Sample records for bipolar cell terminals

  1. Lightweight bipolar storage battery

    NASA Technical Reports Server (NTRS)

    Rowlette, John J. (Inventor)

    1992-01-01

    An apparatus [10] is disclosed for a lightweight bipolar battery of the end-plate cell stack design. Current flow through a bipolar cell stack [12] is collected by a pair of copper end-plates [16a,16b] and transferred edgewise out of the battery by a pair of lightweight, low resistance copper terminals [28a,28b]. The copper terminals parallel the surface of a corresponding copper end-plate [16a,16b] to maximize battery throughput. The bipolar cell stack [12], copper end-plates [16a,16b] and copper terminals [28a,28b] are rigidly sandwiched between a pair of nonconductive rigid end-plates [20] having a lightweight fiber honeycomb core which eliminates distortion of individual plates within the bipolar cell stack due to internal pressures. Insulating foam [30] is injected into the fiber honeycomb core to reduce heat transfer into and out of the bipolar cell stack and to maintain uniform cell performance. A sealed battery enclosure [ 22] exposes a pair of terminal ends [26a,26b] for connection with an external circuit.

  2. Bipolar Cell-Photoreceptor Connectivity in the Zebrafish (Danio rerio) Retina

    PubMed Central

    Li, Yong N.; Tsujimura, Taro; Kawamura, Shoji; Dowling, John E.

    2013-01-01

    Bipolar cells convey luminance, spatial and color information from photoreceptors to amacrine and ganglion cells. We studied the photoreceptor connectivity of 321 bipolar cells in the adult zebrafish retina. 1,1'-Dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) was inserted into whole-mounted transgenic zebrafish retinas to label bipolar cells. The photoreceptors that connect to these DiI-labeled cells were identified by transgenic fluorescence or their positions relative to the fluorescent cones, as cones are arranged in a highly-ordered mosaic: rows of alternating blue- (B) and ultraviolet-sensitive (UV) single cones alternate with rows of red- (R) and green-sensitive (G) double cones. Rod terminals intersperse among cone terminals. As many as 18 connectivity subtypes were observed, 9 of which – G, GBUV, RG, RGB, RGBUV, RGRod, RGBRod, RGBUVRod and RRod bipolar cells – accounted for 96% of the population. Based on their axon terminal stratification, these bipolar cells could be further sub-divided into ON, OFF, and ON-OFF cells. The dendritic spread size, soma depth and size, and photoreceptor connections of the 308 bipolar cells within the 9 common connectivity subtypes were determined, and their dendritic tree morphologies and axonal stratification patterns compared. We found that bipolar cells with the same axonal stratification patterns could have heterogeneous photoreceptor connectivity whereas bipolar cells with the same dendritic tree morphology usually had the same photoreceptor connectivity, although their axons might stratify on different levels. PMID:22907678

  3. Identification of a cone bipolar cell in cat retina which has input from both rod and cone photoreceptors.

    PubMed

    Fyk-Kolodziej, Bozena; Qin, Pu; Pourcho, Roberta G

    2003-09-08

    It has been generally accepted that rod photoreceptor cells in the mammalian retina make synaptic contact with only a single population of rod bipolar cells, whereas cone photoreceptors contact a variety of cone bipolar cells. This assumption has been challenged in rodents by reports of a type of cone bipolar cell which receives input from both rods and cones. Questions remained as to whether similar pathways are present in other mammals. We have used an antiserum against the glutamate transporter GLT1-B to visualize a population of cone bipolar cells in the cat retina which make flat contacts with axon terminals of both rod and cone photoreceptor cells. These cells are identified as OFF-cone bipolar cells and correspond morphologically to type cb1 (CBa2) cone bipolar cells which are a major source of input to OFF-beta ganglion cells in the cat retina. The GLT1-B transporter was also localized to processes making flat contacts with photoreceptor terminals in rat and rabbit retinas. Examination of tissue processed for the GluR1 glutamate receptor subunit showed that cb1 cone bipolar cells, like their rodent counterparts, express this alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-selective receptor at their contacts with rod spherules. Thus, a direct excitatory pathway from rod photoreceptors to OFF-cone bipolar cells appears to be a common feature of mammalian retinas. Copyright 2003 Wiley-Liss, Inc.

  4. Morphological and physiological analysis of type-5 and other bipolar cells in the Mouse Retina.

    PubMed

    Hellmer, C B; Zhou, Y; Fyk-Kolodziej, B; Hu, Z; Ichinose, T

    2016-02-19

    Retinal bipolar cells are second-order neurons in the visual system, which initiate multiple image feature-based neural streams. Among more than ten types of bipolar cells, type-5 cells are thought to play a role in motion detection pathways. Multiple subsets of type-5 cells have been reported; however, detailed characteristics of each subset have not yet been elucidated. Here, we found that they exhibit distinct morphological features as well as unique voltage-gated channel expression. We have conducted electrophysiological and immunohistochemical analysis of retinal bipolar cells. We defined type-5 cells by their axon terminal ramification in the inner plexiform layer between the border of ON/OFF sublaminae and the ON choline acetyltransferase (ChAT) band. We found three subsets of type-5 cells: XBCs had the widest axon terminals that stratified at a close approximation of the ON ChAT band as well as exhibiting large voltage-gated Na(+) channel activity, type-5-1 cells had compact terminals and no Na(+) channel activity, and type-5-2 cells contained umbrella-shaped terminals as well as large voltage-gated Na(+) channel activity. Hyperpolarization-activated cyclic nucleotide-gated (HCN) currents were also evoked in all type-5 bipolar cells. We found that XBCs and type-5-2 cells exhibited larger HCN currents than type-5-1 cells. Furthermore, the former two types showed stronger HCN1 expression than the latter. Our previous observations (Ichinose et al., 2014) match the current study: low temporal tuning cells that we named 5S corresponded to 5-1 in this study, while high temporal tuning 5f cells from the previous study corresponded to 5-2 cells. Taken together, we found three subsets of type-5 bipolar cells based on their morphologies and physiological features. Copyright © 2015 IBRO. Published by Elsevier Ltd. All rights reserved.

  5. Classification of Mouse Retinal Bipolar Cells: Type-Specific Connectivity with Special Reference to Rod-Driven AII Amacrine Pathways

    PubMed Central

    Tsukamoto, Yoshihiko; Omi, Naoko

    2017-01-01

    We confirmed the classification of 15 morphological types of mouse bipolar cells by serial section transmission electron microscopy and characterized each type by identifying chemical synapses and gap junctions at axon terminals. Although whether the previous type 5 cells consist of two or three types was uncertain, they are here clustered into three types based on the vertical distribution of axonal ribbons. Next, while two groups of rod bipolar (RB) cells, RB1, and RB2, were previously proposed, we clarify that a half of RB1 cells have the intermediate characteristics, suggesting that these two groups comprise a single RB type. After validation of bipolar cell types, we examined their relationship with amacrine cells then particularly with AII amacrine cells. We found a strong correlation between the number of amacrine cell synaptic contacts and the number of bipolar cell axonal ribbons. Formation of bipolar cell output at each ribbon synapse may be effectively regulated by a few nearby inhibitory inputs of amacrine cells which are chosen from among many amacrine cell types. We also found that almost all types of ON cone bipolar cells frequently have a minor group of midway ribbons along the axon passing through the OFF sublamina as well as a major group of terminal ribbons in the ON sublamina. AII amacrine cells are connected to five of six OFF bipolar cell types via conventional chemical synapses and seven of eight ON (cone) bipolar cell types via electrical synapses (gap junctions). However, the number of synapses is dependent on bipolar cell types. Type 2 cells have 69% of the total number of OFF bipolar chemical synaptic contacts with AII amacrine cells and type 6 cells have 46% of the total area of ON bipolar gap junctions with AII amacrine cells. Both type 2 and 6 cells gain the greatest access to AII amacrine cell signals also share those signals with other types of bipolar cells via networked gap junctions. These findings imply that the most sensitive scotopic signal may be conveyed to the center by ganglion cells that have the most numerous synapses with type 2 and 6 cells. PMID:29114208

  6. Synaptology of physiologically identified ganglion cells in the cat retina: a comparison of retinal X- and Y-cells.

    PubMed

    Weber, A J; Stanford, L R

    1994-05-15

    It has long been known that a number of functionally different types of ganglion cells exist in the cat retina, and that each responds differently to visual stimulation. To determine whether the characteristic response properties of different retinal ganglion cell types might reflect differences in the number and distribution of their bipolar and amacrine cell inputs, we compared the percentages and distributions of the synaptic inputs from bipolar and amacrine cells to the entire dendritic arbors of physiologically characterized retinal X- and Y-cells. Sixty-two percent of the synaptic input to the Y-cell was from amacrine cell terminals, while the X-cells received approximately equal amounts of input from amacrine and bipolar cells. We found no significant difference in the distributions of bipolar or amacrine cell inputs to X- and Y-cells, or ON-center and OFF-center cells, either as a function of dendritic branch order or distance from the origin of the dendritic arbor. While, on the basis of these data, we cannot exclude the possibility that the difference in the proportion of bipolar and amacrine cell input contributes to the functional differences between X- and Y-cells, the magnitude of this difference, and the similarity in the distributions of the input from the two afferent cell types, suggest that mechanisms other than a simple predominance of input from amacrine or bipolar cells underlie the differences in their response properties. More likely, perhaps, is that the specific response features of X- and Y-cells originate in differences in the visual responses of the bipolar and amacrine cells that provide their input, or in the complex synaptic arrangements found among amacrine and bipolar cell terminals and the dendrites of specific types of retinal ganglion cells.

  7. Progression of neuronal and synaptic remodeling in the rd10 mouse model of retinitis pigmentosa.

    PubMed

    Phillips, M Joseph; Otteson, Deborah C; Sherry, David M

    2010-06-01

    The Pde6b(rd10) (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa (RP). We evaluated the progression of neuronal remodeling of second- and third-order retinal cells and their synaptic terminals in retinas from Pde6b(rd10) (rd10) mice at varying stages of degeneration ranging from postnatal day 30 (P30) to postnatal month 9.5 (PNM9.5) using immunolabeling for well-known cell- and synapse-specific markers. Following photoreceptor loss, changes occurred progressively from outer to inner retina. Horizontal cells and rod and cone bipolar cells underwent morphological remodeling that included loss of dendrites, cell body migration, and the sprouting of ectopic processes. Gliosis, characterized by translocation of Müller cell bodies to the outer retina and thickening of their processes, was evident by P30 and became more pronounced as degeneration progressed. Following rod degeneration, continued expression of VGluT1 in the outer retina was associated with survival and expression of synaptic proteins by nearby second-order neurons. Rod bipolar cell terminals showed a progressive reduction in size and ectopic bipolar cell processes extended into the inner nuclear layer and ganglion cell layer by PNM3.5. Putative ectopic conventional synapses, likely arising from amacrine cells, were present in the inner nuclear layer by PNM9.5. Despite these changes, the laminar organization of bipolar and amacrine cells and the ON-OFF organization in the inner plexiform layer was largely preserved. Surviving cone and bipolar cell terminals continued to express the appropriate cell-specific presynaptic proteins needed for synaptic function up to PNM9.5. (c) 2010 Wiley-Liss, Inc.

  8. Progression of Neuronal and Synaptic Remodeling in the rd10 Mouse Model of Retinitis Pigmentosa

    PubMed Central

    Phillips, M. Joseph; Otteson, Deborah C.; Sherry, David M.

    2010-01-01

    The Pde6brd10 (rd10) mouse has a moderate rate of photoreceptor degeneration and serves as a valuable model for human autosomal recessive retinitis pigmentosa (RP). We evaluated the progression of neuronal remodeling of second- and third-order retinal cells and their synaptic terminals in retinas from Pde6brd10 (rd10) mice at varying stages of degeneration ranging from postnatal day 30 (P30) to postnatal month 9.5 (PNM9.5) using immunolabeling for well known cell- and synapse-specific markers. Following photoreceptor loss, changes occurred progressively from outer to inner retina. Horizontal cells and rod and cone bipolar cells underwent morphological remodeling that included loss of dendrites, cell body migration, and the sprouting of ectopic processes. Gliosis, characterized by translocation of Müller cell bodies to the outer retina and thickening of their processes, was evident by P30 and became more pronounced as degeneration progressed. Following rod degeneration, continued expression of VGluT1 in the outer retina was associated with survival and expression of synaptic proteins by nearby second-order neurons. Rod bipolar cell terminals showed a progressive reduction in size and ectopic bipolar cell processes extended into the inner nuclear layer and ganglion cell layer by PNM3.5. Putative ectopic conventional synapses, likely arising from amacrine cells, were present in the inner nuclear layer by PNM9.5. Despite these changes, the laminar organization of bipolar and amacrine cells and the ON-OFF organization in the inner plexiform layer was largely preserved. Surviving cone and bipolar cell terminals continued to express the appropriate cell-specific presynaptic proteins needed for synaptic function up to PNM9.5. PMID:20394059

  9. Distribution of protein kinase C isoforms in the cat retina.

    PubMed

    Fyk-Kolodziej, Bozena; Cai, Wenhui; Pourcho, Roberta G

    2002-01-01

    Immunocytochemical localization was carried out for five isoforms of protein kinase C (PKC) in the cat retina. In common with other mammalian species, PKCalpha was found in rod bipolar cells. Staining was also seen in a small population of cone bipolar cells with axon terminals ramifying near the middle of the inner plexiform layer (IPL). PKCbetaI was localized to rod bipolar cells, one class of cone bipolar cell, and numerous amacrine and displaced amacrine cells. Staining for PKCbetaI was seen in three types of cone bipolar cells as well as in amacrine and ganglion cells. Immunoreactivity for both PKCepsilon and PKCzeta was found in rod bipolar cells; PKCepsilon was also seen in a population of cone bipolar cells and a few amacrine and ganglion cells whereas PKCzeta was found in all ganglion cells. Double-label immunofluorescence studies showed that dendrites of the two PKCbetaII-positive OFF-cone bipolar cells exhibit immmunoreactivity for the kainate-selective glutamate receptor GluR5. The third PKCbetaII cone bipolar is an ON-type cell and did not stain for GluR5. The retinal distribution of these isoforms of PKC is consistent with a role in modulation of various aspects of neurotransmission including synaptic vesicle release and regulation of receptor molecules.

  10. Transient release kinetics of rod bipolar cells revealed by capacitance measurement of exocytosis from axon terminals in rat retinal slices.

    PubMed

    Oltedal, Leif; Hartveit, Espen

    2010-05-01

    Presynaptic transmitter release has mostly been studied through measurements of postsynaptic responses, but a few synapses offer direct access to the presynaptic terminal, thereby allowing capacitance measurements of exocytosis. For mammalian rod bipolar cells, synaptic transmission has been investigated in great detail by recording postsynaptic currents in AII amacrine cells. Presynaptic measurements of the dynamics of vesicular cycling have so far been limited to isolated rod bipolar cells in dissociated preparations. Here, we first used computer simulations of compartmental models of morphologically reconstructed rod bipolar cells to adapt the 'Sine + DC' technique for capacitance measurements of exocytosis at axon terminals of intact rod bipolar cells in retinal slices. In subsequent physiological recordings, voltage pulses that triggered presynaptic Ca(2+) influx evoked capacitance increases that were proportional to the pulse duration. With pulse durations 100 ms, the increase saturated at 10 fF, corresponding to the size of a readily releasable pool of vesicles. Pulse durations 400 ms evoked additional capacitance increases, probably reflecting recruitment from additional pools of vesicles. By using Ca(2+) tail current stimuli, we separated Ca(2+) influx from Ca(2+) channel activation kinetics, allowing us to estimate the intrinsic release kinetics of the readily releasable pool, yielding a time constant of 1.1 ms and a maximum release rate of 2-3 vesicles (release site)(1) ms(1). Following exocytosis, we observed endocytosis with time constants ranging from 0.7 to 17 s. Under physiological conditions, it is likely that release will be transient, with the kinetics limited by the activation kinetics of the voltage-gated Ca(2+) channels.

  11. Sequential pictorial presentation of neural interaction in the retina. 2. The depolarizing and hyperpolarizing bipolar cells at rod terminals.

    PubMed

    Sjöstrand, F S

    2002-01-01

    Each rod is connected to one depolarizing and one hyperpolarizing bipolar cell. The synaptic connections of cone processes to each bipolar cell and presynaptically to the two rod-bipolar cell synapses establishes conditions for lateral interaction at this level. Thus, the cones raise the threshold for bipolar cell depolarization which is the basis for spatial brightness contrast enhancement and consequently for high visual acuity (Sjöstrand, 2001a). The cones facilitate ganglion cell depolarization by the bipolar cells and cone input prevents horizontal cell blocking of depolarization of the depolarizing bipolar cell, extending rod vision to low illumination. The combination of reduced cone input and transient hyperpolarization of the hyperpolarizing bipolar cell at onset of a light stimulus facilitates ganglion cell depolarization extensively at onset of the stimulus while no corresponding enhancement applies to the ganglion cell response at cessation of the stimulus, possibly establishing conditions for discrimination between on- vs. off-signals in the visual centre. Reduced cone input and hyperpolarization of the hyperpolarizing bipolar cell at onset of a light stimulus accounts for Granit's (1941) 'preexcitatory inhibition'. Presynaptic inhibition maintains transmitter concentration low in the synaptic gap at rod-bipolar cell and bipolar cell-ganglion cell synapses, securing proportional and amplified postsynaptic responses at these synapses. Perfect timing of variations in facilitatory and inhibitory input to the ganglion cell confines the duration of ganglion cell depolarization at onset and at cessation of a light stimulus to that of a single synaptic transmission.

  12. The TRPM1 Channel Is Required for Development of the Rod ON Bipolar Cell-AII Amacrine Cell Pathway in the Retinal Circuit.

    PubMed

    Kozuka, Takashi; Chaya, Taro; Tamalu, Fuminobu; Shimada, Mariko; Fujimaki-Aoba, Kayo; Kuwahara, Ryusuke; Watanabe, Shu-Ichi; Furukawa, Takahisa

    2017-10-11

    Neurotransmission plays an essential role in neural circuit formation in the central nervous system (CNS). Although neurotransmission has been recently clarified as a key modulator of retinal circuit development, the roles of individual synaptic transmissions are not yet fully understood. In the current study, we investigated the role of neurotransmission from photoreceptor cells to ON bipolar cells in development using mutant mouse lines of both sexes in which this transmission is abrogated. We found that deletion of the ON bipolar cation channel TRPM1 results in the abnormal contraction of rod bipolar terminals and a decreased number of their synaptic connections with amacrine cells. In contrast, these histological alterations were not caused by a disruption of total glutamate transmission due to loss of the ON bipolar glutamate receptor mGluR6 or the photoreceptor glutamate transporter VGluT1. In addition, TRPM1 deficiency led to the reduction of total dendritic length, branch numbers, and cell body size in AII amacrine cells. Activated Goα, known to close the TRPM1 channel, interacted with TRPM1 and induced the contraction of rod bipolar terminals. Furthermore, overexpression of Channelrhodopsin-2 partially rescued rod bipolar cell development in the TRPM1 -/- retina, whereas the rescue effect by a constitutively closed form of TRPM1 was lower than that by the native form. Our results suggest that TRPM1 channel opening is essential for rod bipolar pathway establishment in development. SIGNIFICANCE STATEMENT Neurotransmission has been recognized recently as a key modulator of retinal circuit development in the CNS. However, the roles of individual synaptic transmissions are not yet fully understood. In the current study, we focused on neurotransmission between rod photoreceptor cells and rod bipolar cells in the retina. We used genetically modified mouse models which abrogate each step of neurotransmission: presynaptic glutamate release, postsynaptic glutamate reception, or transduction channel function. We found that the TRPM1 transduction channel is required for the development of rod bipolar cells and their synaptic formation with subsequent neurons, independently of glutamate transmission. This study advances our understanding of neurotransmission-mediated retinal circuit refinement. Copyright © 2017 the authors 0270-6474/17/379889-12$15.00/0.

  13. Fuel cell design and assembly

    DOEpatents

    Myerhoff, Alfred

    1984-01-01

    The present invention is directed to a novel bipolar cooling plate, fuel cell design and method of assembly of fuel cells. The bipolar cooling plate used in the fuel cell design and method of assembly has discrete opposite edge and means carried by the plate defining a plurality of channels extending along the surface of the plate toward the opposite edges. At least one edge of the channels terminates short of the edge of the plate defining a recess for receiving a fastener.

  14. Performance evaluation and characterization of metallic bipolar plates in a proton exchange membrane (PEM) fuel cell

    NASA Astrophysics Data System (ADS)

    Hung, Yue

    Bipolar plate and membrane electrode assembly (MEA) are the two most repeated components of a proton exchange membrane (PEM) fuel cell stack. Bipolar plates comprise more than 60% of the weight and account for 30% of the total cost of a fuel cell stack. The bipolar plates perform as current conductors between cells, provide conduits for reactant gases, facilitate water and thermal management through the cell, and constitute the backbone of a power stack. In addition, bipolar plates must have excellent corrosion resistance to withstand the highly corrosive environment inside the fuel cell, and they must maintain low interfacial contact resistance throughout the operation to achieve optimum power density output. Currently, commercial bipolar plates are made of graphite composites because of their relatively low interfacial contact resistance (ICR) and high corrosion resistance. However, graphite composite's manufacturability, permeability, and durability for shock and vibration are unfavorable in comparison to metals. Therefore, metals have been considered as a replacement material for graphite composite bipolar plates. Since bipolar plates must possess the combined advantages of both metals and graphite composites in the fuel cell technology, various methods and techniques are being developed to combat metallic corrosion and eliminate the passive layer formed on the metal surface that causes unacceptable power reduction and possible fouling of the catalyst and the electrolyte. The main objective of this study was to explore the possibility of producing efficient, cost-effective and durable metallic bipolar plates that were capable of functioning in the highly corrosive fuel cell environment. Bulk materials such as Poco graphite, graphite composite, SS310, SS316, incoloy 800, titanium carbide and zirconium carbide were investigated as potential bipolar plate materials. In this work, different alloys and compositions of chromium carbide coatings on aluminum and SS316 substrates were also tested for suitability in performing as PEM fuel cell bipolar plates. Interfacial contact resistance and accelerated corrosion resistance tests were carried out for various bulk materials and chromium carbide coatings. Results of the study showed that chromium carbide protective coatings had relatively low interfacial contact resistance and moderate corrosion resistance in comparison to other metals. Single fuel cells with 6.45cm2 and 50cm2 active areas were fabricated and tested for performance and lifetime durability using chromium carbide coated aluminum bipolar plates and graphite composite bipolar plates as a control reference. Polarization curves and power curves were recorded from these single cells under various load conditions. The results showed that coated aluminum bipolar plates had an advantage of anchoring the terminals directly into the plates resulting in higher power density of the fuel cell. This was due to the elimination of additional ICR to the power stack caused by the need for extra terminal plates. However, this study also revealed that direct terminal anchoring was efficient and useable only with metallic bipolar plates but was inapplicable to graphite composite plates due to the poor mechanical strength and brittleness of the graphite composite material. In addition, the 1000 hour lifetime testing of coated aluminum single cells conducted at 70°C cell temperature under cyclic loading condition showed minimal power degradation (<5%) due to metal corrosion. Surface characterization was also conducted on the bipolar plates and MEAs to identify possible chemical change to their surfaces during the fuel cell operation and the electrochemical reaction. The single cell performance evaluation was complemented by an extended study on the fuel cell stack level. For the latter, a ten-cell graphite composite stack with a 40 cm2 active area was fabricated and evaluated for the effect of humidity and operating temperature on the stack performance. Graphite plates were selected for this study to eliminate any possible metal corrosion. A finite element analysis (FEA) model of a bipolar plate was developed to evaluate the effect of air cooling system design parameters and different bipolar plate materials on maintaining the PEM power stack at a safe operating temperature of 80°C or less. In the final stage of this work, a three-cell metallic stack with a 50 cm2 active area and coated aluminum bipolar plates was fabricated based on the positive results that were obtained from earlier studies. The three-cell stack was successfully operated and tested for 750 hours at different temperatures and power densities. This laboratory testing coupled with characterization studies showed that small amounts of aluminum oxide were observed on the coating surface due to localized imperfections in the coating and a lack of protection in the uncoated areas, such as internal manifolds and mounting plates. However, the scanning electron microscopy (SEM) and the energy dispersive x-ray spectroscopy (EDX) showed that coating thickness, chemistry, and surface morphology remained consistent after 750 hours of operation.

  15. Pivotal roles of Fezf2 in differentiation of cone OFF bipolar cells and functional maturation of cone ON bipolar cells in retina.

    PubMed

    Suzuki-Kerr, Haruna; Iwagawa, Toshiro; Sagara, Hiroshi; Mizota, Atsushi; Suzuki, Yutaka; Watanabe, Sumiko

    2018-06-01

    During development of the retina, common retinal progenitor cells give rise to six classes of neurons that subsequently further diversify into more than 55 subtypes of neuronal subtypes. Here, we have investigated the expression and function of Fezf2, Fez zinc finger family of protein, in the developing mouse retina. Expression of Fezf2 transcripts was strongly observed in the embryonic retinal progenitors at E14.5 and declined quickly in subsequent development of retina. Then, in postnatal stage at around day 8, Fezf2 was transiently expressed then declined again. Loss-of-function analysis using retinas from mice in which Fezf2 coding region was substituted with β-galactosidase showed that Fezf2 is expressed in a subset of cone OFF bipolar cells and required for their differentiation. Using electroretinogram, we found that Fezf2 knockout retina exhibited significantly reduced photopic b-wave, suggesting functional abnormality of cone ON bipolar cells. Furthermore, reduced expression of synaptic protein Trpm1 and structural alteration of ON bipolar cell invagination, both of which affected cone photoreceptor terminal synaptic activity, was identified by transmission electron microscopy and immunohistochemistry, respectively. Taken together, our results show that Fezf2 is indispensable in differentiation of bipolar precursors into cone OFF bipolar cells and in functional maturation of cone ON bipolar cells during development of mouse retina. These results contribute to our understanding of how diversity of neuronal subtypes and hence specificity of neuronal connections are established in the retina by intrinsic cues. Copyright © 2018 Elsevier Ltd. All rights reserved.

  16. Labelling and targeted ablation of specific bipolar cell types in the zebrafish retina

    PubMed Central

    2009-01-01

    Background Development of a functional retina depends on regulated differentiation of several types of neurons and generation of a highly complex network between the different types of neurons. In addition, each type of retinal neuron includes several distinct morphological types. Very little is known about the mechanisms responsible for generating this diversity of retinal neurons, which may also display specific patterns of regional distribution. Results In a screen in zebrafish, using a trapping vector carrying an engineered yeast Gal4 transcription activator and a UAS:eGFP reporter cassette, we have identified two transgenic lines of zebrafish co-expressing eGFP and Gal4 in specific subsets of retinal bipolar cells. The eGFP-labelling facilitated analysis of axon terminals within the inner plexiform layer of the adult retina and showed that the fluorescent bipolar cells correspond to previously defined morphological types. Strong regional restriction of eGFP-positive bipolar cells to the central part of the retina surrounding the optic nerve was observed in adult zebrafish. Furthermore, we achieved specific ablation of the labelled bipolar cells in 5 days old larvae, using a bacterial nitroreductase gene under Gal4-UAS control in combination with the prodrug metronidazole. Following prodrug treatment, nitroreductase expressing bipolar cells were efficiently ablated without affecting surrounding retina architecture, and recovery occurred within a few days due to increased generation of new bipolar cells. Conclusion This report shows that enhancer trapping can be applied to label distinct morphological types of bipolar cells in the zebrafish retina. The genetic labelling of these cells yielded co-expression of a modified Gal4 transcription activator and the fluorescent marker eGFP. Our work also demonstrates the potential utility of the Gal4-UAS system for induction of other transgenes, including a bacterial nitroreductase fusion gene, which can facilitate analysis of bipolar cell differentiation and how the retina recovers from specific ablation of these cells. PMID:19712466

  17. Autoantibodies in melanoma-associated retinopathy target TRPM1 cation channels of retinal ON bipolar cells.

    PubMed

    Dhingra, Anuradha; Fina, Marie E; Neinstein, Adam; Ramsey, David J; Xu, Ying; Fishman, Gerald A; Alexander, Kenneth R; Qian, Haohua; Peachey, Neal S; Gregg, Ronald G; Vardi, Noga

    2011-03-16

    Melanoma-associated retinopathy (MAR) is characterized by night blindness, photopsias, and a selective reduction of the electroretinogram b-wave. In certain cases, the serum contains autoantibodies that react with ON bipolar cells, but the target of these autoantibodies has not been identified. Here we show that the primary target of autoantibodies produced in MAR patients with reduced b-wave is the TRPM1 cation channel, the newly identified transduction channel in ON bipolar cells. Sera from two well characterized MAR patients, but not from a control subject, stained human embryonic kidney cells transfected with the TRPM1 gene, and Western blots probed with these MAR sera showed the expected band size (∼180 kDa). Staining of mouse and primate retina with MAR sera revealed immunoreactivity in all types of ON bipolar cells. Similar to staining for TRPM1, staining with the MAR sera was strong in dendritic tips and somas and was weak or absent in axon terminals. This staining colocalized with GFP in Grm6-GFP transgenic mice, where GFP is expressed in all and only ON bipolar cells, and also colocalized with Gα(o), a marker for all types of ON bipolar cells. The staining in ON bipolar cells was confirmed to be specific to TRPM1 because MAR serum did not stain these cells in a Trpm1(-/-) mouse. Evidence suggests that the recognized epitope is likely intracellular, and the sera can be internalized by retinal cells. We conclude that the vision of at least some patients with MAR is compromised due to autoantibody-mediated inactivation of the TRPM1 channel.

  18. Lrit1, a Retinal Transmembrane Protein, Regulates Selective Synapse Formation in Cone Photoreceptor Cells and Visual Acuity.

    PubMed

    Ueno, Akiko; Omori, Yoshihiro; Sugita, Yuko; Watanabe, Satoshi; Chaya, Taro; Kozuka, Takashi; Kon, Tetsuo; Yoshida, Satoyo; Matsushita, Kenji; Kuwahara, Ryusuke; Kajimura, Naoko; Okada, Yasushi; Furukawa, Takahisa

    2018-03-27

    In the vertebrate retina, cone photoreceptors play crucial roles in photopic vision by transmitting light-evoked signals to ON- and/or OFF-bipolar cells. However, the mechanisms underlying selective synapse formation in the cone photoreceptor pathway remain poorly understood. Here, we found that Lrit1, a leucine-rich transmembrane protein, localizes to the photoreceptor synaptic terminal and regulates the synaptic connection between cone photoreceptors and cone ON-bipolar cells. Lrit1-deficient retinas exhibit an aberrant morphology of cone photoreceptor pedicles, as well as an impairment of signal transmission from cone photoreceptors to cone ON-bipolar cells. Furthermore, we demonstrated that Lrit1 interacts with Frmpd2, a photoreceptor scaffold protein, and with mGluR6, an ON-bipolar cell-specific glutamate receptor. Additionally, Lrit1-null mice showed visual acuity impairments in their optokinetic responses. These results suggest that the Frmpd2-Lrit1-mGluR6 axis regulates selective synapse formation in cone photoreceptors and is essential for normal visual function. Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.

  19. Bipolar Nickel-Metal Hydride Battery Development Project

    NASA Technical Reports Server (NTRS)

    Cole, John H.

    1999-01-01

    This paper reviews the development of the Electro Energy, Inc.'s bipolar nickel metal hydride battery. The advantages of the design are that each cell is individually sealed, and that there are no external cell terminals, no electrode current collectors, it is compatible with plastic bonded electrodes, adaptable to heat transfer fins, scalable to large area, capacity and high voltage. The design will allow for automated flexible manufacturing, improved energy and power density and lower cost. The development and testing of the battery's component are described. Graphic presentation of the results of many of the tests are included.

  20. Quantifying the effect of light activated outer and inner retinal inhibitory pathways on glutamate release from mixed bipolar cells.

    PubMed

    Lipin, Mikhail Y; Vigh, Jozsef

    2018-05-01

    Inhibition mediated by horizontal and amacrine cells in the outer and inner retina, respectively, are fundamental components of visual processing. Here, our purpose was to determine how these different inhibitory processes affect glutamate release from ON bipolar cells when the retina is stimulated with full-field light of various intensities. Light-evoked membrane potential changes (ΔV m ) were recorded directly from axon terminals of intact bipolar cells receiving mixed rod and cone inputs (Mbs) in slices of dark-adapted goldfish retina. Inner and outer retinal inhibition to Mbs was blocked with bath applied picrotoxin (PTX) and NBQX, respectively. Then, control and pharmacologically modified light responses were injected into axotomized Mb terminals as command potentials to induce voltage-gated Ca 2+ influx (Q Ca ) and consequent glutamate release. Stimulus-evoked glutamate release was quantified by the increase in membrane capacitance (ΔC m ). Increasing depolarization of Mb terminals upon removal of inner and outer retinal inhibition enhanced the ΔV m /Q Ca ratio equally at a given light intensity and inhibition did not alter the overall relation between Q Ca and ΔC m . However, relative to control, light responses recorded in the presence of PTX and PTX + NBQX increased ΔC m unevenly across different stimulus intensities: at dim stimulus intensities predominantly the inner retinal GABAergic inhibition controlled release from Mbs, whereas the inner and outer retinal inhibition affected release equally in response to bright stimuli. Furthermore, our results suggest that non-linear relationship between Q Ca and glutamate release can influence the efficacy of inner and outer retinal inhibitory pathways to mediate Mb output at different light intensities. © 2018 Wiley Periodicals, Inc.

  1. Electrical coupling between A17 cells enhances reciprocal inhibitory feedback to rod bipolar cells.

    PubMed

    Elgueta, Claudio; Leroy, Felix; Vielma, Alex H; Schmachtenberg, Oliver; Palacios, Adrian G

    2018-02-15

    A17 amacrine cells are an important part of the scotopic pathway. Their synaptic varicosities receive glutamatergic inputs from rod bipolar cells (RBC) and release GABA onto the same RBC terminal, forming a reciprocal feedback that shapes RBC depolarization. Here, using patch-clamp recordings, we characterized electrical coupling between A17 cells of the rat retina and report the presence of strongly interconnected and non-coupled A17 cells. In coupled A17 cells, evoked currents preferentially flow out of the cell through GJs and cross-synchronization of presynaptic signals in a pair of A17 cells is correlated to their coupling degree. Moreover, we demonstrate that stimulation of one A17 cell can induce electrical and calcium transients in neighboring A17 cells, thus confirming a functional flow of information through electrical synapses in the A17 coupled network. Finally, blocking GJs caused a strong decrease in the amplitude of the inhibitory feedback onto RBCs. We therefore propose that electrical coupling between A17 cells enhances feedback onto RBCs by synchronizing and facilitating GABA release from inhibitory varicosities surrounding each RBC axon terminal. GJs between A17 cells are therefore critical in shaping the visual flow through the scotopic pathway.

  2. Comparison of the ontogeny of the vesicular glutamate transporter 3 (VGLUT3) with VGLUT1 and VGLUT2 in the rat retina.

    PubMed

    Stella, Salvatore L; Li, Stefanie; Sabatini, Andrea; Vila, Alejandro; Brecha, Nicholas C

    2008-06-18

    Glutamate is the major excitatory neurotransmitter in the retina, and most glutamatergic neurons express one of the three known vesicular glutamate transporters (VGLUT1, 2, or 3). However, the expression profiles of these transporters vary greatly in the retina. VGLUT1 is expressed by photoreceptor and bipolar cell terminals, and VGLUT2 appears to be predominately expressed by ganglion cells, and perhaps Müller cells, cone photoreceptor terminals, and horizontal cells in some species. The discovery of a third vesicular glutamate transporter, VGLUT3, has brought about speculation concerning its role and function based on its expression in amacrine cells. To address this we studied the postnatal development of VGLUT3 from day 0 through adult in the rat retina, and compared this with the expression patterns of VGLUT1 and VGLUT2. VGLUT3 expression was restricted to a population of amacrine cells. Expression of VGLUT3 was first observed at postnatal day 10 (P10) in the soma and some processes, which extensively arborized in both the ON and OFF sublamina of the IPL by P15. In contrast, VGLUT1 and VGLUT2 expression appeared earlier than VGLUT3; with VGLUT1 initially detected at P5 in photoreceptor terminals and P6 in bipolar terminals, and VGLUT2 immunoreactivity initially detected at P0 in ganglion cell bodies, and remained prominent throughout all stages of development. Interestingly, VGLUT3 has extensive somatic expression throughout development, which could be involved in non-synaptic modulation by glutamate in developing retina, and could influence trophic and extra-synaptic neuronal signaling by glutamate in the inner retina.

  3. Ionic mechanisms underlying the responses of off-center bipolar cells in the carp retina. II. Studies on responses evoked by transretinal current stimulation.

    PubMed

    Kaneko, A; Saito, T

    1983-04-01

    Transretinal current pulses flowing from the receptor side to the vitreous side of the retina cause transient release of transmitter from the photoreceptor terminals, and in off-center bipolar cells they evoke transient depolarizations with a brief (less than 1 ms) synaptic delay. Since it is known that the presence of Na+ in the external medium is not essential for this type of transmitter release, we used this procedure to examine the role of [Na+]o in the generation of light-evoked responses (hyperpolarizing to spot illumination in the receptive field center and depolarizing to an annulus in the surround) of this type of bipolar cell. When the cell membrane was steadily depolarized by current injection through the recording microelectrode, the depolarizing response evoked by the transretinal current pulses decreased in amplitude and reversed its polarity at above +45 mV. Conversely, the response amplitude increased when the cell was steadily hyperpolarized. The reversal potential seems to be lowered in low [Na+]o (28 mM). Removal of Na+ from the superfusate hyperpolarized the cell and both the light-evoked and current-evoked responses disappeared. From these observations, it is hypothesized that the hyperpolarizing center response of the off-center bipolar cells is a result of removal of sustained depolarization produced by sodium permeability increase.

  4. Parametric and cycle tests of a 40-A-hr bipolar nickel-hydrogen battery

    NASA Technical Reports Server (NTRS)

    Cataldo, R. L.

    1986-01-01

    A series of tests was performed to characterize battery performance relating to certain operating parameters which included charge current, discharge current, temperature and pressure. The parameters were varied to confirm battery design concepts and to determine optimal operating conditions. Spacecraft power requirements are constantly increasing. Special spacecraft such as the Space Station and platforms will require energy storage systems of 130 and 25 kWh, respectively. The complexity of these high power systems will demand high reliability, and reduced mass and volume. A system that uses batteries for storage will require a cell count in excess of 400 units. These cell units must then be assembled into several batteries with over 100 cells in a series connected string. In an attempt to simplify the construction of conventional cells and batteries, the NASA Lewis Research Center battery systems group initiated work on a nickel-hydrogen battery in a bipolar configuration in early 1981. Features of the battery with this bipolar construction show promise in improving both volumetric and gravimetric energy densities as well as thermal management. Bipolar construction allows cooling in closer proximity to the cell components, thus heat removal can be accomplished at a higher rejection temperature than conventional cell designs. Also, higher current densities are achievable because of low cell impedance. Lower cell impedance is achieved via current flow perpendicular to the electrode face, thus reducing voltage drops in the electrode grid and electrode terminals tabs.

  5. White matter microstructure alterations correlate with terminally differentiated CD8+ effector T cell depletion in the peripheral blood in mania: Combined DTI and immunological investigation in the different phases of bipolar disorder.

    PubMed

    Magioncalda, Paola; Martino, Matteo; Tardito, Samuele; Sterlini, Bruno; Conio, Benedetta; Marozzi, Valentina; Adavastro, Giulia; Capobianco, Laura; Russo, Daniel; Parodi, Alessia; Kalli, Francesca; Nasi, Giorgia; Altosole, Tiziana; Piaggio, Niccolò; Northoff, Georg; Fenoglio, Daniela; Inglese, Matilde; Filaci, Gilberto; Amore, Mario

    2018-05-01

    White matter (WM) microstructural abnormalities and, independently, signs of immunological activation were consistently demonstrated in bipolar disorder (BD). However, the relationship between WM and immunological alterations as well as their occurrence in the various phases of BD remain unclear. In 60 type I BD patients - 20 in manic, 20 in depressive, 20 in euthymic phases - and 20 controls we investigated: (i) diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), radial diffusivity (RD) and axial diffusivity (AD) using a tract-based spatial statistics (TBSS) approach; (ii) circulating T cell subpopulations frequencies, as well as plasma levels of different cytokines; (iii) potential relationships between WM and immunological data. We found: (i) a significant widespread combined FA-RD alteration mainly in mania, with involvement of the body of corpus callosum (BCC) and superior corona radiata (SCR); (ii) significant increase in CD4+ T cells as well as significant decrease in CD8+ T cells and their subpopulations effector memory (CD8+ CD28-CD45RA-), terminal effector memory (CD8+ CD28-CD45RA+) and CD8+ IFNγ+ in mania; (iii) a significant relationship between WM and immunological alterations in the whole cohort, and a significant correlation of FA-RD abnormalities in the BCC and SCR with reduced frequencies of CD8+ terminal effector memory and CD8+ IFNγ+ T cells in mania only. Our data show a combined occurrence of WM and immunological alterations in mania. WM abnormalities highly correlated with reduction in circulating CD8+ T cell subpopulations that are terminally differentiated effector cells prone to tissue migration, suggesting that these T cells could play a role in WM alteration in BD. Copyright © 2018 Elsevier Inc. All rights reserved.

  6. Immunocytochemical localization of three vesicular glutamate transporters in the cat retina.

    PubMed

    Fyk-Kolodziej, Bozena; Dzhagaryan, Arturik; Qin, Pu; Pourcho, Roberta G

    2004-08-02

    Vesicular transporters play an essential role in the packaging of glutamate for synaptic release and so are of particular importance in the retina, where glutamate serves as the neurotransmitter for photoreceptors, bipolar cells, and ganglion cells. In the present study, we have examined the distribution of the three known isoforms of vesicular glutamate transporter (VGLUT) in the cat retina. VGLUT1 was localized to all photoreceptor and bipolar cells, whereas VGLUT2 was found in ganglion cells. This basic pattern of complementary distribution for the two transporters among known populations of glutamatergic cells is similar to previous findings in the brain and spinal cord. However, the axon terminals of S-cone photoreceptors were found to express both VGLUT1 and VGLUT2 and some ganglion cells labeled for both VGLUT2 and VGLUT3. Such colocalizations suggest the existence of dual modes of regulation of vesicular glutamate transport in these neurons. Staining for VGLUT2 was also present in a small number of varicose processes, which were seen to ramify throughout the inner plexiform layer. These fibers may represent axon collaterals of ganglion cells. The most prominent site of VGLUT3 immunoreactivity was in a population of amacrine cells; the axon terminals of B-type horizontal cells were also labeled at their contacts with rod spherules. The presence of the VGLUT3 transporter at sites not otherwise implicated in glutamate release may indicate novel modes of glutamate signaling or additional roles for the transporter molecule. Copyright 2004 Wiley-Liss, Inc.

  7. Three-terminal heterojunction bipolar transistor solar cell for high-efficiency photovoltaic conversion.

    PubMed

    Martí, A; Luque, A

    2015-04-22

    Here we propose, for the first time, a solar cell characterized by a semiconductor transistor structure (n/p/n or p/n/p) where the base-emitter junction is made of a high-bandgap semiconductor and the collector is made of a low-bandgap semiconductor. We calculate its detailed-balance efficiency limit and prove that it is the same one than that of a double-junction solar cell. The practical importance of this result relies on the simplicity of the structure that reduces the number of layers that are required to match the limiting efficiency of dual-junction solar cells without using tunnel junctions. The device naturally emerges as a three-terminal solar cell and can also be used as building block of multijunction solar cells with an increased number of junctions.

  8. Three-terminal heterojunction bipolar transistor solar cell for high-efficiency photovoltaic conversion

    PubMed Central

    Martí, A.; Luque, A.

    2015-01-01

    Here we propose, for the first time, a solar cell characterized by a semiconductor transistor structure (n/p/n or p/n/p) where the base–emitter junction is made of a high-bandgap semiconductor and the collector is made of a low-bandgap semiconductor. We calculate its detailed-balance efficiency limit and prove that it is the same one than that of a double-junction solar cell. The practical importance of this result relies on the simplicity of the structure that reduces the number of layers that are required to match the limiting efficiency of dual-junction solar cells without using tunnel junctions. The device naturally emerges as a three-terminal solar cell and can also be used as building block of multijunction solar cells with an increased number of junctions. PMID:25902374

  9. Two R7 RGS proteins shape retinal bipolar cell signaling

    PubMed Central

    Mojumder, Deb Kumar; Qian, Yan; Wensel, Theodore G.

    2009-01-01

    RGS7, RGS11, and their binding partner Gβ5 are localized to the dendritic tips of retinal ON bipolar cells (ON-BPC), where mGluR6 responds to glutamate released from photoreceptor terminals by activation of the RGS7/RGS11 substrate, Gαo. To determine their functions in retinal signaling, we investigated cell-specific expression patterns of RGS7 and RGS11 by immunostaining, and measured light responses by electroretinography (ERG) in mice with targeted disruptions of the genes encoding them. RGS7 staining is present in dendritic tips of all rod ON-BPC, but missing in those for subsets of cone ON-BPC, whereas the converse was true for RGS11 staining. Genetic disruption of either RGS7 or RGS11 produced delays in the ON-BPC-derived electroretinogram b-wave, but no changes in the photoreceptor-derived a-wave. Homozygous RGS7 mutant mice had delays in rod-driven b-waves, whereas, RGS11 mutant mice had delays in rod-driven, and especially in cone-driven b-waves. The b-wave delays were further enhanced in mice homozygous for both RGS7 and RGS11 gene disruptions. Thus, RGS7 and RGS11 act in parallel to regulate the kinetics of ON bipolar cell responses, with differential impacts on the rod and cone pathways. PMID:19535587

  10. Differential cellular and subcellular distribution of glutamate transporters in the cat retina.

    PubMed

    Fyk-Kolodziej, Bozena; Qin, Pu; Dzhagaryan, Arturik; Pourcho, Roberta G

    2004-01-01

    Retrieval of glutamate from extracellular sites in the retina involves at least five excitatory amino acid transporters. Immunocytochemical analysis of the cat retina indicates that each of these transporters exhibits a selective distribution which may reflect its specific function. The uptake of glutamate into Muller cells or astrocytes appears to depend upon GLAST and EAAT4, respectively. Staining for EAAT4 was also seen in the pigment epithelium. The remaining transporters are neuronal with GLT-1alpha localized to a number of cone bipolar, amacrine, and ganglion cells and GLT-1v in cone photoreceptors and several populations of bipolar cells. The EAAC1 transporter was found in horizontal, amacrine, and ganglion cells. Staining for EAAT5 was seen in the axon terminals of both rod and cone photoreceptors as well as in numerous amacrine and ganglion cells. Although some of the glutamate transporter molecules are positioned for presynaptic or postsynaptic uptake at glutamatergic synapses, others with localizations more distant from such contacts may serve in modulatory roles or provide protection against excitoxic or oxidative damage.

  11. Invaginating Structures in Mammalian Synapses

    PubMed Central

    Petralia, Ronald S.; Wang, Ya-Xian; Mattson, Mark P.; Yao, Pamela J.

    2018-01-01

    Invaginating structures at chemical synapses in the mammalian nervous system exist in presynaptic axon terminals, postsynaptic spines or dendrites, and glial processes. These invaginating structures can be divided into three categories. The first category includes slender protrusions invaginating into axonal terminals, postsynaptic spines, or glial processes. Best known examples of this category are spinules extending from postsynaptic spines into presynaptic terminals in forebrain synapses. Another example of this category are protrusions from inhibitory presynaptic terminals invaginating into postsynaptic neuronal somas. Regardless of the direction and location, the invaginating structures of the first category do not have synaptic active zones within the invagination. The second category includes postsynaptic spines invaginating into presynaptic terminals, whereas the third category includes presynaptic terminals invaginating into postsynaptic spines or dendrites. Unlike the first category, the second and third categories have active zones within the invagination. An example of the second category are mossy terminal synapses of the hippocampal CA3 region, in which enlarged spine-like structures invaginate partly or entirely into mossy terminals. An example of the third category is the neuromuscular junction (NMJ) where substantial invaginations of the presynaptic terminals invaginate into the muscle fibers. In the retina, rod and cone synapses have invaginating processes from horizontal and bipolar cells. Because horizontal cells act both as post and presynaptic structures, their invaginating processes represent both the second and third category. These invaginating structures likely play broad yet specialized roles in modulating neuronal cell signaling. PMID:29674962

  12. Stereotyped initiation of retinal waves by bipolar cells via presynaptic NMDA autoreceptors

    PubMed Central

    Zhang, Rong-wei; Li, Xiao-quan; Kawakami, Koichi; Du, Jiu-lin

    2016-01-01

    Glutamatergic retinal waves, the spontaneous patterned neural activities propagating among developing retinal ganglion cells (RGCs), instruct the activity-dependent refinement of visuotopic maps. However, its initiation and underlying mechanism remain largely elusive. Here using larval zebrafish and multiple in vivo approaches, we discover that bipolar cells (BCs) are responsible for the generation of glutamatergic retinal waves. The wave originates from BC axon terminals (ATs) and propagates laterally to nearby BCs and vertically to downstream RGCs and the optic tectum. Its initiation is triggered by the activation of and consequent glutamate release from BC ATs, and is mediated by the N-methyl-D-aspartate subtype of glutamate receptors (NMDARs) expressed at these ATs. Intercellular asymmetry of NMDAR expression at BC ATs enables the preferential initiation of waves at the temporal retina, where BC ATs express more NMDARs. Thus, our findings indicate that glutamatergic retinal waves are initiated by BCs through a presynaptic NMDA autoreceptor-dependent process. PMID:27586999

  13. Nonlinear system analysis in bipolar integrated circuits

    NASA Astrophysics Data System (ADS)

    Fang, T. F.; Whalen, J. J.

    1980-01-01

    Since analog bipolar integrated circuits (IC's) have become important components in modern communication systems, the study of the Radio Frequency Interference (RFI) effects in bipolar IC amplifiers is an important subject for electromagnetic compatibility (EMC) engineering. The investigation has focused on using the nonlinear circuit analysis program (NCAP) to predict RF demodulation effects in broadband bipolar IC amplifiers. The audio frequency (AF) voltage at the IC amplifier output terminal caused by an amplitude modulated (AM) RF signal at the IC amplifier input terminal was calculated and compared to measured values. Two broadband IC amplifiers were investigated: (1) a cascode circuit using a CA3026 dual differential pair; (2) a unity gain voltage follower circuit using a micro A741 operational amplifier (op amp). Before using NCAP for RFI analysis, the model parameters for each bipolar junction transistor (BJT) in the integrated circuit were determined. Probe measurement techniques, manufacturer's data, and other researcher's data were used to obtain the required NCAP BJT model parameter values. An important contribution included in this effort is a complete set of NCAP BJT model parameters for most of the transistor types used in linear IC's.

  14. Lack of the Sodium-Driven Chloride Bicarbonate Exchanger NCBE Impairs Visual Function in the Mouse Retina

    PubMed Central

    Hilgen, Gerrit; Huebner, Antje K.; Tanimoto, Naoyuki; Sothilingam, Vithiyanjali; Seide, Christina; Garrido, Marina Garcia; Schmidt, Karl-Friedrich; Seeliger, Mathias W.; Löwel, Siegrid; Weiler, Reto

    2012-01-01

    Regulation of ion and pH homeostasis is essential for normal neuronal function. The sodium-driven chloride bicarbonate exchanger NCBE (Slc4a10), a member of the SLC4 family of bicarbonate transporters, uses the transmembrane gradient of sodium to drive cellular net uptake of bicarbonate and to extrude chloride, thereby modulating both intracellular pH (pHi) and chloride concentration ([Cl−]i) in neurons. Here we show that NCBE is strongly expressed in the retina. As GABAA receptors conduct both chloride and bicarbonate, we hypothesized that NCBE may be relevant for GABAergic transmission in the retina. Importantly, we found a differential expression of NCBE in bipolar cells: whereas NCBE was expressed on ON and OFF bipolar cell axon terminals, it only localized to dendrites of OFF bipolar cells. On these compartments, NCBE colocalized with the main neuronal chloride extruder KCC2, which renders GABA hyperpolarizing. NCBE was also expressed in starburst amacrine cells, but was absent from neurons known to depolarize in response to GABA, like horizontal cells. Mice lacking NCBE showed decreased visual acuity and contrast sensitivity in behavioral experiments and smaller b-wave amplitudes and longer latencies in electroretinograms. Ganglion cells from NCBE-deficient mice also showed altered temporal response properties. In summary, our data suggest that NCBE may serve to maintain intracellular chloride and bicarbonate concentration in retinal neurons. Consequently, lack of NCBE in the retina may result in changes in pHi regulation and chloride-dependent inhibition, leading to altered signal transmission and impaired visual function. PMID:23056253

  15. ON Cone Bipolar Cell Axonal Synapses in the OFF Inner Plexiform Layer of the Rabbit Retina

    PubMed Central

    Lauritzen, J. Scott; Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Mohammed, Shoeb; Hoang, John V.; Marc, Robert E.

    2012-01-01

    Analysis of the rabbit retinal connectome RC1 reveals that the division between the ON and OFF inner plexiform layer (IPL) is not structurally absolute. ON cone bipolar cells make non-canonical axonal synapses onto specific targets and receive amacrine cell synapses in the nominal OFF layer, creating novel motifs, including inhibitory crossover networks. Automated transmission electron microscope (ATEM) imaging, molecular tagging, tracing, and rendering of ≈ 400 bipolar cells reveals axonal ribbons in 36% of ON cone bipolar cells, throughout the OFF IPL. The targets include GABA-positive amacrine cells (γACs), glycine-positive amacrine cells (GACs) and ganglion cells. Most ON cone bipolar cell axonal contacts target GACs driven by OFF cone bipolar cells, forming new architectures for generating ON-OFF amacrine cells. Many of these ON-OFF GACs target ON cone bipolar cell axons, ON γACs and/or ON-OFF ganglion cells, representing widespread mechanisms for OFF to ON crossover inhibition. Other targets include OFF γACs presynaptic to OFF bipolar cells, forming γAC-mediated crossover motifs. ON cone bipolar cell axonal ribbons drive bistratified ON-OFF ganglion cells in the OFF layer and provide ON drive to polarity-appropriate targets such as bistratified diving ganglion cells (bsdGCs). The targeting precision of ON cone bipolar cell axonal synapses shows that this drive incidence is necessarily a joint distribution of cone bipolar cell axonal frequency and target cell trajectories through a given volume of the OFF layer. Such joint distribution sampling is likely common when targets are sparser than sources and when sources are coupled, as are ON cone bipolar cells. PMID:23042441

  16. Molecular properties of the N-terminal extension of the fission yeast kinesin-5, Cut7.

    PubMed

    Edamatsu, M

    2016-02-11

    Kinesin-5 plays an essential role in spindle formation and function, and serves as a potential target for anti-cancer drugs. The aim of this study was to elucidate the molecular properties of the N-terminal extension of the Schizosaccharomyces pombe kinesin-5, Cut7. This extension is rich in charged amino acids and predicted to be intrinsically disordered. In S. pombe cells, a Cut7 construct lacking half the N-terminal extension failed to localize along the spindle microtubules and formed a monopolar spindle. However, a construct lacking the entire N-terminal extension exhibited normal localization and formed a typical bipolar spindle. In addition, in vitro analyses revealed that the truncated Cut7 constructs demonstrated similar motile velocities and directionalities as the wild-type motor protein, but the microtubule landing rates were significantly reduced. These findings suggest that the N-terminal extension is not required for normal Cut7 intracellular localization or function, but alters the microtubule-binding properties of this protein in vitro.

  17. Electrogenic glutamate uptake is a major current carrier in the membrane of axolotl retinal glial cells

    NASA Astrophysics Data System (ADS)

    Brew, Helen; Attwell, David

    1987-06-01

    Glutamate is taken up avidly by glial cells in the central nervous system1. Glutamate uptake may terminate the transmitter action of glutamate released from neurons1, and keep extracellular glutamate at concentrations below those which are neurotoxic. We report here that glutamate evokes a large inward current in retinal glial cells which have their membrane potential and intracellular ion concentrations controlled by the whole-cell patch-clamp technique2. This current seems to be due to an electrogenic glutamate uptake carrier, which transports at least two sodium ions with every glutamate anion carried into the cell. Glutamate uptake is strongly voltage-dependent, decreasing at depolarized potentials: when fully activated, it contributes almost half of the conductance in the part of the glial cell membrane facing the retinal neurons. The spatial localization, glutamate affinity and magnitude of the uptake are appropriate for terminating the synaptic action of glutamate released from photoreceptors and bipolar cells. These data challenge present explanations of how the b-wave of the electroretinogram is generated, and suggest a mechanism for non-vesicular voltage-dependent release of glutamate from neurons.

  18. Multi-layer coatings for bipolar rechargeable batteries with enhanced terminal voltage

    DOEpatents

    Farmer, Joseph C.; Kaschmitter, James; Pierce, Steve

    2017-06-06

    A method for producing a multi-layer bipolar coated cell according to one embodiment includes applying a first active cathode material above a substrate to form a first cathode; applying a first solid-phase ionically-conductive electrolyte material above the first cathode to form a first electrode separation layer; applying a first active anode material above the first electrode separation layer to form a first anode; applying an electrically conductive barrier layer above the first anode; applying a second active cathode material above the anode material to form a second cathode; applying a second solid-phase ionically-conductive electrolyte material above the second cathode to form a second electrode separation layer; applying a second active anode material above the second electrode separation layer to form a second anode; and applying a metal material above the second anode to form a metal coating section. In another embodiment, the anode is formed prior to the cathode. Cells are also disclosed.

  19. Differential encoding of spatial information among retinal on cone bipolar cells

    PubMed Central

    Purgert, Robert J.

    2015-01-01

    The retina is the first stage of visual processing. It encodes elemental features of visual scenes. Distinct cone bipolar cells provide the substrate for this to occur. They encode visual information, such as color and luminance, a principle known as parallel processing. Few studies have directly examined whether different forms of spatial information are processed in parallel among cone bipolar cells. To address this issue, we examined the spatial information encoded by mouse ON cone bipolar cells, the subpopulation excited by increments in illumination. Two types of spatial processing were identified. We found that ON cone bipolar cells with axons ramifying in the central inner plexiform layer were tuned to preferentially encode small stimuli. By contrast, ON cone bipolar cells with axons ramifying in the proximal inner plexiform layer, nearest the ganglion cell layer, were tuned to encode both small and large stimuli. This dichotomy in spatial tuning is attributable to amacrine cells providing stronger inhibition to central ON cone bipolar cells compared with proximal ON cone bipolar cells. Furthermore, background illumination altered this difference in spatial tuning. It became less pronounced in bright light, as amacrine cell-driven inhibition became pervasive among all ON cone bipolar cells. These results suggest that differential amacrine cell input determined the distinct spatial encoding properties among ON cone bipolar cells. These findings enhance the known parallel processing capacity of the retina. PMID:26203104

  20. High vesicular monoamine transporter binding in asymptomatic bipolar I disorder: sex differences and cognitive correlates.

    PubMed

    Zubieta, J K; Huguelet, P; Ohl, L E; Koeppe, R A; Kilbourn, M R; Carr, J M; Giordani, B J; Frey, K A

    2000-10-01

    It has been hypothesized that anomalies in monoaminergic function underlie some of the manifestations of bipolar disorder. In this study the authors examined the possibility that trait-related abnormalities in the concentration of monoaminergic synaptic terminals may be present in patients with asymptomatic bipolar disorder type I. The concentration of a stable presynaptic marker, the vesicular monoamine transporter protein (VMAT2), was quantified with (+)[(11)C]dihydrotetrabenazine (DTBZ) and positron emission tomography. Sixteen asymptomatic patients with bipolar I disorder who had a prior history of mania with psychosis (nine men and seven women) and individually matched healthy subjects were studied. Correlational analyses were conducted to examine the relationship between regional VMAT2 binding, cognitive function, and clinical variables. VMAT2 binding in the thalamus and ventral brainstem of the bipolar patients was higher than that in the comparison subjects. VMAT2 concentrations in these regions correlated with performance on measures of frontal, executive function. In addition, sex differences in VMAT2 binding were detected in the thalamus of the bipolar patients; the male patients had higher binding than the women. No sex differences in binding were observed in the healthy comparison group. These initial results suggest that higher than normal VMAT2 expression and, by extension, concentration of monoaminergic synaptic terminals, may represent a trait-related abnormality in patients with bipolar I disorder and that male and female patients show different patterns. Also, VMAT2 concentrations may be associated with some of the cognitive deficits encountered in euthymic bipolar disorder.

  1. Roles of ON Cone Bipolar Cell Subtypes in Temporal Coding in the Mouse Retina

    PubMed Central

    Fyk-Kolodziej, Bozena; Cohn, Jesse

    2014-01-01

    In the visual system, diverse image processing starts with bipolar cells, which are the second-order neurons of the retina. Thirteen subtypes of bipolar cells have been identified, which are thought to encode different features of image signaling and to initiate distinct signal-processing streams. Although morphologically identified, the functional roles of each bipolar cell subtype in visual signal encoding are not fully understood. Here, we investigated how ON cone bipolar cells of the mouse retina encode diverse temporal image signaling. We recorded bipolar cell voltage changes in response to two different input functions: sinusoidal light and step light stimuli. Temporal tuning in ON cone bipolar cells was diverse and occurred in a subtype-dependent manner. Subtypes 5s and 8 exhibited low-pass filtering property in response to a sinusoidal light stimulus, and responded with sustained fashion to step-light stimulation. Conversely, subtypes 5f, 6, 7, and XBC exhibited bandpass filtering property in response to sinusoidal light stimuli, and responded transiently to step-light stimuli. In particular, subtypes 7 and XBC were high-temporal tuning cells. We recorded responses in different ways to further examine the underlying mechanisms of temporal tuning. Current injection evoked low-pass filtering, whereas light responses in voltage-clamp mode produced bandpass filtering in all ON bipolar cells. These findings suggest that cone photoreceptor inputs shape bandpass filtering in bipolar cells, whereas intrinsic properties of bipolar cells shape low-pass filtering. Together, our results demonstrate that ON bipolar cells encode diverse temporal image signaling in a subtype-dependent manner to initiate temporal visual information-processing pathways. PMID:24966376

  2. Presynaptic dystroglycan-pikachurin complex regulates the proper synaptic connection between retinal photoreceptor and bipolar cells.

    PubMed

    Omori, Yoshihiro; Araki, Fumiyuki; Chaya, Taro; Kajimura, Naoko; Irie, Shoichi; Terada, Koji; Muranishi, Yuki; Tsujii, Toshinori; Ueno, Shinji; Koyasu, Toshiyuki; Tamaki, Yasuhiro; Kondo, Mineo; Amano, Shiro; Furukawa, Takahisa

    2012-05-02

    Dystroglycan (DG) is a key component of the dystrophin-glycoprotein complex (DGC) at the neuromuscular junction postsynapse. In the mouse retina, the DGC is localized at the presynapse of photoreceptor cells, however, the function of presynaptic DGC is poorly understood. Here, we developed and analyzed retinal photoreceptor-specific DG conditional knock-out (DG CKO) mice. We found that the DG CKO retina showed a reduced amplitude and a prolonged implicit time of the ERG b-wave. Electron microscopic analysis revealed that bipolar dendrite invagination into the photoreceptor terminus is perturbed in the DG CKO retina. In the DG CKO retina, pikachurin, a DG ligand in the retina, is markedly decreased at photoreceptor synapses. Interestingly, in the Pikachurin(-/-) retina, the DG signal at the ribbon synaptic terminus was severely reduced, suggesting that pikachurin is required for the presynaptic accumulation of DG at the photoreceptor synaptic terminus, and conversely DG is required for pikachurin accumulation. Furthermore, we found that overexpression of pikachurin induces formation and clustering of a DG-pikachurin complex on the cell surface. The Laminin G repeats of pikachurin, which are critical for its oligomerization and interaction with DG, were essential for the clustering of the DG-pikachurin complex as well. These results suggest that oligomerization of pikachurin and its interaction with DG causes DG assembly on the synapse surface of the photoreceptor synaptic terminals. Our results reveal that the presynaptic interaction of pikachurin with DG at photoreceptor terminals is essential for both the formation of proper photoreceptor ribbon synaptic structures and normal retinal electrophysiology.

  3. Orphan receptor GPR179 forms macromolecular complexes with components of metabotropic signaling cascade in retina ON-bipolar neurons.

    PubMed

    Orlandi, Cesare; Cao, Yan; Martemyanov, Kirill A

    2013-10-29

    In the mammalian retina, synaptic transmission between light-excited rod photoreceptors and downstream ON-bipolar neurons is indispensable for dim vision, and disruption of this process leads to congenital stationary night blindness in human patients. The ON-bipolar neurons use the metabotropic signaling cascade, initiated by the mGluR6 receptor, to generate depolarizing responses to light-induced changes in neurotransmitter glutamate release from the photoreceptor axonal terminals. Evidence for the identity of the components involved in transducing these signals is growing rapidly. Recently, the orphan receptor, GPR179, a member of the G protein-coupled receptor (GPCR) superfamily, has been shown to be indispensable for the synaptic responses of ON-bipolar cells. In our study, we investigated the interaction of GPR179 with principle components of the signal transduction cascade. We used immunoprecipitation and proximity ligation assays in transfected cells and native retinas to characterize the protein-protein interactions involving GPR179. The influence of cascade components on GPR179 localization was examined through immunohistochemical staining of the retinas from genetic mouse models. We demonstrated that, in mouse retinas, GPR179 forms physical complexes with the main components of the metabotropic cascade, recruiting mGluR6, TRPM1, and the RGS proteins. Elimination of mGluR6 or RGS proteins, but not TRPM1, detrimentally affects postsynaptic targeting or GPR179 expression. These observations suggest that the mGluR6 signaling cascade is scaffolded as a macromolecular complex in which the interactions between the components ensure the optimal spatiotemporal characteristics of signal transduction.

  4. Bipolar Transistors Can Detect Charge in Electrostatic Experiments

    ERIC Educational Resources Information Center

    Dvorak, L.

    2012-01-01

    A simple charge indicator with bipolar transistors is described that can be used in various electrostatic experiments. Its behaviour enables us to elucidate links between 'static electricity' and electric currents. In addition it allows us to relate the sign of static charges to the sign of the terminals of an ordinary battery. (Contains 7 figures…

  5. 'Green mice' display limitations in enhanced green fluorescent protein expression in retina and optic nerve cells.

    PubMed

    Caminos, Elena; Vaquero, Cecilia F; García-Olmo, Dolores C

    2014-12-01

    Characterization of retinal cells, cell transplants and gene therapies may be helped by pre-labeled retinal cells, such as those transfected with vectors for green fluorescent protein expression. The aim of this study was to analyze retinal cells and optic nerve components from transgenic green mice (GM) with the 'enhanced' green fluorescent protein (EGFP) gene under the control of the CAG promoter (a chicken β-actin promoter and a cytomegalovirus enhancer). The structural analysis and electroretinography recordings showed a normal, healthy retina. Surprisingly, EGFP expression was not ubiquitously located in the retina and optic nerve. Epithelial cells, photoreceptors and bipolar cells presented high green fluorescence levels. In contrast, horizontal cells, specific amacrine cells and ganglion cells exhibited a null EGFP expression level. The synaptic terminals of rod bipolar cells displayed a high green fluorescence level when animals were kept in the dark. Immature retinas exhibited different EGFP expression patterns to those noted in adults. Axons and glial cells in the optic nerve revealed a specific regional EGFP expression pattern, which correlated with the presence of myelin. These results suggest that EGFP expression might be related to the activity of both the CAG promoter and β-actin in mature retinal neurons and oligodendrocytes. Moreover, EGFP expression might be regulated by light in both immature and adult animals. Since GM are used in numerous retina bioassays, it is essential to know the differential EGFP expression in order to select cells of interest for each study.

  6. Expression of the LIM-Homeodomain Protein Isl1 in the Developing and Mature Mouse Retina

    PubMed Central

    Elshatory, Yasser; Deng, Min; Xie, Xiaoling; Gan, Lin

    2010-01-01

    The mammalian retina is comprised of six major neuronal cell types and is subdivided into more morphological and physiological subtypes. The transcriptional machinery underlying these subtype fate choices is largely unknown. The LIM-homeodomain protein, Isl1, plays an essential role in central nervous system (CNS) differentiation but its relationship to retinal neurogenesis remains unknown. We report here its dynamic spatiotemporal expression in the mouse retina. Among bipolar interneurons, Isl1 expression commences at postnatal day (P)5 and is later restricted to ON-bipolar cells. The intensity of Isl1 expression is found to segregate the pool of ON-bipolar cells into rod and ON-cone bipolar cells with higher expression in rod bipolar cells. As bipolar cell development proceeds from P5–10 the colocalization of Isl1 and the pan-bipolar cell marker Chx10 reveals the organization of ON-center bipolar cell nuclei to the upper portion of the inner nuclear layer. Further, whereas Isl1 is predominantly a ganglion cell marker prior to embryonic day (E)15.5, at E15.5 and later its expression in nonganglion cells expands. We demonstrate that these Isl1-positive, nonganglion cells acquire the expression of amacrine cell markers embryonically, likely representing nascent cholinergic amacrine cells. Taken together, Isl1 is expressed during the maturation of and is later maintained in retinal ganglion cells and subtypes of amacrine and bipolar cells where it may function in the maintenance of these cells into adulthood. J. Comp. Neurol. 503: 182–197, 2007. PMID:17480014

  7. Islet-1 Controls the Differentiation of Retinal Bipolar and Cholinergic Amacrine Cells

    PubMed Central

    Elshatory, Yasser; Everhart, Drew; Deng, Min; Xie, Xiaoling; Barlow, Robert B.; Gan, Lin

    2010-01-01

    Whereas the mammalian retina possesses a repertoire of factors known to establish general retinal cell types, these factors alone cannot explain the vast diversity of neuronal subtypes. In other CNS regions, the differentiation of diverse neuronal pools is governed by coordinately acting LIM-homeodomain proteins including the Islet-class factor Islet-1 (Isl1). We report that deletion of Isl1 profoundly disrupts retinal function as assessed by electroretinograms and vision as assessed by optomotor behavior. These deficits are coupled with marked reductions in mature ON- and OFF-bipolar (>76%), cholinergic amacrine (93%), and ganglion (71%) cells. Mosaic deletion of Isl1 permitted a chimeric analysis of “wild-type” cells in a predominantly Isl1-null environment, demonstrating a cell-autonomous role for Isl1 in rod bipolar and cholinergic amacrine development. Furthermore, the effects on bipolar cell development appear to be dissociable from the preceding retinal ganglion cell loss, because Pou4f2-null mice are devoid of similar defects in bipolar cell marker expression. Expression of the ON- and OFF-bipolar cell differentiation factors Bhlhb4 and Vsx1, respectively, requires the presence of Isl1, whereas the early bipolar cell marker Prox1 initially did not. Thus, Isl1 is required for engaging bipolar differentiation pathways but not for general bipolar cell specification. Spatiotemporal expression analysis of additional LIM-homeobox genes identifies a LIM-homeobox gene network during bipolar cell development that includes Lhx3 and Lhx4. We conclude that Isl1 has an indispensable role in retinal neuron differentiation within restricted cell populations and this function may reflect a broader role for other LIM-homeobox genes in retinal development, and perhaps in establishing neuronal subtypes. PMID:18003851

  8. Preventing Mania: A Preliminary Examination of the GOALS Program

    PubMed Central

    Johnson, Sheri L.; Fulford, Daniel

    2010-01-01

    There is strong evidence of a relationship between goal dysregulation and mania. Building on these findings, we examined the feasibility of developing a mania prevention treatment program designed to improve goal regulation skills for those with bipolar disorder. Here, we describe the process of developing a manual, delivering the intervention to a series of cases, and then conducting a small open uncontrolled trial. All participants met diagnostic criteria for bipolar I disorder based on the Structured Clinical Interview for DSM-IV and were not currently experiencing episodes of depression or mania. Ten participants (8 female, mean age = 46.7 years) were enrolled in the GOALS program and completed an average of 13.2 weekly sessions. Participants were administered the Bech-Rafaelson Mania Scale (BRMS) and the Modified Hamilton Rating Scale for Depression at baseline and termination. Some participants completed self-report scales including the Altman Self-Rating Mania Scale, the Beck Depression Inventory, and the Willingly Approached Set of Statistically Unrealistic Pursuits at baseline and termination. In addition, participants were administered a consumer satisfaction questionnaire at termination. At termination, all 10 participants found the program highly relevant and helpful. Most importantly, even though levels of mania were low initially, mean levels of manic symptoms on the BRMS decreased significantly from baseline to termination, and all 10 participants were within a healthy range (BRMS <7) at termination. Although the lack of control group or follow-up data limits this study, preliminary evidence suggests that it is feasible to identify treatment targets by drawing from the basic research literature in bipolar disorder. Findings await replication and more careful testing within a randomized controlled trial. PMID:19433142

  9. Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision

    PubMed Central

    Hovhannisyan, Anahit; Kung, Jennifer; Lee, Seungjun; Lee, Dae Yeong; Huie, Philip; Dalal, Roopa; Palanker, Daniel

    2017-01-01

    Upon degeneration of photoreceptors in the adult retina, interneurons, including bipolar cells, exhibit a plastic response leading to their aberrant rewiring. Photoreceptor reintroduction has been suggested as a potential approach to sight restoration, but the ability of deafferented bipolar cells to establish functional synapses with photoreceptors is poorly understood. Here we use photocoagulation to selectively destroy photoreceptors in adult rabbits while preserving the inner retina. We find that rods and cones shift into the ablation zone over several weeks, reducing the blind spot at scotopic and photopic luminances. During recovery, rod and cone bipolar cells exhibit markedly different responses to deafferentation. Rod bipolar cells extend their dendrites to form new synapses with healthy photoreceptors outside the lesion, thereby restoring visual function in the deafferented retina. Secretagogin-positive cone bipolar cells did not exhibit such obvious dendritic restructuring. These findings are encouraging to the idea of photoreceptor reintroduction for vision restoration in patients blinded by retinal degeneration. At the same time, they draw attention to the postsynaptic side of photoreceptor reintroduction; various bipolar cell types, representing different visual pathways, vary in their response to the photoreceptor loss and in their consequent dendritic restructuring. SIGNIFICANCE STATEMENT Loss of photoreceptors during retinal degeneration results in permanent visual impairment. Strategies for vision restoration based on the reintroduction of photoreceptors inherently rely on the ability of the remaining retinal neurons to correctly synapse with new photoreceptors. We show that deafferented bipolar cells in the adult mammalian retina can reconnect to rods and cones and restore retinal sensitivity at scotopic and photopic luminances. Rod bipolar cells extend their dendrites to form new synapses with healthy rod photoreceptors. These findings support the idea that bipolar cells might be able to synapse with reintroduced photoreceptors, thereby restoring vision in patients blinded by retinal degeneration. PMID:28373392

  10. Design considerations for FET-gated power transistors

    NASA Technical Reports Server (NTRS)

    Chen, D. Y.; Chin, S. A.

    1983-01-01

    An FET-bipolar combinational power transistor configuration (tested up to 300 V, 20 A at 100 kHz) is described. The critical parameters for integrating the chips in hybrid form are examined, and an effort to optimize the overall characteristics of the configuration is discussed. Chip considerations are examined with respect to the voltage and current rating of individual chips, the FET surge capability, the choice of triple diffused transistor or epitaxial transistor for the bipolar element, the current tailing effect, and the implementation of the bipolar transistor and an FET as single chip or separate chips. Package considerations are discussed with respect to package material and geometry, surge current capability of bipolar base terminal bonding, and power losses distribution.

  11. Gsg1, Trnp1, and Tmem215 Mark Subpopulations of Bipolar Interneurons in the Mouse Retina

    PubMed Central

    Park, Ko Uoon; Randazzo, Grace; Jones, Kenneth L.; Brzezinski, Joseph A.

    2017-01-01

    Purpose How retinal bipolar cell interneurons are specified and assigned to specialized subtypes is only partially understood. In part, this is due to a lack of early pan- and subtype-specific bipolar cell markers. To discover these factors, we identified genes that were upregulated in Blimp1 (Prdm1) mutant retinas, which exhibit precocious bipolar cell development. Methods Postnatal day (P)2 retinas from Blimp1 conditional knock-out (CKO) mice and controls were processed for RNA sequencing. Genes that increased at least 45% and were statistically different between conditions were considered candidate bipolar-specific factors. Candidates were further evaluated by RT-PCR, in situ hybridization, and immunohistochemistry. Knock-in Tmem215-LacZ mice were used to better trace retinal expression. Results A comparison between Blimp1 CKO and control RNA-seq datasets revealed approximately 40 significantly upregulated genes. We characterized the expression of three genes that have no known function in the retina, Gsg1 (germ cell associated gene), Trnp1 (TMF-regulated nuclear protein), and Tmem215 (a predicted transmembrane protein). Germ cell associated gene appeared restricted to a small subset of cone bipolars while Trnp1 was seen in all ON type bipolar cells. Using Tmem215-LacZ heterozygous knock-in mice, we observed that β-galactosidase expression started early in bipolar cell development. In adults, Tmem215 was expressed by a subset of ON and OFF cone bipolar cells. Conclusions We have identified Gsg1, Tmem215, and Trnp1 as novel bipolar subtype-specific genes. The spatial and temporal pattern of their expression is consistent with a role in controlling bipolar subtype fate choice, differentiation, or physiology. PMID:28199486

  12. Effective killing of the human pathogen Candida albicans by a specific inhibitor of non-essential mitotic kinesin Kip1p

    PubMed Central

    Chua, Penelope R; Roof, David M; Lee, Yan; Sakowicz, Roman; Clarke, David; Pierce, Dan; Stephens, Thoryn; Hamilton, Matthew; Morgan, Brad; Morgans, David; Nakai, Takashi; Tomasi, Adam; Maxon, Mary E

    2007-01-01

    Kinesins from the bipolar (Kinesin-5) family are conserved in eukaryotic organisms and play critical roles during the earliest stages of mitosis to mediate spindle pole body separation and formation of a bipolar mitotic spindle. To date, genes encoding bipolar kinesins have been reported to be essential in all organisms studied. We report the characterization of CaKip1p, the sole member of this family in the human pathogenic yeast Candida albicans. C. albicans Kip1p appears to localize to the mitotic spindle and loss of CaKip1p function interferes with normal progression through mitosis. Inducible excision of CaKIP1 revealed phenotypes unique to C. albicans, including viable homozygous Cakip1 mutants and an aberrant spindle morphology in which multiple spindle poles accumulate in close proximity to each other. Expression of the C. albicans Kip1 motor domain in Escherichia coli produced a protein with microtubule-stimulated ATPase activity that was inhibited by an aminobenzothiazole (ABT) compound in an ATP-competitive fashion. This inhibition results in ‘rigor-like’, tight association with microtubules in vitro. Upon treatment of C. albicans cells with the ABT compound, cells were killed, and terminal phenotype analysis revealed an aberrant spindle morphology similar to that induced by loss of the CaKIP1 gene. The ABT compound discovered is the first example of a fungal spindle inhibitor targeted to a mitotic kinesin. Our results also show that the non-essential nature and implementation of the bipolar motor in C. albicans differs from that seen in other organisms, and suggest that inhibitors of a non-essential mitotic kinesin may offer promise as cidal agents for antifungal drug discovery. PMID:17573815

  13. ON Bipolar Cells in Macaque Retina: Type-Specific Synaptic Connectivity with Special Reference to OFF Counterparts

    PubMed Central

    Tsukamoto, Yoshihiko; Omi, Naoko

    2016-01-01

    To date, 12 macaque bipolar cell types have been described. This list includes all morphology types first outlined by Polyak (1941) using the Golgi method in the primate retina and subsequently identified by other researchers using electron microscopy (EM) combined with the Golgi method, serial section transmission EM (SSTEM), and immunohistochemical imaging. We used SSTEM for the rod-dense perifoveal area of macaque retina, reconfirmed ON (cone) bipolar cells to be classified as invaginating midget bipolar (IMB), diffuse bipolar (DB)4, DB5, DB6, giant bipolar (GB), and blue bipolar (BB) types, and clarified their type-specific connectivity. DB4 cells made reciprocal synapses with a kind of ON-OFF lateral amacrine cell, similar to OFF DB2 cells. GB cells contacted rods and cones, similar to OFF DB3b cells. Retinal circuits formed by GB and DB3b cells are thought to substantiate the psychophysical finding of fast rod signals in mesopic vision. DB6 cell output synapses were directed to ON midget ganglion (MG) cells at 70% of ribbon contacts, similar to OFF DB1 cells that directed 60% of ribbon contacts to OFF MG cells. IMB cells contacted medium- or long-wavelength sensitive (M/L-) cones but not short-wavelength sensitive (S-) cones, while BB cells contacted S-cones but not M/L-cones. However, IMB and BB dendrites had similar morphological architectures, and a BB cell contacting a single S-cone resembled an IMB cell. Thus, both IMB and BB may be the ON bipolar counterparts of the OFF flat midget bipolar (FMB) type, likewise DB4 of DB2, DB5 of DB3a, DB6 of DB1, and GB of DB3b OFF bipolar type. The ON DB plus GB, and OFF DB cells predominantly contacted M/L-cones and their outputs were directed mainly to parasol ganglion (PG) cells but also moderately to MG cells. BB cells directed S-cone-driven outputs almost exclusively to small bistratified ganglion (SBG) cells. Some FMB cells predominantly contacted S-cones and their outputs were directed to OFF MG cells. Thus, two-step synaptic connections largely narrowed down the S-cone component to SBG and some OFF MG cells. The other OFF MG cells, ON MG cells, and ON and OFF PG cells constructed M/L-cone dominant pathways. PMID:27833534

  14. Localized cyclic AMP-dependent protein kinase activity is required for myogenic cell fusion

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Mukai, Atsushi; Hashimoto, Naohiro

    2008-01-15

    Multinucleated myotubes are formed by fusion of mononucleated myogenic progenitor cells (myoblasts) during terminal skeletal muscle differentiation. In addition, myoblasts fuse with myotubes, but terminally differentiated myotubes have not been shown to fuse with each other. We show here that an adenylate cyclase activator, forskolin, and other reagents that elevate intracellular cyclic AMP (cAMP) levels induced cell fusion between small bipolar myotubes in vitro. Then an extra-large myotube, designated a 'myosheet,' was produced by both primary and established mouse myogenic cells. Myotube-to-myotube fusion always occurred between the leading edge of lamellipodia at the polar end of one myotube and themore » lateral plasma membrane of the other. Forskolin enhanced the formation of lamellipodia where cAMP-dependent protein kinase (PKA) was accumulated. Blocking enzymatic activity or anchoring of PKA suppressed forskolin-enhanced lamellipodium formation and prevented fusion of multinucleated myotubes. Localized PKA activity was also required for fusion of mononucleated myoblasts. The present results suggest that localized PKA plays a pivotal role in the early steps of myogenic cell fusion, such as cell-to-cell contact/recognition through lamellipodium formation. Furthermore, the localized cAMP-PKA pathway might be involved in the specification of the fusion-competent areas of the plasma membrane in lamellipodia of myogenic cells.« less

  15. Aurora A regulates the activity of HURP by controlling the accessibility of its microtubule-binding domain.

    PubMed

    Wong, Jim; Lerrigo, Robert; Jang, Chang-Young; Fang, Guowei

    2008-05-01

    HURP is a spindle-associated protein that mediates Ran-GTP-dependent assembly of the bipolar spindle and promotes chromosome congression and interkinetochore tension during mitosis. We report here a biochemical mechanism of HURP regulation by Aurora A, a key mitotic kinase that controls the assembly and function of the spindle. We found that HURP binds to microtubules through its N-terminal domain that hyperstabilizes spindle microtubules. Ectopic expression of this domain generates defects in spindle morphology and function that reduce the level of tension across sister kinetochores and activate the spindle checkpoint. Interestingly, the microtubule binding activity of this N-terminal domain is regulated by the C-terminal region of HURP: in its hypophosphorylated state, C-terminal HURP associates with the microtubule-binding domain, abrogating its affinity for microtubules. However, when the C-terminal domain is phosphorylated by Aurora A, it no longer binds to N-terminal HURP, thereby releasing the inhibition on its microtubule binding and stabilizing activity. In fact, ectopic expression of this C-terminal domain depletes endogenous HURP from the mitotic spindle in HeLa cells in trans, suggesting the physiological importance for this mode of regulation. We concluded that phosphorylation of HURP by Aurora A provides a regulatory mechanism for the control of spindle assembly and function.

  16. Light adaptation alters the source of inhibition to the mouse retinal OFF pathway

    PubMed Central

    Mazade, Reece E.

    2013-01-01

    Sensory systems must avoid saturation to encode a wide range of stimulus intensities. One way the retina accomplishes this is by using both dim-light-sensing rod and bright-light-sensing cone photoreceptor circuits. OFF cone bipolar cells are a key point in this process, as they receive both excitatory input from cones and inhibitory input from AII amacrine cells via the rod pathway. However, in addition to AII amacrine cell input, other inhibitory inputs from cone pathways also modulate OFF cone bipolar cell light signals. It is unknown how these inhibitory inputs to OFF cone bipolar cells change when switching between rod and cone pathways or whether all OFF cone bipolar cells receive rod pathway input. We found that one group of OFF cone bipolar cells (types 1, 2, and 4) receive rod-mediated inhibitory inputs that likely come from the rod-AII amacrine cell pathway, while another group of OFF cone bipolar cells (type 3) do not. In both cases, dark-adapted rod-dominant light responses showed a significant contribution of glycinergic inhibition, which decreased with light adaptation and was, surprisingly, compensated by an increase in GABAergic inhibition. As GABAergic input has distinct timing and spatial spread from glycinergic input, a shift from glycinergic to GABAergic inhibition could significantly alter OFF cone bipolar cell signaling to downstream OFF ganglion cells. Larger GABAergic input could reflect an adjustment of OFF bipolar cell spatial inhibition, which may be one mechanism that contributes to retinal spatial sensitivity in the light. PMID:23926034

  17. Lightweight Stacks of Direct Methanol Fuel Cells

    NASA Technical Reports Server (NTRS)

    Narayanan, Sekharipuram; Valdez, Thomas

    2004-01-01

    An improved design concept for direct methanol fuel cells makes it possible to construct fuel-cell stacks that can weigh as little as one-third as much as do conventional bipolar fuel-cell stacks of equal power. The structural-support components of the improved cells and stacks can be made of relatively inexpensive plastics. Moreover, in comparison with conventional bipolar fuel-cell stacks, the improved fuel-cell stacks can be assembled, disassembled, and diagnosed for malfunctions more easily. These improvements are expected to bring portable direct methanol fuel cells and stacks closer to commercialization. In a conventional bipolar fuel-cell stack, the cells are interspersed with bipolar plates (also called biplates), which are structural components that serve to interconnect the cells and distribute the reactants (methanol and air). The cells and biplates are sandwiched between metal end plates. Usually, the stack is held together under pressure by tie rods that clamp the end plates. The bipolar stack configuration offers the advantage of very low internal electrical resistance. However, when the power output of a stack is only a few watts, the very low internal resistance of a bipolar stack is not absolutely necessary for keeping the internal power loss acceptably low.

  18. Deafferented Adult Rod Bipolar Cells Create New Synapses with Photoreceptors to Restore Vision.

    PubMed

    Beier, Corinne; Hovhannisyan, Anahit; Weiser, Sydney; Kung, Jennifer; Lee, Seungjun; Lee, Dae Yeong; Huie, Philip; Dalal, Roopa; Palanker, Daniel; Sher, Alexander

    2017-04-26

    Upon degeneration of photoreceptors in the adult retina, interneurons, including bipolar cells, exhibit a plastic response leading to their aberrant rewiring. Photoreceptor reintroduction has been suggested as a potential approach to sight restoration, but the ability of deafferented bipolar cells to establish functional synapses with photoreceptors is poorly understood. Here we use photocoagulation to selectively destroy photoreceptors in adult rabbits while preserving the inner retina. We find that rods and cones shift into the ablation zone over several weeks, reducing the blind spot at scotopic and photopic luminances. During recovery, rod and cone bipolar cells exhibit markedly different responses to deafferentation. Rod bipolar cells extend their dendrites to form new synapses with healthy photoreceptors outside the lesion, thereby restoring visual function in the deafferented retina. Secretagogin-positive cone bipolar cells did not exhibit such obvious dendritic restructuring. These findings are encouraging to the idea of photoreceptor reintroduction for vision restoration in patients blinded by retinal degeneration. At the same time, they draw attention to the postsynaptic side of photoreceptor reintroduction; various bipolar cell types, representing different visual pathways, vary in their response to the photoreceptor loss and in their consequent dendritic restructuring. SIGNIFICANCE STATEMENT Loss of photoreceptors during retinal degeneration results in permanent visual impairment. Strategies for vision restoration based on the reintroduction of photoreceptors inherently rely on the ability of the remaining retinal neurons to correctly synapse with new photoreceptors. We show that deafferented bipolar cells in the adult mammalian retina can reconnect to rods and cones and restore retinal sensitivity at scotopic and photopic luminances. Rod bipolar cells extend their dendrites to form new synapses with healthy rod photoreceptors. These findings support the idea that bipolar cells might be able to synapse with reintroduced photoreceptors, thereby restoring vision in patients blinded by retinal degeneration. Copyright © 2017 the authors 0270-6474/17/374635-10$15.00/0.

  19. DSCAM Localization and Function at the Mouse Cone Synapse

    PubMed Central

    de Andrade, Gabriel Belem; Long, Samuel S.; Fleming, Harrison; Li, Wei; Fuerst, Peter G.

    2014-01-01

    The Down Syndrome Cell Adhesion Molecule (DSCAM) is required for regulation of cell number, soma spacing and cell type specific dendrite avoidance in many types of retinal ganglion and amacrine cells. In this study we assay the organization of cells making up the outer plexiform layer of the retina in the absence of Dscam. Some types of OFF bipolar cells, type 3b and type 4 bipolar cells, had defects in dendrite arborization in the Dscam mutant retina, while other cell types appeared similar to wild type. The cone synapses that these cells project their dendrites to were intact, as visualized by electron microscopy, and had a distribution and density that was not significantly different than wild type. The spacing of type 3b bipolar cell dendrites was further analyzed by Voronoi domain analysis, Density Recovery Profiling (DRP) analysis and Nearest Neighbor Analysis (NNA). Spacing was found to be significantly different when comparing wild type and mutant type 3b bipolar cell dendrites. Defects in arborization of these bipolar cells could not be attributed to the disorganization of inner plexiform layer cells that occurs in the Dscam mutant retina or an increase in cell number, as they arborized when Dscam was targeted in retinal ganglion cells only or in the bax null retina. Localization of DSCAM was assayed and the protein was localized near to cone synapses in mouse, macaque and ground squirrel retinas. DSCAM protein was detected in several types of bipolar cells, including type 3b and type 4 bipolar cells. PMID:24477985

  20. Light adaptation alters inner retinal inhibition to shape OFF retinal pathway signaling

    PubMed Central

    Mazade, Reece E.

    2016-01-01

    The retina adjusts its signaling gain over a wide range of light levels. A functional result of this is increased visual acuity at brighter luminance levels (light adaptation) due to shifts in the excitatory center-inhibitory surround receptive field parameters of ganglion cells that increases their sensitivity to smaller light stimuli. Recent work supports the idea that changes in ganglion cell spatial sensitivity with background luminance are due in part to inner retinal mechanisms, possibly including modulation of inhibition onto bipolar cells. To determine how the receptive fields of OFF cone bipolar cells may contribute to changes in ganglion cell resolution, the spatial extent and magnitude of inhibitory and excitatory inputs were measured from OFF bipolar cells under dark- and light-adapted conditions. There was no change in the OFF bipolar cell excitatory input with light adaptation; however, the spatial distributions of inhibitory inputs, including both glycinergic and GABAergic sources, became significantly narrower, smaller, and more transient. The magnitude and size of the OFF bipolar cell center-surround receptive fields as well as light-adapted changes in resting membrane potential were incorporated into a spatial model of OFF bipolar cell output to the downstream ganglion cells, which predicted an increase in signal output strength with light adaptation. We show a prominent role for inner retinal spatial signals in modulating the modeled strength of bipolar cell output to potentially play a role in ganglion cell visual sensitivity and acuity. PMID:26912599

  1. Exploring the retinal connectome

    PubMed Central

    Anderson, James R.; Jones, Bryan W.; Watt, Carl B.; Shaw, Margaret V.; Yang, Jia-Hui; DeMill, David; Lauritzen, James S.; Lin, Yanhua; Rapp, Kevin D.; Mastronarde, David; Koshevoy, Pavel; Grimm, Bradley; Tasdizen, Tolga; Whitaker, Ross

    2011-01-01

    Purpose A connectome is a comprehensive description of synaptic connectivity for a neural domain. Our goal was to produce a connectome data set for the inner plexiform layer of the mammalian retina. This paper describes our first retinal connectome, validates the method, and provides key initial findings. Methods We acquired and assembled a 16.5 terabyte connectome data set RC1 for the rabbit retina at ≈2 nm resolution using automated transmission electron microscope imaging, automated mosaicking, and automated volume registration. RC1 represents a column of tissue 0.25 mm in diameter, spanning the inner nuclear, inner plexiform, and ganglion cell layers. To enhance ultrastructural tracing, we included molecular markers for 4-aminobutyrate (GABA), glutamate, glycine, taurine, glutamine, and the in vivo activity marker, 1-amino-4-guanidobutane. This enabled us to distinguish GABAergic and glycinergic amacrine cells; to identify ON bipolar cells coupled to glycinergic cells; and to discriminate different kinds of bipolar, amacrine, and ganglion cells based on their molecular signatures and activity. The data set was explored and annotated with Viking, our multiuser navigation tool. Annotations were exported to additional applications to render cells, visualize network graphs, and query the database. Results Exploration of RC1 showed that the 2 nm resolution readily recapitulated well known connections and revealed several new features of retinal organization: (1) The well known AII amacrine cell pathway displayed more complexity than previously reported, with no less than 17 distinct signaling modes, including ribbon synapse inputs from OFF bipolar cells, wide-field ON cone bipolar cells and rod bipolar cells, and extensive input from cone-pathway amacrine cells. (2) The axons of most cone bipolar cells formed a distinct signal integration compartment, with ON cone bipolar cell axonal synapses targeting diverse cell types. Both ON and OFF bipolar cells receive axonal veto synapses. (3) Chains of conventional synapses were very common, with intercalated glycinergic-GABAergic chains and very long chains associated with starburst amacrine cells. Glycinergic amacrine cells clearly play a major role in ON-OFF crossover inhibition. (4) Molecular and excitation mapping clearly segregates ultrastructurally defined bipolar cell groups into different response clusters. (5) Finally, low-resolution electron or optical imaging cannot reliably map synaptic connections by process geometry, as adjacency without synaptic contact is abundant in the retina. Only direct visualization of synapses and gap junctions suffices. Conclusions Connectome assembly and analysis using conventional transmission electron microscopy is now practical for network discovery. Our surveys of volume RC1 demonstrate that previously studied systems such as the AII amacrine cell network involve more network motifs than previously known. The AII network, primarily considered a scotopic pathway, clearly derives ribbon synapse input from photopic ON and OFF cone bipolar cell networks and extensive photopic GABAergic amacrine cell inputs. Further, bipolar cells show extensive inputs and outputs along their axons, similar to multistratified nonmammalian bipolar cells. Physiologic evidence of significant ON-OFF channel crossover is strongly supported by our anatomic data, showing alternating glycine-to-GABA paths. Long chains of amacrine cell networks likely arise from homocellular GABAergic synapses between starburst amacrine cells. Deeper analysis of RC1 offers the opportunity for more complete descriptions of specific networks. PMID:21311605

  2. Exploring the retinal connectome.

    PubMed

    Anderson, James R; Jones, Bryan W; Watt, Carl B; Shaw, Margaret V; Yang, Jia-Hui; Demill, David; Lauritzen, James S; Lin, Yanhua; Rapp, Kevin D; Mastronarde, David; Koshevoy, Pavel; Grimm, Bradley; Tasdizen, Tolga; Whitaker, Ross; Marc, Robert E

    2011-02-03

    A connectome is a comprehensive description of synaptic connectivity for a neural domain. Our goal was to produce a connectome data set for the inner plexiform layer of the mammalian retina. This paper describes our first retinal connectome, validates the method, and provides key initial findings. We acquired and assembled a 16.5 terabyte connectome data set RC1 for the rabbit retina at ≈ 2 nm resolution using automated transmission electron microscope imaging, automated mosaicking, and automated volume registration. RC1 represents a column of tissue 0.25 mm in diameter, spanning the inner nuclear, inner plexiform, and ganglion cell layers. To enhance ultrastructural tracing, we included molecular markers for 4-aminobutyrate (GABA), glutamate, glycine, taurine, glutamine, and the in vivo activity marker, 1-amino-4-guanidobutane. This enabled us to distinguish GABAergic and glycinergic amacrine cells; to identify ON bipolar cells coupled to glycinergic cells; and to discriminate different kinds of bipolar, amacrine, and ganglion cells based on their molecular signatures and activity. The data set was explored and annotated with Viking, our multiuser navigation tool. Annotations were exported to additional applications to render cells, visualize network graphs, and query the database. Exploration of RC1 showed that the 2 nm resolution readily recapitulated well known connections and revealed several new features of retinal organization: (1) The well known AII amacrine cell pathway displayed more complexity than previously reported, with no less than 17 distinct signaling modes, including ribbon synapse inputs from OFF bipolar cells, wide-field ON cone bipolar cells and rod bipolar cells, and extensive input from cone-pathway amacrine cells. (2) The axons of most cone bipolar cells formed a distinct signal integration compartment, with ON cone bipolar cell axonal synapses targeting diverse cell types. Both ON and OFF bipolar cells receive axonal veto synapses. (3) Chains of conventional synapses were very common, with intercalated glycinergic-GABAergic chains and very long chains associated with starburst amacrine cells. Glycinergic amacrine cells clearly play a major role in ON-OFF crossover inhibition. (4) Molecular and excitation mapping clearly segregates ultrastructurally defined bipolar cell groups into different response clusters. (5) Finally, low-resolution electron or optical imaging cannot reliably map synaptic connections by process geometry, as adjacency without synaptic contact is abundant in the retina. Only direct visualization of synapses and gap junctions suffices. Connectome assembly and analysis using conventional transmission electron microscopy is now practical for network discovery. Our surveys of volume RC1 demonstrate that previously studied systems such as the AII amacrine cell network involve more network motifs than previously known. The AII network, primarily considered a scotopic pathway, clearly derives ribbon synapse input from photopic ON and OFF cone bipolar cell networks and extensive photopic GABAergic amacrine cell inputs. Further, bipolar cells show extensive inputs and outputs along their axons, similar to multistratified nonmammalian bipolar cells. Physiologic evidence of significant ON-OFF channel crossover is strongly supported by our anatomic data, showing alternating glycine-to-GABA paths. Long chains of amacrine cell networks likely arise from homocellular GABAergic synapses between starburst amacrine cells. Deeper analysis of RC1 offers the opportunity for more complete descriptions of specific networks.

  3. The Synaptic and Morphological Basis of Orientation Selectivity in a Polyaxonal Amacrine Cell of the Rabbit Retina.

    PubMed

    Murphy-Baum, Benjamin L; Taylor, W Rowland

    2015-09-30

    Much of the computational power of the retina derives from the activity of amacrine cells, a large and diverse group of GABAergic and glycinergic inhibitory interneurons. Here, we identify an ON-type orientation-selective, wide-field, polyaxonal amacrine cell (PAC) in the rabbit retina and demonstrate how its orientation selectivity arises from the structure of the dendritic arbor and the pattern of excitatory and inhibitory inputs. Excitation from ON bipolar cells and inhibition arising from the OFF pathway converge to generate a quasi-linear integration of visual signals in the receptive field center. This serves to suppress responses to high spatial frequencies, thereby improving sensitivity to larger objects and enhancing orientation selectivity. Inhibition also regulates the magnitude and time course of excitatory inputs to this PAC through serial inhibitory connections onto the presynaptic terminals of ON bipolar cells. This presynaptic inhibition is driven by graded potentials within local microcircuits, similar in extent to the size of single bipolar cell receptive fields. Additional presynaptic inhibition is generated by spiking amacrine cells on a larger spatial scale covering several hundred microns. The orientation selectivity of this PAC may be a substrate for the inhibition that mediates orientation selectivity in some types of ganglion cells. Significance statement: The retina comprises numerous excitatory and inhibitory circuits that encode specific features in the visual scene, such as orientation, contrast, or motion. Here, we identify a wide-field inhibitory neuron that responds to visual stimuli of a particular orientation, a feature selectivity that is primarily due to the elongated shape of the dendritic arbor. Integration of convergent excitatory and inhibitory inputs from the ON and OFF visual pathways suppress responses to small objects and fine textures, thus enhancing selectivity for larger objects. Feedback inhibition regulates the strength and speed of excitation on both local and wide-field spatial scales. This study demonstrates how different synaptic inputs are regulated to tune a neuron to respond to specific features in the visual scene. Copyright © 2015 the authors 0270-6474/15/3513336-15$15.00/0.

  4. Carbon composite bipolar plate for high-temperature proton exchange membrane fuel cells (HT-PEMFCs)

    NASA Astrophysics Data System (ADS)

    Lee, Dongyoung; Lee, Dai Gil

    2016-09-01

    A carbon/epoxy composite bipolar plate is an ideal substitute for the brittle graphite bipolar plate for lightweight proton exchange membrane fuel cells (PEMFCs) because of its high specific strength and stiffness. However, conventional carbon/epoxy composite bipolar plates are not applicable for high-temperature PEMFCs (HT-PEMFCs) because these systems are operated at higher temperatures than the glass transition temperatures of conventional epoxies. Therefore, in this study, a cyanate ester-modified epoxy is adopted for the development of a carbon composite bipolar plate for HT-PEMFCs. The composite bipolar plate with exposed surface carbon fibers is produced without any surface treatments or coatings to increase the productivity and is integrated with a silicone gasket to reduce the assembly cost. The developed carbon composite bipolar plate exhibits not only superior electrical properties but also high thermo-mechanical properties. In addition, a unit cell test is performed, and the results are compared with those of the conventional graphite bipolar plate.

  5. Kainate receptors mediate signaling in both transient and sustained OFF bipolar cell pathways in mouse retina.

    PubMed

    Borghuis, Bart G; Looger, Loren L; Tomita, Susumu; Demb, Jonathan B

    2014-04-30

    A fundamental question in sensory neuroscience is how parallel processing is implemented at the level of molecular and circuit mechanisms. In the retina, it has been proposed that distinct OFF cone bipolar cell types generate fast/transient and slow/sustained pathways by the differential expression of AMPA- and kainate-type glutamate receptors, respectively. However, the functional significance of these receptors in the intact circuit during light stimulation remains unclear. Here, we measured glutamate release from mouse bipolar cells by two-photon imaging of a glutamate sensor (iGluSnFR) expressed on postsynaptic amacrine and ganglion cell dendrites. In both transient and sustained OFF layers, cone-driven glutamate release from bipolar cells was blocked by antagonists to kainate receptors but not AMPA receptors. Electrophysiological recordings from bipolar and ganglion cells confirmed the essential role of kainate receptors for signaling in both transient and sustained OFF pathways. Kainate receptors mediated responses to contrast modulation up to 20 Hz. Light-evoked responses in all mouse OFF bipolar pathways depend on kainate, not AMPA, receptors.

  6. LRIT3 is essential to localize TRPM1 to the dendritic tips of depolarizing bipolar cells and may play a role in cone synapse formation

    PubMed Central

    Neuillé, Marion; Morgans, Catherine W.; Cao, Yan; Orhan, Elise; Michiels, Christelle; Sahel, José-Alain; Audo, Isabelle; Duvoisin, Robert M.; Martemyanov, Kirill A.; Zeitz, Christina

    2016-01-01

    Mutations in LRIT3 lead to complete congenital stationary night blindness (cCSNB). The exact role of LRIT3 in ON-bipolar cell signaling cascade remains to be elucidated. Recently, we have characterized a novel mouse model lacking Lrit3 (no b-wave 6, (Lrit3nob6/nob6)), which displays similar abnormalities as patients with cCSNB with LRIT3 mutations. Here we compare the localization of components of the ON-bipolar cell signaling cascade in wild-type and Lrit3nob6/nob6 retinal sections by immunofluorescence confocal microscopy. An anti-LRIT3 antibody was generated. Immunofluorescent staining of LRIT3 in wild-type mice revealed a specific punctate labeling in the outer plexiform layer (OPL), which was absent in Lrit3nob6/nob6 mice. LRIT3 did not colocalize with ribeye or calbindin but colocalized with mGluR6. TRPM1 staining was severely decreased at the dendritic tips of all depolarizing bipolar cells in Lrit3nob6/nob6 mice. mGluR6, GPR179, RGS7, RGS11 and Gβ5 immunofluorescence was absent at the dendritic tips of cone ON-bipolar cells in Lrit3nob6/nob6 mice, while it was present at the dendritic tips of rod bipolar cells. Furthermore, PNA labeling was severely reduced in the OPL in Lrit3nob6/nob6 mice. This study confirmed the localization of LRIT3 at the dendritic tips of depolarizing bipolar cells in mouse retina and demonstrated the dependence of TRPM1 localization on the presence of LRIT3. Since tested components of the ON-bipolar cell signaling cascade and PNA revealed disrupted localization, an additional function of LRIT3 in cone synapse formation is suggested. These results point to a possibly different regulation of the mGluR6 signaling cascade between rod and cone ON-bipolar cells. PMID:25997951

  7. Bipolar fuel cell

    DOEpatents

    McElroy, James F.

    1989-01-01

    The present invention discloses an improved fuel cell utilizing an ion transporting membrane having a catalytic anode and a catalytic cathode bonded to opposite sides of the membrane, a wet-proofed carbon sheet in contact with the cathode surface opposite that bonded to the membrane and a bipolar separator positioned in electrical contact with the carbon sheet and the anode of the adjacent fuel cell. Said bipolar separator and carbon sheet forming an oxidant flowpath, wherein the improvement comprises an electrically conductive screen between and in contact with the wet-proofed carbon sheet and the bipolar separator improving the product water removal system of the fuel cell.

  8. Advanced insulated gate bipolar transistor gate drive

    DOEpatents

    Short, James Evans [Monongahela, PA; West, Shawn Michael [West Mifflin, PA; Fabean, Robert J [Donora, PA

    2009-08-04

    A gate drive for an insulated gate bipolar transistor (IGBT) includes a control and protection module coupled to a collector terminal of the IGBT, an optical communications module coupled to the control and protection module, a power supply module coupled to the control and protection module and an output power stage module with inputs coupled to the power supply module and the control and protection module, and outputs coupled to a gate terminal and an emitter terminal of the IGBT. The optical communications module is configured to send control signals to the control and protection module. The power supply module is configured to distribute inputted power to the control and protection module. The control and protection module outputs on/off, soft turn-off and/or soft turn-on signals to the output power stage module, which, in turn, supplies a current based on the signal(s) from the control and protection module for charging or discharging an input capacitance of the IGBT.

  9. Agonist-stimulated cobalt uptake provides selective visualization of neurons expressing AMPA- or kainate-type glutamate receptors in the retina.

    PubMed

    Pourcho, Roberta G; Qin, Pu; Goebel, Dennis J; Fyk-Kolodziej, Bozena

    2002-12-16

    Fast-acting excitatory neurotransmission in the retina is mediated primarily by glutamate, acting at alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA) -selective and kainate-selective receptors. To localize these sites of action, cat retinas were stimulated with either AMPA or kainate and processed for histochemical visualization of cobalt uptake through calcium-permeable channels. Treatment with both agonists resulted in staining of A- and B-type horizontal cells and several types of OFF cone bipolar cells; there was no evidence for staining of ON cone bipolar cells or rod bipolar cells. The subpopulations of OFF cone bipolar cells differed in their responses with two distinct types that stained heavily with cobalt after exposure to AMPA and three different types that were preferentially labeled after exposure to kainate. Although many amacrine and ganglion cells appeared to respond to both agonists, AII amacrine cells were stained after stimulation by AMPA but not by kainate. The OFF cone bipolar cells that exhibit AMPA-stimulated cobalt uptake were found to have a high level of correspondence with cells that show immunocytochemical staining for the AMPA-selective glutamate receptor subunits GluR1 and GluR2/3. Similarly, the cone bipolar cells exhibiting kainate-stimulated cobalt uptake resemble those that are immunoreactive for the kainate subunit GluR5. The results indicate that, whereas many retinal neurons express both AMPA and kainate receptors, AII amacrine cells and subpopulations of OFF cone bipolar cells are limited to the expression of either AMPA or kainate receptors. This differential expression may contribute to the unique character of transmission by these cell types. Copyright 2002 Wiley-Liss, Inc.

  10. Low hydrostatic head electrolyte addition to fuel cell stacks

    DOEpatents

    Kothmann, Richard E.

    1983-01-01

    A fuel cell and system for supply electrolyte, as well as fuel and an oxidant to a fuel cell stack having at least two fuel cells, each of the cells having a pair of spaced electrodes and a matrix sandwiched therebetween, fuel and oxidant paths associated with a bipolar plate separating each pair of adjacent fuel cells and an electrolyte fill path for adding electrolyte to the cells and wetting said matrices. Electrolyte is flowed through the fuel cell stack in a back and forth fashion in a path in each cell substantially parallel to one face of opposite faces of the bipolar plate exposed to one of the electrodes and the matrices to produce an overall head uniformly between cells due to frictional pressure drop in the path for each cell free of a large hydrostatic head to thereby avoid flooding of the electrodes. The bipolar plate is provided with channels forming paths for the flow of the fuel and oxidant on opposite faces thereof, and the fuel and the oxidant are flowed along a first side of the bipolar plate and a second side of the bipolar plate through channels formed into the opposite faces of the bipolar plate, the fuel flowing through channels formed into one of the opposite faces and the oxidant flowing through channels formed into the other of the opposite faces.

  11. Highly conductive thermoplastic composites for rapid production of fuel cell bipolar plates

    DOEpatents

    Huang, Jianhua [Blacksburg, VA; Baird, Donald G [Blacksburg, VA; McGrath, James E [Blacksburg, VA

    2008-04-29

    A low cost method of fabricating bipolar plates for use in fuel cells utilizes a wet lay process for combining graphite particles, thermoplastic fibers, and reinforcing fibers to produce a plurality of formable sheets. The formable sheets are then molded into a bipolar plates with features impressed therein via the molding process. The bipolar plates formed by the process have conductivity in excess of 150 S/cm and have sufficient mechanical strength to be used in fuel cells. The bipolar plates can be formed as a skin/core laminate where a second polymer material is used on the skin surface which provides for enhanced conductivity, chemical resistance, and resistance to gas permeation.

  12. Bipolar plates for PEM fuel cells

    NASA Astrophysics Data System (ADS)

    Middelman, E.; Kout, W.; Vogelaar, B.; Lenssen, J.; de Waal, E.

    The bipolar plates are in weight and volume the major part of the PEM fuel cell stack, and are also a significant contributor to the stack costs. The bipolar plate is therefore a key component if power density has to increase and costs must come down. Three cell plate technologies are expected to reach targeted cost price levels, all having specific advantages and drawbacks. NedStack has developed a conductive composite materials and a production process for fuel cell plates (bipolar and mono-polar). The material has a high electric and thermal conductivity, and can be processed into bipolar plates by a proprietary molding process. Process cycle time has been reduced to less than 10 s, making the material and process suitable for economical mass production. Other development work to increase material efficiency resulted in thin bipolar plates with integrated cooling channels, and integrated seals, and in two-component bipolar plates. Total thickness of the bipolar plates is now less than 3 mm, and will be reduced to 2 mm in the near future. With these thin integrated plates it is possible to increase power density up to 2 kW/l and 2 kW/kg, while at the same time reducing cost by integrating other functions and less material use.

  13. Novel Structured Metal Bipolar Plates for Low Cost Manufacturing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Conghua

    2013-08-15

    Bipolar plates are an important component in fuel cell stacks and accounts for more than 75% of stack weight and volume, and 20% of the stack cost. The technology development of metal bipolar plates can effectively reduce the fuel cells stack weight and volume over 50%. The challenge is to protect metal plate from corrosion at low cost for the broad commercial applications. While most of today’s PEM fuel cell metallic bipolar plate technologies use some precious metal, the focus of this SBIR project is to develop a low cost, novel nano-structured metal bipolar plate technology without using any preciousmore » metal. The technology will meet the performance and cost requirements for automobile applications. Through the Phase I project, TreadStone has identified the corrosion resistant and electrically conductive titanium oxide for the metal bipolar plate surface protection for automotive PEM fuel cell applications. TreadStone has overcome the manufacturing issues to apply the coating on metal substrate surface, and has demonstrated the feasibility of the coated stainless steel plates by ex-situ evaluation tests and the in-situ fuel cell long term durability test. The test results show the feasibility of the proposed nano-structured coating as the low cost metal bipolar plates of PEM fuel cells. The plan for further technology optimization is also outlined for the Phase II project.« less

  14. Short-wavelength cone-opponent retinal ganglion cells in mammals.

    PubMed

    Marshak, David W; Mills, Stephen L

    2014-03-01

    In all of the mammalian species studied to date, the short-wavelength-sensitive (S) cones and the S-cone bipolar cells that receive their input are very similar, but the retinal ganglion cells that receive synapses from the S-cone bipolar cells appear to be quite different. Here, we review the literature on mammalian retinal ganglion cells that respond selectively to stimulation of S-cones and respond with opposite polarity to longer wavelength stimuli. There are at least three basic mechanisms to generate these color-opponent responses, including: (1) opponency is generated in the outer plexiform layer by horizontal cells and is conveyed to the ganglion cells via S-cone bipolar cells, (2) inputs from bipolar cells with different cone inputs and opposite response polarity converge directly on the ganglion cells, and (3) inputs from S-cone bipolar cells are inverted by S-cone amacrine cells. These are not mutually exclusive; some mammalian ganglion cells that respond selectively to S-cone stimulation seem to utilize at least two of them. Based on these findings, we suggest that the small bistratified ganglion cells described in primates are not the ancestral type, as proposed previously. Instead, the known types of ganglion cells in this pathway evolved from monostratified ancestral types and became bistratified in some mammalian lineages.

  15. White blood cell count correlates with mood symptom severity and specific mood symptoms in bipolar disorder.

    PubMed

    Köhler, Ole; Sylvia, Louisa G; Bowden, Charles L; Calabrese, Joseph R; Thase, Michael; Shelton, Richard C; McInnis, Melvin; Tohen, Mauricio; Kocsis, James H; Ketter, Terence A; Friedman, Edward S; Deckersbach, Thilo; Ostacher, Michael J; Iosifescu, Dan V; McElroy, Susan; Nierenberg, Andrew A

    2017-04-01

    Immune alterations may play a role in bipolar disorder etiology; however, the relationship between overall immune system functioning and mood symptom severity is unknown. The two comparative effectiveness trials, the Clinical and Health Outcomes Initiatives in Comparative Effectiveness for Bipolar Disorder Study (Bipolar CHOICE) and the Lithium Treatment Moderate-Dose Use Study (LiTMUS), were similar trials among patients with bipolar disorder. At study entry, white blood cell count and bipolar mood symptom severity (via Montgomery-Aasberg Depression Rating Scale and Bipolar Inventory of Symptoms Scale) were assessed. We performed analysis of variance and linear regression analyses to investigate relationships between deviations from median white blood cell and multinomial regression analysis between higher and lower white blood cell levels. All analyses were adjusted for age, gender, body mass index, smoking, diabetes, hypertension and hyperlipidemia. Among 482 Bipolar CHOICE participants, for each 1.0 × 10 9 /L white blood cell deviation, the overall Bipolar Inventory of Symptoms Scale severity increased significantly among men (coefficient = 2.13; 95% confidence interval = [0.46, -3.79]; p = 0.013), but not among women (coefficient = 0.87; 95% confidence interval = [-0.87, -2.61]; p = 0.33). Interaction analyses showed a trend toward greater Bipolar Inventory of Symptoms Scale symptom severity among men (coefficient = 1.51; 95% confidence interval = [-0.81, -3.82]; p = 0.2). Among 283 LiTMUS participants, higher deviation from the median white blood cell showed a trend toward higher Montgomery-Aasberg Depression Rating Scale scores among men (coefficient = 1.33; 95% confidence interval = [-0.22, -2.89]; p = 0.09), but not among women (coefficient = 0.34; 95% confidence interval = [-0.64, -1.32]; p = 0.50). When combining LiTMUS and Bipolar CHOICE, Montgomery-Aasberg Depression Rating Scale scores increased significantly among men (coefficient = 1.09; 95% confidence interval = [0.31, -1.87]; p = 0.006) for each 1.0 × 10 9 /L white blood cell deviation, whereas we found a weak association among women (coefficient = 0.55; 95% confidence interval = [-0.20, -1.29]; p = 0.14). Lower and higher white blood cell levels correlated with greater symptom severity and specific symptoms, varying according to gender. Deviations in an overall immune system marker, even within the normal white blood cell range, correlated with mood symptom severity in bipolar disorder, mostly among males. Studies are warranted investigating whether white blood cell count may predict response to mood-stabilizing treatment.

  16. Presynaptic excitability.

    PubMed

    Jackson, M B

    1995-01-01

    Based on functional characterizations with electrophysiological techniques, the channels in nerve terminals appear to be as diverse as channels in nerve cell bodies (Table I). While most presynaptic Ca2+ channels superficially resemble either N-type or L-type channels, variations in detail have necessitated the use of subscripts and other notations to indicate a nerve terminal-specific subtype (e.g., Wang et al., 1993). Variations such as these pose a serious obstacle to the identification of presynaptic channels based solely on the effects of channel blockers on synaptic transmission. Pharmacological sensitivity alone is not likely to help in determining functional properties. Crucial details, such as voltage sensitivity and inactivation, require direct examination. It goes without saying that every nerve terminal membrane contains Ca2+ channels as an entry pathway so that Ca2+ can trigger secretion. However, there appears to be no general specification of channel type, other than the exclusion of T-type Ca2+ channels. T-type Ca2+ channels are defined functionally by strong inactivation and low threshold. Some presynaptic Ca2+ channels inactivate (posterior pituitary and Xenopus nerve terminals), and others have a somewhat reduced voltage threshold (retinal bipolar neurons and squid giant synapse). Perhaps it is just a matter of time before a nerve terminal Ca2+ channel is found with both of these properties. The high threshold and strong inactivation of T-type Ca2+ channels are thought to be adaptations for oscillations and the regulation of bursting activity in nerve cell bodies. The nerve terminals thus far examined have no endogenous electrical activity, but rather are driven by the cell body. On functional grounds, it is then reasonable to anticipate finding T-type Ca2+ channels in nerve terminals that can generate electrical activity on their own. The rarity of such behavior in nerve terminals may be associated with the rarity of presynaptic T-type Ca2+ channels. In four of the five preparations reviewed in this chapter--motor nerve, squid giant synapse, ciliary ganglion, and retina bipolar neurons--evidence was presented that supports a location for Ca2+ channels that is very close to active zones of secretion. All of these synapses secrete from clear vesicles, and the speed and specificity of transduction provided by proximity may be a common feature of these rapid synapses. In contrast, the posterior pituitary secretion apparatus may be triggered by higher-affinity Ca2+ receptors and lower concentrations of Ca2+ (Lindau et al., 1992). This would correspond with the slower performance of peptidergic secretion, but because of the large stimuli needed to evoke release from neurosecretosomes, the possibility remains that the threshold for secretion is higher than that reported. While the role of Ca2+ as a trigger of secretion dictates a requirement for voltage-activated Ca2+ channels as universal components of the presynaptic membrane, the presence of other channels is more difficult to predict. Depolarizations caused by voltage-activated Na+ channels activate the presynaptic Ca2+ channels, but whether this depolarization requires Na+ channels in the presynaptic membrane itself may depend on the electrotonic length of the nerve terminal. Variations in density between motor nerve terminals may reflect species differences in geometry. The high Na+ channel density in the posterior pituitary reflects the great electrotonic length of this terminal arbor. Whether Na+ channels are abundant or not in a presynaptic membrane, K+ channels provide the most robust mechanism for limiting depolarization-induced Ca2+ entry. K+ channel blockers enhance transmission at most synapses. In general, K+ channels are abundant in nerve terminals, although their apparent lower priority compared to Ca2+ channels in the eyes of many investigators leaves us with fewer detailed investigations in some preparations. Most nerve terminals have more than

  17. Novel Structured Metal Bipolar Plates for Low Cost Manufacturing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, Conghua

    Bipolar plates are an important component in fuel cell stacks and accounts for more than 75% of stack weight and volume, and 20% of the stack cost. The technology development of metal bipolar plates can effectively reduce the fuel cells stack weight and volume over 50%. The challenge is to protect metal plate from corrosion at low cost for the broad commercial applications. While most of today’s PEM fuel cell metallic bipolar plate technologies use some precious metal, the focus of this SBIR project is to develop a low cost, novel nano-structured metal bipolar plate coating technology without using anymore » precious metal. The technology must meet the performance and cost requirements for automobile applications.« less

  18. The role of retinal bipolar cell in early vision: an implication with analogue networks and regularization theory.

    PubMed

    Yagi, T; Ohshima, S; Funahashi, Y

    1997-09-01

    A linear analogue network model is proposed to describe the neuronal circuit of the outer retina consisting of cones, horizontal cells, and bipolar cells. The model reflects previous physiological findings on the spatial response properties of these neurons to dim illumination and is expressed by physiological mechanisms, i.e., membrane conductances, gap-junctional conductances, and strengths of chemical synaptic interactions. Using the model, we characterized the spatial filtering properties of the bipolar cell receptive field with the standard regularization theory, in which the early vision problems are attributed to minimization of a cost function. The cost function accompanying the present characterization is derived from the linear analogue network model, and one can gain intuitive insights on how physiological mechanisms contribute to the spatial filtering properties of the bipolar cell receptive field. We also elucidated a quantitative relation between the Laplacian of Gaussian operator and the bipolar cell receptive field. From the computational point of view, the dopaminergic modulation of the gap-junctional conductance between horizontal cells is inferred to be a suitable neural adaptation mechanism for transition between photopic and mesopic vision.

  19. Dopamine D1 receptor activation contributes to light-adapted changes in retinal inhibition to rod bipolar cells.

    PubMed

    Flood, Michael Daniel; Moore-Dotson, Johnnie M; Eggers, Erika D

    2018-05-30

    Dopamine modulation of retinal signaling has been shown to be an important part of retinal adaptation to increased background light levels but the role of dopamine modulation of retinal inhibition is not clear. We previously showed that light adaptation causes a large reduction in inhibition to rod bipolar cells, potentially to match the decrease in excitation after rod saturation. In this study we determined how dopamine D1 receptors in the inner retina contribute to this modulation. We found that D1 receptor activation significantly decreased the magnitude of inhibitory light responses from rod bipolar cells, while D1 receptor blockade during light adaptation partially prevented this decline. To determine what mechanisms were involved in the modulation of inhibitory light responses, we measured the effect of D1 receptor activation on spontaneous currents and currents evoked from electrically stimulating amacrine cell inputs to rod bipolar cells. D1 receptor activation decreased the frequency of spontaneous inhibition with no change in event amplitudes, suggesting a presynaptic change in amacrine cell activity in agreement with previous reports that rod bipolar cells lack D1 receptors. Additionally, we found that D1 receptor activation reduced the amplitude of electrically-evoked responses, showing that D1 receptors can modulate amacrine cells directly. Our results suggest that D1 receptor activation can replicate a large portion, but not all of the effects of light adaptation, likely by modulating release from amacrine cells onto rod bipolar cells.

  20. Current density and catalyst-coated membrane resistance distribution of hydro-formed metallic bipolar plate fuel cell short stack with 250 cm2 active area

    NASA Astrophysics Data System (ADS)

    Haase, S.; Moser, M.; Hirschfeld, J. A.; Jozwiak, K.

    2016-01-01

    An automotive fuel cell with an active area of 250 cm2 is investigated in a 4-cell short stack with a current and temperature distribution device next to the bipolar plate with 560 current and 140 temperature segments. The electrical conductivities of the bipolar plate and gas diffusion layer assembly are determined ex-situ with this current scan shunt module. The applied fuel cell consists of bipolar plates constructed of 75-μm-thick, welded stainless-steel foils and a graphitic coating. The electrical conductivities of the bipolar plate and gas diffusion layer assembly are determined ex-situ with this module with a 6% deviation in in-plane conductivity. The current density distribution is evaluated up to 2.4 A cm-2. The entire cell's investigated volumetric power density is 4.7 kW l-1, and its gravimetric power density is 4.3 kW kg-1 at an average cell voltage of 0.5 V. The current density distribution is determined without influencing the operating cell. In addition, the current density distribution in the catalyst-coated membrane and its effective resistivity distribution with a finite volume discretisation of Ohm's law are evaluated. The deviation between the current density distributions in the catalyst-coated membrane and the bipolar plate is determined.

  1. Homer1a protein expression in schizophrenia, bipolar disorder, and major depression.

    PubMed

    Leber, Stefan L; Llenos, Ida C; Miller, Christine L; Dulay, Jeannette R; Haybaeck, Johannes; Weis, Serge

    2017-10-01

    In recent years, there was growing interest in postsynaptic density proteins in the central nervous system. Of the most important candidates of this specialized region are proteins belonging to the Homer protein family. This family of scaffolding proteins is suspected to participate in the pathogenesis of a variety of diseases. The present study aims to compare Homer1a expression in the hippocampus and cingulate gyrus of patients with major psychiatric disorders including schizophrenia, bipolar disorder and major depression. Immunohistochemistry was used to analyze changes of Homer1a protein expression in the hippocampal formation and the cingulate gyrus from the respective disease groups. Glial cells of the cingulate gyrus gray matter showed decreased Homer1a levels in bipolar disorder when compared to controls. The same results were seen when comparing cingulate gyrus gray matter glial cells in bipolar disorder with major depression. Stratum oriens glial cells of the hippocampus showed decreased Homer1a levels in bipolar disorder when compared to controls and major depression. Stratum lacunosum glial cells showed decreased Homer1a levels in bipolar disorder when compared to major depression. In stratum oriens interneurons Homer1a levels were increased in all disease groups when compared to controls. Stratum lucidum axons showed decreased Homer1a levels in bipolar disorder when compared to controls. Our data demonstrate altered Homer1a levels in specific brain regions and cell types of patients suffering from schizophrenia, bipolar disorder and major depression. These findings support the role of Homer proteins as interesting candidates in neuropsychiatric pathophysiology and treatment.

  2. High rate lithium/thionyl chloride bipolar battery development

    NASA Technical Reports Server (NTRS)

    Russell, Philip G.; Goebel, F.

    1994-01-01

    Presented in viewgraph format are results and accomplishments on the development of lithium/thionyl chloride bipolar batteries. Results include the development of manufacturing capability for producing large quantities of uniform cathodes and bipolar plates; the development of assembly, sealing, and activation procedures for fabrication of battery modules containing up to 150 cells in bipolar configuration; and the successful demonstration of a 10.7 kW 150-cell module with constant power pulse discharge, 20 second pulse, and 10 percent duty cycle.

  3. Corrosion test cell for bipolar plates

    DOEpatents

    Weisbrod, Kirk R.

    2002-01-01

    A corrosion test cell for evaluating corrosion resistance in fuel cell bipolar plates is described. The cell has a transparent or translucent cell body having a pair of identical cell body members that seal against opposite sides of a bipolar plate. The cell includes an anode chamber and an cathode chamber, each on opposite sides of the plate. Each chamber contains a pair of mesh platinum current collectors and a catalyst layer pressed between current collectors and the plate. Each chamber is filled with an electrolyte solution that is replenished with fluid from a much larger electrolyte reservoir. The cell includes gas inlets to each chamber for hydrogen gas and air. As the gases flow into a chamber, they pass along the platinum mesh, through the catalyst layer, and to the bipolar plate. The gas exits the chamber through passageways that provide fluid communication between the anode and cathode chambers and the reservoir, and exits the test cell through an exit port in the reservoir. The flow of gas into the cell produces a constant flow of fresh electrolyte into each chamber. Openings in each cell body is member allow electrodes to enter the cell body and contact the electrolyte in the reservoir therein. During operation, while hydrogen gas is passed into one chamber and air into the other chamber, the cell resistance is measured, which is used to evaluate the corrosion properties of the bipolar plate.

  4. Bhlhb5 is Required for the Subtype Development of Retinal Amacrine and Bipolar Cells in Mice

    PubMed Central

    Huang, Liang; Hu, Fang; Feng, Liang; Luo, Xiong-Jian; Liang, Guoqing; Zeng, Xiang-Yun; Yi, Jing-Lin; Gan, Lin

    2014-01-01

    Background BHLHB5, an OLIG-related basic helix-loop-helix transcription factor, is required for the development of a subset of gamma-amino butyric acid–releasing (GABAergic) amacrine cells and OFF-cone bipolar (CB) cells in mouse retinas. In order to determine BHLHB5’s functional mechanism in retinogenesis, we used the Cre-loxP recombination system to genetically trace the lineage of BHLHB5+ cells in normal and Bhlhb5-null retinas. The Bhlhb5-Cre knock-in allele was used to activate the constitutive expression of a GFP reporter in the Bhlhb5-expressing cells, and the cell fates of Bhlhb5-lineage cells were identified by using specific cell markers and were compared between normal and Bhlhb5-null retinas. Results In addition to GABAergic amacrine and OFF-CB cells, Bhlhb5 lineage cells give rise to ganglion, glycinergic amacrine, rod bipolar, ON-bipolar, and rod photoreceptor cells during normal retinal development. Targeted deletion of Bhlhb5 resulted in the loss of GABAergic amacrine, glycinergic amacrine, dopaminergic amacrine, and Type 2 OFF-CB cells. Furthermore, in the absence of BHLHB5, a portion of Bhlhb5 lineage cells switch their fate and differentiate into cholinergic amacrine cells. Conclusions Our data reveal a broad expression pattern of Bhlhb5 throughout retinogenesis and demonstrate the cell-autonomous as well as non-cell-autonomous role of Bhlhb5 in the specification of amacrine and bipolar subtypes. PMID:24123365

  5. Bhlhb5 is required for the subtype development of retinal amacrine and bipolar cells in mice.

    PubMed

    Huang, Liang; Hu, Fang; Feng, Liang; Luo, Xiong-Jian; Liang, Guoqing; Zeng, Xiang-Yun; Yi, Jing-Lin; Gan, Lin

    2014-02-01

    BHLHB5, an OLIG-related basic helix-loop-helix transcription factor, is required for the development of a subset of gamma-amino butyric acid-releasing (GABAergic) amacrine cells and OFF-cone bipolar (CB) cells in mouse retinas. In order to determine BHLHB5's functional mechanism in retinogenesis, we used the Cre-loxP recombination system to genetically trace the lineage of BHLHB5+ cells in normal and Bhlhb5-null retinas. The Bhlhb5-Cre knock-in allele was used to activate the constitutive expression of a GFP reporter in the Bhlhb5-expressing cells, and the cell fates of Bhlhb5-lineage cells were identified by using specific cell markers and were compared between normal and Bhlhb5-null retinas. In addition to GABAergic amacrine and OFF-CB cells, Bhlhb5 lineage cells give rise to ganglion, glycinergic amacrine, rod bipolar, ON-bipolar, and rod photoreceptor cells during normal retinal development. Targeted deletion of Bhlhb5 resulted in the loss of GABAergic amacrine, glycinergic amacrine, dopaminergic amacrine, and Type 2 OFF-CB cells. Furthermore, in the absence of BHLHB5, a portion of Bhlhb5 lineage cells switch their fate and differentiate into cholinergic amacrine cells. Our data reveal a broad expression pattern of Bhlhb5 throughout retinogenesis and demonstrate the cell-autonomous as well as non-cell-autonomous role of Bhlhb5 in the specification of amacrine and bipolar subtypes. Copyright © 2013 Wiley Periodicals, Inc.

  6. Preparation and characterization of mono-sheet bipolar membranes by pre-irradiation grafting method for fuel cell applications

    NASA Astrophysics Data System (ADS)

    Guan, Yingjie; Fang, Jun; Fu, Tao; Zhou, Huili; Wang, Xin; Deng, Zixiang; Zhao, Jinbao

    2016-09-01

    A new method for the preparation of the mono-sheet bipolar membrane applied to fuel cells was developed based on the pre-irradiation grafting technology. A series of bipolar membranes were successfully prepared by simultaneously grafting of styrene onto one side of the poly(ethylene-co-tetrafluoroethylene) base film and 1-vinylimidazole onto the opposite side, followed by the sulfonation and alkylation, respectively. The chemical structures and microstructures of the prepared membranes were investigated by ATR-FTIR and SEM-EDS. The TGA measurements demonstrated the prepared bipolar membranes have reasonable thermal stability. The ion exchange capacity, water uptake and ionic conductivity of the membranes were also characterized. The H2/O2 single fuel cells using these membranes were evaluated and revealed a maximum power density of 107 mW cm-2 at 35 °C with unhumidified hydrogen and oxygen. The preliminary performances suggested the great prospect of these membranes in application of bipolar membrane fuel cells.

  7. Graded junction termination extensions for electronic devices

    NASA Technical Reports Server (NTRS)

    Merrett, J. Neil (Inventor); Isaacs-Smith, Tamara (Inventor); Sheridan, David C. (Inventor); Williams, John R. (Inventor)

    2006-01-01

    A graded junction termination extension in a silicon carbide (SiC) semiconductor device and method of its fabrication using ion implementation techniques is provided for high power devices. The properties of silicon carbide (SiC) make this wide band gap semiconductor a promising material for high power devices. This potential is demonstrated in various devices such as p-n diodes, Schottky diodes, bipolar junction transistors, thyristors, etc. These devices require adequate and affordable termination techniques to reduce leakage current and increase breakdown voltage in order to maximize power handling capabilities. The graded junction termination extension disclosed is effective, self-aligned, and simplifies the implementation process.

  8. Graded junction termination extensions for electronic devices

    NASA Technical Reports Server (NTRS)

    Merrett, J. Neil (Inventor); Isaacs-Smith, Tamara (Inventor); Sheridan, David C. (Inventor); Williams, John R. (Inventor)

    2007-01-01

    A graded junction termination extension in a silicon carbide (SiC) semiconductor device and method of its fabrication using ion implementation techniques is provided for high power devices. The properties of silicon carbide (SiC) make this wide band gap semiconductor a promising material for high power devices. This potential is demonstrated in various devices such as p-n diodes, Schottky diodes, bipolar junction transistors, thyristors, etc. These devices require adequate and affordable termination techniques to reduce leakage current and increase breakdown voltage in order to maximize power handling capabilities. The graded junction termination extension disclosed is effective, self-aligned, and simplifies the implementation process.

  9. Synaptic noise is an information bottleneck in the inner retina during dynamic visual stimulation

    PubMed Central

    Freed, Michael A; Liang, Zhiyin

    2014-01-01

    In daylight, noise generated by cones determines the fidelity with which visual signals are initially encoded. Subsequent stages of visual processing require synapses from bipolar cells to ganglion cells, but whether these synapses generate a significant amount of noise was unknown. To characterize noise generated by these synapses, we recorded excitatory postsynaptic currents from mammalian retinal ganglion cells and subjected them to a computational noise analysis. The release of transmitter quanta at bipolar cell synapses contributed substantially to the noise variance found in the ganglion cell, causing a significant loss of fidelity from bipolar cell array to postsynaptic ganglion cell. Virtually all the remaining noise variance originated in the presynaptic circuit. Circuit noise had a frequency content similar to noise shared by ganglion cells but a very different frequency content from noise from bipolar cell synapses, indicating that these synapses constitute a source of independent noise not shared by ganglion cells. These findings contribute a picture of daylight retinal circuits where noise from cones and noise generated by synaptic transmission of cone signals significantly limit visual fidelity. PMID:24297850

  10. The second phase of bipolar, nanosecond-range electric pulses determines the electroporation efficiency.

    PubMed

    Pakhomov, Andrei G; Grigoryev, Sergey; Semenov, Iurii; Casciola, Maura; Jiang, Chunqi; Xiao, Shu

    2018-03-29

    Bipolar cancellation refers to a phenomenon when applying a second electric pulse reduces ("cancels") cell membrane damage by a preceding electric pulse of the opposite polarity. Bipolar cancellation is a reason why bipolar nanosecond electric pulses (nsEP) cause weaker electroporation than just a single unipolar phase of the same pulse. This study was undertaken to explore the dependence of bipolar cancellation on nsEP parameters, with emphasis on the amplitude ratio of two opposite polarity phases of a bipolar pulse. Individual cells (CHO, U937, or adult mouse ventricular cardiomyocytes (VCM)) were exposed to either uni- or bipolar trapezoidal nsEP, or to nanosecond electric field oscillations (NEFO). The membrane injury was evaluated by time-lapse confocal imaging of the uptake of propidium (Pr) or YO-PRO-1 (YP) dyes and by phosphatidylserine (PS) externalization. Within studied limits, bipolar cancellation showed little or no dependence on the electric field intensity, pulse repetition rate, chosen endpoint, or cell type. However, cancellation could increase for larger pulse numbers and/or for longer pulses. The sole most critical parameter which determines bipolar cancellation was the phase ratio: maximum cancellation was observed with the 2nd phase of about 50% of the first one, whereas a larger 2nd phase could add a damaging effect of its own. "Swapping" the two phases, i.e., delivering the smaller phase before the larger one, reduced or eliminated cancellation. These findings are discussed in the context of hypothetical mechanisms of bipolar cancellation and electroporation by nsEP. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. Test methods and results of the 10-cell bipolar Ni-H2 battery

    NASA Technical Reports Server (NTRS)

    Cataldo, R.

    1983-01-01

    Characterization tests were carried out at three charge levels and four discharge levels. The "c' or capacity of the battery is designated at 6.5 ampere-hours. The recharge ampere-hours was the same for all test conditions, 6.5 A-H, regardless of the discharge capacity removed for any particular discharge rate. Less capacity can be removed at higher discharge rates to the same termination voltage, which was 0.50 volts for the weakest (lowest voltage) cell. The general trend of efficiencies increases as the charge rate increases as noted in results of the table included in the handout package. The data also indicate the efficiency increases as the discharge rate decreases. This is true; however, efficiencies at the discharge rates of c and 2c are penalized because these cycles received more overcharge than necessary.

  12. Unraveling the biology of bipolar disorder using induced pluripotent stem-derived neurons.

    PubMed

    Miller, Nathaniel D; Kelsoe, John R

    2017-11-01

    Bipolar disorder has been studied from numerous angles, from pathological studies to large-scale genomic studies, overall making moderate gains toward an understanding of the disorder. With the advancement of induced pluripotent stem (iPS) cell technology, in vitro models based on patient samples are now available that inherently incorporate the complex genetic variants that largely are the basis for this disorder. A number of groups are starting to apply iPS technology to the study of bipolar disorder. We selectively reviewed the literature related to understanding bipolar disorder based on using neurons derived from iPS cells. So far, most work has used the prototypical iPS cells. However, others have been able to transdifferentiate fibroblasts directly to neurons. Others still have utilized olfactory epithelium tissue as a source of neural-like cells that do not need reprogramming. In general, iPS and related cells can be used for studies of disease pathology, drug discovery, or stem cell therapy. Published studies have primarily focused on understanding bipolar disorder pathology, but initial work is also being done to use iPS technology for drug discovery. In terms of disease pathology, some evidence is pointing toward a differentiation defect with more ventral cell types being prominent. Additionally, there is evidence for a calcium signaling defect, a finding that builds on the genome-wide association study results. Continued work with iPS cells will certainly help us understand bipolar disorder and provide a way forward for improved treatments. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Bipolar rechargeable lithium battery for high power applications

    NASA Technical Reports Server (NTRS)

    Hossain, Sohrab; Kozlowski, G.; Goebel, F.

    1993-01-01

    Viewgraphs of a discussion on bipolar rechargeable lithium battery for high power applications are presented. Topics covered include cell chemistry, electrolytes, reaction mechanisms, cycling behavior, cycle life, and cell assembly.

  14. Endogenous calcium buffering at photoreceptor synaptic terminals in salamander retina

    PubMed Central

    Van Hook, Matthew J.; Thoreson, Wallace B.

    2014-01-01

    Calcium operates by several mechanisms to regulate glutamate release at rod and cone synaptic terminals. In addition to serving as the exocytotic trigger, Ca2+ accelerates replenishment of vesicles in cones and triggers Ca2+-induced Ca2+ release (CICR) in rods. Ca2+ thereby amplifies sustained exocytosis, enabling photoreceptor synapses to encode constant and changing light. A complete picture of the role of Ca2+ in regulating synaptic transmission requires an understanding of the endogenous Ca2+ handling mechanisms at the synapse. We therefore used the “added buffer” approach to measure the endogenous Ca2+ binding ratio (κendo) and extrusion rate constant (γ) in synaptic terminals of photoreceptors in retinal slices from tiger salamander. We found that κendo was similar in both cell types - approximately 25 and 50 in rods and cones, respectively. Using measurements of the decay time constants of Ca2+ transients, we found that γ was also similar, with values of approximately 100 s−1 and 160 s−1 in rods and cones, respectively. The measurements of κendo differ considerably from measurements in retinal bipolar cells, another ribbon-bearing class of retinal neurons, but are comparable to similar measurements at other conventional synapses. The values of γ are slower than at other synapses, suggesting that Ca2+ ions linger longer in photoreceptor terminals, supporting sustained exocytosis, CICR, and Ca2+-dependent ribbon replenishment. The mechanisms of endogenous Ca2+ handling in photoreceptors are thus well-suited for supporting tonic neurotransmission. Similarities between rod and cone Ca2+ handling suggest that neither buffering nor extrusion underlie differences in synaptic transmission kinetics. PMID:25049035

  15. Mindfulness-Based Cognitive Therapy for Bipolar Disorder: Effects on Cognitive Functioning

    PubMed Central

    Stange, Jonathan P.; Eisner, Lori R.; Hölzel, Britta K.; Peckham, Andrew D.; Dougherty, Darin D.; Rauch, Scott L.; Nierenberg, Andrew A.; Lazar, Sara; Deckersbach, Thilo

    2012-01-01

    Bipolar disorder is associated with impairments in cognition, including difficulties in executive functioning, even when patients are euthymic (neither depressed nor manic). The purpose of this study was to assess changes in self-reported cognitive functioning in patients with bipolar disorder who participated in an open pilot trial of mindfulness-based cognitive therapy (MBCT). Following MBCT, patients reported significant improvements in executive functioning, memory, and ability to initiate and complete tasks, as measured by the Behavior Rating Inventory of Executive Function (BRIEF) and the Frontal Systems Behavior Scale (FrSBe). Changes in cognitive functioning were correlated with increases in mindful, nonjudgmental observance and awareness of thoughts, feelings, and sensations, and were not associated with decreases in depression. Improvements tended to diminish after termination of treatment, but some improvements, particularly those in executive functioning, persisted after 3 months. These results provide preliminary evidence that MBCT may be a treatment option that can be used as an adjunct to medication to improve cognitive functioning in bipolar disorder. PMID:22108398

  16. PEM fuel cell bipolar plate material requirements for transportation applications

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Borup, R.L.; Stroh, K.R.; Vanderborgh, N.E.

    1996-04-01

    Cost effective bipolar plates are currently under development to help make proton exchange membrane (PEM) fuel cells commercially viable. Bipolar plates separate individual cells of the fuel cell stack, and thus must supply strength, be electrically conductive, provide for thermal control of the fuel stack, be a non-porous materials separating hydrogen and oxygen feed streams, be corrosion resistant, provide gas distribution for the feed streams and meet fuel stack cost targets. Candidate materials include conductive polymers and metal plates with corrosion resistant coatings. Possible metals include aluminium, titanium, iron/stainless steel and nickel.

  17. Tilted fuel cell apparatus

    DOEpatents

    Cooper, John F.; Cherepy, Nerine; Krueger, Roger L.

    2005-04-12

    Bipolar, tilted embodiments of high temperature, molten electrolyte electrochemical cells capable of directly converting carbon fuel to electrical energy are disclosed herein. The bipolar, tilted configurations minimize the electrical resistance between one cell and others connected in electrical series. The tilted configuration also allows continuous refueling of carbon fuel.

  18. Multipolar Spindle Pole Coalescence Is a Major Source of Kinetochore Mis-Attachment and Chromosome Mis-Segregation in Cancer Cells

    PubMed Central

    Silkworth, William T.; Nardi, Isaac K.; Scholl, Lindsey M.; Cimini, Daniela

    2009-01-01

    Many cancer cells display a CIN (Chromosome Instability) phenotype, by which they exhibit high rates of chromosome loss or gain at each cell cycle. Over the years, a number of different mechanisms, including mitotic spindle multipolarity, cytokinesis failure, and merotelic kinetochore orientation, have been proposed as causes of CIN. However, a comprehensive theory of how CIN is perpetuated is still lacking. We used CIN colorectal cancer cells as a model system to investigate the possible cellular mechanism(s) underlying CIN. We found that CIN cells frequently assembled multipolar spindles in early mitosis. However, multipolar anaphase cells were very rare, and live-cell experiments showed that almost all CIN cells divided in a bipolar fashion. Moreover, fixed-cell analysis showed high frequencies of merotelically attached lagging chromosomes in bipolar anaphase CIN cells, and higher frequencies of merotelic attachments in multipolar vs. bipolar prometaphases. Finally, we found that multipolar CIN prometaphases typically possessed γ-tubulin at all spindle poles, and that a significant fraction of bipolar metaphase/early anaphase CIN cells possessed more than one centrosome at a single spindle pole. Taken together, our data suggest a model by which merotelic kinetochore attachments can easily be established in multipolar prometaphases. Most of these multipolar prometaphase cells would then bi-polarize before anaphase onset, and the residual merotelic attachments would produce chromosome mis-segregation due to anaphase lagging chromosomes. We propose this spindle pole coalescence mechanism as a major contributor to chromosome instability in cancer cells. PMID:19668340

  19. Brazed bipolar plates for PEM fuel cells

    DOEpatents

    Neutzler, Jay Kevin

    1998-01-01

    A liquid-cooled, bipolar plate separating adjacent cells of a PEM fuel cell comprising corrosion-resistant metal sheets brazed together so as to provide a passage between the sheets through which a dielectric coolant flows. The brazement comprises a metal which is substantially insoluble in the coolant.

  20. Brazed bipolar plates for PEM fuel cells

    DOEpatents

    Neutzler, J.K.

    1998-07-07

    A liquid-cooled, bipolar plate separating adjacent cells of a PEM fuel cell comprises corrosion-resistant metal sheets brazed together so as to provide a passage between the sheets through which a dielectric coolant flows. The brazement comprises a metal which is substantially insoluble in the coolant. 6 figs.

  1. Requirements and testing methods for surfaces of metallic bipolar plates for low-temperature PEM fuel cells

    NASA Astrophysics Data System (ADS)

    Jendras, P.; Lötsch, K.; von Unwerth, T.

    2017-03-01

    To reduce emissions and to substitute combustion engines automotive manufacturers, legislature and first users aspire hydrogen fuel cell vehicles. Up to now the focus of research was set on ensuring functionality and increasing durability of fuel cell components. Therefore, expensive materials were used. Contemporary research and development try to substitute these substances by more cost-effective material combinations. The bipolar plate is a key component with the greatest influence on volume and mass of a fuel cell stack and they have to meet complex requirements. They support bending sensitive components of stack, spread reactants over active cell area and form the electrical contact to another cell. Furthermore, bipolar plates dissipate heat of reaction and separate one cell gastight from the other. Consequently, they need a low interfacial contact resistance (ICR) to the gas diffusion layer, high flexural strength, good thermal conductivity and a high durability. To reduce costs stainless steel is a favoured material for bipolar plates in automotive applications. Steel is characterized by good electrical and thermal conductivity but the acid environment requires a high chemical durability against corrosion as well. On the one hand formation of a passivating oxide layer increasing ICR should be inhibited. On the other hand pitting corrosion leading to increased permeation rate may not occur. Therefore, a suitable substrate lamination combination is wanted. In this study material testing methods for bipolar plates are considered.

  2. The composition of the inner nuclear layer of the cat retina.

    PubMed

    Macneil, Margaret A; Purrier, Sheryl; Rushmore, R Jarrett

    2009-01-01

    The cellular composition of the inner nuclear layer (INL) is largely conserved among mammals. Studies of rabbit, monkey, and mouse retinas have shown that bipolar, amacrine, Müller, and horizontal cells make up constant fractions of the INL (42, 35, 20, and 3%, respectively); these proportions remain relatively constant at all retinal eccentricities. The purpose of our study was to test whether the organization of cat retina is similar to that of other mammalian retinas. Fixed retinas were embedded in plastic, serially sectioned at a thickness of 1 microm, stained, and imaged at high power in the light microscope. Bipolar, amacrine, Müller, and horizontal cells were classified and counted according to established morphological criteria. Additional sets of sections were processed for protein kinase C and calretinin immunoreactivity to determine the relative fraction of rod bipolar and AII amacrine cells. Our results show that the organization of INL in the cat retina contains species-specific alterations in the composition of the INL tied to the large fraction of rod photoreceptors. Compared with other mammalian retinas, cat retinas show an expansion of the rod pathway with rod bipolar cells accounting for about 70% of all bipolar cells and AII cells accounting for nearly a quarter of all amacrine cells. Our results suggest that evolutionary pressures in cats over time have refined their retinal organization to suit its ecological niche.

  3. The Investigation and Development of Low Cost Hardware Components for Proton-Exchange Membrane Fuel Cells - Final Report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    George A. Marchetti

    1999-12-15

    Proton exchange membrane (PEM) fuel cell components, which would have a low-cost structure in mass production, were fabricated and tested. A fuel cell electrode structure, comprising a thin layer of graphite (50 microns) and a front-loaded platinum catalyst layer (600 angstroms), was shown to produce significant power densities. In addition, a PEM bipolar plate, comprising flexible graphite, carbon cloth flow-fields and an integrated polymer gasket, was fabricated. Power densities of a two-cell unit using this inexpensive bipolar plate architecture were shown to be comparable to state-of-the-art bipolar plates.

  4. Woven-grid sealed quasi-bipolar lead-acid battery construction and fabricating method

    NASA Technical Reports Server (NTRS)

    Rippel, Wally E. (Inventor)

    1989-01-01

    A quasi-bipolar lead-acid battery construction includes a plurality of bipolar cells disposed in side-by-side relation to form a stack, and a pair of monoplanar plates at opposite ends of the stack, the cell stack and monopolar plates being contained within a housing of the battery. Each bipolar cell is loaded with an electrolyte and composed of a bipolar electrode plate and a pair of separator plates disposed on opposite sides of the electrode plate and peripherally sealed thereto. Each bipolar electrode plate is composed of a partition sheet and two bipolar electrode elements folded into a hairpin configuration and applied over opposite edges of the partition sheet so as to cover the opposite surfaces of the opposite halves thereof. Each bipolar electrode element is comprised of a woven grid with a hot-melt strip applied to a central longitudinal region of the grid along which the grid is folded into the hairpin configuration, and layers of negative and positive active material pastes applied to opposite halves of the grid on opposite sides of the central hot-melt strip. The grid is made up of strands of conductive and non-conductive yarns composing the respective transverse and longitudinal weaves of the grid. The conductive yarn has a multi-stranded glass core surrounded and covered by a lead sheath, whereas the non-conductive yarn has a multi-stranded glass core surrounded and covered by a thermally activated sizing.

  5. Development of a Woven-Grid Quasi-Bipolar Battery

    NASA Technical Reports Server (NTRS)

    Tokumaru, P.; Rippel, W.; Zambrano, T.

    1998-01-01

    This report describes an analytical and experimental investigation of AeroVironment's Quasi-Bipolar battery concept. The modelling/battery design part of the study demonstrates that there is a trade-off between thermal and specified electrical performance. Even so, quasi-bipolar batteries can be designed, with ten times better thermal uniformity, that meet or exceed current state-of-the-art hybrid-electric vehicle battery pack performance, even using the same active materials. The thermal uniformity, power, and energy for these quasi-bipolar battery packs is projected to be very good. The experimental part of the investigation demonstrates the concept of the quasi-bipolar plate applied to a lead foil current collector wrapping around two sides of an inexpensive plastic film core. Approximately 50 quasi-biplate samples were fabricated using a hot laminating press. Hot lamination with "texture" between the plastic and lead shows some promise as a low cost method for fabricating the plates. Five of these plates were assembled into two cells plus one two-cell battery. Data from these test cells were compared with existing data for similar true bipolar batteries. The positive side of the plates exhibited corrosion where not protected by the active material.

  6. Composite Bipolar Plate for Unitized Fuel Cell/Electrolyzer Systems

    NASA Technical Reports Server (NTRS)

    Mittelsteadt, Cortney K.; Braff, William

    2009-01-01

    In a substantial improvement over present alkaline systems, an advanced hybrid bipolar plate for a unitized fuel cell/electrolyzer has been developed. This design, which operates on pure feed streams (H2/O2 and water, respectively) consists of a porous metallic foil filled with a polymer that has very high water transport properties. Combined with a second metallic plate, the pore-filled metallic plates form a bipolar plate with an empty cavity in the center.

  7. Cholinergic neurons and fibres in the rat visual cortex.

    PubMed

    Parnavelas, J G; Kelly, W; Franke, E; Eckenstein, F

    1986-06-01

    Choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme, was localized immunocytochemically in neurons and fibres in the rat visual cortex using a monoclonal antibody. ChAT-labelled cells were non-pyramidal neurons, primarily of the bipolar form, distributed in layers II through VI but concentrated in layers II & III. Their perikarya contained a large nucleus and a small amount of perinuclear cytoplasm. The somata and dendrites of all labelled cells received Gray's type I and type II synapses. ChAT-stained axons formed a dense and diffuse network throughout the visual cortex and particularly in layer V. Electron microscopy revealed that the great majority formed type II synaptic contacts with dendrites of various sizes, unlabelled non-pyramidal somata and, on a few occasions, with ChAT-labelled cells. However, a very small number of terminals appeared to form type I synaptic contacts. This study describes the morphological organization of the cholinergic system in the visual cortex, the function of which has been under extensive investigation.

  8. Bipolar stacked quasi-all-solid-state lithium secondary batteries with output cell potentials of over 6 V

    PubMed Central

    Matsuo, Takahiro; Gambe, Yoshiyuki; Sun, Yan; Honma, Itaru

    2014-01-01

    Designing a lithium ion battery (LIB) with a three-dimensional device structure is crucial for increasing the practical energy storage density by avoiding unnecessary supporting parts of the cell modules. Here, we describe the superior secondary battery performance of the bulk all-solid-state LIB cell and a multilayered stacked bipolar cell with doubled cell potential of 6.5 V, for the first time. The bipolar-type solid LIB cell runs its charge/discharge cycle over 200 times in a range of 0.1–1.0 C with negligible capacity decrease despite their doubled output cell potentials. This extremely high performance of the bipolar cell is a result of the superior battery performance of the single cell; the bulk all-solid-state cell has a charge/discharge cycle capability of over 1500 although metallic lithium and LiFePO4 are employed as anodes and cathodes, respectively. The use of a quasi-solid electrolyte consisting of ionic liquid and Al2O3 nanoparticles is considered to be responsible for the high ionic conductivity and electrochemical stability at the interface between the electrodes and the electrolyte. This paper presents the effective applications of SiO2, Al2O3, and CeO2 nanoparticles and various Li+ conducting ionic liquids for the quasi-solid electrolytes and reports the best ever known cycle performances. Moreover, the results of this study show that the bipolar stacked three-dimensional device structure would be a smart choice for future LIBs with higher cell energy density and output potential. In addition, our report presents the advantages of adopting a three-dimensional cell design based on the solid-state electrolytes, which is of particular interest in energy-device engineering for mobile applications. PMID:25124398

  9. Disinhibition of the extracellular-signal-regulated kinase restores the amplification of circadian rhythms by lithium in cells from bipolar disorder patients.

    PubMed

    McCarthy, Michael J; Wei, Heather; Landgraf, Dominic; Le Roux, Melissa J; Welsh, David K

    2016-08-01

    Bipolar disorder (BD) is characterized by depression, mania, and circadian rhythm abnormalities. Lithium, a treatment for BD stabilizes mood and increases circadian rhythm amplitude. However, in fibroblasts grown from BD patients, lithium has weak effects on rhythm amplitude compared to healthy controls. To understand the mechanism by which lithium differentially affects rhythm amplitude in BD cells, we investigated the extracellular-signal-regulated kinase (ERK) and related signaling molecules linked to BD and circadian rhythms. In fibroblasts from BD patients, controls and mice, we assessed the contribution of the ERK pathway to lithium-induced circadian rhythm amplification. Protein analyses revealed low phospho-ERK1/2 (p-ERK) content in fibroblasts from BD patients vs. Pharmacological inhibition of ERK1/2 by PD98059 attenuated the rhythm amplification effect of lithium, while inhibition of two related kinases, c-Jun N-terminal kinase (JNK), and P38 did not. Knockdown of the transcription factors CREB and EGR-1, downstream effectors of ERK1/2, reduced baseline rhythm amplitude, but did not alter rhythm amplification by lithium. In contrast, ELK-1 knockdown amplified rhythms, an effect that was not increased further by the addition of lithium, suggesting this transcription factor may regulate the effect of lithium on amplitude. Augmentation of ERK1/2 signaling through DUSP6 knockdown sensitized NIH3T3 cells to rhythm amplification by lithium. In BD fibroblasts, DUSP6 knockdown reversed the BD rhythm phenotype, restoring the ability of lithium to increase amplitude in these cells. We conclude that the inability of lithium to regulate circadian rhythms in BD may reflect reduced ERK activity, and signaling through ELK-1. Published by Elsevier B.V.

  10. FoxP2 protein levels regulate cell morphology changes and migration patterns in the vertebrate developing telencephalon.

    PubMed

    Garcia-Calero, Elena; Botella-Lopez, Arancha; Bahamonde, Olga; Perez-Balaguer, Ariadna; Martinez, Salvador

    2016-07-01

    In the mammalian telencephalon, part of the progenitor cells transition from multipolar to bipolar morphology as they invade the mantle zone. This associates with changing patterns of radial migration. However, the molecules implicated in these morphology transitions are not well known. In the present work, we analyzed the function of FoxP2 protein in this process during telencephalic development in vertebrates. We analyzed the expression of FoxP2 protein and its relation with cell morphology and migratory patterns in mouse and chicken developing striatum. We observed FoxP2 protein expressed in a gradient from the subventricular zone to the mantle layer in mice embryos. In the FoxP2 low domain cells showed multipolar migration. In the striatal mantle layer where FoxP2 protein expression is higher, cells showed locomoting migration and bipolar morphology. In contrast, FoxP2 showed a high and homogenous expression pattern in chicken striatum, thus bipolar morphology predominated. Elevation of FoxP2 in the striatal subventricular zone by in utero electroporation promoted bipolar morphology and impaired multipolar radial migration. In mouse cerebral cortex we obtained similar results. FoxP2 promotes transition from multipolar to bipolar morphology by means of gradiental expression in mouse striatum and cortex. Together these results indicate a role of FoxP2 differential expression in cell morphology control of the vertebrate telencephalon.

  11. High Mitotic Activity of Polo-like Kinase 1 Is Required for Chromosome Segregation and Genomic Integrity in Human Epithelial Cells*

    PubMed Central

    Lera, Robert F.; Burkard, Mark E.

    2012-01-01

    Protein kinases play key roles in regulating human cell biology, but manifold substrates and functions make it difficult to understand mechanism. We tested whether we could dissect functions of a pleiotropic mitotic kinase, Polo-like kinase 1 (Plk1), via distinct thresholds of kinase activity. We accomplished this by titrating Plk1 activity in RPE1 human epithelial cells using chemical genetics and verifying results in additional lines. We found that distinct activity thresholds are required for known functions of Plk1 including (from low to high activity) bipolar spindle formation, timely mitotic entry, and formation of a cytokinesis cleavage furrow. Subtle losses in Plk1 activity impaired chromosome congression and produced severe anaphase dysfunction characterized by poor separation of chromosome masses. These two phenotypes were separable, suggesting that they stem from distinct phosphorylation events. Impaired chromosome segregation in anaphase was the most sensitive to modest loss in Plk1 activity. Mechanistically, it was associated with unpaired sister chromatids with stretched kinetochores, suggestive of merotelic attachments. The C-terminal Polo box domain of Plk1 was required for its anaphase function, although it was dispensable for forming a bipolar spindle. The ultimate effect of partial inhibition of Plk1 was the formation of micronuclei, an increase in tetraploid progeny, and senescence. These results demonstrate that different thresholds of Plk1 activity can elicit distinct phenotypes, illustrating a general method for separating pleiotropic functions of a protein kinase even when these are executed close in time. PMID:23105120

  12. SLC6A3 coding variant Ala559Val found in two autism probands alters dopamine transporter function and trafficking.

    PubMed

    Bowton, E; Saunders, C; Reddy, I A; Campbell, N G; Hamilton, P J; Henry, L K; Coon, H; Sakrikar, D; Veenstra-VanderWeele, J M; Blakely, R D; Sutcliffe, J; Matthies, H J G; Erreger, K; Galli, A

    2014-10-14

    Emerging evidence associates dysfunction in the dopamine (DA) transporter (DAT) with the pathophysiology of autism spectrum disorder (ASD). The human DAT (hDAT; SLC6A3) rare variant with an Ala to Val substitution at amino acid 559 (hDAT A559V) was previously reported in individuals with bipolar disorder or attention-deficit hyperactivity disorder (ADHD). We have demonstrated that this variant is hyper-phosphorylated at the amino (N)-terminal serine (Ser) residues and promotes an anomalous DA efflux phenotype. Here, we report the novel identification of hDAT A559V in two unrelated ASD subjects and provide the first mechanistic description of its impaired trafficking phenotype. DAT surface expression is dynamically regulated by DAT substrates including the psychostimulant amphetamine (AMPH), which causes hDAT trafficking away from the plasma membrane. The integrity of DAT trafficking directly impacts DA transport capacity and therefore dopaminergic neurotransmission. Here, we show that hDAT A559V is resistant to AMPH-induced cell surface redistribution. This unique trafficking phenotype is conferred by altered protein kinase C β (PKCβ) activity. Cells expressing hDAT A559V exhibit constitutively elevated PKCβ activity, inhibition of which restores the AMPH-induced hDAT A559V membrane redistribution. Mechanistically, we link the inability of hDAT A559V to traffic in response to AMPH to the phosphorylation of the five most distal DAT N-terminal Ser. Mutation of these N-terminal Ser to Ala restores AMPH-induced trafficking. Furthermore, hDAT A559V has a diminished ability to transport AMPH, and therefore lacks AMPH-induced DA efflux. Pharmacological inhibition of PKCβ or Ser to Ala substitution in the hDAT A559V background restores AMPH-induced DA efflux while promoting intracellular AMPH accumulation. Although hDAT A559V is a rare variant, it has been found in multiple probands with neuropsychiatric disorders associated with imbalances in DA neurotransmission, including ADHD, bipolar disorder, and now ASD. These findings provide valuable insight into a new cellular phenotype (altered hDAT trafficking) supporting dysregulated DA function in these disorders. They also provide a novel potential target (PKCβ) for therapeutic interventions in individuals with ASD.

  13. Nonparametric Bayesian clustering to detect bipolar methylated genomic loci.

    PubMed

    Wu, Xiaowei; Sun, Ming-An; Zhu, Hongxiao; Xie, Hehuang

    2015-01-16

    With recent development in sequencing technology, a large number of genome-wide DNA methylation studies have generated massive amounts of bisulfite sequencing data. The analysis of DNA methylation patterns helps researchers understand epigenetic regulatory mechanisms. Highly variable methylation patterns reflect stochastic fluctuations in DNA methylation, whereas well-structured methylation patterns imply deterministic methylation events. Among these methylation patterns, bipolar patterns are important as they may originate from allele-specific methylation (ASM) or cell-specific methylation (CSM). Utilizing nonparametric Bayesian clustering followed by hypothesis testing, we have developed a novel statistical approach to identify bipolar methylated genomic regions in bisulfite sequencing data. Simulation studies demonstrate that the proposed method achieves good performance in terms of specificity and sensitivity. We used the method to analyze data from mouse brain and human blood methylomes. The bipolar methylated segments detected are found highly consistent with the differentially methylated regions identified by using purified cell subsets. Bipolar DNA methylation often indicates epigenetic heterogeneity caused by ASM or CSM. With allele-specific events filtered out or appropriately taken into account, our proposed approach sheds light on the identification of cell-specific genes/pathways under strong epigenetic control in a heterogeneous cell population.

  14. Glial cell-derived neurotrophic factor gene polymorpisms affect severity and functionality of bipolar disorder.

    PubMed

    Safari, Roghaiyeh; Tunca, Zeliha; Özerdem, Ayşegül; Ceylan, Deniz; Yalçın, Yaprak; Sakizli, Meral

    2017-01-01

    Glial cell-derived neurotrophic factor and other neurotrophins have important role in the development of mental disorders. Here, we aimed to assess the effects of Single nucleotide polymorphisms at potentially regulated regions of GDNF on severity and functionality of bipolar disorder and GDNF serum levels in bipolar disorder patients and healthy volunteers. Severity and functionality of bipolar disorder were evaluated using the Clinical Global Impression and Global Assessment of Functioning scales in sixty-six bipolar disorder patients. The GDNF serum levels obtained from bipolar disorder patients and healthy volunteers who had been already reported SNPs information by our group. GAF scales were lower and GDNF serum levels were higher in Bipolar disorder patients with T/A genotype at 5:37812784 and 5:37812782 compared to patients with T/T genotype. There were significant difference in severity and functionality scores, but not in GDNF serum levels, between patients with G/G and G/A genotype of rs62360370 G > A SNP.rs2075680 C > A and rs79669773 T > C SNPs had no effect on bipolar disorder severity and functionality scores and GDNF serum levels. The results suggest that some SNPs of GDNF have potential association with severity and functionality of bipolar disorder. In addition, except two SNPs, none of GDNF SNPs had association with GDNF serum levels.

  15. Design of metallic bipolar plates for PEM fuel cells.

    DOT National Transportation Integrated Search

    2012-01-01

    This project focused on the design and production of metallic bipolar plates for use in PEM fuel cells. Different metals were explored : and stainless steel was found out to be best suited to our purpose. Following the selection of metal, it was calc...

  16. Development of an Anti-Corrosion Conductive Nano Carbon Coating Layer on Metal Bipolar Plates.

    PubMed

    Yeo, Kiho; Kim, Juyong; Kim, Jongryoul

    2018-09-01

    For automotive applications of polymer electrolyte membrane fuel cells, the enhancement of the corrosion resistance of metal bipolar plates has been a critical issue with regard to the lifespan of fuel cell stacks. In this paper, we present a novel method for increasing the lifespan by means of a conductive carbon coating on bipolar plates. Conductive carbon films were plasma coated onto metal bipolar plates in a vacuum at various temperatures. As a result, 316L stainless plates with a 10-nm-thick carbon coating layer on a 20-nm-thick CrN undercoat layer showed-contact resistance of 10.71 mΩcm2@10 kgf/cm2 and a corrosion current of 0.5 μA/cm2@0.6 V. This thin coating layer with high conductivity and excellent corrosion resistance suggests a new, effective coating method for the mass production of metal bipolar plates.

  17. Characterization of Thermal and Mechanical Properties of Polypropylene-Based Composites for Fuel Cell Bipolar Plates and Development of Educational Tools in Hydrogen and Fuel Cell Technologies

    ERIC Educational Resources Information Center

    Lopez Gaxiola, Daniel

    2011-01-01

    In this project we developed conductive thermoplastic resins by adding varying amounts of three different carbon fillers: carbon black (CB), synthetic graphite (SG) and multi-walled carbon nanotubes (CNT) to a polypropylene matrix for application as fuel cell bipolar plates. This component of fuel cells provides mechanical support to the stack,…

  18. Origin and characteristics of high Shannon entropy at the pivot of locally stable rotors: insights from computational simulation.

    PubMed

    Ganesan, Anand N; Kuklik, Pawel; Gharaviri, Ali; Brooks, Anthony; Chapman, Darius; Lau, Dennis H; Roberts-Thomson, Kurt C; Sanders, Prashanthan

    2014-01-01

    Rotors are postulated to maintain cardiac fibrillation. Despite the importance of bipolar electrograms in clinical electrophysiology, few data exist on the properties of bipolar electrograms at rotor sites. The pivot of a spiral wave is characterized by relative uncertainty of wavefront propagation direction compared to the periphery. The bipolar electrograms used in electrophysiology recording encode information on both direction and timing of approaching wavefronts. To test the hypothesis that bipolar electrograms from the pivot of rotors have higher Shannon entropy (ShEn) than electrograms recorded at the periphery due to the spatial dynamics of spiral waves. We studied spiral wave propagation in 2-dimensional sheets constructed using a simple cell automaton (FitzHugh-Nagumo), atrial (Courtemanche-Ramirez-Nattel) and ventricular (Luo-Rudy) myocyte cell models and in a geometric model spiral wave. In each system, bipolar electrogram recordings were simulated, and Shannon entropy maps constructed as a measure of electrogram information content. ShEn was consistently highest in the pivoting region associated with the phase singularity of the spiral wave. This property was consistently preserved across; (i) variation of model system (ii) alterations in bipolar electrode spacing, (iii) alternative bipolar electrode orientation (iv) bipolar electrogram filtering and (v) in the presence of rotor meander. Directional activation plots demonstrated that the origin of high ShEn at the pivot was the directional diversity of wavefront propagation observed in this location. The pivot of the rotor is consistently associated with high Shannon entropy of bipolar electrograms despite differences in action potential model, bipolar electrode spacing, signal filtering and rotor meander. Maximum ShEn is co-located with the pivot for rotors observed in the bipolar electrogram recording mode, and may be an intrinsic property of spiral wave dynamic behaviour.

  19. Mef2d is essential for the maturation and integrity of retinal photoreceptor and bipolar cells.

    PubMed

    Omori, Yoshihiro; Kitamura, Tamiki; Yoshida, Satoyo; Kuwahara, Ryusuke; Chaya, Taro; Irie, Shoichi; Furukawa, Takahisa

    2015-05-01

    Mef2 transcription factors play a crucial role in cardiac and skeletal muscle differentiation. We found that Mef2d is highly expressed in the mouse retina and its loss causes photoreceptor degeneration similar to that observed in human retinitis pigmentosa patients. Electroretinograms (ERGs) were severely impaired in Mef2d-/- mice. Immunohistochemistry showed that photoreceptor and bipolar cell synapse protein levels severely decreased in the Mef2d-/- retina. Expression profiling by microarray analysis showed that Mef2d is required for the expression of various genes in photoreceptor and bipolar cells, including cone arrestin, Guca1b, Pde6h and Cacna1s, which encode outer segment and synapse proteins. We also observed that Mef2d synergistically activates the cone arrestin (Arr3) promoter with Crx, suggesting that functional cooperation between Mef2d and Crx is important for photoreceptor cell gene regulation. Taken together, our results show that Mef2d is essential for photoreceptor and bipolar cell gene expression, either independently or cooperatively with Crx. © 2015 Institution for Protein Research. Genes to Cells published by Wiley Publishing Asia Pty Ltd and the Molecular Biology Society of Japan.

  20. Lateral interactions in the outer retina

    PubMed Central

    Thoreson, Wallace B.; Mangel, Stuart C.

    2012-01-01

    Lateral interactions in the outer retina, particularly negative feedback from horizontal cells to cones and direct feed-forward input from horizontal cells to bipolar cells, play a number of important roles in early visual processing, such as generating center-surround receptive fields that enhance spatial discrimination. These circuits may also contribute to post-receptoral light adaptation and the generation of color opponency. In this review, we examine the contributions of horizontal cell feedback and feed-forward pathways to early visual processing. We begin by reviewing the properties of bipolar cell receptive fields, especially with respect to modulation of the bipolar receptive field surround by the ambient light level and to the contribution of horizontal cells to the surround. We then review evidence for and against three proposed mechanisms for negative feedback from horizontal cells to cones: 1) GABA release by horizontal cells, 2) ephaptic modulation of the cone pedicle membrane potential generated by currents flowing through hemigap junctions in horizontal cell dendrites, and 3) modulation of cone calcium currents (ICa) by changes in synaptic cleft proton levels. We also consider evidence for the presence of direct horizontal cell feed-forward input to bipolar cells and discuss a possible role for GABA at this synapse. We summarize proposed functions of horizontal cell feedback and feed-forward pathways. Finally, we examine the mechanisms and functions of two other forms of lateral interaction in the outer retina: negative feedback from horizontal cells to rods and positive feedback from horizontal cells to cones. PMID:22580106

  1. Case of paraneoplastic retinopathy with retinal ON-bipolar cell dysfunction and subsequent resolution of ERGs.

    PubMed

    Ueno, Shinji; Nakanishi, Ayami; Nishi, Kayo; Suzuki, Shiro; Terasaki, Hiroko

    2015-02-01

    To report a patient with cancer-associated retinopathy and retinal ON-bipolar cell dysfunction who had a resolution of the electroretinograms (ERGs) after a resection of an ovarian cancer and chemotherapy. A 71-year-old Japanese female patient visited us complaining of night blindness and photopsia in both eyes for 6 months. Her visual acuity was 20/20 in both eyes, and fundus examination, fluorescence angiography, and optical coherence tomography showed no abnormalities in both eyes. The rod responses of the ERGs were absent and bright-flash ERGs were electronegative. The ON responses of the focal macular ERGs and full-field long-flash ERGs were absent. These ERG findings indicate an ON-bipolar cell dysfunction. A general physical examination revealed the presence of ovarian cancer. After resection of the ovarian cancer and adjuvant chemotherapy, the ERGs of the left eye completely recovered within 2 years and those of right eye recovered subsequently. The autoantibody against transient receptor potential melastatin 1 (TRPM1) was not detected in the serum. Our case demonstrates that retinal ON-bipolar dysfunction can be caused by ovarian cancer. Our case indicates that some autoantibodies against other than TRPM1 might cause transient dysfunction of retinal ON-bipolar cells.

  2. A Novel Terminal Web-Like Structure in Cortical Lens Fibers: Architecture and Functional Assessment

    PubMed Central

    Al-Ghoul, Kristin J.; Lindquist, Timothy P.; Kirk, Spencer S.; Donohue, Sean T.

    2010-01-01

    This study describes a novel cytoskeletal array in fiber cells of the ocular lens of the rat and shows its relationship to the classical terminal web of other epithelial tissues. Naive adult Sprague-Dawley rats (n=28) were utilized. F-actin, fodrin, myosin IIA and CP49 distribution was assessed in anterior and posterior polar sections. For functional analysis, lenses were cultured with or without cytochalasin-D for 3 hours, then processed for confocal microscopy or assessed by laser scan analysis along sutures. Phalloidin labeling demonstrated a dense mesh of F-actin adjacent to posterior sutural domains to a subcapsular depth of 400 μm. Anterior polar sections revealed a comparable actin structure adjacent to anterior suture branches however, it was not developed in superficial fibers. Fodrin and myosin were localized within the web-like actin apparatus. The data was used to construct a model showing that the cytoskeletal array is located within the blunt, variable-width fiber ends that abut at sutures such that the ‘terminal web’ flanks the suture on either side. Treatment with cytochalasin-D resulted in partial disassembly of the ‘terminal web’ and perturbed cellular organization. Laser scan analysis revealed that cytochalasin-D treated lenses had significantly greater focal variability than control lenses (p=0.020). We conclude that cortical fibers of rat lenses contain a bipolar structure that is structurally and compositionally analogous to classical terminal webs. The results indicate that the lens ‘terminal web’ functions to stabilize lens fiber ends at sutures thus minimizing structural disorder, which in turn, promotes the establishment and maintenance of lens transparency. PMID:20730867

  3. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Sprague, E.R.; Wang, C.; Baker, D.

    Herpes simplex virus type-1 expresses a heterodimeric Fc receptor, gE-gI, on the surfaces of virions and infected cells that binds the Fc region of host immunoglobulin G and is implicated in the cell-to-cell spread of virus. gE-gI binds immunoglobulin G at the basic pH of the cell surface and releases it at the acidic pH of lysosomes, consistent with a role in facilitating the degradation of antiviral antibodies. Here we identify the C-terminal domain of the gE ectodomain (CgE) as the minimal Fc-binding domain and present a 1.78-{angstrom} CgE structure. A 5-{angstrom} gE-gI/Fc crystal structure, which was independently verified bymore » a theoretical prediction method, reveals that CgE binds Fc at the C{sub H}2-C{sub H}3 interface, the binding site for several mammalian and bacterial Fc-binding proteins. The structure identifies interface histidines that may confer pH-dependent binding and regions of CgE implicated in cell-to-cell spread of virus. The ternary organization of the gE-gI/Fc complex is compatible with antibody bipolar bridging, which can interfere with the antiviral immune response.« less

  4. The projective field of a retinal amacrine cell

    PubMed Central

    de Vries, Saskia E. J.; Baccus, Stephen A.; Meister, Markus

    2011-01-01

    In sensory systems, neurons are generally characterized by their receptive field, namely the sensitivity to activity patterns at the circuit's input. To assess the neuron's role in the system, one must also know its projective field, namely the spatio-temporal effects the neuron exerts on all the circuit's outputs. We studied both the receptive and projective fields of an amacrine interneuron in the salamander retina. This amacrine type has a sustained OFF response with a small receptive field, but its output projects over a much larger region. Unlike other amacrines, this type is remarkably promiscuous and affects nearly every ganglion cell within reach of its dendrites. Its activity modulates the sensitivity of visual responses in ganglion cells, while leaving their kinetics unchanged. The projective field displays a center-surround structure: Depolarizing a single amacrine suppresses the visual sensitivity of ganglion cells nearby, and enhances it at greater distances. This change in sign is seen even within the receptive field of one ganglion cell; thus the modulation occurs presynaptically on bipolar cell terminals, most likely via GABAB receptors. Such an antagonistic projective field could contribute to the retina's mechanisms for predictive coding. PMID:21653863

  5. Early postnatal development of vasoactive intestinal polypeptide- and peptide histidine isoleucine-immunoreactive structures in the cat visual cortex.

    PubMed

    Wahle, P; Meyer, G

    1989-04-08

    The early postnatal development of neurons containing vasoactive intestinal polypeptide (VIP) and peptide histidine isoleucine (PHI) has been analyzed in visual areas 17 and 18 of cats aged from postnatal day (P) 0 to adulthood. Neuronal types are established mainly by axonal criteria. Both peptides occur in the same neuronal types and display the same postnatal chronology of appearance. Several cell types are transient, which means that they are present in the cortex only for a limited period of development. According to their chronology of appearance the VIP/PHI-immunoreactive (ir) cell types are grouped into three neuronal populations. The first population comprises six cell types which appear early in postnatal life. The pseudohorsetail cells of layer I possess a vertically descending axon which initially gives rise to recurrent collaterals, then forms a bundle passing layers III to V, and finally, horizontal terminal fibers in layer VI. The neurons differentiate at P 4 and disappear by degeneration around P 30. The neurons with columnar dendritic fields of layers IV/V are characterized by a vertical arrangement of long dendrites ascending or descending parallel to each other, thus forming an up to 600 microns long dendritic column. Their axons always descend and terminate in broad fields in layer VI. The neurons appear at P 7 and are present until P 20. The multipolar neurons of layer VI occur in isolated positions and have broad axonal territories. The neurons differentiate at P 7 and persist into adulthood. Bitufted to multipolar neurons of layers II/III have axons descending as a single fiber to layer VI, where they terminate. The neurons appear at P 12 and persist into adulthood. The four cell types described above issue a vertically oriented fiber architecture in layers II-V and a horizontal terminal plexus in layer VI which is dense during the second, third and fourth week. Concurrent with the disappearance of the two transient types the number of descending axonal bundles and the density of the layer VI plexus is reduced, but the latter is maintained during adulthood by the two persisting cell types. Two further cell types belong to the first population: The transient bipolar cells of layers IV, V, and VI have long dendrites which extend through the entire cortical width. Their axons always descend, leave the gray matter, and apparently terminate in the upper white matter. The neurons differentiate concurrently with the pseudohorsetail cells at P 4, are very frequent during the following weeks, and eventually disappear at P 30.(ABSTRACT TRUNCATED AT 400 WORDS)

  6. 2017 Bipolar Plate Workshop Summary Report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Kopasz, John P.; Benjamin, Thomas G.; Schenck, Deanna

    The Bipolar Plate (BP) Workshop was held at USCAR1 in Southfield, Michigan on February 14, 2017 and included 63 participants from industry, government agencies, universities, and national laboratories with expertise in the relevant fields. The objective of the workshop was to identify research and development (R&D) needs, in particular early-stage R&D, for bipolar plates for polymer electrolyte membrane (PEM) fuel cells for transportation applications. The focus of the workshop was on materials, manufacturing, and design aspects of bipolar plates with the goal of meeting DOE’s 2020 bipolar plate targets. Of special interest was the cost target of ≤$3/kW for themore » bipolar plate.« less

  7. Reduced Neurite Density in Neuronal Cell Cultures Exposed to Serum of Patients with Bipolar Disorder

    PubMed Central

    Wollenhaupt-Aguiar, Bianca; Pfaffenseller, Bianca; Chagas, Vinicius de Saraiva; Castro, Mauro A A; Passos, Ives Cavalcante; Kauer-Sant’Anna, Márcia; Kapczinski, Flavio

    2016-01-01

    Background: Increased inflammatory markers and oxidative stress have been reported in serum among patients with bipolar disorder (BD). The aim of this study is to assess whether biochemical changes in the serum of patients induces neurotoxicity in neuronal cell cultures. Methods: We challenged the retinoic acid-differentiated human neuroblastoma SH-SY5Y cells with the serum of BD patients at early and late stages of illness and assessed neurite density and cell viability as neurotoxic endpoints. Results: Decreased neurite density was found in neurons treated with the serum of patients, mostly patients at late stages of illness. Also, neurons challenged with the serum of late-stage patients showed a significant decrease in cell viability. Conclusions: Our findings showed that the serum of patients with bipolar disorder induced a decrease in neurite density and cell viability in neuronal cultures. PMID:27207915

  8. Recent Advances in Insect Olfaction, Specifically Regarding the Morphology and Sensory Physiology of Antennal Sensilla of the Female Sphinx Moth Manduca sexta

    PubMed Central

    SHIELDS, VONNIE D.C.; HILDEBRAND, JOHN G.

    2008-01-01

    The antennal flagellum of female Manduca sexta bears eight sensillum types: two trichoid, two basiconic, one auriculate, two coeloconic, and one styliform complex sensilla. The first type of trichoid sensillum averages 34 μm in length and is innervated by two sensory cells. The second type averages 26 μm in length and is innervated by either one or three sensory cells. The first type of basiconic sensillum averages 22 μm in length, while the second type averages 15 μm in length. Both types are innervated by three bipolar sensory cells. The auriculate sensillum averages 4 μm in length and is innervated by two bipolar sensory cells. The coeloconic type-A and type-B both average 2 μm in length. The former type is innervated by five bipolar sensory cells, while the latter type, by three bipolar sensory cells. The styliform complex sensillum occurs singly on each annulus and averages 38-40 μm in length. It is formed by several contiguous sensilla. Each unit is innervated by three bipolar sensory cells. A total of 2,216 sensilla were found on a single annulus (annulus 21) of the flagellum. Electrophysiological responses from type-A trichoid sensilla to a large panel of volatile odorants revealed three different subsets of olfactory receptor cells (ORCs). Two subsets responded strongly to only a narrow range of odorants, while the third responded strongly to a broad range of odorants. Anterograde labeling of ORCs from type-A trichoid sensilla revealed that their axons projected mainly to two large female glomeruli of the antennal lobe. PMID:11754510

  9. Stem cell-derived neurons in the development of targeted treatment for schizophrenia and bipolar disorder.

    PubMed

    Watmuff, Bradley; Liu, Bangyan; Karmacharya, Rakesh

    2017-04-01

    The recent advent of induced pluripotent stem cells has enabled the study of patient-specific and disease-related neurons in vitro and has facilitated new directions of inquiry into disease mechanisms. With these approaches, we now have the possibility of correlating ex vivo cellular phenotypes with individual patient response to treatment and/or side effects, which makes targeted treatments for schizophrenia and bipolar disorder a distinct prospect in the coming years. Here, we briefly review the current state of stem cell-based models and explore studies that are providing new insights into the disease biology of schizophrenia and bipolar disorder, which are laying the foundations for the development of novel targeted therapies.

  10. Formation and disruption of current paths of anodic porous alumina films by conducting atomic force microscopy

    NASA Astrophysics Data System (ADS)

    Oyoshi, K.; Nigo, S.; Inoue, J.; Sakai, O.; Kitazawa, H.; Kido, G.

    2010-11-01

    Anodic porous alumina (APA) films have a honeycomb cell structure of pores and a voltage-induced bi-stable switching effect. We have applied conducting atomic force microscopy (CAFM) as a method to form and to disrupt current paths in the APA films. A bi-polar switching operation was confirmed. We have firstly observed terminals of current paths as spots or areas typically on the center of the triangle formed by three pores. In addition, though a part of the current path showed repetitive switching, most of them were not observed again at the same position after one cycle of switching operations in the present experiments. This suggests that a part of alumina structure and/or composition along the current paths is modified during the switching operations.

  11. Homeostatic plasticity shapes cell-type-specific wiring in the retina

    PubMed Central

    Tien, Nai-Wen; Soto, Florentina; Kerschensteiner, Daniel

    2017-01-01

    SUMMARY Convergent input from different presynaptic partners shapes the responses of postsynaptic neurons. Whether developing postsynaptic neurons establish connections with each presynaptic partner independently, or balance inputs to attain specific responses is unclear. Retinal ganglion cells (RGCs) receive convergent input from bipolar cell types with different contrast responses and temporal tuning. Here, using optogenetic activation and pharmacogenetic silencing, we found that type 6 bipolar cells (B6) dominate excitatory input to ONα-RGCs. We generated mice in which B6 cells were selectively removed from developing circuits (B6-DTA). In B6-DTA mice, ONα-RGCs adjusted connectivity with other bipolar cells in a cell-type-specific manner. They recruited new partners, increased synapses with some existing partners, and maintained constant input from others. Patch clamp recordings revealed that anatomical rewiring precisely preserved contrast- and temporal frequency response functions of ONα-RGCs, indicating that homeostatic plasticity shapes cell-type-specific wiring in the developing retina to stabilize visual information sent to the brain. PMID:28457596

  12. Ankyrin-G isoform imbalance and interneuronopathy link epilepsy and bipolar disorder.

    PubMed

    Lopez, A Y; Wang, X; Xu, M; Maheshwari, A; Curry, D; Lam, S; Adesina, A M; Noebels, J L; Sun, Q-Q; Cooper, E C

    2017-10-01

    ANK3, encoding the adaptor protein Ankyrin-G (AnkG), has been implicated in bipolar disorder by genome-wide association studies. ANK3 has multiple alternative first exons, and a bipolar disorder-associated ANK3 variant has been shown to reduce the expression of exon 1b. Here we identify mechanisms through which reduced ANK3 exon 1b isoform expression disrupts neuronal excitation-inhibition balance. We find that parvalbumin (PV) interneurons and principal cells differentially express ANK3 first exon subtypes. PV interneurons express only isoforms containing exon 1b, whereas excitatory principal cells express exon 1e alone or both 1e and 1b. In transgenic mice deficient for exon 1b, PV interneurons lack voltage-gated sodium channels at their axonal initial segments and have increased firing thresholds and diminished action potential dynamic range. These mice exhibit an Ank3 gene dosage-dependent phenotype including behavior changes modeling bipolar disorder, epilepsy and sudden death. Thus ANK3's important association with human bipolar susceptibility may arise from imbalance between AnkG function in interneurons and principal cells and resultant excessive circuit sensitivity and output. AnkG isoform imbalance is a novel molecular endophenotype and potential therapeutic target.

  13. Preliminary design of 1 kW bipolar Ni-MH battery for LEO-satellite application

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Cole, J.H.; Reisner, D.E.; Klein, M.G.

    1996-12-31

    Electro Energy, Inc. (EEI) is developing a bipolar nickel-metal hydride rechargeable battery based upon the use of stackable wafer cells. The key to viable bipolar operation has been this unique modular (unitized) approach. The patented unit wafer-cell construct exploits the chemical and thermal properties of a proprietary electrically conductive plastic film. Characteristic of bipolar batteries, current flows across the cell interfaces-perpendicular to the electrode plane. EEI has recently contracted with NASA Lewis Research Center (LeRC) to develop an optimized design 1 kW flightweight battery, for low-earth-orbit (LEO) satellite applications, over a 4-year period with a deliverable flightweight design package. Themore » contract includes an option for EEI to deliver up to three flight quality batteries in an 18-month follow-on program. NASA LeRC has promulgated that the program steps include the design, fabrication, and evaluation of four evolutionary stages of the final battery design which have been designated Preliminary, Improved, Optimized, and Flightweight Design. Initial results from the Preliminary Stage are presented including a 1 kW battery design, thermal design, parameter study, and component development in subscale bipolar batteries.« less

  14. Ankyrin-G isoform imbalance and interneuronopathy link epilepsy and bipolar disorder

    PubMed Central

    Lopez, Angel Y.; Wang, Xinjun; Xu, Mingxuan; Maheshwari, Atul; Curry, Daniel; Lam, Sandi; Adesina, Adekunle M.; Noebels, Jeffrey L.; Sun, Qian-Quan; Cooper, Edward C.

    2016-01-01

    ANK3, encoding the adaptor protein Ankyrin-G, has been implicated in bipolar disorder by genome wide association studies. ANK3 has multiple alternative first exons, and a bipolar disorder-associated ANK3 variant has been shown to reduce expression of exon 1b. Here we identify mechanisms through which reduced ANK3 exon 1b isoform expression disrupts neuronal excitation-inhibition balance. We find that parvalbumin interneurons and principal cells differentially express ANK3 first exon subtypes. Parvalbumin interneurons express only isoforms containing exon 1b, whereas excitatory principal cells express exon 1e alone, or both 1e and 1b. In transgenic mice deficient for exon 1b, parvalbumin interneurons lack voltage-gated sodium channels at their axonal initial segments and have increased firing thresholds and diminished action potential dynamic range. These mice exhibit an Ank3 gene dosage-dependent phenotype including behavior changes modeling bipolar disorder, epilepsy, and sudden death. Thus, ANK3’s important association with human bipolar susceptibility may arise from imbalance between ankyrin-G function in interneurons and principal cells and resultant excessive circuit sensitivity and output. Ankyrin-G isoform imbalance is a novel molecular endophenotype and potential therapeutic target. PMID:27956739

  15. Differential responses to lithium in hyperexcitable neurons from patients with bipolar disorder.

    PubMed

    Mertens, Jerome; Wang, Qiu-Wen; Kim, Yongsung; Yu, Diana X; Pham, Son; Yang, Bo; Zheng, Yi; Diffenderfer, Kenneth E; Zhang, Jian; Soltani, Sheila; Eames, Tameji; Schafer, Simon T; Boyer, Leah; Marchetto, Maria C; Nurnberger, John I; Calabrese, Joseph R; Ødegaard, Ketil J; McCarthy, Michael J; Zandi, Peter P; Alda, Martin; Alba, Martin; Nievergelt, Caroline M; Mi, Shuangli; Brennand, Kristen J; Kelsoe, John R; Gage, Fred H; Yao, Jun

    2015-11-05

    Bipolar disorder is a complex neuropsychiatric disorder that is characterized by intermittent episodes of mania and depression; without treatment, 15% of patients commit suicide. Hence, it has been ranked by the World Health Organization as a top disorder of morbidity and lost productivity. Previous neuropathological studies have revealed a series of alterations in the brains of patients with bipolar disorder or animal models, such as reduced glial cell number in the prefrontal cortex of patients, upregulated activities of the protein kinase A and C pathways and changes in neurotransmission. However, the roles and causation of these changes in bipolar disorder have been too complex to exactly determine the pathology of the disease. Furthermore, although some patients show remarkable improvement with lithium treatment for yet unknown reasons, others are refractory to lithium treatment. Therefore, developing an accurate and powerful biological model for bipolar disorder has been a challenge. The introduction of induced pluripotent stem-cell (iPSC) technology has provided a new approach. Here we have developed an iPSC model for human bipolar disorder and investigated the cellular phenotypes of hippocampal dentate gyrus-like neurons derived from iPSCs of patients with bipolar disorder. Guided by RNA sequencing expression profiling, we have detected mitochondrial abnormalities in young neurons from patients with bipolar disorder by using mitochondrial assays; in addition, using both patch-clamp recording and somatic Ca(2+) imaging, we have observed hyperactive action-potential firing. This hyperexcitability phenotype of young neurons in bipolar disorder was selectively reversed by lithium treatment only in neurons derived from patients who also responded to lithium treatment. Therefore, hyperexcitability is one early endophenotype of bipolar disorder, and our model of iPSCs in this disease might be useful in developing new therapies and drugs aimed at its clinical treatment.

  16. Robust syntaxin-4 immunoreactivity in mammalian horizontal cell processes

    PubMed Central

    HIRANO, ARLENE A.; BRANDSTÄTTER, JOHANN HELMUT; VILA, ALEJANDRO; BRECHA, NICHOLAS C.

    2009-01-01

    Horizontal cells mediate inhibitory feed-forward and feedback communication in the outer retina; however, mechanisms that underlie transmitter release from mammalian horizontal cells are poorly understood. Toward determining whether the molecular machinery for exocytosis is present in horizontal cells, we investigated the localization of syntaxin-4, a SNARE protein involved in targeting vesicles to the plasma membrane, in mouse, rat, and rabbit retinae using immunocytochemistry. We report robust expression of syntaxin-4 in the outer plexiform layer of all three species. Syntaxin-4 occurred in processes and tips of horizontal cells, with regularly spaced, thicker sandwich-like structures along the processes. Double labeling with syntaxin-4 and calbindin antibodies, a horizontal cell marker, demonstrated syntaxin-4 localization to horizontal cell processes; whereas, double labeling with PKC antibodies, a rod bipolar cell (RBC) marker, showed a lack of co-localization, with syntaxin-4 immunolabeling occurring just distal to RBC dendritic tips. Syntaxin-4 immunolabeling occurred within VGLUT-1-immunoreactive photoreceptor terminals and underneath synaptic ribbons, labeled by CtBP2/RIBEYE antibodies, consistent with localization in invaginating horizontal cell tips at photoreceptor triad synapses. Vertical sections of retina immunostained for syntaxin-4 and peanut agglutinin (PNA) established that the prominent patches of syntaxin-4 immunoreactivity were adjacent to the base of cone pedicles. Horizontal sections through the OPL indicate a one-to-one co-localization of syntaxin-4 densities at likely all cone pedicles, with syntaxin-4 immunoreactivity interdigitating with PNA labeling. Pre-embedding immuno-electron microscopy confirmed the subcellular localization of syntaxin-4 labeling to lateral elements at both rod and cone triad synapses. Finally, co-localization with SNAP-25, a possible binding partner of syntaxin-4, indicated co-expression of these SNARE proteins in the same subcellular compartment of the horizontal cell. Taken together, the strong expression of these two SNARE proteins in the processes and endings of horizontal cells at rod and cone terminals suggests that horizontal cell axons and dendrites are likely sites of exocytotic activity. PMID:17640443

  17. Design concepts of high power bipolar rechargeable lithium battery

    NASA Technical Reports Server (NTRS)

    Shen, David H.; Halpert, Gerald

    1993-01-01

    The present study shows that current bipolar Li/TiS2 batteries using a 0.38 mm thick TiS2 bipolar plate can yield moderate specific power and also high specific energy battery. The computer design studies project that a 100 V, 10 A h bipolar Li/TiS2 battery can achieve 150 W h/kg, 210 W h/l, and 150 W/kg. The unoptimized experimental bipolar Li/TiS2 batteries (3 cells, 90 mA h) exhibited 47 W h/kg, 90 W h/l, and 140 W/kg. Preliminary results on the cycleability of the bipolar batteries are demonstrated. The results also show that enhanced rate capability can be achieved by using pulse discharge and longer rest period between pulses.

  18. Manufacturing and Performance Assessment of Stamped, Laser Welded, and Nitrided FeCrV Stainless Steel Bipolar Plates for Proton Exchange Membrane Fuel Cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Brady, Michael P; Abdelhamid, Mahmoud; Dadheech, G

    A manufacturing and single-cell fuel cell performance study of stamped, laser welded, and gas nitrided ferritic stainless steel foils in an advanced automotive bipolar plate assembly design was performed. Two developmental foil compositions were studied: Fee20Cre4V and Fee23Cre4V wt.%. Foils 0.1 mm thick were stamped and then laser welded together to create single bipolar plate assemblies with cooling channels. The plates were then surface treated by pre-oxidation and nitridation in N2e4H2 based gas mixtures using either a conventional furnace or a short-cycle quartz lamp infrared heating system. Single-cell fuel cell testing was performed at 80 C for 500 h atmore » 0.3 A/cm2 using 100% humidification and a 100%/40% humidification cycle that stresses the membrane and enhances release of the fluoride ion and promotes a more corrosive environment for the bipolar plates. Periodic high frequency resistance potential-current scans during the 500 h fuel cell test and posttest analysis of the membrane indicated no resistance increase of the plates and only trace levels of metal ion contamination.« less

  19. Types of neural cells in the spinal ganglia of human embryos and early fetuses.

    PubMed

    Olszewska, B; Woźniak, W; Gardner, E; O'Rahilly, R

    1979-01-01

    Spinal ganglial of human embryos and fetuses ranging in C.-R. length from 15 to 74 mm and in age from 6 1/2 to 11 postovulatory weeks were studied by light and electron microscopy. A sequence of events in differentiation and maturation enabled five types of cells to be distinguished: 1. apolar, undifferentiated neuroblasts are the main cells at 6 1/2 to 7 1/2 weeks; 2. early bipolar neuroblasts (strictly speaking, types 2 to 5 are immature neurons) predominate at the end of the embryonic period proper (8 postovulatory weeks); 3. intermediate bipolar neuroblasts are characteristic of the early fetal period; 4. late bipolar neuroblasts, in which two proceses arise separately from one pole of the cell, appear at about 10 postovulatory weeks; 5. unipolar neuroblasts are found within another week and, by that time, cells of types 1 and 2 are no longer present.

  20. Center/surround organization of retinal bipolar cells: High correlation of fundamental responses of center and surround to sinusoidal contrasts

    PubMed Central

    Burkhardt, Dwight A.; Bartoletti, Theodore M.; Thoreson, Wallace B.

    2012-01-01

    Receptive field organization of cone-driven bipolar cells was investigated by intracellular recording in the intact light-adapted retina of the tiger salamander (Ambystoma tigrinum). Centered spots and concentric annuli of optimum dimensions were used to selectively stimulate the receptive field center and surround with sinusoidal modulations of contrast at 3 Hz. At low contrasts, responses of both the center and surround of both ON and OFF bipolar cells were linear, showing high gain and thus contrast enhancement relative to cones. The contrast/response curves for the fundamental response, measured by a Fast Fourier Transform, reached half maximum amplitude quickly at 13% contrast followed by saturation at high contrasts. The variation of the normalized amplitude of the center and surround responses was remarkably similar, showing linear regression over the entire response range with very high correlations, r2 = 0.97 for both ON and OFF cells. The contrast/response curves of both center and surround for both ON and OFF cells were well fit (r2 = 0.98) by an equation for single-site binding. In about half the cells studied, the nonlinear waveforms of center and surround could be brought into coincidence by scaling and shifting the surround response in time. This implies that a nonlinearity, common to both center and surround, occurs after polarity inversion at the cone feedback synapse. Evidence from paired whole-cell recordings between single cones and OFF bipolar cells suggests that substantial nonlinearity is not due to transmission at the cone synapse but instead arises from intrinsic bipolar cell and network mechanisms. When sinusoidal contrast modulations were applied to the center and surround simultaneously, clear additivity was observed for small responses in both ON and OFF cells, whereas the interaction was strikingly nonadditive for large responses. The contribution of the surround was then greatly reduced, suggesting attenuation at the cone feedback synapse. PMID:21439110

  1. Origin and Characteristics of High Shannon Entropy at the Pivot of Locally Stable Rotors: Insights from Computational Simulation

    PubMed Central

    Gharaviri, Ali; Brooks, Anthony; Chapman, Darius; Lau, Dennis H.; Roberts-Thomson, Kurt C.; Sanders, Prashanthan

    2014-01-01

    Background Rotors are postulated to maintain cardiac fibrillation. Despite the importance of bipolar electrograms in clinical electrophysiology, few data exist on the properties of bipolar electrograms at rotor sites. The pivot of a spiral wave is characterized by relative uncertainty of wavefront propagation direction compared to the periphery. The bipolar electrograms used in electrophysiology recording encode information on both direction and timing of approaching wavefronts. Objective To test the hypothesis that bipolar electrograms from the pivot of rotors have higher Shannon entropy (ShEn) than electrograms recorded at the periphery due to the spatial dynamics of spiral waves. Methods and Results We studied spiral wave propagation in 2-dimensional sheets constructed using a simple cell automaton (FitzHugh-Nagumo), atrial (Courtemanche-Ramirez-Nattel) and ventricular (Luo-Rudy) myocyte cell models and in a geometric model spiral wave. In each system, bipolar electrogram recordings were simulated, and Shannon entropy maps constructed as a measure of electrogram information content. ShEn was consistently highest in the pivoting region associated with the phase singularity of the spiral wave. This property was consistently preserved across; (i) variation of model system (ii) alterations in bipolar electrode spacing, (iii) alternative bipolar electrode orientation (iv) bipolar electrogram filtering and (v) in the presence of rotor meander. Directional activation plots demonstrated that the origin of high ShEn at the pivot was the directional diversity of wavefront propagation observed in this location. Conclusions The pivot of the rotor is consistently associated with high Shannon entropy of bipolar electrograms despite differences in action potential model, bipolar electrode spacing, signal filtering and rotor meander. Maximum ShEn is co-located with the pivot for rotors observed in the bipolar electrogram recording mode, and may be an intrinsic property of spiral wave dynamic behaviour. PMID:25401331

  2. Theoretical and experimental characterization of the DUal-BAse transistor (DUBAT)

    NASA Astrophysics Data System (ADS)

    Wu, Chung-Yu; Wu, Ching-Yuan

    1980-11-01

    A new A-type integrated voltage controlled differential negative resistance device using an extra effective base region to form a lateral pnp (npn) bipolar transistor beside the original base region of a vertical npn (pnp) bipolar junction transistor, and so called the DUal BAse Transistor (DUBAT), is studied both experimentally and theoretically, The DUBAT has three terminals and is fully comparible with the existing bipolar integrated circuits technologies. Based upon the equivalent circuit of the DUBAT, a simple first-order analytical theory is developed, and important device parameters, such as: the I-V characteristic, the differential negative resistance, and the peak and valley points, are also characterized. One of the proposed integrated structures of the DUBAT, which is similar in structure to I 2L but with similar high density and a normally operated vertical npn transistor, has been successfully fabricated and studied. Comparisons between the experimental data and theoretical analyses are made, and show in satisfactory agreements.

  3. Deficiency in chromosome congression by the inhibition of Plk1 polo box domain-dependent recognition.

    PubMed

    Watanabe, Nobumoto; Sekine, Tomomi; Takagi, Masatoshi; Iwasaki, Jun-ichi; Imamoto, Naoko; Kawasaki, Hisashi; Osada, Hiroyuki

    2009-01-23

    Polo-like kinase 1 (Plk1) is one of the key regulators of mitotic cell division. In addition to an N-terminal protein kinase catalytic domain, Plk1 possesses a phosphopeptide binding domain named polo box domain (PBD) at its C terminus. PBD is postulated to be essential for Plk1 localization and substrate targeting. Here, we developed a high-throughput screening system to identify inhibitors of PBD-dependent binding and screened a chemical library. We isolated a benzotropolone-containing natural compound derived from nutgalls (purpurogallin (PPG)) that inhibited PBD-dependent binding in vitro and in vivo. PPG not only delayed the onset of mitosis but also prolonged the progression of mitosis in HeLa cells. Although apparently normal bipolar spindles were formed even in the presence of PPG, the perturbation of chromosome alignment at metaphase plates activated the spindle assembly checkpoint pathway. These results demonstrate the predominant role of PBD-dependent binding on smooth chromosome congression at metaphase.

  4. Nutritional and Safety Outcomes from an Open-Label Micronutrient Intervention for Pediatric Bipolar Spectrum Disorders

    PubMed Central

    Gracious, Barbara; Arnold, L. Eugene; Failla, Mark; Chitchumroonchokchai, Chureeporn; Habash, Diane; Fristad, Mary A.

    2013-01-01

    Abstract Objective The purpose of this study was to report the safety, tolerability, and serum micronutrient concentrations and their correlations with mood changes from an 8 week pilot feasibility study of a 36 ingredient multinutrient supplement, EMPowerplus (EMP+), for pediatric bipolar spectrum disorders (BPSD). Methods Ten children ages 6–12 received EMP+ escalating from one to four capsules t.i.d., with four children increased to the maximum suggested dose, five capsules t.i.d. Outcome measures were micronutrient concentrations in serum and red blood cells, vital signs, body mass index (BMI), dietary intake (Food Frequency Questionnaire and 24 hour dietary recall interview), and mood and global functioning ratings. Results Seven children (70%) completed the study. Three (30%) terminated early for tolerability and compliance issues. Adverse effects were mild and transient, and chiefly consisted of initial insomnia or gastrointestinal (GI) upset. No differences occurred in BMI (p=0.310) or waist–hip ratio (WHR; p=0.674) pre- to postsupplementation. Four of the tested serum vitamin concentrations increased from pre- to postsupplementation: vitamin A-retinol, vitamin B6, vitamin E-α-tocopherol; and folate (all p<0.05). The increase in serum 25-OH vitamin D approached significance (p=0.063). No differences were found in dietary intake pre- to postsupplementation, suggesting that blood nutrient level increases were caused by EMP+. Conclusions In this open prospective study, short-term use of EMP+ in children with BPSD appeared safe and well-tolerated, with a side effect profile preferable to first-line psychotropic drugs for pediatric bipolar spectrum disorders. A double-blind, randomized clinical trial is feasible, appears safe, and is warranted by open-label clinical outcomes and plausible mechanisms of action, combined with documentation of increased serum concentrations of specific micronutrients. PMID:24138009

  5. Toluene Inhalation Exposure for 13 Weeks Causes Persistent Changes in Electroretinograms of Long-Evans Rats

    PubMed Central

    Boyes, William K.; Bercegeay, Mark; Degn, Laura; Beasley, Tracey E.; Evansky, Paul A.; Mwanza, Jean Claude; Geller, Andrew M.; Pinckney, Charles; Nork, T. Michael; Bushnell, Philip J.

    2016-01-01

    Studies of humans chronically exposed to volatile organic solvents have reported impaired visual functions, including low contrast sensitivity and reduced color discrimination. These reports, however, lacked confirmation from controlled laboratory experiments. To address this question experimentally, we examined visual function by recording visual evoked potentials (VEP) and/or electroretinograms (ERG) from four sets of rats exposed repeatedly to toluene. In addition, eyes of the rats were examined with an ophthalmoscope and some of the retinal tissues were evaluated for rod and M-cone photoreceptor immunohistochemistry. The first study examined rats following exposure to 0, 10, 100 or 1000 ppm toluene by inhalation (6 hr/d, 5 d/wk) for 13 weeks. One week after the termination of exposure, the rats were implanted with chronically indwelling electrodes and the following week pattern-elicited VEPs were recorded. VEP amplitudes were not significantly changed by toluene exposure. Four to five weeks after completion of exposure, rats were dark-adapted overnight, anesthetized, and several sets of electroretinograms (ERG) were recorded. In dark-adapted ERGs recorded over a 5-log (cd-s/m2) range of flash luminance, b-wave amplitudes were significantly reduced at high stimulus luminance values in rats previously exposed to 1000 ppm toluene. A second set of rats, exposed concurrently with the first set, was tested approximately one year after the termination of 13 weeks of exposure to toluene. Again, dark-adapted ERG b-wave amplitudes were reduced at high stimulus luminance values in rats previously exposed to 1000 ppm toluene. A third set of rats was exposed to the same concentrations of toluene for only 4 weeks, and a fourth set of rats exposed to 0 or 1000 ppm toluene for 4 weeks were tested approximately 1 year after the completion of exposure. No statistically significant reductions of ERG b-wave amplitude were observed in either set of rats exposed for 4 weeks. No significant changes were observed in ERG a-wave amplitude or latency, b-wave latency, UV- or green-flicker ERGs, or in photopic flash ERGs. There were no changes in the density of rod or M-cone photoreceptors. The ERG b-wave reflects the firing patterns of on-bipolar cells. The reductions of b-wave amplitude after 13 weeks of exposure and persisting for 1 year suggest that alterations may have occurred in the inner nuclear layer of the retina, where the bipolar cells reside, or the outer or inner plexiform layers where the bipolar cells make synaptic connections. These data provide experimental evidence that repeated exposure to toluene may lead to subtle persistent changes in visual function. The fact that toluene affected ERGs, but not VEPs, suggests that elements in the rat retina may be more sensitive to organic solvent exposure than the rat visual cortex. PMID:26899397

  6. Bio-inspired color image enhancement model

    NASA Astrophysics Data System (ADS)

    Zheng, Yufeng

    2009-05-01

    Human being can perceive natural scenes very well under various illumination conditions. Partial reasons are due to the contrast enhancement of center/surround networks and opponent analysis on the human retina. In this paper, we propose an image enhancement model to simulate the color processes in the human retina. Specifically, there are two center/surround layers, bipolar/horizontal and ganglion/amacrine; and four color opponents, red (R), green (G), blue (B), and yellow (Y). The central cell (bipolar or ganglion) takes the surrounding information from one or several horizontal or amacrine cells; and bipolar and ganglion both have ON and OFF sub-types. For example, a +R/-G bipolar (red-center- ON/green-surround-OFF) will be excited if only the center is illuminated, or inhibited if only the surroundings (bipolars) are illuminated, or stay neutral if both center and surroundings are illuminated. Likewise, other two color opponents with ON-center/OFF-surround, +G/-R and +B/-Y, follow the same rules. The yellow (Y) channel can be obtained by averaging red and green channels. On the other hand, OFF-center/ON-surround bipolars (i.e., -R/+G and -G/+R, but no - B/+Y) are inhibited when the center is illuminated. An ON-bipolar (or OFF-bipolar) only transfers signals to an ONganglion (or OFF-ganglion), where amacrines provide surrounding information. Ganglion cells have strong spatiotemporal responses to moving objects. In our proposed enhancement model, the surrounding information is obtained using weighted average of neighborhood; excited or inhibited can be implemented with pixel intensity increase or decrease according to a linear or nonlinear response; and center/surround excitations are decided by comparing their intensities. A difference of Gaussian (DOG) model is used to simulate the ganglion differential response. Experimental results using natural scenery pictures proved that, the proposed image enhancement model by simulating the two-layer center/surrounding retinal networks can effectively enhance color images in terms of color contrast and image details.

  7. Development of the anode bipolar plate/membrane assembly unit for air breathing PEMFC stack using silicone adhesive bonding

    NASA Astrophysics Data System (ADS)

    Kim, Minkook; Lee, Dai Gil

    2016-05-01

    Polymer electrolyte membrane fuel cells (PEMFC) exhibit a wide power range, low operating temperature, high energy density and long life time. These advantages favor PEMFC for applications such as vehicle power sources, portable power, and backup power applications. With the push towards the commercialization of PEMFC, especially for portable power applications, the overall balance of plants (BOPs) of the systems should be minimized. To reduce the mass and complexity of the systems, air-breathing PEMFC stack design with open cathode channel configuration is being developed. However, the open cathode channel configuration incurs hydrogen leakage problem. In this study, the bonding strength of a silicon adhesive between the Nafion membrane and the carbon fiber/epoxy composite bipolar plate was measured. Then, an anode bipolar plate/membrane assembly unit which was bonded with the silicone adhesive was developed to solve the hydrogen leakage problem. The reliability of the anode bipolar plate/membrane assembly unit was estimated under the internal pressure of hydrogen by the FE analysis. Additionally, the gas sealability of the developed air breathing PEMFC unit cell was experimentally measured. Finally, unit cell performance of the developed anode bipolar plate/membrane assembly unit was tested and verified under operating conditions without humidity and temperature control.

  8. Bipolar battery

    DOEpatents

    Kaun, Thomas D.

    1992-01-01

    A bipolar battery having a plurality of cells. The bipolar battery includes: a negative electrode; a positive electrode and a separator element disposed between the negative electrode and the positive electrode, the separator element electrically insulating the electrodes from one another; an electrolyte disposed within at least one of the negative electrode, the positive electrode and the separator element; and an electrode containment structure including a cup-like electrode holder.

  9. Passive Diffusion as a Mechanism Underlying Ribbon Synapse Vesicle Release and Resupply

    PubMed Central

    Graydon, Cole W.; Zhang, Jun; Oesch, Nicholas W.; Sousa, Alioscka A.; Leapman, Richard D.

    2014-01-01

    Synaptic ribbons are presynaptic protein structures found at many synapses that convey graded, “analog” sensory signals in the visual, auditory, and vestibular pathways. Ribbons, typically anchored to the presynaptic membrane and surrounded by tethered synaptic vesicles, are thought to regulate or facilitate vesicle delivery to the presynaptic membrane. No direct evidence exists, however, to indicate how vesicles interact with the ribbon or, once attached, move along the ribbon's surface to reach the presynaptic release sites at its base. To address these questions, we have created, validated, and tested a passive vesicle diffusion model of retinal rod bipolar cell ribbon synapses. We used axial (bright-field) electron tomography in the scanning transmission electron microscopy to obtain 3D structures of rat rod bipolar cell terminals in 1-μm-thick sections of retinal tissue at an isotropic spatial resolution of ∼3 nm. The resulting structures were then incorporated with previously published estimates of vesicle diffusion dynamics into numerical simulations that accurately reproduced electrophysiologically measured vesicle release/replenishment rates and vesicle pool sizes. The simulations suggest that, under physiologically realistic conditions, diffusion of vesicles crowded on the ribbon surface gives rise to a flow field that enhances delivery of vesicles to the presynaptic membrane without requiring an active transport mechanism. Numerical simulations of ribbon–vesicle interactions predict that transient binding and unbinding of multiple tethers to each synaptic vesicle may achieve sufficiently tight association of vesicles to the ribbon while permitting the fast diffusion along the ribbon that is required to sustain high release rates. PMID:24990916

  10. Passive diffusion as a mechanism underlying ribbon synapse vesicle release and resupply.

    PubMed

    Graydon, Cole W; Zhang, Jun; Oesch, Nicholas W; Sousa, Alioscka A; Leapman, Richard D; Diamond, Jeffrey S

    2014-07-02

    Synaptic ribbons are presynaptic protein structures found at many synapses that convey graded, "analog" sensory signals in the visual, auditory, and vestibular pathways. Ribbons, typically anchored to the presynaptic membrane and surrounded by tethered synaptic vesicles, are thought to regulate or facilitate vesicle delivery to the presynaptic membrane. No direct evidence exists, however, to indicate how vesicles interact with the ribbon or, once attached, move along the ribbon's surface to reach the presynaptic release sites at its base. To address these questions, we have created, validated, and tested a passive vesicle diffusion model of retinal rod bipolar cell ribbon synapses. We used axial (bright-field) electron tomography in the scanning transmission electron microscopy to obtain 3D structures of rat rod bipolar cell terminals in 1-μm-thick sections of retinal tissue at an isotropic spatial resolution of ∼3 nm. The resulting structures were then incorporated with previously published estimates of vesicle diffusion dynamics into numerical simulations that accurately reproduced electrophysiologically measured vesicle release/replenishment rates and vesicle pool sizes. The simulations suggest that, under physiologically realistic conditions, diffusion of vesicles crowded on the ribbon surface gives rise to a flow field that enhances delivery of vesicles to the presynaptic membrane without requiring an active transport mechanism. Numerical simulations of ribbon-vesicle interactions predict that transient binding and unbinding of multiple tethers to each synaptic vesicle may achieve sufficiently tight association of vesicles to the ribbon while permitting the fast diffusion along the ribbon that is required to sustain high release rates. Copyright © 2014 the authors 0270-6474/14/348948-15$15.00/0.

  11. Nicotinic receptors and functional regulation of GABA cell microcircuitry in bipolar disorder and schizophrenia.

    PubMed

    Benes, Francine M

    2012-01-01

    Studies of the hippocampus in postmortem brains from patients with schizophrenia and bipolar disorder have provided evidence for a defect of GABAergic interneurons. Significant decreases in the expression of GAD67, a marker for GABA cell function, have been found repeatedly in several different brain regions that include the hippocampus. In this region, nicotinic receptors are thought to play an important role in modulating the activity of GABAergic interneurons by influences of excitatory cholinergic afferents on their activity. In bipolar disorder, this influence appears to be particularly prominent in the stratum oriens of sectors CA3/2 and CA1, two sites where these cells constitute the exclusive neuronal cell type. In sector CA3/2, this layer receives a robust excitatory projection from the basolateral amygdala (BLA) and this is thought to play a central role in regulating GABA cells at this locus. Using laser microdissection, recent studies have focused selectively on these two layers and their associated GABA cells using microarray technology. The results have provided support for the idea that nicotinic cholinergic receptors play a particularly important role in regulating the activity of GABA neurons at these loci by regulating the progression of cell cycle and the repair of damaged DNA. In bipolar disorder, there is a prominent reduction in the expression of mRNAs for several different nicotinic subunit isoforms. These decreases could reflect a diminished influence of this receptor system on these GABA cells, particularly in sector CA3/2 where a preponderance of abnormalities have been observed in postmortem studies. In patients with bipolar disorder, excitatory nicotinic cholinergic fibers from the medial septum may converge with glutamatergic fibers from the BLA on GABAergic interneurons in the stratum oriens of CA3/2 and result in disturbances of their genomic and functional integrity, ones that may induce disruptions of the integration of microcircuitry within this region.

  12. Highly conductive composites for fuel cell flow field plates and bipolar plates

    DOEpatents

    Jang, Bor Z; Zhamu, Aruna; Song, Lulu

    2014-10-21

    This invention provides a fuel cell flow field plate or bipolar plate having flow channels on faces of the plate, comprising an electrically conductive polymer composite. The composite is composed of (A) at least 50% by weight of a conductive filler, comprising at least 5% by weight reinforcement fibers, expanded graphite platelets, graphitic nano-fibers, and/or carbon nano-tubes; (B) polymer matrix material at 1 to 49.9% by weight; and (C) a polymer binder at 0.1 to 10% by weight; wherein the sum of the conductive filler weight %, polymer matrix weight % and polymer binder weight % equals 100% and the bulk electrical conductivity of the flow field or bipolar plate is at least 100 S/cm. The invention also provides a continuous process for cost-effective mass production of the conductive composite-based flow field or bipolar plate.

  13. Test Results of a Ten Cell Bipolar Nickel-hydrogen Battery

    NASA Technical Reports Server (NTRS)

    Cataldo, R. L.

    1984-01-01

    A study was initiated to design and evaluate a new design concept for nickel-hydrogen cells. This concept involved constructing a battery in a bipolar stack with cells consisting of a one plate for each nickel and hydrogen electrode. Preliminary designs at the system level of this concept promised improvements in both volumetric and gravimetric energy densities, thermal management, life extension, costs, and peak power capability over more conventional designs. Test results were most encouraging. This preprototype battery, built with less than ideal components and hardware, exceeded expectations. A total of 2000 LEO cycles at 80 percent depth of discharge were accrued. A cycle life goal of 30,000 cycles appears achievable with minor design changes. These improvements include advanced technology nickel electrodes, insulated bipolar plates and specifically designed frames to minimize shunt currents. The discharge rate capability of this design exceeds 25C. At the 10C discharge rate, 80% of the battery capacity can be withdrawn in six minutes. This data shows that the bipolar design is well suited for those applications requiring high peak power pulses.

  14. Requirement for Bhlhb5 in the specification of amacrine and cone bipolar subtypes in mouse retina

    PubMed Central

    Feng, Liang; Xie, Xiaoling; Joshi, Pushkar S.; Yang, Zhiyong; Shibasaki, Koji; Chow, Robert L.; Gan, Lin

    2010-01-01

    The mammalian retina comprises six major neuronal cell types and one glial type that are further classified into multiple subtypes based on their anatomical and functional differences. Nevertheless, how these subtypes arise remains largely unknown at the molecular level. Here, we demonstrate that the expression of Bhlhb5, a bHLH transcription factor of the Olig family, is tightly associated with the generation of selective GABAergic amacrine and Type 2 OFF-cone bipolar subtypes throughout retinogenesis. Targeted deletion of Bhlhb5 results in a significant reduction in the generation of these selective bipolar and amacrine subtypes. Furthermore, although a Bhlhb5-null mutation has no effect on the expression of bHLH-class retinogenic genes, Bhlhb5 expression overlaps with that of the pan-amacrine factor NeuroD and the expression of Bhlhb5 and NeuroD is negatively regulated by ganglion cell-competence factor Math5. Our results reveal that a bHLH transcription factor cascade is involved in regulating retinal cell differentiation and imply that Bhlhb5 functions downstream of retinogenic factors to specify bipolar and amacrine subtypes. PMID:17092954

  15. Chromosome nondisjunction during bipolar mitoses of binucleated intermediates promote aneuploidy formation along with multipolar mitoses rather than chromosome loss in micronuclei induced by asbestos

    PubMed Central

    Zhang, Tianwei; Lv, Lei; Huang, Yun; Ren, Xiaohui; Shi, Qinghua

    2017-01-01

    Asbestos is a well-known occupational carcinogen that can cause aneuploidy during the early stages of neoplastic development. To explore the origins of asbestos-induced aneuploidy, we performed long-term live-cell imaging followed by fluorescence in situ hybridization of chromosomes 8 and 12 in human bronchial epithelial (HBEC) and mesothelial (MeT5A) cells. We demonstrate that asbestos induces aneuploidy via binucleated intermediates resulting from cytokinesis failure. On the one hand, asbestos increases chromosome nondisjunction during bipolar divisions of binucleated intermediates and produces near-tetraploidy. On the other hand, asbestos increases multipolar divisions of binucleated intermediates to produce aneuploidy. Surprisingly, chromosomes in asbestos-induced micronucleated cells are not truly lost by the cells, and do not contribute to aneuploid cell formation in either cell type. These results clarify the cellular source of asbestos-induced aneuploidy. In particular, they show the asbestos-induced disruption of bipolar chromosomal segregation in tetraploid cells, thereby demonstrating the causality between binucleated intermediates and aneuploidy evolution, rather than chromosome loss in micronuclei. PMID:28038458

  16. Chromosome nondisjunction during bipolar mitoses of binucleated intermediates promote aneuploidy formation along with multipolar mitoses rather than chromosome loss in micronuclei induced by asbestos.

    PubMed

    Zhang, Tianwei; Lv, Lei; Huang, Yun; Ren, Xiaohui; Shi, Qinghua

    2017-02-14

    Asbestos is a well-known occupational carcinogen that can cause aneuploidy during the early stages of neoplastic development. To explore the origins of asbestos-induced aneuploidy, we performed long-term live-cell imaging followed by fluorescence in situ hybridization of chromosomes 8 and 12 in human bronchial epithelial (HBEC) and mesothelial (MeT5A) cells. We demonstrate that asbestos induces aneuploidy via binucleated intermediates resulting from cytokinesis failure. On the one hand, asbestos increases chromosome nondisjunction during bipolar divisions of binucleated intermediates and produces near-tetraploidy. On the other hand, asbestos increases multipolar divisions of binucleated intermediates to produce aneuploidy. Surprisingly, chromosomes in asbestos-induced micronucleated cells are not truly lost by the cells, and do not contribute to aneuploid cell formation in either cell type. These results clarify the cellular source of asbestos-induced aneuploidy. In particular, they show the asbestos-induced disruption of bipolar chromosomal segregation in tetraploid cells, thereby demonstrating the causality between binucleated intermediates and aneuploidy evolution, rather than chromosome loss in micronuclei.

  17. A Comparative Genomic Study in Schizophrenic and in Bipolar Disorder Patients, Based on Microarray Expression Profiling Meta-Analysis

    PubMed Central

    Logotheti, Marianthi; Papadodima, Olga; Venizelos, Nikolaos; Chatziioannou, Aristotelis; Kolisis, Fragiskos

    2013-01-01

    Schizophrenia affecting almost 1% and bipolar disorder affecting almost 3%–5% of the global population constitute two severe mental disorders. The catecholaminergic and the serotonergic pathways have been proved to play an important role in the development of schizophrenia, bipolar disorder, and other related psychiatric disorders. The aim of the study was to perform and interpret the results of a comparative genomic profiling study in schizophrenic patients as well as in healthy controls and in patients with bipolar disorder and try to relate and integrate our results with an aberrant amino acid transport through cell membranes. In particular we have focused on genes and mechanisms involved in amino acid transport through cell membranes from whole genome expression profiling data. We performed bioinformatic analysis on raw data derived from four different published studies. In two studies postmortem samples from prefrontal cortices, derived from patients with bipolar disorder, schizophrenia, and control subjects, have been used. In another study we used samples from postmortem orbitofrontal cortex of bipolar subjects while the final study was performed based on raw data from a gene expression profiling dataset in the postmortem superior temporal cortex of schizophrenics. The data were downloaded from NCBI's GEO datasets. PMID:23554570

  18. The Transient Intermediate Plexiform Layer, a Plexiform Layer-like Structure Temporarily Existing in the Inner Nuclear Layer in Developing Rat Retina.

    PubMed

    Park, Hyung Wook; Kim, Hong-Lim; Park, Yong Soo; Kim, In-Beom

    2018-02-01

    The retina is a highly specialised part of the brain responsible for visual processing. It is well-laminated; three layers containing five different types of neurons are compartmentalised by two synaptic layers. Among the retinal layers, the inner nuclear layer (INL) is composed of horizontal, bipolar, and amacrine cell types. Bipolar cells form one sublayer in the distal half of the IPL, while amacrine cells form another sublayer in the proximal half, without any border-like structure. Here, we report that a plexiform layer-like structure exists temporarily in the border between the bipolar and amacrine sublayers in the INL in the rat retina during retinal development. This transient intermediate plexiform layer (TIPL) appeared at postnatal day (PD) 7 and then disappeared around PD 12. Most apoptotic cells in the INL were found near the TIPL. These results suggest that the TIPL may contribute to the formation of sublayers and the cell number limit in the INL.

  19. Efficacy and safety of sublingual ramelteon as an adjunctive therapy in the maintenance treatment of bipolar I disorder in adults: A phase 3, randomized controlled trial.

    PubMed

    Mahableshwarkar, Atul R; Calabrese, Joseph R; Macek, Thomas A; Budur, Kumar; Adefuye, Adedeji; Dong, Xinxin; Hanson, Elizabeth; Sachs, Gary S

    2017-10-15

    The optimal long-term management strategy for bipolar I disorder patients is not yet established. Evidence supports the rationale for circadian rhythm regulation to prevent mood episode relapse in bipolar patients. This study evaluated the efficacy and safety of a new sublingual formulation of the melatonin receptor agonist ramelteon (ramelteon SL) as adjunctive therapy in the maintenance treatment of bipolar I patients. In a double-blinded trial in the United States and Latin America, adult bipolar I disorder patients stable for ≥ 8 weeks before baseline and with a mood episode 8 weeks to 9 months before screening, were randomized to once-daily ramelteon SL 0.1mg (n = 164), 0.4mg (n = 160), or 0.8mg (n = 154), or placebo (n = 164), in addition to their existing treatment. The primary endpoint was time from randomization to relapse of symptoms. The prespecified futility criterion in a planned, unblinded, independent interim analysis was the failure of all ramelteon SL doses to achieve a conditional power ≥ 30% compared with placebo. No significant differences between any dose of ramelteon SL and placebo were observed. The study was terminated after meeting the futility criteria. Ramelteon SL was well tolerated, with a safety profile consistent with that for oral ramelteon. A low rate of relapse events precluded detection of any statistically significant difference between groups. The study failed to demonstrate the efficacy of ramelteon SL as adjunctive maintenance therapy for bipolar disorder. Interim analyses for futility in clinical studies are valuable in preventing unnecessary exposure of subjects to interventions. Copyright © 2017. Published by Elsevier B.V.

  20. Corrosion resistant metallic bipolar plate

    DOEpatents

    Brady, Michael P [Oak Ridge, TN; Schneibel, Joachim H [Knoxville, TN; Pint, Bruce A [Knoxville, TN; Maziasz, Philip J [Oak Ridge, TN

    2007-05-01

    A corrosion resistant, electrically conductive component such as a bipolar plate for a PEM fuel cell includes 20 55% Cr, balance base metal such as Ni, Fe, or Co, the component having thereon a substantially external, continuous layer of chromium nitride.

  1. Effect of filler content on the properties of expanded- graphite-based composite bipolar plates for application in polymer electrolyte membrane fuel cells

    NASA Astrophysics Data System (ADS)

    Masand, Aakash; Borah, Munu; Pathak, Abhishek K.; Dhakate, Sanjay R.

    2017-09-01

    Minimization of the weight and volume of a hydrogen-based PEM fuel cell stack is an essential area of research for the development and commercialization of PEMFCs for various applications. Graphite-based composite bipolar plates have significant advantages over conventional metallic bipolar plates due to their corrosion resistivity and low cost. On the other hand, expanded graphite is seen to be a potential candidate for facilitating the required electrical, thermal and mechanical properties of bipolar plates with a low density. Therefore, in the present study, the focus is on minimization of the high loading of graphite and optimizes its composition to meet the target properties of bipolar plates as per the USDOE target. Three types of expanded graphite (EG)-phenolic-resin-based composite bipolar plates were developed by partially replacing the expanded graphite content with natural graphite (NG) and carbon black as an additional filler. The three types of composite plate with the reinforcing constituent ratio EG:NG:R (25:25:50) give a bending strength of 49 MPa, a modulus of ~6 GPa, electrical conductivity  >100 S cm-1, a shore hardness of 55 and a bulk density of 1.55 g/cc. The 50 wt% loading of resin is sufficient to wet the 50 wt% filler content in the composite plate. This study gives an insight into using hybrid reinforcements in order to achieve the desired properties of bipolar plates.

  2. The balance of electric field and interfacial catalysis in promoting water dissociation in bipolar membranes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yan, Zhifei; Zhu, Liang; Li, Yuguang C.

    Bipolar membranes maintain a steady pH in electrolytic cells through water autodissociation at the interface between their cation- and anion-exchange layers. We analyze the balance of electric field and catalysis in accelerating this reaction.

  3. The balance of electric field and interfacial catalysis in promoting water dissociation in bipolar membranes

    DOE PAGES

    Yan, Zhifei; Zhu, Liang; Li, Yuguang C.; ...

    2018-01-01

    Bipolar membranes maintain a steady pH in electrolytic cells through water autodissociation at the interface between their cation- and anion-exchange layers. We analyze the balance of electric field and catalysis in accelerating this reaction.

  4. Orientational order in bipolar nematic microdroplets close to the phase transition

    NASA Astrophysics Data System (ADS)

    Vilfan, I.; Vilfan, M.; Žumer, S.

    1989-10-01

    The ordering in bipolar liquid-crystal droplets close to the nematic-paranematic phase translation is studied. Here, ``paranematic'' refers to the phase above the nematic-isotropic transition temperature. The structure of spherical droplets is obtained after the minimization of the Landau-de Gennes-type free energy assuming a constant value of the surface order parameter and strong anchoring of the molecules parallel to the surface. Disordered defect regions caused by elastic deformations are found close to the poles. The defect regions grow into the droplet as the coexistence temperature between the paranematic and nematic phases is approached from below. The temperature-radius phase diagram shows the first-order coexistence curve terminating in the critical point and a pronounced decrease of the coexistence temperature on approaching the critical radius.

  5. Requirement of Phosphoinositides Containing Stearic Acid To Control Cell Polarity.

    PubMed

    Doignon, François; Laquel, Patricia; Testet, Eric; Tuphile, Karine; Fouillen, Laetitia; Bessoule, Jean-Jacques

    2015-12-28

    Phosphoinositides (PIPs) are present in very small amounts but are essential for cell signaling, morphogenesis, and polarity. By mass spectrometry, we demonstrated that some PIPs with stearic acyl chains were strongly disturbed in a psi1Δ Saccharomyces cerevisiae yeast strain deficient in the specific incorporation of a stearoyl chain at the sn-1 position of phosphatidylinositol. The absence of PIPs containing stearic acid induced disturbances in intracellular trafficking, although the total amount of PIPs was not diminished. Changes in PIPs also induced alterations in the budding pattern and defects in actin cytoskeleton organization (cables and patches). Moreover, when the PSI1 gene was impaired, a high proportion of cells with bipolar cortical actin patches that occurred concomitantly with the bipolar localization of Cdc42p was specifically found among diploid cells. This bipolar cortical actin phenotype, never previously described, was also detected in a bud9Δ/bud9Δ strain. Very interestingly, overexpression of PSI1 reversed this phenotype. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  6. The suitability of monopolar and bipolar ion exchange membranes as separators for biological fuel cells.

    PubMed

    Harnisch, Falk; Schröder, Uwe; Scholz, Fritz

    2008-03-01

    A proton exchange (Nafion-117), a cation exchange (Ultrex CMI7000), an anion exchange (Fumasep FAD), and a bipolar (FumasepFBM) membrane have been studied to evaluate the principle suitability of ion exchange membranes as separators between the anode and the cathode compartment of biological fuel cells. The applicability of these membranes is severely affected by the neutral pH, and the usually low ionic strength of the electrolyte solutions. Thus, the ohmic resistance of the monopolar membranes was found to greatly increase at neutral pH and at decreasing electrolyte concentrations. None of the studied membranes can prevent the acidification of the anode and the alkalization of the cathode compartment, which occurs in the course of the fuel cell operation. Bipolar membranes are shown to be least suitable for biofuel cell application since they show the highest polarization without being able to prevent pH splitting between the anode and cathode compartments.

  7. Bipolar plate/diffuser for a proton exchange membrane fuel cell

    DOEpatents

    Besmann, Theodore M.; Burchell, Timothy D.

    2001-01-01

    A combination bipolar plate/diffuser fuel cell component includes an electrically conducting solid material having: a porous region having a porous surface; and a hermetic region, the hermetic region defining at least a portion of at least one coolant channel, the porous region defining at least a portion of at least one reactant channel, the porous region defining a flow field medium for diffusing the reactant to the porous surface.

  8. Bipolar plate/diffuser for a proton exchange membrane fuel cell

    DOEpatents

    Besmann, Theodore M.; Burchell, Timothy D.

    2000-01-01

    A combination bipolar plate/diffuser fuel cell component includes an electrically conducting solid material having: a porous region having a porous surface; and a hermetic region, the hermetic region defining at least a portion of at least one coolant channel, the porous region defining at least a portion of at least one reactant channel, the porous region defining a flow field medium for diffusing the reactant to the porous surface.

  9. Electrical coupling of single cardiac rat myocytes to field-effect and bipolar transistors.

    PubMed

    Kind, Thomas; Issing, Matthias; Arnold, Rüdiger; Müller, Bernt

    2002-12-01

    A novel bipolar transistor for extracellular recording the electrical activity of biological cells is presented, and the electrical behavior compared with the field-effect transistor (FET). Electrical coupling is examined between single cells separated from the heart of adults rats (cardiac myocytes) and both types of transistors. To initiate a local extracellular voltage, the cells are periodically stimulated by a patch pipette in voltage clamp and current clamp mode. The local extracellular voltage is measured by the planar integrated electronic sensors: the bipolar and the FET. The small signal transistor currents correspond to the local extracellular voltage. The two types of sensor transistors used here were developed and manufactured in the laboratory of our institute. The manufacturing process and the interfaces between myocytes and transistors are described. The recordings are interpreted by way of simulation based on the point-contact model and the single cardiac myocyte model.

  10. Additive manufactured bipolar plate for high-efficiency hydrogen production in proton exchange membrane electrolyzer cells

    DOE PAGES

    Yang, Gaoqiang; Mo, Jingke; Kang, Zhenye; ...

    2017-05-06

    Additive manufacturing (AM) technology is capable of fast and low-cost prototyping from complex 3D digital models. To take advantage of this technology, a stainless steel (SS) plate with parallel flow field served as a combination of a cathode bipolar plate and a current distributor; it was fabricated using selective laser melting (SLM) techniques and investigated in a proton exchange membrane electrolyzer cell (PEMEC) in-situ for the first time. The experimental results show that the PEMEC with an AM SS cathode bipolar plate can achieve an excellent performance for hydrogen production for a voltage of 1.779 V and a current densitymore » of 2.0 A/cm 2. The AM SS cathode bipolar plate was also characterized by SEM and EDS, and the results show a uniform elemental distribution across the plate with very limited oxidization. As a result, this research demonstrates that AM method could be a route to aid cost-effective and rapid development of PEMECs.« less

  11. Additive manufactured bipolar plate for high-efficiency hydrogen production in proton exchange membrane electrolyzer cells

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Yang, Gaoqiang; Mo, Jingke; Kang, Zhenye

    Additive manufacturing (AM) technology is capable of fast and low-cost prototyping from complex 3D digital models. To take advantage of this technology, a stainless steel (SS) plate with parallel flow field served as a combination of a cathode bipolar plate and a current distributor; it was fabricated using selective laser melting (SLM) techniques and investigated in a proton exchange membrane electrolyzer cell (PEMEC) in-situ for the first time. The experimental results show that the PEMEC with an AM SS cathode bipolar plate can achieve an excellent performance for hydrogen production for a voltage of 1.779 V and a current densitymore » of 2.0 A/cm 2. The AM SS cathode bipolar plate was also characterized by SEM and EDS, and the results show a uniform elemental distribution across the plate with very limited oxidization. As a result, this research demonstrates that AM method could be a route to aid cost-effective and rapid development of PEMECs.« less

  12. Development of a large scale bipolar NiH2 battery

    NASA Technical Reports Server (NTRS)

    Adler, E.; Perez, F.

    1983-01-01

    The bipolar battery concept, developed in cooperation with NASA, is described in the context of the advantages afforded by near-term IPV and CVP cell technology. The projected performance, development requirements, and a possible approach to bipolar battery design are outlined. Consideration is given to packaging electrodes within a common hydrophobic plastic frame, electrode technology that involves a photochemically etched 0.1 mm thick nickel substrate coated with a 10 mg/sq cm mixture of platinum powder and TFE30, and an electrode design that eliminates the screen and doubles the electrode thickness (from the currently used 0.8 mm) while retaining the active material loading of 1.6-1.8 gm/cu cm. Also covered are thermal management, and electrolyte and oxygen management. It is concluded that a high voltage, high capacity, bipolar NiH2 cell can be configured with proper development for use in large power systems, and that it can provide considerable weight savings.

  13. Enhancing the corrosion resistance of the 2205 duplex stainless steel bipolar plates in PEMFCs environment by surface enriched molybdenum

    NASA Astrophysics Data System (ADS)

    Jinlong, Lv; Zhuqing, Wang; Tongxiang, Liang; Ken, Suzuki; Hideo, Miura

    Surface molybdenum enrichment on 2205 duplex stainless steel was obtained by the ball milling technique. The electrochemical results showed molybdenum enrichment on the surface of 2205 duplex stainless steel improved its corrosion resistance in a typical proton exchange membrane fuel cell environment. This was mainly attributed to higher molybdenum content in the passive film formed on 2205 duplex stainless steel after ball milling. The decreased donor and acceptor concentrations improved significantly the corrosion resistance of surface molybdenum-enriched 2205 duplex stainless steel bipolar plates in the simulated cathodic proton exchange membrane fuel cells environment. In addition, the interfacial contact resistance of the 2205 duplex stainless steel bipolar plates slightly decreased due to surface molybdenum enrichment.

  14. Pleated metal bipolar assembly

    DOEpatents

    Wilson, Mahlon S.; Zawodzinski, Christine

    2001-01-01

    A thin low-cost bipolar plate for an electrochemical cell is formed from a polymer support plate with first flow channels on a first side of the support plate and second flow channels on a second side of the support plate, where the first flow channels and second flow channels have intersecting locations and have a depth effective to form openings through the support plate at the intersecting locations. A first foil of electrically conductive material is pressed into the first flow channels. A second foil of electrically conductive material pressed into the second flow channels so that electrical contact is made between the first and second foils at the openings through the support plate. A particular application of the bipolar plate is in polymer electrolyte fuel cells.

  15. Regulation of glycogen synthase kinase-3 during bipolar mania treatment.

    PubMed

    Li, Xiaohong; Liu, Min; Cai, Zhuoji; Wang, Gang; Li, Xiaohua

    2010-11-01

    Bipolar disorder is a debilitating psychiatric illness presenting with recurrent mania and depression. The pathophysiology of bipolar disorder is poorly understood, and molecular targets in the treatment of bipolar disorder remain to be identified. Preclinical studies have suggested that glycogen synthase kinase-3 (GSK3) is a potential therapeutic target in bipolar disorder, but evidence of abnormal GSK3 in human bipolar disorder and its response to treatment is still lacking. This study was conducted in acutely ill type I bipolar disorder subjects who were hospitalized for a manic episode. The protein level and the inhibitory serine phosphorylation of GSK3 in peripheral blood mononuclear cells of bipolar manic and healthy control subjects were compared, and the response of GSK3 to antimanic treatment was evaluated. The levels of GSK3α and GSK3β in this group of bipolar manic subjects were higher than healthy controls. Symptom improvement during an eight-week antimanic treatment with lithium, valproate, and atypical antipsychotics was accompanied by a significant increase in the inhibitory serine phosphorylation of GSK3, but not the total level of GSK3, whereas concomitant electroconvulsive therapy treatment during a manic episode appeared to dampen the response of GSK3 to pharmacological treatment. Results of this study suggest that GSK3 can be modified during the treatment of bipolar mania. This finding in human bipolar disorder is in agreement with preclinical data suggesting that inhibition of GSK3 by increasing serine phosphorylation is a response of GSK3 to psychotropics used in bipolar disorder, supporting the notion that GSK3 is a promising molecular target in the pharmacological treatment of bipolar disorder. © 2010 John Wiley and Sons A/S.

  16. The Effect of PKCα on the Light Response of Rod Bipolar Cells in the Mouse Retina

    PubMed Central

    Xiong, Wei-Hong; Pang, Ji-Jie; Pennesi, Mark E.; Duvoisin, Robert M.; Wu, Samuel M.; Morgans, Catherine W.

    2015-01-01

    Purpose Protein kinase C α (PKCα) is abundantly expressed in rod bipolar cells (RBCs) in the retina, yet the physiological function of PKCα in these cells is not well understood. To elucidate the role of PKCα in visual processing in the eye, we examined the effect of genetic deletion of PKCα on the ERG and on RBC light responses in the mouse. Methods Immunofluorescent labeling was performed on wild-type (WT), TRPM1 knockout, and PKCα knockout (PKC-KO) retina. Scotopic and photopic ERGs were recorded from WT and PKC-KO mice. Light responses of RBCs were measured using whole-cell recordings in retinal slices from WT and PKC-KO mice. Results Protein kinase C alpha expression in RBCs is correlated with the activity state of the cell. Rod bipolar cells dendrites are a major site of PKCα phosphorylation. Electroretinogram recordings indicated that loss of PKCα affects the scotopic b-wave, including a larger peak amplitude, longer implicit time, and broader width of the b-wave. There were no differences in the ERG a- or c-wave between PKCα KO and WT mice, indicating no measurable effect of PKCα in photoreceptors or the RPE. The photopic ERG was unaffected consistent with the lack of detectable PKCα in cone bipolar cells. Whole-cell recordings from RBCs in PKC-KO retinal slices revealed that, compared with WT, RBC light responses in the PKC-KO retina are delayed and of longer duration. Conclusions Protein kinase C alpha plays an important modulatory role in RBCs, regulating both the peak amplitude and temporal properties of the RBC light response in the rod visual pathway. PMID:26230760

  17. Transistor Laser Optical NOR Gate for High Speed Optical Logic Processors

    DTIC Science & Technology

    2017-03-20

    proposes an optical bistable latch can be built with two universal photonic NOR gate circuits, which are implemented by the three-port tunneling ... Tunneling Junction Transistor Laser (TJ-TL); Optical NOR Gate. Introduction To fulfill the future national security and intelligence needs in this...two-terminal diode lasers. Three-Port Transistor Laser – an Integration of Quantum-Wells into Heterojunction Bipolar Transistor Different than

  18. Application of induced pluripotent stem cells to understand neurobiological basis of bipolar disorder and schizophrenia.

    PubMed

    Liu, Yao-Nan; Lu, Si-Yao; Yao, Jun

    2017-09-01

    The etiology of neuropsychiatric disorders, such as schizophrenia and bipolar disorder, usually involves complex combinations of genetic defects/variations and environmental impacts, which hindered, for a long time, research efforts based on animal models and patients' non-neuronal cells or post-mortem tissues. However, the development of human induced pluripotent stem cell (iPSC) technology by the Yamanaka group was immediately applied to establish cell research models for neuronal disorders. Since then, techniques to achieve highly efficient differentiation of different types of neural cells following iPSC modeling have made much progress. The fast-growing iPSC and neural differentiation techniques have brought valuable insights into the pathology and neurobiology of neuropsychiatric disorders. In this article, we first review the application of iPSC technology in modeling neuronal disorders and discuss the progress in the accompanying neural differentiation. Then, we summarize the progress in iPSC-based research that has been accomplished so far regarding schizophrenia and bipolar disorder. © 2017 The Authors. Psychiatry and Clinical Neurosciences © 2017 Japanese Society of Psychiatry and Neurology.

  19. The bipolar filaments formed by Herpes simplex virus type 1 SSB/recombination protein (ICP8) suggest a mechanism for DNA annealing

    PubMed Central

    Makhov, Alexander M.; Sen, Anindito; Yu, Xiong; Simon, Martha N.; Griffith, Jack D.; Egelman, Edward H.

    2009-01-01

    Herpes simplex virus type 1 encodes a multifunctional protein, ICP8, which serves both as a single strand binding protein and recombinase, catalyzing reactions involved in replication and recombination of the viral genome. In the presence of divalent ions and at low temperature, previous electron microscopic (EM) studies showed that ICP8 will form long left-handed helical filaments. Here EM image reconstruction reveals that the filaments are bipolar, with an asymmetric unit containing two subunits of ICP8 that constitute a symmetrical dimer. This organization of the filament has been confirmed using Scanning Transmission Electron Microscopy. The pitch of the filaments is ~ 250 Å, with ~ 6.2 dimers per turn. Docking of a crystal structure of ICP8 into the reconstructed filament shows that the C-terminal domain of ICP8, attached to the body of the subunit by a flexible linker containing ~ 10 residues, is packed into a pocket in the body of a neighboring subunit in the crystal in a similar manner as in the filament. However, the interactions between the large N-terminal domains are quite different in the filament from that observed in the crystal. A previously proposed model for ICP8 binding single-stranded DNA, based upon the crystal structure, leads to a model for a continuous strand of ssDNA near the filament axis. The bipolar nature of the ICP8 filaments means that a second strand of ssDNA would be running through this filament in the opposite orientation, and this provides a potential mechanism for how ICP8 anneals complementary single stranded DNA into double-stranded DNA, where each strand runs in opposite directions. PMID:19138689

  20. The bipolar filaments formed by herpes simplex virus type 1 SSB/recombination protein (ICP8) suggest a mechanism for DNA annealing.

    PubMed

    Makhov, Alexander M; Sen, Anindito; Yu, Xiong; Simon, Martha N; Griffith, Jack D; Egelman, Edward H

    2009-02-20

    Herpes simplex virus type 1 encodes a multifunctional protein, ICP8, which serves both as a single-strand binding protein and as a recombinase, catalyzing reactions involved in replication and recombination of the viral genome. In the presence of divalent ions and at low temperature, previous electron microscopic studies showed that ICP8 will form long left-handed helical filaments. Here, electron microscopic image reconstruction reveals that the filaments are bipolar, with an asymmetric unit containing two subunits of ICP8 that constitute a symmetrical dimer. This organization of the filament has been confirmed using scanning transmission electron microscopy. The pitch of the filaments is approximately 250 A, with approximately 6.2 dimers per turn. Docking of a crystal structure of ICP8 into the reconstructed filament shows that the C-terminal domain of ICP8, attached to the body of the subunit by a flexible linker containing approximately 10 residues, is packed into a pocket in the body of a neighboring subunit in the crystal in a similar manner as in the filament. However, the interactions between the large N-terminal domains are quite different in the filament from that observed in the crystal. A previously proposed model for ICP8 binding single-stranded DNA (ssDNA), based upon the crystal structure, leads to a model for a continuous strand of ssDNA near the filament axis. The bipolar nature of the ICP8 filaments means that a second strand of ssDNA would be running through this filament in the opposite orientation, and this provides a potential mechanism for how ICP8 anneals complementary ssDNA into double-stranded DNA, where each strand runs in opposite directions.

  1. The Bipolar Filaments Formed by Herpes Simplex Virus Type 1 SSB/Recombination Protein (ICP8) Suggest a Mechanism for DNA Annealing

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Makhov, A.M.; Simon, M.; Sen, A.

    2009-02-20

    Herpes simplex virus type 1 encodes a multifunctional protein, ICP8, which serves both as a single-strand binding protein and as a recombinase, catalyzing reactions involved in replication and recombination of the viral genome. In the presence of divalent ions and at low temperature, previous electron microscopic studies showed that ICP8 will form long left-handed helical filaments. Here, electron microscopic image reconstruction reveals that the filaments are bipolar, with an asymmetric unit containing two subunits of ICP8 that constitute a symmetrical dimer. This organization of the filament has been confirmed using scanning transmission electron microscopy. The pitch of the filaments ismore » {approx} 250 {angstrom}, with {approx} 6.2 dimers per turn. Docking of a crystal structure of ICP8 into the reconstructed filament shows that the C-terminal domain of ICP8, attached to the body of the subunit by a flexible linker containing {approx} 10 residues, is packed into a pocket in the body of a neighboring subunit in the crystal in a similar manner as in the filament. However, the interactions between the large N-terminal domains are quite different in the filament from that observed in the crystal. A previously proposed model for ICP8 binding single-stranded DNA (ssDNA), based upon the crystal structure, leads to a model for a continuous strand of ssDNA near the filament axis. The bipolar nature of the ICP8 filaments means that a second strand of ssDNA would be running through this filament in the opposite orientation, and this provides a potential mechanism for how ICP8 anneals complementary ssDNA into double-stranded DNA, where each strand runs in opposite directions.« less

  2. Cellular Distribution and Subcellular Localization of Molecular Components of Vesicular Transmitter Release in Horizontal Cells of Rabbit Retina

    PubMed Central

    HIRANO, ARLENE A.; BRANDSTÄTTER, JOHANN H.; BRECHA, NICHOLAS C.

    2010-01-01

    The mechanism underlying transmitter release from retinal horizontal cells is poorly understood. We investigated the possibility of vesicular transmitter release from mammalian horizontal cells by examining the expression of synaptic proteins that participate in vesicular transmitter release at chemical synapses. Using immunocytochemistry, we evaluated the cellular and subcellular distribution of complexin I/II, syntaxin-1, and synapsin I in rabbit retina. Strong labeling for complexin I/II, proteins that regulate a late step in vesicular transmitter release, was found in both synaptic layers of the retina, and in somata of A- and B-type horizontal cells, of γ-aminobutyric acid (GABA)- and glycinergic amacrine cells, and of ganglion cells. Immunoelectron microscopy demonstrated the presence of complexin I/II in horizontal cell processes postsynaptic to rod and cone ribbon synapses. Syntaxin-1, a core protein of the soluble N-ethylmaleimide-sensitive-factor attachment protein receptor (SNARE) complex known to bind to complexin, and synapsin I, a synaptic vesicle-associated protein involved in the Ca2+-dependent recruitment of synaptic vesicles for transmitter release, were also present in the horizontal cells and their processes at photoreceptor synapses. Photoreceptors and bipolar cells did not express any of these proteins at their axon terminals. The presence of complexin I/II, syntaxin-1, and synapsin I in rabbit horizontal cell processes and tips suggests that a vesicular mechanism may underlie transmitter release from mammalian horizontal cells. PMID:15912504

  3. Advanced nickel-hydrogen cell configuration study

    NASA Technical Reports Server (NTRS)

    Adler, E.; Perez, F.

    1984-01-01

    Three nickel hydrogen battery designs, individual pressure vessel (IPV), common pressure vessel (CPV), and a bipolar battery module were studied. Weight, system complexity and cost were compared for a satellite operating in a 6 hour, 5600 nautical mile orbit. The required energy storage is 52 kWh. A 25% improvement in specific energy is observed by employing a bipolar battery versus a battery comprised of hundreds of IPV's. Further weight benefits are realized by the development of light weight technologies in the bipolar design.

  4. New Electrochemical Methods for Studying Nanoparticle Electrocatalysis and Neuronal Exocytosis

    NASA Astrophysics Data System (ADS)

    Cox, Jonathan T.

    This dissertation presents the construction and application of micro and nanoscale electrodes for electroanalytical analysis. The studies presented herein encompass two main areas: electrochemical catalysis, and studies of the dynamics of single cell exocytosis. The first portion of this dissertation engages the use of Pt nanoelectrodes to study the stability and electrocatalytic properties of materials. A single nanoparticle electrode (SNPE) was fabricated by immobilizing a single Au nanoparticle on a Pt disk nanoelectrode via an amine-terminated silane cross linker. In this manner we were able to effectively study the electrochemistry and electrocatalytic activity of single Au nanoparticles and found that the electrocatalytic activity is dependent on nanoparticle size. This study can further the understanding of the structure-function relationship in nanoparticle based electrocatalysis. Further work was conducted to probe the stability of Pt nanoelectrodes under conditions of potential cycling. Pt based catalysts are known to deteriorate under such conditions due to losses in electrochemical surface area and Pt dissolution. By using Pt disk nanoelectrodes we were able to study Pt dissolution via steady-state voltammetry. We observed an enhanced dissolution rate and higher charge density on nanoelectrodes than that previously found on macro scale electrodes. The goal of the second portion of this dissertation is to develop new analytical methods to study the dynamics of exocytosis from single cells. The secretion of neurotransmitters plays a key role in neuronal communication, and our studies highlight how bipolar electrochemistry can be employed to enhance detection of neurotransmitters from single cells. First, we developed a theory to quantitatively characterize the voltammetric behavior of bipolar carbon fiber microelectrodes and secondly applied those principles to single cell detection. We showed that by simply adding an additional redox mediator to the back-fill solution of a carbon fiber microelectrode, there is a significant enhancement in detection. Additionally we used solid state nanopores to detect individual phospholipid vesicles in solution. Vesicles are key cellular components that play essential biological roles especially in neurotransmission. This work represents preliminary studies in detection and size determination from vesicles isolated from individual cells.

  5. Fine needle aspiration cytology of breast cancer in women aged 70 years and older.

    PubMed

    Tse, Gary M K; Somali, Anjali; Chan, Anthony W H; Chaiwun, Benjaporn; Lui, Philip C W; Moriya, Takuya; Hwang, Jacqueline S G; Chan, Norman H L; Tan, Puay Hoon

    2008-10-01

    Elderly breast cancers are associated with a more favourable biological marker profile and higher proportion of specific subtypes, some of which are of low histological grade. We reviewed the fine needle aspiration cytology (FNAC) to assess the cytological characteristics and any clues to assist in the diagnosis. The aspirates of 140 cancers of various histological types and grades and 39 benign lesions were evaluated for 13 cytological parameters including cellularity of the direct and cytospin smears, epithelial cell clusters, cellular atypism, cytoplasmic features, vacuoles, mitotic figures, presence of myoepithelial cells, single background epithelial cells, the presence of naked nuclei, stromal fragments and necrosis. We found that the presence of background single epithelial cells, atypism of such cells, absence of benign appearing epithelial fragments, nuclear atypism of the epithelial cells within the fragments, presence of moderate amount of cytoplasm of these cells, absence of myoepithelial cells within the cluster, and absence of bipolar nuclei in the background have a strong association with malignancy. Scoring only the presence of single cells in the background, single cell atypism and the absence of bipolar nuclei in a scoring system can differentiate between benign and malignant aspirates with high (>90%) sensitivity and specificity. Assessing the presence of single cells in the background, single cell atypism and the absence of bipolar nuclei facilitates identification of malignancy in the aspiration of breast lesions from elderly patients.

  6. Combinatorial regulation of a Blimp1 (Prdm1) enhancer in the mouse retina

    PubMed Central

    Mills, Taylor S.; Eliseeva, Tatiana; Bersie, Stephanie M.; Randazzo, Grace; Nahreini, Jhenya; Park, Ko Uoon

    2017-01-01

    The mouse retina comprises seven major cell types that exist in differing proportions. They are generated from multipotent progenitors in a stochastic manner, such that the relative frequency of any given type generated changes over time. The mechanisms determining the proportions of each cell type are only partially understood. Photoreceptors and bipolar interneurons are derived from cells that express Otx2. Within this population, Blimp1 (Prdm1) helps set the balance between photoreceptors and bipolar cells by suppressing bipolar identity in most of the cells. How only a subset of these Otx2+ cells decides to upregulate Blimp1 and adopt photoreceptor fate is unknown. To understand this, we investigated how Blimp1 transcription is regulated. We identified several potential Blimp1 retinal enhancer elements using DNase hypersensitivity sequencing. Only one of the elements recapitulated Blimp1 spatial and temporal expression in cultured explant assays and within the retinas of transgenic mice. Mutagenesis of this retinal Blimp1 enhancer element revealed four discrete sequences that were each required for its activity. These included highly conserved Otx2 and ROR (retinoic acid receptor related orphan receptor) binding sites. The other required sequences do not appear to be controlled by Otx2 or ROR factors, increasing the complexity of the Blimp1 gene regulatory network. Our results show that the intersection of three or more transcription factors is required to correctly regulate the spatial and temporal features of Blimp1 enhancer expression. This explains how Blimp1 expression can diverge from Otx2 and set the balance between photoreceptor and bipolar fates. PMID:28829770

  7. Nickel hydrogen bipolar battery electrode design

    NASA Technical Reports Server (NTRS)

    Puglisi, V. J.; Russell, P.; Verrier, D.; Hall, A.

    1985-01-01

    The preferred approach of the NASA development effort in nickel hydrogen battery design utilizes a bipolar plate stacking arrangement to obtain the required voltage-capacity configuration. In a bipolar stack, component designs must take into account not only the typical design considerations such as voltage, capacity and gas management, but also conductivity to the bipolar (i.e., intercell) plate. The nickel and hydrogen electrode development specifically relevant to bipolar cell operation is discussed. Nickel oxide electrodes, having variable type grids and in thicknesses up to .085 inch are being fabricated and characterized to provide a data base. A selection will be made based upon a system level tradeoff. Negative (hydrpogen) electrodes are being screened to select a high performance electrode which can function as a bipolar electrode. Present nickel hydrogen negative electrodes are not capable of conducting current through their cross-section. An electrode was tested which exhibits low charge and discharge polarization voltages and at the same time is conductive. Test data is presented.

  8. Platelet parameters (PLT, MPV, P-LCR) in patients with schizophrenia, unipolar depression and bipolar disorder.

    PubMed

    Wysokiński, Adam; Szczepocka, Ewa

    2016-03-30

    There are no studies comparing platelet parameters platelet parameters (platelet count (PLT), mean platelet volume (MPV) and platelet large cell ratio (P-LCR)) between patients with schizophrenia, bipolar disorder and unipolar depression. Therefore, the aim of this study was to determine and compare differences in PLT, MPV and P-LCR in patients with schizophrenia, unipolar depression and bipolar disorder. This was a retrospective, cross-sectional, naturalistic study of 2377 patients (schizophrenia n=1243; unipolar depression n=791; bipolar disorder n=343, including bipolar depression n=259 and mania n=84). There were significant differences for PLT, MPV and P-LCR values between study groups. A significant percentage of patients with bipolar disorder had abnormal (too low or too high) number of platelets. Negative correlation between PLT and age was found in all study groups and positive correlation between age and MPV and P-LCR was found in patients with schizophrenia. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  9. Cost and performance prospects for composite bipolar plates in fuel cells and redox flow batteries

    NASA Astrophysics Data System (ADS)

    Minke, Christine; Hickmann, Thorsten; dos Santos, Antonio R.; Kunz, Ulrich; Turek, Thomas

    2016-02-01

    Carbon-polymer-composite bipolar plates (BPP) are suitable for fuel cell and flow battery applications. The advantages of both components are combined in a product with high electrical conductivity and good processability in convenient polymer forming processes. In a comprehensive techno-economic analysis of materials and production processes cost factors are quantified. For the first time a technical cost model for BPP is set up with tight integration of material characterization measurements.

  10. Test results of a ten cell bipolar nickel-hydrogen battery

    NASA Technical Reports Server (NTRS)

    Cataldo, R. L.

    1983-01-01

    A ten cell bipolar nickel hydrogen 6.5 ampere-hour battery demonstrated over 2000 low Earth orbit cycles at an 80 percent depth-of-discharge. Charge/discharge cyclic ampere-hour and watt-hour efficiencies of 88 and 76 percent, respectively, observed. Peak power capability was determined at 1.1 kW. A 10C discharge rate yields 83 percent of the nominal stark capacity to the 1.0 volt cut off in just under 6 minutes.

  11. Composite bipolar plate for electrochemical cells

    DOEpatents

    Wilson, Mahlon S.; Busick, Deanna N.

    2001-01-01

    A bipolar separator plate for fuel cells consists of a molded mixture of a vinyl ester resin and graphite powder. The plate serves as a current collector and may contain fluid flow fields for the distribution of reactant gases. The material is inexpensive, electrically conductive, lightweight, strong, corrosion resistant, easily mass produced, and relatively impermeable to hydrogen gas. The addition of certain fiber reinforcements and other additives can improve the properties of the composite material without significantly increasing its overall cost.

  12. Cytokinesis-Based Constraints on Polarized Cell Growth in Fission Yeast

    PubMed Central

    Bohnert, K. Adam; Gould, Kathleen L.

    2012-01-01

    The rod-shaped fission yeast Schizosaccharomyces pombe, which undergoes cycles of monopolar-to-bipolar tip growth, is an attractive organism for studying cell-cycle regulation of polarity establishment. While previous research has described factors mediating this process from interphase cell tips, we found that division site signaling also impacts the re-establishment of bipolar cell growth in the ensuing cell cycle. Complete loss or targeted disruption of the non-essential cytokinesis protein Fic1 at the division site, but not at interphase cell tips, resulted in many cells failing to grow at new ends created by cell division. This appeared due to faulty disassembly and abnormal persistence of the cell division machinery at new ends of fic1Δ cells. Moreover, additional mutants defective in the final stages of cytokinesis exhibited analogous growth polarity defects, supporting that robust completion of cell division contributes to new end-growth competency. To test this model, we genetically manipulated S. pombe cells to undergo new end take-off immediately after cell division. Intriguingly, such cells elongated constitutively at new ends unless cytokinesis was perturbed. Thus, cell division imposes constraints that partially override positive controls on growth. We posit that such constraints facilitate invasive fungal growth, as cytokinesis mutants displaying bipolar growth defects formed numerous pseudohyphae. Collectively, these data highlight a role for previous cell cycles in defining a cell's capacity to polarize at specific sites, and they additionally provide insight into how a unicellular yeast can transition into a quasi-multicellular state. PMID:23093943

  13. A transmission and scanning electron microscopic study of the saccule in five species of catfishes.

    PubMed

    Jenkins, D B

    1979-01-01

    The sacculi of five species of catfishes were studied by transmission and scanning electron microscopy. In four species, the sagitta exhibited a multifluted anterior part and a tapered posterior part; in Corydoras aeneus, however, the fluted part was absent, and a vertical component extended dorsally to terminate near the opening of the transverse canal. In all species, the otoliths had a laminar structure. An otolithic membrane was present, and hair cell bundles projected into cavities on the macular surface of the membrane. Attachments of the otolithic membrane to the neuroepithelium included short extensions of the membrane to the tallest components of the hair cell bundles of the peripheral cells and more delicate connections to the kinocilium and taller stereocilia of central cells; in addition, attachments to the microvilli of supporting cells were present. In both hair cells and supporting cells single microtubules and bundles of microtubules were present; the bundles had an orderly arrangement and were associated with cytoplasmic densities surrounding the desmosomes. The hair cells were innervated by both afferent and efferent nerve endings. Studies of the polarization of the hair cells in all species (except C. aeneus) showed that there was a single longitudinal axis that divided dorsally polarized cells from those oriented ventrally. In Doras spinosissimus and Bunocephalus bicolor, an additional line of polarization was evident in a small area in the anterior part of the macula; therefore, in these forms there was a double bipolar orientation.

  14. ON-retinal bipolar cell survival in RCS rats.

    PubMed

    Zhang, Chen Xing; Yin, Zheng Qin; Chen, Li-Feng; Weng, Chuang-Huang; Zeng, Yu-Xiao

    2010-11-01

    In retinitis pigmentosa (RP), the slow and progressive death of inner retinal neurons is thought to be inevitable after the death of photoreceptors. However, even in the advanced stage of RP, all inner retinal neurons are not completely lost. The morphological and electrophysiological modifications in ON-retinal bipolar cells (ON-RBCs) of Royal College of Surgeons (RCS) rats (RCS-ON-RBCs) were investigated to elucidate the mechanisms of survival of RCS-ON-RBCs in RP. Control (CTR) and RCS rats were divided into age groups according to postnatal stage: postnatal day 21 (Pn21d), postnatal day 30 (Pn30d), postnatal day 60 (Pn60d), and postnatal day 90 (Pn90d). Lucifer yellow staining of single ON-RBCs and double-immunofluorescence of the retinal frozen sections were used to detect the morphological modifications and loss of RCS-ON-RBCs in different retinal regions. The whole-cell patch clamping technique was used to record the electrophysiological properties of ON-RBCs. There was a significant loss of RCS-ON-RBCs compared with CTR (p < 0.01) at Pn60d. Loss of the RCS-ON-RBCs differed by region. From Pn60d onwards, the loss was more severe in the peripheral retinal regions (p < 0.01). From Pn21d, the ectopic neurites from the RCS-ON-RBCs reached the outer and inner nuclear layers. At Pn60d, terminal branches of RCS-ON-RBCs axons vanished and ectopic neurites from the RCS-ON-RBCs became entwined. The resting membrane potential, input resistance and outward membrane current amplitude of RCS-ON-RBCs were significantly higher than those of the ON-RBCs of CTR rats at Pn60d (p < 0.05). Our results indicate that more RCS-ON-RBCs survived in the central retinal area near cone clusters, potentially as a result of ectopic neuritis. Meanwhile the surviving RCS-ON-RBCs remained immature and had no normal electrophysiological characteristics.

  15. Mechanisms underlying the benefits of anticonvulsants over lithium in the treatment of bipolar disorder.

    PubMed

    Corrado, Alisa C; Walsh, John P

    2016-02-10

    Close to 3% of the world's population suffers from bipolar disease (I and II). Of this 3%, bipolar disease affects largely women (∼ 3 : 2 compared with men). The median age of diagnosis is 25 in women and even lower in men. A diagnosis of bipolar disease is an expensive psychiatric diagnosis, costing patients more than twice as much money as a diagnosis of unipolar depression. Bipolar I is characterized by one or more manic or mixed episodes, with both mania and depression occurring each day for at least 1 week, whereas bipolar II is characterized by one or more major depressive episode and at least one episode of hypomania. Bipolar I is the more severe diagnosis. A wide range of medications are available to help patients maintain a healthy lifestyle, including lithium, antidepressants, and anticonvulsants. Improved methods for identifying bipolar disease, including a more structured approach and a more complete use of medical records, have increased the rate of diagnosis, especially in children, which underscores the need for innovation in development and in practice of new treatment options for treating bipolar disease. Although lithium has been the 'gold standard' for treating bipolar disorder for decades, new research into other forms of treatment has shown anticonvulsants to be a particularly useful therapy for treating bipolar disease. Anticonvulsants have remarkable mood-stabilization abilities and they do not lead to serious side effects, which increases the tolerability, and consequently, patient adherence to this form of treatment. Recent studies have shown that anticonvulsants improve behavior in bipolar disease by modulating the balance of excitatory and inhibitory synapses through a number of complementary molecular cascades that affect gene expression and cell survival.

  16. Preparation of corrosion-resistant and conductive trivalent Cr-C coatings on 304 stainless steel for use as bipolar plates in proton exchange membrane fuel cells by electrodeposition

    NASA Astrophysics Data System (ADS)

    Wang, Hsiang-Cheng; Sheu, Hung-Hua; Lu, Chen-En; Hou, Kung-Hsu; Ger, Ming-Der

    2015-10-01

    In this study, Cr-C-coated bipolar plates are produced by electroplating on the SS304 plates with a machined flow channel. The resulting plates were tested using potentiodynamic and potentiostatic measurements in simulated PEMFC environments, which show that the bipolar plate coated with Cr-C exhibited good anticorrosion performance. The corrosive current density of the Cr-C coating formed for a plating time of 10 min for 10 h exhibits a low stable value of 1.51 × 10-10 A/cm2 during the potentiostatic test in a 0.5 M H2SO4 + 2 ppm HF solution at 70 °C with an air purge, indicating that the Cr-C coating plated for 10 min is stable in a cathode environment. The interfacial contact resistance (ICR) of the bipolar plate with the Cr-C coating clearly improved, presenting an ICR of 19.52 mΩ cm2 at a pressure of 138 N/cm2. The results from scanning electron microscopy (SEM) and ICR before and after the corrosion tests indicate that the bipolar plate with the Cr-C coating is electrochemically stable. In this study, the maximum power density (212.41 mW/cm2) is obtained at a cell temperature of 80 °C and a gas flow rate of 300 standard cubic centimeters per minute (sccm) when Cr-C coated SS304 bipolar plates were used.

  17. Energy Storage in a fuel cell with bipolar membranes burning acid and hydroxide

    NASA Astrophysics Data System (ADS)

    Emren, A. T.; Holmstrom, V. J. M.

    1983-04-01

    A battery is described, in which bipolar membranes are used to split water into acid and hydroxide. The liquids may be stored for an indefinite time, and energy may be recovered at room temperature. It is shown that the liquids are able to store about 400 kJ/litre, which roughly corresponds to pumping water up to an altitude of 40 km. Bipolar membranes of low area resistance have been made and tested. The area resistance appears to have been 2-3 ohm sq cm. A battery containing 7 unit cells has been constructed and tested. The maximum output voltage has been 1.8 V. The cost for enrgy storage is estimated to range from $0.1 to 2.5 per kWh depending on the mode of operation.

  18. Surface modification by carbon ion implantation for the application of ni-based amorphous alloys as bipolar plate in proton exchange membrane fuel cells

    NASA Astrophysics Data System (ADS)

    Kim, Min-Uk; Kim, Do-Hyang; Han, Seung-hee; Fleury, Eric; Seok, Hyun-Kwang; Cha, Pil-Ryung; Kim, Yu-Chan

    2011-04-01

    Ni-based amorphous alloys with surface modification by carbon ion implantation are proposed as an alternative bipolar plate material for polymer electrolyte membrane fuel cells (PEMFCs). Both Ni60Nb20Ti10Zr10 alloys with and without carbon ion implantation have corrosion resistance as good as graphite as well as much lower contact resistance than 316L stainless steel in the PEMFC environment. The formation of conductive surface carbide due to carbon ion implantation results in a decrease in the contact resistance to a level comparable to that of graphite. This combination of excellent properties indicates that carbon ion implanted Ni-based amorphous alloys can be potential candidate materials for bipolar plates in PEMFCs.

  19. Development of fuel cell bipolar plates from graphite filled wet-lay thermoplastic composite materials

    NASA Astrophysics Data System (ADS)

    Huang, Jianhua; Baird, Donald G.; McGrath, James E.

    A method with the potential to produce economical bipolar plates with high electrical conductivity and mechanical properties is described. Thermoplastic composite materials consisting of graphite particles, thermoplastic fibers and glass or carbon fibers are generated by means of a wet-lay (paper-making) process to yield highly formable sheets. The sheets are then stacked and compression molded to form bipolar plates with gas flow channels. Poly(phenylene sulfide) (PPS) based wet-lay composite plates have in-plane conductivity of 200-300 S cm -1, tensile strength of 57 MPa, flexural strength of 96 MPa and impact strength (unnotched) of 81 J m -1 (1.5 ft-lb in. -1). These values well exceed industrial as well as Department of Energy requirements or targets and have never been reached before for composite bipolar plates. The use of wet-lay sheets also makes it possible to choose different components including polymer, graphite particle and reinforcement for the core and outer layers of the plate, respectively, to optimize the properties and/or reduce the cost of the plate. The through-plane conductivity (around 20 S cm -1) and half-cell resistance of the bipolar plate indicate that the through-plane conductivity of the material needs some improvement.

  20. Modification of Pulsed Electric Field Conditions Results in Distinct Activation Profiles of Platelet-Rich Plasma.

    PubMed

    Frelinger, Andrew L; Gerrits, Anja J; Garner, Allen L; Torres, Andrew S; Caiafa, Antonio; Morton, Christine A; Berny-Lang, Michelle A; Carmichael, Sabrina L; Neculaes, V Bogdan; Michelson, Alan D

    2016-01-01

    Activated autologous platelet-rich plasma (PRP) used in therapeutic wound healing applications is poorly characterized and standardized. Using pulsed electric fields (PEF) to activate platelets may reduce variability and eliminate complications associated with the use of bovine thrombin. We previously reported that exposing PRP to sub-microsecond duration, high electric field (SMHEF) pulses generates a greater number of platelet-derived microparticles, increased expression of prothrombotic platelet surfaces, and differential release of growth factors compared to thrombin. Moreover, the platelet releasate produced by SMHEF pulses induced greater cell proliferation than plasma. To determine whether sub-microsecond duration, low electric field (SMLEF) bipolar pulses results in differential activation of PRP compared to SMHEF, with respect to profiles of activation markers, growth factor release, and cell proliferation capacity. PRP activation by SMLEF bipolar pulses was compared to SMHEF pulses and bovine thrombin. PRP was prepared using the Harvest SmartPreP2 System from acid citrate dextrose anticoagulated healthy donor blood. PEF activation by either SMHEF or SMLEF pulses was performed using a standard electroporation cuvette preloaded with CaCl2 and a prototype instrument designed to take into account the electrical properties of PRP. Flow cytometry was used to assess platelet surface P-selectin expression, and annexin V binding. Platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), endothelial growth factor (EGF) and platelet factor 4 (PF4), and were measured by ELISA. The ability of supernatants to stimulate proliferation of human epithelial cells in culture was also evaluated. Controls included vehicle-treated, unactivated PRP and PRP with 10 mM CaCl2 activated with 1 U/mL bovine thrombin. PRP activated with SMLEF bipolar pulses or thrombin had similar light scatter profiles, consistent with the presence of platelet-derived microparticles, platelets, and platelet aggregates whereas SMHEF pulses primarily resulted in platelet-derived microparticles. Microparticles and platelets in PRP activated with SMLEF bipolar pulses had significantly lower annexin V-positivity than those following SMHEF activation. In contrast, the % P-selectin positivity and surface P-selectin expression (MFI) for platelets and microparticles in SMLEF bipolar pulse activated PRP was significantly higher than that in SMHEF-activated PRP, but not significantly different from that produced by thrombin activation. Higher levels of EGF were observed following either SMLEF bipolar pulses or SMHEF pulses of PRP than after bovine thrombin activation while VEGF, PDGF, and PF4 levels were similar with all three activating conditions. Cell proliferation was significantly increased by releasates of both SMLEF bipolar pulse and SMHEF pulse activated PRP compared to plasma alone. PEF activation of PRP at bipolar low vs. monopolar high field strength results in differential platelet-derived microparticle production and activation of platelet surface procoagulant markers while inducing similar release of growth factors and similar capacity to induce cell proliferation. Stimulation of PRP with SMLEF bipolar pulses is gentler than SMHEF pulses, resulting in less platelet microparticle generation but with overall activation levels similar to that obtained with thrombin. These results suggest that PEF provides the means to alter, in a controlled fashion, PRP properties thereby enabling evaluation of their effects on wound healing and clinical outcomes.

  1. Energy storage considerations for a robotic Mars surface sampler

    NASA Technical Reports Server (NTRS)

    O'Donnell, P. M.; Cataldo, R. L.; Gonzalez-Sanabria, O. D.

    1988-01-01

    The characteristics of various energy storage systems (including Ni-Cd, Ni-H2, Ag-Zn, Li-XS, Na-S, PbSO4, and regenerative fuel cell systems) considered for a robotic Mars surface sampler are reviewed. It is concluded that the bipolar nickel-hydrogen battery and the sodium-sulfur battery are both viable candidates as storage systems for the rover's Radioisotope Thermoelectric Generator. For a photovoltaic storage system, the regenerative fuel cell and the bipolar nickel-hydrogen battery are the primary candidates.

  2. Test results of a ten cell bipolar nickel-hydrogen battery

    NASA Technical Reports Server (NTRS)

    Cataldo, R. L.

    1983-01-01

    A ten cell bipolar nickel hydrogen 6.5 ampere-hour battery demonstrated over 2000 low earth orbit cycles at an 80 percent depth-of-discharge. Charge/discharge cyclic ampere-hour and watt-hour efficiencies of 88 and 76 percent, respectively, observed. Peak power capability was determined at 1.1 kW. A 10C discharge rate yields 83 percent of the nominal stark capacity to the 1.0 volt cut off in just under 6 minutes. Previously announced in STAR as N83-26253

  3. Bipolar Spintronics: From magnetic diodes to magnetic bipolar transistors

    NASA Astrophysics Data System (ADS)

    Zutic, Igor

    2004-03-01

    We develop a theory of bipolar (electrons and holes) spin-polarized transport [1,2] in semiconductors and discuss its implications for spintronic devices [3]. In our proposal for magnetic bipolar transistors [4,5] we show how bipolar spintronics can lead to spin and magnetic field controlled active devices, not limited by the magnetoresistive effects used in all-metallic structures [3]. We focus on magnetic p-n diodes [1,2] with spatially dependent spin splitting (Zeeman or exchange) of carrier bands. An exchange splitting can be provided by ferromagnetic semiconductors [6], while a large Zeeman splitting can be realized in the presence of magnetic field in magnetically doped or narrow band gap semiconductors [3]. Our theory of magnetic diodes [1,2] can be directly applied to magnetic bipolar transistors--the three-terminal devices which consist of two magnetic p-n diodes connected in series [4,5]. Predictions of exponentially large magnetoresistance [1] and a strong coupling between the spin and charge transport leading to the spin-voltaic effect [1,7] for magnetic diodes are also relevant for magnetic bipolar transistors. In particular, in n-p-n transistors, we show the importance of considering the nonequilibrium spin leading to the spin-voltaic effect. In addition to the applied magnetic filed, the injected nonequilibrium spin can be used to dynamically control the current amplification (gain). Recent experimental progress [8,9] supports the viability of our theoretical proposals. [1] I. Zutic, J. Fabian, S. Das Sarma, Phys. Rev. Lett. 88, 066603 (2002). [2] J. Fabian, I. Zutic, S. Das Sarma, Phys. Rev. B 66, 165301 (2002). [3] I. Zutic, J. Fabian, S. Das Sarma, Rev. Mod. Phys., in press. [4] J. Fabian, I. Zutic, S. Das Sarma, cond-mat/0211639; cond-mat/0307014, Appl. Phys. Lett., in press. [5] J. Fabian and I. Zutic, cond-mat/0311456. [6] H. Ohno, Science 281, 951 (1998). [7] I. Zutic, J. Fabian, S. Das Sarma, Appl. Phys. Lett. 82, 221 (2003). [8] N. Samarth, S. H. Chun, K. C. Ku, S. J. Potashnik, P. Schiffer, Solid State Commun. 127, 173 (2003). [9] F. Tsui, L. Ma, L. He, Appl. Phys. 83, 954 (2003).

  4. Bipolar radiofrequency ablation of the kidney: comparison with monopolar radiofrequency ablation.

    PubMed

    Nakada, Stephen Y; Jerde, Travis J; Warner, Thomas F; Wright, Andrew S; Haemmerich, Dieter; Mahvi, David M; Lee, Fred T

    2003-12-01

    We report initial ex vivo and in vivo studies using bipolar radiofrequency (RF) ablation of porcine kidneys. An internal ground electrode is positioned in the kidney opposite the RF electrode, resulting in ablation of all the intervening renal tissue. Ex vivo preparations of 10 porcine kidneys were perfused continuously with Ringer's solution and treated with either standard external grounded RF (N = 3) or bipolar RF ablation with 1 (N = 2), 2 (N = 3), or 3 (N = 2) cm of separation between the ground probe and the RF probe using a Model 30 RITA generator (RITA, Mountain View, CA). Target temperatures were 90 degrees C for 8 minutes. Gross and histologic assessments were made acutely. Four domestic pigs were treated with monopolar RF ablation of the lower pole of one kidney and bipolar RF with a 12-mm separation between the probes of the contralateral lower pole. Animals were harvested 48 hours later to maximize tissue damage for gross measurements and histologic evaluation. Ex vivo studies revealed grossly monopolar lesions 1.5 cm in maximum diameter and 1.75 cm(3) in volume. In comparison, bipolar lesions were 2.8 cm in maximum diameter and 10.3 cm(3) in volume using 3 cm of electrode separation. There was histologic evidence of cell death in all specimens. In vivo studies showed two distinct gross lesions with RF: one blanched and one hemorrhagic. Using bipolar RF, larger blanched lesions were achievable than with monopolar RF (2.80 cm(3) v 1.63 cm(3)). Overall, the combinations of blanched and hemorrhagic lesions were similar with monopolar and bipolar RF (5.01 v 5.31 cm(3)). Histologic evaluation verified cell death in the blanched lesions and rare areas of normal tissue in the hemorrhagic lesions. As shown by ex vivo data, bipolar RF can create larger lesions than does monopolar RF. In vivo, at 48 hours, both blanched and hemorrhagic gross lesions were seen using RF. In this model, blanched lesions predominated when performing bipolar RF.

  5. Electrochemical Device Comprising Composite Bipolar Plate and Method of Using the Same

    NASA Technical Reports Server (NTRS)

    Mittelsteadt, Cortney K. (Inventor); Braff, William A. (Inventor)

    2013-01-01

    An electrochemical device and methods of using the same. In one embodiment, the electrochemical device may be used as a fuel cell and/or as an electrolyzer and includes a membrane electrode assembly (MEA), an anodic gas diffusion medium in contact with the anode of the MEA, a cathodic gas diffusion medium in contact with the cathode, a first bipolar plate in contact with the anodic gas diffusion medium, and a second bipolar plate in contact with the cathodic gas diffusion medium. Each of the bipolar plates includes an electrically-conductive, chemically-inert, non-porous, liquid-permeable, substantially gas-impermeable membrane in contact with its respective gas diffusion medium, as well as a fluid chamber and a non-porous an electrically-conductive plate.

  6. Electrochemical Device Comprising Composite Bipolar Plate and Method of Using the Same

    NASA Technical Reports Server (NTRS)

    Mittelsteadt, Cortney K. (Inventor); Braff, William A. (Inventor)

    2017-01-01

    An electrochemical device and methods of using the same. In one embodiment, the electrochemical device may be used as a fuel cell and/or as an electrolyzer and includes a membrane electrode assembly (MEA), an anodic gas diffusion medium in contact with the anode of the MEA, a cathodic gas diffusion medium in contact with the cathode, a first bipolar plate in contact with the anodic gas diffusion medium, and a second bipolar plate in contact with the cathodic gas diffusion medium. Each of the bipolar plates includes an electrically-conductive, chemically-inert, non-porous, liquid-permeable, substantially gas-impermeable membrane in contact with its respective gas diffusion medium, as well as a fluid chamber and a non-porous an electrically-conductive plate.

  7. High power bipolar battery/cells with enhanced overcharge tolerance

    DOEpatents

    Kaun, T.D.

    1998-04-07

    A cell or battery of cells having improved overcharge tolerance and increased power capability, and methods for the construction of such cells or batteries, via electrolyte modification, are described. 5 figs.

  8. Scale-up of Carbon/Carbon Bipolar Plates

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    David P. Haack

    2009-04-08

    This project was focused upon developing a unique material technology for use in PEM fuel cell bipolar plates. The carbon/carbon composite material developed in this program is uniquely suited for use in fuel cell systems, as it is lightweight, highly conductive and corrosion resistant. The project further focused upon developing the manufacturing methodology to cost-effectively produce this material for use in commercial fuel cell systems. United Technology Fuel Cells Corp., a leading fuel cell developer was a subcontractor to the project was interested in the performance and low-cost potential of the material. The accomplishments of the program included the developmentmore » and testing of a low-cost, fully molded, net-shape carbon-carbon bipolar plate. The process to cost-effectively manufacture these carbon-carbon bipolar plates was focused on extensively in this program. Key areas for cost-reduction that received attention in this program was net-shape molding of the detailed flow structures according to end-user design. Correlations between feature detail and process parameters were formed so that mold tooling could be accurately designed to meet a variety of flow field dimensions. A cost model was developed that predicted the cost of manufacture for the product in near-term volumes and long-term volumes (10+ million units per year). Because the roduct uses lowcost raw materials in quantities that are less than competitive tech, it was found that the cost of the product in high volume can be less than with other plate echnologies, and can meet the DOE goal of $4/kW for transportation applications. The excellent performance of the all-carbon plate in net shape was verified in fuel cell testing. Performance equivalent to much higher cost, fully machined graphite plates was found.« less

  9. [Case report of melanoma-associated retinopathy associated with positive auto-antibodies against retinal bipolar cells].

    PubMed

    Hanaya, Junko; Nakamura, Yasuko; Nejima, Ryouhei; Miyata, Kazunori; Mera, Kentarou; Ohguro, Hiroshi; Yamamoto, Shuichi

    2011-06-01

    We report a case of melanoma-associated retinopathy (MAR) associated with positive auto-antibodies against retinal bipolar cells, which has been rarely reported in Japan. A 33 year-old woman noticed shimmering vision, photopsias, blurred vision, and night blindness OS in April 2009, and visited Kagoshima Miyata Eye Clinic in May 2009. She had been continuously treated for malignant melanoma on her left finger since 2007. At her initial visit, the corrected visual acuity was 1.5 OD and 1.2 OS, and slit-lamp examination revealed clear ocular media OU. Funduscopic examination showed normal appearance of the retina OU, except for a mild narrowing of the retinal arteries OS. Humphrey field analyzer revealed a reduction of retinal sensitivity within the central 30 degrees OS. The maximum left eye response of electroretinogram (ERG) showed a negative waveform. The immuno-cytochemical test revealed antibodies against retinal bipolar cells, which confirmed the diagnosis of MAR. Characteristic subjective symptoms, Humphrey field analyzer and ERG are useful for the diagnosis of MAR.

  10. Bipolar nickel-hydrogen battery design

    NASA Technical Reports Server (NTRS)

    Koehler, C. W.; Applewhite, A. Z.; Kuo, Y.

    1985-01-01

    The initial design for the NASA-Lewis advanced nickel-hydrogen battery is discussed. Fabrication of two 10-cell boilerplate battery stacks will soon begin. The test batteries will undergo characterization testing and low Earth orbit life cycling. The design effectively deals with waste heat generated in the cell stack. Stack temperatures and temperature gradients are maintained to acceptable limits by utilizing the bipolar conduction plate as a heat path to the active cooling fluid panel external to the edge of the cell stack. The thermal design and mechanical design of the battery stack together maintain a materials balance within the cell. An electrolyte seal on each cell frame prohibits electrolyte bridging. An oxygen recombination site and electrolyte reservoir/separator design does not allow oxygen to leave the cell in which it was generated.

  11. Meta-analysis of erythrocyte polyunsaturated fatty acid biostatus in bipolar disorder.

    PubMed

    McNamara, Robert K; Welge, Jeffrey A

    2016-05-01

    Dietary deficiency in polyunsaturated fatty acids (PUFAs), including the omega-3 fatty acids eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3), and excesses in omega-6 fatty acids, including linoleic acid (LA; 18:2n-6) and arachidonic acid (AA; 20:4n-6), may be associated with the pathophysiology of bipolar disorder. In an effort to provide clarification regarding the relationship between PUFA biostatus and bipolar disorder, this meta-analysis investigated studies comparing erythrocyte (red blood cell) membrane PUFA composition in patients with bipolar disorder and healthy controls. A meta-analysis was performed on case-control studies comparing erythrocyte PUFA (EPA, DHA, LA and AA) levels in patients with bipolar I disorder and healthy controls. Standardized effect sizes were calculated and combined using a random effects model. Six eligible case-control studies comprising n = 118 bipolar I patients and n = 147 healthy controls were included in the analysis. Compared with healthy controls, patients with bipolar I disorder exhibited robust erythrocyte DHA deficits (p = 0.0008) and there was a trend for lower EPA (p = 0.086). There were no significant differences in LA (p = 0.42) or AA (p = 0.64). Bipolar I disorder is associated with robust erythrocyte DHA deficits. These findings add to a growing body of evidence implicating omega-3 PUFA deficiency in the pathophysiology of bipolar disorder. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  12. The Neural Circuit Mechanisms Underlying the Retinal Response to Motion Reversal

    PubMed Central

    Chen, Eric Y.; Chou, Janice; Park, Jeongsook; Schwartz, Greg

    2014-01-01

    To make up for delays in visual processing, retinal circuitry effectively predicts that a moving object will continue moving in a straight line, allowing retinal ganglion cells to anticipate the object's position. However, a sudden reversal of motion triggers a synchronous burst of firing from a large group of ganglion cells, possibly signaling a violation of the retina's motion prediction. To investigate the neural circuitry underlying this response, we used a combination of multielectrode array and whole-cell patch recordings to measure the responses of individual retinal ganglion cells in the tiger salamander to reversing stimuli. We found that different populations of ganglion cells were responsible for responding to the reversal of different kinds of objects, such as bright versus dark objects. Using pharmacology and designed stimuli, we concluded that ON and OFF bipolar cells both contributed to the reversal response, but that amacrine cells had, at best, a minor role. This allowed us to formulate an adaptive cascade model (ACM), similar to the one previously used to describe ganglion cell responses to motion onset. By incorporating the ON pathway into the ACM, we were able to reproduce the time-varying firing rate of fast OFF ganglion cells for all experimentally tested stimuli. Analysis of the ACM demonstrates that bipolar cell gain control is primarily responsible for generating the synchronized retinal response, as individual bipolar cells require a constant time delay before recovering from gain control. PMID:25411485

  13. Mechanisms creating transient and sustained photoresponses in mammalian retinal ganglion cells

    PubMed Central

    Zhao, Xiwu; Jaeckel, Elizabeth R.; Chervenak, Andrew P.

    2017-01-01

    Retinal neurons use sustained and transient light responses to encode visual stimuli of different frequency ranges, but the underlying mechanisms remain poorly understood. In particular, although earlier studies in retinal ganglion cells (RGCs) proposed seven potential mechanisms, all seven have since been disputed, and it remains unknown whether different RGC types use different mechanisms or how many mechanisms are used by each type. Here, we conduct a comprehensive survey in mice and rats of 12 candidate mechanisms that could conceivably produce tonic rod/cone-driven ON responses in intrinsically photosensitive RGCs (ipRGCs) and transient ON responses in three types of direction-selective RGCs (TRHR+, Hoxd10+ ON, and Hoxd10+ ON-OFF cells). We find that the tonic kinetics of ipRGCs arises from their substantially above-threshold resting potentials, input from sustained ON bipolar cells, absence of amacrine cell inhibition of presynaptic ON bipolar cells, and mGluR7-mediated maintenance of light-evoked glutamatergic input. All three types of direction-selective RGCs receive input from transient ON bipolar cells, and each type uses additional strategies to promote photoresponse transience: presynaptic inhibition and dopaminergic modulation for TRHR+ cells, center/surround antagonism and relatively negative resting potentials for Hoxd10+ ON cells, and presynaptic inhibition for Hoxd10+ ON-OFF cells. We find that the sustained nature of ipRGCs’ rod/cone-driven responses depends neither on melanopsin nor on N-methyl-d-aspartate (NMDA) receptors, whereas the transience of the direction-selective cells’ responses is influenced neither by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)/kainate receptor desensitization nor by glutamate uptake. For all cells, we further rule out spike frequency adaptation and intracellular Ca2+ as determinants of photoresponse kinetics. In conclusion, different RGC types use diverse mechanisms to produce sustained or transient light responses. Parenthetically, we find evidence in both mice and rats that the kinetics of light-induced mGluR6 deactivation determines whether an ON bipolar cell responds tonically or transiently to light. PMID:28153865

  14. Design of a 1-kWh bipolar nickel hydrogen battery

    NASA Technical Reports Server (NTRS)

    Cataldo, R. L.

    1984-01-01

    The design of a nickel hydrogen battery utilizing bipolar construction in a common pressure vessel is discussed. Design features are as follows: 40 ampere-hour capcity, 1 kWh stored energy as a 24 cell battery, 1.8 kW delivered in a LEO Cycle and maximum pulse power of 18.0 kW.

  15. Identification of Susceptible Loci and Enriched Pathways for Bipolar II Disorder Using Genome-Wide Association Studies.

    PubMed

    Kao, Chung-Feng; Chen, Hui-Wen; Chen, Hsi-Chung; Yang, Jenn-Hwai; Huang, Ming-Chyi; Chiu, Yi-Hang; Lin, Shih-Ku; Lee, Ya-Chin; Liu, Chih-Min; Chuang, Li-Chung; Chen, Chien-Hsiun; Wu, Jer-Yuarn; Lu, Ru-Band; Kuo, Po-Hsiu

    2016-12-01

    This study aimed to identify susceptible loci and enriched pathways for bipolar disorder subtype II. We conducted a genome-wide association scan in discovery samples with 189 bipolar disorder subtype II patients and 1773 controls, and replication samples with 283 bipolar disorder subtype II patients and 500 controls in a Taiwanese Han population using Affymetrix Axiom Genome-Wide CHB1 Array. We performed single-marker and gene-based association analyses, as well as calculated polygeneic risk scores for bipolar disorder subtype II. Pathway enrichment analyses were employed to reveal significant biological pathways. Seven markers were found to be associated with bipolar disorder subtype II in meta-analysis combining both discovery and replication samples (P<5.0×10 -6 ), including markers in or close to MYO16, HSP90AB3P, noncoding gene LOC100507632, and markers in chromosomes 4 and 10. A novel locus, ETF1, was associated with bipolar disorder subtype II (P<6.0×10 -3 ) in gene-based association tests. Results of risk evaluation demonstrated that higher genetic risk scores were able to distinguish bipolar disorder subtype II patients from healthy controls in both discovery (P=3.9×10 -4 ~1.0×10 -3 ) and replication samples (2.8×10 -4 ~1.7×10 -3 ). Genetic variance explained by chip markers for bipolar disorder subtype II was substantial in the discovery (55.1%) and replication (60.5%) samples. Moreover, pathways related to neurodevelopmental function, signal transduction, neuronal system, and cell adhesion molecules were significantly associated with bipolar disorder subtype II. We reported novel susceptible loci for pure bipolar subtype II disorder that is less addressed in the literature. Future studies are needed to confirm the roles of these loci for bipolar disorder subtype II. © The Author 2016. Published by Oxford University Press on behalf of CINP.

  16. A 37.5-kW point design comparison of the nickel-cadmium battery, bipolar nickel-hydrogen battery, and regenerative hydrogen-oxygen fuel cell energy storage subsystems for low earth orbit

    NASA Technical Reports Server (NTRS)

    Manzo, M. A.; Hoberecht, M. A.

    1984-01-01

    Nickel-cadmium batteries, bipolar nickel-hydrogen batteries, and regenerative fuel cell storage subsystems were evaluated for use as the storage subsystem in a 37.5 kW power system for Space Station. Design requirements were set in order to establish a common baseline for comparison purposes. The storage subsystems were compared on the basis of effective energy density, round trip electrical efficiency, total subsystem weight and volume, and life.

  17. A 37.5-kW point design comparison of the nickel-cadmium battery, bipolar nickel-hydrogen battery, and regenerative hydrogen-oxygen fuel cell energy storage subsystems for low Earth orbit

    NASA Technical Reports Server (NTRS)

    Manzo, M. A.; Hoberecht, M. A.

    1984-01-01

    Nickel-cadmium batteries, bipolar nickel-hydrogen batteries, and regenerative fuel cell storage subsystems were evaluated for use as the storage subsystem in a 37.5 kW power system for space station. Design requirements were set in order to establish a common baseline for comparison purposes. The storage subsystems were compared on the basis of effective energy density, round trip electrical efficiency, total subsystem weight and volume, and life.

  18. Memristors in the electrical network of Aloe vera L.

    PubMed Central

    Volkov, Alexander G; Reedus, Jada; Mitchell, Colee M; Tucket, Clayton; Forde-Tuckett, Victoria; Volkova, Maya I; Markin, Vladislav S; Chua, Leon

    2014-01-01

    A memristor is a resistor with memory, which is a non-linear passive two-terminal electrical element relating magnetic flux linkage and electrical charge. Here we found that memristors exist in vivo. The electrostimulation of the Aloe vera by bipolar sinusoidal or triangle periodic waves induce electrical responses with fingerprints of memristors. Uncouplers carbonylcyanide-3-chlorophenylhydrazone and carbonylcyanide-4-trifluoromethoxy-phenyl hydrazone decrease the amplitude of electrical responses at low and high frequencies of bipolar periodic sinusoidal or triangle electrostimulating waves. Memristive behavior of an electrical network in the Aloe vera is linked to the properties of voltage gated ion channels: the K+ channel blocker TEACl reduces the electric response to a conventional resistor. Our results demonstrate that a voltage gated K+ channel in the excitable tissue of plants has properties of a memristor. The discovery of memristors in plants creates a new direction in the modeling and understanding of electrical phenomena in plants. PMID:25763487

  19. Intercentrosomal angular separation during mitosis plays a crucial role for maintaining spindle stability

    NASA Astrophysics Data System (ADS)

    Sutradhar, S.; Basu, S.; Paul, R.

    2015-10-01

    Cell division through proper spindle formation is one of the key puzzles in cell biology. In most mammalian cells, chromosomes spontaneously arrange to achieve a stable bipolar spindle during metaphase which eventually ensures proper segregation of the DNA into the daughter cells. In this paper, we present a robust three-dimensional mechanistic model to investigate the formation and maintenance of a bipolar mitotic spindle in mammalian cells under different physiological constraints. Using realistic parameters, we test spindle viability by measuring the spindle length and studying the chromosomal configuration. The model strikingly predicts a feature of the spindle instability arising from the insufficient intercentrosomal angular separation and impaired sliding of the interpolar microtubules. In addition, our model successfully reproduces chromosomal patterns observed in mammalian cells, when activity of different motor proteins is perturbed.

  20. Stereotyped Synaptic Connectivity Is Restored during Circuit Repair in the Adult Mammalian Retina.

    PubMed

    Beier, Corinne; Palanker, Daniel; Sher, Alexander

    2018-06-04

    Proper function of the central nervous system (CNS) depends on the specificity of synaptic connections between cells of various types. Cellular and molecular mechanisms responsible for the establishment and refinement of these connections during development are the subject of an active area of research [1-6]. However, it is unknown if the adult mammalian CNS can form new type-selective synapses following neural injury or disease. Here, we assess whether selective synaptic connections can be reestablished after circuit disruption in the adult mammalian retina. The stereotyped circuitry at the first synapse in the retina, as well as the relatively short distances new neurites must travel compared to other areas of the CNS, make the retina well suited to probing for synaptic specificity during circuit reassembly. Selective connections between short-wavelength sensitive cone photoreceptors (S-cones) and S-cone bipolar cells provides the foundation of the primordial blue-yellow vision, common to all mammals [7-18]. We take advantage of the ground squirrel retina, which has a one-to-one S-cone-to-S-cone-bipolar-cell connection, to test if this connectivity can be reestablished following local photoreceptor loss [8, 19]. We find that after in vivo selective photoreceptor ablation, deafferented S-cone bipolar cells expand their dendritic trees. The new dendrites randomly explore the proper synaptic layer, bypass medium-wavelength sensitive cone photoreceptors (M-cones), and selectively synapse with S-cones. However, non-connected dendrites are not pruned back to resemble unperturbed S-cone bipolar cells. We show, for the first time, that circuit repair in the adult mammalian retina can recreate stereotypic selective wiring. Copyright © 2018 Elsevier Ltd. All rights reserved.

  1. Temperament in the clinical differentiation of depressed bipolar and unipolar major depressive patients.

    PubMed

    Mendlowicz, Mauro V; Akiskal, Hagop S; Kelsoe, John R; Rapaport, Mark H; Jean-Louis, Girardin; Gillin, J Christian

    2005-02-01

    To examine differences in temperament profiles between patients with recurrent unipolar and bipolar depression. Depressed individuals with recurrent major depressive disorder (MDD) (n = 94) and those with bipolar (n = 59) disorders (about equally divided between types I and II) were recruited by newspaper advertisement, radio and television announcements, flyers and newsletters, and word of mouth. All patients were interviewed using the Structured Clinical Interview for DSM III-R (SCID) and had the severity of their depressive episode assessed by means of the 17-item Hamilton Rating Scale for Depression. All patients filled out the TEMPS-A, a validated instrument. Temperament differences between bipolar and MDD patients were examined using MANCOVA. Overall significant effect of the fixed factor (bipolar vs. unipolar) was noted for the temperament scores [Hotelling's F((5,142)) = 2.47, p < 0.05]. Overall effects were found for age [F((5,142)) = 2.40, p < 0.05], but not for gender and severity of depression [F((5,142)) = 1.65, p = 0.15 and F((5,142)) = 0.66, p = 0.66, respectively]. Dependent variables included the five subscales of the TEMPS-A, but only the cyclothymic temperament scores showed significant between-group differences. Small bipolar subsample cell sizes did not permit to test the specificity of the findings for bipolar II vs. bipolar I patients. The finding that the clyclothymic subscale is significantly elevated in the bipolar vs. the unipolar depressive group supports the theoretical assumptions upon which the scale is based, and suggests that it might become a useful tool for clinical and research purposes.

  2. Integral gas seal for fuel cell gas distribution assemblies and method of fabrication

    DOEpatents

    Dettling, Charles J.; Terry, Peter L.

    1985-03-19

    A porous gas distribution plate assembly for a fuel cell, such as a bipolar assembly, includes an inner impervious region wherein the bipolar assembly has good surface porosity but no through-plane porosity and wherein electrical conductivity through the impervious region is maintained. A hot-pressing process for forming the bipolar assembly includes placing a layer of thermoplastic sealant material between a pair of porous, electrically conductive plates, applying pressure to the assembly at elevated temperature, and allowing the assembly to cool before removing the pressure whereby the layer of sealant material is melted and diffused into the porous plates to form an impervious bond along a common interface between the plates holding the porous plates together. The distribution of sealant within the pores along the surface of the plates provides an effective barrier at their common interface against through-plane transmission of gas.

  3. Method of fabricating an integral gas seal for fuel cell gas distribution assemblies

    DOEpatents

    Dettling, Charles J.; Terry, Peter L.

    1988-03-22

    A porous gas distribution plate assembly for a fuel cell, such as a bipolar assembly, includes an inner impervious region wherein the bipolar assembly has good surface porosity but no through-plane porosity and wherein electrical conductivity through the impervious region is maintained. A hot-pressing process for forming the bipolar assembly includes placing a layer of thermoplastic sealant material between a pair of porous, electrically conductive plates, applying pressure to the assembly at elevated temperature, and allowing the assembly to cool before removing the pressure whereby the layer of sealant material is melted and diffused into the porous plates to form an impervious bond along a common interface between the plates holding the porous plates together. The distribution of sealant within the pores along the surface of the plates provides an effective barrier at their common interface against through-plane transmission of gas.

  4. Disease signatures for schizophrenia and bipolar disorder using patient-derived induced pluripotent stem cells.

    PubMed

    Watmuff, Bradley; Berkovitch, Shaunna S; Huang, Joanne H; Iaconelli, Jonathan; Toffel, Steven; Karmacharya, Rakesh

    2016-06-01

    Schizophrenia and bipolar disorder are complex psychiatric disorders that present unique challenges in the study of disease biology. There are no objective biological phenotypes for these disorders, which are characterized by complex genetics and prominent roles for gene-environment interactions. The study of the neurobiology underlying these severe psychiatric disorders has been hindered by the lack of access to the tissue of interest - neurons from patients. The advent of reprogramming methods that enable generation of induced pluripotent stem cells (iPSCs) from patient fibroblasts and peripheral blood mononuclear cells has opened possibilities for new approaches to study relevant disease biology using iPSC-derived neurons. While early studies with patient iPSCs have led to promising and intriguing leads, significant hurdles remain in our attempts to capture the complexity of these disorders in vitro. We present here an overview of studies to date of schizophrenia and bipolar disorder using iPSC-derived neuronal cells and discuss potential future directions that can result in the identification of robust and valid cellular phenotypes that in turn can lay the groundwork for meaningful clinical advances. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Nanosecond bipolar pulse generators for bioelectrics.

    PubMed

    Xiao, Shu; Zhou, Chunrong; Yang, Enbo; Rajulapati, Sambasiva R

    2018-04-26

    Biological effects caused by a nanosecond pulse, such as cell membrane permeabilization, peripheral nerve excitation and cell blebbing, can be reduced or cancelled by applying another pulse of reversed polarity. Depending on the degree of cancellation, the pulse interval of these two pulses can be as long as dozens of microseconds. The cancellation effect diminishes as the pulse duration increases. To study the cancellation effect and potentially utilize it in electrotherapy, nanosecond bipolar pulse generators must be made available. An overview of the generators is given in this paper. A pulse forming line (PFL) that is matched at one end and shorted at the other end allows a bipolar pulse to be produced, but no delay can be inserted between the phases. Another generator employs a combination of a resistor, an inductor and a capacitor to form an RLC resonant circuit so that a bipolar pulse with a decaying magnitude can be generated. A third generator is a converter, which converts an existing unipolar pulse to a bipolar pulse. This is done by inserting an inductor in a transmission line. The first phase of the bipolar pulse is provided by the unipolar pulse's rising phase. The second phase is formed during the fall time of the unipolar pulse, when the inductor, which was previously charged during the flat part of the unipolar pulse, discharges its current to the load. The fourth type of generator uses multiple MOSFET switches stacked to turn on a pre-charged, bipolar RC network. This approach is the most flexible in that it can generate multiphasic pulses that have different amplitudes, delays, and durations. However, it may not be suitable for producing short nanosecond pulses (<100 ns), whereas the PFL approach and the RLC approach with gas switches are used for this range. Thus, each generator has its own advantages and applicable range. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. A microtubule polymerase cooperates with the kinesin-6 motor and a microtubule cross-linker to promote bipolar spindle assembly in the absence of kinesin-5 and kinesin-14 in fission yeast.

    PubMed

    Yukawa, Masashi; Kawakami, Tomoki; Okazaki, Masaki; Kume, Kazunori; Tang, Ngang Heok; Toda, Takashi

    2017-12-01

    Accurate chromosome segregation relies on the bipolar mitotic spindle. In many eukaryotes, spindle formation is driven by the plus-end-directed motor kinesin-5 that generates outward force to establish spindle bipolarity. Its inhibition leads to the emergence of monopolar spindles with mitotic arrest. Intriguingly, simultaneous inactivation of the minus-end-directed motor kinesin-14 restores spindle bipolarity in many systems. Here we show that in fission yeast, three independent pathways contribute to spindle bipolarity in the absence of kinesin-5/Cut7 and kinesin-14/Pkl1. One is kinesin-6/Klp9 that engages with spindle elongation once short bipolar spindles assemble. Klp9 also ensures the medial positioning of anaphase spindles to prevent unequal chromosome segregation. Another is the Alp7/TACC-Alp14/TOG microtubule polymerase complex. Temperature-sensitive alp7cut7pkl1 mutants are arrested with either monopolar or very short spindles. Forced targeting of Alp14 to the spindle pole body is sufficient to render alp7cut7pkl1 triply deleted cells viable and promote spindle assembly, indicating that Alp14-mediated microtubule polymerization from the nuclear face of the spindle pole body could generate outward force in place of Cut7 during early mitosis. The third pathway involves the Ase1/PRC1 microtubule cross-linker that stabilizes antiparallel microtubules. Our study, therefore, unveils multifaceted interplay among kinesin-dependent and -independent pathways leading to mitotic bipolar spindle assembly. © 2017 Yukawa et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  7. Efficient treatment of aniline containing wastewater in bipolar membrane microbial electrolysis cell-Fenton system.

    PubMed

    Li, Xiaohu; Jin, Xiangdan; Zhao, Nannan; Angelidaki, Irini; Zhang, Yifeng

    2017-08-01

    Aniline-containing wastewater can cause significant environmental problems and threaten the humans's life. However, rapid degradation of aniline with cost-efficient methods remains a challenge. In this work, a novel microbial electrolysis cell with bipolar membrane was integrated with Fenton reaction (MEC-Fenton) for efficient treatment of real wastewater containing a high concentration (4460 ± 52 mg L -1 ) of aniline. In this system, H 2 O 2 was in situ electro-synthesized from O 2 reduction on the graphite cathode and was simultaneously used as source of OH for the oxidation of aniline wastewater under an acidic condition maintained by the bipolar membrane. The aniline was effectively degraded following first-order kinetics at a rate constant of 0.0166 h -1 under an applied voltage of 0.5 V. Meanwhile, a total organic carbon (TOC) removal efficiency of 93.1 ± 1.2% was obtained, revealing efficient mineralization of aniline. The applicability of bipolar membrane MEC-Fenton system was successfully demonstrated with actual aniline wastewater. Moreover, energy balance showed that the system could be a promising technology for removal of biorefractory organic pollutants from wastewaters. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Daily electronic self-monitoring of subjective and objective symptoms in bipolar disorder--the MONARCA trial protocol (MONitoring, treAtment and pRediCtion of bipolAr disorder episodes): a randomised controlled single-blind trial.

    PubMed

    Faurholt-Jepsen, Maria; Vinberg, Maj; Christensen, Ellen Margrethe; Frost, Mads; Bardram, Jakob; Kessing, Lars Vedel

    2013-01-01

    Electronic self-monitoring of affective symptoms using cell phones is suggested as a practical and inexpensive way to monitor illness activity and identify early signs of affective symptoms. It has never been tested in a randomised clinical trial whether electronic self-monitoring improves outcomes in bipolar disorder. We are conducting a trial testing the effect of using a Smartphone for self-monitoring in bipolar disorder. We developed the MONARCA application for Android-based Smartphones, allowing patients suffering from bipolar disorder to do daily self-monitoring-including an interactive feedback loop between patients and clinicians through a web-based interface. The effect of the application was tested in a parallel-group, single-blind randomised controlled trial so far including 78 patients suffering from bipolar disorder in the age group 18-60 years who were given the use of a Smartphone with the MONARCA application (intervention group) or to the use of a cell phone without the application (placebo group) during a 6-month study period. The study was carried out from September 2011. The outcomes were changes in affective symptoms (primary), social functioning, perceived stress, self-rated depressive and manic symptoms, quality of life, adherence to medication, stress and cognitive functioning (secondary and tertiary). Recruitment is ongoing. Ethical permission has been obtained. Positive, neutral and negative findings of the study will be published. The trial is approved by the Regional Ethics Committee in The Capital Region of Denmark (H-2-2011-056) and The Danish Data Protection Agency (2013-41-1710). The trial is registered at ClinicalTrials.gov as NCT01446406.

  9. Precision absolute-value amplifier for a precision voltmeter

    DOEpatents

    Hearn, W.E.; Rondeau, D.J.

    1982-10-19

    Bipolar inputs are afforded by the plus inputs of first and second differential input amplifiers. A first gain determining resistor is connected between the minus inputs of the differential amplifiers. First and second diodes are connected between the respective minus inputs and the respective outputs of the differential amplifiers. First and second FETs have their gates connected to the outputs of the amplifiers, while their respective source and drain circuits are connected between the respective minus inputs and an output lead extending to a load resistor. The output current through the load resistor is proportional to the absolute value of the input voltage difference between the bipolar input terminals. A third differential amplifier has its plus input terminal connected to the load resistor. A second gain determining resistor is connected between the minus input of the third differential amplifier and a voltage source. A third FET has its gate connected to the output of the third amplifier. The source and drain circuit of the third transistor is connected between the minus input of the third amplifier and a voltage-frequency converter, constituting an output device. A polarity detector is also provided, comprising a pair of transistors having their inputs connected to the outputs of the first and second differential amplifiers. The outputs of the polarity detector are connected to gates which switch the output of the voltage-frequency converter between up and down counting outputs.

  10. Precision absolute value amplifier for a precision voltmeter

    DOEpatents

    Hearn, William E.; Rondeau, Donald J.

    1985-01-01

    Bipolar inputs are afforded by the plus inputs of first and second differential input amplifiers. A first gain determining resister is connected between the minus inputs of the differential amplifiers. First and second diodes are connected between the respective minus inputs and the respective outputs of the differential amplifiers. First and second FETs have their gates connected to the outputs of the amplifiers, while their respective source and drain circuits are connected between the respective minus inputs and an output lead extending to a load resister. The output current through the load resister is proportional to the absolute value of the input voltage difference between the bipolar input terminals. A third differential amplifier has its plus input terminal connected to the load resister. A second gain determining resister is connected between the minus input of the third differential amplifier and a voltage source. A third FET has its gate connected to the output of the third amplifier. The source and drain circuit of the third transistor is connected between the minus input of the third amplifier and a voltage-frequency converter, constituting an output device. A polarity detector is also provided, comprising a pair of transistors having their inputs connected to the outputs of the first and second differential amplifiers. The outputs of the polarity detector are connected to gates which switch the output of the voltage-frequency converter between up and down counting outputs.

  11. Electropermeabilization by uni- or bipolar nanosecond electric pulses: The impact of extracellular conductivity.

    PubMed

    Gianulis, Elena C; Casciola, Maura; Xiao, Shu; Pakhomova, Olga N; Pakhomov, Andrei G

    2018-02-01

    Cellular effects caused by nanosecond electric pulses (nsEP) can be reduced by an electric field reversal, a phenomenon known as bipolar cancellation. The reason for this cancellation effect remains unknown. We hypothesized that assisted membrane discharge is the mechanism for bipolar cancellation. CHO-K1 cells bathed in high (16.1mS/cm; HCS) or low (1.8mS/cm; LCS) conductivity solutions were exposed to either one unipolar (300-ns) or two opposite polarity (300+300-ns; bipolar) nsEP (4-40kV/cm) with increasing interpulse intervals (0.1-50μs). Time-lapse YO-PRO-1 (YP) uptake revealed enhanced membrane permeabilization in LCS compared to HCS at all tested voltages. The time-dependence of bipolar cancellation was similar in both solutions, using either identical (22kV/cm) or isoeffective nsEP treatments (12 and 32kV/cm for LCS and HCS, respectively). However, cancellation was significantly stronger in LCS when the bipolar nsEP had no, or very short (<1μs), interpulse intervals. Finally, bipolar cancellation was still present with interpulse intervals as long as 50μs, beyond the time expected for membrane discharge. Our findings do not support assisted membrane discharge as the mechanism for bipolar cancellation. Instead they exemplify the sustained action of nsEP that can be reversed long after the initial stimulus. Copyright © 2017 Elsevier B.V. All rights reserved.

  12. Bipolar batteries based on Ebonex ® technology

    NASA Astrophysics Data System (ADS)

    Loyns, A. C.; Hill, A.; Ellis, K. G.; Partington, T. J.; Hill, J. M.

    Continuing work by Atraverda on the production of a composite-laminate form of the Ebonex ® material, that can be cheaply formulated and manufactured to form substrate plates for bipolar lead-acid batteries, is described. Ebonex ® is the registered trade name of a range of titanium suboxide ceramic materials, typically Ti 4O 7 and Ti 5O 9, which combine electrical conductivity with high corrosion and oxidation resistance. Details of the structure of the composite, battery construction techniques and methods for filling and forming of batteries are discussed. In addition, lifetime and performance data obtained by Atraverda from laboratory bipolar lead-acid batteries and cells are presented. Battery production techniques for both conventional monopolar and bipolar batteries are reviewed. The findings indicate that substantial time and cost savings may be realised in the manufacture of bipolar batteries in comparison to conventional designs. This is due to the fewer processing steps required and more efficient formation. The results indicate that the use of Ebonex ® composite material as a bipolar substrate will provide lightweight and durable high-voltage lead-acid batteries suitable for a wide range of applications including advanced automotive, stationary power and portable equipment.

  13. Synaptic remodeling generates synchronous oscillations in the degenerated outer mouse retina

    PubMed Central

    Haq, Wadood; Arango-Gonzalez, Blanca; Zrenner, Eberhart; Euler, Thomas; Schubert, Timm

    2014-01-01

    During neuronal degenerative diseases, neuronal microcircuits undergo severe structural alterations, leading to remodeling of synaptic connectivity. The functional consequences of such remodeling are mostly unknown. For instance, in mutant rd1 mouse retina, a common model for Retinitis Pigmentosa, rod bipolar cells (RBCs) establish contacts with remnant cone photoreceptors (cones) as a consequence of rod photoreceptor cell death and the resulting lack of presynaptic input. To assess the functional connectivity in the remodeled, light-insensitive outer rd1 retina, we recorded spontaneous population activity in retinal wholemounts using Ca2+ imaging and identified the participating cell types. Focusing on cones, RBCs and horizontal cells (HCs), we found that these cell types display spontaneous oscillatory activity and form synchronously active clusters. Overall activity was modulated by GABAergic inhibition from interneurons such as HCs and/or possibly interplexiform cells. Many of the activity clusters comprised both cones and RBCs. Opposite to what is expected from the intact (wild-type) cone-ON bipolar cell pathway, cone and RBC activity was positively correlated and, at least partially, mediated by glutamate transporters expressed on RBCs. Deletion of gap junctional coupling between cones reduced the number of clusters, indicating that electrical cone coupling plays a crucial role for generating the observed synchronized oscillations. In conclusion, degeneration-induced synaptic remodeling of the rd1 retina results in a complex self-sustained outer retinal oscillatory network, that complements (and potentially modulates) the recently described inner retinal oscillatory network consisting of amacrine, bipolar and ganglion cells. PMID:25249942

  14. Degradation of graphene coated copper in simulated proton exchange membrane fuel cell environment: Electrochemical impedance spectroscopy study

    NASA Astrophysics Data System (ADS)

    Ren, Y. J.; Anisur, M. R.; Qiu, W.; He, J. J.; Al-Saadi, S.; Singh Raman, R. K.

    2017-09-01

    Metallic materials are most suitable for bipolar plates of proton exchange membrane fuel cell (PEMFC) because they possess the required mechanical strength, durability, gas impermeability, acceptable cost and are suitable for mass production. However, metallic bipolar plates are prone to corrosion or they can passivate under PEMFC environment and interrupt the fuel cell operation. Therefore, it is highly attractive to develop corrosion resistance coating that is also highly conductive. Graphene fits these criteria. Graphene coating is developed on copper by chemical vapor deposition (CVD) with an aim to improving corrosion resistance of copper under PEMFC condition. The Raman Spectroscopy shows the graphene coating to be multilayered. The electrochemical degradation of graphene coated copper is investigated by electrochemical impedance spectroscopy (EIS) in 0.5 M H2SO4 solution at room temperature. After exposure to the electrolyte for up to 720 h, the charge transfer resistance (Rt) of the graphene coated copper is ∼3 times greater than that of the bare copper, indicating graphene coatings could improve the corrosion resistance of copper bipolar plates.

  15. Unidirectional threshold switching in Ag/Si-based electrochemical metallization cells for high-density bipolar RRAM applications

    NASA Astrophysics Data System (ADS)

    Wang, Chao; Song, Bing; Li, Qingjiang; Zeng, Zhongming

    2018-03-01

    We herein present a novel unidirectional threshold selector for cross-point bipolar RRAM array. The proposed Ag/amorphous Si based threshold selector showed excellent threshold characteristics in positive field, such as high selectivity ( 105), steep slope (< 5 mV/decade) and low off-state current (< 300 pA). Meanwhile, the selector exhibited rectifying characteristics in the high resistance state as well and the rectification ratio was as high as 103 at ± 1.5 V. Nevertheless, due to the high reverse current about 9 mA at - 3 V, this unidirectional threshold selector can be used as a selection element for bipolar-type RRAM. By integrating a bipolar RRAM device with the selector, experiments showed that the undesired sneak was significantly suppressed, indicating its potentiality for high-density integrated nonvolatile memory applications.

  16. Assessing the utility of bipolar membranes for use in photoelectrochemical water-splitting cells.

    PubMed

    Vargas-Barbosa, Nella M; Geise, Geoffrey M; Hickner, Michael A; Mallouk, Thomas E

    2014-11-01

    Membranes are important in water-splitting solar cells because they prevent crossover of hydrogen and oxygen. Here, bipolar membranes (BPMs) were tested as separators in water electrolysis cells. Steady-state membrane and solution resistances, electrode overpotentials, and pH gradients were measured at current densities relevant to solar photoelectrolysis. Under forward bias conditions, electrodialysis of phosphate buffer ions creates a pH gradient across a BPM. Under reverse bias, the BPM can maintain a constant buffer pH on both sides of the cell, but a large membrane potential develops. Thus, the BPM does not present a viable solution for electrolysis in buffered electrolytes. However, the membrane potential is minimized when the anode and cathode compartments of the cell contain strongly basic and acidic electrolytes, respectively. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. A comparative evaluation of different types of microbial electrolysis desalination cells for malic acid production.

    PubMed

    Liu, Guangli; Zhou, Ying; Luo, Haiping; Cheng, Xing; Zhang, Renduo; Teng, Wenkai

    2015-12-01

    The aim of this study was to investigate different microbial electrolysis desalination cells for malic acid production. The systems included microbial electrolysis desalination and chemical-production cell (MEDCC), microbial electrolysis desalination cell (MEDC) with bipolar membrane and anion exchange membrane (BP-A MEDC), MEDC with bipolar membrane and cation exchange membrane (BP-C MEDC), and modified microbial desalination cell (M-MDC). The microbial electrolysis desalination cells performed differently in terms of malic acid production and energy consumption. The MEDCC performed best with the highest malic acid production rate (18.4 ± 0.6 mmol/Lh) and the lowest energy consumption (0.35 ± 0.14 kWh/kg). The best performance of MEDCC was attributable to the neutral pH condition in the anode chamber, the lowest internal resistance, and the highest Geobacter percentage of the anode biofilm population among all the reactors. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Electric field with bipolar structure during magnetic reconnection without a guide field

    NASA Astrophysics Data System (ADS)

    Guo, Jun

    2014-05-01

    We present a study on the polarized electric field during the collisionless magnetic reconnection of antiparallel fields using two dimensional particle-in-cell simulations. The simulations demonstrate clearly that electron holes and electric field with bipolar structure are produced during magnetic reconnection without a guide field. The electric field with bipolar structure can be found near the X-line and on the separatrix and the plasma sheet boundary layer, which is consistent with the observations. These structures will elongate electron's time staying in the diffusion region. In addition, the electric fields with tripolar structures are also found in our simulation.

  19. Interdependency of Fission Yeast Alp14/TOG and Coiled Coil Protein Alp7 in Microtubule Localization and Bipolar Spindle FormationD⃞

    PubMed Central

    Sato, Masamitsu; Vardy, Leah; Angel Garcia, Miguel; Koonrugsa, Nirada; Toda, Takashi

    2004-01-01

    The Dis1/TOG family plays a pivotal role in microtubule organization. In fission yeast, Alp14 and Dis1 share an essential function in bipolar spindle formation. Here, we characterize Alp7, a novel coiled-coil protein that is required for organization of bipolar spindles. Both Alp7 and Alp14 colocalize to the spindle pole body (SPB) and mitotic spindles. Alp14 localization to these sites is fully dependent upon Alp7. Conversely, in the absence of Alp14, Alp7 localizes to the SPBs, but not mitotic spindles. Alp7 forms a complex with Alp14, where the C-terminal region of Alp14 interacts with the coiled-coil domain of Alp7. Intriguingly, this Alp14 C terminus is necessary and sufficient for mitotic spindle localization. Overproduction of either full-length or coiled-coil region of Alp7 results in abnormal V-shaped spindles and stabilization of interphase microtubules, which is induced independent of Alp14. Alp7 may be a functional homologue of animal TACC. Our results shed light on an interdependent relationship between Alp14/TOG and Alp7. We propose a two-step model that accounts for the recruitment of Alp7 and Alp14 to the SPB and microtubules. PMID:14742702

  20. Interdependency of fission yeast Alp14/TOG and coiled coil protein Alp7 in microtubule localization and bipolar spindle formation.

    PubMed

    Sato, Masamitsu; Vardy, Leah; Angel Garcia, Miguel; Koonrugsa, Nirada; Toda, Takashi

    2004-04-01

    The Dis1/TOG family plays a pivotal role in microtubule organization. In fission yeast, Alp14 and Dis1 share an essential function in bipolar spindle formation. Here, we characterize Alp7, a novel coiled-coil protein that is required for organization of bipolar spindles. Both Alp7 and Alp14 colocalize to the spindle pole body (SPB) and mitotic spindles. Alp14 localization to these sites is fully dependent upon Alp7. Conversely, in the absence of Alp14, Alp7 localizes to the SPBs, but not mitotic spindles. Alp7 forms a complex with Alp14, where the C-terminal region of Alp14 interacts with the coiled-coil domain of Alp7. Intriguingly, this Alp14 C terminus is necessary and sufficient for mitotic spindle localization. Overproduction of either full-length or coiled-coil region of Alp7 results in abnormal V-shaped spindles and stabilization of interphase microtubules, which is induced independent of Alp14. Alp7 may be a functional homologue of animal TACC. Our results shed light on an interdependent relationship between Alp14/TOG and Alp7. We propose a two-step model that accounts for the recruitment of Alp7 and Alp14 to the SPB and microtubules.

  1. Evaluation of Oxidative Stress in Bipolar Disorder in terms of Total Oxidant Status, Total Antioxidant Status, and Oxidative Stress Index

    PubMed Central

    CİNGİ YİRÜN, Merve; ÜNAL, Kübranur; ALTUNSOY ŞEN, Neslihan; YİRÜN, Onur; AYDEMİR, Çiğdem; GÖKA, Erol

    2016-01-01

    Introduction Bipolar disorder is one of the most debilitating psychiatric disorders characterized by disruptive episodes of mania/hypomania and depression. Considering the complex role of biological and environmental factors in the etiology of affective disorders, recent studies have focused on oxidative stress, which may damage nerve cell components and take part in pathophysiology. The aim of the present study was to contribute to the data about oxidative stress in bipolar disorder by detecting the total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels of manic episode (ME) and euthymic (EU) patients and by comparing these results with those of healthy controls (HCs). Methods The study population consisted of 28 EU outpatients meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for bipolar disorder I and 23 inpatients who were currently hospitalized in a psychiatry ward with the diagnosis of the bipolar disorder ME according to the DSM-5 criteria. Forty-three healthy subjects were included in the study as the control group (HC). Serum TAS, TOS, and OSI levels of all the participants were determined. Results Statistical analysis of serum TAS, TOS, and OSI levels did not show any significant differences between the ME patients, EU patients, and HCs. Comparison between the bipolar disorder patients (ME+EU) and HC also did not reveal any statistically significant difference between these two groups in terms of serum TAS, TOS, and OSI levels. Conclusion To date, studies on oxidative stress in bipolar disorder have led to controversial results. In the present study, no statistically significant difference was detected between the oxidative parameters of bipolar disorder patients and HCs. In order to comprehensively evaluate oxidative stress in bipolar disorder, further studies are needed. PMID:28373794

  2. Evaluation of Oxidative Stress in Bipolar Disorder in terms of Total Oxidant Status, Total Antioxidant Status, and Oxidative Stress Index.

    PubMed

    Cingi Yirün, Merve; Ünal, Kübranur; Altunsoy Şen, Neslihan; Yirün, Onur; Aydemir, Çiğdem; Göka, Erol

    2016-09-01

    Bipolar disorder is one of the most debilitating psychiatric disorders characterized by disruptive episodes of mania/hypomania and depression. Considering the complex role of biological and environmental factors in the etiology of affective disorders, recent studies have focused on oxidative stress, which may damage nerve cell components and take part in pathophysiology. The aim of the present study was to contribute to the data about oxidative stress in bipolar disorder by detecting the total antioxidant status (TAS), total oxidant status (TOS), and oxidative stress index (OSI) levels of manic episode (ME) and euthymic (EU) patients and by comparing these results with those of healthy controls (HCs). The study population consisted of 28 EU outpatients meeting the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) criteria for bipolar disorder I and 23 inpatients who were currently hospitalized in a psychiatry ward with the diagnosis of the bipolar disorder ME according to the DSM-5 criteria. Forty-three healthy subjects were included in the study as the control group (HC). Serum TAS, TOS, and OSI levels of all the participants were determined. Statistical analysis of serum TAS, TOS, and OSI levels did not show any significant differences between the ME patients, EU patients, and HCs. Comparison between the bipolar disorder patients (ME+EU) and HC also did not reveal any statistically significant difference between these two groups in terms of serum TAS, TOS, and OSI levels. To date, studies on oxidative stress in bipolar disorder have led to controversial results. In the present study, no statistically significant difference was detected between the oxidative parameters of bipolar disorder patients and HCs. In order to comprehensively evaluate oxidative stress in bipolar disorder, further studies are needed.

  3. Excitatory synaptic inputs to mouse on-off direction-selective retinal ganglion cells lack direction tuning.

    PubMed

    Park, Silvia J H; Kim, In-Jung; Looger, Loren L; Demb, Jonathan B; Borghuis, Bart G

    2014-03-12

    Direction selectivity represents a fundamental visual computation. In mammalian retina, On-Off direction-selective ganglion cells (DSGCs) respond strongly to motion in a preferred direction and weakly to motion in the opposite, null direction. Electrical recordings suggested three direction-selective (DS) synaptic mechanisms: DS GABA release during null-direction motion from starburst amacrine cells (SACs) and DS acetylcholine and glutamate release during preferred direction motion from SACs and bipolar cells. However, evidence for DS acetylcholine and glutamate release has been inconsistent and at least one bipolar cell type that contacts another DSGC (On-type) lacks DS release. Here, whole-cell recordings in mouse retina showed that cholinergic input to On-Off DSGCs lacked DS, whereas the remaining (glutamatergic) input showed apparent DS. Fluorescence measurements with the glutamate biosensor intensity-based glutamate-sensing fluorescent reporter (iGluSnFR) conditionally expressed in On-Off DSGCs showed that glutamate release in both On- and Off-layer dendrites lacked DS, whereas simultaneously recorded excitatory currents showed apparent DS. With GABA-A receptors blocked, both iGluSnFR signals and excitatory currents lacked DS. Our measurements rule out DS release from bipolar cells onto On-Off DSGCs and support a theoretical model suggesting that apparent DS excitation in voltage-clamp recordings results from inadequate voltage control of DSGC dendrites during null-direction inhibition. SAC GABA release is the apparent sole source of DS input onto On-Off DSGCs.

  4. Morphological Diversity of the Rod Spherule: A Study of Serially Reconstructed Electron Micrographs

    PubMed Central

    Li, Shuai; Mitchell, Joe; Briggs, Deidrie J.; Young, Jaime K.; Long, Samuel S.; Fuerst, Peter G.

    2016-01-01

    Purpose Rod spherules are the site of the first synaptic contact in the retina’s rod pathway, linking rods to horizontal and bipolar cells. Rod spherules have been described and characterized through electron micrograph (EM) and other studies, but their morphological diversity related to retinal circuitry and their intracellular structures have not been quantified. Most rod spherules are connected to their soma by an axon, but spherules of rods on the surface of the Mus musculus outer plexiform layer often lack an axon and have a spherule structure that is morphologically distinct from rod spherules connected to their soma by an axon. Retraction of the rod axon and spherule is often observed in disease processes and aging, and the retracted rod spherule superficially resembles rod spherules lacking an axon. We hypothesized that retracted spherules take on an axonless spherule morphology, which may be easier to maintain in a diseased state. To test our hypothesis, we quantified the spatial organization and subcellular structures of rod spherules with and without axons. We then compared them to the retracted spherules in a disease model, mice that overexpress Dscam (Down syndrome cell adhesion molecule), to gain a better understanding of the rod synapse in health and disease. Methods We reconstructed serial EM images of wild type and DscamGoF (gain of function) rod spherules at a resolution of 7 nm in the X-Y axis and 60 nm in the Z axis. Rod spherules with and without axons, and retracted spherules in the DscamGoF retina, were reconstructed. The rod spherule intracellular organelles, the invaginating dendrites of rod bipolar cells and horizontal cell axon tips were also reconstructed for statistical analysis. Results Stereotypical rod (R1) spherules occupy the outer two-thirds of the outer plexiform layer (OPL), where they present as spherical terminals with large mitochondria. This spherule group is highly uniform and composed more than 90% of the rod spherule population. Rod spherules lacking an axon (R2) were also described and characterized. This rod spherule group consists of a specific spatial organization that is strictly located at the apical OPL-facing layer of the Outer Nuclear Layer (ONL). The R2 spherule displays a large bowl-shaped synaptic terminal that hugs the rod soma. Retracted spherules in the DscamGoF retina were also reconstructed to test if they are structurally similar to R2 spherules. The misplaced rod spherules in DscamGoF have a gross morphology that is similar to R2 spherules but have significant disruption in internal synapse organization. Conclusion We described a morphological diversity within Mus musculus rod spherules. This diversity is correlated with rod location in the ONL and contributes to the intracellular differences within spherules. Analysis of the DscamGoF retina indicated that their R2 spherules are not significantly different than wild type R2 spherules, but that their retracted rod spherules have abnormal synaptic organization. PMID:26930660

  5. Morphological Diversity of the Rod Spherule: A Study of Serially Reconstructed Electron Micrographs.

    PubMed

    Li, Shuai; Mitchell, Joe; Briggs, Deidrie J; Young, Jaime K; Long, Samuel S; Fuerst, Peter G

    2016-01-01

    Rod spherules are the site of the first synaptic contact in the retina's rod pathway, linking rods to horizontal and bipolar cells. Rod spherules have been described and characterized through electron micrograph (EM) and other studies, but their morphological diversity related to retinal circuitry and their intracellular structures have not been quantified. Most rod spherules are connected to their soma by an axon, but spherules of rods on the surface of the Mus musculus outer plexiform layer often lack an axon and have a spherule structure that is morphologically distinct from rod spherules connected to their soma by an axon. Retraction of the rod axon and spherule is often observed in disease processes and aging, and the retracted rod spherule superficially resembles rod spherules lacking an axon. We hypothesized that retracted spherules take on an axonless spherule morphology, which may be easier to maintain in a diseased state. To test our hypothesis, we quantified the spatial organization and subcellular structures of rod spherules with and without axons. We then compared them to the retracted spherules in a disease model, mice that overexpress Dscam (Down syndrome cell adhesion molecule), to gain a better understanding of the rod synapse in health and disease. We reconstructed serial EM images of wild type and DscamGoF (gain of function) rod spherules at a resolution of 7 nm in the X-Y axis and 60 nm in the Z axis. Rod spherules with and without axons, and retracted spherules in the DscamGoF retina, were reconstructed. The rod spherule intracellular organelles, the invaginating dendrites of rod bipolar cells and horizontal cell axon tips were also reconstructed for statistical analysis. Stereotypical rod (R1) spherules occupy the outer two-thirds of the outer plexiform layer (OPL), where they present as spherical terminals with large mitochondria. This spherule group is highly uniform and composed more than 90% of the rod spherule population. Rod spherules lacking an axon (R2) were also described and characterized. This rod spherule group consists of a specific spatial organization that is strictly located at the apical OPL-facing layer of the Outer Nuclear Layer (ONL). The R2 spherule displays a large bowl-shaped synaptic terminal that hugs the rod soma. Retracted spherules in the DscamGoF retina were also reconstructed to test if they are structurally similar to R2 spherules. The misplaced rod spherules in DscamGoF have a gross morphology that is similar to R2 spherules but have significant disruption in internal synapse organization. We described a morphological diversity within Mus musculus rod spherules. This diversity is correlated with rod location in the ONL and contributes to the intracellular differences within spherules. Analysis of the DscamGoF retina indicated that their R2 spherules are not significantly different than wild type R2 spherules, but that their retracted rod spherules have abnormal synaptic organization.

  6. Design and characterization of a three-terminal transcriptional device through polymerase per second.

    PubMed

    Varadarajan, Prasanna Amur; Del Vecchio, Domitilla

    2009-09-01

    In this paper, we provide an in silico input-output characterization of a three-terminal transcriptional device employing polymerase per second (PoPS) as input and output. The device is assembled from well-characterized parts of the bacteriophage lambda switch transcriptional circuit. We draw the analogy between voltage and protein concentration and between current and PoPS to demonstrate that the characteristics of the three-terminal transcriptional device are qualitatively similar to those of a bipolar junction transistor (BJT). In particular, as it occurs in a BJT, the device can be tuned to operate either as a linear amplifier or as a switch. When the device operates as a linear amplifier, gains of twofolds can be obtained, which are considerably smaller than those obtained in a BJT (in which 100-fold amplification gains can be reached). This fact suggests that the parts extracted from natural transcriptional systems may be naturally designed mostly to process and store information as opposed to amplify signals.

  7. Non-canonical features of the Golgi apparatus in bipolar epithelial neural stem cells

    PubMed Central

    Taverna, Elena; Mora-Bermúdez, Felipe; Strzyz, Paulina J.; Florio, Marta; Icha, Jaroslav; Haffner, Christiane; Norden, Caren; Wilsch-Bräuninger, Michaela; Huttner, Wieland B.

    2016-01-01

    Apical radial glia (aRG), the stem cells in developing neocortex, are unique bipolar epithelial cells, extending an apical process to the ventricle and a basal process to the basal lamina. Here, we report novel features of the Golgi apparatus, a central organelle for cell polarity, in mouse aRGs. The Golgi was confined to the apical process but not associated with apical centrosome(s). In contrast, in aRG-derived, delaminating basal progenitors that lose apical polarity, the Golgi became pericentrosomal. The aRG Golgi underwent evolutionarily conserved, accordion-like compression and extension concomitant with cell cycle-dependent nuclear migration. Importantly, in line with endoplasmic reticulum but not Golgi being present in the aRG basal process, its plasma membrane contained glycans lacking Golgi processing, consistent with direct ER-to-cell surface membrane traffic. Our study reveals hitherto unknown complexity of neural stem cell polarity, differential Golgi contribution to their specific architecture, and fundamental Golgi re-organization upon cell fate change. PMID:26879757

  8. Bipolarly stacked electrolyser for energy and space efficient fabrication of supercapacitor electrodes

    NASA Astrophysics Data System (ADS)

    Liu, Xiaojuan; Wu, Tao; Dai, Zengxin; Tao, Keran; Shi, Yong; Peng, Chuang; Zhou, Xiaohang; Chen, George Z.

    2016-03-01

    Stacked electrolysers with titanium bipolar plates are constructed for electrodeposition of polypyrrole electrodes for supercapacitors. The cathode side of the bipolar Ti plates are pre-coated with activated carbon. In this new design, half electrolysis occurs which significantly lowers the deposition voltage. The deposited electrodes are tested in a symmetrical unit cell supercapacitor and an asymmetrical supercapacitor stack. Both devices show excellent energy storage performances and the capacitance values are very close to the design value, suggesting a very high current efficiency during the electrodeposition. The electrolyser stack offers multi-fold benefits for preparation of conducting polymer electrodes, i.e. low energy consumption, facile control of the electrode capacitance and simultaneous preparation of a number of identical electrodes. Therefore, the stacked bipolar electrolyser is a technology advance that offers an engineering solution for mass production of electrodeposited conducting polymer electrodes for supercapacitors.

  9. Electrochemical Device Comprising an Electrically-Conductive, Selectively-Permeable Membrane

    NASA Technical Reports Server (NTRS)

    Laicer, Castro S. T. (Inventor); Mittelsteadt, Cortney K. (Inventor); Harrison, Katherine E. (Inventor); McPheeters, Bryn M. (Inventor)

    2017-01-01

    An electrochemical device, such as a fuel cell or an electrolyzer. In one embodiment, the electrochemical device includes a membrane electrode assembly (MEA), an anodic gas diffusion medium in contact with the anode of the MEA, a cathodic gas diffusion medium in contact with the cathode, a first bipolar plate in contact with the anodic gas diffusion medium, and a second bipolar plate in contact with the cathodic gas diffusion medium. Each of the bipolar plates includes an electrically-conductive, non-porous, liquid-permeable, substantially gas-impermeable membrane in contact with its respective gas diffusion medium, the membrane including a solid polymer electrolyte and a non-particulate, electrically-conductive material, such as carbon nanotubes, carbon nanofibers, and/or metal nanowires. In addition, each bipolar plate also includes an electrically-conductive fluid chamber in contact with the electrically-conductive, selectively-permeable membrane and further includes a non-porous and electrically-conductive plate in contact with the fluid chamber.

  10. The retina of the shovel-nosed ray, Rhinobatos batillum (Rhinobatidae): morphology and quantitative analysis of the ganglion, amacrine and bipolar cell populations.

    PubMed

    Collin, S P

    1988-01-01

    A light microscopy study of the retina of the shovel-nosed ray, Rhinobatos batillum (Rhinobatidae) has revealed a duplex retina with a rod to cone ratio between 4:1 and 6:1. The inner nuclear layer consists of three layers of large horizontal cells, tightly packed, stellate bipolar cells, and up to three substrata of amacrine cells. The collaterals of the many supporting Müller cells project from the inner to the outer limiting membrane and divide the retina into many subunits. The cells of the ganglion cell layer are distributed into two layers, although a large proportion of ganglion cells are also displaced into the inner plexiform and inner nuclear layers. Topographic analysis of the cells in the ganglion cell layer, inner plexiform and inner nuclear layers reveals a number of regional specializations or "areae centrales". Ganglion cells were retrogradely-labelled with cobalt-lysine from the optic nerve, and three sub-populations of neurons characterized on their soma size and position. Small (20-50 microns2), large (80-300 microns2) and giant (greater than 300 microns2) sub-populations of ganglion cells each revealed distinct retinal specializations with peak densities of 3 x 10(3), 1.25 x 10(3) and 1.57 x 10(3) cells per mm2, respectively. Topographical comparison between Nissl-stained and retrogradely-labelled ganglion cell populations have established that a maximum of 20% in the "area centralis", and 75% in unspecialized, peripheral regions of the retina are non-ganglion cells. Out of a total of 210,566 cells in the ganglion cell layer, 49% were found to be non-ganglion cells. Iso-density contour maps of amacrine and bipolar cell distributions also reveal some specializations. These cell concentrations lie in corresponding regions to areas of increased density in the large and giant ganglion cell populations, suggesting some functional association.

  11. Bipolar disorder and diabetes mellitus: evidence for disease-modifying effects and treatment implications.

    PubMed

    Charles, Ellen F; Lambert, Christophe G; Kerner, Berit

    2016-12-01

    Bipolar disorder refers to a group of chronic psychiatric disorders of mood and energy levels. While dramatic psychiatric symptoms dominate the acute phase of the diseases, the chronic course is often determined by an increasing burden of co-occurring medical conditions. High rates of diabetes mellitus in patients with bipolar disorder are particularly striking, yet unexplained. Treatment and lifestyle factors could play a significant role, and some studies also suggest shared pathophysiology and risk factors. In this systematic literature review, we explored data around the relationship between bipolar disorder and diabetes mellitus in recently published population-based cohort studies with special focus on the elderly. A systematic search in the PubMed database for the combined terms "bipolar disorder" AND "elderly" AND "diabetes" in papers published between January 2009 and December 2015 revealed 117 publications; 7 studies were large cohort studies, and therefore, were included in our review. We found that age- and gender- adjusted risk for diabetes mellitus was increased in patients with bipolar disorder and vice versa (odds ratio range between 1.7 and 3.2). Our results in large population-based cohort studies are consistent with the results of smaller studies and chart reviews. Even though it is likely that heterogeneous risk factors may play a role in diabetes mellitus and in bipolar disorder, growing evidence from cell culture experiments and animal studies suggests shared disease mechanisms. Furthermore, disease-modifying effects of bipolar disorder and diabetes mellitus on each other appear to be substantial, impacting both treatment response and outcomes. The risk of diabetes mellitus in patients with bipolar disorder is increased. Our findings add to the growing literature on this topic. Increasing evidence for shared disease mechanisms suggests new disease models that could explain the results of our study. A better understanding of the complex relationship between bipolar disorder and diabetes mellitus could lead to novel therapeutic approaches and improved outcomes.

  12. Life cycle test results of a bipolar nickel hydrogen battery

    NASA Technical Reports Server (NTRS)

    Cataldo, R. L.

    1985-01-01

    A history is given of low Earth orbit (LEO) laboratory test data on a 6.5 ampere-hour bipolar nickel hydrogen battery designed and built at the NASA Lewis Research Center. The bipolar concept is a means of achieving the goal of producing an acceptable battery, of higher energy density, able to withstand the demands of low-Earth-orbit regimes. Over 4100 LEO cycles were established on a ten cell battery. It seems that any perturbation on normal cycling effects the cells performance. Explanations and theories of the battery's behavior are varied and widespread among those closely associated with it. Deep discharging does provide a reconditioning effect and further experimentation is planned in this area. The battery watt-hour efficiency is about 75 percent and the time averaged, discharge voltage is about 1.26 volts for all cells at both the C/4 and LEO rate. Since a significant portion of the electrode capacity has degraded, the LEO cycle discharges are approaching depths of 90 to 100 percent of the high rate capacity. Therefore, the low end-of-discharge voltages occur precipitously after the knee of the discharge curve and is more an indication of electrode capacity and is a lesser indicator of overall cell performance.

  13. Are hematopoietic stem cells involved in hepatocarcinogenesis?

    PubMed

    Facciorusso, Antonio; Antonino, Matteo; Del Prete, Valentina; Neve, Viviana; Scavo, Maria Principia; Barone, Michele

    2014-08-01

    THE LIVER HAS THREE CELL LINEAGES ABLE TO PROLIFERATE AFTER A HEPATIC INJURY: the mature hepatocyte, the ductular "bipolar" progenitor cell termed "oval cell" and the putative periductular stem cell. Hepatocytes can only produce other hepatocytes whereas ductular progenitor cells are considerate bipolar since they can give rise to biliary cells or hepatocytes. Periductular stem cells are rare in the liver, have a very long proliferation potential and may be multipotent, being this aspect still under investigation. They originate in the bone marrow since their progeny express genetic markers of donor hematopoietic cells after bone marrow transplantation. Since the liver is the hematopoietic organ of the fetus, it is possible that hematopoietic stem cells may reside in the liver of the adult. This assumption is proved by the finding that oval cells express hematopoietic markers like CD34, CD45, CD 109, Thy-1, c-kit, and others, which are also expressed by bone marrow-derived hematopoietic stem cells (BMSCs). Few and discordant studies have evaluated the role of BMSC in hepatocarcinogenesis so far and further studies in vitro and in vivo are warranted in order to definitively clarify such an issue.

  14. Tetraploid cells from cytokinesis failure induce aneuploidy and spontaneous transformation of mouse ovarian surface epithelial cells.

    PubMed

    Lv, Lei; Zhang, Tianwei; Yi, Qiyi; Huang, Yun; Wang, Zheng; Hou, Heli; Zhang, Huan; Zheng, Wei; Hao, Qiaomei; Guo, Zongyou; Cooke, Howard J; Shi, Qinghua

    2012-08-01

    Most ovarian cancers originate from the ovarian surface epithelium and are characterized by aneuploid karyotypes. Aneuploidy, a consequence of chromosome instability, is an early event during the development of ovarian cancers. However, how aneuploid cells are evolved from normal diploid cells in ovarian cancers remains unknown. In the present study, cytogenetic analyses of a mouse syngeneic ovarian cancer model revealed that diploid mouse ovarian surface epithelial cells (MOSECs) experienced an intermediate tetraploid cell stage, before evolving to aneuploid (mainly near-tetraploid) cells. Using long-term live-cell imaging followed by fluorescence in situ hybridization (FISH), we demonstrated that tetraploid cells originally arose from cytokinesis failure of bipolar mitosis in diploid cells, and gave rise to aneuploid cells through chromosome mis-segregation during both bipolar and multipolar mitoses. Injection of the late passage aneuploid MOSECs resulted in tumor formation in C57BL/6 mice. Therefore, we reveal a pathway for the evolution of diploid to aneuploid MOSECs and elucidate a mechanism for the development of near-tetraploid ovarian cancer cells.

  15. Molecular Memory of Morphologies by Septins during Neuron Generation Allows Early Polarity Inheritance.

    PubMed

    Boubakar, Leila; Falk, Julien; Ducuing, Hugo; Thoinet, Karine; Reynaud, Florie; Derrington, Edmund; Castellani, Valérie

    2017-08-16

    Transmission of polarity established early during cell lineage history is emerging as a key process guiding cell differentiation. Highly polarized neurons provide a fascinating model to study inheritance of polarity over cell generations and across morphological transitions. Neural crest cells (NCCs) migrate to the dorsal root ganglia to generate neurons directly or after cell divisions in situ. Using live imaging of vertebrate embryo slices, we found that bipolar NCC progenitors lose their polarity, retracting their processes to round for division, but generate neurons with bipolar morphology by emitting processes from the same locations as the progenitor. Monitoring the dynamics of Septins, which play key roles in yeast polarity, indicates that Septin 7 tags process sites for re-initiation of process growth following mitosis. Interfering with Septins blocks this mechanism. Thus, Septins store polarity features during mitotic rounding so that daughters can reconstitute the initial progenitor polarity. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Fabrication process analysis and experimental verification for aluminum bipolar plates in fuel cells by vacuum die-casting

    NASA Astrophysics Data System (ADS)

    Jin, Chul Kyu; Kang, Chung Gil

    2011-10-01

    There are various methods for the fabrication of bipolar plates, but these are still limited to machining and stamping processes. High-pressure die casting (HPDC) is an ideal process for the manufacture of bipolar plates This study aims to investigate the formability of bipolar plates for polymer electrolyte membrane fuel cells (PEMFCs) fabricated by vacuum HPDC of an Al-Mg alloy (ALDC6). The cavity of the mold consisted of a thin-walled plate (200 mm × 200 mm × 0.8 mm) with a layer of serpentine channel (50 mm × 50 mm). The location and direction of the channel in the final mold design was determined by computational simulation (MAGMA soft). In addition, simulation results for different conditions of plunger stroke control were compared to those from actual die-casting experiments. Under a vacuum pressure of 35 kPa and for injection speeds of 0.3 and 2.5 m s-1 in the low and high speed regions, respectively, the samples had few casting defects. In addition, the hardness was higher and porosity in microstructure was less than those of the samples made under other injection speed conditions. In case of thin-walled plates, vacuum die casting is beneficial in terms of formability compared to conventional die casting.

  17. Telomere length in bipolar disorder and lithium response.

    PubMed

    Squassina, Alessio; Pisanu, Claudia; Corbett, Nathan; Alda, Martin

    2017-06-01

    Telomeres consist of exanucleotide tandem repeats and proteins complexes at the end of chromosome ends. Telomeres shorten at each cell division, and as such telomere length is a marker of cellular age. Accelerated telomere shortening and cell senescence have been associated with a number of chronic medical conditions, including psychiatric disorders, where increased prevalence of age-related disorders and shorter telomere length have been reported. Shorter telomeres in psychiatric patients are thought to be the consequence of allostatic load, consisting in the overactivation of allostatic systems due to chronic exposure to severe medical conditions and failure to adapt to chronic stressful stimuli. Most of the studies on telomere length in psychiatry have focused on major depressive disorder, but recent findings have shown shorter leukocyte telomere length in bipolar disorder patients and suggested that lithium may counteract telomeres shortening. These findings provided new insights into the pathophysiology of bipolar disorder and the mechanism of action of lithium. In this review we will present findings from the literature on telomere length in bipolar disorder, with a specific focus on lithium. We will also discuss advances and limitations of published work as well as methodological issues and potential confounding factors that should be taken into account when designing research protocols to study telomere length. Copyright © 2015 Elsevier B.V. and ECNP. All rights reserved.

  18. Properties, ageing behavior and stability of bipolar films containing nano-layers of allylamine and acrylic acid plasma polymers

    NASA Astrophysics Data System (ADS)

    Aziz, Gaelle; Asadian, Mahtab; Declercq, Heidi; Morent, Rino; De Geyter, Nathalie

    2018-06-01

    In this work, a dielectric barrier discharge (DBD) has been used for the deposition of bipolar films containing alternating nano-layers of plasma polymerized allylamine (PPAam) and acrylic acid (PPAac). Various films were obtained by varying the single-layer thickness of each plasma polymer while maintaining a constant total film thickness and two kinds of films were fabricated via different depositing sequences (PPAam/Aac and PPAac/Aam). Films properties, ageing in air and stability in water over a 7 days period were investigated. Results showed that, COO- and NH3+ polar entities, generated from the interaction of PPAam and PPAac, are present in the bipolar films. Concerning the films stability, the different reaction mechanisms involved in the formation of each kind of films resulted in a higher amount of polar groups in the PPAam/Aac films; this conferred these films a higher stability than PPAac/Aam. Concerning the films ageing behavior, all prepared samples underwent some kind of ageing which was found to be dependent on the deposition sequence. Results also showed that bipolar coatings exhibited better cell-material interactions compared to PPAam and PPAac films; with a better cell viability observed on PPAam/Aac coatings after 1 and 7 days culture.

  19. Melanopsin expressing human retinal ganglion cells: Subtypes, distribution, and intraretinal connectivity.

    PubMed

    Hannibal, Jens; Christiansen, Anders Tolstrup; Heegaard, Steffen; Fahrenkrug, Jan; Kiilgaard, Jens Folke

    2017-06-01

    Intrinsically photosensitive retinal ganglion cells (ipRGCs) expressing the photopigment melanopsin belong to a heterogenic population of RGCs which regulate the circadian clock, masking behavior, melatonin suppression, the pupillary light reflex, and sleep/wake cycles. The different functions seem to be associated to different subtypes of melanopsin cells. In rodents, subtype classification has associated subtypes to function. In primate and human retina such classification has so far, not been applied. In the present study using antibodies against N- and C-terminal parts of human melanopsin, confocal microscopy and 3D reconstruction of melanopsin immunoreactive (-ir) RGCs, we applied the criteria used in mouse on human melanopsin-ir RGCs. We identified M1, displaced M1, M2, and M4 cells. We found two other subtypes of melanopsin-ir RGCs, which were named "gigantic M1 (GM1)" and "gigantic displaced M1 (GDM1)." Few M3 cells and no M5 subtypes were labeled. Total cell counts from one male and one female retina revealed that the human retina contains 7283 ± 237 melanopsin-ir (0.63-0.75% of the total number of RGCs). The melanopsin subtypes were unevenly distributed. Most significant was the highest density of M4 cells in the nasal retina. We identified input to the melanopsin-ir RGCs from AII amacrine cells and directly from rod bipolar cells via ribbon synapses in the innermost ON layer of the inner plexiform layer (IPL) and from dopaminergic amacrine cells and GABAergic processes in the outermost OFF layer of the IPL. The study characterizes a heterogenic population of human melanopsin-ir RGCs, which most likely are involved in different functions. © 2017 Wiley Periodicals, Inc.

  20. Quantal amplitude at the cone ribbon synapse can be adjusted by changes in cytosolic glutamate

    PubMed Central

    Bartoletti, Theodore M.

    2011-01-01

    Purpose Vision is encoded at photoreceptor synapses by the number of released vesicles and size of the post-synaptic response. We hypothesized that elevating cytosolic glutamate could enhance quantal size by increasing glutamate in vesicles. Methods We introduced glutamate (10–40 mM) into cone terminals through a patch pipette and recorded excitatory post-synaptic currents (EPSCs) from horizontal or OFF bipolar cells in the Ambystoma tigrinum retinal slice preparation. Results Elevating cytosolic glutamate in cone terminals enhanced EPSCs as well as quantal miniature EPSCs (mEPSCs). Enhancement was prevented by inhibiting vesicular glutamate transport with 1S,3R-1-aminocyclopentane-1,3-dicarboxylate in the patch pipette. A low affinity glutamate receptor antagonist, γD-glutamylglycine (1 mM), less effectively inhibited EPSCs evoked from cones loaded with glutamate than control cones indicating that release from cones with supplemental glutamate produced higher glutamate levels in the synaptic cleft. Raising presynaptic glutamate did not alter exocytotic capacitance responses and exocytosis was observed after inhibiting glutamate loading with the vesicular ATPase inhibitor, concanamycin A, suggesting that release capability is not restricted by low vesicular glutamate levels. Variance-mean analysis of currents evoked by flash photolysis of caged glutamate indicated that horizontal cell AMPA receptors have a single channel conductance of 10.1 pS suggesting that ~8.7 GluRs contribute to each mEPSC. Conclusions Quantal amplitude at the cone ribbon synapse is capable of adjustment by changes in cytosolic glutamate levels. The small number of channels contributing to each mEPSC suggests that stochastic variability in channel opening could be an important source of quantal variability. PMID:21541265

  1. Expression of sigma receptor 1 mRNA and protein in rat retina.

    PubMed

    Liu, L L; Wang, L; Zhong, Y M; Yang, X L

    2010-06-02

    Sigma receptor (sigmaR), known as a unique nonopiate, nonphencyclidine brain receptor, can bind diverse classes of psychotropic drugs, neurosteroids and other synthetic compounds, such as (+)pentazocine, etc. Two types of sigmaRs have been identified: sigmaR1 and sigmaR2. In this work, we examined the expression of sigmaR1 in rat retina by reverse transcription-polymerase chain reactive (RT-PCR) analysis and immunofluorescence double labeling. RT-PCR analysis showed that sigmaR1 mRNA was present in rat retina. Furthermore, labeling for sigmaR1 was diffusely distributed in the outer and inner plexiform layers. The sigmaR1-immunoreactivity (IR) was also observed in many cells in the inner nuclear layer and the ganglion cell layer. In the outer retina sigmaR1 was expressed in all horizontal cells labeled by calbindin. In contrast, no sigmaR1-IR was detected in several subtypes of bipolar cells, including rod-dominant ON-type bipolar cells, types 2, 3, 5 and 8 bipolar cells, labeled by protein kinase C (PKC), recoverin and hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 (HCN4) respectively. In the inner retina, most of GABAergic amacrine cells, including dopaminergic and cholinergic ones, stained by tyrosine hydroxylase (TH) and choline acetyltransferase (ChAT) respectively, expressed sigmaR1. Some glycinergic amacrine cells were also labeled by sigmaR1, but glycinergic AII amacrine cells were not labeled. In addition, sigmaR1-IR was seen in almost all somata of the ganglion cells retrogradely labeled by fluorogold. These results suggest that sigmaR1 may have neuromodulatory and neuroprotective roles in the retina. Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.

  2. Development of the Ni-based Metallic glassy bipolar plates for Proton Exchange Membrane Fuel Cell (PEMFC)

    NASA Astrophysics Data System (ADS)

    Yamaura, S.; Yokoyama, M.; Kimura, H. M.; Inoue, A.

    2009-01-01

    Alloy optimization in the Ni80-xCrxP16B4 (x = 9-30 at%) alloy system was conducted in order to achieve low Tg, Tx and a large ΔTx. From this study, the Ni65Cr15P16B4 glassy alloy was found to be the optimal alloy. The static and potentiodynamic corrosion behaviours of this alloy were measured. As a result of polarization measurements, it was found that the current density of the non-polished glassy alloy sample was smaller than that of a SUS316L sample. By contrast, the current density of the surface-polished glassy sample was slightly larger than that of the SUS316L sample in the voltage range of 0.3-0.8 V. A bipolar plate was successfully produced by hot-pressing the glassy alloy sheet in a supercooled liquid state. The I-V characteristics of a single cell with the glassy bipolar plates were measured.

  3. [Tyrosine hydroxylase in telencephalon and diencephalon of Rhodeus sericeus (Cyprinidae)].

    PubMed

    Pushchina, E V

    2009-01-01

    Immunohistochemical labeling of tyrosine hydroxylase was used to demonstrate catecholaminergic neuronal populations in the telencephalon and diencephalonof adult cypryniform fish Rhodeus sericeus. Various immunoreactive cell populations have been found in the telencephalon (ventral, central and lateral nuclei of ventral telencephalic area). Immunoreactive cells and fibers were discovered in dorsal nucleus of ventral telencephalic area and supracomissural nucleus in the caudal part of the telencephalon. In the diencephalon, periventricular nuclei (preoptic, periventricular nucleus of posterior tuberculum and periventricular organ) contained considerable TH-ergic cells. High activity of tyrosine hydroxylase was revealed in the pretectal, ventro-medial, ventro-lateral and suprachiasmatic nuclei. Periventricular hypothalamic nuclei also displayed high activity of tyrosine hydroxylase. Pseudounipolar neurons prevailed in all TH-immunereactive structures of the telencephalon and diencephalon: numerous bipolar liquor-contacting cells were discovered in the periventricular nuclei. Large pear-shaped cells and bipolar TH-ergic cells were found in posterior tuberculum. These cells may be functionally related to the dopamine-acquiring system.

  4. Component variations and their effects on bipolar nickel-hydrogen cell performance

    NASA Technical Reports Server (NTRS)

    Manzo, Michelle A.; Gahn, Randall F.; Gonzalez-Sanabria, Olga D.; Cataldo, Robert L.; Gemeiner, Russel P.

    1987-01-01

    A 50 cell bipolar nickel-hydrogen battery was assembled to demonstrate the feasibility of constructing a high voltage stack of cells. Various component combinations were tested in this battery. The battery had approximately 1 ampere-hour of capacity and was constructed from components with an active area of 2 x 2 inches. The components were parametrically varied to give a comparison of nickel electrodes, hydrogen electrodes, separators, fill procedures and electrolyte reservoir plate thicknesses. Groups of five cells were constructed using the same components; ten combinations were tested in all. The battery was thoroughly characterized at various change and discharge rates as well as with various pulse patterns and rates. Over a period of 1400 40-percent DOD LEO cycles some of the groups began to exhibit performance differences. In general, only separator variations had a significant effect on cell performance. It also appears that shunt currents may have been operating within the stack, resulting in electrolyte transfer from one cell to another, thus contributing to cell performance variations.

  5. Component variations and their effects on bipolar nickel-hydrogen cell performance

    NASA Technical Reports Server (NTRS)

    Manzo, Michelle A.; Gahn, Randall F.; Gonzalez-Sanabria, Olga D.; Cataldo, Robert L.; Gemeiner, Russel P.

    1987-01-01

    A 50 cell bipolar nickel-hydrogen battery was assembled to demonstrate the feasibility of constructing a high voltage stack of cells. Various component combinations were tested in this battery. The battery had approximately 1 ampere-hour of capacity and was constructed from components with an active area of 2" X 2". The components were parametrically varied to give a comparison of nickel electrodes, hydrogen electrodes, separators, fill procedures and electrolyte reservoir plate thicknesses. Groups of five cells were constructed using the same components; ten combinations were tested in all. The battery was thoroughly characterized at various change and discharge rates as well as with various pulse patterns and rates. Over a period of 1400 40% DOD LEO cycles some of the groups began to exhibit performance differences. In general, only separator variations had a significant effect on cell performance. It also appears that shunt currents may have been operating within the stack, resulting in electrolyte transfer from one cell to another, thus contributing to cell performance variations.

  6. Titanium oxide nonvolatile memory device and its application

    NASA Astrophysics Data System (ADS)

    Wang, Wei

    In recent years, the semiconductor memory industry has seen an ever-increasing demand for nonvolatile memory (NVM), which is fueled by portable consumer electronic applications like the mobile phone and MP3 player. FLASH memory has been the most widely used nonvolatile memories in these systems, and has successfully kept up with CMOS scaling for many generations. However, as FLASH memory faces major scaling challenges beyond 22nm, non-charge-based nonvolatile memories are widely researched as candidates to replace FLASH. Titanium oxide (TiOx) nonvolatile memory device is considered to be a promising choice due to its controllable nonvolatile memory switching, good scalability, compatibility with CMOS processing and potential for 3D stacking. However, several major issues need to be overcome before TiOx NVM device can be adopted in manufacturing. First, there exists a highly undesirable high-voltage stress initiation process (FORMING) before the device can switch between high and low resistance states repeatedly. By analyzing the conductive behaviors of the memory device before and after FORMING, we propose that FORMING involves breaking down an interfacial layer between its Pt electrode and the TiOx thin film, and that FORMING is not needed if the Pt-TiOx interface can be kept clean during fabrication. An in-situ fabrication process is developed for cross-point TiOx NVM device, which enables in-situ deposition of the critical layers of the memory device and thus achieves clean interfaces between Pt electrodes and TiOx film. Testing results show that FORMING is indeed eliminated for memory devices made with the in-situ fabrication process. It verifies the significance of in-situ deposition without vacuum break in the fabrication of TiOx NVM devices. Switching parameters statistics of TiOx NVM devices are studied and compared for unipolar and bipolar switching modes. RESET mechanisms are found to be different for the two switching modes: unipolar switching can be explained by thermal dissolution model, and bipolar switching by local redox reaction model. Since it is generally agreed that the memory switching of TiOx NVM devices is based on conductive filaments, reusability of these conductive filaments becomes an intriguing issue to determine the memory device's endurance. A 1X3 cross-point test structure is built to investigate whether conductive filaments can be reused after RESET. It is found that the conductive filament is destroyed during unipolar switching, while can be reused during bipolar switching. The result is a good indication that bipolar switching should have better endurance than unipolar switching. Finally a novel application of the two-terminal resistive switching NVM devices is demonstrated. To reduce SRAM leakage power, we propose a nonvolatile SRAM cell with two back-up NVM devices. This novel cell offers nonvolatile storage, thus allowing selected blocks of SRAM to be powered down during operation. There is no area penalty in this approach. Only a slight performance penalty is expected.

  7. Coexistence of unipolar and bipolar resistive switching behaviors in NiFe2O4 thin film devices by doping Ag nanoparticles

    NASA Astrophysics Data System (ADS)

    Hao, Aize; Ismail, Muhammad; He, Shuai; Huang, Wenhua; Qin, Ni; Bao, Dinghua

    2018-02-01

    The coexistence of unipolar and bipolar resistive switching (RS) behaviors of Ag-nanoparticles (Ag-NPs) doped NiFe2O4 (NFO) based memory devices was investigated. The switching voltages of required operations in the unipolar mode were smaller than those in the bipolar mode, while ON/OFF resistance levels of both modes were identical. Ag-NPs doped NFO based devices could switch between the unipolar and bipolar modes just by preferring the polarity of RESET voltage. Besides, the necessity of identical compliance current during the SET process of unipolar and bipolar modes provided an additional advantage of simplicity in device operation. Performance characteristics and cycle-to-cycle uniformity (>103 cycles) in unipolar operation were considerably better than those in bipolar mode (>102 cycles) at 25 °C. Moreover, good endurance (>600 cycles) at 200 °C was observed in unipolar mode and excellent nondestructive retention characteristics were obtained on memory cells at 125 °C and 200 °C. On the basis of temperature dependence of resistance at low resistance state, it was believed that physical origin of the RS mechanism involved the formation/rupture of the conducting paths consisting of oxygen vacancies and Ag atoms, considering Joule heating and electrochemical redox reaction effects for the unipolar and bipolar resistive switching behaviors. Our results demonstrate that 0.5% Ag-NPs doped nickel ferrites are promising resistive switching materials for resistive access memory applications.

  8. Theoretical design strategies of bipolar membrane fuel cell with enhanced self-humidification behavior

    NASA Astrophysics Data System (ADS)

    Li, Qiushi; Gong, Jian; Peng, Sikan; Lu, Shanfu; Sui, Pang-Chieh; Djilali, Ned; Xiang, Yan

    2016-03-01

    The bipolar membrane fuel cells (BPMFCs), which have a unique acid-alkaline jointed membrane electrode assembly (MEA) structure, have demonstrated their great potential for self-humidification during operation. Although the self-humidification ability of such bipolar membranes (BPMs) has recently been validated by a one-dimensional BPM model, the transport mechanism and the formation of self-humidification in the MEAs are not well understood. In the present study, a two-dimensional cross-channel MEA model is developed to elucidate the mechanisms and enhancement of water transport on self-humidification with comprehensive consideration of the three electrochemical reaction zones. The water-formation interface model has been successfully investigated by theoretical and experimental interface reaction kinetics, streamlines of water flux present the formation process and mechanism of self-humidification. A critical current (voltage) value, beyond which self-humidification is initiated, is identified. It is also found that such critical current (voltage) can be adjusted by changing the membrane thickness and the water uptake property of the ionomer. It is concluded that fabricating BPMs with proper membrane thickness and water uptake property are effective strategies to enhance the water management and cell performance in BPMFCs.

  9. The effect of lithium on hematopoietic, mesenchymal and neural stem cells.

    PubMed

    Ferensztajn-Rochowiak, Ewa; Rybakowski, Janusz K

    2016-04-01

    Lithium has been used in modern psychiatry for more than 65 years, constituting a cornerstone for the long-term treatment of bipolar disorder. A number of biological properties of lithium have been discovered, including its hematological, antiviral and neuroprotective effects. In this article, a systematic review of the effect of lithium on hematopoietic, mesenchymal and neural stem cells is presented. The beneficial effects of lithium on the level of hematopoietic stem cells (HSC) and growth factors have been reported since 1970s. Lithium improves homing of stem cells, the ability to form colonies and HSC self-renewal. Lithium also exerts a favorable influence on the proliferation and maintenance of mesenchymal stem cells (MSC). Studies on the effect of lithium on neurogenesis have indicated an increased proliferation of progenitor cells in the dentate gyrus of the hippocampus and enhanced mitotic activity of Schwann cells. This may be connected with the neuroprotective and neurotrophic effects of lithium, reflected in an improvement in synaptic plasticity promoting cell survival and inhibiting apoptosis. In clinical studies, lithium treatment increases cerebral gray matter, mainly in the frontal lobes, hippocampus and amygdala. Recent findings also suggest that lithium may reduce the risk of dementia and exert a beneficial effect in neurodegenerative diseases. The most important mediators and signaling pathways of lithium action are the glycogen synthase kinase-3 and Wnt/β-catenin pathways. Recently, to study of bipolar disorder pathogenesis and the mechanism of lithium action, the induced pluripotent stem cells (iPSC) obtained from bipolar patients have been used. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  10. A resettable and reprogrammable keypad lock based on electrochromic Prussian blue films and biocatalysis of immobilized glucose oxidase in a bipolar electrode system.

    PubMed

    Yu, Xue; Liang, Jiying; Yang, Tiangang; Gong, Mengjie; Xi, Dongman; Liu, Hongyun

    2018-01-15

    Herein, a resettable and reprogrammable biomolecular keypad lock on the basis of a closed bipolar electrode (BPE) system was established. In this system, one ITO electrode with immobilized chitosan (CS) and glucose oxidase (GOD), designated as CS-GOD, acted as one pole of BPE in the sensing cell; another ITO with electrodeposited Prussian blue (PB) films as the other pole in the reporting cell. The addition of ascorbic acid (AA) in the sensing cell with driving voltage (V tot ) at +2.5V would make the PB films become Prussian white (PW) in the reporting cell, accompanied by the color change from blue to nearly transparent. On the other hand, with the help of oxygen, the addition of glucose in the sensing cell with V tot at -1.5V would induce PW back to PB. The change of color and the corresponding UV-vis absorbance at 700nm for the PB/PW films in the reporting cell could be reversibly switched by changing the solute in the sensing cell between AA and glucose and then switching V tot between +2.5 and -1.5V. Based on these, a keypad lock was developed with AA, glucose and V tot as 3 inputs, and the color change of the PB/PW films as the output. This keypad lock system combined enzymatic catalysis with bipolar electrochemistry, demonstrating some unique advantages such as good reprogrammability, easy resettability and visual readout by naked eye. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Development of a brazing process for the production of water- cooled bipolar plates made of chromium-coated metal foils for PEM fuel cells

    NASA Astrophysics Data System (ADS)

    Mueller, M.; Hoehlich, D.; Scharf, I.; Lampke, T.; Hollaender, U.; Maier, H. J.

    2016-03-01

    Beside lithium batteries, PEM fuel cells are the most promising strategy as a power source to achieve the targets for introducing and increasing the usage of electric vehicles. Due to limited space and weight problems, water cooled, metallic bipolar plates in a fuel cell metal stack are preferred in motor vehicles. These plates are stamped metal sheets with a complex structure, interconnected media-tight. To meet the multiple tasks and requirements in use, complex and expensive combinations of materials are currently in use (carbon fiber composites, graphite, gold-plated nickel, stainless and acid resistant steel). The production of such plates is expensive as it is connected with considerable effort or the usage of precious metals. As an alternative, metalloid nitrides (CrN, VN, W2N, etc.) show a high chemical resistance, hardness and a good conductivity. So this material category meets the basic requirements of a top layer. However, the standard methods for their production (PVD, CVD) are expensive and have a slow deposition rate and a lower layer thicknesses. Because of these limitations, a full functionality over the life cycle of a bipolar plate is not guaranteed. The contribution shows the development and quantification of an alternative production process for bipolar plates. The expectation is to get significant advantages from the combination of chromium electrodeposition and thermochemical treatment to form chromium nitrides. Both processes are well researched and suitable for series production. The thermochemical treatment of the chromium layer also enables a process-integrated brazing.

  12. CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma: specific technical aspects and clinical results.

    PubMed

    Sommer, C M; Lemm, G; Hohenstein, E; Bellemann, N; Stampfl, U; Goezen, A S; Rassweiler, J; Kauczor, H U; Radeleff, B A; Pereira, P L

    2013-06-01

    This study was designed to evaluate the clinical efficacy of CT-guided bipolar and multipolar radiofrequency ablation (RF ablation) of renal cell carcinoma (RCC) and to analyze specific technical aspects between both technologies. We included 22 consecutive patients (3 women; age 74.2 ± 8.6 years) after 28 CT-guided bipolar or multipolar RF ablations of 28 RCCs (diameter 2.5 ± 0.8 cm). Procedures were performed with a commercially available RF system (Celon AG Olympus, Berlin, Germany). Technical aspects of RF ablation procedures (ablation mode [bipolar or multipolar], number of applicators and ablation cycles, overall ablation time and deployed energy, and technical success rate) were analyzed. Clinical results (local recurrence-free survival and local tumor control rate, renal function [glomerular filtration rate (GFR)]) and complication rates were evaluated. Bipolar RF ablation was performed in 12 procedures and multipolar RF ablation in 16 procedures (2 applicators in 14 procedures and 3 applicators in 2 procedures). One ablation cycle was performed in 15 procedures and two ablation cycles in 13 procedures. Overall ablation time and deployed energy were 35.0 ± 13.6 min and 43.7 ± 17.9 kJ. Technical success rate was 100 %. Major and minor complication rates were 4 and 14 %. At an imaging follow-up of 15.2 ± 8.8 months, local recurrence-free survival was 14.4 ± 8.8 months and local tumor control rate was 93 %. GFR did not deteriorate after RF ablation (50.8 ± 16.6 ml/min/1.73 m(2) before RF ablation vs. 47.2 ± 11.9 ml/min/1.73 m(2) after RF ablation; not significant). CT-guided bipolar and multipolar RF ablation of RCC has a high rate of clinical success and low complication rates. At short-term follow-up, clinical efficacy is high without deterioration of the renal function.

  13. Effects of GABA receptor antagonists on thresholds of P23H rat retinal ganglion cells to electrical stimulation of the retina

    NASA Astrophysics Data System (ADS)

    Jensen, Ralph J.; Rizzo, Joseph F., III

    2011-06-01

    An electronic retinal prosthesis may provide useful vision for patients suffering from retinitis pigmentosa (RP). In animal models of RP, the amount of current needed to activate retinal ganglion cells (RGCs) is higher than in normal, healthy retinas. In this study, we sought to reduce the stimulation thresholds of RGCs in a degenerate rat model (P23H-line 1) by blocking GABA receptor mediated inhibition in the retina. We examined the effects of TPMPA, a GABAC receptor antagonist, and SR95531, a GABAA receptor antagonist, on the electrically evoked responses of RGCs to biphasic current pulses delivered to the subretinal surface through a 400 µm diameter electrode. Both TPMPA and SR95531 reduced the stimulation thresholds of ON-center RGCs on average by 15% and 20% respectively. Co-application of the two GABA receptor antagonists had the greatest effect, on average reducing stimulation thresholds by 32%. In addition, co-application of the two GABA receptor antagonists increased the magnitude of the electrically evoked responses on average three-fold. Neither TPMPA nor SR95531, applied alone or in combination, had consistent effects on the stimulation thresholds of OFF-center RGCs. We suggest that the effects of the GABA receptor antagonists on ON-center RGCs may be attributable to blockage of GABA receptors on the axon terminals of ON bipolar cells.

  14. TMBP200, a XMAP215 homologue of tobacco BY-2 cells, has an essential role in plant mitosis.

    PubMed

    Yasuhara, Hiroki; Oe, Yuki

    2011-07-01

    TMBP200 from tobacco BY-2 cells is a member of the highly conserved family of microtubule-associated proteins that includes Xenopus XMAP215, human TOGp, and Arabidopsis MOR1/GEM1. XMAP215 homologues have an essential role in spindle assembly and function in animals and yeast, but their role in plant mitosis is not fully clarified. Here, we show by immunoblot analysis that TMBP200 levels in synchronously cultured BY-2 cells increased when the cells entered mitosis, thus indicating that TMBP200 plays an important role in mitosis in tobacco. To investigate the role of TMBP200 in mitosis, we employed inducible RNA interference to silence TMBP200 expression in BY-2 cells. The resulting depletion of TMBP200 caused severe defects in bipolar spindle formation and resulted in the appearance of multinucleated cells with variable-sized nuclei. This finding indicates that TMBP200 has an essential role in bipolar spindle formation and function.

  15. Overexpression of the VSSC-associated CAM, β-2, enhances LNCaP cell metastasis associated behavior.

    PubMed

    Jansson, Keith H; Lynch, Jill E; Lepori-Bui, Nadia; Czymmek, Kirk J; Duncan, Randall L; Sikes, Robert A

    2012-07-01

    Prostate cancer (PCa) is the second-leading cause of cancer death in American men. This is due largely to the "silent" nature of the disease until it has progressed to a highly metastatic and castrate resistant state. Voltage sensitive sodium channels (VSSCs) are multimeric transmembrane protein complexes comprised of a pore-forming α subunit and one or two β subunits. The β-subunits modulate surface expression and gating kinetics of the channels but also have inherent cell adhesion molecule (CAM) functions. We hypothesize that PCa cells use VSSC β-subunits as CAMs during PCa progression and metastasis. We overexpressed the beta-2 isoform as a C-terminal fusion protein with enhanced cyan fluorescence protein (ECFP) in the weakly metastatic LNCaP cells. The effect of beta-2 overexpression on cell morphology was examined using confocal microscopy while metastasis-associated behavior was tested by performing several in vitro metastatic functional assays and in vivo subcutaneous tumor studies. We found that cells overexpressing beta-2 (2BECFP) converted to a bipolar fibroblastic morphology. 2BECFP cells were more adhesive than control (ECFP) to vitronectin (twofold) and Matrigel® (1.3-fold), more invasive through Matrigel® (3.6-fold in 72 hr), and had enhanced migration (2.1-fold in 96 hr) independent of proliferation in wound-healing assays. In contrast, 2BECFP cells have a reduced tumor-take and tumor volume in vivo even though the overexpression of beta-2 was maintained. Functional overexpression of VSSC β-subunits in PCa may be one mechanism leading to increased metastatic behavior while decreasing the ability to form localized tumor masses. Copyright © 2011 Wiley Periodicals, Inc.

  16. Biologically based machine vision: signal analysis of monopolar cells in the visual system of Musca domestica.

    PubMed

    Newton, Jenny; Barrett, Steven F; Wilcox, Michael J; Popp, Stephanie

    2002-01-01

    Machine vision for navigational purposes is a rapidly growing field. Many abilities such as object recognition and target tracking rely on vision. Autonomous vehicles must be able to navigate in dynamic enviroments and simultaneously locate a target position. Traditional machine vision often fails to react in real time because of large computational requirements whereas the fly achieves complex orientation and navigation with a relatively small and simple brain. Understanding how the fly extracts visual information and how neurons encode and process information could lead us to a new approach for machine vision applications. Photoreceptors in the Musca domestica eye that share the same spatial information converge into a structure called the cartridge. The cartridge consists of the photoreceptor axon terminals and monopolar cells L1, L2, and L4. It is thought that L1 and L2 cells encode edge related information relative to a single cartridge. These cells are thought to be equivalent to vertebrate bipolar cells, producing contrast enhancement and reduction of information sent to L4. Monopolar cell L4 is thought to perform image segmentation on the information input from L1 and L2 and also enhance edge detection. A mesh of interconnected L4's would correlate the output from L1 and L2 cells of adjacent cartridges and provide a parallel network for segmenting an object's edges. The focus of this research is to excite photoreceptors of the common housefly, Musca domestica, with different visual patterns. The electrical response of monopolar cells L1, L2, and L4 will be recorded using intracellular recording techniques. Signal analysis will determine the neurocircuitry to detect and segment images.

  17. Self-induced redox cycling coupled luminescence on nanopore recessed disk-multiscale bipolar electrodes

    DOE PAGES

    Ma, Chaoxiong; Zaino III, Lawrence P.; Bohn, Paul W.

    2015-03-25

    Self-induced redox cycling at nanopore ring-disk electrodes is coupled, through a bipolar electrode, to a remote fluorigenic reporter reaction. We present a new configuration for coupling fluorescence microscopy and voltammetry using self-induced redox cycling for ultrasensitive electrochemical measurements. An array of nanopores, each supporting a recessed disk electrode separated by 100 nm in depth from a planar multiscale bipolar top electrode, was fabricated using multilayer deposition, nanosphere lithography, and reactive-ion etching. Self-induced redox cycling was induced on the disk electrode producing ~30× current amplification, which was independently confirmed by measuring induced electrogenerated chemiluminescence from Ru(bpy) 3 2/3+/tri-n-propylamine on the floatingmore » bipolar electrode. In this design, redox cycling occurs between the recessed disk and the top planar portion of a macroscopic thin film bipolar electrode in each nanopore. Electron transfer also occurs on a remote (mm-distance) portion of the planar bipolar electrode to maintain electroneutrality. This couples the electrochemical reactions of the target redox pair in the nanopore array with a reporter, such as a potential-switchable fluorescent indicator, in the cell at the distal end of the bipolar electrode. Oxidation or reduction of reversible analytes on the disk electrodes were accompanied by reduction or oxidation, respectively, on the nanopore portion of the bipolar electrode and then monitored by the accompanying oxidation of dihydroresorufin or reduction of resorufin at the remote end of the bipolar electrode, respectively. In both cases, changes in fluorescence intensity were triggered by the reaction of the target couple on the disk electrode, while recovery was largely governed by diffusion of the fluorescent indicator. Reduction of 1 nM of Ru(NH 3) 6 3+ on the nanoelectrode array was detected by monitoring the fluorescence intensity of resorufin, demonstrating high sensitivity fluorescence-mediated electrochemical sensing coupled to self-induced redox cycling.« less

  18. Self-induced redox cycling coupled luminescence on nanopore recessed disk-multiscale bipolar electrodes

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Ma, Chaoxiong; Zaino III, Lawrence P.; Bohn, Paul W.

    Self-induced redox cycling at nanopore ring-disk electrodes is coupled, through a bipolar electrode, to a remote fluorigenic reporter reaction. We present a new configuration for coupling fluorescence microscopy and voltammetry using self-induced redox cycling for ultrasensitive electrochemical measurements. An array of nanopores, each supporting a recessed disk electrode separated by 100 nm in depth from a planar multiscale bipolar top electrode, was fabricated using multilayer deposition, nanosphere lithography, and reactive-ion etching. Self-induced redox cycling was induced on the disk electrode producing ~30× current amplification, which was independently confirmed by measuring induced electrogenerated chemiluminescence from Ru(bpy) 3 2/3+/tri-n-propylamine on the floatingmore » bipolar electrode. In this design, redox cycling occurs between the recessed disk and the top planar portion of a macroscopic thin film bipolar electrode in each nanopore. Electron transfer also occurs on a remote (mm-distance) portion of the planar bipolar electrode to maintain electroneutrality. This couples the electrochemical reactions of the target redox pair in the nanopore array with a reporter, such as a potential-switchable fluorescent indicator, in the cell at the distal end of the bipolar electrode. Oxidation or reduction of reversible analytes on the disk electrodes were accompanied by reduction or oxidation, respectively, on the nanopore portion of the bipolar electrode and then monitored by the accompanying oxidation of dihydroresorufin or reduction of resorufin at the remote end of the bipolar electrode, respectively. In both cases, changes in fluorescence intensity were triggered by the reaction of the target couple on the disk electrode, while recovery was largely governed by diffusion of the fluorescent indicator. Reduction of 1 nM of Ru(NH 3) 6 3+ on the nanoelectrode array was detected by monitoring the fluorescence intensity of resorufin, demonstrating high sensitivity fluorescence-mediated electrochemical sensing coupled to self-induced redox cycling.« less

  19. Adjunctive treatment of manic agitation with lorazepam versus haloperidol: a double-blind study.

    PubMed

    Lenox, R H; Newhouse, P A; Creelman, W L; Whitaker, T M

    1992-02-01

    While lithium is effective in treating the majority of bipolar patients during a manic episode, the addition of neuroleptic during the early phase of treatment has been common clinical practice in inpatient settings. In an earlier open study, we demonstrated the utility of the short-acting benzodiazepine lorazepam as an adjunct to lithium for the clinical management of manic agitation. We now present data from a randomized, double-blind clinical study of lorazepam versus haloperidol in 20 hospitalized patients with a DSM-III-R diagnosis of bipolar disorder who were being treated concomitantly with lithium. Patients were rated using the Mania Rating Scale, Brief Psychiatric Rating Scale, Physician Global Impression Scale, and side effects scales. Data were analyzed using standard group comparisons and survival analysis. There was no evidence for a significant difference between the two treatment groups in the magnitude of or time to response (5.0 +/- .82 days for haloperidol; 6.5 +/- .93 days for lorazepam). Of the patients who were terminated from the protocol early, nonresponse was the primary reason in the lorazepam group while side effects were the reason in the haloperidol group. Lorazepam may offer an efficacious and safe alternative to haloperidol as an adjunctive treatment to lithium in the clinical management of the early phase of manic agitation in a subgroup of bipolar patients.

  20. Nickel-metal hydride battery development. Final technical report

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    NONE

    1995-06-01

    Rechargeable batteries are used as the power source for a broad range of portable equipment. Key battery selection criteria typically are weight, volume, first cost, life cycle cost, and environmental impact. Rechargeable batteries are favored from a life cycle cost and environmental impact standpoint over primary batteries. The nickel-metal hydride (Ni-MH) battery system has emerged as the battery of choice for many applications based on its superior characteristics when judged on the above criteria against other battery types. In most cases commercial Ni-MH batteries are constructed with coiled electrodes in cylindrical metal containers. Electro Energy, Inc. (EEI) has been developingmore » a novel flat bipolar configuration of the Ni-MH system that offers weight, volume, and cost advantages when compared to cylindrical cells. The unique bipolar approach consists of fabricating individual flat wafer cells in conductive, carbon-filled, plastic face plates. The individual cells contain a nonconductive plastic border which is heat sealed around the perimeter to make a totally sealed unit cell. Multi-cell batteries are fabricated by stacking the individual wafer cells in such a way that the positive face of one cell contacts the negative face of the adjacent cell. The stack is then contained in an outer housing with end contacts. The purpose of this program was to develop, evaluate, and demonstrate the capabilities of the EEI Ni-MH battery system for consumer applications. The work was directed at the development and evaluation of the compact bipolar construction for its potential advantages of high power and energy density. Experimental investigations were performed on various nickel electrode types, hydride electrode formulations, and alternate separator materials. Studies were also directed at evaluating various oxygen recombination techniques for low pressure operation during charge and overcharge.« less

  1. Micro-Tubular Fuel Cells

    NASA Technical Reports Server (NTRS)

    Kimble, Michael C.; Anderson, Everett B.; Jayne, Karen D.; Woodman, Alan S.

    2004-01-01

    Micro-tubular fuel cells that would operate at power levels on the order of hundreds of watts or less are under development as alternatives to batteries in numerous products - portable power tools, cellular telephones, laptop computers, portable television receivers, and small robotic vehicles, to name a few examples. Micro-tubular fuel cells exploit advances in the art of proton-exchange-membrane fuel cells. The main advantage of the micro-tubular fuel cells over the plate-and-frame fuel cells would be higher power densities: Whereas the mass and volume power densities of low-pressure hydrogen-and-oxygen-fuel plate-and-frame fuel cells designed to operate in the targeted power range are typically less than 0.1 W/g and 0.1 kW/L, micro-tubular fuel cells are expected to reach power densities much greater than 1 W/g and 1 kW/L. Because of their higher power densities, micro-tubular fuel cells would be better for powering portable equipment, and would be better suited to applications in which there are requirements for modularity to simplify maintenance or to facilitate scaling to higher power levels. The development of PEMFCs has conventionally focused on producing large stacks of cells that operate at typical power levels >5 kW. The usual approach taken to developing lower-power PEMFCs for applications like those listed above has been to simply shrink the basic plate-and-frame configuration to smaller dimensions. A conventional plate-and-frame fuel cell contains a membrane/electrode assembly in the form of a flat membrane with electrodes of the same active area bonded to both faces. In order to provide reactants to both electrodes, bipolar plates that contain flow passages are placed on both electrodes. The mass and volume overhead of the bipolar plates amounts to about 75 percent of the total mass and volume of a fuel-cell stack. Removing these bipolar plates in the micro-tubular fuel cell significantly increases the power density.

  2. A combined analysis of genome-wide expression profiling of bipolar disorder in human prefrontal cortex.

    PubMed

    Wang, Jinglu; Qu, Susu; Wang, Weixiao; Guo, Liyuan; Zhang, Kunlin; Chang, Suhua; Wang, Jing

    2016-11-01

    Numbers of gene expression profiling studies of bipolar disorder have been published. Besides different array chips and tissues, variety of the data processes in different cohorts aggravated the inconsistency of results of these genome-wide gene expression profiling studies. By searching the gene expression databases, we obtained six data sets for prefrontal cortex (PFC) of bipolar disorder with raw data and combinable platforms. We used standardized pre-processing and quality control procedures to analyze each data set separately and then combined them into a large gene expression matrix with 101 bipolar disorder subjects and 106 controls. A standard linear mixed-effects model was used to calculate the differentially expressed genes (DEGs). Multiple levels of sensitivity analyses and cross validation with genetic data were conducted. Functional and network analyses were carried out on basis of the DEGs. In the result, we identified 198 unique differentially expressed genes in the PFC of bipolar disorder and control. Among them, 115 DEGs were robust to at least three leave-one-out tests or different pre-processing methods; 51 DEGs were validated with genetic association signals. Pathway enrichment analysis showed these DEGs were related with regulation of neurological system, cell death and apoptosis, and several basic binding processes. Protein-protein interaction network further identified one key hub gene. We have contributed the most comprehensive integrated analysis of bipolar disorder expression profiling studies in PFC to date. The DEGs, especially those with multiple validations, may denote a common signature of bipolar disorder and contribute to the pathogenesis of disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. A comparison of the neutrophil-lymphocyte, platelet-lymphocyte and monocyte-lymphocyte ratios in schizophrenia and bipolar disorder patients - a retrospective file review.

    PubMed

    Özdin, Selçuk; Sarisoy, Gökhan; Böke, Ömer

    2017-10-01

    Neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR) and monocyte-lymphocyte ratio (MLR) have recently been used as indicators of inflammation. Higher MLR and PLR values have been determined in the euthymic and manic periods in patients with bipolar disorder compared to a control group. High NLR values were determined in the only study investigating this ratio in schizophrenia patients. The purpose of this study was to compare NLR, PLR and MLR values and complete blood count elements in patients receiving treatment and hospitalized due to schizophrenic psychotic episode and bipolar disorder manic episode. All patients meeting the inclusion criteria among subjects receiving treatment and hospitalized due to schizophrenia-psychotic episode and bipolar affective disorder-manic episode at the Ondokuz Mayıs University Medical Faculty Psychiatry Department, Turkey, in 2012-2016 were included in our study. A total of 157 healthy donors were included as a control group. White blood cell (WBC), neutrophil, lymphocyte, platelet and monocyte numbers were noted retrospectively from complete blood counts at time of admission, and NLR, PLR and MLR were calculated from these. NLR, PLR and MLR values and platelet numbers in this study were higher and lymphocyte numbers were lower in bipolar disorder patients compared to the controls. Elevation in NLR, MLR and PLR values and neutrophil numbers and lower lymphocyte numbers were determined in schizophrenia patients compared to the controls. Higher NLR and MLR values were found in schizophrenia patients compared to bipolar disorder. Findings of our study supported the inflammation hypothesis for schizophrenia and bipolar disorder.

  4. A microtubule polymerase cooperates with the kinesin-6 motor and a microtubule cross-linker to promote bipolar spindle assembly in the absence of kinesin-5 and kinesin-14 in fission yeast

    PubMed Central

    Yukawa, Masashi; Kawakami, Tomoki; Okazaki, Masaki; Kume, Kazunori; Tang, Ngang Heok; Toda, Takashi

    2017-01-01

    Accurate chromosome segregation relies on the bipolar mitotic spindle. In many eukaryotes, spindle formation is driven by the plus-end–directed motor kinesin-5 that generates outward force to establish spindle bipolarity. Its inhibition leads to the emergence of monopolar spindles with mitotic arrest. Intriguingly, simultaneous inactivation of the minus-end–directed motor kinesin-14 restores spindle bipolarity in many systems. Here we show that in fission yeast, three independent pathways contribute to spindle bipolarity in the absence of kinesin-5/Cut7 and kinesin-14/Pkl1. One is kinesin-6/Klp9 that engages with spindle elongation once short bipolar spindles assemble. Klp9 also ensures the medial positioning of anaphase spindles to prevent unequal chromosome segregation. Another is the Alp7/TACC-Alp14/TOG microtubule polymerase complex. Temperature-sensitive alp7cut7pkl1 mutants are arrested with either monopolar or very short spindles. Forced targeting of Alp14 to the spindle pole body is sufficient to render alp7cut7pkl1 triply deleted cells viable and promote spindle assembly, indicating that Alp14-mediated microtubule polymerization from the nuclear face of the spindle pole body could generate outward force in place of Cut7 during early mitosis. The third pathway involves the Ase1/PRC1 microtubule cross-linker that stabilizes antiparallel microtubules. Our study, therefore, unveils multifaceted interplay among kinesin-dependent and -independent pathways leading to mitotic bipolar spindle assembly. PMID:29021344

  5. Aqueous based asymmetrical-bipolar electrochemical capacitor with a 2.4 V operating voltage

    NASA Astrophysics Data System (ADS)

    Wu, Haoran; Lian, Keryn

    2018-02-01

    A novel asymmetrical-bipolar electrochemical capacitor system leveraging the contributions of a Zn-CNT asymmetrical electrode and a KOH-H2SO4 dual-pH electrolyte was developed. The positive and negative electrodes operated in electrolytes with different pH, exploiting the maximum potential of both electrodes, which led to a cell voltage of 2.4 V. The potential tracking of both electrodes revealed that the Zn negative electrode could maintain a potential at -1.2 V, while the CNT positive electrode can be charged to +1.2 V without significant irreversible reactions. A bipolar ion exchange membrane has effectively separated the acid and alkaline from neutralization, which resulted in stable performance of the device with capacitance retention of 94% and coulombic efficiency of 99% over 10,000 cycles. This asymmetrical-bipolar design overcomes the thermodynamic limit of water decomposition, opening a new avenue towards high energy and high power density aqueous-based ECs.

  6. Deletion of the Tail Domain of the Kinesin-5 Cin8 Affects Its Directionality*

    PubMed Central

    Düselder, André; Fridman, Vladimir; Thiede, Christina; Wiesbaum, Alice; Goldstein, Alina; Klopfenstein, Dieter R.; Zaitseva, Olga; Janson, Marcel E.; Gheber, Larisa; Schmidt, Christoph F.

    2015-01-01

    The bipolar kinesin-5 motors are one of the major players that govern mitotic spindle dynamics. Their bipolar structure enables them to cross-link and slide apart antiparallel microtubules (MTs) emanating from the opposing spindle poles. The budding yeast kinesin-5 Cin8 was shown to switch from fast minus-end- to slow plus-end-directed motility upon binding between antiparallel MTs. This unexpected finding revealed a new dimension of cellular control of transport, the mechanism of which is unknown. Here we have examined the role of the C-terminal tail domain of Cin8 in regulating directionality. We first constructed a stable dimeric Cin8/kinesin-1 chimera (Cin8Kin), consisting of head and neck linker of Cin8 fused to the stalk of kinesin-1. As a single dimeric motor, Cin8Kin switched frequently between plus and minus directionality along single MTs, demonstrating that the Cin8 head domains are inherently bidirectional, but control over directionality was lost. We next examined the activity of a tetrameric Cin8 lacking only the tail domains (Cin8Δtail). In contrast to wild-type Cin8, the motility of single molecules of Cin8Δtail in high ionic strength was slow and bidirectional, with almost no directionality switches. Cin8Δtail showed only a weak ability to cross-link MTs in vitro. In vivo, Cin8Δtail exhibited bias toward the plus-end of the MTs and was unable to support viability of cells as the sole kinesin-5 motor. We conclude that the tail of Cin8 is not necessary for bidirectional processive motion, but is controlling the switch between plus- and minus-end-directed motility. PMID:25991727

  7. Vesicle Pool Size at the Salamander Cone Ribbon Synapse

    PubMed Central

    Bartoletti, Theodore M.; Babai, Norbert

    2010-01-01

    Cone light responses are transmitted to postsynaptic neurons by changes in the rate of synaptic vesicle release. Vesicle pool size at the cone synapse constrains the amount of release and can thus shape contrast detection. We measured the number of vesicles in the rapidly releasable and reserve pools at cone ribbon synapses by performing simultaneous whole cell recording from cones and horizontal or off bipolar cells in the salamander retinal slice preparation. We found that properties of spontaneously occurring miniature excitatory postsynaptic currents (mEPSCs) are representative of mEPSCs evoked by depolarizing presynaptic stimulation. Strong, brief depolarization of the cone stimulated release of the entire rapidly releasable pool (RRP) of vesicles. Comparing charge transfer of the EPSC with mEPSC charge transfer, we determined that the fast component of the EPSC reflects release of ∼40 vesicles. Comparing EPSCs with simultaneous presynaptic capacitance measurements, we found that horizontal cell EPSCs constitute 14% of the total number of vesicles released from a cone terminal. Using a fluorescent ribeye-binding peptide, we counted ∼13 ribbons per cone. Together, these results suggest each cone contacts a single horizontal cell at ∼2 ribbons. The size of discrete components in the EPSC amplitude histogram also suggested ∼2 ribbon contacts per cell pair. We therefore conclude there are ∼20 vesicles per ribbon in the RRP, similar to the number of vesicles contacting the plasma membrane at the ribbon base. EPSCs evoked by lengthy depolarization suggest a reserve pool of ∼90 vesicles per ribbon, similar to the number of additional docking sites further up the ribbon. PMID:19923246

  8. Design principles for nickel hydrogen cells and batteries

    NASA Technical Reports Server (NTRS)

    Thaller, L. H.

    1985-01-01

    Nickel hydrogen cells, and more recently, bipolar batteries have been built by a variety of organizations. The design principles that have been used by the technology group at the Lewis Research Center draw upon their extensive background in separator technology, alkaline fuel cell technology, and several alkaline cell technology areas. These design principles have been incorporated into both the more contemporary individual pressure vessel (IPV) designs that were pioneered by other groups, as well as the more recent bipolar battery designs using active cooling that are being developed at LeRC and their contractors. These principles are rather straightforward applications of capillary force formalisms, coupled with the slowly developing data base resulting from careful post test analyses. The objective of this overall effort is directed towards the low Earth orbit (LEO) application where the cycle life requirements are much more severe than the geosynchronous orbit (GEO) application. Nickel hydrogen cells have already been successfully flown in an increasing number of GEO missions.

  9. High surface area bio-waste based carbon as a superior electrode for vanadium redox flow battery

    NASA Astrophysics Data System (ADS)

    Maharjan, Makhan; Bhattarai, Arjun; Ulaganathan, Mani; Wai, Nyunt; Oo, Moe Ohnmar; Wang, Jing-Yuan; Lim, Tuti Mariana

    2017-09-01

    Activated carbon (AC) with high surface area (1901 m2 g-1) is synthesized from low cost bio-waste orange (Citrus sinensis) peel for vanadium redox flow battery (VRB). The composition, structure and electrochemical properties of orange peel derived AC (OP-AC) are characterized by elemental analyzer, field emission-scanning electron microscopy, X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, cyclic voltammetry (CV), and electrochemical impedance spectroscopy. CV results show that OP-AC coated bipolar plate demonstrates improved electro-catalytic activity in both positive and negative side redox couples than the pristine bipolar plate electrode and this is ascribed to the high surface area of OP-AC which provides effective electrode area and better contact between the porous electrode and bipolar plate. Consequently, the performance of VRB in a static cell shows higher energy efficiency for OP-AC electrode than the pristine electrode at all current densities tested. The results suggest the OP-AC to be a promising electrode for VRB applications and can be incorporated into making conducting plastics electrode to lower the VRB cell stack weight and cost.

  10. Sustained and Transient Contributions to the Rat Dark-Adapted Electroretinogram b-Wave

    PubMed Central

    Dang, Trung M.; Vingrys, Algis J.; Bui, Bang V.

    2013-01-01

    The most dominant feature of the electroretinogram, the b-wave, is thought to reflect ON-bipolar cell responses. However, a number of studies suggest that the b-wave is made up of several components. We consider the composition of the rat b-wave by subtracting corneal negative components obtained using intravitreal application of pharmacological agents to remove postreceptoral responses. By analyzing the intensity-response characteristic of the PII across a range of fixed times during and after a light step, we find that the rat isolated PII has 2 components. The first has fast rise and decay characteristics with a low sensitivity to light. GABAc-mediated inhibitory pathways enhance this transient-ON component to manifest increased and deceased sensitivity to light at shorter (<160 ms) and longer times, respectively. The second component has slower temporal characteristics but is more sensitive to light. GABAc-mediated inhibition enhances this sustained-ON component but has little effect on its sensitivity to light. After stimulus offset, both transient and sustained components return to baseline, and a long latency sustained positive component becomes apparent. The light sensitivities of transient-ON and sustained-OFF components are consistent with activity arising from cone ON- and OFF-bipolar cells, whereas the sustained-ON component is likely to arise from rod bipolar cells. PMID:23533706

  11. Gene therapy restores vision in rd1 mice after removal of a confounding mutation in Gpr179.

    PubMed

    Nishiguchi, Koji M; Carvalho, Livia S; Rizzi, Matteo; Powell, Kate; Holthaus, Sophia-Martha kleine; Azam, Selina A; Duran, Yanai; Ribeiro, Joana; Luhmann, Ulrich F O; Bainbridge, James W B; Smith, Alexander J; Ali, Robin R

    2015-01-23

    The rd1 mouse with a mutation in the Pde6b gene was the first strain of mice identified with a retinal degeneration. However, AAV-mediated gene supplementation of rd1 mice only results in structural preservation of photoreceptors, and restoration of the photoreceptor-mediated a-wave, but not in restoration of the bipolar cell-mediated b-wave. Here we show that a mutation in Gpr179 prevents the full restoration of vision in rd1 mice. Backcrossing rd1 with C57BL6 mice reveals the complete lack of b-wave in a subset of mice, consistent with an autosomal recessive Mendelian inheritance pattern. We identify a mutation in the Gpr179 gene, which encodes for a G-protein coupled receptor localized to the dendrites of ON-bipolar cells. Gene replacement in rd1 mice that are devoid of the mutation in Gpr179 successfully restores the function of both photoreceptors and bipolar cells, which is maintained for up to 13 months. Our discovery may explain the failure of previous gene therapy attempts in rd1 mice, and we propose that Grp179 mutation status should be taken into account in future studies involving rd1 mice.

  12. Evaluation of coated metallic bipolar plates for polymer electrolyte membrane fuel cells

    NASA Astrophysics Data System (ADS)

    Yoon, Wonseok; Huang, Xinyu; Fazzino, Paul; Reifsnider, Kenneth L.; Akkaoui, Michael A.

    Metallic bipolar plates for polymer electrolyte membrane (PEM) fuel cells typically require coatings for corrosion protection. Other requirements for the corrosion protective coatings include low electrical contact resistance, good mechanical robustness, low material and fabrication cost. The authors have evaluated a number of protective coatings deposited on stainless steel substrates by electroplating and physical vapor deposition (PVD) methods. The coatings are screened with an electrochemical polarization test for corrosion resistance; then the contact resistance test was performed on selected coatings. The coating investigated include Gold with various thicknesses (2 nm, 10 nm, and 1 μm), Titanium, Zirconium, Zirconium Nitride (ZrN), Zirconium Niobium (ZrNb), and Zirconium Nitride with a Gold top layer (ZrNAu). The substrates include three types of stainless steel: 304, 310, and 316. The results show that Zr-coated samples satisfy the DOE target for corrosion resistance at both anode and cathode sides in typical PEM fuel cell environments in the short-term, but they do not meet the DOE contact resistance goal. Very thin gold coating (2 nm) can significantly decrease the electrical contact resistance, however a relatively thick gold coating (>10 nm) with our deposition method is necessary for adequate corrosion resistance, particularly for the cathode side of the bipolar plate.

  13. Ionotropic GABA Receptors and Distal Retinal ON and OFF Responses

    PubMed Central

    Popova, E.

    2014-01-01

    In the vertebrate retina, visual signals are segregated into parallel ON and OFF pathways, which provide information for light increments and decrements. The segregation is first evident at the level of the ON and OFF bipolar cells in distal retina. The activity of large populations of ON and OFF bipolar cells is reflected in the b- and d-waves of the diffuse electroretinogram (ERG). The role of gamma-aminobutyric acid (GABA), acting through ionotropic GABA receptors in shaping the ON and OFF responses in distal retina, is a matter of debate. This review summarized current knowledge about the types of the GABAergic neurons and ionotropic GABA receptors in the retina as well as the effects of GABA and specific GABAA and GABAC receptor antagonists on the activity of the ON and OFF bipolar cells in both nonmammalian and mammalian retina. Special emphasis is put on the effects on b- and d-waves of the ERG as a useful tool for assessment of the overall function of distal retinal ON and OFF channels. The role of GABAergic system in establishing the ON-OFF asymmetry concerning the time course and absolute and relative sensitivity of the ERG responses under different conditions of light adaptation in amphibian retina is also discussed. PMID:25143858

  14. Effect of formation temperature on properties of graphite/stannum composite for bipolar plate

    NASA Astrophysics Data System (ADS)

    Selamat, Mohd Zulkefli; Yusuf, Muhammad Yusri Md; Wer, Tio Kok; Sahadan, Siti Norbaya; Malingam, Sivakumar Dhar; Mohamad, Noraiham

    2016-03-01

    Bipolar plates are key components in Proton Exchange Membrane (PEM) fuel cells. They carry current away from the cell and withstand the clamping force of the stack assembly. Therefore, PEM fuel cell bipolar plates must have high electrical conductivity and adequate mechanical strength, in addition to being light weight and low cost in terms of both applicable materials and production methods. In this research, the raw materials used to fabricate the high performance bipolar plate are Graphite (Gr), Stannum (Sn) and Polypropylene (PP). All materials used was in powder form and Gr and Sn act as fillers and the PP acts as binder. The ratio of fillers (Gr/Sn) and binder (PP) was fixed at 80:20. For the multi-conductive filler, small amount of Sn, which is 10 up to 20wt% (from the total weight of fillers 80%) have been added into Gr/Sn/PP composite. The fillers were mixed by using the ball mill machine. The second stage of mixing process between the mixer of fillers and binder is also carried out by using ball mill machine before the compaction process by the hot press machine. The effect of formation temperatures (160°C-170°C) on the properties of Gr/Sn/PP composite had been studied in detail, especially the electrical conductivity, bulk density, hardness and microstructure analysis of Gr/Sn/PP composite. The result shows that there are significant improvement in the electrical conductivity and bulk density, which are exceeding the US-DoE target with the maximum value of 265.35 S/cm and 1.682g/cm3 respectively.

  15. Sialic Acids in the Brain: Gangliosides and Polysialic Acid in Nervous System Development, Stability, Disease, and Regeneration

    PubMed Central

    Gerardy-Schahn, Rita; Hildebrandt, Herbert

    2014-01-01

    Every cell in nature carries a rich surface coat of glycans, its glycocalyx, which constitutes the cell's interface with its environment. In eukaryotes, the glycocalyx is composed of glycolipids, glycoproteins, and proteoglycans, the compositions of which vary among different tissues and cell types. Many of the linear and branched glycans on cell surface glycoproteins and glycolipids of vertebrates are terminated with sialic acids, nine-carbon sugars with a carboxylic acid, a glycerol side-chain, and an N-acyl group that, along with their display at the outmost end of cell surface glycans, provide for varied molecular interactions. Among their functions, sialic acids regulate cell-cell interactions, modulate the activities of their glycoprotein and glycolipid scaffolds as well as other cell surface molecules, and are receptors for pathogens and toxins. In the brain, two families of sialoglycans are of particular interest: gangliosides and polysialic acid. Gangliosides, sialylated glycosphingolipids, are the most abundant sialoglycans of nerve cells. Mouse genetic studies and human disorders of ganglioside metabolism implicate gangliosides in axon-myelin interactions, axon stability, axon regeneration, and the modulation of nerve cell excitability. Polysialic acid is a unique homopolymer that reaches >90 sialic acid residues attached to select glycoproteins, especially the neural cell adhesion molecule in the brain. Molecular, cellular, and genetic studies implicate polysialic acid in the control of cell-cell and cell-matrix interactions, intermolecular interactions at cell surfaces, and interactions with other molecules in the cellular environment. Polysialic acid is essential for appropriate brain development, and polymorphisms in the human genes responsible for polysialic acid biosynthesis are associated with psychiatric disorders including schizophrenia, autism, and bipolar disorder. Polysialic acid also appears to play a role in adult brain plasticity, including regeneration. Together, vertebrate brain sialoglycans are key regulatory components that contribute to proper development, maintenance, and health of the nervous system. PMID:24692354

  16. Asymmetry between ON and OFF α ganglion cells of mouse retina: integration of signal and noise from synaptic inputs.

    PubMed

    Freed, Michael A

    2017-11-15

    Bipolar and amacrine cells presynaptic to the ON sustained α cell of mouse retina provide currents with a higher signal-to-noise power ratio (SNR) than those presynaptic to the OFF sustained α cell. Yet the ON cell loses proportionately more SNR from synaptic inputs to spike output than the OFF cell does. The higher SNR of ON bipolar cells at the beginning of the ON pathway compensates for losses incurred by the ON ganglion cell, and improves the processing of positive contrasts. ON and OFF pathways in the retina include functional pairs of neurons that, at first glance, appear to have symmetrically similar responses to brightening and darkening, respectively. Upon careful examination, however, functional pairs exhibit asymmetries in receptive field size and response kinetics. Until now, descriptions of how light-adapted retinal circuitry maintains a preponderance of signal over the noise have not distinguished between ON and OFF pathways. Here I present evidence of marked asymmetries between members of a functional pair of sustained α ganglion cells in the mouse retina. The ON cell exhibited a proportionately greater loss of signal-to-noise power ratio (SNR) from its presynaptic arrays to its postsynaptic currents. Thus the ON cell combines signal and noise from its presynaptic arrays of bipolar and amacrine cells less efficiently than the OFF cell does. Yet the inefficiency of the ON cell is compensated by its presynaptic arrays providing a higher SNR than the arrays presynaptic to the OFF cell, apparently to improve visual processing of positive contrasts. Dynamic clamp experiments were performed that introduced synaptic conductances into ON and OFF cells. When the amacrine-modulated conductance was removed, the ON cell's spike train exhibited an increase in SNR. The OFF cell, however, showed the opposite effect of removing amacrine input, which was a decrease in SNR. Thus ON and OFF cells have different modes of synaptic integration with direct effects on the SNR of the spike output. © 2017 The Authors. The Journal of Physiology © 2017 The Physiological Society.

  17. N-terminal nesprin-2 variants regulate β-catenin signalling

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Zhang, Qiuping; Minaisah, Rose-Marie; Ferraro, Elisa

    2016-07-15

    The spatial compartmentalisation of biochemical signalling pathways is essential for cell function. Nesprins are a multi-isomeric family of proteins that have emerged as signalling scaffolds, herein, we investigate the localisation and function of novel nesprin-2 N-terminal variants. We show that these nesprin-2 variants display cell specific distribution and reside in both the cytoplasm and nucleus. Immunofluorescence microscopy revealed that nesprin-2 N-terminal variants colocalised with β-catenin at cell-cell junctions in U2OS cells. Calcium switch assays demonstrated that nesprin-2 and β-catenin are lost from cell-cell junctions in low calcium conditions whereas emerin localisation at the NE remained unaltered, furthermore, an N-terminal fragmentmore » of nesprin-2 was sufficient for cell-cell junction localisation and interacted with β-catenin. Disruption of these N-terminal nesprin-2 variants, using siRNA depletion resulted in loss of β-catenin from cell-cell junctions, nuclear accumulation of active β-catenin and augmented β-catenin transcriptional activity. Importantly, we show that U2OS cells lack nesprin-2 giant, suggesting that the N-terminal nesprin-2 variants regulate β-catenin signalling independently of the NE. Together, these data identify N-terminal nesprin-2 variants as novel regulators of β-catenin signalling that tether β-catenin to cell-cell contacts to inhibit β-catenin transcriptional activity. - Highlights: • N-terminal nesprin-2 variants display cell specific expression patterns. • N-terminal spectrin repeats of nesprin-2 interact with β-catenin. • N-terminal nesprin-2 variants scaffold β-catenin at cell-cell junctions.. • Nesprin-2 variants play multiple roles in β-catenin signalling.« less

  18. Bipolar Ag-Zn battery

    NASA Astrophysics Data System (ADS)

    Giltner, L. John

    1994-02-01

    The silver-zinc (AgZn) battery system has been unique in its ability to safely satisfy high power demand applications with low mass and volume. However, a new generation of defense, aerospace, and commercial applications will impose even higher power demands. These new power demands can be satisfied by the development of a bipolar battery design. In this configuration the power consuming, interelectrode current conductors are eliminated while the current is then conducted via the large cross-section electrode substrate. Negative and positive active materials are applied to opposite sides of a solid silver foil substrate. In addition to reducing the weight and volume required for a specified power level, the output voltage performance is also improved as follows. Reduced weight through: elimination of the plastic cell container; elimination of plate leads and intercell connector; and elimination of internal plate current collector. Increased voltage through: elimination of resistance of current collector; elimination of resistance of plate lead; and elimination of resistance of intercell connector. EPI worked previously on development of a secondary bipolar silver zinc battery. This development demonstrated the electrical capability of the system and manufacturing techniques. One difficulty with this development was mechanical problems with the seals. However, recent improvements in plastics and adhesives should eliminate the major problem of maintaining a seal around the periphery of the bipolar module. The seal problem is not as significant for a primary battery application or for a requirement for only a few discharge cycles. A second difficulty encountered was with activation (introducing electrolyte into the cell) and with venting gas from the cell without loss of electrolyte. During previous work, the following projections for energy density were made from test data for a high power system which demonstrated in excess of 50 discharge/charge cycles. Projected system power = 100 kilowatts; discharge time = 30 seconds; discharge current density = 1.75 amps/sq in.; system weight = 86 lbs (9.7 WH/lb); and system volume = 1071 cu. in. (.78 WH/cu. in.). EPI is currently working on a development program to produce a bipolar silver-zinc battery design for NASA. The potential application would be to power electromechanical actuators for space launch vehicles.

  19. Bipolar Ag-Zn battery

    NASA Technical Reports Server (NTRS)

    Giltner, L. John

    1994-01-01

    The silver-zinc (AgZn) battery system has been unique in its ability to safely satisfy high power demand applications with low mass and volume. However, a new generation of defense, aerospace, and commercial applications will impose even higher power demands. These new power demands can be satisfied by the development of a bipolar battery design. In this configuration the power consuming, interelectrode current conductors are eliminated while the current is then conducted via the large cross-section electrode substrate. Negative and positive active materials are applied to opposite sides of a solid silver foil substrate. In addition to reducing the weight and volume required for a specified power level, the output voltage performance is also improved as follows. Reduced weight through: elimination of the plastic cell container; elimination of plate leads and intercell connector; and elimination of internal plate current collector. Increased voltage through: elimination of resistance of current collector; elimination of resistance of plate lead; and elimination of resistance of intercell connector. EPI worked previously on development of a secondary bipolar silver zinc battery. This development demonstrated the electrical capability of the system and manufacturing techniques. One difficulty with this development was mechanical problems with the seals. However, recent improvements in plastics and adhesives should eliminate the major problem of maintaining a seal around the periphery of the bipolar module. The seal problem is not as significant for a primary battery application or for a requirement for only a few discharge cycles. A second difficulty encountered was with activation (introducing electrolyte into the cell) and with venting gas from the cell without loss of electrolyte. During previous work, the following projections for energy density were made from test data for a high power system which demonstrated in excess of 50 discharge/charge cycles. Projected system power = 100 kilowatts; discharge time = 30 seconds; discharge current density = 1.75 amps/sq in.; system weight = 86 lbs (9.7 WH/lb); and system volume = 1071 cu. in. (.78 WH/cu. in.). EPI is currently working on a development program to produce a bipolar silver-zinc battery design for NASA. The potential application would be to power electromechanical actuators for space launch vehicles.

  20. The KMO allele encoding Arg452 is associated with psychotic features in bipolar disorder type 1, and with increased CSF KYNA level and reduced KMO expression.

    PubMed

    Lavebratt, C; Olsson, S; Backlund, L; Frisén, L; Sellgren, C; Priebe, L; Nikamo, P; Träskman-Bendz, L; Cichon, S; Vawter, M P; Osby, U; Engberg, G; Landén, M; Erhardt, S; Schalling, M

    2014-03-01

    The kynurenine pathway metabolite kynurenic acid (KYNA), modulating glutamatergic and cholinergic neurotransmission, is increased in cerebrospinal fluid (CSF) of patients with schizophrenia or bipolar disorder type 1 with psychotic features. KYNA production is critically dependent on kynurenine 3-monooxygenase (KMO). KMO mRNA levels and activity in prefrontal cortex (PFC) are reduced in schizophrenia. We hypothesized that KMO expression in PFC would be reduced in bipolar disorder with psychotic features and that a functional genetic variant of KMO would associate with this disease, CSF KYNA level and KMO expression. KMO mRNA levels were reduced in PFC of bipolar disorder patients with lifetime psychotic features (P=0.005, n=19) or schizophrenia (P=0.02, n=36) compared with nonpsychotic patients and controls. KMO genetic association to psychotic features in bipolar disorder type 1 was studied in 493 patients and 1044 controls from Sweden. The KMO Arg(452) allele was associated with psychotic features during manic episodes (P=0.003). KMO Arg(452) was studied for association to CSF KYNA levels in an independent sample of 55 Swedish patients, and to KMO expression in 717 lymphoblastoid cell lines and 138 hippocampal biopsies. KMO Arg(452) associated with increased levels of CSF KYNA (P=0.03) and reduced lymphoblastoid and hippocampal KMO expression (P≤0.05). Thus, findings from five independent cohorts suggest that genetic variation in KMO influences the risk for psychotic features in mania of bipolar disorder patients. This provides a possible mechanism for the previous findings of elevated CSF KYNA levels in those bipolar patients with lifetime psychotic features and positive association between KYNA levels and number of manic episodes.

  1. The deep muscular plexus of the pig duodenum: a histochemical and ultrastructural study with special reference to the interstitial cells.

    PubMed

    Henry, M; Porcher, C; Julé, Y

    1998-06-10

    The aim of the present study was to describe the deep muscular plexus of the pig duodenum and to characterize its cellular components. Numerous nerve varicosities have been detected in the deep muscular plexus using anti-synaptophysin antibodies. Nerve fibres were also detected here in the outer circular muscle layer, whereas no nerve fibres were observed in the inner circular muscle layer. In the deep muscular plexus, nerve fibres projected to interstitial cells which were characterized at the ultrastructural level. The interstitial cells were of two kinds: the interstitial fibroblastic-like cells (FLC) and the interstitial dense cells (IDC), both of which were interposed between nerve fibres and smooth muscle cells. The FLC were characterized by their elongated bipolar shape, the lack of basal lamina, a well-developed endoplasmic reticulum, a Golgi apparatus, and intermediate filaments. They were closely apposed to axon terminals containing small clear synaptic vesicles and/or dense-cored vesicles. They were frequently connected to each other and to smooth muscle cells of the inner and outer circular layer by desmosomes and more rarely by gap junctions. The IDC are myoid-like cells. They had a stellate appearance and were characterized by a dense cell body, numerous caveolae, and a discontinuous basal lamina. The IDC were always closely apposed to nerve fibres and were connected to smooth muscle cells by desmosomes and small gap junctions. The present results show the unique pattern of cellular organization of the deep muscular plexus of the pig small intestine. They suggest that the interstitial cells in the deep muscular plexus are involved in the integration and transmission of nervous inputs from myenteric neurons to the inner and outer circular muscle layers. The clear-cut distinction observed here between the two types of interstitial cells (fibroblastic and myoid-like) suggests that the interstitial cells of each type may also be involved in some other specific activity, which still remains to be determined.

  2. Advanced high-temperature batteries

    NASA Technical Reports Server (NTRS)

    Nelson, P. A.

    1989-01-01

    Recent results for Li-Al/FeS2 cells and bipolar battery design have shown the possibility of achieving high specific energy (210 Wh/kg) and high specific power (239 W/kg) at the cell level for an electric vehicle application. Outstanding performance is also projected for sodium/metal chloride cells having large electrolyte areas and thin positive electrodes.

  3. Simulation and Experimental Study of Bipolar Plate on the Performance PEM Fuel cell

    NASA Astrophysics Data System (ADS)

    Chinnasa, Pornchai; Khamsuk, Pattama; Seechalee, Sarunya; Swatsitang, Ekaphan

    2017-09-01

    This research is a simulated and experimental study on effects of bipolar electrodes of a PEM fuel cell on its power conversion efficiency. The PEM fuel cell structure consists of bipolar electrodes, proton exchange membrane with catalysts, flow channels of gases. This research used fuel cell of 49 cm2 in active area as a research sample and the Comsol 4.4 was employed to simulate flow channels which are serpentine pattern for anode and parallel pattern for cathode. The parameters used were calculated effects of such parameters using Comsol 4.4. After the calculation has been completed, the prototype of the PEM fuel cell were fabricated using graphite plate as electrodes which had the channel height of 0.20 cm, proton exchange membrane using carbon-platinum catalyst. Finally, further it was found that the effect of temperature on the power conversion efficiency is not severely. And for anode, the concentration of hydrogen gas was reduced 64 wt% due to the reaction whereas in parallel channel of cathode the oxygen concentration was reduced by only 6 wt% from 23 wt% at the entrance to 17 wt% at the end. The maximum power output of the prototype operated under such condition was 0.28 W/cm2 calculated from maximum power output voltage (Vmp) of 0.70 V and maximum power output current density of 0.42 A/cm2 which was in good agreement with that simulated using Comsol 4.4 which revealed the power output of 0.29 W/cm2.

  4. Primary cell culture of LHRH neurones from embryonic olfactory placode in the sheep (Ovis aries).

    PubMed

    Duittoz, A H; Batailler, M; Caldani, M

    1997-09-01

    The aim of this study was to establish an in vitro model of ovine luteinizing hormone-releasing hormone (LHRH) neurones. Olfactory placodes from 26 day-old sheep embryos (E26) were used for explant culture. Cultures were maintained successfully up to 35 days, but were usually used at 17 days for immunocytochemistry. LHRH and neuronal markers such as neurofilament (NF) were detected by immunocytochemistry within and/or outside the explant. Three main types of LHRH positive cells are described: (1) neuroblastic LHRH and NF immunoreactive cells with round cell body and very short neurites found mainly within the explant, (2) migrating LHRH bipolar neurones with an fusiform cell body, found outside the explant, (3) network LHRH neuron, bipolar or multipolar with long neurites connecting other LHRH neurons. Cell morphology was very similar to that which has been described in the adult sheep brain. These results strongly suggest that LHRH neurones in the sheep originate from the olfactory placode. This mode may represent a useful tool to study LHRH neurones directly in the sheep.

  5. Loss of Citron Kinase Affects a Subset of Progenitor Cells That Alters Late but Not Early Neurogenesis in the Developing Rat Retina

    PubMed Central

    Karunakaran, Devi Krishna Priya; Chhaya, Nisarg; Lemoine, Christopher; Congdon, Sean; Black, Amye; Kanadia, Rahul

    2015-01-01

    Purpose. To understand how loss of citron kinase (CitK) affects retinal progenitor cells (RPCs) in the developing rat retina. Methods. We compared knockout (KO) and wild-type (WT) retinae by immunohistochemistry. The TdT-mediated dUTP terminal nick-end labeling (TUNEL) assay was performed to determine cell death. Pulse-chase experiments using 5-ethynyl-2’-deoxyuridine (EdU) were carried out to interrogate RPC behavior and in turn neurogenesis. Results. Reverse transcription–polymerase chain reaction analysis showed that CitK was expressed at embryonic day (E)12 and was turned off at approximately postnatal day (P)4. Immunohistochemistry showed CitK being localized as puncta at the apical end of the outer neuroblastic layer (ONBL). Analyses during embryonic development showed that the KO retina was of comparable size to that of WT until E13. However, by E14, there was a reduction in the number of S-phase RPCs with a concomitant increase in TUNEL+ cells in the KO retina. Moreover, early neurogenesis, as reflected by retinal ganglion cell production, was not affected. Postnatal analysis of the retina showed that ONBL in the KO retina was reduced to half the size of that in WT and showed further degeneration. Immunohistochemistry revealed absence of Islet1+ bipolar cells at P2, which was further confirmed by EdU pulse-chase experiments. The CitK KO retinae underwent complete degeneration by P14. Conclusions. Our study showed that CitK is not required for a subset of RPCs before E14, but is necessary for RPC survival post E14. This in turn results in normal early embryonic neurogenesis, but severely compromised later embryonic and postnatal neurogenesis. PMID:25593024

  6. A phenanthrene derived PARP inhibitor is an extra-centrosomes de-clustering agent exclusively eradicating human cancer cells

    PubMed Central

    2011-01-01

    Background Cells of most human cancers have supernumerary centrosomes. To enable an accurate chromosome segregation and cell division, these cells developed a yet unresolved molecular mechanism, clustering their extra centrosomes at two poles, thereby mimicking mitosis in normal cells. Failure of this bipolar centrosome clustering causes multipolar spindle structures and aberrant chromosomes segregation that prevent normal cell division and lead to 'mitotic catastrophe cell death'. Methods We used cell biology and biochemical methods, including flow cytometry, immunocytochemistry and live confocal imaging. Results We identified a phenanthrene derived PARP inhibitor, known for its activity in neuroprotection under stress conditions, which exclusively eradicated multi-centrosomal human cancer cells (mammary, colon, lung, pancreas, ovarian) while acting as extra-centrosomes de-clustering agent in mitosis. Normal human proliferating cells (endothelial, epithelial and mesenchymal cells) were not impaired. Despite acting as PARP inhibitor, the cytotoxic activity of this molecule in cancer cells was not attributed to PARP inhibition alone. Conclusion We identified a water soluble phenanthridine that exclusively targets the unique dependence of most human cancer cells on their supernumerary centrosomes bi-polar clustering for their survival. This paves the way for a new selective cancer-targeting therapy, efficient in a wide range of human cancers. PMID:21943092

  7. Elimination of image flicker in a fringe-field switching liquid crystal display by applying a bipolar voltage wave.

    PubMed

    Oh, Seung-Won; Park, Jun-Hee; Lee, Ji-Hoon; Yoon, Tae-Hoon

    2015-09-07

    Recently, low-frequency driving of liquid crystal display (LCD) panels to minimize power consumption has drawn much attention. In the case in which an LCD panel is driven by a fringe-field at a low frequency, the image flickering phenomenon occurs when the sign of the applied electric field is reversed. We investigated image flickering induced by the flexoelectric effect in a fringe-field switching (FFS) liquid crystal cell in terms of the transmittance difference between frames and the ripple phenomenon. Experimental results show that image flicker due to transmittance difference can be eliminated completely and that the ripple phenomena can be reduced significantly by applying a bipolar voltage wave to the FFS cell.

  8. G-protein-mediated inhibition of the Trp channel TRPM1 requires the Gβγ dimer.

    PubMed

    Shen, Yin; Rampino, Melissa Ann F; Carroll, Reed C; Nawy, Scott

    2012-05-29

    ON bipolar cells are critical for the function of the ON pathway in the visual system. They express a metabotropic glutamate receptor (mGluR6) that, when activated, couples to the G(o) class of G protein. The channel that is primarily responsible for the synaptic response has been recently identified as the transient receptor potential cation channel subfamily M member 1 (TRPM1); TRPM1 is negatively coupled to the mGluR6/Go cascade such that activation of the cascade results in closure of the channel. Light indirectly opens TRPM1 by reducing transmitter release from presynaptic photoreceptors, resulting in a decrease in mGluR6 activation. Conversely, in the dark, binding of synaptic glutamate to mGluR6 inhibits TRPM1 current. Closure of TRPM1 by G-protein activation in the dark is a critical step in the process of ON bipolar cell signal transduction, but the precise pathway linking these two events is not understood. To address this question, we measured TRPM1 activity in retinal bipolar cells, in human ependymal melanocytes (HEMs) that endogenously express TRPM1, and in HEK293 cells transfected with TRPM1. Dialysis of the Gβγ subunit dimer, but not Gα(o), closed TRPM1 channels in every cell type that we tested. In addition, activation of an endogenous G-protein-coupled receptor pathway in HEK293 cells that releases Gβγ without activating Go protein also closed TRPM1 channels. These results suggest a model in which the Gβγ dimer that is released as a result of the dissociation from Gα(o) upon activation of mGluR6 closes the TRPM1 channel, perhaps via a direct interaction.

  9. Principles of a multistack electrochemical wastewater treatment design

    NASA Astrophysics Data System (ADS)

    Elsahwi, Essam S.; Dawson, Francis P.; Ruda, Harry E.

    2018-02-01

    Electrolyzer stacks in a bipolar architecture (cells connected in series) are desirable since power provided to a stack can be transferred at high voltages and low currents and thus the losses in the power bus can be reduced. The anode electrodes (active electrodes) considered as part of this study are single sided but there are manufacturing cost advantages to implementing double side anodes in the future. One of the main concerns with a bipolar stack implementation is the existence of leakage currents (bypass currents). The leakage current is associated with current paths that are not between adjacent anode and cathode pairs. This leads to non uniform current density distributions which compromise the electrochemical conversion efficiency of the stack and can also lead to unwanted side reactions. The objective of this paper is to develop modelling tools for a bipolar architecture consisting of two single sided cells that use single sided anodes. It is assumed that chemical reactions are single electron transfer rate limited and that diffusion and convection effects can be ignored. The design process consists of the flowing two steps: development of a large signal model for the stack, and then the extraction of a small signal model from the large signal model. The small signal model facilitates the design of a controller that satisfies current or voltage regulation requirements. A model has been developed for a single cell and two cells in series but can be generalized to more than two cells in series and to incorporate double sided anode configurations in the future. The developed model is able to determine the leakage current and thus provide a quantitative assessment on the performance of the cell.

  10. Sensitive electrochemiluminescence biosensor based on Au-ITO hybrid bipolar electrode amplification system for cell surface protein detection.

    PubMed

    Wu, Mei-Sheng; Yuan, Da-Jing; Xu, Jing-Juan; Chen, Hong-Yuan

    2013-12-17

    Here we developed a novel hybrid bipolar electrode (BPE)-electrochemiluminescence (ECL) biosensor based on hybrid bipolar electrode (BPE) for the measurement of cancer cell surface protein using ferrocence (Fc) labeled aptamer as signal recognition and amplification probe. According to the electric neutrality of BPE, the cathode of U-shaped ITO BPE was electrochemically deposited by Au nanoparticles (NPs) to enhance its conductivity and surface area, decrease the overpotential of O2 reduction, which would correspondingly increase the oxidation current of Ru(bpy)3(2+)/tripropylamine (TPA) on the anode of BPE and resulting a ∼4-fold enhancement of ECL intensity. Then a signal amplification strategy was designed by introducing Fc modified aptamer on the anode surface of BPE through hybridization for detecting the amount of mucin-1 on MCF-7 cells. The presence of Fc could not only inhibit the oxidation of Ru(bpy)3(2+) because of its lower oxidation potential, its oxidation product Fc(+) could also quench the ECL of Ru(bpy)3(2+)/TPA by efficient energy-transfer from the excited-state Ru(bpy)3(2+)* to Fc(+), making the ECL intensity greatly quenched. On the basis of the cathodic Au NPs induced ECL enhancing coupled with anodic Fc induced signal quenching amplification, the approach allowed detection of mucin-1 aptamer at a concentration down to 0.5 fM and was capable of detecting a minimum of 20 MCF-7 cells. Besides, the amount of mucin-1 on MCF-7 cells was calculated to be 9041 ± 388 molecules/cell. This approach therefore shows great promise in bioanalysis.

  11. Single residue AAV capsid mutation improves transduction of photoreceptors in the Abca4-/- mouse and bipolar cells in the rd1 mouse and human retina ex vivo.

    PubMed

    De Silva, Samantha R; Charbel Issa, Peter; Singh, Mandeep S; Lipinski, Daniel M; Barnea-Cramer, Alona O; Walker, Nathan J; Barnard, Alun R; Hankins, Mark W; MacLaren, Robert E

    2016-11-01

    Gene therapy using adeno-associated viral (AAV) vectors for the treatment of retinal degenerations has shown safety and efficacy in clinical trials. However, very high levels of vector expression may be necessary for the treatment of conditions such as Stargardt disease where a dual vector approach is potentially needed, or in optogenetic strategies for end-stage degeneration in order to achieve maximal light sensitivity. In this study, we assessed two vectors with single capsid mutations, rAAV2/2(Y444F) and rAAV2/8(Y733F) in their ability to transduce retina in the Abca4 -/- and rd1 mouse models of retinal degeneration. We noted significantly increased photoreceptor transduction using rAAV2/8(Y733F) in the Abca4 -/- mouse, in contrast to previous work where vectors tested in this model have shown low levels of photoreceptor transduction. Bipolar cell transduction was achieved following subretinal delivery of both vectors in the rd1 mouse, and via intravitreal delivery of rAAV2/2(Y444F). The successful use of rAAV2/8(Y733F) to target bipolar cells was further validated on human tissue using an ex vivo culture system of retinal explants. Capsid mutant AAV vectors transduce human retinal cells and may be particularly suited to treat retinal degenerations in which high levels of transgene expression are required.

  12. Bipolar localization of the group II intron Ll.LtrB is maintained in Escherichia coli deficient in nucleoid condensation, chromosome partitioning and DNA replication.

    PubMed

    Beauregard, Arthur; Chalamcharla, Venkata R; Piazza, Carol Lyn; Belfort, Marlene; Coros, Colin J

    2006-11-01

    Group II introns are mobile genetic elements that invade their cognate intron-minus alleles via an RNA intermediate, in a process known as retrohoming. They can also retrotranspose to ectopic sites at low frequency. In Escherichia coli, retrotransposition of the lactococcal group II intron, Ll.LtrB, occurs preferentially within the Ori and Ter macrodomains of the E. coli chromosome. These macrodomains migrate towards the poles of the cell, where the intron-encoded protein, LtrA, localizes. Here we investigate whether alteration of nucleoid condensation, chromosome partitioning and replication affect retrotransposition frequencies, as well as bipolar localization of the Ll.LtrB intron integration and LtrA distribution in E. coli. We thus examined these properties in the absence of the nucleoid-associated proteins H-NS, StpA and MukB, in variants of partitioning functions including the centromere-like sequence migS and the actin homologue MreB, as well as in the replication mutants DeltaoriC, seqA, tus and topoIV (ts). Although there were some dramatic fluctuations in retrotransposition levels in these hosts, bipolar localization of integration events was maintained. LtrA was consistently found in nucleoid-free regions, with its localization to the cellular poles being largely preserved in these hosts. Together, these results suggest that bipolar localization of group II intron retrotransposition results from the residence of the intron-encoded protein at the poles of the cell.

  13. Force-balance model of suppression of multipolar division in cancer cells with extra centrosomes

    NASA Astrophysics Data System (ADS)

    Zhu, Jie

    2013-03-01

    Cancer cells often possess extra centrosomes which have the potential to cause cell death due to catastrophic multipolar division. Many cancer cells, however, are able to escape multipolar mitosis by clustering the extra centrosomes to form bipolar spindles. The mechanism of centrosome clustering is therefore of great interest to the development of anti-cancer drugs because the de-clustering of extra centrosomes provides an appealing way to eliminate cancer cells while keeping healthy cells intact. We present a physical model assuming 1) dynamic centrosomal microtubules interact with chromosomes by both pushing on chromosome arms and pulling along kinetochores; 2) these microtubules interact with force generators associated with actin/adhesion structures at the cell boundary; and 3) motors act on anti-parallel microtubules from different centrosomes. We find via computer simulations that chromosomes tend to aggregate near the cell center while centrosomes can be either clustered to form bipolar spindles or scattered to form multipolar spindles, depending on the strengths of relative forces, cell shape and adhesion geometry. The model predictions agree with data from cells plated on adhesive micropatterns and from biochemically or genetically perturbed cells. Furthermore, our model is able to explain various microtubule distributions in interphase cells on patterned substrates. This work was supported by NSF

  14. Catalytic bipolar interconnection plate for use in a fuel cell

    DOEpatents

    Lessing, Paul A.

    1996-01-01

    A bipolar interconnection plate for use between adjacent fuel cell units in a stacked fuel cell assembly. Each plate is manufactured from an intermetallic composition, examples of which include NiAl or Ni.sub.3 Al which can catalyze steam reforming of hydrocarbons. Distributed within the intermetallic structure of the plate is a ceramic filler composition. The plate includes a first side with gas flow channels therein and a second side with fuel flow channels therein. A protective coating is applied to the first side, with exemplary coatings including strontium-doped or calcium-doped lanthanum chromite. To produce the plate, Ni and Al powders are combined with the filler composition, compressed at a pressure of about 10,000-30,000 psi, and heated to about 600.degree.-1000.degree. C. The coating is then applied to the first side of the completed plate using liquid injection plasma deposition or other deposition techniques.

  15. Catalytic bipolar interconnection plate for use in a fuel cell

    DOEpatents

    Lessing, P.A.

    1996-03-05

    A bipolar interconnection plate is described for use between adjacent fuel cell units in a stacked fuel cell assembly. Each plate is manufactured from an intermetallic composition, examples of which include NiAl or Ni{sub 3}Al which can catalyze steam reforming of hydrocarbons. Distributed within the intermetallic structure of the plate is a ceramic filler composition. The plate includes a first side with gas flow channels therein and a second side with fuel flow channels therein. A protective coating is applied to the first side, with exemplary coatings including strontium-doped or calcium-doped lanthanum chromite. To produce the plate, Ni and Al powders are combined with the filler composition, compressed at a pressure of about 10,000--30,000 psi, and heated to about 600--1000 C. The coating is then applied to the first side of the completed plate using liquid injection plasma deposition or other deposition techniques. 6 figs.

  16. A high voltage dielectrically isolated smart power technology based on silicon direct bonding

    NASA Astrophysics Data System (ADS)

    Macary, Veronique

    1992-09-01

    The feasibility of a dielectrically isolated technology based on the silicon direct bonding technique, for high voltage smart power applications in the 1000 to 1550 V/1 to 20 A range, where a vertical power switch is necessary, is investigated and demonstrated. Static and dynamic isolation of the low voltage circuitry integrated beside the vertical power transistor is the main concern of this family of circuits. The dielectric isolation offers better protection to the low voltage part than does the junction isolation, because of the elimination of the parasitic bipolar transistor inherent to the latter isolation technique. Silicon direct bonding provides a cost effective way to obtain a buried oxide isolation layer. In addition, the application requires a Si/Si bonded area in the active region of the vertical power switch. Strong influence of the prebonding cleaning in the electrical characteristics of the Si/Si interface is pointed out, and presence of crystalline defects is assumed to be at the origin of electrical failures. The main problems of silicon direct bonding process compatibility with standard processes were overcome, and a complete process flow, including the simultaneous integration of a vertical power bipolar transistor together with a bipolar control circuitry, was validated. Using a peripheral biased ring is shown to provide an easy way to optimize high voltage termination for the smart power circuit, while adding a non-additional technological step. This technique was studied by dimensional electrical simulations (BIDIM2 software), as well as analytically computed.

  17. Compensatory branching morphogenesis of stalk cells in the Drosophila trachea.

    PubMed

    Francis, Deanne; Ghabrial, Amin S

    2015-06-01

    Tubes are essential for nutrient transport and gas exchange in multicellular eukaryotes, but how connections between different tube types are maintained over time is unknown. In the Drosophila tracheal system, mutations in oak gall (okg) and conjoined (cnj) confer identical defects, including late onset blockage near the terminal cell-stalk cell junction and the ectopic extension of autocellular, seamed tubes into the terminal cell. We determined that okg and cnj encode the E and G subunits of the vacuolar ATPase (vATPase) and showed that both the V0 and V1 domains are required for terminal cell morphogenesis. Remarkably, the ectopic seamed tubes running along vATPase-deficient terminal cells belonged to the neighboring stalk cells. All vATPase-deficient tracheal cells had reduced apical domains and terminal cells displayed mislocalized apical proteins. Consistent with recent reports that the mTOR and vATPase pathways intersect, we found that mTOR pathway mutants phenocopied okg and cnj. Furthermore, terminal cells depleted for the apical determinants Par6 or aPKC had identical ectopic seamed tube defects. We thus identify a novel mechanism of compensatory branching in which stalk cells extend autocellular tubes into neighboring terminal cells with undersized apical domains. This compensatory branching also occurs in response to injury, with damaged terminal cells being rapidly invaded by their stalk cell neighbor. © 2015. Published by The Company of Biologists Ltd.

  18. Static and dynamic behavior of a Si/Si0.8Ge0.2/Si heterojunction bipolar transistor using Monte Carlo simulation

    NASA Astrophysics Data System (ADS)

    Galdin, Sylvie; Dollfus, Philippe; Hesto, Patrice

    1994-03-01

    A theoretical study of a Si/Si1-xGex/Si heterojunction bipolar transistor using Monte Carlo simulations is reported. The geometry and composition of the emitter-base junction are optimized using one-dimensional simulations with a view to improving electron transport in the base. It is proposed to introduce a thin Si-P spacer layer, between the Si-N emitter and the SiGe-P base, which allows launching hot electrons into the base despite the lack of natural conduction-band discontinuity between Si and strain SiGe. The high-frequency behavior of the complete transistor is then studied using 2D modeling. A method of microwave analysis using small signal Monte Carlo simulations that consists of expanding the terminal currents in Fourier series is presented. A cutoff frequency fT of 68 GHz has been extracted. Finally, the occurrence of a parasitic electron barrier at the collector-base junction is responsible for the fT fall-off at high collector current density. This parasitic barrier is lowered through the influence of the collector potential.

  19. Potential for neural regeneration after neurotoxic injury in the adult mammalian retina

    NASA Astrophysics Data System (ADS)

    Ooto, Sotaro; Akagi, Tadamichi; Kageyama, Ryoichiro; Akita, Joe; Mandai, Michiko; Honda, Yoshihito; Takahashi, Masayo

    2004-09-01

    It has long been believed that the retina of mature mammals is incapable of regeneration. In this study, using the N-methyl-D-aspartate neurotoxicity model of adult rat retina, we observed that some Müller glial cells were stimulated to proliferate in response to a toxic injury and produce bipolar cells and rod photoreceptors. Although these newly produced neurons were limited in number, retinoic acid treatment promoted the number of regenerated bipolar cells. Moreover, misexpression of basic helix-loop-helix and homeobox genes promoted the induction of amacrine, horizontal, and rod photoreceptor specific phenotypes. These findings demonstrated that retinal neurons regenerated even in adult mammalian retina after toxic injury. Furthermore, we could partially control the fate of the regenerated neurons with extrinsic factors or intrinsic genes. The Müller glial cells constitute a potential source for the regeneration of adult mammalian retina and can be a target for drug delivery and gene therapy in retinal degenerative diseases.

  20. DSCAM-mediated control of dendritic and axonal arbor outgrowth enforces tiling and inhibits synaptic plasticity

    PubMed Central

    Simmons, Aaron B.; Bloomsburg, Samuel J.; Sukeena, Joshua M.; Miller, Calvin J.; Ortega-Burgos, Yohaniz; Borghuis, Bart G.

    2017-01-01

    Mature mammalian neurons have a limited ability to extend neurites and make new synaptic connections, but the mechanisms that inhibit such plasticity remain poorly understood. Here, we report that OFF-type retinal bipolar cells in mice are an exception to this rule, as they form new anatomical connections within their tiled dendritic fields well after retinal maturity. The Down syndrome cell-adhesion molecule (Dscam) confines these anatomical rearrangements within the normal tiled fields, as conditional deletion of the gene permits extension of dendrite and axon arbors beyond these borders. Dscam deletion in the mature retina results in expanded dendritic fields and increased cone photoreceptor contacts, demonstrating that DSCAM actively inhibits circuit-level plasticity. Electrophysiological recordings from Dscam−/− OFF bipolar cells showed enlarged visual receptive fields, demonstrating that expanded dendritic territories comprise functional synapses. Our results identify cell-adhesion molecule-mediated inhibition as a regulator of circuit-level neuronal plasticity in the adult retina. PMID:29114051

  1. The bipolar plate of AISI 1045 steel with chromized coatings prepared by low-temperature pack cementation for proton exchange membrane fuel cell

    NASA Astrophysics Data System (ADS)

    Bai, Ching-Yuan; Wen, Tse-Min; Hou, Kung-Hsu; Ger, Ming-Der

    The low-temperature pack chromization, a reforming pack cementation process, is employed to modify AISI 1045 steel for the application of bipolar plates in PEMFC. The process is conducted to yield a coating, containing major Cr-carbides and minor Cr-nitrides, on the substrate in view of enhancing the steel's corrosion resistance and lowering interfacial contact resistance between the bipolar plate and gas diffusion layer. Electrical discharge machining and rolling approach are used as the pretreatment to produce an activated surface on the steel before pack chromization process to reduce operating temperatures and increase deposition rates. The rolled-chromized steel shows the lowest corrosion current density, 3 × 10 -8 A cm -2, and the smallest interfacial contact resistance, 5.9 mΩ cm 2, at 140 N cm -2 among all tested steels. This study clearly states the performance of 1045 carbon steel modified by activated and low-temperature pack chromization processes, which possess the potential to be bipolar plates in the application of PEMFC.

  2. Morphology, classification, and distribution of the projection neurons in the dorsal lateral geniculate nucleus of the rat.

    PubMed

    Ling, Changying; Hendrickson, Michael L; Kalil, Ronald E

    2012-01-01

    The morphology of confirmed projection neurons in the dorsal lateral geniculate nucleus (dLGN) of the rat was examined by filling these cells retrogradely with biotinylated dextran amine (BDA) injected into the visual cortex. BDA-labeled projection neurons varied widely in the shape and size of their cell somas, with mean cross-sectional areas ranging from 60-340 µm(2). Labeled projection neurons supported 7-55 dendrites that spanned up to 300 µm in length and formed dendritic arbors with cross-sectional areas of up to 7.0 × 10(4) µm(2). Primary dendrites emerged from cell somas in three broad patterns. In some dLGN projection neurons, primary dendrites arise from the cell soma at two poles spaced approximately 180° apart. In other projection neurons, dendrites emerge principally from one side of the cell soma, while in a third group of projection neurons primary dendrites emerge from the entire perimeter of the cell soma. Based on these three distinct patterns in the distribution of primary dendrites from cell somas, we have grouped dLGN projection neurons into three classes: bipolar cells, basket cells and radial cells, respectively. The appendages seen on dendrites also can be grouped into three classes according to differences in their structure. Short "tufted" appendages arise mainly from the distal branches of dendrites; "spine-like" appendages, fine stalks with ovoid heads, typically are seen along the middle segments of dendrites; and "grape-like" appendages, short stalks that terminate in a cluster of ovoid bulbs, appear most often along the proximal segments of secondary dendrites of neurons with medium or large cell somas. While morphologically diverse dLGN projection neurons are intermingled uniformly throughout the nucleus, the caudal pole of the dLGN contains more small projection neurons of all classes than the rostral pole.

  3. A comparison of recovered bipolar patients, healthy relatives of bipolar probands, and normal controls using the short TEMPS-A.

    PubMed

    Mendlowicz, Mauro V; Jean-Louis, Girardin; Kelsoe, John R; Akiskal, Hagop S

    2005-03-01

    To investigate the presence of temperament dysregulation in healthy relatives of bipolar probands (RBP), a population at high risk for developing mood disorders, by comparing them with clinically recovered bipolar patients (BP) and normal controls (NC). 52 RBP and 23 BP were originally recruited for a multicenter genetic study in bipolar disorders. NC (n=102) were also recruited by newspaper advertisement, radio and television announcements, flyers, newsletters, or word of mouth. All volunteers were asked to complete the TEMPS-A Scale, a self-report questionnaire designed to measure temperamental variations in psychiatric patients and healthy volunteers. In scoring temperaments, we relied upon the short validated version of the TEMPS-A [J. Affect. Disord. (2004)], from which traits with loadings <0.035 had been deleted. To examine differences in temperament dimensions among the three groups, a MANCOVA model was constructed using diagnostic group as the fixed factor (BP vs. RBP vs. NC); effects of age and gender were adjusted as covariates. MANCOVA showed overall group effect on the dependent variables (Hotelling's F5,175=6.64, p<0.001). Four dependent variables (dysthymic, cyclothymic, irritable, and anxious temperaments) showed significant between-group differences. RBP showed lower cyclothymic temperament scores than BP, but higher scores than NC. BP and RBP showed higher anxious temperament scores than NC. Hyperthymic scores were significantly highest in the NC. In view of the small cell sizes, bipolar I vs. bipolar II subanalyses could not be conducted. Methodologic strengths of the present analyses is that the BP group had clinically recovered, and we used the validated short version of the TEMPS-A for the present analyses. Our findings suggest that some clinically healthy relatives of bipolar probands exhibit a subclinical cyclothymic instability in mood, interest, self-confidence, sleep, and/or energy as well as anxiety proneness that is not observed among normal controls. These traits may represent vulnerability markers and could presumably be used to identify individuals at high risk for developing bipolar spectrum disorders, or specific clinical subtypes (e.g., bipolar I, bipolar II) within this spectrum. This is a conceptual perspective with many unanswered questions. Resolution of these questions will require innovative definitions of phenotypes to be included in the analyses of the temperament subscales in different populations. The temperament subscales themselves need to be calibrated properly, to find out which traits or specific combinations of trains are most promising. More extensive and complex quantitative trait analyses of these temperaments in a much expanded sample are reported elsewhere in this issue [J. Affect. Disord. (2004)].

  4. Inhibitory masking controls the threshold sensitivity of retinal ganglion cells

    PubMed Central

    Pan, Feng; Toychiev, Abduqodir; Zhang, Yi; Atlasz, Tamas; Ramakrishnan, Hariharasubramanian; Roy, Kaushambi; Völgyi, Béla; Akopian, Abram

    2016-01-01

    Key points Retinal ganglion cells (RGCs) in dark‐adapted retinas show a range of threshold sensitivities spanning ∼3 log units of illuminance.Here, we show that the different threshold sensitivities of RGCs reflect an inhibitory mechanism that masks inputs from certain rod pathways.The masking inhibition is subserved by GABAC receptors, probably on bipolar cell axon terminals.The GABAergic masking inhibition appears independent of dopaminergic circuitry that has been shown also to affect RGC sensitivity.The results indicate a novel mechanism whereby inhibition controls the sensitivity of different cohorts of RGCs. This can limit and thereby ensure that appropriate signals are carried centrally in scotopic conditions when sensitivity rather than acuity is crucial. Abstract The responses of rod photoreceptors, which subserve dim light vision, are carried through the retina by three independent pathways. These pathways carry signals with largely different sensitivities. Retinal ganglion cells (RGCs), the output neurons of the retina, show a wide range of sensitivities in the same dark‐adapted conditions, suggesting a divergence of the rod pathways. However, this organization is not supported by the known synaptic morphology of the retina. Here, we tested an alternative idea that the rod pathways converge onto single RGCs, but inhibitory circuits selectively mask signals so that one pathway predominates. Indeed, we found that application of GABA receptor blockers increased the sensitivity of most RGCs by unmasking rod signals, which were suppressed. Our results indicate that inhibition controls the threshold responses of RGCs under dim ambient light. This mechanism can ensure that appropriate signals cross the bottleneck of the optic nerve in changing stimulus conditions. PMID:27350405

  5. Highly conductive, multi-layer composite precursor composition to fuel cell flow field plate or bipolar plate

    DOEpatents

    Jang, Bor Z [Centerville, OH; Zhamu, Aruna [Centerville, OH; Guo, Jiusheng [Centerville, OH

    2011-02-15

    This invention provides a moldable, multiple-layer composite composition, which is a precursor to an electrically conductive composite flow field plate or bipolar plate. In one preferred embodiment, the composition comprises a plurality of conductive sheets and a plurality of mixture layers of a curable resin and conductive fillers, wherein (A) each conductive sheet is attached to at least one resin-filler mixture layer; (B) at least one of the conductive sheets comprises flexible graphite; and (C) at least one resin-filler mixture layer comprises a thermosetting resin and conductive fillers with the fillers being present in a sufficient quantity to render the resulting flow field plate or bipolar plate electrically conductive with a conductivity no less than 100 S/cm and thickness-direction areal conductivity no less than 200 S/cm.sup.2.

  6. Thin graphite bipolar plate with associated gaskets and carbon cloth flow-field for use in an ionomer membrane fuel cell

    DOEpatents

    Marchetti, George A.

    2003-01-03

    The present invention comprises a thin graphite plate with associated gaskets and pieces of carbon cloth that comprise a flow-field. The plate, gaskets and flow-field comprise a "plate and gasket assembly" for use in an ionomer membrane fuel cell, fuel cell stack or battery.

  7. Calcium channel dynamics limit synaptic release in response to prosthetic stimulation with sinusoidal waveforms

    PubMed Central

    Freeman, Daniel K.; Jeng, Jed S.; Kelly, Shawn K.; Hartveit, Espen; Fried, Shelley I.

    2011-01-01

    Extracellular electric stimulation with sinusoidal waveforms has been shown to allow preferential activation of individual types of retinal neurons by varying stimulus frequency. It is important to understand the mechanisms underlying this frequency dependence as a step towards improving methods of preferential activation. In order to elucidate these mechanisms, we implemented a morphologically realistic model of a retinal bipolar cell and measured the response to extracellular stimulation with sinusoidal waveforms. We compared the frequency response of a passive membrane model to the kinetics of voltage-gated calcium channels that mediate synaptic release. The passive electrical properties of the membrane exhibited lowpass filtering with a relatively high cutoff frequency (nominal value = 717 Hz). This cutoff frequency was dependent on intra-axonal resistance, with shorter and wider axons yielding higher cutoff frequencies. However, we found that the cutoff frequency of bipolar cell synaptic release was primarily limited by the relatively slow opening kinetics of Land T-type calcium channels. The cutoff frequency of calcium currents depended nonlinearly on stimulus amplitude, but remained lower than the cutoff frequency of the passive membrane model for a large range of membrane potential fluctuations. These results suggest that while it may be possible to modulate the membrane potential of bipolar cells over a wide range of stimulus frequencies, synaptic release will only be initiated at the lower end of this range. PMID:21628768

  8. High-performance symmetric sodium-ion batteries using a new, bipolar O3-type material, Na 0.8 Ni 0.4 Ti 0.6 O 2

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Guo, Shaohua; Yu, Haijun; Liu, Pan

    2015-01-01

    Based on low-cost and rich resources, sodium-ion batteries have been regarded as a promising candidate for next-generation energy storage batteries in the large-scale energy applications of renewable energy and smart grids. However, there are some critical drawbacks limiting its application, such as safety and stability problems. In this work, a stable symmetric sodium-ion battery based on the bipolar, active O3-type material, Na0.8Ni0.4Ti0.6O2, is developed. This bipolar material shows a typical O3-type layered structure, containing two electrochemically active transition metals with redox couples of Ni4+/Ni2+ and Ti4+/Ti3+, respectively. This Na0.8Ni0.4Ti0.6O2-based symmetric cell exhibits a high average voltage of 2.8 V, amore » reversible discharge capacity of 85 mA h g(-1), 75% capacity retention after 150 cycles and good rate capability. This full symmetric cell will greatly contribute to the development of room-temperature sodium-ion batteries with a view towards safety, low cost and long life, and it will stimulate further research on symmetric cells using the same active materials as both cathode and anode.« less

  9. Molecular dynamics simulations of oxide memory resistors (memristors).

    PubMed

    Savel'ev, S E; Alexandrov, A S; Bratkovsky, A M; Williams, R Stanley

    2011-06-24

    Reversible bipolar nanoswitches that can be set and read electronically in a solid-state two-terminal device are very promising for applications. We have performed molecular dynamics simulations that mimic systems with oxygen vacancies interacting via realistic potentials and driven by an external bias voltage. The competing short- and long-range interactions among charged mobile vacancies lead to density fluctuations and short-range ordering, while illustrating some aspects of observed experimental behavior, such as memristor polarity inversion. The simulations show that the 'localized conductive filaments' and 'uniform push/pull' models for memristive switching are actually two extremes of the one stochastic mechanism.

  10. Electronic monitoring in bipolar disorder.

    PubMed

    Faurholt-Jepsen, Maria

    2018-03-01

    Major reasons for the insufficient effects of current treatment options in bipolar disorder include delayed intervention for prodromal depressive and manic symptoms and decreased adherence to psychopharmacological treatment. The reliance on subjective information and clinical evaluations when diagnosing and assessing the severity of depressive and manic symptoms calls for less biased and more objective markers. By using electronic devices, fine-grained data on complex psychopathological aspects of bipolar disorder can be evaluated unobtrusively over the long term. Moreover, electronic data could possibly represent candidate markers of diagnosis and illness activity in bipolar disorder and allow for early and individualized intervention for prodromal symptoms outside clinical settings. 
The present dissertation concerns the use of electronic monitoring as a marker and treatment intervention in bipolar disorder and investigated the scientific literature and body of evidence within the area, which includes ten original study reports and two systematic reviews, one of which included a meta-analysis, conducted by the author of the dissertation. 
Taken together, the literature presented in this dissertation illustrates that 1) smartphone-based electronic self-monitoring of mood seems to reflect clinically assessed depressive and manic symptoms and enables the long-term characterization of mood

instability in bipolar disorder; 2) preliminary results suggest that smartphone-based automatically generated data (e.g. the number of text messages sent/day; the number of incoming and outgoing calls/day; the number of changes in cell tower IDs/day; and voice features) seem to reflect clinically assessed depressive and manic symptoms in bipolar disorder; 3) smartphone-based electronic self-monitoring had no effects on the severity of depressive and manic symptoms in bipolar disorder, according to a randomized controlled trial; and 4) electronic monitoring of psychomotor activity and heart rate variability seems to reflect illness activity in bipolar disorder and differentiate between patients with bipolar disorder and healthy control individuals. 
These findings point toward the usefulness of electronic monitoring as a marker of illness in bipolar disorder. Using electronic monitoring as a treatment intervention could provide innovative and novel interventions on-demand with a potential global reach, filling the gap between availability and the need for treatment. However, future studies using rigorous methodology and more randomized controlled trials that carefully investigate the positive effects and possible harmful effects of electronic monitoring in bipolar disorder are needed. In addition, patient safety, privacy issues, data security and legal aspects are major concerns that must be considered and addressed when using electronic monitoring. Articles published in the Danish Medical Journal are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.

  11. Alert Response to Motion Onset in the Retina

    PubMed Central

    Chen, Eric Y.; Marre, Olivier; Fisher, Clark; Schwartz, Greg; Levy, Joshua; da Silveira, Rava Azeredo

    2013-01-01

    Previous studies have shown that motion onset is very effective at capturing attention and is more salient than smooth motion. Here, we find that this salience ranking is present already in the firing rate of retinal ganglion cells. By stimulating the retina with a bar that appears, stays still, and then starts moving, we demonstrate that a subset of salamander retinal ganglion cells, fast OFF cells, responds significantly more strongly to motion onset than to smooth motion. We refer to this phenomenon as an alert response to motion onset. We develop a computational model that predicts the time-varying firing rate of ganglion cells responding to the appearance, onset, and smooth motion of a bar. This model, termed the adaptive cascade model, consists of a ganglion cell that receives input from a layer of bipolar cells, represented by individual rectified subunits. Additionally, both the bipolar and ganglion cells have separate contrast gain control mechanisms. This model captured the responses to our different motion stimuli over a wide range of contrasts, speeds, and locations. The alert response to motion onset, together with its computational model, introduces a new mechanism of sophisticated motion processing that occurs early in the visual system. PMID:23283327

  12. Mapping Kainate Activation of Inner Neurons in the Rat Retina

    PubMed Central

    Nivison-Smith, Lisa; Sun, Daniel; Fletcher, Erica L.; Marc, Robert E.; Kalloniatis, Michael

    2014-01-01

    Kainate receptors mediate fast, excitatory synaptic transmission for a range of inner neurons in the mammalian retina. However, allocation of functional kainate receptors to known cell types and their sensitivity remains unresolved. Using the cation channel probe 1-amino-4-guanidobutane agmatine (AGB), we investigated kainate sensitivity of neurochemically identified cell populations within the structurally intact rat retina. Most inner retinal neuron populations responded to kainate in a concentration-dependent manner. OFF cone bipolar cells demonstrated the highest sensitivity of all inner neurons to kainate. Immunocytochemical localization of AGB and macromolecular markers confirmed that type 2 bipolar cells were part of this kainate-sensitive population. The majority of amacrine (ACs) and ganglion cells (GCs) showed kainate responses with different sensitivities between major neurochemical classes (γ-aminobutyric acid [GABA]/glycine ACs > glycine ACs > GABA ACs; glutamate [Glu]/weakly GABA GCs > Glu GCs). Conventional and displaced cholinergic ACs were highly responsive to kainate, whereas dopaminergic ACs do not appear to express functional kainate receptors. These findings further contribute to our understanding of neuronal networks in complex multicellular tissues. PMID:23348566

  13. Hsp90 N- and C-terminal double inhibition synergistically suppresses Bcr-Abl-positive human leukemia cells

    PubMed Central

    Chen, Xianling; Chen, Xiaole; Li, Ding; Fan, Yingjuan; Xu, Jianhua; Chen, Yuanzhong; Wu, Lixian

    2017-01-01

    Heat shock protein 90 (Hsp90) contains amino (N)–terminal domain, carboxyl(C)-terminal domain, and middle domains, which activate Hsp90 chaperone function cooperatively in tumor cells. One terminal occupancy might influence another terminal binding with inhibitor. The Bcr-Abl kinase is one of the Hsp90 clients implicated in the pathogenesis of chronic myeloid leukemia (CML). Present studies demonstrate that double inhibition of the N- and C-terminal termini can disrupt Hsp90 chaperone function synergistically, but not antagonistically, in Bcr-Abl-positive human leukemia cells. Furthermore, both the N-terminal inhibitor 17-AAG and the C-terminal inhibitor cisplatin (CP) have the capacity to suppress progenitor cells; however, only CP is able to inhibit leukemia stem cells (LSCs) significantly, which implies that the combinational treatment is able to suppress human leukemia in different mature states. PMID:28036294

  14. Comparison of characteristics of fluorine doped zinc and gallium tin oxide composite thin films deposited on stainless steel 316 bipolar plate by electron cyclotron resonance-metal organic chemical vapor deposition for proton exchange membrane fuel cells.

    PubMed

    Park, Jihun; Hudaya, Chairul; Lee, Joong Kee

    2011-09-01

    In order to replace the brittle graphite bipolar plates currently used for the PEMFC stack, coated SUS 316 was employed. As a metallic bipolar plate, coated SUS 316 can provide higher mechanical strength, better durability to shocks and vibration, less permeability, improved thermal and bulk electrical conductivity, as well as being thinner and lighter. To enhance the interfacial contact resistance and corrosion resistance of SUS 316, the deposition of GTO:F and ZTO:F composite films was carried out by ECR-MOCVD. The surface morphology of the films consisted of tiny elliptically shaped grains with a thickness of 1 microm. The corrosion current for GTO:F was 0.13 Acm(-2) which was much lower than that of bare SUS 316 (50.16 Acm(-2)). The GTO:F coated film had the smallest corrosion current due to the formation of a tight surface morphology with very few pin-holes. The GTO:F coated film exhibited the highest cell voltage and power density due to its lower ICR values.

  15. Wide-field Diffuse Amacrine Cells in the Monkey Retina Contain Immunoreactive Cocaine- and Amphetamine-Regulated Transcript (CART)

    PubMed Central

    Liu, Weiley S.; Davis, Elizabeth P.; Lee, Stephen J.; Tseng, Luke; Chuang, Alice Z.; Whitaker, Christopher M.; Massey, Stephen C.; Sherman, Michael B.; Marshak, David W.

    2016-01-01

    The goals of this study were to localize the neuropeptide Cocaine- and Amphetamine-Regulated Transcript (CART) in primate retinas and to describe the morphology, neurotransmitter content and synaptic connections of the neurons that contain it. Using in situ hybridization, light and electron microscopic immunolabeling, CART was localized to GABAergic amacrine cells in baboon retinas. The CART-positive cells had thin, varicose dendrites that gradually descended through the inner plexiform layer and ramified extensively in the innermost stratum. They resembled two types of wide-field diffuse amacrine cells that had been described previously in macaque retinas using the Golgi method and also A17, serotonin-accumulating and waterfall cells of other mammals. The CART-positive cells received synapses from rod bipolar cell axons and made synapses onto the axons in a reciprocal configuration. The CART-positive cells also received synapses from other amacrine cells. Some of these were located on their primary dendrites, and the presynaptic cells there included dopaminergic amacrine cells. Although some CART-positive somas were localized in the ganglion cell layer, they did not contain the ganglion cell marker RNA binding protein with multiple splicing (RBPMS). Based on these results and electrophysiological studies in other mammals, the CART-positive amacrine cells would be expected to play a major role in the primary rod pathway of primates, providing feedback inhibition to rod bipolar cells. PMID:27568514

  16. Group III metabotropic glutamate receptors and exocytosed protons inhibit L-type calcium currents in cones but not in rods.

    PubMed

    Hosoi, Nobutake; Arai, Itaru; Tachibana, Masao

    2005-04-20

    Light responses of photoreceptors (rods and cones) are transmitted to the second-order neurons (bipolar cells and horizontal cells) via glutamatergic synapses located in the outer plexiform layer of the retina. Although it has been well established that postsynaptic group III metabotropic glutamate receptors (mGluRs) of ON bipolar cells contribute to generating the ON signal, presynaptic roles of group III mGluRs remain to be elucidated at this synaptic connection. We addressed this issue by applying the slice patch-clamp technique to the newt retina. OFF bipolar cells and horizontal cells generate a steady inward current in the dark and a transient inward current at light offset, both of which are mediated via postsynaptic non-NMDA receptors. A group III mGluR-specific agonist, L-2-amino-4-phosphonobutyric acid (L-AP-4), inhibited both the steady and off-transient inward currents but did not affect the glutamate-induced current in these postsynaptic neurons. L-AP-4 inhibited the presynaptic L-type calcium current (ICa) in cones by shifting the voltage dependence of activation to more positive membrane potentials. The inhibition of ICa was most prominent around the physiological range of cone membrane potentials. In contrast, L-AP-4 did not affect L-type ICa in rods. Paired recordings from photoreceptors and the synaptically connected second-order neurons confirmed that L-AP-4 inhibited both ICa and glutamate release in cones but not in rods. Furthermore, we found that exocytosed protons also inhibited ICa in cones but not in rods. Selective modulation of ICa in cones may help broaden the dynamic range of synaptic transfer by controlling the amount of transmitter release from cones.

  17. The Andalusian Bipolar Family (ABiF) Study: Protocol and sample description.

    PubMed

    Guzman-Parra, Jose; Rivas, Fabio; Strohmaier, Jana; Forstner, Andreas; Streit, Fabian; Auburger, Georg; Propping, Peter; Orozco-Diaz, Guillermo; González, Maria José; Gil-Flores, Susana; Cabaleiro-Fabeiro, Francisco Javier; Del Río-Noriega, Francisco; Perez-Perez, Fermin; Haro-González, Jesus; de Diego-Otero, Yolanda; Romero-Sanchiz, Pablo; Moreno-Küstner, Berta; Cichon, Sven; Nöthen, Markus M; Rietschel, Marcella; Mayoral, Fermin

    2017-06-12

    Here, we present the first description of the Andalusian Bipolar Family (ABiF) Study. This longitudinal investigation of families from Andalusia, Spain commenced in 1997 with the aim of elucidating the molecular genetic causes of bipolar affective disorder. The cohort has since contributed to a number of key genetic findings, as reported in international journals. However, insight into the genetic underpinnings of the disorder in these families remains limited. In the initial 1997-2003 study phase, 100 multiplex bipolar disorder and other mood disorder families were recruited. The ongoing second phase of the project commenced in 2013, and involves follow-up of a subgroup of the originally recruited families. The aim of the follow-up investigation is to generate: i) longitudinal clinical data; ii) results from detailed neuropsychological assessments; and iii) a more extensive collection of biomaterials for future molecular biological studies. The ABiF Study will thus generate a valuable resource for future investigations into the aetiology of bipolar affective disorder; in particular the causes of high disease loading within multiply affected families. We discuss the value of this approach in terms of new technologies for the identification of high-penetrance genetic factors. These new technologies include exome and whole genome sequencing, and the use of induced pluripotent stem cells or model organisms to determine functional consequences. Copyright © 2017 SEP y SEPB. Publicado por Elsevier España, S.L.U. All rights reserved.

  18. Vitamin D receptor FokI genotype may modify the susceptibility to schizophrenia and bipolar mood disorder by regulation of dopamine D1 receptor gene expression.

    PubMed

    Ahmadi, S; Mirzaei, K; Hossein-Nezhad, A; Shariati, G

    2012-10-01

    This study is designed to test association of FOKI polymorphism in Vitamin D receptor (VDR) gene and its potential effect on expression of dopamine D1 receptor in schizophrenia and bipolar mood disorder as well as in healthy individuals. In this case-control study 196 patient with schizophrenia, 119 patients with bipolar mood disorder and 192 healthy individuals as the control group were recruited. All psychiatric disorders were diagnosed according to DSM IV criteria. Healthy control group denied any family history of such disorders. FOKI was genotyped by means of PCR-RFLP method. The mRNA was extracted from the peripheral blood mononuclear cells (PBMC) and the cDNA was synthesized. Frequency of ff genotype was more common in patients with bipolar disorders compared to the healthy control group (Odds ratio=1.84, 95% CI; 0.81 to 4.17) with increased relative risk (Relative risk=1.31, CI 95%; 0.86 to 1.99). There were significant differences between relative expressions of dopamine D1 receptor gene in various genotypes. Our results indicated that the ff genotype was associated with lower expression of dopamine D1 receptor gene. VDR as a nuclear receptor may contribute to bipolar disorders via modification of the expression of the neurotransmitters receptor such as dopamine.

  19. Transforming growth factor-beta in the chicken fundal layers: an immunohistochemical study.

    PubMed

    Mathis, Ute; Schaeffel, Frank

    2010-06-01

    In the chicken model of myopia, it has first been shown that imposing defocus to the retina results in active remodelling of the sclera which, in turn, results in axial length changes of the eye. Transforming growth factor-beta (TGF-beta) is one of the scleral growth modulators but its cellular localization in the fundal layers, colocalization and function are not well known. The aim of the current study was to investigate the cellular distribution of the three isoforms TGF-beta1, 2 and 3 by immunohistochemical labelling. Furthermore, the effects of visual experience that induces refractive errors on TGF-beta2 labelling were examined. Transversal cryostat sections of the fundal layers were analyzed by indirect immunofluorescent labelling and cell counts. Visual experience was changed by having the chicks wear either diffusers, or positive or negative lenses of 7D power in front of the right eyes for various periods of time. Left eyes served as uncovered controls. All TGF-beta isoforms were localized in both scleral layers. In choroid, diffuse labelling of all isoforms was found. In retina, TGF-beta1 and 3 were detected in bipolar, amacrine and ganglion cells and TGF-beta2 in amacrine and ganglion cells. To further characterize these cells, double-labelling with known amacrine and bipolar cell markers was performed (calbindin, cellular retinoic acid binding protein (CRABP), Islet1, Lim3 and protein kinase C (PKC)). TGF-beta1, 2 and 3 could be colocalized with calbindin and CRABP in single amacrine cells. TGF-beta1-positive bipolar cells were immunoreactive to Lim3. TGF-beta1 and 3 were never colocalized with PKC in bipolar cells. Also, colocalization with peptides known to be involved in myopia development in chicks, such as glucagon, or vasointestinal polypeptide and the key enzyme for dopamine synthesis, tyrosine hydroxylase, was not observed. Lenses or diffusers, worn by the chicks for various periods of time, had no effect on TGF-beta2 immunoreactivity in choroid or sclera, or on the number of TGF-beta2 (active and latent form) expressing amacrine cells. This result did not change when the two identified populations of TGF-beta2 expressing amacrine cells (one calbindin-positive and the other CRABP-positive) were separately considered. Also no modulation was seen in choroid, although an earlier study had found changes in TGF-beta2 mRNA after lens treatment. The lack of any visually-induced changes in retina or choroid suggests that TGF-beta may not represent a key molecule in the retino-choroidal signalling cascade although it has previously been shown to have a primary role in scleral remodelling. Copyright 2010 Elsevier Ltd. All rights reserved.

  20. Atypia in fine needle aspirates of breast lesions.

    PubMed

    Tran, Phuong Viet The; Lui, Philip C W; Yu, Alex M C; Vinh, Pham The; Chau, Helen H L; Ma, Tony K F; Tan, Puay-Hoon; Tse, Gary M

    2010-07-01

    The atypical category is controversial in fine needle aspiration cytology (FNAC) of the breast; most are benign, but a significant number are malignant. To date, no morphological criterion has been found to be consistent in predicting malignancy. To evaluate specific cytological parameters and assess their usefulness in predicting histological outcome in a cohort of atypical breast FNAC, in order to establish a set of objective criteria in defining 'high risk' atypical breast FNAC. A retrospective review of 98 cases of atypical breast FNAC with histological correlation was undertaken. The cytological preparations were evaluated for cellularity, percentage of epithelial cell cluster and single epithelial cells, nuclear atypia, nucleus:cytoplasm ratio, percentage of bipolar nuclei, and the presence of stromal fragments, histiocytes and necrosis. 66 of 98 cases (67.35%) showed benign histology and 32 cases (32.65%) showed malignant histology. Compared with the malignant group, the benign group had significantly lower patient age (p=0.05), higher bipolar nuclei (p<0.0001), less degree of nuclear pleomorphism (p<0.0001), lower nucleus:cytoplasm ratio (p<0.0001), lower cellularity (p=0.05) and less necrosis (p<0.001). There was no difference in the percentage of epithelial clusters and single cells, or the presence of stromal fragments and histiocytes. The presence of nuclear pleomorphism, high nucleus:cytoplasm ratio, epithelial cell atypia, low number of bipolar nuclei and necrosis are useful parameters to predict malignancy in atypical FNAC of the breast. Assessment of these factors in atypical FNAC may be helpful in predicting cancer risk and subsequent management decision making.

  1. Phosphoric Acid Fuel Cell Technology Status

    NASA Technical Reports Server (NTRS)

    Simons, S. N.; King, R. B.; Prokopius, P. R.

    1981-01-01

    A review of the current phosphoric acid fuel cell system technology development efforts is presented both for multimegawatt systems for electric utility applications and for multikilowatt systems for on-site integrated energy system applications. Improving fuel cell performance, reducing cost, and increasing durability are the technology drivers at this time. Electrodes, matrices, intercell cooling, bipolar/separator plates, electrolyte management, and fuel selection are discussed.

  2. Dry compliant seal for phosphoric acid fuel cell

    DOEpatents

    Granata, Jr., Samuel J.; Woodle, Boyd M.

    1990-01-01

    A dry compliant overlapping seal for a phosphoric acid fuel cell preformed f non-compliant Teflon to make an anode seal frame that encircles an anode assembly, a cathode seal frame that encircles a cathode assembly and a compliant seal frame made of expanded Teflon, generally encircling a matrix assembly. Each frame has a thickness selected to accommodate various tolerances of the fuel cell elements and are either bonded to one of the other frames or to a bipolar or end plate. One of the non-compliant frames is wider than the other frames forming an overlap of the matrix over the wider seal frame, which cooperates with electrolyte permeating the matrix to form a wet seal within the fuel cell that prevents process gases from intermixing at the periphery of the fuel cell and a dry seal surrounding the cell to keep electrolyte from the periphery thereof. The frames may be made in one piece, in L-shaped portions or in strips and have an outer perimeter which registers with the outer perimeter of bipolar or end plates to form surfaces upon which flanges of pan shaped, gas manifolds can be sealed.

  3. Multiple cone pathways are involved in photic regulation of retinal dopamine.

    PubMed

    Qiao, Sheng-Nan; Zhang, Zhijing; Ribelayga, Christophe P; Zhong, Yong-Mei; Zhang, Dao-Qi

    2016-06-30

    Dopamine is a key neurotransmitter in the retina and plays a central role in the light adaptive processes of the visual system. The sole source of retinal dopamine is dopaminergic amacrine cells (DACs). We and others have previously demonstrated that DACs are activated by rods, cones, and intrinsically photosensitive retinal ganglion cells (ipRGCs) upon illumination. However, it is still not clear how each class of photosensitive cells generates light responses in DACs. We genetically isolated cone function in mice to specifically examine the cone-mediated responses of DACs and their neural pathways. In addition to the reported excitatory input to DACs from light-increment (ON) bipolar cells, we found that cones alternatively signal to DACs via a retrograde signalling pathway from ipRGCs. Cones also produce ON and light-decrement (OFF) inhibitory responses in DACs, which are mediated by other amacrine cells, likely driven by type 1 and type 2/3a OFF bipolar cells, respectively. Dye injections indicated that DACs had similar morphological profiles with or without ON/OFF inhibition. Our data demonstrate that cones utilize specific parallel excitatory and inhibitory circuits to modulate DAC activity and efficiently regulate dopamine release and the light-adaptive state of the retina.

  4. The Retina of Asian and African Elephants: Comparison of Newborn and Adult.

    PubMed

    Kuhrt, Heidrun; Bringmann, Andreas; Härtig, Wolfgang; Wibbelt, Gudrun; Peichl, Leo; Reichenbach, Andreas

    2017-01-01

    Elephants are precocial mammals that are relatively mature as newborns and mobile shortly after birth. To determine whether the retina of newborn elephants is capable of supporting the mobility of elephant calves, we compared the retinal structures of 2 newborn elephants (1 African and 1 Asian) and 2 adult animals of both species by immunohistochemical and morphometric methods. For the first time, we present here a comprehensive qualitative and quantitative characterization of the cellular composition of the newborn and the adult retinas of 2 elephant species. We found that the retina of elephants is relatively mature at birth. All retinal layers were well discernible, and various retinal cell types were detected in the newborns, including Müller glial cells (expressing glutamine synthetase and cellular retinal binding protein; CRALBP), cone photoreceptors (expressing S-opsin or M/L-opsin), protein kinase Cα-expressing bipolar cells, tyrosine hydroxylase-, choline acetyltransferase (ChAT)-, calbindin-, and calretinin-expressing amacrine cells, and calbindin-expressing horizontal cells. The retina of newborn elephants contains discrete horizontal cells which coexpress ChAT, calbindin, and calretinin. While the overall structure of the retina is very similar between newborn and adult elephants, various parameters change after birth. The postnatal thickening of the retinal ganglion cell axons and the increase in ganglion cell soma size are explained by the increase in body size after birth, and the decreases in the densities of neuronal and glial cells are explained by the postnatal expansion of the retinal surface area. The expression of glutamine synthetase and CRALBP in the Müller cells of newborn elephants suggests that the cells are already capable of supporting the activities of photoreceptors and neurons. As a peculiarity, the elephant retina contains both normally located and displaced giant ganglion cells, with single cells reaching a diameter of more than 50 µm in adults and therefore being almost in the range of giant retinal ganglion cells found in aquatic mammals. Some of these ganglion cells are displaced into the inner nuclear layer, a unique feature of terrestrial mammals. For the first time, we describe here the occurrence of many bistratified rod bipolar cells in the elephant retina. These bistratified bipolar cells may improve nocturnal contrast perception in elephants given their arrhythmic lifestyle. © 2017 S. Karger AG, Basel.

  5. AII amacrine cells discriminate between heterocellular and homocellular locations when assembling connexin36-containing gap junctions

    PubMed Central

    Meyer, Arndt; Hilgen, Gerrit; Dorgau, Birthe; Sammler, Esther M.; Weiler, Reto; Monyer, Hannah; Dedek, Karin; Hormuzdi, Sheriar G.

    2014-01-01

    ABSTRACT Electrical synapses (gap junctions) rapidly transmit signals between neurons and are composed of connexins. In neurons, connexin36 (Cx36) is the most abundant isoform; however, the mechanisms underlying formation of Cx36-containing electrical synapses are unknown. We focus on homocellular and heterocellular gap junctions formed by an AII amacrine cell, a key interneuron found in all mammalian retinas. In mice lacking native Cx36 but expressing a variant tagged with enhanced green fluorescent protein at the C-terminus (KO-Cx36-EGFP), heterocellular gap junctions formed between AII cells and ON cone bipolar cells are fully functional, whereas homocellular gap junctions between two AII cells are not formed. A tracer injected into an AII amacrine cell spreads into ON cone bipolar cells but is excluded from other AII cells. Reconstruction of Cx36–EGFP clusters on an AII cell in the KO-Cx36-EGFP genotype confirmed that the number, but not average size, of the clusters is reduced – as expected for AII cells lacking a subset of electrical synapses. Our studies indicate that some neurons exhibit at least two discriminatory mechanisms for assembling Cx36. We suggest that employing different gap-junction-forming mechanisms could provide the means for a cell to regulate its gap junctions in a target-cell-specific manner, even if these junctions contain the same connexin. PMID:24463820

  6. Pseudoautosomal abnormalities in terminal AZFb+c deletions are associated with isochromosomes Yp and may lead to abnormal growth and neuropsychiatric function.

    PubMed

    Castro, A; Rodríguez, F; Flórez, M; López, P; Curotto, B; Martínez, D; Maturana, A; Lardone, M C; Palma, C; Mericq, V; Ebensperger, M; Cassorla, F

    2017-02-01

    Are copy number variations (CNVs) in the pseudoautosomal regions (PARs) frequent in subjects with Y-chromosome microdeletions and can they lead to abnormal stature and/or neuropsychiatric disorders? Only subjects diagnosed with azoospermia factor (AZF)b+c deletions spanning to the end of the Y chromosome (i.e. terminal deletions) harbor Y isochromosomes and/or cells 45,X that lead to pseudoautosomal gene CNVs, which were associated with abnormal stature and/or neuropsychiatric disorders. The microdeletions in the long arm of the Y chromosome (Yq) that include the loss of one to three AZF regions, referred to as Yq microdeletions, constitute the most important known etiological factor for primary spermatogenic failure. Recently, controversy has arisen about whether Yq microdeletions are associated with gain or loss of PAR genes, which are implicated in skeletal development and neuropsychiatric function. We studied a cohort of 42 Chilean patients with complete AZF deletions (4 AZFa, 4 AZFb, 23 AZFc, 11 AZFb+c) from a university medical center, diagnosed over a period of 15 years. The subjects underwent complete medical examinations with special attention to their stature and neuropsychiatric function. All subjects were characterized for Yq breakpoints by PCR, and for CNVs in PARs by multiplex ligation-dependent probe amplification (MLPA), followed by qPCR analysis for genes in PAR1 (SHOX and ZBED1), PAR2 (IL9R) and two single copy genes (SRY and DDX3Y, respectively located in Yp11.3 and AZFa). In addition, karyotypes revision and fluorescence in situ hybridization (FISH) for SRY and centromeric probes for X (DXZ1) and Y (DYZ3) chromosomes were performed in males affected with CNVs. We did not detect CNVs in any of the 35 AZF-deleted men with interstitial deletions (AZFa, AZFb, AZFc or AZFb+c). However, six of the seven patients with terminal AZFb+c deletions showed CNVs: two patients showed a loss and four patients showed a gain of PAR1 genes, with the expected loss of VAMP-7 in PAR2. In these patients, the Yq breakpoints localized to the palindromes P8, P5 or P4. In the four cases with gain of PAR1, qPCR analysis showed duplicated signals for SRY and DDX3Y and one copy of IL9R, indicating isodicentric Yp chromosomes [idic(Y)] with breakpoint in Yq11.22. The two patients who had loss of PAR1, as shown by MLPA, had an additional reduction for SRY and DDX3Y, as shown by qPCR, associated with a high proportion of 45,X cells, as determined by FISH and karyotype. In agreement with the karyotype analysis, we detected DYZ3++ and DYZ3+ cells by FISH in the six patients, confirming idic(Y) and revealing additional monocentric Y chromosome [i(Y)]. Five patients had a history of major depressive disorders or bipolar disorder, and three had language impairment, whereas two patients showed severe short stature (Z score: -2.75 and -2.62), while a man with bipolar disorder was very tall (Z score: +2.56). N/A. The number of males studied with Y-chromosome microdeletions and normozoospermic controls with normal karyotypes may not be enough to rule out an association between AZF deletions and PAR abnormalities. The prevalence of Y isochromosomes and/or 45,X cells detected in peripheral blood does not necessarily reflect the variations of PAR genes in target tissues. This study shows that CNVs in PARs were present exclusively in patients with terminal AZFb+c deletions associated with the presence of Y isochromosomes and 45,X cells, and may lead to neuropsychiatric and growth disorders. In contrast, we show that men with interstitial Yq microdeletions with normal karyotypes do not have an increased risk of PAR abnormalities and of phenotypical consequences. Moreover, our results highlight the importance of performing molecular studies, which are not considered in the usual screening for patients with Yq microdeletions. This work was supported by the National Fund for Scientific and Technological Development of Chile (FONDECYT), grant no. 1120176 (A.C.). The authors declare that no conflicting interests exist. © The Author 2017. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  7. Innovative approaches to bipolar disorder and its treatment

    PubMed Central

    Cipriani, Andrea; Harmer, Catherine J.; Nobre, Anna C.; Saunders, Kate; Goodwin, Guy M.; Geddes, John R.

    2016-01-01

    All psychiatric disorders have suffered from a dearth of truly novel pharmacological interventions. In bipolar disorder, lithium remains a mainstay of treatment, six decades since its effects were serendipitously discovered. The lack of progress reflects several factors, including ignorance of the disorder's pathophysiology and the complexities of the clinical phenotype. After reviewing the current status, we discuss some ways forward. First, we highlight the need for a richer characterization of the clinical profile, facilitated by novel devices and new forms of data capture and analysis; such data are already promoting a reevaluation of the phenotype, with an emphasis on mood instability rather than on discrete clinical episodes. Second, experimental medicine can provide early indications of target engagement and therapeutic response, reducing the time, cost, and risk involved in evaluating potential mood stabilizers. Third, genomic data can inform target identification and validation, such as the increasing evidence for involvement of calcium channel genes in bipolar disorder. Finally, new methods and models relevant to bipolar disorder, including stem cells and genetically modified mice, are being used to study key pathways and drug effects. A combination of these approaches has real potential to break the impasse and deliver genuinely new treatments. PMID:27111134

  8. Bipolar Disorder: Role of Inflammation and the Development of Disease Biomarkers

    PubMed Central

    2016-01-01

    Bipolar disorder is a severe and enduring psychiatric condition which in many cases starts during early adulthood and follows a relapsing and remitting course throughout life. In many patients the disease follows a progressive path with brief periods of inter-episode recovery, sub-threshold symptoms, treatment resistance and increasing functional impairment in the biopsychosocial domains. Knowledge about the neurobiology of bipolar disorder is increasing steadily and evidence from several lines of research implicates immuno-inflammatory mechanisms in the brain and periphery in the etiopathogenesis of this illness and its comorbidities. The main findings are an increase in the levels of proinflammatory cytokines during acute episodes with a decrease in neurotrophic support. Related to these factors are glial cell dysfunction, neuro-endocrine abnormalities and neurotransmitter aberrations which together cause plastic changes in the mood regulating areas of the brain and neuroprogression of the bipolar diathesis. Research in the above mentioned areas is providing an opportunity to discover novel biomarkers for the disease and the field is reaching a point where major breakthroughs can be expected in the not too distant future. It is hoped that with new discoveries fresh avenues will be found to better treat an otherwise recalcitrant disease. PMID:26766943

  9. The unique C- and N-terminal sequences of Metallothionein isoform 3 mediate growth inhibition and Vectorial active transport in MCF-7 cells.

    PubMed

    Voels, Brent; Wang, Liping; Sens, Donald A; Garrett, Scott H; Zhang, Ke; Somji, Seema

    2017-05-25

    The 3rd isoform of the metallothionein (MT3) gene family has been shown to be overexpressed in most ductal breast cancers. A previous study has shown that the stable transfection of MCF-7 cells with the MT3 gene inhibits cell growth. The goal of the present study was to determine the role of the unique C-terminal and N-terminal sequences of MT3 on phenotypic properties and gene expression profiles of MCF-7 cells. MCF-7 cells were transfected with various metallothionein gene constructs which contain the insertion or the removal of the unique MT3 C- and N-terminal domains. Global gene expression analysis was performed on the MCF-7 cells containing the various constructs and the expression of the unique C- and N- terminal domains of MT3 was correlated to phenotypic properties of the cells. The results of the present study demonstrate that the C-terminal sequence of MT3, in the absence of the N-terminal sequence, induces dome formation in MCF-7 cells, which in cell cultures is the phenotypic manifestation of a cell's ability to perform vectorial active transport. Global gene expression analysis demonstrated that the increased expression of the GAGE gene family correlated with dome formation. Expression of the C-terminal domain induced GAGE gene expression, whereas the N-terminal domain inhibited GAGE gene expression and that the effect of the N-terminal domain inhibition was dominant over the C-terminal domain of MT3. Transfection with the metallothionein 1E gene increased the expression of GAGE genes. In addition, both the C- and the N-terminal sequences of the MT3 gene had growth inhibitory properties, which correlated to an increased expression of the interferon alpha-inducible protein 6. Our study shows that the C-terminal domain of MT3 confers dome formation in MCF-7 cells and the presence of this domain induces expression of the GAGE family of genes. The differential effects of MT3 and metallothionein 1E on the expression of GAGE genes suggests unique roles of these genes in the development and progression of breast cancer. The finding that interferon alpha-inducible protein 6 expression is associated with the ability of MT3 to inhibit growth needs further investigation.

  10. A review of empirically supported psychological therapies for mood disorders in adults

    PubMed Central

    Hollon, Steven D.; Ponniah, Kathryn

    2010-01-01

    Background The mood disorders are prevalent and problematic. We review randomized controlled psychotherapy trials to find those that are empirically supported with respect to acute symptom reduction and the prevention of subsequent relapse and recurrence. Methods We searched the PsycINFO and PubMed databases and the reference sections of chapters and journal articles to identify appropriate articles. Results One hundred twenty-five studies were found evaluating treatment efficacy for the various mood disorders. With respect to the treatment of major depressive disorder (MDD), interpersonal psychotherapy (IPT), cognitive behavior therapy (CBT), and behavior therapy (BT) are efficacious and specific and brief dynamic therapy (BDT) and emotion-focused therapy (EFT) are possibly efficacious. CBT is efficacious and specific, mindfulness-based cognitive therapy (MBCT) efficacious, and BDT and EFT possibly efficacious in the prevention of relapse/recurrence following treatment termination and IPT and CBT are each possibly efficacious in the prevention of relapse/recurrence if continued or maintained. IPT is possibly efficacious in the treatment of dysthymic disorder. With respect to bipolar disorder, CBT and family-focused therapy (FFT) are efficacious and interpersonal social rhythm therapy (IPSRT) possibly efficacious as adjuncts to medication in the treatment of depression. Psycho-education (PE) is efficacious in the prevention of mania/hypomania (and possibly depression) and FFT is efficacious and IPSRT and CBT possibly efficacious in preventing bipolar episodes. Conclusions The newer psychological interventions are as efficacious as and more enduring than medications in the treatment of MDD and may enhance the efficacy of medications in the treatment of bipolar disorder. PMID:20830696

  11. From the Psychiatrist’s Couch to Induced Pluripotent Stem Cells: Bipolar Disease in a Dish

    PubMed Central

    Hoffmann, Anke; Sportelli, Vincenza; Ziller, Michael; Spengler, Dietmar

    2018-01-01

    Bipolar disease (BD) is one of the major public health burdens worldwide and more people are affected every year. Comprehensive genetic studies have associated thousands of single nucleotide polymorphisms (SNPs) with BD risk; yet, very little is known about their functional roles. Induced pluripotent stem cells (iPSCs) are powerful tools for investigating the relationship between genotype and phenotype in disease-relevant tissues and cell types. Neural cells generated from BD-specific iPSCs are thought to capture associated genetic risk factors, known and unknown, and to allow the analysis of their effects on cellular and molecular phenotypes. Interestingly, an increasing number of studies on BD-derived iPSCs report distinct alterations in neural patterning, postmitotic calcium signaling, and neuronal excitability. Importantly, these alterations are partly normalized by lithium, a first line treatment in BD. In light of these exciting findings, we discuss current challenges to the field of iPSC-based disease modelling and future steps to be taken in order to fully exploit the potential of this approach for the investigation of BD and the development of new therapies. PMID:29517996

  12. Impact of heat and water management on proton exchange membrane fuel cells degradation in automotive application

    NASA Astrophysics Data System (ADS)

    Nandjou, F.; Poirot-Crouvezier, J.-P.; Chandesris, M.; Blachot, J.-F.; Bonnaud, C.; Bultel, Y.

    2016-09-01

    In Proton Exchange Membrane Fuel Cells, local temperature is a driving force for many degradation mechanisms such as hygrothermal deformation and creep of the membrane, platinum dissolution and bipolar plates corrosion. In order to investigate and quantify those effects in automotive application, durability testing is conducted in this work. During the ageing tests, the local performance and temperature are investigated using in situ measurements of a printed circuit board. At the end of life, post-mortem analyses of the aged components are conducted. The experimental results are compared with the simulated temperature and humidity in the cell obtained from a pseudo-3D multiphysics model in order to correlate the observed degradations to the local conditions inside the stack. The primary cause of failure in automotive cycling is pinhole/crack formation in the membrane, induced by high variations of its water content over time. It is also observed that water condensation largely increases the probability of the bipolar plates corrosion while evaporation phenomena induce local deposits in the cell.

  13. Design and simulation of novel flow field plate geometry for proton exchange membrane fuel cells

    NASA Astrophysics Data System (ADS)

    Ruan, Hanxia; Wu, Chaoqun; Liu, Shuliang; Chen, Tao

    2016-10-01

    Bipolar plate is one of the many important components of proton exchange membrane fuel cell (PEMFC) stacks as it supplies fuel and oxidant to the membrane-electrode assembly (MEA), removes water, collects produced current and provides mechanical support for the single cells in the stack. The flow field design of a bipolar plate greatly affects the performance of a PEMFC. It must uniformly distribute the reactant gases over the MEA and prevent product water flooding. This paper aims at improving the fuel cell performance by optimizing flow field designs and flow channel configurations. To achieve this, a novel biomimetic flow channel for flow field designs is proposed based on Murray's Law. Computational fluid dynamics based simulations were performed to compare three different designs (parallel, serpentine and biomimetic channel, respectively) in terms of current density distribution, power density distribution, pressure distribution, temperature distribution, and hydrogen mass fraction distribution. It was found that flow field designs with biomimetic flow channel perform better than that with convectional flow channel under the same operating conditions.

  14. Analysis of multiple cell upset sensitivity in bulk CMOS SRAM after neutron irradiation

    NASA Astrophysics Data System (ADS)

    Pan, Xiaoyu; Guo, Hongxia; Luo, Yinhong; Zhang, Fengqi; Ding, Lili

    2018-03-01

    In our previous studies, we have proved that neutron irradiation can decrease the single event latch-up (SEL) sensitivity of CMOS SRAM. And one of the key contributions to the multiple cell upset (MCU) is the parasitic bipolar amplification, it bring us to study the impact of neutron irradiation on the SRAM’s MCU sensitivity. After the neutron experiment, we test the devices’ function and electrical parameters. Then, we use the heavy ion fluence to examine the changes on the devices’ MCU sensitivity pre- and post-neutron-irradiation. Unfortunately, neutron irradiation makes the MCU phenomenon worse. Finally, we use the electric static discharge (ESD) testing technology to deduce the experimental results and find that the changes on the WPM region take the lead rather than the changes on the parasitic bipolar amplification for the 90 nm process.

  15. Encoding of luminance and contrast by linear and nonlinear synapses in the retina.

    PubMed

    Odermatt, Benjamin; Nikolaev, Anton; Lagnado, Leon

    2012-02-23

    Understanding how neural circuits transmit information is technically challenging because the neural code is contained in the activity of large numbers of neurons and synapses. Here, we use genetically encoded reporters to image synaptic transmission across a population of sensory neurons-bipolar cells in the retina of live zebrafish. We demonstrate that the luminance sensitivities of these synapses varies over 10(4) with a log-normal distribution. About half the synapses made by ON and OFF cells alter their polarity of transmission as a function of luminance to generate a triphasic tuning curve with distinct maxima and minima. These nonlinear synapses signal temporal contrast with greater sensitivity than linear ones. Triphasic tuning curves increase the dynamic range over which bipolar cells signal light and improve the efficiency with which luminance information is transmitted. The most efficient synapses signaled luminance using just 1 synaptic vesicle per second per distinguishable gray level. Copyright © 2012 Elsevier Inc. All rights reserved.

  16. Cell morphology and flagellation of nitrogen-fixing spirilla.

    PubMed

    Hegazi, N A; Vlassak, K

    1979-01-01

    Twenty isolates of N2-fixing spirilla were isolated from the rhizosphere of maize and sugar cane grown in Egyptian and Belgian soils. Electron microscopy distinguished two morphological groups. The first includes short and thick curved rods with an unipolar flagellum while cells of the second group are much longer with the typical appearance of spiral cells and most probably possess a bipolar tuft of flagella.

  17. Interface of the transport systems research vehicle monochrome display system to the digital autonomous terminal access communication data bus

    NASA Technical Reports Server (NTRS)

    Easley, W. C.; Tanguy, J. S.

    1986-01-01

    An upgrade of the transport systems research vehicle (TSRV) experimental flight system retained the original monochrome display system. The original host computer was replaced with a Norden 11/70, a new digital autonomous terminal access communication (DATAC) data bus was installed for data transfer between display system and host, while a new data interface method was required. The new display data interface uses four split phase bipolar (SPBP) serial busses. The DATAC bus uses a shared interface ram (SIR) for intermediate storage of its data transfer. A display interface unit (DIU) was designed and configured to read from and write to the SIR to properly convert the data from parallel to SPBP serial and vice versa. It is found that separation of data for use by each SPBP bus and synchronization of data tranfer throughout the entire experimental flight system are major problems which require solution in DIU design. The techniques used to accomplish these new data interface requirements are described.

  18. Energy storage cell impedance measuring apparatus, methods and related systems

    DOEpatents

    Morrison, John L.; Morrison, William H.; Christophersen, Jon P.

    2017-12-26

    Energy storage cell impedance testing devices, circuits, and related methods are disclosed. An energy storage cell impedance measuring device includes a sum of sinusoids (SOS) current excitation circuit including differential current sources configured to isolate a ground terminal of the differential current sources from a positive terminal and a negative terminal of an energy storage cell. A method includes applying an SOS signal comprising a sum of sinusoidal current signals to the energy storage cell with the SOS current excitation circuit, each of the sinusoidal current signals oscillating at a different one of a plurality of different frequencies. The method also includes measuring an electrical signal at a positive terminal and a negative terminal of the energy storage cell, and computing an impedance of the energy storage cell at each of the plurality of different frequencies using the measured electrical signal.

  19. Disease and Stem Cell-Based Analysis of the 2014 ASNTR Meeting

    PubMed Central

    Eve, David J.

    2015-01-01

    A wide variety of subjects are presented at the annual American Society of Neural Therapy and Repair meeting every year, as typified by this summary of the 2014 meeting. Parkinson’s disease-related presentations were again the most popular topic, with traumatic brain injury, spinal cord injury, and stroke being close behind. Other disorders included Huntington’s disease, brain cancer, and bipolar disorders. Several studies were related to multiple diseases, and many studies attempted to reveal more about the disease process. The use of scaffolds, drugs, and gene therapy as disease models and/or potential therapies were also featured. An increasing proportion of presentations related to stem cells, with the study of multiple stem cell types being the most common. Induced pluripotent stem cells were increasingly popular, including two presentations each on a muscle-derived dedifferentiated cell type and cells derived from bipolar patients. Other stem cells, including neural stem cells, mesenchymal stem cells, umbilical cord blood cells, and embryonic stem cells, were featured. More than 55% of the stem cell studies involved transplantation, with human-derived cells being the most frequently transplanted, while rats were the most common recipient. Two human autologous studies for spinal cord injury and hypoxia-derived encephalopathy, while a further three allogenic studies for stroke and spinal cord injury, were also featured. This year’s meeting highlights the increasing promise of stem cells and other therapies for the treatment of neurodegenerative disorders. PMID:26858901

  20. Anodic oxidation of textile wastewaters on boron-doped diamond electrodes.

    PubMed

    Abdessamad, NourElHouda; Akrout, Hanene; Bousselmi, Latifa

    2015-01-01

    The objective of this study is to investigate the potential application of the anodic oxidation (AO) on two electrolytic cells (monopolar (Cell 1) and bipolar (Cell 2)) containing boron-doped diamond electrodes on the treatment of real textile effluents to study the reuse possibility of treated wastewater in the textile industry process. AO is applied in the flocculation coagulation pretreatment of both upstream (BH) and downstream (BS) effluents. The chemical oxygen demand (COD) results show that the final COD removal obtained for the BH effluent in the case of Cell 1 and Cell 2 is 800 and 150 mg O₂L⁻¹ after 5 and 6 h of electrolysis, respectively. The treatments of the BS effluent allow for obtaining a final COD of 76 mg L⁻¹ for Cell 1 and a total mineralization for Cell 2. The obtained results demonstrate that the apparent mineralization kinetics of both effluents when using Cell 2 are about four times faster than the one obtained by Cell 1 and highlight the important contribution of the bipolar cell. Besides, the energy consumption values show that the treatment of the BH effluent by Cell 1 consumes 865 kWh kg COD⁻¹ against 411 kWh kg COD(-1) by Cell 2. Therefore, the use of Cell 2 decreases the energy cost by 2.1-6.65 times when compared to Cell 1 in the case of the BH and BS effluent treatment, respectively.

  1. Corrosion resistant PEM fuel cell

    DOEpatents

    Li, Y.; Meng, W.J.; Swathirajan, S.; Harris, S.J.; Doll, G.L.

    1997-04-29

    The present invention contemplates a PEM fuel cell having electrical contact elements (including bipolar plates/septums) comprising a titanium nitride coated light weight metal (e.g., Al or Ti) core, having a passivating, protective metal layer intermediate the core and the titanium nitride. The protective layer forms a barrier to further oxidation/corrosion when exposed to the fuel cell`s operating environment. Stainless steels rich in Cr, Ni, and Mo are particularly effective protective interlayers. 6 figs.

  2. The fine structure of the terminal segment of the bovine seminiferous tubule.

    PubMed

    Wrobel, K H; Sinowatz, F; Mademann, R

    1982-01-01

    The intratesticular excurrent duct system of the bull is composed of rete testis, tubuli recti, and the terminal segment of the seminiferous tubules. Each terminal segment is surrounded by a vascular plexus and may be subdivided into a transitional region, middle portion, and terminal plug. The modified supporting cells of the middle portion and the terminal plug no longer display the typical Sertoli-Sertoli junctions seen in the transitional region and the seminiferous tubule proper. In the region of the terminal plug a distinct central lumen is generally not observed: spermatozoa and tubular fluid must pass through an intricate system of communicating clefts between the apices of the closely attached modified supporting cells. Vacuoles in the supranuclear region of the cells in the middle portion indicate strong transepithelial fluid transport. In analogy to the epithelium of rete testis and tubuli recti, the supporting cells of the terminal segment are capable of phagocytosing spermatozoa. The vascular plexus investing the terminal segment serves a dual purpose: it is a regulatory device for fluid and sperm transport, as well as an area of increased diapedesis for white blood cells.

  3. Distinct compartmentalization of dentin matrix protein 1 fragments in mineralized tissues and cells.

    PubMed

    Maciejewska, Izabela; Qin, Disheng; Huang, Bingzhen; Sun, Yao; Mues, Gabrielle; Svoboda, Kathy; Bonewald, Lynda; Butler, William T; Feng, Jerry Q; Qin, Chunlin

    2009-01-01

    Dentin matrix protein 1 (DMP1) has been shown to be critical for the formation of dentin and bone. However, the precise pathway by which DMP1 participates in dentinogenesis and osteogenesis remains to be clarified. DMP1 is present in the extracellular matrix of dentin and bone as processed NH(2)- and COOH-terminal fragments. The NH(2)-terminal fragment occurs as a proteoglycan, whereas the COOH-terminal fragment is highly phosphorylated. The differences in biochemical properties suggest that these fragments may have different tissue and cell distribution in association with distinct functions. In this study, we analyzed the distribution of the NH(2)- and COOH-terminal fragments of DMP1 in tooth, bone, osteocytes as well as MC3T3-E1 and HEK-293 cells. Immunohistochemical analyses were performed using antibodies specific to the NH(2)- or COOH-terminal region of DMP1. Clear differences in the distribution of these fragments were observed. In the teeth and bone, the NH(2)-terminal fragment was primarily located in the nonmineralized predentin and cartilage of the growth plate, while the COOH-terminal fragment accumulated in the mineralized zones. In osteocytes, the NH(2)-terminal fragment appeared more abundant along cell membrane and processes of osteocytes, while the COOH-terminal fragment was often found in the nuclei. This pattern of distribution in cellular compartments was further confirmed by analyses on MC3T3-E1 and HEK-293 cells transfected with a construct containing DMP1 cDNA. In these cell lines, the COOH-terminal fragment accumulated in cell nuclei, while the NH(2)-terminal fragment was in the cytosol. The different distribution of DMP1 fragments indicates that these DMP1 variants must perform distinct functions. Copyright 2008 S. Karger AG, Basel.

  4. Assembly of bipolar microtubule structures by passive cross-linkers and molecular motors

    NASA Astrophysics Data System (ADS)

    Johann, D.; Goswami, D.; Kruse, K.

    2016-06-01

    During cell division, sister chromatids are segregated by the mitotic spindle, a bipolar assembly of interdigitating antiparallel polar filaments called microtubules. The spindle contains the midzone, a stable region of overlapping antiparallel microtubules, that is essential for maintaining bipolarity. Although a lot is known about the molecular players involved, the mechanism underlying midzone formation and maintenance is still poorly understood. We study the interaction of polar filaments that are cross-linked by molecular motors moving directionally and by passive cross-linkers diffusing along microtubules. Using a particle-based stochastic model, we find that the interplay of motors and passive cross-linkers can generate a stable finite overlap between a pair of antiparallel polar filaments. We develop a mean-field theory to study this mechanism in detail and investigate the influence of steric interactions between motors and passive cross-linkers on the overlap dynamics. In the presence of interspecies steric interactions, passive cross-linkers mimic the behavior of molecular motors and stable finite overlaps are generated even for non-cross-linking motors. Finally, we develop a mean-field theory for a bundle of aligned polar filaments and show that they can self-organize into a spindlelike pattern. Our work suggests possible ways as to how cells can generate spindle midzones and control their extensions.

  5. Scale dependence of the mechanics of active gels with increasing motor concentration.

    PubMed

    Sonn-Segev, Adar; Bernheim-Groswasser, Anne; Roichman, Yael

    2017-10-18

    Actin is a protein that plays an essential role in maintaining the mechanical integrity of cells. In response to strong external stresses, it can assemble into large bundles, but it grows into a fine branched network to induce cell motion. In some cases, the self-organization of actin fibers and networks involves the action of bipolar filaments of the molecular motor myosin. Such self-organization processes mediated by large myosin bipolar filaments have been studied extensively in vitro. Here we create active gels, composed of single actin filaments and small myosin bipolar filaments. The active steady state in these gels persists long enough to enable the characterization of their mechanical properties using one and two point microrheology. We study the effect of myosin concentration on the mechanical properties of this model system for active matter, for two different motor assembly sizes. In contrast to previous studies of networks with large motor assemblies, we find that the fluctuations of tracer particles embedded in the network decrease in amplitude as motor concentration increases. Nonetheless, we show that myosin motors stiffen the actin networks, in accordance with bulk rheology measurements of networks containing larger motor assemblies. This implies that such stiffening is of universal nature and may be relevant to a wider range of cytoskeleton-based structures.

  6. Ultrastructural Alterations of Von Economo Neurons in the Anterior Cingulate Cortex in Schizophrenia.

    PubMed

    Krause, Martin; Theiss, Carsten; Brüne, Martin

    2017-11-01

    Von Economo neurons (VENs) are large bipolar projection neurons mainly located in layer Vb of anterior cingulate cortex (ACC) and anterior insula. Both regions are involved in cognitive and emotional procedures and are functionally and anatomically altered in schizophrenia. Although the detailed function of VEN remains unclear, it has been suggested that these neurons are involved in the pathomechanism of schizophrenia. Here, we were interested in the question whether or not the VEN of schizophrenia patients would show abnormalities at the ultrastructural level. Accordingly, we examined the amount of lysosomal aggregations of the VEN in post-mortem tissue of patients with schizophrenia, bipolar disorder and psychologically unaffected individuals, and compared the findings with aggregations in adjacent pyramidal cells in layer Vb of the ACC. VEN of patients with schizophrenia, and to a lesser degree individuals with bipolar disorder contained significantly more lysosomal aggregations compared with tissue from unaffected controls. Specifically, the larger amount of lysosomal aggregations in schizophrenia seemed to be selective for VEN, with no differences occurring in pyramidal cells. These findings may indicate that the VEN of schizophrenia patients are selectively vulnerable to neuronal damage. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:2017-2024, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  7. Influence of Sintering Temperature on Mechanical and Physical properties of Mill Scale based Bipolar Plates for PEMFC

    NASA Astrophysics Data System (ADS)

    Khaerudini, Deni S.; Berliana, Rina; Prakoso, Gatra B.; Insiyanda, Dita R.; Alva, Sagir

    2018-03-01

    This work concerns the utilization of mill scale, a by-product of iron and steel formed during the hot rolling of steel, as a potential material for use as bipolar plates in proton exchange membrane fuel cells (PEMFCs). On the other hand, mill scale is considered a very rich in iron source having characteristic required such as for current collector in bipolar plate and would significantly contribute to lower the overall cost of PEMFC based fuel cell systems. In this study, the iron reach source of mill scale powder, after sieving of 150 mesh, was mechanically alloyed with the aluminium source containing 30 wt.% using a shaker mill for 3 h. The mixed powders were then pressed at 300 MPa and sintered at various temperatures of 400, 450 and 500 °C for 1 h under inert gas atmosphere. The structural changes of powder particles during mechanical alloying and after sintering were studied by x-ray diffractometry, scanning electron microscopy (SEM) with energy dispersive X-ray spectroscopy (EDX), microhardness measurement, and density - porosity analysis. The details of the performance variation of three different sintering conditions can be preliminary explained by the metallographic and crystallographic structure and phase analysis as well as sufficient mechanical strength of the sintered materials was presented in this report.

  8. Sequential activities of Dynein, Mud and Asp in centrosome-spindle coupling maintain centrosome number upon mitosis.

    PubMed

    Bosveld, Floris; Ainslie, Anna; Bellaïche, Yohanns

    2017-10-15

    Centrosomes nucleate microtubules and are tightly coupled to the bipolar spindle to ensure genome integrity, cell division orientation and centrosome segregation. While the mechanisms of centrosome-dependent microtubule nucleation and bipolar spindle assembly have been the focus of numerous works, less is known about the mechanisms ensuring the centrosome-spindle coupling. The conserved NuMA protein (Mud in Drosophila ) is best known for its role in spindle orientation. Here, we analyzed the role of Mud and two of its interactors, Asp and Dynein, in the regulation of centrosome numbers in Drosophila epithelial cells. We found that Dynein and Mud mainly initiate centrosome-spindle coupling prior to nuclear envelope breakdown (NEB) by promoting correct centrosome positioning or separation, while Asp acts largely independently of Dynein and Mud to maintain centrosome-spindle coupling. Failure in the centrosome-spindle coupling leads to mis-segregation of the two centrosomes into one daughter cell, resulting in cells with supernumerary centrosomes during subsequent divisions. Altogether, we propose that Dynein, Mud and Asp operate sequentially during the cell cycle to ensure efficient centrosome-spindle coupling in mitosis, thereby preventing centrosome mis-segregation to maintain centrosome number. © 2017. Published by The Company of Biologists Ltd.

  9. Metal hydrides as negative electrode materials for Ni- MH batteries

    NASA Astrophysics Data System (ADS)

    Yartys, V.; Noreus, D.; Latroche, M.

    2016-01-01

    Structural, thermodynamical and electrochemical properties of metallic hydrides belonging to the pseudo-binary family A-Mg-Ni ( A: rare earths) are reviewed and compared. Technology aspects of bipolar cells are also discussed.

  10. Complex inhibitory microcircuitry regulates retinal signaling near visual threshold

    PubMed Central

    Grimes, William N.; Zhang, Jun; Tian, Hua; Graydon, Cole W.; Hoon, Mrinalini; Rieke, Fred

    2015-01-01

    Neuronal microcircuits, small, localized signaling motifs involving two or more neurons, underlie signal processing and computation in the brain. Compartmentalized signaling within a neuron may enable it to participate in multiple, independent microcircuits. Each A17 amacrine cell in the mammalian retina contains within its dendrites hundreds of synaptic feedback microcircuits that operate independently to modulate feedforward signaling in the inner retina. Each of these microcircuits comprises a small (<1 μm) synaptic varicosity that typically receives one excitatory synapse from a presynaptic rod bipolar cell (RBC) and returns two reciprocal inhibitory synapses back onto the same RBC terminal. Feedback inhibition from the A17 sculpts the feedforward signal from the RBC to the AII, a critical component of the circuitry mediating night vision. Here, we show that the two inhibitory synapses from the A17 to the RBC express kinetically distinct populations of GABA receptors: rapidly activating GABAARs are enriched at one synapse while more slowly activating GABACRs are enriched at the other. Anatomical and electrophysiological data suggest that macromolecular complexes of voltage-gated (Cav) channels and Ca2+-activated K+ channels help to regulate GABA release from A17 varicosities and limit GABACR activation under certain conditions. Finally, we find that selective elimination of A17-mediated feedback inhibition reduces the signal to noise ratio of responses to dim flashes recorded in the feedforward pathway (i.e., the AII amacrine cell). We conclude that A17-mediated feedback inhibition improves the signal to noise ratio of RBC-AII transmission near visual threshold, thereby improving visual sensitivity at night. PMID:25972578

  11. X-linked juvenile retinoschisis: Clinical diagnosis, genetic analysis, and molecular mechanisms

    PubMed Central

    Molday, Robert S.; Kellner, Ulrich; Weber, Bernhard H.F.

    2012-01-01

    X-linked juvenile retinoschisis (XLRS, MIM 312700) is a common early onset macular degeneration in males characterized by mild to severe loss in visual acuity, splitting of retinal layers, and a reduction in the b-wave of the electroretinogram (ERG). The RS1 gene (MIM 300839) associated with the disease encodes retinoschisin, a 224 amino acid protein containing a discoidin domain as the major structural unit, an N-terminal cleavable signal sequence, and regions responsible for subunit oligomerization. Retinoschisin is secreted from retinal cells as a disulphide-linked homo-octameric complex which binds to the surface of photoreceptors and bipolar cells to help maintain the integrity of the retina. Over 190 disease-causing mutations in the RS1 gene are known with most mutations occurring as non-synonymous changes in the discoidin domain. Cell expression studies have shown that disease-associated missense mutations in the discoidin domain cause severe protein misfolding and retention in the endoplasmic reticulum, mutations in the signal sequence result in aberrant protein synthesis, and mutations in regions flanking the discoidin domain cause defective disulphide-linked subunit assembly, all of which produce a non-functional protein. Knockout mice deficient in retinoschisin have been generated and shown to display most of the characteristic features found in XLRS patients. Recombinant adeno-associated virus (rAAV) mediated delivery of the normal RS1 gene to the retina of young knockout mice result in long term retinoschisin expression and rescue of retinal structure and function providing a ‘proof of concept’ that gene therapy may be an effective treatment for XLRS. PMID:22245536

  12. X-linked juvenile retinoschisis: clinical diagnosis, genetic analysis, and molecular mechanisms.

    PubMed

    Molday, Robert S; Kellner, Ulrich; Weber, Bernhard H F

    2012-05-01

    X-linked juvenile retinoschisis (XLRS, MIM 312700) is a common early onset macular degeneration in males characterized by mild to severe loss in visual acuity, splitting of retinal layers, and a reduction in the b-wave of the electroretinogram (ERG). The RS1 gene (MIM 300839) associated with the disease encodes retinoschisin, a 224 amino acid protein containing a discoidin domain as the major structural unit, an N-terminal cleavable signal sequence, and regions responsible for subunit oligomerization. Retinoschisin is secreted from retinal cells as a disulphide-linked homo-octameric complex which binds to the surface of photoreceptors and bipolar cells to help maintain the integrity of the retina. Over 190 disease-causing mutations in the RS1 gene are known with most mutations occurring as non-synonymous changes in the discoidin domain. Cell expression studies have shown that disease-associated missense mutations in the discoidin domain cause severe protein misfolding and retention in the endoplasmic reticulum, mutations in the signal sequence result in aberrant protein synthesis, and mutations in regions flanking the discoidin domain cause defective disulphide-linked subunit assembly, all of which produce a non-functional protein. Knockout mice deficient in retinoschisin have been generated and shown to display most of the characteristic features found in XLRS patients. Recombinant adeno-associated virus (rAAV) mediated delivery of the normal RS1 gene to the retina of young knockout mice result in long-term retinoschisin expression and rescue of retinal structure and function providing a 'proof of concept' that gene therapy may be an effective treatment for XLRS. Copyright © 2012 Elsevier Ltd. All rights reserved.

  13. Alterations in BDNF (brain derived neurotrophic factor) and GDNF (glial cell line-derived neurotrophic factor) serum levels in bipolar disorder: The role of lithium.

    PubMed

    Tunca, Zeliha; Ozerdem, Aysegul; Ceylan, Deniz; Yalçın, Yaprak; Can, Güneş; Resmi, Halil; Akan, Pınar; Ergör, Gül; Aydemir, Omer; Cengisiz, Cengiz; Kerim, Doyuran

    2014-09-01

    Brain-derived neurotrophic factor (BDNF) has been consistently reported to be decreased in mania or depression in bipolar disorders. Evidence suggests that Glial cell line-derived neurotrophic factor (GDNF) has a role in the pathogenesis of mood disorders. Whether GDNF and BDNF act in the same way across different episodes in bipolar disorders is unclear. BDNF and GDNF serum levels were measured simultaneously by enzyme-linked immunosorbent assay (ELISA) method in 96 patients diagnosed with bipolar disorder according to DSM-IV (37 euthymic, 33 manic, 26 depressed) in comparison to 61 healthy volunteers. SCID- I and SCID-non patient version were used for clinical evaluation of the patients and healthy volunteers respectively. Correlations between the two trophic factor levels, and medication dose, duration and serum levels of lithium or valproate were studied across different episodes of illness. Patients had significantly lower BDNF levels during mania and depression compared to euthymic patients and healthy controls. GDNF levels were not distinctive. However GDNF/BDNF ratio was higher in manic state compared to euthymia and healthy controls. Significant negative correlation was observed between BDNF and GDNF levels in euthymic patients. While BDNF levels correlated positively, GDNF levels correlated negatively with lithium levels. Regression analysis confirmed that lithium levels predicted only GDNF levels positively in mania, and negatively in euthymia. Small sample size in different episodes and drug-free patients was the limitation of thestudy. Current data suggests that lithium exerts its therapeutic action by an inverse effect on BDNF and GDNF levels, possibly by up-regulating BDNF and down-regulating GDNF to achieve euthymia. Copyright © 2014 Elsevier B.V. All rights reserved.

  14. Mcl1 regulates the terminal mitosis of neural precursor cells in the mammalian brain through p27Kip1.

    PubMed

    Hasan, S M Mahmudul; Sheen, Ashley D; Power, Angela M; Langevin, Lisa Marie; Xiong, Jieying; Furlong, Michael; Day, Kristine; Schuurmans, Carol; Opferman, Joseph T; Vanderluit, Jacqueline L

    2013-08-01

    Cortical development requires the precise timing of neural precursor cell (NPC) terminal mitosis. Although cell cycle proteins regulate terminal mitosis, the factors that influence the cell cycle machinery are incompletely understood. Here we show in mice that myeloid cell leukemia 1 (Mcl1), an anti-apoptotic Bcl-2 protein required for the survival of NPCs, also regulates their terminal differentiation through the cell cycle regulator p27(Kip1). A BrdU-Ki67 cell profiling assay revealed that in utero electroporation of Mcl1 into NPCs in the embryonic neocortex increased NPC cell cycle exit (the leaving fraction). This was further supported by a decrease in proliferating NPCs (Pax6(+) radial glial cells and Tbr2(+) neural progenitors) and an increase in differentiating cells (Dcx(+) neuroblasts and Tbr1(+) neurons). Similarly, BrdU birth dating demonstrated that Mcl1 promotes premature NPC terminal mitosis giving rise to neurons of the deeper cortical layers, confirming their earlier birthdate. Changes in Mcl1 expression within NPCs caused concomitant changes in the levels of p27(Kip1) protein, a key regulator of NPC differentiation. Furthermore, in the absence of p27(Kip1), Mcl1 failed to induce NPC cell cycle exit, demonstrating that p27(Kip1) is required for Mcl1-mediated NPC terminal mitosis. In summary, we have identified a novel physiological role for anti-apoptotic Mcl1 in regulating NPC terminal differentiation.

  15. DNA replication fading as proliferating cells advance in their commitment to terminal differentiation.

    PubMed

    Estefanía, Monturus Ma; Ganier, Olivier; Hernández, Pablo; Schvartzman, Jorge B; Mechali, Marcel; Krimer, Dora B

    2012-01-01

    Terminal differentiation is the process by which cycling cells stop proliferating to start new specific functions. It involves dramatic changes in chromatin organization as well as gene expression. In the present report we used cell flow cytometry and genome wide DNA combing to investigate DNA replication during murine erythroleukemia-induced terminal cell differentiation. The results obtained indicated that the rate of replication fork movement slows down and the inter-origin distance becomes shorter during the precommitment and commitment periods before cells stop proliferating and accumulate in G1. We propose this is a general feature caused by the progressive heterochromatinization that characterizes terminal cell differentiation.

  16. Progression along the Bipolar Spectrum: A Longitudinal Study of Predictors of Conversion from Bipolar Spectrum Conditions to Bipolar I and II Disorders

    PubMed Central

    Alloy, Lauren B.; Urošević, Snežana; Abramson, Lyn Y.; Jager-Hyman, Shari; Nusslock, Robin; Whitehouse, Wayne G.; Hogan, Michael

    2011-01-01

    Little longitudinal research has examined progression to more severe bipolar disorders in individuals with “soft” bipolar spectrum conditions. We examine rates and predictors of progression to bipolar I and II diagnoses in a non-patient sample of college-age participants (n = 201) with high General Behavior Inventory scores and childhood or adolescent onset of “soft” bipolar spectrum disorders followed longitudinally for 4.5 years from the Longitudinal Investigation of Bipolar Spectrum (LIBS) project. Of 57 individuals with initial cyclothymia or bipolar disorder not otherwise specified (BiNOS) diagnoses, 42.1% progressed to a bipolar II diagnosis and 10.5% progressed to a bipolar I diagnosis. Of 144 individuals with initial bipolar II diagnoses, 17.4% progressed to a bipolar I diagnosis. Consistent with hypotheses derived from the clinical literature and the Behavioral Approach System (BAS) model of bipolar disorder, and controlling for relevant variables (length of follow-up, initial depressive and hypomanic symptoms, treatment-seeking, and family history), high BAS sensitivity (especially BAS Fun Seeking) predicted a greater likelihood of progression to bipolar II disorder, whereas early age of onset and high impulsivity predicted a greater likelihood of progression to bipolar I (high BAS sensitivity and Fun-Seeking also predicted progression to bipolar I when family history was not controlled). The interaction of high BAS and high Behavioral Inhibition System (BIS) sensitivities also predicted greater likelihood of progression to bipolar I. We discuss implications of the findings for the bipolar spectrum concept, the BAS model of bipolar disorder, and early intervention efforts. PMID:21668080

  17. Comparative familial aggregation of bipolar disorder in patients with bipolar I and bipolar II disorders.

    PubMed

    Parker, Gordon B; Romano, Mia; Graham, Rebecca K; Ricciardi, Tahlia

    2018-05-01

    We sought to quantify the prevalence and differential prevalence of a bipolar disorder among family members of patients with a bipolar I or II disorder. The sample comprised 1165 bipolar and 1041 unipolar patients, with the former then sub-typed as having either a bipolar I or II condition. Family history data was obtained via an online self-report tool. Prevalence of a family member having a bipolar disorder (of either sub-type) was distinctive (36.8%). Patients with a bipolar I disorder reported a slightly higher family history (41.2%) compared to patients with a bipolar II disorder (36.3%), and with both significantly higher than the rate of bipolar disorder in family members of unipolar depressed patients (18.5%). Findings support the view that bipolar disorder is heritable. The comparable rates in the two bipolar sub-types support the positioning of bipolar II disorder as a valid condition with strong genetic underpinnings.

  18. Timing of insolation forcing, CO2 and sea level changes around the current and last four interglacial periods

    NASA Astrophysics Data System (ADS)

    Kawamura, K.; Aoki, S.; Nakazawa, T.; Abe-Ouchi, A.; Saito, F.

    2013-12-01

    Investigation of the roles of different forcings (e.g. orbital variations and greenhouse gases) on climate and sea level requires a paleoclimate chronology with high accuracy. Such a chronology for the past 360 ky was constructed through orbital tuning of O2/N2 ratio of trapped air in the Dome Fuji and Vostok ice cores with local summer insolation (Kawamura et al., 2007). We extend the O2/N2 chronology back to ~500 kyr by analyzing the second Dome Fuji ice core, and find the duration of 11 ka, 5 ka, 9 ka, and 20 ka for MIS 5e, 7e, 9e and 11c interglacial periods in Antarctica, with similar variations in atmospheric CO2. The termination timings are consistent with the rising phase of Northern Hemisphere summer insolation. Marine sediment cores from northern North Atlantic contain millennial-scale signatures in various proxy records (e.g. SST, IRD), including abrupt climatic shifts and bipolar seesaw. Based on the bipolar correlation of millennial-scale events, it is possible to transfer our accurate chronology to marine cores from the North Atlantic. As a first attempt, we correlate the planktonic δ18O and IRD records from the marine core ODP 980 with the ice-core δ18O and CH4 around MIS 11. We find that the durations of interglacial plateaus of planktonic δ18O (proxy for sea surface environments) and benthic δ18O (proxy for ice volume and deep-sea temperature) for MIS 11c are 20 and 15 ka, respectively, which are significantly shorter than originally suggested. These durations are similar to that of Antarctic climate and atmospheric CO2. However, the onsets of interglacial levels in ODP980 for MIS 11 are significantly later than those in Antarctic δ18O and atmospheric CO2 (by as much as ~10 ka), suggesting very long duration (more than one precession cycle) for the complete deglaciation and northern high-latitude warming for Termination V. Atmospheric CO2 may have been the critical forcing for this termination. The long duration of Termination V is consistent with our new ice sheet simulations (extended from the work of Abe-Ouchi et al., 2013) in which an ice-sheet/climate model is forced by insolation and CO2 variations. In the presentation, comparisons for other interglacial periods will also be reported.

  19. Lewis Research Center battery overview

    NASA Technical Reports Server (NTRS)

    Odonnell, Patricia

    1993-01-01

    The topics covered are presented in viewgraph form and include the following: the Advanced Communications Technology Satellite; the Space Station Freedom (SSF) photovoltaic power module division; Ni/H2 battery and cell design; individual pressure vessel (IPV) nickel-hydrogen cell testing SSF support; the LeRC Electrochemical Technology Branch; improved design IPV nickel-hydrogen cells; advanced technology for IPV nickel-hydrogen flight cells; a lightweight nickel-hydrogen cell; bipolar nickel-hydrogen battery development and technology; aerospace nickel-metal hydride cells; the NASA Sodium-Sulfur Cell Technology Flight Experiment; and the lithium-carbon dioxide battery thermodynamic model.

  20. Corrosion resistant PEM fuel cell

    DOEpatents

    Li, Yang; Meng, Wen-Jin; Swathirajan, Swathy; Harris, Stephen Joel; Doll, Gary Lynn

    2001-07-17

    The present invention contemplates a PEM fuel cell having electrical contact elements (including bipolar plates/septums) comprising a titanium nitride coated light weight metal (e.g., Al or Ti) core, having a passivating, protective metal layer intermediate the core and the titanium nitride. The protective layer forms a barrier to further oxidation/corrosion when exposed to the fuel cell's operating environment. Stainless steels rich in CR, Ni, and Mo are particularly effective protective interlayers.

  1. Corrosion resistant PEM fuel cell

    DOEpatents

    Li, Yang; Meng, Wen-Jin; Swathirajan, Swathy; Harris, Stephen Joel; Doll, Gary Lynn

    2002-01-01

    The present invention contemplates a PEM fuel cell having electrical contact elements (including bipolar plates/septums) comprising a titanium nitride coated light weight metal (e.g., Al or Ti) core, having a passivating, protective metal layer intermediate the core and the titanium nitride. The protective layer forms a barrier to further oxidation/corrosion when exposed to the fuel cell's operating environment. Stainless steels rich in CR, Ni, and Mo are particularly effective protective interlayers.

  2. Corrosion resistant PEM fuel cell

    DOEpatents

    Li, Yang; Meng, Wen-Jin; Swathirajan, Swathy; Harris, Stephen J.; Doll, Gary L.

    1997-01-01

    The present invention contemplates a PEM fuel cell having electrical contact elements (including bipolar plates/septums) comprising a titanium nitride coated light weight metal (e.g., Al or Ti) core, having a passivating, protective metal layer intermediate the core and the titanium nitride. The protective layer forms a barrier to further oxidation/corrosion when exposed to the fuel cell's operating environment. Stainless steels rich in CR, Ni, and Mo are particularly effective protective interlayers.

  3. Fuel cell with metal screen flow-field

    DOEpatents

    Wilson, M.S.; Zawodzinski, C.

    1998-08-25

    A polymer electrolyte membrane (PEM) fuel cell is provided with electrodes supplied with a reactant on each side of a catalyzed membrane assembly (CMA). The fuel cell includes a metal mesh defining a rectangular flow-field pattern having an inlet at a first corner and an outlet at a second corner located on a diagonal from the first corner, wherein all flow paths from the inlet to the outlet through the square flow field pattern are equivalent to uniformly distribute the reactant over the CMA. In a preferred form of metal mesh, a square weave screen forms the flow-field pattern. In a particular characterization of the present invention, a bipolar plate electrically connects adjacent fuel cells, where the bipolar plate includes a thin metal foil having an anode side and a cathode side; a first metal mesh on the anode side of the thin metal foil; and a second metal mesh on the cathode side of the thin metal foil. In another characterization of the present invention, a cooling plate assembly cools adjacent fuel cells, where the cooling plate assembly includes an anode electrode and a cathode electrode formed of thin conducting foils; and a metal mesh flow field there between for distributing cooling water flow over the electrodes to remove heat generated by the fuel cells. 11 figs.

  4. Fuel cell with metal screen flow-field

    DOEpatents

    Wilson, Mahlon S.; Zawodzinski, Christine

    2001-01-01

    A polymer electrolyte membrane (PEM) fuel cell is provided with electrodes supplied with a reactant on each side of a catalyzed membrane assembly (CMA). The fuel cell includes a metal mesh defining a rectangular flow-field pattern having an inlet at a first corner and an outlet at a second corner located on a diagonal from the first corner, wherein all flow paths from the inlet to the outlet through the square flow field pattern are equivalent to uniformly distribute the reactant over the CMA. In a preferred form of metal mesh, a square weave screen forms the flow-field pattern. In a particular characterization of the present invention, a bipolar plate electrically connects adjacent fuel cells, where the bipolar plate includes a thin metal foil having an anode side and a cathode side; a first metal mesh on the anode side of the thin metal foil; and a second metal mesh on the cathode side of the thin metal foil. In another characterization of the present invention, a cooling plate assembly cools adjacent fuel cells, where the cooling plate assembly includes an anode electrode and a cathode electrode formed of thin conducting foils; and a metal mesh flow field therebetween for distributing cooling water flow over the electrodes to remove heat generated by the fuel cells.

  5. Fuel cell with metal screen flow-field

    DOEpatents

    Wilson, Mahlon S.; Zawodzinski, Christine

    1998-01-01

    A polymer electrolyte membrane (PEM) fuel cell is provided with electrodes supplied with a reactant on each side of a catalyzed membrane assembly (CMA). The fuel cell includes a metal mesh defining a rectangular flow-field pattern having an inlet at a first corner and an outlet at a second corner located on a diagonal from the first corner, wherein all flow paths from the inlet to the outlet through the square flow field pattern are equivalent to uniformly distribute the reactant over the CMA. In a preferred form of metal mesh, a square weave screen forms the flow-field pattern. In a particular characterization of the present invention, a bipolar plate electrically connects adjacent fuel cells, where the bipolar plate includes a thin metal foil having an anode side and a cathode side; a first metal mesh on the anode side of the thin metal foil; and a second metal mesh on the cathode side of the thin metal foil. In another characterization of the present invention, a cooling plate assembly cools adjacent fuel cells, where the cooling plate assembly includes an anode electrode and a cathode electrode formed of thin conducting foils; and a metal mesh flow field therebetween for distributing cooling water flow over the electrodes to remove heat generated by the fuel cells.

  6. The Escherichia coli Subtilase Cytotoxin A Subunit Specifically Cleaves Cell-surface GRP78 Protein and Abolishes COOH-terminal-dependent Signaling

    PubMed Central

    Ray, Rupa; de Ridder, Gustaaf G.; Eu, Jerry P.; Paton, Adrienne W.; Paton, James C.; Pizzo, Salvatore V.

    2012-01-01

    GRP78, a molecular chaperone with critical endoplasmic reticulum functions, is aberrantly expressed on the surface of cancer cells, including prostate and melanoma. Here it functions as a pro-proliferative and anti-apoptotic signaling receptor via NH2-terminal domain ligation. Auto-antibodies to this domain may appear in cancer patient serum where they are a poor prognostic indicator. Conversely, GRP78 COOH-terminal domain ligation is pro-apoptotic and anti-proliferative. There is no method to disrupt cell-surface GRP78 without compromising the total GRP78 pool, making it difficult to study cell-surface GRP78 function. We studied six cell lines representing three cancer types. One cell line per group expresses high levels of cell-surface GRP78, and the other expresses low levels (human hepatoma: Hep3B and HepG2; human prostate cancer: PC3 and 1-LN; murine melanoma: B16F0 and B16F1). We investigated the effect of Escherichia coli subtilase cytoxin catalytic subunit (SubA) on GRP78. We report that SubA specifically cleaves cell-surface GRP78 on HepG2, 1-LN, and B16F1 cells without affecting intracellular GRP78. B16F0 cells (GRP78low) have lower amounts of cleaved cell-surface GRP78. SubA has no effect on Hep3B and PC3 cells. The predicted 28-kDa GRP78 COOH-terminal fragment is released into the culture medium by SubA treatment, and COOH-terminal domain signal transduction is abrogated, whereas pro-proliferative signaling mediated through NH2-terminal domain ligation is unaffected. These experiments clarify cell-surface GRP78 topology and demonstrate that the COOH-terminal domain is necessary for pro-apoptotic signal transduction occurring upon COOH-terminal antibody ligation. SubA is a powerful tool to specifically probe the functions of cell-surface GRP78. PMID:22851173

  7. The Escherichia coli subtilase cytotoxin A subunit specifically cleaves cell-surface GRP78 protein and abolishes COOH-terminal-dependent signaling.

    PubMed

    Ray, Rupa; de Ridder, Gustaaf G; Eu, Jerry P; Paton, Adrienne W; Paton, James C; Pizzo, Salvatore V

    2012-09-21

    GRP78, a molecular chaperone with critical endoplasmic reticulum functions, is aberrantly expressed on the surface of cancer cells, including prostate and melanoma. Here it functions as a pro-proliferative and anti-apoptotic signaling receptor via NH(2)-terminal domain ligation. Auto-antibodies to this domain may appear in cancer patient serum where they are a poor prognostic indicator. Conversely, GRP78 COOH-terminal domain ligation is pro-apoptotic and anti-proliferative. There is no method to disrupt cell-surface GRP78 without compromising the total GRP78 pool, making it difficult to study cell-surface GRP78 function. We studied six cell lines representing three cancer types. One cell line per group expresses high levels of cell-surface GRP78, and the other expresses low levels (human hepatoma: Hep3B and HepG2; human prostate cancer: PC3 and 1-LN; murine melanoma: B16F0 and B16F1). We investigated the effect of Escherichia coli subtilase cytoxin catalytic subunit (SubA) on GRP78. We report that SubA specifically cleaves cell-surface GRP78 on HepG2, 1-LN, and B16F1 cells without affecting intracellular GRP78. B16F0 cells (GRP78(low)) have lower amounts of cleaved cell-surface GRP78. SubA has no effect on Hep3B and PC3 cells. The predicted 28-kDa GRP78 COOH-terminal fragment is released into the culture medium by SubA treatment, and COOH-terminal domain signal transduction is abrogated, whereas pro-proliferative signaling mediated through NH(2)-terminal domain ligation is unaffected. These experiments clarify cell-surface GRP78 topology and demonstrate that the COOH-terminal domain is necessary for pro-apoptotic signal transduction occurring upon COOH-terminal antibody ligation. SubA is a powerful tool to specifically probe the functions of cell-surface GRP78.

  8. Centromere replication timing determines different forms of genomic instability in Saccharomyces cerevisiae checkpoint mutants during replication stress.

    PubMed

    Feng, Wenyi; Bachant, Jeff; Collingwood, David; Raghuraman, M K; Brewer, Bonita J

    2009-12-01

    Yeast replication checkpoint mutants lose viability following transient exposure to hydroxyurea, a replication-impeding drug. In an effort to understand the basis for this lethality, we discovered that different events are responsible for inviability in checkpoint-deficient cells harboring mutations in the mec1 and rad53 genes. By monitoring genomewide replication dynamics of cells exposed to hydroxyurea, we show that cells with a checkpoint deficient allele of RAD53, rad53K227A, fail to duplicate centromeres. Following removal of the drug, however, rad53K227A cells recover substantial DNA replication, including replication through centromeres. Despite this recovery, the rad53K227A mutant fails to achieve biorientation of sister centromeres during recovery from hydroxyurea, leading to secondary activation of the spindle assembly checkpoint (SAC), aneuploidy, and lethal chromosome segregation errors. We demonstrate that cell lethality from this segregation defect could be partially remedied by reinforcing bipolar attachment. In contrast, cells with the mec1-1 sml1-1 mutations suffer from severely impaired replication resumption upon removal of hydroxyurea. mec1-1 sml1-1 cells can, however, duplicate at least some of their centromeres and achieve bipolar attachment, leading to abortive segregation and fragmentation of incompletely replicated chromosomes. Our results highlight the importance of replicating yeast centromeres early and reveal different mechanisms of cell death due to differences in replication fork progression.

  9. Acetylation within the N- and C-Terminal Domains of Src Regulates Distinct Roles of STAT3-Mediated Tumorigenesis.

    PubMed

    Huang, Chao; Zhang, Zhe; Chen, Lihan; Lee, Hank W; Ayrapetov, Marina K; Zhao, Ting C; Hao, Yimei; Gao, Jinsong; Yang, Chunzhang; Mehta, Gautam U; Zhuang, Zhengping; Zhang, Xiaoren; Hu, Guohong; Chin, Y Eugene

    2018-06-01

    Posttranslational modifications of mammalian c-Src N-terminal and C-terminal domains regulate distinct functions. Myristoylation of G 2 controls its cell membrane association and phosphorylation of Y419/Y527 controls its activation or inactivation, respectively. We provide evidence that Src-cell membrane association-dissociation and catalytic activation-inactivation are both regulated by acetylation. In EGF-treated cells, CREB binding protein (CBP) acetylates an N-terminal lysine cluster (K5, K7, and K9) of c-Src to promote dissociation from the cell membrane. CBP also acetylates the C-terminal K401, K423, and K427 of c-Src to activate intrinsic kinase activity for STAT3 recruitment and activation. N-terminal domain phosphorylation (Y14, Y45, and Y68) of STAT3 by c-Src activates transcriptionally active dimers of STAT3. Moreover, acetyl-Src translocates into nuclei, where it forms the Src-STAT3 enhanceosome for gene regulation and cancer cell proliferation. Thus, c-Src acetylation in the N-terminal and C-terminal domains play distinct roles in Src activity and regulation. Significance: CBP-mediated acetylation of lysine clusters in both the N-terminal and C-terminal regions of c-Src provides additional levels of control over STAT3 transcriptional activity. Cancer Res; 78(11); 2825-38. ©2018 AACR . ©2018 American Association for Cancer Research.

  10. Anodic Behaviour of High Nitrogen-Bearing Steel in PEMFC Environments

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Wang, H.; Turner, J. A.

    2008-02-01

    High nitrogen-bearing stainless steels, AISI Type 201 and AL219, were investigated in simulated polymer electrolyte membrane fuel cell (PEMFC) environments to assess the use of these materials in fuel cell bipolar plate applications. Both steels exhibit better corrosion behavior than 316L steel in the same environments. Type 201 steel shows similar but lower interfacial contact resistance (ICR) than 316L, while AL219 steel shows higher ICR than 316L. X-ray photoelectron spectroscopy (XPS) analysis shows that the air-formed films on Type 201 and AL219 are composed of iron oxides, chromium oxide, and manganese oxide. Iron oxides dominate the composition of the air-formedmore » film, specially the outer layer. Chromium oxide dominates passive films. Surface film thicknesses were estimated. The results suggest that high nitrogen-bearing stainless steels are promising materials for PEMFC bipolar plates.« less

  11. Ribbon synapses compute temporal contrast and encode luminance in retinal rod bipolar cells

    PubMed Central

    Oesch, Nicholas W.; Diamond, Jeffrey S.

    2011-01-01

    Contrast is computed throughout the nervous system to encode changing inputs efficiently. The retina encodes luminance and contrast over a wide range of visual conditions and so must adapt its responses to maintain sensitivity and avoid saturation. Here we show how one type of adaptation allows individual synapses to compute contrast and encode luminance in biphasic responses to step changes in light levels. Light-evoked depletion of the readily releasable vesicle pool (RRP) at rod bipolar cell (RBC) ribbon synapses in rat retina limits the dynamic range available to encode transient but not sustained responses, thereby allowing the transient and sustained components of release to compute temporal contrast and encode mean light levels, respectively. A release/replenishment model shows that a single, homogeneous pool of synaptic vesicles is sufficient to generate this behavior and reveals that the dominant mechanism shaping the biphasic contrast/luminance response is the partial depletion of the RRP. PMID:22019730

  12. Renal cell carcinoma metastasis involving vertebral hemangioma: dual percutaneous treatment by navigational bipolar radiofrequency ablation and high viscosity cement vertebroplasty.

    PubMed

    Zerlauth, Jean-Baptiste; Meuli, Reto; Dunet, Vincent

    2017-02-02

    The case of a 70-year-old woman with progressive renal cell carcinoma (RCC) metastatic invasion of a L3 vertebral hemangioma treated by dual percutaneous radiofrequency ablation (RFA) and vertebroplasty is reported. The patient was surgically treated for RCC in 2001. Chemotherapy and immunotherapy were introduced in 2013 for ovarian, bladder and cerebral metastatic disease. An asymptomatic L3 benign hemangioma was noticed at this time. One-year CT and MRI follow-up studies demonstrated a nodular isolated soft tissue lesion involving the anterior edge of the hemangioma. Percutaneous treatment consisted of a L3 vertebral body unipedicular approach to perform a biopsy, RFA with a navigational bipolar RFA device and vertebroplasty using high viscosity cement. Histopathological examination confirmed metastasis of RCC. The 5-month spinal MRI and CT examinations demonstrated complete disappearance of the tumor. 2017 BMJ Publishing Group Ltd.

  13. Surface modified stainless steels for PEM fuel cell bipolar plates

    DOEpatents

    Brady, Michael P [Oak Ridge, TN; Wang, Heli [Littleton, CO; Turner, John A [Littleton, CO

    2007-07-24

    A nitridation treated stainless steel article (such as a bipolar plate for a proton exchange membrane fuel cell) having lower interfacial contact electrical resistance and better corrosion resistance than an untreated stainless steel article is disclosed. The treated stainless steel article has a surface layer including nitrogen-modified chromium-base oxide and precipitates of chromium nitride formed during nitridation wherein oxygen is present in the surface layer at a greater concentration than nitrogen. The surface layer may further include precipitates of titanium nitride and/or aluminum oxide. The surface layer in the treated article is chemically heterogeneous surface rather than a uniform or semi-uniform surface layer exclusively rich in chromium, titanium or aluminum. The precipitates of titanium nitride and/or aluminum oxide are formed by the nitriding treatment wherein titanium and/or aluminum in the stainless steel are segregated to the surface layer in forms that exhibit a low contact resistance and good corrosion resistance.

  14. Iron-based alloy and nitridation treatment for PEM fuel cell bipolar plates

    DOEpatents

    Brady, Michael P [Oak Ridge, TN; Yang, Bing [Oak Ridge, TN; Maziasz, Philip J [Oak Ridge, TN

    2010-11-09

    A corrosion resistant electrically conductive component that can be used as a bipolar plate in a PEM fuel cell application is composed of an alloy substrate which has 10-30 wt. % Cr, 0.5 to 7 wt. % V, and base metal being Fe, and a continuous surface layer of chromium nitride and vanadium nitride essentially free of base metal. A oxide layer of chromium vanadium oxide can be disposed between the alloy substrate and the continuous surface nitride layer. A method to prepare the corrosion resistant electrically conductive component involves a two-step nitridization sequence by exposing the alloy to a oxygen containing gas at an elevated temperature, and subsequently exposing the alloy to an oxygen free nitrogen containing gas at an elevated temperature to yield a component where a continuous chromium nitride layer free of iron has formed at the surface.

  15. Particle-in-cell simulations of asymmetric guide-field reconnection: quadrupolar structure of Hall magnetic field

    NASA Astrophysics Data System (ADS)

    Schmitz, R. G.; Alves, M. V.; Barbosa, M. V. G.

    2017-12-01

    One of the most important processes that occurs in Earth's magnetosphere is known as magnetic reconnection (MR). This process can be symmetric or asymmetric, depending basically on the plasma density and magnetic field in both sides of the current sheet. A good example of symmetric reconnection in terrestrial magnetosphere occurs in the magnetotail, where these quantities are similar on the north and south lobes. In the dayside magnetopause MR is asymmetric, since the plasma regimes and magnetic fields of magnetosheath and magnetosphere are quite different. Symmetric reconnection has some unique signatures. For example, the formation of a quadrupolar structure of Hall magnetic field and a bipolar Hall electric field that points to the center of the current sheet. The different particle motions in the presence of asymmetries change these signatures, causing the quadrupolar pattern to be distorted and forming a bipolar structure. Also, the bipolar Hall electric field is modified and gives rise to a single peak pointing toward the magnetosheat, considering an example of magnetopause reconnection. The presence of a guide-field can also distort the quadrupolar pattern, by giving a shear angle across the current sheet and altering the symmetric patterns, according to previous simulations and observations. Recently, a quadrupolar structure was observed in an asymmetric guide-field MR event using MMS (Magnetospheric Multiscale) mission data [Peng et al., JGR, 2017]. This event shows clearly that the density asymmetry and the guide-field were not sufficient to form signatures of asymmetric reconnection. Using the particle-in-cell code iPIC3D [Markidis et al, Mathematics and Computers in Simulation, 2010] with the MMS data from this event used to define input parameters, we found a quadrupolar structure of Hall magnetic field and a bipolar pattern of Hall electric field in ion scales, showing that our results are in an excellent agreement with the MMS observations. To our knowledge, this is the first time PIC simulations show this kind of results, since previous simulations have predicted bipolar pattern in the asymmetric guide-field reconnection.

  16. Regional Differences in Stem and Transit Cell Proliferation and Apoptosis in the Terminal Ileum and Colon of Mice After 12 Gy

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Gandara, Ricardo M.C.; Mahida, Yashwant R., E-mail: yash.mahida@nottingham.ac.uk; Potten, Christopher S.

    2012-03-01

    Purpose: The intestinal epithelium has a high rate of cell turnover, which is regulated by stem cells located near the base of crypts. We aimed to investigate stem cell-dependent characteristics of cell proliferation, apoptosis, and crypt size in terminal ileum and different regions of the colon. Methods and Materials: Mice were studied under steady-state conditions and after radiation-induced stem cell apoptosis. Percentage of proliferating or apoptotic cells at a particular cell position (cp) along the crypt axis was expressed as labeling or apoptotic index. Results: Under steady-state conditions: crypt size was smallest in the ascending colon. In contrast to othermore » regions of the colon, the distribution profile of proliferating cells in ascending colon showed some similarity to that in the terminal ileum. Postirradiation: apoptotic cells were prominent at the bottom of the crypt of mid- and descending colon but in the ascending colon, they were seen with similar frequency from cp 1 to 4. During regeneration, a constant proliferative capacity was seen above Paneth cells in the terminal ileum. In the ascending (but not mid- or descending) colon, the profile of proliferating cells over the first 4 days after irradiation showed a similarity to that in the terminal ileum. Conclusions: Profiles of proliferating epithelial cells (under steady-state conditions and postirradiation) and apoptotic cells (postirradiation) suggest similarities in the location of stem cells in the ascending colon and terminal ileum.« less

  17. The nucleus of the optic tract (NOT) and the dorsal terminal nucleus (DTN) of opossums (Didelphis marsupialis aurita).

    PubMed

    Vargas, C D; Volchan, E; Nasi, J P; Bernardes, R F; Rocha-Miranda, C E

    1996-01-01

    Wheat germ agglutinin conjugated to horseradish peroxidase (WGA-HRP) was injected unilaterally into the pretectocollicular region of opossums (Didelphis marsupialis aurita), primarily to investigate the existence of a commissural subcortical pathway but also to reveal afferents and efferents of the nucleus of the optic tract (NOT) and dorsal terminal nucleus (DTN) in this species. Labelled cells and terminals were observed in the contralateral NOT-DTN. Furthermore, HRP was injected bilaterally in the region of the inferior olive (IO) to verify if the distribution of labelled cells in the NOT-DTN overlapped the region of commissural labelled cells. The two subpopulations of retrogradely labelled cells coincided, being distributed within the retinal terminal field attributed to the NOT-DTN, as revealed by contralateral eye injections of HRP. The commissural cells were located slightly more ventral than the olivary cells in the optic tract. The pretectocollicular WGA-HRP injections also labelled cells and terminals bilaterally in the lateral terminal nucleus (LTN), interstitial nucleus of the superior fasciculus, posterior fibers (INSFp), ventral lateral geniculate nucleus (vLGN), and superior colliculus (SC) and ipsilaterally in the medial terminal nucleus (MTN). In addition, further caudally, labelled cells and terminals were observed bilaterally in the nuclei prepositus hypoglossi (PH) and in the medial (MVN) and lateral (LVN) vestibular nuclei. Labelled terminals were found in the ipsilateral nucleus reticularis tegmenti pontis (NRTP) and in the IO with ipsilateral predominance. This study allowed an anatomical delimitation of the NOT-DTN in this opossum species, as defined by the olivary and commissural subpopulations, as well as a hodological evaluation of this region. The existence of some common anatomical aspects with other mammalian species is discussed.

  18. Linkage of mating-type loci distinguishes bipolar from tetrapolar mating in basidiomycetous smut fungi.

    PubMed Central

    Bakkeren, G; Kronstad, J W

    1994-01-01

    Sexual compatibility requires self vs. non-self recognition. Genetically, two compatibility or mating-type systems govern recognition in heterothallic basidiomycete fungi such as the edible and woodrotting mushrooms and the economically important rust and smut phytopathogens. A bipolar system is defined by a single genetic locus (MAT) that can have two or multiple alleles. A tetrapolar system has two loci, each with two or more specificities. We have employed two species from the genus Ustilago (smut fungi) to discover a molecular explanation for the genetic difference in mating systems. Ustilago maydis, a tetrapolar species, has two genetically unlinked loci that encode the distinct mating functions of cell fusion (a locus) and subsequent sexual development and pathogenicity (b locus). We have recently described a b locus in a bipolar species, Ustilago hordei, wherein the existence of an a locus has been suspected, but not demonstrated. We report here the cloning of an allele of the a locus (a1) from U. hordei and the discovery that physical linkage of the a and b loci in this bipolar fungus accounts for the distinct mating system. Linkage establishes a large complex MAT locus in U. hordei; this locus appears to be in a region suppressed for recombination. Images PMID:7913746

  19. WAVE2-Abi2 complex controls growth cone activity and regulates the multipolar-bipolar transition as well as the initiation of glia-guided migration.

    PubMed

    Xie, Min-Jue; Yagi, Hideshi; Kuroda, Kazuki; Wang, Chen-Chi; Komada, Munekazu; Zhao, Hong; Sakakibara, Akira; Miyata, Takaki; Nagata, Koh-Ichi; Oka, Yuichiro; Iguchi, Tokuichi; Sato, Makoto

    2013-06-01

    Glia-guided migration (glia-guided locomotion) during radial migration is a characteristic yet unique mode of migration. In this process, the directionality of migration is predetermined by glial processes and not by growth cones. Prior to the initiation of glia-guided migration, migrating neurons transform from multipolar to bipolar, but the molecular mechanisms underlying this multipolar-bipolar transition and the commencement of glia-guided migration are not fully understood. Here, we demonstrate that the multipolar-bipolar transition is not solely a cell autonomous event; instead, the interaction of growth cones with glial processes plays an essential role. Time-lapse imaging with lattice assays reveals the importance of vigorously active growth cones in searching for appropriate glial scaffolds, completing the transition, and initiating glia-guided migration. These growth cone activities are regulated by Abl kinase and Cdk5 via WAVE2-Abi2 through the phosphorylation of tyrosine 150 and serine 137 of WAVE2. Neurons that do not display such growth cone activities are mispositioned in a more superficial location in the neocortex, suggesting the significance of growth cones for the final location of the neurons. This process occurs in spite of the "inside-out" principle in which later-born neurons are situated more superficially.

  20. Regulation of floral stem cell termination in Arabidopsis

    PubMed Central

    Sun, Bo; Ito, Toshiro

    2015-01-01

    In Arabidopsis, floral stem cells are maintained only at the initial stages of flower development, and they are terminated at a specific time to ensure proper development of the reproductive organs. Floral stem cell termination is a dynamic and multi-step process involving many transcription factors, chromatin remodeling factors and signaling pathways. In this review, we discuss the mechanisms involved in floral stem cell maintenance and termination, highlighting the interplay between transcriptional regulation and epigenetic machinery in the control of specific floral developmental genes. In addition, we discuss additional factors involved in floral stem cell regulation, with the goal of untangling the complexity of the floral stem cell regulatory network. PMID:25699061

  1. Scaling Effect on Unipolar and Bipolar Resistive Switching of Metal Oxides

    PubMed Central

    Yanagida, Takeshi; Nagashima, Kazuki; Oka, Keisuke; Kanai, Masaki; Klamchuen, Annop; Park, Bae Ho; Kawai, Tomoji

    2013-01-01

    Electrically driven resistance change in metal oxides opens up an interdisciplinary research field for next-generation non-volatile memory. Resistive switching exhibits an electrical polarity dependent “bipolar-switching” and a polarity independent “unipolar-switching”, however tailoring the electrical polarity has been a challenging issue. Here we demonstrate a scaling effect on the emergence of the electrical polarity by examining the resistive switching behaviors of Pt/oxide/Pt junctions over 8 orders of magnitudes in the areas. We show that the emergence of two electrical polarities can be categorised as a diagram of an electric field and a cell area. This trend is qualitatively common for various oxides including NiOx, CoOx, and TiO2-x. We reveal the intrinsic difference between unipolar switching and bipolar switching on the area dependence, which causes a diversity of an electrical polarity for various resistive switching devices with different geometries. This will provide a foundation for tailoring resistive switching behaviors of metal oxides. PMID:23584551

  2. Beyond the therapeutic shackles of the monoamines: New mechanisms in bipolar disorder biology.

    PubMed

    Data-Franco, João; Singh, Ajeet; Popovic, Dina; Ashton, Melanie; Berk, Michael; Vieta, Eduard; Figueira, M L; Dean, Olivia M

    2017-01-04

    Multiple novel biological mechanisms putatively involved in the etiology of bipolar disorders are being explored. These include oxidative stress, altered glutamatergic neurotransmission, mitochondrial dysfunction, inflammation, cell signaling, apoptosis and impaired neurogenesis. Important clinical translational potential exists for such mechanisms to help underpin development of novel therapeutics - much needed given limitations of current therapies. These new mechanisms also help improve our understanding of how current therapeutics might exert their effects. Lithium, for example, appears to have antioxidant, immunomodulatory, signaling, anti-apoptotic and neuroprotective properties. Similar properties have been attributed to other mood stabilizers such as valproate, lamotrigine, and quetiapine. Perhaps of greatest translational value has been the recognition of such mechanisms leading to the emergence of novel therapeutics for bipolar disorders. These include the antioxidant N-acetylcysteine, the anti-inflammatory celecoxib, and ketamine - with effects on the glutamatergic system and microglial inhibition. We review these novel mechanisms and emerging therapeutics, and comment on next steps in this space. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Differences in Cell Division Rates Drive the Evolution of Terminal Differentiation in Microbes

    PubMed Central

    Matias Rodrigues, João F.; Rankin, Daniel J.; Rossetti, Valentina; Wagner, Andreas; Bagheri, Homayoun C.

    2012-01-01

    Multicellular differentiated organisms are composed of cells that begin by developing from a single pluripotent germ cell. In many organisms, a proportion of cells differentiate into specialized somatic cells. Whether these cells lose their pluripotency or are able to reverse their differentiated state has important consequences. Reversibly differentiated cells can potentially regenerate parts of an organism and allow reproduction through fragmentation. In many organisms, however, somatic differentiation is terminal, thereby restricting the developmental paths to reproduction. The reason why terminal differentiation is a common developmental strategy remains unexplored. To understand the conditions that affect the evolution of terminal versus reversible differentiation, we developed a computational model inspired by differentiating cyanobacteria. We simulated the evolution of a population of two cell types –nitrogen fixing or photosynthetic– that exchange resources. The traits that control differentiation rates between cell types are allowed to evolve in the model. Although the topology of cell interactions and differentiation costs play a role in the evolution of terminal and reversible differentiation, the most important factor is the difference in division rates between cell types. Faster dividing cells always evolve to become the germ line. Our results explain why most multicellular differentiated cyanobacteria have terminally differentiated cells, while some have reversibly differentiated cells. We further observed that symbioses involving two cooperating lineages can evolve under conditions where aggregate size, connectivity, and differentiation costs are high. This may explain why plants engage in symbiotic interactions with diazotrophic bacteria. PMID:22511858

  4. DOE Office of Scientific and Technical Information (OSTI.GOV)

    Selamat, Mohd Zulkefli, E-mail: azulkeflis@utem.edu.my; Yusuf, Muhammad Yusri Md, E-mail: yusri.cheras@gmail.com; Wer, Tio Kok, E-mail: to91@hotmail.my

    Bipolar plates are key components in Proton Exchange Membrane (PEM) fuel cells. They carry current away from the cell and withstand the clamping force of the stack assembly. Therefore, PEM fuel cell bipolar plates must have high electrical conductivity and adequate mechanical strength, in addition to being light weight and low cost in terms of both applicable materials and production methods. In this research, the raw materials used to fabricate the high performance bipolar plate are Graphite (Gr), Stannum (Sn) and Polypropylene (PP). All materials used was in powder form and Gr and Sn act as fillers and the PPmore » acts as binder. The ratio of fillers (Gr/Sn) and binder (PP) was fixed at 80:20. For the multi-conductive filler, small amount of Sn, which is 10 up to 20wt% (from the total weight of fillers 80%) have been added into Gr/Sn/PP composite. The fillers were mixed by using the ball mill machine. The second stage of mixing process between the mixer of fillers and binder is also carried out by using ball mill machine before the compaction process by the hot press machine. The effect of formation temperatures (160°C-170°C) on the properties of Gr/Sn/PP composite had been studied in detail, especially the electrical conductivity, bulk density, hardness and microstructure analysis of Gr/Sn/PP composite. The result shows that there are significant improvement in the electrical conductivity and bulk density, which are exceeding the US-DoE target with the maximum value of 265.35 S/cm and 1.682g/cm{sup 3} respectively.« less

  5. Technical Assistance to Developers

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Rockward, Tommy; Borup, Rodney L.; Garzon, Fernando H.

    2012-07-17

    This task supports the allowance of technical assistance to fuel-cell component and system developers as directed by the DOE. This task includes testing of novel materials and participation in the further development and validation of single cell test protocols. This task also covers technical assistance to DOE Working Groups, the U.S. Council for Automotive Research (USCAR) and the USCAR/DOE Driving Research and Innovation for Vehicle efficiency and Energy sustainability (U.S. Drive) Fuel Cell Technology Team. Assistance includes technical validation of new fuel cell materials and methods, single cell fuel cell testing to support the development of targets and test protocols,more » and regular advisory participation in other working groups and reviews. This assistance is made available to PEM fuel cell developers by request and DOE Approval. The objectives are to: (1) Support technically, as directed by DOE, fuel cell component and system developers; (2) Assess fuel cell materials and components and give feedback to developers; (3) Assist the DOE Durability Working Group with the development of various new material durability Testing protocols; and (4) Provide support to the U.S. Council for Automotive Research (USCAR) and the USCAR/DOE Fuel Cell Technology Team. FY2012 specific technical objectives are: (1) Evaluate novel MPL materials; (2) Develop of startup/ shutdown protocol; (3) Test the impact of hydrophobic treatment on graphite bi-polar plates; (4) Perform complete diagnostics on metal bi-polar plates for corrosion; and (5) Participate and lead efforts in the DOE Working Groups.« less

  6. Association of the AMPA receptor-related postsynaptic density proteins GRIP and ABP with subsets of glutamate-sensitive neurons in the rat retina.

    PubMed

    Gábriel, Robert; de Souza, Sunita; Ziff, Edward B; Witkovsky, Paul

    2002-07-22

    We used specific antibodies against two postsynaptic density proteins, GRIP (glutamate receptor interacting protein) and ABP (AMPA receptor-binding protein), to study their distribution in the rat retina. In the central nervous system, it has been shown that both proteins bind strongly to the AMPA glutamate receptor (GluR) 2/3 subunits, but not other GluRs, through a set of three PDZ domains. Western blots detected a single GRIP protein that was virtually identical in retina and brain, whereas retinal ABP corresponded to only one of three ABP peptides found in brain. The retinal distributions of GluR2/3, GRIP, and ABP immunoreactivity (IR) were similar but not identical. GluR2/3 immunoreactivity (IR) was abundant in both plexiform layers and in large perikarya. ABP IR was concentrated in large perikarya but was sparse in the plexiform layers, whereas GRIP IR was relatively more abundant in the plexiform layers than in perikarya. Immunolabel for these three antibodies consisted of puncta < or = 0.2 microm in diameter. The cellular localization of GRIP and ABP IR was examined by double labeling subclasses of retinal neuron with characteristic marker proteins, e.g., calbindin. GRIP, ABP, and GluR2/3 IR were detected in horizontal cells, dopaminergic and glycinergic AII amacrine cells and large ganglion cells. Immunolabel was absent in rod bipolar and weak or absent in cholinergic amacrine cells. By using the tyramide method of signal amplification, a colocalization of GluR2/3 was found with either GRIP or ABP in horizontal cell terminals, and perikarya of amacrine and ganglion cells. Our results show that ABP and GRIP colocalize with GluR2/3 in particular subsets of retinal neuron, as was previously established for certain neurons in the brain. Copyright 2002 Wiley-Liss, Inc.

  7. Long-Term Clinical and Histological Effects of a Bipolar Fractional Radiofrequency System in the Treatment of Facial Atrophic Acne Scars and Acne Vulgaris in Japanese Patients: A Series of Eight Cases.

    PubMed

    Kaminaka, Chikako; Furukawa, Fukumi; Yamamoto, Yuki

    2016-12-01

    This retrospective case series was designed to compare the long-term safety and efficacy of bipolar fractional radiofrequency (FRF) therapy as a treatment for atrophic acne scars (ASs) and acne vulgaris. Few clinical and histological studies have examined the long-term utility of bipolar FRF therapy as a treatment for ASs and acne in people with darker skin. Eight Japanese patients with ASs and mild-to-severe acne on both cheeks were treated with a bipolar FRF system (eMatrix; Syneron). Five treatment sessions with the same settings (coverage rate: 10%; peak energy: 62 mJ/pin; two passes) were carried out at 1-month intervals, and the patients were followed up for at least 1 year after the final treatment. Assessments of ASs and acne severity were performed and samples were removed for histological examination. We demonstrated that mild ASs responded better than moderate and severe ASs, and at least 50% improvement in scar severity was seen in 50% of patients after the final treatment. Six patients remained disease free at 1.5 years without the use of any additional therapies. The biopsy specimens showed a marked improvement characterized by a decrease in dermal pilosebaceous units and perivascular inflammatory cell infiltrates with an increase in elastin content and collagen deposition in the upper dermis. Bipolar FRF treatment showed long-term effectiveness against mild ASs and acne in Asian patients and had minimal side effects.

  8. Bipolar sealer device reduces blood loss and transfusion requirements in posterior spinal fusion for adolescent idiopathic scoliosis.

    PubMed

    Gordon, Zachary L; Son-Hing, Jochen P; Poe-Kochert, Connie; Thompson, George H

    2013-01-01

    Reducing perioperative blood loss and transfusion requirements is important in the operative treatment of idiopathic scoliosis. This can be achieved with special frames, cell saver systems, pharmacologic aspects, and other techniques. Recently there has been interest in bipolar sealer devices as an adjunct to traditional monopolar electrocautery. However, there is limited information on this device in pediatric spinal deformity surgery. We reviewed our experience with this device in a setting of a standard institutional operative carepath. Perioperative blood loss and transfusion requirements of 50 consecutive patients with adolescent idiopathic scoliosis undergoing a posterior spinal fusion and segmental spinal instrumentation and who had a bipolar sealer device used during their surgery was compared with a control group of the 50 preceding consecutive patients who did not. Anesthesia, surgical technique, use of intraoperative epsilon aminocaproic acid (Amicar), postoperative protocol, and indications for transfusions (hemoglobin≤7.0 g/dL) were identical in both groups. The preoperative demographics for the patients in both groups were statistically the same. The bipolar sealer group demonstrated a significant reduction in intraoperative estimated blood loss, total perioperative blood loss, volume of blood products transfused, and overall transfusion rate when compared with the control group. When subgroups consisting of only hybrid or all-pedicle screw constructs were considered individually, these findings remained consistent. There were no complications associated with the use of this device. Using the bipolar sealer device is a significant adjunct in decreasing perioperative blood loss and transfusion requirements in patients undergoing surgery for adolescent idiopathic scoliosis. Level III-retrospective comparative study.

  9. The Terminator mouse is a diphtheria toxin-receptor knock-in mouse strain for rapid and efficient enrichment of desired cell lineages.

    PubMed

    Guo, Jian-Kan; Shi, Hongmei; Koraishy, Farrukh; Marlier, Arnaud; Ding, Zhaowei; Shan, Alan; Cantley, Lloyd G

    2013-11-01

    Biomedical research often requires primary cultures of specific cell types, which are challenging to obtain at high purity in a reproducible manner. Here we engineered the murine Rosa26 locus by introducing the diphtheria toxin receptor flanked by loxP sites. The resultant strain was nicknamed the Terminator mouse. This approach results in diphtheria toxin-receptor expression in all non-Cre expressing cell types, making these cells susceptible to diphtheria toxin exposure. In primary cultures of kidney cells derived from the Terminator mouse, over 99.99% of cells were dead within 72 h of diphtheria toxin treatment. After crossing the Terminator with the podocin-Cre (podocyte specific) mouse or the Ggt-Cre (proximal tubule specific) mouse, diphtheria toxin treatment killed non-Cre expressing cells but spared podocytes and proximal tubule cells, respectively, enriching the primary cultures to over 99% purity, based on both western blotting and immunostaining of marker proteins. Thus, the Terminator mouse can be a useful tool to selectively and reproducibly obtain even low-abundant cell types at high quantity and purity.

  10. The Scaffolding Protein, Grb2-associated Binder-1, in Skeletal Muscles and Terminal Schwann Cells Regulates Postnatal Neuromuscular Synapse Maturation

    PubMed Central

    Park, So Young; Jang, So Young; Shin, Yoon Kyoung; Jung, Dong Keun; Yoon, Byeol A; Kim, Jong Kook; Jo, Young Rae; Lee, Hye Jeong

    2017-01-01

    The vertebrate neuromuscular junction (NMJ) is considered as a “tripartite synapse” consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system. PMID:28680299

  11. The Scaffolding Protein, Grb2-associated Binder-1, in Skeletal Muscles and Terminal Schwann Cells Regulates Postnatal Neuromuscular Synapse Maturation.

    PubMed

    Park, So Young; Jang, So Young; Shin, Yoon Kyoung; Jung, Dong Keun; Yoon, Byeol A; Kim, Jong Kook; Jo, Young Rae; Lee, Hye Jeong; Park, Hwan Tae

    2017-06-01

    The vertebrate neuromuscular junction (NMJ) is considered as a "tripartite synapse" consisting of a motor axon terminal, a muscle endplate, and terminal Schwann cells that envelope the motor axon terminal. The neuregulin 1 (NRG1)-ErbB2 signaling pathway plays an important role in the development of the NMJ. We previously showed that Grb2-associated binder 1 (Gab1), a scaffolding mediator of receptor tyrosine kinase signaling, is required for NRG1-induced peripheral nerve myelination. Here, we determined the role of Gab1 in the development of the NMJ using muscle-specific conditional Gab1 knockout mice. The mutant mice showed delayed postnatal maturation of the NMJ. Furthermore, the selective loss of the gab1 gene in terminal Schwann cells produced delayed synaptic elimination with abnormal morphology of the motor endplate, suggesting that Gab1 in both muscles and terminal Schwann cells is required for proper NMJ development. Gab1 in terminal Schwann cells appeared to regulate the number and process elongation of terminal Schwann cells during synaptic elimination. However, Gab2 knockout mice did not show any defects in the development of the NMJ. Considering the role of Gab1 in postnatal peripheral nerve myelination, our findings suggest that Gab1 is a pleiotropic and important component of NRG1 signals during postnatal development of the peripheral neuromuscular system.

  12. Amphiastral Mitotic Spindle Assembly in Vertebrate Cells Lacking Centrosomes

    PubMed Central

    Hornick, Jessica E.; Mader, Christopher C.; Tribble, Emily K.; Bagne, Cydney C.; Vaughan, Kevin T.; Shaw, Sidney L.; Hinchcliffe, Edward H.

    2011-01-01

    Summary The role of centrosomes/centrioles during mitotic spindle assembly in vertebrates remains controversial. In cell-free extracts and experimentally derived acentrosomal cells, randomly oriented microtubules (MTs) self-organize around mitotic chromosomes and assemble anastral spindles [1, 2, 3]. However, vertebrate somatic cells normally assemble a connected pair of polarized, astral MT arrays – termed an amphiaster (“a star on both sides” [4]) – that is formed by the splitting and separation of the microtubule-organizing center (MTOC) well before nuclear envelope breakdown (NEB) [5]. Whether amphiaster formation requires splitting of duplicated centrosomes is not known. We found that when centrosomes were removed from living vertebrate cells early in their cell cycle, an acentriolar MTOC re-assembled, and prior to NEB, a functional amphiastral spindle formed. Cytoplasmic dynein, dynactin, and pericentrin are all recruited to the interphase aMTOC, and the activity of kinesin-5 is needed for amphiaster formation. Mitosis proceeded on time and these karyoplasts divided in two. However, ~35% of aMTOCs failed to split/separate before NEB, and these entered mitosis with persistent monastral spindles. The chromatin-mediated RAN-GTP pathway could not restore bipolarity to monastral spindles, and these cells exited mitosis as single daughters. Our data reveal the novel finding that MTOC separation and amphiaster formation does not absolutely require the centrosome, but in its absence, the fidelity of bipolar spindle assembly is highly compromised. PMID:21439826

  13. RdgB2 is required for dim-light input into intrinsically photosensitive retinal ganglion cells

    PubMed Central

    Walker, Marquis T.; Rupp, Alan; Elsaesser, Rebecca; Güler, Ali D.; Sheng, Wenlong; Weng, Shijun; Berson, David M.; Hattar, Samer; Montell, Craig

    2015-01-01

    A subset of retinal ganglion cells is intrinsically photosensitive (ipRGCs) and contributes directly to the pupillary light reflex and circadian photoentrainment under bright-light conditions. ipRGCs are also indirectly activated by light through cellular circuits initiated in rods and cones. A mammalian homologue (RdgB2) of a phosphoinositide transfer/exchange protein that functions in Drosophila phototransduction is expressed in the retinal ganglion cell layer. This raised the possibility that RdgB2 might function in the intrinsic light response in ipRGCs, which depends on a cascade reminiscent of Drosophila phototransduction. Here we found that under high light intensities, RdgB2−/− mutant mice showed normal pupillary light responses and circadian photoentrainment. Consistent with this behavioral phenotype, the intrinsic light responses of ipRGCs in RdgB2−/− were indistinguishable from wild-type. In contrast, under low-light conditions, RdgB2−/− mutants displayed defects in both circadian photoentrainment and the pupillary light response. The RdgB2 protein was not expressed in ipRGCs but was in GABAergic amacrine cells, which provided inhibitory feedback onto bipolar cells. We propose that RdgB2 is required in a cellular circuit that transduces light input from rods to bipolar cells that are coupled to GABAergic amacrine cells and ultimately to ipRGCs, thereby enabling ipRGCs to respond to dim light. PMID:26269578

  14. Universal solar-cell terminal

    NASA Technical Reports Server (NTRS)

    Bashin, S.; Kelley, F. G.

    1977-01-01

    Terminal, which replaces stakes or lugs in conventional design with loop receptacles for wires from cell and harness, uses dissimilar bonding properties (metal-to-glass and/or ceramics) of iron-nickel-cobalt alloy in conjunction with standard termination.

  15. Cloning and Immunocytochemical Localization of a Cyclic Nucleotide–Gated Channel α-Subunit to All Cone Photoreceptors in the Mouse Retina

    PubMed Central

    HIRANO, ARLENE A.; HACK, IRIS; WÄSSLE, HEINZ; DUVOISIN, ROBERT M.

    2010-01-01

    Cyclic nucleotide–gated channels (CNGC) are ligand-gated ion channels that open and close in response to changes in the intracellular concentration of the second messengers, 3′,5′-cyclic adenosine monophosphate and 3′,5′-cyclic guanosine monophosphate. Most notably, they transduce the chemical signal produced by the absorption of light in photoreceptors into a membrane potential change, which is then transmitted to the ascending visual pathway. CNGCs have also been implicated in the signal transduction of other neurons downstream of the photoreceptors, in particular the ON-bipolar cells, as well as in other areas of the central nervous system. We therefore undertook a search for additional cyclic nucleotide–gated channels expressed in the retina. Following a degenerate reverse transcription polymerase chain reaction approach to amplify low-copy number messages, a cDNA encoding a new splice variant of CNGC α-subunit was isolated from mouse retina and classified as mCNG3. An antiserum raised against the carboxy-terminal sequence identified the retinal cell type expressing mCNG3 as cone photoreceptors. Preembedding immunoelectron microscopy demonstrated its membrane localization in the outer segments, consistent with its role in phototransduction. Double-labeling experiments with cone-specific markers indicated that all cone photoreceptors in the murid retina use the same or a highly conserved cyclic nucleotide–gated channel. Therefore, defects in this channel would be predicted to severely impair photopic vision. PMID:10813773

  16. Design principles for nickel-hydrogen cells and batteries

    NASA Technical Reports Server (NTRS)

    Thaller, L. H.; Manzo, M. A.; Gonzalez-Sanabria, O. D.

    1985-01-01

    Nickel-hydrogen cells and, more recently, bipolar batteries have been built by a variety of organizations. The design principles that have been used by the technology group at the NASA Lewis Research Center draw upon their extensive background in separator technology, alkaline fuel cell technology, and several alkaline cell technology areas. These design principles have been incorporated into both the more contemporary individual pressure vessel (IPV) designs that were pioneered by other groups, as well as the more recent bipolar battery designs using active cooling that are being developed at NASA Lewis Research Center and under contract. These principles are rather straightforward applications of capillary force formalisms, coupled with the slowly developing data base resulting from careful post test analyses. The objective of this overall effort is directed towards the low-Earth-orbit (LEO) application where the cycle life requirements are much more severe than the geosynchronous-orbit (GEO) application. A summary of the design principles employed is presented along with a discussion of the recommendations for component pore sizes and pore size distributions, as well as suggested materials of construction. These will be made based on our experience in these areas to show how these design principles have been translated into operating hardware.

  17. Design principles for nickel-hydrogen cells and batteries

    NASA Technical Reports Server (NTRS)

    Thaller, L. H.; Manzo, M. A.; Gonzalez-Sanabria, O. D.

    1985-01-01

    Nickel-hydrogen cells and, more recently, bipolar batteries have been built by a variety of organizations. The design principles that have been used by the technology group at the NASA Lewis Research Center draw upon their extensive background in separator technology, alkaline fuel cell technology, and several alkaline cell technology areas. These design principles have been incorporated into both the more contemporary individual pressure vessel (IPV) designs that were pioneered by other groups, as well as the more recent bipolar battery designs using active cooling that are being developed at NASA Lewis Research Center and under contract. These principles are rather straightforward applications of capillary force formalisms, coupled with the slowly developing data base resulting from careful post test analyses. The objective of this overall effort is directed towards the low-earth-orbit (LEO) application where the cycle life requirements are much more severe than the geosynchronous-orbit (GEO) application. A summary of the design principles employed is presented along with a discussion of the recommendations for component pore sizes and pore size distributions, as well as suggested materials of construction. These will be made based on our experience in these areas to show how these design principles have been translated into operating hardware.

  18. Bipolar Disorder in Nursing Homes: Impact on Antipsychotic Use, Diagnosis Patterns, and New Diagnoses in People with Dementia.

    PubMed

    Carnahan, Ryan M; Letuchy, Elena M

    2018-01-01

    Nursing home quality measures include the proportion of residents who receive antipsychotics. Residents with bipolar disorder are included even though antipsychotics are FDA-approved for this indication. We evaluated how including residents with bipolar disorder impacted the antipsychotic use quality measure for long-stay residents. We evaluated the agreement of minimum data set (MDS) bipolar disorder diagnoses with Medicare data, whether dementia was diagnosed before bipolar disorder, and how less-specific bipolar disorder diagnoses impacted findings. Cross-sectional study. Nursing homes in Iowa. 21,955 long-stay nursing home residents in the first quarter of 2014. We identified antipsychotic use and bipolar disorder using MDS data. We compared MDS bipolar disorder diagnoses with Chronic Conditions Warehouse (CCW) "ever" bipolar disorder indicators, and prior year claims. We compared CCW condition onset dates to identify bipolar disorder diagnosed after dementia. The mean (SD) proportion receiving antipsychotics was 19.6% (11.1%) with bipolar disorder and 18.3% (10.8%) without. The positive predictive value (PPV) of MDS bipolar disorder diagnoses was 80.2% versus CCW lifetime indicators, and 74.6% versus claims. PPV decreased by 27.1% when "bipolar disorder, unspecified" and "other bipolar disorders" diagnoses were excluded. Nearly three-quarters of residents with bipolar disorder had dementia. Over half of those with dementia had dementia first per CCW records. This proportion was lower among those with more specific bipolar disorder diagnoses or MDS bipolar disorder indicators. Bipolar disorder in nursing home residents is often first diagnosed after dementia using nonspecific diagnoses. This practice deserves further evaluation. Copyright © 2017 American Association for Geriatric Psychiatry. Published by Elsevier Inc. All rights reserved.

  19. Design Principles for Nickel/Hydrogen Cells and Batteries

    NASA Technical Reports Server (NTRS)

    Thaller, Lawrence H.; Manzo, Michelle A.; Gonzalez-Sanabria, Olga D.

    1987-01-01

    Individual-pressure-vessel (IPV) nickel/hydrogen cells and bipolar batteries developed for use as energy-storage subsystems for satelite applications. Design principles applied draw upon extensive background in separator technology, alkaline-fuel-cell technology and several alkaline-cell technology areas. Principals are rather straightforward applications of capillary-force formalisms, coupled with slowly developing data base resulting from careful post-test analyses. Based on preconceived assumptions relative to how devices work and how to be designed so they display longer cycle lives at deep discharge.

  20. Improvement in the statistical operation of a Blumlein pulse forming line in bipolar pulse mode

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Pushkarev, A. I., E-mail: aipush@mail.ru; Isakova, Y. I.; Khaylov, I. P.

    The paper presents the results of studies on shot-to-shot performance of a water Blumlein pulse forming line of 1–1.2 kJ of stored energy. The experiments were carried using the TEMP-4M pulsed ion beam accelerator during its operation in both unipolar pulse mode (150 ns, 250–300 kV) and bipolar-pulse mode with the first negative (300–600 ns, 100–150 kV) followed by a second positive (120 ns, 250–300 kV) pulse. The analysis was carried out for two cases when the Blumlein was terminated with a resistive load and with a self-magnetically insulated ion diode. It was found that in bipolar pulse mode themore » shot-to-shot variation in breakdown voltage of a preliminary spark gap is small, the standard deviation (1σ) does not exceed 2%. At the same time, the shot-to-shot variation in the breakdown voltage of the main spark gap in both bipolar-pulse and unipolar pulse mode is 3–4 times higher than that for the preliminary spark gap. To improve the statistical performance of the main spark gap we changed the regime of its operation from a self-triggered mode to an externally triggered mode. In the new arrangement the first voltage pulse at the output of Blumlein was used to trigger the main spark gap. The new trigatron-type regime of the main spark gap operation showed a good stability of breakdown voltage and thus allowed to stabilize the duration of the first pulse. The standard deviation of the breakdown voltage and duration of the first pulse did not exceed 2% for a set of 50 pulses. The externally triggered mode of the main gap operation also allowed for a decrease in the charging voltage of the Blumlein to a 0.9–0.95 of self-breakdown voltage of the main spark gap while the energy stored in Marx generator was decreased from 4 kJ to 2.5 kJ. At the same time the energy stored in Blumlein remained the same.« less

  1. Ultrastructure of the protonephridia of larval Rugiloricus cf. cauliculus, male Armorloricus elegans, and female Nanaloricus mysticus (Loricifera).

    PubMed

    Neuhaus, Birger; Kristensen, Reinhardt Møbjerg

    2007-04-01

    The protonephridial system of several Loricifera was studied by transmission electron microscopy. A larval specimen of Rugiloricus cf. cauliculus possesses two protonephridia, which are "capped" frontally by a compact mass of still undifferentiated gonadal cells. Each protonephridium consists of four monociliary terminal cells and four canal cells with a diplosome but no cilia. Because of incomplete series of sections and unsatisfactory fixation, the outleading cell(s) could not be detected. In a male specimen of Armorloricus elegans, each gonad contains two protonephridia that open into the gonadal lumen. Each protonephridium consists of two monociliary terminal cells, each forming a filter, two nonciliated canal cells, and two nephroporus cells. The protonephridial lumina of the latter cells fuse to one common lumen, which unites with the gonadal lumen. Preliminary observations on the protonephridia of a female Nanaloricus mysticus reveal a more complicated arrangement of interdigitating terminal and canal cells. One or two terminal cells form their own individual filter or four cells form a common compound filter. The cilium of the terminal cells of all species investigated are surrounded by a palisade of nine microvilli that support the filter barrier made of an extracellular matrix. An additional filter diaphragm could be traced between the pores in the cell wall of each terminal cell of A. elegans. The urogenital system of the Loricifera differs from that of the Priapulida in that the protonephridia of the former are completely integrated into the gonad, whereas the excretory organs of the latter open into the urogenital duct caudally of the gonads. Copyright (c) 2007 Wiley-Liss, Inc.

  2. The diagnostic usefulness of the negative electroretinogram.

    PubMed

    Fuente García, C; González-López, J J; Muñoz-Negrete, F J; Rebolleda, G

    2018-03-01

    The definition of the negative response of the full field electroretinogram is the presence of a b-wave with less amplitude than the a-wave (b/a ratio<1) in the combined response of cones and rods. The presence of this pattern reflects an alteration in the bipolar cells, the Müller cells, or in the transmission of the stimulus from the photoreceptors to the bipolar cells, with preserved photoreceptor function. This finding can be seen bilaterally and symmetrically in different hereditary conditions, such as congenital stationary night blindness, juvenile X-linked retinoschisis, and Duchenne and Becker muscular dystrophies. On the other hand, it can also be found unilaterally (or asymmetrically) in acquired pathologies, such as some types of immuno-mediated retinitis (Birdshot retinochoroiditis), autoimmune retinopathies, cancer/melanoma associated retinopathy, or retinal toxicity. The objective of this review is to summarise the characteristics of the pathologies in which this finding can be observed, in order to highlight its usefulness in the differential diagnosis of retinal conditions. Copyright © 2017 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  3. An investigation of the typical corrosion parameters used to test polymer electrolyte fuel cell bipolar plate coatings, with titanium nitride coated stainless steel as a case study

    NASA Astrophysics Data System (ADS)

    Orsi, A.; Kongstein, O. E.; Hamilton, P. J.; Oedegaard, A.; Svenum, I. H.; Cooke, K.

    2015-07-01

    Stainless steel bipolar plates (BPP) for polymer electrolyte membrane fuel cells (PEMFCs) have good manufacturability, durability and low costs, but inadequate corrosion resistance and elevated interfacial contact resistance (ICR) in the fuel cell environment. Thin film coatings of titanium nitride (TiN) of 1 μm in thickness, were deposited by means of physical vapour deposition (PVD) process on to stainless steel (SS) 316L substrates and were evaluated, in a series of tests, for their level of corrosion protection and ICR. In the ex-situ corrosion tests, variables such as applied potential, experimental duration and pH of the sulphate electrolyte at 80 °C were altered. The ICR values were found to increase after exposure to greater applied potentials and electrolytes of a higher pH. In terms of experimental duration, the ICR increased most rapidly at the beginning of each experiment. It was also found that the oxidation of TiN was accelerated after exposure to electrolytes of a higher pH. When coated BPPs were incorporated into an accelerated fuel cell test, the degradation of the fuel cell cathode resembled the plates that were tested at the highest anodic potential (1.4 VSHE).

  4. Interaction of poly(amidoamine) dendrimers with supported lipid bilayers and cells: hole formation and the relation to transport.

    PubMed

    Hong, Seungpyo; Bielinska, Anna U; Mecke, Almut; Keszler, Balazs; Beals, James L; Shi, Xiangyang; Balogh, Lajos; Orr, Bradford G; Baker, James R; Banaszak Holl, Mark M

    2004-01-01

    We have investigated poly(amidoamine) (PAMAM) dendrimer interactions with supported 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) lipid bilayers and KB and Rat2 cell membranes using atomic force microscopy (AFM), enzyme assays, flow cell cytometry, and fluorescence microscopy. Amine-terminated generation 7 (G7) PAMAM dendrimers (10-100 nM) were observed to form holes of 15-40 nm in diameter in aqueous, supported lipid bilayers. G5 amine-terminated dendrimers did not initiate hole formation but expanded holes at existing defects. Acetamide-terminated G5 PAMAM dendrimers did not cause hole formation in this concentration range. The interactions between PAMAM dendrimers and cell membranes were studied in vitro using KB and Rat 2 cell lines. Neither G5 amine- nor acetamide-terminated PAMAM dendrimers were cytotoxic up to a 500 nM concentration. However, the dose dependent release of the cytoplasmic proteins lactate dehydrogenase (LDH) and luciferase (Luc) indicated that the presence of the amine-terminated G5 PAMAM dendrimer decreased the integrity of the cell membrane. In contrast, the presence of acetamide-terminated G5 PAMAM dendrimer had little effect on membrane integrity up to a 500 nM concentration. The induction of permeability caused by the amine-terminated dendrimers was not permanent, and leaking of cytosolic enzymes returned to normal levels upon removal of the dendrimers. The mechanism of how PAMAM dendrimers altered cells was investigated using fluorescence microscopy, LDH and Luc assays, and flow cytometry. This study revealed that (1) a hole formation mechanism is consistent with the observations of dendrimer internalization, (2) cytosolic proteins can diffuse out of the cell via these holes, and (3) dye molecules can be detected diffusing into the cell or out of the cell through the same membrane holes. Diffusion of dendrimers through holes is sufficient to explain the uptake of G5 amine-terminated PAMAM dendrimers into cells and is consistent with the lack of uptake of G5 acetamide-terminated PAMAM dendrimers.

  5. Pure cultures and characterization of yak Sertoli cells.

    PubMed

    Zhang, Hua; Liu, Ben; Qiu, Yuan; Fan, Jiang feng; Yu, Si jiu

    2013-12-01

    The culture of primary Sertoli cells has become an important resource in the study of their function. However, their use is limited because of contamination of isolated cells with other testicular cells, mainly germ cells. The aim was to establish technique to obtain pure yak Sertoli cells as well as to study the growth kinetics and biological characteristics of Sertoli cells in vitro. Two-step enzyme digestion was used to separate and culture yak Sertoli cells. Cultured using starvation method and the hypotonic treatment were also invented to get pure yak Sertoli cells. Furthermore, the purification of Yak Sertoli cells were identified according to their characteristics, such as bipolar corpuscular around the nucleus and expression of Fasl, in addition to their morphology. The average viability of the Sertoli cells was 97% before freezing and 94.5% after thawing, indicating that cryopreservation in liquid nitrogen had little influence on the viability of Sertoli cells. The growth tendency of yak Sertoli cells was similar to an S-shaped growth curve. Purified yak Sertoli cells frequently exhibited bipolar corpuscula in nucleus after Feulgen staining, and did have a positive reaction of Fasl by the immunocytochemical identification. After recovery chromosomal analysis of Sertoli cells had a normal chromosomal number of 60, comprising 29 pairs of autosomes and one pair of sex chromosomes. Assays for bacteria, fungi and mycoplasmas were negative. In conclusion, yak Sertoli cells have been successfully purified and cultured in vitro, and maintain stable biological characteristics after thawing. Therefore, it will not only preserve the genetic resources of yaks at the cellular level, but also provide valuable materials for transgenic research and feeder layer and nuclear donor cells in yak somatic cell cloning technology. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Cell separator for use in bipolar-stack energy storage devices

    DOEpatents

    Mayer, Steven T.; Feikert, John H.; Kachmitter, James L.; Pekala, Richard W.

    1995-01-01

    An improved multi-cell electrochemical energy storage device, such as a battery, fuel cell, or double layer capacitor using a cell separator which allows cells to be stacked and interconnected with low electrical resistance and high reliability while maximizing packaging efficiency. By adding repeating cells, higher voltages can be obtained. The cell separator is formed by applying an organic adhesive on opposing surfaces of adjacent carbon electrodes or surfaces of aerogel electrodes of a pair of adjacent cells prior to or after pyrolysis thereof to form carbon aerogel electrodes. The cell separator is electronically conductive, but ionically isolating, preventing an electrolytic conduction path between adjacent cells in the stack.

  7. Six years of evidence-based adult dissection tonsillectomy with ultrasonic scalpel, bipolar electrocautery, bipolar radiofrequency or 'cold steel' dissection.

    PubMed

    Ragab, S M

    2012-10-01

    To conduct an adequately powered, prospective, randomised, controlled trial comparing adult dissection tonsillectomy using either ultrasonic scalpel, bipolar electrocautery, bipolar radiofrequency or 'cold steel' dissection. Three hundred patients were randomised into four tonsillectomy technique groups. The operative time, intra-operative bleeding, post-operative pain, tonsillar fossa healing, return to full diet, return to work and post-operative complications were recorded. The bipolar radiofrequency group had a shorter mean operative time. The mean intra-operative blood loss during bipolar radiofrequency tonsillectomy was significantly less compared with cold dissection and ultrasonic scalpel tonsillectomy. Pain scores were significantly higher after bipolar electrocautery tonsillectomy. Patients undergoing bipolar electrocautery tonsillectomy required significantly more days to return to full diet and work. The bipolar electrocautery group showed significantly reduced tonsillar fossa healing during the first and second post-operative weeks. In this adult series, bipolar radiofrequency tonsillectomy was superior to ultrasonic, bipolar electrocautery and cold dissection tonsillectomies. This method combines the advantages of 'hot' and 'cold' tonsillectomy.

  8. LASER APPLICATIONS AND OTHER TOPICS IN QUANTUM ELECTRONICS: Speckle suppression using a liquid-crystal cell

    NASA Astrophysics Data System (ADS)

    Andreev, A. L.; Kompanets, I. N.; Minchenko, M. V.; Pozhidaev, E. P.; Andreeva, T. B.

    2008-12-01

    A simple method for suppressing speckles in images produced by laser projectors is proposed. The coherence of the laser beam and, therefore, speckles can be destroyed when the beam passes through an electrooptical cell in which a special ferroelectric liquid crystal is used as a modulating medium. The effect is achieved due to the spatially inhomogeneous phase modulation of light when specially shaped bipolar electric pulses are applied to the cell.

  9. Bipolar and monopolar radiofrequency treatment of osteoarthritic knee articular cartilage: acute and temporal effects on cartilage compressive stiffness, permeability, cell synthesis, and extracellular matrix composition.

    PubMed

    Cook, James L; Kuroki, Keiichi; Kenter, Keith; Marberry, Kevin; Brawner, Travis; Geiger, Timothy; Jayabalan, Prakash; Bal, B Sonny

    2004-04-01

    The cellular, biochemical, biomechanical, and histologic effects of radiofrequency-generated heat on osteoarthritic cartilage were assessed. Articular cartilage explants (n=240) from 26 patients undergoing total knee arthroplasty were divided based on Outerbridge grade (I or II/III) and randomly assigned to receive no treatment (controls) or monopolar or bipolar radiofrequency at 15 or 30 W. Both potentially beneficial and harmful effects of radiofrequency treatment of articular cartilage were noted. It will be vital to correlate data from in vitro and in vivo study of radiofrequency thermal chondroplasty to determine the clinical usefulness of this technique.

  10. Isotropic Versus Bipolar Functionalized Biomimetic Artificial Basement Membranes and Their Evaluation in Long-Term Human Cell Co-Culture.

    PubMed

    Rossi, Angela; Wistlich, Laura; Heffels, Karl-Heinz; Walles, Heike; Groll, Jürgen

    2016-08-01

    In addition to dividing tissues into compartments, basement membranes are crucial as cell substrates and to regulate cellular behavior. The development of artificial basement membranes is indispensable for the ultimate formation of functional engineered tissues; however, pose a challenge due to their complex structure. Herein, biodegradable electrospun polyester meshes are presented, exhibiting isotropic or bipolar bioactivation as a biomimetic and biofunctional model of the natural basement membrane. In a one-step preparation process, reactive star-shaped prepolymer additives, which generate a hydrophilic fiber surface, are electrospun with cell-adhesion-mediating peptides, derived from major components of the basement membrane. Human skin cells adhere to the functionalized meshes, and long-term co-culture experiments confirm that the artificial basement membranes recapitulate and preserve tissue specific functions. Several layers of immortalized human keratinocytes grow on the membranes, differentiating toward the surface and expressing typical epithelial markers. Fibroblasts migrate into the reticular lamina mimicking part of the mesh. Both cells types begin to produce extracellular matrix proteins and to remodel the initial membrane. It is shown at the example of skin that the artificial basement membrane design provokes biomimetic responses of different cell types and can thus be used as basis for the future development of basement membrane containing tissues. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  11. The effect of long-term lithium treatment of bipolar disorder on stem cells circulating in peripheral blood.

    PubMed

    Ferensztajn-Rochowiak, Ewa; Kucharska-Mazur, Jolanta; Samochowiec, Jerzy; Ratajczak, Mariusz Z; Michalak, Michal; Rybakowski, Janusz K

    2017-02-01

    To investigate the effect of long-term lithium treatment on very small embryonic-like stem cells (VSELs), haematopoietic stem cells (HSCs), mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs) circulating in peripheral blood (PB), in bipolar disorder (BD). The study included 15 BD patients (aged 55 ± 6 years) treated with lithium for 8-40 years (mean 16 years), 15 BD patients (aged 53 ± 7 years) with duration of illness >10 years, who had never received lithium, and 15 healthy controls (aged 50 ± 5 years). The VSELs, HSCs, MSCs and EPCs were measured by flow cytometric analysis. In BD subjects not taking lithium the number of CD34 +  VSELs was significantly higher, and MSCs and EPCs numerically higher, than in control subjects and the number of CD34 +  VSELs correlated with the duration of illness. In lithium-treated patients these values were similar to controls and the number of CD34 +  VSELs correlated negatively with the duration of lithium treatment and serum lithium concentration. Long-term treatment with lithium may suppress the activation of regenerative processes by reducing the number of VSELs circulating in PB. These cells, in BD patients not treated with lithium, may provide a new potential biological marker of the illness and its clinical progress.

  12. A family of ParA-like ATPases promotes cell pole maturation by facilitating polar localization of chemotaxis proteins

    PubMed Central

    Ringgaard, Simon; Schirner, Kathrin; Davis, Brigid M.; Waldor, Matthew K.

    2011-01-01

    Stochastic processes are thought to mediate localization of membrane-associated chemotaxis signaling clusters in peritrichous bacteria. Here, we identified a new family of ParA-like ATPases (designated ParC [for partitioning chemotaxis]) encoded within chemotaxis operons of many polar-flagellated γ-proteobacteria that actively promote polar localization of chemotaxis proteins. In Vibrio cholerae, a single ParC focus is found at the flagellated old pole in newborn cells, and later bipolar ParC foci develop as the cell matures. The cell cycle-dependent redistribution of ParC occurs by its release from the old pole and subsequent relocalization at the new pole, consistent with a “diffusion and capture” model for ParC dynamics. Chemotaxis proteins encoded in the same cluster as ParC have a similar unipolar-to-bipolar transition; however, they reach the new pole after the arrival of ParC. Cells lacking ParC exhibit aberrantly localized foci of chemotaxis proteins, reduced chemotaxis, and altered motility, which likely accounts for their enhanced colonization of the proximal small intestine in an animal model of cholera. Collectively, our findings indicate that ParC promotes the efficiency of chemotactic signaling processes. In particular, ParC-facilitated development of a functional chemotaxis apparatus at the new pole readies this site for its development into a functional old pole after cell division. PMID:21764856

  13. On the functional anatomy of the nucleus of the optic tract-dorsal terminal nucleus commissural connection in the opossum (Didelphis marsupialis aurita).

    PubMed

    Vargas, C D; Volchan, E; Hokoç, J N; Pereira, A; Bernardes, R F; Rocha-Miranda, C E

    1997-01-01

    Immunocytochemical methods revealed the presence of GABA in cell bodies and terminals in the nucleus of the optic tract-dorsal terminal nucleus, the medial terminal nucleus, the lateral terminal nucleus and the interstitial nucleus of the superior fasciculus of the opossum (Didelphis marsupialis aurita). Moreover, after unilateral injections of rhodamine beads in the nucleus of the optic tract-dorsal terminal nucleus complex and processing for GABA, double-labelled cells were detected in the ipsilateral complex, up to 400 microns from the injected site, but not in the opposite. Analysis of the distributions of GABAergic and retrogradely-labelled cells throughout the contralateral nucleus of the optic tract-dorsal terminal nucleus showed that the highest density of GABAergic and rhodamine-labelled cells overlapped at the middle third of the complex. Previous electrophysiological data obtained in the opossum had suggested the existence, under certain conditions, of an inhibitory action between the nucleus of the optic tract-dorsal terminal nucleus of one side over the other. The absence of GABAergic commissural neurons may imply that this inhibition is mediated by an excitatory commissural pathway that activates GABAergic interneurons.

  14. Advances in nickel hydrogen technology at Yardney Battery Division

    NASA Technical Reports Server (NTRS)

    Bentley, J. G.; Hall, A. M.

    1987-01-01

    The current major activites in nickel hydrogen technology being addressed at Yardney Battery Division are outlined. Five basic topics are covered: an update on life cycle testing of ManTech 50 AH NiH2 cells in the LEO regime; an overview of the Air Force/industry briefing; nickel electrode process upgrading; 4.5 inch cell development; and bipolar NiH2 battery development.

  15. Novel Afferent Terminal Structure in the Crista Ampullaris of the Goldfish, Carassius auratus

    NASA Technical Reports Server (NTRS)

    Lanford, Pamela J.; Popper, Arthur N.

    1996-01-01

    Using transmission electron microscopy, we have identified a new type of afferent terminal structure in the crista ampullaris of the goldfish Carassius auratus. In addition to the bouton-type afferent terminals previously described in the ear of this species, the crista also contained enlarged afferent terminals that enveloped a portion of the basolateral hair cell membrane. The hair cell membrane was evaginated and protruded into the afferent terminal in a glove-and-finger configuration. The membranes of the two cells were regularly aligned in the protruded region of the contact and had a distinct symmetrical electron density. The electron-dense profiles of these contacts were easily identified and were present in every crista sampled. In some cases, efferent terminals synapsed onto the afferents at a point where the hair cell protruded into the terminal. The ultrastructural similarities of the goldfish crista afferents to calyx afferents found in amniotes (birds, reptiles, and mammals) are discussed. The results of the study support the hypothesis that structural variation in the vertebrate inner ear may have evolved much earlier in evolution than previously supposed.

  16. Effect of disorder on longitudinal resistance of a graphene p-n junction in the quantum Hall regime

    NASA Astrophysics Data System (ADS)

    Chen, Jiang-Chai; Yeung, T. C. Au; Sun, Qing-Feng

    2010-06-01

    The longitudinal resistances of a six-terminal graphene p-n junction under a perpendicular magnetic field are investigated. Because of the chirality of the Hall edge states, the longitudinal resistances on top and bottom edges of the graphene ribbon are not equal. In the presence of suitable disorder, the top-edge and bottom-edge resistances well show the plateau structures in the both unipolar and bipolar regimes, and the plateau values are determined by the Landau filling factors only. These plateau structures are in excellent agreement with the recent experiment. For the unipolar junction, the resistance plateaus emerge in the absence of impurity and they are destroyed by strong disorder. But for the bipolar junction, the resistances are very large without the plateau structures in the clean junction. The disorder can strongly reduce the resistances and leads the formation of the resistance plateaus due to the mixture of the Hall edge states in virtue of the disorder. In addition, the size effect of the junction on the resistances is studied and some extra resistance plateaus are found in the long graphene junction case. This is explained by the fact that only part of the edge states participate in the full mixing.

  17. Electrophysiology of pumpkin seeds: Memristors in vivo.

    PubMed

    Volkov, Alexander G; Nyasani, Eunice K; Tuckett, Clayton; Greeman, Esther A; Markin, Vladislav S

    2016-01-01

    Leon Chua, the discoverer of a memristor, theoretically predicted that voltage gated ion channels can be memristors. We recently found memristors in different plants such as the Venus flytrap, Mimosa pudica, Aloe vera, apple fruits, and in potato tubers. There are no publications in literature about the existence of memristors in seeds. The goal of this work was to discover if pumpkin seeds might have memristors. We selected Cucurbita pepo L., cv. Cinderella, Cucurbita maxima L. cv Warty Goblin, and Cucurbita maxima L., cv. Jarrahdale seeds for this analysis. In these seeds, we found the presence of resistors with memory. The analysis was based on cyclic voltammetry where a memristor should manifest itself as a nonlinear two-terminal electrical element, which exhibits a pinched hysteresis loop on a current-voltage plane for any bipolar cyclic voltage input signal. Dry dormant pumpkin seeds have very high electrical resistance without memristive properties. The electrostimulation by bipolar sinusoidal or triangular periodic waves induces electrical responses in imbibed pumpkin seeds with fingerprints of memristors. Tetraethylammonium chloride, an inhibitor of voltage gated K(+) channels, transforms a memristor to a resistor in pumpkin seeds. NPPB (5-Nitro-2-(3-phenylpropylamino)benzoic acid) inhibits the memristive properties of imbibed pumpkin seeds. The discovery of memristors in pumpkin seeds creates a new direction in the understanding of electrophysiological phenomena in seeds.

  18. Microbiota-derived butyrate suppresses group 3 innate lymphoid cells in terminal ileal Peyer's patches.

    PubMed

    Kim, Sae-Hae; Cho, Byeol-Hee; Kiyono, Hiroshi; Jang, Yong-Suk

    2017-06-21

    The regional specialization of intestinal immune cells is affected by the longitudinal heterogeneity of environmental factors. Although the distribution of group 3 innate lymphoid cells (ILC3s) is well characterized in the lamina propria, it is poorly defined in Peyer's patches (PPs) along the intestine. Given that PP ILC3s are closely associated with mucosal immune regulation, it is important to characterize the regulatory mechanism of ILC3s. Here, we found that terminal ileal PPs of specific pathogen-free (SPF) mice have fewer NKp46 + ILC3s than jejunal PPs, while there was no difference in NKp46 + ILC3 numbers between terminal ileal and jejunal PPs in antibiotics (ABX)-treated mice. We also found that butyrate levels in the terminal ileal PPs of SPF mice were higher than those in the jejunal PPs of SPF mice and terminal ileal PPs of ABX-treated mice. The reduced number of NKp46 + ILC3s in terminal ileal PPs resulted in a decrease in Csf2 expression and, in turn, resulted in reduced regulatory T cells and enhanced antigen-specific T-cell proliferation. Thus, we suggest that NKp46 + ILC3s are negatively regulated by microbiota-derived butyrate in terminal ileal PPs and the reduced ILC3 frequency is closely associated with antigen-specific immune induction in terminal ileal PPs.

  19. A YinYang bipolar fuzzy cognitive TOPSIS method to bipolar disorder diagnosis.

    PubMed

    Han, Ying; Lu, Zhenyu; Du, Zhenguang; Luo, Qi; Chen, Sheng

    2018-05-01

    Bipolar disorder is often mis-diagnosed as unipolar depression in the clinical diagnosis. The main reason is that, different from other diseases, bipolarity is the norm rather than exception in bipolar disorder diagnosis. YinYang bipolar fuzzy set captures bipolarity and has been successfully used to construct a unified inference mathematical modeling method to bipolar disorder clinical diagnosis. Nevertheless, symptoms and their interrelationships are not considered in the existing method, circumventing its ability to describe complexity of bipolar disorder. Thus, in this paper, a YinYang bipolar fuzzy multi-criteria group decision making method to bipolar disorder clinical diagnosis is developed. Comparing with the existing method, the new one is more comprehensive. The merits of the new method are listed as follows: First of all, multi-criteria group decision making method is introduced into bipolar disorder diagnosis for considering different symptoms and multiple doctors' opinions. Secondly, the discreet diagnosis principle is adopted by the revised TOPSIS method. Last but not the least, YinYang bipolar fuzzy cognitive map is provided for the understanding of interrelations among symptoms. The illustrated case demonstrates the feasibility, validity, and necessity of the theoretical results obtained. Moreover, the comparison analysis demonstrates that the diagnosis result is more accurate, when interrelations about symptoms are considered in the proposed method. In a conclusion, the main contribution of this paper is to provide a comprehensive mathematical approach to improve the accuracy of bipolar disorder clinical diagnosis, in which both bipolarity and complexity are considered. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Enhanced neurocognitive functioning and positive temperament in twins discordant for bipolar disorder.

    PubMed

    Higier, Rachel G; Jimenez, Amy M; Hultman, Christina M; Borg, Jacqueline; Roman, Cristina; Kizling, Isabelle; Larsson, Henrik; Cannon, Tyrone D

    2014-11-01

    Based on evidence linking creativity and bipolar disorder, a model has been proposed whereby factors influencing liability to bipolar disorder confer certain traits with positive effects on reproductive fitness. The authors tested this model by examining key traits known to be associated with evolutionary fitness, namely, temperament and neurocognition, in individuals carrying liability for bipolar disorder. Schizophrenia probands and their co-twins were included as psychiatric controls. Twin pairs discordant for bipolar disorder and schizophrenia and control pairs were identified through the Swedish Twin Registry. The authors administered a neuropsychological test battery and temperament questionnaires to samples of bipolar probands, bipolar co-twins, schizophrenia probands, schizophrenia co-twins, and controls. Multivariate mixed-model analyses of variance were conducted to compare groups on temperament and neurocognitive scores. Bipolar co-twins showed elevated scores on a "positivity" temperament scale compared with controls and bipolar probands, while bipolar probands scored higher on a "negativity" scale compared with their co-twins and controls, who did not differ. Additionally, bipolar co-twins showed superior performance compared with controls on tests of verbal learning and fluency, while bipolar probands showed performance decrements across all neurocognitive domains. In contrast, schizophrenia co-twins showed attenuated impairments in positivity and overall neurocognitive functioning relative to their ill proband counterparts. These findings suggest that supra-normal levels of sociability and verbal functioning may be associated with liability for bipolar disorder. These effects were specific to liability for bipolar disorder and did not apply to schizophrenia. Such benefits may provide a partial explanation for the persistence of bipolar illness in the population.

  1. Enhanced Corrosion Resistance and Interfacial Conductivity of TiC x/a-C Nanolayered Coatings via Synergy of Substrate Bias Voltage for Bipolar Plates Applications in PEMFCs.

    PubMed

    Yi, Peiyun; Zhang, Weixin; Bi, Feifei; Peng, Linfa; Lai, Xinmin

    2018-06-06

    Proton-exchange membrane fuel cells are one kind of renewable and clean energy conversion device, whose metallic bipolar plates are one of the key components. However, high interfacial contact resistance and poor corrosion resistance are still great challenges for the commercialization of metallic bipolar plates. In this study, we demonstrated a novel strategy for depositing TiC x /amorphous carbon (a-C) nanolayered coatings by synergy of 60 and 300 V bias voltage to enhance corrosion resistance and interfacial conductivity. The synergistic effects of bias voltage on the composition, microstructure, surface roughness, electrochemical corrosion behaviors, and interfacial conductivity of TiC x /a-C coatings were explored. The results revealed that the columnar structures in the inner layer were suppressed and the surface became rougher with the 300 V a-C layer outside. The composition analysis indicated that the sp 2 content increased with an increase of 300 V sputtering time. Due to the synergy strategy of bias voltage, lower corrosion current densities were achieved both in potentiostatic polarization (1.6 V vs standard hydrogen electrode) and potentiodynamic polarization. With the increase of 300 V sputtering time, the interfacial conductivity was improved. The enhanced corrosion resistance and interfacial conductivity of the TiC x /a-C coatings would provide new opportunities for commercial bipolar plates.

  2. Neural correlates of improved recognition of happy faces after erythropoietin treatment in bipolar disorder.

    PubMed

    Miskowiak, K W; Petersen, N A; Harmer, C J; Ehrenreich, E; Kessing, L V; Vinberg, M; Macoveanu, J; Siebner, H R

    2018-06-07

    Bipolar disorder is associated with impairments in social cognition including the recognition of happy faces. This is accompanied by imbalanced cortico-limbic response to emotional faces. We found that EPO improved the recognition of happy faces in patients with bipolar disorder. This randomized, controlled, longitudinal fMRI study explores the neuronal underpinnings of this effect. Forty-four patients with bipolar disorder in full or partial remission were randomized to eight weekly erythropoietin (EPO; 40 000 IU) or saline (NaCl 0.9%) infusions in a double-blind, parallel-group design. Participants underwent whole-brain fMRI at 3T, mood ratings and blood tests at baseline and week 14. During fMRI, participants viewed happy and fearful faces and performed a gender discrimination task. Thirty-four patients had complete pre- and post-treatment fMRI data (EPO: N = 18, saline: N = 16). Erythropoietin vs. saline increased right superior frontal response to happy vs. fearful faces. This correlated with improved happiness recognition in the EPO group. Erythropoietin also enhanced gender discrimination accuracy for happy faces. These effects were not influenced by medication, mood, red blood cells or blood pressure. Together with previous findings, the present observation suggests that increased dorsal prefrontal attention control is a common mechanism of EPO-associated improvements across several cognitive domains. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  3. Mice that lack the C-terminal region of Reelin exhibit behavioral abnormalities related to neuropsychiatric disorders

    PubMed Central

    Sakai, Kaori; Shoji, Hirotaka; Kohno, Takao; Miyakawa, Tsuyoshi; Hattori, Mitsuharu

    2016-01-01

    The secreted glycoprotein Reelin is believed to play critical roles in the pathogenesis of several neuropsychiatric disorders. The highly basic C-terminal region (CTR) of Reelin is necessary for efficient activation of its downstream signaling, and the brain structure of knock-in mice that lack the CTR (ΔC-KI mice) is impaired. Here, we performed a comprehensive behavioral test battery on ΔC-KI mice, in order to evaluate the effects of partial loss-of-function of Reelin on brain functions. The ΔC-KI mice were hyperactive and exhibited reduced anxiety-like and social behaviors. The working memory in ΔC-KI mice was impaired in a T-maze test. There was little difference in spatial reference memory, depression-like behavior, prepulse inhibition, or fear memory between ΔC-KI and wild-type mice. These results suggest that CTR-dependent Reelin functions are required for some specific normal brain functions and that ΔC-KI mice recapitulate some aspects of neuropsychiatric disorders, such as schizophrenia, bipolar disorder, and autism spectrum disorder. PMID:27346785

  4. Brief Report: A Family Risk Study Exploring Bipolar Spectrum Problems and Cognitive Biases in Adolescent Children of Bipolar Parents

    ERIC Educational Resources Information Center

    Espie, Jonathan; Jones, Steven H.; Vance, Yvonne H.; Tai, Sara J.

    2012-01-01

    Children of parents with bipolar disorder are at increased risk of bipolar spectrum diagnoses. This cross-sectional study explores cognitive factors in the prediction of vulnerability to bipolar disorder. Adolescents at high-risk (with a parent with bipolar disorder; n = 23) and age and gender matched adolescents (n = 24) were recruited. Parent…

  5. Markers of inflammation and stress distinguish subsets of individuals with schizophrenia and bipolar disorder

    PubMed Central

    Fillman, S G; Sinclair, D; Fung, S J; Webster, M J; Shannon Weickert, C

    2014-01-01

    Schizophrenia and bipolar disorder share a number of common features, both symptomatically and biologically. Abnormalities in the neuroimmune and the stress-signaling pathways have been previously identified in brains of individuals with both diseases. However, the possible relationship between abnormalities in stress and neuroimmune signaling within the cortex of people with psychotic illness has not been defined. To test the hypothesis that combined alterations in brain stress responsiveness and neuroimmune/inflammatory status are characteristic of some individuals suffering from major mental illness, we examined gene expression in the Stanley Array Cohort of 35 controls, 35 individuals with schizophrenia and 34 individuals with bipolar disorder. We used levels of 8 inflammatory-related transcripts, of which SERPINA3 was significantly elevated in individuals with schizophrenia (F(2,88)=4.137, P<0.05), and 12 glucocorticoid receptor signaling (stress) pathway transcripts previously examined, to identify two clusters of individuals: a high inflammation/stress group (n=32) and a low (n=68) inflammation/stress group. The high inflammation/stress group has a significantly greater number of individuals with schizophrenia (n=15), and a trend toward having more bipolar disorder individuals (n=11), when compared with controls (n=6). Using these subgroups, we tested which microarray-assessed transcriptional changes may be associated with high inflammatory/stress groups using ingenuity analysis and found that an extended network of gene expression changes involving immune, growth factors, inhibitory signaling and cell death factors also distinguished these groups. Our work demonstrates that some of the heterogeneity in schizophrenia and bipolar disorder may be partially explained by inflammation/stress interactions, and that this biological subtype cuts across Diagnostic and Statistical Manual of Mental Disorders (DSM)-defined categories. PMID:24569695

  6. Pattern of heat shock factor and heat shock protein expression in lymphocytes of bipolar patients: increased HSP70-glucocorticoid receptor heterocomplex.

    PubMed

    Bei, E S; Salpeas, V; Alevizos, B; Anagnostara, C; Pappa, D; Moutsatsou, P

    2013-11-01

    Bipolar disorder (BD), a stress-related disease, is characterized by altered glucocorticoid receptor (GR) signalling. Stress response includes activation of heat shock factor (HSF) and subsequent heat shock protein (HSP) synthesis which regulate GR folding and function. The objective of this study was to investigate the possible role of HSFs, HSPs and their interaction with GR in BD. We applied immunoprecipitation, SDS-PAGE/Western blot analysis and electrophoretic mobility shift assay (EMSA) in lymphocytes (whole cell or nuclear extracts) from BD patients and healthy subjects and determined the HSPs (HSP90 and HSP70), the heterocomplexes HSP90-GR and HSP70-GR, the HSFs (HSF1 and HSF4) as well as the HSF-DNA binding. The HSP70-GR heterocomplex was elevated (p < 0.05) in BD patients vs healthy subjects, and nuclear HSP70 was reduced (p ≤ 0.01) in bipolar manic patients. Protein levels of HSF1, HSF4, HSP90, HSP90-GR heterocomplex, and HSF-DNA binding remained unaltered in BD patients vs healthy subjects. The corresponding effect sizes (ES) indicated a large ES for HSP70-GR, HSP70, HSF-DNA binding and HSF4, and a medium ES for HSP90, HSF1 and HSP90-GR between healthy subjects and bipolar patients. Significant correlations among HSFs, HSPs, GR and HSP70-GR heterocomplex were observed in healthy subjects, which were abrogated in bipolar patients. The higher interaction between GR and HSP70 and the disturbances in the relations among heat shock response parameters and GR as observed in our BD patients may provide novel insights into the contribution of these factors in BD aetiopathogenesis. Copyright © 2013. Published by Elsevier Ltd.

  7. Diversity and wiring variability of visual local neurons in the Drosophila medulla M6 stratum.

    PubMed

    Chin, An-Lun; Lin, Chih-Yung; Fu, Tsai-Feng; Dickson, Barry J; Chiang, Ann-Shyn

    2014-12-01

    Local neurons in the vertebrate retina are instrumental in transforming visual inputs to extract contrast, motion, and color information and in shaping bipolar-to-ganglion cell transmission to the brain. In Drosophila, UV vision is represented by R7 inner photoreceptor neurons that project to the medulla M6 stratum, with relatively little known of this downstream substrate. Here, using R7 terminals as references, we generated a 3D volume model of the M6 stratum, which revealed a retinotopic map for UV representations. Using this volume model as a common 3D framework, we compiled and analyzed the spatial distributions of more than 200 single M6-specific local neurons (M6-LNs). Based on the segregation of putative dendrites and axons, these local neurons were classified into two families, directional and nondirectional. Neurotransmitter immunostaining suggested a signal routing model in which some visual information is relayed by directional M6-LNs from the anterior to the posterior M6 and all visual information is inhibited by a diverse population of nondirectional M6-LNs covering the entire M6 stratum. Our findings suggest that the Drosophila medulla M6 stratum contains diverse LNs that form repeating functional modules similar to those found in the vertebrate inner plexiform layer. © 2014 Wiley Periodicals, Inc.

  8. The pattern of expression of guanine nucleotide-binding protein β3 (GNB3) in the retina is conserved across vertebrate species

    PubMed Central

    Ritchey, Eric R.; Bongini, Rachel E.; Code, Kimberly A.; Zelinka, Christopher; Petersen-Jones, Simon; Fischer, Andy J.

    2010-01-01

    Guanine nucleotide-binding protein β3 (GNB3) is an isoform of the β subunit of the heterotrimeric G protein second messenger complex that is commonly associated with transmembrane receptors. The presence of GNB3 in photoreceptors, and possibly bipolar cells, has been confirmed in murine, bovine and primate retinas (Lee et al., 1992, Peng et al., 1992, Huang et al., 2003). Studies have indicated that a mutation in the GNB3 gene causes progressive retinopathy and globe enlargement (RGE) in chickens. The goals of this study were to 1) examine the expression pattern of GNB3 in wild-type and RGE mutant chickens, 2) characterize the types of bipolar cells that express GNB3 and 3) examine whether the expression of GNB3 in the retina is conserved across vertebrate species. We find that chickens homozygous for the RGE allele completely lack GNB3 protein. We find that the pattern of expression of GNB3 in the retina is highly conserved across vertebrate species, including teleost fish (Carassius auratus), frogs (Xenopus laevis), chickens (Gallus domesticus), mice (Mus musculata), guinea pigs (Cavia porcellus), dogs (Canis familiaris) and non-human primates (Macaca fasicularis). Regardless of the species, we find that GNB3 is expressed by Islet1-positive cone ON-bipolar cells and by cone photoreceptors. In some vertebrates, GNB3-immunoreactivity was observed in both rod and cone photoreceptors. A protein-protein alignment of GNB3 across different vertebrates, from fish to humans, indicates a high degree (>92%) of sequence conservation. Given that analogous types of retinal neurons express GNB3 in different species, we propose that the functions and the mechanisms that regulate the expression of GNB3 are highly conserved. PMID:20538044

  9. Clinical variables and implications of the personality on the outcome of bipolar illness: a pilot study

    PubMed Central

    Casas-Barquero, Nieves; García-López, Olga; Fernández-Argüelles, Pedro; Camacho-Laraña, Manuel

    2007-01-01

    Outcome in bipolar patients is affected by comorbidity. Comorbid personality disorders are frequent and may complicate the course of bipolar illness. This pilot study examined a series of 40 euthymic bipolar patients (DSM-IV criteria) (bipolar I disorder 31, bipolar II disorder 9) to assess the effect of clinical variables and the influence of comorbid personality on the clinical course of bipolar illness. Bipolar patients with a diagnosis of comorbid personality disorder (n = 30) were compared with “pure” bipolar patients (n = 10) with regard to demographic, clinical, and course of illness variables. Comorbid personality disorder was diagnosed in 75% of patients according to ICD-10 criteria, with obsessive-compulsive personality disorder being the most frequent type. Sixty-three per cent of subjects had more than one comorbid personality disorder. Bipolar patients with and without comorbid personality disorder showed no significant differences regarding features of the bipolar illness, although the group with comorbid personality disorder showed a younger age at onset, more depressive episodes, and longer duration of bipolar illness. In subjects with comorbid personality disorders, the number of hospitalizations correlated significantly with depressive episodes and there was an inverse correlation between age at the first episode and duration of bipolar illness. These findings, however, should be interpreted taking into account the preliminary nature of a pilot study and the contamination of the sample with too many bipolar II patients. PMID:19300559

  10. Dual Role of Jun N-Terminal Kinase Activity in Bone Morphogenetic Protein-Mediated Drosophila Ventral Head Development.

    PubMed

    Park, Sung Yeon; Stultz, Brian G; Hursh, Deborah A

    2015-12-01

    The Drosophila bone morphogenetic protein encoded by decapentaplegic (dpp) controls ventral head morphogenesis by expression in the head primordia, eye-antennal imaginal discs. These are epithelial sacs made of two layers: columnar disc proper cells and squamous cells of the peripodial epithelium. dpp expression related to head formation occurs in the peripodial epithelium; cis-regulatory mutations disrupting this expression display defects in sensory vibrissae, rostral membrane, gena, and maxillary palps. Here we document that disruption of this dpp expression causes apoptosis in peripodial cells and underlying disc proper cells. We further show that peripodial Dpp acts directly on the disc proper, indicating that Dpp must cross the disc lumen to act. We demonstrate that palp defects are mechanistically separable from the other mutant phenotypes; both are affected by the c-Jun N-terminal kinase pathway but in opposite ways. Slight reduction of both Jun N-terminal kinase and Dpp activity in peripodial cells causes stronger vibrissae, rostral membrane, and gena defects than Dpp alone; additionally, strong reduction of Jun N-terminal kinase activity alone causes identical defects. A more severe reduction of dpp results in similar vibrissae, rostral membrane, and gena defects, but also causes mutant maxillary palps. This latter defect is correlated with increased peripodial Jun N-terminal kinase activity and can be caused solely by ectopic activation of Jun N-terminal kinase. We conclude that formation of sensory vibrissae, rostral membrane, and gena tissue in head morphogenesis requires the action of Jun N-terminal kinase in peripodial cells, while excessive Jun N-terminal kinase signaling in these same cells inhibits the formation of maxillary palps. Copyright © 2015 by the Genetics Society of America.

  11. III-V/Si Tandem Cells Utilizing Interdigitated Back Contact Si Cells and Varying Terminal Configurations: Preprint

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Schnabel, Manuel; Klein, Talysa R.; Jain, Nikhil

    Solar cells made from bulk crystalline silicon (c-Si) dominate the market, but laboratory efficiencies have stagnated because the current record efficiency of 26.3% is already very close to the theoretical limit of 29.4% for a single-junction c-Si cell. In order to substantially boost the efficiency of Si solar cells we have been developing stacked III-V/Si tandem cells, recently attaining efficiencies above 32% in four-terminal configuration. In this contribution, we use state-of-the-art III-V cells coupled with equivalent circuit simulations to compare four-terminal (4T) to three- and two-terminal (3T, 2T) operation. Equivalent circuit simulations are used to show that tandem cells canmore » be operated just as efficiently using three terminals as with four terminals. However, care must be taken not to overestimate 3T efficiency, as the two circuits used to extract current interact, and a method is described to accurately determine this efficiency. Experimentally, a 4T GaInP/Si tandem cell utilizing an interdigitated back contact cell is shown, exhibiting a 4T efficiency of 31.5% and a 2T efficiency of 28.1%. In 3T configuration, it is used to verify the finding from simulation that 3T efficiency is overestimated when interactions between the two circuits are neglected. Considering these, a 3T efficiency approaching the 4T efficiency is found, showing that 3T operation is efficient, and an outlook on fully integrated high-efficiency 3T and 2T tandem cells is given.« less

  12. Ankyrin 3: genetic association with bipolar disorder and relevance to disease pathophysiology.

    PubMed

    Leussis, Melanie P; Madison, Jon M; Petryshen, Tracey L

    2012-10-01

    Bipolar disorder (BD) is a multi-factorial disorder caused by genetic and environmental influences. It has a large genetic component, with heritability estimated between 59-93%. Recent genome-wide association studies (GWAS) using large BD patient populations have identified a number of genes with strong statistical evidence for association with susceptibility for BD. Among the most significant and replicated genes is ankyrin 3 (ANK3), a large gene that encodes multiple isoforms of the ankyrin G protein. This article reviews the current evidence for genetic association of ANK3 with BD, followed by a comprehensive overview of the known biology of the ankyrin G protein, focusing on its neural functions and their potential relevance to BD. Ankyrin G is a scaffold protein that is known to have many essential functions in the brain, although the mechanism by which it contributes to BD is unknown. These functions include organizational roles for subcellular domains in neurons including the axon initial segment and nodes of Ranvier, through which ankyrin G orchestrates the localization of key ion channels and GABAergic presynaptic terminals, as well as creating a diffusion barrier that limits transport into the axon and helps define axo-dendritic polarity. Ankyrin G is postulated to have similar structural and organizational roles at synaptic terminals. Finally, ankyrin G is implicated in both neurogenesis and neuroprotection. ANK3 and other BD risk genes participate in some of the same biological pathways and neural processes that highlight several mechanisms by which they may contribute to BD pathophysiology. Biological investigation in cellular and animal model systems will be critical for elucidating the mechanism through which ANK3 confers risk of BD. This knowledge is expected to lead to a better understanding of the brain abnormalities contributing to BD symptoms, and to potentially identify new targets for treatment and intervention approaches.

  13. Ulcerative colitis: ultrastructure of interstitial cells in myenteric plexus.

    PubMed

    Rumessen, J J; Vanderwinden, J-M; Horn, T

    2010-10-01

    Interstitial cells of Cajal (ICC) are key regulatory cells in the gut. In the colon of patients with severe ulcerative colitis (UC), myenteric ICC had myoid ultrastructural features and were in close contact with nerve terminals. In all patients as opposed to controls, some ICC profiles showed degenerative changes, such as lipid droplets and irregular vacuoles. Nerve terminals often appeared swollen and empty. Glial cells, muscle cells, and fibroblast-like cells (FLC) showed no alterations. FLC enclosed macrophages (MLC), which were in close contact with naked axon terminals. The organization and cytological changes may be of pathophysiological significance in patients with UC.

  14. The effect of dexamethasone and triiodothyronine on terminal differentiation of primary bovine chondrocytes and chondrogenically differentiated mesenchymal stem cells.

    PubMed

    Randau, Thomas M; Schildberg, Frank A; Alini, Mauro; Wimmer, Matthias D; Haddouti, El-Mustapha; Gravius, Sascha; Ito, Keita; Stoddart, Martin J

    2013-01-01

    The newly evolved field of regenerative medicine is offering solutions in the treatment of bone or cartilage loss and deficiency. Mesenchymal stem cells, as well as articular chondrocytes, are potential cells for the generation of bone or cartilage. The natural mechanism of bone formation is that of endochondral ossification, regulated, among other factors, through the hormones dexamethasone and triiodothyronine. We investigated the effects of these hormones on articular chondrocytes and chondrogenically differentiated mesenchymal stem cells, hypothesizing that these hormones would induce terminal differentiation, with chondrocytes and differentiated stem cells being similar in their response. Using a 3D-alginate cell culture model, bovine chondrocytes and chondrogenically differentiated stem cells were cultured in presence of triiodothyronine or dexamethasone, and cell proliferation and extracellular matrix production were investigated. Collagen mRNA expression was measured by real-time PCR. Col X mRNA and alkaline phosphatase were monitored as markers of terminal differentiation, a prerequisite of endochondral ossification. The alginate culture system worked well, both for the culture of chondrocytes and for the chondrogenic differentiation of mesenchymal stem cells. Dexamethasone led to an increase in glycosaminoglycan production. Triiodothyronine increased the total collagen production only in chondrocytes, where it also induced signs of terminal differentiation, increasing both collagen X mRNA and alkaline phosphatase activity. Dexamethasone induced terminal differentiation in the differentiated stem cells. The immature articular chondrocytes used in this study seem to be able to undergo terminal differentiation, pointing to their possible role in the onset of degenerative osteoarthritis, as well as their potential for a cell source in bone tissue engineering. When chondrocyte-like cells, after their differentiation, can indeed be moved on towards terminal differentiation, they can be used to generate a model of endochondral ossification, but this limitation must be kept in mind when using them in cartilage tissue engineering application.

  15. Terminal addition in a cellular world.

    PubMed

    Torday, J S; Miller, William B

    2018-07-01

    Recent advances in our understanding of evolutionary development permit a reframed appraisal of Terminal Addition as a continuous historical process of cellular-environmental complementarity. Within this frame of reference, evolutionary terminal additions can be identified as environmental induction of episodic adjustments to cell-cell signaling patterns that yield the cellular-molecular pathways that lead to differing developmental forms. Phenotypes derive, thereby, through cellular mutualistic/competitive niche constructions in reciprocating responsiveness to environmental stresses and epigenetic impacts. In such terms, Terminal Addition flows according to a logic of cellular needs confronting environmental challenges over space-time. A reconciliation of evolutionary development and Terminal Addition can be achieved through a combined focus on cell-cell signaling, molecular phylogenies and a broader understanding of epigenetic phenomena among eukaryotic organisms. When understood in this manner, Terminal Addition has an important role in evolutionary development, and chronic disease might be considered as a form of 'reverse evolution' of the self-same processes. Copyright © 2017. Published by Elsevier Ltd.

  16. The terminator mouse: salvation for primary cell culture.

    PubMed

    Kabgani, Nazanin; Moeller, Marcus J

    2013-11-01

    The Terminator had to come back from the future already several times in an effort to bring salvation to mankind. In the present issue of Kidney International, Guo et al. brought us a novel transgenic mouse model: the terminator mouse. This highly elegant mouse may facilitate significantly the derivation of primary cultures of a specific cell type from a tissue containing multiple cell populations.

  17. Immunocytochemical localization of the NMDA-R2A receptor subunit in the cat retina.

    PubMed

    Goebel, D J; Aurelia, J L; Tai, Q; Jojich, L; Poosch, M S

    1998-10-19

    Immunocytochemical studies were performed to determine the distribution and cellular localization of the NMDA-R2A receptor subunit (R2A) in the cat retina. R2A-immunoreactivity (R2A-IR) was noted in all layers of the retina, with specific localizations in the outer segments of red/green and blue cone photoreceptors, B-type horizontal cells, several types of amacrine cells, Müller cells and the majority of cells in the ganglion cell layer. In the inner nuclear layer, 48% of all cells residing in the amacrine cell layer were R2A-IR including a cell resembling the GABAergic A17 amacrine cell. Interestingly, the AII rod amacrine cell was devoid of R2A-IR. Although the localization of the R2A subunit was anticipated in ganglion cells, amacrines and Müller cells, the presence of this receptor subunit to the cells in the outer retina was not expected. Here, both the R2A and the R2B subunits were found to be present in the outer segments of cone photoreceptors and to the tips of rod outer segments. Although the function of these receptor subunits in rod and cone photoreceptors remains to be determined, the fact that both R2A and R2B receptor subunits are localized to cone outer segments suggests a possible alternative pathway for calcium entry into a region where this cation plays such a crucial role in the process of phototransduction. To further classify the cells that display NR2A-IR, we performed dual labeling experiments showing the relationship between R2A-labeled cells with GABA. Results showed that all GABAergic-amacrines and displaced amacrines express the R2A-subunit protein. In addition, approximately 11% of the NR2A-labeled amacrines, did not stain for GABA. These findings support pharmacological data showing that NMDA directly facilitates GABA release in retina and retinal cultures [I.L. Ferreira, C.B. Duarte, P.F. Santos, C.M. Carvalho, A.P. Carvalho, Release of [3H]GABA evoked by glutamate receptor agonist in cultured chick retinal cells: effect of Ca2+, Brain Res. 664 (1994) 252-256; G.D. Zeevalk, W.J. Nicklas, Action of the anti-ischemic agent ifenprodil on N-methyl-d-aspartate and kainate-mediated excitotoxicity, Brain Res. 522 (1990) 135-139; R. Huba, H.D. Hofmann, Transmitter-gated currents of GABAergic amacrine-like cells in chick retinal cultures, Vis. Neurosci. 6 (1991) 303-314; M. Yamashita, R. Huba, H.D. Hofmann, Early in vitro development of voltage- and transmitter-gated currents in GABAergic amacrine cells, Dev. Brain Res. 82 (1994) 95-102; R. Ientile, S. Pedale, V. Picciurro, V. Macaione, C. Fabiano, S. Macaione, Nitric oxide mediates NMDA-evoked [3H]GABA release from chick retina cells, FEBS Lett. 417 (1997) 345-348; R.C. Kubrusly, M.C. deMello, F.G. deMello, Aspartate as a selective NMDA agonist in cultured cells from the avian retina, Neurochem. Intl. 32 (1998) 47-52] or reduction of GABA in vivo [N.N. Osborn, A.J. Herrera, The effect of experimental ischaemia and excitatory amino acid agonist on the GABA and serotonin immunoreactivities in the rabbit retina, Neurosci. 59 (1994) 1071-1081]. Since the majority of GABAergic synapses in the inner retina are onto both rod and cone bipolar axon terminals [R.G. Pourcho, M.T. Owzcarzak, Distribution of GABA immunoreactivity in the cat retina: A light and electron-microscopic study, Vis. Neurosci. 2 (1989) 425-435], we hypothesize that the NMDA-receptor plays a crucial role in providing feedback inhibition onto rod and cone bipolar cells. Copyright 1998 Elsevier Science B.V.

  18. The bHLH transcription factor, hairy, refines the terminal cell fate in the Drosophila embryonic trachea.

    PubMed

    Zhan, Yaoyao; Maung, Saw W; Shao, Bing; Myat, Monn Monn

    2010-11-30

    The pair-rule gene, hairy, encodes a basic helix-loop-helix transcription factor and is required for patterning of the early Drosophila embryo and for morphogenesis of the embryonic salivary gland. Although hairy was shown to be expressed in the tracheal primordia and in surrounding mesoderm, whether hairy plays a role in tracheal development is not known. Here, we report that hairy is required for refining the terminal cell fate in the embryonic trachea and that hairy's tracheal function is distinct from its earlier role in embryonic patterning. In hairy mutant embryos where the repressive activity of hairy is lost due to lack of its co-repressor binding site, extra terminal cells are specified in the dorsal branches. We show that hairy functions in the muscle to refine the terminal cell fate to a single cell at the tip of the dorsal branch by limiting the expression domain of branchless (bnl), encoding the FGF ligand, in surrounding muscle cells. Abnormal activation of the Bnl signaling pathway in hairy mutant tracheal cells is exemplified by increased number of dorsal branch cells expressing Bnl receptor, Breathless (Btl) and Pointed, a downstream target of the Bnl/Btl signaling pathway. We also show that hairy genetically interacts with bnl in TC fate restriction and that overexpression of bnl in a subset of the muscle surrounding tracheal cells phenocopied the hairy mutant phenotype. Our studies demonstrate a novel role for Hairy in restriction of the terminal cell fate by limiting the domain of bnl expression in surrounding muscle cells such that only a single dorsal branch cell becomes specified as a terminal cell. These studies provide the first evidence for Hairy in regulation of the FGF signaling pathway during branching morphogenesis.

  19. Maximizing tandem solar cell power extraction using a three-terminal design

    DOE PAGES

    Warren, Emily L.; Deceglie, Michael G.; Rienacker, Michael; ...

    2018-04-09

    Three-terminal tandem solar cells can provide a robust operating mechanism to efficiently capture the solar spectrum without the need to current match sub-cells or fabricate complicated metal interconnects.

  20. Maximizing tandem solar cell power extraction using a three-terminal design

    DOE PAGES

    Warren, Emily L.; Deceglie, Michael G.; Rienäcker, Michael; ...

    2018-01-01

    Three-terminal tandem solar cells can provide a robust operating mechanism to efficiently capture the solar spectrum without the need to current match sub-cells or fabricate complicated metal interconnects.

  1. The Use of Transcription Terminators to Generate Transgenic Lines of Chinese Hamster Ovary Cells (CHO) with Stable and High Level of Reporter Gene Expression.

    PubMed

    Gasanov, N B; Toshchakov, S V; Georgiev, P G; Maksimenko, O G

    2015-01-01

    Mammalian cell lines are widely used to produce recombinant proteins. Stable transgenic cell lines usually contain many insertions of the expression vector in one genomic region. Transcription through transgene can be one of the reasons for target gene repression after prolonged cultivation of cell lines. In the present work, we used the known transcription terminators from the SV40 virus, as well as the human β- and γ-globin genes, to prevent transcription through transgene. The transcription terminators were shown to increase and stabilize the expression of the EGFP reporter gene in transgenic lines of Chinese hamster ovary (CHO) cells. Hence, transcription terminators can be used to create stable mammalian cells with a high and stable level of recombinant protein production.

  2. Amorphous silicon cell array powered solar tracking apparatus

    DOEpatents

    Hanak, Joseph J.

    1985-01-01

    An array of an even number of amorphous silicon solar cells are serially connected between first and second terminals of opposite polarity. The terminals are connected to one input terminal of a DC motor whose other input terminal is connected to the mid-cell of the serial array. Vane elements are adjacent the end cells to selectively shadow one or the other of the end cells when the array is oriented from a desired attitude relative to the sun. The shadowing of one cell of a group of cells on one side of the mid-cell reduces the power of that group substantially so that full power from the group of cells on the other side of the mid-cell drives the motor to reorient the array to the desired attitude. The cell groups each have a full power output at the power rating of the motor. When the array is at the desired attitude the power output of the two groups of cells balances due to their opposite polarity so that the motor remains unpowered.

  3. Biallelic Mutations in GNB3 Cause a Unique Form of Autosomal-Recessive Congenital Stationary Night Blindness

    PubMed Central

    Vincent, Ajoy; Audo, Isabelle; Tavares, Erika; Maynes, Jason T.; Tumber, Anupreet; Wright, Thomas; Li, Shuning; Michiels, Christelle; Banin, Eyal; Bocquet, Beatrice; De Baere, Elfride; Casteels, Ingele; Defoort-Dhellemmes, Sabine; Drumare, Isabelle; Friedburg, Christoph; Gottlob, Irene; Jacobson, Samuel G.; Kellner, Ulrich; Koenekoop, Robert; Kohl, Susanne; Leroy, Bart P.; Lorenz, Birgit; McLean, Rebecca; Meire, Francoise; Meunier, Isabelle; Munier, Francis; de Ravel, Thomy; Reiff, Charlotte M.; Mohand-Saïd, Saddek; Sharon, Dror; Schorderet, Daniel; Schwartz, Sharon; Zanlonghi, Xavier; Condroyer, Christel; MacDonald, Heather; Verdet, Robert; Sahel, José-Alain; Hamel, Christian P.; Zeitz, Christina; Héon, Elise

    2016-01-01

    Congenital stationary night blindness (CSNB) is a heterogeneous group of non-progressive inherited retinal disorders with characteristic electroretinogram (ERG) abnormalities. Riggs and Schubert-Bornschein are subtypes of CSNB and demonstrate distinct ERG features. Riggs CSNB demonstrates selective rod photoreceptor dysfunction and occurs due to mutations in genes encoding proteins involved in rod phototransduction cascade; night blindness is the only symptom and eye examination is otherwise normal. Schubert-Bornschein CSNB is a consequence of impaired signal transmission between the photoreceptors and bipolar cells. Schubert-Bornschein CSNB is subdivided into complete CSNB with an ON bipolar signaling defect and incomplete CSNB with both ON and OFF pathway involvement. Both subtypes are associated with variable degrees of night blindness or photophobia, reduced visual acuity, high myopia, and nystagmus. Whole-exome sequencing of a family screened negative for mutations in genes associated with CSNB identified biallelic mutations in the guanine nucleotide-binding protein subunit beta-3 gene (GNB3). Two siblings were compound heterozygous for a deletion (c.170_172delAGA [p.Lys57del]) and a nonsense mutation (c.1017G>A [p.Trp339∗]). The maternal aunt was homozygous for the nonsense mutation (c.1017G>A [p.Trp339∗]). Mutational analysis of GNB3 in a cohort of 58 subjects with CSNB identified a sporadic case individual with a homozygous GNB3 mutation (c.200C>T [p.Ser67Phe]). GNB3 encodes the β subunit of G protein heterotrimer (Gαβγ) and is known to modulate ON bipolar cell signaling and cone transducin function in mice. Affected human subjects showed an unusual CSNB phenotype with variable degrees of ON bipolar dysfunction and reduced cone sensitivity. This unique retinal disorder with dual anomaly in visual processing expands our knowledge about retinal signaling. PMID:27063057

  4. Cloning a balanced t(9;11)(p24;q23.1) chromosomal translocation breakpoint segregating with bipolar affective disorder in a small pedigree

    DOE Office of Scientific and Technical Information (OSTI.GOV)

    Duggan, D.J.; Baysal, B.E.; Gollin, S.M.

    A small multigenerational pedigree was previously identified in which a balanced 9;11 chromosomal translocation was cosegregating with bipolar affective disorder. We hypothesize that genes or gene regulatory sequences disrupted by the translocation are contributing to bipolar affective disorder in a dominant fashion. The general strategy involves (1) using somatic cell hybrids containing the derivative 9 or 11 chromosomes to identify the closest chromosome 9 and 11 flanking markers, (2) using the nearest markers as PCR and hybridization probes to isolate both normal DNA (YAC) and patient DNA (cosmid) adjacent to and incorporating the translocation breakpoint, and (3) identifying expressed sequencesmore » in the genomic DNA that may be disrupted by the translocation. From a fusion of the translocation patient cell line and a recipient hamster cell line, somatic cell hybrids were isolated which contain either the human derivative 9 or derivative 11 chromosome. Using PCR-based STS assays with these hybrids, the location of the translocation breakpoint was localized to an estimated 500 kb region at chromosome 11 band q23.1 and a 1 cM region in 9 band p24 (more telomeric than originally reported). From a large set of CEPH and Roswell Park yeast artificial chromosomes (YACs), six chromosome 11 YACs spanning the 11q23.1 breakpoint have now been identified. A combination of pulsed field gel eletrophoresis and YAC mapping has narrowed the chromosome 11 region to less than 430 kb. Current efforts are focused on generating new chromosome 11 probes within the flanking markers, mapping these probes back to the der(9) and der(11) containing hybrids and the chromosome 11 YAC mapping panel. As the region is physically narrowed, we will identify candidate genes whose expression may be altered by this t(9:11) translocation.« less

  5. CENP-W Plays a Role in Maintaining Bipolar Spindle Structure

    PubMed Central

    Kaczmarczyk, Agnieszka; Sullivan, Kevin F.

    2014-01-01

    The CENP-W/T complex was previously reported to be required for mitosis. HeLa cells depleted of CENP-W displayed profound mitotic defects, with mitotic timing delay, disorganized prometaphases and multipolar spindles as major phenotypic consequences. In this study, we examined the process of multipolar spindle formation induced by CENP-W depletion. Depletion of CENP-W in HeLa cells labeled with histone H2B and tubulin fluorescent proteins induced rapid fragmentation of originally bipolar spindles in a high proportion of cells. CENP-W depletion was associated with depletion of Hec1 at kinetochores. The possibility of promiscuous centrosomal duplication was ruled out by immunofluorescent examination of centrioles. However, centrioles were frequently observed to be abnormally split. In addition, a large proportion of the supernumerary poles lacked centrioles, but were positively stained with different centrosomal markers. These observations suggested that perturbation in spindle force distribution caused by defective kinetochores could contribute to a mechanical mechanism for spindle pole disruption. ‘Spindle free’ nocodazole arrested cells did not exhibit pole fragmentation after CENP-W depletion, showing that pole fragmentation is microtubule dependent. Inhibition of centrosome separation by monastrol reduced the incidence of spindle pole fragmentation, indicating that Eg5 plays a role in spindle pole disruption. Surprisingly, CENP-W depletion rescued the monopolar spindle phenotype of monastrol treatment, with an increased frequency of bipolar spindles observed after CENP-W RNAi. We overexpressed the microtubule cross-linking protein TPX2 to create spindle poles stabilized by the microtubule cross-linking activity of TPX2. Spindle pole fragmentation was suppressed in a TPX2-dependent fashion. We propose that CENP-W, by influencing proper kinetochore assembly, particularly microtubule docking sites, can confer spindle pole resistance to traction forces exerted by motor proteins during chromosome congression. Taken together, our findings are consistent with a model in which centrosome integrity is controlled by the pathways regulating kinetochore-microtubule attachment stability. PMID:25329824

  6. Optimization of an integrated electrodisinfection/electrocoagulation process with Al bipolar electrodes for urban wastewater reclamation.

    PubMed

    Cotillas, Salvador; Llanos, Javier; Cañizares, Pablo; Mateo, Sara; Rodrigo, Manuel A

    2013-04-01

    In this work, a novel integrated electrochemical process for urban wastewater regeneration is described. The electrochemical cell consists in a Boron Doped Diamond (BDD) or a Dimensionally Stable Anode (DSA) as anode, a Stainless Steel (SS) as cathode and a perforated aluminum plate, which behaves as bipolar electrode, between anode and cathode. Thus, in this cell, it is possible to carry out, at the same time, two different electrochemical processes: electrodisinfection (ED) and electrocoagulation (EC). The treatment of urban wastewater with different anodes and different operating conditions is studied. First of all, in order to check the process performance, experiments with synthetic wastewaters were carried out, showing that it is possible to achieve a 100% of turbidity removal by the electrodissolution of the bipolar electrode. Next, the effect of the current density and the anode material are studied during the ED-EC process of actual effluents. Results show that it is possible to remove Escherichia coli and turbidity simultaneously of an actual effluent from a WasteWater Treatment Facility (WWTF). The use of BDD anodes allows to remove the E. coli completely at an applied electric charge of 0.0077 A h dm(-3) when working with a current density of 6.65 A m(-2). On the other hand, with DSA anodes, the current density necessary to achieve the total removal of E. coli is higher (11.12 A m(-2)) than that required with BDD anodes. Finally, the influence of cell flow path and flow rate have been studied. Results show that the performance of the process strongly depends on the characteristics of the initial effluent (E. coli concentration and Cl(-)/NH(4)(+) initial ratio) and that a cell configuration cathode (inlet)-anode (outlet) and a higher flow rate enhance the removal of the turbidity from the treated effluent. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Afferent innervation of the utricular macula in pigeons

    NASA Technical Reports Server (NTRS)

    Si, Xiaohong; Zakir, Mridha Md; Dickman, J. David

    2003-01-01

    Biotinylated dextran amine (BDA) was used to retrogradely label afferents innervating the utricular macula in adult pigeons. The pigeon utriclar macula consists of a large rectangular-shaped neuroepithelium with a dorsally curved anterior edge and an extended medioposterior tail. The macula could be demarcated into several regions based on cytoarchitectural differences. The striola occupied 30% of the macula and contained a large density of type I hair cells with fewer type II hair cells. Medial and lateral extrastriola zones were located outside the striola and contained only type II hair cells. A six- to eight-cell-wide band of type II hair cells existed near the center of the striola. The reversal line marked by the morphological polarization of hair cells coursed throughout the epithelium, near the peripheral margin, and through the center of the type II band. Calyx afferents innervated type I hair cells with calyceal terminals that contained between 2 and 15 receptor cells. Calyx afferents were located only in the striola region, exclusive of the type II band, had small total fiber innervation areas and low innervation densities. Dimorph afferents innervated both type I and type II hair cells with calyceal and bouton terminals and were primarily located in the striola region. Dimorph afferents had smaller calyceal terminals with few type I hair cells, extended fiber branches with bouton terminals and larger innervation areas. Bouton afferents innervated only type II hair cells in the extrastriola and type II band regions. Bouton afferents innervating the type II band had smaller terminal fields with fewer bouton terminals and smaller innervation areas than fibers located in the extrastriolar zones. Bouton afferents had the most bouton terminals on the longest fibers, the largest innervation areas with the highest innervation densities of all afferents. Among all afferents, smaller terminal innervation fields were observed in the striola and large fields were located in the extrastriola. The cellular organization and innervation patterns of the utricular maculae in birds appear to represent an organ in adaptive evolution, different from that observed for amphibians or mammals.

  8. Development of Bipolar All-solid-state Lithium Battery Based on Quasi-solid-state Electrolyte Containing Tetraglyme-LiTFSA Equimolar Complex

    PubMed Central

    Gambe, Yoshiyuki; Sun, Yan; Honma, Itaru

    2015-01-01

    The development of high energy–density lithium-ion secondary batteries as storage batteries in vehicles is attracting increasing attention. In this study, high-voltage bipolar stacked batteries with a quasi-solid-state electrolyte containing a Li-Glyme complex were prepared, and the performance of the device was evaluated. Via the successful production of double-layered and triple-layered high-voltage devices, it was confirmed that these stacked batteries operated properly without any internal short-circuits of a single cell within the package: Their plateau potentials (6.7 and 10.0 V, respectively) were two and three times that (3.4 V) of the single-layered device, respectively. Further, the double-layered device showed a capacity retention of 99% on the 200th cycle at 0.5 C, which is an indication of good cycling properties. These results suggest that bipolar stacked batteries with a quasi-solid-state electrolyte containing a Li-Glyme complex could readily produce a high voltage of 10 V. PMID:25746860

  9. Intra-spindle Microtubule Assembly Regulates Clustering of Microtubule-Organizing Centers during Early Mouse Development.

    PubMed

    Watanabe, Sadanori; Shioi, Go; Furuta, Yasuhide; Goshima, Gohta

    2016-04-05

    Errors during cell division in oocytes and early embryos are linked to birth defects in mammals. Bipolar spindle assembly in early mouse embryos is unique in that three or more acentriolar microtubule-organizing centers (MTOCs) are initially formed and are then clustered into two spindle poles. Using a knockout mouse and live imaging of spindles in embryos, we demonstrate that MTOC clustering during the blastocyst stage requires augmin, a critical complex for MT-dependent MT nucleation within the spindle. Functional analyses in cultured cells with artificially increased numbers of centrosomes indicate that the lack of intra-spindle MT nucleation, but not loss of augmin per se or overall reduction of spindle MTs, is the cause of clustering failure. These data suggest that onset of mitosis with three or more MTOCs is turned into a typical bipolar division through augmin-dependent intra-spindle MT assembly. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  10. Thermal conductivity of a graphite bipolar plate (BPP) and its thermal contact resistance with fuel cell gas diffusion layers: Effect of compression, PTFE, micro porous layer (MPL), BPP out-of-flatness and cyclic load

    NASA Astrophysics Data System (ADS)

    Sadeghifar, Hamidreza; Djilali, Ned; Bahrami, Majid

    2015-01-01

    This paper reports on measurements of thermal conductivity of a graphite bipolar plate (BPP) as a function of temperature and its thermal contact resistance (TCR) with treated and untreated gas diffusion layers (GDLs). The thermal conductivity of the BPP decreases with temperature and its thermal contact resistance with GDLs, which has been overlooked in the literature, is found to be dominant over a relatively wide range of compression. The effects of PTFE loading, micro porous layer (MPL), compression, and BPP out-of-flatness are also investigated experimentally. It is found that high PTFE loadings, MPL and even small BPP out-of-flatness increase the BPP-GDL thermal contact resistance dramatically. The paper also presents the effect of cyclic load on the total resistance of a GDL-BPP assembly, which sheds light on the behavior of these materials under operating conditions in polymer electrolyte membrane fuel cells.

  11. Fabrication of gas impervious edge seal for a bipolar gas distribution assembly for use in a fuel cell

    DOEpatents

    Kaufman, Arthur; Werth, John

    1986-01-01

    A bipolar gas reactant distribution assembly for use in a fuel cell is disclosed, the assembly having a solid edge seal to prevent leakage of gaseous reactants wherein a pair of porous plates are provided with peripheral slits generally parallel to, and spaced apart from two edges of the plate, the slit being filled with a solid, fusible, gas impervious edge sealing compound. The plates are assembled with opposite faces adjacent one another with a layer of a fusible sealant material therebetween the slits in the individual plates being approximately perpendicular to one another. The plates are bonded to each other by the simultaneous application of heat and pressure to cause a redistribution of the sealant into the pores of the adjacent plate surfaces and to cause the edge sealing compound to flow and impregnate the region of the plates adjacent the slits and comingle with the sealant layer material to form a continuous layer of sealant along the edges of the assembled plates.

  12. Osteogenic cell differentiation on H-terminated and O-terminated nanocrystalline diamond films

    PubMed Central

    Liskova, Jana; Babchenko, Oleg; Varga, Marian; Kromka, Alexander; Hadraba, Daniel; Svindrych, Zdenek; Burdikova, Zuzana; Bacakova, Lucie

    2015-01-01

    Nanocrystalline diamond (NCD) films are promising materials for bone implant coatings because of their biocompatibility, chemical resistance, and mechanical hardness. Moreover, NCD wettability can be tailored by grafting specific atoms. The NCD films used in this study were grown on silicon substrates by microwave plasma-enhanced chemical vapor deposition and grafted by hydrogen atoms (H-termination) or oxygen atoms (O-termination). Human osteoblast-like Saos-2 cells were used for biological studies on H-terminated and O-terminated NCD films. The adhesion, growth, and subsequent differentiation of the osteoblasts on NCD films were examined, and the extracellular matrix production and composition were quantified. The osteoblasts that had been cultivated on the O-terminated NCD films exhibited a higher growth rate than those grown on the H-terminated NCD films. The mature collagen fibers were detected in Saos-2 cells on both the H-terminated and O-terminated NCD films; however, the quantity of total collagen in the extracellular matrix was higher on the O-terminated NCD films, as were the amounts of calcium deposition and alkaline phosphatase activity. Nevertheless, the expression of genes for osteogenic markers – type I collagen, alkaline phosphatase, and osteocalcin – was either comparable on the H-terminated and O-terminated films or even lower on the O-terminated films. In conclusion, the higher wettability of the O-terminated NCD films is promising for adhesion and growth of osteoblasts. In addition, the O-terminated surface also seems to support the deposition of extracellular matrix proteins and extracellular matrix mineralization, and this is promising for better osteoconductivity of potential bone implant coatings. PMID:25670900

  13. Thwarted interpersonal needs and suicide ideation: Comparing psychiatric inpatients with bipolar and non-bipolar mood disorders.

    PubMed

    Taylor, Nathanael J; Mitchell, Sean M; Roush, Jared F; Brown, Sarah L; Jahn, Danielle R; Cukrowicz, Kelly C

    2016-12-30

    Psychiatric inpatients are at heightened risk for suicide, and evidence suggests that psychiatric inpatients with bipolar mood disorders may be at greater risk for suicide ideation compared to those with non-bipolar mood disorders. There is a paucity of research directly comparing risk factors for suicide ideation in bipolar versus non-bipolar mood disorders in an inpatient sample. The current study sought to clarify the association between two constructs from the interpersonal theory of suicide (i.e., perceived burdensomeness and thwarted belongingness) in leading to suicide ideation among psychiatric inpatients with bipolar and non-bipolar mood disorders. Participants were (N=90) psychiatric inpatients with a bipolar (n = 20) or non-bipolar mood disorder (n=70; per their medical charts). Perceived burdensomeness, but not thwarted belongingness, was significantly associated with suicide ideation after adjusting for other covariates. This suggests perceived burdensomeness may play a key role in suicide ideation among psychiatric inpatients with any mood disorder and highlights the importance of assessment and intervention of perceived burdensomeness in this population. Contrary to our hypothesis, mood disorder group (i.e., bipolar versus non-bipolar) did not moderate the relations between perceived burdensomeness/thwarted belongingness and suicide ideation. Published by Elsevier Ireland Ltd.

  14. Hypnotic susceptibility and affective states in bipolar I and II disorders.

    PubMed

    Zhang, Bingren; Wang, Jiawei; Zhu, Qisha; Ma, Guorong; Shen, Chanchan; Fan, Hongying; Wang, Wei

    2017-11-09

    Highly hypnotizable individuals have impaired executive function, elevated motor impulsivity and increased emotional sensitivity, which are sometimes found in bipolar disorder patients. It is then reasonable to assume that certain aspects of hypnotic susceptibility differ with the types of bipolar disorder. The Stanford Hypnotic Susceptibility Scale: Form C (SHSS:C) test, the Mood Disorder Questionnaire (MDQ), the Hypomanic Checklist-32 (HCL-32) and the Plutchick-van Praag Depression Inventory (PVP) were applied to 62 patients with bipolar I disorder, 33 bipolar II disorder, and 120 healthy volunteers. The passing rate of the SHSS:C 'Moving hands apart' item was higher in bipolar I patients than in controls, whereas for 'Mosquito hallucination' the rate was lower. Bipolar I and II patients scored significantly higher on MDQ, HCL-32 and PVP scales than controls. The passing rates of 'Mosquito hallucination' in controls, 'Arm rigidity' in bipolar I, and 'Age regression' in bipolar II predicted the respective MDQ scores. In contrast to cognitive suggestions, bipolar I patients followed motor suggestions more often under hypnosis. Furthermore, both bipolar disorder patients and healthy volunteers demonstrated associations between mania levels and certain hypnotic susceptibility features. Our study aids in better understanding the altered conscious states in bipolar disorders, and encourages the use of related psychotherapy for these patients.

  15. Where is the spike generator of the cochlear nerve? Voltage-gated sodium channels in the mouse cochlea.

    PubMed

    Hossain, Waheeda A; Antic, Srdjan D; Yang, Yang; Rasband, Matthew N; Morest, D Kent

    2005-07-20

    The origin of the action potential in the cochlea has been a long-standing puzzle. Because voltage-dependent Na+ (Nav) channels are essential for action potential generation, we investigated the detailed distribution of Nav1.6 and Nav1.2 in the cochlear ganglion, cochlear nerve, and organ of Corti, including the type I and type II ganglion cells. In most type I ganglion cells, Nav1.6 was present at the first nodes flanking the myelinated bipolar cell body and at subsequent nodes of Ranvier. In the other ganglion cells, including type II, Nav1.6 clustered in the initial segments of both of the axons that flank the unmyelinated bipolar ganglion cell bodies. In the organ of Corti, Nav1.6 was localized in the short segments of the afferent axons and their sensory endings beneath each inner hair cell. Surprisingly, the outer spiral fibers and their sensory endings were well labeled beneath the outer hair cells over their entire trajectory. In contrast, Nav1.2 in the organ of Corti was localized to the unmyelinated efferent axons and their endings on the inner and outer hair cells. We present a computational model illustrating the potential role of the Nav channel distribution described here. In the deaf mutant quivering mouse, the localization of Nav1.6 was disrupted in the sensory epithelium and ganglion. Together, these results suggest that distinct Nav channels generate and regenerate action potentials at multiple sites along the cochlear ganglion cells and nerve fibers, including the afferent endings, ganglionic initial segments, and nodes of Ranvier.

  16. Risk of sexual transmitted infection following bipolar disorder: a nationwide population-based cohort study.

    PubMed

    Lee, Shyh-Chyang; Hu, Chang-Kuo; Hung, Jeng-Hsiu; Yang, Albert C; Tsai, Shih-Jen; Huang, Min-Wei; Hu, Li-Yu; Shen, Cheng-Che

    2018-04-03

    Bipolar disorder is a severe mental disorder associated with functional and cognitive impairment. Numerous studies have investigated associations between sexually transmitted infections (STIs) and psychiatric illnesses. However, the results of these studies are controversial. We explored the association between bipolar disorder and the subsequent development of STIs, including human immunodeficiency virus infection; primary, secondary, and latent syphilis; genital warts; gonorrhea; chlamydial infection; and trichomoniasis. The bipolar cohort consisted of 1293 patients, and the comparison cohort consisted of 5172 matched control subjects without bipolar disorder. The incidence of subsequent STIs (hazard ratio (HR) = 2.23, 95% confidence interval (CI) 1.68-2.96) was higher among the patients with bipolar disorder than in the comparison cohort. Furthermore, female gender is a risk factor for acquisition of STIs (HR = 2.36, 95% CI 1.73-4.89) among patients with bipolar disorder. For individual STIs, the results indicated that the patients with bipolar disorder exhibited a markedly higher risk for subsequently contracting syphilis, genital warts, and trichomoniasis. Bipolar disorder might increase the risk of subsequent newly diagnosed STIs, including syphilis, genital warts, and trichomoniasis. Clinicians should pay particular attention to STIs in patients with bipolar disorder. Patients with bipolar disorder, especially those with a history of high-risk sexual behaviors, should be routinely screened for STIs. We identified patients who were diagnosed with bipolar disorder in the Taiwan National Health Insurance Research Database. A comparison cohort was constructed of patients without bipolar disorder who were matched with the bipolar cohort according to age and gender. The occurrence of subsequent new-onset STIs was evaluated in both cohorts.

  17. Patients With Co-Occurring Bipolar Disorder and Posttraumatic Stress Disorder: A Rapid Review of the Literature.

    PubMed

    Cerimele, Joseph M; Bauer, Amy M; Fortney, John C; Bauer, Mark S

    2017-05-01

    To summarize the current literature on epidemiology, clinical correlates, and treatment of individuals with co-occurring bipolar disorder and posttraumatic stress disorder (PTSD). We conducted a focused, time-sensitive review called "rapid review" in November 2015, using keyword searches (including keywords bipolar disorder, post-traumatic stress disorder, PTSD, and others) in PubMed for studies of adults with co-occurring bipolar disorder and PTSD. Results were sorted and systematically searched. An article was excluded if it did not describe adult patients with co-occurring PTSD and bipolar disorder or did not report original data on epidemiology, clinical correlates, or treatment. Information on study characteristics including population studied and key findings were extracted onto a data collection tool. Thirty-two articles were included. Over two-thirds of articles reported epidemiology of co-occurring bipolar disorder and PTSD. Prevalence of PTSD among individuals with bipolar disorder ranged from 4% to 40%, with women and those with bipolar I versus bipolar II disorder experiencing higher prevalence of PTSD. Prevalence of bipolar disorder among individuals with PTSD ranged from 6% to 55%. Baseline PTSD or bipolar disorder was associated with incidence of the other illness. Individuals with co-occurring bipolar disorder and PTSD experienced high symptom burden and low quality of life. No studies evaluated prospective treatment of patients with co-occurring bipolar disorder and PTSD. Bipolar disorder and PTSD commonly co-occur and result in greater symptom burden than either condition alone. Few published treatment strategies exist for patients with both conditions. © Copyright 2017 Physicians Postgraduate Press, Inc.

  18. Bariatric surgery in patients with bipolar spectrum disorders: Selection factors, post-operative visit attendance, and weight outcomes

    PubMed Central

    Friedman, Kelli E.; Applegate, Katherine; Portenier, Dana; McVay, Megan

    2017-01-01

    Background As many of 3% of bariatric surgery candidates are diagnosed with a bipolar spectrum disorder. Objectives 1) To describe differences between patients with bipolar spectrum disorders who are approved and not approved for surgery by the mental health evaluator. 2) To examine surgical outcomes of patients with bipolar spectrum disorders. Setting Academic medical center, United States. Methods A retrospective record review was conducted of consecutive patients who applied for bariatric surgery between 2004 and 2009. Patients diagnosed with bipolar spectrum disorders who were approved for surgery (n=42) were compared with patients with a bipolar spectrum disorder who were not approved (n=31) and to matched control surgical patients without a bipolar spectrum diagnosis (n=29) on a variety of characteristics and surgical outcomes. Results Of bariatric surgery candidates diagnosed with a bipolar spectrum disorder who applied for surgery, 57% were approved by the psychologist and 48% ultimately had surgery. Patients with a bipolar spectrum disorder who were approved for surgery were less likely to have had a previous psychiatric hospitalizations than those who were not approved for surgery. Bariatric surgery patients diagnosed with a bipolar spectrum disorder were less likely to attend follow-up care appointments 2 or more years post-surgery compared to matched patients without bipolar disorder. Among patients with available data, those with a bipolar spectrum disorder and matched patients had similar weight loss at 12 months (n=21 for bipolar, n=24 for matched controls) and at 2 or more years (mean=51 months; n=11 for bipolar, n=20 for matched controls). Conclusions Patients diagnosed with a bipolar spectrum disorder have a high rate of delay/denial for bariatric surgery based on the psychosocial evaluation and are less likely to attend medical follow-up care 2 or more years post-surgery. Carefully screened patients with bipolar disorder who engage in long-term follow-up care may benefit from bariatric surgery. PMID:28169206

  19. Bipolar Disorder - Multiple Languages

    MedlinePlus

    ... Russian (Русский) Expand Section Bipolar Disorder (An Introduction) - English PDF Bipolar Disorder (An Introduction) - Русский (Russian) PDF Bipolar Disorder (An Introduction) - English MP3 Bipolar Disorder (An Introduction) - Русский (Russian) MP3 ...

  20. Discovery of a novel inhibitor of kinesin-like protein KIFC1.

    PubMed

    Zhang, Wei; Zhai, Ling; Wang, Yimin; Boohaker, Rebecca J; Lu, Wenyan; Gupta, Vandana V; Padmalayam, Indira; Bostwick, Robert J; White, E Lucile; Ross, Larry J; Maddry, Joseph; Ananthan, Subramaniam; Augelli-Szafran, Corinne E; Suto, Mark J; Xu, Bo; Li, Rongbao; Li, Yonghe

    2016-04-15

    Historically, drugs used in the treatment of cancers also tend to cause damage to healthy cells while affecting cancer cells. Therefore, the identification of novel agents that act specifically against cancer cells remains a high priority in the search for new therapies. In contrast with normal cells, most cancer cells contain multiple centrosomes which are associated with genome instability and tumorigenesis. Cancer cells can avoid multipolar mitosis, which can cause cell death, by clustering the extra centrosomes into two spindle poles, thereby enabling bipolar division. Kinesin-like protein KIFC1 plays a critical role in centrosome clustering in cancer cells, but is not essential for normal cells. Therefore, targeting KIFC1 may provide novel insight into selective killing of cancer cells. In the present study, we identified a small-molecule KIFC1 inhibitor, SR31527, which inhibited microtubule (MT)-stimulated KIFC1 ATPase activity with an IC50 value of 6.6 μM. By using bio layer interferometry technology, we further demonstrated that SR31527 bound directly to KIFC1 with high affinity (Kd=25.4 nM). Our results from computational modelling and saturation-transfer difference (STD)-NMR experiments suggest that SR31527 bound to a novel allosteric site of KIFC1 that appears suitable for developing selective inhibitors of KIFC1. Importantly, SR31527 prevented bipolar clustering of extra centrosomes in triple negative breast cancer (TNBC) cells and significantly reduced TNBC cell colony formation and viability, but was less toxic to normal fibroblasts. Therefore, SR31527 provides a valuable tool for studying the biological function of KIFC1 and serves as a potential lead for the development of novel therapeutic agents for breast cancer treatment. © 2016 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  1. Changes in optical properties of electroporated cells as revealed by digital holographic microscopy

    PubMed Central

    Calin, Violeta L.; Mihailescu, Mona; Mihale, Nicolae; Baluta, Alexandra V.; Kovacs, Eugenia; Savopol, Tudor; Moisescu, Mihaela G.

    2017-01-01

    Changes in optical and shape-related characteristics of B16F10 cells after electroporation were investigated using digital holographic microscopy (DHM). Bipolar rectangular pulses specific for electrochemotherapy were used. Electroporation was performed in an “off-axis” DHM set-up without using exogenous markers. Two types of cell parameters were monitored seconds and minutes after pulse train application: parameters addressing a specifically defined area of the cell (refractive index and cell height) and global cell parameters (projected area, optical phase shift profile and dry mass). The biphasic behavior of cellular parameters was explained by water and mannitol dynamics through the electropermeabilized cell membrane. PMID:28736667

  2. Photostable bipolar fluorescent probe for video tracking plasma membranes related cellular processes.

    PubMed

    Zhang, Xinfu; Wang, Chao; Jin, Liji; Han, Zhuo; Xiao, Yi

    2014-08-13

    Plasma membranes can sense the stimulations and transmit the signals from extracellular environment and then make further responses through changes in locations, shapes or morphologies. Common fluorescent membrane markers are not well suited for long time tracking due to their shorter retention time inside plasma membranes and/or their lower photostability. To this end, we develop a new bipolar marker, Mem-SQAC, which can stably insert into plasma membranes of different cells and exhibits a long retention time over 30 min. Mem-SQAC also inherits excellent photostability from the BODIPY dye family. Large two-photon absorption cross sections and long wavelength fluorescence emissions further enhance the competitiveness of Mem-SQAC as a membrane marker. By using Mem-SQAC, significant morphological changes of plasma membranes have been monitored during heavy metal poisoning and drug induced apoptosis of MCF-7 cells; the change tendencies are so distinctly different from each other that they can be used as indicators to distinguish different cell injuries. Further on, the complete processes of endocytosis toward Staphylococcus aureus and Escherichia coli by RAW 264.7 cells have been dynamically tracked. It is discovered that plasma membranes take quite different actions in response to the two bacteria, information unavailable in previous research reports.

  3. Homeostatic Plasticity Mediated by Rod-Cone Gap Junction Coupling in Retinal Degenerative Dystrophic RCS Rats

    PubMed Central

    Hou, Baoke; Fu, Yan; Weng, Chuanhuang; Liu, Weiping; Zhao, Congjian; Yin, Zheng Qin

    2017-01-01

    Rod-cone gap junctions open at night to allow rod signals to pass to cones and activate the cone-bipolar pathway. This enhances the ability to detect large, dim objects at night. This electrical synaptic switch is governed by the circadian clock and represents a novel form of homeostatic plasticity that regulates retinal excitability according to network activity. We used tracer labeling and ERG recording in the retinae of control and retinal degenerative dystrophic RCS rats. We found that in the control animals, rod-cone gap junction coupling was regulated by the circadian clock via the modulation of the phosphorylation of the melatonin synthetic enzyme arylalkylamine N-acetyltransferase (AANAT). However, in dystrophic RCS rats, AANAT was constitutively phosphorylated, causing rod-cone gap junctions to remain open. A further b/a-wave ratio analysis revealed that dystrophic RCS rats had stronger synaptic strength between photoreceptors and bipolar cells, possibly because rod-cone gap junctions remained open. This was despite the fact that a decrease was observed in the amplitude of both a- and b-waves as a result of the progressive loss of rods during early degenerative stages. These results suggest that electric synaptic strength is increased during the day to allow cone signals to pass to the remaining rods and to be propagated to rod bipolar cells, thereby partially compensating for the weak visual input caused by the loss of rods. PMID:28473754

  4. Central projections of the lateral line and eighth nerves in the bowfin, Amia calva.

    PubMed

    McCormick, C A

    1981-03-20

    The first-order connections of the anterior and posterior lateral line nerves and of the eighth nerve were determined in the bowfin, Amia calva, using experimental degeneration and anterograde HRP transport techniques. The termination sites of these nerves define a dorsal lateralis cell column and a ventral octavus cell column. The anterior and posterior lateralis nerves distribute ipsilaterally to two medullary nuclei-nucleus medialis and nucleus caudalis. Nucleus medialis comprises the rostral two-thirds of the lateralis column and contains large, Purkinje-like cells dorsally and polygonal, granule, and fusiform cells ventrally. Nucleus caudalis is located posterior to nucleus medialis and consists of small, granule cells. Anterior lateralis fibers terminate ventrally to ventromedially in both nucleus medialis and nucleus caudalis. Posterior lateralis fibers terminate dorsally to dorsolaterally within these two nuclei. A sparse anterior lateralis input may also be present on the dendrites of one of the nuclei within the octavus cell column, nucleus magnocellularis. In contrast, the anterior and posterior rami of the eighth nerve each terminate within four medullary nuclei which comprise the octavus cell column: the anterior, magnocellular, descending, and posterior octavus nuclei. An eighth nerve projection to the medial reticular formation is also present. Some fibers of the lateralis and eighth nerves terminate within the ipsilateral eminentia granularis of the cerebellum. Lateralis fibers distribute to approximately the lateral half of this structure with posterior lateral line fibers terminating laterally and anterior lateral line fibers terminating medially. Eighth nerve fibers distribute to the medial half of the eminentia granularis.

  5. Method for forming a cell separator for use in bipolar-stack energy storage devices

    DOEpatents

    Mayer, Steven T.; Feikert, John H.; Kaschmitter, James L.; Pekala, Richard W.

    1994-01-01

    An improved multi-cell electrochemical energy storage device, such as a battery, fuel cell, or double layer capacitor using a cell separator which allows cells to be stacked and interconnected with low electrical resistance and high reliability while maximizing packaging efficiency. By adding repeating cells, higher voltages can be obtained. The cell separator is formed by applying an organic adhesive on opposing surfaces of adjacent carbon electrodes or surfaces of aerogel electrodes of a pair of adjacent cells prior to or after pyrolysis thereof to form carbon aerogel electrodes. The cell separator is electronically conductive, but ionically isolating, preventing an electrolytic conduction path between adjacent cells in the stack.

  6. Cell separator for use in bipolar-stack energy storage devices

    DOEpatents

    Mayer, S.T.; Feikert, J.H.; Kachmitter, J.L.; Pekala, R.W.

    1995-02-28

    An improved multi-cell electrochemical energy storage device is described, such as a battery, fuel cell, or double layer capacitor using a cell separator which allows cells to be stacked and interconnected with low electrical resistance and high reliability while maximizing packaging efficiency. By adding repeating cells, higher voltages can be obtained. The cell separator is formed by applying an organic adhesive on opposing surfaces of adjacent carbon electrodes or surfaces of aerogel electrodes of a pair of adjacent cells prior to or after pyrolysis thereof to form carbon aerogel electrodes. The cell separator is electronically conductive, but ionically isolating, preventing an electrolytic conduction path between adjacent cells in the stack. 2 figs.

  7. Method for forming a cell separator for use in bipolar-stack energy storage devices

    DOEpatents

    Mayer, S.T.; Feikert, J.H.; Kaschmitter, J.L.; Pekala, R.W.

    1994-08-09

    An improved multi-cell electrochemical energy storage device, such as a battery, fuel cell, or double layer capacitor using a cell separator which allows cells to be stacked and interconnected with low electrical resistance and high reliability while maximizing packaging efficiency. By adding repeating cells, higher voltages can be obtained. The cell separator is formed by applying an organic adhesive on opposing surfaces of adjacent carbon electrodes or surfaces of aerogel electrodes of a pair of adjacent cells prior to or after pyrolysis thereof to form carbon aerogel electrodes. The cell separator is electronically conductive, but ionically isolating, preventing an electrolytic conduction path between adjacent cells in the stack. 2 figs.

  8. Meta-Analysis of Amygdala Volumes in Children and Adolescents with Bipolar Disorder

    ERIC Educational Resources Information Center

    Pfeifer, Jonathan C.; Welge, Jeffrey; Strakowski. Stephen M.; Adler, Caleb M.; Delbello, Melissa P.

    2008-01-01

    The size of amygdala of bipolar youths and adults is investigated using neuroimaging studies. Findings showed that smaller volumes of amygdala were observed in youths with bipolar youths compared with children and adolescents without bipolar disorder. The structural amygdala abnormalities in bipolar youths are examined further.

  9. The relationship between borderline personality disorder and bipolar disorder

    PubMed Central

    Zimmerman, Mark; Morgan, Theresa A.

    2013-01-01

    It is clinically important to recognize both bipolar disorder and borderline personality disorder (BPD) in patients seeking treatment for depression, and it is important to distinguish between the two. Research considering whether BPD should be considered part of a bipolar spectrum reaches differing conclusions. We reviewed the most studied question on the relationship between BPD and bipolar disorder: their diagnostic concordance. Across studies, approximately 10% of patients with BPD had bipolar I disorder and another 10% had bipolar II disorder. Likewise, approximately 20% of bipolar II patients were diagnosed with BPD, though only 10% of bipolar I patients were diagnosed with BPD. While the comorbidity rates are substantial, each disorder is nontheless diagnosed in the absence of the other in the vast majority of cases (80% to 90%). In studies examining personality disorders broadly, other personality disorders were more commonly diagnosed in bipolar patients than was BPD. Likewise, the converse is also true: other axis I disorders such as major depression, substance abuse, and post-traumatic stress disorder are also more commonly diagnosed in patients with BPD than is bipolar disorder. These findings challenge the notion that BPD is part of the bipolar spectrum. PMID:24174890

  10. Emotion in Bipolar I Disorder: Implications for Functional and Symptom Outcomes

    PubMed Central

    Johnson, Sheri L.; Tharp, Jordan A.; Peckham, Andrew D.; McMaster, Kaja J.

    2015-01-01

    Despite the centrality of emotion disturbance in neurobiological models of bipolar disorder, the behavioral literature has not yet clearly identified the most central aspects of emotion disturbance in bipolar disorder. Toward this aim, we gathered a battery of emotion-related measures in 67 persons diagnosed with bipolar I disorder as assessed with SCID and a well-matched control group of 58 persons without a history of mood disorders. Those with bipolar disorder were interviewed monthly until they achieved remission, and then tested on emotion measures. A subset of 36 participants with bipolar disorder completed symptom severity interviews at 12-month follow-up. Factor analyses indicated four emotion factor scores: Negative Emotion, Positive Emotion, Reappraisal and Suppression. Bivariate analyses suggested that bipolar disorder was tied to a host of emotion disturbances, but multivariate analyses suggested that bipolar disorder was particularly tied to elevations of Negative Emotion. High Negative Emotion, low Positive Emotion, and high Suppression were conjointly related to lower functioning. Reappraisal predicted declines in depression over time for those with bipolar disorder. Findings highlight the importance of considering the overall profile of emotion disturbance in bipolar disorder. Emotion and emotion regulation appear central to a broad range of outcomes in bipolar disorder. PMID:26480234

  11. Toward the definition of a bipolar prodrome: Dimensional predictors of bipolar spectrum disorder in at-risk youth

    PubMed Central

    Hafeman, Danella M.; Merranko, John; Axelson, David; Goldstein, Benjamin I.; Goldstein, Tina; Monk, Kelly; Hickey, Mary Beth; Sakolsky, Dara; Diler, Rasim; Iyengar, Satish; Brent, David; Kupfer, David; Birmaher, Boris

    2016-01-01

    Objective We aimed to assess dimensional symptomatic predictors of new-onset bipolar spectrum disorder in youth at familial risk of bipolar disorder (“at-risk” youth). Method Offspring aged 6–18 of parents with bipolar-I/II disorder (n=391) and offspring of community controls (n=248) were recruited without regard to non-bipolar psychopathology. At baseline, 8.4% (33/391) of offspring of bipolar parents had bipolar spectrum; 14.7% (44/299) of offspring with follow-up developed new-onset bipolar spectrum (15 with bipolar-I/II) over eight years. Scales collected at baseline and follow-up were reduced using factor analyses; factors (both at baseline and visit proximal to conversion or last contact) were then assessed as predictors of new-onset bipolar spectrum. Results Relative to community control offspring, at-risk and bipolar offspring had higher baseline levels of anxiety/depression, inattention/disinhibition, externalizing, subsydromal manic, and affective lability symptoms (p<.05). The strongest predictors of new-onset bipolar spectrum were: baseline anxiety/depression, baseline and proximal affective lability, and proximal subsyndromal manic symptoms (p<.05). While affective lability and anxiety/depression were elevated throughout follow-up in those who later developed bipolar spectrum, manic symptoms increased up to the point of conversion. A path analysis supported the hypothesized model that affective lability at baseline predicted new-onset bipolar spectrum, in part, through increased manic symptoms at the visit prior to conversion; earlier parental age of mood disorder onset also significantly increased risk of conversion (p<.001). While youth without anxiety/depression, affective lability, and mania (and with a parent with older age of mood disorder onset) had a 2% predicted chance of conversion to bipolar spectrum, those with all risk factors had a 49% predicted chance of conversion. Conclusions Dimensional measures of anxiety/depression, affective lability, and mania are important predictors of new-onset bipolar spectrum in this population of at-risk youth. These symptoms emerged from among numerous other candidates, underscoring the potential clinical and research utility of these findings. PMID:26892940

  12. Technical Note: Interleaved Bipolar Acquisition and Low-rank Reconstruction for Water-Fat Separation in MRI.

    PubMed

    Cho, JaeJin; Park, HyunWook

    2018-05-17

    To acquire interleaved bipolar data and reconstruct the full data using low-rank property for water fat separation. Bipolar acquisition suffers from issues related to gradient switching, the opposite gradient polarities, and other system imperfections, which prevent accurate water-fat separation. In this study, an interleaved bipolar acquisition scheme and a low-rank reconstruction method were proposed to reduce issues from the bipolar gradients while achieving a short imaging time. The proposed interleaved bipolar acquisition scheme collects echo-time signals from both gradient polarities; however, the sequence increases the imaging time. To reduce the imaging time, the signals were subsampled at every dimension of k-space. The low-rank property of the bipolar acquisition was defined and exploited to estimate the full data from the acquired subsampled data. To eliminate the bipolar issues, in the proposed method, the water-fat separation was performed separately for each gradient polarity, and the results for the positive and negative gradient polarities were combined after the water-fat separation. A phantom study and in-vivo experiments were conducted on a 3T Siemens Verio system. The results for the proposed method were compared with the results of the fully sampled interleaved bipolar acquisition and Soliman's method, which was the previous water-fat separation approach for reducing the issues of bipolar gradients and accelerating the interleaved bipolar acquisition. The proposed method provided accurate water and fat images without the issues of bipolar gradients and demonstrated a better performance compared with the results of the previous methods. The water-fat separation using the bipolar acquisition has several benefits including a short echo-spacing time. However, it suffers from bipolar-gradient issues such as strong gradient switching, system imperfection, and eddy current effects. This study demonstrated that accurate water-fat separated images can be obtained using the proposed interleaved bipolar acquisition and low-rank reconstruction by using the benefits of the bipolar acquisition while reducing the bipolar-gradient issues with a short imaging time. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

  13. 14-3-3γ Prevents Centrosome Amplification and Neoplastic Progression.

    PubMed

    Mukhopadhyay, Amitabha; Sehgal, Lalit; Bose, Arunabha; Gulvady, Anushree; Senapati, Parijat; Thorat, Rahul; Basu, Srikanta; Bhatt, Khyati; Hosing, Amol S; Balyan, Renu; Borde, Lalit; Kundu, Tapas K; Dalal, Sorab N

    2016-06-02

    More than 80% of malignant tumors show centrosome amplification and clustering. Centrosome amplification results from aberrations in the centrosome duplication cycle, which is strictly coordinated with DNA-replication-cycle. However, the relationship between cell-cycle regulators and centrosome duplicating factors is not well understood. This report demonstrates that 14-3-3γ localizes to the centrosome and 14-3-3γ loss leads to centrosome amplification. Loss of 14-3-3γ results in the phosphorylation of NPM1 at Thr-199, causing early centriole disjunction and centrosome hyper-duplication. The centrosome amplification led to aneuploidy and increased tumor formation in mice. Importantly, an increase in passage of the 14-3-3γ-knockdown cells led to an increase in the number of cells containing clustered centrosomes leading to the generation of pseudo-bipolar spindles. The increase in pseudo-bipolar spindles was reversed and an increase in the number of multi-polar spindles was observed upon expression of a constitutively active 14-3-3-binding-defective-mutant of cdc25C (S216A) in the 14-3-3γ knockdown cells. The increase in multi-polar spindle formation was associated with decreased cell viability and a decrease in tumor growth. Our findings uncover the molecular basis of regulation of centrosome duplication by 14-3-3γ and inhibition of tumor growth by premature activation of the mitotic program and the disruption of centrosome clustering.

  14. Single Grain Boundary Modeling and Design of Microcrystalline Si Solar Cells.

    PubMed

    Lin, Chu-Hsuan; Hsu, Wen-Tzu; Tai, Cheng-Hung

    2013-01-21

    For photovoltaic applications, microcrystalline silicon has a lot of advantages, such as the ability to absorb the near-infrared part of the solar spectrum. However, there are many dangling bonds at the grain boundary in microcrystalline Si. These dangling bonds would lead to the recombination of photo-generated carriers and decrease the conversion efficiency. Therefore, we included the grain boundary in the numerical study in order to simulate a microcrystalline Si solar cell accurately, designing new three-terminal microcrystalline Si solar cells. The 3-μm-thick three-terminal cell achieved a conversion efficiency of 10.8%, while the efficiency of a typical two-terminal cell is 9.7%. The three-terminal structure increased the J SC but decreased the V OC , and such phenomena are discussed. High-efficiency and low-cost Si-based thin film solar cells can now be designed based on the information provided in this paper.

  15. Single Grain Boundary Modeling and Design of Microcrystalline Si Solar Cells

    PubMed Central

    Lin, Chu-Hsuan; Hsu, Wen-Tzu; Tai, Cheng-Hung

    2013-01-01

    For photovoltaic applications, microcrystalline silicon has a lot of advantages, such as the ability to absorb the near-infrared part of the solar spectrum. However, there are many dangling bonds at the grain boundary in microcrystalline Si. These dangling bonds would lead to the recombination of photo-generated carriers and decrease the conversion efficiency. Therefore, we included the grain boundary in the numerical study in order to simulate a microcrystalline Si solar cell accurately, designing new three-terminal microcrystalline Si solar cells. The 3-μm-thick three-terminal cell achieved a conversion efficiency of 10.8%, while the efficiency of a typical two-terminal cell is 9.7%. The three-terminal structure increased the JSC but decreased the VOC, and such phenomena are discussed. High-efficiency and low-cost Si-based thin film solar cells can now be designed based on the information provided in this paper. PMID:28809309

  16. Transmitter release modulation by intracellular Ca2+ buffers in facilitating and depressing nerve terminals of pyramidal cells in layer 2/3 of the rat neocortex indicates a target cell-specific difference in presynaptic calcium dynamics

    PubMed Central

    Rozov, A; Burnashev, N; Sakmann, B; Neher, E

    2001-01-01

    In connections formed by nerve terminals of layer 2/3 pyramidal cells onto bitufted interneurones in young (postnatal day (P)14–15) rat somatosensory cortex, the efficacy and reliability of synaptic transmission were low. At these connections release was facilitated by paired-pulse stimulation (at 10 Hz). In connections formed by terminals of layer 2/3 pyramids with multipolar interneurones efficacy and reliability were high and release was depressed by paired-pulse stimulation. In both types of terminal, however, the voltage-dependent Ca2+ channels that controlled transmitter release were predominantly of the P/Q- and N-subtypes. The relationship between unitary EPSP amplitude and extracellular calcium concentration ([Ca2+]o) was steeper for facilitating than for depressing terminals. Fits to a Hill equation with nH= 4 indicated that the apparent KD of the Ca2+ sensor for vesicle release was two- to threefold lower in depressing terminals than in facilitating ones. Intracellular loading of pyramidal neurones with the fast and slowly acting Ca2+ buffers BAPTA and EGTA differentially reduced transmitter release in these two types of terminal. Unitary EPSPs evoked by pyramidal cell stimulation in bitufted cells were reduced by presynaptic BAPTA and EGTA with half-effective concentrations of ∼0.1 and ∼1 mm, respectively. Unitary EPSPs evoked in multipolar cells were reduced to one-half of control at higher concentrations of presynaptic BAPTA and EGTA (∼0.5 and ∼7 mm, respectively). Frequency-dependent facilitation of EPSPs in bitufted cells was abolished by EGTA at concentrations of > 0.2 mm, suggesting that accumulation of free Ca2+ is essential for facilitation in the terminals contacting bitufted cells. In contrast, facilitation was unaffected or even slightly increased in the terminals loaded with BAPTA in the concentration range 0.02–0.5 mm. This is attributed to partial saturation of exogenously added BAPTA. However, BAPTA at concentrations > 1 mm also abolished facilitation. Frequency-dependent depression of EPSPs in multipolar cells was not significantly reduced by EGTA. With BAPTA, the depression decreased at concentrations > 0.5 mm, concomitant with a reduction in amplitude of the first EPSP in a train. An analysis is presented that interprets the effects of EGTA and BAPTA on synaptic efficacy and its short-term modification during paired-pulse stimulation in terms of changes in [Ca2+] at the release site ([Ca2+]RS) and that infers the affinity of the Ca2+ sensor from the dependence of unitary EPSPs on [Ca2+]o. The results suggest that the target cell-specific difference in release from the terminals on bitufted or multipolar cells can be explained by a longer diffusional distance between Ca2+ channels and release sites and/or lower Ca2+ channels density in the terminals that contact bitufted cells. This would lead to a lower [Ca2+] at release sites and would also explain the higher apparent KD of the Ca2+ sensor in facilitating terminals. PMID:11251060

  17. Bipolar Sealer Devices Used in Posterior Spinal Fusion for Neuromuscular Scoliosis Reduce Blood Loss and Transfusion Requirements.

    PubMed

    Hardesty, Christina K; Gordon, Zachary L; Poe-Kochert, Connie; Son-Hing, Jochen P; Thompson, George H

    2018-02-01

    Reducing perioperative blood loss and the need for transfusions in patients undergoing spinal surgery is especially important for those with neuromuscular disorders. These patients require extensive spino-pelvic exposure and are often medically fragile. We have used Amicar to decrease blood loss since 2001. As an effort to further reduce blood loss and transfusions, we use a bipolar sealer device (Aquamantys) as an adjunct to electrocautery. We present the results of our first 64 neuromuscular patients to show the efficacy of the device. Using a prospectively maintained database we reviewed the operative time, estimated perioperative blood loss, cell saver use, and intraoperative and postoperative transfusion rate in patients who underwent posterior spinal fusion for neuromuscular scoliosis. Sixty-four patients were identified who fit these criteria since the use of the bipolar sealer device was instituted.We compared these patients with a control group of the preceding 65 patients in whom this device was not used for hemostasis. All patients, including those in the study group, received Amicar (infusion of 100 mg/kg over 15 to 20 min, then 10 mg/kg/h throughout the remainder of the procedure). The surgical technique did not differ between the 2 groups. Baseline characteristics between the 2 groups were similar except for the number of patients having an all-screw construct which was larger in the investigational group (25% vs. 8%, P=0.03). There were no significant differences in operative time or duration of hospital stay. Intraoperative blood loss was lower in the study group (741 mL) as compared with the control group (1052 mL, P=0.003). Total perioperative blood loss, however, showed no significant difference. Thirty-five (55%) patients in the study group and 50 (77%) patients in the control group required additional intraoperative or postoperative transfusions (P=0.01). The number of packed red cell units transfused per patient was 0.81 in the study group and 1.57 in the control group (P=0.001). Although the intraoperative cell saver transfusion was same, the total blood volume transfused, which includes cell saver and any other transfusions, was significantly lower in the study group, 425 mL versus 671 mL (P=0.002). Use of a bipolar sealer device in posterior spinal fusion for neuromuscular scoliosis significantly reduced intraoperative blood loss and transfusion rate when compared with a control group in this retrospective review. Level III-retrospective comparative study.

  18. A Cre Mouse Line for Probing Irradiance- and Direction-Encoding Retinal Networks

    PubMed Central

    Sabbah, Shai

    2017-01-01

    Abstract Cell type-specific Cre driver lines have revolutionized the analysis of retinal cell types and circuits. We show that the transgenic mouse Rbp4-Cre selectively labels several retinal neuronal types relevant to the encoding of absolute light intensity (irradiance) and visual motion. In the ganglion cell layer (GCL), most marked cells are wide-field spiking polyaxonal amacrine cells (ACs) with sustained irradiance-encoding ON responses that persist during chemical synaptic blockade. Their arbors spread about 1 mm across the retina and are restricted to the inner half of the ON sublamina of the inner plexiform layer (IPL). There, they costratify with dendrites of M2 intrinsically photosensitive retinal ganglion cells (ipRGCs), to which they are tracer coupled. We propose that synaptically driven and intrinsic photocurrents of M2 cells pass through gap junctions to drive AC light responses. Also marked in this mouse are two types of RGCs. R-cells have a bistratified dendritic arbor, weak directional tuning, and irradiance-encoding ON responses. However, they also receive excitatory OFF input, revealed during ON-channel blockade. Serial blockface electron microscopic (SBEM) reconstruction confirms OFF bipolar input, and reveals that some OFF input derives from a novel type of OFF bipolar cell (BC). R-cells innervate specific layers of the dorsal lateral geniculate nucleus (dLGN) and superior colliculus (SC). The other marked RGC type (RDS) is bistratified, transient, and ON-OFF direction selective (DS). It apparently innervates the nucleus of the optic tract (NOT). The Rbp4-Cre mouse will be valuable for targeting these cell types for further study and for selectively manipulating them for circuit analysis. PMID:28466070

  19. The double layers in the plasma sheet boundary layer during magnetic reconnection

    NASA Astrophysics Data System (ADS)

    Guo, J.; Yu, B.

    2014-11-01

    We studied the evolutions of double layers which appear after the magnetic reconnection through two-dimensional electromagnetic particle-in-cell simulation. The simulation results show that the double layers are formed in the plasma sheet boundary layer after magnetic reconnection. At first, the double layers which have unipolar structures are formed. And then the double layers turn into bipolar structures, which will couple with another new weak bipolar structure. Thus a new double layer or tripolar structure comes into being. The double layers found in our work are about several ten Debye lengths, which accords with the observation results. It is suggested that the electron beam formed during the magnetic reconnection is responsible for the production of the double layers.

  20. Ion bipolar junction transistors

    PubMed Central

    Tybrandt, Klas; Larsson, Karin C.; Richter-Dahlfors, Agneta; Berggren, Magnus

    2010-01-01

    Dynamic control of chemical microenvironments is essential for continued development in numerous fields of life sciences. Such control could be achieved with active chemical circuits for delivery of ions and biomolecules. As the basis for such circuitry, we report a solid-state ion bipolar junction transistor (IBJT) based on conducting polymers and thin films of anion- and cation-selective membranes. The IBJT is the ionic analogue to the conventional semiconductor BJT and is manufactured using standard microfabrication techniques. Transistor characteristics along with a model describing the principle of operation, in which an anionic base current amplifies a cationic collector current, are presented. By employing the IBJT as a bioelectronic circuit element for delivery of the neurotransmitter acetylcholine, its efficacy in modulating neuronal cell signaling is demonstrated. PMID:20479274

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