, a multi-threaded operating system programmed in Lisp for the Deep-Space 1 spacecraft, and of previous work in applying existing model checkers and theorem provers to real applications.

  11. PAPPA: Primordial Anisotropy Polarization Pathfinder Array

    Kogut, A; Fixsen, D; Hinshaw, G F; Limon, M; Moseley, S H; Phillips, N; Sharp, E; Wollack, E J; U-Yen, K; Cao, N; Stevenson, T; Hsieh, W; Devlin, M; Dicker, S; Semisch, C; Irwin, K

    2006-01-01

    The Primordial Anisotropy Polarization Pathfinder Array (PAPPA) is a balloon-based instrument to measure the polarization of the cosmic microwave background and search for the signal from gravity waves excited during an inflationary epoch in the early universe. PAPPA will survey a 20 x 20 deg patch at the North Celestial Pole using 32 pixels in 3 passbands centered at 89, 212, and 302 GHz. Each pixel uses MEMS switches in a superconducting microstrip transmission line to combine the phase modulation techniques used in radio astronomy with the sensitivity of transition-edge superconducting bolometers. Each switched circuit modulates the incident polarization on a single detector, allowing nearly instantaneous characterization of the Stokes I, Q, and U parameters. We describe the instrument design and status.

  12. Modal analysis of PATHFINDER unmanned air vehicle

    Woehrle, T.G.; Costerus, B.W.; Lee, C.L.

    1994-10-19

    An experimental modal analysis was performed on PATHFINDER, a 450-lb, 100-ft wing span, flying-wing-design aircraft powered by solar/electric motors. The aircraft was softly suspended and then excited using random input from a long-stroke shaker. Modal data was taken from 92 measurement locations on the aircraft using newly designed, lightweight, tri-axial accelerometers. A conventional PC-based data acquisition system provided data handling. Modal parameters were calculated, and animated mode shapes were produced using SMS STARStruct{trademark} Modal Analysis System software. The modal parameters will be used for validation of finite element models, optimum placement of onboard accelerometers during flight testing, and vibration isolation design of sensor platforms.

  13. APECS - The Atacama Pathfinder Experiment Control System

    Muders, D; Hafok, H; Hatchell, J; Koenig, C; Polehampton, E; Schaaf, R; Schuller, F; Tak, F; Wyrowski, F

    2006-01-01

    APECS is the distributed control system of the new Atacama Pathfinder EXperiment (APEX) telescope located on the Llano de Chajnantor at an altitude of 5107 m in the Atacama desert in northern Chile. APECS is based on Atacama Large Millimeter Array (ALMA) software and employs a modern, object-oriented design using the Common Object Request Broker Architecture (CORBA) as the middleware. New generic device interfaces simplify adding instruments to the control system. The Python based observer command scripting language allows using many existing software libraries and facilitates creating more complex observing modes. A new self-descriptive raw data format (Multi-Beam FITS or MBFITS) has been defined to store the multi-beam, multi-frequency data. APECS provides an online pipeline for initial calibration, observer feedback and a quick-look display. APECS is being used for regular science observations in local and remote mode since August 2005.

  14. Imager for Mars Pathfinder (IMP) image calibration

    Reid, R.J.; Smith, P.H.; Lemmon, M.; Tanner, R.; Burkland, M.; Wegryn, E.; Weinberg, J.; Marcialis, R.; Britt, D.T.; Thomas, N.; Kramm, R.; Dummel, A.; Crowe, D.; Bos, B.J.; Bell, J.F.; Rueffer, P.; Gliem, F.; Johnson, J. R.; Maki, J.N.; Herkenhoff, K. E.; Singer, Robert B.

    1999-01-01

    The Imager for Mars Pathfinder returned over 16,000 high-quality images from the surface of Mars. The camera was well-calibrated in the laboratory, with <5% radiometric uncertainty. The photometric properties of two radiometric targets were also measured with 3% uncertainty. Several data sets acquired during the cruise and on Mars confirm that the system operated nominally throughout the course of the mission. Image calibration algorithms were developed for landed operations to correct instrumental sources of noise and to calibrate images relative to observations of the radiometric targets. The uncertainties associated with these algorithms as well as current improvements to image calibration are discussed. Copyright 1999 by the American Geophysical Union.

  15. Birdseye View of Pathfinder Landing Site

    1997-01-01

    This image is one frame of an animation that was created by using two mosaics: a color image of the Gallery Pan and an image which indicates the distance to the nearest object at each pixel location, referred to as a range image. The range data set is treated as a displacement map with respect to a sphere's surface, and the color image mosaic is draped onto the inside of the sphere. The position of the camera is fixed at the sphere's center, while its viewing direction is in this case looking at the south pole of the sphere. The mosaics were projected onto a continuous cylindrical/perspective coordinate system spanning 360 degrees of azimuth. The distortion visible near the edges of this image is due to the large field of view, as well as the limitation introduced by using cylindrically-projected images on the sphere - the effects of which are less apparent when smaller fields of view are used.The image has been rotated so that the main points of interest, which are the 'Rock Garden,' the rover Sojourner and the rock 'Yogi,' are easily seen arching across the upper hemisphere. In fixed Mars Surface coordinates, the top of the image looks out towards a point a few degrees north of West. Color has been enhanced to improve contrast in features, and is derived from IMP spectral filters 5, 9 and 0.Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is a division of the California Institute of Technology (Caltech).

  16. The genetics of axonal transport and axonal transport disorders.

    Jason E Duncan

    2006-09-01

    Full Text Available Neurons are specialized cells with a complex architecture that includes elaborate dendritic branches and a long, narrow axon that extends from the cell body to the synaptic terminal. The organized transport of essential biological materials throughout the neuron is required to support its growth, function, and viability. In this review, we focus on insights that have emerged from the genetic analysis of long-distance axonal transport between the cell body and the synaptic terminal. We also discuss recent genetic evidence that supports the hypothesis that disruptions in axonal transport may cause or dramatically contribute to neurodegenerative diseases.

  17. Lithium-Thionyl Chloride Batteries for the Mars Pathfinder Microrover

    Deligiannis, F.; Frank, H.; Staniewicz, R.J.; Willson, J. [SAFT America, Inc., Cockeysville, MD (United States)

    1996-02-01

    A discussion of the power requirements for the Mars Pathfinder Mission is given. Topics include: battery requirements; cell design; battery design; test descriptions and results. A summary of the results is also included.

  18. Lithium-Thionyl Chloride Batteries for the Mars Pathfinder Microrover

    Deligiannis, Frank; Frank, Harvey; Staniewicz, R. J.; Willson, John

    1996-01-01

    A discussion of the power requirements for the Mars Pathfinder Mission is given. Topics include: battery requirements; cell design; battery design; test descriptions and results. A summary of the results is also included.

  19. Narrative report Pathfinder National Wildlife Refuge: January through December, 1969

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments during the 1969 calendar year. The report begins by summarizing...

  20. Narrative report Pathfinder National Wildlife Refuge: January through December, 1970

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments during the 1970 calendar year. The report begins by summarizing...

  1. Narrative report Pathfinder National Wildlife Refuge: January through December, 1964

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments during the 1964 calendar year. The report begins by summarizing...

  2. Narrative report: Pathfinder National Wildlife Refuge: January through December 1972

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments during the 1972 calendar year. The report begins by summarizing...

  3. Narrative report Pathfinder National Wildlife Refuge: January through December, 1966

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments during the 1966 calendar year. The report begins by summarizing...

  4. Narrative report Pathfinder National Wildlife Refuge: January through December, 1971

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments during the 1971 calendar year. The report begins by summarizing...

  5. Narrative report Pathfinder National Wildlife Refuge: January through December, 1967

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments during the 1967 calendar year. The report begins by summarizing...

  6. Narrative report Pathfinder National Wildlife Refuge: January through December, 1968

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments during the 1968 calendar year. The report begins by summarizing...

  7. CRED REA Algal Assessment, Pathfinder Bank 2003 (NODC Accession 0010352)

    National Oceanic and Atmospheric Administration, Department of Commerce — Random collections of algae were made at 2 sites at Pathfinder Bank in the Commonwealth of the Northern Mariana Islands in August and September, 2003 from the NOAA...

  8. Giant lens, a gene involved in cell determination and axon guidance in the visual system of Drosophila melanogaster.

    Kretzschmar, D; Brunner, A; Wiersdorff, V; Pflugfelder, G O; Heisenberg, M; Schneuwly, S

    1992-01-01

    Mutations in the Drosophila gene giant lens (gil) affect ommatidial development, photoreceptor axon guidance and optic lobe development. We have cloned the gene using an enhancer trap line. Molecular analysis of gil suggests that it encodes a secreted protein with an epidermal-growth-factor-like motif. We have generated mutations at the gil locus by imprecise excision of the enhancer trap P-element. In the absence of gil, additional photoreceptors develop at the expense of pigment cells, suggesting an involvement of gil in cell determination during eye development. In addition, gil mutants show drastic effects on photoreceptor axon guidance and optic lobe development. In wildtype flies, photoreceptor axons grow from the eye disc through the optic stalk into the larval brain hemisphere, where retinal innervation is required for the normal development of the lamina and distal medulla. The projection pattern of these axons in the developing lamina and medulla is highly regular and reproducible. In gil, photoreceptor axons enter the larval brain but fail to establish proper connections in the lamina or medulla. We propose that gil encodes a new type of signalling molecule involved in the process of axon pathfinding and cell determination in the visual system of Drosophila. Images PMID:1628618

  9. Serial Section Registration of Axonal Confocal Microscopy Datasets for Long-Range Neural Circuit Reconstruction

    Hogrebe, Luke; Paiva, Antonio R.; Jurrus, Elizabeth R.; Christensen, Cameron; Bridge, Michael; Dai, Li; Pfeiffer, Rebecca; Hof, Patrick; Roysam, Badrinath; Korenberg, Julie; Tasdizen, Tolga

    2012-06-15

    In the context of long-range digital neural circuit reconstruction, this paper investigates an approach for registering axons across histological serial sections. Tracing distinctly labeled axons over large distances allows neuroscientists to study very explicit relationships between the brain's complex interconnects and, for example, diseases or aberrant development. Large scale histological analysis requires, however, that the tissue be cut into sections. In immunohistochemical studies thin sections are easily distorted due to the cutting, preparation, and slide mounting processes. In this work we target the registration of thin serial sections containing axons. Sections are first traced to extract axon centerlines, and these traces are used to define registration landmarks where they intersect section boundaries. The trace data also provides distinguishing information regarding an axon's size and orientation within a section. We propose the use of these features when pairing axons across sections in addition to utilizing the spatial relationships amongst the landmarks. The global rotation and translation of an unregistered section are accounted for using a random sample consensus (RANSAC) based technique. An iterative nonrigid refinement process using B-spline warping is then used to reconnect axons and produce the sought after connectivity information.

  10. Data Acquisition System for the UFFO Pathfinder

    Na, G W; Choi, H S; Choi, Y J; Grossan, B; Hermann, I; Jeong, S; Jung, A; Kim, J E; Kim, S -W; Kim, Y W; Lee, J; Lim, H; Linder, E V; Min, K W; Nam, J W; Nam, K H; Panayuk, M I; Park, I H; Smoot, G F; Suh, Y D; Svelitov, S; Vedenken, N; Yashin, I; Zhao, M H

    2011-01-01

    The Ultra-Fast Flash Observatory (UFFO) Pathfinder is a payload on the Russian Lomonosov satellite, scheduled to be launched in November 2011. The Observatory is designed to detect early UV/Optical photons from Gamma-Ray Bursts (GRBs). There are two telescopes and one main data acquisition system: the UFFO Burst Alert & Trigger Telescope (UBAT), the Slewing Mirror Telescope (SMT), and the UFFO Data Acquisition (UDAQ) system. The UDAQ controls and manages the operation and communication of each telescope, and is also in charge of the interface with the satellite. It will write the data taken by each telescope to the NOR flash memory and sends them to the satellite via the Bus-Interface system (BI). It also receives data from the satellite including the coordinates and time of an external trigger from another payload, and distributes them to two telescopes. These functions are implemented in field programmable gates arrays (FPGA) for low power consumption and fast processing without a microprocessor. The UD...

  11. Rectangle expansion A∗ pathfinding for grid maps

    Zhang An

    2016-10-01

    Full Text Available Search speed, quality of resulting paths and the cost of pre-processing are the principle evaluation metrics of a pathfinding algorithm. In this paper, a new algorithm for grid-based maps, rectangle expansion A∗ (REA∗, is presented that improves the performance of A∗ significantly. REA∗ explores maps in units of unblocked rectangles. All unnecessary points inside the rectangles are pruned and boundaries of the rectangles (instead of individual points within those boundaries are used as search nodes. This makes the algorithm plot fewer points and have a much shorter open list than A∗. REA∗ returns jump and grid-optimal path points, but since the line of sight between jump points is protected by the unblocked rectangles, the resulting path of REA∗ is usually better than grid-optimal. The algorithm is entirely online and requires no offline pre-processing. Experimental results for typical benchmark problem sets show that REA∗ can speed up a highly optimized A∗ by an order of magnitude and more while preserving completeness and optimality. This new algorithm is competitive with other highly successful variants of A∗.

  12. Bayesian Model Selection for LISA Pathfinder

    Karnesis, Nikolaos; Sopuerta, Carlos F; Gibert, Ferran; Armano, Michele; Audley, Heather; Congedo, Giuseppe; Diepholz, Ingo; Ferraioli, Luigi; Hewitson, Martin; Hueller, Mauro; Korsakova, Natalia; Plagnol, Eric; Vitale, and Stefano

    2013-01-01

    The main goal of the LISA Pathfinder (LPF) mission is to fully characterize the acceleration noise models and to test key technologies for future space-based gravitational-wave observatories similar to the LISA/eLISA concept. The Data Analysis (DA) team has developed complex three-dimensional models of the LISA Technology Package (LTP) experiment on-board LPF. These models are used for simulations, but more importantly, they will be used for parameter estimation purposes during flight operations. One of the tasks of the DA team is to identify the physical effects that contribute significantly to the properties of the instrument noise. A way of approaching to this problem is to recover the essential parameters of the LTP which describe the data. Thus, we want to define the simplest model that efficiently explains the observations. To do so, adopting a Bayesian framework, one has to estimate the so-called Bayes Factor between two competing models. In our analysis, we use three main different methods to estimate...

  13. The Mars Pathfinder Mission and Science Results

    Golombek, M. P.

    1999-01-01

    Mars Pathfinder, the first low-cost, quick Discovery class mission to be completed, successfully landed on the surface of Mars on July 4, 1997, deployed and navigated a small rover, and collected data from 3 science instruments and 10 technology experiments. The mission operated on Mars for 3 months and returned 2.3 Gbits of new data, including over 16,500 lander and 550 rover images, 16 chemical analyses of rocks and soil, and 8.5 million individual temperature, pressure and wind measurements. The rover traversed 100 m clockwise around the lander, exploring about 200 square meters of the surface. The mission captured the imagination of the public, and garnered front page headlines during the first week. A total of about 566 million internet "hits" were registered during the first month of the mission, with 47 million "hits" on July 8th alone, making the Pathfinder landing by far the largest internet event in history at the time. Pathfinder was the first mission to deploy a rover on Mars. It carried a chemical analysis instrument, to characterize the rocks and soils in a landing area over hundreds of square meters on Mars, which provided a calibration point or "ground truth" for orbital remote sensing observations. The combination of spectral imaging of the landing area by the lander camera, chemical analyses aboard the rover, and close-up imaging of colors, textures and fabrics with the rover cameras offered the potential of identifying rocks (petrology and mineralogy). With this payload, a landing site in Ares Vallis was selected because it appeared acceptably safe and offered the prospect of analyzing a variety of rock types expected to be deposited by catastrophic floods, which enabled addressing first-order scientific questions such as differentiation of the crust, the development of weathering products, and the nature of the early Martian environment and its subsequent evolution. The 3 instruments and rover allowed seven areas of scientific investigation: the

  14. Expression of the Wnt signaling system in central nervous system axon guidance and regeneration

    Edmund eHollis

    2012-02-01

    Full Text Available Wnt signaling is essential for axon wiring throughout the development of the nervous system in vertebrates and invertebrates. In vertebrates, Wnts are expressed in gradients that span the entire anterior-posterior axis in the spinal cord and the medial-lateral axis in the superior colliculus. In the brainstem, Wnts are expressed in more complex gradients along the anterior-posterior axis. These gradients provide directional information for axon pathfinding and positional information for topographic mapping and are detected by cell polarity signaling pathways. The gradient expression of Wnts and the coordinated expression of Wnt signaling systems are regulated by mechanisms which are currently unknown. Injury to the adult spinal cord results in the re-induction of Wnts in multiple cell types around the lesion site and their signaling system in injured axons. Reinduced Wnts form gradients around the lesion site, with the lesion site being the peak. The reinduced Wnts may be responsible for the well-known retraction of descending motor axons through the atypical kinase receptor Ryk. Wnt signaling is an appealing therapeutic target for CNS repair. The mechanisms regulating the reinduction will be informative for therapeutic design.

  15. The Microtubule Regulatory Protein Stathmin Is Required to Maintain the Integrity of Axonal Microtubules in Drosophila.

    Jason E Duncan

    Full Text Available Axonal transport, a form of long-distance, bi-directional intracellular transport that occurs between the cell body and synaptic terminal, is critical in maintaining the function and viability of neurons. We have identified a requirement for the stathmin (stai gene in the maintenance of axonal microtubules and regulation of axonal transport in Drosophila. The stai gene encodes a cytosolic phosphoprotein that regulates microtubule dynamics by partitioning tubulin dimers between pools of soluble tubulin and polymerized microtubules, and by directly binding to microtubules and promoting depolymerization. Analysis of stai function in Drosophila, which has a single stai gene, circumvents potential complications with studies performed in vertebrate systems in which mutant phenotypes may be compensated by genetic redundancy of other members of the stai gene family. This has allowed us to identify an essential function for stai in the maintenance of the integrity of axonal microtubules. In addition to the severe disruption in the abundance and architecture of microtubules in the axons of stai mutant Drosophila, we also observe additional neurological phenotypes associated with loss of stai function including a posterior paralysis and tail-flip phenotype in third instar larvae, aberrant accumulation of transported membranous organelles in stai deficient axons, a progressive bang-sensitive response to mechanical stimulation reminiscent of the class of Drosophila mutants used to model human epileptic seizures, and a reduced adult lifespan. Reductions in the levels of Kinesin-1, the primary anterograde motor in axonal transport, enhance these phenotypes. Collectively, our results indicate that stai has an important role in neuronal function, likely through the maintenance of microtubule integrity in the axons of nerves of the peripheral nervous system necessary to support and sustain long-distance axonal transport.

  16. CBM a Pathfinder of Petroleum System?

    Swapan Kumar Bhattacharya

    2014-04-01

    Full Text Available The present study aims to understand if there is any relation of commercial methane in CBM producers with oil producing kerogen. This is necessary because methane in coal, by default, is assigned to be sourced by bacterial/thermal actions on biomass during coalification process but critical analysis suggests it cannot be commercial because coal bears a ratio of molar concentrations of Hydrogen to Carbon (H/C around 0.8 whereas methane require H/C = 4.0. A simple calculation reveals 1Tcf of methane generation may come from around 25 trillion tonnes of coal, suggesting commercial methane cannot be sourced only from coal. Generation of methane can be biogenic or thermogenic, either from coal or related organic biomass or from oil generating kerogen. Technically, we can distinguish biogenic methane from thermogenic but we cannot distinguish same methane either from coal or from oil generating kerogen unless it is evident that one is distinctly biogenic and the other is thermogenic. Further, a review of successful major CBM projects also reveals that most of them are geologically associated with some producing petroliferous basin. This suggests that a close genetic relationship between the occurrence of coal bed methane and petroliferous basin probably exists whereby adsorbed methane in coal bed is possibly sourced from the same oil generating kerogen in the basin. Therefore, discovery of commercial coal bed methane may suggest possible existence of mature source rock in the basin and may act as pathfinder of possible new petroleum system attached to it.

  17. SST, Pathfinder Ver 5.0, Night, 4.4 km, Global, Science Quality

    National Oceanic and Atmospheric Administration, Department of Commerce — AVHRR Pathfinder Oceans Project seeks to create a long-term, continuous sea surface temperature data series for use in climate research. The Pathfinder SST data...

  18. SST, Pathfinder Ver 5.0, Day, 4.4 km, Global, Science Quality

    National Oceanic and Atmospheric Administration, Department of Commerce — AVHRR Pathfinder Oceans Project seeks to create a long-term, continuous sea surface temperature data series for use in climate research. The Pathfinder SST data...

  19. SST, Pathfinder Ver 5.0, Day and Night, 4.4 km, Global, Science Quality

    National Oceanic and Atmospheric Administration, Department of Commerce — AVHRR Pathfinder Oceans Project seeks to create a long-term, continuous sea surface temperature data series for use in climate research. The Pathfinder SST data...

  20. Transcellular degradation of axonal mitochondria.

    Davis, Chung-ha O; Kim, Keun-Young; Bushong, Eric A; Mills, Elizabeth A; Boassa, Daniela; Shih, Tiffany; Kinebuchi, Mira; Phan, Sebastien; Zhou, Yi; Bihlmeyer, Nathan A; Nguyen, Judy V; Jin, Yunju; Ellisman, Mark H; Marsh-Armstrong, Nicholas

    2014-07-01

    It is generally accepted that healthy cells degrade their own mitochondria. Here, we report that retinal ganglion cell axons of WT mice shed mitochondria at the optic nerve head (ONH), and that these mitochondria are internalized and degraded by adjacent astrocytes. EM demonstrates that mitochondria are shed through formation of large protrusions that originate from otherwise healthy axons. A virally introduced tandem fluorophore protein reporter of acidified mitochondria reveals that acidified axonal mitochondria originating from the retinal ganglion cell are associated with lysosomes within columns of astrocytes in the ONH. According to this reporter, a greater proportion of retinal ganglion cell mitochondria are degraded at the ONH than in the ganglion cell soma. Consistently, analyses of degrading DNA reveal extensive mtDNA degradation within the optic nerve astrocytes, some of which comes from retinal ganglion cell axons. Together, these results demonstrate that surprisingly large proportions of retinal ganglion cell axonal mitochondria are normally degraded by the astrocytes of the ONH. This transcellular degradation of mitochondria, or transmitophagy, likely occurs elsewhere in the CNS, because structurally similar accumulations of degrading mitochondria are also found along neurites in superficial layers of the cerebral cortex. Thus, the general assumption that neurons or other cells necessarily degrade their own mitochondria should be reconsidered.

  1. From laboratory experiments to LISA Pathfinder: achieving LISA geodesic motion

    Antonucci, F; Audley, H; Auger, G; Benedetti, M; Binetruy, P; Boatella, C; Bogenstahl, J; Bortoluzzi, D; Bosetti, P; Brandt, N; Caleno, M; Cavalleri, A; Cesa, M; Chmeissani, M; Ciani, G; Conchillo, A; Congedo, G; Cristofolini, I; Cruise, M; Danzmann, K; De Marchi, F; Diaz-Aguilo, M; Diepholz, I; Dixon, G; Dolesi, R; Dunbar, N; Fauste, J; Ferraioli, L; Fertin, D; Fichter, W; Fitzsimons, E; Freschi, M; Marin, A García; Marirrodriga, C García; Gerndt, R; Gesa, L; Giardini, D; Gibert, F; Grimani, C; Grynagier, A; Guillaume, B; Guzmán, F; Harrison, I; Heinzel, G; Hewitson, M; Hollington, D; Hough, J; Hoyland, D; Hueller, M; Huesler, J; Jeannin, O; Jennrich, O; Jetzer, P; Johlander, B; Killow, C; Llamas, X; Lloro, I; Lobo, A; Maarschalkerweerd, R; Madden, S; Mance, D; Mateos, I; McNamara, P W; Mendestì, J; Mitchell, E; Monsky, A; Nicolini, D; Nicolodi, D; Nofrarias, M; Pedersen, F; Perreur-Lloyd, M; Perreca, A; Plagnol, E; Prat, P; Racca, G D; Rais, B; Ramos-Castro, J; Reiche, J; Perez, J A Romera; Robertson, D; Rozemeijer, H; Sanjuan, J; Schleicher, A; Schulte, M; Shaul, D; Stagnaro, L; Strandmoe, S; Steier, F; Sumner, T J; Taylor, A; Texier, D; Trenkel, C; Tombolato, D; Vitale, S; Wanner, G; Ward, H; Waschke, S; Wass, P; Weber, W J; Zweifel, P

    2010-01-01

    This paper presents a quantitative assessment of the performance of the upcoming LISA Pathfinder geodesic explorer mission. The findings are based on the results of extensive ground testing and simulation campaigns using flight hardware and flight control and operations algorithms. The results show that, for the central experiment of measuring the stray differential acceleration between the LISA test masses, LISA Pathfinder will be able to verify the overall acceleration noise to within a factor two of the LISA requirement at 1 mHz and within a factor 10 at 0.1 mHz. We also discuss the key elements of the physical model of disturbances, coming from LISA Pathfinder and ground measurement, that will guarantee the LISA performance.

  2. From laboratory experiments to LISA Pathfinder: achieving LISA geodesic motion

    Antonucci, F.; Armano, M.; Audley, H.; Auger, G.; Benedetti, M.; Binetruy, P.; Boatella, C.; Bogenstahl, J.; Bortoluzzi, D.; Bosetti, P.; Brandt, N.; Caleno, M.; Cavalleri, A.; Cesa, M.; Chmeissani, M.; Ciani, G.; Conchillo, A.; Congedo, G.; Cristofolini, I.; Cruise, M.; Danzmann, K.; De Marchi, F.; Diaz-Aguilo, M.; Diepholz, I.; Dixon, G.; Dolesi, R.; Dunbar, N.; Fauste, J.; Ferraioli, L.; Fertin, D.; Fichter, W.; Fitzsimons, E.; Freschi, M.; García Marin, A.; García Marirrodriga, C.; Gerndt, R.; Gesa, L.; Giardini, D.; Gibert, F.; Grimani, C.; Grynagier, A.; Guillaume, B.; Guzmán, F.; Harrison, I.; Heinzel, G.; Hewitson, M.; Hollington, D.; Hough, J.; Hoyland, D.; Hueller, M.; Huesler, J.; Jeannin, O.; Jennrich, O.; Jetzer, P.; Johlander, B.; Killow, C.; Llamas, X.; Lloro, I.; Lobo, A.; Maarschalkerweerd, R.; Madden, S.; Mance, D.; Mateos, I.; McNamara, P. W.; Mendes, J.; Mitchell, E.; Monsky, A.; Nicolini, D.; Nicolodi, D.; Nofrarias, M.; Pedersen, F.; Perreur-Lloyd, M.; Perreca, A.; Plagnol, E.; Prat, P.; Racca, G. D.; Rais, B.; Ramos-Castro, J.; Reiche, J.; Romera Perez, J. A.; Robertson, D.; Rozemeijer, H.; Sanjuan, J.; Schleicher, A.; Schulte, M.; Shaul, D.; Stagnaro, L.; Strandmoe, S.; Steier, F.; Sumner, T. J.; Taylor, A.; Texier, D.; Trenkel, C.; Tombolato, D.; Vitale, S.; Wanner, G.; Ward, H.; Waschke, S.; Wass, P.; Weber, W. J.; Zweifel, P.

    2011-05-01

    This paper presents a quantitative assessment of the performance of the upcoming LISA Pathfinder geodesic explorer mission. The findings are based on the results of extensive ground testing and simulation campaigns using flight hardware, flight control and operations algorithms. The results show that, for the central experiment of measuring the stray differential acceleration between the LISA test masses, LISA Pathfinder will be able to verify the overall acceleration noise to within a factor 2 of the LISA requirement at 1 mHz and within a factor 6 at 0.1 mHz. We also discuss the key elements of the physical model of disturbances, coming from LISA Pathfinder and ground measurement that will guarantee the LISA performance.

  3. From laboratory experiments to LISA Pathfinder: achieving LISA geodesic motion

    Antonucci, F; Cavalleri, A; Congedo, G [Dipartimento di Fisica, Universita di Trento and INFN, Gruppo Collegato di Trento, 38050 Povo, Trento (Italy); Armano, M [European Space Astronomy Centre, European Space Agency, Villanueva de la Canada, 28692 Madrid (Spain); Audley, H; Bogenstahl, J [Albert-Einstein-Institut, Max-Planck-Institut fuer Gravitationsphysik und Universitaet Hannover, 30167 Hannover (Germany); Auger, G; Binetruy, P [APC UMR7164, Universite Paris Diderot, Paris (France); Benedetti, M [Dipartimento di Ingegneria dei Materiali e Tecnologie Industriali, Universita di Trento and INFN, Gruppo Collegato di Trento, Mesiano, Trento (Italy); Boatella, C [CNES, DCT/AQ/EC, 18 Avenue Edouard Belin, 31401 Toulouse, Cedex 9 (France); Bortoluzzi, D; Bosetti, P; Cristofolini, I [Dipartimento di Ingegneria Meccanica e Strutturale, Universita di Trento and INFN, Gruppo Collegato di Trento, Mesiano, Trento (Italy); Brandt, N [Astrium GmbH Claude-Dornier-Strasse, 88090 Immenstaad (Germany); Caleno, M; Cesa, M [European Space Technology Centre, European Space Agency, Keplerlaan 1, 2200 AG Noordwijk (Netherlands); Chmeissani, M [IFAE, Universitat Autonoma de Barcelona, E-08193 Bellaterra, Barcelona (Spain); Ciani, G [Department of Physics, University of Florida, Gainesville, FL 32611-8440 (United States); Conchillo, A [ICE-CSIC/IEEC, Facultat de Ciencies, E-08193 Bellaterra, Barcelona (Spain); Cruise, M, E-mail: Stefano.Vitale@unitn.it [Department of Physics and Astronomy, University of Birmingham, Birmingham (United Kingdom)

    2011-05-07

    This paper presents a quantitative assessment of the performance of the upcoming LISA Pathfinder geodesic explorer mission. The findings are based on the results of extensive ground testing and simulation campaigns using flight hardware, flight control and operations algorithms. The results show that, for the central experiment of measuring the stray differential acceleration between the LISA test masses, LISA Pathfinder will be able to verify the overall acceleration noise to within a factor 2 of the LISA requirement at 1 mHz and within a factor 6 at 0.1 mHz. We also discuss the key elements of the physical model of disturbances, coming from LISA Pathfinder and ground measurement that will guarantee the LISA performance.

  4. Design Overview of the DM Radio Pathfinder Experiment

    Silva-Feaver, Maximiliano; Cho, Hsiao-Mei; Dawson, Carl; Graham, Peter; Irwin, Kent; Kuenstner, Stephen; Li, Dale; Mardon, Jeremy; Moseley, Harvey; Mule, Richard; Phipps, Arran; Rajendran, Surjeet; Steffen, Zach; Young, Betty

    2016-01-01

    We introduce the DM Radio, a dual search for axion and hidden photon dark matter using a tunable superconducting lumped-element resonator. We discuss the prototype DM Radio Pathfinder experiment, which will probe hidden photons in the 500 peV (100 kHz)-50 neV (10 MHz) mass range. We detail the design of the various components: the LC resonant detector, the resonant frequency tuning procedure, the differential SQUID readout circuit, the shielding, and the cryogenic mounting structure. We present the current status of the pathfinder experiment and illustrate its potential science reach in the context of the larger experimental program.

  5. Implementasi Algoritma A* Berbasis Pathfinding Dalam Pengembangan Game Menanam Pohon

    Pohan, Rahmat Irfan

    2016-01-01

    Anyone would take the path that they consider to be the shortest path when they travel from one place to another. But it would be difficult for such a person to choose which path is the shortest, because it could be the chosen path is not the shortest path. The method for determining the shortest path is pathfinding. Pathfinding is widely used in various fields of Computer Science, one of them on the field of video game development. In this research, the authors will design and analyze the pa...

  6. Lincoln Pathfinder: Internet Resources on Studying and Teaching Abraham Lincoln

    Andreas Hübner

    2009-09-01

    Full Text Available Apart from encouraging an innumerable quantity of scholarly works and projects, the subject matter of Lincoln’s Legacy has also produced an increasing amount of online ventures and digital resource collections. The Lincoln Pathfinder aims to provide a quick guide to these Web sites and to initiate a controversial debate, likely to take place in the EFL classroom. Divided into five categories—general, primary, secondary, visual, and teaching resources—the Lincoln Pathfinder may function as a helpful research tool and a basis of discussion.

  7. Holographic Beam Mapping of the CHIME Pathfinder Array

    Berger, Philippe; Amiri, Mandana; Bandura, Kevin; Cliche, Jean-Francois; Connor, Liam; Deng, Meiling; Denman, Nolan; Dobbs, Matt; Fandino, Mateus; Gilbert, Adam J; Good, Deborah; Halpern, Mark; Hanna, David; Hincks, Adam D; Hinshaw, Gary; Hofer, Carolin; Johnson, Andre M; Landecker, Tom L; Masui, Kiyoshi W; Parra, Juan Mena; Oppermann, Niels; Pen, Ue-Li; Peterson, Jeffrey B; Recnik, Andre; Robishaw, Timothy; Shaw, J Richard; Siegel, Seth; Sigurdson, Kris; Smith, Kendrick; Storer, Emilie; Tretyakov, Ian; Van Gassen, Kwinten; Vanderlinde, Keith; Wiebe, Donald

    2016-01-01

    The Canadian Hydrogen Intensity Mapping Experiment (CHIME) Pathfinder radio telescope is currently surveying the northern hemisphere between 400 and 800 MHz. By mapping the large scale structure of neutral hydrogen through its redshifted 21 cm line emission between $z \\sim 0.8-2.5$ CHIME will contribute to our understanding of Dark Energy. Bright astrophysical foregrounds must be separated from the neutral hydrogen signal, a task which requires precise characterization of the polarized telescope beams. Using the DRAO John A. Galt 26 m telescope, we have developed a holography instrument and technique for mapping the CHIME Pathfinder beams. We report the status of the instrument and initial results of this effort.

  8. Action-potential modulation during axonal conduction.

    Sasaki, Takuya; Matsuki, Norio; Ikegaya, Yuji

    2011-02-04

    Once initiated near the soma, an action potential (AP) is thought to propagate autoregeneratively and distribute uniformly over axonal arbors. We challenge this classic view by showing that APs are subject to waveform modulation while they travel down axons. Using fluorescent patch-clamp pipettes, we recorded APs from axon branches of hippocampal CA3 pyramidal neurons ex vivo. The waveforms of axonal APs increased in width in response to the local application of glutamate and an adenosine A(1) receptor antagonist to the axon shafts, but not to other unrelated axon branches. Uncaging of calcium in periaxonal astrocytes caused AP broadening through ionotropic glutamate receptor activation. The broadened APs triggered larger calcium elevations in presynaptic boutons and facilitated synaptic transmission to postsynaptic neurons. This local AP modification may enable axonal computation through the geometry of axon wiring.

  9. Sparing of descending axons rescues interneuron plasticity in the lumbar cord to allow adaptive learning after thoracic spinal cord injury

    Christopher Nelson Hansen

    2016-03-01

    Full Text Available This study evaluated the role of spared axons on structural and behavioral neuroplasticity in the lumbar enlargement after a thoracic spinal cord injury (SCI. Previous work has demonstrated that recovery in the presence of spared axons after an incomplete lesion increases behavioral output after a subsequent complete spinal cord transection (TX. This suggests that spared axons direct adaptive changes in below-level neuronal networks of the lumbar cord. In response to spared fibers, we postulate that lumbar neuron networks support behavioral gains by preventing aberrant plasticity. As such, the present study measured histological and functional changes in the isolated lumbar cord after complete TX or incomplete contusion (SCI. To measure functional plasticity in the lumbar cord, we used an established instrumental learning paradigm. In this paradigm, neural circuits within isolated lumbar segments demonstrate learning by an increase in flexion duration that reduces exposure to a noxious leg shock. We employed this model using a proof-of-principle design to evaluate the role of sparing on lumbar learning and plasticity early (7 days or late (42 days after midthoracic SCI in a rodent model. Early after SCI or TX at 7d, spinal learning was unattainable regardless of whether the animal recovered with or without axonal substrate. Failed learning occurred alongside measures of cell soma atrophy and aberrant dendritic spine expression within interneuron populations responsible for sensorimotor integration and learning. Alternatively, exposure of the lumbar cord to a small amount of spared axons for 6 weeks produced near-normal learning late after SCI. This coincided with greater cell soma volume and fewer aberrant dendritic spines on interneurons. Thus, an opportunity to influence activity-based learning in locomotor networks depends on spared axons limiting maladaptive plasticity. Together, this work identifies a time dependent interaction between

  10. Sparing of Descending Axons Rescues Interneuron Plasticity in the Lumbar Cord to Allow Adaptive Learning After Thoracic Spinal Cord Injury.

    Hansen, Christopher N; Faw, Timothy D; White, Susan; Buford, John A; Grau, James W; Basso, D Michele

    2016-01-01

    This study evaluated the role of spared axons on structural and behavioral neuroplasticity in the lumbar enlargement after a thoracic spinal cord injury (SCI). Previous work has demonstrated that recovery in the presence of spared axons after an incomplete lesion increases behavioral output after a subsequent complete spinal cord transection (TX). This suggests that spared axons direct adaptive changes in below-level neuronal networks of the lumbar cord. In response to spared fibers, we postulate that lumbar neuron networks support behavioral gains by preventing aberrant plasticity. As such, the present study measured histological and functional changes in the isolated lumbar cord after complete TX or incomplete contusion (SCI). To measure functional plasticity in the lumbar cord, we used an established instrumental learning paradigm (ILP). In this paradigm, neural circuits within isolated lumbar segments demonstrate learning by an increase in flexion duration that reduces exposure to a noxious leg shock. We employed this model using a proof-of-principle design to evaluate the role of sparing on lumbar learning and plasticity early (7 days) or late (42 days) after midthoracic SCI in a rodent model. Early after SCI or TX at 7 days, spinal learning was unattainable regardless of whether the animal recovered with or without axonal substrate. Failed learning occurred alongside measures of cell soma atrophy and aberrant dendritic spine expression within interneuron populations responsible for sensorimotor integration and learning. Alternatively, exposure of the lumbar cord to a small amount of spared axons for 6 weeks produced near-normal learning late after SCI. This coincided with greater cell soma volume and fewer aberrant dendritic spines on interneurons. Thus, an opportunity to influence activity-based learning in locomotor networks depends on spared axons limiting maladaptive plasticity. Together, this work identifies a time dependent interaction between spared

  11. A Pathfinder for Animal Research and Animal Rights.

    Anderson, David C.

    1992-01-01

    This pathfinder was originally prepared for "Biomedical Research and Animal Rights," a session sponsored by the Veterinary Medical Libraries and Research Libraries Sections of the Medical Library Association. Current resources are described, from bibliographies to electronic bulletin boards, which relate to the issue of laboratory animal…

  12. A Pathfinder for Animal Research and Animal Rights.

    Anderson, David C.

    1992-01-01

    This pathfinder was originally prepared for "Biomedical Research and Animal Rights," a session sponsored by the Veterinary Medical Libraries and Research Libraries Sections of the Medical Library Association. Current resources are described, from bibliographies to electronic bulletin boards, which relate to the issue of laboratory animal welfare…

  13. Fasciculation and guidance of spinal motor axons in the absence of FGFR2 signaling.

    Rosa-Eva Huettl

    Full Text Available During development, fibroblast growth factors (FGF are essential for early patterning events along the anterior-posterior axis, conferring positional identity to spinal motor neurons by activation of different Hox codes. In the periphery, signaling through one of four fibroblast growth factor receptors supports the development of the skeleton, as well as induction and maintenance of extremities. In previous studies, FGF receptor 2 (FGFR2 was found to interact with axon bound molecules involved in axon fasciculation and extension, thus rendering this receptor an interesting candidate for the promotion of proper peripheral innervation. However, while the involvement of FGFR2 in limb bud induction has been extensively studied, its role during axon elongation and formation of distinct nervous projections has not been addressed so far. We show here that motor neurons in the spinal cord express FGFR2 and other family members during the establishment of motor connections to the forelimb and axial musculature. Employing a conditional genetic approach to selectively ablate FGFR2 from motor neurons we found that the patterning of motor columns and the expression patterns of other FGF receptors and Sema3A in the motor columns of mutant embryos are not altered. In the absence of FGFR2 signaling, pathfinding of motor axons is intact, and also fasciculation, distal advancement of motor nerves and gross morphology and positioning of axonal projections are not altered. Our findings therefore show that FGFR2 is not required cell-autonomously in motor neurons during the formation of initial motor projections towards limb and axial musculature.

  14. Mitochondrial Dynamics Decrease Prior to Axon Degeneration Induced by Vincristine and are Partially Rescued by Overexpressed cytNmnat1.

    Gregory Berbusse

    2016-07-01

    Full Text Available Axon degeneration is a prominent feature of various neurodegenerative diseases, such as Parkinson’s and Alzheimer’s, and is often characterized by aberrant mitochondrial dynamics. Mitochondrial fission, fusion, and motility have been shown to be particularly important in progressive neurodegeneration. Thus we investigated these imperative dynamics, as well as mitochondrial fragmentation in vincristine induced axon degradation in cultured DRG neurons. CytNmnat1 inhibits axon degeneration in various paradigms including vincristine toxicity. The mechanism of its protection is not yet fully understood; therefore, we also investigated the effect of cytNmnat1 on mitochondrial dynamics in vincristine treated neurons. We observed that vincristine treatment decreases the rate of mitochondrial fission, fusion and motility and induces mitochondrial fragmentation. These mitochondrial events precede visible axon degeneration. Overexpression of cytNmnat1 inhibits axon degeneration and preserves the normal mitochondrial dynamics and motility in vincristine treated neurons. We suggest the alterations in mitochondrial structure and dynamics are early events which lead to axon degeneration and cytNmnat1 blocks axon degeneration by halting the vincristine induced changes to mitochondrial structure and dynamics.

  15. Aberration Correction in Electron Microscopy

    Rose, Harald H

    2005-01-01

    The resolution of conventional electron microscopes is limited by spherical and chromatic aberrations. Both defects are unavoidable in the case of static rotationally symmetric electromagnetic fields (Scherzer theorem). Multipole correctors and electron mirrros have been designed and built, which compensate for these aberrations. The principles of correction will be demonstrated for the tetrode mirror, the quadrupole-octopole corrector and the hexapole corrector. Electron mirrors require a magnetic beam separator free of second-order aberrations. The multipole correctors are highly symmetric telescopic systems compensating for the defects of the objective lens. The hexapole corrector has the most simple structure yet eliminates only the spherical aberration, whereas the mirror and the quadrupole-octopole corrector are able to correct for both aberrations. Chromatic correction is achieved in the latter corrector by cossed electric and magnetic quadrupoles acting as first-order Wien filters. Micrographs obtaine...

  16. Camera processing with chromatic aberration.

    Korneliussen, Jan Tore; Hirakawa, Keigo

    2014-10-01

    Since the refractive index of materials commonly used for lens depends on the wavelengths of light, practical camera optics fail to converge light to a single point on an image plane. Known as chromatic aberration, this phenomenon distorts image details by introducing magnification error, defocus blur, and color fringes. Though achromatic and apochromatic lens designs reduce chromatic aberration to a degree, they are complex and expensive and they do not offer a perfect correction. In this paper, we propose a new postcapture processing scheme designed to overcome these problems computationally. Specifically, the proposed solution is comprised of chromatic aberration-tolerant demosaicking algorithm and post-demosaicking chromatic aberration correction. Experiments with simulated and real sensor data verify that the chromatic aberration is effectively corrected.

  17. Inflight magnetic characterization of the test masses onboard LISA Pathfinder

    Diaz-Aguiló, Marc; Lobo, Alberto

    2012-01-01

    LISA Pathfinder is a science and technology demonstrator of the European Space Agency within the framework of its LISA mission, the latter aiming to be the first space-borne gravitational wave observatory. The payload of LISA Pathfinder is the so-called LISA Technology Package, which is designed to measure relative accelerations between two test masses in nominal free fall. The diagnostics subsystem consists of several modules, one of which is the magnetic diagnostics unit. Its main function is the assessment of the differential acceleration noise between the test masses due to magnetic effects. This subsystem is composed of two onboard coils intended to produce controlled magnetic fields at the location of the test masses. These magnetic fields couple with the remanent magnetic moment and susceptibility and produce forces and torques on the test masses. These, in turn, produce kinematic excursions of the test masses which are sensed by the onboard interferometer. We prove that adequately processing these exc...

  18. Interface Generation and Compositional Verification in JavaPathfinder

    Giannakopoulou, Dimitra; Pasareanu, Corina

    2009-01-01

    We present a novel algorithm for interface generation of software components. Given a component, our algorithm uses learning techniques to compute a permissive interface representing legal usage of the component. Unlike our previous work, this algorithm does not require knowledge about the component s environment. Furthermore, in contrast to other related approaches, our algorithm computes permissive interfaces even in the presence of non-determinism in the component. Our algorithm is implemented in the JavaPathfinder model checking framework for UML statechart components. We have also added support for automated assume-guarantee style compositional verification in JavaPathfinder, using component interfaces. We report on the application of the presented approach to the generation of interfaces for flight software components.

  19. True Color of Mars - Pathfinder Sol 39 Sunrise

    1999-01-01

    Sunrise, sol 39. This true color, pre-sunrise image (approximately 0530LST) is composed of six images extending 30 o in azimuth and 45 o in elevation and shows the brownish gray predawn sky. A description of the techniques used to generate this color image from IMP data can be found in Maki et al., 1999. Note: a calibrated output device is required accurately reproduce the correct colors.Mars Pathfinder is the second in NASA's Discovery program of low-cost spacecraft with highly focused science goals. The Jet Propulsion Laboratory, Pasadena, CA, developed and manages the Mars Pathfinder mission for NASA's Office of Space Science, Washington, D.C. JPL is an operating division of the California Institute of Technology (Caltech). The IMP was developed by the University of Arizona Lunar and Planetary Laboratory under contract to JPL. Peter Smith is the Principal investigator.

  20. Design of the magnetic diagnostics unit onboard LISA Pathfinder

    Diaz-Aguiló, Marc; Ramos-Castro, Juan; Lobo, Alberto; García-Berro, Enrique

    2012-01-01

    LISA (Laser Interferometer Space Antenna) is a joint mission of ESA and NASA which aims to be the first space-borne gravita- tional wave observatory. Due to the high complexity and technological challenges that LISA will face, ESA decided to launch a technological demonstrator, LISA Pathfinder. The payload of LISA Pathfinder is the so-called LISA Technology Package, and will be the highest sensitivity geodesic explorer flown to date. The LISA Technology Package is designed to measure relative accelerations between two test masses in nominal free fall (geodesic motion). The magnetic, thermal and radiation disturbances affecting the payload are monitored and dealt by the diagnostics subsystem. The diagnostics subsystem consists of several modules, and one of these is the magnetic diagnostics unit. Its main function is the assessment of differential acceleration noise between test masses due to the magnetic effects. To do so, it has to determine the magnetic characteristics of the test masses, namely their magne...

  1. RPP Game Edukasi Pathfinding Adventures - Materi Sistem Koordinat - Kelas 8

    Hidayatullah, Aulia Muslim

    2016-01-01

    Pathfinding Adventures bertujuan untuk membantu pemain dalam memahami konsep matematika kelas 8 mengenai sistem koordinat. Pada game ini pemain dapat berpetualang di area khusus untuk mencari dan menggambar peta dari hasil perjalanan dalam melaksanakan misi di setiap tingkatan permainan. Pemain diberikan akses kontrol pada game dalam format “Third Person” atau dari sudut pandang luar karakter pada permainan. Menyelesaikan tantangan-tantangan yang diberikan di setiap tingkatan ...

  2. Mirror movement-like defects in startle behavior of zebrafish dcc mutants are caused by aberrant midline guidance of identified descending hindbrain neurons.

    Jain, Roshan A; Bell, Hannah; Lim, Amy; Chien, Chi-Bin; Granato, Michael

    2014-02-19

    Mirror movements are involuntary movements on one side of the body that occur simultaneously with intentional movements on the contralateral side. Humans with heterozygous mutations in the axon guidance receptor DCC display such mirror movements, where unilateral stimulation results in inappropriate bilateral motor output. Currently, it is unclear whether mirror movements are caused by incomplete midline crossing and reduced commissural connectivity of DCC-dependent descending pathways or by aberrant ectopic ipsilateral axonal projections of normally commissural neurons. Here, we show that in response to unilateral tactile stimuli, zebrafish dcc mutant larvae perform involuntary turns on the inappropriate body side. We show that these mirror movement-like deficits are associated with axonal guidance defects of two identified groups of commissural reticulospinal hindbrain neurons. Moreover, we demonstrate that in dcc mutants, axons of these identified neurons frequently fail to cross the midline and instead project ipsilaterally. Whereas laser ablation of these neurons in wild-type animals does not affect turning movements, their ablation in dcc mutants restores turning movements. Thus, our results demonstrate that in dcc mutants, turns on the inappropriate side of the body are caused by aberrant ipsilateral axonal projections, and suggest that aberrant ipsilateral connectivity of a very small number of descending axons is sufficient to induce incorrect movement patterns.

  3. LISA Pathfinder: First steps to observing gravitational waves from space

    McNamara, Paul; LISA Pathfinder Collaboration

    2017-01-01

    With the first direct detection of gravitational waves a little over a year ago, the gravitational window to the Universe has been opened. The gravitational wave spectrum spans many orders of magnitude in frequency, with several of the most interesting astronomical sources emitting gravitational waves at frequencies only observable from space The European Space Agency (ESA) has been active in the field of space-borne gravitational wave detection for many years, and in 2013 selected the Gravitational Universe as the science theme for the third large class mission in the Cosmic Vision science programme. In addition, ESA took the step of developing the LISA Pathfinder mission to demonstrate the critical technologies required for a future mission. The goal of the LISA Pathfinder mission is to place a test body in free fall such that any external forces (acceleration) are reduced to levels lower than those expected from the passage of a gravitational wave LISA Pathfinder was launched on the 3rd December 2015 from the European Spaceport in Kourou, French Guiana. After a series of 6 apogee raising manoeuvres, the satellite left earth orbit, and travelled to its final science orbit around the first Sun-Earth Lagrange point (L1). Following a relatively short commissioning phase, science operations began on 1st March 2016. In the following 3 months over 100 experiments and over 1500hours of noise measurements have been performed, demonstrating that the observation of gravitational waves from space can be realised.

  4. Analysis of pathfinder SST algorithm for global and regional conditions

    Ajoy Kumar; P Minnett; G Podesta; R Evans; K Kilpatrick

    2000-12-01

    As part of the Pathfinder program developed jointly by National Aeronautics and Space Administration (NASA) and National Oceanic and Atmospheric Administration (NOAA) a large database of in situ sea surface temperature (SST) measurements coincident with satellite data is now available to the user community. The Pathfinder Matchup Database (PMDB) is a multi-year, multi-satellite collection of coincident measurements from the Advanced Very High Resolution Radiometer (AVHRR) and broadly distributed buoy data (matchups). This database allows the user community to test and validate new SST algorithms to improve the present accuracy of surface temperature measurements from satellites. In this paper we investigate the performance of a global Pathfinder algorithm to specific regional conditions. It is shown that for zenith angles less than 45°, the best-expected statistical discrepancy between satellite and buoy data is about ∼0.5 K. In general, the bias of the residuals (satellite - buoy) is negative in most regions, except in the North Atlantic and adjacent seas, where the residuals are always positive. A seasonal signal in SST residuals is observed in all regions and is strongest in the Indian Ocean. The channel-difference term used as a proxy for atmospheric water vapor correction is observed to be unresponsive for columnar water vapor values greater than 45 mm and high zenith angles. This unresponsiveness of the channels leads to underestimation of sea surface temperature from satellites in these conditions.

  5. The importance of combinatorial gene expression in early mammalian thalamic patterning and thalamocortical axonal guidance

    David J Price

    2012-03-01

    Full Text Available The thalamus is essential for sensory perception. In mammals, work on the mouse has taught us most of what we know about how it develops and connects to the cortex. The mature thalamus of all mammalian species comprises numerous anatomically distinct collections of neurons called nuclei that differ in function, connectivity and molecular constitution. At the time of its initial appearance as a distinct structure following neural tube closure, the thalamus is already patterned by the regional expression of numerous regulatory genes. This patterning, which lays down the blueprint for later development of thalamic nuclei, predates the development of thalamocortical projections. In this review we apply novel analytical methods to gene expression data available in the Allen Developing Mouse Brain Atlas to highlight the complex organized molecular heterogeneity already present among cells in the thalamus from the earliest stages at which it contains differentiating neurons. This early patterning is likely to invest in axons growing from different parts of the thalamus the ability to navigate in an ordered way to their appropriate area in the cerebral cortex. We review the mechanisms and cues that thalamic axons use, encounter and interpret to attain the cortex. Mechanisms include guidance by previously-generated guidepost cells, such as those in the subpallium that maintain thalamic axonal order and direction, and axons such as those of reciprocal projections from intermediate structures or from the cortex itself back towards the thalamus. We show how thalamocortical pathfinding involves numerous guidance cues operating at a series of steps along their route. We stress the importance of the combinatorial actions of multiple genes for the development of the numerous specific identities and functions of cells in this exquisitely complex system and their orderly innervation of the cortex.

  6. AxonSeg: Open Source Software for Axon and Myelin Segmentation and Morphometric Analysis.

    Zaimi, Aldo; Duval, Tanguy; Gasecka, Alicja; Côté, Daniel; Stikov, Nikola; Cohen-Adad, Julien

    2016-01-01

    Segmenting axon and myelin from microscopic images is relevant for studying the peripheral and central nervous system and for validating new MRI techniques that aim at quantifying tissue microstructure. While several software packages have been proposed, their interface is sometimes limited and/or they are designed to work with a specific modality (e.g., scanning electron microscopy (SEM) only). Here we introduce AxonSeg, which allows to perform automatic axon and myelin segmentation on histology images, and to extract relevant morphometric information, such as axon diameter distribution, axon density and the myelin g-ratio. AxonSeg includes a simple and intuitive MATLAB-based graphical user interface (GUI) and can easily be adapted to a variety of imaging modalities. The main steps of AxonSeg consist of: (i) image pre-processing; (ii) pre-segmentation of axons over a cropped image and discriminant analysis (DA) to select the best parameters based on axon shape and intensity information; (iii) automatic axon and myelin segmentation over the full image; and (iv) atlas-based statistics to extract morphometric information. Segmentation results from standard optical microscopy (OM), SEM and coherent anti-Stokes Raman scattering (CARS) microscopy are presented, along with validation against manual segmentations. Being fully-automatic after a quick manual intervention on a cropped image, we believe AxonSeg will be useful to researchers interested in large throughput histology. AxonSeg is open source and freely available at: https://github.com/neuropoly/axonseg.

  7. Phase aberration effects in elastography.

    Varghese, T; Bilgen, M; Ophir, J

    2001-06-01

    In sonography, phase aberration plays a role in the corruption of sonograms. Phase aberration does not have a significant impact on elastography, if statistically similar phase errors are present in both the pre- and postcompression signals. However, if the phase errors are present in only one of the pre- or postcompression signal pairs, the precision of the strain estimation process will be reduced. In some cases, increased phase errors may occur only in the postcompression signal due to changes in the tissue structure with the applied compression. Phase-aberration effects increase with applied strain and may be viewed as an image quality derating factor, much like frequency-dependent attenuation or undesired lateral tissue motion. In this paper, we present a theoretical and simulation study of the effects of phase aberration on the elastographic strain-estimation process, using the strain filter approach.

  8. Axonal interferon responses and alphaherpesvirus neuroinvasion

    Song, Ren

    Infection by alphaherpesviruses, including herpes simplex virus (HSV) and pseudorabies virus (PRV), typically begins at a peripheral epithelial surface and continues into the peripheral nervous system (PNS) that innervates this tissue. Inflammatory responses are induced at the infected peripheral site prior to viral invasion of the PNS. PNS neurons are highly polarized cells with long axonal processes that connect to distant targets. When the peripheral tissue is first infected, only the innervating axons are exposed to this inflammatory milieu, which include type I interferon (e.g. IFNbeta) and type II interferon (i.e. IFNgamma). IFNbeta can be produced by all types of cells, while IFNgamma is secreted by some specific types of immune cells. And both types of IFN induce antiviral responses in surrounding cells that express the IFN receptors. The fundamental question is how do PNS neurons respond to the inflammatory milieu experienced only by their axons. Axons must act as potential front-line barriers to prevent PNS infection and damage. Using compartmented cultures that physically separate neuron axons from cell bodies, I found that pretreating isolated axons with IFNbeta or IFNgamma significantly diminished the number of HSV-1 and PRV particles moving from axons to the cell bodies in an IFN receptor-dependent manner. Furthermore, I found the responses in axons are activated differentially by the two types of IFNs. The response to IFNbeta is a rapid, axon-only response, while the response to IFNgamma involves long distance signaling to the PNS cell body. For example, exposing axons to IFNbeta induced STAT1 phosphorylation (p-STAT1) only in axons, while exposure of axons to IFNgamma induced p-STAT1 accumulation in distant cell body nuclei. Blocking transcription in cell bodies eliminated IFNgamma-, but not IFNbeta-mediated antiviral effects. Proteomic analysis of IFNbeta- or IFNgamma-treated axons identified several differentially regulated proteins. Therefore

  9. Cable energy function of cortical axons.

    Ju, Huiwen; Hines, Michael L; Yu, Yuguo

    2016-01-01

    Accurate estimation of action potential (AP)-related metabolic cost is essential for understanding energetic constraints on brain connections and signaling processes. Most previous energy estimates of the AP were obtained using the Na(+)-counting method, which seriously limits accurate assessment of metabolic cost of ionic currents that underlie AP conduction along the axon. Here, we first derive a full cable energy function for cortical axons based on classic Hodgkin-Huxley (HH) neuronal equations and then apply the cable energy function to precisely estimate the energy consumption of AP conduction along axons with different geometric shapes. Our analytical approach predicts an inhomogeneous distribution of metabolic cost along an axon with either uniformly or nonuniformly distributed ion channels. The results show that the Na(+)-counting method severely underestimates energy cost in the cable model by 20-70%. AP propagation along axons that differ in length may require over 15% more energy per unit of axon area than that required by a point model. However, actual energy cost can vary greatly depending on axonal branching complexity, ion channel density distributions, and AP conduction states. We also infer that the metabolic rate (i.e. energy consumption rate) of cortical axonal branches as a function of spatial volume exhibits a 3/4 power law relationship.

  10. Motor axon excitability during Wallerian degeneration

    Moldovan, Mihai; Alvarez, Susana; Krarup, Christian

    2008-01-01

    , action potential propagation and structural integrity of the distal segment are maintained. The aim of this study was to investigate in vivo the changes in membrane function of motor axons during the 'latent' phase of Wallerian degeneration. Multiple indices of axonal excitability of the tibial nerve...

  11. Commissural axons of the mouse cochlear nucleus.

    Brown, M Christian; Drottar, Marie; Benson, Thane E; Darrow, Keith

    2013-05-01

    The axons of commissural neurons that project from one cochlear nucleus to the other were studied after labeling with anterograde tracer. Injections were made into the dorsal subdivision of the cochlear nucleus in order to restrict labeling only to the group of commissural neurons that gave off collaterals to, or were located in, this subdivision. The number of labeled commissural axons in each injection was correlated with the number of labeled radiate multipolar neurons, suggesting radiate neurons as the predominant origin of the axons. The radiate commissural axons are thick and myelinated, and they exit the dorsal acoustic stria of the injected cochlear nucleus to cross the brainstem in the dorsal half, near the crossing position of the olivocochlear bundle. They enter the opposite cochlear nucleus via the dorsal and ventral acoustic stria and at its medial border. Reconstructions of single axons demonstrate that terminations are mostly in the core and typically within a single subdivision of the cochlear nucleus. Extents of termination range from narrow to broad along both the dorsoventral (i.e., tonotopic) and the rostrocaudal dimensions. In the electron microscope, labeled swellings form synapses that are symmetric (in that there is little postsynaptic density), a characteristic of inhibitory synapses. Our labeled axons do not appear to include excitatory commissural axons that end in edge regions of the nucleus. Radiate commissural axons could mediate the broadband inhibition observed in responses to contralateral sound, and they may balance input from the two ears with a quick time course.

  12. Early events in axon/dendrite polarization.

    Cheng, Pei-lin; Poo, Mu-ming

    2012-01-01

    Differentiation of axons and dendrites is a critical step in neuronal development. Here we review the evidence that axon/dendrite formation during neuronal polarization depends on the intrinsic cytoplasmic asymmetry inherited by the postmitotic neuron, the exposure of the neuron to extracellular chemical factors, and the action of anisotropic mechanical forces imposed by the environment. To better delineate the functions of early signals among a myriad of cellular components that were shown to influence axon/dendrite formation, we discuss their functions by distinguishing their roles as determinants, mediators, or modulators and consider selective degradation of these components as a potential mechanism for axon/dendrite polarization. Finally, we examine whether these early events of axon/dendrite formation involve local autocatalytic activation and long-range inhibition, as postulated by Alan Turing for the morphogenesis of patterned biological structure.

  13. Dynamics of mitochondrial transport in axons

    Robert Francis Niescier

    2016-05-01

    Full Text Available The polarized structure and long neurites of neurons pose a unique challenge for proper mitochondrial distribution. It is widely accepted that mitochondria move from the cell body to axon ends and vice versa; however, we have found that mitochondria originating from the axon ends moving in the retrograde direction never reach to the cell body, and only a limited number of mitochondria moving in the anterograde direction from the cell body arrive at the axon ends of mouse hippocampal neurons. Furthermore, we have derived a mathematical formula using the Fokker-Planck equation to characterize features of mitochondrial transport, and the equation could determine altered mitochondrial transport in axons overexpressing parkin. Our analysis will provide new insights into the dynamics of mitochondrial transport in axons of normal and unhealthy neurons.

  14. NASA Ocean Altimeter Pathfinder Project. Report 1; Data Processing Handbook

    Koblinsky, C. J.; Beckley, Brian D.; Ray, Richard D.; Wang, Yan-Ming; Tsaoussi, Lucia; Brenner, Anita; Williamson, Ron

    1998-01-01

    The NOAA/NASA Pathfinder program was created by the Earth Observing System (EOS) Program Office to determine how satellite-based data sets can be processed and used to study global change. The data sets are designed to be long time-sedes data processed with stable calibration and community consensus algorithms to better assist the research community. The Ocean Altimeter Pathfinder Project involves the reprocessing of all altimeter observations with a consistent set of improved algorithms, based on the results from TOPEX/POSEIDON (T/P), into easy-to-use data sets for the oceanographic community for climate research. This report describes the processing schemes used to produce a consistent data set and two of the products derived f rom these data. Other reports have been produced that: a) describe the validation of these data sets against tide gauge measurements and b) evaluate the statistical properties of the data that are relevant to climate change. The use of satellite altimetry for earth observations was proposed in the early 1960s. The first successful space based radar altimeter experiment was flown on SkyLab in 1974. The first successful satellite radar altimeter was flown aboard the Geos-3 spacecraft between 1975 and 1978. While a useful data set was collected from this mission for geophysical studies, the noise in the radar measured and incomplete global coverage precluded ft from inclusion in the Ocean Altimeter Pathfinder program. This program initiated its analysis with the Seasat mission, which was the first satellite radar altimeter flown for oceanography.

  15. Periodontal status among adolescents in Georgia. A pathfinder study

    Liran Levin

    2013-09-01

    Full Text Available Objectives. The aim of the present pathfinder study was to screen and map the periodontal status of Georgian population in accordance with the guidelines of the World Health Organization for population based surveys. Methods. During 2012, a pathfinder study was conducted to collect this data. For the periodontal portion of the study, 15-year-old school children were examined in the capital city of Tbilisi as well as in two other large cities and 4 smaller villages. All participants were examined by a trained dental team in a classroom using a dental mirror and a periodontal probe. Periodontal examination included plaque scores, calculus scores, probing depth measurements and bleeding on probing. These measurements were recorded for the Ramfjord index teeth. Results. A total of 397 15-year-old participants were examined in this pathfinder study. There were 240 females (60.45% and 157 males (39.55%. Of the total participants 196 (49.37% were urban adolescents while 201 (50.63% were from rural communities. Mean probing depth was 3.34 ± 0.57 mm with a range of 1 to 10 mm; a relatively high proportion (34.26% of these subjects presented with at least one site with pockets of 5 mm or deeper. Males presented with greater plaque, calculus and probing depths than females. When urban and rural populations were compared, urban participants presented with more plaque, probing depths and bleeding on probing. Greater pocket depths were found to be related to the presence of plaque calculus and bleeding on probing. Conclusions. Overall, rather high incidences of periodontal pockets ≥ 5 mm were detected in this population. This data should serve to prepare further more detailed epidemiological studies that will serve to plan and implement prevent and treat strategies for periodontal diseases in Georgia and also help make manpower decisions.

  16. Dynamic real-time hierarchical heuristic search for pathfinding.

    Naveed, Munir; Kitchin, Diane E.; Crampton, Andrew

    2009-01-01

    Movement of Units in Real-Time Strategy (RTS) Games is a non-trivial and challenging task mainly due to three factors which are constraints on CPU and memory usage, dynamicity of the game world, and concurrency. In this paper, we are focusing on finding a novel solution for solving the pathfinding problem in RTS Games for the units which are controlled by the computer. The novel solution combines two AI Planning approaches: Hierarchical Task Network (HTN) and Real-Time Heuristic Search (RHS)....

  17. Closed loop simulations of the thermal experiments in LISA Pathfinder

    Gibert, Ferran; Karnesis, Nikolaos; Díaz-Aguiló, Marc; Mateos, Ignacio; Lobo, Alberto; Gesa, Lluís; Martín, Víctor; Lloro, Ivan

    2013-01-01

    The thermal experiments to be carried out onboard LISA Pathfinder (LPF) will provide essential information of the dependences of the instrument with respect to temperature variations. These thermal experiments must be modelled and simulated both to be validated for mission operations purposes and also to develop a data analysis tool able to characterise the temperature noise contribution to the instrument performance. Here we will present the models developed and the simulated signals for some of the experiments together with the corresponding interferometer readouts, the latter being computed by combining the thermal models with the global LTP (LISA Technology Package) simulator of the LTP Data Analysis team.

  18. Design Overview of the DM Radio Pathfinder Experiment

    Silva-Feaver, Maximiliano; Chaudhuri, Saptarshi; Cho, Hsiao-Mei; Dawson, Carl; Graham, Peter; Irwin, Kent; Kuenstner, Stephen; Li, Dale; Mardon, Jeremy; Moseley, Harvey; Mule, Richard; Phipps, Arran; Rajendran, Surjeet; Steffen, Zach; Young, Betty

    2016-01-01

    We introduce the DM Radio, a dual search for axion and hidden photon dark matter using a tunable superconducting lumped-element resonator. We discuss the prototype DM Radio Pathfinder experiment, which will probe hidden photons in the 500 peV (100 kHz)-50 neV (10 MHz) mass range. We detail the design of the various components: the LC resonant detector, the resonant frequency tuning procedure, the differential SQUID readout circuit, the shielding, and the cryogenic mounting structure. We prese...

  19. The LISA PathFinder DMU and Radiation Monitor

    Canizares, Priscilla; Diaz--Aguilo, Marc; Garcia-Berro, Enrique; Gesa, Lluis; Gibert, Ferran; Grimani, Catia; Lloro, Ivan; Lobo, Alberto; Mateos, Ignacio; Nofrarias, Miquel; Ramos-Castro, Juan; Sanjuan, Josep; Sopuerta, Carlos F

    2010-01-01

    The LISA PathFinder DMU (Data Management Unit) flight model was formally accepted by ESA and ASD on 11 February 2010, after all hardware and software tests had been successfully completed. The diagnostics items are scheduled to be delivered by the end of 2010. In this paper we review the requirements and performance of this instrumentation, specially focusing on the Radiation Monitor and the DMU, as well as the status of their programmed use during mission operations, on which work is ongoing at the time of writing.

  20. Symbolic PathFinder: Symbolic Execution of Java Bytecode

    Pasareanu, Corina S.; Rungta, Neha

    2010-01-01

    Symbolic Pathfinder (SPF) combines symbolic execution with model checking and constraint solving for automated test case generation and error detection in Java programs with unspecified inputs. In this tool, programs are executed on symbolic inputs representing multiple concrete inputs. Values of variables are represented as constraints generated from the analysis of Java bytecode. The constraints are solved using off-the shelf solvers to generate test inputs guaranteed to achieve complex coverage criteria. SPF has been used successfully at NASA, in academia, and in industry.

  1. 77 FR 6554 - Zephyr Power Transmission, LLC; Pathfinder Power Transmission, LLC; Duke-American Transmission...

    2012-02-08

    ... Energy Regulatory Commission Zephyr Power Transmission, LLC; Pathfinder Power Transmission, LLC; Duke... (Commission), 18 CFR 381.302, Zephyr Power Transmission, LLC (Zephyr), Pathfinder Power Transmission, LLC (PPT... to exercise its negotiated rate authority for Zephyr Power Transmission Project; (2) that...

  2. Mars Pathfinder. (Latest citations from the EI Compendex*Plus database)

    1996-11-01

    The bibliography contains citations concerning the Mars pathfinder mission launch. Topics discuss instrumentation, altimetry, and previous Mars Observer mission data. Concepts and goals of the Mars pathfinder program are examined. (Contains 50-250 citations and includes a subject term index and title list.)

  3. Inhibition of fast axonal transport by pathogenic SOD1 involves activation of p38 MAP kinase.

    Gerardo A Morfini

    Full Text Available Dying-back degeneration of motor neuron axons represents an established feature of familial amyotrophic lateral sclerosis (FALS associated with superoxide dismutase 1 (SOD1 mutations, but axon-autonomous effects of pathogenic SOD1 remained undefined. Characteristics of motor neurons affected in FALS include abnormal kinase activation, aberrant neurofilament phosphorylation, and fast axonal transport (FAT deficits, but functional relationships among these pathogenic events were unclear. Experiments in isolated squid axoplasm reveal that FALS-related SOD1 mutant polypeptides inhibit FAT through a mechanism involving a p38 mitogen activated protein kinase pathway. Mutant SOD1 activated neuronal p38 in mouse spinal cord, neuroblastoma cells and squid axoplasm. Active p38 MAP kinase phosphorylated kinesin-1, and this phosphorylation event inhibited kinesin-1. Finally, vesicle motility assays revealed previously unrecognized, isoform-specific effects of p38 on FAT. Axon-autonomous activation of the p38 pathway represents a novel gain of toxic function for FALS-linked SOD1 proteins consistent with the dying-back pattern of neurodegeneration characteristic of ALS.

  4. Wnt/planar cell polarity signaling controls the anterior-posterior organization of monoaminergic axons in the brainstem.

    Fenstermaker, Ali G; Prasad, Asheeta A; Bechara, Ahmad; Adolfs, Youri; Tissir, Fadel; Goffinet, Andre; Zou, Yimin; Pasterkamp, R Jeroen

    2010-11-24

    Monoaminergic neurons [serotonergic (5-HT) and dopaminergic (mdDA)] in the brainstem project axons along the anterior-posterior axis. Despite their important physiological functions and implication in disease, the molecular mechanisms that dictate the formation of these projections along the anterior-posterior axis remain unknown. Here we reveal a novel requirement for Wnt/planar cell polarity signaling in the anterior-posterior organization of the monoaminergic system. We find that 5-HT and mdDA axons express the core planar cell polarity components Frizzled3, Celsr3, and Vangl2. In addition, monoaminergic projections show anterior-posterior guidance defects in Frizzled3, Celsr3, and Vangl2 mutant mice. The only known ligands for planar cell polarity signaling are Wnt proteins. In culture, Wnt5a attracts 5-HT but repels mdDA axons, and Wnt7b attracts mdDA axons. However, mdDA axons from Frizzled3 mutant mice are unresponsive to Wnt5a and Wnt7b. Both Wnts are expressed in gradients along the anterior-posterior axis, consistent with their role as directional cues. Finally, Wnt5a mutants show transient anterior-posterior guidance defects in mdDA projections. Furthermore, we observe during development that the cell bodies of migrating descending 5-HT neurons eventually reorient along the direction of their axons. In Frizzled3 mutants, many 5-HT and mdDA neuron cell bodies are oriented abnormally along the direction of their aberrant axon projections. Overall, our data suggest that Wnt/planar cell polarity signaling may be a global anterior-posterior guidance mechanism that controls axonal and cellular organization beyond the spinal cord.

  5. Laser-based single-axon transection for high-content axon injury and regeneration studies.

    Darío Kunik

    Full Text Available The investigation of the regenerative response of the neurons to axonal injury is essential to the development of new axoprotective therapies. Here we study the retinal neuronal RGC-5 cell line after laser transection, demonstrating that the ability of these cells to initiate a regenerative response correlates with axon length and cell motility after injury. We show that low energy picosecond laser pulses can achieve transection of unlabeled single axons in vitro and precisely induce damage with micron precision. We established the conditions to achieve axon transection, and characterized RGC-5 axon regeneration and cell body response using time-lapse microscopy. We developed an algorithm to analyze cell trajectories and established correlations between cell motility after injury, axon length, and the initiation of the regeneration response. The characterization of the motile response of axotomized RGC-5 cells showed that cells that were capable of repair or regrowth of damaged axons migrated more slowly than cells that could not. Moreover, we established that RGC-5 cells with long axons could not recover their injured axons, and such cells were much more motile. The platform we describe allows highly controlled axonal damage with subcellular resolution and the performance of high-content screening in cell cultures.

  6. Axon initial segment Kv1 channels control axonal action potential waveform and synaptic efficacy.

    Kole, Maarten H P; Letzkus, Johannes J; Stuart, Greg J

    2007-08-16

    Action potentials are binary signals that transmit information via their rate and temporal pattern. In this context, the axon is thought of as a transmission line, devoid of a role in neuronal computation. Here, we show a highly localized role of axonal Kv1 potassium channels in shaping the action potential waveform in the axon initial segment (AIS) of layer 5 pyramidal neurons independent of the soma. Cell-attached recordings revealed a 10-fold increase in Kv1 channel density over the first 50 microm of the AIS. Inactivation of AIS and proximal axonal Kv1 channels, as occurs during slow subthreshold somatodendritic depolarizations, led to a distance-dependent broadening of axonal action potentials, as well as an increase in synaptic strength at proximal axonal terminals. Thus, Kv1 channels are strategically positioned to integrate slow subthreshold signals, providing control of the presynaptic action potential waveform and synaptic coupling in local cortical circuits.

  7. Genetics Home Reference: giant axonal neuropathy

    ... R. Proteomic analysis in giant axonal neuropathy: new insights into disease mechanisms. Muscle Nerve. 2012 Aug;46( ... healthcare professional . About Genetics Home Reference Site Map Customer Support Selection Criteria for Links USA.gov Copyright ...

  8. Genetic dissection of myelinated axons in zebrafish

    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...

  9. Crossing axons in the third nerve nucleus.

    Bienfang, D C

    1975-12-01

    The research presented in this paper studied the pathway taken by the crossed fibers of the third nerve nucleus in an animal whose nucleus has been well mapped and found to correlate well with higher mammals and man. Autoradiography using tritiated amino acid labeled the cell bodies an axons of the left side of the oculomotor nucleus of the cat. Axons so labeled could be seen emerging from the ventral portion of the left nucleus through the median longitudinal fasciculus (mlf) to join the left oculomotor nerve. Labeled axons were also seen to emerge from the medial border of the caudal left nucleus, cross the midline, and pass through the right nucleus and the right mlf to join the right oculomotor nerve. These latter axons must be the crossed axons of the superior rectus and levator palpebrae subnuclei. Since the path of these crossed axons is through the caudal portion of the nucleus of the opposite side, the destruction of one lateral half of the oculomotor nucleus would result in a bilateral palsy of the crossed subnuclei. Bilateral palsy of the superior rectus and bilateral assymetrical palsy of the levator palpebrae muscles would result.

  10. Differential calcium signaling mediated by voltage-gated calcium channels in rat retinal ganglion cells and their unmyelinated axons.

    Allison Sargoy

    Full Text Available Aberrant calcium regulation has been implicated as a causative factor in the degeneration of retinal ganglion cells (RGCs in numerous injury models of optic neuropathy. Since calcium has dual roles in maintaining homeostasis and triggering apoptotic pathways in healthy and injured cells, respectively, investigation of voltage-gated Ca channel (VGCC regulation as a potential strategy to reduce the loss of RGCs is warranted. The accessibility and structure of the retina provide advantages for the investigation of the mechanisms of calcium signalling in both the somata of ganglion cells as well as their unmyelinated axons. The goal of the present study was to determine the distribution of VGCC subtypes in the cell bodies and axons of ganglion cells in the normal retina and to define their contribution to calcium signals in these cellular compartments. We report L-type Ca channel α1C and α1D subunit immunoreactivity in rat RGC somata and axons. The N-type Ca channel α1B subunit was in RGC somata and axons, while the P/Q-type Ca channel α1A subunit was only in the RGC somata. We patch clamped isolated ganglion cells and biophysically identified T-type Ca channels. Calcium imaging studies of RGCs in wholemounted retinas showed that selective Ca channel antagonists reduced depolarization-evoked calcium signals mediated by L-, N-, P/Q- and T-type Ca channels in the cell bodies but only by L-type Ca channels in the axons. This differential contribution of VGCC subtypes to calcium signals in RGC somata and their axons may provide insight into the development of target-specific strategies to spare the loss of RGCs and their axons following injury.

  11. The case for testing MOND using LISA Pathfinder

    Magueijo, Joao

    2011-01-01

    We quantify the potential for testing MOdified Newtonian Dynamics (MOND) with LISA Pathfinder (LPF), should a saddle point flyby be incorporated into the mission. We forecast the expected signal to noise ratio (SNR) for a variety of instrument noise models and trajectories past the saddle. For standard theoretical parameters the SNR reaches middle to high double figures even with modest assumptions about instrument performance and saddle approach. Obvious concerns, like systematics arising from LPF self-gravity, or the Newtonian background, are examined and shown not to be a problem. We also investigate the impact of a negative observational result upon the free-function determining the theory. We demonstrate that, if Newton's gravitational constant is constrained not be re-normalized by more than a few percent, only very contrived MONDian free-functions would survive a negative result. Finally we scan the structure of all proposed relativistic MONDian theories. We conclude that only the Einstein-Aether formu...

  12. The Australian SKA Pathfinder: operations management and user engagement

    Harvey-Smith, Lisa

    2016-07-01

    This paper describes the science operations model for the Australian Square Kilometre Array Pathfinder (ASKAP) telescope. ASKAP is a radio interferometer currently being commissioned in Western Australia. It will be operated by a dedicated team of observatory staff with the support of telescope monitoring, control and scheduling software. These tools, as well as the proposal tools and data archive will enable the telescope to operate with little direct input from the astronomy user. The paper also discusses how close engagement with the telescope user community has been maintained throughout the ASKAP construction and commissioning phase, leading to positive outcomes including early input into the design of telescope systems and a vibrant early science program.

  13. Drill/borescope System for the Mars Polar Pathfinder

    Paige, D. A.; Wood, S. E.; Vasavada, A. R.

    1993-01-01

    The primary goals of the Mars Polar Pathfinder (MPP) Discovery Mission are to characterize the composition and structure of Mars' north polar ice cap, and to determine whether a climate record may be preserved in layers of ice and dust. The MPP would land as close as possible to the geographic north pole of Mars and use a set of instruments similar to those used by glaciologists to study polar ice caps on Earth: a radar sounder, a drill/borescope system, and a thermal probe. The drill/borescope system will drill approximately 50 cm into the surface and image the sides of the hole at 10 micron resolution for compositional and stratigraphic analysis. Several uncertainties have guided the development of this instrument, and they are discussed.

  14. State space modelling and data analysis exercises in LISA Pathfinder

    Nofrarias, M; Armano, M; Audley, H; Auger, G; Benedetti, M; Binetruy, P; Bogenstahl, J; Bortoluzzi, D; Bosetti, P; Brandt, N; Caleno, M; Cañizares, P; Cavalleri, A; Cesa, M; Chmeissani, M; Conchillo, A; Congedo, G; Cristofolin, I; Cruise, M; Danzmann, K; De Marchi, F; Diaz-Aguilo, M; Diepholz, I; Dixon, G; Dolesi, R; Dunbar, N; Fauste, J; Ferraioli, L; Fichter, V Ferroni W; Fitzsimons, E; Freschi, M; Marin, A García; Marirrodriga, C García; Gesa, R Gerndt L; Gibert, F; Giardini, D; Grimani, C; Grynagier, A; Guillaume, B; Guzmán, F; Harrison, I; Heinzel, G; Hernández, V; Hewitson, M; Hollington, D; Hough, J; Hoyland, D; Hueller, M; Huesler, J; Jennrich, O; Jetzer, P; Johlander, B; Killow, C; Llamas, X; Lloro, I; Lobo, A; Maarschalkerweerd, R; Madden, S; Mance, D; Mateos, I; McNamara, P W; Mendes, J; Mitchell, E; Monsky, A; Nicolini, D; Nicolodi, D; Pedersen, F; Perreur-Lloyd, M; Plagnol, E; Prat, P; Racca, G D; Ramos-Castro, J; Reiche, J; Perez, J A Romera; Robertson, D; Rozemeijer, H; Sanjuan, J; Schleicher, A; Schulte, M; Shaul, D; Stagnaro, L; Strandmoe, S; Steier, F; Sumner, T J; Taylor, A; Texier, D; Trenkel, C; Vitale, H-B Tu S; Wanner, G; Ward, H; Waschke, S; Wass, P; Weber, W J; Ziegler, T; Zweifel, P

    2013-01-01

    LISA Pathfinder is a mission planned by the European Space Agency to test the key technologies that will allow the detection of gravitational waves in space. The instrument on-board, the LISA Technology package, will undergo an exhaustive campaign of calibrations and noise characterisation campaigns in order to fully describe the noise model. Data analysis plays an important role in the mission and for that reason the data analysis team has been developing a toolbox which contains all the functionalities required during operations. In this contribution we give an overview of recent activities, focusing on the improvements in the modelling of the instrument and in the data analysis campaigns performed both with real and simulated data.

  15. Exploring MEDLINE space with random indexing and pathfinder networks.

    Cohen, Trevor

    2008-11-06

    The integration of disparate research domains is a prerequisite for the success of the translational science initiative. MEDLINE abstracts contain content from a broad range of disciplines, presenting an opportunity for the development of methods able to integrate the knowledge they contain. Latent Semantic Analysis (LSA) and related methods learn human-like associations between terms from unannotated text. However, their computational and memory demands limits their ability to address a corpus of this size. Furthermore, visualization methods previously used in conjunction with LSA have limited ability to define the local structure of the associative networks LSA learns. This paper explores these issues by (1) processing the entire MEDLINE corpus using Random Indexing, a variant of LSA, and (2) exploring learned associations using Pathfinder Networks. Meaningful associations are inferred from MEDLINE, including a drug-disease association undetected by PUBMED search.

  16. State Space Modelling and Data Analysis Exercises in LISA Pathfinder

    Nofrarias, M.; Antonucci, F.; Armano, M.; Audley, H.; Auger, G.; Benedetti, M.; Binetruy, P.; Bogenstahl, J.; Bortoluzzi, D.; Brandt, N.; Caleno, M.; Cavalleri, A.; Congedo, G.; Cruise, M.; Danzmann, K.; De Marchi, F.; Diaz-Aguilo, M.; Diepholz, I.; Dixon, G.; Dolesi, R.; Dunbar, N.; Fauste, J.; Ferraioli, L.; Ferroni, V.; Fichter, W.; Fitzsimons, E.; Freschi, M.; García Marirrodriga, C.; Gerndt, R.; Gesa, L.; Gibert, F.; Giardini, D.; Grimani, C.; Grynagier, A.; Guzmán, F.; Harrison, I.; Heinzel, G.; Hewitson, M.; Hollington, D.; Hoyland, D.; Hueller, M.; Huesler, J.; Jennrich, O.; Jetzer, P.; Johlander, B.; Karnesis, N.; Korsakova, N.; Killow, C.; Llamas, X.; Lloro, I.; Lobo, A.; Maarschalkerweerd, R.; Madden, S.; Mance, D.; Martin, V.; Mateos, I.; McNamara, P.; Mendes, J.; Mitchell, E.; Nicolodi, D.; Perreur-Lloyd, M.; Plagnol, E.; Prat, P.; Ramos-Castro, J.; Reiche, J.; Romera Perez, J. A.; Robertson, D.; Rozemeijer, H.; Russano, G.; Schleicher, A.; Shaul, D.; Sopuerta, C. F.; Sumner, T. J.; Taylor, A.; Texier, D.; Trenkel, C.; Tu, H. B.; Vitale, S.; Wanner, G.; Ward, H.; Waschke, S.; Wass, P.; Wealthy, D.; Wen, S.; Weber, W.; Ziegler, T.; Zweifel, P.

    2013-01-01

    LISA Pathfinder is a mission planned by the European Space Agency (ESA) to test the key technologies that will allow the detection of gravitational waves in space. The instrument on-board, the LISA Technology package, will undergo an exhaustive campaign of calibrations and noise characterisation campaigns in order to fully describe the noise model. Data analysis plays an important role in the mission and for that reason the data analysis team has been developing a toolbox which contains all the functionality required during operations. In this contribution we give an overview of recent activities, focusing on the improvements in the modelling of the instrument and in the data analysis campaigns performed both with real and simulated data.

  17. Source-finding for the Australian Square Kilometre Array Pathfinder

    Whiting, Matthew

    2012-01-01

    The Australian Square Kilometre Array Pathfinder (ASKAP) presents a number of challenges in the area of source finding and cataloguing. The data rates and image sizes are very large, and require automated processing in a high-performance computing environment. This requires development of new tools, that are able to operate in such an environment and can reliably handle large datasets. These tools must also be able to accommodate the different types of observations ASKAP will make: continuum imaging, spectral-line imaging, transient imaging. The ASKAP project has developed a source-finder known as Selavy, built upon the Duchamp source-finder (Whiting 2012). Selavy incorporates a number of new features, which we describe here. Since distributed processing of large images and cubes will be essential, we describe the algorithms used to distribute the data, find an appropriate threshold and search to that threshold and form the final source catalogue. We describe the algorithm used to define a varying threshold t...

  18. The LISA Pathfinder interferometry—hardware and system testing

    Audley, H.; Danzmann, K.; García Marín, A.; Heinzel, G.; Monsky, A.; Nofrarias, M.; Steier, F.; Gerardi, D.; Gerndt, R.; Hechenblaikner, G.; Johann, U.; Luetzow-Wentzky, P.; Wand, V.; Antonucci, F.; Armano, M.; Auger, G.; Benedetti, M.; Binetruy, P.; Boatella, C.; Bogenstahl, J.; Bortoluzzi, D.; Bosetti, P.; Caleno, M.; Cavalleri, A.; Cesa, M.; Chmeissani, M.; Ciani, G.; Conchillo, A.; Congedo, G.; Cristofolini, I.; Cruise, M.; De Marchi, F.; Diaz-Aguilo, M.; Diepholz, I.; Dixon, G.; Dolesi, R.; Fauste, J.; Ferraioli, L.; Fertin, D.; Fichter, W.; Fitzsimons, E.; Freschi, M.; García Marirrodriga, C.; Gesa, L.; Gibert, F.; Giardini, D.; Grimani, C.; Grynagier, A.; Guillaume, B.; Guzmán, F.; Harrison, I.; Hewitson, M.; Hollington, D.; Hough, J.; Hoyland, D.; Hueller, M.; Huesler, J.; Jeannin, O.; Jennrich, O.; Jetzer, P.; Johlander, B.; Killow, C.; Llamas, X.; Lloro, I.; Lobo, A.; Maarschalkerweerd, R.; Madden, S.; Mance, D.; Mateos, I.; McNamara, P. W.; Mendes, J.; Mitchell, E.; Nicolini, D.; Nicolodi, D.; Pedersen, F.; Perreur-Lloyd, M.; Perreca, A.; Plagnol, E.; Prat, P.; Racca, G. D.; Rais, B.; Ramos-Castro, J.; Reiche, J.; Romera Perez, J. A.; Robertson, D.; Rozemeijer, H.; Sanjuan, J.; Schulte, M.; Shaul, D.; Stagnaro, L.; Strandmoe, S.; Sumner, T. J.; Taylor, A.; Texier, D.; Trenkel, C.; Tombolato, D.; Vitale, S.; Wanner, G.; Ward, H.; Waschke, S.; Wass, P.; Weber, W. J.; Zweifel, P.

    2011-05-01

    Preparations for the LISA Pathfinder mission have reached an exciting stage. Tests of the engineering model (EM) of the optical metrology system have recently been completed at the Albert Einstein Institute, Hannover, and flight model tests are now underway. Significantly, they represent the first complete integration and testing of the space-qualified hardware and are the first tests on an optical system level. The results and test procedures of these campaigns will be utilized directly in the ground-based flight hardware tests, and subsequently during in-flight operations. In addition, they allow valuable testing of the data analysis methods using the MATLAB-based LTP data analysis toolbox. This paper presents an overview of the results from the EM test campaign that was successfully completed in December 2009.

  19. Discrete derivative estimation in LISA Pathfinder data reduction

    Ferraioli, Luigi; Vitale, Stefano

    2009-01-01

    Data analysis for the LISA Technology package (LTP) experiment to be flown aboard the LISA Pathfinder mission requires the solution of the system dynamics for the calculation of the force acting on the test masses (TMs) starting from interferometer position data. The need for a solution to this problem has prompted us to implement a discrete time domain derivative estimator suited for the LTP experiment requirements. We first report on the mathematical procedures for the definition of two methods; the first based on a parabolic fit approximation and the second based on a Taylor series expansion. These two methods are then generalized and incorporated in a more general class of five point discrete derivative estimators. The same procedure employed for the second derivative can be applied to the estimation of the first derivative and of a data smoother allowing defining a class of simple five points estimators for both. The performances of three particular realization of the five point second derivative estimat...

  20. Using geometric algebra to study optical aberrations

    Hanlon, J.; Ziock, H.

    1997-05-01

    This paper uses Geometric Algebra (GA) to study vector aberrations in optical systems with square and round pupils. GA is a new way to produce the classical optical aberration spot diagrams on the Gaussian image plane and surfaces near the Gaussian image plane. Spot diagrams of the third, fifth and seventh order aberrations for square and round pupils are developed to illustrate the theory.

  1. Axon injury triggers EFA-6 mediated destabilization of axonal microtubules via TACC and doublecortin like kinase.

    Chen, Lizhen; Chuang, Marian; Koorman, Thijs; Boxem, Mike; Jin, Yishi; Chisholm, Andrew D

    2015-09-04

    Axon injury triggers a series of changes in the axonal cytoskeleton that are prerequisites for effective axon regeneration. In Caenorhabditis elegans the signaling protein Exchange Factor for ARF-6 (EFA-6) is a potent intrinsic inhibitor of axon regrowth. Here we show that axon injury triggers rapid EFA-6-dependent inhibition of axonal microtubule (MT) dynamics, concomitant with relocalization of EFA-6. EFA-6 relocalization and axon regrowth inhibition require a conserved 18-aa motif in its otherwise intrinsically disordered N-terminal domain. The EFA-6 N-terminus binds the MT-associated proteins TAC-1/Transforming-Acidic-Coiled-Coil, and ZYG-8/Doublecortin-Like-Kinase, both of which are required for regenerative growth cone formation, and which act downstream of EFA-6. After injury TAC-1 and EFA-6 transiently relocalize to sites marked by the MT minus end binding protein PTRN-1/Patronin. We propose that EFA-6 acts as a bifunctional injury-responsive regulator of axonal MT dynamics, acting at the cell cortex in the steady state and at MT minus ends after injury.

  2. Phase Aberrations in Diffraction Microscopy

    Marchesini, S; Chapman, H N; Barty, A; Howells, M R; Spence, J H; Cui, C; Weierstall, U; Minor, A M

    2005-09-29

    In coherent X-ray diffraction microscopy the diffraction pattern generated by a sample illuminated with coherent x-rays is recorded, and a computer algorithm recovers the unmeasured phases to synthesize an image. By avoiding the use of a lens the resolution is limited, in principle, only by the largest scattering angles recorded. However, the imaging task is shifted from the experiment to the computer, and the algorithm's ability to recover meaningful images in the presence of noise and limited prior knowledge may produce aberrations in the reconstructed image. We analyze the low order aberrations produced by our phase retrieval algorithms. We present two methods to improve the accuracy and stability of reconstructions.

  3. Narrative report Pathfinder National Wildlife Refuge: September, October, November, December, 1963

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from September through December of 1963. The report begins by...

  4. NOAA Climate Data Record (CDR) of AVHRR Polar Pathfinder (APP) Cryosphere

    National Oceanic and Atmospheric Administration, Department of Commerce — This NOAA Climate Data Record (CDR) contains the AVHRR Polar Pathfinder (APP) product. APP is a fundamental CDR comprised of calibrated and navigated AVHRR channel...

  5. CRED REA Algal Assessments at Pathfinder Reef, Marianas Archipelago in 2005

    National Oceanic and Atmospheric Administration, Department of Commerce — As part of Rapid Ecological Assessments (REA), Twelve quadrats were sampled along 2 consecutively-placed, 25m transect lines, conducted at 2 sites at Pathfinder Reef...

  6. CRED REA Fish Team Belt Transect Survey at Pathfinder Reef, Marianas Archipelago, 2005

    National Oceanic and Atmospheric Administration, Department of Commerce — Belt transects along 3 consecutively-placed, 25m transect lines were surveyed as part of Rapid Ecological Assessments conducted at 2 sites at Pathfinder Reef in the...

  7. Narrative report Pathfinder National Wildlife Refuge: September, October, November, December, 1961

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from September through December of 1961. The report begins by...

  8. Narrative report Pathfinder National Wildlife Refuge: September, October, November, December, 1962

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from September through December of 1962. The report begins by...

  9. Narrative report Pathfinder National Wildlife Refuge: May, June, July, August, 1963

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from May through August of 1963. The report begins by summarizing the...

  10. Narrative report Pathfinder National Wildlife Refuge: January, February, March, April, 1961

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from January through April of 1961. The report begins by summarizing...

  11. Narrative report Pathfinder National Wildlife Refuge: May, June, July, August, 1962

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from May through August of 1962. The report begins by summarizing the...

  12. Pathfinder National Wildlife Refuge Narrative report: January, February, March, April, 1958

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from January through April of 1958. The report begins by summarizing...

  13. Pathfinder National Wildlife Refuge, Narrative report: May, June, July, August, 1958

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from May through August of 1958. The report begins by summarizing the...

  14. Pathfinder National Wildlife Refuge Narrative report: January, February, March, April, 1959

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from January through April of 1959. The report begins by summarizing...

  15. Pathfinder National Wildlife Refuge Narrative report: January, February, March, April, 1960

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from January through April of 1960. The report begins by summarizing...

  16. Narrative report Pathfinder National Wildlife Refuge: May, June, July, August, 1961

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from May through August of 1961. The report begins by summarizing the...

  17. Pathfinder National Wildlife Refuge, Narrative report: May, June, July, August, 1960

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from May through August of 1960. The report begins by summarizing the...

  18. Pathfinder National Wildlife Refuge, Narrative report: September, October, November, December, 1957

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from September through December of 1957. The report begins by...

  19. Pathfinder National Wildlife Refuge, Narrative report: May, June, July, August, 1959

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from May through August of 1959. The report begins by summarizing the...

  20. Pathfinder National Wildlife Refuge Narrative report: September, October, November, December, 1959

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from September through December of 1959. The report begins by...

  1. Pathfinder National Wildlife Refuge, Narrative report: September, October, November, December, 1956

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from September through December of 1956. The report begins by...

  2. Pathfinder National Wildlife Refuge, Narrative report: January, February, March, April, 1957

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from January through April of 1957. The report begins by summarizing...

  3. Narrative report Pathfinder National Wildlife Refuge: January, February, March, April, 1962

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from January through April of 1962. The report begins by summarizing...

  4. Pathfinder National Wildlife Refuge, Narrative report: May, June, July, August, 1957

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from May through August of 1957. The report begins by summarizing the...

  5. Pathfinder National Wildlife Refuge Narrative report: September, October, November, December, 1960

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from September through December of 1960. The report begins by...

  6. Pathfinder National Wildlife Refuge, Narrative report: May, June, July, August, 1956

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from May through August of 1956. The report begins by summarizing the...

  7. Narrative report Pathfinder National Wildlife Refuge: January, February, March, April, 1963

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from January through April of 1963. The report begins by summarizing...

  8. Pathfinder National Wildlife Refuge Narrative report: September, October, November, December, 1958

    US Fish and Wildlife Service, Department of the Interior — This narrative report for Pathfinder National Wildlife Refuge outlines Refuge accomplishments from September through December of 1958. The report begins by...

  9. NOAA Climate Data Record (CDR) of AVHRR Polar Pathfinder Extended (APP-X) Cryosphere

    National Oceanic and Atmospheric Administration, Department of Commerce — NOAA Climate Data Record (CDR) of the extended AVHRR Polar Pathfinder (APP-x) cryosphere contains 19 geophysical variables over the Arctic and Antarctic for the...

  10. How Schwann Cells Sort Axons: New Concepts.

    Feltri, M Laura; Poitelon, Yannick; Previtali, Stefano Carlo

    2016-06-01

    Peripheral nerves contain large myelinated and small unmyelinated (Remak) fibers that perform different functions. The choice to myelinate or not is dictated to Schwann cells by the axon itself, based on the amount of neuregulin I-type III exposed on its membrane. Peripheral axons are more important in determining the final myelination fate than central axons, and the implications for this difference in Schwann cells and oligodendrocytes are discussed. Interestingly, this choice is reversible during pathology, accounting for the remarkable plasticity of Schwann cells, and contributing to the regenerative potential of the peripheral nervous system. Radial sorting is the process by which Schwann cells choose larger axons to myelinate during development. This crucial morphogenetic step is a prerequisite for myelination and for differentiation of Remak fibers, and is arrested in human diseases due to mutations in genes coding for extracellular matrix and linkage molecules. In this review we will summarize progresses made in the last years by a flurry of reverse genetic experiments in mice and fish. This work revealed novel molecules that control radial sorting, and contributed unexpected ideas to our understanding of the cellular and molecular mechanisms that control radial sorting of axons.

  11. Protein phosphorylation: Localization in regenerating optic axons

    Larrivee, D. (Cornell Univ. Medical College, New York, NY (USA))

    1990-09-01

    A number of axonal proteins display changes in phosphorylation during goldfish optic nerve regeneration. (1) To determine whether the phosphorylation of these proteins was closely linked to their synthesis in the retinal ganglion cell body, cycloheximide was injected intraocularly into goldfish whose optic nerves had been regenerating for 3 weeks. Cycloheximide reduced the incorporation of (3H)proline and 32P orthophosphate into total nerve protein by 84% and 46%, respectively. Of the 20 individual proteins examined, 17 contained less than 15% of the (3H)proline label measured in corresponding controls, whereas 18 proteins contained 50% or more of the 32P label, suggesting that phosphorylation was largely independent of synthesis. (2) To determine whether the proteins were phosphorylated in the ganglion cell axons, axonal transport of proteins was blocked by intraocular injection of vincristine. Vincristine reduced (3H)proline labeling of total protein by 88% and 32P labeling by 49%. Among the individual proteins (3H)proline labeling was reduced by 90% or more in 18 cases but 32P labeling was reduced only by 50% or less. (3) When 32P was injected into the cranial cavity near the ends of the optic axons, all of the phosphoproteins were labeled more intensely in the optic tract than in the optic nerve. These results suggest that most of the major phosphoproteins that undergo changes in phosphorylation in the course of regeneration are phosphorylated in the optic axons.

  12. Pathfinding with Hard Constraints : Mobile Systems and Real Time Strategy Games Combined

    Erdtman, Samuel; Fylling, Johan

    2008-01-01

    There is an abundance of pathfinding solutions, but are any of those solutions suitable for usage in a real time strategy (RTS) game designed for mobile systems with limited processing and storage capabilities (such as the Nintendo DS, PSP, cellular phones, etc.)? The RTS domain puts great requirements on the pathfinding mechanics used in the game; in the form of de- mands on responsiveness and path optimality. Furthermore, the Nintendo DS, and its portable, distant relatives, bring hard con-...

  13. The semantic pathfinder: using an authoring metaphor for generic multimedia indexing.

    Snoek, Cees G M; Worring, Marcel; Geusebroek, Jan-Mark; Koelma, Dennis C; Seinstra, Frank J; Smeulders, Arnold W M

    2006-10-01

    This paper presents the semantic pathfinder architecture for generic indexing of multimedia archives. The semantic pathfinder extracts semantic concepts from video by exploring different paths through three consecutive analysis steps, which we derive from the observation that produced video is the result of an authoring-driven process. We exploit this authoring metaphor for machine-driven understanding. The pathfinder starts with the content analysis step. In this analysis step, we follow a data-driven approach of indexing semantics. The style analysis step is the second analysis step. Here, we tackle the indexing problem by viewing a video from the perspective of production. Finally, in the context analysis step, we view semantics in context. The virtue of the semantic pathfinder is its ability to learn the best path of analysis steps on a per-concept basis. To show the generality of this novel indexing approach, we develop detectors for a lexicon of 32 concepts and we evaluate the semantic pathfinder against the 2004 NIST TRECVID video retrieval benchmark, using a news archive of 64 hours. Top ranking performance in the semantic concept detection task indicates the merit of the semantic pathfinder for generic indexing of multimedia archives.

  14. Correlations between corneal and total wavefront aberrations

    Mrochen, Michael; Jankov, Mirko; Bueeler, Michael; Seiler, Theo

    2002-06-01

    Purpose: Corneal topography data expressed as corneal aberrations are frequently used to report corneal laser surgery results. However, the optical image quality at the retina depends on all optical elements of the eye such as the human lens. Thus, the aim of this study was to investigate the correlations between the corneal and total wavefront aberrations and to discuss the importance of corneal aberrations for representing corneal laser surgery results. Methods: Thirty three eyes of 22 myopic subjects were measured with a corneal topography system and a Tschernig-type wavefront analyzer after the pupils were dilated to at least 6 mm in diameter. All measurements were centered with respect to the line of sight. Corneal and total wavefront aberrations were calculated up to the 6th Zernike order in the same reference plane. Results: Statistically significant correlations (p corneal and total wavefront aberrations were found for the astigmatism (C3,C5) and all 3rd Zernike order coefficients such as coma (C7,C8). No statistically significant correlations were found for all 4th to 6th order Zernike coefficients except for the 5th order horizontal coma C18 (p equals 0.003). On average, all Zernike coefficients for the corneal aberrations were found to be larger compared to Zernike coefficients for the total wavefront aberrations. Conclusions: Corneal aberrations are only of limited use for representing the optical quality of the human eye after corneal laser surgery. This is due to the lack of correlation between corneal and total wavefront aberrations in most of the higher order aberrations. Besides this, the data present in this study yield towards an aberration balancing between corneal aberrations and the optical elements within the eye that reduces the aberration from the cornea by a certain degree. Consequently, ideal customized ablations have to take both, corneal and total wavefront aberrations, into consideration.

  15. Automated Axon Counting in Rodent Optic Nerve Sections with AxonJ

    Zarei, Kasra; Scheetz, Todd E.; Christopher, Mark; Miller, Kathy; Hedberg-Buenz, Adam; Tandon, Anamika; Anderson, Michael G.; Fingert, John H.; Abràmoff, Michael David

    2016-05-01

    We have developed a publicly available tool, AxonJ, which quantifies the axons in optic nerve sections of rodents stained with paraphenylenediamine (PPD). In this study, we compare AxonJ’s performance to human experts on 100x and 40x images of optic nerve sections obtained from multiple strains of mice, including mice with defects relevant to glaucoma. AxonJ produced reliable axon counts with high sensitivity of 0.959 and high precision of 0.907, high repeatability of 0.95 when compared to a gold-standard of manual assessments and high correlation of 0.882 to the glaucoma damage staging of a previously published dataset. AxonJ allows analyses that are quantitative, consistent, fully-automated, parameter-free, and rapid on whole optic nerve sections at 40x. As a freely available ImageJ plugin that requires no highly specialized equipment to utilize, AxonJ represents a powerful new community resource augmenting studies of the optic nerve using mice.

  16. Diverse modes of axon elaboration in the developing neocortex.

    2005-08-01

    Full Text Available The development of axonal arbors is a critical step in the establishment of precise neural circuits, but relatively little is known about the mechanisms of axonal elaboration in the neocortex. We used in vivo two-photon time-lapse microscopy to image axons in the neocortex of green fluorescent protein-transgenic mice over the first 3 wk of postnatal development. This period spans the elaboration of thalamocortical (TC and Cajal-Retzius (CR axons and cortical synaptogenesis. Layer 1 collaterals of TC and CR axons were imaged repeatedly over time scales ranging from minutes up to days, and their growth and pruning were analyzed. The structure and dynamics of TC and CR axons differed profoundly. Branches of TC axons terminated in small, bulbous growth cones, while CR axon branch tips had large growth cones with numerous long filopodia. TC axons grew rapidly in straight paths, with frequent interstitial branch additions, while CR axons grew more slowly along tortuous paths. For both types of axon, new branches appeared at interstitial sites along the axon shaft and did not involve growth cone splitting. Pruning occurred via retraction of small axon branches (tens of microns, at both CR and TC axons or degeneration of large portions of the arbor (hundreds of microns, for TC axons only. The balance between growth and retraction favored overall growth, but only by a slight margin. Given the identical layer 1 territory upon which CR and TC axons grow, the differences in their structure and dynamics likely reflect distinct intrinsic growth programs for axons of long projection neurons versus local interneurons.

  17. Neural Progenitor Cells Promote Axonal Growth and Alter Axonal mRNA Localization in Adult Neurons

    Merianda, Tanuja T.; Jin, Ying

    2017-01-01

    Abstract The inhibitory environment of the spinal cord and the intrinsic properties of neurons prevent regeneration of axons following CNS injury. However, both ascending and descending axons of the injured spinal cord have been shown to regenerate into grafts of embryonic neural progenitor cells (NPCs). Previous studies have shown that grafts composed of glial-restricted progenitors (GRPs) and neural-restricted progenitors (NRPs) can provide a permissive microenvironment for axon growth. We have used cocultures of adult rat dorsal root ganglion (DRG) neurons together with NPCs, which have shown significant enhancement of axon growth by embryonic rat GRP and GRPs/NRPs, both in coculture conditions and when DRGs are exposed to conditioned medium from the NPC cultures. This growth-promoting effect of NPC-conditioned medium was also seen in injury-conditioned neurons. DRGs cocultured with GRPs/NRPs showed altered expression of regeneration-associated genes at transcriptional and post-transcriptional levels. We found that levels of GAP-43 mRNA increased in DRG cell bodies and axons. However, hepcidin antimicrobial peptide (HAMP) mRNA decreased in the cell bodies of DRGs cocultured with GRPs/NRPs, which is distinct from the increase in cell body HAMP mRNA levels seen in DRGs after injury conditioning. Endogenous GAP-43 and β-actin mRNAs as well as reporter RNAs carrying axonally localizing 3'UTRs of these transcripts showed significantly increased levels in distal axons in the DRGs cocultured with GRPs/NRPs. These results indicate that axon growth promoted by NPCs is associated not only with enhanced transcription of growth-associated genes but also can increase localization of some mRNAs into growing axons. PMID:28197547

  18. Chromosome aberrations induced by zebularine in triticale.

    Ma, Xuhui; Wang, Qing; Wang, Yanzhi; Ma, Jieyun; Wu, Nan; Ni, Shuang; Luo, Tengxiao; Zhuang, Lifang; Chu, Chenggen; Cho, Seong-Woo; Tsujimoto, Hisashi; Qi, Zengjun

    2016-07-01

    Chromosome engineering is an important approach for generating wheat germplasm. Efficient development of chromosome aberrations will facilitate the introgression and application of alien genes in wheat. In this study, zebularine, a DNA methylation transferase inhibitor, was successfully used to induce chromosome aberrations in the octoploid triticale cultivar Jinghui#1. Dry seeds were soaked in zebularine solutions (250, 500, and 750 μmol/L) for 24 h, and the 500 μmol/L treatment was tested in three additional treatment times, i.e., 12, 36, and 48 h. All treatments induced aberrations involving wheat and rye chromosomes. Of the 920 cells observed in 67 M1 plants, 340 (37.0%) carried 817 aberrations with an average of 0.89 aberrations per cell (range: 0-12). The aberrations included probable deletions, telosomes and acentric fragments (49.0%), large segmental translocations (28.9%), small segmental translocations (17.1%), intercalary translocations (2.6%), long chromosomes that could carry more than one centromere (2.0%), and ring chromosomes (0.5%). Of 510 M2 plants analyzed, 110 (21.6%) were found to carry stable aberrations. Such aberrations included 79 with varied rye chromosome numbers, 7 with wheat and rye chromosome translocations, 15 with possible rye telosomes/deletions, and 9 with complex aberrations involving variation in rye chromosome number and wheat-rye translocations. These indicated that aberrations induced by zebularine can be steadily transmitted, suggesting that zebularine is a new efficient agent for chromosome manipulation.

  19. Atom lens without chromatic aberrations

    Efremov, Maxim A; Schleich, Wolfgang P

    2012-01-01

    We propose a lens for atoms with reduced chromatic aberrations and calculate its focal length and spot size. In our scheme a two-level atom interacts with a near-resonant standing light wave formed by two running waves of slightly different wave vectors, and a far-detuned running wave propagating perpendicular to the standing wave. We show that within the Raman-Nath approximation and for an adiabatically slow atom-light interaction, the phase acquired by the atom is independent of the incident atomic velocity.

  20. Unc-51/ATG1 controls axonal and dendritic development via kinesin-mediated vesicle transport in the Drosophila brain.

    Hiroaki Mochizuki

    Full Text Available BACKGROUND: Members of the evolutionary conserved Ser/Thr kinase Unc-51 family are key regulatory proteins that control neural development in both vertebrates and invertebrates. Previous studies have suggested diverse functions for the Unc-51 protein, including axonal elongation, growth cone guidance, and synaptic vesicle transport. METHODOLOGY/PRINCIPAL FINDINGS: In this work, we have investigated the functional significance of Unc-51-mediated vesicle transport in the development of complex brain structures in Drosophila. We show that Unc-51 preferentially accumulates in newly elongating axons of the mushroom body, a center of olfactory learning in flies. Mutations in unc-51 cause disintegration of the core of the developing mushroom body, with mislocalization of Fasciclin II (Fas II, an IgG-family cell adhesion molecule important for axonal guidance and fasciculation. In unc-51 mutants, Fas II accumulates in the cell bodies, calyx, and the proximal peduncle. Furthermore, we show that mutations in unc-51 cause aberrant overshooting of dendrites in the mushroom body and the antennal lobe. Loss of unc-51 function leads to marked accumulation of Rab5 and Golgi components, whereas the localization of dendrite-specific proteins, such as Down syndrome cell adhesion molecule (DSCAM and No distributive disjunction (Nod, remains unaltered. Genetic analyses of kinesin light chain (Klc and unc-51 double heterozygotes suggest the importance of kinesin-mediated membrane transport for axonal and dendritic development. Moreover, our data demonstrate that loss of Klc activity causes similar axonal and dendritic defects in mushroom body neurons, recapitulating the salient feature of the developmental abnormalities caused by unc-51 mutations. CONCLUSIONS/SIGNIFICANCE: Unc-51 plays pivotal roles in the axonal and dendritic development of the Drosophila brain. Unc-51-mediated membrane vesicle transport is important in targeted localization of guidance molecules

  1. Myelin-associated glycoprotein and its axonal receptors.

    Schnaar, Ronald L; Lopez, Pablo H H

    2009-11-15

    Myelin-associated glycoprotein (MAG) is expressed on the innermost myelin membrane wrap, directly apposed to the axon surface. Although it is not required for myelination, MAG enhances long-term axon-myelin stability, helps to structure nodes of Ranvier, and regulates the axon cytoskeleton. In addition to its role in axon-myelin stabilization, MAG inhibits axon regeneration after injury; MAG and a discrete set of other molecules on residual myelin membranes at injury sites actively signal axons to halt elongation. Both the stabilizing and the axon outgrowth inhibitory effects of MAG are mediated by complementary MAG receptors on the axon surface. Two MAG receptor families have been described, sialoglycans (specifically gangliosides GD1a and GT1b) and Nogo receptors (NgRs). Controversies remain about which receptor(s) mediates which of MAG's biological effects. Here we review the findings and challenges in associating MAG's biological effects with specific receptors.

  2. Polar Geophysics Products Derived from AVHRR: The "AVHRR Polar Pathfinder

    Maslanik, James; Fowler, Charles; Scambos, Theodore

    1999-01-01

    This NOAA/NASA Pathfinder effort was established to locate, acquire, and process Advanced Very High Resolution Radiometer (AVHRR) imagery into geo-located and calibrated radiances, cloud masks, surface clear-sky broadband albedo, clear-sky skin temperatures, satellite viewing times, and viewing and solar geometry for the, high-latitude portions of the northern and southern hemispheres (all area north of 48N and south of 53S). AVHRR GAC data for August 1981 - July 1998 were acquired, with some gaps remaining, and processed into twice-daily 5-km grids, with some products also provided at 25-km resolution. AVHRR LAC data for 3.5 years of coverage in the northern hemisphere and 2.75 years of coverage in the southern hemisphere were processed into 1.25-km grids for the same suite of products. The resulting data sets are presently being transferred to the National Snow and Ice Data Center (NSIDC) for archiving and distribution. Using these data, researchers now have at their disposal an extensive AVHRR data set for investigations of high-latitude processes. In addition, the data lend themselves to development and testing of algorithms. The products are particularly relevant for climate research and algorithm development as applied to relatively long time periods and large areas.

  3. Optical Performances of Slewing Mirror Telescope for UFFO-Pathfinder

    Jeong, S; Nam, J W; Park, I H; Kim, S -W; Choi, H S; Grossan, B; Hermann, I; Jung, A; Kim, Y W; Kim, J E; Linder, E V; Lee, J; Lim, H; Min, K W; Na, G W; Nam, K H; Panasyuk, M I; Smoot, G F; Svelitov, S; Suh, Y D; Vedenken, N; Yashin, I; Zhao, M H

    2011-01-01

    The Ultra-Fast Flash Observatory-Pathfinder (UFFO-P) is to be launched onboard Lomonosov spacecraft in November 2011. It is to measure early UV/Optical photons from Gamma Ray Bursts (GRBs). Slewing Mirror Telescope (SMT) is one of two instruments designed for detection of UV/Optical images of the GRBs. SMT is a Ritchey-Chr\\'etien telescope of 100 mm in diameter with a motorized slewing mirror at the entrance providing 17\\times17 arcmin2 in Field of View (FOV) and 4 arcsec in pixel resolution. Its sky coverage can be further expanded up to 35 degrees in FOV by tilting a motorized slewing mirror. All mirrors were fabricated to about RMS 0.02 waves in wave front error (WFE) and 84.7% (in average reflectivity) over 200nm~650nm range. SMT was aligned to RMS 0.05 waves in WFE (test wavelength 632.8nm). From the static gravity test result, SMT optics system is expected to survive during launch. The technical details of SMT assembly and laboratory performance test results are reported.

  4. MONDian three-body predictions for LISA Pathfinder

    Bevis, Neil; Magueijo, Joao [Theoretical Physics, Blackett Laboratory, Imperial College, London, SW7 2BZ (United Kingdom); Trenkel, Christian; Kemble, Steve, E-mail: n.bevis@imperial.ac.u, E-mail: magueijo@ic.ac.u, E-mail: Christian.Trenkel@astrium.eads.ne [Astrium Ltd, Gunnels Wood Road, Stevenage SG1 2AS (United Kingdom)

    2010-11-07

    In previous work it was shown that modified Newtonian dynamics (MOND) theories predict anomalously strong tidal stresses near the saddle points of the Newtonian gravitational potential. An analytical examination of the saddle between two bodies revealed a linear and a nonlinear solution, valid for the outer and inner regions. Here we present a numerical algorithm for solving the MOND equations. We check the code against the two-body analytical solutions and explore the region transitioning between them. We then develop a realistic model for the MONDian effects on the saddles of the Sun-Earth-Moon system (including further sources is straightforward). For the Sun-Earth saddle we find that the two-body results are almost unchanged, with corrections increasing from full to new Moon. In contrast, the Moon saddle is an intrinsically three-body problem, but we numerically find a recipe for adapting the two-body solution to this case, by means of a suitable rescaling and axis reorientation. We explore possible experimental scenarios for LISA Pathfinder and the prospect of a visit to the saddle(s) at the end of the mission. Given the chaotic nature of the orbits, awareness of the full range of the possibilities is crucial for a realistic prediction. We conclude that even with very conservative assumptions on the impact parameter, the accelerometers are abundantly sensitive to vindicate or rule out the theory.

  5. Slope Morphology of Twin Peaks, Mars Pathfinder Landing Site

    Hobbs, Steven; Paine, Colin; Clarke, Jon; Caprarelli, Graziella

    2010-05-01

    Development of slope form over time has long been a concern of geomorphologists, although recently this concern has been moved to slope processes rather than form. There are two basic approaches. The first is theoretical, involving modeling of different types and rates of processes, and calculation of results in terms of slope evolution over time. Comparisons with real-life slopes can follow this approach [1], [2]. The second, inductive, approach involves field measurements to test ideas about slope evolution starting from the assumption that observed slopes represent different stages of an essentially similar evolution [3]. Space is substituted for time, and a number of slopes, assumed to be of increasing age, are measured and placed in an evolutionary sequence (e.g. [4], [5], [6]). [5] showed that slope angles are modally distributed, with the modal angles controlled by the materials (regolith) of which the slopes are formed, and by the processes operating on them. Data can be obtained directly from field work or from digital elevation models (DEM) derived from remote sensing investigations [7]. DEMs are particularly useful to study inaccessible planets, such as Mars, where on site observations are restricted to only a few landing sites. Here we present a study of slopes on the Twin Peaks, two small hills located 780 m north and 910 m south of the Mars Pathfinder landing site at the mouth of the Ares and Tiu flood channels. The presence of streamlined hills, jumbled surfaces and conglomerates suggested the region was modified by massive flooding 1.8 - 3.5 billion years ago [8], [9]. The streamlined forms and terraces of the Twin Peaks were taken to indicate catastrophic flood conditions that were believed to be prevalent in the area [8]. It was also suggested that the northernmost peak was topped by floodwater, causing its flatter appearance. Other researchers postulated alternative geomorphological origins for the features observed at the Pathfinder landing site

  6. Detection and Characterization of Micrometeoroids with LISA Pathfinder

    Thorpe, James Ira; Trigo-Rodriguez, Josep

    2015-01-01

    The Solar System contains a population of dust and small particles originating from asteroids, comets, and other bodies. These particles have been studied using a number of techniques ranging from in-situ satellite detectors to analysis of lunar microcraters to ground-based observations of zodiacal light. In this paper, we describe an approach for using the LISA Pathfinder (LPF) mission as an instrument to detect and characterize the dynamics of dust particles in the vicinity of Earth-Sun L1. Launching in late 2015, LPF is a dedicated technology demonstrator mission that will validate several key technologies for a future space-based gravitational-wave observatory. The primary science instrument aboard LPF is a precision accelerometer which we show will be capable of sensing discrete momentum impulses as small as $4\\times 10^{-8}\\,\\textrm{N}\\cdot\\textrm{s}$. We then estimate the rate of such impulses resulting from impacts of micrometeoroids based on standard models of the micrometeoroid environment in the in...

  7. Rectangle expansion A*pathfinding for grid maps

    Zhang An; Li Chong; Bi Wenhao

    2016-01-01

    Search speed, quality of resulting paths and the cost of pre-processing are the principle evaluation metrics of a pathfinding algorithm. In this paper, a new algorithm for grid-based maps, rectangle expansion A* (REA*), is presented that improves the performance of A* significantly. REA*explores maps in units of unblocked rectangles. All unnecessary points inside the rectangles are pruned and boundaries of the rectangles (instead of individual points within those boundaries) are used as search nodes. This makes the algorithm plot fewer points and have a much shorter open list than A*. REA*returns jump and grid-optimal path points, but since the line of sight between jump points is protected by the unblocked rectangles, the resulting path of REA*is usually better than grid-optimal. The algorithm is entirely online and requires no offline pre-processing. Experi-mental results for typical benchmark problem sets show that REA*can speed up a highly optimized A* by an order of magnitude and more while preserving completeness and optimality. This new algorithm is competitive with other highly successful variants of A*.

  8. Antenna Deployment for a Pathfinder Lunar Radio Observatory

    MacDowall, Robert J.; Minetto, F. A.; Lazio, T. W.; Jones, D. L.; Kasper, J. C.; Burns, J. O.; Stewart, K. P.; Weiler, K. W.

    2012-01-01

    A first step in the development of a large radio observatory on the moon for cosmological or other astrophysical and planetary goals is to deploy a few antennas as a pathfinder mission. In this presentation, we describe a mechanism being developed to deploy such antennas from a small craft, such as a Google Lunar X-prize lander. The antenna concept is to deposit antennas and leads on a polyimide film, such as Kapton, and to unroll the film on the lunar surface. The deployment technique utilized is to launch an anchor which pulls a double line from a reel at the spacecraft. Subsequently, the anchor is set by catching on the surface or collecting sufficient regolith. A motor then pulls in one end of the line, pulling the film off of its roller onto the lunar surface. Detection of a low frequency cutoff of the galactic radio background or of solar radio bursts by such a system would determine the maximum lunar ionospheric density at the time of measurement. The current design and testing, including videos of the deployment, will be presented. These activities are funded in part by the NASA Lunar Science Institute as an activity of the Lunar University Network for Astrophysical Research (LUNAR) consortium. Part of this research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration.

  9. The pathophysiology of axonal transport in alzheimer’s disease

    Vicario Orri, Elena; Opazo, Carlos; Muñoz López, Francisco José, 1964-

    2015-01-01

    Neurons communicate in the nervous system by carrying out information along the length of their axons to finally transmit it at the synapse. Proper function of axons and axon terminals relies on the transport of proteins, organelles, vesicles, and other elements from the site of synthesis in the cell body. Conversely, neurotrophins secreted from axonal targets and other components at nerve terminals need to travel toward the cell body for clearance. Molecular motors, namely kinesins and dynei...

  10. Modeling molecular mechanisms in the axon

    de Rooij, R.; Miller, K. E.; Kuhl, E.

    2017-03-01

    Axons are living systems that display highly dynamic changes in stiffness, viscosity, and internal stress. However, the mechanistic origin of these phenomenological properties remains elusive. Here we establish a computational mechanics model that interprets cellular-level characteristics as emergent properties from molecular-level events. We create an axon model of discrete microtubules, which are connected to neighboring microtubules via discrete crosslinking mechanisms that obey a set of simple rules. We explore two types of mechanisms: passive and active crosslinking. Our passive and active simulations suggest that the stiffness and viscosity of the axon increase linearly with the crosslink density, and that both are highly sensitive to the crosslink detachment and reattachment times. Our model explains how active crosslinking with dynein motors generates internal stresses and actively drives axon elongation. We anticipate that our model will allow us to probe a wide variety of molecular phenomena—both in isolation and in interaction—to explore emergent cellular-level features under physiological and pathological conditions.

  11. A Microfluidics Approach to Investigate Axon Guidance

    2007-03-26

    coat the substrate with PLL. The cells of one dissociated embryonic spinal cord was re-suspended in 3 µl of freshly-prepared Modified Frog Ringer’s...Surround repulsion of spinal sensory axons in higher vertebrate embryos . Neuron 18, 889-897 (1997). 8. Colamarino, S. & Tessier-Lavigne, M. The

  12. Mechanisms of axon degeneration: from development to disease.

    Saxena, Smita; Caroni, Pico

    2007-10-01

    Axon degeneration is an active, tightly controlled and versatile process of axon segment self-destruction. Although not involving cell death, it resembles apoptosis in its logics. It involves three distinct steps: induction of competence in specific neurons, triggering of degeneration at defined axon segments of competent neurons, and rapid fragmentation and removal of the segments. The mechanisms that initiate degeneration are specific to individual settings, but the final pathway of pruning is shared; it involves microtubule disassembly, axon swellings, axon fragmentation, and removal of the remnants by locally recruited phagocytes. The tight regulatory properties of axon degeneration distinguish it from passive loss phenomena, and confer significance to processes that involve it. Axon degeneration has prominent roles in development, upon lesions and in disease. In development, it couples the progressive specification of neurons and circuits to the removal of defined axon branches. Competence might involve transcriptional switches, and local triggering can involve axon guidance molecules and synaptic activity patterns. Lesion-induced Wallerian degeneration is inhibited in the presence of Wld(S) fusion protein in neurons; it involves early local, and later, distal degeneration. It has recently become clear that like in other settings, axon degeneration in disease is a rapid and specific process, which should not be confused with a variety of disease-related pathologies. Elucidating the specific mechanisms that initiate axon degeneration should open up new avenues to investigate principles of circuit assembly and plasticity, to uncover mechanisms of disease progression, and to identify ways of protecting synapses and axons in disease.

  13. Morphometry of Axons in Optic Nerves of Siamese's Twins

    Xinzu Gu; Zhenping Zhang; Qi Lin; Jiongji Liang; Wenyu Lu; Xiulan Ye; A A Sadun

    2002-01-01

    Purpose: To observe the development of optic nerve, we examined four optic nerves from Siameses Twins by absolute counts of axons.Methods: Mean axon diameter, mean axon density, totally axonal population and optic nerve area were noted for each optic nerve. The mean axon diameter and the mean axon density were compared between paraxial (inner sectors)and cortical (outer sectors)areas of the nerves.Results: More myelinated axons were seen in the inner sectors as compared to the outer sectors(average 11 axons/1 000 μm2 in inner sectors and 34 axons/l 000 μm2 in outer sectors( P=0. 036) . The myelinated fibers were also smaller(63 microns) in the outer sectors as compared to the inner sectors(72 microns) ( P = 0. 001 ). The average cross sectors area for the four 40 week stage optical nerves of Siamese Twins was 3.32 × 103 as compared to 1 million axons for 32-week-old normals.Conclusion: Our finding of fewer axonal number and small myelinated fibers in the Siamese Twins suggests hypoplasia. Myelination was more abnormal in the paraxial optic nerve than that in the peripheral sectors, suggesting anomalous development of optic nerve peripherally and delayed developnent centrally. Axonal density is higher in inner sectors than that in outer sectors, suggesting delayed development of the outer nerve sector.

  14. R-type calcium channels are crucial for semaphorin 3A-induced DRG axon growth cone collapse.

    Rimantas Treinys

    Full Text Available Semaphorin 3A (Sema3A is a secreted protein involved in axon path-finding during nervous system development. Calcium signaling plays an important role during axonal growth in response to different guidance cues; however it remains unclear whether this is also the case for Sema3A. In this study we used intracellular calcium imaging to figure out whether Sema3A-induced growth cone collapse is a Ca2+ dependent process. Intracellular Ca2+ imaging results using Fura-2 AM showed Ca2+ increase in E15 mice dorsal root ganglia neurons upon Sema3A treatment. Consequently we analyzed Sema3A effect on growth cones after blocking or modifying intracellular and extracellular Ca2+ channels that are expressed in E15 mouse embryos. Our results demonstrate that Sema3A increased growth cone collapse rate is blocked by the non-selective R- and T- type Ca2+ channel blocker NiCl2 and by the selective R-type Ca2+ channel blocker SNX482. These Ca2+ channel blockers consistently decreased the Sema3A-induced intracellular Ca2+ concentration elevation. Overall, our results demonstrate that Sema3A-induced growth cone collapses are intimately related with increase in intracellular calcium concentration mediated by R-type calcium channels.

  15. Chromatic aberration measurement for transmission interferometric testing.

    Seong, Kibyung; Greivenkamp, John E

    2008-12-10

    A method of chromatic aberration measurement is described based on the transmitted wavefront of an optical element obtained from a Mach-Zehnder interferometer. The chromatic aberration is derived from transmitted wavefronts measured at five different wavelengths. Reverse ray tracing is used to remove induced aberrations associated with the interferometer from the measurement. In the interferometer, the wavefront transmitted through the sample is tested against a plano reference, allowing for the absolute determination of the wavefront radius of curvature. The chromatic aberrations of a singlet and a doublet have been measured.

  16. MAPK signaling promotes axonal degeneration by speeding the turnover of the axonal maintenance factor NMNAT2

    Walker, Lauren J; Summers, Daniel W; Sasaki, Yo; Brace, EJ; Milbrandt, Jeffrey; DiAntonio, Aaron

    2017-01-01

    Injury-induced (Wallerian) axonal degeneration is regulated via the opposing actions of pro-degenerative factors such as SARM1 and a MAPK signal and pro-survival factors, the most important of which is the NAD+ biosynthetic enzyme NMNAT2 that inhibits activation of the SARM1 pathway. Here we investigate the mechanism by which MAPK signaling facilitates axonal degeneration. We show that MAPK signaling promotes the turnover of the axonal survival factor NMNAT2 in cultured mammalian neurons as well as the Drosophila ortholog dNMNAT in motoneurons. The increased levels of NMNAT2 are required for the axonal protection caused by loss of MAPK signaling. Regulation of NMNAT2 by MAPK signaling does not require SARM1, and so cannot be downstream of SARM1. Hence, pro-degenerative MAPK signaling functions upstream of SARM1 by limiting the levels of the essential axonal survival factor NMNAT2 to promote injury-dependent SARM1 activation. These findings are consistent with a linear molecular pathway for the axonal degeneration program. DOI: http://dx.doi.org/10.7554/eLife.22540.001 PMID:28095293

  17. AxonQuant: A Microfluidic Chamber Culture-Coupled Algorithm That Allows High-Throughput Quantification of Axonal Damage

    Yang Li

    2014-02-01

    Full Text Available Published methods for imaging and quantitatively analyzing morphological changes in neuronal axons have serious limitations because of their small sample sizes, and their time-consuming and nonobjective nature. Here we present an improved microfluidic chamber design suitable for fast and high-throughput imaging of neuronal axons. We developed the AxonQuant algorithm, which is suitable for automatic processing of axonal imaging data. This microfluidic chamber-coupled algorithm allows calculation of an ‘axonal continuity index' that quantitatively measures axonal health status in a manner independent of neuronal or axonal density. This method allows quantitative analysis of axonal morphology in an automatic and nonbiased manner. Our method will facilitate large-scale high-throughput screening for genes or therapeutic compounds for neurodegenerative diseases involving axonal damage. When combined with imaging technologies utilizing different gene markers, this method will provide new insights into the mechanistic basis for axon degeneration. Our microfluidic chamber culture-coupled AxonQuant algorithm will be widely useful for studying axonal biology and neurodegenerative disorders. © 2014 S. Karger AG, Basel

  18. The Pathfinder Testbed: Exploring Techniques for Achieving Precision Radial Velocities in the Near-Infrared

    Ramsey, Larry; Redman, Stephen; Bender, Chad; Roy, Arpita; Zonak, Stephanie; Sigurdsson, Steinn; Wolszczan, Alex

    2010-01-01

    The Penn State Pathfinder is a prototype warm fiber-fed Echelle spectrograph with a Hawaii-1 NIR detector that has already demonstrated 7-10 m/s radial velocity precision on integrated sunlight. The Pathfinder testbed was initially setup for the Gemini PRVS design study to enable a systematic exploration of the challenges of achieving high radial velocity precision in the near-infrared, as well as to test possible solutions to these calibration challenges. The current version of the Pathfinder has an R3 echelle grating, and delivers a resolution of R~50,000 in the Y, J or H bands of the spectrum. We will discuss the on sky-performance of the Pathfinder during an engineering test run at the Hobby Eberly Telescope as well the results of velocity observations of M dwarfs. We will also discuss the unique calibration techniques we have explored, like Uranium-Neon hollow cathode lamps, notch filter, and modal noise mitigation to enable high precision radial velocity observation in the NIR. The Pathfinder is a proto...

  19. Aberrations of Gradient-Index Lenses.

    Matthews, A. L.

    Available from UMI in association with The British Library. In this thesis, the primary aberrations of lenses with a radial focussing gradient-of-index are analysed. Such a lens has a refractive index profile which decreases continuously and radially outward from the optical axis, so that the surfaces of constant refractive index are circular cylinders which are coaxial with the optical axis. Current applications of these lenses include photocopiers, medical endoscopes, telecommunications systems and compact disc systems. Closed formulae for the primary wavefront aberrations for a gradient-index lens with curved or plane entry and exit faces are obtained from the differential equations of such a lens to assess the primary transverse ray aberrations that it introduces. Identical expressions are then obtained by using the difference in optical path length produced between two rays by the lens. This duplication of the derivations of the primary wavefront aberrations acts as a confirmation of the validity of the expressions. One advantage of these equations is that the contributions due to the primary spherical aberration, coma, astigmatism, field curvature and distortion can be assessed individually. A Fortran 77 program has been written to calculate each of these individual contributions, the total primary wavefront aberrations and the primary transverse ray aberrations. Further confirmation of the validity of the expressions is obtained by using this program to show that the coma and distortion were both zero for fully symmetric systems working at unit magnification. The program is then used to assess the primary wavefront aberrations for a gradient-index lens which is currently of interest to the telecommunications industry. These results are compared with values obtained using a finite ray-tracing program for the total wavefront aberrations. This shows that the primary wavefront aberrations are the completely dominant contribution to the total wavefront

  20. The unique axon trajectory of the accessory nerve is determined by intrinsic properties of the neural tube in the avian embryo.

    Bai, Zhongtian; Pu, Qin; Haque, Ziaul; Wang, Jianlin; Huang, Ruijin

    2016-05-01

    The accessory nerve is a cranial nerve, composed of only motor axons, which control neck muscles. Its axons ascend many segments along the lateral surface of the cervical spinal cord and hindbrain. At the level of the first somite, they pass ventrally through the somitic mesoderm into the periphery. The factors governing the unique root trajectory are unknown. Ablation experiments at the accessory nerve outlet points have shown that somites do not regulate the trajectory of the accessory nerve fibres. Factors from the neural tube that may control the longitudinal pathfinding of the accessory nerve fibres were tested by heterotopic transplantations of an occipital neural tube to the cervical and thoracic level. These transplantations resulted in a typical accessory nerve trajectory in the cervical and thoracic spinal cord. In contrast, cervical neural tube grafts were unable to give rise to the typical accessory nerve root pattern when transplanted to occipital level. Our results show that the formation of the unique axon root pattern of the accessory nerve is an intrinsic property of the neural tube.

  1. Motor and dorsal root ganglion axons serve as choice points for the ipsilateral turning of dI3 axons.

    Avraham, Oshri; Hadas, Yoav; Vald, Lilach; Hong, Seulgi; Song, Mi-Ryoung; Klar, Avihu

    2010-11-17

    The axons of the spinal intersegmental interneurons are projected longitudinally along various funiculi arrayed along the dorsal-ventral axis of the spinal cord. The roof plate and the floor plate have a profound role in patterning their initial axonal trajectory. However, other positional cues may guide the final architecture of interneuron tracks in the spinal cord. To gain more insight into the organization of specific axonal tracks in the spinal cord, we focused on the trajectory pattern of a genetically defined neuronal population, dI3 neurons, in the chick spinal cord. Exploitation of newly characterized enhancer elements allowed specific labeling of dI3 neurons and axons. dI3 axons are projected ipsilaterally along two longitudinal fascicules at the ventral lateral funiculus (VLF) and the dorsal funiculus (DF). dI3 axons change their trajectory plane from the transverse to the longitudinal axis at two novel checkpoints. The axons that elongate at the DF turn at the dorsal root entry zone, along the axons of the dorsal root ganglion (DRG) neurons, and the axons that elongate at the VLF turn along the axons of motor neurons. Loss and gain of function of the Lim-HD protein Isl1 demonstrate that Isl1 is not required for dI3 cell fate. However, Isl1 is sufficient to impose ipsilateral turning along the motor axons when expressed ectopically in the commissural dI1 neurons. The axonal patterning of dI3 neurons, revealed in this study, highlights the role of established axonal cues-the DRG and motor axons-as intermediate guidepost cues for dI3 axons.

  2. Axon Membrane Skeleton Structure is Optimized for Coordinated Sodium Propagation

    Zhang, Yihao; Li, He; Tzingounis, Anastasios V; Lykotrafitis, George

    2016-01-01

    Axons transmit action potentials with high fidelity and minimal jitter. This unique capability is likely the result of the spatiotemporal arrangement of sodium channels along the axon. Super-resolution microscopy recently revealed that the axon membrane skeleton is structured as a series of actin rings connected by spectrin filaments that are held under entropic tension. Sodium channels also exhibit a periodic distribution pattern, as they bind to ankyrin G, which associates with spectrin. Here, we elucidate the relationship between the axon membrane skeleton structure and the function of the axon. By combining cytoskeletal dynamics and continuum diffusion modeling, we show that spectrin filaments under tension minimize the thermal fluctuations of sodium channels and prevent overlap of neighboring channel trajectories. Importantly, this axon skeletal arrangement allows for a highly reproducible band-like activation of sodium channels leading to coordinated sodium propagation along the axon.

  3. Aberration coefficients of curved holographic optical elements

    Verboven, P. E.; Lagasse, P. E.

    1986-11-01

    A general formula is derived that gives all aberration terms of holographic optical elements on substrates of any shape. The spherical substrate shape and the planar substrate shape are treated as important special cases. A numerical example illustrates the need of including higher-order aberrations.

  4. Psychometric Characteristics of the Aberrant Behavior Checklist.

    Aman, Michael G.; And Others

    1985-01-01

    Information is presented on the psychometric characteristics of the Aberrant Behavior Checklist, a measure of psychotropic drug effects. Internal consistency and test-retest reliability of the checklist appeared very good. Interrater reliability was generally in the moderate range. In general, validity was established for most Aberrant Behavior…

  5. Preliminary Findings of the Photovoltaic Cell Calibration Experiment on Pathfinder Flight 95-3

    Vargas-Aburto, Carlos

    1997-01-01

    The objective of the photovoltaic (PV) cell calibration experiment for Pathfinder was to develop an experiment compatible with an ultralight UAV to predict the performance of PV cells at AM0, the solar spectrum in space, using the Langley plot technique. The Langley plot is a valuable technique for this purpose and requires accurate measurements of air mass (pressure), cell temperature, solar irradiance, and current-voltage(IV) characteristics with the cells directed normal to the direct ray of the sun. Pathfinder's mission objective (95-3) of 65,000 ft. maximum altitude, is ideal for performing the Langley plot measurements. Miniaturization of electronic data acquisition equipment enabled the design and construction of an accurate and light weight measurement system that meets Pathfinder's low payload weight requirements.

  6. LISA and LISA PathFinder, the endeavour to detect low frequency GWs

    Araujo, H; Chmeissani, M; Conchillo, A; García-Berro, E; Grimani, C; Hajdas, W; Lobo, A; Martínez, L; Nofrarias, M; Ortega, J A; Puigdengoles, C; Ramos-Castro, J; Sanjuan, J; Wass, P; Xirgu, X; Araujo, Henrique; Boatella, Cesar; Chmeissani, Mokhtar; Conchillo, Aleix; Garcia-Berro, Enrique; Grimani, Catia; Hajdas, Wojtek; Lobo, Alberto; Martinez, Lluis; Nofrarias, Miquel; Ortega, Jose Antonio; Puigdengoles, Carles; Ramos-Castro, Juan; Sanjuan, Josep; Wass, Peter; Xirgu, Xevi

    2006-01-01

    This is a review about LISA and its technology demonstrator, LISA PathFinder. We first describe the conceptual problems which need to be overcome in order to set up a working interferometric detector of low frequency Gravitational Waves (GW), then summarise the solutions to them as currently conceived by the LISA mission team. This will show that some of these solutions require new technological abilities which are still under development, and which need proper test before being fully implemented. LISA PathFinder (LPF) is the the testbed for such technologies. The final part of the paper will address the ideas and concepts behind the PathFinder as well as their impact on LISA.

  7. Schwann cells-axon interaction in myelination.

    Taveggia, Carla

    2016-08-01

    The remarkable interaction between glial cells and axons is crucial for nervous system development and homeostasis. Alterations in this continuous communication can cause severe pathologies that can compromise the integrity of the nervous system. The most dramatic consequence of this interaction is the generation of the myelin sheath, made by myelinating glial cells: Schwann cells in the peripheral nervous system and oligodendrocytes in the central nervous system. In this review I will focus on signals coming from axons in the first part and then on those from Schwann cells that promote the formation and the maintenance of peripheral myelin. I will discuss their inter-relationship together with seminal and important advances recently made.

  8. Higher-Order Aberrations in Myopic Eyes

    Farid Karimian

    2010-01-01

    Full Text Available Purpose: To evaluate the correlation between refractive error and higher-order aberrations (HOAs in patients with myopic astigmatism. Methods: HOAs were measured using the Zywave II aberrometer over a 6 mm pupil. Correlations between HOAs and myopia, astigmatism, and age were analyzed. Results: One hundred and twenty-six eyes of 63 subjects with mean age of 26.4±5.9 years were studied. Mean spherical equivalent refractive error and refractive astigmatism were -4.94±1.63 D and 0.96±1.06 D, respectively. The most common higher-order aberration was primary horizontal trefoil with mean value of 0.069±0.152 μm followed by spherical aberration (-0.064±0.130 μm and primary vertical coma (-0.038±0.148 μm. As the order of aberration increased from third to fifth, its contribution to total HOA decreased: 53.9% for third order, 31.9% for fourth order, and 14.2% for fifth order aberrations. Significant correlations were observed between spherical equivalent refractive error and primary horizontal coma (R=0.231, P=0.022, and root mean square (RMS of spherical aberration (R=0.213, P=0.031; between astigmatism and RMS of total HOA (R=0.251, P=0.032, RMS of fourth order aberration (R=0.35, P<0.001, and primary horizontal coma (R=0.314, P=0.004. Spherical aberration (R=0.214, P=0.034 and secondary vertical coma (R=0.203, P=0.031 significantly increased with age. Conclusion: Primary horizontal trefoil, spherical aberration and primary vertical coma are the predominant higher-order aberrations in eyes with myopic astigmatism.

  9. Multifunctional Silk Nerve Guides for Axon Outgrowth

    Tupaj, Marie C.

    Peripheral nerve regeneration is a critical issue as 2.8% of trauma patients present with this type of injury, estimating a total of 200,000 nerve repair procedures yearly in the United States. While the peripheral nervous system exhibits slow regeneration, at a rate of 0.5 mm -- 9 mm/day following trauma, this regenerative ability is only possible under certain conditions. Clinical repairs have changed slightly in the last 30 years and standard methods of treatment include suturing damaged nerve ends, allografting, and autografting, with the autograft the gold standard of these approaches. Unfortunately, the use of autografts requires a second surgery and there is a shortage of nerves available for grafting. Allografts are a second option however allografts have lower success rates and are accompanied by the need of immunosuppressant drugs. Recently there has been a focus on developing nerve guides as an "off the shelf" approach. Although some natural and synthetic guidance channels have been approved by the FDA, these nerve guides are unfunctionalized and repair only short gaps, less than 3 cm in length. The goal of this project was to identify strategies for functionalizing peripheral nerve conduits for the outgrowth of neuron axons in vitro . To accomplish this, two strategies (bioelectrical and biophysical) were indentified for increasing axon outgrowth and promoting axon guidance. Bioelectrical strategies exploited electrical stimulation for increasing neurite outgrowth. Biophysical strategies tested a range of surface topographies for axon guidance. Novel methods were developed for integrating electrical and biophysical strategies into silk films in 2D. Finally, a functionalized nerve conduit system was developed that integrated all strategies for the purpose of attaching, elongating, and guiding nervous tissue in vitro. Future directions of this work include silk conduit translation into a rat sciatic nerve model in vivo for the purpose of repairing long

  10. Interspecies variation in axon-myelin relationships.

    Fraher, J P; O'Sullivan, A W

    2000-01-01

    The primary objective of this paper was to determine the extent and nature of interspecies differences in axon calibre and myelin sheath thickness and in the various relationships between these. Morphometric analysis of the axon perimeter-myelin sheath thickness relationship was performed on an equivalent nerve fibre population in a mammal, the rat, a bird, the chicken, an amphibian, the frog, a bony fish, the trout, and a cartilaginous fish, the dogfish. The abducent nerve was studied. It is especially suitable for this purpose because its fibres are closely similar in type and in peripheral distribution across the species studied. The relationship differed substantially between species. Differences were present in its setting, as described by the positions of the scatterplots, in the g ratio and in the regression and correlation data relating the parameters. Both parameters were markedly larger in the fish species than in all of the others. In addition, in rat, chicken, frog and trout, where large and small fibre classes could be differentiated clearly, the setting of the relationship between the two parameters was different for the two classes. In the main, variation in each of the parameters was greater between than within species. The larger fibres in the fish species were closely similar in axon perimeter and sheath thickness despite their long evolutionary separation. From this study and from others in the series, it may be concluded that there is no fixed or constant relationship between axon calibre and the thickness of the surrounding myelin sheath. Each nerve tends to have its own particular relationship and this differs between species.

  11. Retinoic acid signaling in axonal regeneration

    Radhika ePuttagunta

    2012-01-01

    Full Text Available Following an acute central nervous system injury, axonal regeneration and functional recovery are extremely limited. This is due to an extrinsic inhibitory growth environment and the lack of intrinsic growth competence. Retinoic acid (RA signaling, essential in developmental dorsoventral patterning and specification of spinal motor neurons, has been shown through its receptor, the transcription factor RA receptor β2 (RARß2, to induce axonal regeneration following spinal cord injury (SCI. Recently, it has been shown that in dorsal root ganglia neurons, cAMP levels were greatly increased by lentiviral RARβ2 expression and contributed to neurite outgrowth. Moreover, RARβ agonists, in cerebellar granule neurons and in the brain in vivo, induced phosphoinositide 3-kinase dependent phosphorylation of AKT that was involved in RARβ-dependent neurite outgrowth. More recently, RA-RARß pathways were shown to directly transcriptionally repress a member of the inhibitory Nogo receptor complex, Lingo-1, under an axonal growth inhibitory environment in vitro as well as following spinal injury in vivo. This perspective focuses on these newly discovered molecular mechanisms and future directions in the field.

  12. Synaptic Democracy and Vesicular Transport in Axons

    Bressloff, Paul C.; Levien, Ethan

    2015-04-01

    Synaptic democracy concerns the general problem of how regions of an axon or dendrite far from the cell body (soma) of a neuron can play an effective role in neuronal function. For example, stimulated synapses far from the soma are unlikely to influence the firing of a neuron unless some sort of active dendritic processing occurs. Analogously, the motor-driven transport of newly synthesized proteins from the soma to presynaptic targets along the axon tends to favor the delivery of resources to proximal synapses. Both of these phenomena reflect fundamental limitations of transport processes based on a localized source. In this Letter, we show that a more democratic distribution of proteins along an axon can be achieved by making the transport process less efficient. This involves two components: bidirectional or "stop-and-go" motor transport (which can be modeled in terms of advection-diffusion), and reversible interactions between motor-cargo complexes and synaptic targets. Both of these features have recently been observed experimentally. Our model suggests that, just as in human societies, there needs to be a balance between "efficiency" and "equality".

  13. MRI of the diffuse axonal injury

    Joo, Yang Gu; Woo, Young Hoon; Suh, Soo Jhi [Keimyung University School of Medicine, Daegu (Korea, Republic of)

    1992-01-15

    CT has facilitated early recognition and treatment of focal brain injuries in patients with head trauma. However, CT shows relatively low sensitivity in identifying non hemorrhage contusion and injuries of white matter. MR is known to be superior to CT in detection of white matter injuries, such as diffuse axonal injury. MR imaging in 14 cases of diffuse axonal injury on 2.0T was studied. The corpus callosum, especially the body portion, was the most commonly involved site. The lesions ranged from 5 to 20mm in size with ovoid to elliptical shape. T2WI was the most sensitive pulse sequence in detecting lesions such as white matter degeneration, hemorrhagic and non hemorrhagic contusion. The lesions were nonspecific as high and low signal intensities on T2WI and T1WI respectively. CT showed white matter abnormality in only 1 case of 14 cases. We propose MR imaging as the primary imaging procedure for the detection of diffuse axonal injury because of its multiplanar capabilities and higher sensitivity.

  14. Where does slow axonal transport go?

    Terada, Sumio

    2003-12-01

    Axonal transport is the specialized and well-developed intracellular transport system for regulated and/or long-distance transport based on generalized cellular machineries. Among them, slow axonal transport conveys cytoplasmic proteins. The motor molecule, the nature of transporting complex and the transport regulation mechanism for slow transport are still unclarified. There has been a dispute regarding the nature of transporting complex of cytoskeletal proteins, polymer-sliding hypothesis versus subunit-transport theory. Recent data supporting the hypothesis of polymer sliding in cultured neurons only reconfirm the previously reported structure and this inference suffers from the lack of ultrastructural evidence and the direct relevance to the physiological slow transport phenomenon in vivo. Observation of the moving cytoskeletal proteins in vivo using transgenic mice or squid giant axons revealed that subunits do move in a microtubule-dependent manner, strongly indicating the involvement of microtubule-based motor kinesin. If the slow transport rate reflects the intermittent fast transport dependent on kinesin motor, we have to investigate the molecular constituents of the transporting complex in more detail and evaluate why the motor and cargo interaction is so unstable. This kind of weak and fluctuating interaction between various molecular pairs could not be detected by conventional techniques, thus necessitating the establishment of a new experimental system before approaching the molecular regulation problem.

  15. Shh goes multidirectional in axon guidance

    Paola Bovolenta; Luisa Sanchez-Arrones

    2012-01-01

    Shh and Wnts,secreted by the floor and roof plate of the spinal cord,direct longitudinal growth of the axons from the adjacent ventral funiculus and cortico-spinal tract.Whether these midline cues influencethe directionality of axons elongating in more lateral positions of the spinal cord is unexplored.Song and colleagues investigate this possibility and demonstrate that the location of descending raphe-spinal tract in the ventrolateral spinal cord is dictated by the simultaneous repellent activity of Shh gradients in both the anteriorto-posterior (A-P) and medial-tolateral (M-L) axis. The spinal cord is the main pathway for exchange of information between the brain and the rest of the body.Sensory information collected in the body periphery is conveyed to the brain by axonal tracts that ascend along the spinal cord whereas motor information travels from the brain to the periphery in descending tracts.Precise spatial organization of these fiber tracts is thus essential for animal behavior and survival.

  16. Axon-glial relations during regeneration of axons in the adult rat anterior medullary velum.

    Berry, M; Hunter, A S; Duncan, A; Lordan, J; Kirvell, S; Tsang, W L; Butt, A M

    1998-12-01

    The anterior medullary velum (AMV) of adult Wistar rats was lesioned in the midsagittal plane, transecting all decussating axons including those of the central projection of the IVth nerve. At selected times up to 200 days after transection, the degenerative and regenerative responses of axons and glia were analyzed using transmission and scanning electron microscopy and immunohistochemistry. In particular, both the capacity of oligodendrocytes to remyelinate regenerated fibers and the stability of the CNS/PNS junctional zone of the IVth nerve rootlet were documented. Transected central AMV axons exhibited four patterns of fiber regeneration in which fibers grew: rostrocaudally in the reactive paralesion neuropil (Group 1); randomly within the AMV (Group 2); into the ipsilateral IVth nerve rootlet, after turning at the lesion edge and growing recurrently through the old degenerated contralateral central trochlear nerve trajectory (Group 3); and ectopically through paralesion tears in the ependyma onto the surface of the IVth ventricle (Group 4). Group 1-3 axons regenerated unperturbed through degenerating central myelin, reactive astrocytes, oligodendrocytes, microglia, and large accumulations of hematogenous macrophages. Only Group 3 axons survived long term in significant numbers, and all became myelinated by oligodendrocytes, ultimately establishing thin sheaths with relatively normal nodal gaps and intersegmental myelin sheath lengths. Schwann cells at the CNS/PNS junction of the IVth nerve rootlet did not invade the CNS, but astrocyte processes grew across the junction into the PNS portion of the IVth nerve. The basal lamina of the junctional glia limitans remained stable throughout the experimental period.

  17. Analysis of the Aberration in Directly-writing Atom Lithography

    LI Chuanwen; CAI Weiquan; WANG Yuzhu

    2000-01-01

    After deriving the approximation solution which describes the motion of neutral atoms in an optical standing wave field with large detuning, the spherical aberration and the chromatic aberration are analyzed and possible methods to reduce these aberrations are discussed.

  18. Image-based EUVL aberration metrology

    Fenger, Germain Louis

    A significant factor in the degradation of nanolithographic image fidelity is optical wavefront aberration. As resolution of nanolithography systems increases, effects of wavefront aberrations on aerial image become more influential. The tolerance of such aberrations is governed by the requirements of features that are being imaged, often requiring lenses that can be corrected with a high degree of accuracy and precision. Resolution of lithographic systems is driven by scaling wavelength down and numerical aperture (NA) up. However, aberrations are also affected from the changes in wavelength and NA. Reduction in wavelength or increase in NA result in greater impact of aberrations, where the latter shows a quadratic dependence. Current demands in semiconductor manufacturing are constantly pushing lithographic systems to operate at the diffraction limit; hence, prompting a need to reduce all degrading effects on image properties to achieve maximum performance. Therefore, the need for highly accurate in-situ aberration measurement and correction is paramount. In this work, an approach has been developed in which several targets including phase wheel, phase disk, phase edges, and binary structures are used to generate optical images to detect and monitor aberrations in extreme ultraviolet (EUV) lithographic systems. The benefit of using printed patterns as opposed to other techniques is that the lithography system is tested under standard operating conditions. Mathematical models in conjunction with iterative lithographic simulations are used to determine pupil phase wavefront errors and describe them as combinations of Zernike polynomials.

  19. Chromosome aberration assays in Allium

    Grant, W.F.

    1982-01-01

    The common onion (Allium cepa) is an excellent plant for the assay of chromosome aberrations after chemical treatment. Other species of Allium (A. cepa var. proliferum, A. carinatum, A. fistulosum and A. sativum) have also been used but to a much lesser extent. Protocols have been given for using root tips from either bulbs or seeds of Allium cepa to study the cytological end-points, such as chromosome breaks and exchanges, which follow the testing of chemicals in somatic cells. It is considered that both mitotic and meiotic end-points should be used to a greater extent in assaying the cytogenetic effects of a chemical. From a literature survey, 148 chemicals are tabulated that have been assayed in 164 Allium tests for their clastogenic effect. Of the 164 assays which have been carried out, 75 are reported as giving a positive reaction, 49 positive and with a dose response, 1 positive and temperature-related, 9 borderline positive, and 30 negative; 76% of the chemicals gave a definite positive response. It is proposed that the Allium test be included among those tests routinely used for assessing chromosomal damage induced by chemicals.

  20. On aberration in gravitational lensing

    Sereno, M

    2008-01-01

    It is known that a relative translational motion between the deflector and the observer affects gravitational lensing. In this paper, a lens equation is obtained to describe such effects on actual lensing observables. Results can be easily interpreted in terms of aberration of light-rays. Both radial and transverse motions with relativistic velocities are considered. The lens equation is derived by first considering geodesic motion of photons in the rest-frame Schwarzschild spacetime of the lens, and, then, light-ray detection in the moving observer's frame. Due to the transverse motion images are displaced and distorted in the observer's celestial sphere, whereas the radial velocity along the line of sight causes an effective re-scaling of the lens mass. The Einstein ring is distorted to an ellipse whereas the caustics in the source plane are still point-like. Either for null transverse motion or up to linear order in velocities, the critical curve is still a circle with its radius corrected by a factor (1+z...

  1. Dynamics of axon fasciculation in the presence of neuronal turnover

    Chaudhuri, Debasish; Mohanty, P K; Zapotocky, Martin

    2008-01-01

    We formulate and characterize a model aiming to describe the formation of fascicles of axons mediated by contact axon-axon interactions. The growing axons are represented as interacting directed random walks in two spatial dimensions. To mimic axonal turnover in the mammalian olfactory system, the random walkers are injected and removed at specified rates. In the dynamical steady state, the position-dependent distribution of fascicle sizes obeys a scaling law. We identify several distinct time scales that emerge from the dynamics, are sensitive functions of the microscopic parameters of the model, and can exceed the average axonal lifetime by orders of magnitude. We discuss our findings in terms of an analytically tractable, effective model of fascicle dynamics.

  2. Chlorpyrifos-Oxon Disrupts Zebrafish Axonal Growth and Motor Behavior

    Yang, Dongren; Lauridsen, Holly; Buels, Kalmia; Chi, Lai-Har; La Du, Jane; Bruun, Donald A.; Olson, James R.; Tanguay, Robert L.; Lein, Pamela J.

    2011-01-01

    Axonal morphology is a critical determinant of neuronal connectivity, and perturbation of the rate or extent of axonal growth during development has been linked to neurobehavioral deficits in animal models and humans. We previously demonstrated that the organophosphorus pesticide (OP) chlorpyrifos (CPF) inhibits axonal growth in cultured neurons. In this study, we used a zebrafish model to determine whether CPF, its oxon metabolite (CPFO), or the excreted metabolite trichloro-2-pyridinol (TCP...

  3. A unified cell biological perspective on axon-myelin injury

    Simons, Mikael; Misgeld, Thomas; Kerschensteiner, Martin

    2014-01-01

    Demyelination and axon loss are pathological hallmarks of the neuroinflammatory disorder multiple sclerosis (MS). Although we have an increasingly detailed understanding of how immune cells can damage axons and myelin individually, we lack a unified view of how the axon–myelin unit as a whole is affected by immune-mediated attack. In this review, we propose that as a result of the tight cell biological interconnection of axons and myelin, damage to either can spread, which might convert a loc...

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

    2014-01-01

    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 specialized glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarization followed by targeted myelin membrane expansion and compaction. Thereby, a myelin sheath of complex subdomain structure is...

  5. Development of Slewing Mirror Telescope Optical System for the UFFO-pathfinder

    Jeong, S.; Nam, J.W.; Ahn, K.-B.

    2013-01-01

    The Slewing Mirror Telescope (SMT) is the UV/optical telescope of UFFO-pathfinder. The SMT optical system is a Ritchey-Chrétien (RC) telescope of 100 mm diameter pointed by means of a gimbal-mounted flat mirror in front of the telescope. The RC telescope has a 17 × 17arcmin2 in Field of View and ...

  6. Slewing Mirror Telescope and the Data-Acquisition System for the UFFO-Pathfinder

    Lim, H.; Ahmad, S.; Barrillon, P.

    2013-01-01

    The Ultra-Fast Flash Observatory (UFFO) aims to detect the earliest moment of Gamma-Ray Bursts (GRBs) which is not well known, resulting into the enhancement of GRB mechanism understanding. The pathfinder mission was proposed to be a scaled-down version of UFFO, and only contains the UFFO Burst A...

  7. A Strategy to Characterize the LISA-Pathfinder Cold Gas Thruster System

    Armano, M.; Audley, H.; Auger, G.; Baird, J.; Binetruy, P.; Born, M.; Bortoluzzi, D.; Brandt, N.; Bursi, A.; Caleno, M.; Cavalleri, A.; Cesarini, A.; Cruise, M.; Danzmann, K.; Diepholz, I.; Dolesi, R.; Dunbar, N.; Ferraioli, L.; Ferroni, V.; Fitzsimons, E.; Freschi, M.; Gallegos, J.; Garcia Marirrodriga, C.; Gerndt, R.; Gesa, L. I.; Gibert, F.; Giardini, D.; Giusteri, R.; Grimani, C.; Harrison, I.; Heinzel, G.; Hewitson, M.; Hollington, D.; Hueller, M.; Huesler, J.; Inchauspé, H.; Jennrich, O.; Jetzer, P.; Johlander, B.; Karnesis, N.; Kaune, B.; Korsakova, N.; Killow, C.; Lloro, I.; Maarschalkerweerd, R.; Madden, S.; Mance, D.; Martin, V.; Martin-Porqueras, F.; Mateos, I.; McNamara, P.; Mendes, J.; Mendes, L.; Moroni, A.; Nofrarias, M.; Paczkowski, S.; Perreur-Lloyd, M.; Petiteau, A.; Pivato, P.; Plagnol, E.; Prat, P.; Ragnit, U.; Ramos-Castro, J.; Reiche, J.; Romera Perez, J. A.; Robertson, D.; Rozemeijer, H.; Russano, G.; Sarra, P.; Schleicher, A.; Slutsky, J.; Sopuerta, C. F.; Sumner, T.; Texier, D.; Thorpe, J.; Trenkel, C.; Tu, H. B.; Vitale, S.; Wanner, G.; Ward, H.; Waschke, S.; Wass, P.; Wealthy, D.; Wen, S.; Weber, W.; Wittchen, A.; Zanoni, C.; Ziegler, T.; Zweifel, P.

    2015-05-01

    The cold gas micro-propulsion system that will be used during the LISA-Pathfinder mission will be one of the most important component used to ensure the "free-fall" of the enclosed test masses. In this paper we present a possible strategy to characterize the effective direction and amplitude gain of each of the 6 thrusters of this system.

  8. Optimal path-finding through mental exploration based on neural energy field gradients.

    Wang, Yihong; Wang, Rubin; Zhu, Yating

    2017-02-01

    Rodent animal can accomplish self-locating and path-finding task by forming a cognitive map in the hippocampus representing the environment. In the classical model of the cognitive map, the system (artificial animal) needs large amounts of physical exploration to study spatial environment to solve path-finding problems, which costs too much time and energy. Although Hopfield's mental exploration model makes up for the deficiency mentioned above, the path is still not efficient enough. Moreover, his model mainly focused on the artificial neural network, and clear physiological meanings has not been addressed. In this work, based on the concept of mental exploration, neural energy coding theory has been applied to the novel calculation model to solve the path-finding problem. Energy field is constructed on the basis of the firing power of place cell clusters, and the energy field gradient can be used in mental exploration to solve path-finding problems. The study shows that the new mental exploration model can efficiently find the optimal path, and present the learning process with biophysical meaning as well. We also analyzed the parameters of the model which affect the path efficiency. This new idea verifies the importance of place cell and synapse in spatial memory and proves that energy coding is effective to study cognitive activities. This may provide the theoretical basis for the neural dynamics mechanism of spatial memory.

  9. Observation of early photons from gamma-ray bursts with the Lomonosov / UFFO-pathfinder

    Jeong, S.; Brandt, Søren; Budtz-Jørgensen, Carl

    2014-01-01

    UFFO-pathfinder is a pioneering space mission to observe the early evolution of Gamma-ray Bursts using a fast slewing strategy. It consists of the Slewing Mirror Telescope, for rapid pointing at UV/optical wavelengths and the UFFO Burst Alert and Trigger Telescope. It has a total weight of ~ 20 k...

  10. In vivo imaging of alphaherpesvirus infection reveals synchronized activity dependent on axonal sorting of viral proteins.

    Granstedt, Andrea E; Bosse, Jens B; Thiberge, Stephan Y; Enquist, Lynn W

    2013-09-10

    A clinical hallmark of human alphaherpesvirus infections is peripheral pain or itching. Pseudorabies virus (PRV), a broad host range alphaherpesvirus, causes violent pruritus in many different animals, but the mechanism is unknown. Previous in vitro studies have shown that infected, cultured peripheral nervous system (PNS) neurons exhibited aberrant electrical activity after PRV infection due to the action of viral membrane fusion proteins, yet it is unclear if such activity occurs in infected PNS ganglia in living animals and if it correlates with disease symptoms. Using two-photon microscopy, we imaged autonomic ganglia in living mice infected with PRV strains expressing GCaMP3, a genetically encoded calcium indicator, and used the changes in calcium flux to monitor the activity of many neurons simultaneously with single-cell resolution. Infection with virulent PRV caused these PNS neurons to fire synchronously and cyclically in highly correlated patterns among infected neurons. This activity persisted even when we severed the presynaptic axons, showing that infection-induced firing is independent of input from presynaptic brainstem neurons. This activity was not observed after infections with an attenuated PRV recombinant used for circuit tracing or with PRV mutants lacking either viral glycoprotein B, required for membrane fusion, or viral membrane protein Us9, required for sorting virions and viral glycoproteins into axons. We propose that the viral fusion proteins produced by virulent PRV infection induce electrical coupling in unmyelinated axons in vivo. This action would then give rise to the synchronous and cyclical activity in the ganglia and contribute to the characteristic peripheral neuropathy.

  11. Catadioptric aberration correction in cathode lens microscopy

    Tromp, R.M. [IBM T.J. Watson Research Center, PO Box 218, Yorktown Heights, NY 10598 (United States); Kamerlingh Onnes Laboratory, Leiden Institute of Physics, Niels Bohrweg 2, 2333 CA Leiden (Netherlands)

    2015-04-15

    In this paper I briefly review the use of electrostatic electron mirrors to correct the aberrations of the cathode lens objective lens in low energy electron microscope (LEEM) and photo electron emission microscope (PEEM) instruments. These catadioptric systems, combining electrostatic lens elements with a reflecting mirror, offer a compact solution, allowing simultaneous and independent correction of both spherical and chromatic aberrations. A comparison with catadioptric systems in light optics informs our understanding of the working principles behind aberration correction with electron mirrors, and may point the way to further improvements in the latter. With additional developments in detector technology, 1 nm spatial resolution in LEEM appears to be within reach. - Highlights: • The use of electron mirrors for aberration correction in LEEM/PEEM is reviewed. • A comparison is made with similar systems in light optics. • Conditions for 1 nm spatial resolution are discussed.

  12. Flow cytometric detection of aberrant chromosomes

    Gray, J.W.; Lucas, J.; Yu, L.C.; Langlois, R.

    1983-05-11

    This report describes the quantification of chromosomal aberrations by flow cytometry. Both homogeneously and heterogeneously occurring chromosome aberrations were studied. Homogeneously occurring aberrations were noted in chromosomes isolated from human colon carcinoma (LoVo) cells, stained with Hoechst 33258 and chromomycin A3 and analyzed using dual beam flow cytometry. The resulting bivariate flow karyotype showed a homogeneously occurring marker chromosome of intermediate size. Heterogeneously occurring aberrations were quantified by slit-scan flow cytometry in chromosomes isolated from control and irradiated Chinese hamster cells and stained with propidium iodide. Heterogeneously occurring dicentric chromosomes were detected by their shapes (two centrometers). The frequencies of such chromosomes estimated by slit-scan flow cytometry correlated well with the frequencies determined by visual microscopy.

  13. Corticostriatal combinatorics: the implications of corticostriatal axonal arborizations.

    Zheng, T; Wilson, C J

    2002-02-01

    The complete striatal axonal arborizations of 16 juxtacellularly stained cortical pyramidal cells were analyzed. Corticostriatal neurons were located in the medial agranular or anterior cingulate cortex of rats. All axons were of the extended type and formed synaptic contacts in both the striosomal and matrix compartments as determined by counterstaining for the mu-opiate receptor. Six axonal arborizations were from collaterals of brain stem-projecting cells and the other 10 from bilaterally projecting cells with no brain stem projections. The distribution of synaptic boutons along the axons were convolved with the average dendritic tree volume of spiny projection neurons to obtain an axonal innervation volume and innervation density map for each axon. Innervation volumes varied widely, with single axons occupying between 0.4 and 14.2% of the striatum (average = 4%). The total number of boutons formed by individual axons ranged from 25 to 2,900 (average = 879). Within the innervation volume, the density of innervation was extremely sparse but inhomogeneous. The pattern of innervation resembled matrisomes, as defined by bulk labeling and functional mapping experiments, superimposed on a low background innervation. Using this sample as representative of all corticostriatal axons, the total number of corticostriatal neurons was estimated to be 17 million, about 10 times the number of striatal projection neurons.

  14. Molecular analysis of axon repulsion by the notochord.

    Anderson, Christopher N G; Ohta, Kunimasa; Quick, Marie M; Fleming, Angeleen; Keynes, Roger; Tannahill, David

    2003-03-01

    During development of the amniote peripheral nervous system, the initial trajectory of primary sensory axons is determined largely by the action of axon repellents. We have shown previously that tissues flanking dorsal root ganglia, the notochord lying medially and the dermamyotomes lying laterally, are sources of secreted molecules that prevent axons from entering inappropriate territories. Although there is evidence suggesting that SEMA3A contributes to the repellent activity of the dermamyotome, the nature of the activity secreted by the notochord remains undetermined. We have employed an expression cloning strategy to search for axon repellents secreted by the notochord, and have identified SEMA3A as a candidate repellent. Moreover, using a spectrum of different axon populations to assay the notochord activity, together with neuropilin/Fc receptor reagents to block semaphorin activity in collagen gel assays, we show that SEMA3A probably contributes to notochord-mediated repulsion. Sympathetic axons that normally avoid the midline in vivo are also repelled, in part, by a semaphorin-based notochord activity. Although our results implicate semaphorin signalling in mediating repulsion by the notochord, repulsion of early dorsal root ganglion axons is only partially blocked when using neuropilin/Fc reagents. Moreover, retinal axons, which are insensitive to SEMA3A, are also repelled by the notochord. We conclude that multiple factors act in concert to guide axons in this system, and that further notochord repellents remain to be identified.

  15. Differences in excitability properties of FDI and ADM motor axons.

    Bae, Jong Seok; Sawai, Setsu; Misawa, Sonoko; Kanai, Kazuaki; Isose, Sagiri; Kuwabara, Satoshi

    2009-03-01

    The first dorsal interosseous (FDI) and abductor digiti minimi (ADM) muscles are innervated by the same ulnar nerve, but studies have shown that the former is much more severely affected in amyotrophic lateral sclerosis. In this study, threshold tracking was used to investigate whether membrane properties differ between FDI and ADM motor axons. In 12 normal subjects, compound muscle action potentials were recorded from FDI and ADM after ulnar nerve stimulation at the wrist. The strength-duration time constant was significantly longer in the FDI axons than in the ADM axons, and latent addition studies showed greater threshold changes at the conditioning-test stimulus of 0.2 ms in FDI than in ADM axons. These findings suggest that nodal persistent sodium conductances are more prominent in FDI axons than in ADM axons, and therefore excitability is physiologically higher in FDI axons. Even in the same nerve at the same sites, membrane properties of FDI and ADM motor axons differ significantly, and thus their axonal/neuronal responses to disease may also differ.

  16. Fast axonal transport in early experimental disc edema.

    Radius, R L; Anderson, D R

    1980-02-01

    Previous work has documented impairment of slow axonal transport in papilledema, but the abnormalities in rapid transport were less certain. Therefore fast axonal transport was studied in 19 primate eyes subjected to ocular hypotony for 6 to 72 hr following surgical fistulization of the anterior chamber. Mild, irregular alterations in fast axonal transport were detected only after nerve head swelling was apparent. These changes in fast transport mechanisms in cases of nerve head edema occur after, and may be secondary to, impaired slow axoplasmic flow and the resultant axonal swelling. Furthermore, since prolonged complete interruption of axonal transport is theoretically inconsistent with the continued normal neuron function characteristic of papilledema and, moreover, since previous data shows a "slowdown" rather than complete blockade of axonal transport in papilledema, it is likely that in eyes with papilledema there does not exist a complete flock of axonal transport. Therefore we hypothesize that the swelling results when slow axoplasmic flow is locally slowed down but not totally stopped, with the axon distention producing secondary mild, irregular changes in fast axonal transport.

  17. Axonal autophagy during regeneration of the rat sciatic nerve

    Kangrong Lu; Zhongxian Piao; Zhenxi Liu; Weiwang Gu; Wanshan Wang; Nngjie Piao

    2008-01-01

    BACKGROUND: The removal of degenerated axonal debris during Wallerian degeneration is very important for nerve regeneration. However, the mechanism by which debris is removed is not been completely understood. Considerable controversy remains as to the clearance pathway and cells that are involved. OBJECTIVE: To investigate axonal autophagy during removal of degenerated axonal debris by transecting the sciatic nerve in a rat Wallerian degeneration model.DESIGN, TIME AND SETTING: Experimental neuropathological analysis. The experiment was conducted at the Laboratory Animal Service Center of the Southern Medical University between January and June 2005. MATERIALS: Fifty-four adult, Wistar rats of either sex, weighing 180-250 g, were obtained from the Laboratory Animal Service Center of the Southern Medical University. Animals were randomly divided into nine groups of six rats. METHODS: Wallerian degeneration was induced by transecting the rat sciatic nerve, and tissue samples from the distal stump were obtained 0.2, 0.4, 1, 2, 3, 4, 7, 10, and 15 days post-transection. Ultrathin sections were prepared for electron microscopy to study ultrastructure and enzyme cytochemistry staining. MAIN OUTCOME MEASURES: Ultrastructure (axon body, autophagic body, and cystoskeleton) of axons and myelin sheaths observed with electron microscopy; acidic phosphatase activity detected by Gomori staining using electron microscopy. RESULTS: The major changes of degenerating axons after transection were axoplasm swelling and separation of axons from their myelin sheath between five hours and two days post-transection. At four days post-transection, the axoplasm condensed and axons were completely separated from the myelin sheath, forming dissociative axon bodies. Vacuoles of different sizes formed in axons during the early phase after lesion. Larger dissociative axon bodies were formed when the axons were completely separated from the myelin sheath during a late phase. The axolemma

  18. A unified cell biological perspective on axon-myelin injury.

    Simons, Mikael; Misgeld, Thomas; Kerschensteiner, Martin

    2014-08-04

    Demyelination and axon loss are pathological hallmarks of the neuroinflammatory disorder multiple sclerosis (MS). Although we have an increasingly detailed understanding of how immune cells can damage axons and myelin individually, we lack a unified view of how the axon-myelin unit as a whole is affected by immune-mediated attack. In this review, we propose that as a result of the tight cell biological interconnection of axons and myelin, damage to either can spread, which might convert a local inflammatory disease process early in MS into the global progressive disorder seen during later stages. This mode of spreading could also apply to other neurological disorders.

  19. Present status of studies on diffuse axonal injury

    Jie Ma; Chonggong Zhang; Yi Li

    2006-01-01

    OBJECTIVE: To explain the present status of study on diffuse axonal injury,investigate its pathogenesis and pathophysiological changes ,and suggest principles for the diagnosis and treatment.DATA SOURCES: Articles about diffuse axonal injury published in English from January 1994 to October 2006 were searched in Pubmed database using the keywords of "diffuse axonal injury,pathogenesis,therapy".STUDY SELECTION: The collected articles were primarily screened to select those associated with diffuse axonal injury,the obviously irrelated articles were excluded,and the rest ones were retrieved manually,and the full-texes were searched.DATA EXTRACTION: Totally 98 articles were collected,41 of them were involved.and the other 57 were excluded.DATA SYNTHESIS: Diffuse axonal injury is mainly caused by acceleratory or deceleratory injury,and its pathophysiological change is a progressive duration,local axonal injury finally develops to axonal breakage,mainly includes inactivation of natrium channel,intracellular Ca2+ overloading,activation of calcium protease,caspase etc.,and mitochondrial injury.At present,there is still lack of effective therapeutic methods for diffuse axonal injury,so we should actively explore more effective methods to relieve the pain of patients and improve their prognosis.CONCLUSION: At present,diffuse axonal injury has not attracted enough attentions in China,the mechanisms for its diagnosis and attack are still unclear,and the treatments are mainly aiming at the symptoms.

  20. Dopaminergic axon guidance: which makes what?

    Laetitia ePrestoz

    2012-07-01

    Full Text Available Mesotelencephalic pathways in the adult central nervous system have been studied in great detail because of their implication in major physiological functions as well as in psychiatric, neurological and neurodegenerative diseases. However, the ontogeny of these pathways and the molecular mechanisms that guide dopaminergic axons during embryogenesis have been only recently studied. This line of research is of crucial interest for the repair of lesioned circuits in adulthood following neurodegenerative diseases or common traumatic injuries. For instance, in the adult, the anatomic and functional repair of the nigrostriatal pathway following dopaminergic embryonic neuron transplantation suggests that specific guidance cues exist which govern embryonic fibers outgrowth, and suggests that axons from transplanted embryonic cells are able to respond to theses cues, which then guide them to their final targets. In this review, we first synthesize the work that has been performed in the last few years on developing mesotelencephalic pathways, and summarize the current knowledge on the identity of cellular and molecular signals thought to be involved in establishing mesotelencephalic dopaminergic neuronal connectivity during embryogenesis in the central nervous system of rodents. Then, we review the modulation of expression of these molecular signals in the lesioned adult brain and discuss their potential role in remodeling the mesotelencephalic dopaminergic circuitry, with a particular focus on Parkinson’s disease. Identifying guidance molecules involved in the connection of grafted cells may be useful for cellular therapy in Parkinsonian patients, as these molecules may help direct axons from grafted cells along the long distance they have to travel from the substantia nigra to the striatum.

  1. Sensing Phase Aberrations behind Lyot Coronagraphs

    Sivaramakrishnan, Anand; Soummer, Rémi; Pueyo, Laurent; Wallace, J. Kent; Shao, Michael

    2008-11-01

    Direct detection of young extrasolar planets orbiting nearby stars can be accomplished from the ground with extreme adaptive optics and coronagraphy in the near-infrared, as long as this combination can provide an image with a dynamic range of 107 after the data are processed. Slowly varying speckles due to residual phase aberrations that are not measured by the primary wave-front sensor are the primary obstacle to achieving such a dynamic range. In particular, non-common optical path aberrations occurring between the wave-front sensor and the coronagraphic occulting spot degrade performance the most. We analyze the passage of both low and high spatial frequency phase ripples, as well as low-order Zernike aberrations, through an apodized pupil Lyot coronagraph in order to demonstrate the way coronagraphic filtering affects various aberrations. We derive the coronagraphically induced cutoff frequency of the filtering and estimate coronagraphic contrast losses due to low-order Zernike aberrations: tilt, astigmatism, defocus, coma, and spherical aberration. Such slowly varying path errors can be measured behind a coronagraph and corrected by a slowly updated optical path delay precompensation or offset asserted on the wave front by the adaptive optics (AO) system. We suggest ways of measuring and correcting all but the lowest spatial frequency aberrations using Lyot plane wave-front data, in spite of the complex interaction between the coronagraph and those mid-spatial frequency aberrations that cause image plane speckles near the coronagraphic focal plane mask occulter's edge. This investigation provides guidance for next-generation coronagraphic instruments currently under construction.

  2. Axonal regeneration and development of de novo axons from distal dendrites of adult feline commissural interneurons after a proximal axotomy

    Fenrich, Keith K; Skelton, Nicole; MacDermid, Victoria E

    2007-01-01

    at 4-5 weeks post injury. The somata of axotomized CINs were identified by the presence of immunoreactivity for the axonal growth-associated protein-43 (GAP-43). Nearly half of the CINs had de novo axons that emerged from distal dendrites. These axons lacked immunoreactivity for the dendritic protein......Following proximal axotomy, several types of neurons sprout de novo axons from distal dendrites. These processes may represent a means of forming new circuits following spinal cord injury. However, it is not know whether mammalian spinal interneurons, axotomized as a result of a spinal cord injury......, develop de novo axons. Our goal was to determine whether spinal commissural interneurons (CINs), axotomized by 3-4-mm midsagittal transection at C3, form de novo axons from distal dendrites. All experiments were performed on adult cats. CINs in C3 were stained with extracellular injections of Neurobiotin...

  3. IMP2 axonal localization, RNA interactome, and function in the development of axon trajectories

    Preitner, Nicolas; Quan, Jie; Li, Xinmin

    2016-01-01

    RNA-based regulatory mechanisms play important roles in the development and plasticity of neural circuits and neurological disease. Developing axons provide a model well suited to the study of RNA-based regulation, and contain specific subsets of mRNAs that are locally translated and have roles i...

  4. White-matter astrocytes, axonal energy metabolism, and axonal degeneration in multiple sclerosis

    Cambron, Melissa; D'haeseleer, Miguel; Laureys, Guy; Clinckers, Ralph; Debruyne, Jan; De Keyser, Jacques

    2012-01-01

    In patients with multiple sclerosis (MS), a diffuse axonal degeneration occurring throughout the white matter of the central nervous system causes progressive neurologic disability. The underlying mechanism is unclear. This review describes a number of pathways by which dysfunctional astrocytes in M

  5. Simulation and template generation for LISA Pathfinder Data Analysis

    Rais, Boutheina; Grynagier, Adrien; Diaz-Aguiló, Marc; Armano, Michele

    The LISA PathFinder (LPF) mission is a technology demonstration mission which aims at testing a number of critical technical challenges that the future LISA (Gravitational wave detection in space) mission will face: LPF can be seen as a complex laboratory experiment in space. It is therefore critical to be able to define which measurements and which actuations will be applied during the scientific part of the mission. The LISA Technology Package (LTP), part of ESA's hardware contribution to LPF, outlines hence the importance of developing an appropriate simulation tool in order to test these strate-gies before launch and to analyse the dynamical behaviour of the system during the mission. The detailed model of the simulation can be used in an off-line mode for further planning: cor-rect estimation of timeline priorities, risk factors, duty cycles, data analysis readiness. The Lisa Technology Package Data Analysis (LTPDA) team has developed an object-oriented MATLAB toolbox for general case of data analysis needs. However, to meet specific needs of LPF mis-sion, a template generation tool has been developed. It provides a recognizable data pattern, avoiding the risk of missing the model during mission's analysis. The aim of the template generator tool is to provide tools to analyse LTP system modeled in State Space Model (SSM). The SSM class, the aim of this poster, includes this tools within the LTPDA toolbox. It can be used to generate the time-domain response for any given actuation and/or noise, the frequency response using bode diagrams and the steady state of the system. It allows the user to project noises on system outputs to get spectra of outputs for given input noises spectra. This class is sufficiently general to be used with a variety of systems once the SSM of the system is provided in the library. Furthermore, one of the main objectives of the data analysis for LPF (the estimation of different parameters of the system), can be achieved by a new

  6. Individual eye model based on wavefront aberration

    Guo, Huanqing; Wang, Zhaoqi; Zhao, Qiuling; Quan, Wei; Wang, Yan

    2005-03-01

    Based on the widely used Gullstrand-Le Grand eye model, the individual human eye model has been established here, which has individual corneal data, anterior chamber depth and the eyeball depth. Furthermore, the foremost thing is that the wavefront aberration calculated from the individual eye model is equal to the eye's wavefront aberration measured with the Hartmann-shack wavefront sensor. There are four main steps to build the model. Firstly, the corneal topography instrument was used to measure the corneal surfaces and depth. And in order to input cornea into the optical model, high-order aspheric surface-Zernike Fringe Sag surface was chosen to fit the corneal surfaces. Secondly, the Hartmann-shack wavefront sensor, which can offer the Zernike polynomials to describe the wavefront aberration, was built to measure the wavefront aberration of the eye. Thirdly, the eye's axial lengths among every part were measured with A-ultrasonic technology. Then the data were input into the optical design software-ZEMAX and the crystalline lens's shapes were optimized with the aberration as the merit function. The individual eye model, which has the same wavefront aberrations with the real eye, is established.

  7. AxonPacking: An Open-Source Software to Simulate Arrangements of Axons in White Matter.

    Mingasson, Tom; Duval, Tanguy; Stikov, Nikola; Cohen-Adad, Julien

    2017-01-01

    HIGHLIGHTS AxonPacking: Open-source software for simulating white matter microstructure.Validation on a theoretical disk packing problem.Reproducible and stable for various densities and diameter distributions.Can be used to study interplay between myelin/fiber density and restricted fraction. Quantitative Magnetic Resonance Imaging (MRI) can provide parameters that describe white matter microstructure, such as the fiber volume fraction (FVF), the myelin volume fraction (MVF) or the axon volume fraction (AVF) via the fraction of restricted water (fr). While already being used for clinical application, the complex interplay between these parameters requires thorough validation via simulations. These simulations required a realistic, controlled and adaptable model of the white matter axons with the surrounding myelin sheath. While there already exist useful algorithms to perform this task, none of them combine optimisation of axon packing, presence of myelin sheath and availability as free and open source software. Here, we introduce a novel disk packing algorithm that addresses these issues. The performance of the algorithm is tested in term of reproducibility over 50 runs, resulting density, and stability over iterations. This tool was then used to derive multiple values of FVF and to study the impact of this parameter on fr and MVF in light of the known microstructure based on histology sample. The standard deviation of the axon density over runs was lower than 10(-3) and the expected hexagonal packing for monodisperse disks was obtained with a density close to the optimal density (obtained: 0.892, theoretical: 0.907). Using an FVF ranging within [0.58, 0.82] and a mean inter-axon gap ranging within [0.1, 1.1] μm, MVF ranged within [0.32, 0.44] and fr ranged within [0.39, 0.71], which is consistent with the histology. The proposed algorithm is implemented in the open-source software AxonPacking (https://github.com/neuropoly/axonpacking) and can be useful for

  8. Selective loss and axonal sprouting of GABAergic interneurons in the sclerotic hippocampus induced by LiCl-pilocarpine.

    Long, Lili; Xiao, Bo; Feng, Li; Yi, Fang; Li, Guoliang; Li, Shuyu; Mutasem, M Abuhamed; Chen, Si; Bi, Fangfang; Li, Yi

    2011-02-01

    In this study, we performed immunohistochemistry for somatostatin (SS), neuropeptide Y (NPY), and parvalbumin (PV) in LiCl-pilocarpine-treated rats to observe quantitative changes and axonal sprouting of GABAergic interneurons in the hippocampus, especially in the sclerotic hippocampus. Fluoro-Jade B (FJB) was performed to detect the specific degeneration of GABAergic interneurons. Compared with age-matched control rats, there were fewer SS/NPY/PV-immunoreactive (IR) interneurons in the hilus of the sclerotic hippocampus in pilocarpine-treated rats; hilar dentritic inhibitory interneurons were most vulnerable. FJB stain revealed degeneration was evident at 2 months after status epilepticus. Some SS-IR and NPY-IR interneurons were also stained for FJB, but there was no evidence of degeneration of PV-IR interneurons. Axonal sprouting of GABAergic interneurons was present in the hippocampus of epileptic rats, and a dramatic increase of SS-IR fibers was observed throughout all layers of CA1 region in the sclerotic hippocampus. These results confirm selective loss and degeneration of a specific subset of GABAergic interneurons in specific subfields of the hippocampus. Axonal sprouting of inhibitory GABAergic interneurons, especially numerous increase of SS-IR neutrophils within CA1 region of the sclerotic hippocampus, may constitute the aberrant inhibitory circum and play a significant role in the generation and compensation of temporal lobe epilepsy.

  9. Pulse compressor with aberration correction

    Mankos, Marian [Electron Optica, Inc., Palo Alto, CA (United States)

    2015-11-30

    In this SBIR project, Electron Optica, Inc. (EOI) is developing an electron mirror-based pulse compressor attachment to new and retrofitted dynamic transmission electron microscopes (DTEMs) and ultrafast electron diffraction (UED) cameras for improving the temporal resolution of these instruments from the characteristic range of a few picoseconds to a few nanoseconds and beyond, into the sub-100 femtosecond range. The improvement will enable electron microscopes and diffraction cameras to better resolve the dynamics of reactions in the areas of solid state physics, chemistry, and biology. EOI’s pulse compressor technology utilizes the combination of electron mirror optics and a magnetic beam separator to compress the electron pulse. The design exploits the symmetry inherent in reversing the electron trajectory in the mirror in order to compress the temporally broadened beam. This system also simultaneously corrects the chromatic and spherical aberration of the objective lens for improved spatial resolution. This correction will be found valuable as the source size is reduced with laser-triggered point source emitters. With such emitters, it might be possible to significantly reduce the illuminated area and carry out ultrafast diffraction experiments from small regions of the sample, e.g. from individual grains or nanoparticles. During phase I, EOI drafted a set of candidate pulse compressor architectures and evaluated the trade-offs between temporal resolution and electron bunch size to achieve the optimum design for two particular applications with market potential: increasing the temporal and spatial resolution of UEDs, and increasing the temporal and spatial resolution of DTEMs. Specialized software packages that have been developed by MEBS, Ltd. were used to calculate the electron optical properties of the key pulse compressor components: namely, the magnetic prism, the electron mirror, and the electron lenses. In the final step, these results were folded

  10. Stress-Induced CDK5 Activation Disrupts Axonal Transport via Lis1/Ndel1/Dynein

    Eva Klinman

    2015-07-01

    Full Text Available Axonal transport is essential for neuronal function, and defects in transport are associated with multiple neurodegenerative diseases. Aberrant cyclin-dependent kinase 5 (CDK5 activity, driven by the stress-induced activator p25, also is observed in these diseases. Here we show that elevated CDK5 activity increases the frequency of nonprocessive events for a range of organelles, including lysosomes, autophagosomes, mitochondria, and signaling endosomes. Transport disruption induced by aberrant CDK5 activation depends on the Lis1/Ndel1 complex, which directly regulates dynein activity. CDK5 phosphorylation of Ndel1 favors a high affinity Lis1/Ndel/dynein complex that blocks the ATP-dependent release of dynein from microtubules, inhibiting processive motility of dynein-driven cargo. Similar transport defects observed in neurons from a mouse model of amyotrophic lateral sclerosis are rescued by CDK5 inhibition. Together, these studies identify CDK5 as a Lis1/Ndel1-dependent regulator of transport in stressed neurons, and suggest that dysregulated CDK5 activity contributes to the transport deficits observed during neurodegeneration.

  11. Differential extraction of axonally transported proteoglycans

    Elam, J.S. (Florida State Univ., Tallahassee (USA))

    1990-10-01

    Axonally transported proteoglycans were differentially solubilized by a sequence of extractions designed to infer their relationship to nerve terminal membranes. Groups of goldfish were injected unilaterally with 35SO4 and contralateral optic tecta containing axonally transported molecules were removed 16 h later. Tecta were homogenized in isotonic buffer and centrifuged at 100,000 g for 60 min to create a total supernatant fraction. Subsequent homogenizations followed by recentrifugation were with hypotonic buffer (lysis extract), 1 M NaCl, Triton X-100 or alternatively Triton-1 M NaCl. Populations of proteoglycans in each extract were isolated on DEAE ion exchange columns and evaluated for content of glycosaminoglycans (GAGs). Results show the distribution of transported proteoglycans to be 26.3% total soluble, 13.7% lysis extract, 13.8% NaCl extract, 12.2% Triton extract, and 46.2% Triton-NaCl extract. Proteoglycans from all fractions contained heparan sulfate as the predominant GAG, with lesser amounts of chondroitin (4 or 6) sulfate. The possible localizations of transported proteoglycans suggested by the extraction results are discussed.

  12. Nuclear kinesis, neurite sprouting and abnormal axonal projections of cone photoreceptors in the aged and AMD-afflicted human retina.

    Pow, David V; Sullivan, Robert K P

    2007-05-01

    Tissues often respond to damage by recapitulating developmental programs. We have investigated whether anatomical signs of developmental recapitulation are evident in cone photoreceptors of the aged and AMD-afflicted human retina. Radial migration of cell nuclei mediated by microtubules is a characteristic feature of cells in the developing retina. Similarly, neurite outgrowth is a feature of developing neurons. We have examined whether nuclear kinesis and neurite outgrowth from cone photoreceptors is evident. Calbindin-positive cone photoreceptor nuclei are normally positioned as a single layer of somata at the outer border of the outer nuclear layer. In AMD-afflicted retinae, many nuclei are translocated, with some somata abutting the outer plexiform layer (OPL) and others outside the outer limiting membrane whilst many nuclei are present at intermediate levels. The axonal processes of many cones were also aberrant, displaying tortuous pathways as they projected to the OPL, with occasional evidence for bifurcation at points where the axon changed direction. We suggest that tangential extension of collateral neurites and the rapid retraction of the original process may give rise to the tortuous axonal projections observed. Since microtubules are key mediators of both neurite extension and nuclear kinesis we examined expression of microtubule associated protein 2 (MAP2) which is an important regulator of neurite extension. The strong expression of MAP2 observed in those cells with aberrant morphologies supports the notion that abnormal microtubule-mediated remodelling events are present in the AMD retina and to a lesser extent in normal aged retinas, allowing cone photoreceptors to recapitulate two key features of development.

  13. Neuronal Logistics : Axonal Transport in Development and Disease

    R. van den Berg (Robert)

    2016-01-01

    markdownabstractBrain cells are uniquely shaped among the many cell types of the body. While most cells are more or less rounded or square-shaped, neurons grow one or more long axons that can reach lengths of a meter or more. To keep these axons alive and functional, neurons are dependent on an intr

  14. Molecular Determinants Fundamental to Axon Regeneration after SCI

    2014-09-01

    TITLE: Molecular Determinants Fundamental to Axon Regeneration after SCI PRINCIPAL INVESTIGATOR: Jeffrey Alan Plunkett, Ph.D. Martin...TYPE FINAL 3. DATES COVERED (From - To) 1 Sept 2011 - 1 Sept 2014 4. TITLE AND SUBTITLE Molecular Determinants Fundamental to Axon Regeneration...available that restore motor impairments resulting fromspinal cord injury (SCI). Soldiers with SCI are permanently paralyzed and in needof lifelong care

  15. Molecular Determinants Fundamental to Axon Regeneration after SCI

    2012-06-01

    currently employed to investigate the evolution of the scar and the time course of axon regeneration after spinal cord injury. The data from these...Medicine, Pittsburgh, PA. It has been established in amphibians and fish that neurons can successfully regenerate their axons in the damaged central

  16. Spontaneous axonal regeneration in rodent spinal cord after ischemic injury

    von Euler, Mia; Janson, A M; Larsen, Jytte Overgaard;

    2002-01-01

    Here we present evidence for spontaneous and long-lasting regeneration of CNS axons after spinal cord lesions in adult rats. The length of 200 kD neurofilament (NF)-immunolabeled axons was estimated after photochemically induced ischemic spinal cord lesions using a stereological tool. The total l...

  17. Inhibiting poly(ADP-ribosylation) improves axon regeneration

    Byrne, Alexandra B; McWhirter, Rebecca D; Sekine, Yuichi; Strittmatter, Stephen M; Miller, David M; Hammarlund, Marc

    2016-01-01

    The ability of a neuron to regenerate its axon after injury depends in part on its intrinsic regenerative potential. Here, we identify novel intrinsic regulators of axon regeneration: poly(ADP-ribose) glycohodrolases (PARGs) and poly(ADP-ribose) polymerases (PARPs). PARGs, which remove poly(ADP-ribose) from proteins, act in injured C. elegans GABA motor neurons to enhance axon regeneration. PARG expression is regulated by DLK signaling, and PARGs mediate DLK function in enhancing axon regeneration. Conversely, PARPs, which add poly(ADP-ribose) to proteins, inhibit axon regeneration of both C. elegans GABA neurons and mammalian cortical neurons. Furthermore, chemical PARP inhibitors improve axon regeneration when administered after injury. Our results indicate that regulation of poly(ADP-ribose) levels is a critical function of the DLK regeneration pathway, that poly-(ADP ribosylation) inhibits axon regeneration across species, and that chemical inhibition of PARPs can elicit axon regeneration. DOI: http://dx.doi.org/10.7554/eLife.12734.001

  18. Axon guidance of rat cortical neurons by microcontact printed gradients.

    Fricke, Rita; Zentis, Peter D; Rajappa, Lionel T; Hofmann, Boris; Banzet, Marko; Offenhäusser, Andreas; Meffert, Simone H

    2011-03-01

    Substrate-bound gradients expressed in numerous spatio-temporal patterns play a crucial role during the development of complex neural circuits. A deeper understanding of the axon guidance mechanism is provided by studying the effect of a defined substrate-bound cue on a confined neural network. In this study, we constructed a discontinuous substrate-bound gradient to control neuronal cell position, the path of neurite growth, and axon directionality. A variety of gradient patterns, with slight changes in slope, width, and length were designed and fabricated by microcontact printing using laminin/poly-l-lysine (PLL) or PLL alone. The gradients were tested for neurite growth and their impact on axon guidance of embryonic rat cortical neurons. The neurite length was determined and the axon was evaluated by Tau-1 immunostaining. We found that the microgradients of laminin/PLL and PLL directed neurons' adhesion, differentially controlled the neurite growth, and guided up to 84% of the axons. The effect of the protein micropattern on axon guidance and neurite growth depended on the protein and geometric parameters used. Our approach proved to be very successful in guiding axons of single multipolar neurons with very high efficiency. It could thereby be useful to engineer defined neural networks for analyzing signal processing of functional circuits, as well as to unravel fundamental questions of the axon guidance mechanism.

  19. Increased Human Wildtype Tau Attenuates Axonal Transport Deficits Caused by Loss of APP in Mouse Models

    Smith, Karen D.B.; Erica Peethumnongsin; Han Lin; Hui Zheng; Pautler, Robia G.

    2010-01-01

    Amyloid precursor protein (APP) is implicated in axonal elongation, synaptic plasticity, and axonal transport. However, the role of APP on axonal transport in conjunction with the microtubule associated protein tau continues to be debated. Here we measured in vivo axonal transport in APP knockout mice with Manganese Enhanced MRI (MEMRI) to determine whether APP is necessary for maintaining normal axonal transport. We also tested how overexpression and mutations of tau affect axonal transport ...

  20. SnoN facilitates axonal regeneration after spinal cord injury.

    Jiun L Do

    Full Text Available Adult CNS neurons exhibit a reduced capacity for growth compared to developing neurons, due in part to downregulation of growth-associated genes as development is completed. We tested the hypothesis that SnoN, an embryonically regulated transcription factor that specifies growth of the axonal compartment, can enhance growth in injured adult neurons. In vitro, SnoN overexpression in dissociated adult DRG neuronal cultures significantly enhanced neurite outgrowth. Moreover, TGF-β1, a negative regulator of SnoN, inhibited neurite outgrowth, and SnoN over-expression overcame this inhibition. We then examined whether SnoN influenced axonal regeneration in vivo: indeed, expression of a mutant form of SnoN resistant to degradation significantly enhanced axonal regeneration following cervical spinal cord injury, despite peri-lesional upregulation of TGF-β1. Thus, a developmental mechanism that specifies extension of the axonal compartment also promotes axonal regeneration after adult CNS injury.

  1. Internodal function in normal and regenerated mammalian axons

    Moldovan, M; Krarup, C

    2007-01-01

    AIM: Following Wallerian degeneration, peripheral myelinated axons have the ability to regenerate and, given a proper pathway, establish functional connections with targets. In spite of this capacity, the clinical outcome of nerve regeneration remains unsatisfactory. Early studies have found...... that regenerated internodes remain persistently short though this abnormality did not seem to influence recovery in conduction. It remains unclear to which extent abnormalities in axonal function itself may contribute to the poor outcome of nerve regeneration. METHODS: We review experimental evidence indicating...... that internodes play an active role in axonal function. RESULTS: By investigating internodal contribution to axonal excitability we have found evidence that axonal function may be permanently compromised in regenerated nerves. Furthermore, we illustrate that internodal function is also abnormal in regenerated...

  2. NOAA Climate Data Record (CDR) of Sea Surface Temperature (SST) from AVHRR Pathfinder, Version 5.2

    National Oceanic and Atmospheric Administration, Department of Commerce — The AVHRR Pathfinder Version 5.2 Sea Surface Temperature data set (PFV52) is a collection of global, twice-daily 4km sea surface temperature data produced in a...

  3. Annual narrative report: Calendar year 2000: Arapaho National Wildlife Refuge, Bamforth, Hutton Lake, Morenson Lake and Pathfinder National Wildlife Refuges

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Arapaho NWR, Bamforth NWR, Hutton Lake NWR, Morenson Lake NWR, and Pathfinder NWR outlines Refuge accomplishments during the 2000...

  4. Arapaho National Wildlife Refuge also Bamforth, Hutton Lake and Pathfinder National Wildlife Refuges: Annual narrative report: Calendar year 1991

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Arapaho NWR, Bamforth NWR, Hutton Lake NWR, and Pathfinder NWR outlines Refuge accomplishments during the 1991 calendar year. The...

  5. NOAA Climate Data Record (CDR) of Cloud Properties from AVHRR Pathfinder Atmospheres - Extended (PATMOS-x), Version 5.3

    National Oceanic and Atmospheric Administration, Department of Commerce — This NOAA Climate Data Record (CDR) of cloud products was produced by the University of Wisconsin using the AVHRR Pathfinder Atmospheres - Extended (PATMOS-X)...

  6. NOAA Climate Data Record (CDR) of Reflectance from AVHRR Pathfinder Atmospheres - Extended (PATMOS-x), Version 5.2

    National Oceanic and Atmospheric Administration, Department of Commerce — This dataset has been superseded by Version 5.3. The Pathfinder Atmospheres - Extended (PATMOS-x) Reflectance data contain derived atmospheric variables from the...

  7. 4 km NODC/RSMAS AVHRR Pathfinder v.5.0 Sea Surface Temperature (SST) Climatologies (1985-2001)

    National Oceanic and Atmospheric Administration, Department of Commerce — The 4 km Pathfinder effort at the National Oceanic and Atmospheric Administration (NOAA) National Oceanographic Data Center (NODC) and the University of Miami's...

  8. Signaling mechanisms in cortical axon growth, guidance and branching

    Katherine eKalil

    2011-09-01

    Full Text Available Precise wiring of cortical circuits during development depends upon axon extension, guidance and branching to appropriate targets. Motile growth cones at axon tips navigate through the nervous system by responding to molecular cues, which modulate signaling pathways within axonal growth cones. Intracellular calcium signaling has emerged as a major transducer of guidance cues but exactly how calcium signaling pathways modify the actin and microtubule cytoskeleton to evoke growth cone behaviors and axon branching is still mysterious. Axons must often pause in their outgrowth while their branches extend into targets. Some evidence suggests a competition between growth of axons and branches but the mechanisms are poorly understood. Since it is difficult to study growing axons deep within the mammalian brain, much of what we know about signaling pathways and cytoskeletal dynamics has come from studies of axonal growth cones, in many cases from non-mammalian species, growing in tissue culture. Consequently it is not well understood how guidance cues relevant to mammalian neural development in vivo signal to the growth cone cytoskeleton during axon outgrowth and guidance. In this review we describe our recent work in dissociated cultures of developing rodent sensorimotor cortex in the context of the current literature on molecular guidance cues, calcium signaling pathways and cytoskeletal dynamics that regulate growth cone behaviors. A major challenge is to relate findings in tissue culture to mechanisms of cortical development in vivo. Toward this goal, we describe our recent work in cortical slices, which preserve the complex cellular and molecular environment of the mammalian brain but allow direct visualization of growth cone behaviors and calcium signaling. Findings from this work suggest that mechanisms regulating axon growth and guidance in dissociated culture neurons also underlie development of cortical connectivity in vivo.

  9. Clinical features of diffuse axonal injury

    2001-01-01

    Objective: To analyze the mechanism of diffuse axonal injury (DAI) and study the relationship between DAI and brain concussion, brain contusion, and primary brain stem injury.Methods: The clinical data and iconographic characteristics of 56 patients with DAI were analyzed retrospectively.Results: Traffic accidents were the main cause of DAI. Among the 56 cases, 34 were injured for at least twice, and 71.43% of the patients were complicated with contusion.Conclusions: It is considered that DAI is a common pattern of primary brain injury, which is often underestimated. And DAI includes cerebral concussion and primary brain injury, and is often complicated by cerebral cortex contusion. Therefore, it is very simple and practical to divide primary brain injuries into local and diffuse injuries.

  10. William Herschel Telescope site characterization using the MOAO pathfinder CANARY on-sky data

    Martin, O A; Gendron, E; Rousset, G; Vidal, F; Morris, T J; Basden, A G; Myers, R M; Ono, Y H; Neichel, B; Fusco, T

    2016-01-01

    Canary is the Multi-Object Adaptive Optics (MOAO) pathfinder for the future MOAO-assisted Integral-Field Units (IFU) proposed for Extremely Large Telescopes (ELT). The MOAO concept relies on tomographically reconstructing the turbulence using multiple measurements along different lines of sight. Tomography requires the knowledge of the statistical turbulence parameters, commonly recovered from the system telemetry using a dedicated profiling technique. For demonstration purposes with the MOAO pathfinder Canary , this identification is performed thanks to the Learn & Apply (L&A) algorithm, that consists in model- fitting the covariance matrix of WFS measurements dependent on relevant parameters: $C_n^2(h)$ profile, outer scale profile and system mis-registration. We explore an upgrade of this algorithm, the Learn 3 Steps (L3S) approach, that allows one to dissociate the identification of the altitude layers from the ground in order to mitigate the lack of convergence of the required empirical covarianc...

  11. Neural network interpolation of the magnetic field for the LISA Pathfinder Diagnostics Subsystem

    Diaz-Aguilo, Marc; García-Berro, Enrique

    2011-01-01

    LISA Pathfinder is a science and technology demonstrator of the European Space Agency within the framework of its LISA mission, which aims to be the first space-borne gravitational wave observatory. The payload of LISA Pathfinder is the so-called LISA Technology Package, which is designed to measure relative accelerations between two test masses in nominal free fall. Its disturbances are monitored and dealt by the diagnostics subsystem. This subsystem consists of several modules, and one of these is the magnetic diagnostics system, which includes a set of four tri-axial fluxgate magnetometers, intended to measure with high precision the magnetic field at the positions of the test masses. However, since the magnetometers are located far from the positions of the test masses, the magnetic field at their positions must be interpolated. It has been recently shown that because there are not enough magnetic channels, classical interpolation methods fail to derive reliable measurements at the positions of the test m...

  12. An Analysis of Coupling between the x1 and x12 Interferometers for LISA Pathfinder

    Howard, Brittany

    2017-01-01

    Due to tolerances in the manufacturing process, noise from the jittering of the spacecraft housing LISA Pathfinder (LPF) is appearing in the differential measurement between its two test masses (TM's). This phenomenon manifests as a small but measurable coupling between the readouts of LPF's two heterodyne interferometers, x1 and x12. In this study, two LISA Pathfinder experiments are analyzed using three methods in an effort to characterize and quantify the coupling as well as to potentially identify its source. The main question considered is this: does the coupling change with the absolute displacement between the TM's? As a result of this work, reliable values for coupling between LPF's x1 and x12 interferometers are found, and they are seen to depend on the absolute displacement between the test masses to some degree. Completed at the Albert Einstein Institute for Gravitational Physics under the International REU program from the University of Florida.

  13. Indoor A* Pathfinding Through an Octree Representation of a Point Cloud

    Rodenberg, O. B. P. M.; Verbree, E.; Zlatanova, S.

    2016-10-01

    There is a growing demand of 3D indoor pathfinding applications. Researched in the field of robotics during the last decades of the 20th century, these methods focussed on 2D navigation. Nowadays we would like to have the ability to help people navigate inside buildings or send a drone inside a building when this is too dangerous for people. What these examples have in common is that an object with a certain geometry needs to find an optimal collision free path between a start and goal point. This paper presents a new workflow for pathfinding through an octree representation of a point cloud. We applied the following steps: 1) the point cloud is processed so it fits best in an octree; 2) during the octree generation the interior empty nodes are filtered and further processed; 3) for each interior empty node the distance to the closest occupied node directly under it is computed; 4) a network graph is computed for all empty nodes; 5) the A* pathfinding algorithm is conducted. This workflow takes into account the connectivity for each node to all possible neighbours (face, edge and vertex and all sizes). Besides, a collision avoidance system is pre-processed in two steps: first, the clearance of each empty node is computed, and then the maximal crossing value between two empty neighbouring nodes is computed. The clearance is used to select interior empty nodes of appropriate size and the maximal crossing value is used to filter the network graph. Finally, both these datasets are used in A* pathfinding.

  14. The Ultraviolet Spectro-Coronagraph Pathfinder Mission for the Detection of Coronal Suprathermal Seed Particles

    Strachan, Leonard; Laming, J. Martin; Ko, Yuan-Kuen; Korendyke, Clarence M.; Tun Beltran, Samuel; Socker, Dennis G.; Brown, Charles; Provornikova, Elena

    2016-05-01

    The Ultraviolet Spectro-Coronagraph (UVSC) Pathfinder is a Naval Research Laboratory experiment designed to make the first detection of suprathermal seed particles close to the Sun. It uses an innovative “stacked” occulting system to significantly increase the effective light gathering power of a traditional, 1-meter length, externally occulted coronagraph. The external occultation in combination with a low scatter variable line spaced grating provide the stray light suppression needed to measure non-Maxwellian departures in the wings of the H Lyman alpha emission line profile. After the removal of other factors, these departures may be interpreted as the signature of suprathermal tails of the proton velocity distribution in the corona. UVSC Pathfinder will provide information on the origins and spatial/temporal variability of proton seed particle populations. We will discuss the accuracy needed to make such measurements and describe how the results can be used to develop a capability for predicting the onset of Solar Energetic Particle (SEP) storms. The experiment is scheduled for a launch by the DoD Space Test Program in late 2018/early 2019 and should have excellent overlap with the Solar Orbiter and Solar Probe Plus missions.UVSC Pathfinder is supported by funds from the Chief of Naval Research (via the NRL basic research program) and from NASA (via NDPR NNG13WF951 and NNH16AC29I).

  15. The end-to-end testbed of the Optical Metrology System on-board LISA Pathfinder

    Steier, Frank; Marín, Antonio F García; Gerardi, Domenico; Heinzel, Gerhard; Danzmann, Karsten; 10.1088/0264-9381/26/9/094010

    2012-01-01

    LISA Pathfinder is a technology demonstration mission for the Laser Interferometer Space Antenna (LISA). The main experiment on-board LISA Pathfinder is the so-called LISA Technology Package (LTP) which has the aim to measure the differential acceleration between two free-falling test masses with an accuracy of 3x10^(-14) ms^(-2)/sqrt[Hz] between 1 mHz and 30 mHz. This measurement is performed interferometrically by the Optical Metrology System (OMS) on-board LISA Pathfinder. In this paper we present the development of an experimental end-to-end testbed of the entire OMS. It includes the interferometer and its sub-units, the interferometer back-end which is a phasemeter and the processing of the phasemeter output data. Furthermore, 3-axes piezo actuated mirrors are used instead of the free-falling test masses for the characterisation of the dynamic behaviour of the system and some parts of the Drag-free and Attitude Control System (DFACS) which controls the test masses and the satellite. The end-to-end testbe...

  16. Calpains mediate axonal cytoskeleton disintegration during Wallerian degeneration.

    Ma, Marek; Ferguson, Toby A; Schoch, Kathleen M; Li, Jian; Qian, Yaping; Shofer, Frances S; Saatman, Kathryn E; Neumar, Robert W

    2013-08-01

    In both the central nervous system (CNS) and peripheral nervous system (PNS), transected axons undergo Wallerian degeneration. Even though Augustus Waller first described this process after transection of axons in 1850, the molecular mechanisms may be shared, at least in part, by many human diseases. Early pathology includes failure of synaptic transmission, target denervation, and granular disintegration of the axonal cytoskeleton (GDC). The Ca(2+)-dependent protease calpains have been implicated in GDC but causality has not been established. To test the hypothesis that calpains play a causal role in axonal and synaptic degeneration in vivo, we studied transgenic mice that express human calpastatin (hCAST), the endogenous calpain inhibitor, in optic and sciatic nerve axons. Five days after optic nerve transection and 48 h after sciatic nerve transection, robust neurofilament proteolysis observed in wild-type controls was reduced in hCAST transgenic mice. Protection of the axonal cytoskeleton in sciatic nerves of hCAST mice was nearly complete 48 h post-transection. In addition, hCAST expression preserved the morphological integrity of neuromuscular junctions. However, compound muscle action potential amplitudes after nerve transection were similar in wild-type and hCAST mice. These results, in total, provide direct evidence that calpains are responsible for the morphological degeneration of the axon and synapse during Wallerian degeneration.

  17. Local erythropoietin signaling enhances regeneration in peripheral axons.

    Toth, C; Martinez, J A; Liu, W Q; Diggle, J; Guo, G F; Ramji, N; Mi, R; Hoke, A; Zochodne, D W

    2008-06-23

    Erythropoietin (EPO) and its receptor (EPO-R), mediate neuroprotection from axonopathy and apoptosis in the peripheral nervous system (PNS). We examined the impact and potential mechanisms of local EPO signaling on regenerating PNS axons in vivo and in vitro. As a consequence of injury, peripheral nerve axons and DRG neurons have a marked increase in the expression of EPO and EPO-R. Local delivery of EPO via conduit over 2 weeks to rat sciatic nerve following crush injury increased the density and maturity of regenerating myelinated axons growing distally from the crush site. In addition, EPO also rescued retrograde degeneration and atrophy of axons. EPO substantially increased the density and intensity of calcitonin gene-related peptide (CGRP) expression within outgrowing axons. Behavioral improvements in sensorimotor function also occurred in rats exposed to near nerve EPO delivery. EPO delivery led to decreased nuclear factor kappaB (NFkB) activation but increased phosphorylation of Akt and STAT3 within nerve and dorsal root ganglia neurons indicating rescue from an injury phenotype. Spinal cord explant studies also demonstrated a similar dose-dependent effect of EPO upon motor axonal outgrowth. Local EPO signaling enhances regenerating peripheral nervous system axons in addition to its known neuroprotection. Exogenous EPO may have a therapeutic role in a large number of peripheral nerve diseases through its impact on regeneration.

  18. Review of A* (A Star) Navigation Mesh Pathfinding as the Alternative of Artificial Intelligent for Ghosts Agent on the Pacman Game

    Moh. Zikky

    2016-01-01

    Shortest pathfinding problem has become a populer issue in Game’s Artificial Intelligent (AI). This paper discussed the effective way to optimize the shortest pathfinding problem, namely Navigation Mesh (NavMesh). This method is very interesting because it has a large area of implementation, especially in games world. In this paper, NavMesh was implemented by using A* (A star) algorithm and examined in Unity 3D game engine. A* was an effective algorithm in shortest pathfinding problem because...

  19. Axon guidance and neuronal migration research in China

    2010-01-01

    Proper migration of neuronal somas and axonal growth cones to designated locations in the developing brain is essential for the assembly of functional neuronal circuits.Rapid progress in research of axon guidance and neuronal migration has been made in the last twenty years.Chinese researchers began their exploration in this field ten years ago and have made significant contributions in clarifying the signal transduction of axon guidance and neuronal migration.Several unique experimental approaches,including the migration assay of single isolated neurons in response to locally delivered guidance cues,have been developed by Chinese neuroscientists to investigate the molecular machinery underlying these guidance events.

  20. Anti-forensics of chromatic aberration

    Mayer, Owen; Stamm, Matthew C.

    2015-03-01

    Over the past decade, a number of information forensic techniques have been developed to identify digital image manipulation and falsification. Recent research has shown, however, that an intelligent forger can use anti-forensic countermeasures to disguise their forgeries. In this paper, an anti-forensic technique is proposed to falsify the lateral chromatic aberration present in a digital image. Lateral chromatic aberration corresponds to the relative contraction or expansion between an image's color channels that occurs due to a lens's inability to focus all wavelengths of light on the same point. Previous work has used localized inconsistencies in an image's chromatic aberration to expose cut-and-paste image forgeries. The anti-forensic technique presented in this paper operates by estimating the expected lateral chromatic aberration at an image location, then removing deviations from this estimate caused by tampering or falsification. Experimental results are presented that demonstrate that our anti-forensic technique can be used to effectively disguise evidence of an image forgery.

  1. Assessing the construct validity of aberrant salience.

    Schmidt, Kristin; Roiser, Jonathan P

    2009-01-01

    We sought to validate the psychometric properties of a recently developed paradigm that aims to measure salience attribution processes proposed to contribute to positive psychotic symptoms, the Salience Attribution Test (SAT). The "aberrant salience" measure from the SAT showed good face validity in previous results, with elevated scores both in high-schizotypy individuals, and in patients with schizophrenia suffering from delusions. Exploring the construct validity of salience attribution variables derived from the SAT is important, since other factors, including latent inhibition/learned irrelevance (LIrr), attention, probabilistic reward learning, sensitivity to probability, general cognitive ability and working memory could influence these measures. Fifty healthy participants completed schizotypy scales, the SAT, a LIrr task, and a number of other cognitive tasks tapping into potentially confounding processes. Behavioural measures of interest from each task were entered into a principal components analysis, which yielded a five-factor structure accounting for approximately 75% of the variance in behaviour. Implicit aberrant salience was found to load onto its own factor, which was associated with elevated "Introvertive Anhedonia" schizotypy, replicating our previous finding. LIrr loaded onto a separate factor, which also included implicit adaptive salience, but was not associated with schizotypy. Explicit adaptive and aberrant salience, along with a measure of probabilistic learning, loaded onto a further factor, though this also did not correlate with schizotypy. These results suggest that the measures of LIrr and implicit adaptive salience might be based on similar underlying processes, which are dissociable both from implicit aberrant salience and explicit measures of salience.

  2. Optical advantages of astigmatic aberration corrected heliostats

    van Rooyen, De Wet; Schöttl, Peter; Bern, Gregor; Heimsath, Anna; Nitz, Peter

    2016-05-01

    Astigmatic aberration corrected heliostats adapt their shape in dependence of the incidence angle of the sun on the heliostat. Simulations show that this optical correction leads to a higher concentration ratio at the target and thus in a decrease in required receiver aperture in particular for smaller heliostat fields.

  3. [Aberrant pancreas with a double intestinal location].

    Yenon, K; Lethurgie, C; Bokobza, B

    2005-01-01

    The authors report one exceptional case of aberrant pancreas with a double intestinal location (jejunum and Meckel's diverticulum) in a thirty-year-old patient. Digestive haemorrhage and the abdominal colic were the revealing clinical signs. The enteroscopy guided by the enteroscanner, was the indicated complementary investigation for the preoperative diagnosis. The research of other locations during the operation should be systematic.

  4. Functional Analysis and Treatment of Aberrant Behavior.

    Mace, F. Charles; And Others

    1991-01-01

    This article reviews general classes of variables which help to maintain aberrant behavior including attention seeking, sensory and perceptual consequences, and access to materials or activities. Suggestions for a methodology providing a comprehensive functional analysis are offered which include descriptive analysis, hypothesis forming,…

  5. The correction of electron lens aberrations

    Hawkes, P.W., E-mail: peter.hawkes@cemes.fr

    2015-09-15

    The progress of electron lens aberration correction from about 1990 onwards is chronicled. Reasonably complete lists of publications on this and related topics are appended. A present for Max Haider and Ondrej Krivanek in the year of their 65th birthdays. By a happy coincidence, this review was completed in the year that both Max Haider and Ondrej Krivanek reached the age of 65. It is a pleasure to dedicate it to the two leading actors in the saga of aberration corrector design and construction. They would both wish to associate their colleagues with such a tribute but it is the names of Haider and Krivanek (not forgetting Joachim Zach) that will remain in the annals of electron optics, next to that of Harald Rose. I am proud to know that both regard me as a friend as well as a colleague. - Highlights: • Geometrical aberration correction. • Chromatic aberration correction. • 50 pm resolution. • High-resolution electron energy-loss spectroscopy. • Extensive bibliographies.

  6. Prenatal hydronephrosis caused by aberrant renal vessels

    Lenz, K; Thorup, Jørgen Mogens; Rabol, A;

    1996-01-01

    With routine use of obstetric ultrasonography, fetal low-grade hydronephrosis is commonly detected, but may resolve spontaneously after birth. Two cases are presented to illustrate that in some cases such findings can express intermittent hydronephrosis caused by aberrant renal vessels. Renal...

  7. Action potentials initiate in the axon initial segment and propagate through axon collaterals reliably in cerebellar Purkinje neurons.

    Foust, Amanda; Popovic, Marko; Zecevic, Dejan; McCormick, David A

    2010-05-19

    Purkinje neurons are the output cells of the cerebellar cortex and generate spikes in two distinct modes, known as simple and complex spikes. Revealing the point of origin of these action potentials, and how they conduct into local axon collaterals, is important for understanding local and distal neuronal processing and communication. By using a recent improvement in voltage-sensitive dye imaging technique that provided exceptional spatial and temporal resolution, we were able to resolve the region of spike initiation as well as follow spike propagation into axon collaterals for each action potential initiated on single trials. All fast action potentials, for both simple and complex spikes, whether occurring spontaneously or in response to a somatic current pulse or synaptic input, initiated in the axon initial segment. At discharge frequencies of less than approximately 250 Hz, spikes propagated faithfully through the axon and axon collaterals, in a saltatory manner. Propagation failures were only observed for very high frequencies or for the spikelets associated with complex spikes. These results demonstrate that the axon initial segment is a critical decision point in Purkinje cell processing and that the properties of axon branch points are adjusted to maintain faithful transmission.

  8. Structural plasticity of axon terminals in the adult.

    Gogolla, Nadine; Galimberti, Ivan; Caroni, Pico

    2007-10-01

    There is now conclusive evidence for widespread ongoing structural plasticity of presynaptic boutons and axon side-branches in the adult brain. The plasticity complements that of postsynaptic spines, but axonal plasticity samples larger volumes of neuropil, and has a larger impact on circuit remodeling. Axons from distinct neurons exhibit unique ratios of stable (t1/2>9 months) and dynamic (t1/2 5-20 days) boutons, which persist as spatially intermingled subgroups along terminal arbors. In addition, phases of side-branch dynamics mediate larger scale remodeling guided by synaptogenesis. The plasticity is most pronounced during critical periods; its patterns and outcome are controlled by Hebbian mechanisms and intrinsic neuronal factors. Novel experience, skill learning, life-style, and age can persistently modify local circuit structure through axonal structural plasticity.

  9. Sodium Channels, Mitochondria, and Axonal Degeneration in Peripheral Neuropathy.

    Persson, Anna-Karin; Hoeijmakers, Janneke G J; Estacion, Mark; Black, Joel A; Waxman, Stephen G

    2016-05-01

    Peripheral neuropathy results from damage to peripheral nerves and is often accompanied by pain in affected limbs. Treatment represents an unmet medical need and a thorough understanding of the mechanisms underlying axonal injury is needed. Longer nerve fibers tend to degenerate first (length-dependence), and patients carrying pathogenic mutations throughout life usually become symptomatic in mid- or late-life (time-dependence). The activity of voltage-gated sodium channels can contribute to axonal injury and sodium channel gain-of-function mutations have been linked to peripheral neuropathy. Recent studies have implicated sodium channel activity, mitochondrial compromise, and reverse-mode Na(+)/Ca(2+) exchange in time- and length-dependent axonal injury. Elucidation of molecular mechanisms underlying axonal injury in peripheral neuropathy may provide new therapeutic strategies for this painful and debilitating condition.

  10. Glycidol induces axonopathy and aberrations of hippocampal neurogenesis affecting late-stage differentiation by exposure to rats in a framework of 28-day toxicity study.

    Akane, Hirotoshi; Shiraki, Ayako; Imatanaka, Nobuya; Akahori, Yumi; Itahashi, Megu; Abe, Hajime; Shibutani, Makoto

    2014-01-30

    Developmental exposure to glycidol induces aberrations of late-stage neurogenesis in the hippocampal dentate gyrus of rat offspring, whereas maternal animals develop axonopathy. To investigate the possibility whether similar effects on adult neurogenesis could be induced by exposure in a framework of 28-day toxicity study, glycidol was orally administered to 5-week-old male Sprague-Dawley rats by gavage at 0, 30 or 200 mg/kg for 28 days. At 200 mg/kg, animals revealed progressively worsening gait abnormalities as well as histopathological and immunohistochemical changes suggestive of axonal injury as evidenced by generation of neurofilament-L(+) spheroids in the cerebellar granule layer and dorsal funiculus of the medulla oblongata, central chromatolysis in the trigeminal nerve ganglion cells and axonal degeneration in the sciatic nerves. At the same dose, animals revealed aberrations in neurogenesis at late-stage differentiation as evidenced by decreases of both doublecortin(+) and dihydropyrimidinase-like 3(+) cells in the subgranular zone (SGZ) and increased reelin(+) or calbindin-2(+) γ-aminobutyric acid-ergic interneurons and neuron-specific nuclear protein(+) mature neurons in the dentate hilus. These effects were essentially similar to that observed in offspring after maternal exposure to glycidol. These results suggest that glycidol causes aberrations in adult neurogenesis in the SGZ at the late stage involving the process of neurite extension similar to the developmental exposure study in a standard 28-day toxicity study.

  11. Morphology of axonal transport abnormalities in primate eyes.

    Radius, R L; Anderson, D R

    1981-11-01

    The ultrastructure of the retina and optic nerve head was studied in primate eyes after central retinal artery occlusion. Within 2 hours of the vascular occlusion the inner retinal layers undergo watery (isosmotic) swelling. This watery swelling of axons and astroglia extends into the nerve head as far back as the anterior boundary of the scleral lamina cribrosa. The swelling is increased 4 hours after the occlusion, and by 24 hours disintegration has occurred. At the optic nerve head mitochondria and vesicles of smooth endoplasmic reticulum begin to accumulate within 2 hours. The accumulation increases at 4 hours and persists to 24 hours. The watery swelling seems characteristic of ischaemic axons. Membranous organelles accumulate at the boundary of an ischaemic zone when material carried by axonal transport is brought via the healthy axon segment to the boundary, but they cannot proceed further into the ischaemic zone. Such accumulation is typical of locations where rapid orthograde axonal transport or retrograde axonal transport is blocked. In contrast, when slow axonal flow is impaired, the swelling is characterised by an excess of cytoplasmic gel without a marked accumulation of organelles. Rapid orthograde transport and retrograde transport seem to be closely related to one another, while slow axoplasmic flow seems fundamentally different. From morphological findings we suspect that, in experimental glaucoma, intraocular pressure first affects the intracellular physiological process of rapid orthograde and retrograde axonal transport. Watery swelling may not occur unless the ischaemic injury to cell metabolism is more advanced. In contrast, in experimental papilloedema, the swelling results predominantly from impaired slow axoplasmic flow.

  12. Modality-Specific Axonal Regeneration: Towards selective regenerative neural interfaces

    Parisa eLotfi

    2011-10-01

    Full Text Available Regenerative peripheral nerve interfaces have been proposed as viable alternatives for the natural control of robotic prosthetic devices. However, sensory and motor axons at the neural interface are of mixed submodality types, which difficult the specific recording from motor axons and the eliciting of precise sensory modalities through selective stimulation. Here we evaluated the possibility of using type-specific neurotrophins to preferentially entice the regeneration of defined axonal populations from transected peripheral nerves into separate compartments. Segregation of mixed sensory fibers from dorsal root ganglion neurons was evaluated in vitro by compartmentalized diffusion delivery of nerve growth factor (NGF and neurotrophin-3 (NT-3, to preferentially entice the growth of TrkA+ nociceptive and TrkC+ proprioceptive subsets of sensory neurons, respectively. The average axon length in the NGF channel increased 2.5 fold compared to that in saline or NT-3, whereas the number of branches increased 3 fold in the NT-3 channels. These results were confirmed using a 3-D Y-shaped in vitro assay showing that the arm containing NGF was able to entice a 5-fold increase in axonal length of unbranched fibers. To address if such segregation can be enticed in vivo, a Y-shaped tubing was used to allow regeneration of the transected adult rat sciatic nerve into separate compartments filled with either NFG or NT-3. A significant increase in the number of CGRP+ pain fibers were attracted towards the sural nerve, while N-52+ large diameter axons were observed in the tibial and NT-3 compartments. This study demonstrates the guided enrichment of sensory axons in specific regenerative chambers, and supports the notion that neurotrophic factors can be used to segregate sensory and perhaps motor axons in separate peripheral interfaces.

  13. Electrophysiology of a nonmyelinated glutamatergic axon in rat hippocampus

    Alle, Henrik

    2012-01-01

    The common theme of the presented work on the nonmyelinated hippocampal mossy fiber (the axon of the granule cell in the dentate gyrus) is the generation of subthreshold and suprathreshold electrical signals. Subthreshold depolarizations in the axon can occur due to passive propagation of excitatory postsynaptic potentials, which are generated in the somato-dendritic domain. The remote passive propagation of these comparatively slow but transient signals is due to a space constant...

  14. 6-Sulphated chondroitins have a positive influence on axonal regeneration.

    Rachel Lin

    Full Text Available Chondroitin sulphate proteoglycans (CSPGs upregulated in the glial scar inhibit axon regeneration via their sulphated glycosaminoglycans (GAGs. Chondroitin 6-sulphotransferase-1 (C6ST-1 is upregulated after injury leading to an increase in 6-sulphated GAG. In this study, we ask if this increase in 6-sulphated GAG is responsible for the increased inhibition within the glial scar, or whether it represents a partial reversion to the permissive embryonic state dominated by 6-sulphated glycosaminoglycans (GAGs. Using C6ST-1 knockout mice (KO, we studied post-injury changes in chondroitin sulphotransferase (CSST expression and the effect of chondroitin 6-sulphates on both central and peripheral axon regeneration. After CNS injury, wild-type animals (WT showed an increase in mRNA for C6ST-1, C6ST-2 and C4ST-1, but KO did not upregulate any CSSTs. After PNS injury, while WT upregulated C6ST-1, KO showed an upregulation of C6ST-2. We examined regeneration of nigrostriatal axons, which demonstrate mild spontaneous axon regeneration in the WT. KO showed many fewer regenerating axons and more axonal retraction than WT. However, in the PNS, repair of the median and ulnar nerves led to similar and normal levels of axon regeneration in both WT and KO. Functional tests on plasticity after the repair also showed no evidence of enhanced plasticity in the KO. Our results suggest that the upregulation of 6-sulphated GAG after injury makes the extracellular matrix more permissive for axon regeneration, and that the balance of different CSs in the microenvironment around the lesion site is an important factor in determining the outcome of nervous system injury.

  15. Fast and reliable identification of axons, axon initial segments and dendrites with local field potential recording

    Petersen, Anders V.; Johansen, Emil O.; Perrier, Jean-Francois

    2015-01-01

    The axon initial segment (AIS) is an essential neuronal compartment. It is usually where action potentials are initiated. Recent studies demonstrated that the AIS is a plastic structure that can be regulated by neuronal activity and by the activation of metabotropic receptors. Studying the AIS...... of neurons, we can detect sinks caused by inward currents flowing across the membrane. We determine the location of the AIS by comparing the timing of these events with the action potential. We demonstrate that this method allows the unequivocal identification of the AIS of different types of neurons from...

  16. A review of gigaxonin mutations in giant axonal neuropathy (GAN) and cancer.

    Kang, James J; Liu, Isabelle Y; Wang, Marilene B; Srivatsan, Eri S

    2016-07-01

    Gigaxonin, the product of GAN gene localized to chromosome 16, is associated with the early onset neuronal degeneration disease giant axonal neuropathy (GAN). Gigaxonin is an E3 ubiquitin ligase adaptor protein involved in intermediate filament processing in neural cells, and vimentin filaments in fibroblasts. Mutations of the gene cause pre-neural filaments to accumulate and form giant axons resulting in the inhibition of neural cell signaling. Analysis of the catalog of somatic mutations in cancer, driver DB and IDGC data portal databases containing 21,000 tumor genomic sequences has identified GAN patient mutations in cancer cell lines and primary tumors. The database search has also shown the presence of identical missense and nonsense gigaxonin mutations in GAN and colon cancer. These mutations frequently occur in the domains associated with protein homodimerization and substrate interaction such as Broad-Complex, Tramtrack and Bric a brac (BTB), BTB associated C-terminal KELCH (BACK), and KELCH repeats. Analysis of the International HapMap Project database containing 1200 normal genomic sequences has identified a single nucleotide polymorphism (SNP), rs2608555, in exon 8 of the gigaxonin sequence. While this SNP is present in >40 % of Caucasian population, it is present in less than 10 % of Japanese and Chinese populations. Although the role of gigaxonin polymorphism is not yet known, CFTR and MDR1 gene studies have shown that silent mutations play a role in the instability and aberrant splicing and folding of mRNAs. We believe that molecular and functional investigation of gigaxonin mutations including the exon 8 polymorphism could lead to an improved understanding of the relationship between GAN and cancer.

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

    White, Robin; Krämer-Albers, Eva-Maria

    2014-01-06

    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 specialized glial cells which ensheath axons with a lipid-rich insulating membrane. Myelination is a multi-step process initiated by axon-glia recognition triggering glial polarization 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 emphasizing the central role of the Src-family kinase Fyn during central nervous system (CNS) myelination. Furthermore, we discuss myelin membrane trafficking with particular focus on endocytic recycling and the control of proteolipid protein (PLP) transport by soluble N-ethylmaleimide-sensitive factor attachment protein receptor (SNARE) proteins. Finally, PLP mistrafficking is considered in the context of myelin diseases.

  18. Axon morphology at the lamina cribrosa in monkey eyes.

    Radius, R L; Klewin, K M

    1986-01-01

    The eyes of 8 monkeys (Aotus trivirgatus) were studied. The mean cross-section area and the least diameter of axon cylinders were calculated from measurements made by computer assisted planimetry of electron photomicrographs of sections through the optic nerve head at the level of the lamina cribrosa. The density of intrabundle connective tissue and glial cell elements in nerve fiber bundles was also calculated. The mean cross-section area and minimum diameter of axons in the temporal part were less than in the nasal part of the nerve. The values for axons in the superior and inferior parts of the nerve were intermediate. A similar pattern of increasing dimensions was seen in axons from the more axial nerve compared to neurons in the more circumferential nerve sectors. The density of the intrabundle, nonaxonal tissue elements did not differ significantly across the nerve. Although axon dimensions may play some role in defining the vulnerability of neuronal tissue to a pressure insult, the results of this anatomic investigation do not support the hypothesis that differences in axonal distribution by size across the nerve section define the regional vulnerability of the nerve head to elevated intraocular pressure.

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

    Robin eWhite

    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.

  20. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy.

    Sung, Jia-Ying; Tani, Jowy; Chang, Tsui-San; Lin, Cindy Shin-Yi

    2017-01-01

    This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (Pmotor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (Pdevelopment of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches.

  1. Ultrastructural observation of effect of moderate hypothermia on axonal damage in an animal model of diffuse axonal injury

    孙晓川; 唐文渊; 郑履平

    2002-01-01

    Objective: To investigate the effect of moderate hypothermia on responses of axonal cytoskeleton to axonal injury in the acute stage of injury. Methods: Of fifteen adult guinea pigs, twelve animals were subjected to stretch injury to the right optic nerves and divided into the normothermic group (n=6) in which the animal's core temperature was maintained at 36.0-37.5℃ and the hypothermia group (n=6) in which the core temperature was reduced to 32.0-32.5℃ after stretch injury. Remaining three animals sustained no injury to the right optic nerves and served as control group. Half of injured animals (n=3) of either normothermic group or hypothermic group were killed at either 2 hours or 4 hours after injury. The ultrastructural changes of axonal cytoskeleton of the right optic nerve fibers from the animals were examined under a transmission electron microscope and analyzed by quantitative analysis with a computer image analysis system. Results: At 2 hours after stretch injury, there was a significant reduction in the mean number of microtubules (P<0.001), and a significant increase in the mean intermicrotubule spacing (P<0.05 or P<0.01) in axons of all sizes in normothermic animals. The mean number of neurofilaments also decreased statistically (P<0.01) in large and medium subgroups of axons in the same experimental group at 2 hours. By 4 hours, the large subgroup of axons in normothermic animals still demonstrated a significant decline in the mean number of microtubules (P<0.01) and an increase in the mean intermicrotubule spacing (P<0.05), while the medium and small subgroups of axons displayed a significant increase in the mean number of neurofilaments (P<0.05) and reduction in the mean interneurofilament spacing (P<0.05). On the contrary, either the mean number of microtubules and the mean intermicrotubule spacing, or the mean number of neurofilaments and interneurofilament spacing in axons of all sizes in hypothermic stretch-injured animals was not

  2. White matter involvement after TBI: Clues to axon and myelin repair capacity.

    Armstrong, Regina C; Mierzwa, Amanda J; Marion, Christina M; Sullivan, Genevieve M

    2016-01-01

    Impact-acceleration forces to the head cause traumatic brain injury (TBI) with damage in white matter tracts comprised of long axons traversing the brain. White matter injury after TBI involves both traumatic axonal injury (TAI) and myelin pathology that evolves throughout the post-injury time course. The axon response to initial mechanical forces and secondary insults follows the process of Wallerian degeneration, which initiates as a potentially reversible phase of intra-axonal damage and proceeds to an irreversible phase of axon fragmentation. Distal to sites of axon disconnection, myelin sheaths remain for prolonged periods, which may activate neuroinflammation and inhibit axon regeneration. In addition to TAI, TBI can cause demyelination of intact axons. These evolving features of axon and myelin pathology also represent opportunities for repair. In experimental TBI, demyelinated axons exhibit remyelination, which can serve to both protect axons and facilitate recovery of function. Myelin remodeling may also contribute to neuroplasticity. Efficient clearance of myelin debris is a potential target to attenuate the progression of chronic pathology. During the early phase of Wallerian degeneration, interventions that prevent the transition from reversible damage to axon disconnection warrant the highest priority, based on the poor regenerative capacity of axons in the CNS. Clinical evaluation of TBI will need to address the challenge of accurately detecting the extent and stage of axon damage. Distinguishing the complex white matter changes associated with axons and myelin is necessary for interpreting advanced neuroimaging approaches and for identifying a broader range of therapeutic opportunities to improve outcome after TBI.

  3. Assessing the construct validity of aberrant salience

    Kristin Schmidt

    2009-12-01

    Full Text Available We sought to validate the psychometric properties of a recently developed paradigm that aims to measure salience attribution processes proposed to contribute to positive psychotic symptoms, the Salience Attribution Test (SAT. The “aberrant salience” measure from the SAT showed good face validity in previous results, with elevated scores both in high-schizotypy individuals, and in patients with schizophrenia suffering from delusions. Exploring the construct validity of salience attribution variables derived from the SAT is important, since other factors, including latent inhibition/learned irrelevance, attention, probabilistic reward learning, sensitivity to probability, general cognitive ability and working memory could influence these measures. Fifty healthy participants completed schizotypy scales, the SAT, a learned irrelevance task, and a number of other cognitive tasks tapping into potentially confounding processes. Behavioural measures of interest from each task were entered into a principal components analysis, which yielded a five-factor structure accounting for ~75% percent of the variance in behaviour. Implicit aberrant salience was found to load onto its own factor, which was associated with elevated “Introvertive Anhedonia” schizotypy, replicating our previous finding. Learned irrelevance loaded onto a separate factor, which also included implicit adaptive salience, but was not associated with schizotypy. Explicit adaptive and aberrant salience, along with a measure of probabilistic learning, loaded onto a further factor, though this also did not correlate with schizotypy. These results suggest that the measures of learned irrelevance and implicit adaptive salience might be based on similar underlying processes, which are dissociable both from implicit aberrant salience and explicit measures of salience.

  4. Cosmological parameter estimation: impact of CMB aberration

    Catena, Riccardo

    2012-01-01

    The peculiar motion of an observer with respect to the CMB rest frame induces an apparent deflection of the observed CMB photons, i.e. aberration, and a shift in their frequency, i.e. Doppler effect. Both effects distort the temperature multipoles a_lm's via a mixing matrix at any l. The common lore when performing a CMB based cosmological parameter estimation is to consider that Doppler affects only the l=1 multipole, and neglect any other corrections. In this paper we reconsider the validity of this assumption, showing that it is actually not robust when sky cuts are included to model CMB foreground contaminations. Assuming a simple fiducial cosmological model with five parameters, we simulated CMB temperature maps of the sky in a WMAP-like and in a Planck-like experiment and added aberration and Doppler effects to the maps. We then analyzed with a MCMC in a Bayesian framework the maps with and without aberration and Doppler effects in order to assess the ability of reconstructing the parameters of the fidu...

  5. [Familial, structural aberration of the Y chromosome with fertility disorders].

    Gall, H; Schmid, M; Schmidtke, J; Schempp, W; Weber, L

    1985-11-01

    Cytogenetic studies on a patient with Klinefelter's syndrome revealed an inherited, structural aberration of the Y-chromosome which has not been described before. The aberrant Y-chromosome was characterized by eight different banding methods. The value of individual staining techniques in studies on Y-heterochromatin aberrations is emphasized. Analysis of the cytogenetic studies (banding methods, restriction endonuclease of DNA, and measurement of the length of the Y-chromosome) permits an interpretation to be made on how the aberrant Y-chromosome originated. The functions of the Y-chromosome are discussed. The decrease in fertility (cryptozoospermia) in the two brothers with the same aberrant Y-chromosome was striking.

  6. The readout system and the trigger algorithm implementation for the UFFO Pathfinder

    Na, G. W.; Ahmad, S.; Barrillon, P.; Brandt, S.; Budtz-Jørgensen, C.; Castro-Tirado, A. J.; Chen, P.; Choi, Y. J.; Connell, P.; Dagoret-Campagne, S.; Eyles, C.; Grossan, B.; Huang, M.-H. A.; Jeong, S.; Jung, A.; Kim, J. E.; Kim, M. B.; Kim, S.-W.; Kim, Y. W.; Krasnov, Aleksey S.; Lee, J.; Lim, H.; Linder, E. V.; Liu, T.-C.; Lund, N.; Min, K. W.; Nam, J. W.; Park, I. H.; Panasyuk, M. I.; Ripa, J.; Reglero, V.; Rodrigo, J. M.; Smoot, G. F.; Suh, J. E.; Svertilov, S.; Vedenkin, N.; Wang, M.-Z.; Yashin, I.

    2012-09-01

    Since the launch of the SWIFT, Gamma-Ray Bursts (GRBs) science has been much progressed. Especially supporting many measurements of GRB events and sharing them with other telescopes by the Gamma-ray Coordinate Network (GCN) have resulted the richness of GRB events, however, only a few of GRB events have been measured within a minute after the gamma ray signal. This lack of sub-minute data limits the study for the characteristics of the UV-optical light curve of the short-hard type GRB and the fast-rising GRB. Therefore, we have developed the telescope named the Ultra-Fast Flash Observatory (UFFO) Pathfinder, to take the sub-minute data for the early photons from GRB. The UFFO Pathfinder has a coded-mask X-ray camera to search the GRB location by the UBAT trigger algorithm. To determine the direction of GRB as soon as possible it requires the fast processing. We have ultimately implemented all algorithms in field programmable gate arrays (FPGA) without microprocessor. Although FPGA, when compared with microprocessor, is generally estimated to support the fast processing rather than the complex processing, we have developed the implementation to overcome the disadvantage and to maximize the advantage. That is to measure the location as accurate as possible and to determine the location within the sub-second timescale. In the particular case for a accuracy of the X-ray trigger, it requires special information from the satellite based on the UFFO central control system. We present the implementation of the UBAT trigger algorithm as well as the readout system of the UFFO Pathfinder.

  7. Atomic Force Microscopy Reveals Important Differences in Axonal Resistance to Injury

    Magdesian, Margaret H.; Sanchez, Fernando S.; Lopez, Monserratt; Thostrup, Peter; Durisic, Nela; Belkaid, Wiam; Liazoghli, Dalinda; Grütter, Peter; Colman, David R.

    2012-01-01

    Axonal degeneration after traumatic brain injury and nerve compression is considered a common underlying cause of temporary as well as permanent disability. Because a proper functioning of neural network requires phase coherence of all components, even subtle changes in circuitry may lead to network failure. However, it is still not possible to determine which axons will recover or degenerate after injury. Several groups have studied the pressure threshold for axonal injury within a nerve, but difficulty accessing the injured region; insufficient imaging methods and the extremely small dimensions involved have prevented the evaluation of the response of individual axons to injury. We combined microfluidics with atomic force microscopy and in vivo imaging to estimate the threshold force required to 1), uncouple axonal transport without impairing axonal survival, and 2), compromise axonal survival in both individual and bundled axons. We found that rat hippocampal axons completely recover axonal transport with no detectable axonal loss when compressed with pressures up to 65 ± 30 Pa for 10 min, while dorsal root ganglia axons can resist to pressures up to 540 ± 220 Pa. We investigated the reasons for the differential susceptibility of hippocampal and DRG axons to mechanical injury and estimated the elasticity of live axons. We found that dorsal root ganglia axons have a 20% lower elastic modulus than hippocampal axons. Our results emphasize the importance of the integrity of the axonal cytoskeleton in deciding the axonal fate after damage and open up new avenues to improve injury diagnosis and to identify ways to protect axons. PMID:22947856

  8. Open access and knowledge sharing: reflections on the Pathfinder projects and Open Access Good Practice initiative

    Hannah DeGroff

    2016-07-01

    Full Text Available The following article provides a selection of reflections from a number of higher education institutions and their staff about participation in the UK-wide Pathfinder project scheme. These nine projects (comprising 30 institutions form the core of the Jisc-funded Open Access Good Practice initiative. They have produced a wide range of outputs which endorse and encourage best practice when implementing open access across institutions. Each project has a blog where progress and outputs can be tracked. Details are listed at the end of this article.

  9. Implications of Mars Pathfinder data for the accretion history of the terrestrial planets.

    Bertka, C M; Fei, Y

    1998-09-18

    Accretion models of the terrestrial planets often assume planetary bulk compositions with nonvolatile element abundance ratios equivalent to those of C1 carbonaceous chondrites. The moment of inertia factor of Mars reported by the Pathfinder team is inconsistent with a bulk planet C1 Fe/Si ratio or Fe content, which suggests that C1 chondrite accretion models are insufficient to explain the formation of Mars and the other terrestrial planets. Future planetary accretion models will have to account for variations in bulk Fe/Si ratios among the terrestrial planets.

  10. Towards a Framework for Generating Tests to Satisfy Complex Code Coverage in Java Pathfinder

    Staats, Matt

    2009-01-01

    We present work on a prototype tool based on the JavaPathfinder (JPF) model checker for automatically generating tests satisfying the MC/DC code coverage criterion. Using the Eclipse IDE, developers and testers can quickly instrument Java source code with JPF annotations covering all MC/DC coverage obligations, and JPF can then be used to automatically generate tests that satisfy these obligations. The prototype extension to JPF enables various tasks useful in automatic test generation to be performed, such as test suite reduction and execution of generated tests.

  11. Thermo-elastic induced phase noise in the LISA Pathfinder spacecraft

    Gibert, F; Nofrarias, M; Karnesis, N; Gesa, L.; Martín, V.; Mateos, I; Lobo, A; Flatscher, R.; Gerardi, D; Burkhardt, J.; Gerndt, R.; Robertson, D; Ward, H; McNamara, P; Guzman, F.

    2014-01-01

    During the On-Station Thermal Test campaign of the LISA Pathfinder the data and diagnostics subsystem was tested in nearly space conditions for the first time after integration in the satellite. The results showed the compliance of the temperature measurement system, obtaining temperature noise around $10^{-4}\\,{\\rm K}\\, {\\rm Hz}^{-1/2}$ in the frequency band of $1-30\\;{\\rm mHz}$. In addition, controlled injection of heat signals to the suspension struts anchoring the LISA Technology Package ...

  12. A New Approach in Agent Path-Finding using State Mark Gradients

    Florin Leon

    2005-01-01

    Full Text Available Since searching is one of the most important problem-solving methods, especially in Artificial Intelligence where it is often difficult to devise straightforward solutions, it has been given continuous attention by researchers. In this paper a new algorithm for agent path-finding is presented. Our approach is based on environment marking during exploration. We tested the performances of Q-learning and Learning Real-Time A* algorithm for three proposed mazes and then a comparison was made between our algorithm, two variants of Q-learning and LRTA* algorithm.

  13. DNA Repair Defects and Chromosomal Aberrations

    Hada, Megumi; George, K. A.; Huff, J. L.; Pluth, J. M.; Cucinotta, F. A.

    2009-01-01

    Yields of chromosome aberrations were assessed in cells deficient in DNA doublestrand break (DSB) repair, after exposure to acute or to low-dose-rate (0.018 Gy/hr) gamma rays or acute high LET iron nuclei. We studied several cell lines including fibroblasts deficient in ATM (ataxia telangiectasia mutated; product of the gene that is mutated in ataxia telangiectasia patients) or NBS (nibrin; product of the gene mutated in the Nijmegen breakage syndrome), and gliomablastoma cells that are proficient or lacking in DNA-dependent protein kinase (DNA-PK) activity. Chromosomes were analyzed using the fluorescence in situ hybridization (FISH) chromosome painting method in cells at the first division post irradiation, and chromosome aberrations were identified as either simple exchanges (translocations and dicentrics) or complex exchanges (involving >2 breaks in 2 or more chromosomes). Gamma irradiation induced greater yields of both simple and complex exchanges in the DSB repair-defective cells than in the normal cells. The quadratic dose-response terms for both simple and complex chromosome exchanges were significantly higher for the ATM- and NBS-deficient lines than for normal fibroblasts. However, in the NBS cells the linear dose-response term was significantly higher only for simple exchanges. The large increases in the quadratic dose-response terms in these repair-defective cell lines points the importance of the functions of ATM and NBS in chromatin modifications to facilitate correct DSB repair and minimize the formation of aberrations. The differences found between ATM- and NBS-deficient cells at low doses suggest that important questions should with regard to applying observations of radiation sensitivity at high dose to low-dose exposures. For aberrations induced by iron nuclei, regression models preferred purely linear dose responses for simple exchanges and quadratic dose responses for complex exchanges. Relative biological effectiveness (RBE) factors of all of

  14. Radiotherapeutical chromosomal aberrations in laryngeal cancer patients

    Stošić-Divjak Svetlana L.

    2009-01-01

    Full Text Available Introduction. The authors present the results of cytogenetic analysis of 21 patients with laryngeal carcinomas diagnosed and treated in the period 1995-2000 at the Institute of Otorhinolaryngology and Maxillofacial Surgery, Clinical Center of Serbia and Clinical Center of Novi Sad. Material and methods. The patients were specially monitored and the material was analyzed at the Institute of Human Genetics of the School of Medicine in Belgrade as well as in the Laboratory for Radiological Protection of the Institute of Occupational and Radiological Health 'Dr Dragomir Karajovic' in Belgrade. Results. The incidence of chromosomal aberrations and incidence of exchange of material between sister chromatids were observed in the preparation of the metaphasic lymphocyte chromosomes of the peripheral blood obtained in the culture. Structural aberrations were found on the chromosomes in the form of breakups, rings, translocations and dicentrics as early as after a single exposure of patients to tumor radiation dose of 2 Gy in the field sized 5x7. Out of the total number of 35 cultivated blood samples obtained from 13 patients, 21 were successfully cultivated and they were proved to contain chromosomal aberrations. Some of the peripheral blood samples failed to show cell growth in vitro due to the lethal cell damages in vivo. Discussion.. We have consluded that the number of structural aberrations cannot be used as a biological measure of the absorbed ionizing radiation dose. The presence of aberrations per se is indicative of the mutagenic effect of the ionizing radiation, which was also confirmed in our series on the original model by cultivation of the peripheral blood lymphocytes in the culture of the cells of the volunteer donors upon in vitro radiation. Using the method of bromdeoxyuridylreductase, the increased incidence of SCE as a mutagenic effect was registered. Conclusion. It has been concluded that the increase of absorbed radiation dose in

  15. Axonal synapses utilize multiple synaptic ribbons in the mammalian retina.

    Hong-Lim Kim

    Full Text Available In the mammalian retina, bipolar cells and ganglion cells which stratify in sublamina a of the inner plexiform layer (IPL show OFF responses to light stimuli while those that stratify in sublamina b show ON responses. This functional relationship between anatomy and physiology is a key principle of retinal organization. However, there are at least three types of retinal neurons, including intrinsically photosensitive retinal ganglion cells (ipRGCs and dopaminergic amacrine cells, which violate this principle. These cell types have light-driven ON responses, but their dendrites mainly stratify in sublamina a of the IPL, the OFF sublayer. Recent anatomical studies suggested that certain ON cone bipolar cells make axonal or ectopic synapses as they descend through sublamina a, thus providing ON input to cells which stratify in the OFF sublayer. Using immunoelectron microscopy with 3-dimensional reconstruction, we have identified axonal synapses of ON cone bipolar cells in the rabbit retina. Ten calbindin ON cone bipolar axons made en passant ribbon synapses onto amacrine or ganglion dendrites in sublamina a of the IPL. Compared to the ribbon synapses made by bipolar terminals, these axonal ribbon synapses were characterized by a broad postsynaptic element that appeared as a monad and by the presence of multiple short synaptic ribbons. These findings confirm that certain ON cone bipolar cells can provide ON input to amacrine and ganglion cells whose dendrites stratify in the OFF sublayer via axonal synapses. The monadic synapse with multiple ribbons may be a diagnostic feature of the ON cone bipolar axonal synapse in sublamina a. The presence of multiple ribbons and a broad postsynaptic density suggest these structures may be very efficient synapses. We also identified axonal inputs to ipRGCs with the architecture described above.

  16. Chromatic variation of aberration: the role of induced aberrations and raytrace direction

    Berner, A.; Nobis, T.; Shafer, D.; Gross, H.

    2015-09-01

    The design and optimization process of an optical system contains several first order steps. The definition of the appropriate lens type and the fixation of the raytrace direction are some of them. The latter can be understood as a hidden assumption rather than an aware design step. This is usually followed by the determination of the paraxial lens layout calculated for the primary wavelength. It is obvious, that for this primary wavelength the paraxial calculations are independent of raytrace direction. Today, most of the lens designs are specified not to work only for one wavelength, but in a certain wavelength range. Considering such rays of other wavelengths, one can observe that depending on the direction there will already occur differences in the first order chromatic aberrations and additionally in the chromatic variation of the third-order aberrations. The reason for this effect are induced aberrations emerging from one surface to the following surfaces by perturbed ray heights and ray angles. It can be shown, that the total amount of surface-resolved first order chromatic aberrations and the chromatic variation of the five primary aberrations can be split into an intrinsic part and an induced part. The intrinsic part is independent of the raytrace direction whereas the induced part is not.

  17. Nodal aberration theory for wild-filed asymmetric optical systems

    Chen, Yang; Cheng, Xuemin; Hao, Qun

    2016-10-01

    Nodal Aberration Theory (NAT) was used to calculate the zero field position in Full Field Display (FFD) for the given aberration term. Aiming at wide-filed non-rotational symmetric decentered optical systems, we have presented the nodal geography behavior of the family of third-order and fifth-order aberrations. Meanwhile, we have calculated the wavefront aberration expressions when one optical element in the system is tilted, which was not at the entrance pupil. By using a three-piece-cellphone lens example in optical design software CodeV, the nodal geography is testified under several situations; and the wavefront aberrations are calculated when the optical element is tilted. The properties of the nodal aberrations are analyzed by using Fringe Zernike coefficients, which are directly related with the wavefront aberration terms and usually obtained by real ray trace and wavefront surface fitting.

  18. Myelinated sensory and alpha motor axon regeneration in peripheral nerve neuromas

    Macias, M. Y.; Lehman, C. T.; Sanger, J. R.; Riley, D. A.

    1998-01-01

    Histochemical staining for carbonic anhydrase and cholinesterase (CE) activities was used to analyze sensory and motor axon regeneration, respectively, during neuroma formation in transected and tube-encapsulated peripheral nerves. Median-ulnar and sciatic nerves in the rodent model permitted testing whether a 4 cm greater distance of the motor neuron soma from axotomy site or intrinsic differences between motor and sensory neurons influenced regeneration and neuroma formation 10, 30, and 90 days later. Ventral root radiculotomy confirmed that CE-stained axons were 97% alpha motor axons. Distance significantly delayed axon regeneration. When distance was negligible, sensory axons grew out sooner than motor axons, but motor axons regenerated to a greater quantity. These results indicate regeneration differences between axon subtypes and suggest more extensive branching of motor axons within the neuroma. Thus, both distance from injury site to soma and inherent motor and sensory differences should be considered in peripheral nerve repair strategies.

  19. Schwann cell-derived exosomes enhance axonal regeneration in the peripheral nervous system.

    Lopez-Verrilli, María Alejandra; Picou, Frederic; Court, Felipe A

    2013-11-01

    Axonal regeneration in the peripheral nervous system is greatly supported by Schwann cells (SCs). After nerve injury, SCs dedifferentiate to a progenitor-like state and efficiently guide axons to their original target tissues. Contact and soluble factors participate in the crosstalk between SCs and axons during axonal regeneration. Here we show that dedifferentiated SCs secrete nano-vesicles known as exosomes which are specifically internalized by axons. Surprisingly, SC-derived exosomes markedly increase axonal regeneration in vitro and enhance regeneration after sciatic nerve injury in vivo. Exosomes shift the growth cone morphology to a pro-regenerating phenotype and decrease the activity of the GTPase RhoA, involved in growth cone collapse and axon retraction. Altogether, our work identifies a novel mechanism by which SCs communicate with neighboring axons during regenerative processes. We propose that SC exosomes represent an important mechanism by which these cells locally support axonal maintenance and regeneration after nerve damage.

  20. Subtypes of GABAergic neurons project axons in the neocortex

    Shigeyoshi Higo

    2009-11-01

    Full Text Available γ-aminobutyric acid (GABAergic neurons in the neocortex have been regarded as interneurons and speculated to modulate the activity of neurons locally. Recently, however, several experiments revealed that neuronal nitric oxide synthase (nNOS-positive GABAergic neurons project cortico-cortically with long axons. In this study, we illustrate Golgi-like images of the nNOS-positive GABAergic neurons using a nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d reaction and follow the emanating axon branches in cat brain sections. These axon branches projected cortico-cortically with other non-labeled arcuate fibers, contra-laterally via the corpus callosum and anterior commissure. The labeled fibers were not limited to the neocortex but found also in the fimbria of the hippocampus. In order to have additional information on these GABAergic neuron projections, we investigated green fluorescent protein (GFP-labeled GABAergic neurons in GAD67-Cre knock-in / GFP Cre-reporter mice. GFP-labeled axons emanate densely, especially in the fimbria, a small number in the anterior commissure, and very sparsely in the corpus callosum. These two different approaches confirm that not only nNOS-positive GABAergic neurons but also other subtypes of GABAergic neurons project long axons in the cerebral cortex and are in a position to be involved in information processing.

  1. A novel technique using hydrophilic polymers to promote axonal fusion

    Ravinder Bamba

    2016-01-01

    Full Text Available The management of traumatic peripheral nerve injury remains a considerable concern for clinicians. With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve injury, outcomes of surgical intervention have been unpredictable. The inability to manipulate the pathophysiology of nerve injury (i.e., Wallerian degeneration has left scientists and clinicians depending on the slow and lengthy process of axonal regeneration (~1 mm/day. When axons are severed, the endings undergo calcium-mediated plasmalemmal sealing, which limits the ability of the axon to be primarily repaired. Polythethylene glycol (PEG in combination with a bioengineered process overcomes the inability to fuse axons. The mechanism for PEG axonal fusion is not clearly understood, but multiple studies have shown that a providing a calcium-free environment is essential to the process known as PEG fusion. The proposed mechanism is PEG-induced lipid bilayer fusion by removing the hydration barrier surrounding the axolemma and reducing the activation energy required for membrane fusion to occur. This review highlights PEG fusion, its past and current studies, and future directions in PEG fusion.

  2. A novel technique using hydrophilic polymers to promote axonal fusion

    Ravinder Bamba; D Colton Riley; Nathaniel D Kelm; Mark D Does; Richard D Dortch; Wesley P hTayer

    2016-01-01

    The management of traumatic peripheral nerve injury remains a considerable concern for clinicians. With minimal innovations in surgical technique and a limited number of specialists trained to treat peripheral nerve injury, outcomes of surgical intervention have been unpredictable. The inability to manipulate the pathophysiology of nerve injury (i.e., Wallerian degeneration) has left scientists and clinicians depending on the slow and lengthy process of axonal regeneration (~1 mm/day). When axons are severed, the endings undergo calcium-mediated plasmalemmal sealing, which limits the ability of the axon to be primarily re-paired. Polythethylene glycol (PEG) in combination with a bioengineered process overcomes the inability to fuse axons. The mechanism for PEG axonal fusion is not clearly understood, but multiple studies have shown that a providing a calcium-free environment is essential to the process known as PEG fusion. The proposed mechanism is PEG-induced lipid bilayer fusion by removing the hydration barrier surrounding the axolemma and reducing the activation energy required for membrane fusion to occur. This review highlights PEG fusion, its past and current studies, and future directions in PEG fusion.

  3. Calpain Inhibition Reduces Axolemmal Leakage in Traumatic Axonal Injury

    János Sándor

    2009-12-01

    Full Text Available Calcium-induced, calpain-mediated proteolysis (CMSP has recently been implicated to the pathogenesis of diffuse (traumatic axonal injury (TAI. Some studies suggested that subaxolemmal CMSP may contribute to axolemmal permeability (AP alterations observed in TAI. Seeking direct evidence for this premise we investigated whether subaxolemmal CMSP may contribute to axolemmal permeability alterations (APA and pre-injury calpain-inhibition could reduce AP in a rat model of TAI. Horseradish peroxidase (HRP, a tracer that accumulates in axons with APA was administered one hour prior to injury into the lateral ventricle; 30 min preinjury a single tail vein bolus injection of 30 mg/kg MDL-28170 (a calpain inhibitor or its vehicle was applied in Wistar rats exposed to impact acceleration brain injury. Histological detection of traumatically injured axonal segments accumulating HRP and statistical analysis revealed that pre-injury administration of the calpain inhibitor MDL-28170 significantly reduced the average length of HRP-labeled axonal segments. The axono-protective effect of pre-injury calpain inhibition recently demonstrated with classical immunohistochemical markers of TAI was further corroborated in this experiment; significant reduction of the length of labeled axons in the drug-treated rats implicate CMSP in the progression of altered AP in TAI.

  4. Improving Markov Chain Monte Carlo algorithms in LISA Pathfinder Data Analysis

    Karnesis, N.; Nofrarias, M.; Sopuerta, C. F.; Lobo, A.

    2012-06-01

    The LISA Pathfinder mission (LPF) aims to test key technologies for the future LISA mission. The LISA Technology Package (LTP) on-board LPF will consist of an exhaustive suite of experiments and its outcome will be crucial for the future detection of gravitational waves. In order to achieve maximum sensitivity, we need to have an understanding of every instrument on-board and parametrize the properties of the underlying noise models. The Data Analysis team has developed algorithms for parameter estimation of the system. A very promising one implemented for LISA Pathfinder data analysis is the Markov Chain Monte Carlo. A series of experiments are going to take place during flight operations and each experiment is going to provide us with essential information for the next in the sequence. Therefore, it is a priority to optimize and improve our tools available for data analysis during the mission. Using a Bayesian framework analysis allows us to apply prior knowledge for each experiment, which means that we can efficiently use our prior estimates for the parameters, making the method more accurate and significantly faster. This, together with other algorithm improvements, will lead us to our main goal, which is no other than creating a robust and reliable tool for parameter estimation during the LPF mission.

  5. Visualizing Mars Using Virtual Reality: A State of the Art Mapping Technique Used on Mars Pathfinder

    Stoker, C.; Zbinden, E.; Blackmon, T.; Nguyen, L.

    1999-01-01

    We describe an interactive terrain visualization system which rapidly generates and interactively displays photorealistic three-dimensional (3-D) models produced from stereo images. This product, first demonstrated in Mars Pathfinder, is interactive, 3-D, and can be viewed in an immersive display which qualifies it for the name Virtual Reality (VR). The use of this technology on Mars Pathfinder was the first use of VR for geologic analysis. A primary benefit of using VR to display geologic information is that it provides an improved perception of depth and spatial layout of the remote site. The VR aspect of the display allows an operator to move freely in the environment, unconstrained by the physical limitations of the perspective from which the data were acquired. Virtual Reality offers a way to archive and retrieve information in a way that is intuitively obvious. Combining VR models with stereo display systems can give the user a sense of presence at the remote location. The capability, to interactively perform measurements from within the VR model offers unprecedented ease in performing operations that are normally time consuming and difficult using other techniques. Thus, Virtual Reality can be a powerful a cartographic tool. Additional information is contained in the original extended abstract.

  6. ERASMUS-F: pathfinder for an E-ELT 3D instrumentation

    Kelz, Andreas; Roth, Martin M.; Bacon, Roland; Bland-Hawthorn, Joss; Nicklas, Harald E.; Bryant, Julia J.; Colless, Matthew; Croom, Scott; Ellis, Simon; Fleischmann, Andreas; Gillingham, Peter; Haynes, Roger; Hopkins, Andrew; Kosmalski, Johan; O'Byrne, John W.; Olaya, Jean-Christophe; Rambold, William N.; Robertson, Gordon

    2010-07-01

    ERASMUS-F is a pathfinder study for a possible E-ELT 3D-instrumentation, funded by the German Ministry for Education and Research (BMBF). The study investigates the feasibility to combine a broadband optical spectrograph with a new generation of multi-object deployable fibre bundles. The baseline approach is to modify the spectrograph of the Multi-Unit Spectroscopic Explorer (MUSE), which is a VLT integral-field instrument using slicers, with a fibre-fed input. Taking advantage of recent developments in astrophotonics, it is planed to equip such an instrument with fused fibre bundles (hexabundles) that offer larger filling factors than dense-packed classical fibres. The overall project involves an optical and mechanical design study, the specifications of a software package for 3Dspectrophotometry, based upon the experiences with the P3d Data Reduction Software and an investigation of the science case for such an instrument. As a proof-of-concept, the study also involves a pathfinder instrument for the VLT, called the FIREBALL project.

  7. A torsion pendulum test of the Lisa Pathfinder free-fall mode

    Russano, Giuliana; Dolesi, Rita; Cavalleri, Antonella; Hueller, Mauro; Vitale, Stefano; Weber, William Joseph; Tu, HaiBo

    The LISA Pathfinder geodesic explorer mission for gravitational wave astronomy aims to demonstrate the proof of a low acceleration noise level. The relative acceleration between two test masses free falling in orbit is perturbed by the presence of a larger constant relative acceleration that must be actively compensated in order to keep the test particles centered inside an orbiting apparatus. The actuation force applied to compensate this effect introduces a dominant source of force noise. To suppress this noise source, a “free-fall” actuation control scheme has been designed: actuation is limited to brief impulses, with test masses in free fall in between two “kicks”, with this actuation-free motion then analyzed for the remaining sources of acceleration ultra noise. In this work, we will discuss and present preliminary data for an on-ground torsion pendulum experiment to test this technique, and the associated analysis algorithms, at a level nearing the sub-femto-g/sqrt(Hz) performance required for LISA Pathfinder.

  8. Coupling characterization and noise studies of the optical metrology system onboard the LISA Pathfinder mission.

    Hechenblaikner, Gerald; Gerndt, Rüdiger; Johann, Ulrich; Luetzow-Wentzky, Peter; Wand, Vinzenz; Audley, Heather; Danzmann, Karsten; Garcia-Marin, Antonio; Heinzel, Gerhard; Nofrarias, Miquel; Steier, Frank

    2010-10-10

    We describe the first investigations of the complete engineering model of the optical metrology system (OMS), a key subsystem of the LISA Pathfinder science mission to space. The latter itself is a technological precursor mission to LISA, a spaceborne gravitational wave detector. At its core, the OMS consists of four heterodyne Mach-Zehnder interferometers, a highly stable laser with an external modulator, and a phase meter. It is designed to monitor and track the longitudinal motion and attitude of two floating test masses in the optical reference frame with (relative) precision in the picometer and nanorad range, respectively. We analyze sensor signal correlations and determine a physical sensor noise limit. The coupling parameters between motional degrees of freedom and interferometer signals are analytically derived and compared to measurements. We also measure adverse cross-coupling effects originating from system imperfections and limitations and describe algorithmic mitigation techniques to overcome some of them. Their impact on system performance is analyzed within the context of the Pathfinder mission.

  9. Relevance and feasibility of Diagnostics Subsystems in LISA PathFinder and LISA

    Lobo, Alberto; Grimani, Catia; Canizares, Priscilla; Chmeissani, Mokhtar; Diaz-Aguilo, Marc; Conchillo, Aleix; Gesa, Lluis; Lloro, Ivan; Mateos, Ignacio; Nofrarias, Miquel; Ramos-Castro, Juan; Sanjuan, Josep; Sopuerta, Carlos

    LISA PathFinder will fly equipped with a Diagnostics Subsystem which includes: 1) a Radi-ation Monitor, providing almost real time charged particle counting and spectral resolution, 2) a thermal diagnostics set with high sensitivity temperature sensors and precision heaters, and 3) four fluxgate vector magnetometers plus a pair of induction coils. The role of this in-strumentation in LISA PathFinder is to provide the necessary tools to evaluate the effect of charging, temperature and magnetic fluctuations on the interferometer readout. The use of this is to understand how the mentioned fluctuations in the LTP (LISA Technology Package) can be modelled, then use the measured data to quantify their contribution to the overall LTP noise. In this presentation we will review the LPF Diagnostics System, recently delivered for LTP and spacecraft integration. We will also make some considerations on the meaning of the diagnostics for the future LISA, and propose lines of action to meet the more severe requirements which LISA will impose on environmental conditions.

  10. Wavefront aberrations of x-ray dynamical diffraction beams.

    Liao, Keliang; Hong, Youli; Sheng, Weifan

    2014-10-01

    The effects of dynamical diffraction in x-ray diffractive optics with large numerical aperture render the wavefront aberrations difficult to describe using the aberration polynomials, yet knowledge of them plays an important role in a vast variety of scientific problems ranging from optical testing to adaptive optics. Although the diffraction theory of optical aberrations was established decades ago, its application in the area of x-ray dynamical diffraction theory (DDT) is still lacking. Here, we conduct a theoretical study on the aberration properties of x-ray dynamical diffraction beams. By treating the modulus of the complex envelope as the amplitude weight function in the orthogonalization procedure, we generalize the nonrecursive matrix method for the determination of orthonormal aberration polynomials, wherein Zernike DDT and Legendre DDT polynomials are proposed. As an example, we investigate the aberration evolution inside a tilted multilayer Laue lens. The corresponding Legendre DDT polynomials are obtained numerically, which represent balanced aberrations yielding minimum variance of the classical aberrations of an anamorphic optical system. The balancing of classical aberrations and their standard deviations are discussed. We also present the Strehl ratio of the primary and secondary balanced aberrations.

  11. Chromosomal aberrations in ISS crew members

    Johannes, Christian; Goedecke, Wolfgang; Antonopoulos, Alexandra

    2012-07-01

    High energy radiation is a major risk factor in manned space missions. Astronauts and cosmonauts are exposed to ionising radiations of cosmic and solar origin, while on the Earth's surface people are well protected by the atmosphere and a deflecting magnetic field. There are now data available describing the dose and the quality of ionising radiation on-board of the International Space Station (ISS). Nonetheless, the effect of increased radiation dose on mutation rates of ISS crew members are hard to predict. Therefore, direct measurements of mutation rates are required in order to better estimate the radiation risk for longer duration missions. The analysis of chromosomal aberrations in peripheral blood lymphocytes is a well established method to measure radiation-induced mutations. We present data of chromosome aberration analyses from lymphocyte metaphase spreads of ISS crew members participating in short term (10-14 days) or long term (around 6 months) missions. From each subject we received two blood samples. The first sample was drawn about 10 days before launch and a second one within 3 days after return from flight. From lymphocyte cultures metaphase plates were prepared on glass slides. Giemsa stained and in situ hybridised metaphases were scored for chromosome changes in pre-flight and post-flight blood samples and the mutation rates were compared. Results obtained in chromosomal studies on long-term flight crew members showed pronounced inter-individual differences in the response to elevated radiation levels. Overall slight but significant elevations of typical radiation induced aberrations, i.e., dicentric chromosomes and reciprocal translocations have been observed. Our data indicate no elevation of mutation rates due to short term stays on-board the ISS.

  12. Aberrations in Fresnel Lenses and Mirrors

    Gregory, Don

    1999-01-01

    The NASA/MSFC Shooting Star program revealed a number of technical problems that must be solved before solar thermal propulsion can become a reality. The fundamental problem of interest here is the collection of solar energy. This is the first step in the propulsion process and indeed the most important. Everything else depends on the efficiency and focusing ability of the collection lens or mirror. An initial model of Fresnel lens behavior using a wave optics approach has been completed and the results were encouraging enough to warrant an experimental investigation. This experimental investigation confirmed some of the effects predicted and produced invaluable photographic evidence of coherence based diffraction and aberration.

  13. Neurofilament proteins in axonal regeneration and neurodegenerative diseases

    Haitao Wang; Minfei Wu; Chuanjun Zhan; Enyuan Ma; Maoguang Yang; Xiaoyu Yang; Yingpu Li

    2012-01-01

    Neurofilament protein is a component of the mature neuronal cytoskeleton, and it interacts with the zygosome, which is mediated by neurofilament-related proteins. Neurofilament protein regulates enzyme function and the structure of linker proteins. In addition, neurofilament gene expression plays an important role in nervous system development. Previous studies have shown that neurofilament gene transcriptional regulation is crucial for neurofilament protein expression, especially in axonal regeneration and degenerative diseases. Post-transcriptional regulation increased neurofilament protein gene transcription during axonal regeneration, ultimately resulting in a pattern of neurofilament protein expression. An expression imbalance of post-transcriptional regulatory proteins and other disorders could lead to amyotrophic lateral sclerosis or other neurodegenerative diseases. These findings indicated that after transcription, neurofilament protein regulated expression of related proteins and promoted regeneration of damaged axons, suggesting that regulation disorders could lead to neurodegenerative diseases.

  14. Pili canaliculi as manifestation of giant axonal neuropathy*

    de Almeida Jr., Hiram Larangeira; Garcias, Gilberto; Silva, Ricardo Marques e; Batista, Stela Laner; Pasetto, Fernanda

    2016-01-01

    Giant axonal neuropathy is a rare autosomal recessive neurodegenerative disease. The condition is characterized by neurons with abnormally large axons due to intracellular filament accumulation. The swollen axons affect both the peripheral and central nervous system. A 6-year old female patient had been referred to a geneticist reporting problems with walking and hypotonia. At the age of 10, she became wheelchair dependent. Scanning electron microscopy of a curly hair classified it as pili canaliculi. GAN gene sequencing demonstrated mutation c.1456G>A (p.GLU486LYS). At the age of 12, the patient died due to respiratory complications. Dermatologists should be aware of this entity since hair changes are considered suggestive of GAN.

  15. Using quantum filters to process images of diffuse axonal injury

    Pineda Osorio, Mateo

    2014-06-01

    Some images corresponding to a diffuse axonal injury (DAI) are processed using several quantum filters such as Hermite Weibull and Morse. Diffuse axonal injury is a particular, common and severe case of traumatic brain injury (TBI). DAI involves global damage on microscopic scale of brain tissue and causes serious neurologic abnormalities. New imaging techniques provide excellent images showing cellular damages related to DAI. Said images can be processed with quantum filters, which accomplish high resolutions of dendritic and axonal structures both in normal and pathological state. Using the Laplacian operators from the new quantum filters, excellent edge detectors for neurofiber resolution are obtained. Image quantum processing of DAI images is made using computer algebra, specifically Maple. Quantum filter plugins construction is proposed as a future research line, which can incorporated to the ImageJ software package, making its use simpler for medical personnel.

  16. Uncovering sensory axonal dysfunction in asymptomatic type 2 diabetic neuropathy

    Sung, Jia-Ying; Tani, Jowy; Chang, Tsui-San; Lin, Cindy Shin-Yi

    2017-01-01

    This study investigated sensory and motor nerve excitability properties to elucidate the development of diabetic neuropathy. A total of 109 type 2 diabetes patients were recruited, and 106 were analyzed. According to neuropathy severity, patients were categorized into G0, G1, and G2+3 groups using the total neuropathy score-reduced (TNSr). Patients in the G0 group were asymptomatic and had a TNSr score of 0. Sensory and motor nerve excitability data from diabetic patients were compared with data from 33 healthy controls. Clinical assessment, nerve conduction studies, and sensory and motor nerve excitability testing data were analyzed to determine axonal dysfunction in diabetic neuropathy. In the G0 group, sensory excitability testing revealed increased stimulus for the 50% sensory nerve action potential (P<0.05), shortened strength-duration time constant (P<0.01), increased superexcitability (P<0.01), decreased subexcitability (P<0.05), decreased accommodation to depolarizing current (P<0.01), and a trend of decreased accommodation to hyperpolarizing current in threshold electrotonus. All the changes progressed into G1 (TNSr 1–8) and G2+3 (TNSr 9–24) groups. In contrast, motor excitability only had significantly increased stimulus for the 50% compound motor nerve action potential (P<0.01) in the G0 group. This study revealed that the development of axonal dysfunction in sensory axons occurred prior to and in a different fashion from motor axons. Additionally, sensory nerve excitability tests can detect axonal dysfunction even in asymptomatic patients. These insights further our understanding of diabetic neuropathy and enable the early detection of sensory axonal abnormalities, which may provide a basis for neuroprotective therapeutic approaches. PMID:28182728

  17. Giant Axonal Neuropathy Among Two Siblings - A Case Report

    John Jhon. K

    2001-01-01

    Full Text Available Giant axonal neuropathy is a rate disorder with an autosomal recessive inheritance. It should be differentiated from toxic neuropathies, and hereditary degenerative disorders of nervous system like Friedreich′s ataxia and HMSN. Thick curly hair, though may not be present always is a useful clinical clue to identify cases. Prognosis is generally poor though course of the illness is variable. We report here a clinically and hisopathologically characteristic familial case of giant axonal neuropathy, which occurred in a 17-year-old boy, and his 21-year-old sister.

  18. Aberration measurement from specific photolithographic images: a different approach.

    Nomura, H; Tawarayama, K; Kohno, T

    2000-03-01

    Techniques for measurement of higher-order aberrations of a projection optical system in photolithographic exposure tools have been established. Even-type and odd-type aberrations are independently obtained from printed grating patterns on a wafer by three-beam interference under highly coherent illumination. Even-type aberrations, i.e., spherical aberration and astigmatism, are derived from the best focus positions of vertical, horizontal, and oblique grating patterns by an optical microscope. Odd-type aberrations, i.e., coma and three-foil, are obtained by detection of relative shifts of a fine grating pattern to a large pattern by an overlay inspection tool. Quantitative diagnosis of lens aberrations with a krypton fluoride (KrF) excimer laser scanner is demonstrated.

  19. AVHRR Pathfinder version 5.3 level 3 collated (L3C) global 4km sea surface temperature

    National Oceanic and Atmospheric Administration, Department of Commerce — The AVHRR Pathfinder Version 5.3 (PFV53) L3C Sea Surface Temperature data set is a collection of global, twice-daily (Day and Night) 4km sea surface temperature...

  20. Mars Pathfinder

    Murdin, P.

    2000-11-01

    First of NASA's Discovery missions. Launched in December 1996 and arrived at Mars on 4 July 1997. Mainly intended as a technology demonstration mission. Used airbags to cushion the landing on Mars. The Carl Sagan Memorial station returned images of an ancient flood plain in Ares Vallis. The 10 kg Sojourner rover used an x-ray spectrometer to study the composition of rocks and travelled about 100 ...

  1. Calibration and removal of lateral chromatic aberration in images

    Mallon, John; Whelan, Paul F.

    2007-01-01

    This paper addresses the problem of compensating for lateral chromatic aberration in digital images through colour plane realignment. Two main contributions are made: the derivation of a model for lateral chromatic aberration in images, and the subsequent calibration of this model from a single view of a chess pattern. These advances lead to a practical and accurate alternative for the compensation of lateral chromatic aberrations. Experimental results validate the proposed models and calibra...

  2. Correcting Aberrations in Complex Magnet Systems for Muon Cooling Channels

    J.A. Maloney, B. Erdelyi, A. Afanaciev, R.P. Johnson, Y.S. Derbenev, V.S. Morozov

    2011-03-01

    Designing and simulating complex magnet systems needed for cooling channels in both neutrino factories and muon colliders requires innovative techniques to correct for both chromatic and spherical aberrations. Optimizing complex systems, such as helical magnets for example, is also difficult but essential. By using COSY INFINITY, a differential algebra based code, the transfer and aberration maps can be examined to discover what critical terms have the greatest influence on these aberrations.

  3. Regulation of Axonal Midline Guidance by Prolyl 4-Hydroxylation in Caenorhabditis elegans

    Torpe, Nanna; Pocock, Roger David John

    2014-01-01

    Neuronal wiring during development requires that the growth cones of axons and dendrites are correctly guided to their appropriate targets. As in other animals, axon growth cones in Caenorhabditis elegans integrate information in their extracellular environment via interactions among transiently...

  4. Rapid axonal transport in primate optic nerve. Distribution of pressure-induced interruption.

    Radius, R L; Anderson, D R

    1981-04-01

    Six primate eyes were studied after four hours of elevated intraocular pressure. Tissue specimens from the region of the lamina cribrosa were examined in cross section by transmission electron microscopy. Interruption in fast orthograde and retrograde axonal transport was identified in individual axons by noting accumulation of membraneous microorganelles, such as mitochondria and microvesicles within axon cylinders. Although organelle accumulation varied from bundle to bundle, involvement of individual axons was diffuse across the extent of a specific axon bundle. This observation contradicts the apparent association of axonal transport block with crosswise-oriented trabecular beams at the level of the lamina cribrosa as seen in tissue specimens examined in longitudinal section. It also fails to support the notion that blocked axonal transport with elevated pressure is produced by kinking of axons at the lamina.

  5. Cellular origin of prognostic chromosomal aberrations in AML patients

    Mora-Jensen, H.; Jendholm, J.; Rapin, N.;

    2015-01-01

    karyotype have demonstrated the presence of prognostic driver aberrations (that is, NPM1, FLT3-ITD and FLT3-TKD) in committed HPCs but not in multipotent HSCs. However, the HSC populations lacking the prognostic driver aberrations contained preleukemic clones harboring a series of recurrent molecular...... aberrations that were present in the fully transformed committed HPCs together with the prognostic driver aberration. Adding to this vast heterogeneity and complexity of AML genomes and their clonal evolution, a recent study of a murine AML model demonstrated that t(9;11) AML originating from HSCs responded...

  6. Axon diameter and intra-axonal volume fraction of the corticospinal tract in idiopathic normal pressure hydrocephalus measured by q-space imaging.

    Kouhei Kamiya

    Full Text Available PURPOSE: Previous studies suggest that compression and stretching of the corticospinal tract (CST potentially cause treatable gait disturbance in patients with idiopathic normal pressure hydrocephalus (iNPH. Measurement of axon diameter with diffusion MRI has recently been used to investigate microstructural alterations in neurological diseases. In this study, we investigated alterations in the axon diameter and intra-axonal fraction of the CST in iNPH by q-space imaging (QSI analysis. METHODS: Nineteen patients with iNPH and 10 age-matched controls were recruited. QSI data were obtained with a 3-T system by using a single-shot echo planar imaging sequence with the diffusion gradient applied parallel to the antero-posterior axis. By using a two-component low-q fit model, the root mean square displacements of intra-axonal space ( =  axon diameter and intra-axonal volume fraction of the CST were calculated at the levels of the internal capsule and body of the lateral ventricle, respectively. RESULTS: Wilcoxon's rank-sum test revealed a significant increase in CST intra-axonal volume fraction at the paraventricular level in patients (p<0.001, whereas no significant difference was observed in the axon diameter. At the level of the internal capsule, neither axon diameter nor intra-axonal volume fraction differed significantly between the two groups. CONCLUSION: Our results suggest that in patients with iNPH, the CST does not undergo irreversible axonal damage but is rather compressed and/or stretched owing to pressure from the enlarged ventricle. These analyses of axon diameter and intra-axonal fraction yield insights into microstructural alterations of the CST in iNPH.

  7. Computational Analysis of Axonal Transport: A Novel Assessment of Neurotoxicity, Neuronal Development and Functions

    Toshiyuki Gotoh

    2012-03-01

    Full Text Available Axonal transport plays a crucial role in neuronal morphogenesis, survival and function. Despite its importance, however, the molecular mechanisms of axonal transport remain mostly unknown because a simple and quantitative assay system for monitoring this cellular process has been lacking. In order to better characterize the mechanisms involved in axonal transport, we formulate a novel computer-assisted monitoring system of axonal transport. Potential uses of this system and implications for future studies will be discussed.

  8. IFNgamma enhances microglial reactions to hippocampal axonal degeneration

    Jensen, M B; Hegelund, I V; Lomholt, N D;

    2000-01-01

    periods. Message for the immune cytokine interferon-gamma (IFNgamma) was undetectable, and glial reactivity to axonal lesions occurred as normal in IFNgamma-deficient mice. Microglial responses to lesion-induced neuronal injury were markedly enhanced in myelin basic protein promoter-driven transgenic mice...

  9. PTEN inhibition and axon regeneration and neural repair

    Yosuke Ohtake; Umar Hayat; Shuxin Li

    2015-01-01

    The intrinsic growth ability of all the neurons declines during development although some may grow better than others. Numerous intracellular signaling proteins and transcription factors have been shown to regulate the intrinsic growth capacity in mature neurons. Among them, PI3 kinase/Akt pathway is important for controlling axon elongation. As a negative regulator of this pathway, the tumor suppressor phosphatase and tensin homolog (PTEN) appears critical to con-trol the regenerative ability of young and adult neurons. This review will focus on recent research progress in axon regeneration and neural repair by PTEN inhibition and therapeutic potential of blocking this phosphatase for neurological disorders. Inhibition of PTEN by deletion in con-ditional knockout mice, knockdown by short-hairpin RNA, or blockade by pharmacological approaches, including administration of selective PTEN antagonist peptides, stimulates various degrees of axon regrowth in juvenile or adult rodents with central nervous system injuries. Im-portantly, post-injury PTEN suppression could enhance axonal growth and functional recovery in adult central nervous system after injury.

  10. Life-or-death decisions upon axonal damage.

    Roselli, Francesco; Caroni, Pico

    2012-02-01

    In this issue of Neuron, Hu et al. (2012) report that upon axonal damage, CHOP and XBP1 unfolded protein response pathways are not recruited equally and have opposite effects on neuronal survival. XBP1 pathway boosting may represent a valuable neuroprotective strategy.

  11. Drosophila Ryks and their roles in axon and muscle guidance

    Lahaye, Liza Lucia

    2015-01-01

    In the last decade it has become clear that a number of the molecular mechanisms that are required for proper navigation of axons in complex nervous systems are also employed to guide muscles to their appropriate attachment sites. Among the gene families that mediate these diverse processes is the R

  12. Quantifying mechanical force in axonal growth and guidance

    Ahmad Ibrahim Mahmoud Athamneh

    2015-09-01

    Full Text Available Mechanical force plays a fundamental role in neuronal development, physiology, and regeneration. In particular, research has shown that force is involved in growth cone-mediated axonal growth and guidance as well as stretch-induced elongation when an organism increases in size after forming initial synaptic connections. However, much of the details about the exact role of force in these fundamental processes remain unknown. In this review, we highlight (1 standing questions concerning the role of mechanical force in axonal growth and guidance and (2 different experimental techniques used to quantify forces in axons and growth cones. We believe that satisfying answers to these questions will require quantitative information about the relationship between elongation, forces, cytoskeletal dynamics, axonal transport, signaling, substrate adhesion, and stiffness contributing to directional growth advance. Furthermore, we address why a wide range of force values have been reported in the literature, and what these values mean in the context of neuronal mechanics. We hope that this review will provide a guide for those interested in studying the role of force in development and regeneration of neuronal networks.

  13. Traction Force and Tension Fluctuations During Axon Growth

    Jamison ePolackwich

    2015-10-01

    Full Text Available Actively generated mechanical forces play a central role in axon growthand guidance, but the mechanisms that underly force generation andregulation in growing axons remain poorly understood. We reportmeasurements of the dynamics of traction stresses from growth cones ofactively advancing axons from postnatal rat DRG neurons. By tracking themovement of the growth cone and analyzing the traction stress field froma reference frame that moves with it, we are able to show that there isa clear and consistent average stress field that underlies the complexspatial stresses present at any one time. The average stress field hasstrong maxima on the sides of the growth cone, directed inward towardthe growth cone neck. This pattern represents a contractile stresscontained within the growth cone, and a net force that is balanced bythe axon tension. Using high time-resolution measurements of the growthcone traction stresses, we show that the stress field is composed offluctuating local stress peaks, with a large number peaks that live fora short time, a population of peaks whose lifetime distribution followsan exponential decay, and a small number of very long-lived peaks. Weshow that the high time-resolution data also reveal that the tensionappears to vary randomly over short time scales, roughly consistent withthe lifetime of the stress peaks, suggesting that the tensionfluctuations originate from stochastic adhesion dynamics.

  14. Unravelling the incidence and etiology of chronic idiopathic axonal polyneuropathy

    Visser, N.A.

    2016-01-01

    Chronic idiopathic axonal polyneuropathy (CIAP) is a sensory or sensorimotor polyneuropathy that has a slowly progressive course without severe disability. CIAP is diagnosed in a significant proportion of patients with polyneuropathy, but precise figures on the incidence of polyneuropathy and CIAP w

  15. Axon diameter mapping in crossing fibers with diffusion MRI

    Zhang, Hui; Dyrby, Tim B; Alexander, Daniel C

    2011-01-01

    This paper proposes a technique for a previously unaddressed problem, namely, mapping axon diameter in crossing fiber regions, using diffusion MRI. Direct measurement of tissue microstructure of this kind using diffusion MRI offers a new class of biomarkers that give more specific information abo...

  16. Axonal dynamics of excitatory and inhibitory neurons in somatosensory cortex.

    Sally A Marik

    Full Text Available Cortical topography can be remapped as a consequence of sensory deprivation, suggesting that cortical circuits are continually modified by experience. To see the effect of altered sensory experience on specific components of cortical circuits, we imaged neurons, labeled with a genetically modified adeno-associated virus, in the intact mouse somatosensory cortex before and after whisker plucking. Following whisker plucking we observed massive and rapid reorganization of the axons of both excitatory and inhibitory neurons, accompanied by a transient increase in bouton density. For horizontally projecting axons of excitatory neurons there was a net increase in axonal projections from the non-deprived whisker barrel columns into the deprived barrel columns. The axon collaterals of inhibitory neurons located in the deprived whisker barrel columns retracted in the vicinity of their somata and sprouted long-range projections beyond their normal reach towards the non-deprived whisker barrel columns. These results suggest that alterations in the balance of excitation and inhibition in deprived and non-deprived barrel columns underlie the topographic remapping associated with sensory deprivation.

  17. Chronic excitotoxin-induced axon degeneration in a compartmented neuronal culture model

    Katherine A Hosie

    2012-02-01

    Full Text Available Glutamate excitotoxicity is a major pathogenic process implicated in many neurodegenerative conditions, including AD (Alzheimer's disease and following traumatic brain injury. Occurring predominantly from over-stimulation of ionotropic glutamate receptors located along dendrites, excitotoxic axonal degeneration may also occur in white matter tracts. Recent identification of axonal glutamate receptor subunits within axonal nanocomplexes raises the possibility of direct excitotoxic effects on axons. Individual neuronal responses to excitotoxicity are highly dependent on the complement of glutamate receptors expressed by the cell, and the localization of the functional receptors. To enable isolation of distal axons and targeted excitotoxicity, murine cortical neuron cultures were prepared in compartmented microfluidic devices, such that distal axons were isolated from neuronal cell bodies. Within the compartmented culture system, cortical neurons developed to relative maturity at 11 DIV (days in vitro as demonstrated by the formation of dendritic spines and clustering of the presynaptic protein synaptophysin. The isolated distal axons retained growth cone structures in the absence of synaptic targets, and expressed glutamate receptor subunits. Glutamate treatment (100 μM to the cell body chamber resulted in widespread degeneration within this chamber and degeneration of distal axons in the other chamber. Glutamate application to the distal axon chamber triggered a lesser degree of axonal degeneration without degenerative changes in the untreated somal chamber. These data indicate that in addition to current mechanisms of indirect axonal excitotoxicity, the distal axon may be a primary target for excitotoxicity in neurodegenerative conditions.

  18. Differential Axonal Projection of Mitral and Tufted Cells in the Mouse Main Olfactory System

    Shin Nagayama

    2010-09-01

    Full Text Available In the past decade, much has been elucidated regarding the functional organization of the axonal connection of olfactory sensory neurons to olfactory bulb (OB glomeruli. However, the manner in which projection neurons of the OB process odorant input and send this information to higher brain centers remains unclear. Here, we report long-range, large-scale tracing of the axonal projection patterns of OB neurons using two-photon microscopy. Tracer injection into a single glomerulus demonstrated widely distributed mitral/tufted cell axonal projections on the lateroventral surface of the mouse brain, including the anterior/posterior piriform cortex (PC and olfactory tubercle (OT. We noted two distinct groups of labeled axons: PC-orienting axons and OT-orienting axons. Each group occupied distinct parts of the lateral olfactory tract. PC-orienting axons projected axon collaterals to a wide area of the PC but only a few collaterals to the OT. OT-orienting axons densely projected axon collaterals primarily to the anterolateral OT (alOT. Different colored dye injections into the superficial and deep portions of the OB external plexiform layer revealed that the PC-orienting axon populations originated in presumed mitral cells and the OT-orienting axons in presumed tufted cells. These data suggest that although mitral and tufted cells receive similar odor signals from a shared glomerulus, they process the odor information in different ways and send their output to different higher brain centers via the PC and alOT.

  19. Wnt-induced calcium signaling mediates axon growth and guidance in the developing corpus callosum.

    Hutchins, B Ian; Li, Li; Kalil, Katherine

    2012-01-10

    Wnt5a gradients guide callosal axons by repulsion through Ryk receptors in vivo. We recently found that Wnt5a repels cortical axons and promotes axon outgrowth through calcium signaling in vitro. Here, using cortical slices, we show that Wnt5a signals through Ryk to guide and promote outgrowth of callosal axons after they cross the midline. Calcium transient frequencies in callosal growth cones positively correlate with axon outgrowth rates in vitro. In cortical slices, calcium release through inositol 1,4,5-trisphosphate (IP(3)) receptors and calcium entry through transient receptor potential channels modulate axon growth and guidance. Knocking down Ryk inhibits calcium signaling in cortical axons, reduces rates of axon outgrowth subsequent to midline crossing, and causes axon guidance defects. Calcium- and calmodulin-dependent protein kinase II (CaMKII) is required downstream of Wnt-induced calcium signaling for postcrossing callosal axon growth and guidance. Taken together, these results suggest that growth and guidance of postcrossing callosal axons by Wnt-Ryk-calcium signaling involves axon repulsion through CaMKII.

  20. The Australian Square Kilometre Array Pathfinder: Performance of the Boolardy Engineering Test Array

    McConnell, D; Bannister, K; Bell, M E; Bignall, H E; Chippendale, A P; Edwards, P G; Harvey-Smith, L; Hegarty, S; Heywood, I; Hotan, A W; Indermuehle, B T; Lenc, E; Marvil, J; Popping, A; Raja, W; Reynolds, J E; Sault, R J; Serra, P; Voronkov, M A; Whiting, M; Amy, S W; Axtens, P; Ball, L; Bateman, T J; Bock, D C -J; Bolton, R; Brodrick, D; Brothers, M; Brown, A J; Bunton, J D; Cheng, W; Cornwell, T; DeBoer, D; Feain, I; Gough, R; Gupta, N; Guzman, J C; Hampson, G A; Hay, S; Hayman, D B; Hoyle, S; Humphreys, B; Jacka, C; Jackson, C A; Jackson, S; Jeganathan, K; Joseph, J; Koribalski, B S; Leach, M; Lensson, E S; MacLeod, A; Mackay, S; Marquarding, M; McClure-Griffiths, N M; Mirtschin, P; Mitchell, D; Neuhold, S; Ng, A; Norris, R; Pearce, S; Qiao, R Y; Schinckel, A E T; Shields, M; Shimwell, T W; Storey, M; Troup, E; Turner, B; Tuthill, J; Tzioumis, A; Wark, R M; Westmeier, T; Wilson, C; Wilson, T

    2016-01-01

    We describe the performance of the Boolardy Engineering Test Array (BETA), the prototype for the Australian Square Kilometre Array Pathfinder telescope ASKAP. BETA is the first aperture synthesis radio telescope to use phased array feed technology, giving it the ability to electronically form up to nine dual-polarization beams. We report the methods developed for forming and measuring the beams, and the adaptations that have been made to the traditional calibration and imaging procedures in order to allow BETA to function as a multi-beam aperture synthesis telescope. We describe the commissioning of the instrument and present details of BETA's performance: sensitivity, beam characteristics, polarimetric properties and image quality. We summarise the astronomical science that it has produced and draw lessons from operating BETA that will be relevant to the commissioning and operation of the final ASKAP telescope.

  1. The Joint Milli-Arcsecond Pathfinder Survey (JMAPS): Mission Overview and Attitude Sensing Applications

    Dorland, Bryan N; Dugan, Zachary; nessy, Gregory S Hen-

    2009-01-01

    The Joint Milliarcsecond Pathfinder Survey (JMAPS) is a Department of Navy bright star astrometric all-sky survey scheduled for launch in the 2012 timeframe. Mission objectives include a complete update of star positions for the 2015 epoch to accuracy levels of 1 milliarcsecond (5 nano-radians) for bright stars, as well as demonstration of 10 milliarcsecond attitude determination capability and 50 milli-arcsecond attitude control on-orbit. In the following paper, we describe the general instrument design and expected performance. We also discuss the new mission capabilities enabled by the unprecedented attitude determination accuracy of such an instrument, and focus specifically on the application to long distance (50,000-100,00 km) formation flying and solar system navigation.

  2. Pathfinder: multiresolution region-based searching of pathology images using IRM.

    Wang, J Z

    2000-01-01

    The fast growth of digitized pathology slides has created great challenges in research on image database retrieval. The prevalent retrieval technique involves human-supplied text annotations to describe slide contents. These pathology images typically have very high resolution, making it difficult to search based on image content. In this paper, we present Pathfinder, an efficient multiresolution region-based searching system for high-resolution pathology image libraries. The system uses wavelets and the IRM (Integrated Region Matching) distance. Experiments with a database of 70,000 pathology image fragments have demonstrated high retrieval accuracy and high speed. The algorithm can be combined with our previously developed wavelet-based progressive pathology image transmission and browsing algorithm and is expandable for medical image databases.

  3. EUSO-BALLOON a pathfinder for detecting UHECR's from the edge of space

    Scotti V.

    2013-06-01

    Full Text Available EUSO-Balloon has been conceived as a pathfinder mission for JEM-EUSO, to perform an end-to-end test of the subsystems and components, and to prove the global detection chain while improving our knowledge of the atmospheric and terrestrial UV background. Through a series of stratospheric balloon flights performed by the French Space Agency CNES, EUSO-BALLOON will serve as an evolutive test-bench for all the key technologies of JEM-EUSO. EUSO-Balloon also has the potential to detect Extensive Air Showers from above, marking a key milestone in the development of UHECR science, and paving the way for any future large scale, space-based UHECR observatory.

  4. The Mars Pathfinder atmospheric structure investigation/meteorology (ASI/MET) experiment

    Schofield, J.T.; Barnes, J.R.; Crisp, D.

    1997-01-01

    The Mars Pathfinder atmospheric structure investigation/meteorology (ASI/MET) experiment measured the vertical density, pressure, and temperature structure of the martian atmosphere from the surface to 160 km, and monitored surface meteorology and climate for 83 sols (1 sol = 1 martian day = 24...... nighttime upper atmosphere; atmospheric temperatures that are 10 to 12 degrees kelvin warmer near the surface; light slope-controlled winds; and dust devils, identified by their pressure, wind, and temperature signatures. The results are consistent with the warm, moderately dusty atmosphere seen by VL-1........7 hours). The atmospheric structure and the weather record are similar to those observed by the Viking 1 lander (VL-1) at the same latitude, altitude, and season 21 years ago, but there are differences related to diurnal effects and the surface properties of the landing site. These include a cold...

  5. Hierarchical Pathfinding and AI-Based Learning Approach in Strategy Game Design

    Le Minh Duc

    2008-01-01

    Full Text Available Strategy game and simulation application are an exciting area with many opportunities for study and research. Currently most of the existing games and simulations apply hard coded rules so the intelligence of the computer generated forces is limited. After some time, player gets used to the simulation making it less attractive and challenging. It is also costly and tedious to incorporate new rules for an existing game. The main motivation behind this research project is to improve the quality of artificial intelligence- (AI- based on various techniques such as qualitative spatial reasoning (Forbus et al., 2002, near-optimal hierarchical pathfinding (HPA* (Botea et al., 2004, and reinforcement learning (RL (Sutton and Barto, 1998.

  6. The Australian Square Kilometre Array Pathfinder: Performance of the Boolardy Engineering Test Array

    McConnell, D.; Allison, J. R.; Bannister, K.; Bell, M. E.; Bignall, H. E.; Chippendale, A. P.; Edwards, P. G.; Harvey-Smith, L.; Hegarty, S.; Heywood, I.; Hotan, A. W.; Indermuehle, B. T.; Lenc, E.; Marvil, J.; Popping, A.; Raja, W.; Reynolds, J. E.; Sault, R. J.; Serra, P.; Voronkov, M. A.; Whiting, M.; Amy, S. W.; Axtens, P.; Ball, L.; Bateman, T. J.; Bock, D. C.-J.; Bolton, R.; Brodrick, D.; Brothers, M.; Brown, A. J.; Bunton, J. D.; Cheng, W.; Cornwell, T.; DeBoer, D.; Feain, I.; Gough, R.; Gupta, N.; Guzman, J. C.; Hampson, G. A.; Hay, S.; Hayman, D. B.; Hoyle, S.; Humphreys, B.; Jacka, C.; Jackson, C. A.; Jackson, S.; Jeganathan, K.; Joseph, J.; Koribalski, B. S.; Leach, M.; Lensson, E. S.; MacLeod, A.; Mackay, S.; Marquarding, M.; McClure-Griffiths, N. M.; Mirtschin, P.; Mitchell, D.; Neuhold, S.; Ng, A.; Norris, R.; Pearce, S.; Qiao, R. Y.; Schinckel, A. E. T.; Shields, M.; Shimwell, T. W.; Storey, M.; Troup, E.; Turner, B.; Tuthill, J.; Tzioumis, A.; Wark, R. M.; Westmeier, T.; Wilson, C.; Wilson, T.

    2016-09-01

    We describe the performance of the Boolardy Engineering Test Array, the prototype for the Australian Square Kilometre Array Pathfinder telescope. Boolardy Engineering Test Array is the first aperture synthesis radio telescope to use phased array feed technology, giving it the ability to electronically form up to nine dual-polarisation beams. We report the methods developed for forming and measuring the beams, and the adaptations that have been made to the traditional calibration and imaging procedures in order to allow BETA to function as a multi-beam aperture synthesis telescope. We describe the commissioning of the instrument and present details of Boolardy Engineering Test Array's performance: sensitivity, beam characteristics, polarimetric properties, and image quality. We summarise the astronomical science that it has produced and draw lessons from operating Boolardy Engineering Test Array that will be relevant to the commissioning and operation of the final Australian Square Kilometre Array Path telescope.

  7. Bayesian Inference for LISA Pathfinder using Markov Chain Monte Carlo Methods

    Ferraioli, Luigi; Plagnol, Eric

    2012-01-01

    We present a parameter estimation procedure based on a Bayesian framework by applying a Markov Chain Monte Carlo algorithm to the calibration of the dynamical parameters of a space based gravitational wave detector. The method is based on the Metropolis-Hastings algorithm and a two-stage annealing treatment in order to ensure an effective exploration of the parameter space at the beginning of the chain. We compare two versions of the algorithm with an application to a LISA Pathfinder data analysis problem. The two algorithms share the same heating strategy but with one moving in coordinate directions using proposals from a multivariate Gaussian distribution, while the other uses the natural logarithm of some parameters and proposes jumps in the eigen-space of the Fisher Information matrix. The algorithm proposing jumps in the eigen-space of the Fisher Information matrix demonstrates a higher acceptance rate and a slightly better convergence towards the equilibrium parameter distributions in the application to...

  8. Theory and modeling of the magnetic field measurement in LISA PathFinder

    Diaz-Aguilo, M; Lobo, A

    2009-01-01

    The magnetic diagnostics subsystem of the LISA Technology Package (LTP) on board the LISA PathFinder (LPF) spacecraft includes a set of four tri-axial fluxgate magnetometers, intended to measure with high precision the magnetic field at their respective positions. However, their readouts do not provide a direct measurement of the magnetic field at the positions of the test masses, and hence an interpolation method must be designed and implemented to obtain the values of the magnetic field at these positions. However, such interpolation process faces serious difficulties. Indeed, the size of the interpolation region is excessive for a linear interpolation to be reliable while, on the other hand, the number of magnetometer channels does not provide sufficient data to go beyond the linear approximation. We describe an alternative method to address this issue, by means of neural network algorithms. The key point in this approach is the ability of neural networks to learn from suitable training data representing t...

  9. A GPU-based Correlator X-engine Implemented on the CHIME Pathfinder

    Denman, Nolan; Bandura, Kevin; Connor, Liam; Dobbs, Matt; Fandino, Mateus; Halpern, Mark; Hincks, Adam; Hinshaw, Gary; Höfer, Carolin; Klages, Peter; Masui, Kiyoshi; Parra, Juan Mena; Newburgh, Laura; Recnik, Andre; Shaw, Richard; Sigurdson, Kris; Smith, Kendrick; Vanderlinde, Keith

    2015-01-01

    We present the design and implementation of a custom GPU-based compute cluster that provides the correlation X-engine of the CHIME Pathfinder radio telescope. It is among the largest such systems in operation, correlating 32,896 baselines (256 inputs) over 400MHz of radio bandwidth. Making heavy use of consumer-grade parts and a custom software stack, the system was developed at a small fraction of the cost of comparable installations. Unlike existing GPU backends, this system is built around OpenCL kernels running on consumer-level AMD GPUs, taking advantage of low-cost hardware and leveraging packed integer operations to double algorithmic efficiency. The system achieves the required 105TOPS in a 10kW power envelope, making it among the most power-efficient X-engines in use today.

  10. LISA and LISA PathFinder, the endeavour to detect low frequency GWs

    Araújo, H.; Boatella, C.; Chmeissani, M.; Conchillo, A.; García-Berro, E.; Grimani, C.; Hajdas, W.; Lobo, A.; Martínez, Ll; Nofrarias, M.; Ortega, J. A.; Puigdengoles, C.; Ramos-Castro, J.; Sanjuán, J.; Wass, P.; Xirgu, X.

    2007-05-01

    This is a review about LISA and its technology demonstrator, LISAPathFinder. We first describe the conceptual problems which need to be overcome in order to set up a working interferometric detector of low frequency Gravitational Waves (GW), then summarise the solutions to them as currently conceived by the LISA mission team. This will show that some of these solutions require new technological abilities which are still under development, and which need proper test before being fully implemented. LISAPathFinder (LPF) is the the testbed for such technologies. The final part of the paper will address the ideas and concepts behind the PathFinder as well as their impact on LISA.

  11. LISA and LISA PathFinder, the endeavour to detect low frequency GWs

    Araujo, H [Blackett Laboratory, Imperial College London, Prince Consort Road, London SW7 2BW (United Kingdom); Boatella, C [Institut d' Estudis Espacials de Catalunya (IEEC), Edifici Nexus, Gran Capita 2-4, 08034 Barcelona (Spain); Chmeissani, M [Institut de Fisica d' Altes Energies (IFAE), Edifici C, Universitat Autonoma de Barcelona, 08193 Bellaterra (Barcelona) (Spain); Conchillo, A [Institut d' Estudis Espacials de Catalunya (IEEC), Edifici Nexus, Gran Capita 2-4, 08034 Barcelona (Spain); Garcia-Berro, E [Institut d' Estudis Espacials de Catalunya (IEEC), Edifici Nexus, Gran Capita 2-4, 08034 Barcelona (Spain); Grimani, C [Universita degli Studi di Urbino, and INFN Florence, Istituto di Fisica, Via Santa Chiara 27, 61029 Urbino (Italy); Hajdas, W [Department of Particles and Matter, Paul Scherrer Institut, ODRA 120, 5232 Villigen (Switzerland); Lobo, A [Institut d' Estudis Espacials de Catalunya (IEEC), Edifici Nexus, Gran Capita 2-4, 08034 Barcelona (Spain); Martinez, L [AtIpic, Parc Tecnologic del Valles, 08290 Cerdanyola del Valles, Barcelona (Spain); Nofrarias, M [Institut d' Estudis Espacials de Catalunya (IEEC), Edifici Nexus, Gran Capita 2-4, 08034 Barcelona (Spain); Ortega, J A [Institut d' Estudis Espacials de Catalunya (IEEC), Edifici Nexus, Gran Capita 2-4, 08034 Barcelona (Spain); Puigdengoles, C [Institut de Fisica d' Altes Energies (IFAE), Edifici C, Universitat Autonoma de Barcelona, 08193 Bellaterra (Barcelona) (Spain); Ramos-Castro, J [Departament d' Enginyeria Electronica, UPC, Campus Nord, Edif. C4, Jordi Girona 1-3, 08034 Barcelona (Spain); Sanjuan, J [Institut d' Estudis Espacials de Catalunya (IEEC), Edifici Nexus, Gran Capita 2-4, 08034 Barcelona (Spain); Wass, P [Blackett Laboratory, Imperial College London, Prince Consort Road, London SW7 2BW (United Kingdom); Xirgu, X [Institut d' Estudis Espacials de Catalunya (IEEC), Edifici Nexus, Gran Capita 2-4, 08034 Barcelona (Spain)

    2007-05-15

    This is a review about LISA and its technology demonstrator, LISAPathFinder. We first describe the conceptual problems which need to be overcome in order to set up a working interferometric detector of low frequency Gravitational Waves (GW), then summarise the solutions to them as currently conceived by the LISA mission team. This will show that some of these solutions require new technological abilities which are still under development, and which need proper test before being fully implemented. LISAPathFinder (LPF) is the the testbed for such technologies. The final part of the paper will address the ideas and concepts behind the PathFinder as well as their impact on LISA.

  12. The Australian Square Kilometre Array Pathfinder: System Architecture and Specifications of the Boolardy Engineering Test Array

    Hotan, A W; Harvey-Smith, L; Humphreys, B; Jeffs, B D; Shimwell, T; Tuthill, J; Voronkov, M; Allen, G; Amy, S; Ardern, K; Axtens, P; Ball, L; Bannister, K; Barker, S; Bateman, T; Beresford, R; Bock, D; Bolton, R; Bowen, M; Boyle, B; Braun, R; Broadhurst, S; Brodrick, D; Brooks, K; Brothers, M; Brown, A; Cantrall, C; Carrad, G; Chapman, J; Cheng, W; Chippendale, A; Chung, Y; Cooray, F; Cornwell, T; Davis, E; de Souza, L; DeBoer, D; Diamond, P; Edwards, P; Ekers, R; Feain, I; Ferris, D; Forsyth, R; Gough, R; Grancea, A; Gupta, N; Guzman, JC; Hampson, G; Haskins, C; Hay, S; Hayman, D; Hoyle, S; Jacka, C; Jackson, C; Jackson, S; Jeganathan, K; Johnston, S; Joseph, J; Kendall, R; Kesteven, M; Kiraly, D; Koribalski, B; Leach, M; Lenc, E; Lensson, E; Li, L; Mackay, S; Macleod, A; Maher, T; Marquarding, M; McClure-Griffiths, N; McConnell, D; Mickle, S; Mirtschin, P; Norris, R; Neuhold, S; Ng, A; O'Sullivan, J; Pathikulangara, J; Pearce, S; Phillips, C; Qiao, RY; Reynolds, J E; Rispler, A; Roberts, P; Roxby, D; Schinckel, A; Shaw, R; Shields, M; Storey, M; Sweetnam, T; Troup, E; Turner, B; Tzioumis, A; Westmeier, T; Whiting, M; Wilson, C; Wilson, T; Wormnes, K; Wu, X

    2014-01-01

    This paper describes the system architecture of a newly constructed radio telescope - the Boolardy Engineering Test Array, which is a prototype of the Australian Square Kilometre Array Pathfinder telescope. Phased array feed technology is used to form multiple simultaneous beams per antenna, providing astronomers with unprecedented survey speed. The test array described here is a 6-antenna interferometer, fitted with prototype signal processing hardware capable of forming at least 9 dual-polarisation beams simultaneously, allowing several square degrees to be imaged in a single pointed observation. The main purpose of the test array is to develop beamforming and wide-field calibration methods for use with the full telescope, but it will also be capable of limited early science demonstrations.

  13. State-space modelling for heater induced thermal effects on LISA Pathfinder's Test Masses

    Gibert, Ferran; Diaz-Aguiló, Marc; Lobo, Alberto; Karnesis, Nikolaos; Mateos, Ignacio; Sanjuán, Josep; Lloro, Ivan; Gesa, Lluís; Martín, Víctor; 10.1088/1742-6596/363/1/012044

    2012-01-01

    The OSE (Offline Simulations Environment) simulator of the LPF (LISA Pathfinder) mission is intended to simulate the different experiments to be carried out in flight. Amongst these, the thermal diagnostics experiments are intended to relate thermal disturbances and interferometer readouts, thereby allowing the subtraction of thermally induced interferences from the interferometer channels. In this paper we report on the modelling of these simulated experiments, including the parametrisation of different thermal effects (radiation pressure effect, radiometer effect) that will appear in the Inertial Sensor environment of the LTP (LISA Technology Package). We report as well how these experiments are going to be implemented in the LTPDA toolbox, which is a dedicated tool for LPF data analysis that will allow full traceability and reproducibility of the analysis thanks to complete recording of the processes.

  14. The eLISA gravitational reference sensor and its test aboard LISA Pathfinder

    Weber, William Joseph; Dolesi, Rita; Vitale, Stefano

    The upcoming LISA Pathfinder (LPF) mission represents the state-of-the-art in realizing a set of free-falling reference test masses for gravitational wave astronomy. The key hardware for achieving the smallest possible deviation from pure geodesic motion lies in the gravitational reference sensor or GRS. We present the GRS designed for achieving sub-femto-g/sqrt{mathrm{Hz}} performance with LPF and eLISA and discuss our current experimental estimates for the upcoming mission, including the latest results from the flight hardware test campaigns. Finally, we will address the LPF in-flight tests that will complete our physical model for test mass acceleration noise for eLISA and other possible experimental gravitational measurements in space.

  15. Thermo-elastic induced phase noise in the LISA Pathfinder spacecraft

    Gibert, F.; Nofrarias, M.; Karnesis, N.; Gesa, L.; Martín, V.; Mateos, I.; Lobo, A.; Flatscher, R.; Gerardi, D.; Burkhardt, J.; Gerndt, R.; Robertson, D. I.; Ward, H.; McNamara, P. W.; Guzmán, F.; Hewitson, M.; Diepholz, I.; Reiche, J.; Heinzel, G.; Danzmann, K.

    2015-02-01

    During the on-station thermal test campaign of the LISA Pathfinder, the diagnostics subsystem was tested in nearly space conditions for the first time after integration in the satellite. The results showed the compliance of the temperature measurement system, obtaining temperature noise around {{10}-4} K H{{z}-1/2} in the frequency band 1-30 mHz. In addition, controlled injection of heat signals to the suspension struts anchoring the LISA Technology Package (LTP) core assembly to the satellite structure allowed us to experimentally estimate, for the first time, the phase noise contribution through thermo-elastic distortion of the LTP interferometer, the satellite's main instrument. Such contribution was found to be at {{10}-12} mH{{z}-1/2}, a factor of 30 below the measured noise at the lower end of the measurement bandwidth (1 mHz).

  16. Thermo-elastic induced phase noise in the LISA Pathfinder spacecraft

    Gibert, Ferran; Karnesis, Nikolaos; Gesa, Lluís; Martín, Víctor; Mateos, Ignacio; Lobo, Alberto; Flatscher, Reinhold; Gerardi, Domenico; Burkhardt, Johannes; Guzmán, Felipe; Heinzel, Gerhard; Danzmann, Karsten

    2014-01-01

    During the On-Station Thermal Test campaign of the LISA Pathfinder the data and diagnostics subsystem was tested in nearly space conditions for the first time after integration in the satellite. The results showed the compliance of the temperature measurement system, obtaining temperature noise around $10^{-4}\\,{\\rm K}\\, {\\rm Hz}^{-1/2}$ in the frequency band of $1-30\\;{\\rm mHz}$. In addition, controlled injection of heat signals to the suspension struts anchoring the LISA Technology Package (LTP) Core Assembly to the satellite structure allowed to experimentally estimate for the first time the phase noise contribution through thermo-elastic distortion of the LTP interferometer, the satellite's main instrument. Such contribution was found to be at $10^{-12}\\,{\\rm m}\\, {\\rm Hz}^{-1/2}$, a factor of 30 below the measured noise at the lower end of the measurement bandwidth ($1\\,{\\rm mHz}$).

  17. Nicotine elicits prolonged calcium signaling along ventral hippocampal axons.

    Zhong, Chongbo; Talmage, David A; Role, Lorna W

    2013-01-01

    Presynaptic nicotinic acetylcholine receptors (nAChRs) have long been implicated in the modulation of CNS circuits. We previously reported that brief exposure to low concentrations of nicotine induced sustained potentiation of glutamatergic transmission at ventral hippocampal (vHipp)-striatal synapses. Here, we exploited nAChR subtype-selective antagonists and agonists and α7*nAChR knockout mutant mice (α7-/-) to elucidate the signaling mechanisms underlying nAChR-mediated modulation of synaptic transmission. Using a combination of micro-slices culture from WT and α7-/-mice, calcium imaging, and immuno-histochemical techniques, we found that nicotine elicits localized and oscillatory increases in intracellular Ca(2+) along vHipp axons that persists for up to 30 minutes. The sustained phase of the nicotine-induced Ca(2+) response was blocked by α-BgTx but not by DHβE and was mimicked by α7*nAChR agonists but not by non-α7*nAChR agonists. In vHipp slices from α7-/- mice, nicotine elicited only transient increases of axonal Ca(2+) signals and did not activate CaMKII. The sustained phase of the nicotine-induced Ca(2+) response required localized activation of CaMKII, phospholipase C, and IP3 receptor mediated Ca(2+)-induced Ca(2+) release (CICR). In conclusion, activation of presynaptic nAChRs by nicotine elicits Ca(2+) influx into the presynaptic axons, the sustained phase of the nicotine-induced Ca(2+) response requires that axonal α7*nAChR activate a downstream signaling network in the vHipp axons.

  18. Aberrant angiogenesis: The gateway to diabetic complications

    Sunil K Kota

    2012-01-01

    Full Text Available Diabetes Mellitus is a metabolic cum vascular syndrome with resultant abnormalities in both micro- and macrovasculature. The adverse long-term effects of diabetes mellitus have been described to involve many organ systems. Apart from hyperglycemia, abnormalities of angiogenesis may cause or contribute toward many of the clinical manifestations of diabetes. These are implicated in the pathogenesis of vascular abnormalities of the retina, kidneys, and fetus, impaired wound healing, increased risk of rejection of transplanted organs, and impaired formation of coronary collaterals. A perplexing feature of the aberrant angiogenesis is that excessive and insufficient angiogenesis can occur in different organs in the same individual. The current article hereby reviews the molecular mechanisms including abnormalities in growth factors, cytokines, and metabolic derangements, clinical implications, and therapeutic options of dealing with abnormal angiogenesis in diabetes.

  19. Aberrant Gene Expression in Acute Myeloid Leukaemia

    Bagger, Frederik Otzen

    model to investigate the role of telomerase in AML, we were able to translate the observed effect into human AML patients and identify specific genes involved, which also predict survival patterns in AML patients. During these studies we have applied methods for investigating differentially expressed......Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects....... Here GEPs from purified healthy haematopoietic populations, with different levels of differentiation, form the basis for comparison with diseased samples. We present a mathematical transformation of mRNA microarray data to make it possible to compare AML samples, carrying expanded aberrant...

  20. Pathfinding the Flight Advanced Stirling Convertor Design with the ASC-E3

    Wong, Wayne A.; Wilson, Kyle; Smith, Eddie; Collins, Josh

    2012-01-01

    The Advanced Stirling Convertor (ASC) was initially developed by Sunpower, Inc. under contract to NASA Glenn Research Center (GRC) as a technology development project. The ASC technology fulfills NASA's need for high efficiency power convertors for future Radioisotope Power Systems (RPS). Early successful technology demonstrations between 2003 to 2005 eventually led to the expansion of the project including the decision in 2006 to use the ASC technology on the Advanced Stirling Radioisotope Generator (ASRG). Sunpower has delivered 22 ASC convertors of progressively mature designs to date to GRC. Currently, Sunpower with support from GRC, Lockheed Martin Space System Company (LMSSC), and the Department of Energy (DOE) is developing the flight ASC-F in parallel with the ASC-E3 pathfinders. Sunpower will deliver four pairs of ASC-E3 convertors to GRC which will be used for extended operation reliability assessment, independent validation and verification testing, system interaction tests, and to support LMSSC controller verification. The ASC-E3 and -F convertors are being built to the same design and processing documentation and the same product specification. The initial two pairs of ASC-E3 are built before the flight units and will validate design and processing changes prior to implementation on the ASC-F flight convertors. This paper provides a summary on development of the ASC technology and the status of the ASC-E3 build and how they serve the vital pathfinder role ahead of the flight build for ASRG. The ASRG is part of two of the three candidate missions being considered for selection for the Discovery 12 mission.

  1. Sub-Femto-g Free Fall for Space-Based Gravitational Wave Observatories: LISA Pathfinder Results.

    Armano, M; Audley, H; Auger, G; Baird, J T; Bassan, M; Binetruy, P; Born, M; Bortoluzzi, D; Brandt, N; Caleno, M; Carbone, L; Cavalleri, A; Cesarini, A; Ciani, G; Congedo, G; Cruise, A M; Danzmann, K; de Deus Silva, M; De Rosa, R; Diaz-Aguiló, M; Di Fiore, L; Diepholz, I; Dixon, G; Dolesi, R; Dunbar, N; Ferraioli, L; Ferroni, V; Fichter, W; Fitzsimons, E D; Flatscher, R; Freschi, M; García Marín, A F; García Marirrodriga, C; Gerndt, R; Gesa, L; Gibert, F; Giardini, D; Giusteri, R; Guzmán, F; Grado, A; Grimani, C; Grynagier, A; Grzymisch, J; Harrison, I; Heinzel, G; Hewitson, M; Hollington, D; Hoyland, D; Hueller, M; Inchauspé, H; Jennrich, O; Jetzer, P; Johann, U; Johlander, B; Karnesis, N; Kaune, B; Korsakova, N; Killow, C J; Lobo, J A; Lloro, I; Liu, L; López-Zaragoza, J P; Maarschalkerweerd, R; Mance, D; Martín, V; Martin-Polo, L; Martino, J; Martin-Porqueras, F; Madden, S; Mateos, I; McNamara, P W; Mendes, J; Mendes, L; Monsky, A; Nicolodi, D; Nofrarias, M; Paczkowski, S; Perreur-Lloyd, M; Petiteau, A; Pivato, P; Plagnol, E; Prat, P; Ragnit, U; Raïs, B; Ramos-Castro, J; Reiche, J; Robertson, D I; Rozemeijer, H; Rivas, F; Russano, G; Sanjuán, J; Sarra, P; Schleicher, A; Shaul, D; Slutsky, J; Sopuerta, C F; Stanga, R; Steier, F; Sumner, T; Texier, D; Thorpe, J I; Trenkel, C; Tröbs, M; Tu, H B; Vetrugno, D; Vitale, S; Wand, V; Wanner, G; Ward, H; Warren, C; Wass, P J; Wealthy, D; Weber, W J; Wissel, L; Wittchen, A; Zambotti, A; Zanoni, C; Ziegler, T; Zweifel, P

    2016-06-10

    We report the first results of the LISA Pathfinder in-flight experiment. The results demonstrate that two free-falling reference test masses, such as those needed for a space-based gravitational wave observatory like LISA, can be put in free fall with a relative acceleration noise with a square root of the power spectral density of 5.2±0.1  fm s^{-2}/sqrt[Hz], or (0.54±0.01)×10^{-15}  g/sqrt[Hz], with g the standard gravity, for frequencies between 0.7 and 20 mHz. This value is lower than the LISA Pathfinder requirement by more than a factor 5 and within a factor 1.25 of the requirement for the LISA mission, and is compatible with Brownian noise from viscous damping due to the residual gas surrounding the test masses. Above 60 mHz the acceleration noise is dominated by interferometer displacement readout noise at a level of (34.8±0.3)  fm/sqrt[Hz], about 2 orders of magnitude better than requirements. At f≤0.5  mHz we observe a low-frequency tail that stays below 12  fm s^{-2}/sqrt[Hz] down to 0.1 mHz. This performance would allow for a space-based gravitational wave observatory with a sensitivity close to what was originally foreseen for LISA.

  2. Axonal action-potential initiation and Na+ channel densities in the soma and axon initial segment of subicular pyramidal neurons.

    Colbert, C M; Johnston, D

    1996-11-01

    A long-standing hypothesis is that action potentials initiate first in the axon hillock/initial segment (AH-IS) region because of a locally high density of Na+ channels. We tested this idea in subicular pyramidal neurons by using patch-clamp recordings in hippocampal slices. Simultaneous recordings from the soma and IS confirmed that orthodromic action potentials initiated in the axon and then invaded the soma. However, blocking Na+ channels in the AH-IS with locally applied tetrodotoxin (TTX) did not raise the somatic threshold membrane potential for orthodromic spikes. TTX applied to the axon beyond the AH-IS (30-60 microm from the soma) raised the apparent somatic threshold by approximately 8 mV. We estimated the Na+ current density in the AH-IS and somatic membranes by using cell-attached patch-clamp recordings and found similar magnitudes (3-4 pA/microm2). Thus, the present results suggest that orthodromic action potentials initiate in the axon beyond the AH-IS and that the minimum threshold for spike initiation of the neuron is not determined by a high density of Na+ channels in the AH-IS region.

  3. ALS Along the Axons – Expression of Coding and Noncoding RNA Differs in Axons of ALS models

    Rotem, Nimrod; Magen, Iddo; Ionescu, Ariel; Gershoni-Emek, Noga; Altman, Topaz; Costa, Christopher J.; Gradus, Tal; Pasmanik-Chor, Metsada; Willis, Dianna E.; Ben-Dov, Iddo Z.; Hornstein, Eran; Perlson, Eran

    2017-01-01

    Amyotrophic lateral sclerosis (ALS) is a multifactorial lethal motor neuron disease with no known treatment. Although the basic mechanism of its degenerative pathogenesis remains poorly understood, a subcellular spatial alteration in RNA metabolism is thought to play a key role. The nature of these RNAs remains elusive, and a comprehensive characterization of the axonal RNAs involved in maintaining neuronal health has yet to be described. Here, using cultured spinal cord (SC) neurons grown using a compartmented platform followed by next-generation sequencing (NGS) technology, we find that RNA expression differs between the somatic and axonal compartments of the neuron, for both mRNA and microRNA (miRNA). Further, the introduction of SOD1G93A and TDP43A315T, established ALS-related mutations, changed the subcellular expression and localization of RNAs within the neurons, showing a spatial specificity to either the soma or the axon. Altogether, we provide here the first combined inclusive profile of mRNA and miRNA expression in two ALS models at the subcellular level. These data provide an important resource for studies on the roles of local protein synthesis and axon degeneration in ALS and can serve as a possible target pool for ALS treatment. PMID:28300211

  4. Effect of chromatic aberration on atomic-resolved spherical aberration corrected STEM images.

    Kuramochi, Koji; Yamazaki, Takashi; Kotaka, Yasutoshi; Ohtsuka, Masahiro; Hashimoto, Iwao; Watanabe, Kazuto

    2009-12-01

    The effect of the chromatic aberration (C(c)) coefficient in a spherical aberration (C(s))- corrected electromagnetic lens on high-resolution high-angle annular dark field (HAADF) scanning transmission electron microscope (STEM) images is explored in detail. A new method for precise determination of the C(c) coefficient is demonstrated, requiring measurement of an atomic-resolution one-frame through-focal HAADF STEM image. This method is robust with respect to instrumental drift, sample thickness, all lens parameters except C(c), and experimental noise. It is also demonstrated that semi-quantitative structural analysis on the nanometer scale can be achieved by comparing experimental C(s)- corrected HAADF STEM images with their corresponding simulated images when the effects of the C(c) coefficient and spatial incoherence are included.

  5. Midline crossing is not required for subsequent pathfinding decisions in commissural neurons

    Bonner Jennifer

    2012-06-01

    Full Text Available Abstract Background Growth cone navigation across the vertebrate midline is critical in the establishment of nervous system connectivity. While midline crossing is achieved through coordinated signaling of attractive and repulsive cues, this has never been demonstrated at the single cell level. Further, though growth cone responsiveness to guidance cues changes after crossing the midline, it is unclear whether midline crossing itself is required for subsequent guidance decisions in vivo. In the zebrafish, spinal commissures are initially formed by a pioneer neuron called CoPA (Commissural Primary Ascending. Unlike in other vertebrate models, CoPA navigates the midline alone, allowing for single-cell analysis of axon guidance mechanisms. Results We provide evidence that CoPA expresses the known axon guidance receptors dcc, robo3 and robo2. Using loss of function mutants and gene knockdown, we show that the functions of these genes are evolutionarily conserved in teleosts and that they are used consecutively by CoPA neurons. We also reveal novel roles for robo2 and robo3 in maintaining commissure structure. When midline crossing is prevented in robo3 mutants and dcc gene knockdown, ipsilaterally projecting neurons respond to postcrossing guidance cues. Furthermore, DCC inhibits Robo2 function before midline crossing to allow a midline approach and crossing. Conclusions Our results demonstrate that midline crossing is not required for subsequent guidance decisions by pioneer axons and that this is due, in part, to DCC inhibition of Robo2 function prior to midline crossing.

  6. Adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) and Nasu-Hakola disease: lesion staging and dynamic changes of axons and microglial subsets.

    Oyanagi, Kiyomitsu; Kinoshita, Michiaki; Suzuki-Kouyama, Emi; Inoue, Teruhiko; Nakahara, Asa; Tokiwai, Mika; Arai, Nobutaka; Satoh, Jun-Ichi; Aoki, Naoya; Jinnai, Kenji; Yazawa, Ikuru; Arai, Kimihito; Ishihara, Kenji; Kawamura, Mitsuru; Ishizawa, Keisuke; Hasegawa, Kazuko; Yagisita, Saburo; Amano, Naoji; Yoshida, Kunihiro; Terada, Seishi; Yoshida, Mari; Akiyama, Haruhiko; Mitsuyama, Yoshio; Ikeda, Shu-Ichi

    2016-09-08

    The brains of 10 Japanese patients with adult onset leukoencephalopathy with axonal spheroids and pigmented glia (ALSP) encompassing hereditary diffuse leukoencephalopathy with axonal spheroids (HDLS) and pigmentary orthochromatic leukodystrophy (POLD) and eight Japanese patients with Nasu-Hakola disease (N-HD) and five age-matched Japanese controls were examined neuropathologically with special reference to lesion staging and dynamic changes of microglial subsets. In both diseases, the pathognomonic neuropathological features included spherically swollen axons (spheroids and globules), axon loss and changes of microglia in the white matter. In ALSP, four lesion stages based on the degree of axon loss were discernible: Stage I, patchy axon loss in the cerebral white matter without atrophy; Stage II, large patchy areas of axon loss with slight atrophy of the cerebral white matter and slight dilatation of the lateral ventricles; Stage III, extensive axon loss in the cerebral white matter and dilatation of the lateral and third ventricles without remarkable axon loss in the brainstem and cerebellum; Stage IV, devastated cerebral white matter with marked dilatation of the ventricles and axon loss in the brainstem and/or cerebellum. Internal capsule and pontine base were relatively well preserved in the N-HD, even at Stage IV, and the swollen axons were larger with a higher density in the ALSP. Microglial cells immunopositive for CD68, CD163 or CD204 were far more obvious in ALSP, than in N-HD, and the shape and density of the cells changed in each stage. With progression of the stage, clinical symptoms became worse to apathetic state, and epilepsy was frequently observed in patients at Stages III and IV in both diseases. From these findings, it is concluded that (i) shape, density and subsets of microglia change dynamically along the passage of stages and (ii) increase of IBA-1-, CD68-, CD163- and CD204-immunopositive cells precedes loss of axons in ALSP.

  7. IH activity is increased in populations of slow versus fast motor axons of the rat.

    Chad eLorenz

    2014-09-01

    Full Text Available Much is known about the electrophysiological variation in motoneuron somata across different motor units. However comparatively less is known about electrophysiological variation in motor axons and how this could impact function or electrodiagnosis in healthy or diseased states. We performed nerve excitability testing on two groups of motor axons in Sprague-Dawley rats that are known to differ significantly in their chronic daily activity patterns and in the relative proportion of motor unit types: one group innervating the soleus (slow motor axons and the other group innervating the tibialis anterior (fast motor axons muscles. We found that slow motor axons have significantly larger accommodation compared to fast motor axons upon application of a 100 ms hyperpolarizing conditioning stimulus that is 40% of axon threshold (Z = 3.24, p = 0.001 or 20% of axon threshold (Z = 2.67, p = 0.008. Slow motor axons had larger accommodation to hyperpolarizing currents in the current-threshold measurement (-80% Z = 3.07, p = 0.002; -90% Z = 2.98, p = 0.003. In addition, we found that slow motor axons have a significantly smaller rheobase than fast motor axons (Z = -1.99, p = 0.047 accompanied by a lower threshold in stimulus-response curves. The results provide evidence that slow motor axons have greater activity of the hyperpolarization-activated inwardly rectifying cation conductance (IH than fast motor axons. It is possible that this difference between fast and slow axons is caused by an adaptation to their chronic differences in daily activity patterns, and that this adaptation might have a functional effect on the motor unit. Moreover, these findings indicate that slow and fast motor axons may react differently to pathological conditions.

  8. Design of an aberration corrected low-voltage SEM

    Aken, R.H. van; Maas, D.J.; Hagen, C.W.; Barth, J.E.; Kruit, P.

    2010-01-01

    The low-voltage foil corrector is a novel type of foil aberration corrector that can correct for both the spherical and chromatic aberration simultaneously. In order to give a realistic example of the capabilities of this corrector, a design for a low-voltage scanning electron microscope with the lo

  9. Adaptive aberration correction using a triode hyperbolic electron mirror.

    Fitzgerald, J P S; Word, R C; Könenkamp, R

    2011-01-01

    A converging electron mirror can be used to compensate spherical and chromatic aberrations in an electron microscope. This paper presents an analytical solution to a novel triode (three electrode) hyperbolic mirror as an improvement to the well-known diode (two electrode) hyperbolic mirror for aberration correction. A weakness of the diode mirror is a lack of flexibility in changing the chromatic and spherical aberration coefficients independently without changes in the mirror geometry. In order to remove this limitation, a third electrode can be added. We calculate the optical properties of the resulting triode mirror analytically on the basis of a simple model field distribution. We present the optical properties-the object/image distance, z(0), and the coefficients of spherical and chromatic aberration, C(s) and C(c), of both mirror types from an analysis of electron trajectories in the mirror field. From this analysis, we demonstrate that while the properties of both designs are similar, the additional parameters in the triode mirror improve the range of aberration that can be corrected. The triode mirror is also able to provide a dynamic adjustment range of chromatic aberration for fixed spherical aberration and focal length, or any permutation of these three parameters. While the dynamic range depends on the values of aberration correction needed, a nominal 10% tuning range is possible for most configurations accompanied by less than 1% change in the other two properties.

  10. Expressions for third-order aberration theory for holographic images

    S K Tripathy; S Ananda Rao

    2003-01-01

    Expressions for third-order aberration in the reconstructed wave front of point objects are established by Meier. But Smith, Neil Mohon, Sweatt independently reported that their results differ from that of Meier. We found that coefficients for spherical aberration, astigmatism, tally with Meier’s while coefficients for distortion and coma differ.

  11. Numerical correction of aberrations via phase retrieval with speckle illumination

    Almoro, Percival; Gundu, Phanindra Narayan; Hanson, Steen Grüner

    2009-01-01

    What we believe to be a novel technique for wavefront aberration measurement using speckle patterns is presented. The aberration correction is done numerically. A tilted lens is illuminated with a partially developed speckle field, and the transmitted light intensity is sampled at axially displaced...

  12. Simultaneous measurements of magnesium, calcium and sodium influxes in perfused squid giant axons under membrane potential control.

    Rojas, E; Taylor, R E

    1975-10-01

    1. Giant axons from the squids Dosidicus gigas, Loligo forbesi and Loligo vulgaris were internally perfused with 550 or 275 mM KF plus sucrose and bathed in artificial sea water containing 45Ca, 28Mg or mixtures of 45Ca-28Mg or 45Ca-22Na. Resting influxes and extra influxes during voltage-clamp pulses were measured by collecting and counting the internal perfusate. 2. For Dosidicus axons in 10 mM-CaCl2 the resting influx of calcium was 0-016 +/- 0-007 p-mole/cm2 sec and a linear function of external concentration. For two experiments in 10 and 84-7 mM-CaCl2, 100 nM tetrodotoxin had no effect. Resting calcium influx in 10 mM-CaCl2 was 0-017 +/- 0-013 p-mole/cm2 sec for Loligo axons. 3. With 55 mM-MgCl2 outside the average resting magnesium influx was 0-124 +/- 0-080 p-mole/cm2 sec for Loligo axons. Discarding one aberrant point the value is 0-105 +/- 0-046 which is not significantly different from the resting calcium influx for Dosidicus fibres in 55 mM-CaCl2, given as 0-094 p-mole/cm2 sec by the regression line shown in Fig. 1. In two experiments 150 nM tetrodotoxin had no effect. 4. With 430 mM-NaCl outside 100 nM tetrodotoxin reduced the average resting influx of sodium in Dosidicus axon from 27-7 +/- 4-5 to 25-1 +/- 6-2 p-mole/cm2 sec and for Loligo fibres in 460 mM-NaCl from 50-5 +/- 4 to 20 +/- 8 p-mole/cm2 sec. 5. Using depolarizing pulses of various durations, the extra calcium influx occurred in two phases. The early phase was eliminated by external application of tetrodotoxin. The results of analysis are consistent with, but do not rigorously demonstrate, the conclusion that the tetrodotoxin sensitive calcium entry is flowing through the normal sodium channels (cf. Baker, Hodgkin & Ridgway, 1971). 6. Measurements of extra influxes using 22Na and 45Ca simultaneously indicate that the time courses of tetrodotoxin sensitive calcium and sodium entry are similar but not necessarily identical. It is very doubtful that any significant calcium entry occurs before

  13. Effects of aberrations in spatiotemporal focusing of ultrashort laser pulses.

    Sun, Bangshan; Salter, Patrick S; Booth, Martin J

    2014-04-01

    Spatiotemporal focusing, or simultaneous spatial and temporal focusing (SSTF), has already been adopted for various applications in microscopy, photoactivation for biological studies, and laser fabrication. We investigate the effects of aberrations on focus formation in SSTF, in particular, the effects of phase aberrations related to low-order Zernike modes and a refractive index mismatch between the immersion medium and sample. By considering a line focus, we are able to draw direct comparison between the performance of SSTF and conventional spatial focusing (SF). Wide-field SSTF is also investigated and is found to be much more robust to aberrations than either line SSTF or SF. These results show the sensitivity of certain focusing methods to specific aberrations, and can inform on the necessity and benefit of aberration correction.

  14. Age-related changes in ocular aberrations with accommodation.

    Radhakrishnan, Hema; Charman, W Neil

    2007-05-30

    This study investigates the changes in aberrations with monocular accommodation as a function of age. Second-order and higher order wavefront aberrations and pupil size were measured as a function of accommodation demand over the range of 0-4 D in the right eyes of 47 normal subjects with ages between 17 and 56 years. Higher order ocular Zernike aberrations were analyzed for the natural pupil size in terms of their equivalent defocus and were also determined for fixed pupil diameters of 4.5 mm in the unaccommodated eyes and 2.5 mm in the accommodating eyes. With relaxed accommodation (0 D accommodation stimulus), the major change with age was in the value of C4(0), which increased in positive value over the age range studied, although the total higher order RMS wavefront aberration did not increase. When the data were analyzed for natural pupils, spherical aberration was again found to change systematically in the positive direction with age. The equivalent defocus of total higher order RMS error for natural pupils showed no significant correlation with age (p > .05). With active accommodation, spherical aberration was found to decrease and become negative as the accommodative response increased in the younger subjects (40 years), the spherical aberration showed only small changes, some of which were positive, within the limited amplitude of accommodation available. Other higher order aberrations and the RMS of higher order aberrations did not appear to change systematically with accommodation, except in the oldest subjects. The change with age in the relationship between aberration and accommodation is interpreted in terms of the changing gradients of refractive index and surface curvatures of the crystalline lens.

  15. 4 km AVHRR Pathfinder v5.0 Global Day-Night Sea Surface Temperature Monthly and Yearly Averages, 1985-2009 (NODC Accession 0077816)

    National Oceanic and Atmospheric Administration, Department of Commerce — This data set contains a set of monthly and yearly global day-night sea surface temperature averages, derived from the AVHRR Pathfinder Version 5 sea surface...

  16. Arapaho National Wildlife Refuge also Bamforth, Hutton Lake, Morenson Lake and Pathfinder National Wildlife Refuges: Annual narrative report: Calendar year 1995

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Arapaho NWR, Bamforth NWR, Hutton Lake NWR, Morenson Lake NWR, and Pathfinder NWR outlines Refuge accomplishments during the 1995...

  17. Arapaho National Wildlife Refuge also Bamforth, Hutton Lake, Morenson Lake and Pathfinder National Wildlife Refuges: Annual narrative report: Calendar year 1997

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Arapaho NWR, Bamforth NWR, Hutton Lake NWR, Morenson Lake NWR, and Pathfinder NWR outlines Refuge accomplishments during the 1997...

  18. Arapaho National Wildlife Refuge also Bamforth, Hutton Lake, Morenson Lake and Pathfinder National Wildlife Refuges: Annual narrative report: Calendar year 1994

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Arapaho NWR, Bamforth NWR, Hutton Lake NWR, Morenson Lake NWR, and Pathfinder NWR outlines Refuge accomplishments during the 1994...

  19. Arapaho National Wildlife Refuge also Bamforth, Hutton Lake, Morenson Lake and Pathfinder National Wildlife Refuges: Annual narrative report: Calendar year 1993

    US Fish and Wildlife Service, Department of the Interior — This annual narrative report for Arapaho NWR, Bamforth NWR, Hutton Lake NWR, Morenson Lake NWR, and Pathfinder NWR outlines Refuge accomplishments during the 1993...

  20. 4 km NODC/RSMAS AVHRR Pathfinder Version 5.0 and 5.1 Daily Harmonic Climatologies (1982-2008) (NODC Accession 0071181)

    National Oceanic and Atmospheric Administration, Department of Commerce — This accession contains a global, 4km daily sea surface temperature climatology derived from harmonic analysis of the AVHRR Pathfinder Version 5.0 and 5.1 sea...

  1. 4 km NODC/RSMAS AVHRR Pathfinder Version 5.0 and 5.1 Monthly Harmonic Climatologies (1982-2008) (NODC Accession 0075098)

    National Oceanic and Atmospheric Administration, Department of Commerce — This accession contains a global, 4km monthly sea surface temperature climatology derived from harmonic analysis of the AVHRR Pathfinder Version 5.0 and 5.1 sea...

  2. 4 km NODC/RSMAS AVHRR Pathfinder Version 5.0 and 5.1 5-day Harmonic Climatologies (1982-2008) (NODC Accession 0071182)

    National Oceanic and Atmospheric Administration, Department of Commerce — This accession contains a global, 4km 5-day sea surface temperature climatology derived from harmonic analysis of the AVHRR Pathfinder Version 5.0 and 5.1 sea...

  3. AVHRR Pathfinder Version 5.2 Level 3 Collated (L3C) Global 4km Sea Surface Temperature for 1981-2012

    National Oceanic and Atmospheric Administration, Department of Commerce — The AVHRR Pathfinder Version 5.2 Sea Surface Temperature data set (PFV52) is a collection of global, twice-daily 4km sea surface temperature data produced in a...

  4. New Insights into the Geology of the Mars Pathfinder Landing Site from Spectral and Morphologic Analysis of the 12-Color Superpan Panorama

    Murchie, S.; Barnouin-Jha, O.; Barnouin-Jha, K.; Bishop, J.; Johnson, J.; McSween, H.; Morris, R.

    2003-07-01

    The Pathfinder landing site contains a second lithology in addition to gray rock, consistent with highlands excavated from beneath a veneer of northern plains. Many rocks have cemented coatings that formed during an early, probably wetter climate.

  5. NOAA Climate Data Record (CDR) of Reflectance and Brightness Temperatures from AVHRR Pathfinder Atmospheres - Extended (PATMOS-x), Version 5.3

    National Oceanic and Atmospheric Administration, Department of Commerce — This NOAA Climate Data Record (CDR) of AVHRR reflectance and brightness temperatures was produced by the University of Wisconsin using the AVHRR Pathfinder...

  6. Quality Assurance statistics for AVHRR Pathfinder Version 5.2 L3-Collated (L3C) sea surface temperature in global and selected regions (NODC Accession 0111871)

    National Oceanic and Atmospheric Administration, Department of Commerce — These quality monitoring data for Pathfinder Version 5.2 (PFV5.2) Sea Surface Temperature (SST) are based on the concept of a Rich Inventory developed by the...

  7. Changes in microtubule stability and density in myelin-deficient shiverer mouse CNS axons

    Kirkpatrick, L. L.; Witt, A. S.; Payne, H. R.; Shine, H. D.; Brady, S. T.

    2001-01-01

    Altered axon-Schwann cell interactions in PNS myelin-deficient Trembler mice result in changed axonal transport rates, neurofilament and microtubule-associated protein phosphorylation, neurofilament density, and microtubule stability. To determine whether PNS and CNS myelination have equivalent effects on axons, neurofilaments, and microtubules in CNS, myelin-deficient shiverer axons were examined. The genetic defect in shiverer is a deletion in the myelin basic protein (MBP) gene, an essential component of CNS myelin. As a result, shiverer mice have little or no compact CNS myelin. Slow axonal transport rates in shiverer CNS axons were significantly increased, in contrast to the slowing in demyelinated PNS nerves. Even more striking were substantial changes in the composition and properties of microtubules in shiverer CNS axons. The density of axonal microtubules is increased, reflecting increased expression of tubulin in shiverer, and the stability of microtubules is drastically reduced in shiverer axons. Shiverer transgenic mice with two copies of a wild-type myelin basic protein transgene have an intermediate level of compact myelin, making it possible to determine whether the actual level of compact myelin is an important regulator of axonal microtubules. Both increased microtubule density and reduced microtubule stability were still observed in transgenic mouse nerves, indicating that signals beyond synaptogenesis and the mere presence of compact myelin are required for normal regulation of the axonal microtubule cytoskeleton.

  8. The importance of axonal undulation in diffusion MR measurements: a Monte Carlo simulation study.

    Nilsson, Markus; Lätt, Jimmy; Ståhlberg, Freddy; van Westen, Danielle; Hagslätt, Håkan

    2012-05-01

    Many axons follow wave-like undulating courses. This is a general feature of extracranial nerve segments, but is also found in some intracranial nervous tissue. The importance of axonal undulation has previously been considered, for example, in the context of biomechanics, where it has been shown that posture affects undulation properties. However, the importance of axonal undulation in the context of diffusion MR measurements has not been investigated. Using an analytical model and Monte Carlo simulations of water diffusion, this study compared undulating and straight axons in terms of diffusion propagators, diffusion-weighted signal intensities and parameters derived from diffusion tensor imaging, such as the mean diffusivity (MD), the eigenvalues and the fractional anisotropy (FA). All parameters were strongly affected by the presence of undulation. The diffusivity perpendicular to the undulating axons increased with the undulation amplitude, thus resembling that of straight axons with larger diameters. Consequently, models assuming straight axons for the estimation of the axon diameter from diffusion MR measurements might overestimate the diameter if undulation is present. FA decreased from approximately 0.7 to 0.5 when axonal undulation was introduced into the simulation model structure. Our results indicate that axonal undulation may play a role in diffusion measurements when investigating, for example, the optic and sciatic nerves and the spinal cord. The simulations also demonstrate that the stretching or compression of neuronal tissue comprising undulating axons alters the observed water diffusivity, suggesting that posture may be of importance for the outcome of diffusion MRI measurements.

  9. Neuroinflammation by cytotoxic T-lymphocytes impairs retrograde axonal transport in an oligodendrocyte mutant mouse.

    Chi Wang Ip

    Full Text Available Mice overexpressing proteolipid protein (PLP develop a leukodystrophy-like disease involving cytotoxic, CD8+ T-lymphocytes. Here we show that these cytotoxic T-lymphocytes perturb retrograde axonal transport. Using fluorogold stereotactically injected into the colliculus superior, we found that PLP overexpression in oligodendrocytes led to significantly reduced retrograde axonal transport in retina ganglion cell axons. We also observed an accumulation of mitochondria in the juxtaparanodal axonal swellings, indicative for a disturbed axonal transport. PLP overexpression in the absence of T-lymphocytes rescued retrograde axonal transport defects and abolished axonal swellings. Bone marrow transfer from wildtype mice, but not from perforin- or granzyme B-deficient mutants, into lymphocyte-deficient PLP mutant mice led again to impaired axonal transport and the formation of axonal swellings, which are predominantly located at the juxtaparanodal region. This demonstrates that the adaptive immune system, including cytotoxic T-lymphocytes which release perforin and granzyme B, are necessary to perturb axonal integrity in the PLP-transgenic disease model. Based on our observations, so far not attended molecular and cellular players belonging to the immune system should be considered to understand pathogenesis in inherited myelin disorders with progressive axonal damage.

  10. Eph:ephrin-B1 forward signaling controls fasciculation of sensory and motor axons.

    Luxey, Maëva; Jungas, Thomas; Laussu, Julien; Audouard, Christophe; Garces, Alain; Davy, Alice

    2013-11-15

    Axon fasciculation is one of the processes controlling topographic innervation during embryonic development. While axon guidance steers extending axons in the accurate direction, axon fasciculation allows sets of co-extending axons to grow in tight bundles. The Eph:ephrin family has been involved both in axon guidance and fasciculation, yet it remains unclear how these two distinct types of responses are elicited. Herein we have characterized the role of ephrin-B1, a member of the ephrinB family in sensory and motor innervation of the limb. We show that ephrin-B1 is expressed in sensory axons and in the limb bud mesenchyme while EphB2 is expressed in motor and sensory axons. Loss of ephrin-B1 had no impact on the accurate dorso-ventral innervation of the limb by motor axons, yet EfnB1 mutants exhibited decreased fasciculation of peripheral motor and sensory nerves. Using tissue-specific excision of EfnB1 and in vitro experiments, we demonstrate that ephrin-B1 controls fasciculation of axons via a surround repulsion mechanism involving growth cone collapse of EphB2-expressing axons. Altogether, our results highlight the complex role of Eph:ephrin signaling in the development of the sensory-motor circuit innervating the limb.

  11. The corpus callosum in primates: processing speed of axons and the evolution of hemispheric asymmetry

    Phillips, Kimberley A.; Stimpson, Cheryl D.; Smaers, Jeroen B.; Raghanti, Mary Ann; Jacobs, Bob; Popratiloff, Anastas; Hof, Patrick R.; Sherwood, Chet C.

    2015-01-01

    Interhemispheric communication may be constrained as brain size increases because of transmission delays in action potentials over the length of axons. Although one might expect larger brains to have progressively thicker axons to compensate, spatial packing is a limiting factor. Axon size distributions within the primate corpus callosum (CC) may provide insights into how these demands affect conduction velocity. We used electron microscopy to explore phylogenetic variation in myelinated axon density and diameter of the CC from 14 different anthropoid primate species, including humans. The majority of axons were less than 1 µm in diameter across all species, indicating that conduction velocity for most interhemispheric communication is relatively constant regardless of brain size. The largest axons within the upper 95th percentile scaled with a progressively higher exponent than the median axons towards the posterior region of the CC. While brain mass among the primates in our analysis varied by 97-fold, estimates of the fastest cross-brain conduction times, as conveyed by axons at the 95th percentile, varied within a relatively narrow range between 3 and 9 ms across species, whereas cross-brain conduction times for the median axon diameters differed more substantially between 11 and 38 ms. Nonetheless, for both size classes of axons, an increase in diameter does not entirely compensate for the delay in interhemispheric transmission time that accompanies larger brain size. Such biophysical constraints on the processing speed of axons conveyed by the CC may play an important role in the evolution of hemispheric asymmetry. PMID:26511047

  12. Effect of vesicle traps on traffic jam formation in fast axonal transport.

    Kuznetsov, A V

    2010-08-01

    The purpose of this paper is to develop a model for simulation of the formation of organelle traps in fast axonal transport. Such traps may form in the regions of microtubule polar mismatching. Depending on the orientation of microtubules pointing toward the trap region, these traps can accumulate either plus-end or minus-end oriented vesicles. The model predicts that the maximum concentrations of organelles occur at the boundaries of the trap regions; the overall concentration of organelles in the axon with traps is greatly increased compared to that in a healthy axon, which is expected to contribute to mechanical damages of the axon. The organelle traps induce hindrance to organelle transport down the axon; the total organelle flux down the axon with traps is found to be significantly reduced compared to that in a healthy axon.

  13. Regulation of neuronal axon specification by glia-neuron gap junctions in C. elegans

    Meng, Lingfeng; Zhang, Albert; Jin, Yishi; Yan, Dong

    2016-01-01

    Axon specification is a critical step in neuronal development, and the function of glial cells in this process is not fully understood. Here, we show that C. elegans GLR glial cells regulate axon specification of their nearby GABAergic RME neurons through GLR-RME gap junctions. Disruption of GLR-RME gap junctions causes misaccumulation of axonal markers in non-axonal neurites of RME neurons and converts microtubules in those neurites to form an axon-like assembly. We further uncover that GLR-RME gap junctions regulate RME axon specification through activation of the CDK-5 pathway in a calcium-dependent manner, involving a calpain clp-4. Therefore, our study reveals the function of glia-neuron gap junctions in neuronal axon specification and shows that calcium originated from glial cells can regulate neuronal intracellular pathways through gap junctions. DOI: http://dx.doi.org/10.7554/eLife.19510.001 PMID:27767956

  14. Interplay between kinesin-1 and cortical dynein during axonal outgrowth and microtubule organization in Drosophila neurons.

    del Castillo, Urko; Winding, Michael; Lu, Wen; Gelfand, Vladimir I

    2015-12-28

    In this study, we investigated how microtubule motors organize microtubules in Drosophila neurons. We showed that, during the initial stages of axon outgrowth, microtubules display mixed polarity and minus-end-out microtubules push the tip of the axon, consistent with kinesin-1 driving outgrowth by sliding antiparallel microtubules. At later stages, the microtubule orientation in the axon switches from mixed to uniform polarity with plus-end-out. Dynein knockdown prevents this rearrangement and results in microtubules of mixed orientation in axons and accumulation of microtubule minus-ends at axon tips. Microtubule reorganization requires recruitment of dynein to the actin cortex, as actin depolymerization phenocopies dynein depletion, and direct recruitment of dynein to the membrane bypasses the actin requirement. Our results show that cortical dynein slides 'minus-end-out' microtubules from the axon, generating uniform microtubule arrays. We speculate that differences in microtubule orientation between axons and dendrites could be dictated by differential activity of cortical dynein.

  15. Squid Giant Axon Contains Neurofilament Protein mRNA but does not Synthesize Neurofilament Proteins.

    Gainer, Harold; House, Shirley; Kim, Dong Sun; Chin, Hemin; Pant, Harish C

    2017-04-01

    When isolated squid giant axons are incubated in radioactive amino acids, abundant newly synthesized proteins are found in the axoplasm. These proteins are translated in the adaxonal Schwann cells and subsequently transferred into the giant axon. The question as to whether any de novo protein synthesis occurs in the giant axon itself is difficult to resolve because the small contribution of the proteins possibly synthesized intra-axonally is not easily distinguished from the large amounts of the proteins being supplied from the Schwann cells. In this paper, we reexamine this issue by studying the synthesis of endogenous neurofilament (NF) proteins in the axon. Our laboratory previously showed that NF mRNA and protein are present in the squid giant axon, but not in the surrounding adaxonal glia. Therefore, if the isolated squid axon could be shown to contain newly synthesized NF protein de novo, it could not arise from the adaxonal glia. The results of experiments in this paper show that abundant 3H-labeled NF protein is synthesized in the squid giant fiber lobe containing the giant axon's neuronal cell bodies, but despite the presence of NF mRNA in the giant axon no labeled NF protein is detected in the giant axon. This lends support to the glia-axon protein transfer hypothesis which posits that the squid giant axon obtains newly synthesized protein by Schwann cell transfer and not through intra-axonal protein synthesis, and further suggests that the NF mRNA in the axon is in a translationally repressed state.

  16. Axon and muscle spindle hyperplasia in the myostatin null mouse.

    Elashry, Mohamed I; Otto, Anthony; Matsakas, Antonios; El-Morsy, Salah E; Jones, Lisa; Anderson, Bethan; Patel, Ketan

    2011-02-01

    Germline deletion of the myostatin gene results in hyperplasia and hypertrophy of the tension-generating (extrafusal) fibres in skeletal muscle. As this gene is expressed predominantly in myogenic tissues it offers an excellent model with which to investigate the quantitative relationship between muscle and axonal development. Here we show that skeletal muscle hyperplasia in myostatin null mouse is accompanied by an increase in nerve fibres in major nerves of both the fore- and hindlimbs. We show that axons within these nerves undergo hypertrophy. Furthermore, we provide evidence that the age-related neural atrophic process is delayed in the absence of myostatin. Finally, we show that skeletal muscle hyperplasia in the myostatin null mouse is accompanied by an increase in the number of muscle spindles (also called stretch receptors or proprioceptors). However, our work demonstrates that the mechanisms regulating intrafusal fibre hyperplasia and hypertrophy differ from those that control the aetiology of extrafusal fibres.

  17. Coevolution of axon guidance molecule Slit and its receptor Robo.

    Yu, Qi; Li, Xiao-Tong; Zhao, Xiao; Liu, Xun-Li; Ikeo, Kazuho; Gojobori, Takashi; Liu, Qing-Xin

    2014-01-01

    Coevolution is important for the maintenance of the interaction between a ligand and its receptor during evolution. The interaction between axon guidance molecule Slit and its receptor Robo is critical for the axon repulsion in neural tissues, which is evolutionarily conserved from planarians to humans. However, the mechanism of coevolution between Slit and Robo remains unclear. In this study, we found that coordinated amino acid changes took place at interacting sites of Slit and Robo by comparing the amino acids at these sites among different organisms. In addition, the high level correlation between evolutionary rate of Slit and Robo was identified in vertebrates. Furthermore, the sites under positive selection of slit and robo were detected in the same lineage such as mosquito and teleost. Overall, our results provide evidence for the coevolution between Slit and Robo.

  18. Antiretroviral Therapy-Associated Acute Motor and Sensory Axonal Neuropathy

    Kimberly N. Capers

    2011-01-01

    Full Text Available Guillain-Barré syndrome (GBS has been reported in HIV-infected patients in association with the immune reconstitution syndrome whose symptoms can be mimicked by highly active antiretroviral therapy (HAART-mediated mitochondrial toxicity. We report a case of a 17-year-old, HIV-infected patient on HAART with a normal CD4 count and undetectable viral load, presenting with acute lower extremity weakness associated with lactatemia. Electromyography/nerve conduction studies revealed absent sensory potentials and decreased compound muscle action potentials, consistent with a diagnosis of acute motor and sensory axonal neuropathy. Lactatemia resolved following cessation of HAART; however, neurological deficits minimally improved over several months in spite of immune modulatory therapy. This case highlights the potential association between HAART, mitochondrial toxicity and acute axonal neuropathies in HIV-infected patients, distinct from the immune reconstitution syndrome.

  19. Coevolution of axon guidance molecule Slit and its receptor Robo.

    Qi Yu

    Full Text Available Coevolution is important for the maintenance of the interaction between a ligand and its receptor during evolution. The interaction between axon guidance molecule Slit and its receptor Robo is critical for the axon repulsion in neural tissues, which is evolutionarily conserved from planarians to humans. However, the mechanism of coevolution between Slit and Robo remains unclear. In this study, we found that coordinated amino acid changes took place at interacting sites of Slit and Robo by comparing the amino acids at these sites among different organisms. In addition, the high level correlation between evolutionary rate of Slit and Robo was identified in vertebrates. Furthermore, the sites under positive selection of slit and robo were detected in the same lineage such as mosquito and teleost. Overall, our results provide evidence for the coevolution between Slit and Robo.

  20. Morphology of axonal transport abnormalities in primate eyes.

    Radius, R L; Anderson, D. R.

    1981-01-01

    The ultrastructure of the retina and optic nerve head was studied in primate eyes after central retinal artery occlusion. Within 2 hours of the vascular occlusion the inner retinal layers undergo watery (isosmotic) swelling. This watery swelling of axons and astroglia extends into the nerve head as far back as the anterior boundary of the scleral lamina cribrosa. The swelling is increased 4 hours after the occlusion, and by 24 hours disintegration has occurred. At the optic nerve head mitocho...

  1. Cortical Interneuron Subtypes Vary in Their Axonal Action Potential Properties

    Casale, Amanda E.; Foust, Amanda J.; Bal, Thierry; McCormick, David A.

    2015-01-01

    The role of interneurons in cortical microcircuits is strongly influenced by their passive and active electrical properties. Although different types of interneurons exhibit unique electrophysiological properties recorded at the soma, it is not yet clear whether these differences are also manifested in other neuronal compartments. To address this question, we have used voltage-sensitive dye to image the propagation of action potentials into the fine collaterals of axons and dendrites in two o...

  2. Experiments and Spectral Studies of Martian Volcanic Rocks: Implications for the Origin of Pathfinder Rocks and Soils

    Rutherford, Malcolm J.; Mustard, Jack; Weitz, Catherine

    2002-01-01

    The composition and spectral properties of the Mars Pathfinder rocks and soils together with the identification of basaltic and andesitic Mars terrains based on Thermal Emission Spectrometer (TES) data raised interesting questions regarding the nature and origin of Mars surface rocks. We have investigated the following questions: (1) are the Pathfinder rocks igneous and is it possible these rocks could have formed by known igneous processes, such as equilibrium or fractional crystallization, operating within SNC magmas known to exist on Mars? If it is possible, what P (depth) and PH2O conditions are required? (2) whether TES-based interpretations of plagioclase-rich basalt and andesitic terrains in the south and north regions of Mars respectively are unique. Are the surface compositions of these regions plagioclase-rich, possibly indicating the presence of old AI-rich crust of Mars, or are the spectra being affected by something like surface weathering processes that might determine the spectral pyroxene to plagioclase ratio?

  3. Chromosome aberrations in solid tumors have a stochastic nature

    Castro, Mauro A.A. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil) and Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil) and Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil) and Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil)]. E-mail: mauro@ufrgs.br; Onsten, Tor G.H. [Departamento de Medicina Interna, Hospital de Clinicas de Porto Alegre, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2350, Porto Alegre 90035-903 (Brazil); Universidade Luterana do Brasil, Rua Miguel Tostes 101, Canoas 92420-280 (Brazil); Moreira, Jose C.F. [Departamento de Bioquimica, Universidade Federal do Rio Grande do Sul, Rua Ramiro Barcelos 2600-anexo, Porto Alegre 90035-003 (Brazil); Almeida, Rita M.C. de [Instituto de Fisica, Universidade Federal do Rio Grande do Sul, Av. Bento Goncalves 9500, Porto Alegre 91501-970 (Brazil)

    2006-08-30

    An important question nowadays is whether chromosome aberrations are random events or arise from an internal deterministic mechanism, which leads to the delicate task of quantifying the degree of randomness. For this purpose, we have defined several Shannon information functions to evaluate disorder inside a tumor and between tumors of the same kind. We have considered 79 different kinds of solid tumors with 30 or more karyotypes retrieved from the Mitelman Database of Chromosome Aberrations in Cancer. The Kaplan-Meier cumulative survival was also obtained for each solid tumor type in order to correlate data with tumor malignance. The results here show that aberration spread is specific for each tumor type, with high degree of diversity for those tumor types with worst survival indices. Those tumor types with preferential variants (e.g. high proportion of a given karyotype) have shown better survival statistics, indicating that aberration recurrence is a good prognosis. Indeed, global spread of both numerical and structural abnormalities demonstrates the stochastic nature of chromosome aberrations by setting a signature of randomness associated to the production of disorder. These results also indicate that tumor malignancy correlates not only with karyotypic diversity taken from different tumor types but also taken from single tumors. Therefore, by quantifying aberration spread, we could confront diverse models and verify which of them points to the most likely outcome. Our results suggest that the generating process of chromosome aberrations is neither deterministic nor totally random, but produces variations that are distributed between these two boundaries.

  4. Aberrant DNA methylation in cloned ovine embryos

    LIU Lei; HOU Jian; LEI TingHua; BAI JiaHua; GUAN Hong; AN XiaoRong

    2008-01-01

    By using the approach of immunofluorescence staining with an antibody against 5-methylcytosine (5MeC), the present study detected the DNA methylation patterns of cloned ovine embryos. The em-bryos derived from in vitro fertilization were also examined for reference purpose. The results showed that: (1) during the pre-implantation development, cloned embryos displayed a similar demethylation profile to the fertilized embryos; that is, the methylation level decreased to the lowest at 8-cell stage, and then increased again at morulae stage. However, methylation level was obviously higher in cloned embryos than in stage-matched fertilized embryos, especially at 8-cell stage and afterwards; (2) at blastocyst stage, the methylation pattern in cloned embryos was different from that in fertilized em-bryos. In cloned blastocyst, inner cell mass (ICM) exhibited a comparable level to trophectoderm cells (TE), while in in-vitro fertilized blastocyst the methylation level of ICM was lower than that of TE, which is not consistent with that reported by other authors. These results indicate that DNA methylation is abnormally reprogrammed in cloned embryos, implying that aberrant DNA methylation reprogramming may be one of the factors causing cloned embryos developmental failure.

  5. Epigenetic aberrations and therapeutic implications in gliomas.

    Natsume, Atsushi; Kondo, Yutaka; Ito, Motokazu; Motomura, Kazuya; Wakabayashi, Toshihiko; Yoshida, Jun

    2010-06-01

    Almost all cancer cells have multiple epigenetic abnormalities, which combine with genetic changes to affect many cellular processes, including cell proliferation and invasion, by silencing tumor-suppressor genes. In this review, we focus on the epigenetic mechanisms of DNA hypomethylation and CpG island hypermethylation in gliomas. Aberrant hypermethylation in promoter CpG islands has been recognized as a key mechanism involved in the silencing of cancer-associated genes and occurs at genes with diverse functions related to tumorigenesis and tumor progression. Such promoter hypermethylation can modulate the sensitivity of glioblastomas to drugs and radiotherapy. As an example, the methylation of the O6-methylguanine DNA methyltransferase (MGMT) promoter is a specific predictive biomarker of tumor responsiveness to chemotherapy with alkylating agents. Further, we reviewed reports on pyrosequencing - a simple technique for the accurate and quantitative analysis of DNA methylation. We believe that the quantification of MGMT methylation by pyrosequencing might enable the selection of patients who are most likely to benefit from chemotherapy. Finally, we also evaluated the potential of de novo NY-ESO-1, the most immunogenic cancer/testis antigen (CTA) discovered thus far, as an immunotherapy target. The use of potent epigenetics-based therapy for cancer cells might restore the abnormally regulated epigenomes to a more normal state through epigenetic reprogramming. Thus, epigenetic therapy may be a promising and potent treatment for human neoplasia.

  6. Axonal Dysfunction Precedes Motor Neuronal Death in Amyotrophic Lateral Sclerosis.

    Yuta Iwai

    Full Text Available Wide-spread fasciculations are a characteristic feature in amyotrophic lateral sclerosis (ALS, suggesting motor axonal hyperexcitability. Previous excitability studies have shown increased nodal persistent sodium conductances and decreased potassium currents in motor axons of ALS patients, both of the changes inducing hyperexcitability. Altered axonal excitability potentially contributes to motor neuron death in ALS, but the relationship of the extent of motor neuronal death and abnormal excitability has not been fully elucidated. We performed multiple nerve excitability measurements in the median nerve at the wrist of 140 ALS patients and analyzed the relationship of compound muscle action potential (CMAP amplitude (index of motor neuronal loss and excitability indices, such as strength-duration time constant, threshold electrotonus, recovery cycle and current-threshold relationships. Compared to age-matched normal controls (n = 44, ALS patients (n = 140 had longer strength-duration time constant (SDTC: a measure of nodal persistent sodium current; p 5mV. Regression analyses showed that SDTC (R = -0.22 and depolarizing threshold electrotonus (R = -0.22 increased with CMAP decline. These findings suggest that motor nerve hyperexcitability occurs in the early stage of the disease, and precedes motor neuronal loss in ALS. Modulation of altered ion channel function could be a treatment option for ALS.

  7. Efficient simulations of tubulin-driven axonal growth.

    Diehl, Stefan; Henningsson, Erik; Heyden, Anders

    2016-08-01

    This work concerns efficient and reliable numerical simulations of the dynamic behaviour of a moving-boundary model for tubulin-driven axonal growth. The model is nonlinear and consists of a coupled set of a partial differential equation (PDE) and two ordinary differential equations. The PDE is defined on a computational domain with a moving boundary, which is part of the solution. Numerical simulations based on standard explicit time-stepping methods are too time consuming due to the small time steps required for numerical stability. On the other hand standard implicit schemes are too complex due to the nonlinear equations that needs to be solved in each step. Instead, we propose to use the Peaceman-Rachford splitting scheme combined with temporal and spatial scalings of the model. Simulations based on this scheme have shown to be efficient, accurate, and reliable which makes it possible to evaluate the model, e.g. its dependency on biological and physical model parameters. These evaluations show among other things that the initial axon growth is very fast, that the active transport is the dominant reason over diffusion for the growth velocity, and that the polymerization rate in the growth cone does not affect the final axon length.

  8. Axon clinical chemistry analyzer evaluated according to ECCLS protocol.

    Brenna, S; Prencipe, L

    1992-10-01

    We assessed the analytical performance of the Axon system (Bayer Diagnostici), according to the European Committee for Clinical Laboratory Standards guidelines, for assay of 12 analytes: cholesterol, creatinine, glucose, total protein, urea, uric acid, alkaline phosphatase, alpha-amylase, aspartate aminotransferase, creatine kinase, sodium, and potassium. The field evaluation lasted approximately 5 months and involved the collection of approximately 10,000 data points with the Axon. The following results were obtained: The highest CVs for controls and human sera at different concentration/activity values were 2.2% for within-run imprecision (n = 60; 3 days, pooled estimate) and 3.5% for the between-day imprecision (n = 20 days). Close correlation was found with results for patients' specimens assayed with comparative instruments (Hitachi 717 for substrates and enzymes, Beckman Synchron EL/E4A for electrolytes). No drift was observed during 8 h of operation. The linearity range was broad, sometimes exceeding the manufacturer's claims. No sample-, reagent-, or cuvette-related carryover was found. Measurement of control sera gave results within +/- 5% of the assigned values. We conclude that good reliability and practicability make the Axon system suitable for laboratories with various needs.

  9. Apical root canal transportation of different pathfinding systems and their effects on shaping ability of ProTaper Next

    Turker, Sevinc Aktemur; Uzunoglu, Emel

    2015-01-01

    Background This study aimed to compare glide path preparation of different pathfinding systems and their effects on the apical transportation of ProTaper Next (Dentsply Maillefer, Ballaigues, Switzerland) in mesial root canals of extracted human mandibular molars, using digital subtraction radiography. Material and Methods The mesial canals of 40 mandibular first molars (with curvature angles between 25° and 35°) were selected for this study. The specimens were divided randomly into 4 groups ...

  10. Ciliary neurotrophic factor reverses aberrant mitochondrial bioenergetics through the JAK/STAT pathway in cultured sensory neurons derived from streptozotocin-induced diabetic rodents.

    Chowdhury, Subir Roy; Saleh, Ali; Akude, Eli; Smith, Darrell R; Morrow, Dwane; Tessler, Lori; Calcutt, Nigel A; Fernyhough, Paul

    2014-07-01

    Mitochondrial dysfunction occurs in sensory neurons and contributes to diabetic neuropathy. Ciliary neurotrophic factor (CNTF) stimulates axon regeneration in type 1 diabetic rodents and prevents deficits in axonal caliber, nerve conduction, and thermal sensation. We tested the hypothesis that CNTF enhances sensory neuron function in diabetes through JAK/STAT (Janus kinase/signal transducers and activators of transcription) signaling to normalize impaired mitochondrial bioenergetics. The effect of CNTF on gene expression and neurite outgrowth of cultured adult dorsal root ganglia (DRG) sensory neurons derived from control and streptozotocin (STZ)-induced diabetic rodents was quantified. Polarization status and bioenergetics profile of mitochondria from cultured sensory neurons were determined. CNTF treatment prevented reduced STAT3 phosphorylation (Tyr 705) in DRG of STZ-diabetic mice and also enhanced STAT3 phosphorylation in rat DRG cultures. CNTF normalized polarization status of the mitochondrial inner membrane and corrected the aberrant oligomycin-induced mitochondrial hyperpolarization in axons of diabetic neurons. The mitochondrial bioenergetics profile demonstrated that spare respiratory capacity and respiratory control ratio were significantly depressed in sensory neurons cultured from STZ-diabetic rats and were corrected by acute CNTF treatment. The positive effects of CNTF on neuronal mitochondrial function were significantly inhibited by the specific JAK inhibitor, AG490. Neurite outgrowth of sensory neurons from age-matched control and STZ-induced diabetic rats was elevated by CNTF and blocked by AG490. We propose that CNTF's ability to enhance axon regeneration and protect from fiber degeneration in diabetes is associated with its targeting of mitochondrial function and improvement of cellular bioenergetics, in part, through JAK/STAT signaling.

  11. Study of residual aberration for non-imaging focusing heliostat

    Chen, Y.T.; Chong, K.K.; Lim, B.H.; Lim, C.S. [Institute of Energy and Environment, Malaysia University of Science and Technology, No. 17, Jalan SS7/26, Kelana Jaya, 47301 Petaling Jaya, Selangor (Malaysia)

    2003-08-01

    Instead of using a specific focusing geometry, a non-imaging focusing heliostat has no fixed geometry but is composed of many small movable element mirrors that can be manoeuvred to eliminate the first-order aberration. Following our previous publication on the principle of non-imaging focusing heliostat, this paper further explores higher order residual aberration that limits the size of the focusing spot. The residual aberration can be partially corrected by offsetting the pivot point of mirrors and pre-setting the tilting angles of mirrors.

  12. William Herschel Telescope site characterization using the MOAO pathfinder CANARY on-sky data

    Martin, O. A.; Correia, C. M.; Gendron, E.; Rousset, G.; Vidal, F.; Morris, T. J.; Basden, A. G.; Myers, R. M.; Ono, Y. H.; Neichel, B.; Fusco, T.

    2016-07-01

    CANARY is the Multi-Object Adaptive Optics (MOAO) pathfinder for the future MOAO-assisted Integral-Field Units (IFU) proposed for Extremely Large Telescopes (ELT). The MOAO concept relies on tomographically reconstructing the turbulence using multiple measurements along different lines of sight. Tomography requires the knowledge of the statistical turbulence parameters, commonly recovered from the system telemetry using a dedicated profiling technique. For demonstration purposes with the MOAO pathfinder CANARY, this identification is performed thanks to the Learn & Apply (L&A) algorithm, that consists in model-fitting the covariance matrix of WFS measurements dependant on relevant parameters: Cn2(h) profile, outer scale profile and system mis-registration. We explore an upgrade of this algorithm, the Learn 3 Steps (L3S) approach, that allows one to dissociate the identification of the altitude layers from the ground in order to mitigate the lack of convergence of the required empirical covariance matrices therefore reducing the required length of data time-series for reaching a given accuracy. For nominal observation conditions, the L3S can reach the same level of tomographic error in using five times less data frames than the L&A approach. The L3S technique has been applied over a large amount of CANARY data to characterize the turbulence above the William Herschel Telescope (WHT). These data have been acquired the 13th, 15th, 16th, 17th and 18th September 2013 and we find 0.67"/8.9m/3.07m.s-1 of total seeing/outer scale/wind-speed, with 0.552"/9.2m/2.89m.s-1 below 1.5 km and 0.263"/10.3m/5.22m.s-1 between 1.5 and 20 km. We have also determined the high altitude layers above 20 km, missed by the tomographic reconstruction on CANARY , have a median seeing of 0.187" and have occurred 16% of observation time.

  13. Selection and Assessment of Predictions of the Mars Pathfinder Landing Site

    Golombek, M. P.; Moore, H. J.; Haldemann, A. F. C.; Cook, R. A.; Parker, T. J.; Schofield, J. T.

    1998-01-01

    The successful landing of the Mars Pathfinder spacecraft on Mars allows the review of the process of selecting the landing site and assessing predictions made for the site based on Viking and Earth-based data. Selection of the landing site for Mars Pathfinder was a two-phase process. The first phase took place from October 1993 to June 1994 and involved: initial identification of engineering constraints, definition of environmental conditions at the site for spacecraft design, and evaluation of the scientific potential of different landing sites. This phase culminated with the first "Mars Pathfinder Landing Site Workshop", held at the Lunar and Planetary Institute in Houston, Texas on April 18-19, 1994, in which suggested approaches and landing sites were solicited from the entire scientific community. A preliminary site was selected by the project for design purposes in June 1994. The second phase took place from July 1994 to March 1996 and involved: developing criteria for evaluating site safety using images and remote sensing data, testing of the spacecraft and landing subsystems (with design improvements) to establish quantitative engineering constraints on landing site characteristics, evaluating all potential landing sites on Mars, and certification of the site by the project. This phase included a second open workshop, "Mars Pathfinder Landing Site Workshop II: Characteristics of the Ares Vallis Region and Field Trips in the Channeled Scabland, Washington" held in Spokane and Moses Lake September 24-30, 1995 and formal acceptance of the site by NASA Headquarters. Engineering constraints on Pathfinder landing sites were developed from the initial design of the spacecraft and the entry, descent and landing scenario. The site must be within 5 degrees of the subsolar latitude at the time of landing (15N for maximum solar power and flexible communications with Earth. It also must be below 0 km elevation to enable enough time for the parachute to bring the lander

  14. Loss of Saltation and Presynaptic Action Potential Failure in Demyelinated Axons

    Hamada, Mustafa S.; Popovic, Marko A.; Kole, Maarten H. P.

    2017-01-01

    In cortical pyramidal neurons the presynaptic terminals controlling transmitter release are located along unmyelinated axon collaterals, far from the original action potential (AP) initiation site, the axon initial segment (AIS). Once initiated, APs will need to reliably propagate over long distances and regions of geometrical inhomogeneity like branch points (BPs) to rapidly depolarize the presynaptic terminals and confer temporally precise synaptic transmission. While axon pathologies such as demyelinating diseases are well established to impede the fidelity of AP propagation along internodes, to which extent myelin loss affects propagation along BPs and axon collaterals is not well understood. Here, using the cuprizone demyelination model, we performed optical voltage-sensitive dye (VSD) imaging from control and demyelinated layer 5 pyramidal neuron axons. In the main axon, we find that myelin loss switches the modality of AP propagation from rapid saltation towards a slow continuous wave. The duration of single AP waveforms at BPs or nodes was, however, only slightly briefer. In contrast, by using two-photon microscopy-guided loose-seal patch recordings from axon collaterals we revealed a presynaptic AP broadening in combination with a reduced velocity and frequency-dependent failure. Finally, internodal myelin loss was also associated with de novo sprouting of axon collaterals starting from the primary (demyelinated) axon. Thus, the loss of oligodendrocytes and myelin sheaths bears functional consequences beyond the main axon, impeding the temporal fidelity of presynaptic APs and affecting the functional and structural organization of synaptic connectivity within the neocortex.

  15. Regulation of action potential waveforms by axonal GABAA receptors in cortical pyramidal neurons.

    Yang Xia

    Full Text Available GABAA receptors distributed in somatodendritic compartments play critical roles in regulating neuronal activities, including spike timing and firing pattern; however, the properties and functions of GABAA receptors at the axon are still poorly understood. By recording from the cut end (bleb of the main axon trunk of layer -5 pyramidal neurons in prefrontal cortical slices, we found that currents evoked by GABA iontophoresis could be blocked by picrotoxin, indicating the expression of GABAA receptors in axons. Stationary noise analysis revealed that single-channel properties of axonal GABAA receptors were similar to those of somatic receptors. Perforated patch recording with gramicidin revealed that the reversal potential of the GABA response was more negative than the resting membrane potential at the axon trunk, suggesting that GABA may hyperpolarize the axonal membrane potential. Further experiments demonstrated that the activation of axonal GABAA receptors regulated the amplitude and duration of action potentials (APs and decreased the AP-induced Ca2+ transients at the axon. Together, our results indicate that the waveform of axonal APs and the downstream Ca2+ signals are modulated by axonal GABAA receptors.

  16. Intra-axonal protein synthesis - a new target for neural repair?

    Jeffery L Twiss

    2016-01-01

    Full Text Available Although initially argued to be a feature of immature neurons with incomplete polarization, there is clear evidence that neurons in the peripheral nervous system retain the capacity for intra-axonal protein synthesis well into adulthood. This localized protein synthesis has been shown to contribute to injury signaling and axon regeneration in peripheral nerves. Recent works point to potential for protein synthesis in axons of the vertebrate central nervous system. mRNAs and protein synthesis machinery have now been documented in lamprey, mouse, and rat spinal cord axons. Intra-axonal protein synthesis appears to be activated in adult vertebrate spinal cord axons when they are regeneration-competent. Rat spinal cord axons regenerating into a peripheral nerve graft contain mRNAs and markers of activated translational machinery. Indeed, levels of some growth-associated mRNAs in these spinal cord axons are comparable to the regenerating sciatic nerve. Markers of active translation tend to decrease when these axons stop growing, but can be reactivated by a second axotomy. These emerging observations raise the possibility that mRNA transport into and translation within axons could be targeted to facilitate regeneration in both the peripheral and central nervous systems.

  17. Intra-axonal protein synthesis - a new target for neural repair?

    Twiss, Jeffery L; Kalinski, Ashley L; Sachdeva, Rahul; Houle, John D

    2016-09-01

    Although initially argued to be a feature of immature neurons with incomplete polarization, there is clear evidence that neurons in the peripheral nervous system retain the capacity for intra-axonal protein synthesis well into adulthood. This localized protein synthesis has been shown to contribute to injury signaling and axon regeneration in peripheral nerves. Recent works point to potential for protein synthesis in axons of the vertebrate central nervous system. mRNAs and protein synthesis machinery have now been documented in lamprey, mouse, and rat spinal cord axons. Intra-axonal protein synthesis appears to be activated in adult vertebrate spinal cord axons when they are regeneration-competent. Rat spinal cord axons regenerating into a peripheral nerve graft contain mRNAs and markers of activated translational machinery. Indeed, levels of some growth-associated mRNAs in these spinal cord axons are comparable to the regenerating sciatic nerve. Markers of active translation tend to decrease when these axons stop growing, but can be reactivated by a second axotomy. These emerging observations raise the possibility that mRNA transport into and translation within axons could be targeted to facilitate regeneration in both the peripheral and central nervous systems.

  18. Intra-axonal protein synthesis - a new target for neural repair?

    Jeffery L Twiss; Ashley L Kalinski; Rahul Sachdeva; John D Houle

    2016-01-01

    Although initially argued to be a feature of immature neurons with incomplete polarization, there is clear evidence that neurons in the peripheral nervous system retain the capacity for intra-axonal protein synthe-sis well into adulthood. This localized protein synthesis has been shown to contribute to injury signaling and axon regeneration in peripheral nerves. Recent works point to potential for protein synthesis in axons of the vertebrate central nervous system. mRNAs and protein synthesis machinery have now been docu-mented in lamprey, mouse, and rat spinal cord axons. Intra-axonal protein synthesis appears to be activated in adult vertebrate spinal cord axons when they are regeneration-competent. Rat spinal cord axons regen-erating into a peripheral nerve graft contain mRNAs and markers of activated translational machinery. Indeed, levels of some growth-associated mRNAs in these spinal cord axons are comparable to the regen-erating sciatic nerve. Markers of active translation tend to decrease when these axons stop growing, but can be reactivated by a second axotomy. These emerging observations raise the possibility that mRNA transport into and translation within axons could be targeted to facilitate regeneration in both the peripheral and central nervous systems.

  19. High order aberration and straylight evaluation after cataract surgery with implantation of an aspheric,aberration correcting monofocal intraocular lens

    Florian; T; A; Kretz; Tamer; Tandogan; Ramin; Khoramnia; Gerd; U; Auffarth

    2015-01-01

    ·AIM: To evaluate the quality of vision in respect to high order aberrations and straylight perception after implantation of an aspheric, aberration correcting,monofocal intraocular lens(IOL).·METHODS: Twenty-one patients(34 eyes) aged 50 to83 y underwent cataract surgery with implantation of an aspheric, aberration correcting IOL(Tecnis ZCB00,Abbott Medical Optics). Three months after surgery they were examined for uncorrected(UDVA) and corrected distance visual acuity(CDVA), contrast sensitivity(CS)under photopic and mesopic conditions with and without glare source, ocular high order aberrations(HOA, Zywave II) and retinal straylight(C-Quant).· RESULTS: Postoperatively, patients achieved a postoperative CDVA of 0.0 log MAR or better in 97.1% of eyes. Mean values of high order abberations were +0.02±0.27(primary coma components) and-0.04 ±0.16(spherical aberration term). Straylight values of the C-Quant were 1.35±0.44 log which is within normal range of age matched phakic patients. The CS measurements under mesopic and photopic conditions in combination with and without glare did not show any statistical significance in the patient group observed(P ≥0.28).· CONCLUSION: The implantation of an aspherical aberration correcting monofocal IOL after cataractsurgery resulted in very low residual higher order aberration(HOA) and normal straylight.

  20. ROCK2 is a major regulator of axonal degeneration, neuronal death and axonal regeneration in the CNS.

    Koch, J C; Tönges, L; Barski, E; Michel, U; Bähr, M; Lingor, P

    2014-05-15

    The Rho/ROCK/LIMK pathway is central for the mediation of repulsive environmental signals in the central nervous system. Several studies using pharmacological Rho-associated protein kinase (ROCK) inhibitors have shown positive effects on neurite regeneration and suggest additional pro-survival effects in neurons. However, as none of these drugs is completely target specific, it remains unclear how these effects are mediated and whether ROCK is really the most relevant target of the pathway. To answer these questions, we generated adeno-associated viral vectors to specifically downregulate ROCK2 and LIM domain kinase (LIMK)-1 in rat retinal ganglion cells (RGCs) in vitro and in vivo. We show here that specific knockdown of ROCK2 and LIMK1 equally enhanced neurite outgrowth of RGCs on inhibitory substrates and both induced substantial neuronal regeneration over distances of more than 5 mm after rat optic nerve crush (ONC) in vivo. However, only knockdown of ROCK2 but not LIMK1 increased survival of RGCs after optic nerve axotomy. Moreover, knockdown of ROCK2 attenuated axonal degeneration of the proximal axon after ONC assessed by in vivo live imaging. Mechanistically, we demonstrate here that knockdown of ROCK2 resulted in decreased intraneuronal activity of calpain and caspase 3, whereas levels of pAkt and collapsin response mediator protein 2 and autophagic flux were increased. Taken together, our data characterize ROCK2 as a specific therapeutic target in neurodegenerative diseases and demonstrate new downstream effects of ROCK2 including axonal degeneration, apoptosis and autophagy.

  1. Anisoplanatism in adaptive optics systems due to pupil aberrations

    Bauman, B

    2005-08-01

    Adaptive optics systems typically include an optical relay that simultaneously images the science field to be corrected and also a set of pupil planes conjugate to the deformable mirror of the system. Often, in the optical spaces where DM's are placed, the pupils are aberrated, leading to a displacement and/or distortion of the pupil that varies according to field position--producing a type of anisoplanatism, i.e., a degradation of the AO correction with field angle. The pupil aberration phenomenon is described and expressed in terms of Seidel aberrations. An expression for anisoplanatism as a function of pupil distortion is derived, an example of an off-axis parabola is given, and a convenient method for controlling pupil-aberration-generated anisoplanatism is proposed.

  2. Automated spherical aberration correction in scanning confocal microscopy

    Yoo, H.W.; Royen, M.E.; van Cappellen, W.A.; Houtsmuller, A.B.; Verhaegen, M.H.G.; Schitter, G.

    2014-01-01

    Mismatch between the refractive indexes of immersion media and glass coverslips introduces spherical aberrations in microscopes especially for high numerical aperture objectives. This contribution demonstrates an automated adjustment of the coverslip correction collar in scanning confocal microscopy

  3. Impact of primary aberrations on coherent lidar performance

    Hu, Qi; Rodrigo, Peter John; Iversen, Theis Faber Quist;

    2014-01-01

    In this work we investigate the performance of a monostatic coherent lidar system in which the transmit beam is under the influence of primary phase aberrations: spherical aberration (SA) and astigmatism. The experimental investigation is realized by probing the spatial weighting function...... of the lidar system using different optical transceiver configurations. A rotating belt is used as a hard target. Our study shows that the lidar weighting function suffers from both spatial broadening and shift in peak position in the presence of aberration. It is to our knowledge the first experimental...... effciency, the optimum truncation of the transmit beam and the spatial sensitivity of a CW coherent lidar system. Under strong degree of aberration, the spatial confinement is significantly degraded. However for SA, the degradation of the spatial confinement can be reduced by tuning the truncation...

  4. Automated computational aberration correction method for broadband interferometric imaging techniques.

    Pande, Paritosh; Liu, Yuan-Zhi; South, Fredrick A; Boppart, Stephen A

    2016-07-15

    Numerical correction of optical aberrations provides an inexpensive and simpler alternative to the traditionally used hardware-based adaptive optics techniques. In this Letter, we present an automated computational aberration correction method for broadband interferometric imaging techniques. In the proposed method, the process of aberration correction is modeled as a filtering operation on the aberrant image using a phase filter in the Fourier domain. The phase filter is expressed as a linear combination of Zernike polynomials with unknown coefficients, which are estimated through an iterative optimization scheme based on maximizing an image sharpness metric. The method is validated on both simulated data and experimental data obtained from a tissue phantom, an ex vivo tissue sample, and an in vivo photoreceptor layer of the human retina.

  5. Aberrant internal carotid artery in the middle ear

    Roh, Keun Tak; Kang, Hyun Koo [Dept. of Radiology, Seoul Veterans Hospital, Seoul (Korea, Republic of)

    2014-10-15

    The knowledge about the aberrant internal carotid artery (ICA) in the middle ear is essential for clinicians, because a misdiagnosis of the aberrant ICA could have serious consequences such as excessive aural bleeding during a middle ear surgery. A 38-year-old woman presented with tinnitus and hearing difficulties of the left ear that had started 5 years ago. During otoscopy, an anteroinferior bluish mass was seen in the tympanic space. Computed tomography and magnetic resonance imaging demonstrated a left-side aberrant ICA with bony dehiscence of the carotid canal in the middle ear and a reduced diameter of the tympanic ICA. Herein we report a case of an aberrant ICA in the middle ear. We also review the literature regarding this important vascular anomaly of the temporal bone which may lead to disastrous surgical complications.

  6. Intrinsic Third Order Aberrations in Electrostatic and Magnetic Quadrupoles

    Baartman, R

    2015-01-01

    Intrinsic aberrations are those which occur due to the finite length of the desired field configuration. They are often loosely ascribed to the fringing field. This is misleading as it implies that the effects can be minimized by shaping the fields. In fact, there is an irreducible component related to the broken symmetry. It is present even in the hard-edge limit, and moreover, the other (soft-edge) effects can be simply ascribed to the intrinsic aberration spread over a finite length. We rederive the aberration formulas for quadrupoles using a Hamiltonian formalism. This allows for an easy comparison of electrostatic and magnetic quadrupoles. For different combinations of large and small emittances in the two transverse planes, it is found that in some situations electrostatic quadrupoles have lower aberrations, while in others, magnetic quadrupoles are better. As well, we discuss the ways in which existing transport codes handle quadrupole fringe fields. Pitfalls are pointed out and improvements proposed.

  7. Are persistent delusions in schizophrenia associated with aberrant salience?

    Rafeef Abboud

    2016-06-01

    Conclusion: These findings do not support the hypothesis that persistent delusions are related to aberrant motivational salience processing in TRS patients. However, they do support the view that patients with schizophrenia have impaired reward learning.

  8. PETER: A Hardware Simulator for the Test Mass-GRS System of LISA Pathfinder

    Marconi, L.; Stanga, R.; Bassan, M.; De Marchi, F.; Pucacco, G.; Visco, M.; Di Fiore, L.; De Rosa, R.; Garufi, F.

    2013-01-01

    Each LISA PathFinder test mass (TM) will be sensitive to forces along all its 6 Degrees of Freedom (DoFs). Extensive ground testing is required in order to evaluate the influence of cross-talks from the read-out and actuator channels. In the INFN laboratory of Firenze we have developed a facility for a good representation of the free fall conditions of the TM on flight. A hollow replica of a TM hanging from a double torsion pendulum can move inside a Gravitational Reference Sensor (GRS) with quasi free fall condition on two Dofs, in the frequency band (0.1 ÷ 100)mHz. On both DoFs, the target residual accelerations (yet to be achieved) at the low end frequency range are ≤ 3 × 10-13ms-2, limited by the thermal noise of the fibres. At higher frequencies, the sensitivity is limited by the readout noise of the readout, a replica of the flight electronics. After a long commissioning, we are now in operating conditions, and can carry out a series of experiments to better qualify the interaction between TM and GRS. In this paper we will show some significant qualification measurements and a first scientific measurements, i.e. the measurement and compensation of the DC bias in the GRS using two independent channels, as well as a measurement of the residual acceleration of the translational DoF, with the feedback loop closed on the rotational one, and viceversa.

  9. SZ effects in the Magneticum Pathfinder Simulation: Comparison with the Planck, SPT, and ACT results

    Dolag, Klaus; Sunyaev, Rashid

    2015-01-01

    We calculate the one-point probability density distribution functions (PDF) and the power spectra of the thermal and kinetic Sunyaev-Zeldovich (tSZ and kSZ) effects and the mean Compton Y parameter using the Magneticum Pathfinder simulations, state-of-the-art cosmological hydrodynamical simulations of a large cosmological volume of (896 Mpc/h)^3. These simulations follow in detail the thermal and chemical evolution of the intracluster medium as well as the evolution of super-massive black holes and their associated feedback processes. We construct full-sky maps of tSZ and kSZ from the light-cones out to z=0.17, and one realization of 8.8x8.8 degree wide, deep light-cone out to z=5.2. The local universe at z=1.18x10^{-6} for \\Omega_m=0.272 and \\sigma_8=0.809. Nearly half (~ 5x10^{-7}) of the signal comes from halos below a virial mass of 10^{13}M_\\odot/h. Scaling this to the Planck 2015 parameters, we find =1.57x10^{-6}. The PDF and the power spectrum of kSZ from our simulation agree broadly with the previous ...

  10. Scientific Potential of DECIGO Pathfinder and Testing GR with Space-Borne Gravitational Wave Interferometers

    Yagi, Kent

    2013-01-01

    DECIGO Pathfinder (DPF) has an ability to detect gravitational waves from galactic intermediate-mass black hole binaries. If the signal is detected, it would be possible to determine parameters of the binary components. Furthermore, by using future space-borne gravitational wave interferometers, it would be possible to test alternative theories of gravity in the strong field regime. In this review article, we first explain how the detectors like DPF and DECIGO/BBO work and discuss the expected event rates. Then, we review how the observed gravitational waveforms from precessing compact binaries with slightly eccentric orbits can be calculated both in general relativity and in alternative theories of gravity. For the latter, we focus on Brans-Dicke and massive gravity theories. After reviewing these theories, we show the results of the parameter estimation with DPF using the Fisher analysis. We also discuss a possible joint search of DPF and ground-based interferometers. Then, we show the results of testing al...

  11. Theoretical foundations for on-ground tests of LISA PathFinder thermal diagnostics

    Lobo, A; Ramos-Castro, J; Sanjuan, J; Lobo, Alberto; Nofrarias, Miquel; Ramos-Castro, Juan; Sanjuan, Josep

    2006-01-01

    This paper reports on the methods and results of a theoretical analysis to design an insulator which must provide a thermally quiet environment to test on ground delicate temperature sensors and associated electronics. These will fly on board ESA's LISA PathFinder (LPF) mission as part of the thermal diagnostics subsystem of the LISA Test-flight Package (LTP). We evaluate the heat transfer function (in frequency domain) of a central body of good thermal conductivity surrounded by a layer of a very poorly conducting substrate. This is applied to assess the materials and dimensions necessary to meet temperature stability requirements in the metal core, where sensors will be implanted for test. The analysis is extended to evaluate the losses caused by heat leakage through connecting wires, linking the sensors with the electronics in a box outside the insulator. The results indicate that, in spite of the very demanding stability conditions, a sphere of outer diameter of the order one metre is sufficient.

  12. HI Observations of two New Dwarf Galaxies: Pisces A & B with the SKA Pathfinder KAT-7

    Carignan, C; Lucero, D M; Randriamampandry, T H; Jarrett, T H; Oosterloo, T A; Tollerud, E J

    2016-01-01

    Context. Pisces A & Pisces B are the only two galaxies found via optical imaging and spectroscopy out of 22 HI clouds identified in the GALFAHI survey as dwarf galaxy candidates. Aims. Derive the HI content and kinematics of Pisces A & B. Methods. Aperture synthesis HI observations using the seven dish Karoo Array Telescope (KAT-7), which is a pathfinder instrument for MeerKAT, the South African precursor to the mid-frequency Square Kilometre Array (SKA-MID). Results. The small rotation velocities detected of ~5 km/sec and ~10 km/sec in Pisces A & B respectively, and their HI content show that they are really dwarf irregular galaxies (dIrr). Despite that small rotation component, it is more the random motions ~9-11 km/sec that provide most of the gravitational support, especially in the outer parts. The study of their kinematics, especially the strong gradients of random motions, suggest that those two dwarf galaxies are not yet in equilibrium. Conclusions. These HI rich galaxies may be indicative...

  13. LISA Pathfinder test-mass charging during galactic cosmic-ray flux short-term variations

    Grimani, C.; Fabi, M.; Lobo, A.; Mateos, I.; Telloni, D.

    2015-02-01

    Metal free-floating test masses aboard the future interferometers devoted to gravitational wave detection in space are charged by galactic and solar cosmic rays with energies \\gt 100 MeV/n. This process represents one of the main sources of noise in the lowest frequency band (\\lt 10-3 Hz) of these experiments. We study here the charging of the LISA Pathfinder (LISA-PF) gold-platinum test masses due to galactic cosmic-ray (GCR) protons and helium nuclei with the Fluka Monte Carlo toolkit. Projections of the energy spectra of GCRs during the LISA-PF operations in 2015 are considered. This work was carried out on the basis of the solar activity level and solar polarity epoch expected for LISA-PF. The effects of GCR short-term variations are evaluated here for the first time. Classical Forbush decreases, GCR variations induced by the Sun rotation, and fluctuations in the LISA-PF frequency bandwidth are discussed.

  14. Oral health related behaviors among adult Tanzanians: a national pathfinder survey

    Senkoro Ahadieli R

    2009-09-01

    Full Text Available Abstract Background The oral health education programs which have been organised and delivered in Tanzania were not based on a thorough understanding of behaviours which influence oral health. Therefore, evaluation of these programs became difficult. This study aimed at investigating the oral health related behaviours and their determinants among Tanzanian adults. Methods A national pathfinder cross sectional survey was conducted in 2006 involving 1759 respondents from the six geographic zones of mainland Tanzania. Frequency distributions, Chi square and multiple logistic regression analyses were performed using SPSS version 13.0. Results The rates of abstinence from alcohol for the past 30 days and life time smoking were 61.6% and 16.7% respectively, with males being more likely to smoke (OR 9.2, CI 6.3 -12.9, p Conclusion The findings of this study demonstrated social demographic disparities in relation to oral health related behaviors, while dental pain was associated with low consumption of sugar and high likelihood to take alcohol.

  15. OBSERVATION OF EARLY PHOTONS FROM GAMMA-RAY BURSTS WITH THE LOMONOSOV/UFFO-PATHFINDER

    S. Jeong

    2014-01-01

    Full Text Available UFFO-pathfinder es la misi ́on pionera para observar la evoluci ́on temprana de los Estallidos de Rayos Gamma u s a n d o s u e s t r a t e g i a d e a p u n t a d o r ́ a p i d o . E s t ́ a e q u i p a d o c o n e l S l e w i n g M i r r o r T e l e s c o p e p a r a a p u n t a d o r ́ a p i d o en las longitudes de onda ́ Opticas y Ultravioleta, al mismo tiempo que tien e el telescopio de Estallidos y Alerta UFFO. Tiene un total de ∼ 20 kg de peso y ser ́a lanzado a bordo de un sat ́elite ruso al final del 2014. Los d e t a l l e s d e l i n s t r u m e n t o y s u d e s e m p e ̃ n o s o n d i s c u t i d o s b r e v e m e n t e a c ́ a.

  16. CubeSats as pathfinders for planetary detection: the FIRST-S satellite

    Lacour, S.; Lapeyrère, V.; Gauchet, L.; Arroud, S.; Gourgues, R.; Martin, G.; Heidmann, S.; Haubois, X.; Perrin, G.

    2014-08-01

    The idea behind FIRST (Fibered Imager foR a Single Telescope) is to use single-mode fibers to combine multiple apertures in a pupil plane as such as to synthesize a bigger aperture. The advantages with respect to a pure imager are i) relaxed tolerance on the pointing and cophasing, ii) higher accuracy in phase measurement, and iii) availability of compact, precise, and active single-mode optics like Lithium Niobate. The latter point being a huge asset in the context of a space mission. One of the problems of DARWIN or SIM-like projects was the difficulty to find low cost pathfinders missions. But the fact that Lithium Niobate optic is small and compact makes it easy to test through small nanosats missions. Moreover, they are commonly used in the telecom industry, and have already been tested on communication satellites. The idea of the FIRST-S demonstrator is to spatialize a 3U CubeSat with a Lithium Niobate nulling interferometer. The technical challenges of the project are: star tracking, beam combination, and nulling capabilities. The optical baseline of the interferometer would be 30 cm, giving a 2.2AU spatial resolution at distance of 10 pc. The scientific objective of this mission would be to study the visible emission of exozodiacal light in the habitable zone around the closest stars.

  17. CubeSats as pathfinders for planetary detection: the FIRST-S satellite

    Lacour, S; Gauchet, L; Arroud, S; Gourgues, R; Martin, G; Heidmann, S; Haubois, X; Perrin, G

    2014-01-01

    The idea behind FIRST (Fibered Imager foR a Single Telescope) is to use single-mode fibers to combine multiple apertures in a pupil plane as such as to synthesize a bigger aperture. The advantages with respect to a pure imager are i) relaxed tolerance on the pointing and cophasing, ii) higher accuracy in phase measurement, and iii) availability of compact, precise, and active single-mode optics like Lithium Niobate. The latter point being a huge asset in the context of a space mission. One of the problems of DARWIN or SIM-like projects was the difficulty to find low cost pathfinders missions. But the fact that Lithium Niobate optic is small and compact makes it easy to test through small nanosats missions. Moreover, they are commonly used in the telecom industry, and have already been tested on communication satellites. The idea of the FIRST-S demonstrator is to spatialize a 3U CubeSat with a Lithium Niobate nulling interferometer. The technical challenges of the project are: star tracking, beam combination, ...

  18. Concept of Science Data Management for the Korea Pathfinder Lunar Orbiter

    Kim, Joo Hyeon

    2016-10-01

    South Korea has a plan to explore the Moon in 2018 or 2019. For the plan, the Korea Aerospace Research Institute which is a government funded research institute kicked off the Korea Lunar Exploration Development Program in January, 2016 in support of Ministry of Science, ICT and Future Planning, South Korea.As the 1st stage mission of the program, named as the Korea Pathfinder Lunar Orbiter(KPLO), will perform acquisition of high resolution images and science data for investigation of lunar environment as well as the core technology demonstration and validation for space explorations. The scientific instruments consists of three Korean domestic developed science instruments except an imaging instrument and several foreign provided instruments. We are developing a science data management plan to encourage scientific activities using science data acquired by the science instruments.I introduce the Korean domestic developed science instruments and present concept of the science data management plan for data delivery, processing, and distribution for the science instruments.

  19. The slewing mirror telescope of the Ultra Fast Flash Observatory Pathfinder

    Jeong, S.; Ahmad, S.; Barrillon, P.

    2012-01-01

    The Slewing Mirror Telescope (SMT) is a key telescope of Ultra-Fast Flash Observatory (UFFO) space project to explore the first sub-minute or sub-seconds early photons from the Gamma Ray Bursts (GRBs) afterglows. As the realization of UFFO, 20kg of UFFO-Pathfinder (UFFO-P) is going to be on board...... the Russian Lomonosov satellite in November 2012 by Soyuz-2 rocket. Once the UFFO Burst Alert & Trigger Telescope (UBAT) detects the GRBs, Slewing mirror (SM) will slew to bring new GRB into the SMT’s field of view rather than slewing the entire spacecraft. SMT can give a UV/Optical counterpart position...... is the reflecting telescope with 10cm Ritchey-Chretien type and 256 x 256 pixilated Intensified Charge-Coupled Device (ICCD). In this paper, we discuss the overall design of UFFO-P SMT instrument and payloads development status.© (2012) COPYRIGHT Society of Photo-Optical Instrumentation Engineers (SPIE...

  20. Alignment Test Results of the JWST Pathfinder Telescope Mirrors in the Cryogenic Environment

    Whitman, Tony L.; Wells, Conrad; Hadaway, James; Knight, J. Scott; Lunt, Sharon

    2016-01-01

    After integration of the Optical Telescope Element (OTE) to the Integrated Science Instrument Module (ISIM) to become the OTIS, the James Webb Space Telescope OTIS is tested at NASAs Johnson Space Center (JSC) in the cryogenic vacuum Chamber A for alignment and optical performance. The alignment of the mirrors comprises a sequence of steps as follows: The mirrors are coarsely aligned using photogrammetry cameras with reflective targets attached to the sides of the mirrors. Then a multi-wavelength interferometer is aligned to the 18-segment primary mirror using cameras at the center of curvature to align reflected light from the segments and using fiducials at the edge of the primary mirror. Once the interferometer is aligned, the 18 primary mirror segments are then adjusted to optimize wavefront error of the aggregate mirror. This process phases the piston and tilt positions of all the mirror segments. An optical fiber placed at the Cassegrain focus of the telescope then emits light towards the secondary mirror to create a collimated beam emitting from the primary mirror. Portions of the collimated beam are retro-reflected from flat mirrors at the top of the chamber to pass through the telescope to the SI detector. The image on the detector is used for fine alignment of the secondary mirror and a check of the primary mirror alignment using many of the same analysis techniques used in the on-orbit alignment. The entire process was practiced and evaluated in 2015 at cryogenic temperature with the Pathfinder telescope.