Sample records for circuit linking wingless

  1. Drosophila S2 cells secrete wingless on exosome-like vesicles but the wingless gradient forms independently of exosomes.

    PubMed

    Beckett, Karen; Monier, Solange; Palmer, Lucy; Alexandre, Cyrille; Green, Hannah; Bonneil, Eric; Raposo, Graca; Thibault, Pierre; Le Borgne, Roland; Vincent, Jean-Paul

    2013-01-01

    Wingless acts as a morphogen in Drosophila wing discs, where it specifies cell fates and controls growth several cell diameters away from its site of expression. Thus, despite being acylated and membrane associated, Wingless spreads in the extracellular space. Recent studies have focussed on identifying the route that Wingless follows in the secretory pathway and determining how it is packaged for release. We have found that, in medium conditioned by Wingless-expressing Drosophila S2 cells, Wingless is present on exosome-like vesicles and that this fraction activates signal transduction. Proteomic analysis shows that Wingless-containing exosome-like structures contain many Drosophila proteins that are homologous to mammalian exosome proteins. In addition, Evi, a multipass transmembrane protein, is also present on exosome-like vesicles. Using these exosome markers and a cell-based RNAi assay, we found that the small GTPase Rab11 contributes significantly to exosome production. This finding allows us to conclude from in vivo Rab11 knockdown experiments, that exosomes are unlikely to contribute to Wingless secretion and gradient formation in wing discs. Consistent with this conclusion, extracellularly tagged Evi expressed from a Bacterial Artificial Chromosome is not released from imaginal disc Wingless-expressing cells. © 2012 John Wiley & Sons A/S.

  2. Wingless promotes proliferative growth in a gradient-independent manner.

    PubMed

    Baena-Lopez, Luis Alberto; Franch-Marro, Xavier; Vincent, Jean-Paul

    2009-10-06

    Morphogens form concentration gradients that organize patterns of cells and control growth. It has been suggested that, rather than the intensity of morphogen signaling, it is its gradation that is the relevant modulator of cell proliferation. According to this view, the ability of morphogens to regulate growth during development depends on their graded distributions. Here, we describe an experimental test of this model for Wingless, one of the key organizers of wing development in Drosophila. Maximal Wingless signaling suppresses cellular proliferation. In contrast, we found that moderate and uniform amounts of exogenous Wingless, even in the absence of endogenous Wingless, stimulated proliferative growth. Beyond a few cell diameters from the source, Wingless was relatively constant in abundance and thus provided a homogeneous growth-promoting signal. Although morphogen signaling may act in combination with as yet uncharacterized graded growth-promoting pathways, we suggest that the graded nature of morphogen signaling is not required for proliferation, at least in the developing Drosophila wing, during the main period of growth.

  3. Competing signals drive telencephalon diversity.

    PubMed

    Sylvester, J B; Rich, C A; Yi, C; Peres, J N; Houart, C; Streelman, J T

    2013-01-01

    The telencephalon is the most complex brain region, controlling communication, emotion, movement and memory. Its adult derivatives develop from the dorsal pallium and ventral subpallium. Despite knowledge of genes required in these territories, we do not understand how evolution has shaped telencephalon diversity. Here, using rock- and sand-dwelling cichlid fishes from Lake Malawi, we demonstrate that differences in strength and timing of opposing Hedgehog and Wingless signals establish evolutionary divergence in dorsal-ventral telencephalon patterning. Rock dwellers exhibit early, extensive Hedgehog activity in the ventral forebrain resulting in expression of foxg1 before dorsal Wingless signals, and a larger subpallium. Sand dwellers show rapid deployment of Wingless, later foxg1 expression and a larger pallium. Manipulation of the Hedgehog and Wingless pathways in cichlid and zebrafish embryos is sufficient to mimic differences between rock- versus sand-dweller brains. Our data suggest that competing ventral Hedgehog and dorsal Wingless signals mediate evolutionary diversification of the telencephalon.

  4. Wingless is a positive regulator of eyespot color patterns in Bicyclus anynana butterflies.

    PubMed

    Özsu, Nesibe; Chan, Qian Yi; Chen, Bin; Gupta, Mainak Das; Monteiro, Antónia

    2017-09-01

    Eyespot patterns of nymphalid butterflies are an example of a novel trait yet, the developmental origin of eyespots is still not well understood. Several genes have been associated with eyespot development but few have been tested for function. One of these genes is the signaling ligand, wingless, which is expressed in the eyespot centers during early pupation and may function in eyespot signaling and color ring differentiation. Here we tested the function of wingless in wing and eyespot development by down-regulating it in transgenic Bicyclus anynana butterflies via RNAi driven by an inducible heat-shock promoter. Heat-shocks applied during larval and early pupal development led to significant decreases in wingless mRNA levels and to decreases in eyespot size and wing size in adult butterflies. We conclude that wingless is a positive regulator of eyespot and wing development in B. anynana butterflies. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Evolution of female-specific wingless forms in bagworm moths.

    PubMed

    Niitsu, Shuhei; Sugawara, Hirotaka; Hayashi, Fumio

    2017-01-01

    The evolution of winglessness in insects has been typically interpreted as a consequence of developmental and other adaptations to various environments that are secondarily derived from a winged morph. Several species of bagworm moths (Insecta: Lepidoptera, Psychidae) exhibit a case-dwelling larval life style along with one of the most extreme cases of sexual dimorphism: wingless female adults. While the developmental process that led to these wingless females is well known, the origins and evolutionary transitions are not yet understood. To examine the evolutionary patterns of wing reduction in bagworm females, we reconstruct the molecular phylogeny of over 30 Asian species based on both mitochondrial (cytochrome c oxidase subunit I) and nuclear (28S rRNA) DNA sequences. Under a parsimonious assumption, the molecular phylogeny implies that: (i) the evolutionary wing reduction towards wingless females consisted of two steps: (Step I) from functional wings to vestigial wings (nonfunctional) and (Step II) from vestigial wings to the most specialized vermiform adults (lacking wings and legs); and (ii) vermiform morphs evolved independently at least twice. Based on the results of our study, we suggest that the evolutionary changes in the developmental system are essential for the establishment of different wingless forms in insects. © 2016 Wiley Periodicals, Inc.

  6. Notch signalling coordinates tissue growth and wing fate specification in Drosophila.

    PubMed

    Rafel, Neus; Milán, Marco

    2008-12-01

    During the development of a given organ, tissue growth and fate specification are simultaneously controlled by the activity of a discrete number of signalling molecules. Here, we report that these two processes are extraordinarily coordinated in the Drosophila wing primordium, which extensively proliferates during larval development to give rise to the dorsal thoracic body wall and the adult wing. The developmental decision between wing and body wall is defined by the opposing activities of two secreted signalling molecules, Wingless and the EGF receptor ligand Vein. Notch signalling is involved in the determination of a variety of cell fates, including growth and cell survival. We present evidence that growth of the wing primordium mediated by the activity of Notch is required for wing fate specification. Our data indicate that tissue size modulates the activity range of the signalling molecules Wingless and Vein. These results highlight a crucial role of Notch in linking proliferation and fate specification in the developing wing primordium.

  7. The thorax of the cave cricket Troglophilus neglectus: anatomical adaptations in an ancient wingless insect lineage (Orthoptera: Rhaphidophoridae).

    PubMed

    Leubner, Fanny; Hörnschemeyer, Thomas; Bradler, Sven

    2016-02-18

    Secondary winglessness is a common phenomenon found among neopteran insects. With an estimated age of at least 140 million years, the cave crickets (Rhaphidophoridae) form the oldest exclusively wingless lineage within the long-horned grasshoppers (Ensifera). With respect to their morphology, cave crickets are generally considered to represent a `primitive' group of Ensifera, for which no apomorphic character has been reported so far. We present the first detailed investigation and description of the thoracic skeletal and muscular anatomy of the East Mediterranean cave cricket Troglophilus neglectus (Ensifera: Rhaphidophoridae). T. neglectus possesses sternopleural muscles that are not yet reported from other neopteran insects. Cave crickets in general exhibit some unique features with respect to their thoracic skeletal anatomy: an externally reduced prospinasternum, a narrow median sclerite situated between the meso- and metathorax, a star-shaped prospina, and a triramous metafurca. The thoracic muscle equipment of T. neglectus compared to that of the bush cricket Conocephalus maculatus (Ensifera: Tettigoniidae) and the house cricket Acheta domesticus (Ensifera: Gryllidae) reveals a number of potentially synapomorphic characters between these lineages. Based on the observed morphology we favor a closer relationship of Rhaphidophoridae to Tettigoniidae rather than to Gryllidae. In addition, the comparison of the thoracic morphology of T. neglectus to that of other wingless Polyneoptera allows reliable conclusions about anatomical adaptations correlated with secondary winglessness. The anatomy in apterous Ensifera, viz. the reduction of discrete direct and indirect flight muscles as well as the strengthening of specific leg muscles, largely resembles the condition found in wingless stick insects (Euphasmatodea), but is strikingly different from that of other related wingless insects, e.g. heel walkers (Mantophasmatodea), ice crawlers (Grylloblattodea), and certain grasshoppers (Caelifera). The composition of direct flight muscles largely follows similar patterns in winged respectively wingless species within major polyneopteran lineages, but it is highly heterogeneous between those lineages.

  8. Male fighting and "territoriality" within colonies of the ant Cardiocondyla venustula.

    PubMed

    Frohschammer, Sabine; Heinze, Jürgen

    2009-01-01

    The ant genus Cardiocondyla is characterized by a bizarre male polymorphism with wingless fighter males and winged disperser males. Winged males have been lost convergently in several clades, and in at least one of them, wingless males have evolved mutual tolerance. To better understand the evolutionary pathways of reproductive tactics, we investigated Cardiocondyla venustula, a species, which in a phylogenetic analysis clusters with species with fighting and species with mutually tolerant, wingless males. Wingless males of C. venustula use their strong mandibles to kill freshly eclosed rival males and also engage in short fights with other adult males, but in addition show a novel behavior hitherto not reported from social insect males: they spread out in the natal nest and defend "territories" against other males. Ant males therefore show a much larger variety of reproductive tactics than previously assumed.

  9. Male fighting and ``territoriality'' within colonies of the ant Cardiocondyla venustula

    NASA Astrophysics Data System (ADS)

    Frohschammer, Sabine; Heinze, Jürgen

    2009-01-01

    The ant genus Cardiocondyla is characterized by a bizarre male polymorphism with wingless fighter males and winged disperser males. Winged males have been lost convergently in several clades, and in at least one of them, wingless males have evolved mutual tolerance. To better understand the evolutionary pathways of reproductive tactics, we investigated Cardiocondyla venustula, a species, which in a phylogenetic analysis clusters with species with fighting and species with mutually tolerant, wingless males. Wingless males of C. venustula use their strong mandibles to kill freshly eclosed rival males and also engage in short fights with other adult males, but in addition show a novel behavior hitherto not reported from social insect males: they spread out in the natal nest and defend “territories” against other males. Ant males therefore show a much larger variety of reproductive tactics than previously assumed.

  10. Narrowing the wingless-2 mutation to a 227 Kb candidate region on chicken chromosome 12

    USDA-ARS?s Scientific Manuscript database

    Wingless-2 (wg-2) is an autosomal recessive mutation in chicken that results in an embryonic lethal condition. Affected individuals exhibit a multisystem syndrome characterized by absent wings, truncated legs, and craniofacial, kidney, and feather malformations. Previously, work focused on phenotype...

  11. Demonstration of a Wingless Electromagnetic Air Vehicle

    DTIC Science & Technology

    2011-12-20

    moving parts and assures near instantaneous response time. For the first time, the aircraft structure, propulsion, energy production and storage, and...of an electromagnetically driven wingless aircraft * with no moving component that will be able to self- lift, hover and fly reliably especially...8217&)?$@&;! First successful lift-off using plasma propulsion. Main Achievement Aerogel actuators are thus far the lightest plasma actuators with minimum

  12. Inhibitors of endocytosis prevent Wnt/Wingless signalling by reducing the level of basal β-catenin/Armadillo.

    PubMed

    Gagliardi, Maria; Hernandez, Ana; McGough, Ian J; Vincent, Jean-Paul

    2014-11-15

    A key step in the canonical Wnt signalling pathway is the inhibition of GSK3β, which results in the accumulation of nuclear β-catenin (also known as CTNNB1), and hence regulation of target genes. Evidence suggests that endocytosis is required for signalling, yet its role and the molecular understanding remains unclear. A recent and controversial model suggests that endocytosis contributes to Wnt signalling by causing the sequestration of the ligand-receptor complex, including LRP6 and GSK3 to multivesicular bodies (MVBs), thus preventing GSK3β from accessing β-catenin. Here, we use specific inhibitors (Dynasore and Dyngo-4a) to confirm the essential role of endocytosis in Wnt/Wingless signalling in human and Drosophila cells. However, we find no evidence that, in Drosophila cells or wing imaginal discs, LRP6/Arrow traffics to MVBs or that MVBs are required for Wnt/Wingless signalling. Moreover, we show that activation of signalling through chemical blockade of GSK3β is prevented by endocytosis inhibitors, suggesting that endocytosis impacts on Wnt/Wingless signalling downstream of the ligand-receptor complex. We propose that, through an unknown mechanism, endocytosis boosts the resting pool of β-catenin upon which GSK3β normally acts. © 2014. Published by The Company of Biologists Ltd.

  13. Carrier of Wingless (Cow), a Secreted Heparan Sulfate Proteoglycan, Promotes Extracellular Transport of Wingless

    PubMed Central

    Chang, Yung-Heng; Sun, Yi Henry

    2014-01-01

    Morphogens are signaling molecules that regulate growth and patterning during development by forming a gradient and activating different target genes at different concentrations. The extracellular distribution of morphogens is tightly regulated, with the Drosophila morphogen Wingless (Wg) relying on Dally-like (Dlp) and transcytosis for its distribution. However, in the absence of Dlp or endocytic activity, Wg can still move across cells along the apical (Ap) surface. We identified a novel secreted heparan sulfate proteoglycan (HSPG) that binds to Wg and promotes its extracellular distribution by increasing Wg mobility, which was thus named Carrier of Wg (Cow). Cow promotes the Ap transport of Wg, independent of Dlp and endocytosis, and this function addresses a previous gap in the understanding of Wg movement. This is the first example of a diffusible HSPG acting as a carrier to promote the extracellular movement of a morphogen. PMID:25360738

  14. Human Factors Lessons Learned from Flight Testing Wingless Lifting Body Vehicles

    NASA Technical Reports Server (NTRS)

    Merlin, Peter William

    2014-01-01

    Since the 1960s, NASA, the Air Force, and now private industry have attempted to develop an operational human crewed reusable spacecraft with a wingless, lifting body configuration. This type of vehicle offers increased mission flexibility and greater reentry cross range than capsule type craft, and is particularly attractive due to the capability to land on a runway. That capability, however, adds complexity to the human factors engineering requirements of developing such aircraft.

  15. The effect of female wings on male courtship behavior in the cricket Gryllus bimaculatus

    NASA Astrophysics Data System (ADS)

    Itoh, Masanori; Murakami, Shio

    2002-03-01

    Sexual dimorphism exists in the shape and the structure of the forewings of the cricket (Gryllus bimaculatus). However, the functional significance of the wings in the G. bimaculatus female has been unclear. In common blue butterflies (Polyommatus icarus), wings in females have been suggested as being important for attracting males. To test whether female crickets need wings for conspecific males to recognize them and initiate mating behavior, we removed all wings from females and observed the behavior of males towards them. Most males (87.5%) showed mating behavior towards the wingless females: they produced courtship song and transferred spermatophores to the wingless females. Similarly, 88.5% of the males showed mating behavior towards intact females. When males were placed with both a wingless female and an intact female, no significant difference was detected in male mate choice. The findings demonstrate that the wing of the G. bimaculatus female is not necessary for female recognition by conspecific males and the initiation of male mating behavior, and that it is not important in male mate choice.

  16. Variable Delay Element For Jitter Control In High Speed Data Links

    DOEpatents

    Livolsi, Robert R.

    2002-06-11

    A circuit and method for decreasing the amount of jitter present at the receiver input of high speed data links which uses a driver circuit for input from a high speed data link which comprises a logic circuit having a first section (1) which provides data latches, a second section (2) which provides a circuit generates a pre-destorted output and for compensating for level dependent jitter having an OR function element and a NOR function element each of which is coupled to two inputs and to a variable delay element as an input which provides a bi-modal delay for pulse width pre-distortion, a third section (3) which provides a muxing circuit, and a forth section (4) for clock distribution in the driver circuit. A fifth section is used for logic testing the driver circuit.

  17. Circuit-level simulation of transistor lasers and its application to modelling of microwave photonic links

    NASA Astrophysics Data System (ADS)

    Iezekiel, Stavros; Christou, Andreas

    2015-03-01

    Equivalent circuit models of a transistor laser are used to investigate the suitability of this relatively new device for analog microwave photonic links. The three-terminal nature of the device enables transistor-based circuit design techniques to be applied to optoelectronic transmitter design. To this end, we investigate the application of balanced microwave amplifier topologies in order to enable low-noise links to be realized with reduced intermodulation distortion and improved RF impedance matching compared to conventional microwave photonic links.

  18. Optical analog data link with simple self-test feature

    DOEpatents

    Witkover, Richard L.

    1986-01-01

    A communications circuit for optically transmitting analog data signals free of excessive ripple, while having rapid response time. The invention is further characterized by being adapted to provide an immediate indication of the failure of the optical transmission link of the circuit. Commercially available voltage to frequency converter chips are used in conjunction with suitable wiring arrays and in combination with readily available indicator means for constructing the communication circuit of the invention. A V/F converter in the communications circuit is coupled to an offset adjustment means to cause the converter to continuously produce a string of output voltage pulses having a frequency of about 1 Khz responsive to the input analog signal to the converter being zero. The continuous presence of the 1 Khz frequency on the optical transmission link is monitored at the receiving end of the communication circuit and the indicator means is connected to immediately provide an easily detected indication of a failure of the optical transmission link to transmit the 1 Khz frequency pulses.

  19. Optical analog data link with simple self-test feature

    DOEpatents

    Witkover, R.L.

    1984-02-01

    A communications circuit for optically transmitting analog data signals free of excessive ripple, while having rapid response time. The invention is further characterized by being adapted to provide an immediate indication of the failure of the optical transmission link of the circuit. Commerically available voltage to frequency converter chips are used in conjunction with suitable wiring arrays and in combination with readily available indicator means for constructing the communication circuit of the invention. A V/F converter in the communications circuit is coupled to an offset adjustment means to cause the converter to continuously produce a string of output voltage pulses having a frequency of about 1Khz responsive to the input analog signal to the converter being zero. The continuous presence of the 1Khz frequency on the optical transmission link is monitored at the receiving end of the communication circuit and the indicator means is connected to immediately provide an easily detected indication of a failure of the optical transmission link to transmit the 1Khz frequency pulses.

  20. Drosophila VAMP7 regulates Wingless intracellular trafficking.

    PubMed

    Gao, Han; He, Fang; Lin, Xinhua; Wu, Yihui

    2017-01-01

    Drosophila Wingless (Wg) is a morphogen that determines cell fate during development. Previous studies have shown that endocytic pathways regulate Wg trafficking and signaling. Here, we showed that loss of vamp7, a gene required for vesicle fusion, dramatically increased Wg levels and decreased Wg signaling. Interestingly, we found that levels of Dally-like (Dlp), a glypican that can interact with Wg to suppress Wg signaling at the dorsoventral boundary of the Drosophila wing, were also increased in vamp7 mutant cells. Moreover, Wg puncta in Rab4-dependent recycling endosomes were Dlp positive. We hypothesize that VAMP7 is required for Wg intracellular trafficking and the accumulation of Wg in Rab4-dependent recycling endosomes might affect Wg signaling.

  1. Genome-wide SNPs reveal fine-scale differentiation among wingless alpine stonefly populations and introgression between winged and wingless forms.

    PubMed

    Dussex, Nicolas; Chuah, Aaron; Waters, Jonathan M

    2016-01-01

    Insect flight loss is a repeated phenomenon in alpine habitats, where wing reduction is thought to enhance local recruitment and increase fecundity. One predicted consequence of flight loss is reduced dispersal ability, which should lead to population genetic differentiation and perhaps ultimately to speciation. Using a dataset of 15,123 SNP loci, we present comparative analyses of fine-scale population structure in codistributed Zelandoperla stonefly species, across three parallel altitudinal transects in New Zealand's Rock and Pillar mountain range. We find that winged populations (altitude 200-500 m; Zelandoperla decorata) show no genetic structuring within or among streams, suggesting substantial dispersal mediated by flight. By contrast, wingless populations (Zelandoperla fenestrata; altitude 200-1100 m) exhibit distinct genetic clusters associated with each stream, and additional evidence of isolation by distance within streams. Our data support the hypothesis that wing-loss can initiate diversification in alpine insect populations over small spatial scales. The often deep phylogenetic placement of lowland Z. fenestrata within their stream-specific clades suggests the possibility of independent alpine colonization events for each stream. Additionally, the detection of winged, interspecific hybrid individuals raises the intriguing possibility that a previously flightless lineage could reacquire flight via introgression. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  2. Sperm traits differ between winged and wingless males of the ant Cardiocondyla obscurior.

    PubMed

    Schrempf, Alexandra; Moser, Astrid; Delabie, Jacques; Heinze, Jürgen

    2016-11-01

    Size and shape of sperm cells vary tremendously throughout the animal kingdom. The adaptive significance of this variation is not fully understood. In addition to sperm-female interactions and the environmental conditions, the risk of sperm competition might affect number, morphology and other "quality" traits of sperm. In the male-diphenic ant Cardiocondyla obscurior, winged sneaker males have limited sperm number, because their testes degenerate shortly after adult emergence, as is typical for males of social Hymenoptera. In contrast, wingless fighter males continuously replenish their sperm supply due to their exceptional lifelong spermatogenesis. While winged males usually have to compete with several other winged males for virgin queens, wingless males are able to monopolize queens by killing all other rivals. Hence, this presents a unique system to investigate how alternative reproductive tactics and associated physiology affect sperm morphology and viability. We found that sperm-limited males invest into sperm number instead of sperm size. Variance in sperm length is smaller in winged males, probably reflecting that they have to compete with several other males. Finally, sperm viability is equally high in both male phenotypes. © 2016 International Society of Zoological Sciences, Institute of Zoology/Chinese Academy of Sciences and John Wiley & Sons Australia, Ltd.

  3. Moving the boundary between wavelength resources in optical packet and circuit integrated ring network.

    PubMed

    Furukawa, Hideaki; Miyazawa, Takaya; Wada, Naoya; Harai, Hiroaki

    2014-01-13

    Optical packet and circuit integrated (OPCI) networks provide both optical packet switching (OPS) and optical circuit switching (OCS) links on the same physical infrastructure using a wavelength multiplexing technique in order to deal with best-effort services and quality-guaranteed services. To immediately respond to changes in user demand for OPS and OCS links, OPCI networks should dynamically adjust the amount of wavelength resources for each link. We propose a resource-adjustable hybrid optical packet/circuit switch and transponder. We also verify that distributed control of resource adjustments can be applied to the OPCI ring network testbed we developed. In cooperation with the resource adjustment mechanism and the hybrid switch and transponder, we demonstrate that automatically allocating a shared resource and moving the wavelength resource boundary between OPS and OCS links can be successfully executed, depending on the number of optical paths in use.

  4. Whole-exome sequencing reveals LRP5 mutations and canonical Wnt signaling associated with hepatic cystogenesis

    PubMed Central

    Cnossen, Wybrich R.; te Morsche, René H. M.; Hoischen, Alexander; Gilissen, Christian; Chrispijn, Melissa; Venselaar, Hanka; Mehdi, Soufi; Bergmann, Carsten; Veltman, Joris A.; Drenth, Joost P. H.

    2014-01-01

    Polycystic livers are seen in the rare inherited disorder isolated polycystic liver disease (PCLD) and are recognized as the most common extrarenal manifestation in autosomal dominant polycystic kidney disease. Hepatic cystogenesis is characterized by progressive proliferation of cholangiocytes, ultimately causing hepatomegaly. Genetically, polycystic liver disease is a heterogeneous disorder with incomplete penetrance and caused by mutations in PRKCSH, SEC63, PKD1, or PKD2. Genome-wide SNP typing and Sanger sequencing revealed no pathogenic variants in hitherto genes in an extended PCLD family. We performed whole-exome sequencing of DNA samples from two members. A heterozygous variant c.3562C > T located at a highly conserved amino acid position (p.R1188W) in the low density lipoprotein receptor-related protein 5 (LRP5) gene segregated with the disease (logarithm of odds score, 4.62) but was not observed in more than 1,000 unaffected individuals. Screening of LRP5 in a PCLD cohort identified three additional mutations in three unrelated families with polycystic livers (p.V454M, p.R1529S, and p.D1551N), again all undetected in controls. All variants were predicted to be damaging with profound structural effects on LRP5 protein domains. Liver cyst tissue and normal hepatic tissue samples from patients and controls showed abundant LRP5 expression by immunohistochemistry. Functional activity analyses indicated that mutant LRP5 led to reduced wingless signal activation. In conclusion, we demonstrate that germ-line LRP5 missense mutations are associated with hepatic cystogenesis. The findings presented in this study link the pathophysiology of PCLD to deregulation of the canonical wingless signaling pathway. PMID:24706814

  5. Interchip link system using an optical wiring method.

    PubMed

    Cho, In-Kui; Ryu, Jin-Hwa; Jeong, Myung-Yung

    2008-08-15

    A chip-scale optical link system is presented with a transmitter/receiver and optical wire link. The interchip link system consists of a metal optical bench, a printed circuit board module, a driver/receiver integrated circuit, a vertical cavity surface-emitting laser/photodiode array, and an optical wire link composed of plastic optical fibers (POFs). We have developed a downsized POF and an optical wiring method that allows on-site installation with a simple annealing as optical wiring technologies for achieving high-density optical interchip interconnection within such devices. Successful data transfer measurements are presented.

  6. Narrowing the wingless-2 mutation to a 227 kb candidate region on chicken chromosome 12

    PubMed Central

    Webb, A E; Youngworth, I A; Kaya, M; Gitter, C L; O’Hare, E A; May, B; Cheng, H H; Delany, M E

    2018-01-01

    ABSTRACT Wingless-2 (wg-2) is an autosomal recessive mutation in chicken that results in an embryonic lethal condition. Affected individuals exhibit a multisystem syndrome characterized by absent wings, truncated legs, and craniofacial, kidney, and feather malformations. Previously, work focused on phenotype description, establishing the autosomal recessive pattern of Mendelian inheritance and placing the mutation on an inbred genetic background to create the congenic line UCD Wingless-2.331. The research described in this paper employed the complementary tools of breeding, genetics, and genomics to map the chromosomal location of the mutation and successively narrow the size of the region for analysis of the causative element. Specifically, the wg-2 mutation was initially mapped to a 7 Mb region of chromosome 12 using an Illumina 3 K SNP array. Subsequent SNP genotyping and exon sequencing combined with analysis from improved genome assemblies narrowed the region of interest to a maximum size of 227 kb. Within this region, 3 validated and 3 predicted candidate genes are found, and these are described. The wg-2 mutation is a valuable resource to contribute to an improved understanding of the developmental pathways involved in chicken and avian limb development as well as serving as a model for human development, as the resulting syndrome shares features with human congenital disorders. PMID:29562287

  7. Termites, hemimetabolous diploid white ants?

    PubMed

    Korb, Judith

    2008-09-29

    Ants and termites are the most abundant animals on earth. Their ecological success is attributed to their social life. They live in colonies consisting of few reproducing individuals, while the large majority of colony members (workers/soldiers) forego reproduction at least temporarilly. Despite their apparent resemblance in social organisation, both groups evolved social life independently. Termites are basically social cockroaches, while ants evolved from predatory wasps. In this review, I will concentrate on termites with an ancestral life type, the wood-dwelling termites, to compare them with ants. Their different ancestries provided both groups with different life history pre-adaptations for social evolution. Like their closest relatives, the woodroaches, wood-dwelling termites live inside their food, a piece of wood. Thus, intensive costly food provisioning of their young is not necessary, especially as young instars are rather independent due to their hemimetabolous development. In contrast, ants are progressive food provisioners which have to care intensively for their helpless brood. Corresponding to the precocial - altricial analogy, helping by workers is selected in ants, while new evidence suggests that wood-dwelling termite workers are less engaged in brood care. Rather they seem to stay in the nest because there is generally low selection for dispersal. The nest presents a safe haven with no local resource competition as long as food is abundant (which is generally the case), while founding a new colony is very risky. Despite these differences between ants and termites, their common dwelling life style resulted in convergent evolution, especially winglessness, that probably accounts for the striking similarity between both groups. In ants, all workers are wingless and winglessness in sexuals evolved in several taxa as a derived trait. In wood-dwelling termites, workers are by default wingless as they are immatures. These immatures can develop into winged sexuals that disperse and found a new nest or into neotenic replacement reproductives that inherit the natal colony. Depending on the worker instar from which the latter develop, the neotenic reproductives are either apterous or brachypterous, but never winged. I propose that this wing polyphenism might present a basis for the evolution of social life in termites.

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

    Silva, E.R.C. da; Filho, B.J.C.

    This paper presents a PWM current clamping circuit for improving a series resonant DC link converter. This circuit is capable of reducing current peaks to about 1.2--1.4 times the DC bias current. When desired, resonant transition creates notches in the dc link current, allowing the converter`s switches to synchronize with external PWM strategy. A regulated DC current source may be obtained--by using a conventional rectifier source--to feed a DC load or a current source inverter. Phase plane approach makes ease the understanding the operation, control and design procedure of the circuit. Another topology is derived and its features compared tomore » the first circuit. Simulation results for the simplified circuit and for a three-phase induction motor driven by such inverter will be presented. Moreover, the principle is corroborated by experimental results.« less

  9. Myoblast cytonemes mediate Wg signaling from the wing imaginal disc and Delta-Notch signaling to the air sac primordium.

    PubMed

    Huang, Hai; Kornberg, Thomas B

    2015-05-07

    The flight muscles, dorsal air sacs, wing blades, and thoracic cuticle of the Drosophila adult function in concert, and their progenitor cells develop together in the wing imaginal disc. The wing disc orchestrates dorsal air sac development by producing decapentaplegic and fibroblast growth factor that travel via specific cytonemes in order to signal to the air sac primordium (ASP). Here, we report that cytonemes also link flight muscle progenitors (myoblasts) to disc cells and to the ASP, enabling myoblasts to relay signaling between the disc and the ASP. Frizzled (Fz)-containing myoblast cytonemes take up Wingless (Wg) from the disc, and Delta (Dl)-containing myoblast cytonemes contribute to Notch activation in the ASP. Wg signaling negatively regulates Dl expression in the myoblasts. These results reveal an essential role for cytonemes in Wg and Notch signaling and for a signal relay system in the myoblasts.

  10. Imperfect chemical female mimicry in males of the ant Cardiocondyla obscurior

    NASA Astrophysics Data System (ADS)

    Cremer, Sylvia; D'Ettorre, Patrizia; Drijfhout, Falko P.; Sledge, Matthew F.; Turillazzi, Stefano; Heinze, Jürgen

    2008-11-01

    Winged and wingless males coexist in the ant Cardiocondyla obscurior. Wingless (“ergatoid”) males never leave their maternal colony and fight remorselessly among each other for the access to emerging females. The peaceful winged males disperse after about 10 days, but beforehand also mate in the nest. In the first 5 days of their life, winged males perform a chemical female mimicry that protects them against attack and even makes them sexually attractive to ergatoid males. When older, the chemical profile of winged males no longer matches that of virgin females; nevertheless, they are still tolerated, which so far has been puzzling. Contrasting this general pattern, we have identified a single aberrant colony in which all winged males were attacked and killed by the ergatoid males. A comparative analysis of the morphology and chemical profile of these untypical attacked winged males and the tolerated males from several normal colonies revealed that normal old males are still performing some chemical mimicry to the virgin queens, though less perfect than in their young ages. The anomalous attacked winged males, on the other hand, had a very different odour to the females. Our study thus exemplifies that the analysis of rare malfunctioning can add valuable insight on functioning under normal conditions and allows the conclusion that older winged males from normal colonies of the ant C. obscurior are guarded through an imperfect chemical female mimicry, still close enough to protect against attacks by the wingless fighters yet dissimilar enough not to elicit their sexual interest.

  11. Computer-aided design of large-scale integrated circuits - A concept

    NASA Technical Reports Server (NTRS)

    Schansman, T. T.

    1971-01-01

    Circuit design and mask development sequence are improved by using general purpose computer with interactive graphics capability establishing efficient two way communications link between design engineer and system. Interactive graphics capability places design engineer in direct control of circuit development.

  12. Plasticity in single neuron and circuit computations

    NASA Astrophysics Data System (ADS)

    Destexhe, Alain; Marder, Eve

    2004-10-01

    Plasticity in neural circuits can result from alterations in synaptic strength or connectivity, as well as from changes in the excitability of the neurons themselves. To better understand the role of plasticity in the brain, we need to establish how brain circuits work and the kinds of computations that different circuit structures achieve. By linking theoretical and experimental studies, we are beginning to reveal the consequences of plasticity mechanisms for network dynamics, in both simple invertebrate circuits and the complex circuits of mammalian cerebral cortex.

  13. 2 Gbit/s 0.5 μm complementary metal-oxide semiconductor optical transceiver with event-driven dynamic power-on capability

    NASA Astrophysics Data System (ADS)

    Wang, Xingle; Kiamilev, Fouad; Gui, Ping; Wang, Xiaoqing; Ekman, Jeremy; Zuo, Yongrong; Blankenberg, Jason; Haney, Michael

    2006-06-01

    A 2 Gb/s0.5 μm complementary metal-oxide semiconductor optical transceiver designed for board- or backplane level power-efficient interconnections is presented. The transceiver supports optical wake-on-link (OWL), an event-driven dynamic power-on technique. Depending on external events, the transceiver resides in either the active mode or the sleep mode and switches accordingly. The active-to-sleep transition shuts off the normal, gigabit link and turns on dedicated circuits to establish a low-power (~1.8 mW), low data rate (less than 100 Mbits/s) link. In contrast the normal, gigabit link consumes over 100 mW. Similarly the sleep-to-active transition shuts off the low-power link and turns on the normal, gigabit link. The low-power link, sharing the same optical channel with the normal, gigabit link, is used to achieve transmitter/receiver pair power-on synchronization and greatly reduces the power consumption of the transceiver. A free-space optical platform was built to evaluate the transceiver performance. The experiment successfully demonstrated the event-driven dynamic power-on operation. To our knowledge, this is the first time a dynamic power-on scheme has been implemented for optical interconnects. The areas of the circuits that implement the low-power link are approximately one-tenth of the areas of the gigabit link circuits.

  14. Dual role of wingless signaling in stem-like hematopoietic precursor maintenance in Drosophila.

    PubMed

    Sinenko, Sergey A; Mandal, Lolitika; Martinez-Agosto, Julian A; Banerjee, Utpal

    2009-05-01

    In Drosophila, blood development occurs in a specialized larval hematopoietic organ, the lymph gland (LG), within which stem-like hemocyte precursors or prohemocytes differentiate to multiple blood cell types. Here we show that components of the Wingless (Wg) signaling pathway are expressed in prohemocytes. Loss- and gain-of-function analysis indicates that canonical Wg signaling is required for maintenance of prohemocytes and negatively regulates their differentiation. Wg signals locally in a short-range fashion within different compartments of the LG. In addition, Wg signaling positively regulates the proliferation and maintenance of cells that function as a hematopoietic niche in Drosophila, the posterior signaling center (PSC), and in the proliferation of crystal cells. Our studies reveal a conserved function of Wg signaling in the maintenance of stem-like blood progenitors and reveal an involvement of this pathway in the regulation of hemocyte differentiation through its action in the hematopoietic niche.

  15. Identification of a new stem cell population that generates Drosophila flight muscles.

    PubMed

    Gunage, Rajesh D; Reichert, Heinrich; VijayRaghavan, K

    2014-08-18

    How myoblast populations are regulated for the formation of muscles of different sizes is an essentially unanswered question. The large flight muscles of Drosophila develop from adult muscle progenitor (AMP) cells set-aside embryonically. The thoracic segments are all allotted the same small AMP number, while those associated with the wing-disc proliferate extensively to give rise to over 2500 myoblasts. An initial amplification occurs through symmetric divisions and is followed by a switch to asymmetric divisions in which the AMPs self-renew and generate post-mitotic myoblasts. Notch signaling controls the initial amplification of AMPs, while the switch to asymmetric division additionally requires Wingless, which regulates Numb expression in the AMP lineage. In both cases, the epidermal tissue of the wing imaginal disc acts as a niche expressing the ligands Serrate and Wingless. The disc-associated AMPs are a novel muscle stem cell population that orchestrates the early phases of adult flight muscle development.

  16. Gated high speed optical detector

    NASA Technical Reports Server (NTRS)

    Green, S. I.; Carson, L. M.; Neal, G. W.

    1973-01-01

    The design, fabrication, and test of two gated, high speed optical detectors for use in high speed digital laser communication links are discussed. The optical detectors used a dynamic crossed field photomultiplier and electronics including dc bias and RF drive circuits, automatic remote synchronization circuits, automatic gain control circuits, and threshold detection circuits. The equipment is used to detect binary encoded signals from a mode locked neodynium laser.

  17. A simple structure wavelet transform circuit employing function link neural networks and SI filters

    NASA Astrophysics Data System (ADS)

    Mu, Li; Yigang, He

    2016-12-01

    Signal processing by means of analog circuits offers advantages from a power consumption viewpoint. Implementing wavelet transform (WT) using analog circuits is of great interest when low-power consumption becomes an important issue. In this article, a novel simple structure WT circuit in analog domain is presented by employing functional link neural network (FLNN) and switched-current (SI) filters. First, the wavelet base is approximated using FLNN algorithms for giving a filter transfer function that is suitable for simple structure WT circuit implementation. Next, the WT circuit is constructed with the wavelet filter bank, whose impulse response is the approximated wavelet and its dilations. The filter design that follows is based on a follow-the-leader feedback (FLF) structure with multiple output bilinear SI integrators and current mirrors as the main building blocks. SI filter is well suited for this application since the dilation constant across different scales of the transform can be precisely implemented and controlled by the clock frequency of the circuit with the same system architecture. Finally, to illustrate the design procedure, a seventh-order FLNN-approximated Gaussian wavelet is implemented as an example. Simulations have successfully verified that the designed simple structure WT circuit has low sensitivity, low-power consumption and litter effect to the imperfections.

  18. Logic circuits from zero forcing.

    PubMed

    Burgarth, Daniel; Giovannetti, Vittorio; Hogben, Leslie; Severini, Simone; Young, Michael

    We design logic circuits based on the notion of zero forcing on graphs; each gate of the circuits is a gadget in which zero forcing is performed. We show that such circuits can evaluate every monotone Boolean function. By using two vertices to encode each logical bit, we obtain universal computation. We also highlight a phenomenon of "back forcing" as a property of each function. Such a phenomenon occurs in a circuit when the input of gates which have been already used at a given time step is further modified by a computation actually performed at a later stage. Finally, we show that zero forcing can be also used to implement reversible computation. The model introduced here provides a potentially new tool in the analysis of Boolean functions, with particular attention to monotonicity. Moreover, in the light of applications of zero forcing in quantum mechanics, the link with Boolean functions may suggest a new directions in quantum control theory and in the study of engineered quantum spin systems. It is an open technical problem to verify whether there is a link between zero forcing and computation with contact circuits.

  19. Circuit theory and model-based inference for landscape connectivity

    USGS Publications Warehouse

    Hanks, Ephraim M.; Hooten, Mevin B.

    2013-01-01

    Circuit theory has seen extensive recent use in the field of ecology, where it is often applied to study functional connectivity. The landscape is typically represented by a network of nodes and resistors, with the resistance between nodes a function of landscape characteristics. The effective distance between two locations on a landscape is represented by the resistance distance between the nodes in the network. Circuit theory has been applied to many other scientific fields for exploratory analyses, but parametric models for circuits are not common in the scientific literature. To model circuits explicitly, we demonstrate a link between Gaussian Markov random fields and contemporary circuit theory using a covariance structure that induces the necessary resistance distance. This provides a parametric model for second-order observations from such a system. In the landscape ecology setting, the proposed model provides a simple framework where inference can be obtained for effects that landscape features have on functional connectivity. We illustrate the approach through a landscape genetics study linking gene flow in alpine chamois (Rupicapra rupicapra) to the underlying landscape.

  20. Head Lice (For Parents)

    MedlinePlus

    ... Videos for Educators Search English Español First Aid: Head Lice KidsHealth / For Parents / First Aid: Head Lice Print A head louse is a tiny, wingless ... Prevention! You can help protect your kids from head lice by teaching them to: avoid head-to-head ...

  1. Reconstruction and in vivo analysis of the extinct tbx5 gene from ancient wingless moa (Aves: Dinornithiformes)

    PubMed Central

    2014-01-01

    Background The forelimb-specific gene tbx5 is highly conserved and essential for the development of forelimbs in zebrafish, mice, and humans. Amongst birds, a single order, Dinornithiformes, comprising the extinct wingless moa of New Zealand, are unique in having no skeletal evidence of forelimb-like structures. Results To determine the sequence of tbx5 in moa, we used a range of PCR-based techniques on ancient DNA to retrieve all nine tbx5 exons and splice sites from the giant moa, Dinornis. Moa Tbx5 is identical to chicken Tbx5 in being able to activate the downstream promotors of fgf10 and ANF. In addition we show that missexpression of moa tbx5 in the hindlimb of chicken embryos results in the formation of forelimb features, suggesting that Tbx5 was fully functional in wingless moa. An alternatively spliced exon 1 for tbx5 that is expressed specifically in the forelimb region was shown to be almost identical between moa and ostrich, suggesting that, as well as being fully functional, tbx5 is likely to have been expressed normally in moa since divergence from their flighted ancestors, approximately 60 mya. Conclusions The results suggests that, as in mice, moa tbx5 is necessary for the induction of forelimbs, but is not sufficient for their outgrowth. Moa Tbx5 may have played an important role in the development of moa’s remnant forelimb girdle, and may be required for the formation of this structure. Our results further show that genetic changes affecting genes other than tbx5 must be responsible for the complete loss of forelimbs in moa. PMID:24885927

  2. Comparative thoracic anatomy of the wild type and wingless (wg1cn1) mutant of Drosophila melanogaster (Diptera).

    PubMed

    Fabian, Benjamin; Schneeberg, Katharina; Beutel, Rolf Georg

    2016-11-01

    Genetically modified organisms are crucial for our understanding of gene regulatory networks, physiological processes and ontogeny. With modern molecular genetic techniques allowing the rapid generation of different Drosophila melanogaster mutants, efficient in-depth morphological investigations become an important issue. Anatomical studies can elucidate the role of certain genes in developmental processes and point out which parts of gene regulatory networks are involved in evolutionary changes of morphological structures. The wingless mutation wg 1 of D. melanogaster was discovered more than 40 years ago. While early studies addressed the external phenotype of these mutants, the documentation of the internal organization was largely restricted to the prominent indirect flight muscles. We used SEM micrographs, histological serial sections, μ-computed tomography, CLSM and 3D reconstructions to study and document the thoracic skeletomuscular system of the wild type and mutant. A recently introduced nomenclature for the musculature of neopteran insects was applied to facilitate comparisons with closely or more distantly related taxa. The mutation is phenotypically mainly characterized by the absence of one or both wings and halteres. The wing is partly or entirely replaced by duplications of mesonotal structures, whereas the haltere and its associated muscles are completely absent on body sides showing the reduction. Both the direct and indirect mesothoracic flight muscles are affected by loss and reorientation of bundles or fibers. Our observations lead to the conclusion that the wingless mutation causes a homeotic transformation in the imaginal discs of wings and halteres with a direct effect on the development of skeletal structures and an indirect effect on the associated muscular system. Copyright © 2016 Elsevier Ltd. All rights reserved.

  3. Wide-band polarization controller for Si photonic integrated circuits.

    PubMed

    Velha, P; Sorianello, V; Preite, M V; De Angelis, G; Cassese, T; Bianchi, A; Testa, F; Romagnoli, M

    2016-12-15

    A circuit for the management of any arbitrary polarization state of light is demonstrated on an integrated silicon (Si) photonics platform. This circuit allows us to adapt any polarization into the standard fundamental TE mode of a Si waveguide and, conversely, to control the polarization and set it to any arbitrary polarization state. In addition, the integrated thermal tuning allows kilohertz speed which can be used to perform a polarization scrambler. The circuit was used in a WDM link and successfully used to adapt four channels into a standard Si photonic integrated circuit.

  4. Design and characterization of a 20 Gbit/s clock recovery circuit

    NASA Astrophysics Data System (ADS)

    Monteiro, Paulo M.; Matos, J. N.; Gameiro, Atilio M. S.; da Rocha, Jose F.

    1995-02-01

    In this communication we report the design of a clock recovery circuit produced for the 20 Gbit/s demonstrator of the RACE 2011 project `TRAVEL' of the European Community. The clock recovery circuit is based on an open loop structure using a dielectric resonator narrow bandpass filter with a high quality factor. A detailed electrical characterization of the circuit and also its sensitivity to temperature and detuning variations are presented. The experimental results show that the circuit is a very attractive solution for the forthcoming STM-128 optical links.

  5. Unified Ultrasonic/Eddy-Current Data Acquisition

    NASA Technical Reports Server (NTRS)

    Chern, E. James; Butler, David W.

    1993-01-01

    Imaging station for detecting cracks and flaws in solid materials developed combining both ultrasonic C-scan and eddy-current imaging. Incorporation of both techniques into one system eliminates duplication of computers and of mechanical scanners; unifies acquisition, processing, and storage of data; reduces setup time for repetitious ultrasonic and eddy-current scans; and increases efficiency of system. Same mechanical scanner used to maneuver either ultrasonic or eddy-current probe over specimen and acquire point-by-point data. For ultrasonic scanning, probe linked to ultrasonic pulser/receiver circuit card, while, for eddy-current imaging, probe linked to impedance-analyzer circuit card. Both ultrasonic and eddy-current imaging subsystems share same desktop-computer controller, containing dedicated plug-in circuit boards for each.

  6. Visual Confirmation of Voice Takeoff Clearance (VICON) Operational Evaluation. Volume 2. Operations and Maintenance Manual

    DTIC Science & Technology

    1981-02-01

    cabinet and the field. The momentary contacts from the switches of the control panel trigger the respective circuits in module I. This circuit then... module (approximately 40 milliamperes at 70-100 detector, filter, threshold circuit and alarm relay. A block volts) Into microwave energy at X-band...advantageous to use different N.C. Terminals. NOTE: If open circuit tamper switch is modulation frequencies on links operating within close prox

  7. Control of Bovicola Equi (Phthiraptera: Trichodectidae) with Dimilin and Permethrin

    USDA-ARS?s Scientific Manuscript database

    Lice are wingless ectoparasitic insects that can irritate and injure their hosts and transmit pathogens. Horses and ponies can be infested with a chewing louse, Bovicola equi (Denny) (Phthiraptera: Trichodectidae) that irritates the animals, creates skin lesions, causes hair loss, and generally redu...

  8. Evolution of thorax architecture in ant castes highlights trade-off between flight and ground behaviors

    PubMed Central

    Keller, Roberto A; Peeters, Christian; Beldade, Patrícia

    2014-01-01

    The concerted evolution of morphological and behavioral specializations has compelling examples in ant castes. Unique to ants is a marked divergence between winged queens and wingless workers, but morphological specializations for behaviors on the ground have been overlooked. We analyzed thorax morphology of queens and workers in species from 21 of the 25 ant subfamilies. We uncovered unique skeletomuscular modifications in workers that presumably increase power and flexibility of head–thorax articulation, emphasizing that workers are not simply wingless versions of queens. We also identified two distinct types of queens and showed repeated evolutionary associations with strategies of colony foundation. Solitary founding queens that hunt have a more worker-like thorax. Our results reveal that ants invest in the relative size of thorax segments according to their tasks. Versatility of head movements allows for better manipulation of food and objects, which arguably contributed to the ants’ ecological and evolutionary success. DOI: http://dx.doi.org/10.7554/eLife.01539.001 PMID:24399458

  9. Composition and biological activity of essential oils against Metopolophium dirhodum (Hemiptera: Aphididae) cereal crop pest.

    PubMed

    Chopa, Carolina Sánchez; Descamps, Lilian R

    2012-11-01

    Natural pesticides based on plant essential oils may represent alternative crop protectants. This study analysed the chemical constituents and bioactivities of essential oils from Schinus areira L., Rosmarinus officinalis L. and Tagetes terniflora Kunth against winged and wingless adults of Metopolophium dirhodum (Walk.). The major component of S. areira was α-phellandrene, that of R. officinalis was 1,8-cineole and that of T. terniflora was cis-ocimene. Rosemary essential oil was more effective than the others in immersion method tests. In contact toxicity, the rosemary oil was the most toxic to wingless adults and the S. areira leaf oil was the most toxic to winged adults. All the EOs produced some degrees of repellency in adults and effects on the reproduction and demographic parameters. These results showed that the essential oils from S. areira, R. officinalis and T. terniflora could be used as an alternative in the management of M. dirhodum. Copyright © 2012 Society of Chemical Industry.

  10. Evolution of thorax architecture in ant castes highlights trade-off between flight and ground behaviors.

    PubMed

    Keller, Roberto A; Peeters, Christian; Beldade, Patrícia

    2014-01-01

    The concerted evolution of morphological and behavioral specializations has compelling examples in ant castes. Unique to ants is a marked divergence between winged queens and wingless workers, but morphological specializations for behaviors on the ground have been overlooked. We analyzed thorax morphology of queens and workers in species from 21 of the 25 ant subfamilies. We uncovered unique skeletomuscular modifications in workers that presumably increase power and flexibility of head-thorax articulation, emphasizing that workers are not simply wingless versions of queens. We also identified two distinct types of queens and showed repeated evolutionary associations with strategies of colony foundation. Solitary founding queens that hunt have a more worker-like thorax. Our results reveal that ants invest in the relative size of thorax segments according to their tasks. Versatility of head movements allows for better manipulation of food and objects, which arguably contributed to the ants' ecological and evolutionary success. DOI: http://dx.doi.org/10.7554/eLife.01539.001.

  11. Micropower circuits for bidirectional wireless telemetry in neural recording applications.

    PubMed

    Neihart, Nathan M; Harrison, Reid R

    2005-11-01

    State-of-the art neural recording systems require electronics allowing for transcutaneous, bidirectional data transfer. As these circuits will be implanted near the brain, they must be small and low power. We have developed micropower integrated circuits for recovering clock and data signals over a transcutaneous power link. The data recovery circuit produces a digital data signal from an ac power waveform that has been amplitude modulated. We have also developed an FM transmitter with the lowest power dissipation reported for biosignal telemetry. The FM transmitter consists of a low-noise biopotential amplifier and a voltage controlled oscillator used to transmit amplified neural signals at a frequency near 433 MHz. All circuits were fabricated in a standard 0.5-microm CMOS VLSI process. The resulting chip is powered through a wireless inductive link. The power consumption of the clock and data recovery circuits is measured to be 129 microW; the power consumption of the transmitter is measured to be 465 microW when using an external surface mount inductor. Using a parasitic antenna less than 2 mm long, a received power level was measured to be -59.73 dBm at a distance of one meter.

  12. Role of intraglomerular circuits in shaping temporally structured responses to naturalistic inhalation-driven sensory input to the olfactory bulb

    PubMed Central

    Carey, Ryan M.; Sherwood, William Erik; Shipley, Michael T.; Borisyuk, Alla

    2015-01-01

    Olfaction in mammals is a dynamic process driven by the inhalation of air through the nasal cavity. Inhalation determines the temporal structure of sensory neuron responses and shapes the neural dynamics underlying central olfactory processing. Inhalation-linked bursts of activity among olfactory bulb (OB) output neurons [mitral/tufted cells (MCs)] are temporally transformed relative to those of sensory neurons. We investigated how OB circuits shape inhalation-driven dynamics in MCs using a modeling approach that was highly constrained by experimental results. First, we constructed models of canonical OB circuits that included mono- and disynaptic feedforward excitation, recurrent inhibition and feedforward inhibition of the MC. We then used experimental data to drive inputs to the models and to tune parameters; inputs were derived from sensory neuron responses during natural odorant sampling (sniffing) in awake rats, and model output was compared with recordings of MC responses to odorants sampled with the same sniff waveforms. This approach allowed us to identify OB circuit features underlying the temporal transformation of sensory inputs into inhalation-linked patterns of MC spike output. We found that realistic input-output transformations can be achieved independently by multiple circuits, including feedforward inhibition with slow onset and decay kinetics and parallel feedforward MC excitation mediated by external tufted cells. We also found that recurrent and feedforward inhibition had differential impacts on MC firing rates and on inhalation-linked response dynamics. These results highlight the importance of investigating neural circuits in a naturalistic context and provide a framework for further explorations of signal processing by OB networks. PMID:25717156

  13. Communications circuit including a linear quadratic estimator

    DOEpatents

    Ferguson, Dennis D.

    2015-07-07

    A circuit includes a linear quadratic estimator (LQE) configured to receive a plurality of measurements a signal. The LQE is configured to weight the measurements based on their respective uncertainties to produce weighted averages. The circuit further includes a controller coupled to the LQE and configured to selectively adjust at least one data link parameter associated with a communication channel in response to receiving the weighted averages.

  14. Software defined network architecture based research on load balancing strategy

    NASA Astrophysics Data System (ADS)

    You, Xiaoqian; Wu, Yang

    2018-05-01

    As a new type network architecture, software defined network has the key idea of separating the control place of the network from the transmission plane, to manage and control the network in a concentrated way; in addition, the network interface is opened on the control layer and the data layer, so as to achieve programmable control of the network. Considering that only the single shortest route is taken into the calculation of traditional network data flow transmission, and congestion and resource consumption caused by excessive load of link circuits are ignored, a link circuit load based flow media business QoS gurantee system is proposed in this article to divide the flow in the network into ordinary data flow and QoS flow. In this way, it supervises the link circuit load with the controller so as to calculate reasonable route rapidly and issue the flow table to the exchanger, to finish rapid data transmission. In addition, it establishes a simulation platform to acquire optimized result through simulation experiment.

  15. Electronic Position Sensor for Power Operated Accessory

    DOEpatents

    Haag, Ronald H.; Chia, Michael I.

    2005-05-31

    An electronic position sensor for use with a power operated vehicle accessory, such as a power liftgate. The position sensor includes an elongated resistive circuit that is mounted such that it is stationary and extends along the path of a track portion of the power operated accessory. The position sensor further includes a contact nub mounted to a link member that moves within the track portion such that the contact nub is slidingly biased against the elongated circuit. As the link member moves under the force of a motor-driven output gear, the contact nub slides along the surface of the resistive circuit, thereby affecting the overall resistance of the circuit. The position sensor uses the overall resistance to provide an electronic position signal to an ECU, wherein the signal is indicative of the absolute position of the power operated accessory. Accordingly, the electronic position sensor is capable of providing an electronic signal that enables the ECU to track the absolute position of the power operated accessory.

  16. Quantum mechanical settings inspired by RLC circuits

    NASA Astrophysics Data System (ADS)

    Alicata, G.; Bagarello, F.; Gargano, F.; Spagnolo, S.

    2018-04-01

    In some recent papers, several authors used electronic circuits to construct loss and gain systems. This is particularly interesting in the context of PT-quantum mechanics, where this kind of effects appears quite naturally. The electronic circuits used so far are simple, but not so much. Surprisingly enough, a rather trivial RLC circuit can be analyzed with the same perspective and it produces a variety of unexpected results, both from a mathematical and on a physical side. In this paper, we show that this circuit produces two biorthogonal bases associated with the Liouville matrix L used in the treatment of its dynamics, with a biorthogonality which is linked to the value of the parameters of the circuit. We also show that the related loss RLC circuit is naturally associated with a gain RLC circuit and that the relation between the two is rather naturally encoded in L . We propose a pseudo-fermionic analysis of the circuit, and we introduce the notion of m-equivalence between electronic circuits.

  17. Law Library - Alaska Court System

    Science.gov Websites

    , Federal Info, US Supreme Court, State Links, 9th Circuit Links Library Databases & eBooks WestlawNext state agencies Alaska Supreme Court briefs (1960-current) Alaska Court of Appeals briefs (1980-current

  18. Circuit engineering principles for construction of bipolar large-scale integrated circuit storage devices and very large-scale main memory

    NASA Astrophysics Data System (ADS)

    Neklyudov, A. A.; Savenkov, V. N.; Sergeyez, A. G.

    1984-06-01

    Memories are improved by increasing speed or the memory volume on a single chip. The most effective means for increasing speeds in bipolar memories are current control circuits with the lowest extraction times for a specific power consumption (1/4 pJ/bit). The control current circuitry involves multistage current switches and circuits accelerating transient processes in storage elements and links. Circuit principles for the design of bipolar memories with maximum speeds for an assigned minimum of circuit topology are analyzed. Two main classes of storage with current control are considered: the ECL type and super-integrated injection type storage with data capacities of N = 1/4 and N 4/16, respectively. The circuits reduce logic voltage differentials and the volumes of lexical and discharge buses and control circuit buses. The limiting speed is determined by the antiinterference requirements of the memory in storage and extraction modes.

  19. Comparative profiling of microRNAs in the winged and wingless English grain aphid, Sitobion avenae (F.) (Homoptera: Aphididae)

    USDA-ARS?s Scientific Manuscript database

    English green aphid, Sitobion avenae (F.), show a classic polyphenic wing dimorphism among isogenic adults that is an intriguing model for the study of morphological plasticity in response to the environment. Short non-coding microRNA (miRNA) molecules regulate gene expression by post-transcriptiona...

  20. Aerial manoeuvrability in wingless gliding ants (Cephalotes atratus)

    PubMed Central

    Yanoviak, Stephen P.; Munk, Yonatan; Kaspari, Mike; Dudley, Robert

    2010-01-01

    In contrast to the patagial membranes of gliding vertebrates, the aerodynamic surfaces used by falling wingless ants to direct their aerial descent are unknown. We conducted ablation experiments to assess the relative contributions of the hindlegs, midlegs and gaster to gliding success in workers of the Neotropical arboreal ant Cephalotes atratus (Hymenoptera: Formicidae). Removal of hindlegs significantly reduced the success rate of directed aerial descent as well as the glide index for successful flights. Removal of the gaster alone did not significantly alter performance relative to controls. Equilibrium glide angles during successful targeting to vertical columns were statistically equivalent between control ants and ants with either the gaster or the hindlegs removed. High-speed video recordings suggested possible use of bilaterally asymmetric motions of the hindlegs to effect body rotations about the vertical axis during targeting manoeuvre. Overall, the control of gliding flight was remarkably robust to dramatic anatomical perturbations, suggesting effective control mechanisms in the face of adverse initial conditions (e.g. falling upside down), variable targeting decisions and turbulent wind gusts during flight. PMID:20236974

  1. A Wingless and Notch double-repression mechanism regulates G1–S transition in the Drosophila wing

    PubMed Central

    Herranz, Héctor; Pérez, Lidia; Martín, Francisco A; Milán, Marco

    2008-01-01

    The control of tissue growth and patterning is orchestrated in various multicellular tissues by the coordinated activity of the signalling molecules Wnt/Wingless (Wg) and Notch, and mutations in these pathways can cause cancer. The role of these molecules in the control of cell proliferation and the crosstalk between their corresponding pathways remain poorly understood. Crosstalk between Notch and Wg has been proposed to organize pattern and growth in the Drosophila wing primordium. Here we report that Wg and Notch act in a surprisingly linear pathway to control G1–S progression. We present evidence that these molecules exert their function by regulating the expression of the dmyc proto-oncogene and the bantam micro-RNA, which positively modulated the activity of the E2F transcription factor. Our results demonstrate that Notch acts in this cellular context as a repressor of cell-cycle progression and Wg has a permissive role in alleviating Notch-mediated repression of G1–S progression in wing cells. PMID:18451803

  2. Life-history evolution in ants: the case of Cardiocondyla

    PubMed Central

    2017-01-01

    Ants are important components of most terrestrial habitats, and a better knowledge of the diversity of their life histories is essential to understand many aspects of ecosystem functioning. The myrmicine genus Cardiocondyla shows a wide range of colony structures, reproductive behaviours, queen and male lifespans, and habitat use. Reconstructing the evolutionary pathways of individual and social phenotypic traits suggests that the ancestral life history of Cardiocondyla was characterized by the presence of multiple, short-lived queens in small-sized colonies and a male polyphenism with winged dispersers and wingless fighters, which engage in lethal combat over female sexuals within their natal nests. Single queening, queen polyphenism, the loss of winged males and tolerance among wingless males appear to be derived traits that evolved with changes in nesting habits, colony size and the spread from tropical to seasonal environments. The aim of this review is to bring together the information on life-history evolution in Cardiocondyla and to highlight the suitability of this genus for functional genomic studies of adaptation, phenotypic plasticity, senescence, invasiveness and other key life-history traits of ants. PMID:28298341

  3. Arachnid aloft: directed aerial descent in neotropical canopy spiders.

    PubMed

    Yanoviak, Stephen P; Munk, Yonatan; Dudley, Robert

    2015-09-06

    The behaviour of directed aerial descent has been described for numerous taxa of wingless hexapods as they fall from the tropical rainforest canopy, but is not known in other terrestrial arthropods. Here, we describe similar controlled aerial behaviours for large arboreal spiders in the genus Selenops (Selenopidae). We dropped 59 such spiders from either canopy platforms or tree crowns in Panama and Peru; the majority (93%) directed their aerial trajectories towards and then landed upon nearby tree trunks. Following initial dorsoventral righting when necessary, falling spiders oriented themselves and then translated head-first towards targets; directional changes were correlated with bilaterally asymmetric motions of the anterolaterally extended forelegs. Aerial performance (i.e. the glide index) decreased with increasing body mass and wing loading, but not with projected surface area of the spider. Along with the occurrence of directed aerial descent in ants, jumping bristletails, and other wingless hexapods, this discovery of targeted gliding in selenopid spiders further indicates strong selective pressures against uncontrolled falls into the understory for arboreal taxa. © 2015 The Author(s).

  4. Novel Directions for Diabetes Mellitus Drug Discovery

    PubMed Central

    Maiese, Kenneth; Chong, Zhao Zhong; Shang, Yan Chen; Wang, Shaohui

    2012-01-01

    Introduction Diabetes mellitus impacts almost 200 million individuals worldwide and leads to debilitating complications. New avenues of drug discovery must target the underlying cellular processes of oxidative stress, apoptosis, autophagy, and inflammation that can mediate multi-system pathology during diabetes mellitus. Areas Covered We examine novel directions for drug discovery that involve the β-nicotinamide adenine dinucleotide (NAD+) precursor nicotinamide, the cytokine erythropoietin, the NAD+-dependent protein histone deacetylase SIRT1, the serine/threonine-protein kinase mammalian target of rapamycin (mTOR), and the wingless pathway. Implications for the targeting of these pathways that oversee gluconeogenic genes, insulin signaling and resistance, fatty acid beta-oxidation, inflammation, and cellular survival are presented. Expert Opinion Nicotinamide, erythropoietin, and the downstram pathways of SIRT1, mTOR, forkhead transcription factors, and wingless signaling offer exciting prospects for novel directions of drug discovery for the treatment of metabolic disorders. Future investigations must dissect the complex relationship and fine modulation of these pathways for the successful translation of robust reparative and regenerative strategies against diabetes mellitus and the complications of this disorder. PMID:23092114

  5. The APC/C Coordinates Retinal Differentiation with G1 Arrest through the Nek2-Dependent Modulation of Wingless Signaling.

    PubMed

    Martins, Torcato; Meghini, Francesco; Florio, Francesca; Kimata, Yuu

    2017-01-09

    The cell cycle is coordinated with differentiation during animal development. Here we report a cell-cycle-independent developmental role for a master cell-cycle regulator, the anaphase-promoting complex or cyclosome (APC/C), in the regulation of cell fate through modulation of Wingless (Wg) signaling. The APC/C controls both cell-cycle progression and postmitotic processes through ubiquitin-dependent proteolysis. Through an RNAi screen in the developing Drosophila eye, we found that partial APC/C inactivation severely inhibits retinal differentiation independently of cell-cycle defects. The differentiation inhibition coincides with hyperactivation of Wg signaling caused by the accumulation of a Wg modulator, Drosophila Nek2 (dNek2). The APC/C degrades dNek2 upon synchronous G1 arrest prior to differentiation, which allows retinal differentiation through local suppression of Wg signaling. We also provide evidence that decapentaplegic signaling may posttranslationally regulate this APC/C function. Thus, the APC/C coordinates cell-fate determination with the cell cycle through the modulation of developmental signaling pathways. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  6. Imbalanced functional link between reward circuits and the cognitive control system in patients with obsessive-compulsive disorder.

    PubMed

    Xie, Chunming; Ma, Lisha; Jiang, Nan; Huang, Ruyan; Li, Li; Gong, Liang; He, Cancan; Xiao, Chaoyong; Liu, Wen; Xu, Shu; Zhang, Zhijun

    2017-08-01

    Altered reward processing and cognitive deficits are often observed in patients with obsessive-compulsive disorder (OCD); however, whether the imbalance in activity between reward circuits and the cognitive control (CC) system is associated with compulsive behavior remains unknown. Sixty-eight OCD patients and 33 cognitively normal (CN) healthy subjects participated in this resting-state functional magnetic resonance imaging study. Alterations in the functional connectivity between reward circuits and the CC system were quantitatively assessed and compared between the groups. A Granger causality analysis was used to determine the causal informational influence between and within reward circuits and the CC system across all subjects. OCD patients showed a dichotomous pattern of enhanced functional coupling in their reward circuits and a weakened functional coupling in their CC system when compared to CN subjects. Neural correlates of compulsive behavior were primarily located in the reward circuits and CC system in OCD patients. Importantly, the CC system exerted a reduced interregional causal influence over the reward system in OCD patients relative to its effect in CN subjects. The limitations of this study are that it was a cross-sectional study and the potential effects of environmental and genetic factors were not explored. OCD patients showed an imbalance in the functional link between reward circuits and the CC system at rest. This bias toward a loss of control may define a pathological state in which subjects are more vulnerable to engaging in compulsive behaviors.

  7. Laser Direct Routing for High Density Interconnects

    NASA Astrophysics Data System (ADS)

    Moreno, Wilfrido Alejandro

    The laser restructuring of electronic circuits fabricated using standard Very Large Scale Integration (VLSI) process techniques, is an excellent alternative that allows low-cost quick turnaround production with full circuit similarity between the Laser Restructured prototype and the customized product for mass production. Laser Restructurable VLSI (LRVLSI) would allow design engineers the capability to interconnect cells that implement generic logic functions and signal processing schemes to achieve a higher level of design complexity. LRVLSI of a particular circuit at the wafer or packaged chip level is accomplished using an integrated computer controlled laser system to create low electrical resistance links between conductors and to cut conductor lines. An infrastructure for rapid prototyping and quick turnaround using Laser Restructuring of VLSI circuits was developed to meet three main parallel objectives: to pursue research on novel interconnect technologies using LRVLSI, to develop the capability of operating in a quick turnaround mode, and to maintain standardization and compatibility with commercially available equipment for feasible technology transfer. The system is to possess a high degree of flexibility, high data quality, total controllability, full documentation, short downtime, a user-friendly operator interface, automation, historical record keeping, and error indication and logging. A specially designed chip "SLINKY" was used as the test vehicle for the complete characterization of the Laser Restructuring system. With the use of Design of Experiment techniques the Lateral Diffused Link (LDL), developed originally at MIT Lincoln Laboratories, was completely characterized and for the first time a set of optimum process parameters was obtained. With the designed infrastructure fully operational, the priority objective was the search for a substitute for the high resistance, high current leakage to substrate, and relatively low density Lateral Diffused Link. A high density Laser Vertical Link with resistance values below 10 ohms was developed, studied and tested using design of experiment methodologies. The vertical link offers excellent advantages in the area of quick prototyping of electronic circuits, but even more important, due to having similar characteristics to a foundry produced via, it gives quick transfer from the prototype system verification stage to the mass production stage.

  8. 2D bifurcations and Newtonian properties of memristive Chua's circuits

    NASA Astrophysics Data System (ADS)

    Marszalek, W.; Podhaisky, H.

    2016-01-01

    Two interesting properties of Chua's circuits are presented. First, two-parameter bifurcation diagrams of Chua's oscillatory circuits with memristors are presented. To obtain various 2D bifurcation images a substantial numerical effort, possibly with parallel computations, is needed. The numerical algorithm is described first and its numerical code for 2D bifurcation image creation is available for free downloading. Several color 2D images and the corresponding 1D greyscale bifurcation diagrams are included. Secondly, Chua's circuits are linked to Newton's law φ ''= F(t,φ,φ')/m with φ=\\text{flux} , constant m > 0, and the force term F(t,φ,φ') containing memory terms. Finally, the jounce scalar equations for Chua's circuits are also discussed.

  9. European Non-Dissipative Bypass Switch For Li-Ion Batteries And Prospective

    NASA Astrophysics Data System (ADS)

    Pasquier, E.; Castric, AF.; Mosset, E.; Chandeneau, A.

    2011-10-01

    Li-ion batteries are made of cells or modules connected in series. In case one may be too weak or failed, it becomes necessary to remove it from the serial circuit. This is the by-pass operation which provides overcharge/open-circuitprotection,limitation of possible constraints linked to over- discharge/reversal/"self-short" and avoid to jeopardize rest of battery. One system is particularly adapted to Space Li-ion batteries: the "make before break" Single Pole Double Throw (SPDT) switch which avoids open- circuit on power circuit when correctly activated. This paper presents the component constraints, the development in the frame of ESA Artès 3 program up to its qualification, as well as the motorization approach linked to ECSS-E-30 (mechanical - Part 3: Mechanisms) and future opportunities of such system.

  10. Control model design to limit DC-link voltage during grid fault in a dfig variable speed wind turbine

    NASA Astrophysics Data System (ADS)

    Nwosu, Cajethan M.; Ogbuka, Cosmas U.; Oti, Stephen E.

    2017-08-01

    This paper presents a control model design capable of inhibiting the phenomenal rise in the DC-link voltage during grid- fault condition in a variable speed wind turbine. Against the use of power circuit protection strategies with inherent limitations in fault ride-through capability, a control circuit algorithm capable of limiting the DC-link voltage rise which in turn bears dynamics that has direct influence on the characteristics of the rotor voltage especially during grid faults is here proposed. The model results so obtained compare favorably with the simulation results as obtained in a MATLAB/SIMULINK environment. The generated model may therefore be used to predict near accurately the nature of DC-link voltage variations during fault given some factors which include speed and speed mode of operation, the value of damping resistor relative to half the product of inner loop current control bandwidth and the filter inductance.

  11. Nanophotonic integrated circuits from nanoresonators grown on silicon.

    PubMed

    Chen, Roger; Ng, Kar Wei; Ko, Wai Son; Parekh, Devang; Lu, Fanglu; Tran, Thai-Truong D; Li, Kun; Chang-Hasnain, Connie

    2014-07-07

    Harnessing light with photonic circuits promises to catalyse powerful new technologies much like electronic circuits have in the past. Analogous to Moore's law, complexity and functionality of photonic integrated circuits depend on device size and performance scale. Semiconductor nanostructures offer an attractive approach to miniaturize photonics. However, shrinking photonics has come at great cost to performance, and assembling such devices into functional photonic circuits has remained an unfulfilled feat. Here we demonstrate an on-chip optical link constructed from InGaAs nanoresonators grown directly on a silicon substrate. Using nanoresonators, we show a complete toolkit of circuit elements including light emitters, photodetectors and a photovoltaic power supply. Devices operate with gigahertz bandwidths while consuming subpicojoule energy per bit, vastly eclipsing performance of prior nanostructure-based optoelectronics. Additionally, electrically driven stimulated emission from an as-grown nanostructure is presented for the first time. These results reveal a roadmap towards future ultradense nanophotonic integrated circuits.

  12. Bedbugs: An Equal Opportunist and Cosmopolitan Creature

    ERIC Educational Resources Information Center

    Krause-Parello, Cheryl A.; Sciscione, Patricia

    2009-01-01

    Currently there is a rise in bedbugs seen in schools. The wingless, blood-sucking insects can arrive at school via student book bags, student clothing, or other personal items. If a student presents in the health office with a bite mark, the school nurse will need to differentiate between a bedbug bite and other insect bites, such as fleas,…

  13. A new method of radio frequency links by coplanar coils for implantable medical devices.

    PubMed

    Xue, L; Hao, H W; Li, L; Ma, B Z

    2005-01-01

    A new method based on coplanar coils for the design of radio frequency links has been developed, to realize the communication between the programming wand and the implantable medical devices with shielding container simply and reliably. With the analysis of electronic and magnetic field theory, the communication model has been established and simulated, and the circuit has been designed and tested. The experimental results are consistent with the simulation fairly well. The voltage transfer ratio of the typical circuit with present parameters can reach as high as 0.02, which can fulfill the requirements of communication.

  14. Performance of circuit switching in the Internet

    NASA Astrophysics Data System (ADS)

    Molinero-Fernández, Pablo; McKeown, Nick

    2003-04-01

    We study the performance of an Internet that uses circuit switching (CS) instead of, or in addition to, packet switching (PS). On the face of it, this would seem a pointless exercise; the Internet is packet switched, and it was deliberately built that way to enable the efficiencies afforded by statistical multiplexing and the robustness of fast rerouting around failures. But link utilization is low particularly at the core of the Internet, which makes statistical multiplexing less important than it once was. Moreover, circuit switches today are capable of rapid reconfiguration around failures. There is also renewed interest in CS because of the ease of building very-high-capacity optical circuit switches. Although several proposals have suggested ways in which CS may be introduced into the Internet, the research presented here is based on Transmission Control Protocol (TCP) switching, in which a new circuit is created for each application flow. Here we explore the performance of a network that uses TCP switching, with particular emphasis on the response time experienced by users. We use simple M/GI/1 and M/GI/N queues to model application flows in both packet-switched and circuit-switched networks, as well as ns-2 simulations. We conclude that because of high-bandwidth long-lived flows, it does not make sense to use CS in shared-access or local area networks. But our results suggest that in the core of the network, where high capacity is needed most, and where peak flow rate is limited by the access link, there is little or no difference in performance between CS and PS. Given that circuit switches can be built to be much faster than packet switches, this suggests that a circuit-switched core warrants further investigation.

  15. Wiring Together Synthetic Bacterial Consortia to Create a Biological Integrated Circuit.

    PubMed

    Perry, Nicolas; Nelson, Edward M; Timp, Gregory

    2016-12-16

    The promise of adapting biology to information processing will not be realized until engineered gene circuits, operating in different cell populations, can be wired together to express a predictable function. Here, elementary biological integrated circuits (BICs), consisting of two sets of transmitter and receiver gene circuit modules with embedded memory placed in separate cell populations, were meticulously assembled using live cell lithography and wired together by the mass transport of quorum-sensing (QS) signal molecules to form two isolated communication links (comlinks). The comlink dynamics were tested by broadcasting "clock" pulses of inducers into the networks and measuring the responses of functionally linked fluorescent reporters, and then modeled through simulations that realistically captured the protein production and molecular transport. These results show that the comlinks were isolated and each mimicked aspects of the synchronous, sequential networks used in digital computing. The observations about the flow conditions, derived from numerical simulations, and the biofilm architectures that foster or silence cell-to-cell communications have implications for everything from decontamination of drinking water to bacterial virulence.

  16. Spontaneous network activity and synaptic development

    PubMed Central

    Kerschensteiner, Daniel

    2014-01-01

    Throughout development, the nervous system produces patterned spontaneous activity. Research over the last two decades has revealed a core group of mechanisms that mediate spontaneous activity in diverse circuits. Many circuits engage several of these mechanisms sequentially to accommodate developmental changes in connectivity. In addition to shared mechanisms, activity propagates through developing circuits and neuronal pathways (i.e. linked circuits in different brain areas) in stereotypic patterns. Increasing evidence suggests that spontaneous network activity shapes synaptic development in vivo. Variations in activity-dependent plasticity may explain how similar mechanisms and patterns of activity can be employed to establish diverse circuits. Here, I will review common mechanisms and patterns of spontaneous activity in emerging neural networks and discuss recent insights into their contribution to synaptic development. PMID:24280071

  17. Circuit to Construct Mapping: A Mathematical Tool for Assisting the Diagnosis and Treatment in Major Depressive Disorder

    PubMed Central

    Bielczyk, Natalia Z.; Buitelaar, Jan K.; Glennon, Jeffrey C.; Tiesinga, Paul H. E.

    2015-01-01

    Major depressive disorder (MDD) is a serious condition with a lifetime prevalence exceeding 16% worldwide. MDD is a heterogeneous disorder that involves multiple behavioral symptoms on the one hand and multiple neuronal circuits on the other hand. In this review, we integrate the literature on cognitive and physiological biomarkers of MDD with the insights derived from mathematical models of brain networks, especially models that can be used for fMRI datasets. We refer to the recent NIH research domain criteria initiative, in which a concept of “constructs” as functional units of mental disorders is introduced. Constructs are biomarkers present at multiple levels of brain functioning – cognition, genetics, brain anatomy, and neurophysiology. In this review, we propose a new approach which we called circuit to construct mapping (CCM), which aims to characterize causal relations between the underlying network dynamics (as the cause) and the constructs referring to the clinical symptoms of MDD (as the effect). CCM involves extracting diagnostic categories from behavioral data, linking circuits that are causal to these categories with use of clinical neuroimaging data, and modeling the dynamics of the emerging circuits with attractor dynamics in order to provide new, neuroimaging-related biomarkers for MDD. The CCM approach optimizes the clinical diagnosis and patient stratification. It also addresses the recent demand for linking circuits to behavior, and provides a new insight into clinical treatment by investigating the dynamics of neuronal circuits underneath cognitive dimensions of MDD. CCM can serve as a new regime toward personalized medicine, assisting the diagnosis and treatment of MDD. PMID:25767450

  18. Encyclopedia of bacterial gene circuits whose presence or absence correlate with pathogenicity--a large-scale system analysis of decoded bacterial genomes.

    PubMed

    Shestov, Maksim; Ontañón, Santiago; Tozeren, Aydin

    2015-10-13

    Bacterial infections comprise a global health challenge as the incidences of antibiotic resistance increase. Pathogenic potential of bacteria has been shown to be context dependent, varying in response to environment and even within the strains of the same genus. We used the KEGG repository and extensive literature searches to identify among the 2527 bacterial genomes in the literature those implicated as pathogenic to the host, including those which show pathogenicity in a context dependent manner. Using data on the gene contents of these genomes, we identified sets of genes highly abundant in pathogenic but relatively absent in commensal strains and vice versa. In addition, we carried out genome comparison within a genus for the seventeen largest genera in our genome collection. We projected the resultant lists of ortholog genes onto KEGG bacterial pathways to identify clusters and circuits, which can be linked to either pathogenicity or synergy. Gene circuits relatively abundant in nonpathogenic bacteria often mediated biosynthesis of antibiotics. Other synergy-linked circuits reduced drug-induced toxicity. Pathogen-abundant gene circuits included modules in one-carbon folate, two-component system, type-3 secretion system, and peptidoglycan biosynthesis. Antibiotics-resistant bacterial strains possessed genes modulating phagocytosis, vesicle trafficking, cytoskeletal reorganization, and regulation of the inflammatory response. Our study also identified bacterial genera containing a circuit, elements of which were previously linked to Alzheimer's disease. Present study produces for the first time, a signature, in the form of a robust list of gene circuitry whose presence or absence could potentially define the pathogenicity of a microbiome. Extensive literature search substantiated a bulk majority of the commensal and pathogenic circuitry in our predicted list. Scanning microbiome libraries for these circuitry motifs will provide further insights into the complex and context dependent pathogenicity of bacteria.

  19. Free-space coherent optical communication with orbital angular, momentum multiplexing/demultiplexing using a hybrid 3D photonic integrated circuit.

    PubMed

    Guan, Binbin; Scott, Ryan P; Qin, Chuan; Fontaine, Nicolas K; Su, Tiehui; Ferrari, Carlo; Cappuzzo, Mark; Klemens, Fred; Keller, Bob; Earnshaw, Mark; Yoo, S J B

    2014-01-13

    We demonstrate free-space space-division-multiplexing (SDM) with 15 orbital angular momentum (OAM) states using a three-dimensional (3D) photonic integrated circuit (PIC). The hybrid device consists of a silica planar lightwave circuit (PLC) coupled to a 3D waveguide circuit to multiplex/demultiplex OAM states. The low excess loss hybrid device is used in individual and two simultaneous OAM states multiplexing and demultiplexing link experiments with a 20 Gb/s, 1.67 b/s/Hz quadrature phase shift keyed (QPSK) signal, which shows error-free performance for 379,960 tested bits for all OAM states.

  20. Communication-Link Approach to Actuation of Grade-Crossing Motorist-Warning Systems

    DOT National Transportation Integrated Search

    1975-07-01

    Previous studies indicate that one promising avenue to grade-crossing motorist-warning systems, offering lower cost and independent of railroad-track circuits, is use of a radio-communication link for signal activation. By this means, the presence of...

  1. First record of Otibazo (Coleoptera: Curculionidae: Molytinae) outside of Japan, with description of a new species from Vietnam.

    PubMed

    Grebennikov, Vasily V; Pham, Hong Thai

    2014-10-03

    A new species of wingless leaf litter weevil, Otibazo polyphemus sp. n., is described from Tam Dao, northern Vietnam. This is the fourth named species in the genus, with its three other species known only from Japan. Habitus and genitalia of the male holotype are illustrated and DNA barcoding data are provided. 

  2. Limber pine seed and seedling planting experiment in Waterton Lakes National Park, Canada

    Treesearch

    Cyndi M. Smith; Graeme Poll; Cameron Gillies; Celina Praymak; Eileen Miranda; Justin Hill

    2011-01-01

    Limber pine plays an important role in the harsh environments in which it lives, providing numerous ecological services, especially because its large, wingless seeds serve as a high energy food source for many animals. Limber pine populations are declining due to a combination of white pine blister rust, mountain pine beetle, drought, and fire suppression. Outplanting...

  3. Dietary vitamin A regulates wingless-related MMTV integration site signaling to alter the hair cycle.

    PubMed

    Suo, Liye; Sundberg, John P; Everts, Helen B

    2015-05-01

    Alopecia areata (AA) is an autoimmune hair loss disease caused by a cell-mediated immune attack of the lower portion of the cycling hair follicle. Feeding mice 3-7 times the recommended level of dietary vitamin A accelerated the progression of AA in the graft-induced C3H/HeJ mouse model of AA. In this study, we also found that dietary vitamin A, in a dose dependent manner, activated the hair follicle stem cells (SCs) to induce the development and growth phase of the hair cycle (anagen), which may have made the hair follicle more susceptible to autoimmune attack. Our purpose here is to determine the mechanism by which dietary vitamin A regulates the hair cycle. We found that vitamin A in a dose-dependent manner increased nuclear localized beta-catenin (CTNNB1; a marker of canonical wingless-type Mouse Mammary Tumor Virus integration site family (WNT) signaling) and levels of WNT7A within the hair follicle bulge in these C3H/HeJ mice. These findings suggest that feeding mice high levels of dietary vitamin A increases WNT signaling to activate hair follicle SCs. © 2014 by the Society for Experimental Biology and Medicine.

  4. Regulation of the protein kinase activity of Shaggy(Zeste-white3) by components of the wingless pathway in Drosophila cells and embryos.

    PubMed

    Ruel, L; Stambolic, V; Ali, A; Manoukian, A S; Woodgett, J R

    1999-07-30

    The protein-serine kinase Shaggy(Zeste-white3) (Sgg(Zw3)) is the Drosophila homolog of mammalian glycogen synthase kinase-3 and has been genetically implicated in signal transduction pathways necessary for the establishment of patterning. Sgg(Zw3) is a putative component of the Wingless (Wg) pathway, and epistasis analyses suggest that Sgg(Zw3) function is repressed by Wg signaling. Here, we have investigated the biochemical consequences of Wg signaling with respect to the Sgg(Zw3) protein kinase in two types of Drosophila cell lines and in embryos. Our results demonstrate that Sgg(Zw3) activity is inhibited following exposure of cells to Wg protein and by expression of downstream components of Wg signaling, Drosophila frizzled 2 and dishevelled. Wg-dependent inactivation of Sgg(Zw3) is accompanied by serine phosphorylation. We also show that the level of Sgg(Zw3) activity regulates the stability of Armadillo protein and modulates the level of phosphorylation of D-Axin and Armadillo. Together, these results provide direct biochemical evidence in support of the genetic model of Wg signaling and provide a model for dissecting the molecular interactions between the signaling proteins.

  5. Lesions in the wingless gene of the Apollo butterfly (Parnassius apollo, Lepidoptera: Papilionidae) individuals with deformed or reduced wings, coming from the isolated population in Pieniny (Poland).

    PubMed

    Łukasiewicz, Kinga; Sanak, Marek; Węgrzyn, Grzegorz

    2016-02-01

    Parnassius apollo (Lepidoptera: Papilionidae) is a butterfly species which was common in Europe in 19th century, but now it is considered as near threatened. Various programs devoted to protect and save P. apollo have been established, between others the one in Pieniny National Park (Poland). An isolated population of this butterfly has been restored there from a small group of 20-30 individuals in early 1990s. However, deformations or reductions of wings occur in this population in a relatively large number of insects, and the cause of this phenomenon is not known. In this report, the occurrence of lesions in the wingless (wg) gene is demonstrated in most of tested butterflies with deformed or reduced wings, but not in normal insects. Although the analyses indicated that wg lesion(s) cannot be the sole cause of the deformed or reduced wings in the population of P. apollo from Pieniny, the discovery that this genetic defect occurs in most of malformed individuals, can be considered as an important step in understanding this phenomenon. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Monogenic Mouse Models of Autism Spectrum Disorders: Common Mechanisms and Missing Links

    PubMed Central

    Hulbert, Samuel W.; Jiang, Yong-hui

    2016-01-01

    Autism Spectrum Disorders (ASDs) present unique challenges in the fields of genetics and neurobiology because of the clinical and molecular heterogeneity underlying these disorders. Genetic mutations found in ASD patients provide opportunities to dissect the molecular and circuit mechanisms underlying autistic behaviors using animal models. Ongoing studies of genetically modified models have offered critical insight into possible common mechanisms arising from different mutations, but links between molecular abnormalities and behavioral phenotypes remain elusive. The challenges encountered in modeling autism in mice demand a new analytic paradigm that integrates behavioral analysis with circuit-level analysis in genetically modified models with strong construct validity. PMID:26733386

  7. Visual Circuit Development Requires Patterned Activity Mediated by Retinal Acetylcholine Receptors

    PubMed Central

    Burbridge, Timothy J.; Xu, Hong-Ping; Ackman, James B.; Ge, Xinxin; Zhang, Yueyi; Ye, Mei-Jun; Zhou, Z. Jimmy; Xu, Jian; Contractor, Anis; Crair, Michael C.

    2014-01-01

    SUMMARY The elaboration of nascent synaptic connections into highly ordered neural circuits is an integral feature of the developing vertebrate nervous system. In sensory systems, patterned spontaneous activity before the onset of sensation is thought to influence this process, but this conclusion remains controversial largely due to the inherent difficulty recording neural activity in early development. Here, we describe novel genetic and pharmacological manipulations of spontaneous retinal activity, assayed in vivo, that demonstrate a causal link between retinal waves and visual circuit refinement. We also report a de-coupling of downstream activity in retinorecipient regions of the developing brain after retinal wave disruption. Significantly, we show that the spatiotemporal characteristics of retinal waves affect the development of specific visual circuits. These results conclusively establish retinal waves as necessary and instructive for circuit refinement in the developing nervous system and reveal how neural circuits adjust to altered patterns of activity prior to experience. PMID:25466916

  8. A general design strategy for block copolymer directed self-assembly patterning of integrated circuits contact holes using an alphabet approach.

    PubMed

    Yi, He; Bao, Xin-Yu; Tiberio, Richard; Wong, H-S Philip

    2015-02-11

    Directed self-assembly (DSA) is a promising lithography candidate for technology nodes beyond 14 nm. Researchers have shown contact hole patterning for random logic circuits using DSA with small physical templates. This paper introduces an alphabet approach that uses a minimal set of small physical templates to pattern all contacts configurations on integrated circuits. We illustrate, through experiments, a general and scalable template design strategy that links the DSA material properties to the technology node requirements.

  9. An analog method of cross-talk compensation for a RGB wavelength division multiplexed optical link

    NASA Astrophysics Data System (ADS)

    Chisholm, George; Leveneur, Jérôme; Futter, John; Kennedy, John

    2018-06-01

    Pulse-width modulation (PWM) over optical fiber can be a very advantageous data transmission approach when an electrically isolated data link is required. The use of wavelength division multiplexing allows multiple data streams to be sent through a single fiber independently. The present investigation aims to demonstrate a novel approach to reduce cross-talk in a three-channel RGB optical link without the need for complex optical componentry. An op-amp circuit is developed to reduce the cross-talk so that the resolution of the PWM data is preserved. An iterative Monte-Carlo simulation approach is used to optimize the op-amp circuit. The approach is developed for a set of three PWM Hall effect magnetometers with 12-bit resolution and 128 Hz sampling rate. We show that, in these conditions, the loss of resolution due to cross-talk is prevented. We also show that the cross-talk compensation allows the RGB PWM link to outperform other transmission schemes.

  10. Power electronic interface circuits for batteries and ultracapacitors in electric vehicles and battery storage systems

    DOEpatents

    King, Robert Dean; DeDoncker, Rik Wivina Anna Adelson

    1998-01-01

    A method and apparatus for load leveling of a battery in an electrical power system includes a power regulator coupled to transfer power between a load and a DC link, a battery coupled to the DC link through a first DC-to-DC converter and an auxiliary passive energy storage device coupled to the DC link through a second DC-to-DC converter. The battery is coupled to the passive energy storage device through a unidirectional conducting device whereby the battery can supply power to the DC link through each of the first and second converters when battery voltage exceeds voltage on the passive storage device. When the load comprises a motor capable of operating in a regenerative mode, the converters are adapted for transferring power to the battery and passive storage device. In this form, resistance can be coupled in circuit with the second DC-to-DC converter to dissipate excess regenerative power.

  11. Power electronic interface circuits for batteries and ultracapacitors in electric vehicles and battery storage systems

    DOEpatents

    King, R.D.; DeDoncker, R.W.A.A.

    1998-01-20

    A method and apparatus for load leveling of a battery in an electrical power system includes a power regulator coupled to transfer power between a load and a DC link, a battery coupled to the DC link through a first DC-to-DC converter and an auxiliary passive energy storage device coupled to the DC link through a second DC-to-DC converter. The battery is coupled to the passive energy storage device through a unidirectional conducting device whereby the battery can supply power to the DC link through each of the first and second converters when battery voltage exceeds voltage on the passive storage device. When the load comprises a motor capable of operating in a regenerative mode, the converters are adapted for transferring power to the battery and passive storage device. In this form, resistance can be coupled in circuit with the second DC-to-DC converter to dissipate excess regenerative power. 8 figs.

  12. Linking Alzheimer's disease to insulin resistance: the FoxO response to oxidative stress.

    PubMed

    Manolopoulos, K N; Klotz, L-O; Korsten, P; Bornstein, S R; Barthel, A

    2010-11-01

    Oxidative stress is an important determinant not only in the pathogenesis of Alzheimer's disease (AD), but also in insulin resistance (InsRes) and diabetic complications. Forkhead box class O (FoxO) transcription factors are involved in both insulin action and the cellular response to oxidative stress, thereby providing a potential integrative link between AD and InsRes. For example, the expression of intra- and extracellular antioxidant enzymes, such as manganese-superoxide dismutase and selenoprotein P, is regulated by FoxO proteins, as is the expression of important hepatic enzymes of gluconeogenesis. Here, we review the molecular mechanisms involved in the pathogenesis of AD and InsRes and discuss the function of FoxO proteins in these processes. Both InsRes and oxidative stress may promote the transcriptional activity of FoxO proteins, resulting in hyperglycaemia and a further increased production of reactive oxygen species (ROS). The consecutive activation of c-Jun N-terminal kinases and inhibition of Wingless (Wnt) signalling may result in the formation of β-amyloid plaques and τ protein phosphorylation. Wnt inhibition may also result in a sustained activation of FoxO proteins with induction of apoptosis and neuronal loss, thereby completing a vicious circle from oxidative stress, InsRes and hyperglycaemia back to the formation of ROS and consecutive neurodegeneration. In view of their central function in this model, FoxO proteins may provide a potential molecular target for the treatment of both InsRes and AD.

  13. Dynamic Training Elements in a Circuit Theory Course to Implement a Self-Directed Learning Process

    ERIC Educational Resources Information Center

    Krouk, B. I.; Zhuravleva, O. B.

    2009-01-01

    This paper reports on the implementation of a self-directed learning process in a circuit theory course, incorporating dynamic training elements which were designed on the basis of a cybernetic model of cognitive process management. These elements are centrally linked in a dynamic learning frame, created on the monitor screen, which displays the…

  14. Exploring Alternative Conceptions from Newtonian Dynamics and Simple DC Circuits: Links between Item Difficulty and Item Confidence

    ERIC Educational Resources Information Center

    Planinic, Maja; Boone, William J.; Krsnik, Rudolf; Beilfuss, Meredith L.

    2006-01-01

    Croatian 1st-year and 3rd-year high-school students (N = 170) completed a conceptual physics test. Students were evaluated with regard to two physics topics: Newtonian dynamics and simple DC circuits. Students answered test items and also indicated their confidence in each answer. Rasch analysis facilitated the calculation of three linear…

  15. Nonreciprocal Signal Routing in an Active Quantum Network

    NASA Astrophysics Data System (ADS)

    Tureci, Hakan E.; Metelmann, Anja

    As superconductor quantum technologies are moving towards large-scale integrated circuits, a robust and flexible approach to routing photons at the quantum level becomes a critical problem. Active circuits, which contain driven linear or non-linear elements judiciously embedded in the circuit offer a viable solution. We present a general strategy for routing non-reciprocally quantum signals between two sites of a given lattice of resonators, implementable with existing superconducting circuit components. Our approach makes use of a dual lattice of superconducting non-linear elements on the links connecting the nodes of the main lattice. Solutions for spatially selective driving of the link-elements can be found, which optimally balance coherent and dissipative hopping of microwave photons to non-reciprocally route signals between two given nodes. In certain lattices these optimal solutions are obtained at the exceptional point of the scattering matrix of the network. The presented strategy provides a design space that is governed by a dynamically tunable non-Hermitian generator that can be used to minimize the added quantum noise as well. This work was supported by the U.S. Army Research Office (ARO) under Grant No. W911NF-15-1-0299.

  16. Dynamics of fluidic devices with applications to rotor pitch links

    NASA Astrophysics Data System (ADS)

    Scarborough, Lloyd H., III

    Coupling a Fluidic Flexible Matrix Composite (F2MC) to an air-pressurized fluid port produces a fundamentally new class of tunable vibration isolator. This fluidlastic device provides significant vibration reduction at an isolation frequency that can be tuned over a broad frequency range. The material properties and geometry of the F2MC element, as well as the port inertance, determine the isolation frequency. A unique feature of this device is that the port inertance depends on pressure so the isolation frequency can be adjusted by changing the air pressure. For constant port inertance, the isolation frequency is largely independent of the isolated mass so the device is robust to changes in load. A nonlinear model is developed to predict isolator length and port inertance. The model is linearized and the frequency response calculated. Experiments agree with theory, demonstrating a tunable isolation range from 9 Hz to 36 Hz and transmitted force reductions of up to 60 dB at the isolation frequency. Replacing rigid pitch links on rotorcraft with coupled fluidic devices has the potential to reduce the aerodynamic blade loads transmitted through the pitch links to the swashplate. Analytical models of two fluidic devices coupled with three different fluidic circuits are derived. These passive fluidlastic systems are tuned, by varying the fluid inertances and capacitances of each fluidic circuit, to reduce the transmitted pitch-link loads. The different circuit designs result in transmitted pitch link loads reduction at up to three main rotor harmonics. The simulation results show loads reduction at the targeted out-of-phase and in-phase harmonics of up to 88% and 93%, respectively. Experimental validation of two of the fluidic circuits demonstrates loads reduction of up to 89% at the out-of-phase isolation frequencies and up to 81% at the in-phase isolation frequencies. Replacing rigid pitch links on rotorcraft with fluidic pitch links changes the blade torsional impedance. At low frequency, the pitch link must have high impedance to pass through the pilot's collective and cyclic commands to control the aircraft. At higher frequencies, however, the pitch-link impedance can be tuned to change the blade pitching response to higher harmonic loads. Active blade control to produce higher harmonic pitch motions has been shown to reduce hub loads and increase rotor efficiency. This work investigates whether fluidic pitch links can passively provide these benefits. An analytical model of a fluidic pitch link is derived and incorporated into a rotor aeroelastic simulation for a rotor similar to that of the UH-60. Eighty-one simulations with varied fluidic pitch link parameters demonstrate that their impedance can be tailored to reduce rotor power and all six hub forces and moments. While no impedance was found that simultaneously reduced all components, the results include cases with reductions in the lateral 4/rev hub force of up to 91% and 4/rev hub pitching moment of up to 67%, and main rotor power of up to 5%.

  17. A modified quadrupole mass spectrometer with custom RF link rods driver for remote operation

    NASA Technical Reports Server (NTRS)

    Tashbar, P. W.; Nisen, D. B.; Moore, W. W., Jr.

    1973-01-01

    A commercial quadrupole residual gas analyzer system has been upgraded for operation at extended cable lengths. Operation inside a vacuum chamber for the standard quadrupole nude head is limited to approximately 2 m from its externally located rf/dc generator because of the detuning of the rf oscillator circuits by the coaxial cable reactance. The advance of long distance remote operation inside a vacuum chamber for distances of 45 and 60 m was made possible without altering the quadrupole's rf/dc generator circuit by employing an rf link to drive the quadrupole rods. Applications of the system have been accomplished for in situ space simulation thermal/vacuum testing of sophisticated payloads.

  18. Dissecting the links between cerebellum and dystonia.

    PubMed

    Malone, Ailish; Manto, Mario; Hass, Chris

    2014-12-01

    Dystonia is a common movement disorder characterized by sustained muscle contractions. These contractions generate twisting and repetitive movements or typical abnormal postures, often exacerbated by voluntary movement. Dystonia can affect almost all the voluntary muscles. For several decades, the discussion on the pathogenesis has been focused on basal ganglia circuits, especially striatal networks. So far, although dystonia has been observed in some forms of ataxia such as dominant ataxias, the link between the cerebellum and dystonia has remained unclear. Recent human studies and experimental data mainly in rodents show that the cerebellum circuitry could also be a key player in the pathogenesis of some forms of dystonia. In particular, studies based on behavioral adaptation paradigm shed light on the links between dystonia and cerebellum. The spectrum of movement disorders in which the cerebellum is implicated is continuously expanding, and manipulation of cerebellar circuits might even emerge as a candidate therapy in the coming years.

  19. Circuit design of an EMCCD camera

    NASA Astrophysics Data System (ADS)

    Li, Binhua; Song, Qian; Jin, Jianhui; He, Chun

    2012-07-01

    EMCCDs have been used in the astronomical observations in many ways. Recently we develop a camera using an EMCCD TX285. The CCD chip is cooled to -100°C in an LN2 dewar. The camera controller consists of a driving board, a control board and a temperature control board. Power supplies and driving clocks of the CCD are provided by the driving board, the timing generator is located in the control board. The timing generator and an embedded Nios II CPU are implemented in an FPGA. Moreover the ADC and the data transfer circuit are also in the control board, and controlled by the FPGA. The data transfer between the image workstation and the camera is done through a Camera Link frame grabber. The software of image acquisition is built using VC++ and Sapera LT. This paper describes the camera structure, the main components and circuit design for video signal processing channel, clock driver, FPGA and Camera Link interfaces, temperature metering and control system. Some testing results are presented.

  20. Genetics and language: a neurobiological perspective on the missing link (-ing hypotheses).

    PubMed

    Poeppel, David

    2011-12-01

    The paper argues that both evolutionary and genetic approaches to studying the biological foundations of speech and language could benefit from fractionating the problem at a finer grain, aiming not to map genetics to "language"-or even subdomains of language such as "phonology" or "syntax"-but rather to link genetic results to component formal operations that underlie processing the comprehension and production of linguistic representations. Neuroanatomic and neurophysiological research suggests that language processing is broken down in space (distributed functional anatomy along concurrent pathways) and time (concurrent processing on multiple time scales). These parallel neuronal pathways and their local circuits form the infrastructure of speech and language and are the actual targets of evolution/genetics. Therefore, investigating the mapping from gene to brain circuit to linguistic phenotype at the level of generic computational operations (subroutines actually executable in these circuits) stands to provide a new perspective on the biological foundations in the healthy and challenged brain.

  1. Sensitive detection of proteasomal activation using the Deg-On mammalian synthetic gene circuit.

    PubMed

    Zhao, Wenting; Bonem, Matthew; McWhite, Claire; Silberg, Jonathan J; Segatori, Laura

    2014-04-08

    The ubiquitin proteasome system (UPS) has emerged as a drug target for diverse diseases characterized by altered proteostasis, but pharmacological agents that enhance UPS activity have been challenging to establish. Here we report the Deg-On system, a genetic inverter that translates proteasomal degradation of the transcriptional regulator TetR into a fluorescent signal, thereby linking UPS activity to an easily detectable output, which can be tuned using tetracycline. We demonstrate that this circuit responds to modulation of UPS activity in cell culture arising from the inhibitor MG-132 and activator PA28γ. Guided by predictive modelling, we enhanced the circuit's signal sensitivity and dynamic range by introducing a feedback loop that enables self-amplification of TetR. By linking UPS activity to a simple and tunable fluorescence output, these genetic inverters will enable a variety of applications, including screening for UPS activating molecules and selecting for mammalian cells with different levels of proteasome activity.

  2. CHEETAH: circuit-switched high-speed end-to-end transport architecture

    NASA Astrophysics Data System (ADS)

    Veeraraghavan, Malathi; Zheng, Xuan; Lee, Hyuk; Gardner, M.; Feng, Wuchun

    2003-10-01

    Leveraging the dominance of Ethernet in LANs and SONET/SDH in MANs and WANs, we propose a service called CHEETAH (Circuit-switched High-speed End-to-End Transport ArcHitecture). The service concept is to provide end hosts with high-speed, end-to-end circuit connectivity on a call-by-call shared basis, where a "circuit" consists of Ethernet segments at the ends that are mapped into Ethernet-over-SONET long-distance circuits. This paper focuses on the file-transfer application for such circuits. For this application, the CHEETAH service is proposed as an add-on to the primary Internet access service already in place for enterprise hosts. This allows an end host that is sending a file to first attempt setting up an end-to-end Ethernet/EoS circuit, and if rejected, fall back to the TCP/IP path. If the circuit setup is successful, the end host will enjoy a much shorter file-transfer delay than on the TCP/IP path. To determine the conditions under which an end host with access to the CHEETAH service should attempt circuit setup, we analyze mean file-transfer delays as a function of call blocking probability in the circuit-switched network, probability of packet loss in the IP network, round-trip times, link rates, and so on.

  3. Psoriasis: in between the skin and the fat.

    PubMed

    Ståhle, Mona

    2015-03-01

    Substantial epidemiological evidence indicates that psoriasis associates with a predisposition to develop metabolic dysregulation leading to obesity and insulin resistance. However, the nature of this association and the potential underlying mechanisms remain unclear. In a recent report, Gerdes et al. explored the hypothesis that wingless-type MMTV integration site, Wnt5a, which has been linked to aberrant fat cell metabolism, may be driving this process. In this study, the authors compare circulating serum levels of Wnt5a in individuals with psoriasis and compare with healthy controls matched for age, gender and BMI. The bottom-line results show higher levels of Wnt5a in psoriasis patients irrespective of BMI compared to the matched non-psoriatic controls, indicating that psoriasis per se may result in increased secretion of Wnt5a into the circulation. In addition, there was a significant difference among patients with higher levels of Wnt5a in the obese psoriasis population. The study, even though being purely descriptive, may serve to inspire a more mechanistic approach exploring not only Wnt5a, but other inflammatory pathways in between the skin and the fat. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  4. RAD hard PROM design study

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The results of a preliminary study on the design of a radiation hardened fusible link programmable read-only memory (PROM) are presented. Various fuse technologies and the effects of radiation on MOS integrated circuits are surveyed. A set of design rules allowing the fabrication of a radiation hardened PROM using a Si-gate CMOS process is defined. A preliminary cell layout was completed and the programming concept defined. A block diagram is used to describe the circuit components required for a 4 K design. A design goal data sheet giving target values for the AC, DC, and radiation parameters of the circuit is presented.

  5. Simulation of 100-300 GHz solid-state harmonic sources

    NASA Technical Reports Server (NTRS)

    Zybura, Michael F.; Jones, J. Robert; Jones, Stephen H.; Tait, Gregory B.

    1995-01-01

    Accurate and efficient simulations of the large-signal time-dependent characteristics of second-harmonic Transferred Electron Oscillators (TEO's) and Heterostructure Barrier Varactor (HBV) frequency triplers have been obtained. This is accomplished by using a novel and efficient harmonic-balance circuit analysis technique which facilitates the integration of physics-based hydrodynamic device simulators. The integrated hydrodynamic device/harmonic-balance circuit simulators allow TEO and HBV circuits to be co-designed from both a device and a circuit point of view. Comparisons have been made with published experimental data for both TEO's and HBV's. For TEO's, excellent correlation has been obtained at 140 GHz and 188 GHz in second-harmonic operation. Excellent correlation has also been obtained for HBV frequency triplers operating near 200 GHz. For HBV's, both a lumped quasi-static equivalent circuit model and the hydrodynamic device simulator have been linked to the harmonic-balance circuit simulator. This comparison illustrates the importance of representing active devices with physics-based numerical device models rather than analytical device models.

  6. Computer-Aided Design of Low-Noise Microwave Circuits

    NASA Astrophysics Data System (ADS)

    Wedge, Scott William

    1991-02-01

    Devoid of most natural and manmade noise, microwave frequencies have detection sensitivities limited by internally generated receiver noise. Low-noise amplifiers are therefore critical components in radio astronomical antennas, communications links, radar systems, and even home satellite dishes. A general technique to accurately predict the noise performance of microwave circuits has been lacking. Current noise analysis methods have been limited to specific circuit topologies or neglect correlation, a strong effect in microwave devices. Presented here are generalized methods, developed for computer-aided design implementation, for the analysis of linear noisy microwave circuits comprised of arbitrarily interconnected components. Included are descriptions of efficient algorithms for the simultaneous analysis of noisy and deterministic circuit parameters based on a wave variable approach. The methods are therefore particularly suited to microwave and millimeter-wave circuits. Noise contributions from lossy passive components and active components with electronic noise are considered. Also presented is a new technique for the measurement of device noise characteristics that offers several advantages over current measurement methods.

  7. A SMN-Dependent U12 Splicing Event Essential for Motor Circuit Function

    PubMed Central

    Lotti, Francesco; Imlach, Wendy L.; Saieva, Luciano; Beck, Erin S.; Hao, Le T.; Li, Darrick K.; Jiao, Wei; Mentis, George Z.; Beattie, Christine E.; McCabe, Brian D.; Pellizzoni, Livio

    2012-01-01

    SUMMARY Spinal muscular atrophy (SMA) is a motor neuron disease caused by deficiency of the ubiquitous survival motor neuron (SMN) protein. To define the mechanisms of selective neuronal dysfunction in SMA, we investigated the role of SMN-dependent U12 splicing events in the regulation of motor circuit activity. We show that SMN deficiency perturbs splicing and decreases the expression of a subset of U12 intron-containing genes in mammalian cells and Drosophila larvae. Analysis of these SMN target genes identifies Stasimon as a novel protein required for motor circuit function. Restoration of Stasimon expression in the motor circuit corrects defects in neuromuscular junction transmission and muscle growth in Drosophila SMN mutants and aberrant motor neuron development in SMN-deficient zebrafish. These findings directly link defective splicing of critical neuronal genes induced by SMN deficiency to motor circuit dysfunction, establishing a molecular framework for the selective pathology of SMA. PMID:23063131

  8. Optical waveguide circuit board with a surface-mounted optical receiver array

    NASA Astrophysics Data System (ADS)

    Thomson, J. E.; Levesque, Harold; Savov, Emil; Horwitz, Fred; Booth, Bruce L.; Marchegiano, Joseph E.

    1994-03-01

    A photonic circuit board is fabricated for potential application to interchip and interboard parallel optical links. The board comprises photolithographically patterned polymer optical waveguides on a conventional glass-epoxy electrical circuit board and a surface-mounted integrated circuit (IC) package that optically and electrically couples to an optoelectronic IC. The waveguide circuits include eight-channel arrays of straights, cross-throughs, curves, self- aligning interconnects to multi-fiber ribbon, and out-of-plane turning mirrors. A coherent, fused bundle of optical fibers couples light between 45-deg waveguide mirrors and a GaAs receiver array in the IC package. The fiber bundle is easily aligned to the mirrors and the receivers and is amenable to surface mounting and hermetic sealing. The waveguide-receiver- array board achieved error-free data rates up to 1.25 Gbits/s per channel, and modal noise was shown to be negligible.

  9. Experimental research and design planning in the field of liquid-propellant rocket engines conducted between 1934 - 1944 by the followers of F. A. Tsander

    NASA Technical Reports Server (NTRS)

    Dushkin, L. S.

    1977-01-01

    The development of the following Liquid-Propellant Rocket Engines (LPRE) is reviewed: (1) an alcohol-oxygen single-firing LPRE for use in wingless and winged rockets, (2) a similar multifiring LPRE for use in rocket gliders, (3) a combined solid-liquid propellant rocket engine, and (4) an aircraft LPRE operating on nitric acid and kerosene.

  10. Keep Your Wits Not Your Nits: A Rational Approach to Head Lice from the National Pediculosis Association. Second Edition.

    ERIC Educational Resources Information Center

    Altschuler, Deborah Z.; And Others

    This booklet was intended to teach parents about head lice, which are small, wingless, crawling insects that feed on human blood. The booklet briefly discusses: (1) physical characteristics of lice; (2) ways of becoming infested with head lice, such as sharing combs; (3) nits, which are the eggs of lice; (4) the difference between nits and hair…

  11. B-Catenin Stability in Breast Cancer

    DTIC Science & Technology

    1997-07-01

    basic understanding of the cellular processes underlying breast cancer is mandated before effective therapies can be developed or even attempted. P3...Z dorso-anterior body axis, giving rise to two heads, notochords , and neural tubes (24). Wnt-1, dsh dsh hanqgg the vertebrate homologue of wingless is...stability by the ubiquitin-proteasome pathway. The ubiquitin-proteasome pathway is involved in the processing and rapid degradation of many short-lived

  12. Development of a Self Powered Vehicle Detector

    DTIC Science & Technology

    1978-10-01

    Low Power RFTelemetry Link, Audio Tone kncoder/Decoder, 9mn’dlrectional Microstrip Antenna, RF Oscillator , RF Transmitter, Battery/ Solar Cell Tests...tuned Colpitts oscillator using a fundamental mode crystal, a reactance modulator (varactor diode), and a collector tank circuit tuned to the second...papers discussing this type of VCXO. The basic Colpitts oscillator equivalent circuit is shown in Figure 29 having a collector tank tuned to the 2nd

  13. From Spontaneous Motor Activity to Coordinated Behaviour: A Developmental Model

    PubMed Central

    Marques, Hugo Gravato; Bharadwaj, Arjun; Iida, Fumiya

    2014-01-01

    In mammals, the developmental path that links the primary behaviours observed during foetal stages to the full fledged behaviours observed in adults is still beyond our understanding. Often theories of motor control try to deal with the process of incremental learning in an abstract and modular way without establishing any correspondence with the mammalian developmental stages. In this paper, we propose a computational model that links three distinct behaviours which appear at three different stages of development. In order of appearance, these behaviours are: spontaneous motor activity (SMA), reflexes, and coordinated behaviours, such as locomotion. The goal of our model is to address in silico four hypotheses that are currently hard to verify in vivo: First, the hypothesis that spinal reflex circuits can be self-organized from the sensor and motor activity induced by SMA. Second, the hypothesis that supraspinal systems can modulate reflex circuits to achieve coordinated behaviour. Third, the hypothesis that, since SMA is observed in an organism throughout its entire lifetime, it provides a mechanism suitable to maintain the reflex circuits aligned with the musculoskeletal system, and thus adapt to changes in body morphology. And fourth, the hypothesis that by changing the modulation of the reflex circuits over time, one can switch between different coordinated behaviours. Our model is tested in a simulated musculoskeletal leg actuated by six muscles arranged in a number of different ways. Hopping is used as a case study of coordinated behaviour. Our results show that reflex circuits can be self-organized from SMA, and that, once these circuits are in place, they can be modulated to achieve coordinated behaviour. In addition, our results show that our model can naturally adapt to different morphological changes and perform behavioural transitions. PMID:25057775

  14. Complex Phenomena Understanding in Electricity through Dynamically Linked Concrete and Abstract Representations

    ERIC Educational Resources Information Center

    Taramopoulos, A.; Psillos, D.

    2017-01-01

    The present study investigates the impact of utilizing virtual laboratory environments combining dynamically linked concrete and abstract representations in investigative activities on the ability of students to comprehend simple and complex phenomena in the field of electric circuits. Forty-two 16- to 17-year-old high school students participated…

  15. Exploration and design of smart home circuit based on ZigBee

    NASA Astrophysics Data System (ADS)

    Luo, Huirong

    2018-05-01

    To apply ZigBee technique in smart home circuit design, in the hardware design link of ZigBee node, TI Company's ZigBee wireless communication chip CC2530 was used to complete the design of ZigBee RF module circuit and peripheral circuit. In addition, the function demand and the overall scheme of the intelligent system based on smart home furnishing were proposed. Finally, the smart home system was built by combining ZigBee network and intelligent gateway. The function realization, reliability and power consumption of ZigBee network were tested. The results showed that ZigBee technology was applied to smart home system, making it have some advantages in terms of flexibility, scalability, power consumption and indoor aesthetics. To sum up, the system has high application value.

  16. WNT-1 Signaling in Mammary Carcinogenesis

    DTIC Science & Technology

    2002-04-01

    segment polarity gene whose mutant phenotype resembles that of the wingless (Drosophila Wnt-1) mutation (3). arrow encodes a transmembrane receptor...and function ofSpemann’s organizer. Annu. Rev. C Drv. of those caused by mutations in individual Wnt genes . Further- Biaol 13, 611-667 (1997). more, we... mutations of multiple Wnt genes [31]. In the 0.5 nM and thus is significantly higher than Wnt-Fz bind- Xenopus embryo, inhibition of LRP6 function

  17. Conjugate-Gradient Algorithms For Dynamics Of Manipulators

    NASA Technical Reports Server (NTRS)

    Fijany, Amir; Scheid, Robert E.

    1993-01-01

    Algorithms for serial and parallel computation of forward dynamics of multiple-link robotic manipulators by conjugate-gradient method developed. Parallel algorithms have potential for speedup of computations on multiple linked, specialized processors implemented in very-large-scale integrated circuits. Such processors used to stimulate dynamics, possibly faster than in real time, for purposes of planning and control.

  18. Aircraft lightning-induced voltage test technique developments

    NASA Technical Reports Server (NTRS)

    Crouch, K. E.

    1983-01-01

    High voltage safety, fuels safety, simulation, and response/measurement techniques are discussed. Travelling wave transit times, return circuit conductor configurations, LC ladder network generators, and repetitive pulse techniques are also discussed. Differential conductive coaxial cable, analog fiber optic link, repetitive pulse sampled data instrumentation system, flash A/D optic link system, and an FM telemetry system are considered.

  19. Thin glass based packaging and photonic single-mode waveguide integration by ion-exchange technology on board and module level

    NASA Astrophysics Data System (ADS)

    Brusberg, Lars; Lang, Günter; Schröder, Henning

    2011-01-01

    The proposed novel packaging approach merges micro-system packaging and glass integrated optics. It provides 3D optical single-mode intra system links to bridge the gap between novel photonic integrated circuits and the glass fibers for inter system interconnects. We introduce our hybrid 3D photonic packaging approach based on thin glass substrates with planar integrated optical single-mode waveguides for fiber-to-chip and chip-to-chip links. Optical mirrors and lenses provide optical mode matching for photonic IC assemblies and optical fiber interconnects. Thin glass is commercially available in panel and wafer formats and characterizes excellent optical and high-frequency properties as reviewed in the paper. That makes it perfect for micro-system packaging. The adopted planar waveguide process based on ion-exchange technology is capable for high-volume manufacturing. This ion-exchange process and the optical propagation are described in detail for thin glass substrates. An extensive characterization of all basic circuit elements like straight and curved waveguides, couplers and crosses proves the low attenuation of the optical circuit elements.

  20. A cortical circuit for voluntary laryngeal control: Implications for the evolution language.

    PubMed

    Hickok, Gregory

    2017-02-01

    The development of voluntary laryngeal control has been argued to be a key innovation in the evolution of language. Part of the evidence for this hypothesis comes from neuroscience. For example, comparative research has shown that humans have direct cortical innervation of motor neurons controlling the larynx, whereas nonhuman primates do not. Research on cortical motor control circuits has shown that the frontal lobe cortical motor system does not work alone; it is dependent on sensory feedback control circuits. Thus, the human brain must have evolved not only the required efferent motor pathway but also the cortical circuit for controlling those efferent signals. To fill this gap, I propose a link between the evolution of laryngeal control and neuroscience research on the human dorsal auditory-motor speech stream. Specifically, I argue that the dorsal stream Spt (Sylvian parietal-temporal) circuit evolved in step with the direct cortico-laryngeal control pathway and together represented a key advance in the evolution of speech. I suggest that a cortical laryngeal control circuit may play an important role in language by providing a prosodic frame for speech planning.

  1. Li-Ion Battery By-Pass Removal Qualification

    NASA Astrophysics Data System (ADS)

    Borthomieu, Y.; Pasquier, E.

    2005-05-01

    The reasons of the by-pass use on Space batteries is to avoid open circuit, short-circuit and dramatic performances drift on the power system. By-pass diodes are currently used in NiH2 batteries due to the high probability of open circuit at cell level. This probability is mainly linked to the possibility to have a hydrogen leak within the pressure vessel due to the high operating pressure (70 bars) that can induce cell open circuit.For the Lithium-Ion batteries, first items had bypass implemented by similarity, but:All the cell failure cases have been analyzed at battery level:- Cell Open circuit:In contrast to NiCd and NiH2 cells, Li-Ion cells can be put in parallel due to the fact the open circuit voltage (OCV) is linked to the State Of Charge (SOC).With cells in parallel, a battery open circuit failure can never be encountered even with a cell in open circuit.- Cell Short circuit:In case of cell short, the entire cells within the module will be shorted.- Cell capacity spread:If the capacities of cells in series are strongly diverging, the worst module limits the battery. In case the battery is no more able to deliver the requested power for which it was designed, the worst module has to be reversed. In reversal, a Li-Ion cell is self-shorted. So, the strong capacity decrease in one module leads to the short of this module.These three failure cases cover all the possible Li-Ion failure root causes.Considering these three events, the analysis demonstrates that the Li-Ion battery still functions in any case without any by-pass system because the design of the battery size always takes into account the loss of one module.Nevertheless, the by-pass removal should allow to:- Improve the battery reliability as each bypass unit represents a single - Reduce by at least 30 % of the total price of the battery,- Reduce significant weight at battery level,- Shorten the battery manufacturing lead time (at least8 months for by-pass purchasing), - Avoid US export licenses.A formal qualification of a Li-Ion battery without by- pass system is on going in the frame of an ESA ARTES 3 contract.

  2. Wireless neural recording with single low-power integrated circuit.

    PubMed

    Harrison, Reid R; Kier, Ryan J; Chestek, Cynthia A; Gilja, Vikash; Nuyujukian, Paul; Ryu, Stephen; Greger, Bradley; Solzbacher, Florian; Shenoy, Krishna V

    2009-08-01

    We present benchtop and in vivo experimental results from an integrated circuit designed for wireless implantable neural recording applications. The chip, which was fabricated in a commercially available 0.6- mum 2P3M BiCMOS process, contains 100 amplifiers, a 10-bit analog-to-digital converter (ADC), 100 threshold-based spike detectors, and a 902-928 MHz frequency-shift-keying (FSK) transmitter. Neural signals from a selected amplifier are sampled by the ADC at 15.7 kSps and telemetered over the FSK wireless data link. Power, clock, and command signals are sent to the chip wirelessly over a 2.765-MHz inductive (coil-to-coil) link. The chip is capable of operating with only two off-chip components: a power/command receiving coil and a 100-nF capacitor.

  3. Breathing and Vocal Control: The Respiratory System as both a Driver and Target of Telencephalic Vocal Motor Circuits in Songbirds

    PubMed Central

    Schmidt, Marc F.; McLean, Judith; Goller, Franz

    2011-01-01

    The production of vocalizations is intimately linked to the respiratory system. Despite our understanding of neural circuits that generate normal respiratory patterns, very little is understood regarding how these ponto-medullary circuits become engaged during vocal production. Songbirds offer a potentially powerful model system for addressing this relationship. Songs dramatically alter the respiratory pattern in ways that are often highly predictable and songbirds have a specialized telencephalic vocal motor circuit that provides massive innervation to a brainstem respiratory network that shares many similarities with its mammalian counterpart. In this review, we highlight interactions between the song motor circuit and the respiratory system, describing how both systems likely interact to produce the complex respiratory patterns that are observed during vocalization. We also discuss how the respiratory system, through its bilateral bottom-up projections to thalamus, might play a key role in sending precisely timed signals that synchronize premotor activity in both hemispheres. PMID:21984733

  4. Two-dimensional lattice gauge theories with superconducting quantum circuits

    PubMed Central

    Marcos, D.; Widmer, P.; Rico, E.; Hafezi, M.; Rabl, P.; Wiese, U.-J.; Zoller, P.

    2014-01-01

    A quantum simulator of U(1) lattice gauge theories can be implemented with superconducting circuits. This allows the investigation of confined and deconfined phases in quantum link models, and of valence bond solid and spin liquid phases in quantum dimer models. Fractionalized confining strings and the real-time dynamics of quantum phase transitions are accessible as well. Here we show how state-of-the-art superconducting technology allows us to simulate these phenomena in relatively small circuit lattices. By exploiting the strong non-linear couplings between quantized excitations emerging when superconducting qubits are coupled, we show how to engineer gauge invariant Hamiltonians, including ring-exchange and four-body Ising interactions. We demonstrate that, despite decoherence and disorder effects, minimal circuit instances allow us to investigate properties such as the dynamics of electric flux strings, signaling confinement in gauge invariant field theories. The experimental realization of these models in larger superconducting circuits could address open questions beyond current computational capability. PMID:25512676

  5. Cell type-specific genetic and optogenetic tools reveal hippocampal CA2 circuits.

    PubMed

    Kohara, Keigo; Pignatelli, Michele; Rivest, Alexander J; Jung, Hae-Yoon; Kitamura, Takashi; Suh, Junghyup; Frank, Dominic; Kajikawa, Koichiro; Mise, Nathan; Obata, Yuichi; Wickersham, Ian R; Tonegawa, Susumu

    2014-02-01

    The formation and recall of episodic memory requires precise information processing by the entorhinal-hippocampal network. For several decades, the trisynaptic circuit entorhinal cortex layer II (ECII)→dentate gyrus→CA3→CA1 and the monosynaptic circuit ECIII→CA1 have been considered the primary substrates of the network responsible for learning and memory. Circuits linked to another hippocampal region, CA2, have only recently come to light. Using highly cell type-specific transgenic mouse lines, optogenetics and patch-clamp recordings, we found that dentate gyrus cells, long believed to not project to CA2, send functional monosynaptic inputs to CA2 pyramidal cells through abundant longitudinal projections. CA2 innervated CA1 to complete an alternate trisynaptic circuit, but, unlike CA3, projected preferentially to the deep, rather than to the superficial, sublayer of CA1. Furthermore, contrary to existing knowledge, ECIII did not project to CA2. Our results allow a deeper understanding of the biology of learning and memory.

  6. A Small-Molecule Inducible Synthetic Circuit for Control of the SOS Gene Network without DNA Damage.

    PubMed

    Kubiak, Jeffrey M; Culyba, Matthew J; Liu, Monica Yun; Mo, Charlie Y; Goulian, Mark; Kohli, Rahul M

    2017-11-17

    The bacterial SOS stress-response pathway is a pro-mutagenic DNA repair system that mediates bacterial survival and adaptation to genotoxic stressors, including antibiotics and UV light. The SOS pathway is composed of a network of genes under the control of the transcriptional repressor, LexA. Activation of the pathway involves linked but distinct events: an initial DNA damage event leads to activation of RecA, which promotes autoproteolysis of LexA, abrogating its repressor function and leading to induction of the SOS gene network. These linked events can each independently contribute to DNA repair and mutagenesis, making it difficult to separate the contributions of the different events to observed phenotypes. We therefore devised a novel synthetic circuit to unlink these events and permit induction of the SOS gene network in the absence of DNA damage or RecA activation via orthogonal cleavage of LexA. Strains engineered with the synthetic SOS circuit demonstrate small-molecule inducible expression of SOS genes as well as the associated resistance to UV light. Exploiting our ability to activate SOS genes independently of upstream events, we further demonstrate that the majority of SOS-mediated mutagenesis on the chromosome does not readily occur with orthogonal pathway induction alone, but instead requires DNA damage. More generally, our approach provides an exemplar for using synthetic circuit design to separate an environmental stressor from its associated stress-response pathway.

  7. Drosophila Lyra mutations are gain-of-function mutations of senseless

    NASA Technical Reports Server (NTRS)

    Nolo, R.; Abbott, L. A.; Bellen, H. J.

    2001-01-01

    The Lyra mutation was first described by Jerry Coyne in 1935. Lyra causes recessive pupal lethality and adult heterozygous Lyra mutants exhibit a dominant loss of the anterior and posterior wing margins. Unlike many mutations that cause loss of wing tissue (e.g., scalloped, Beadex, cut, and apterous-Xasta), Lyra wing discs do not exhibit increased necrotic or apoptotic cell death, nor do they show altered BrdU incorporation. However, during wing disc eversion, loss of the anterior and posterior wing margins is apparent. We have previously shown that senseless, a gene that is necessary and sufficient for peripheral nervous system (PNS) development, is allelic to Lyra. Here we show by several genetic criteria that Lyra alleles are neomorphic alleles of senseless that cause ectopic expression of SENSELESS in the wing pouch. Similarly, overexpression of SENSELESS in the wing disc causes loss of wing margin tissue, thereby mimicking the Lyra phenotype. Lyra mutants display aberrant expression of DELTA, VESTIGIAL, WINGLESS, and CUT. As in Lyra mutants, overexpression of SENSELESS in some areas of the wing pouch also leads to loss of WINGLESS and CUT. In summary, our data indicate that overexpression of SENSELESS causes a severe reduction in NOTCH signaling that in turn may lead to decreased transcription of several key genes required for wing development, leading to a failure in cell proliferation and loss of wing margin tissue.

  8. Association between autism and variants in the wingless-type MMTV integration site family member 2 ( WNT2) gene.

    PubMed

    Marui, Tetsuya; Funatogawa, Ikuko; Koishi, Shinko; Yamamoto, Kenji; Matsumoto, Hideo; Hashimoto, Ohiko; Jinde, Seiichiro; Nishida, Hisami; Sugiyama, Toshiro; Kasai, Kiyoto; Watanabe, Keiichiro; Kano, Yukiko; Kato, Nobumasa

    2010-05-01

    Autism is a severe neurodevelopmental disorder with a complex genetic aetiology. The wingless-type MMTV integration site family member 2 (WNT2) gene has been considered as a candidate gene for autism. We conducted a case-control study and followed up with a transmission disequilibrium test (TDT) analysis to confirm replication of the significant results for the first time. We conducted a case-control study of nine single nucleotide polymorphisms (SNPs) within the WNT2 gene in 170 patients with autism and 214 normal controls in a Japanese population. We then conducted a TDT analysis in 98 autistic families (trios) to replicate the results of the case-control study. In the case-control study, three SNPs (rs3779547, rs4727847 and rs3729629), two major individual haplotypes (A-T-C and G-G-G, consisting of rs3779547, rs4727847, and rs3729629), and global probability values of the haplotype distributions in the same region (global p=0.0091) showed significant associations with autism. Furthermore, all of these significant associations were also observed in the TDT analysis. Our findings provide evidence for a significant association between WNT2 and autism. Considering the important role of the WNT2 gene in brain development, our results therefore indicate that the WNT2 gene is one of the strong candidate genes for autism.

  9. Insights into insect wing origin provided by functional analysis of vestigial in the red flour beetle, Tribolium castaneum.

    PubMed

    Clark-Hachtel, Courtney M; Linz, David M; Tomoyasu, Yoshinori

    2013-10-15

    Despite accumulating efforts to unveil the origin of insect wings, it remains one of the principal mysteries in evolution. Currently, there are two prominent models regarding insect wing origin: one connecting the origin to the paranotal lobe and the other to the proximodorsal leg branch (exite). However, neither hypothesis has been able to surpass the other. To approach this conundrum, we focused our analysis on vestigial (vg), a critical wing gene initially identified in Drosophila. Our investigation in Tribolium (Coleoptera) has revealed that, despite the well-accepted view of vg as an essential wing gene, there are two groups of vg-dependent tissues in the "wingless" first thoracic segment (T1). We show that one of these tissues, the carinated margin, also depends on other factors essential for wing development (such as Wingless signal and apterous), and has nubbin enhancer activity. In addition, our homeotic mutant analysis shows that wing transformation in T1 originates from both the carinated margin and the other vg-dependent tissue, the pleural structures (trochantin and epimeron). Intriguingly, these two tissues may actually be homologous to the two proposed wing origins (paranotal lobes and exite bearing proximal leg segments). Therefore, our findings suggest that the vg-dependent tissues in T1 could be wing serial homologs present in a more ancestral state, thus providing compelling functional evidence for the dual origin of insect wings.

  10. Monolithically mode division multiplexing photonic integrated circuit for large-capacity optical interconnection.

    PubMed

    Chen, Guanyu; Yu, Yu; Zhang, Xinliang

    2016-08-01

    We propose and fabricate an on-chip mode division multiplexed (MDM) photonic interconnection system. Such a monolithically photonic integrated circuit (PIC) is composed of a grating coupler, two micro-ring modulators, mode multiplexer/demultiplexer, and two germanium photodetectors. The signals' generation, multiplexing, transmission, demultiplexing, and detection are successfully demonstrated on the same chip. Twenty Gb/s MDM signals are successfully processed with clear and open eye diagrams, validating the feasibility of the proposed circuit. The measured power penalties show a good performance of the MDM link. The proposed on-chip MDM system can be potentially used for large-capacity optical interconnection in future high-performance computers and big data centers.

  11. Positive selection in glycolysis among Australasian stick insects

    PubMed Central

    2013-01-01

    Background The glycolytic pathway is central to cellular energy production. Selection on individual enzymes within glycolysis, particularly phosphoglucose isomerase (Pgi), has been associated with metabolic performance in numerous organisms. Nonetheless, how whole energy-producing pathways evolve to allow organisms to thrive in different environments and adopt new lifestyles remains little explored. The Lanceocercata radiation of Australasian stick insects includes transitions from tropical to temperate climates, lowland to alpine habitats, and winged to wingless forms. This permits a broad investigation to determine which steps within glycolysis and what sites within enzymes are the targets of positive selection. To address these questions we obtained transcript sequences from seven core glycolysis enzymes, including two Pgi paralogues, from 29 Lanceocercata species. Results Using maximum likelihood methods a signature of positive selection was inferred in two core glycolysis enzymes. Pgi and Glyceraldehyde 3-phosphate dehydrogenase (Gaphd) genes both encode enzymes linking glycolysis to the pentose phosphate pathway. Positive selection among Pgi paralogues and orthologues predominately targets amino acids with residues exposed to the protein’s surface, where changes in physical properties may alter enzyme performance. Conclusion Our results suggest that, for Lancerocercata stick insects, adaptation to new stressful lifestyles requires a balance between maintaining cellular energy production, efficiently exploiting different energy storage pools and compensating for stress-induced oxidative damage. PMID:24079656

  12. High-resolution mapping of bifurcations in nonlinear biochemical circuits

    NASA Astrophysics Data System (ADS)

    Genot, A. J.; Baccouche, A.; Sieskind, R.; Aubert-Kato, N.; Bredeche, N.; Bartolo, J. F.; Taly, V.; Fujii, T.; Rondelez, Y.

    2016-08-01

    Analog molecular circuits can exploit the nonlinear nature of biochemical reaction networks to compute low-precision outputs with fewer resources than digital circuits. This analog computation is similar to that employed by gene-regulation networks. Although digital systems have a tractable link between structure and function, the nonlinear and continuous nature of analog circuits yields an intricate functional landscape, which makes their design counter-intuitive, their characterization laborious and their analysis delicate. Here, using droplet-based microfluidics, we map with high resolution and dimensionality the bifurcation diagrams of two synthetic, out-of-equilibrium and nonlinear programs: a bistable DNA switch and a predator-prey DNA oscillator. The diagrams delineate where function is optimal, dynamics bifurcates and models fail. Inverse problem solving on these large-scale data sets indicates interference from enzymatic coupling. Additionally, data mining exposes the presence of rare, stochastically bursting oscillators near deterministic bifurcations.

  13. Dendritic nonlinearities are tuned for efficient spike-based computations in cortical circuits.

    PubMed

    Ujfalussy, Balázs B; Makara, Judit K; Branco, Tiago; Lengyel, Máté

    2015-12-24

    Cortical neurons integrate thousands of synaptic inputs in their dendrites in highly nonlinear ways. It is unknown how these dendritic nonlinearities in individual cells contribute to computations at the level of neural circuits. Here, we show that dendritic nonlinearities are critical for the efficient integration of synaptic inputs in circuits performing analog computations with spiking neurons. We developed a theory that formalizes how a neuron's dendritic nonlinearity that is optimal for integrating synaptic inputs depends on the statistics of its presynaptic activity patterns. Based on their in vivo preynaptic population statistics (firing rates, membrane potential fluctuations, and correlations due to ensemble dynamics), our theory accurately predicted the responses of two different types of cortical pyramidal cells to patterned stimulation by two-photon glutamate uncaging. These results reveal a new computational principle underlying dendritic integration in cortical neurons by suggesting a functional link between cellular and systems--level properties of cortical circuits.

  14. Efficient quantum walk on a quantum processor

    PubMed Central

    Qiang, Xiaogang; Loke, Thomas; Montanaro, Ashley; Aungskunsiri, Kanin; Zhou, Xiaoqi; O'Brien, Jeremy L.; Wang, Jingbo B.; Matthews, Jonathan C. F.

    2016-01-01

    The random walk formalism is used across a wide range of applications, from modelling share prices to predicting population genetics. Likewise, quantum walks have shown much potential as a framework for developing new quantum algorithms. Here we present explicit efficient quantum circuits for implementing continuous-time quantum walks on the circulant class of graphs. These circuits allow us to sample from the output probability distributions of quantum walks on circulant graphs efficiently. We also show that solving the same sampling problem for arbitrary circulant quantum circuits is intractable for a classical computer, assuming conjectures from computational complexity theory. This is a new link between continuous-time quantum walks and computational complexity theory and it indicates a family of tasks that could ultimately demonstrate quantum supremacy over classical computers. As a proof of principle, we experimentally implement the proposed quantum circuit on an example circulant graph using a two-qubit photonics quantum processor. PMID:27146471

  15. Nonreciprocal signal routing in an active quantum network

    NASA Astrophysics Data System (ADS)

    Metelmann, A.; Türeci, H. E.

    2018-04-01

    As superconductor quantum technologies are moving towards large-scale integrated circuits, a robust and flexible approach to routing photons at the quantum level becomes a critical problem. Active circuits, which contain parametrically driven elements selectively embedded in the circuit, offer a viable solution. Here, we present a general strategy for routing nonreciprocally quantum signals between two sites of a given lattice of oscillators, implementable with existing superconducting circuit components. Our approach makes use of a dual lattice of overdamped oscillators linking the nodes of the main lattice. Solutions for spatially selective driving of the lattice elements can be found, which optimally balance coherent and dissipative hopping of microwave photons to nonreciprocally route signals between two given nodes. In certain lattices these optimal solutions are obtained at the exceptional point of the dynamical matrix of the network. We also demonstrate that signal and noise transmission characteristics can be separately optimized.

  16. Toward Wireless Health Monitoring via an Analog Signal Compression-Based Biosensing Platform.

    PubMed

    Zhao, Xueyuan; Sadhu, Vidyasagar; Le, Tuan; Pompili, Dario; Javanmard, Mehdi

    2018-06-01

    Wireless all-analog biosensor design for the concurrent microfluidic and physiological signal monitoring is presented in this paper. The key component is an all-analog circuit capable of compressing two analog sources into one analog signal by the analog joint source-channel coding (AJSCC). Two circuit designs are discussed, including the stacked-voltage-controlled voltage source (VCVS) design with the fixed number of levels, and an improved design, which supports a flexible number of AJSCC levels. Experimental results are presented on the wireless biosensor prototype, composed of printed circuit board realizations of the stacked-VCVS design. Furthermore, circuit simulation and wireless link simulation results are presented on the improved design. Results indicate that the proposed wireless biosensor is well suited for sensing two biological signals simultaneously with high accuracy, and can be applied to a wide variety of low-power and low-cost wireless continuous health monitoring applications.

  17. BK channels are required for multisensory plasticity in the oculomotor system

    PubMed Central

    Nelson, Alexandra; Faulstich, Michael; Moghadam, Setareh; Onori, Kimberly; Meredith, Andrea; du Lac, Sascha

    2017-01-01

    SUMMARY Neural circuits are endowed with several forms of intrinsic and synaptic plasticity that could contribute to adaptive changes in behavior, but circuit complexities have hindered linking specific cellular mechanisms with their behavioral consequences. Eye movements generated by simple brainstem circuits provide a means for relating cellular plasticity to behavioral gain control. Here we show that firing rate potentiation, a form of intrinsic plasticity mediated by reductions in BK-type calcium activated potassium currents in spontaneously firing neurons, is engaged during optokinetic reflex compensation for inner ear dysfunction. Vestibular loss triggers transient increases in postsynaptic excitability, occlusion of firing rate potentiation, and reductions in BK currents in vestibular nucleus neurons. Concurrently, adaptive increases in visually-evoked eye movements rapidly restore oculomotor function in wildtype mice but are profoundly impaired in BK channel null mice. Activity-dependent regulation of intrinsic excitability may be a general mechanism for adaptive control of behavioral output in multisensory circuits. PMID:27989457

  18. Tomonaga-Luttinger physics in electronic quantum circuits.

    PubMed

    Jezouin, S; Albert, M; Parmentier, F D; Anthore, A; Gennser, U; Cavanna, A; Safi, I; Pierre, F

    2013-01-01

    In one-dimensional conductors, interactions result in correlated electronic systems. At low energy, a hallmark signature of the so-called Tomonaga-Luttinger liquids is the universal conductance curve predicted in presence of an impurity. A seemingly different topic is the quantum laws of electricity, when distinct quantum conductors are assembled in a circuit. In particular, the conductances are suppressed at low energy, a phenomenon called dynamical Coulomb blockade. Here we investigate the conductance of mesoscopic circuits constituted by a short single-channel quantum conductor in series with a resistance, and demonstrate a proposed link to Tomonaga-Luttinger physics. We reformulate and establish experimentally a recently derived phenomenological expression for the conductance using a wide range of circuits, including carbon nanotube data obtained elsewhere. By confronting both conductance data and phenomenological expression with the universal Tomonaga-Luttinger conductance curve, we demonstrate experimentally the predicted mapping between dynamical Coulomb blockade and the transport across a Tomonaga-Luttinger liquid with an impurity.

  19. AIN-Based Packaging for SiC High-Temperature Electronics

    NASA Technical Reports Server (NTRS)

    Savrun, Ender

    2004-01-01

    Packaging made primarily of aluminum nitride has been developed to enclose silicon carbide-based integrated circuits (ICs), including circuits containing SiC-based power diodes, that are capable of operation under conditions more severe than can be withstood by silicon-based integrated circuits. A major objective of this development was to enable packaged SiC electronic circuits to operate continuously at temperatures up to 500 C. AlN-packaged SiC electronic circuits have commercial potential for incorporation into high-power electronic equipment and into sensors that must withstand high temperatures and/or high pressures in diverse applications that include exploration in outer space, well logging, and monitoring of nuclear power systems. This packaging embodies concepts drawn from flip-chip packaging of silicon-based integrated circuits. One or more SiC-based circuit chips are mounted on an aluminum nitride package substrate or sandwiched between two such substrates. Intimate electrical connections between metal conductors on the chip(s) and the metal conductors on external circuits are made by direct bonding to interconnections on the package substrate(s) and/or by use of holes through the package substrate(s). This approach eliminates the need for wire bonds, which have been the most vulnerable links in conventional electronic circuitry in hostile environments. Moreover, the elimination of wire bonds makes it possible to pack chips more densely than was previously possible.

  20. Wireless Neural Recording With Single Low-Power Integrated Circuit

    PubMed Central

    Harrison, Reid R.; Kier, Ryan J.; Chestek, Cynthia A.; Gilja, Vikash; Nuyujukian, Paul; Ryu, Stephen; Greger, Bradley; Solzbacher, Florian; Shenoy, Krishna V.

    2010-01-01

    We present benchtop and in vivo experimental results from an integrated circuit designed for wireless implantable neural recording applications. The chip, which was fabricated in a commercially available 0.6-μm 2P3M BiCMOS process, contains 100 amplifiers, a 10-bit analog-to-digital converter (ADC), 100 threshold-based spike detectors, and a 902–928 MHz frequency-shift-keying (FSK) transmitter. Neural signals from a selected amplifier are sampled by the ADC at 15.7 kSps and telemetered over the FSK wireless data link. Power, clock, and command signals are sent to the chip wirelessly over a 2.765-MHz inductive (coil-to-coil) link. The chip is capable of operating with only two off-chip components: a power/command receiving coil and a 100-nF capacitor. PMID:19497825

  1. Merging parallel optics packaging and surface mount technologies

    NASA Astrophysics Data System (ADS)

    Kopp, Christophe; Volpert, Marion; Routin, Julien; Bernabé, Stéphane; Rossat, Cyrille; Tournaire, Myriam; Hamelin, Régis

    2008-02-01

    Optical links are well known to present significant advantages over electrical links for very high-speed data rate at 10Gpbs and above per channel. However, the transition towards optical interconnects solutions for short and very short reach applications requires the development of innovative packaging solutions that would deal with very high volume production capability and very low cost per unit. Moreover, the optoelectronic transceiver components must be able to move from the edge to anywhere on the printed circuit board, for instance close to integrated circuits with high speed IO. In this paper, we present an original packaging design to manufacture parallel optic transceivers that are surface mount devices. The package combines highly integrated Multi-Chip-Module on glass and usual IC ceramics packaging. The use of ceramic and the development of sealing technologies achieve hermetic requirements. Moreover, thanks to a chip scale package approach the final device exhibits a much minimized footprint. One of the main advantages of the package is its flexibility to be soldered or plugged anywhere on the printed circuit board as any other electronic device. As a demonstrator we present a 2 by 4 10Gbps transceiver operating at 850nm.

  2. A Multi-Cycle Q-Modulation for Dynamic Optimization of Inductive Links.

    PubMed

    Lee, Byunghun; Yeon, Pyungwoo; Ghovanloo, Maysam

    2016-08-01

    This paper presents a new method, called multi-cycle Q-modulation, which can be used in wireless power transmission (WPT) to modulate the quality factor (Q) of the receiver (Rx) coil and dynamically optimize the load impedance to maximize the power transfer efficiency (PTE) in two-coil links. A key advantage of the proposed method is that it can be easily implemented using off-the-shelf components without requiring fast switching at or above the carrier frequency, which is more suitable for integrated circuit design. Moreover, the proposed technique does not need any sophisticated synchronization between the power carrier and Q-modulation switching pulses. The multi-cycle Q-modulation is analyzed theoretically by a lumped circuit model, and verified in simulation and measurement using an off-the-shelf prototype. Automatic resonance tuning (ART) in the Rx, combined with multi-cycle Q-modulation helped maximizing PTE of the inductive link dynamically in the presence of environmental and loading variations, which can otherwise significantly degrade the PTE in multi-coil settings. In the prototype conventional 2-coil link, the proposed method increased the power amplifier (PA) plus inductive link efficiency from 4.8% to 16.5% at ( R L = 1 kΩ, d 23 = 3 cm), and from 23% to 28.2% at ( R L = 100 Ω, d 23 = 3 cm) after 11% change in the resonance capacitance, while delivering 168.1 mW to the load (PDL).

  3. A Small-Molecule Inducible Synthetic Circuit for Control of the SOS Gene Network without DNA Damage

    PubMed Central

    2017-01-01

    The bacterial SOS stress-response pathway is a pro-mutagenic DNA repair system that mediates bacterial survival and adaptation to genotoxic stressors, including antibiotics and UV light. The SOS pathway is composed of a network of genes under the control of the transcriptional repressor, LexA. Activation of the pathway involves linked but distinct events: an initial DNA damage event leads to activation of RecA, which promotes autoproteolysis of LexA, abrogating its repressor function and leading to induction of the SOS gene network. These linked events can each independently contribute to DNA repair and mutagenesis, making it difficult to separate the contributions of the different events to observed phenotypes. We therefore devised a novel synthetic circuit to unlink these events and permit induction of the SOS gene network in the absence of DNA damage or RecA activation via orthogonal cleavage of LexA. Strains engineered with the synthetic SOS circuit demonstrate small-molecule inducible expression of SOS genes as well as the associated resistance to UV light. Exploiting our ability to activate SOS genes independently of upstream events, we further demonstrate that the majority of SOS-mediated mutagenesis on the chromosome does not readily occur with orthogonal pathway induction alone, but instead requires DNA damage. More generally, our approach provides an exemplar for using synthetic circuit design to separate an environmental stressor from its associated stress-response pathway. PMID:28826208

  4. Traveling Culture: Circuit Chautauqua in the Twentieth Century - The

    Science.gov Websites

    Libraries Archival Collections Records of the Redpath Chautauqua Related Links Essay: What Was Chautauqua spoken word recordings, and programs drawn from the Records of the Redpath Lyceum Bureau, the largest

  5. Electric Currents Generated by Gabbro during Dynamic Uniaxial Loading

    NASA Astrophysics Data System (ADS)

    Jones, H. H.; Lau, B. W.; Takeuchi, A. T.; Freund, F. T.

    2006-12-01

    Igneous rocks, when subjected to deviatory stress, turn into a battery. Dynamically stressed rocks can generate large currents. We report on gabbro (Shanxi, China). We use steel pistons to load ~10 cm3 in the center of 30 x 30 x 0.9 cm3 tiles, from 0 to 60 MPa, 1/3 failure strength. Instantly upon loading, a current begins to flow, increasing rapidly to 200-300 pA. One part of the current is carried by electrons, which flow from the stressed rock into the steel pistons and through the external circuit to the edges of the tile. The other part is carried by holes, which flow inside the rock, from the stressed to the unstressed rock and the edges of the tile. At the edges the two charge carriers meet, thereby closing the circuit. Changing the stress rates from 0.0002 to 100 MPa/sec causes the steady currents to increase from ~30,000 A/km3 to ~50,000 A/km3 and an initial spike to develop reaching 300,000 A/km3 at the highest stress rate. Both, electrons and holes, are associated with oxygen anions that changed their valence from 2- to 1- (peroxy). An O- among O2- represents a defect electron in the O2- sublattice, known as positive hole or p-hole for short. In unstressed rocks the O- exist in an electrically inactive form as O- pairs, chemically equivalent to peroxy links, O3X-OO-XO3 with X = Si4+, Al3+ etc. Stresses cause the peroxy links to break, allowing electrons from neighboring O2- to jump in and p-holes to jump out. The p-holes can spread through unstressed rocks using energy levels in the valence band. Sustained large battery currents can flow, for instance in the aftermath of an impact, when the holes can close the circuit by linking up with the electrons. If the circuit is not closed, no battery currents flow.

  6. Dissecting Immune Circuits by Linking CRISPR-Pooled Screens with Single-Cell RNA-Seq.

    PubMed

    Jaitin, Diego Adhemar; Weiner, Assaf; Yofe, Ido; Lara-Astiaso, David; Keren-Shaul, Hadas; David, Eyal; Salame, Tomer Meir; Tanay, Amos; van Oudenaarden, Alexander; Amit, Ido

    2016-12-15

    In multicellular organisms, dedicated regulatory circuits control cell type diversity and responses. The crosstalk and redundancies within these circuits and substantial cellular heterogeneity pose a major research challenge. Here, we present CRISP-seq, an integrated method for massively parallel single-cell RNA sequencing (RNA-seq) and clustered regularly interspaced short palindromic repeats (CRISPR)-pooled screens. We show that profiling the genomic perturbation and transcriptome in the same cell enables us to simultaneously elucidate the function of multiple factors and their interactions. We applied CRISP-seq to probe regulatory circuits of innate immunity. By sampling tens of thousands of perturbed cells in vitro and in mice, we identified interactions and redundancies between developmental and signaling-dependent factors. These include opposing effects of Cebpb and Irf8 in regulating the monocyte/macrophage versus dendritic cell lineages and differential functions for Rela and Stat1/2 in monocyte versus dendritic cell responses to pathogens. This study establishes CRISP-seq as a broadly applicable, comprehensive, and unbiased approach for elucidating mammalian regulatory circuits. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. Tool for use in lifting pin supported objects

    NASA Technical Reports Server (NTRS)

    Marzek, R. A.; Read, W. S. (Inventor)

    1974-01-01

    A tool for use in lifting a pin-supported, electronic package mounted in juxtaposition with the surface of an electronic circuit board is described. The tool is configured to be received beneath a pin-supported package and is characterized by a manually operable linkage, including an elongated, rigid link is supported for axial reciprocation and a pivotal link pinned to the body and supported for oscillation induced in response to axial motion imparted to the rigid link. A lifting plate is pivotally coupled to the distal end of the pivotal link so that oscillatory motion imparted to the pivotal link serves to move the plate vertically for elevating the plate into lifting engagement with the electronic package positioned thereabove.

  8. Enhancer modularity and the evolution of new traits.

    PubMed

    Koshikawa, Shigeyuki

    2015-01-01

    Animals have modular cis-regulatory regions in their genomes, and expression of a single gene is often regulated by multiple enhancers residing in such a region. In the laboratory, and also in natural populations, loss of an enhancer can result in a loss of gene expression. Although only a few examples have been well characterized to date, some studies have suggested that an evolutionary gain of a new enhancer function can establish a new gene expression domain. Our recent study showed that Drosophila guttifera has more enhancers and additional expression domains of the wingless gene during the pupal stage, compared to D. melanogaster, and that these new features appear to have evolved in the ancestral lineage leading to D. guttifera. (1) Gain of a new expression domain of a developmental regulatory gene (toolkit gene), such as wingless, can cause co-option of the expression of its downstream genes to the new domain, resulting in duplication of a preexisting structure at this new body position. Recently, with the advancement of evo-devo studies, we have learned that the developmental regulatory systems are strikingly similar across various animal taxa, in spite of the great diversity of the animals' morphology. Even behind "new" traits, co-options of essential developmental genes from known systems are very common. We previously provided concrete evidence of gains of enhancer activities of a developmental regulatory gene underlying gains of new traits. (1) Broad occurrence of this scenario is testable and should be validated in the future.

  9. Cospeciation of Psyllids and Their Primary Prokaryotic Endosymbionts

    PubMed Central

    Thao, MyLo L.; Moran, Nancy A.; Abbot, Patrick; Brennan, Eric B.; Burckhardt, Daniel H.; Baumann, Paul

    2000-01-01

    Psyllids are plant sap-feeding insects that harbor prokaryotic endosymbionts in specialized cells within the body cavity. Four-kilobase DNA fragments containing 16S and 23S ribosomal DNA (rDNA) were amplified from the primary (P) endosymbiont of 32 species of psyllids representing three psyllid families and eight subfamilies. In addition, 0.54-kb fragments of the psyllid nuclear gene wingless were also amplified from 26 species. Phylogenetic trees derived from 16S-23S rDNA and from the host wingless gene are very similar, and tests of compatibility of the data sets show no significant conflict between host and endosymbiont phylogenies. This result is consistent with a single infection of a shared psyllid ancestor and subsequent cospeciation of the host and the endosymbiont. In addition, the phylogenies based on DNA sequences generally agreed with psyllid taxonomy based on morphology. The 3′ end of the 16S rDNA of the P endosymbionts differs from that of other members of the domain Bacteria in the lack of a sequence complementary to the mRNA ribosome binding site. The rate of sequence change in the 16S-23S rDNA of the psyllid P endosymbiont was considerably higher than that of other bacteria, including other fast-evolving insect endosymbionts. The lineage consisting of the P endosymbionts of psyllids was given the designation Candidatus Carsonella (gen. nov.) with a single species, Candidatus Carsonella ruddii (sp. nov.). PMID:10877784

  10. The Intersection of the Extrinsic Hedgehog and WNT/Wingless Signals with the Intrinsic Hox Code Underpins Branching Pattern and Tube Shape Diversity in the Drosophila Airways

    PubMed Central

    Matsuda, Ryo; Hosono, Chie; Saigo, Kaoru; Samakovlis, Christos

    2015-01-01

    The tubular networks of the Drosophila respiratory system and our vasculature show distinct branching patterns and tube shapes in different body regions. These local variations are crucial for organ function and organismal fitness. Organotypic patterns and tube geometries in branched networks are typically controlled by variations of extrinsic signaling but the impact of intrinsic factors on branch patterns and shapes is not well explored. Here, we show that the intersection of extrinsic hedgehog(hh) and WNT/wingless (wg) signaling with the tube-intrinsic Hox code of distinct segments specifies the tube pattern and shape of the Drosophila airways. In the cephalic part of the airways, hh signaling induces expression of the transcription factor (TF) knirps (kni) in the anterior dorsal trunk (DTa1). kni represses the expression of another TF spalt major (salm), making DTa1 a narrow and long tube. In DTa branches of more posterior metameres, Bithorax Complex (BX-C) Hox genes autonomously divert hh signaling from inducing kni, thereby allowing DTa branches to develop as salm-dependent thick and short tubes. Moreover, the differential expression of BX-C genes is partly responsible for the anterior-to-posterior gradual increase of the DT tube diameter through regulating the expression level of Salm, a transcriptional target of WNT/wg signaling. Thus, our results highlight how tube intrinsic differential competence can diversify tube morphology without changing availabilities of extrinsic factors. PMID:25615601

  11. The Effects of Pressure on Gases in Solution: Possible Insights to Improve Microbubble Filtration for Extracorporeal Circulation

    PubMed Central

    Herbst, Daniel P.

    2013-01-01

    Abstract: Improvements in micropore arterial line filter designs used for extracorporeal circulation are still needed because microbubbles larger than the rated pore sizes are being detected beyond the filter outlet. Linked to principles governing the function of micropore filters, fluid pressures contained in extracorporeal circuits also influence the behavior of gas bubbles and the extent to which they are carried in a fluid flow. To better understand the relationship between pressure and microbubble behavior, two ex vivo test circuits with and without inline resistance were designed to assess changes in microbubble load with changes in pressure. Ultrasound Doppler probes were used to measure and compare the quality and quantity of microbubbles generated in each test circuit. Analysis of microbubble load was separated into two distinct phases, the time periods during and immediately after bubble generation. Although microbubble number decreased similarly in both test circuits, changes in microbubble volume were significant only in the test circuit with inline resistance. The test circuit with inline resistance also showed a decrease in the rate of volume transferred across each ultrasound Doppler probe and the microbubble number and size range measured in the postbubble generation period. The present research proposes that fluid pressures contained in extracorporeal circuits may be used to affect gases in solution as a possible method to improve microbubble filtration during extracorporeal circulation. PMID:23930378

  12. The effects of pressure on gases in solution: possible insights to improve microbubble filtration for extracorporeal circulation.

    PubMed

    Herbst, Daniel P

    2013-06-01

    Improvements in micropore arterial line filter designs used for extracorporeal circulation are still needed because microbubbles larger than the rated pore sizes are being detected beyond the filter outlet. Linked to principles governing the function of micropore filters, fluid pressures contained in extracorporeal circuits also influence the behavior of gas bubbles and the extent to which they are carried in a fluid flow. To better understand the relationship between pressure and microbubble behavior, two ex vivo test circuits with and without inline resistance were designed to assess changes in microbubble load with changes in pressure. Ultrasound Doppler probes were used to measure and compare the quality and quantity of microbubbles generated in each test circuit. Analysis of microbubble load was separated into two distinct phases, the time periods during and immediately after bubble generation. Although microbubble number decreased similarly in both test circuits, changes in microbubble volume were significant only in the test circuit with inline resistance. The test circuit with inline resistance also showed a decrease in the rate of volume transferred across each ultrasound Doppler probe and the microbubble number and size range measured in the postbubble generation period. The present research proposes that fluid pressures contained in extracorporeal circuits may be used to affect gases in solution as a possible method to improve microbubble filtration during extracorporeal circulation.

  13. Behavioral modeling of VCSELs for high-speed optical interconnects

    NASA Astrophysics Data System (ADS)

    Szczerba, Krzysztof; Kocot, Chris

    2018-02-01

    Transition from on-off keying to 4-level pulse amplitude modulation (PAM) in VCSEL based optical interconnects allows for an increase of data rates, at the cost of 4.8 dB sensitivity penalty. The resulting strained link budget creates a need for accurate VCSEL models for driver integrated circuit (IC) design and system level simulations. Rate equation based equivalent circuit models are convenient for the IC design, but system level analysis requires computationally efficient closed form behavioral models based Volterra series and neural networks. In this paper we present and compare these models.

  14. Wingless Flight: The Lifting Body Story

    NASA Technical Reports Server (NTRS)

    Reed, R. Dale; Lister, Darlene (Editor); Huntley, J. D. (Editor)

    1997-01-01

    Wingless Flight tells the story of the most unusual flying machines ever flown, the lifting bodies. It is my story about my friends and colleagues who committed a significant part of their lives in the 1960s and 1970s to prove that the concept was a viable one for use in spacecraft of the future. This story, filled with drama and adventure, is about the twelve-year period from 1963 to 1975 in which eight different lifting-body configurations flew. It is appropriate for me to write the story, since I was the engineer who first presented the idea of flight-testing the concept to others at the NASA Flight Research Center. Over those twelve years, I experienced the story as it unfolded day by day at that remote NASA facility northeast of los Angeles in the bleak Mojave Desert. Benefits from this effort immediately influenced the design and operational concepts of the winged NASA Shuttle Orbiter. However, the full benefits would not be realized until the 1990s when new spacecraft such as the X-33 and X-38 would fully employ the lifting-body concept. A lifting body is basically a wingless vehicle that flies due to the lift generated by the shape of its fuselage. Although both a lifting reentry vehicle and a ballistic capsule had been considered as options during the early stages of NASA's space program, NASA initially opted to go with the capsule. A number of individuals were not content to close the book on the lifting-body concept. Researchers including Alfred Eggers at the NASA Ames Research Center conducted early wind-tunnel experiments, finding that half of a rounded nose-cone shape that was flat on top and rounded on the bottom could generate a lift-to-drag ratio of about 1.5 to 1. Eggers' preliminary design sketch later resembled the basic M2 lifting-body design. At the NASA Langley Research Center, other researchers toyed with their own lifting-body shapes. Meanwhile, some of us aircraft-oriented researchers at the, NASA Flight Research Center at Edwards Air Force Base (AFB) in California were experiencing our own fascination with the lifting-body concept. A model-aircraft builder and private pilot on my own time, I found the lifting-body idea intriguing. I built a model based on Eggers' design, tested it repeatedly, made modifications in its control and balance characteristics along the way, then eventually presented the concept to others at the Center, using a film of its flights that my wife, Donna and I had made with our 8-mm home camera.

  15. All optical programmable logic array (PLA)

    NASA Astrophysics Data System (ADS)

    Hiluf, Dawit

    2018-03-01

    A programmable logic array (PLA) is an integrated circuit (IC) logic device that can be reconfigured to implement various kinds of combinational logic circuits. The device has a number of AND and OR gates which are linked together to give output or further combined with more gates or logic circuits. This work presents the realization of PLAs via the physics of a three level system interacting with light. A programmable logic array is designed such that a number of different logical functions can be combined as a sum-of-product or product-of-sum form. We present an all optical PLAs with the aid of laser light and observables of quantum systems, where encoded information can be considered as memory chip. The dynamics of the physical system is investigated using Lie algebra approach.

  16. Modification of feeding circuits in the evolution of social behavior.

    PubMed

    Fischer, Eva K; O'Connell, Lauren A

    2017-01-01

    Adaptive trade-offs between foraging and social behavior intuitively explain many aspects of individual decision-making. Given the intimate connection between social behavior and feeding/foraging at the behavioral level, we propose that social behaviors are linked to foraging on a mechanistic level, and that modifications of feeding circuits are crucial in the evolution of complex social behaviors. In this Review, we first highlight the overlap between mechanisms underlying foraging and parental care and then expand this argument to consider the manipulation of feeding-related pathways in the evolution of other complex social behaviors. We include examples from diverse taxa to highlight that the independent evolution of complex social behaviors is a variation on the theme of feeding circuit modification. © 2017. Published by The Company of Biologists Ltd.

  17. Dendritic nonlinearities are tuned for efficient spike-based computations in cortical circuits

    PubMed Central

    Ujfalussy, Balázs B; Makara, Judit K; Branco, Tiago; Lengyel, Máté

    2015-01-01

    Cortical neurons integrate thousands of synaptic inputs in their dendrites in highly nonlinear ways. It is unknown how these dendritic nonlinearities in individual cells contribute to computations at the level of neural circuits. Here, we show that dendritic nonlinearities are critical for the efficient integration of synaptic inputs in circuits performing analog computations with spiking neurons. We developed a theory that formalizes how a neuron's dendritic nonlinearity that is optimal for integrating synaptic inputs depends on the statistics of its presynaptic activity patterns. Based on their in vivo preynaptic population statistics (firing rates, membrane potential fluctuations, and correlations due to ensemble dynamics), our theory accurately predicted the responses of two different types of cortical pyramidal cells to patterned stimulation by two-photon glutamate uncaging. These results reveal a new computational principle underlying dendritic integration in cortical neurons by suggesting a functional link between cellular and systems--level properties of cortical circuits. DOI: http://dx.doi.org/10.7554/eLife.10056.001 PMID:26705334

  18. Study of the effect of distance and misalignment between magnetically coupled coils for wireless power transfer in intraocular pressure measurement.

    PubMed

    Rendon-Nava, Adrian E; Díaz-Méndez, J Alejandro; Nino-de-Rivera, Luis; Calleja-Arriaga, Wilfrido; Gil-Carrasco, Felix; Díaz-Alonso, Daniela

    2014-01-01

    An analysis of the effect of distance and alignment between two magnetically coupled coils for wireless power transfer in intraocular pressure measurement is presented. For measurement purposes, a system was fabricated consisting of an external device, which is a Maxwell-Wien bridge circuit variation, in charge of transferring energy to a biomedical implant and reading data from it. The biomedical implant is an RLC tank circuit, encapsulated by a polyimide coating. Power transfer was done by magnetic induction coupling method, by placing one of the inductors of the Maxwell-Wien bridge circuit and the inductor of the implant in close proximity. The Maxwell-Wien bridge circuit was biased with a 10 MHz sinusoidal signal. The analysis presented in this paper proves that wireless transmission of power for intraocular pressure measurement is feasible with the measurement system proposed. In order to have a proper inductive coupling link, special care must be taken when placing the two coils in proximity to avoid misalignment between them.

  19. Tomonaga–Luttinger physics in electronic quantum circuits

    PubMed Central

    Jezouin, S.; Albert, M.; Parmentier, F. D.; Anthore, A.; Gennser, U.; Cavanna, A.; Safi, I.; Pierre, F.

    2013-01-01

    In one-dimensional conductors, interactions result in correlated electronic systems. At low energy, a hallmark signature of the so-called Tomonaga–Luttinger liquids is the universal conductance curve predicted in presence of an impurity. A seemingly different topic is the quantum laws of electricity, when distinct quantum conductors are assembled in a circuit. In particular, the conductances are suppressed at low energy, a phenomenon called dynamical Coulomb blockade. Here we investigate the conductance of mesoscopic circuits constituted by a short single-channel quantum conductor in series with a resistance, and demonstrate a proposed link to Tomonaga–Luttinger physics. We reformulate and establish experimentally a recently derived phenomenological expression for the conductance using a wide range of circuits, including carbon nanotube data obtained elsewhere. By confronting both conductance data and phenomenological expression with the universal Tomonaga–Luttinger conductance curve, we demonstrate experimentally the predicted mapping between dynamical Coulomb blockade and the transport across a Tomonaga–Luttinger liquid with an impurity. PMID:23653214

  20. Evolution of Acid-Sensing Olfactory Circuits in Drosophilids.

    PubMed

    Prieto-Godino, Lucia L; Rytz, Raphael; Cruchet, Steeve; Bargeton, Benoîte; Abuin, Liliane; Silbering, Ana F; Ruta, Vanessa; Dal Peraro, Matteo; Benton, Richard

    2017-02-08

    Animals adapt their behaviors to specific ecological niches, but the genetic and cellular basis of nervous system evolution is poorly understood. We have compared the olfactory circuits of the specialist Drosophila sechellia-which feeds exclusively on Morinda citrifolia fruit-with its generalist cousins D. melanogaster and D. simulans. We show that D. sechellia exhibits derived odor-evoked attraction and physiological sensitivity to the abundant Morinda volatile hexanoic acid and characterize how the responsible sensory receptor (the variant ionotropic glutamate receptor IR75b) and attraction-mediating circuit have evolved. A single amino acid change in IR75b is sufficient to recode it as a hexanoic acid detector. Expanded representation of this sensory pathway in the brain relies on additional changes in the IR75b promoter and trans-acting loci. By contrast, higher-order circuit adaptations are not apparent, suggesting conserved central processing. Our work links olfactory ecology to structural and regulatory genetic changes influencing nervous system anatomy and function. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. BK Channels Are Required for Multisensory Plasticity in the Oculomotor System.

    PubMed

    Nelson, Alexandra B; Faulstich, Michael; Moghadam, Setareh; Onori, Kimberly; Meredith, Andrea; du Lac, Sascha

    2017-01-04

    Neural circuits are endowed with several forms of intrinsic and synaptic plasticity that could contribute to adaptive changes in behavior, but circuit complexities have hindered linking specific cellular mechanisms with their behavioral consequences. Eye movements generated by simple brainstem circuits provide a means for relating cellular plasticity to behavioral gain control. Here we show that firing rate potentiation, a form of intrinsic plasticity mediated by reductions in BK-type calcium-activated potassium currents in spontaneously firing neurons, is engaged during optokinetic reflex compensation for inner ear dysfunction. Vestibular loss triggers transient increases in postsynaptic excitability, occlusion of firing rate potentiation, and reductions in BK currents in vestibular nucleus neurons. Concurrently, adaptive increases in visually evoked eye movements rapidly restore oculomotor function in wild-type mice but are profoundly impaired in BK channel-null mice. Activity-dependent regulation of intrinsic excitability may be a general mechanism for adaptive control of behavioral output in multisensory circuits. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. An NFC on Two-Coil WPT Link for Implantable Biomedical Sensors under Ultra-Weak Coupling.

    PubMed

    Gong, Chen; Liu, Dake; Miao, Zhidong; Wang, Wei; Li, Min

    2017-06-11

    The inductive link is widely used in implantable biomedical sensor systems to achieve near-field communication (NFC) and wireless power transfer (WPT). However, it is tough to achieve reliable NFC on an inductive WPT link when the coupling coefficient is ultra-low (0.01 typically), since the NFC signal (especially for the uplink from the in-body part to the out-body part) could be too weak to be detected. Traditional load shift keying (LSK) requires strong coupling to pass the load modulation information to the power source. Instead of using LSK, we propose a dual-carrier NFC scheme for the weak-coupled inductive link; using binary phase shift keying (BPSK) modulation, its downlink data are modulated on the power carrier (2 MHz), while its uplink data are modulated on another carrier (125 kHz). The two carriers are transferred through the same coil pair. To overcome the strong interference of the power carrier, dedicated circuits are introduced. In addition, to minimize the power transfer efficiency decrease caused by adding NFC, we optimize the inductive link circuit parameters and approach the receiver sensitivity limit. In the prototype experiments, even though the coupling coefficient is as low as 0.008, the in-body transmitter costs only 0.61 mW power carrying 10 kbps of data, and achieves a 1 × 10 - 7 bit error rate under the strong interference of WPT. This dual-carrier NFC scheme could be useful for small-sized implantable biomedical sensor applications.

  3. Visuomotor Transformations Underlying Hunting Behavior in Zebrafish

    PubMed Central

    Bianco, Isaac H.; Engert, Florian

    2015-01-01

    Summary Visuomotor circuits filter visual information and determine whether or not to engage downstream motor modules to produce behavioral outputs. However, the circuit mechanisms that mediate and link perception of salient stimuli to execution of an adaptive response are poorly understood. We combined a virtual hunting assay for tethered larval zebrafish with two-photon functional calcium imaging to simultaneously monitor neuronal activity in the optic tectum during naturalistic behavior. Hunting responses showed mixed selectivity for combinations of visual features, specifically stimulus size, speed, and contrast polarity. We identified a subset of tectal neurons with similar highly selective tuning, which show non-linear mixed selectivity for visual features and are likely to mediate the perceptual recognition of prey. By comparing neural dynamics in the optic tectum during response versus non-response trials, we discovered premotor population activity that specifically preceded initiation of hunting behavior and exhibited anatomical localization that correlated with motor variables. In summary, the optic tectum contains non-linear mixed selectivity neurons that are likely to mediate reliable detection of ethologically relevant sensory stimuli. Recruitment of small tectal assemblies appears to link perception to action by providing the premotor commands that release hunting responses. These findings allow us to propose a model circuit for the visuomotor transformations underlying a natural behavior. PMID:25754638

  4. Visuomotor transformations underlying hunting behavior in zebrafish.

    PubMed

    Bianco, Isaac H; Engert, Florian

    2015-03-30

    Visuomotor circuits filter visual information and determine whether or not to engage downstream motor modules to produce behavioral outputs. However, the circuit mechanisms that mediate and link perception of salient stimuli to execution of an adaptive response are poorly understood. We combined a virtual hunting assay for tethered larval zebrafish with two-photon functional calcium imaging to simultaneously monitor neuronal activity in the optic tectum during naturalistic behavior. Hunting responses showed mixed selectivity for combinations of visual features, specifically stimulus size, speed, and contrast polarity. We identified a subset of tectal neurons with similar highly selective tuning, which show non-linear mixed selectivity for visual features and are likely to mediate the perceptual recognition of prey. By comparing neural dynamics in the optic tectum during response versus non-response trials, we discovered premotor population activity that specifically preceded initiation of hunting behavior and exhibited anatomical localization that correlated with motor variables. In summary, the optic tectum contains non-linear mixed selectivity neurons that are likely to mediate reliable detection of ethologically relevant sensory stimuli. Recruitment of small tectal assemblies appears to link perception to action by providing the premotor commands that release hunting responses. These findings allow us to propose a model circuit for the visuomotor transformations underlying a natural behavior. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. The immobilization of a direct thrombin inhibitor to a polyurethane as a nonthrombogenic surface coating for extracorporeal circulation.

    PubMed

    Yu, Jane; Brisbois, Elizabeth; Handa, Hitesh; Annich, Gail; Meyerhoff, Mark; Bartlett, Robert; Major, Terry

    2016-04-07

    A biomaterial with both antithrombin and antiplatelet properties is the ideal surface for use in extracorporeal circulation (ECC) as it targets both fibrin generation and platelet adhesion. A hemocompatible surface coating avoids the need for systemic anticoagulation by providing a local anticoagulant effect at the polymer-blood interface. Previous work has demonstrated the potential use of argatroban, a direct thrombin inhibitor, as a nonthrombogenic material for extracorporeal devices. The work reported here focuses on the characterization of argatroban linked to a polyurethane-silicone polymer, CarboSil®. Chemical immobilization, the amount of argatroban, incubation times, and saturation point were evaluated to achieve maximal antithrombin activity at the polymer surface. Cross-linked polymer coatings reacted with 10 and 30 µmole of argatroban were prepared and tested. These coatings resulted in argatroban activity levels of 0.131 µM and 0.446 µM, respectively. After refining the cross-linking process, argatroban activity increased by approximately 3.6 fold. Maintenance of activity and leaching from the polymer surface were also evaluated. Using the refined process for linking argatroban to polymer, the resulting polymer was applied as a surface coating to the inner lumen of poly(vinyl chloride) ECC circuit tubing and its antithrombin effect evaluated using a 4 h rabbit ECC model. Following 4 h of blood exposure, the argatroban circuit demonstrated significantly less thrombus formation compared to the control CarboSil® coating with a 4.1 cm 2 thrombus average area for the control coating compared to 1.2 cm 2 for the argatroban coating (n=4). There was no significant change in thrombin time from baseline in plasma from animals in which the argatroban coated circuit was used, with a thrombin time of 16.2 s at t=0 and 14.5 s after 4 h. These results demonstrate the potential efficacy of immobilized argatroban as a hemocompatible biomaterial for extracorporeal life support devices.

  6. The immobilization of a direct thrombin inhibitor to a polyurethane as a nonthrombogenic surface coating for extracorporeal circulation

    PubMed Central

    Yu, Jane; Brisbois, Elizabeth; Handa, Hitesh; Annich, Gail; Meyerhoff, Mark; Bartlett, Robert; Major, Terry

    2016-01-01

    A biomaterial with both antithrombin and antiplatelet properties is the ideal surface for use in extracorporeal circulation (ECC) as it targets both fibrin generation and platelet adhesion. A hemocompatible surface coating avoids the need for systemic anticoagulation by providing a local anticoagulant effect at the polymer-blood interface. Previous work has demonstrated the potential use of argatroban, a direct thrombin inhibitor, as a nonthrombogenic material for extracorporeal devices. The work reported here focuses on the characterization of argatroban linked to a polyurethane-silicone polymer, CarboSil®. Chemical immobilization, the amount of argatroban, incubation times, and saturation point were evaluated to achieve maximal antithrombin activity at the polymer surface. Cross-linked polymer coatings reacted with 10 and 30 µmole of argatroban were prepared and tested. These coatings resulted in argatroban activity levels of 0.131 µM and 0.446 µM, respectively. After refining the cross-linking process, argatroban activity increased by approximately 3.6 fold. Maintenance of activity and leaching from the polymer surface were also evaluated. Using the refined process for linking argatroban to polymer, the resulting polymer was applied as a surface coating to the inner lumen of poly(vinyl chloride) ECC circuit tubing and its antithrombin effect evaluated using a 4 h rabbit ECC model. Following 4 h of blood exposure, the argatroban circuit demonstrated significantly less thrombus formation compared to the control CarboSil® coating with a 4.1 cm2 thrombus average area for the control coating compared to 1.2 cm2 for the argatroban coating (n=4). There was no significant change in thrombin time from baseline in plasma from animals in which the argatroban coated circuit was used, with a thrombin time of 16.2 s at t=0 and 14.5 s after 4 h. These results demonstrate the potential efficacy of immobilized argatroban as a hemocompatible biomaterial for extracorporeal life support devices. PMID:27458521

  7. Connective Tissue Growth Factor (CTGF) as a Regulator of Lactogenic Differentiation

    DTIC Science & Technology

    2009-06-09

    1 1.62 Myeloid leukemia factor 1, Mlf1 1.57 ADAMTS-l4 1.55 E2F transcription factor, E2F2 1.44 Tensin 4 -1.5 BCL2/adenovirus E1B interacting... Mlf1 1.57 ADAMTS-l4 1.55 Ras homolog gene family, member B, RhoB 1.48 Cell Differentiation-associated Wingless-type MMTV integration site family...B, relB 1.92 Myeloid leukemia factor 1, Mlf1 1.57 Growth Factor, Catalytic Activity-associated Dual specificity protein phosphatase 8, Dusp8

  8. Cerebral causes and consequences of parkinsonian resting tremor: a tale of two circuits?

    PubMed Central

    Hallett, Mark; Deuschl, Günther; Toni, Ivan; Bloem, Bastiaan R.

    2012-01-01

    Tremor in Parkinson's disease has several mysterious features. Clinically, tremor is seen in only three out of four patients with Parkinson's disease, and tremor-dominant patients generally follow a more benign disease course than non-tremor patients. Pathophysiologically, tremor is linked to altered activity in not one, but two distinct circuits: the basal ganglia, which are primarily affected by dopamine depletion in Parkinson's disease, and the cerebello-thalamo-cortical circuit, which is also involved in many other tremors. The purpose of this review is to integrate these clinical and pathophysiological features of tremor in Parkinson's disease. We first describe clinical and pathological differences between tremor-dominant and non-tremor Parkinson's disease subtypes, and then summarize recent studies on the pathophysiology of tremor. We also discuss a newly proposed ‘dimmer-switch model’ that explains tremor as resulting from the combined actions of two circuits: the basal ganglia that trigger tremor episodes and the cerebello-thalamo-cortical circuit that produces the tremor. Finally, we address several important open questions: why resting tremor stops during voluntary movements, why it has a variable response to dopaminergic treatment, why it indicates a benign Parkinson's disease subtype and why its expression decreases with disease progression. PMID:22382359

  9. Investigation and evaluation of shuttle/GPS navigation system

    NASA Technical Reports Server (NTRS)

    Nilsen, P. W.

    1977-01-01

    Iterative procedures were used to analyze the performance of two preliminary shuttle/GPS navigation system configurations: an early OFT experimental system and a more sophisticated system which consolidates several separate navigation functions thus permitting net cost savings from decreased shuttle avionics weight and power consumption, and from reduced ground data processing. The GPS system can provide on-orbit navigation accuracy an order of magnitude better than the baseline system, with very adequate link margins. The worst-case link margin is 4.3 dB. This link margin accounts for shuttle RF circuit losses which were minimized under the constraints of program schedule and environmental limitations. Implicit in the link analyses are the location trade-offs for preamplifiers and antennas.

  10. Phylogeography of pink pineapple mealybugs, Dysmicoccus brevipes (Cockerell) reveals the history of pineapple introduction and cultivation in China.

    PubMed

    He, Y B; Zhan, R L; Sun, G M; Wu, J B; Zhao, Y L

    2015-08-19

    The pink pineapple mealybug (PPM), Dysmicoccus brevipes (Cockerell) (Hemiptera: Pseudococcidae), is a widespread plant-sucking insect of considerable concern because it transmits the pineapple mealybug wilt-associated virus. Its distribution is closely linked with its host, the pineapple [Ananas comosus (L.) Merrill] because of its wingless and parthenogenetic characteristics. To investigate the history of D. brevipes introduction and the cultivation of pineapple in China, samples of D. brevipes were collected from the main pineapple production region in China, and from Thailand, and the mitochondrial cytochrome c oxidase subunit I (COI) gene was analyzed. Homologous sequences of D. brevipes COI from Brazil, Thailand, and Philippines that are deposited in GenBank were compared. Phylogenetic analyses suggest there are close genetic relationships between PPM populations from Hawaii, Brazil, the Philippines, and from Thailand and China, which probably originate from South America. It is suggested that most PPMs in China were introduced from South America by way of Southeast Asia, being accompanied by the pineapple seedling. Conversely, some PPMs represented by Haplotype-WN from Wanning of China, and Lampang of Thailand were found to differ greatly from populations in Hawaii, Brazil, the Philippines, Thailand, and China. It is possible that another route was used for the introduction and distribution of pineapple, or that pineapple might have originated in Southeast Asia.

  11. Tumor budding cells, cancer stem cells and epithelial-mesenchymal transition-type cells in pancreatic cancer.

    PubMed

    Karamitopoulou, Eva

    2012-01-01

    Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers with a 5-year survival rate of less than 5%. Moreover, PDAC escapes early detection and resists treatment. Multiple combinations of genetic alterations are known to occur in PDAC including mutational activation of KRAS, inactivation of p16/CDKN2A and SMAD4 (DPC4) and dysregulation of PTEN/PI3K/AKT signaling. Through their interaction with Wingless-INT pathway, the downstream molecules of these pathways have been implicated in the promotion of epithelial-mesenchymal transition (EMT). Emerging evidence has demonstrated that cancer stem cells (CSCs), small populations of which have been identified in PDAC, and EMT-type cells play critical roles in drug resistance, invasion, and metastasis in pancreatic cancer. EMT may be histologically represented by the presence of tumor budding which is described as the occurrence of single tumor cells or small clusters (<5) of dedifferentiated cells at the invasive front of gastrointestinal (including colorectal, oesophageal, gastric, and ampullary) carcinomas and is linked to poor prognosis. Tumor budding has recently been shown to occur frequently in PDAC and to be associated with adverse clinicopathological features and decreased disease-free and overall survival. The aim of this review is to present a short overview on the morphological and molecular aspects that underline the relationship between tumor budding cells, CSCs, and EMT-type cells in PDAC.

  12. Demonstration of a neural circuit critical for imprinting behavior in chicks.

    PubMed

    Nakamori, Tomoharu; Sato, Katsushige; Atoji, Yasuro; Kanamatsu, Tomoyuki; Tanaka, Kohichi; Ohki-Hamazaki, Hiroko

    2010-03-24

    Imprinting behavior in birds is elicited by visual and/or auditory cues. It has been demonstrated previously that visual cues are recognized and processed in the visual Wulst (VW), and imprinting memory is stored in the intermediate medial mesopallium (IMM) of the telencephalon. Alteration of neural responses in these two regions according to imprinting has been reported, yet direct evidence of the neural circuit linking these two regions is lacking. Thus, it remains unclear how memory is formed and expressed in this circuit. Here, we present anatomical as well as physiological evidence of the neural circuit connecting the VW and IMM and show that imprinting training during the critical period strengthens and refines this circuit. A functional connection established by imprint training resulted in an imprinting behavior. After the closure of the critical period, training could not activate this circuit nor induce the imprinting behavior. Glutamatergic neurons in the ventroposterior region of the VW, the core region of the hyperpallium densocellulare (HDCo), sent their axons to the periventricular part of the HD, just dorsal and afferent to the IMM. We found that the HDCo is important in imprinting behavior. The refinement and/or enhancement of this neural circuit are attributed to increased activity of HDCo cells, and the activity depended on NR2B-containing NMDA receptors. These findings show a neural connection in the telencephalon in Aves and demonstrate that NR2B function is indispensable for the plasticity of HDCo cells, which are key mediators of imprinting.

  13. Temporal Loss of Tsc1: Neural Development and Brain Disease in Tuberous Sclerosis

    DTIC Science & Technology

    2013-06-01

    2001). The thalamus has also been linked to the autism component in human TS (Asano et al., 2001) and is poised to play an important role in brain...and Autism -related Disorders. June 10-15, 2012, Stonehill College, MA. Normand E, Browning C, Machan JT, Voelcker B, Zervas M (2012) The deletion of...Foundation Autism Research Initiative Annual RFA (2013) Linking genetic mosaicism, neural circuit abnormalities and behavior. Simons Foundation Autism

  14. Communications processor for C3 analysis and wargaming

    NASA Astrophysics Data System (ADS)

    Clark, L. N.; Pless, L. D.; Rapp, R. L.

    1982-03-01

    This thesis developed the software capability to allow the investigation of c3 problems, procedures and methodologies. The resultant communications model, that while independent of a specific wargame, is currently implemented in conjunction with the McClintic Theater Model. It provides a computerized message handling system (C3 Model) which allows simulation of communication links (circuits) with user-definable delays; garble and loss rates; and multiple circuit types, addresses, and levels of command. It is designed to be used for test and evaluation of command and control problems in the areas of organizational relationships, communication networks and procedures, and combat doctrine or tactics.

  15. Visual complexity: a review.

    PubMed

    Donderi, Don C

    2006-01-01

    The idea of visual complexity, the history of its measurement, and its implications for behavior are reviewed, starting with structuralism and Gestalt psychology at the beginning of the 20th century and ending with visual complexity theory, perceptual learning theory, and neural circuit theory at the beginning of the 21st. Evidence is drawn from research on single forms, form and texture arrays and visual displays. Form complexity and form probability are shown to be linked through their reciprocal relationship in complexity theory, which is in turn shown to be consistent with recent developments in perceptual learning and neural circuit theory. Directions for further research are suggested.

  16. Fabrication of a multiplexed microfluidic system for scaled up production of cross-linked biocatalytic microspheres

    NASA Astrophysics Data System (ADS)

    Mbanjwa, Mesuli B.; Chen, Hao; Fourie, Louis; Ngwenya, Sibusiso; Land, Kevin

    2014-06-01

    Multiplexed or parallelised droplet microfluidic systems allow for increased throughput in the production of emulsions and microparticles, while maintaining a small footprint and utilising minimal ancillary equipment. The current paper demonstrates the design and fabrication of a multiplexed microfluidic system for producing biocatalytic microspheres. The microfluidic system consists of an array of 10 parallel microfluidic circuits, for simultaneous operation to demonstrate increased production throughput. The flow distribution was achieved using a principle of reservoirs supplying individual microfluidic circuits. The microfluidic devices were fabricated in poly (dimethylsiloxane) (PDMS) using soft lithography techniques. The consistency of the flow distribution was determined by measuring the size variations of the microspheres produced. The coefficient of variation of the particles was determined to be 9%, an indication of consistent particle formation and good flow distribution between the 10 microfluidic circuits.

  17. Genome sequencing of the winged midge, Parochlus steinenii, from the Antarctic Peninsula

    PubMed Central

    Kim, Sanghee; Oh, Mijin; Jung, Woongsic; Park, Joonho; Choi, Han-Gu

    2017-01-01

    Abstract Background: In the Antarctic, only two species of Chironomidae occur naturally—the wingless midge, Belgica antarctica, and the winged midge, Parochlus steinenii. B. antarctica is an extremophile with unusual adaptations. The larvae of B. antarctica are desiccation- and freeze-tolerant and the adults are wingless. Recently, the compact genome of B. antarctica was reported and it is the first Antarctic eukaryote to be sequenced. Although P. steinenii occurs naturally in the Antarctic with B. antarctica, the larvae of P. steinenii are cold-tolerant but not freeze-tolerant and the adults are winged. Differences in adaptations in the Antarctic midges are interesting in terms of evolutionary processes within an extreme environment. Herein, we provide the genome of another Antarctic midge to help elucidate the evolution of these species. Results: The draft genome of P. steinenii had a total size of 138 Mbp, comprising 9513 contigs with an N50 contig size of 34,110 bp, and a GC content of 32.2%. Overall, 13,468 genes were predicted using the MAKER annotation pipeline, and gene ontology classified 10,801 (80.2%) predicted genes to a function. Compared with the assembled genome architecture of B. antarctica, that of P. steinenii was approximately 50 Mbp longer with 6.2-fold more repeat sequences, whereas gene regions were as similarly compact as in B. antarctica. Conclusions: We present an annotated draft genome of the Antarctic midge, P. steinenii. The genomes of P. steinenii and B. antarctica will aid in the elucidation of evolution in harsh environments and provide new resources for functional genomic analyses of the order Diptera. PMID:28327954

  18. miR-142-3p is associated with aberrant Wingless/Integrase I (WNT) signaling during airway remodeling in asthma.

    PubMed

    Bartel, Sabine; Carraro, Gianni; Alessandrini, Francesca; Krauss-Etschmann, Susanne; Ricciardolo, Fabio L M; Bellusci, Saverio

    2018-05-03

    Asthma is characterized by a chronic inflammation and remodeling of the airways. While inflammation can be controlled, therapeutic options to revert remodeling do not exist. Thus, there is a large and unmet need to understand the underlying molecular mechanisms in order to develop novel therapies. we previously identified a pivotal role for miR-142-3p in regulating airway smooth muscle precursor (ASM) cell proliferation during lung development by fine-tuning the Wingless/Integrase I (WNT) signaling. Thus, we here aimed to investigate the relevance of this interaction in asthma. We performed qRT-PCR and immune-staining in a murine model for ovalbumin-induced allergic airway inflammation and in bronchial biopsies from patients with asthma and isolated primary fibroblasts thereof. miR-142-3p was increased in hyper-proliferative regions of lung in murine and human asthma, while this miRNA was excluded from regions with differentiated ASM cells. Increases in miR-142-3p were associated with a decrease of its known target Adenomatous polyposis coli (Apc). Further, we observed a differential expression of miR-142-3p in bronchial biopsies from patients with early or late onset severe asthma, which coincided with a differential WNT signature. Our data suggest that miR-142-3p is involved in regulating the balance between proliferation and differentiation of ASM cells in asthma, possibly via controlling WNT signaling. Thus, this miRNA might be an interesting target to prevent airway smooth muscle hyper-proliferation in asthma.

  19. Fronto-Limbic Functioning in Children and Adolescents with and without Autism

    ERIC Educational Resources Information Center

    Loveland, Katherine A.; Bachevalier, Jocelyne; Pearson, Deborah A.; Lane, David M.

    2008-01-01

    We used neuropsychological tasks to investigate integrity of brain circuits linking orbitofrontal cortex and amygdala (orbitofrontal-amygdala), and dorsolateral prefrontal cortex and hippocampus (dorsolateral prefrontal-hippocampus), in 138 individuals aged 7-18 years, with and without autism. We predicted that performance on…

  20. TEMP, TEXAS EDUCATIONAL MICROWAVE PROJECT. FINAL REPORT.

    ERIC Educational Resources Information Center

    SCHENKKAN, R.F.; AND OTHERS

    A PILOT EFFORT TO LINK 11 INSTITUTIONS OF HIGHER LEARNING BY MICROWAVE TRANSMITTERS FOR INSTRUCTIONAL PURPOSES WAS DEMONSTRATED. THIS MICROWAVE LINKAGE PROVIDED A SINGLE CLOSED-CIRCUIT TELEVISION SYSTEM THROUGHOUT THE PARTICIPATING INSTITUTIONS. THROUGH THE FORMATION OF THE "ELECTRONIC CAMPUS," THE FACULTY RESOURCES OF ALL 11 SCHOOLS…

  1. 47 CFR 74.431 - Special rules applicable to remote pickup stations.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... damaged, stations licensed under Subpart D may be used to provide temporary circuits for a period not... SERVICES Remote Pickup Broadcast Stations § 74.431 Special rules applicable to remote pickup stations. (a..., frequency coordination, establishing microwave links, and operational communications. Operational...

  2. 47 CFR 74.431 - Special rules applicable to remote pickup stations.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... damaged, stations licensed under Subpart D may be used to provide temporary circuits for a period not... SERVICES Remote Pickup Broadcast Stations § 74.431 Special rules applicable to remote pickup stations. (a..., frequency coordination, establishing microwave links, and operational communications. Operational...

  3. 47 CFR 74.431 - Special rules applicable to remote pickup stations.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... damaged, stations licensed under Subpart D may be used to provide temporary circuits for a period not... SERVICES Remote Pickup Broadcast Stations § 74.431 Special rules applicable to remote pickup stations. (a..., frequency coordination, establishing microwave links, and operational communications. Operational...

  4. 47 CFR 74.431 - Special rules applicable to remote pickup stations.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... damaged, stations licensed under Subpart D may be used to provide temporary circuits for a period not... SERVICES Remote Pickup Broadcast Stations § 74.431 Special rules applicable to remote pickup stations. (a..., frequency coordination, establishing microwave links, and operational communications. Operational...

  5. Army Medical Imaging System - ARMIS

    DTIC Science & Technology

    1992-08-08

    modems , scanners, hard disk drives, dot matrix printers, erasable-optical disc drives, CD-ROM drives, WORM disc drives and tape drives are fully...can use 56K leased lines, TI links, digital data circuits, or public telephone lines. 3. ISDN The Integrated Services Digital Network, ISDN, is a

  6. Transient flow analysis linked to fast pressure disturbance monitored in pipe systems

    NASA Astrophysics Data System (ADS)

    Kueny, J. L.; Lourenco, M.; Ballester, J. L.

    2012-11-01

    EDF Hydro Division has launched the RENOUVEAU program in order to increase performance and improve plant availability through anticipation. Due to this program, a large penstocks fleet is equipped with pressure transducers linked to a special monitoring system. Any significant disturbance of the pressure is captured in a snapshot and the waveform of the signal is stored and analyzed. During these transient states, variations in flow are unknown. In order to determine the structural impact of such overpressure occurring during complex transients conditions over the entire circuit, EDF DTG has asked ENSE3 GRENOBLE to develop a code called ACHYL CF*. The input data of ACHYL CF are circuit topology and pressure boundaries conditions. This article provide a description of the computer code developed for modeling the transient flow in a pipe network using the signals from pressure transducers as boundary conditions. Different test cases will be presented, simulating real hydro power plants for which measured pressure signals are available.

  7. Linking Neurons to Network Function and Behavior by Two-Photon Holographic Optogenetics and Volumetric Imaging.

    PubMed

    Dal Maschio, Marco; Donovan, Joseph C; Helmbrecht, Thomas O; Baier, Herwig

    2017-05-17

    We introduce a flexible method for high-resolution interrogation of circuit function, which combines simultaneous 3D two-photon stimulation of multiple targeted neurons, volumetric functional imaging, and quantitative behavioral tracking. This integrated approach was applied to dissect how an ensemble of premotor neurons in the larval zebrafish brain drives a basic motor program, the bending of the tail. We developed an iterative photostimulation strategy to identify minimal subsets of channelrhodopsin (ChR2)-expressing neurons that are sufficient to initiate tail movements. At the same time, the induced network activity was recorded by multiplane GCaMP6 imaging across the brain. From this dataset, we computationally identified activity patterns associated with distinct components of the elicited behavior and characterized the contributions of individual neurons. Using photoactivatable GFP (paGFP), we extended our protocol to visualize single functionally identified neurons and reconstruct their morphologies. Together, this toolkit enables linking behavior to circuit activity with unprecedented resolution. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. An NFC on Two-Coil WPT Link for Implantable Biomedical Sensors under Ultra-Weak Coupling

    PubMed Central

    Gong, Chen; Liu, Dake; Miao, Zhidong; Wang, Wei; Li, Min

    2017-01-01

    The inductive link is widely used in implantable biomedical sensor systems to achieve near-field communication (NFC) and wireless power transfer (WPT). However, it is tough to achieve reliable NFC on an inductive WPT link when the coupling coefficient is ultra-low (0.01 typically), since the NFC signal (especially for the uplink from the in-body part to the out-body part) could be too weak to be detected. Traditional load shift keying (LSK) requires strong coupling to pass the load modulation information to the power source. Instead of using LSK, we propose a dual-carrier NFC scheme for the weak-coupled inductive link; using binary phase shift keying (BPSK) modulation, its downlink data are modulated on the power carrier (2 MHz), while its uplink data are modulated on another carrier (125 kHz). The two carriers are transferred through the same coil pair. To overcome the strong interference of the power carrier, dedicated circuits are introduced. In addition, to minimize the power transfer efficiency decrease caused by adding NFC, we optimize the inductive link circuit parameters and approach the receiver sensitivity limit. In the prototype experiments, even though the coupling coefficient is as low as 0.008, the in-body transmitter costs only 0.61 mW power carrying 10 kbps of data, and achieves a 1 × 10−7 bit error rate under the strong interference of WPT. This dual-carrier NFC scheme could be useful for small-sized implantable biomedical sensor applications. PMID:28604610

  9. Acute neuroinflammation impairs context discrimination memory and disrupts pattern separation processes in hippocampus.

    PubMed

    Czerniawski, Jennifer; Guzowski, John F

    2014-09-10

    Although it is known that immune system activation can impair cognition, no study to date has linked cognitive deficits during acute neuroinflammation to dysregulation of task-relevant neuronal ensemble activity. Here, we assessed both neural circuit activity and context discrimination memory retrieval, in a within-subjects design, of male rats given systemic administration of saline or lipopolysaccharide (LPS). Rats were exposed over several days to two similar contexts: one of which was paired with weak foot shock and the other was not. After reaching criteria for discriminative freezing, rats were given systemic LPS or saline injection and tested for retrieval of context discrimination 6 h later. Importantly, LPS administration produced an acute neuroinflammatory response in dorsal hippocampus at this time (as assessed by elevation of proinflammatory cytokine mRNA levels) and abolished retrieval of the previously acquired discrimination. The impact of neuroinflammation on hippocampal CA3 and CA1 neural circuit activity was assessed using the Arc/Homer1a cellular analysis of temporal activity by fluorescence in situ hybridization imaging method. Whereas the saline-treated subjects discriminated and had low overlap of hippocampal ensembles activated in the two contexts, LPS-treated subjects did not discriminate and had greater ensemble overlap (i.e., reduced orthogonalization). Additionally, retrieval of standard contextual fear conditioning, which does not require context discrimination, was not affected by pretesting LPS administration. Together, the behavioral and circuit analyses data provide compelling evidence that LPS administration impairs context discrimination memory by disrupting cellular pattern separation processes within the hippocampus, thus linking acute neuroinflammation to disruption of specific neural circuit functions and cognitive impairment. Copyright © 2014 the authors 0270-6474/14/3412470-11$15.00/0.

  10. Acute Neuroinflammation Impairs Context Discrimination Memory and Disrupts Pattern Separation Processes in Hippocampus

    PubMed Central

    Czerniawski, Jennifer

    2014-01-01

    Although it is known that immune system activation can impair cognition, no study to date has linked cognitive deficits during acute neuroinflammation to dysregulation of task-relevant neuronal ensemble activity. Here, we assessed both neural circuit activity and context discrimination memory retrieval, in a within-subjects design, of male rats given systemic administration of saline or lipopolysaccharide (LPS). Rats were exposed over several days to two similar contexts: one of which was paired with weak foot shock and the other was not. After reaching criteria for discriminative freezing, rats were given systemic LPS or saline injection and tested for retrieval of context discrimination 6 h later. Importantly, LPS administration produced an acute neuroinflammatory response in dorsal hippocampus at this time (as assessed by elevation of proinflammatory cytokine mRNA levels) and abolished retrieval of the previously acquired discrimination. The impact of neuroinflammation on hippocampal CA3 and CA1 neural circuit activity was assessed using the Arc/Homer1a cellular analysis of temporal activity by fluorescence in situ hybridization imaging method. Whereas the saline-treated subjects discriminated and had low overlap of hippocampal ensembles activated in the two contexts, LPS-treated subjects did not discriminate and had greater ensemble overlap (i.e., reduced orthogonalization). Additionally, retrieval of standard contextual fear conditioning, which does not require context discrimination, was not affected by pretesting LPS administration. Together, the behavioral and circuit analyses data provide compelling evidence that LPS administration impairs context discrimination memory by disrupting cellular pattern separation processes within the hippocampus, thus linking acute neuroinflammation to disruption of specific neural circuit functions and cognitive impairment. PMID:25209285

  11. Millimeter-wave interconnects for microwave-frequency quantum machines

    NASA Astrophysics Data System (ADS)

    Pechal, Marek; Safavi-Naeini, Amir H.

    2017-10-01

    Superconducting microwave circuits form a versatile platform for storing and manipulating quantum information. A major challenge to further scalability is to find approaches for connecting these systems over long distances and at high rates. One approach is to convert the quantum state of a microwave circuit to optical photons that can be transmitted over kilometers at room temperature with little loss. Many proposals for electro-optic conversion between microwave and optics use optical driving of a weak three-wave mixing nonlinearity to convert the frequency of an excitation. Residual absorption of this optical pump leads to heating, which is problematic at cryogenic temperatures. Here we propose an alternative approach where a nonlinear superconducting circuit is driven to interconvert between microwave-frequency (7 ×109 Hz) and millimeter-wave-frequency photons (3 ×1011 Hz). To understand the potential for quantum state conversion between microwave and millimeter-wave photons, we consider the driven four-wave mixing quantum dynamics of nonlinear circuits. In contrast to the linear dynamics of the driven three-wave mixing converters, the proposed four-wave mixing converter has nonlinear decoherence channels that lead to a more complex parameter space of couplings and pump powers that we map out. We consider physical realizations of such converter circuits by deriving theoretically the upper bound on the maximum obtainable nonlinear coupling between any two modes in a lossless circuit, and synthesizing an optimal circuit based on realistic materials that saturates this bound. Our proposed circuit dissipates less than 10-9 times the energy of current electro-optic converters per qubit. Finally, we outline the quantum link budget for optical, microwave, and millimeter-wave connections, showing that our approach is viable for realizing interconnected quantum processors for intracity or quantum data center environments.

  12. Coating of human decay accelerating factor (hDAF) onto medical devices to improve biocompatibility.

    PubMed

    Watkins, N J; Braidley, P; Bray, C J; Savill, C M; White, D J

    1997-12-01

    In passing blood through an artificial circulatory system, the blood is exposed to surfaces that result in activation of the complement system. The consequences of the activation of complement can be extremely serious for the patient ranging from mild discomfort to respiratory distress and even anaphylaxis. An entirely novel approach was to express recombinant GPI anchored human decay accelerating factor (hDAF) using the baculovirus system and then coat the recombinant protein onto the surfaces of these materials to reduce complement activation. Expression of hDAF in Sf9 cells was shown by ELISA, FACS analysis, and Western blot. Functional activity was tested by CH50 assay. For the coating experiments a small scale model of a cardiovascular bypass circuit constructed from COBE tubing was used. hDAF was either coated onto the circuit using adsorption or covalently linked via the photoreactive crosslinker, p-azidobenzoyl hydrazide. After coating, heparinised human blood was pumped around the circuit and samples were collected into EDTA collection tubes at different time points. Complement activation was measured using a Quidel C3a-des-arg EIA. The photolinked circuits gave a reduction in C3a production of 20-50%, compared to 10-20% seen with an absorbed hDAF circuit. Furthermore, the inhibition of complement was seen over the whole time scale of the photolinked circuit, 60-90 min, whilst in the adsorbed circuit inhibition was not seen to a significant degree after 60 min. The time scale of a standard cardiac bypass is 45-90 min, therefore, the photolinked circuit results are encouraging, as significant inhibition of complement activation is seen within this time frame.

  13. Preserved number of entorhinal cortex layer II neurons in aged macaque monkeys

    NASA Technical Reports Server (NTRS)

    Gazzaley, A. H.; Thakker, M. M.; Hof, P. R.; Morrison, J. H.; Bloom, F. E. (Principal Investigator)

    1997-01-01

    The perforant path, which consists of the projection from the layer II neurons of the entorhinal cortex to the outer molecular layer of the dentate gyrus, is a critical circuit involved in learning and memory formation. Accordingly, disturbances in this circuit may contribute to age-related cognitive deficits. In a previous study, we demonstrated a decrease in N-methyl-D-aspartate receptor subunit 1 immunofluorescence intensity in the outer molecular layer of aged macaque monkeys. In this study, we used the optical fractionator, a stereological method, to determine if a loss of layer II neurons occurred in the same animals in which the N-methyl-D-aspartate receptor subunit 1 alteration was observed. Our results revealed no significant differences in the number of layer II neurons between juvenile, young adult, and aged macaque monkeys. These results suggest that the circuit-specific decrease in N-methyl-D-aspartate receptor subunit 1 reported previously occurs in the absence of structural compromise of the perforant path, and thus may be linked to an age-related change in the physiological properties of this circuit.

  14. The human phosphotyrosine signaling network: Evolution and hotspots of hijacking in cancer

    PubMed Central

    Li, Lei; Tibiche, Chabane; Fu, Cong; Kaneko, Tomonori; Moran, Michael F.; Schiller, Martin R.; Li, Shawn Shun-Cheng; Wang, Edwin

    2012-01-01

    Phosphotyrosine (pTyr) signaling, which plays a central role in cell–cell and cell–environment interactions, has been considered to be an evolutionary innovation in multicellular metazoans. However, neither the emergence nor the evolution of the human pTyr signaling system is currently understood. Tyrosine kinase (TK) circuits, each of which consists of a TK writer, a kinase substrate, and a related reader, such as Src homology (SH) 2 domains and pTyr-binding (PTB) domains, comprise the core machinery of the pTyr signaling network. In this study, we analyzed the evolutionary trajectories of 583 literature-derived and 50,000 computationally predicted human TK circuits in 19 representative eukaryotic species and assigned their evolutionary origins. We found that human TK circuits for intracellular pTyr signaling originated largely from primitive organisms, whereas the inter- or extracellular signaling circuits experienced significant expansion in the bilaterian lineage through the “back-wiring” of newly evolved kinases to primitive substrates and SH2/PTB domains. Conversely, the TK circuits that are involved in tissue-specific signaling evolved mainly in vertebrates by the back-wiring of vertebrate substrates to primitive kinases and SH2/PTB domains. Importantly, we found that cancer signaling preferentially employs the pTyr sites, which are linked to more TK circuits. Our work provides insights into the evolutionary paths of the human pTyr signaling circuits and suggests the use of a network approach for cancer intervention through the targeting of key pTyr sites and their associated signaling hubs in the network. PMID:22194470

  15. Comparative analysis of gene regulatory networks: from network reconstruction to evolution.

    PubMed

    Thompson, Dawn; Regev, Aviv; Roy, Sushmita

    2015-01-01

    Regulation of gene expression is central to many biological processes. Although reconstruction of regulatory circuits from genomic data alone is therefore desirable, this remains a major computational challenge. Comparative approaches that examine the conservation and divergence of circuits and their components across strains and species can help reconstruct circuits as well as provide insights into the evolution of gene regulatory processes and their adaptive contribution. In recent years, advances in genomic and computational tools have led to a wealth of methods for such analysis at the sequence, expression, pathway, module, and entire network level. Here, we review computational methods developed to study transcriptional regulatory networks using comparative genomics, from sequence to functional data. We highlight how these methods use evolutionary conservation and divergence to reliably detect regulatory components as well as estimate the extent and rate of divergence. Finally, we discuss the promise and open challenges in linking regulatory divergence to phenotypic divergence and adaptation.

  16. Wireless Data Transmission at Terahertz Carrier Waves Generated from a Hybrid InP-Polymer Dual Tunable DBR Laser Photonic Integrated Circuit.

    PubMed

    Carpintero, Guillermo; Hisatake, Shintaro; de Felipe, David; Guzman, Robinson; Nagatsuma, Tadao; Keil, Norbert

    2018-02-14

    We report for the first time the successful wavelength stabilization of two hybrid integrated InP/Polymer DBR lasers through optical injection. The two InP/Polymer DBR lasers are integrated into a photonic integrated circuit, providing an ideal source for millimeter and Terahertz wave generation by optical heterodyne technique. These lasers offer the widest tuning range of the carrier wave demonstrated to date up into the Terahertz range, about 20 nm (2.5 THz) on a single photonic integrated circuit. We demonstrate the application of this source to generate a carrier wave at 330 GHz to establish a wireless data transmission link at a data rate up to 18 Gbit/s. Using a coherent detection scheme we increase the sensitivity by more than 10 dB over direct detection.

  17. Quantum-enabled temporal and spectral mode conversion of microwave signals

    PubMed Central

    Andrews, R. W.; Reed, A. P.; Cicak, K.; Teufel, J. D.; Lehnert, K. W.

    2015-01-01

    Electromagnetic waves are ideal candidates for transmitting information in a quantum network as they can be routed rapidly and efficiently between locations using optical fibres or microwave cables. Yet linking quantum-enabled devices with cables has proved difficult because most cavity or circuit quantum electrodynamics systems used in quantum information processing can only absorb and emit signals with a specific frequency and temporal envelope. Here we show that the temporal and spectral content of microwave-frequency electromagnetic signals can be arbitrarily manipulated with a flexible aluminium drumhead embedded in a microwave circuit. The aluminium drumhead simultaneously forms a mechanical oscillator and a tunable capacitor. This device offers a way to build quantum microwave networks using separate and otherwise mismatched components. Furthermore, it will enable the preparation of non-classical states of motion by capturing non-classical microwave signals prepared by the most coherent circuit quantum electrodynamics systems. PMID:26617386

  18. Gigahertz flexible graphene transistors for microwave integrated circuits.

    PubMed

    Yeh, Chao-Hui; Lain, Yi-Wei; Chiu, Yu-Chiao; Liao, Chen-Hung; Moyano, David Ricardo; Hsu, Shawn S H; Chiu, Po-Wen

    2014-08-26

    Flexible integrated circuits with complex functionalities are the missing link for the active development of wearable electronic devices. Here, we report a scalable approach to fabricate self-aligned graphene microwave transistors for the implementation of flexible low-noise amplifiers and frequency mixers, two fundamental building blocks of a wireless communication receiver. A devised AlOx T-gate structure is used to achieve an appreciable increase of device transconductance and a commensurate reduction of the associated parasitic resistance, thus yielding a remarkable extrinsic cutoff frequency of 32 GHz and a maximum oscillation frequency of 20 GHz; in both cases the operation frequency is an order of magnitude higher than previously reported. The two frequencies work at 22 and 13 GHz even when subjected to a strain of 2.5%. The gigahertz microwave integrated circuits demonstrated here pave the way for applications which require high flexibility and radio frequency operations.

  19. Stressing out the Social Network.

    PubMed

    Kirkby, Lowry A; Sohal, Vikaas S

    2016-07-20

    In this issue of Neuron, Hultman et al. (2016) find that stress-induced abnormal social behavior reflects aberrant prefrontal regulation of downstream limbic networks. This illustrates how linking aberrant network dynamics to neuropsychiatric disorders may lead to new circuit-based therapeutic interventions. Copyright © 2016. Published by Elsevier Inc.

  20. Integrated Cryogenic Electronics Testbed (ICE-T) for Evaluation of Superconductor and Cryo-Semiconductor Integrated Circuits

    NASA Astrophysics Data System (ADS)

    Dotsenko, V. V.; Sahu, A.; Chonigman, B.; Tang, J.; Lehmann, A. E.; Gupta, V.; Talalevskii, A.; Ruotolo, S.; Sarwana, S.; Webber, R. J.; Gupta, D.

    2017-02-01

    Research and development of cryogenic application-specific integrated circuits (ASICs), such as high-frequency (tens of GHz) semiconductor and superconductor mixed-signal circuits and large-scale (>10,000 Josephson Junctions) superconductor digital circuits, have long been hindered by the absence of specialized cryogenic test apparatus. During their iterative development phase, most ASICs require many additional input-output lines for applying independent bias controls, injecting test signals, and monitoring outputs of different sub-circuits. We are developing a full suite of modular test apparatus based on cryocoolers that do not consume liquid helium, and support extensive electrical interfaces to standard and custom test equipment. Our design separates the cryogenics from electrical connections, allowing even inexperienced users to conduct testing by simply mounting their ASIC on a removable electrical insert. Thermal connections between the cold stages and the inserts are made with robust thermal links. ICE-T accommodates two independent electrical inserts at the same time. We have designed various inserts, such as universal ones with all 40 or 80 coaxial cables and those with customized wiring and temperature-controlled stages. ICE-T features fast thermal cycling for rapid testing, enables detailed testing over long periods (days to months, if necessary), and even supports automated testing of digital ICs with modular additions.

  1. Adult neurogenesis is necessary to refine and maintain circuit specificity.

    PubMed

    Cummings, Diana M; Snyder, Jason S; Brewer, Michelle; Cameron, Heather A; Belluscio, Leonardo

    2014-10-08

    The circuitry of the olfactory bulb contains a precise anatomical map that links isofunctional regions within each olfactory bulb. This intrabulbar map forms perinatally and undergoes activity-dependent refinement during the first postnatal weeks. Although this map retains its plasticity throughout adulthood, its organization is remarkably stable despite the addition of millions of new neurons to this circuit. Here we show that the continuous supply of new neuroblasts from the subventricular zone is necessary for both the restoration and maintenance of this precise central circuit. Using pharmacogenetic methods to conditionally ablate adult neurogenesis in transgenic mice, we find that the influx of neuroblasts is required for recovery of intrabulbar map precision after disruption due to sensory block. We further demonstrate that eliminating adult-born interneurons in naive animals leads to an expansion of tufted cell axons that is identical to the changes caused by sensory block, thus revealing an essential role for new neurons in circuit maintenance under baseline conditions. These findings show, for the first time, that inhibiting adult neurogenesis alters the circuitry of projection neurons in brain regions that receive new interneurons and points to a critical role for adult-born neurons in stabilizing a brain circuit that exhibits high levels of plasticity. Copyright © 2014 the authors 0270-6474/14/3413801-10$15.00/0.

  2. Mathematical model for calculation of the heat-hydraulic modes of heating points of heat-supplying systems

    NASA Astrophysics Data System (ADS)

    Shalaginova, Z. I.

    2016-03-01

    The mathematical model and calculation method of the thermal-hydraulic modes of heat points, based on the theory of hydraulic circuits, being developed at the Melentiev Energy Systems Institute are presented. The redundant circuit of the heat point was developed, in which all possible connecting circuits (CC) of the heat engineering equipment and the places of possible installation of control valve were inserted. It allows simulating the operating modes both at central heat points (CHP) and individual heat points (IHP). The configuration of the desired circuit is carried out automatically by removing the unnecessary links. The following circuits connecting the heating systems (HS) are considered: the dependent circuit (direct and through mixing elevator) and independent one (through the heater). The following connecting circuits of the load of hot water supply (HWS) were considered: open CC (direct water pumping from pipelines of heat networks) and a closed CC with connecting the HWS heaters on single-level (serial and parallel) and two-level (sequential and combined) circuits. The following connecting circuits of the ventilation systems (VS) were also considered: dependent circuit and independent one through a common heat exchanger with HS load. In the heat points, water temperature regulators for the hot water supply and ventilation and flow regulators for the heating system, as well as to the inlet as a whole, are possible. According to the accepted decomposition, the model of the heat point is an integral part of the overall heat-hydraulic model of the heat-supplying system having intermediate control stages (CHP and IHP), which allows to consider the operating modes of the heat networks of different levels connected with each other through CHP as well as connected through IHP of consumers with various connecting circuits of local systems of heat consumption: heating, ventilation and hot water supply. The model is implemented in the Angara data-processing complex. An example of the multilevel calculation of the heat-hydraulic modes of main heat networks and those connected to them through central heat point distribution networks in Petropavlovsk-Kamchatskii is examined.

  3. Final Report for the project titled "Enabling Supernova Computations by Integrated Transport and Provisioning Methods Optimized for Dedicated Channels"

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

    Malathi Veeraraghavan

    2007-10-31

    A high-speed optical circuit network is one that offers users rate-guaranteed connectivity between two endpoints, unlike today’s IP-routed Internet in which the rate available to a pair of users fluctuates based on the volume of competing traffic. This particular research project advanced our understanding of circuit networks in two ways. First, transport protocols were developed for circuit networks. In a circuit network, since bandwidth resources are reserved for each circuit on an end-to-end basis (much like how a person reserves a seat on every leg of a multi-segment flight), and the sender is limited to send at the rate ofmore » the circuit, there is no possibility of congestion during data transfer. Therefore, no congestion control functions are necessary in a transport protocol designed for circuits. However, error control and flow control are still required because bits can become errored due to noise and interference even on highly reliable optical links, and receivers can, due to multitasking or other reasons, not deplete the receive buffer fast enough to keep up with the sending rate (e.g., if the receiving host is multitasking between receiving a file transfer and some other computation). In this work, we developed two transport protocols for circuits, both of which are described below. Second, this project developed techniques for internetworking different types of connection-oriented networks, which are of two types: circuit-switched or packet-switched. In circuit-switched networks, multiplexing on links is “position based,” where “position” refers to the frequency, time slot, and port (fiber), while connection-oriented packet-switched networks use packet header information to demultiplex packets and switch them from node to node. The latter are commonly referred to as virtual circuit networks. Examples of circuit networks are time-division multiplexed Synchronous Optical Network/Synchronous Digital Hierarchy (SONET/SDH) and Wavelength Division Multiplexing (WDM) networks, while examples of virtual-circuit networks are MultiProtocol Label Switched (MPLS) networks and Ethernet Virtual Local Area Network (VLAN) networks. A series of new technologies have been developed to carry Ethernet VLAN tagged frames on SONET/SDH and WDM networks, such as Generic Framing Procedure (GFP) and ITU G.709, respectively. These technologies form the basis of our solution for connection-oriented internetworking. The benefit of developing such an architecture is that it allows different providers to choose different connection-oriented networking technologies for their networks, and yet be able to allow their customers to connect to those of other providers. As Metcalfe, the inventor of Ethernet, noted, the value of a network service grows exponentially with the number of endpoints to which any single endpoint can connect. Therefore internetworking solutions are key to commercial success. The technical effectiveness of our solutions was measured with proof-of-concept prototypes and experiments. These solutions were shown to be highly effective. Economic feasibility requires business case analyses that were beyond the scope of this project. The project results are beneficial to the public as they demonstrate the viability of simultaneously supporting different types of networks and data communication services much like the variety of services available for the transportation of people and goods. For example, Fedex service offers a deadline based delivery while the USPS offers basic package delivery service. Similarly, a circuit network can offer a deadline based delivery of a data file while the IP-routed network offers only basic delivery service with no guarantees. Two project Web sites, 13 publications, 7 software programs, 21 presentations resulted from this work. This report provides the complete list of publications, software programs and presentations. As for student education and training (human resources), this DOE project, along with an NSF project, jointly supported two postdoctoral fellowships, three PhDs, three Masters, and two undergraduate students. Specifically, two of the Masters students were directly funded on this DOE project.« less

  4. A High Efficiency, Miniaturized Ka Band Traveling Wave Tube Based on a Novel Finned Ladder RF Circuit Design

    NASA Technical Reports Server (NTRS)

    Wintucky, E. G.; Wilson, J. D.; Vaden, K. R.; Force, D. A.; Freeman, J. C.; Lesny, G. G.; Kory, C. L.; Chevalier, C. T.; Ebihara, B.; Dayton, J. A.; hide

    2001-01-01

    Space communications architectures are being planned to meet the high rate data distribution requirements of future NASA Enterprise missions. These will require the use of traveling wave tube amplifiers (TWTAs) to provide the high frequency, RF (radio frequency) power and efficiency needed for many of the communications links. A program addressing these requirements is currently underway at NASA Glenn Research Center (GRC) for the development of a high efficiency, 20 watt, 32 GHz TWT of reduced size and weight that is based on a novel high gain n circuit design, termed the 'finned ladder'.

  5. Motor cognition-motor semantics: action perception theory of cognition and communication.

    PubMed

    Pulvermüller, Friedemann; Moseley, Rachel L; Egorova, Natalia; Shebani, Zubaida; Boulenger, Véronique

    2014-03-01

    A new perspective on cognition views cortical cell assemblies linking together knowledge about actions and perceptions not only as the vehicles of integrated action and perception processing but, furthermore, as a brain basis for a wide range of higher cortical functions, including attention, meaning and concepts, sequences, goals and intentions, and even communicative social interaction. This article explains mechanisms relevant to mechanistic action perception theory, points to concrete neuronal circuits in brains along with artificial neuronal network simulations, and summarizes recent brain imaging and other experimental data documenting the role of action perception circuits in cognition, language and communication. © 2013 Published by Elsevier Ltd.

  6. New insights on food intake control by olfactory processes: the emerging role of the endocannabinoid system.

    PubMed

    Soria-Gomez, Edgar; Bellocchio, Luigi; Marsicano, Giovanni

    2014-11-01

    The internal state of the organism is an important modulator of perception and behavior. The link between hunger, olfaction and feeding behavior is one of the clearest examples of these connections. At the neurobiological level, olfactory circuits are the targets of several signals (i.e. hormones and nutrients) involved in energy balance. This indicates that olfactory areas are potential sensors of the internal state of the organism. Thus, the aim of this manuscript is to review the literature showing the interplay between metabolic signals in olfactory circuits and its impact on food intake. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  7. Nanowires and nanoribbons as subwavelength optical waveguides and their use as components in photonic circuits and devices

    DOEpatents

    Yang, Peidong; Law, Matt; Sirbuly, Donald J.; Johnson, Justin C.; Saykally, Richard; Fan, Rong; Tao, Andrea

    2012-10-02

    Nanoribbons and nanowires having diameters less than the wavelength of light are used in the formation and operation of optical circuits and devices. Such nanostructures function as subwavelength optical waveguides which form a fundamental building block for optical integration. The extraordinary length, flexibility and strength of these structures enable their manipulation on surfaces, including the precise positioning and optical linking of nanoribbon/wire waveguides and other nanoribbon/wire elements to form optical networks and devices. In addition, such structures provide for waveguiding in liquids, enabling them to further be used in other applications such as optical probes and sensors.

  8. Is social attachment an addictive disorder?

    PubMed

    Insel, Thomas R

    2003-08-01

    There is a considerable literature on the neurobiology of reward, based largely on studies of addiction or substance abuse. This review considers the possibility that the neural circuits that mediate reward evolved for ethologically relevant cues, such as social attachment. Specifically, mesocorticolimbic dopamine appears important for maternal behavior in rats and pair bonding in monogamous voles. It is not yet clear that dopamine in this pathway mediates the hedonic properties of social bond formation or whether dopamine's role is more relevant to developing associative networks or assigning salience to social stimuli. The neuropeptides oxytocin (OT) and vasopressin (AVP) appear to be critical for linking social signals to the mesocorticolimbic circuit.

  9. Genes and Social Behavior

    PubMed Central

    Robinson, Gene E.; Fernald, Russell D.; Clayton, David F.

    2011-01-01

    What specific genes and regulatory sequences contribute to the organization and functioning of brain circuits that support social behavior? How does social experience interact with information in the genome to modulate these brain circuits? Here we address these questions by highlighting progress that has been made in identifying and understanding two key “vectors of influence” that link genes, brain, and social behavior: 1) social information alters gene readout in the brain to influence behavior; and 2) genetic variation influences brain function and social behavior. We also briefly discuss how evolutionary changes in genomic elements influence social behavior and outline prospects for a systems biology of social behavior. PMID:18988841

  10. Unfractionated heparin activity measured by anti-factor Xa levels is associated with the need for extracorporeal membrane oxygenation circuit/membrane oxygenator change: a retrospective pediatric study.

    PubMed

    Irby, Katherine; Swearingen, Christopher; Byrnes, Jonathan; Bryant, Joshua; Prodhan, Parthak; Fiser, Richard

    2014-05-01

    Investigate whether anti-Factor Xa levels are associated with the need for change of circuit/membrane oxygenator secondary to thrombus formation in pediatric patients. Retrospective single institution study. Retrospective record review of 62 pediatric patients supported with extracorporeal membrane oxygenation from 2009 to 2011. Data on standard demographic characteristics, indications for extracorporeal membrane oxygenation, duration of extracorporeal membrane oxygenation, activated clotting time measurements, anti-Factor Xa measurements, and heparin infusion rate were collected. Generalized linear models were used to associate anti-Factor Xa concentrations and need for change of either entire circuit/membrane oxygenator secondary to thrombus formation. Sixty-two patients met study inclusion criteria. No-circuit change was required in 45 of 62 patients. Of 62 patients, 17 required change of circuit/membrane oxygenator due to thrombus formation. Multivariate analysis of daily anti-Factor Xa measurements throughout duration of extracorporeal membrane oxygenation support estimated a mean anti-Factor Xa concentration of 0.20 IU/mL (95% CI, 0.16, 0.24) in no-complete-circuit group that was significantly higher than the estimated concentration of 0.13 IU/mL (95% CI, 0.12, 0.14) in complete-circuit group (p = 0.001). A 0.01 IU/mL decrease in anti-Factor Xa increased odds of need for circuit/membrane oxygenator change by 5% (odds ratio = 1.105; 95% CI, 1.00, 1.10; p = 0.044). Based on the observed anti-Factor Xa concentrations, complete-circuit group had 41% increased odds for requiring circuit/membrane oxygenator change compared with no-complete-circuit group (odds ratio = 1.41; 95% CI, 1.01, 1.96; p = 0.044). Mean daily activated clotting time measurement (p = 0.192) was not different between groups, but mean daily heparin infusion rate (p < 0.001) was significantly different between the two groups. Higher anti-Factor Xa concentrations were associated with freedom from circuit/membrane oxygenator change due to thrombus formation in pediatric patients during extracorporeal membrane oxygenation support. Activated clotting time measurements did not differ significantly between groups with or without circuit/membrane oxygenator change. This is the first study to link anti-Factor Xa concentrations with a clinically relevant measure of thrombosis in pediatric patients during extracorporeal membrane oxygenation support. Further prospective study is warranted.

  11. Fiber Optic Wink-around Speed of Light Experiment.

    ERIC Educational Resources Information Center

    Blackburn, James A.

    1980-01-01

    Describes an experiment in which a recycling oscillator has been designed having a fiber optic data link that closes the loop. Outlines the use of this wink-around system to determine the speed of light and suggests additional application for measuring integrated circuit propagation delays to subnanosecond resolution. (GS)

  12. The Art of Electronics

    NASA Astrophysics Data System (ADS)

    Horowitz, Paul; Hill, Winfield

    2015-04-01

    1. Foundations; 2. Bipolar transistors; 3. Field effect transistors; 4. Operational amplifiers; 5. Precision circuits; 6. Filters; 7. Oscillators and timers; 8. Low noise techniques and transimpedance; 9. Power regulation; 10. Digital electronics; 11. Programmable logic devices; 12. Logical interfacing; 13. Digital meets analog; 14. Computers, controllers, and data links; 15. Microcontrollers.

  13. FACTORS CONTRIBUTING TO FACULTY AND STUDENT ACCEPTANCE OF INSTRUCTIONAL TELEVISION, TEMP II.

    ERIC Educational Resources Information Center

    SANFORD, FILLMORE H.

    PERTINENT FACTORS WERE DELINEATED IN THE ACCEPTANCE OR REJECTION OF TELEVISED INSTRUCTIONAL PROGRAMS USED WITH THE TEXAS EDUCATIONAL MICROWAVE PROJECT (TEMP)--AN EFFORT LINKING 11 COLLEGES AND UNIVERSITIES BY MICROWAVE TRANSMITTERS TO PROVIDE AN INTEGRATED CLOSED-CIRCUIT TELEVISION SYSTEM. DATA-GATHERING INSTRUMENTS WERE INTERVIEWS,…

  14. Energy Transfer and a Recurring Mathematical Function

    ERIC Educational Resources Information Center

    Atkin, Keith

    2013-01-01

    This paper extends the interesting work of a previous contributor concerning the analogies between physical phenomena such as mechanical collisions and the transfer of power in an electric circuit. Emphasis is placed on a mathematical function linking these different areas of physics. This unifying principle is seen as an exciting opportunity to…

  15. Intersatellite Link Design Issues

    DTIC Science & Technology

    1985-01-01

    of Science degree by Richard S. Fuhrmann has been approved for the Tel ecommunications Program by Frank S. Barnes Sadel W.’MaleyK Date --- 45 N... means , the holier of a monopoly when it comes to satellites. In the early . 70"s, the low cost per circuit qenerated interest in Nil Fj domestic

  16. Network origin-destination demand estimation using limited link traffic counts : strategic deployment of vehicle detectors through an integrated corridor management framework.

    DOT National Transportation Integrated Search

    2009-10-15

    In typical road traffic corridors, freeway systems are generally well-equipped with traffic surveillance systems such as vehicle detector (VD) and/or closed circuit television (CCTV) systems in order to gather timely traffic information for traffic c...

  17. System and component design and test of a 10 hp, 18,000 rpm AC dynamometer utilizing a high frequency AC voltage link, part 1

    NASA Technical Reports Server (NTRS)

    Lipo, Thomas A.; Alan, Irfan

    1991-01-01

    Hard and soft switching test results conducted with one of the samples of first generation MOS-controlled thyristor (MCTs) and similar test results with several different samples of second generation MCT's are reported. A simple chopper circuit is used to investigate the basic switching characteristics of MCT under hard switching and various types of resonant circuits are used to determine soft switching characteristics of MCT under both zero voltage and zero current switching. Next, operation principles of a pulse density modulated converter (PDMC) for three phase (3F) to 3F two-step power conversion via parallel resonant high frequency (HF) AC link are reviewed. The details for the selection of power switches and other power components required for the construction of the power circuit for the second generation 3F to 3F converter system are discussed. The problems encountered in the first generation system are considered. Design and performance of the first generation 3F to 3F power converter system and field oriented induction moter drive based upon a 3 kVA, 20 kHz parallel resonant HF AC link are described. Low harmonic current at the input and output, unity power factor operation of input, and bidirectional flow capability of the system are shown via both computer and experimental results. The work completed on the construction and testing of the second generation converter and field oriented induction motor drive based upon specifications for a 10 hp squirrel cage dynamometer and a 20 kHz parallel resonant HF AC link is discussed. The induction machine is designed to deliver 10 hp or 7.46 kW when operated as an AC-dynamo with power fed back to the source through the converter. Results presented reveal that the proposed power level requires additional energy storage elements to overcome difficulties with a peak link voltage variation problem that limits reaching to the desired power level. The power level test of the second generation converter after the addition of extra energy storage elements to the HF link are described. The importance of the source voltage level to achieve a better current regulation for the source side PDMC is also briefly discussed. The power levels achieved in the motoring mode of operation show that the proposed power levels achieved in the generating mode of operation can also be easily achieved provided that no mechanical speed limitation were present to drive the induction machine at the proposed power level.

  18. Active superconducting devices formed of thin films

    DOEpatents

    Martens, Jon S.; Beyer, James B.; Nordman, James E.; Hohenwarter, Gert K. G.

    1991-05-28

    Active superconducting devices are formed of thin films of superconductor which include a main conduction channel which has an active weak link region. The weak link region is composed of an array of links of thin film superconductor spaced from one another by voids and selected in size and thickness such that magnetic flux can propagate across the weak link region when it is superconducting. Magnetic flux applied to the weak link region will propagate across the array of links causing localized loss of superconductivity in the links and changing the effective resistance across the links. The magnetic flux can be applied from a control line formed of a superconducting film deposited coplanar with the main conduction channel and weak link region on a substrate. The devices can be formed of any type to superconductor but are particularly well suited to the high temperature superconductors since the devices can be entirely formed from coplanar films with no overlying regions. The devices can be utilized for a variety of electrical components, including switching circuits, amplifiers, oscillators and modulators, and are well suited to microwave frequency applications.

  19. Wingless, decapentaplegic and EGF receptor signaling pathways interact to specify dorso-ventral pattern in the adult abdomen of Drosophila.

    PubMed

    Kopp, A; Blackman, R K; Duncan, I

    1999-08-01

    Adult abdominal segments of Drosophila are subdivided along the dorso-ventral axis into a dorsal tergite, a ventral sternite and ventro-lateral pleural cuticle. We report that this pattern is largely specified during the pupal stage by Wingless (Wg), Decapentaplegic (Dpp) and Drosophila EGF Receptor (DER) signaling. Expression of wg and dpp is activated at the posterior edge of the anterior compartment by Hedgehog signaling. Within this region, wg and dpp are expressed in domains that are mutually exclusive along the dorso-ventral axis: wg is expressed in the sternite and medio-lateral tergite, whereas dpp expression is confined to the pleura and the dorsal midline. Neither gene is expressed in the lateral tergite. Shirras and Couso (1996, Dev. Biol. 175, 24-36) have shown that tergite and sternite cell fates are specified by Wg signaling. We find that DER acts synergistically with Wg to promote tergite and sternite identities, and that Wg and DER activities are opposed by Dpp signaling, which promotes pleural identity. Wg and Dpp interact antagonistically at two levels. First, their expression is confined to complementary domains by mutual transcriptional repression. Second, Wg and Dpp compete directly with one another by exerting opposite effects on cell fate. DER signaling does not affect the expression of wg or dpp, indicating that it interacts with Wg and Dpp at the level of cell fate determination. Within the tergite, the requirements for Wg and DER function are roughly complementary: Wg is required mainly in the medial region, whereas DER is most important laterally. Finally, we show that Dpp signaling at the dorsal midline controls dorso-ventral patterning within the tergite by promoting pigmentation in the medial region.

  20. The thoracic morphology of the wingless dune cricket Comicus calcaris (Orthoptera: Schizodactylidae): Novel apomorphic characters for the group and adaptations to sand desert environments.

    PubMed

    Leubner, Fanny; Bradler, Sven; Wipfler, Benjamin

    2017-07-01

    Schizodactylidae, splay-footed or dune crickets, represents a distinct lineage among the highly diverse orthopteran subgroup Ensifera (crickets, katydids and allies). Only two extant genera belong to the Schizodactylidae: the winged Eurasian genus Schizodactylus, whose ecology and morphology is well documented, and the wingless South African Comicus, for which hardly any studies providing morphological descriptions have been conducted since its taxonomic description in 1888. Based on the first in-depth study of the skeletomuscular system of the thorax of Comicus calcaris Irish 1986, we provide information on some unique characteristics of this character complex in Schizodactylidae. They include a rigid connection of prospinasternite and mesosternum, a T-shaped mesospina, and a fused meso- and metasternum. Although Schizodactylidae is mainly characterized by group-specific anatomical traits of the thorax, its bifurcated profuca supports a closer relationship to the tettigonioid ensiferans, like katydids, wetas, and hump-winged crickets. Some specific features of the thoracic musculature of Comicus seem to be correlated to the skeletal morphology, e.g., due to the rigid connection of the tergites and pleurites in the pterothorax not a single direct flight muscle is developed. We show that many of the thoracic adaptations in these insects are directly related to their psammophilous way of life. These include a characteristic setation of thoracic sclerites that prevent sand grains from intrusion into vulnerable membranous areas, the striking decrease in size of the thoracic spiracles that reduces the respirational water loss, and a general trend towards a fusion of sclerites in the thorax. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Genome sequencing of the winged midge, Parochlus steinenii, from the Antarctic Peninsula.

    PubMed

    Kim, Sanghee; Oh, Mijin; Jung, Woongsic; Park, Joonho; Choi, Han-Gu; Shin, Seung Chul

    2017-03-01

    In the Antarctic, only two species of Chironomidae occur naturally-the wingless midge, Belgica antarctica , and the winged midge, Parochlus steinenii . B. antarctica is an extremophile with unusual adaptations. The larvae of B. antarctica are desiccation- and freeze-tolerant and the adults are wingless. Recently, the compact genome of B. antarctica was reported and it is the first Antarctic eukaryote to be sequenced. Although P. steinenii occurs naturally in the Antarctic with B. antarctica , the larvae of P. steinenii are cold-tolerant but not freeze-tolerant and the adults are winged. Differences in adaptations in the Antarctic midges are interesting in terms of evolutionary processes within an extreme environment. Herein, we provide the genome of another Antarctic midge to help elucidate the evolution of these species. The draft genome of P. steinenii had a total size of 138 Mbp, comprising 9513 contigs with an N50 contig size of 34,110 bp, and a GC content of 32.2%. Overall, 13,468 genes were predicted using the MAKER annotation pipeline, and gene ontology classified 10,801 (80.2%) predicted genes to a function. Compared with the assembled genome architecture of B. antarctica , that of P. steinenii was approximately 50 Mbp longer with 6.2-fold more repeat sequences, whereas gene regions were as similarly compact as in B. antarctica . We present an annotated draft genome of the Antarctic midge, P. steinenii . The genomes of P. steinenii and B. antarctica will aid in the elucidation of evolution in harsh environments and provide new resources for functional genomic analyses of the order Diptera. © The Authors 2017. Published by Oxford University Press.

  2. [Expression and significance of wingless-type MMTV integration site family, member 5A/receptor tyrosine kinase-like orphan receptor 2 in the rat dental follicle].

    PubMed

    Liping, Wang; Boqi, Li; Qi, Wang; Xiaomin, Tie; Yishan, Liu

    2016-08-01

    To observe the expression of wingless-type MMTV integration site family, member 5A (Wnt5A)/receptor tyrosine kinase-like orphan receptor 2 (Ror2) signal in the dental follicle cells during the normal eruption of the teeth as well as to explore the relationship between the expression of dental follicle cells and the formation of mature osteoclasts and eruption of the teeth. The mandibulars of 1-13 d old SD rats were separated to observe the growth and develop-ment of the teeth and alveolar bone through hematoxylin-eosin(HE) staining. Ror2 and Wnt5A expressions in rat dental follicle were also observed through immunohistochemistry. Dental follicle cells from the lower first intact molar germs of 5-6-day old SD rats were separated and cultured. On the second day after birth, the dental follicle began to differentiate into periodontal tissues, but no obvious changes were observed in the alveolar bone one to three days after birth. On the fourth day, the number of osteoclasts increased significantly. The results of immunohistochemistry showed that Wnt5A was not significantly expressed in rat dental follicle tissues before the fourth day, but positive expression was expressed in the next day and continued to express to thirteenth days. Ror2 was expressed in the rat dental follicle at postnatal days 1-3, but weak expression was found in days 4-13. Wnt5A and Ror2 expressions in the process of tooth eruption have specific time distributions, suggesting that these expressions may participate in the regulation of the eruption of the teeth.

  3. Evolution of a new sense for wind in flying phasmids? Afferents and interneurons

    NASA Astrophysics Data System (ADS)

    Hustert, Reinhold; Klug, Rebecca

    2009-12-01

    The evolution of winged stick insects (phasmids) from secondarily wingless ancestors was proposed in recent studies. We explored the cuticle of flying phasmids for wind sensors that could be involved in their flight control, comparable to those known for locusts. Surprisingly, wind-sensitive hairs (wsH) occur on the palps of mouthparts and on the antennae of the winged phasmid Sipyloidea sipylus which can fly in tethered position only when air currents blow over the mouthparts. The present study describes the morphology and major functional properties of these “new” wsH with soft and bulging hair bases which are different from the beaker-like hair bases of the wsH on the cerci of phasmids and the wsH described in other insects. The most sensitive wsH of antennae and palps respond with phasic-tonic afferents to air currents exceeding 0.2 ms-1. The fields of wsH on one side of the animal respond mainly to ventral, lateral, and frontal wind on the ipsilateral side of the head. Afferent inputs from the wsH converge but also diverge to a group of specific interneurons at their branches in the suboesophageal ganglion and can send their integrated input from wsH fields of the palps and antennae to the thoracic central nervous system. Response types of individual wsH-interneurons are either phasic or phasic-tonic to air puffs or constant air currents and also, the receptive fields of individual interneurons differ. We conclude that the “new” wsH system and its interneurons mainly serve to maintain flight activity in airborne phasmids and also, the “new” wsH must have emerged together with the integrating interneurons during the evolution from wingless to the recent winged forms of phasmids.

  4. Advanced optical fiber communication systems

    NASA Astrophysics Data System (ADS)

    Kazovsky, Leonid G.

    1994-03-01

    Our research is focused on three major aspects of advanced optical fiber communication systems: dynamic wavelength division multiplexing (WDM) networks, fiber nonlinearities, and high dynamic range coherent analog optical links. In the area of WDM networks, we have designed and implemented two high-speed interface boards and measured their throughput and latency. Furthermore, we designed and constructed an experimental PSK/ASK transceiver that simultaneously transmits packet-switched ASK data and circuit-switched PSK data on the same optical carrier. In the area of fiber nonlinearities, we investigated the theoretical impact of modulation frequency on cross-phase modulation (XPM) in dispersive fibers. In the area of high dynamic range coherent analog optical links, we developed theoretical expressions for the RF power transfer ratio (or RF power gain) and the noise figure (NF) of angle-modulated links. We then compared the RF power gains and noise figures of these links to that of an intensity modulated direct detection (DD) link.

  5. An alternative explanation for the occurrence of short circuit current increases in the small intestine following challenge by bacterial enterotoxins.

    PubMed

    Lucas, M L

    2013-10-01

    Secretory diarrhoeal disease due to enterotoxins is thought to arise from the enhancement to pathologically high rates of normally occurring chloride ion and therefore fluid secretion from enterocytes. In support of this concept, many enterotoxins increase intestinal short-circuit current, regarded now as faithfully reflecting the increased chloride ion secretion. Contradicting this assumption, STa reduces absorption but does not cause secretion in vivo although short-circuit current is increased in vitro. There is therefore a mismatch between an assumed enterocyte mediated secretory event that should but does not cause net fluid secretion and an undoubtedly increased short-circuit current. It is proposed here that short-circuit current increases are not themselves secretory events but result from interrupted fluid absorption. A noteworthy feature of compounds that inhibit the increase in short-circuit current is that the majority are vasoactive, neuroactive or both. In general, vasodilator substances increase current. An alternative hypothesis for the origin of short-circuit current increases is that these result from reflex induction of electrogenic fluid absorption. This reflex enhances a compensatory response that is also present at a cellular level. An intestinal reflex is therefore proposed by which decreases in interstitial and intravascular volume or pressure within the intestine initiate an electrogenic fluid absorption mechanism that compensates for the loss of electrically neutral fluid absorption. This hypothesis would explain the apparently complex pharmacology of short-circuit current increases since many depressor substances have receptors in common with enterocytes and enteric nerves. The proposed alternative view of the origin of short-circuit current increases assumes that these do not represent chloride secretion from the enterocytes. This view may therefore aid the successful development of anti-diarrhoeal drugs to overcome a major cause of infant mortality worldwide, if short-circuit current data are being persistently misinterpreted. The putative but testable link between interstitial volume or pressure and fluid absorption also provides support for the alternative view of secretion; namely, that enhanced capillary and epithelial cell tight junctional permeability together with increased intracapillary pressure may cause secretion and not chloride exit from the enterocytes. Copyright © 2013. Published by Elsevier Ltd.

  6. Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways.

    PubMed

    Sancho, Rosa M; Law, Bernard M H; Harvey, Kirsten

    2009-10-15

    Mutations in PARK8, encoding LRRK2, are the most common known cause of Parkinson's disease. The LRRK2 Roc-COR tandem domain exhibits GTPase activity controlling LRRK2 kinase activity via an intramolecular process. We report the interaction of LRRK2 with the dishevelled family of phosphoproteins (DVL1-3), key regulators of Wnt (Wingless/Int) signalling pathways important for axon guidance, synapse formation and neuronal maintenance. Interestingly, DVLs can interact with and mediate the activation of small GTPases with structural similarity to the LRRK2 Roc domain. The LRRK2 Roc-COR domain and the DVL1 DEP domain were necessary and sufficient for LRRK2-DVL1 interaction. Co-expression of DVL1 increased LRRK2 steady-state protein levels, an effect that was dependent on the DEP domain. Strikingly, LRRK2-DVL1-3 interactions were disrupted by the familial PARK8 mutation Y1699C, whereas pathogenic mutations at residues R1441 and R1728 strengthened LRRK2-DVL1 interactions. Co-expression of DVL1 with LRRK2 in mammalian cells resulted in the redistribution of LRRK2 to typical cytoplasmic DVL1 aggregates in HEK293 and SH-SY5Y cells and co-localization in neurites and growth cones of differentiated dopaminergic SH-SY5Y cells. This is the first report of the modulation of a key LRRK2-accessory protein interaction by PARK8 Roc-COR domain mutations segregating with Parkinson's disease. Since the DVL1 DEP domain is known to be involved in the regulation of small GTPases, we propose that: (i) DVLs may influence LRRK2 GTPase activity, and (ii) Roc-COR domain mutations modulating LRRK2-DVL interactions indirectly influence kinase activity. Our findings also link LRRK2 to Wnt signalling pathways, suggesting novel pathogenic mechanisms and new targets for genetic analysis in Parkinson's disease.

  7. Mutations in the LRRK2 Roc-COR tandem domain link Parkinson's disease to Wnt signalling pathways

    PubMed Central

    Sancho, Rosa M.; Law, Bernard M.H.; Harvey, Kirsten

    2009-01-01

    Mutations in PARK8, encoding LRRK2, are the most common known cause of Parkinson's disease. The LRRK2 Roc-COR tandem domain exhibits GTPase activity controlling LRRK2 kinase activity via an intramolecular process. We report the interaction of LRRK2 with the dishevelled family of phosphoproteins (DVL1-3), key regulators of Wnt (Wingless/Int) signalling pathways important for axon guidance, synapse formation and neuronal maintenance. Interestingly, DVLs can interact with and mediate the activation of small GTPases with structural similarity to the LRRK2 Roc domain. The LRRK2 Roc-COR domain and the DVL1 DEP domain were necessary and sufficient for LRRK2–DVL1 interaction. Co-expression of DVL1 increased LRRK2 steady-state protein levels, an effect that was dependent on the DEP domain. Strikingly, LRRK2–DVL1-3 interactions were disrupted by the familial PARK8 mutation Y1699C, whereas pathogenic mutations at residues R1441 and R1728 strengthened LRRK2–DVL1 interactions. Co-expression of DVL1 with LRRK2 in mammalian cells resulted in the redistribution of LRRK2 to typical cytoplasmic DVL1 aggregates in HEK293 and SH-SY5Y cells and co-localization in neurites and growth cones of differentiated dopaminergic SH-SY5Y cells. This is the first report of the modulation of a key LRRK2-accessory protein interaction by PARK8 Roc-COR domain mutations segregating with Parkinson's disease. Since the DVL1 DEP domain is known to be involved in the regulation of small GTPases, we propose that: (i) DVLs may influence LRRK2 GTPase activity, and (ii) Roc-COR domain mutations modulating LRRK2–DVL interactions indirectly influence kinase activity. Our findings also link LRRK2 to Wnt signalling pathways, suggesting novel pathogenic mechanisms and new targets for genetic analysis in Parkinson's disease. PMID:19625296

  8. Connecting a Connectome to Behavior: An Ensemble of Neuroanatomical Models of C. elegans Klinotaxis

    PubMed Central

    Izquierdo, Eduardo J.; Beer, Randall D.

    2013-01-01

    Increased efforts in the assembly and analysis of connectome data are providing new insights into the principles underlying the connectivity of neural circuits. However, despite these considerable advances in connectomics, neuroanatomical data must be integrated with neurophysiological and behavioral data in order to obtain a complete picture of neural function. Due to its nearly complete wiring diagram and large behavioral repertoire, the nematode worm Caenorhaditis elegans is an ideal organism in which to explore in detail this link between neural connectivity and behavior. In this paper, we develop a neuroanatomically-grounded model of salt klinotaxis, a form of chemotaxis in which changes in orientation are directed towards the source through gradual continual adjustments. We identify a minimal klinotaxis circuit by systematically searching the C. elegans connectome for pathways linking chemosensory neurons to neck motor neurons, and prune the resulting network based on both experimental considerations and several simplifying assumptions. We then use an evolutionary algorithm to find possible values for the unknown electrophsyiological parameters in the network such that the behavioral performance of the entire model is optimized to match that of the animal. Multiple runs of the evolutionary algorithm produce an ensemble of such models. We analyze in some detail the mechanisms by which one of the best evolved circuits operates and characterize the similarities and differences between this mechanism and other solutions in the ensemble. Finally, we propose a series of experiments to determine which of these alternatives the worm may be using. PMID:23408877

  9. Engineering dynamical control of cell fate switching using synthetic phospho-regulons

    PubMed Central

    Gordley, Russell M.; Williams, Reid E.; Bashor, Caleb J.; Toettcher, Jared E.; Yan, Shude; Lim, Wendell A.

    2016-01-01

    Many cells can sense and respond to time-varying stimuli, selectively triggering changes in cell fate only in response to inputs of a particular duration or frequency. A common motif in dynamically controlled cells is a dual-timescale regulatory network: although long-term fate decisions are ultimately controlled by a slow-timescale switch (e.g., gene expression), input signals are first processed by a fast-timescale signaling layer, which is hypothesized to filter what dynamic information is efficiently relayed downstream. Directly testing the design principles of how dual-timescale circuits control dynamic sensing, however, has been challenging, because most synthetic biology methods have focused solely on rewiring transcriptional circuits, which operate at a single slow timescale. Here, we report the development of a modular approach for flexibly engineering phosphorylation circuits using designed phospho-regulon motifs. By then linking rapid phospho-feedback with slower downstream transcription-based bistable switches, we can construct synthetic dual-timescale circuits in yeast in which the triggering dynamics and the end-state properties of the ON state can be selectively tuned. These phospho-regulon tools thus open up the possibility to engineer cells with customized dynamical control. PMID:27821768

  10. Origin of bistability underlying mammalian cell cycle entry

    PubMed Central

    Yao, Guang; Tan, Cheemeng; West, Mike; Nevins, Joseph R; You, Lingchong

    2011-01-01

    Precise control of cell proliferation is fundamental to tissue homeostasis and differentiation. Mammalian cells commit to proliferation at the restriction point (R-point). It has long been recognized that the R-point is tightly regulated by the Rb–E2F signaling pathway. Our recent work has further demonstrated that this regulation is mediated by a bistable switch mechanism. Nevertheless, the essential regulatory features in the Rb–E2F pathway that create this switching property have not been defined. Here we analyzed a library of gene circuits comprising all possible link combinations in a simplified Rb–E2F network. We identified a minimal circuit that is able to generate robust, resettable bistability. This minimal circuit contains a feed-forward loop coupled with a mutual-inhibition feedback loop, which forms an AND-gate control of the E2F activation. Underscoring its importance, experimental disruption of this circuit abolishes maintenance of the activated E2F state, supporting its importance for the bistability of the Rb–E2F system. Our findings suggested basic design principles for the robust control of the bistable cell cycle entry at the R-point. PMID:21525871

  11. Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism.

    PubMed

    Wang, Xiaoming; Bey, Alexandra L; Katz, Brittany M; Badea, Alexandra; Kim, Namsoo; David, Lisa K; Duffney, Lara J; Kumar, Sunil; Mague, Stephen D; Hulbert, Samuel W; Dutta, Nisha; Hayrapetyan, Volodya; Yu, Chunxiu; Gaidis, Erin; Zhao, Shengli; Ding, Jin-Dong; Xu, Qiong; Chung, Leeyup; Rodriguiz, Ramona M; Wang, Fan; Weinberg, Richard J; Wetsel, William C; Dzirasa, Kafui; Yin, Henry; Jiang, Yong-Hui

    2016-05-10

    Human neuroimaging studies suggest that aberrant neural connectivity underlies behavioural deficits in autism spectrum disorders (ASDs), but the molecular and neural circuit mechanisms underlying ASDs remain elusive. Here, we describe a complete knockout mouse model of the autism-associated Shank3 gene, with a deletion of exons 4-22 (Δe4-22). Both mGluR5-Homer scaffolds and mGluR5-mediated signalling are selectively altered in striatal neurons. These changes are associated with perturbed function at striatal synapses, abnormal brain morphology, aberrant structural connectivity and ASD-like behaviour. In vivo recording reveals that the cortico-striatal-thalamic circuit is tonically hyperactive in mutants, but becomes hypoactive during social behaviour. Manipulation of mGluR5 activity attenuates excessive grooming and instrumental learning differentially, and rescues impaired striatal synaptic plasticity in Δe4-22(-/-) mice. These findings show that deficiency of Shank3 can impair mGluR5-Homer scaffolding, resulting in cortico-striatal circuit abnormalities that underlie deficits in learning and ASD-like behaviours. These data suggest causal links between genetic, molecular, and circuit mechanisms underlying the pathophysiology of ASDs.

  12. Altered mGluR5-Homer scaffolds and corticostriatal connectivity in a Shank3 complete knockout model of autism

    PubMed Central

    Wang, Xiaoming; Bey, Alexandra L.; Katz, Brittany M.; Badea, Alexandra; Kim, Namsoo; David, Lisa K.; Duffney, Lara J.; Kumar, Sunil; Mague, Stephen D.; Hulbert, Samuel W.; Dutta, Nisha; Hayrapetyan, Volodya; Yu, Chunxiu; Gaidis, Erin; Zhao, Shengli; Ding, Jin-Dong; Xu, Qiong; Chung, Leeyup; Rodriguiz, Ramona M.; Wang, Fan; Weinberg, Richard J.; Wetsel, William C.; Dzirasa, Kafui; Yin, Henry; Jiang, Yong-hui

    2016-01-01

    Human neuroimaging studies suggest that aberrant neural connectivity underlies behavioural deficits in autism spectrum disorders (ASDs), but the molecular and neural circuit mechanisms underlying ASDs remain elusive. Here, we describe a complete knockout mouse model of the autism-associated Shank3 gene, with a deletion of exons 4–22 (Δe4–22). Both mGluR5-Homer scaffolds and mGluR5-mediated signalling are selectively altered in striatal neurons. These changes are associated with perturbed function at striatal synapses, abnormal brain morphology, aberrant structural connectivity and ASD-like behaviour. In vivo recording reveals that the cortico-striatal-thalamic circuit is tonically hyperactive in mutants, but becomes hypoactive during social behaviour. Manipulation of mGluR5 activity attenuates excessive grooming and instrumental learning differentially, and rescues impaired striatal synaptic plasticity in Δe4–22−/− mice. These findings show that deficiency of Shank3 can impair mGluR5-Homer scaffolding, resulting in cortico-striatal circuit abnormalities that underlie deficits in learning and ASD-like behaviours. These data suggest causal links between genetic, molecular, and circuit mechanisms underlying the pathophysiology of ASDs. PMID:27161151

  13. Functional connectivity decreases in autism in emotion, self, and face circuits identified by Knowledge-based Enrichment Analysis.

    PubMed

    Cheng, Wei; Rolls, Edmund T; Zhang, Jie; Sheng, Wenbo; Ma, Liang; Wan, Lin; Luo, Qiang; Feng, Jianfeng

    2017-03-01

    A powerful new method is described called Knowledge based functional connectivity Enrichment Analysis (KEA) for interpreting resting state functional connectivity, using circuits that are functionally identified using search terms with the Neurosynth database. The method derives its power by focusing on neural circuits, sets of brain regions that share a common biological function, instead of trying to interpret single functional connectivity links. This provides a novel way of investigating how task- or function-related networks have resting state functional connectivity differences in different psychiatric states, provides a new way to bridge the gap between task and resting-state functional networks, and potentially helps to identify brain networks that might be treated. The method was applied to interpreting functional connectivity differences in autism. Functional connectivity decreases at the network circuit level in 394 patients with autism compared with 473 controls were found in networks involving the orbitofrontal cortex, anterior cingulate cortex, middle temporal gyrus cortex, and the precuneus, in networks that are implicated in the sense of self, face processing, and theory of mind. The decreases were correlated with symptom severity. Copyright © 2017. Published by Elsevier Inc.

  14. Poly-4-vinylphenol (PVP) and Poly(melamine-co-formaldehyde) (PMF)-Based Atomic Switching Device and Its Application to Logic Gate Circuits with Low Operating Voltage.

    PubMed

    Kang, Dong-Ho; Choi, Woo-Young; Woo, Hyunsuk; Jang, Sungkyu; Park, Hyung-Youl; Shim, Jaewoo; Choi, Jae-Woong; Kim, Sungho; Jeon, Sanghun; Lee, Sungjoo; Park, Jin-Hong

    2017-08-16

    In this study, we demonstrate a high-performance solid polymer electrolyte (SPE) atomic switching device with low SET/RESET voltages (0.25 and -0.5 V, respectively), high on/off-current ratio (10 5 ), excellent cyclic endurance (>10 3 ), and long retention time (>10 4 s), where poly-4-vinylphenol (PVP)/poly(melamine-co-formaldehyde) (PMF) is used as an SPE layer. To accomplish these excellent device performance parameters, we reduce the off-current level of the PVP/PMF atomic switching device by improving the electrical insulating property of the PVP/PMF electrolyte through adjustment of the number of cross-linked chains. We then apply a titanium buffer layer to the PVP/PMF switching device for further improvement of bipolar switching behavior and device stability. In addition, we first implement SPE atomic switch-based logic AND and OR circuits with low operating voltages below 2 V by integrating 5 × 5 arrays of PVP/PMF switching devices on the flexible substrate. In particular, this low operating voltage of our logic circuits was much lower than that (>5 V) of the circuits configured by polymer resistive random access memory. This research successfully presents the feasibility of PVP/PMF atomic switches for flexible integrated circuits for next-generation electronic applications.

  15. A Point-process Response Model for Spike Trains from Single Neurons in Neural Circuits under Optogenetic Stimulation

    PubMed Central

    Luo, X.; Gee, S.; Sohal, V.; Small, D.

    2015-01-01

    Optogenetics is a new tool to study neuronal circuits that have been genetically modified to allow stimulation by flashes of light. We study recordings from single neurons within neural circuits under optogenetic stimulation. The data from these experiments present a statistical challenge of modeling a high frequency point process (neuronal spikes) while the input is another high frequency point process (light flashes). We further develop a generalized linear model approach to model the relationships between two point processes, employing additive point-process response functions. The resulting model, Point-process Responses for Optogenetics (PRO), provides explicit nonlinear transformations to link the input point process with the output one. Such response functions may provide important and interpretable scientific insights into the properties of the biophysical process that governs neural spiking in response to optogenetic stimulation. We validate and compare the PRO model using a real dataset and simulations, and our model yields a superior area-under-the- curve value as high as 93% for predicting every future spike. For our experiment on the recurrent layer V circuit in the prefrontal cortex, the PRO model provides evidence that neurons integrate their inputs in a sophisticated manner. Another use of the model is that it enables understanding how neural circuits are altered under various disease conditions and/or experimental conditions by comparing the PRO parameters. PMID:26411923

  16. A Role of Phase-Resetting in Coordinating Large Scale Neural Networks During Attention and Goal-Directed Behavior

    PubMed Central

    Voloh, Benjamin; Womelsdorf, Thilo

    2016-01-01

    Short periods of oscillatory activation are ubiquitous signatures of neural circuits. A broad range of studies documents not only their circuit origins, but also a fundamental role for oscillatory activity in coordinating information transfer during goal directed behavior. Recent studies suggest that resetting the phase of ongoing oscillatory activity to endogenous or exogenous cues facilitates coordinated information transfer within circuits and between distributed brain areas. Here, we review evidence that pinpoints phase resetting as a critical marker of dynamic state changes of functional networks. Phase resets: (1) set a “neural context” in terms of narrow band frequencies that uniquely characterizes the activated circuits; (2) impose coherent low frequency phases to which high frequency activations can synchronize, identifiable as cross-frequency correlations across large anatomical distances; (3) are critical for neural coding models that depend on phase, increasing the informational content of neural representations; and (4) likely originate from the dynamics of canonical E-I circuits that are anatomically ubiquitous. These multiple signatures of phase resets are directly linked to enhanced information transfer and behavioral success. We survey how phase resets re-organize oscillations in diverse task contexts, including sensory perception, attentional stimulus selection, cross-modal integration, Pavlovian conditioning, and spatial navigation. The evidence we consider suggests that phase-resets can drive changes in neural excitability, ensemble organization, functional networks, and ultimately, overt behavior. PMID:27013986

  17. Improved PLL For FM Demodulator

    NASA Technical Reports Server (NTRS)

    Kirkham, Harold; Jackson, Shannon P.

    1992-01-01

    Phase-locked loop (PLL) for frequency demodulator contains improved frequency-to-voltage converter producing less ripple than conventional phase detector. In improved PLL, phase detector replaced by state estimator, implemented by ramp/sample-and-hold circuit. Intended to reduce noise in receiver of frequency-modulated (FM) telemetry link without sacrificing bandwidth. Also applicable to processing received FM signals.

  18. TEXAS EDUCATIONAL MICROWAVE PROJECT, TEMP III.

    ERIC Educational Resources Information Center

    SCHENKKAN, R.F.; AND OTHERS

    MICROWAVE TRANSMITTERS WERE USED TO LINK 11 INSTITUTIONS OF HIGHER LEARNING IN THE CENTRAL TEXAS AREA. THIS DEMONSTRATION WAS PLANNED AS A PILOT PROGRAM FOR THE USE OF MICROWAVE CHANNELS TO ACHIEVE A SINGLE CLOSED-CIRCUIT SYSTEM AMONG A NUMBER OF INSTITUTIONS. THE OBJECTIVES WERE (1) TO DEMONSTRATE THE FEASIBILITY, BOTH ECONOMIC AND PROGRAMMATIC,…

  19. A CRTCal link between energy and life span.

    PubMed

    Brunet, Anne

    2011-04-06

    Cutting down calories prolongs life, but how this works remains largely unknown. A recent study in Nature (Mair et al., 2011) shows that life span extension triggered by the energy-sensing protein kinase AMPK is mediated by an evolutionarily conserved transcriptional circuit involving CRTC-1 and CREB. Copyright © 2011 Elsevier Inc. All rights reserved.

  20. Microfabrication techniques for integrated sensors and microsystems.

    PubMed

    Wise, K D; Najafi, K

    1991-11-29

    Integrated sensors and actuators are rapidly evolving to provide an important link between very large scale integrated circuits and nonelectronic monitoring and control applications ranging from biomedicine to automated manufacturing. As they continue to expand, entire microsystems merging electrical, mechanical, thermal, optical, magnetic, and perhaps chemical components should be possible on a common substrate.

  1. Ratiometric fluorescent receptors for both Zn2+ and H2PO4(-) ions based on a pyrenyl-linked triazole-modified homooxacalix[3]arene: a potential molecular traffic signal with an R-S latch logic circuit.

    PubMed

    Ni, Xin-long; Zeng, Xi; Redshaw, Carl; Yamato, Takehiko

    2011-07-15

    A ratiometric fluorescent receptor with a C(3) symmetric structure based on a pyrene-linked triazole-modified homooxacalix[3]arene (L) was synthesized and characterized. This system exhibited an interesting ratiometric detection signal output for targeting cations and anions through switching the excimer emission of pyrene from the "on-off" to the "off-on" type in neutral solution. (1)H NMR titration results suggested that the Zn(2+) center of receptor L·Zn(2+) provided an excellent pathway of organizing anion binding groups for optimal host-guest interactions. It is thus believed that this receptor has potential application in sensing, detection, and recognition of both Zn(2+) and H(2)PO(4)(-) ions with different optical signals. In addition, the fluorescence emission changes by the inputs of Zn(2+) and H(2)PO(4)(-) ions can be viewed as a combinational R-S latch logic circuit at the molecular level.

  2. Silicon compilation: From the circuit to the system

    NASA Astrophysics Data System (ADS)

    Obrien, Keven

    The methodology used for the compilation of silicon from a behavioral level to a system level is presented. The aim was to link the heretofore unrelated areas of high level synthesis and system level design. This link will play an important role in the development of future design automation tools as it will allow hardware/software co-designs to be synthesized. A design methodology that alllows, through the use of an intermediate representation, SOLAR, a System level Design Language (SDL), to be combined with a Hardware Description Language (VHDL) is presented. Two main steps are required in order to transform this specification into a synthesizable one. Firstly, a system level synthesis step including partitioning and communication synthesis is required in order to split the model into a set of interconnected subsystems, each of which will be processed by a high level synthesis tool. For this latter step AMICAL is used and this allows powerful scheduling techniques to be used, that accept very abstract descriptions of control flow dominated circuits as input, and interconnected RTL blocks that may feed existing logic-level synthesis tools to be generated.

  3. Dependence of NMR noise line shapes on tuning, matching, and transmission line properties

    PubMed Central

    Bendet-Taicher, Eli; Müller, Norbert; Jerschow, Alexej

    2014-01-01

    The tuning and matching conditions of rf circuits, as well as the properties of the transmission lines connecting these to the preamplifier, have direct consequences for NMR probe sensitivity and as for the optimum delivery of rf power to the sample. In addition, tuning/matching conditions influence radiation damping effects, which manifest themselves as fast signal flip-back and line broadening effects, and can lead to concentration-dependent frequency shifts. Previous studies have also shown that the appearance of spin-noise and absorbed circuit noise signals heavily depended on tuning settings. Consequently, all these phenomena are linked together. The mutual connections and interdependences of these effects are highlighted and reviewed here. PMID:25505374

  4. Bidirectional global spontaneous network activity precedes the canonical unidirectional circuit organization in the developing hippocampus.

    PubMed

    Shi, Yulin; Ikrar, Taruna; Olivas, Nicholas D; Xu, Xiangmin

    2014-06-15

    Spontaneous network activity is believed to sculpt developing neural circuits. Spontaneous giant depolarizing potentials (GDPs) were first identified with single-cell recordings from rat CA3 pyramidal neurons, but here we identify and characterize a large-scale spontaneous network activity we term global network activation (GNA) in the developing mouse hippocampal slices, which is measured macroscopically by fast voltage-sensitive dye imaging. The initiation and propagation of GNA in the mouse is largely GABA-independent and dominated by glutamatergic transmission via AMPA receptors. Despite the fact that signal propagation in the adult hippocampus is strongly unidirectional through the canonical trisynaptic circuit (dentate gyrus [DG] to CA3 to CA1), spontaneous GNA in the developing hippocampus originates in distal CA3 and propagates both forward to CA1 and backward to DG. Photostimulation-evoked GNA also shows prominent backward propagation in the developing hippocampus from CA3 to DG. Mouse GNA is strongly correlated to electrophysiological recordings of highly localized single-cell and local field potential events. Photostimulation mapping of neural circuitry demonstrates that the enhancement of local circuit connections to excitatory pyramidal neurons occurs over the same time course as GNA and reveals the underlying pathways accounting for GNA backward propagation from CA3 to DG. The disappearance of GNA coincides with a transition to the adult-like unidirectional circuit organization at about 2 weeks of age. Taken together, our findings strongly suggest a critical link between GNA activity and maturation of functional circuit connections in the developing hippocampus. Copyright © 2013 Wiley Periodicals, Inc.

  5. Sensation-to-Cognition Cortical Streams in Attention-Deficit/Hyperactivity Disorder

    PubMed Central

    Carmona, Susana; Hoekzema, Elseline; Castellanos, Francisco X.; García-García, David; Lage-Castellanos, Agustín; Dijk, Koene R.A.Van; Navas-Sánchez, Francisco J.; Martínez, Kenia; Desco, Manuel; Sepulcre, Jorge

    2015-01-01

    We sought to determine whether functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits are atypical in attention-deficit/hyperactivity disorder (ADHD). We applied a graph-theory method to the resting-state functional magnetic resonance imaging data of 120 children with ADHD and 120 age-matched typically developing children (TDC). Starting in unimodal primary cortex—visual, auditory, and somatosensory—we used stepwise functional connectivity to calculate functional connectivity paths at discrete numbers of relay stations (or link-step distances). First, we characterized the functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits in TDC and found that systems do not reach the level of integration achieved by adults. Second, we searched for stepwise functional connectivity differences between children with ADHD and TDC. We found that, at the initial steps of sensory functional connectivity streams, patients display significant enhancements of connectivity degree within neighboring areas of primary cortex, while connectivity to attention-regulatory areas is reduced. Third, at subsequent link-step distances from primary sensory cortex, children with ADHD show decreased connectivity to executive processing areas and increased degree of connections to default mode regions. Fourth, in examining medication histories in children with ADHD, we found that children medicated with psychostimulants present functional connectivity streams with higher degree of connectivity to regions subserving attentional and executive processes compared to medication-naïve children. We conclude that predominance of local sensory processing and lesser influx of information to attentional and executive regions may reduce the ability to organize and control the balance between external and internal sources of information in ADHD. PMID:25821110

  6. Strength of word-specific neural memory traces assessed electrophysiologically.

    PubMed

    Alexandrov, Alexander A; Boricheva, Daria O; Pulvermüller, Friedemann; Shtyrov, Yury

    2011-01-01

    Memory traces for words are frequently conceptualized neurobiologically as networks of neurons interconnected via reciprocal links developed through associative learning in the process of language acquisition. Neurophysiological reflection of activation of such memory traces has been reported using the mismatch negativity brain potential (MMN), which demonstrates an enhanced response to meaningful words over meaningless items. This enhancement is believed to be generated by the activation of strongly intraconnected long-term memory circuits for words that can be automatically triggered by spoken linguistic input and that are absent for unfamiliar phonological stimuli. This conceptual framework critically predicts different amounts of activation depending on the strength of the word's lexical representation in the brain. The frequent use of words should lead to more strongly connected representations, whereas less frequent items would be associated with more weakly linked circuits. A word with higher frequency of occurrence in the subject's language should therefore lead to a more pronounced lexical MMN response than its low-frequency counterpart. We tested this prediction by comparing the event-related potentials elicited by low- and high-frequency words in a passive oddball paradigm; physical stimulus contrasts were kept identical. We found that, consistent with our prediction, presenting the high-frequency stimulus led to a significantly more pronounced MMN response relative to the low-frequency one, a finding that is highly similar to previously reported MMN enhancement to words over meaningless pseudowords. Furthermore, activation elicited by the higher-frequency word peaked earlier relative to low-frequency one, suggesting more rapid access to frequently used lexical entries. These results lend further support to the above view on word memory traces as strongly connected assemblies of neurons. The speed and magnitude of their activation appears to be linked to the strength of internal connections in a memory circuit, which is in turn determined by the everyday use of language elements.

  7. Optomotor-blind negatively regulates Drosophila eye development by blocking Jak/STAT signaling.

    PubMed

    Tsai, Yu-Chen; Grimm, Stefan; Chao, Ju-Lan; Wang, Shih-Chin; Hofmeyer, Kerstin; Shen, Jie; Eichinger, Fred; Michalopoulou, Theoni; Yao, Chi-Kuang; Chang, Chih-Hsuan; Lin, Shih-Han; Sun, Y Henry; Pflugfelder, Gert O

    2015-01-01

    Organ formation requires a delicate balance of positive and negative regulators. In Drosophila eye development, wingless (wg) is expressed at the lateral margins of the eye disc and serves to block retinal development. The T-box gene optomotor-blind (omb) is expressed in a similar pattern and is regulated by Wg. Omb mediates part of Wg activity in blocking eye development. Omb exerts its function primarily by blocking cell proliferation. These effects occur predominantly in the ventral margin. Our results suggest that the primary effect of Omb is the blocking of Jak/STAT signaling by repressing transcription of upd which encodes the Jak receptor ligand Unpaired.

  8. Data Transfer Efficiency Over Satellite Circuits Using a Multi-Socket Extension to the File Transfer Protocol (FTP)

    NASA Technical Reports Server (NTRS)

    Allman, Mark; Ostermann, Shawn; Kruse, Hans

    1996-01-01

    In several experiments using NASA's Advanced Communications Technology Satellite (ACTS), investigators have reported disappointing throughput using the transmission control protocol/Internet protocol (TCP/IP) protocol suite over 1.536Mbit/sec (T1) satellite circuits. A detailed analysis of file transfer protocol (FTP) file transfers reveals that both the TCP window size and the TCP 'slow starter' algorithm contribute to the observed limits in throughput. In this paper we summarize the experimental and and theoretical analysis of the throughput limit imposed by TCP on the satellite circuit. We then discuss in detail the implementation of a multi-socket FTP, XFTP client and server. XFTP has been tested using the ACTS system. Finally, we discuss a preliminary set of tests on a link with non-zero bit error rates. XFTP shows promising performance under these conditions, suggesting the possibility that a multi-socket application may be less effected by bit errors than a single, large-window TCP connection.

  9. Simplified Design Equations for Class-E Neural Prosthesis Transmitters

    PubMed Central

    Troyk, Philip; Hu, Zhe

    2013-01-01

    Extreme miniaturization of implantable electronic devices is recognized as essential for the next generation of neural prostheses, owing to the need for minimizing the damage and disruption of the surrounding neural tissue. Transcutaneous power and data transmission via a magnetic link remains the most effective means of powering and controlling implanted neural prostheses. Reduction in the size of the coil, within the neural prosthesis, demands the generation of a high-intensity radio frequency magnetic field from the extracoporeal transmitter. The Class-E power amplifier circuit topology has been recognized as a highly effective means of producing large radio frequency currents within the transmitter coil. Unfortunately, design of a Class-E circuit is most often fraught by the need to solve a complex set of equations so as to implement both the zero-voltage-switching and zero-voltage-derivative-switching conditions that are required for efficient operation. This paper presents simple explicit design equations for designing the Class-E circuit topology. Numerical design examples are presented to illustrate the design procedure. PMID:23292784

  10. System and method for controlling remote devices

    DOEpatents

    Carrender, Curtis Lee [Richland, WA; Gilbert, Ronald W [Benton City, WA; Scott, Jeff W [Pasco, WA; Clark, David A [Kennewick, WA

    2006-02-07

    A system and method for controlling remote devices utilizing a radio frequency identification (RFID) tag device having a control circuit adapted to render the tag device, and associated objects, permanently inoperable in response to radio-frequency control signals. The control circuit is configured to receive the control signals that can include an enable signal, and in response thereto enable an associated object, such as a weapon; and in response to a disable signal, to disable the tag itself, or, if desired, to disable the associated weapon or both the device and the weapon. Permanent disabling of the tag can be accomplished by several methods, including, but not limited to, fusing a fusable link, breaking an electrically conductive path, permanently altering the modulation or backscattering characteristics of the antenna circuit, and permanently erasing an associated memory. In this manner, tags in the possession of unauthorized employees can be remotely disabled, and weapons lost on a battlefield can be easily tracked and enabled or disabled automatically or at will.

  11. Neural circuits. Labeling of active neural circuits in vivo with designed calcium integrators.

    PubMed

    Fosque, Benjamin F; Sun, Yi; Dana, Hod; Yang, Chao-Tsung; Ohyama, Tomoko; Tadross, Michael R; Patel, Ronak; Zlatic, Marta; Kim, Douglas S; Ahrens, Misha B; Jayaraman, Vivek; Looger, Loren L; Schreiter, Eric R

    2015-02-13

    The identification of active neurons and circuits in vivo is a fundamental challenge in understanding the neural basis of behavior. Genetically encoded calcium (Ca(2+)) indicators (GECIs) enable quantitative monitoring of cellular-resolution activity during behavior. However, such indicators require online monitoring within a limited field of view. Alternatively, post hoc staining of immediate early genes (IEGs) indicates highly active cells within the entire brain, albeit with poor temporal resolution. We designed a fluorescent sensor, CaMPARI, that combines the genetic targetability and quantitative link to neural activity of GECIs with the permanent, large-scale labeling of IEGs, allowing a temporally precise "activity snapshot" of a large tissue volume. CaMPARI undergoes efficient and irreversible green-to-red conversion only when elevated intracellular Ca(2+) and experimenter-controlled illumination coincide. We demonstrate the utility of CaMPARI in freely moving larvae of zebrafish and flies, and in head-fixed mice and adult flies. Copyright © 2015, American Association for the Advancement of Science.

  12. Neuronal Calcium Signaling in Metabolic Regulation and Adaptation to Nutrient Stress.

    PubMed

    Jayakumar, Siddharth; Hasan, Gaiti

    2018-01-01

    All organisms can respond physiologically and behaviorally to environmental fluxes in nutrient levels. Different nutrient sensing pathways exist for specific metabolites, and their inputs ultimately define appropriate nutrient uptake and metabolic homeostasis. Nutrient sensing mechanisms at the cellular level require pathways such as insulin and target of rapamycin (TOR) signaling that integrates information from different organ systems like the fat body and the gut. Such integration is essential for coordinating growth with development. Here we review the role of a newly identified set of integrative interneurons and the role of intracellular calcium signaling within these neurons, in regulating nutrient sensing under conditions of nutrient stress. A comparison of the identified Drosophila circuit and cellular mechanisms employed in this circuit, with vertebrate systems, suggests that the identified cell signaling mechanisms may be conserved for neural circuit function related to nutrient sensing by central neurons. The ideas proposed are potentially relevant for understanding the molecular basis of metabolic disorders, because these are frequently linked to nutritional stress.

  13. AgRP Neural Circuits Mediate Adaptive Behaviors in the Starved State

    PubMed Central

    Padilla, Stephanie L.; Qiu, Jian; Soden, Marta E.; Sanz, Elisenda; Nestor, Casey C; Barker, Forrest D.; Quintana, Albert; Zweifel, Larry S.; Rønnekleiv, Oline K.; Kelly, Martin J.; Palmiter, Richard D.

    2016-01-01

    In the face of starvation animals will engage in high-risk behaviors that would normally be considered maladaptive. Starving rodents for example will forage in areas that are more susceptible to predators and will also modulate aggressive behavior within a territory of limited or depleted nutrients. The neural basis of these adaptive behaviors likely involves circuits that link innate feeding, aggression, and fear. Hypothalamic AgRP neurons are critically important for driving feeding and project axons to brain regions implicated in aggression and fear. Using circuit-mapping techniques, we define a disynaptic network originating from a subset of AgRP neurons that project to the medial nucleus of the amygdala and then to the principle bed nucleus of the stria terminalis, which plays a role in suppressing territorial aggression and reducing contextual fear. We propose that AgRP neurons serve as a master switch capable of coordinating behavioral decisions relative to internal state and environmental cues. PMID:27019015

  14. An Adenosine-Mediated Glial-Neuronal Circuit for Homeostatic Sleep.

    PubMed

    Bjorness, Theresa E; Dale, Nicholas; Mettlach, Gabriel; Sonneborn, Alex; Sahin, Bogachan; Fienberg, Allen A; Yanagisawa, Masashi; Bibb, James A; Greene, Robert W

    2016-03-30

    Sleep homeostasis reflects a centrally mediated drive for sleep, which increases during waking and resolves during subsequent sleep. Here we demonstrate that mice deficient for glial adenosine kinase (AdK), the primary metabolizing enzyme for adenosine (Ado), exhibit enhanced expression of this homeostatic drive by three independent measures: (1) increased rebound of slow-wave activity; (2) increased consolidation of slow-wave sleep; and (3) increased time constant of slow-wave activity decay during an average slow-wave sleep episode, proposed and validated here as a new index for homeostatic sleep drive. Conversely, mice deficient for the neuronal adenosine A1 receptor exhibit significantly decreased sleep drive as judged by these same indices. Neuronal knock-out of AdK did not influence homeostatic sleep need. Together, these findings implicate a glial-neuronal circuit mediated by intercellular Ado, controlling expression of homeostatic sleep drive. Because AdK is tightly regulated by glial metabolic state, our findings suggest a functional link between cellular metabolism and sleep homeostasis. The work presented here provides evidence for an adenosine-mediated regulation of sleep in response to waking (i.e., homeostatic sleep need), requiring activation of neuronal adenosine A1 receptors and controlled by glial adenosine kinase. Adenosine kinase acts as a highly sensitive and important metabolic sensor of the glial ATP/ADP and AMP ratio directly controlling intracellular adenosine concentration. Glial equilibrative adenosine transporters reflect the intracellular concentration to the extracellular milieu to activate neuronal adenosine receptors. Thus, adenosine mediates a glial-neuronal circuit linking glial metabolic state to neural-expressed sleep homeostasis. This indicates a metabolically related function(s) for this glial-neuronal circuit in the buildup and resolution of our need to sleep and suggests potential therapeutic targets more directly related to sleep function. Copyright © 2016 the authors 0270-6474/16/363709-13$15.00/0.

  15. VLSI technology for smaller, cheaper, faster return link systems

    NASA Technical Reports Server (NTRS)

    Nanzetta, Kathy; Ghuman, Parminder; Bennett, Toby; Solomon, Jeff; Dowling, Jason; Welling, John

    1994-01-01

    Very Large Scale Integration (VLSI) Application-specific Integrated Circuit (ASIC) technology has enabled substantially smaller, cheaper, and more capable telemetry data systems. However, the rapid growth in available ASIC fabrication densities has far outpaced the application of this technology to telemetry systems. Available densities have grown by well over an order magnitude since NASA's Goddard Space Flight Center (GSFC) first began developing ASIC's for ground telemetry systems in 1985. To take advantage of these higher integration levels, a new generation of ASIC's for return link telemetry processing is under development. These new submicron devices are designed to further reduce the cost and size of NASA return link processing systems while improving performance. This paper describes these highly integrated processing components.

  16. Linking mitochondrial bioenergetics to insulin resistance via redox biology

    PubMed Central

    Fisher-Wellman, Kelsey H.; Neufer, P. Darrell

    2012-01-01

    Chronic overnutrition and physical inactivity are major risk factors for insulin resistance and type 2 diabetes. Recent research indicates that overnutrition generates an increase in hydrogen peroxide (H2O2) emission from mitochondria, serving as a release valve to relieve the reducing pressure created by fuel overload, as well as a primary signal to ultimately decrease insulin sensitivity. H2O2 is a major input to cellular redox circuits that link to cysteine residues throughout the entire proteome to regulate cell function. Here we review the principles of mitochondrial bioenergetics and redox systems biology and offer new insight as to how H2O2 emission may be linked via redox biology to the etiology of insulin resistance. PMID:22305519

  17. Bioluminescent bioreporter integrated circuit devices and methods for detecting estrogen

    DOEpatents

    Simpson, Michael L.; Paulus, Michael J.; Sayler, Gary S.; Applegate, Bruce M.; Ripp, Steven A.

    2006-08-15

    Bioelectronic devices for the detection of estrogen include a collection of eukaryotic cells which harbor a recombinant lux gene from a high temperature microorganism wherein the gene is operably linked with a heterologous promoter gene. A detectable light-emitting lux gene product is expressed in the presence of the estrogen and detected by the device.

  18. M2-F1 under tow across lakebed by car

    NASA Technical Reports Server (NTRS)

    1963-01-01

    This 20-second clip shows the M2-F1 being towed by the Pontiac across Rogers Dry Lakebed. The M2-F1 lifting body, dubbed the 'flying bathtub' by the media, was the precursor of a remarkable series of wingless flying vehicles that contributed data used in the Space Shuttles, the X-33 Advanced Technology Demonstrator for the next century's Reusable Launch Vehicle, and the X-38 Technology Demonstrator for crew return from the International Space Station. Based on the ideas and basic design of Alfred J. Eggers and others at the Ames Aeronautical Laboratory (now the Ames Research Center), Mountain View, California, in the mid-1950's, the M2-F1 was built in 1962-63 over a four-month period for a cost of only about $30,000, plus an additional $8,000-$10,000 for an ejection seat. Engineers and technicians at the NASA Flight Research Center (now NASA Dryden) kept costs low by designing and fabricating it partly in-house, with the plywood shell constructed by a local sailplane builder. Someone at the time estimated that it would have cost a major aircraft company $150,000 to build the same vehicle. Unlike the later lifting bodies, the M2-F1 was unpowered and was initially towed by a souped-up Pontiac convertible until it was airborne. Later a C-47 took over the towing duties. Flown by such famous research pilots as Milt Thompson, Bruce Peterson, Chuck Yeager, and Bill Dana, the lightweight flying bathtub demonstrated that a wingless vehicle shaped for reentry into the Earth's atmosphere from space could be flown and landed safely. Flown from 1963 to 1966, the lightweight M2-F1 paved the way for the heavyweight M2-F2, M2`F3, HL-10, X-24A, and X-24B lifting bodies that flew under rocket power after launch from a B-52 mothership. The heavyweights flew from 1966 to 1975, demonstrating the viability and versatility of the wingless configuration and the ability of a vehicle with low lift-over-drag characteristics to fly to high altitudes and then to land precisely with their rocket engines no longer burning. Their unpowered approaches and landings showed that the Space Shuttles need not decrease their payloads by carrying fuel and engines that would have been required for conventional, powered landings. The lifting bodies also prepared the way for the later X-33 and X-38 programs that feature lifting-body shapes. The entire lifting-body program was carried out at comparatively low cost in partnership with the Ames and Langley Research Centers, the Air Force, and their Northrop and Martin industrial partners. It was a harbinger of NASA's current philosophy, 'faster, better, cheaper,' and as such, it epitomizes the innovation, technical agility, and discovery through flight research that have characterized the Dryden Flight Research Center for more than fifty years.

  19. Adaptive neural coding: from biological to behavioral decision-making

    PubMed Central

    Louie, Kenway; Glimcher, Paul W.; Webb, Ryan

    2015-01-01

    Empirical decision-making in diverse species deviates from the predictions of normative choice theory, but why such suboptimal behavior occurs is unknown. Here, we propose that deviations from optimality arise from biological decision mechanisms that have evolved to maximize choice performance within intrinsic biophysical constraints. Sensory processing utilizes specific computations such as divisive normalization to maximize information coding in constrained neural circuits, and recent evidence suggests that analogous computations operate in decision-related brain areas. These adaptive computations implement a relative value code that may explain the characteristic context-dependent nature of behavioral violations of classical normative theory. Examining decision-making at the computational level thus provides a crucial link between the architecture of biological decision circuits and the form of empirical choice behavior. PMID:26722666

  20. Capacitive proximity sensor

    DOEpatents

    Kronberg, James W.

    1994-01-01

    A proximity sensor based on a closed field circuit. The circuit comprises a ring oscillator using a symmetrical array of plates that creates an oscillating displacement current. The displacement current varies as a function of the proximity of objects to the plate array. Preferably the plates are in the form of a group of three pair of symmetric plates having a common center, arranged in a hexagonal pattern with opposing plates linked as a pair. The sensor produces logic level pulses suitable for interfacing with a computer or process controller. The proximity sensor can be incorporated into a load cell, a differential pressure gauge, or a device for measuring the consistency of a characteristic of a material where a variation in the consistency causes the dielectric constant of the material to change.

  1. Evolution of Courtship Songs in Xenopus : Vocal Pattern Generation and Sound Production.

    PubMed

    Leininger, Elizabeth C; Kelley, Darcy B

    2015-01-01

    The extant species of African clawed frogs (Xenopus and Silurana) provide an opportunity to link the evolution of vocal characters to changes in the responsible cellular and molecular mechanisms. In this review, we integrate several robust lines of research: evolutionary trajectories of Xenopus vocalizations, cellular and circuit-level mechanisms of vocalization in selected Xenopus model species, and Xenopus evolutionary history and speciation mechanisms. Integrating recent findings allows us to generate and test specific hypotheses about the evolution of Xenopus vocal circuits. We propose that reduced vocal sex differences in some Xenopus species result from species-specific losses of sexually differentiated neural and neuromuscular features. Modification of sex-hormone-regulated developmental mechanisms is a strong candidate mechanism for reduced vocal sex differences.

  2. SpikingLab: modelling agents controlled by Spiking Neural Networks in Netlogo.

    PubMed

    Jimenez-Romero, Cristian; Johnson, Jeffrey

    2017-01-01

    The scientific interest attracted by Spiking Neural Networks (SNN) has lead to the development of tools for the simulation and study of neuronal dynamics ranging from phenomenological models to the more sophisticated and biologically accurate Hodgkin-and-Huxley-based and multi-compartmental models. However, despite the multiple features offered by neural modelling tools, their integration with environments for the simulation of robots and agents can be challenging and time consuming. The implementation of artificial neural circuits to control robots generally involves the following tasks: (1) understanding the simulation tools, (2) creating the neural circuit in the neural simulator, (3) linking the simulated neural circuit with the environment of the agent and (4) programming the appropriate interface in the robot or agent to use the neural controller. The accomplishment of the above-mentioned tasks can be challenging, especially for undergraduate students or novice researchers. This paper presents an alternative tool which facilitates the simulation of simple SNN circuits using the multi-agent simulation and the programming environment Netlogo (educational software that simplifies the study and experimentation of complex systems). The engine proposed and implemented in Netlogo for the simulation of a functional model of SNN is a simplification of integrate and fire (I&F) models. The characteristics of the engine (including neuronal dynamics, STDP learning and synaptic delay) are demonstrated through the implementation of an agent representing an artificial insect controlled by a simple neural circuit. The setup of the experiment and its outcomes are described in this work.

  3. A novel architecture of recovered data comparison for high speed clock and data recovery

    NASA Astrophysics Data System (ADS)

    Gao, Susan; Li, Fei; Wang, Zhigong; Cui, Hongliang

    2005-05-01

    A clock and data recovery (CDR) circuit is one of the crucial blocks in high-speed serial link communication systems. The data received in these systems are asynchronous and noisy, requiring that a clock be extracted to allow synchronous operations. Furthermore, the data must be "retimed" so that the jitter accumulated during transmission is removed. This paper presents a novel architecture of CDR, which is very tolerant to long sequences of serial ones or zeros and also robust to occasional long absence of transitions. The design is based on the fact that a basic clock recovery having a clock recovery circuit (CRC) and a data decision circuit separately would generate a high jitter clock when the received non-return-to-zero (NRZ) data with long sequences of ones or zeros. To eliminate this drawback, the proposed architecture incorporates a data circuit decision circuit within the phase-locked loop (PLL) CRC. Other than this, a new phase detector (PD) is also proposed, which was easy to accomplish and robust at high speed. This PD is functional with a random input and automatically turns to disable during both the locked state and long absence of transitions. The voltage-controlled oscillator (VCO) is also designed delicately to suppress the jitter. Due to the high stability, the jitter is highly reduced when the loop is locked. The simulation results of such CDR working at 1.25Gb/s particularly for 1000BASE-X Gigabit Ethernet by using TSMC 0.25μm technology are presented to prove the feasibility of this architecture. One more CDR based on edge detection architecture is also built in the circuit for performance comparisons.

  4. The relative phases of basal ganglia activities dynamically shape effective connectivity in Parkinson's disease.

    PubMed

    Cagnan, Hayriye; Duff, Eugene Paul; Brown, Peter

    2015-06-01

    Optimal phase alignment between oscillatory neural circuits is hypothesized to optimize information flow and enhance system performance. This theory is known as communication-through-coherence. The basal ganglia motor circuit exhibits exaggerated oscillatory and coherent activity patterns in Parkinson's disease. Such activity patterns are linked to compromised motor system performance as evinced by bradykinesia, rigidity and tremor, suggesting that network function might actually deteriorate once a certain level of net synchrony is exceeded in the motor circuit. Here, we characterize the processes underscoring excessive synchronization and its termination. To this end, we analysed local field potential recordings from the subthalamic nucleus and globus pallidus of five patients with Parkinson's disease (four male and one female, aged 37-64 years). We observed that certain phase alignments between subthalamic nucleus and globus pallidus amplified local neural synchrony in the beta frequency band while others either suppressed it or did not induce any significant change with respect to surrogates. The increase in local beta synchrony directly correlated with how long the two nuclei locked to beta-amplifying phase alignments. Crucially, administration of the dopamine prodrug, levodopa, reduced the frequency and duration of periods during which subthalamic and pallidal populations were phase-locked to beta-amplifying alignments. Conversely ON dopamine, the total duration over which subthalamic and pallidal populations were aligned to phases that left beta-amplitude unchanged with respect to surrogates increased. Thus dopaminergic input shifted circuit dynamics from persistent periods of locking to amplifying phase alignments, associated with compromised motoric function, to more dynamic phase alignment and improved motoric function. This effect of dopamine on local circuit resonance suggests means by which novel electrical interventions might prevent resonance-related pathological circuit interactions. © The Author (2015). Published by Oxford University Press on behalf of the Guarantors of Brain.

  5. Principles of motivation revealed by the diverse functions of neuropharmacological and neuroanatomical substrates underlying feeding behavior

    PubMed Central

    Baldo, Brian A.; Pratt, Wayne E.; Will, Matthew J.; Hanlon, Erin C.; Bakshi, Vaishali P.; Cador, Martine

    2013-01-01

    Circuits that participate in specific subcomponents of feeding (e.g., gustatory perception, peripheral feedback relevant to satiety and energy balance, reward coding, etc.) are found at all levels of the neural axis. Further complexity is conferred by the wide variety of feeding-modulatory neurotransmitters and neuropeptides that act within these circuits. An ongoing challenge has been to refine the understanding of the functional specificity of these neurotransmitters and circuits, and there have been exciting advances in recent years. We focus here on foundational work of Dr. Ann Kelley that identified distinguishable actions of striatal opioid peptide modulation and dopamine transmission in subcomponents of reward processing. We also discuss her work in overlaying these neuropharmacological effects upon anatomical pathways that link the telencephalon (cortex and basal ganglia) with feeding-control circuits in the hypothalamus. Using these seminal contributions as a starting point, we will discuss new findings that expand our understanding of (1) the specific, differentiable motivational processes that are governed by central dopamine and opioid transmission, (2) the manner in which other striatal neuromodulators, specifically acetylcholine, endocannabinoids and adenosine, modulate these motivational processes (including via interactions with opioid systems), and (3) the organization of the cortical-subcortical network that subserves opioid-driven feeding. The findings discussed here strengthen the view that incentive-motivational properties of food are coded by substrates and neural circuits that are distinguishable from those that mediate the acute hedonic experience of food reward. Striatal opioid transmission modulates reward processing by engaging frontotemporal circuits, possibly via a hypothalamic-thalamic axis, that ultimately impinges upon hypothalamic modules dedicated to autonomic function and motor pattern control. We will conclude by discussing implications for understanding disorders of “non-homeostatic” feeding. PMID:23466532

  6. Principles of motivation revealed by the diverse functions of neuropharmacological and neuroanatomical substrates underlying feeding behavior.

    PubMed

    Baldo, Brian A; Pratt, Wayne E; Will, Matthew J; Hanlon, Erin C; Bakshi, Vaishali P; Cador, Martine

    2013-11-01

    Circuits that participate in specific subcomponents of feeding (e.g., gustatory perception, peripheral feedback relevant to satiety and energy balance, reward coding, etc.) are found at all levels of the neural axis. Further complexity is conferred by the wide variety of feeding-modulatory neurotransmitters and neuropeptides that act within these circuits. An ongoing challenge has been to refine the understanding of the functional specificity of these neurotransmitters and circuits, and there have been exciting advances in recent years. We focus here on foundational work of Dr. Ann Kelley that identified distinguishable actions of striatal opioid peptide modulation and dopamine transmission in subcomponents of reward processing. We also discuss her work in overlaying these neuropharmacological effects upon anatomical pathways that link the telencephalon (cortex and basal ganglia) with feeding-control circuits in the hypothalamus. Using these seminal contributions as a starting point, we will discuss new findings that expand our understanding of (1) the specific, differentiable motivational processes that are governed by central dopamine and opioid transmission, (2) the manner in which other striatal neuromodulators, specifically acetylcholine, endocannabinoids and adenosine, modulate these motivational processes (including via interactions with opioid systems), and (3) the organization of the cortical-subcortical network that subserves opioid-driven feeding. The findings discussed here strengthen the view that incentive-motivational properties of food are coded by substrates and neural circuits that are distinguishable from those that mediate the acute hedonic experience of food reward. Striatal opioid transmission modulates reward processing by engaging frontotemporal circuits, possibly via a hypothalamic-thalamic axis, that ultimately impinges upon hypothalamic modules dedicated to autonomic function and motor pattern control. We will conclude by discussing implications for understanding disorders of "non-homeostatic" feeding. Copyright © 2013 Elsevier Ltd. All rights reserved.

  7. Raclopride or high-frequency stimulation of the subthalamic nucleus stops cocaine-induced motor stereotypy and restores related alterations in prefrontal basal ganglia circuits.

    PubMed

    Aliane, Verena; Pérez, Sylvie; Deniau, Jean-Michel; Kemel, Marie-Louise

    2012-11-01

    Motor stereotypy is a key symptom of various neurological or neuropsychiatric disorders. Neuroleptics or the promising treatment using deep brain stimulation stops stereotypies but the mechanisms underlying their actions are unclear. In rat, motor stereotypies are linked to an imbalance between prefrontal and sensorimotor cortico-basal ganglia circuits. Indeed, cortico-nigral transmission was reduced in the prefrontal but not sensorimotor basal ganglia circuits and dopamine and acetylcholine release was altered in the prefrontal but not sensorimotor territory of the dorsal striatum. Furthermore, cholinergic transmission in the prefrontal territory of the dorsal striatum plays a crucial role in the arrest of motor stereotypy. Here we found that, as previously observed for raclopride, high-frequency stimulation of the subthalamic nucleus (HFS STN) rapidly stopped cocaine-induced motor stereotypies in rat. Importantly, raclopride and HFS STN exerted a strong effect on cocaine-induced alterations in prefrontal basal ganglia circuits. Raclopride restored the cholinergic transmission in the prefrontal territory of the dorsal striatum and the cortico-nigral information transmissions in the prefrontal basal ganglia circuits. HFS STN also restored the N-methyl-d-aspartic-acid-evoked release of acetylcholine and dopamine in the prefrontal territory of the dorsal striatum. However, in contrast to raclopride, HFS STN did not restore the cortico-substantia nigra pars reticulata transmissions but exerted strong inhibitory and excitatory effects on neuronal activity in the prefrontal subdivision of the substantia nigra pars reticulata. Thus, both raclopride and HFS STN stop cocaine-induced motor stereotypy, but exert different effects on the related alterations in the prefrontal basal ganglia circuits. © 2012 The Authors. European Journal of Neuroscience © 2012 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.

  8. Critical brain circuits at the intersection between stress and learning.

    PubMed

    Bangasser, Debra A; Shors, Tracey J

    2010-07-01

    The effects of stressful life experience on learning are pervasive and vary greatly both within and between individuals. It is therefore unlikely that any one mechanism will underlie these complicated processes. Nonetheless, without identifying the necessary and sufficient circuitry, no complete mechanism or set of mechanisms can be identified. In this review, we provide two anatomical frameworks through which stressful life experience can influence processes related to learning and memory. In the first, stressful experience releases stress hormones, primarily from the adrenals, which directly impact brain areas engaged in learning. In the second, stressful experience indirectly alters the circuits used in learning via intermediary brain regions. Importantly, these intermediary brain regions are not integral to the stress response or learning itself, but rather link the consequences of a stressful experience with circuits used to learn associations. As reviewed, the existing literature provides support for both frameworks, with somewhat more support for the first but sufficient evidence for the latter which involves intermediary structures. Once we determine the circumstances that engage each framework and identify which one is most predominant, we can begin to focus our efforts on describing the neuronal and hormonal mechanisms that operate within these circuits to influence cognitive processes after stressful life experience.

  9. Nutritional State-Dependent Ghrelin Activation of Vasopressin Neurons via Retrograde Trans-Neuronal–Glial Stimulation of Excitatory GABA Circuits

    PubMed Central

    Haam, Juhee; Halmos, Katalin C.; Di, Shi

    2014-01-01

    Behavioral and physiological coupling between energy balance and fluid homeostasis is critical for survival. The orexigenic hormone ghrelin has been shown to stimulate the secretion of the osmoregulatory hormone vasopressin (VP), linking nutritional status to the control of blood osmolality, although the mechanism of this systemic crosstalk is unknown. Here, we show using electrophysiological recordings and calcium imaging in rat brain slices that ghrelin stimulates VP neurons in the hypothalamic paraventricular nucleus (PVN) in a nutritional state-dependent manner by activating an excitatory GABAergic synaptic input via a retrograde neuronal–glial circuit. In slices from fasted rats, ghrelin activation of a postsynaptic ghrelin receptor, the growth hormone secretagogue receptor type 1a (GHS-R1a), in VP neurons caused the dendritic release of VP, which stimulated astrocytes to release the gliotransmitter adenosine triphosphate (ATP). ATP activation of P2X receptors excited presynaptic GABA neurons to increase GABA release, which was excitatory to the VP neurons. This trans-neuronal–glial retrograde circuit activated by ghrelin provides an alternative means of stimulation of VP release and represents a novel mechanism of neuronal control by local neuronal–glial circuits. It also provides a potential cellular mechanism for the physiological integration of energy and fluid homeostasis. PMID:24790191

  10. Magnetic Random Access Memory based non-volatile asynchronous Muller cell for ultra-low power autonomous applications

    NASA Astrophysics Data System (ADS)

    Di Pendina, G.; Zianbetov, E.; Beigne, E.

    2015-05-01

    Micro and nano electronic integrated circuit domain is today mainly driven by the advent of the Internet of Things for which the constraints are strong, especially in terms of power consumption and autonomy, not only during the computing phases but also during the standby or idle phases. In such ultra-low power applications, the circuit has to meet new constraints mainly linked to its changing energetic environment: long idle phases, automatic wake up, data back-up when the circuit is sporadically turned off, and ultra-low voltage power supply operation. Such circuits have to be completely autonomous regarding their unstable environment, while remaining in an optimum energetic configuration. Therefore, we propose in this paper the first MRAM-based non-volatile asynchronous Muller cell. This cell has been simulated and characterized in a very advanced 28 nm CMOS fully depleted silicon-on-insulator technology, presenting good power performance results due to an extremely efficient body biasing control together with ultra-wide supply voltage range from 160 mV up to 920 mV. The leakage current can be reduced to 154 pA thanks to reverse body biasing. We also propose an efficient standard CMOS bulk version of this cell in order to be compatible with different fabrication processes.

  11. Applications of Emerging Parallel Optical Link Technology to High Energy Physics Experiments

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

    Chramowicz, J.; Kwan, S.; Prosser, A.

    2011-09-01

    Modern particle detectors depend upon optical fiber links to deliver event data to upstream trigger and data processing systems. Future detector systems can benefit from the development of dense arrangements of high speed optical links emerging from the telecommunications and storage area network market segments. These links support data transfers in each direction at rates up to 120 Gbps in packages that minimize or even eliminate edge connector requirements. Emerging products include a class of devices known as optical engines which permit assembly of the optical transceivers in close proximity to the electrical interfaces of ASICs and FPGAs which handlemore » the data in parallel electrical format. Such assemblies will reduce required printed circuit board area and minimize electromagnetic interference and susceptibility. We will present test results of some of these parallel components and report on the development of pluggable FPGA Mezzanine Cards equipped with optical engines to provide to collaborators on the Versatile Link Common Project for the HI-LHC at CERN.« less

  12. Sensation-to-cognition cortical streams in attention-deficit/hyperactivity disorder.

    PubMed

    Carmona, Susana; Hoekzema, Elseline; Castellanos, Francisco X; García-García, David; Lage-Castellanos, Agustín; Van Dijk, Koene R A; Navas-Sánchez, Francisco J; Martínez, Kenia; Desco, Manuel; Sepulcre, Jorge

    2015-07-01

    We sought to determine whether functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits are atypical in attention-deficit/hyperactivity disorder (ADHD). We applied a graph-theory method to the resting-state functional magnetic resonance imaging data of 120 children with ADHD and 120 age-matched typically developing children (TDC). Starting in unimodal primary cortex-visual, auditory, and somatosensory-we used stepwise functional connectivity to calculate functional connectivity paths at discrete numbers of relay stations (or link-step distances). First, we characterized the functional connectivity streams that link sensory, attentional, and higher-order cognitive circuits in TDC and found that systems do not reach the level of integration achieved by adults. Second, we searched for stepwise functional connectivity differences between children with ADHD and TDC. We found that, at the initial steps of sensory functional connectivity streams, patients display significant enhancements of connectivity degree within neighboring areas of primary cortex, while connectivity to attention-regulatory areas is reduced. Third, at subsequent link-step distances from primary sensory cortex, children with ADHD show decreased connectivity to executive processing areas and increased degree of connections to default mode regions. Fourth, in examining medication histories in children with ADHD, we found that children medicated with psychostimulants present functional connectivity streams with higher degree of connectivity to regions subserving attentional and executive processes compared to medication-naïve children. We conclude that predominance of local sensory processing and lesser influx of information to attentional and executive regions may reduce the ability to organize and control the balance between external and internal sources of information in ADHD. © 2015 Wiley Periodicals, Inc.

  13. Adaptive arrays for satellite communications

    NASA Technical Reports Server (NTRS)

    Gupta, I. J.; Ksienski, A. A.

    1984-01-01

    The suppression of interfering signals in a satellite communication system was studied. Adaptive arrays are used to suppress interference at the reception site. It is required that the interference be suppressed to very low levels and a modified adaptive circuit is used which accomplishes the desired objective. Techniques for the modification of the transmit patterns to minimize interference with neighboring communication links are explored.

  14. Use of Two-Way Interactive Television in Education. Training and Development Research Center. Project Number Eighteen.

    ERIC Educational Resources Information Center

    McClelland, Jerry

    Four case studies in varying stages of completion are currently being conducted in the Department of Vocational and Technical Education at the University of Minnesota using live, two-way television to link multiple sites for interactive television classes. Two of the four classes, which are offered via closed-circuit television, are a vocational…

  15. Proceedings of the Pennsylvania Adult and Continuing Education Research Conference (Harrisburg, Pennsylvania, March 20, 1999).

    ERIC Educational Resources Information Center

    King, Kathleen P., Ed.; Ferro, Trenton R., Ed.

    These proceedings consist of 18 papers from a conference to provide researchers and practitioners with a forum for sharing research findings that focus on the link between research and practice in adult, continuing, and community education. The five invited papers are as follows: "Towards a Pedagogy of Ethical Coercion" (Ian Baptiste); "Circuit of…

  16. Interaction Between Hippocampus and Cerebellum Crus I in Sequence-Based but not Place-Based Navigation

    PubMed Central

    Iglói, Kinga; Doeller, Christian F.; Paradis, Anne-Lise; Benchenane, Karim; Berthoz, Alain; Burgess, Neil; Rondi-Reig, Laure

    2015-01-01

    To examine the cerebellar contribution to human spatial navigation we used functional magnetic resonance imaging and virtual reality. Our findings show that the sensory-motor requirements of navigation induce activity in cerebellar lobules and cortical areas known to be involved in the motor loop and vestibular processing. By contrast, cognitive aspects of navigation mainly induce activity in a different cerebellar lobule (VIIA Crus I). Our results demonstrate a functional link between cerebellum and hippocampus in humans and identify specific functional circuits linking lobule VIIA Crus I of the cerebellum to medial parietal, medial prefrontal, and hippocampal cortices in nonmotor aspects of navigation. They further suggest that Crus I belongs to 2 nonmotor loops, involved in different strategies: place-based navigation is supported by coherent activity between left cerebellar lobule VIIA Crus I and medial parietal cortex along with right hippocampus activity, while sequence-based navigation is supported by coherent activity between right lobule VIIA Crus I, medial prefrontal cortex, and left hippocampus. These results highlight the prominent role of the human cerebellum in both motor and cognitive aspects of navigation, and specify the cortico-cerebellar circuits by which it acts depending on the requirements of the task. PMID:24947462

  17. Proteomic Characterization of the World Trade Center dust-activated mdig and c-myc signaling circuit linked to multiple myeloma

    PubMed Central

    Wu, Kai; Li, Lingzhi; Thakur, Chitra; Lu, Yongju; Zhang, Xiangmin; Yi, Zhengping; Chen, Fei

    2016-01-01

    Several epidemiological studies suggested an increased incidence rate of multiple myeloma (MM) among first responders and other individuals who exposed to World Trade Center (WTC) dust. In this report, we provided evidence showing that WTC dust is potent in inducing mdig protein and/or mRNA in bronchial epithelial cells, B cells and MM cell lines. An increased mdig expression in MM bone marrow was observed, which is associated with the disease progression and prognosis of the MM patients. Through integrative genomics and proteomics approaches, we further demonstrated that mdig directly interacts with c-myc and JAK1 in MM cell lines, which contributes to hyperactivation of the IL-6-JAK-STAT3 signaling important for the pathogenesis of MM. Genetic silencing of mdig reduced activity of the major downstream effectors in the IL-6-JAK-STAT3 pathway. Taken together, these data suggest that WTC dust may be one of the key etiological factors for those who had been exposed for the development of MM by activating mdig and c-myc signaling circuit linked to the IL-6-JAK-STAT3 pathway essential for the tumorigenesis of the malignant plasma cells. PMID:27833099

  18. Serotonergic neurosecretory synapse targeting is controlled by Netrin-releasing guidepost neurons in C. elegans

    PubMed Central

    Nelson, Jessica C.; Colón-Ramos, Daniel A.

    2013-01-01

    Neurosecretory release sites lack distinct post-synaptic partners, yet target to specific circuits. This targeting specificity regulates local release of neurotransmitters and modulation of adjacent circuits. How neurosecretory release sites target to specific regions is not understood. Here we identify a molecular mechanism that governs the spatial specificity of extrasynaptic neurosecretory terminal formation in the serotonergic NSM neurons of C. elegans. We show that post-embryonic arborization and neurosecretory terminal targeting of the C. elegans NSM neuron is dependent on the Netrin receptor UNC-40/DCC. We observe that UNC-40 localizes to specific neurosecretory terminals at the time of axon arbor formation. This localization is dependent on UNC-6/Netrin, which is expressed by nerve ring neurons that act as guideposts to instruct local arbor and release site formation. We find that both UNC-34/Enabled and MIG-10/Lamellipodin are required downstream of UNC-40 to link the sites of ENT formation to nascent axon arbor extensions. Our findings provide a molecular link between release site development and axon arborization, and introduce a novel mechanism that governs the spatial specificity of serotonergic extrasynaptic neurosecretory terminals in vivo. PMID:23345213

  19. Environmental test program for superconducting materials and devices

    NASA Technical Reports Server (NTRS)

    Haertling, Gene; Randolph, Henry; Hsi, Chi-Shiung; Verbelyi, Darren

    1991-01-01

    This report is divided into two parts. The first dealing with work involved with Clemson University and the second with the results from Westinghouse/Savannah River. Both areas of work involved low noise, low thermal conductivity superconducting grounding links used in the NASA-sponsored Spectroscopy of the Atmosphere using Far Infrared Emission (SAFIRE) Project. Clemson prepared the links from YBa2Cu3O(7-x) superconductor tape that was mounted on a printed circuit board and encapsulated with epoxy resin. The Clemson program includes temperature vs. resistance, liquid nitrogen immersion, water immersion, thermal cycling, humidity, and radiation testing. The evaluation of the links under a long term environmental test program is described. The Savannah River program includes gamma irradiation, vibration, and long-term evaluation. The progress made in these evaluations is discussed.

  20. Feasibility Study on Active Back Telemetry and Power Transmission Through an Inductive Link for Millimeter-Sized Biomedical Implants.

    PubMed

    Yeon, Pyungwoo; Mirbozorgi, S Abdollah; Lim, Jaemyung; Ghovanloo, Maysam

    2017-12-01

    This paper presents a feasibility study of wireless power and data transmission through an inductive link to a 1-mm 2 implant, to be used as a free-floating neural probe, distributed across a brain area of interest. The proposed structure utilizes a four-coil inductive link for back telemetry, shared with a three-coil link for wireless power transmission. We propose a design procedure for geometrical optimization of the inductive link in terms of power transmission efficiency (PTE) considering specific absorption rate and data rate. We have designed a low-power pulse-based active data transmission circuit and characterized performance of the proposed inductive link in terms of its data rate and bit error rate (BER). The 1-mm 2 data-Tx/power-Rx coil is implemented using insulated bonding wire with diameter, resulting in measured PTE in tissue media of 2.01% at 131 MHz and 1.8-cm coil separation distance when the resonator coil inner radius is 1 cm. The measured BER at 1-Mbps data rate was and in the air and tissue environments, respectively.

  1. Silicon photonics devices for metro applications

    NASA Astrophysics Data System (ADS)

    Fukuda, H.; Kikuchi, K.; Jizodo, M.; Kawamura, Y.; Takeda, K.; Honda, K.

    2017-01-01

    Digital coherent technology is considered an attractive way of realizing both high-speed metro links and long distance transmissions. In metro areas, there is a strong demand for a smaller, faster transceiver module. This demand is mainly driven by the rapidly increasing data center interconnection traffic, where transmission capacity per faceplane is a key feature. Therefore, optical integration technology is desired. Since compensation in digital coherent technology is performed in the electrical or digital domain, users can deal with those optics performances that are not compensated for digitally. This means using a new material that cannot provide perfect characteristics but that is suitable for miniaturization and integration is possible. Silicon photonics (SiPh) is considered an attractive technology that would enable the significant miniaturization of optical circuits and be capable of optical integration with high manufacturability. While SiPh-based devices have begun to be deployed for very short or short reach links on the basis of direct detection technology, their digital coherent applications have recently been investigated in view of their integration capability. This paper describes recent progress on SiPh-based integrated optical devices for high-speed digital coherent transceivers targeting metro links. An optical modulator and receiver with related circuits have been integrated into a single SiPh chip. TEC-free operation under non-hermetic conditions and the direct attachment of optical fibers have both been realized. Very thin and small packaging with sufficient performance has been demonstrated by using the SiPh chip co-packaged with high-speed ICs.

  2. Ring resonator-based on-chip modulation transformer for high-performance phase-modulated microwave photonic links.

    PubMed

    Zhuang, Leimeng; Taddei, Caterina; Hoekman, Marcel; Leinse, Arne; Heideman, René; van Dijk, Paulus; Roeloffzen, Chris

    2013-11-04

    In this paper, we propose and experimentally demonstrate a novel wideband on-chip photonic modulation transformer for phase-modulated microwave photonic links. The proposed device is able to transform phase-modulated optical signals into intensity-modulated versions (or vice versa) with nearly zero conversion of laser phase noise to intensity noise. It is constructed using waveguide-based ring resonators, which features simple architecture, stable operation, and easy reconfigurability. Beyond the stand-alone functionality, the proposed device can also be integrated with other functional building blocks of photonic integrated circuits (PICs) to create on-chip complex microwave photonic signal processors. As an application example, a PIC consisting of two such modulation transformers and a notch filter has been designed and realized in TriPleX(TM) waveguide technology. The realized device uses a 2 × 2 splitting circuit and 3 ring resonators with a free spectral range of 25 GHz, which are all equipped with continuous tuning elements. The device can perform phase-to-intensity modulation transform and carrier suppression simultaneously, which enables high-performance phase-modulated microwave photonics links (PM-MPLs). Associated with the bias-free and low-complexity advantages of the phase modulators, a single-fiber-span PM-MPL with a RF bandwidth of 12 GHz (3 dB-suppression band 6 to 18 GHz) has been demonstrated comprising the proposed PIC, where the achieved spurious-free dynamic range performance is comparable to that of Class-AB MPLs using low-biased Mach-Zehnder modulators.

  3. Experimental and theoretical study of shuttle lee-side heat transfer rates

    NASA Technical Reports Server (NTRS)

    Mruk, G. K.; Bertin, J.; Lamb, J. P.

    1975-01-01

    The experimental program which was conducted in the Calspan 96-inch hypersonic shock tunnel to investigate what effect the windward surface temperature had on the heat transfer to the leeward surface of the space shuttle orbiter is discussed. Heat-transfer distributions, surface-pressure distributions, and schlieren photographs were obtained for an 0.01-scale model of the 139 configuration space shuttle orbiter at angles-of-attack of 30 and 40 deg. Similar data were obtained for an 0.01 scale wingless model of the 139 configuration at angles-of-attack of 30 and 90 deg. Data were obtained for Mach numbers from Reynolds numbers, and surface temperatures and compared with theoretical results.

  4. Optomotor-Blind Negatively Regulates Drosophila Eye Development by Blocking Jak/STAT Signaling

    PubMed Central

    Tsai, Yu-Chen; Grimm, Stefan; Chao, Ju-Lan; Wang, Shih-Chin; Hofmeyer, Kerstin; Shen, Jie; Eichinger, Fred; Michalopoulou, Theoni; Yao, Chi-Kuang; Chang, Chih-Hsuan; Lin, Shih-Han; Sun, Y. Henry; Pflugfelder, Gert O.

    2015-01-01

    Organ formation requires a delicate balance of positive and negative regulators. In Drosophila eye development, wingless (wg) is expressed at the lateral margins of the eye disc and serves to block retinal development. The T-box gene optomotor-blind (omb) is expressed in a similar pattern and is regulated by Wg. Omb mediates part of Wg activity in blocking eye development. Omb exerts its function primarily by blocking cell proliferation. These effects occur predominantly in the ventral margin. Our results suggest that the primary effect of Omb is the blocking of Jak/STAT signaling by repressing transcription of upd which encodes the Jak receptor ligand Unpaired. PMID:25781970

  5. A Kinome RNAi Screen in Drosophila Identifies Novel Genes Interacting with Lgl, aPKC, and Crb Cell Polarity Genes in Epithelial Tissues.

    PubMed

    Parsons, Linda M; Grzeschik, Nicola A; Amaratunga, Kasun; Burke, Peter; Quinn, Leonie M; Richardson, Helena E

    2017-08-07

    In both Drosophila melanogaster and mammalian systems, epithelial structure and underlying cell polarity are essential for proper tissue morphogenesis and organ growth. Cell polarity interfaces with multiple cellular processes that are regulated by the phosphorylation status of large protein networks. To gain insight into the molecular mechanisms that coordinate cell polarity with tissue growth, we screened a boutique collection of RNAi stocks targeting the kinome for their capacity to modify Drosophila "cell polarity" eye and wing phenotypes. Initially, we identified kinase or phosphatase genes whose depletion modified adult eye phenotypes associated with the manipulation of cell polarity complexes (via overexpression of Crb or aPKC). We next conducted a secondary screen to test whether these cell polarity modifiers altered tissue overgrowth associated with depletion of Lgl in the wing. These screens identified Hippo, Jun kinase (JNK), and Notch signaling pathways, previously linked to cell polarity regulation of tissue growth. Furthermore, novel pathways not previously connected to cell polarity regulation of tissue growth were identified, including Wingless (Wg/Wnt), Ras, and lipid/Phospho-inositol-3-kinase (PI3K) signaling pathways. Additionally, we demonstrated that the "nutrient sensing" kinases Salt Inducible Kinase 2 and 3 ( SIK2 and 3 ) are potent modifiers of cell polarity phenotypes and regulators of tissue growth. Overall, our screen has revealed novel cell polarity-interacting kinases and phosphatases that affect tissue growth, providing a platform for investigating molecular mechanisms coordinating cell polarity and tissue growth during development. Copyright © 2017 Parsons et al.

  6. Wnt/β-Catenin Regulates the Activity of Epiprofin/Sp6, SHH, FGF, and BMP to Coordinate the Stages of Odontogenesis

    PubMed Central

    Aurrekoetxea, Maitane; Irastorza, Igor; García-Gallastegui, Patricia; Jiménez-Rojo, Lucia; Nakamura, Takashi; Yamada, Yoshihiko; Ibarretxe, Gaskon; Unda, Fernando J.

    2016-01-01

    Background: We used an in vitro tooth development model to investigate the effects of overactivation of the Wnt/β-catenin pathway during odontogenesis by bromoindirubin oxime reagent (BIO), a specific inhibitor of GSK-3 activity. Results: Overactivating the Wnt/β-catenin pathway at tooth initiation upregulated and ectopically expressed the epithelial markers Sonic Hedgehog (Shh), Epiprofin (Epfn), and Fibroblast growth factor8 (Fgf8), which are involved in the delimitation of odontogenic fields in the oral ectoderm. This result indicated an ectopic extension of the odontogenic potential. During tooth morphogenesis, Fibroblast growth factor4 (Fgf4), Fibroblast growth factor10 (Fgf10), Muscle segment homeobox 1 (Msx-1), Bone Morphogenetic protein 4 (Bmp4), and Dickkopf WNT signaling pathway inhibitor 1 (Dkk-1) were overexpressed in first molars cultured with BIO. Conversely, the expression levels of Wingless integration site 10b (Wnt-10b) and Shh were reduced. Additionally, the odontoblast differentiation markers Nestin and Epfn showed ectopic overexpression in the dental mesenchyme of BIO-treated molars. Moreover, alkaline phosphatase activity increased in the dental mesenchyme, again suggesting aberrant, ectopic mesenchymal cell differentiation. Finally, Bmp4 downregulated Epfn expression during dental morphogenesis. Conclusions: We suggest the presence of a positive feedback loop wherein Epfn and β-catenin activate each other. The balance of the expression of these two molecules is essential for proper tooth development. We propose a possible link between Wnt, Bmp, and Epfn that would critically determine the correct patterning of dental cusps and the differentiation of odontoblasts and ameloblasts. PMID:27066482

  7. Murine J774 Macrophages Recognize LPS/IFN-g, Non-CpG DNA or Two-CpG DNA-containing Sequences as Immunologically Distinct

    PubMed Central

    Crosby, Lynn; Casey, Warren; Morgan, Kevin; Ni, Hong; Yoon, Lawrence; Easton, Marilyn; Misukonis, Mary; Burleson, Gary; Ghosh, Dipak K.

    2010-01-01

    Specific bacterial lipopolysaccharides (LPS), IFN-γ, and unmethylated cytosine or guanosine-phosphorothioate containing DNAs (CpG) activate host immunity, influencing infectious responses. Macrophages detect, inactivate and destroy infectious particles, and synthetic CpG sequences invoke similar responses of the innate immune system. Previously, murine macrophage J774 cells treated with CpG induced the expression of nitric oxide synthase 2 (NOS2) and cyclo-oxygenase 2 (COX2) mRNA and protein. In this study murine J774 macrophages were exposed to vehicle, interferon γ + lipopolysaccharide (IFN-g/LPS), non-CpG (SAK1), or two-CpG sequence-containing DNA (SAK2) for 0–18 hr and gene expression changes measured. A large number of immunostimulatory and inflammatory changes were observed. SAK2 was a stronger activator of TNFα- and chemokine expression-related changes than LPS/IFN-g. Up regulation included tumor necrosis factor receptor superfamily genes (TNFRSF’s), IL-1 receptor signaling via stress-activated protein kinase (SAPK), NF-κB activation, hemopoietic maturation factors and sonic hedgehog/wingless integration site (SHH/Wnt) pathway genes. Genes of the TGF-β pathway were down regulated. In contrast, LPS/IFN-g -treated cells showed increased levels for TGF-β signaling genes, which may be linked to the observed up regulation of numerous collagens and down regulation of Wnt pathway genes. SAK1 produced distinct changes from LPS/IFN-g or SAK2. Therefore, J774 macrophages recognize LPS/IFN-g, non-CpG DNA or two-CpG DNA-containing sequences as immunologically distinct. PMID:20097302

  8. ICGC PedBrain: Dissecting the genomic complexity underlying medulloblastoma

    PubMed Central

    Jones, David TW; Jäger, Natalie; Kool, Marcel; Zichner, Thomas; Hutter, Barbara; Sultan, Marc; Cho, Yoon-Jae; Pugh, Trevor J; Hovestadt, Volker; Stütz, Adrian M; Rausch, Tobias; Warnatz, Hans-Jörg; Ryzhova, Marina; Bender, Sebastian; Sturm, Dominik; Pleier, Sabrina; Cin, Huriye; Pfaff, Elke; Sieber, Laura; Wittmann, Andrea; Remke, Marc; Witt, Hendrik; Hutter, Sonja; Tzaridis, Theophilos; Weischenfeldt, Joachim; Raeder, Benjamin; Avci, Meryem; Amstislavskiy, Vyacheslav; Zapatka, Marc; Weber, Ursula D; Wang, Qi; Lasitschka, Bärbel; Bartholomae, Cynthia C; Schmidt, Manfred; von Kalle, Christof; Ast, Volker; Lawerenz, Chris; Eils, Jürgen; Kabbe, Rolf; Benes, Vladimir; van Sluis, Peter; Koster, Jan; Volckmann, Richard; Shih, David; Betts, Matthew J; Russell, Robert B; Coco, Simona; Tonini, Gian Paolo; Schüller, Ulrich; Hans, Volkmar; Graf, Norbert; Kim, Yoo-Jin; Monoranu, Camelia; Roggendorf, Wolfgang; Unterberg, Andreas; Herold-Mende, Christel; Milde, Till; Kulozik, Andreas E; von Deimling, Andreas; Witt, Olaf; Maass, Eberhard; Rössler, Jochen; Ebinger, Martin; Schuhmann, Martin U; Frühwald, Michael C; Hasselblatt, Martin; Jabado, Nada; Rutkowski, Stefan; von Bueren, André O; Williamson, Dan; Clifford, Steven C; McCabe, Martin G; Collins, V. Peter; Wolf, Stephan; Wiemann, Stefan; Lehrach, Hans; Brors, Benedikt; Scheurlen, Wolfram; Felsberg, Jörg; Reifenberger, Guido; Northcott, Paul A; Taylor, Michael D; Meyerson, Matthew; Pomeroy, Scott L; Yaspo, Marie-Laure; Korbel, Jan O; Korshunov, Andrey; Eils, Roland; Pfister, Stefan M; Lichter, Peter

    2013-01-01

    Summary Medulloblastoma is an aggressively-growing tumour, arising in the cerebellum or medulla/brain stem. It is the most common malignant brain tumour in children, and displays tremendous biological and clinical heterogeneity1. Despite recent treatment advances, approximately 40% of children experience tumour recurrence, and 30% will die from their disease. Those who survive often have a significantly reduced quality of life. Four tumour subgroups with distinct clinical, biological and genetic profiles are currently discriminated2,3. WNT tumours, displaying activated wingless pathway signalling, carry a favourable prognosis under current treatment regimens4. SHH tumours show hedgehog pathway activation, and have an intermediate prognosis2. Group 3 & 4 tumours are molecularly less well-characterised, and also present the greatest clinical challenges2,3,5. The full repertoire of genetic events driving this distinction, however, remains unclear. Here we describe an integrative deep-sequencing analysis of 125 tumour-normal pairs. Tetraploidy was identified as a frequent early event in Group 3 & 4 tumours, and a positive correlation between patient age and mutation rate was observed. Several recurrent mutations were identified, both in known medulloblastoma-related genes (CTNNB1, PTCH1, MLL2, SMARCA4) and in genes not previously linked to this tumour (DDX3X, CTDNEP1, KDM6A, TBR1), often in subgroup-specific patterns. RNA-sequencing confirmed these alterations, and revealed the expression of the first medulloblastoma fusion genes. Chromatin modifiers were frequently altered across all subgroups. These findings enhance our understanding of the genomic complexity and heterogeneity underlying medulloblastoma, and provide several potential targets for new therapeutics, especially for Group 3 & 4 patients. PMID:22832583

  9. Improvement of wireless power transmission efficiency of implantable subcutaneous devices by closed magnetic circuit mechanism.

    PubMed

    Jo, Sung-Eun; Joung, Sanghoon; Suh, Jun-Kyo Francis; Kim, Yong-Jun

    2012-09-01

    Induction coils were fabricated based on flexible printed circuit board for inductive transcutaneous power transmission. The coil had closed magnetic circuit (CMC) structure consisting of inner and outer magnetic core. The power transmission efficiency of the fabricated device was measured in the air and in vivo condition. It was confirmed that the CMC coil had higher transmission efficiency than typical air-core coil. The power transmission efficiency during a misalignment between primary coil and implanted secondary coil was also evaluated. The decrease of mutual inductance between the two coils caused by the misalignment led to a low efficiency of the inductive link. Therefore, it is important to properly align the primary coil and implanted secondary coil for effective power transmission. To align the coils, a feedback coil was proposed. This was integrated on the backside of the primary coil and enabled the detection of a misalignment of the primary and secondary coils. As a result of using the feedback coil, the primary and secondary coils could be aligned without knowledge of the position of the implanted secondary coil.

  10. Serotonin 1B Receptors Regulate Prefrontal Function by Gating Callosal and Hippocampal Inputs.

    PubMed

    Kjaerby, Celia; Athilingam, Jegath; Robinson, Sarah E; Iafrati, Jillian; Sohal, Vikaas S

    2016-12-13

    Both medial prefrontal cortex (mPFC) and serotonin play key roles in anxiety; however, specific mechanisms through which serotonin might act on the mPFC to modulate anxiety-related behavior remain unknown. Here, we use a combination of optogenetics and synaptic physiology to show that serotonin acts presynaptically via 5-HT1B receptors to selectively suppress inputs from the contralateral mPFC and ventral hippocampus (vHPC), while sparing those from mediodorsal thalamus. To elucidate how these actions could potentially regulate prefrontal circuit function, we infused a 5-HT1B agonist into the mPFC of freely behaving mice. Consistent with previous studies that have optogenetically inhibited vHPC-mPFC projections, activating prefrontal 5-HT1B receptors suppressed theta-frequency mPFC activity (4-12 Hz), and reduced avoidance of anxiogenic regions in the elevated plus maze. These findings suggest a potential mechanism, linking specific receptors, synapses, patterns of circuit activity, and behavior, through which serotonin may regulate prefrontal circuit function, including anxiety-related behaviors. Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

  11. Elevated CaMKIIα and hyperphosphorylation of Homer mediate circuit dysfunction in a Fragile X Syndrome mouse model

    PubMed Central

    Guo, Weirui; Ceolin, Laura; Collins, Katie; Perroy, Julie; Huber, Kimberly M.

    2015-01-01

    Summary Abnormal metabotropic glutamate receptor 5 (mGluR5) function, as a result of disrupted scaffolding with its binding partner Homer, contributes to the pathophysiology of Fragile X Syndrome, a common inherited from of intellectual disability and autism caused by mutations in Fmr1. How loss of Fmr1 disrupts mGluR5-Homer scaffolds is unknown, and little is known about the dynamic regulation of mGluR5-Homer scaffolds in wildtype neurons. Here we demonstrate that brief (minutes) elevations in neural activity cause CaMKIIα-mediated phosphorylation of long Homer proteins and dissociation from mGluR5 at synapses. In Fmr1 knockout cortex, Homers are hyperphosphorylated as a result of elevated CaMKIIα protein. Genetic or pharmacological inhibition of CaMKIIα or replacement of Homers with dephosphomimetics restores mGluR5-Homer scaffolds and multiple Fmr1 KO phenotypes, including circuit hyperexcitability and/or seizures. This work links translational control of an FMRP target mRNA, CaMKIIα, to the molecular, cellular and circuit level brain dysfunction in a complex neurodevelopmental disorder. PMID:26670047

  12. Development of optical packet and circuit integrated ring network testbed.

    PubMed

    Furukawa, Hideaki; Harai, Hiroaki; Miyazawa, Takaya; Shinada, Satoshi; Kawasaki, Wataru; Wada, Naoya

    2011-12-12

    We developed novel integrated optical packet and circuit switch-node equipment. Compared with our previous equipment, a polarization-independent 4 × 4 semiconductor optical amplifier switch subsystem, gain-controlled optical amplifiers, and one 100 Gbps optical packet transponder and seven 10 Gbps optical path transponders with 10 Gigabit Ethernet (10GbE) client-interfaces were newly installed in the present system. The switch and amplifiers can provide more stable operation without equipment adjustments for the frequent polarization-rotations and dynamic packet-rate changes of optical packets. We constructed an optical packet and circuit integrated ring network testbed consisting of two switch nodes for accelerating network development, and we demonstrated 66 km fiber transmission and switching operation of multiplexed 14-wavelength 10 Gbps optical paths and 100 Gbps optical packets encapsulating 10GbE frames. Error-free (frame error rate < 1×10(-4)) operation was achieved with optical packets of various packet lengths and packet rates, and stable operation of the network testbed was confirmed. In addition, 4K uncompressed video streaming over OPS links was successfully demonstrated. © 2011 Optical Society of America

  13. The intralaminar thalamus—an expressway linking visual stimuli to circuits determining agency and action selection

    PubMed Central

    Fisher, Simon D.; Reynolds, John N. J.

    2014-01-01

    Anatomical investigations have revealed connections between the intralaminar thalamic nuclei and areas such as the superior colliculus (SC) that receive short latency input from visual and auditory primary sensory areas. The intralaminar nuclei in turn project to the major input nucleus of the basal ganglia, the striatum, providing this nucleus with a source of subcortical excitatory input. Together with a converging input from the cerebral cortex, and a neuromodulatory dopaminergic input from the midbrain, the components previously found necessary for reinforcement learning in the basal ganglia are present. With this intralaminar sensory input, the basal ganglia are thought to play a primary role in determining what aspect of an organism’s own behavior has caused salient environmental changes. Additionally, subcortical loops through thalamic and basal ganglia nuclei are proposed to play a critical role in action selection. In this mini review we will consider the anatomical and physiological evidence underlying the existence of these circuits. We will propose how the circuits interact to modulate basal ganglia output and solve common behavioral learning problems of agency determination and action selection. PMID:24765070

  14. Pharmacological induction of skin pigmentation unveils the neuroendocrine circuit regulated by light.

    PubMed

    Bertolesi, Gabriel E; Vazhappilly, Sherene T; Hehr, Carrie L; McFarlane, Sarah

    2016-03-01

    Light-regulated skin colour change is an important physiological process in invertebrates and lower vertebrates, and includes daily circadian variation and camouflage (i.e. background adaptation). The photoactivation of melanopsin-expressing retinal ganglion cells (mRGCs) in the eye initiates an uncharacterized neuroendocrine circuit that regulates melanin dispersion/aggregation through the secretion of alpha-melanocyte-stimulating hormone (α-MSH). We developed experimental models of normal or enucleated Xenopus embryos, as well as in situ cultures of skin of isolated dorsal head and tails, to analyse pharmacological induction of skin pigmentation and α-MSH synthesis. Both processes are triggered by a melanopsin inhibitor, AA92593, as well as chloride channel modulators. The AA9253 effect is eye-dependent, while functional data in vivo point to GABAA receptors expressed on pituitary melanotrope cells as the chloride channel blocker target. Based on the pharmacological data, we suggest a neuroendocrine circuit linking mRGCs with α-MSH secretion, which is used normally during background adaptation. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. Developmental programming of hypothalamic neuronal circuits: impact on energy balance control

    PubMed Central

    Gali Ramamoorthy, Thanuja; Begum, Ghazala; Harno, Erika; White, Anne

    2015-01-01

    The prevalence of obesity in adults and children has increased globally at an alarming rate. Mounting evidence from both epidemiological studies and animal models indicates that adult obesity and associated metabolic disorders can be programmed by intrauterine and early postnatal environment- a phenomenon known as “fetal programming of adult disease.” Data from nutritional intervention studies in animals including maternal under- and over-nutrition support the developmental origins of obesity and metabolic syndrome. The hypothalamic neuronal circuits located in the arcuate nucleus controlling appetite and energy expenditure are set early in life and are perturbed by maternal nutritional insults. In this review, we focus on the effects of maternal nutrition in programming permanent changes in these hypothalamic circuits, with experimental evidence from animal models of maternal under- and over-nutrition. We discuss the epigenetic modifications which regulate hypothalamic gene expression as potential molecular mechanisms linking maternal diet during pregnancy to the offspring's risk of obesity at a later age. Understanding these mechanisms in key metabolic genes may provide insights into the development of preventative intervention strategies. PMID:25954145

  16. Electromechanical millimotor

    DOEpatents

    Garcia, E.J.; Christenson, T.R.; Polosky, M.A.

    1999-06-29

    A millimeter-sized machine, including electromagnetic circuits adapted to convert electromagnetic energy to mechanical energy, for engaging and operating external mechanical loads. A plurality of millimeter-sized magnetic actuators operate out of phase with each other to control a plurality of millimeter-sized structural elements to drive an external mechanical load. Each actuator is connected to a link. Each link, in turn, is connected to a drive pinion at another similar pivoting joint. When the magnetic actuators are energized, each drive pinion is then capable of driving a larger output gear in gear-like fashion to produce positive torque about the drive pinion center at all angular positions of the output gear. 29 figs.

  17. Electromechanical millimotor

    DOEpatents

    Garcia, Ernest J.; Christenson, Todd R.; Polosky, Marc A.

    1999-01-01

    A millimeter-sized machine, including electromagnetic circuits adapted to convert electromagnetic energy to mechanical energy, for engaging and operating external mechanical loads. A plurality of millimeter-sized magnetic actuators operate out of phase with each other to control a plurality of millimeter-sized structural elements to drive an external mechanical load. Each actuator is connected to a link. Each link, in turn, is connected to a drive pinion at another similar pivoting joint. When the magnetic actuators are energized, each drive pinion is then capable of driving a larger output gear in gear-like fashion to produce positive torque about the drive pinion center at all angular positions of the output gear.

  18. The neuropsychology of self-reflection in psychiatric illness

    PubMed Central

    Philippi, Carissa L.; Koenigs, Michael

    2014-01-01

    The development of robust neuropsychological measures of social and affective function—which link critical dimensions of mental health to their underlying neural circuitry—could be a key step in achieving a more pathophysiologically-based approach to psychiatric medicine. In this article, we summarize research indicating that self-reflection (the inward attention to personal thoughts, memories, feelings, and actions) may be a useful model for developing such a paradigm, as there is evidence that self-reflection is (1) measurable with self-report scales and performance-based tests, (2) linked to the activity of a specific neural circuit, and (3) dimensionally related to mental health and various forms of psychopathology. PMID:24685311

  19. The latency validation of the optical link for the ATLAS Liquid Argon Calorimeter Phase-I trigger upgrade

    NASA Astrophysics Data System (ADS)

    Deng, B.; Xiao, L.; Zhao, X.; Baker, E.; Gong, D.; Guo, D.; He, H.; Hou, S.; Liu, C.; Liu, T.; Sun, Q.; Thomas, J.; Wang, J.; Xiang, A. C.; Yang, D.; Ye, J.; Zhou, W.

    2018-05-01

    Two optical data link data transmission Application Specific Integrated Circuits (ASICs), the baseline and its backup, have been designed for the ATLAS Liquid Argon (LAr) Calorimeter Phase-I trigger upgrade. The latency of each ASIC and that of its corresponding receiver implemented in a back-end Field-Programmable Gate Array (FPGA) are critical specifications. In this paper, we present the latency measurements and simulation of two ASICs. The measurement results indicate that both ASICs achieve their design goals and meet the latency specifications. The consistency between the simulation and measurements validates the ASIC latency characterization.

  20. Programmable genetic circuits for pathway engineering.

    PubMed

    Hoynes-O'Connor, Allison; Moon, Tae Seok

    2015-12-01

    Synthetic biology has the potential to provide decisive advances in genetic control of metabolic pathways. However, there are several challenges that synthetic biologists must overcome before this vision becomes a reality. First, a library of diverse and well-characterized sensors, such as metabolite-sensing or condition-sensing promoters, must be constructed. Second, robust programmable circuits that link input conditions with a specific gene regulation response must be developed. Finally, multi-gene targeting strategies must be integrated with metabolically relevant sensors and complex, robust logic. Achievements in each of these areas, which employ the CRISPR/Cas system, in silico modeling, and dynamic sensor-regulators, among other tools, provide a strong basis for future research. Overall, the future for synthetic biology approaches in metabolic engineering holds immense promise. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Axial Pump

    NASA Technical Reports Server (NTRS)

    Bozeman, Richard J., Jr. (Inventor); Akkerman, James W. (Inventor); Aber, Gregory S. (Inventor); VanDamm, George Arthur (Inventor); Bacak, James W. (Inventor); Svejkovsky, Paul A. (Inventor); Benkowski, Robert J. (Inventor)

    1997-01-01

    A rotary blood pump includes a pump housing for receiving a flow straightener, a rotor mounted on rotor bearings and having an inducer portion and an impeller portion, and a diffuser. The entrance angle, outlet angle, axial and radial clearances of blades associated with the flow straightener, inducer portion, impeller portion and diffuser are optimized to minimize hemolysis while maintaining pump efficiency. The rotor bearing includes a bearing chamber that is filled with cross-linked blood or other bio-compatible material. A back emf integrated circuit regulates rotor operation and a microcomputer may be used to control one or more back emf integrated circuits. A plurality of magnets are disposed in each of a plurality of impeller blades with a small air gap. A stator may be axially adjusted on the pump housing to absorb bearing load and maximize pump efficiency.

  2. Central nervous system mechanisms linking the consumption of palatable high-fat diets to the defense of greater adiposity.

    PubMed

    Ryan, Karen K; Woods, Stephen C; Seeley, Randy J

    2012-02-08

    The central nervous system (CNS) plays key role in the homeostatic regulation of body weight. Satiation and adiposity signals, providing acute and chronic information about available fuel, are produced in the periphery and act in the brain to influence energy intake and expenditure, resulting in the maintenance of stable adiposity. Diet-induced obesity (DIO) does not result from a failure of these central homeostatic circuits. Rather, the threshold for defended adiposity is increased in environments providing ubiquitous access to palatable, high-fat foods, making it difficult to achieve and maintain weight loss. Consequently, mechanisms by which nutritional environments interact with central homeostatic circuits to influence the threshold for defended adiposity represent critical targets for therapeutic intervention. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Capacitive proximity sensor

    DOEpatents

    Kronberg, J.W.

    1994-05-31

    A proximity sensor based on a closed field circuit is disclosed. The circuit comprises a ring oscillator using a symmetrical array of plates that creates an oscillating displacement current. The displacement current varies as a function of the proximity of objects to the plate array. Preferably the plates are in the form of a group of three pair of symmetric plates having a common center, arranged in a hexagonal pattern with opposing plates linked as a pair. The sensor produces logic level pulses suitable for interfacing with a computer or process controller. The proximity sensor can be incorporated into a load cell, a differential pressure gauge, or a device for measuring the consistency of a characteristic of a material where a variation in the consistency causes the dielectric constant of the material to change. 14 figs.

  4. Digital coincidence counting

    NASA Astrophysics Data System (ADS)

    Buckman, S. M.; Ius, D.

    1996-02-01

    This paper reports on the development of a digital coincidence-counting system which comprises a custom-built data acquisition card and associated PC software. The system has been designed to digitise the pulse-trains from two radiation detectors at a rate of 20 MSamples/s with 12-bit resolution. Through hardware compression of the data, the system can continuously record both individual pulse-shapes and the time intervals between pulses. Software-based circuits are used to process the stored pulse trains. These circuits are constructed simply by linking together icons representing various components such as coincidence mixers, time delays, single-channel analysers, deadtimes and scalers. This system enables a pair of pulse trains to be processed repeatedly using any number of different methods. Some preliminary results are presented in order to demonstrate the versatility and efficiency of this new method.

  5. A canonical neural mechanism for behavioral variability

    NASA Astrophysics Data System (ADS)

    Darshan, Ran; Wood, William E.; Peters, Susan; Leblois, Arthur; Hansel, David

    2017-05-01

    The ability to generate variable movements is essential for learning and adjusting complex behaviours. This variability has been linked to the temporal irregularity of neuronal activity in the central nervous system. However, how neuronal irregularity actually translates into behavioural variability is unclear. Here we combine modelling, electrophysiological and behavioural studies to address this issue. We demonstrate that a model circuit comprising topographically organized and strongly recurrent neural networks can autonomously generate irregular motor behaviours. Simultaneous recordings of neurons in singing finches reveal that neural correlations increase across the circuit driving song variability, in agreement with the model predictions. Analysing behavioural data, we find remarkable similarities in the babbling statistics of 5-6-month-old human infants and juveniles from three songbird species and show that our model naturally accounts for these `universal' statistics.

  6. Functional optical probing of the hippocampal trisynaptic circuit in vitro: network dynamics, filter properties, and polysynaptic induction of CA1 LTP.

    PubMed

    Stepan, Jens; Dine, Julien; Eder, Matthias

    2015-01-01

    Decades of brain research have identified various parallel loops linking the hippocampus with neocortical areas, enabling the acquisition of spatial and episodic memories. Especially the hippocampal trisynaptic circuit [entorhinal cortex layer II → dentate gyrus (DG) → cornu ammonis (CA)-3 → CA1] was studied in great detail because of its seemingly simple connectivity and characteristic structures that are experimentally well accessible. While numerous researchers focused on functional aspects, obtained from a limited number of cells in distinct hippocampal subregions, little is known about the neuronal network dynamics which drive information across multiple synapses for subsequent long-term storage. Fast voltage-sensitive dye imaging in vitro allows real-time recording of activity patterns in large/meso-scale neuronal networks with high spatial resolution. In this way, we recently found that entorhinal theta-frequency input to the DG most effectively passes filter mechanisms of the trisynaptic circuit network, generating activity waves which propagate across the entire DG-CA axis. These "trisynaptic circuit waves" involve high-frequency firing of CA3 pyramidal neurons, leading to a rapid induction of classical NMDA receptor-dependent long-term potentiation (LTP) at CA3-CA1 synapses (CA1 LTP). CA1 LTP has been substantially evidenced to be essential for some forms of explicit learning in mammals. Here, we review data with particular reference to whole network-level approaches, illustrating how activity propagation can take place within the trisynaptic circuit to drive formation of CA1 LTP.

  7. Linking local circuit inhibition to olfactory behavior: a critical role for granule cells in olfactory discrimination.

    PubMed

    Strowbridge, Ben W

    2010-02-11

    In this issue of Neuron, Abraham et al. report a direct connection between inhibitory function and olfactory behavior. Using molecular methods to alter glutamate receptor subunit composition in olfactory bulb granule cells, the authors found a selective modulation in the time required for difficult, but not simple, olfactory discrimination tasks. Copyright 2010 Elsevier Inc. All rights reserved.

  8. Determining Changes in Neural Circuits in Tuberous Sclerosis

    DTIC Science & Technology

    2013-05-01

    features of human Tuberous Sclerosis including mosaicism, autism and epilepsy. This research progress deepened our understanding of Tuberous Sclerosis by... autism and epilepsy. This research progress deepened our understanding of Tuberous Sclerosis by linking temporal gene function, mTOR function, physiology...of function of Tsc1 in the brain causes intellectual disability, seizures, sleep disorders, and autism . We took advantage of our CreER/loxP based

  9. Cryptanalysis of the Sodark Family of Cipher Algorithms

    DTIC Science & Technology

    2017-09-01

    software project for building three-bit LUT circuit representations of S- boxes is available as a GitHub repository [40]. It contains several improvements...DISTRIBUTION / AVAILABILITY STATEMENT Approved for public release. Distribution is unlimited. 12b. DISTRIBUTION CODE 13. ABSTRACT (maximum 200 words) The...second- and third-generation automatic link establishment (ALE) systems for high frequency radios. Radios utilizing ALE technology are in use by a

  10. Electromagnetic Compatibility in the Defense Systems of Future Years

    DTIC Science & Technology

    2002-06-01

    Technology activities. Its mission is to conduct and promote cooperative research and information exchange . The objective is to support the development...testing CLEARANCE PRODUCTION AND IN-SERVICE SUPPORT Modelling in support of conceptual design (structure & installation design) EMH Design guides for the... marketed by Advanced Electromagnetics [6-1]. Transmission Line Matrix Method The link between field theory and circuit theory, the major theories on

  11. Understanding the dynamical control of animal movement

    NASA Astrophysics Data System (ADS)

    Edwards, Donald

    2008-03-01

    Over the last 50 years, neurophysiologists have described many neural circuits that transform sensory input into motor commands, while biomechanicians and behavioral biologists have described many patterns of animal movement that occur in response to sensory input. Attempts to link these two have been frustrated by our technical inability to record from the necessary neurons in a freely behaving animal. As a result, we don't know how these neural circuits function in the closed loop context of free behavior, where the sensory and motor context changes on a millisecond time-scale. To address this problem, we have developed a software package, AnimatLab (www.AnimatLab.com), that enables users to reconstruct an animal's body and its relevant neural circuits, to link them at the sensory and motor ends, and through simulation, to test their ability to reproduce appropriate patterns of the animal's movements in a simulated Newtonian world. A Windows-based program, AnimatLab consists of a neural editor, a body editor, a world editor, stimulus and recording facilities, neural and physics engines, and an interactive 3-D graphical display. We have used AnimatLab to study three patterns of behavior: the grasshopper jump, crayfish escape, and crayfish leg movements used in postural control, walking, reaching and grasping. In each instance, the simulation helped identify constraints on both nervous function and biomechanical performance that have provided the basis for new experiments. Colleagues elsewhere have begun to use AnimatLab to study control of paw movements in cats and postural control in humans. We have also used AnimatLab simulations to guide the development of an autonomous hexapod robot in which the neural control circuitry is downloaded to the robot from the test computer.

  12. Effect of Joule heating and current crowding on electromigration in mobile technology

    NASA Astrophysics Data System (ADS)

    Tu, K. N.; Liu, Yingxia; Li, Menglu

    2017-03-01

    In the present era of big data and internet of things, the use of microelectronic products in all aspects of our life is manifested by the ubiquitous presence of mobile devices as i-phones and wearable i-products. These devices are facing the need for higher power and greater functionality applications such as in i-health, yet they are limited by physical size. At the moment, software (Apps) is much ahead of hardware in mobile technology. To advance hardware, the end of Moore's law in two-dimensional integrated circuits can be extended by three-dimensional integrated circuits (3D ICs). The concept of 3D ICs has been with us for more than ten years. The challenge in 3D IC technology is dense packing by using both vertical and horizontal interconnections. Mass production of 3D IC devices is behind schedule due to cost because of low yield and uncertain reliability. Joule heating is serious in a dense structure because of heat generation and dissipation. A change of reliability paradigm has advanced from failure at a specific circuit component to failure at a system level weak-link. Currently, the electronic industry is introducing 3D IC devices in mainframe computers, where cost is not an issue, for the purpose of collecting field data of failure, especially the effect of Joule heating and current crowding on electromigration. This review will concentrate on the positive feedback between Joule heating and electromigration, resulting in an accelerated system level weak-link failure. A new driving force of electromigration, the electric potential gradient force due to current crowding, will be reviewed critically. The induced failure tends to occur in the low current density region.

  13. Bi-Directional Theta Modulation between the Septo-Hippocampal System and the Mammillary Area in Free-Moving Rats

    PubMed Central

    Ruan, Ming; Young, Calvin K.; McNaughton, Neil

    2017-01-01

    Hippocampal (HPC) theta oscillations have long been linked to various functions of the brain. Many cortical and subcortical areas that also exhibit theta oscillations have been linked to functional circuits with the hippocampus on the basis of coupled activities at theta frequencies. We examine, in freely moving rats, the characteristics of diencephalic theta local field potentials (LFPs) recorded in the supramammillary/mammillary (SuM/MM) areas that are bi-directionally connected to the HPC through the septal complex. Using partial directed coherence (PDC), we find support for previous suggestions that SuM modulates HPC theta at higher frequencies. We find weak separation of SuM and MM by dominant theta frequency recorded locally. Contrary to oscillatory cell activities under anesthesia where SuM is insensitive, but MM is sensitive to medial septal (MS) inactivation, theta LFPs persisted and became indistinguishable after MS-inactivation. However, MS-inactivation attenuated SuM/MM theta power, while increasing the frequency of SuM/MM theta. MS-inactivation also reduced root mean squared power in both HPC and SuM/MM equally, but reduced theta power differentially in the time domain. We provide converging evidence that SuM is preferentially involved in coding HPC theta at higher frequencies, and that the MS-HPC circuit normally imposes a frequency-limiting modulation over the SuM/MM area as suggested by cell-based recordings in anesthetized animals. In addition, we provide evidence that the postulated SuM-MS-HPC-MM circuit is under complex bi-directional control, rather than SuM and MM having roles as unidirectional relays in the network. PMID:28955209

  14. Cullin-4 regulates Wingless and JNK signaling-mediated cell death in the Drosophila eye

    PubMed Central

    Tare, Meghana; Sarkar, Ankita; Bedi, Shimpi; Kango-Singh, Madhuri; Singh, Amit

    2016-01-01

    In all multicellular organisms, the fundamental processes of cell proliferation and cell death are crucial for growth regulation during organogenesis. Strict regulation of cell death is important to maintain tissue homeostasis by affecting processes like regulation of cell number, and elimination of unwanted/unfit cells. The developing Drosophila eye is a versatile model to study patterning and growth, where complex signaling pathways regulate growth and cell survival. However, the molecular mechanisms underlying regulation of these processes is not fully understood. In a gain-of-function screen, we found that misexpression of cullin-4 (cul-4), an ubiquitin ligase, can rescue reduced eye mutant phenotypes. Previously, cul-4 has been shown to regulate chromatin remodeling, cell cycle and cell division. Genetic characterization of cul-4 in the developing eye revealed that loss-of-function of cul-4 exhibits a reduced eye phenotype. Analysis of twin-spots showed that in comparison with their wild-type counterparts, the cul-4 loss-of-function clones fail to survive. Here we show that cul-4 clones are eliminated by induction of cell death due to activation of caspases. Aberrant activation of signaling pathways is known to trigger cell death in the developing eye. We found that Wingless (Wg) and c-Jun-amino-terminal-(NH2)-Kinase (JNK) signaling are ectopically induced in cul-4 mutant clones, and these signals co-localize with the dying cells. Modulating levels of Wg and JNK signaling by using agonists and antagonists of these pathways demonstrated that activation of Wg and JNK signaling enhances cul-4 mutant phenotype, whereas downregulation of Wg and JNK signaling rescues the cul-4 mutant phenotypes of reduced eye. Here we present evidences to demonstrate that cul-4 is involved in restricting Wg signaling and downregulation of JNK signaling-mediated cell death during early eye development. Overall, our studies provide insights into a novel role of cul-4 in promoting cell survival in the developing Drosophila eye. PMID:28032862

  15. A network model of behavioural performance in a rule learning task.

    PubMed

    Hasselmo, Michael E; Stern, Chantal E

    2018-04-19

    Humans demonstrate differences in performance on cognitive rule learning tasks which could involve differences in properties of neural circuits. An example model is presented to show how gating of the spread of neural activity could underlie rule learning and the generalization of rules to previously unseen stimuli. This model uses the activity of gating units to regulate the pattern of connectivity between neurons responding to sensory input and subsequent gating units or output units. This model allows analysis of network parameters that could contribute to differences in cognitive rule learning. These network parameters include differences in the parameters of synaptic modification and presynaptic inhibition of synaptic transmission that could be regulated by neuromodulatory influences on neural circuits. Neuromodulatory receptors play an important role in cognitive function, as demonstrated by the fact that drugs that block cholinergic muscarinic receptors can cause cognitive impairments. In discussions of the links between neuromodulatory systems and biologically based traits, the issue of mechanisms through which these linkages are realized is often missing. This model demonstrates potential roles of neural circuit parameters regulated by acetylcholine in learning context-dependent rules, and demonstrates the potential contribution of variation in neural circuit properties and neuromodulatory function to individual differences in cognitive function.This article is part of the theme issue 'Diverse perspectives on diversity: multi-disciplinary approaches to taxonomies of individual differences'. © 2018 The Author(s).

  16. Dopamine modulation of emotional processing in cortical and subcortical neural circuits: evidence for a final common pathway in schizophrenia?

    PubMed

    Laviolette, Steven R

    2007-07-01

    The neural regulation of emotional perception, learning, and memory is essential for normal behavioral and cognitive functioning. Many of the symptoms displayed by individuals with schizophrenia may arise from fundamental disturbances in the ability to accurately process emotionally salient sensory information. The neurotransmitter dopamine (DA) and its ability to modulate neural regions involved in emotional learning, perception, and memory formation has received considerable research attention as a potential final common pathway to account for the aberrant emotional regulation and psychosis present in the schizophrenic syndrome. Evidence from both human neuroimaging studies and animal-based research using neurodevelopmental, behavioral, and electrophysiological techniques have implicated the mesocorticolimbic DA circuit as a crucial system for the encoding and expression of emotionally salient learning and memory formation. While many theories have examined the cortical-subcortical interactions between prefrontal cortical regions and subcortical DA substrates, many questions remain as to how DA may control emotional perception and learning and how disturbances linked to DA abnormalities may underlie the disturbed emotional processing in schizophrenia. Beyond the mesolimbic DA system, increasing evidence points to the amygdala-prefrontal cortical circuit as an important processor of emotionally salient information and how neurodevelopmental perturbances within this circuitry may lead to dysregulation of DAergic modulation of emotional processing and learning along this cortical-subcortical emotional processing circuit.

  17. Repetitive behaviors in autism are linked to imbalance of corticostriatal connectivity: a functional connectivity MRI study.

    PubMed

    Abbott, Angela E; Linke, Annika C; Nair, Aarti; Jahedi, Afrooz; Alba, Laura A; Keown, Christopher L; Fishman, Inna; Müller, Ralph-Axel

    2018-01-01

    The neural underpinnings of repetitive behaviors (RBs) in autism spectrum disorders (ASDs), ranging from cognitive to motor characteristics, remain unknown. We assessed RB symptomatology in 50 ASD and 52 typically developing (TD) children and adolescents (ages 8-17 years), examining intrinsic functional connectivity (iFC) of corticostriatal circuitry, which is important for reward-based learning and integration of emotional, cognitive and motor processing, and considered impaired in ASDs. Connectivity analyses were performed for three functionally distinct striatal seeds (limbic, frontoparietal and motor). Functional connectivity with cortical regions of interest was assessed for corticostriatal circuit connectivity indices and ratios, testing the balance of connectivity between circuits. Results showed corticostriatal overconnectivity of limbic and frontoparietal seeds, but underconnectivity of motor seeds. Correlations with RBs were found for connectivity between the striatal motor seeds and cortical motor clusters from the whole-brain analysis, and for frontoparietal/limbic and motor/limbic connectivity ratios. Division of ASD participants into high (n = 17) and low RB subgroups (n = 19) showed reduced frontoparietal/limbic and motor/limbic circuit ratios for high RB compared to low RB and TD groups in the right hemisphere. Results suggest an association between RBs and an imbalance of corticostriatal iFC in ASD, being increased for limbic, but reduced for frontoparietal and motor circuits. © The Author (2017). Published by Oxford University Press.

  18. Repetitive behaviors in autism are linked to imbalance of corticostriatal connectivity: a functional connectivity MRI study

    PubMed Central

    Abbott, Angela E; Linke, Annika C; Nair, Aarti; Jahedi, Afrooz; Alba, Laura A; Keown, Christopher L; Fishman, Inna

    2018-01-01

    Abstract The neural underpinnings of repetitive behaviors (RBs) in autism spectrum disorders (ASDs), ranging from cognitive to motor characteristics, remain unknown. We assessed RB symptomatology in 50 ASD and 52 typically developing (TD) children and adolescents (ages 8–17 years), examining intrinsic functional connectivity (iFC) of corticostriatal circuitry, which is important for reward-based learning and integration of emotional, cognitive and motor processing, and considered impaired in ASDs. Connectivity analyses were performed for three functionally distinct striatal seeds (limbic, frontoparietal and motor). Functional connectivity with cortical regions of interest was assessed for corticostriatal circuit connectivity indices and ratios, testing the balance of connectivity between circuits. Results showed corticostriatal overconnectivity of limbic and frontoparietal seeds, but underconnectivity of motor seeds. Correlations with RBs were found for connectivity between the striatal motor seeds and cortical motor clusters from the whole-brain analysis, and for frontoparietal/limbic and motor/limbic connectivity ratios. Division of ASD participants into high (n = 17) and low RB subgroups (n = 19) showed reduced frontoparietal/limbic and motor/limbic circuit ratios for high RB compared to low RB and TD groups in the right hemisphere. Results suggest an association between RBs and an imbalance of corticostriatal iFC in ASD, being increased for limbic, but reduced for frontoparietal and motor circuits. PMID:29177509

  19. Pyruvate dehydrogenase complex and nicotinamide nucleotide transhydrogenase constitute an energy consuming redox circuit

    PubMed Central

    Fisher-Wellman, Kelsey H.; Lin, Chien-Te; Ryan, Terence E.; Reese, Lauren R.; Gilliam, Laura A. A.; Cathey, Brook L.; Lark, Daniel S.; Smith, Cody D.; Muoio, Deborah M.; Neufer, P. Darrell

    2015-01-01

    SUMMARY Cellular proteins rely on reversible redox reactions to establish and maintain biological structure and function. How redox catabolic (NAD+:NADH) and anabolic (NADP+:NADPH) processes integrate during metabolism to maintain cellular redox homeostasis however is unknown. The present work identifies a continuously cycling, mitochondrial membrane potential-dependent redox circuit between the pyruvate dehydrogenase complex (PDHC) and nicotinamide nucleotide transhydrogenase (NNT). PDHC is shown to produce H2O2 in relation to reducing pressure within the complex. The H2O2 produced however is effectively masked by a continuously cycling redox circuit that links, via glutathione/thioredoxin, to NNT, which catalyzes the regeneration of NADPH from NADH at the expense of the mitochondrial membrane potential. The net effect is an automatic fine tuning of NNT-mediated energy expenditure to metabolic balance at the level of PDHC. In mitochondria, genetic or pharmacological disruptions in the PDHC-NNT redox circuit negate counterbalance changes in energy expenditure. At the whole animal level, mice lacking functional NNT (C57BL/6J) are characterized by lower energy expenditure rates, consistent with their well known susceptibility to diet-induced obesity. These findings suggest the integration of redox sensing of metabolic balance with compensatory changes in energy expenditure provides a potential mechanism by which cellular redox homeostasis is maintained and body weight is defended during periods of positive and negative energy balance. PMID:25643703

  20. Magnetic Random Access Memory based non-volatile asynchronous Muller cell for ultra-low power autonomous applications

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

    Di Pendina, G., E-mail: gregory.dipendina@cea.fr, E-mail: eldar.zianbetov@cea.fr, E-mail: edith.beigne@cea.fr; Zianbetov, E., E-mail: gregory.dipendina@cea.fr, E-mail: eldar.zianbetov@cea.fr, E-mail: edith.beigne@cea.fr; CNRS, SPINTEC, F-38000 Grenoble

    2015-05-07

    Micro and nano electronic integrated circuit domain is today mainly driven by the advent of the Internet of Things for which the constraints are strong, especially in terms of power consumption and autonomy, not only during the computing phases but also during the standby or idle phases. In such ultra-low power applications, the circuit has to meet new constraints mainly linked to its changing energetic environment: long idle phases, automatic wake up, data back-up when the circuit is sporadically turned off, and ultra-low voltage power supply operation. Such circuits have to be completely autonomous regarding their unstable environment, while remainingmore » in an optimum energetic configuration. Therefore, we propose in this paper the first MRAM-based non-volatile asynchronous Muller cell. This cell has been simulated and characterized in a very advanced 28 nm CMOS fully depleted silicon-on-insulator technology, presenting good power performance results due to an extremely efficient body biasing control together with ultra-wide supply voltage range from 160 mV up to 920 mV. The leakage current can be reduced to 154 pA thanks to reverse body biasing. We also propose an efficient standard CMOS bulk version of this cell in order to be compatible with different fabrication processes.« less

  1. Multi-objective optimization of MOSFETs channel widths and supply voltage in the proposed dual edge-triggered static D flip-flop with minimum average power and delay by using fuzzy non-dominated sorting genetic algorithm-II.

    PubMed

    Keivanian, Farshid; Mehrshad, Nasser; Bijari, Abolfazl

    2016-01-01

    D Flip-Flop as a digital circuit can be used as a timing element in many sophisticated circuits. Therefore the optimum performance with the lowest power consumption and acceptable delay time will be critical issue in electronics circuits. The newly proposed Dual-Edge Triggered Static D Flip-Flop circuit layout is defined as a multi-objective optimization problem. For this, an optimum fuzzy inference system with fuzzy rules is proposed to enhance the performance and convergence of non-dominated sorting Genetic Algorithm-II by adaptive control of the exploration and exploitation parameters. By using proposed Fuzzy NSGA-II algorithm, the more optimum values for MOSFET channel widths and power supply are discovered in search space than ordinary NSGA types. What is more, the design parameters involving NMOS and PMOS channel widths and power supply voltage and the performance parameters including average power consumption and propagation delay time are linked. To do this, the required mathematical backgrounds are presented in this study. The optimum values for the design parameters of MOSFETs channel widths and power supply are discovered. Based on them the power delay product quantity (PDP) is 6.32 PJ at 125 MHz Clock Frequency, L = 0.18 µm, and T = 27 °C.

  2. A programmable microsystem using system-on-chip for real-time biotelemetry.

    PubMed

    Wang, Lei; Johannessen, Erik A; Hammond, Paul A; Cui, Li; Reid, Stuart W J; Cooper, Jonathan M; Cumming, David R S

    2005-07-01

    A telemetry microsystem, including multiple sensors, integrated instrumentation and a wireless interface has been implemented. We have employed a methodology akin to that for System-on-Chip microelectronics to design an integrated circuit instrument containing several "intellectual property" blocks that will enable convenient reuse of modules in future projects. The present system was optimized for low-power and included mixed-signal sensor circuits, a programmable digital system, a feedback clock control loop and RF circuits integrated on a 5 mm x 5 mm silicon chip using a 0.6 microm, 3.3 V CMOS process. Undesirable signal coupling between circuit components has been investigated and current injection into sensitive instrumentation nodes was minimized by careful floor-planning. The chip, the sensors, a magnetic induction-based transmitter and two silver oxide cells were packaged into a 36 mm x 12 mm capsule format. A base station was built in order to retrieve the data from the microsystem in real-time. The base station was designed to be adaptive and timing tolerant since the microsystem design was simplified to reduce power consumption and size. The telemetry system was found to have a packet error rate of 10(-3) using an asynchronous simplex link. Trials in animal carcasses were carried out to show that the transmitter was as effective as a conventional RF device whilst consuming less power.

  3. Pyruvate dehydrogenase complex and nicotinamide nucleotide transhydrogenase constitute an energy-consuming redox circuit.

    PubMed

    Fisher-Wellman, Kelsey H; Lin, Chien-Te; Ryan, Terence E; Reese, Lauren R; Gilliam, Laura A A; Cathey, Brook L; Lark, Daniel S; Smith, Cody D; Muoio, Deborah M; Neufer, P Darrell

    2015-04-15

    Cellular proteins rely on reversible redox reactions to establish and maintain biological structure and function. How redox catabolic (NAD+/NADH) and anabolic (NADP+/NADPH) processes integrate during metabolism to maintain cellular redox homoeostasis, however, is unknown. The present work identifies a continuously cycling mitochondrial membrane potential (ΔΨm)-dependent redox circuit between the pyruvate dehydrogenase complex (PDHC) and nicotinamide nucleotide transhydrogenase (NNT). PDHC is shown to produce H2O2 in relation to reducing pressure within the complex. The H2O2 produced, however, is effectively masked by a continuously cycling redox circuit that links, via glutathione/thioredoxin, to NNT, which catalyses the regeneration of NADPH from NADH at the expense of ΔΨm. The net effect is an automatic fine-tuning of NNT-mediated energy expenditure to metabolic balance at the level of PDHC. In mitochondria, genetic or pharmacological disruptions in the PDHC-NNT redox circuit negate counterbalance changes in energy expenditure. At the whole animal level, mice lacking functional NNT (C57BL/6J) are characterized by lower energy-expenditure rates, consistent with their well-known susceptibility to diet-induced obesity. These findings suggest the integration of redox sensing of metabolic balance with compensatory changes in energy expenditure provides a potential mechanism by which cellular redox homoeostasis is maintained and body weight is defended during periods of positive and negative energy balance.

  4. Maximum efficiency of state-space models of nanoscale energy conversion devices

    NASA Astrophysics Data System (ADS)

    Einax, Mario; Nitzan, Abraham

    2016-07-01

    The performance of nano-scale energy conversion devices is studied in the framework of state-space models where a device is described by a graph comprising states and transitions between them represented by nodes and links, respectively. Particular segments of this network represent input (driving) and output processes whose properly chosen flux ratio provides the energy conversion efficiency. Simple cyclical graphs yield Carnot efficiency for the maximum conversion yield. We give general proof that opening a link that separate between the two driving segments always leads to reduced efficiency. We illustrate these general result with simple models of a thermoelectric nanodevice and an organic photovoltaic cell. In the latter an intersecting link of the above type corresponds to non-radiative carriers recombination and the reduced maximum efficiency is manifested as a smaller open-circuit voltage.

  5. Maximum efficiency of state-space models of nanoscale energy conversion devices.

    PubMed

    Einax, Mario; Nitzan, Abraham

    2016-07-07

    The performance of nano-scale energy conversion devices is studied in the framework of state-space models where a device is described by a graph comprising states and transitions between them represented by nodes and links, respectively. Particular segments of this network represent input (driving) and output processes whose properly chosen flux ratio provides the energy conversion efficiency. Simple cyclical graphs yield Carnot efficiency for the maximum conversion yield. We give general proof that opening a link that separate between the two driving segments always leads to reduced efficiency. We illustrate these general result with simple models of a thermoelectric nanodevice and an organic photovoltaic cell. In the latter an intersecting link of the above type corresponds to non-radiative carriers recombination and the reduced maximum efficiency is manifested as a smaller open-circuit voltage.

  6. Monolithic Microwave Integrated Circuit (MMIC) Phased Array Demonstrated With ACTS

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Monolithic Microwave Integrated Circuit (MMIC) arrays developed by the NASA Lewis Research Center and the Air Force Rome Laboratory were demonstrated in aeronautical terminals and in mobile or fixed Earth terminals linked with NASA's Advanced Communications Technology Satellite (ACTS). Four K/Ka-band experimental arrays were demonstrated between May 1994 and May 1995. Each array had GaAs MMIC devices at each radiating element for electronic beam steering and distributed power amplification. The 30-GHz transmit array used in uplinks to ACTS was developed by Lewis and Texas Instruments. The three 20-GHz receive arrays used in downlinks from ACTS were developed in cooperation with the Air Force Rome Laboratory, taking advantage of existing Air Force integrated-circuit, active-phased-array development contracts with the Boeing Company and Lockheed Martin Corporation. Four demonstrations, each related to an application of high interest to both commercial and Department of Defense organizations, were conducted. The location, type of link, and the data rate achieved for each of the applications is shown. In one demonstration-- an aeronautical terminal experiment called AERO-X--a duplex voice link between an aeronautical terminal on the Lewis Learjet and ACTS was achieved. Two others demonstrated duplex voice links (and in one case, interactive video links as well) between ACTS and an Army high-mobility, multipurpose wheeled vehicle (HMMWV, or "humvee"). In the fourth demonstration, the array was on a fixed mount and was electronically steered toward ACTS. Lewis served as project manager for all demonstrations and as overall system integrator. Lewis engineers developed the array system including a controller for open-loop tracking of ACTS during flight and HMMWV motion, as well as a laptop data display and recording system used in all demonstrations. The Jet Propulsion Laboratory supported the AERO-X program, providing elements of the ACTS Mobile Terminal. The successful performance of experimental, proof-of-concept MMIC K/Ka-band arrays developed with U.S. industry in field demonstrations with ACTS indicates that high density MMIC integration at 20 and 30 GHz is indeed feasible. The successful development and demonstration of the MMIC array systems was possible only because of significant intergovernmental and Government/industry cooperation and the high level of teamwork within Lewis. The results provide a strong incentive for continuing the focused development of MMIC-array technology for satellite communications applications, with emphasis on packaging and cost issues, and for continuing the planning and conducting of other appropriate demonstrations or experiments of phased-array technology with ACTS. Given the present pressures on reducing funding for research and development in Government and industry, the extent to which this can be continued in a cooperative manner will determine whether MMIC array technology will make the transition from the proof-of-concept level to the operational system level.

  7. Carotid chemoreceptors tune breathing via multipath routing: reticular chain and loop operations supported by parallel spike train correlations.

    PubMed

    Morris, Kendall F; Nuding, Sarah C; Segers, Lauren S; Iceman, Kimberly E; O'Connor, Russell; Dean, Jay B; Ott, Mackenzie M; Alencar, Pierina A; Shuman, Dale; Horton, Kofi-Kermit; Taylor-Clark, Thomas E; Bolser, Donald C; Lindsey, Bruce G

    2018-02-01

    We tested the hypothesis that carotid chemoreceptors tune breathing through parallel circuit paths that target distinct elements of an inspiratory neuron chain in the ventral respiratory column (VRC). Microelectrode arrays were used to monitor neuronal spike trains simultaneously in the VRC, peri-nucleus tractus solitarius (p-NTS)-medial medulla, the dorsal parafacial region of the lateral tegmental field (FTL-pF), and medullary raphe nuclei together with phrenic nerve activity during selective stimulation of carotid chemoreceptors or transient hypoxia in 19 decerebrate, neuromuscularly blocked, and artificially ventilated cats. Of 994 neurons tested, 56% had a significant change in firing rate. A total of 33,422 cell pairs were evaluated for signs of functional interaction; 63% of chemoresponsive neurons were elements of at least one pair with correlational signatures indicative of paucisynaptic relationships. We detected evidence for postinspiratory neuron inhibition of rostral VRC I-Driver (pre-Bötzinger) neurons, an interaction predicted to modulate breathing frequency, and for reciprocal excitation between chemoresponsive p-NTS neurons and more downstream VRC inspiratory neurons for control of breathing depth. Chemoresponsive pericolumnar tonic expiratory neurons, proposed to amplify inspiratory drive by disinhibition, were correlationally linked to afferent and efferent "chains" of chemoresponsive neurons extending to all monitored regions. The chains included coordinated clusters of chemoresponsive FTL-pF neurons with functional links to widespread medullary sites involved in the control of breathing. The results support long-standing concepts on brain stem network architecture and a circuit model for peripheral chemoreceptor modulation of breathing with multiple circuit loops and chains tuned by tegmental field neurons with quasi-periodic discharge patterns. NEW & NOTEWORTHY We tested the long-standing hypothesis that carotid chemoreceptors tune the frequency and depth of breathing through parallel circuit operations targeting the ventral respiratory column. Responses to stimulation of the chemoreceptors and identified functional connectivity support differential tuning of inspiratory neuron burst duration and firing rate and a model of brain stem network architecture incorporating tonic expiratory "hub" neurons regulated by convergent neuronal chains and loops through rostral lateral tegmental field neurons with quasi-periodic discharge patterns.

  8. Development of superconducting links for the Large Hadron Collider machine

    NASA Astrophysics Data System (ADS)

    Ballarino, Amalia

    2014-04-01

    In the framework of the upgrade of the Large Hadron Collider (LHC) machine, new superconducting lines are being developed for the feeding of the LHC magnets. The proposed electrical layout envisages the location of the power converters in surface buildings, and the transfer of the current from the surface to the LHC tunnel, where the magnets are located, via superconducting links containing tens of cables feeding different circuits and transferring altogether more than 150 kA. Depending on the location, the links will have a length ranging from 300 m to 500 m, and they will span a vertical distance of about 80 m. An overview of the R&D program that has been launched by CERN is presented, with special attention to the development of novel types of cables made from MgB2 and high temperature superconductors (Bi-2223 and REBCO) and to the results of the tests performed on prototype links. Plans for future activities are presented, together with a timeline for potential future integration in the LHC machine.

  9. A data-driven network model of primary myelofibrosis: transcriptional and post-transcriptional alterations in CD34+ cells.

    PubMed

    Calura, E; Pizzini, S; Bisognin, A; Coppe, A; Sales, G; Gaffo, E; Fanelli, T; Mannarelli, C; Zini, R; Norfo, R; Pennucci, V; Manfredini, R; Romualdi, C; Guglielmelli, P; Vannucchi, A M; Bortoluzzi, S

    2016-06-24

    microRNAs (miRNAs) are relevant in the pathogenesis of primary myelofibrosis (PMF) but our understanding is limited to specific target genes and the overall systemic scenario islacking. By both knowledge-based and ab initio approaches for comparative analysis of CD34+ cells of PMF patients and healthy controls, we identified the deregulated pathways involving miRNAs and genes and new transcriptional and post-transcriptional regulatory circuits in PMF cells. These converge in a unique and integrated cellular process, in which the role of specific miRNAs is to wire, co-regulate and allow a fine crosstalk between the involved processes. The PMF pathway includes Akt signaling, linked to Rho GTPases, CDC42, PLD2, PTEN crosstalk with the hypoxia response and Calcium-linked cellular processes connected to cyclic AMP signaling. Nested on the depicted transcriptional scenario, predicted circuits are reported, opening new hypotheses. Links between miRNAs (miR-106a-5p, miR-20b-5p, miR-20a-5p, miR-17-5p, miR-19b-3p and let-7d-5p) and key transcription factors (MYCN, ATF, CEBPA, REL, IRF and FOXJ2) and their common target genes tantalizingly suggest new path to approach the disease. The study provides a global overview of transcriptional and post-transcriptional deregulations in PMF, and, unifying consolidated and predicted data, could be helpful to identify new combinatorial therapeutic strategy. Interactive PMF network model: http://compgen.bio.unipd.it/pmf-net/.

  10. Phylogenetic placement of the Pacific Northwest subterranean endemic diving beetle Stygoporus oregonensis Larson & LaBonte (Dytiscidae, Hydroporinae)

    PubMed Central

    Kanda, Kojun; Gomez, R. Antonio; Van Driesche, Richard; Miller, Kelly B.; Maddison, David R.

    2016-01-01

    Abstract Stygoporus oregonensis Larson & LaBonte is a little-known subterranean diving beetle, which, until recently, had not been collected since the type series was taken from a shallow well in western Oregon, USA, in 1984. Here we report the discovery of additional specimens collected from a nearby well in the Willamette Valley. Sequence data from four mitochondrial genes, wingless, and histone III place Stygoporus Larson & LaBonte in the predominantly Mediterranean subtribe Siettitiina of the Hydroporini. Morphological support for these results is discussed, and details of the collecting circumstances of the new specimens are presented. We argue that the biogeographic patterns of Nearctic Siettitiina highlight the likelihood of additional undiscovered subterranean dytiscids in North America. PMID:27920606

  11. Isolation of a novel orthobunyavirus from bat flies (Eucampsipoda africana)

    PubMed Central

    Palacios, Gustavo; Storm, Nadia; Markotter, Wanda; Birkhead, Monica; Kemp, Alan

    2017-01-01

    The Bunyaviridae family comprises viruses causing diseases of public and veterinary health importance, including viral haemorrhagic and arboviral fevers. We report the isolation, identification and genome characterization of a novel orthobunyavirus, named Wolkberg virus (WBV), from wingless bat fly ectoparasites (Eucampsipoda africana) of Egyptian fruit bats (Rousettus aegyptiacus) in South Africa. Complete genome sequence data of WBV suggests it is most closely related to two bat viruses (Mojuí dos Campos and Kaeng Khoi viruses) and an arbovirus (Nyando virus) previously shown to infect humans. WBV replicates to high titres in VeroE6 and C6-36 cells, characteristic of mosquito-borne arboviruses. These findings expand our knowledge of the diversity of orthobunyaviruses and their insect vector host range. PMID:28488954

  12. The deployable, inflatable wing technology demonstrator experiment aircraft looks good during a flig

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The deployable, inflatable wing technology demonstrator experiment aircraft looks good during a flight conducted by the NASA Dryden Flight Research Center, Edwards, California. The inflatable wing project represented a basic flight research effort by Dryden personnel. Three successful flights of the I2000 inflatable wing aircraft occurred. During the flights, the team air-launched the radio-controlled (R/C) I2000 from an R/C utility airplane at an altitude of 800-1000 feet. As the I2000 separated from the carrier aircraft, its inflatable wings 'popped-out,' deploying rapidly via an on-board nitrogen bottle. The aircraft remained stable as it transitioned from wingless to winged flight. The unpowered I2000 glided down to a smooth landing under complete control.

  13. Composite embedded fiber optic data links in Standard Electronic Modules

    NASA Astrophysics Data System (ADS)

    Ehlers, S. L.; Jones, K. J.; Morgan, R. E.; Hixson, Jay

    1990-12-01

    The goal of this project is to fabricate a chassis/circuit card demonstration entirely 'wired' with embedded and interconnected optical fibers. Graphite/epoxy Standard Electronic Module E (SEM-E) configured panels have been successfully fabricated. Fiber-embedded SEM-E configured panels have been subjected to simultaneous signal transmission and vibration testing. Packaging constraints will require tapping composite-embedded optical fibers at right angles to the direction of optical transmission.

  14. Rotary Blood Pump

    NASA Technical Reports Server (NTRS)

    Bozeman, Richard J., Jr. (Inventor); Akkerman, James W. (Inventor); Aber, Gregory S. (Inventor); VanDamm, George A. (Inventor); Bacak, James W. (Inventor); Svejkovsky, Paul A. (Inventor); Benkowski, Robert J. (Inventor)

    1996-01-01

    A rotary blood pump includes a pump housing for receiving a flow straightener, a rotor mounted on rotor bearings and having an inducer portion and an impeller portion, and a diffuser. The entrance angle, outlet angle, axial and radial clearances of blades associated with the flow straightener, inducer portion, impeller portion and diffuser are optimized to minimize hemolysis while maintaining pump efficiency. The rotor bearing includes a bearing chamber that is filled with cross-linked blood or other bio-compatible material. A back emf integrated circuit regulates rotor operation and a microcomputer may be used to control one or more back emf integrated circuits. A plurality of magnets are disposed in each of a plurality of impeller blades with a small air gap. A stator may be axially adjusted on the pump housing to absorb bearing load and maximize pump efficiency.

  15. A canonical neural mechanism for behavioral variability

    PubMed Central

    Darshan, Ran; Wood, William E.; Peters, Susan; Leblois, Arthur; Hansel, David

    2017-01-01

    The ability to generate variable movements is essential for learning and adjusting complex behaviours. This variability has been linked to the temporal irregularity of neuronal activity in the central nervous system. However, how neuronal irregularity actually translates into behavioural variability is unclear. Here we combine modelling, electrophysiological and behavioural studies to address this issue. We demonstrate that a model circuit comprising topographically organized and strongly recurrent neural networks can autonomously generate irregular motor behaviours. Simultaneous recordings of neurons in singing finches reveal that neural correlations increase across the circuit driving song variability, in agreement with the model predictions. Analysing behavioural data, we find remarkable similarities in the babbling statistics of 5–6-month-old human infants and juveniles from three songbird species and show that our model naturally accounts for these ‘universal' statistics. PMID:28530225

  16. The neural basis of financial risk taking.

    PubMed

    Kuhnen, Camelia M; Knutson, Brian

    2005-09-01

    Investors systematically deviate from rationality when making financial decisions, yet the mechanisms responsible for these deviations have not been identified. Using event-related fMRI, we examined whether anticipatory neural activity would predict optimal and suboptimal choices in a financial decision-making task. We characterized two types of deviations from the optimal investment strategy of a rational risk-neutral agent as risk-seeking mistakes and risk-aversion mistakes. Nucleus accumbens activation preceded risky choices as well as risk-seeking mistakes, while anterior insula activation preceded riskless choices as well as risk-aversion mistakes. These findings suggest that distinct neural circuits linked to anticipatory affect promote different types of financial choices and indicate that excessive activation of these circuits may lead to investing mistakes. Thus, consideration of anticipatory neural mechanisms may add predictive power to the rational actor model of economic decision making.

  17. Electro-optical co-simulation for integrated CMOS photonic circuits with VerilogA.

    PubMed

    Sorace-Agaskar, Cheryl; Leu, Jonathan; Watts, Michael R; Stojanovic, Vladimir

    2015-10-19

    We present a Cadence toolkit library written in VerilogA for simulation of electro-optical systems. We have identified and described a set of fundamental photonic components at the physical level such that characteristics of composite devices (e.g. ring modulators) are created organically - by simple instantiation of fundamental primitives. Both the amplitude and phase of optical signals as well as optical-electrical interactions are simulated. We show that the results match other simulations and analytic solutions that have previously been compared to theory for both simple devices, such as ring resonators, and more complicated devices and systems such as single-sideband modulators, WDM links and Pound Drever Hall Locking loops. We also illustrate the capability of such toolkit for co-simulation with electronic circuits, which is a key enabler of the electro-optic system development and verification.

  18. Infrared readout electronics; Proceedings of the Meeting, Orlando, FL, Apr. 21, 22, 1992

    NASA Technical Reports Server (NTRS)

    Fossum, Eric R. (Editor)

    1992-01-01

    The present volume on IR readout electronics discusses cryogenic readout using silicon devices, cryogenic readout using III-V and LTS devices, multiplexers for higher temperatures, and focal-plane signal processing electronics. Attention is given to the optimization of cryogenic CMOS processes for sub-10-K applications, cryogenic measurements of aerojet GaAs n-JFETs, inP-based heterostructure device technology for ultracold readout applications, and a three-terminal semiconductor-superconductor transimpedance amplifier. Topics addressed include unfulfilled needs in IR astronomy focal-plane readout electronics, IR readout integrated circuit technology for tactical missile systems, and radiation-hardened 10-bit A/D for FPA signal processing. Also discussed are the implementation of a noise reduction circuit for spaceflight IR spectrometers, a real-time processor for staring receivers, and a fiber-optic link design for INMOS transputers.

  19. Assessment of satellite communications quality study. Addendum 1: Impact of propagation delay on data transmission

    NASA Technical Reports Server (NTRS)

    Campanella, S. J.; Chitre, D. M.

    1988-01-01

    The single factor that irrevocably distinguishes geostationary satellite telephony transmission from terrestrial transmission is the greater propagation delay over satellite links. This difference has always provoked vigorous debate over the impact of delay on the subscribers using services incorporating satellite links. The issue is addressed from a variety of directions including human factors studies, laboratory subjective tests that evaluate delay with and without echo, and field tests that obtain data on the opinion of subscribers regarding the quality of service of operational circuits in both national U.S. domestic and international trans-Atlantic network. The tests involved the use of both echo suppressors and echo cancellers.

  20. Miniature Release Mechanism or Diminutive Assembly for Nanosatellite Deployables (DANY)

    NASA Technical Reports Server (NTRS)

    Santos Soto, Luis H. (Inventor); Hesh, Scott V. (Inventor); Hudeck, John D. (Inventor)

    2017-01-01

    Miniature release mechanisms constrain objects, such as deployables during the launch of space vehicles, such as small satellites and nanosatellites, and enable the release of the objects once a desired destination is reached by the space vehicle. Constraint and release of the objects are achieved by providing a secure threaded interface that may be released by the release mechanisms. The release mechanisms include a housing structure; a release block can include a threaded interface; one or more retracting pins; one or more release springs; a breakable link, such as a plastic link; a cable harness clamp; and a circuit board. The release mechanism can be 0.1875 inches (approximately 4.8 mm) thick.

  1. The neuropsychology of self-reflection in psychiatric illness.

    PubMed

    Philippi, Carissa L; Koenigs, Michael

    2014-07-01

    The development of robust neuropsychological measures of social and affective function-which link critical dimensions of mental health to their underlying neural circuitry-could be a key step in achieving a more pathophysiologically-based approach to psychiatric medicine. In this article, we summarize research indicating that self-reflection (the inward attention to personal thoughts, memories, feelings, and actions) may be a useful model for developing such a paradigm, as there is evidence that self-reflection is (1) measurable with self-report scales and performance-based tests, (2) linked to the activity of a specific neural circuit, and (3) dimensionally related to mental health and various forms of psychopathology. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. A circuit for saccadic suppression in the primate brain

    PubMed Central

    Cavanaugh, James; McAlonan, Kerry; Wurtz, Robert H.

    2017-01-01

    Saccades should cause us to see a blur as the eyes sweep across a visual scene. Specific brain mechanisms prevent this by producing suppression during saccades. Neuronal correlates of such suppression were first established in the visual superficial layers of the superior colliculus (SC) and subsequently have been observed in cortical visual areas, including the middle temporal visual area (MT). In this study, we investigated suppression in a recently identified circuit linking visual SC (SCs) to MT through the inferior pulvinar (PI). We examined responses to visual stimuli presented just before saccades to reveal a neuronal correlate of suppression driven by a copy of the saccade command, referred to as a corollary discharge. We found that visual responses were similarly suppressed in SCs, PI, and MT. Within each region, suppression of visual responses occurred with saccades into both visual hemifields, but only in the contralateral hemifield did this suppression consistently begin before the saccade (~100 ms). The consistency of the signal along the circuit led us to hypothesize that the suppression in MT was influenced by input from the SC. We tested this hypothesis in one monkey by inactivating neurons within the SC and found evidence that suppression in MT depends on corollary discharge signals from motor SC (SCi). Combining these results with recent findings in rodents, we propose a complete circuit originating with corollary discharge signals in SCi that produces suppression in visual SCs, PI, and ultimately, MT cortex. NEW & NOTEWORTHY A fundamental puzzle in visual neuroscience is that we frequently make rapid eye movements (saccades) but seldom perceive the visual blur accompanying each movement. We investigated neuronal correlates of this saccadic suppression by recording from and perturbing a recently identified circuit from brainstem to cortex. We found suppression at each stage, with evidence that it was driven by an internally generated signal. We conclude that this circuit contributes to neuronal suppression of visual signals during eye movements. PMID:28003409

  3. Circuit-Detour Design and Implementation - Enhancing the Southern California's Seismic Network Reliability through Redundant Network Paths

    NASA Astrophysics Data System (ADS)

    Watkins, M.; Busby, R.; Rico, H.; Johnson, M.; Hauksson, E.

    2003-12-01

    We provide enhanced network robustness by apportioning redundant data communications paths for seismic stations in the field. By providing for more than one telemetry route, either physical or logical, network operators can improve availability of seismic data while experiencing occasional network outages, and also during the loss of key gateway interfaces such as a router or central processor. This is especially important for seismic stations in sparsely populated regions where a loss of a single site may result in a significant gap in the network's monitoring capability. A number of challenges arise in the application of a circuit-detour mechanism. One requirement is that it fits well within the existing framework of our real-time system processing. It is also necessary to craft a system that is not needlessly complex to maintain or implement, particularly during a crisis. The method that we use for circuit-detours does not require the reconfiguration of dataloggers or communications equipment in the field. Remote network configurations remain static, changes are only required at the central site. We have implemented standardized procedures to detour circuits on similar transport mediums, such as virtual circuits on the same leased line; as well as physically different communications pathways, such as a microwave link backed up by a leased line. The lessons learned from these improvements in reliability, and optimization efforts could be applied to other real-time seismic networks. A fundamental tenant of most seismic networks is that they are reliable and have a high percentage of real-time data availability. A reasonable way to achieve these expectations is to provide alternate means of delivering data to the central processing sites, with a simple method for utilizing these alternate paths.

  4. Daily rhythms in locomotor circuits in Drosophila involve PDF

    PubMed Central

    Pírez, Nicolás; Christmann, Bethany L.

    2013-01-01

    The neuropeptide pigment-dispersing factor (PDF) has been studied extensively in Drosophila, and its role in circadian time-keeping has been firmly established. The role of PDF outside of the clock circuit, however, is poorly understood. A recent study suggested that PDF may act on the ellipsoid body (EB) to link the clock and sleep/activity circuits. We performed whole brain optical imaging with the fluorescence resonance energy transfer (FRET)-based cAMP sensor Epac1-camps expressed under control of the pdfR promoter to address how the clock and sleep deprivation affect the physiology of these cells. Basal cAMP levels in EB were regulated both by PDF and synaptic inputs that are controlled by the circadian clock. Acute application of PDF to the brain caused a significant, and PDF-receptor-dependent, increase in cAMP in EB cells. Application of TTX to block circuit-mediated effects of PDF increased the morning response but not the response at night, implying the existence of a temporally regulated, PDF-stimulated input that blocks cAMP generation. ACh produced both direct (TTX-insensitive) and indirect (TTX-sensitive) increases in cAMP during the day but was totally TTX-insensitive at night, indicating that ACh-stimulated inputs to the EB are suppressed at night. Sleep deprivation did not affect the cAMP responses of these cells to either PDF or ACh. These results suggest a novel role for PDF as a modulator of activity outside of the clock circuit. By elucidating the mechanisms by which the neuropeptide PDF act on its target cells, our work contributes to our understating of how the central clock coordinates activity and sleep. PMID:23678016

  5. Daily rhythms in locomotor circuits in Drosophila involve PDF.

    PubMed

    Pírez, Nicolás; Christmann, Bethany L; Griffith, Leslie C

    2013-08-01

    The neuropeptide pigment-dispersing factor (PDF) has been studied extensively in Drosophila, and its role in circadian time-keeping has been firmly established. The role of PDF outside of the clock circuit, however, is poorly understood. A recent study suggested that PDF may act on the ellipsoid body (EB) to link the clock and sleep/activity circuits. We performed whole brain optical imaging with the fluorescence resonance energy transfer (FRET)-based cAMP sensor Epac1-camps expressed under control of the pdfR promoter to address how the clock and sleep deprivation affect the physiology of these cells. Basal cAMP levels in EB were regulated both by PDF and synaptic inputs that are controlled by the circadian clock. Acute application of PDF to the brain caused a significant, and PDF-receptor-dependent, increase in cAMP in EB cells. Application of TTX to block circuit-mediated effects of PDF increased the morning response but not the response at night, implying the existence of a temporally regulated, PDF-stimulated input that blocks cAMP generation. ACh produced both direct (TTX-insensitive) and indirect (TTX-sensitive) increases in cAMP during the day but was totally TTX-insensitive at night, indicating that ACh-stimulated inputs to the EB are suppressed at night. Sleep deprivation did not affect the cAMP responses of these cells to either PDF or ACh. These results suggest a novel role for PDF as a modulator of activity outside of the clock circuit. By elucidating the mechanisms by which the neuropeptide PDF act on its target cells, our work contributes to our understating of how the central clock coordinates activity and sleep.

  6. AgRP to Kiss1 neuron signaling links nutritional state and fertility

    PubMed Central

    Padilla, Stephanie L.; Qiu, Jian; Nestor, Casey C; Zhang, Chunguang; Smith, Arik W.; Whiddon, Benjamin B.; Rønnekleiv, Oline K.; Kelly, Martin J.; Palmiter, Richard D.

    2017-01-01

    Mammalian reproductive function depends upon a neuroendocrine circuit that evokes the pulsatile release of gonadotropin hormones (luteinizing hormone and follicle-stimulating hormone) from the pituitary. This reproductive circuit is sensitive to metabolic perturbations. When challenged with starvation, insufficient energy reserves attenuate gonadotropin release, leading to infertility. The reproductive neuroendocrine circuit is well established, composed of two populations of kisspeptin-expressing neurons (located in the anteroventral periventricular hypothalamus, Kiss1AVPV, and arcuate hypothalamus, Kiss1ARH), which drive the pulsatile activity of gonadotropin-releasing hormone (GnRH) neurons. The reproductive axis is primarily regulated by gonadal steroid and circadian cues, but the starvation-sensitive input that inhibits this circuit during negative energy balance remains controversial. Agouti-related peptide (AgRP)-expressing neurons are activated during starvation and have been implicated in leptin-associated infertility. To test whether these neurons relay information to the reproductive circuit, we used AgRP-neuron ablation and optogenetics to explore connectivity in acute slice preparations. Stimulation of AgRP fibers revealed direct, inhibitory synaptic connections with Kiss1ARH and Kiss1AVPV neurons. In agreement with this finding, Kiss1ARH neurons received less presynaptic inhibition in the absence of AgRP neurons (neonatal toxin-induced ablation). To determine whether enhancing the activity of AgRP neurons is sufficient to attenuate fertility in vivo, we artificially activated them over a sustained period and monitored fertility. Chemogenetic activation with clozapine N-oxide resulted in delayed estrous cycles and decreased fertility. These findings are consistent with the idea that, during metabolic deficiency, AgRP signaling contributes to infertility by inhibiting Kiss1 neurons. PMID:28196880

  7. Superconductor Digital Electronics: -- Current Status, Future Prospects

    NASA Astrophysics Data System (ADS)

    Mukhanov, Oleg

    2011-03-01

    Two major applications of superconductor electronics: communications and supercomputing will be presented. These areas hold a significant promise of a large impact on electronics state-of-the-art for the defense and commercial markets stemming from the fundamental advantages of superconductivity: simultaneous high speed and low power, lossless interconnect, natural quantization, and high sensitivity. The availability of relatively small cryocoolers lowered the foremost market barrier for cryogenically-cooled superconductor electronic systems. These fundamental advantages enabled a novel Digital-RF architecture - a disruptive technological approach changing wireless communications, radar, and surveillance system architectures dramatically. Practical results were achieved for Digital-RF systems in which wide-band, multi-band radio frequency signals are directly digitized and digital domain is expanded throughout the entire system. Digital-RF systems combine digital and mixed signal integrated circuits based on Rapid Single Flux Quantum (RSFQ) technology, superconductor analog filter circuits, and semiconductor post-processing circuits. The demonstrated cryocooled Digital-RF systems are the world's first and fastest directly digitizing receivers operating with live satellite signals, enabling multi-net data links, and performing signal acquisition from HF to L-band with 30 GHz clock frequencies. In supercomputing, superconductivity leads to the highest energy efficiencies per operation. Superconductor technology based on manipulation and ballistic transfer of magnetic flux quanta provides a superior low-power alternative to CMOS and other charge-transfer based device technologies. The fundamental energy consumption in SFQ circuits defined by flux quanta energy 2 x 10-19 J. Recently, a novel energy-efficient zero-static-power SFQ technology, eSFQ/ERSFQ was invented, which retains all advantages of standard RSFQ circuits: high-speed, dc power, internal memory. The voltage bias regulation, determined by SFQ clock, enables the zero-power at zero-activity regimes, indispensable for sensor and quantum bit readout.

  8. Habenula Circuit Development: Past, Present, and Future

    PubMed Central

    Beretta, Carlo A.; Dross, Nicolas; Guiterrez-Triana, Jose A.; Ryu, Soojin; Carl, Matthias

    2012-01-01

    The habenular neural circuit is attracting increasing attention from researchers in fields as diverse as neuroscience, medicine, behavior, development, and evolution. Recent studies have revealed that this part of the limbic system in the dorsal diencephalon is involved in reward, addiction, and other behaviors and its impairment is associated with various neurological conditions and diseases. Since the initial description of the dorsal diencephalic conduction system (DDC) with the habenulae in its center at the end of the nineteenth century, increasingly sophisticated techniques have resolved much of its anatomy and have shown that these pathways relay information from different parts of the forebrain to the tegmentum, midbrain, and hindbrain. The first part of this review gives a brief historical overview on how the improving experimental approaches have allowed the stepwise uncovering much of the architecture of the habenula circuit as we know it today. Our brain distributes tasks differentially between left and right and it has become a paradigm that this functional lateralization is a universal feature of vertebrates. Moreover, task dependent differential brain activities have been linked to anatomical differences across the left–right axis in humans. A good way to further explore this fundamental issue will be to study the functional consequences of subtle changes in neural network formation, which requires that we fully understand DDC system development. As the habenular circuit is evolutionarily highly conserved, researchers have the option to perform such difficult experiments in more experimentally amenable vertebrate systems. Indeed, research in the last decade has shown that the zebrafish is well suited for the study of DDC system development and the phenomenon of functional lateralization. We will critically discuss the advantages of the zebrafish model, available techniques, and others that are needed to fully understand habenular circuit development. PMID:22536170

  9. Habenula circuit development: past, present, and future.

    PubMed

    Beretta, Carlo A; Dross, Nicolas; Guiterrez-Triana, Jose A; Ryu, Soojin; Carl, Matthias

    2012-01-01

    The habenular neural circuit is attracting increasing attention from researchers in fields as diverse as neuroscience, medicine, behavior, development, and evolution. Recent studies have revealed that this part of the limbic system in the dorsal diencephalon is involved in reward, addiction, and other behaviors and its impairment is associated with various neurological conditions and diseases. Since the initial description of the dorsal diencephalic conduction system (DDC) with the habenulae in its center at the end of the nineteenth century, increasingly sophisticated techniques have resolved much of its anatomy and have shown that these pathways relay information from different parts of the forebrain to the tegmentum, midbrain, and hindbrain. The first part of this review gives a brief historical overview on how the improving experimental approaches have allowed the stepwise uncovering much of the architecture of the habenula circuit as we know it today. Our brain distributes tasks differentially between left and right and it has become a paradigm that this functional lateralization is a universal feature of vertebrates. Moreover, task dependent differential brain activities have been linked to anatomical differences across the left-right axis in humans. A good way to further explore this fundamental issue will be to study the functional consequences of subtle changes in neural network formation, which requires that we fully understand DDC system development. As the habenular circuit is evolutionarily highly conserved, researchers have the option to perform such difficult experiments in more experimentally amenable vertebrate systems. Indeed, research in the last decade has shown that the zebrafish is well suited for the study of DDC system development and the phenomenon of functional lateralization. We will critically discuss the advantages of the zebrafish model, available techniques, and others that are needed to fully understand habenular circuit development.

  10. Modeling and control of fuel cell based distributed generation systems

    NASA Astrophysics Data System (ADS)

    Jung, Jin Woo

    This dissertation presents circuit models and control algorithms of fuel cell based distributed generation systems (DGS) for two DGS topologies. In the first topology, each DGS unit utilizes a battery in parallel to the fuel cell in a standalone AC power plant and a grid-interconnection. In the second topology, a Z-source converter, which employs both the L and C passive components and shoot-through zero vectors instead of the conventional DC/DC boost power converter in order to step up the DC-link voltage, is adopted for a standalone AC power supply. In Topology 1, two applications are studied: a standalone power generation (Single DGS Unit and Two DGS Units) and a grid-interconnection. First, dynamic model of the fuel cell is given based on electrochemical process. Second, two full-bridge DC to DC converters are adopted and their controllers are designed: an unidirectional full-bridge DC to DC boost converter for the fuel cell and a bidirectional full-bridge DC to DC buck/boost converter for the battery. Third, for a three-phase DC to AC inverter without or with a Delta/Y transformer, a discrete-time state space circuit model is given and two discrete-time feedback controllers are designed: voltage controller in the outer loop and current controller in the inner loop. And last, for load sharing of two DGS units and power flow control of two DGS units or the DGS connected to the grid, real and reactive power controllers are proposed. Particularly, for the grid-connected DGS application, a synchronization issue between an islanding mode and a paralleling mode to the grid is investigated, and two case studies are performed. To demonstrate the proposed circuit models and control strategies, simulation test-beds using Matlab/Simulink are constructed for each configuration of the fuel cell based DGS with a three-phase AC 120 V (L-N)/60 Hz/50 kVA and various simulation results are presented. In Topology 2, this dissertation presents system modeling, modified space vector PWM implementation (MSVPWM) and design of a closed-loop controller of the Z-source converter which utilizes L and C components and shoot-through zero vectors for the standalone AC power generation. The fuel cell system is modeled by an electrical R-C circuit in order to include slow dynamics of the fuel cells and a voltage-current characteristic of a cell is also considered. A discrete-time state space model is derived to implement digital control and a space vector pulse-width modulation (SVPWM) technique is modified to realize the shoot-through zero vectors that boost the DC-link voltage. Also, three discrete-time feedback controllers are designed: a discrete-time optimal voltage controller, a discrete-time sliding mode current controller, and a discrete-time PI DC-link voltage controller. Furthermore, an asymptotic observer is used to reduce the number of sensors and enhance the reliability of the system. To demonstrate the analyzed circuit model and proposed control strategy, various simulation results using Matlab/Simulink are presented under both light/heavy loads and linear/nonlinear loads for a three-phase AC 208 V (L-L)/60 Hz/10 kVA.

  11. A Review of Marine Geophysical Constraints on the Motion Between East and West Antarctica in the Cenozoic (Invited)

    NASA Astrophysics Data System (ADS)

    Cande, S. C.; Stock, J. M.

    2010-12-01

    Motion between East and West Antarctica in the Late Cretaceous and Cenozoic is derived by summing the plate circuit(s) linking East Antarctica to Australia to the Lord Howe Rise to the Pacific plate to West Antarctica (the Aus-Pac plate circuit). We discuss this motion in two parts: motion before and after 42 Ma. For the younger time interval, motion is directly constrained by magnetic anomalies in the Adare Basin, which opened by ultraslow seafloor spreading between 42 and 26 Ma (anomalies 18 to 9). The Adare Basin magnetic anomaly constraints can be combined with magnetic anomaly and fracture zone data from the SEIR (Aus-East Ant to the west of the Balleny FZ and Aus - West Ant to the east) to set up an Aus-East Ant - West Ant three-plate problem. The original solution of this three-plate configuration (Cande et al., 2000) only had data from a very short section of the Adare Basin and obtained an answer with very large uncertainties on the East-West Ant rotation. Better estimates of the East-West Ant rotation have been calculated by adding constraints based on seismically controlled estimates of extension in the Victoria Land Basin (Davey et al., 2006) and constraints from Damaske et al’s (2007) detailed aeromagnetic survey of the Adare Basin and adjacent Northern Basin (Granot et al., 2010). Currently, we are working on improving the accuracy of rotations for the post-42 Ma time interval by taking advantage of an unusual plate geometry that enables us to solve a five-boundary, four-plate configuration. Specifically, motion between the four plates (East Ant, West Ant, Aus and Pac) encompasses two related triple junction systems with five spreading ridge segments (Aus-East Ant, Aus-West Ant, Aus-Pac, Pac-West Ant and East Ant-West Ant) which can be combined and solved simultaneously. For the older, pre-42 Ma time interval, the only way to calculate motion between East and West Antarctica is via the long Aus-Pac plate circuit (although it is possible that magnetic anomalies formed by direct spreading between East and West Antarctica, akin to the Adare Basin anomalies, may exist in the poorly mapped Central Basin between the Hallett Ridge and the Iselin Bank). The weakest link in this time interval is the Aus - East Ant boundary; for the time interval from 84 to 42 Ma there are distinctly different results depending on how the tectonic constraints are prioritized (Royer and Rollett, 1997; Tikku and Cande, 1999; Whittaker et al., 2007). The disagreement over the pre-42 Ma motion between Australia and East Antarctica leads to large differences in the predicted motion in the Western Ross Sea and near Ellsworth Land. Another weak link in this circuit is the pattern of sea floor spreading in the Tasman Sea, which is difficult to unravel because of the complex history of motion between Australia, the Lord Howe Rise, and Tasmania (Gaina et al., 1999). Resolution of these issues is required before a well constrained history of East -West Antarctic motion back to the Late Cretaceous is obtained

  12. Driver-receiver combined optical transceiver modules for bidirectional optical interconnection

    NASA Astrophysics Data System (ADS)

    Park, Hyo-Hoon; Kang, Sae-Kyoung; Kim, Do-Won; Nga, Nguyen T. H.; Hwang, Sung-Hwan; Lee, Tae-Woo

    2008-02-01

    We review a bidirectional optical link scheme for memory-interface applications. A driver-receiver combined optical transceiver (TRx) modules was demonstrated on an optical printed-circuit board (OPCB) platform. To select the bidirectional electric input/output signals, a driver-receiver combined TRx IC with a switching function was designed in 0.18-μm CMOS technology. The TRx IC was integrated with VCSEL/PD chips for optical link in the TRx module. The optical TRx module was assembled on a fiber-embedded OPCB, employing a 90°-bent fiber connector for 90° deflection of light beams between the TRx module and the OPCB. The TRx module and the 90° connector were passively assembled on the OPCB, using ferrule-type guide pins/ holes. Employing these constituent components, the bidirectional optical link between a pair of TRx modules has been successfully demonstrated up to 1.25 Gb/s on the OPCB.

  13. Wire like link for cycle reproducible and cycle accurate hardware accelerator

    DOEpatents

    Asaad, Sameh; Kapur, Mohit; Parker, Benjamin D

    2015-04-07

    First and second field programmable gate arrays are provided which implement first and second blocks of a circuit design to be simulated. The field programmable gate arrays are operated at a first clock frequency and a wire like link is provided to send a plurality of signals between them. The wire like link includes a serializer, on the first field programmable gate array, to serialize the plurality of signals; a deserializer on the second field programmable gate array, to deserialize the plurality of signals; and a connection between the serializer and the deserializer. The serializer and the deserializer are operated at a second clock frequency, greater than the first clock frequency, and the second clock frequency is selected such that latency of transmission and reception of the plurality of signals is less than the period corresponding to the first clock frequency.

  14. Architectures and Design for Next-Generation Hybrid Circuit/Packet Networks

    NASA Astrophysics Data System (ADS)

    Vadrevu, Sree Krishna Chaitanya

    Internet traffic is increasing rapidly at an annual growth rate of 35% with aggregate traffic exceeding several Exabyte's per month. The traffic is also becoming heterogeneous in bandwidth and quality-of-service (QoS) requirements with growing popularity of cloud computing, video-on-demand (VoD), e-science, etc. Hybrid circuit/packet networks which can jointly support circuit and packet services along with the adoption of high-bit-rate transmission systems form an attractive solution to address the traffic growth. 10 Gbps and 40 Gbps transmission systems are widely deployed in telecom backbone networks such as Comcast, AT&T, etc., and network operators are considering migration to 100 Gbps and beyond. This dissertation proposes robust architectures, capacity migration strategies, and novel service frameworks for next-generation hybrid circuit/packet architectures. In this dissertation, we study two types of hybrid circuit/packet networks: a) IP-over-WDM networks, in which the packet (IP) network is overlaid on top of the circuit (optical WDM) network and b) Hybrid networks in which the circuit and packet networks are deployed side by side such as US DoE's ESnet. We investigate techniques to dynamically migrate capacity between the circuit and packet sections by exploiting traffic variations over a day, and our methods show that significant bandwidth savings can be obtained with improved reliability of services. Specifically, we investigate how idle backup circuit capacity can be used to support packet services in IP-over-WDM networks, and similarly, excess capacity in packet network to support circuit services in ESnet. Control schemes that enable our mechanisms are also discussed. In IP-over-WDM networks, with upcoming 100 Gbps and beyond, dedicated protection will induce significant under-utilization of backup resources. We investigate design strategies to loan idle circuit backup capacity to support IP/packet services. However, failure of backup circuits will preempt IP services routed over them, and thus it is important to ensure IP topology survivability to successfully re-route preempted IP services. Integer-linear-program (ILP) and heuristic solutions have been developed and network cost reduction up to 60% has been observed. In ESnet, we study loaning packet links to support circuit services. Mixed-line-rate (MLR) networks supporting 10/40/100 Gbps on the same fiber are becoming increasingly popular. Services that accept degradation in bandwidth, latency, jitter, etc. under failure scenarios for lower cost are known as degraded services. We study degradation in bandwidth for lower cost under failure scenarios, a concept called partial protection, in the context of MLR networks. We notice partial protection enables significant cost savings compared to full protection. To cope with traffic growth, network operators need to deploy equipment at periodic time intervals, and this is known as the multi-period planning and upgrade problem. We study three important multi-period planning approaches, namely incremental planning, all-period planning, and two-period planning with mixed line rates. Our approaches predict the network equipment that needs to be deployed optimally at which nodes and at which time periods in the network to meet QoS requirements.

  15. Optimization and development of solar power system under diffused sunlight condition in rural areas with supercapacitor integration

    NASA Astrophysics Data System (ADS)

    Castelino, Roystan V.; Jana, Suman; Kumhar, Rajesh; Singh, Niraj K.

    2018-04-01

    The simulation and hardware based experiment in this presented paper shows a possibility of increasing the reliability of solar power under diffused condition by using super capacitor module. This experimental setup can be used in those areas where the sun light is intermittent and under the diffused radiation condition. Due to diffused radiation, solar PV cells operate very poorly, but by using this setup the power efficiency can be increased greatly. Sometimes dependent numerical models are used to measure the voltage and current response of the hardware setup in MATLAB Simulink based environment. To convert the scattered solar radiation to electricity using the conventional solar PV module, batteries have to be linked with the rapid charging or discharging device like super capacitor module. The conventional method consists of a charging circuit, which dumps the power if the voltage is below certain voltage level, but this circuit utilizes the entire power even if the voltage is low under diffused sun light conditions. There is no power dumped in this circuit. The efficiency and viability of this labscale experimental setup can be examined with further experiment and industrial model.

  16. Elevated CaMKIIα and Hyperphosphorylation of Homer Mediate Circuit Dysfunction in a Fragile X Syndrome Mouse Model.

    PubMed

    Guo, Weirui; Ceolin, Laura; Collins, Katie A; Perroy, Julie; Huber, Kimberly M

    2015-12-15

    Abnormal metabotropic glutamate receptor 5 (mGluR5) function, as a result of disrupted scaffolding with its binding partner Homer, contributes to the pathophysiology of fragile X syndrome, a common inherited form of intellectual disability and autism caused by mutations in Fmr1. How loss of Fmr1 disrupts mGluR5-Homer scaffolds is unknown, and little is known about the dynamic regulation of mGluR5-Homer scaffolds in wild-type neurons. Here, we demonstrate that brief (minutes-long) elevations in neural activity cause CaMKIIα-mediated phosphorylation of long Homer proteins and dissociation from mGluR5 at synapses. In Fmr1 knockout (KO) cortex, Homers are hyperphosphorylated as a result of elevated CaMKIIα protein. Genetic or pharmacological inhibition of CaMKIIα or replacement of Homers with dephosphomimetics restores mGluR5-Homer scaffolds and multiple Fmr1 KO phenotypes, including circuit hyperexcitability and/or seizures. This work links translational control of an FMRP target mRNA, CaMKIIα, to the molecular-, cellular-, and circuit-level brain dysfunction in a complex neurodevelopmental disorder. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  17. The performance of a mobile air conditioning system with a water cooled condenser

    NASA Astrophysics Data System (ADS)

    Di Battista, Davide; Cipollone, Roberto

    2015-11-01

    Vehicle technological evolution lived, in recent years, a strong acceleration due to the increased awareness of environmental issues related to pollutants and climate altering emissions. This resulted in a series of international regulations on automotive sector which put technical challenges that must consider the engine and the vehicle as a global system, in order to improve the overall efficiency of the system. The air conditioning system of the cabin, for instance, is the one of the most important auxiliaries in a vehicle and requires significant powers. Its performances can be significantly improved if it is integrated within the engine cooling circuit, eventually modified with more temperature levels. In this paper, the Authors present a mathematical model of the A/C system, starting from its single components: compressors, condenser, flush valve and evaporator and a comparison between different refrigerant fluid. In particular, it is introduced the opportunity to have an A/C condenser cooled by a water circuit instead of the external air linked to the vehicle speed, as in the actual traditional configuration. The A/C condenser, in fact, could be housed on a low temperature water circuit, reducing the condensing temperature of the refrigeration cycle with a considerable efficiency increase.

  18. Gigantic jets between a thundercloud and the ionosphere.

    PubMed

    Su, H T; Hsu, R R; Chen, A B; Wang, Y C; Hsiao, W S; Lai, W C; Lee, L C; Sato, M; Fukunishi, H

    2003-06-26

    Transient luminous events in the atmosphere, such as lighting-induced sprites and upwardly discharging blue jets, were discovered recently in the region between thunderclouds and the ionosphere. In the conventional picture, the main components of Earth's global electric circuit include thunderstorms, the conducting ionosphere, the downward fair-weather currents and the conducting Earth. Thunderstorms serve as one of the generators that drive current upward from cloud tops to the ionosphere, where the electric potential is hundreds of kilovolts higher than Earth's surface. It has not been clear, however, whether all the important components of the global circuit have even been identified. Here we report observations of five gigantic jets that establish a direct link between a thundercloud (altitude approximately 16 km) and the ionosphere at 90 km elevation. Extremely-low-frequency radio waves in four events were detected, while no cloud-to-ground lightning was observed to trigger these events. Our result indicates that the extremely-low-frequency waves were generated by negative cloud-to-ionosphere discharges, which would reduce the electrical potential between ionosphere and ground. Therefore, the conventional picture of the global electric circuit needs to be modified to include the contributions of gigantic jets and possibly sprites.

  19. Integrating perspectives on vocal performance and consistency

    PubMed Central

    Sakata, Jon T.; Vehrencamp, Sandra L.

    2012-01-01

    SUMMARY Recent experiments in divergent fields of birdsong have revealed that vocal performance is important for reproductive success and under active control by distinct neural circuits. Vocal consistency, the degree to which the spectral properties (e.g. dominant or fundamental frequency) of song elements are produced consistently from rendition to rendition, has been highlighted as a biologically important aspect of vocal performance. Here, we synthesize functional, developmental and mechanistic (neurophysiological) perspectives to generate an integrated understanding of this facet of vocal performance. Behavioral studies in the field and laboratory have found that vocal consistency is affected by social context, season and development, and, moreover, positively correlated with reproductive success. Mechanistic investigations have revealed a contribution of forebrain and basal ganglia circuits and sex steroid hormones to the control of vocal consistency. Across behavioral, developmental and mechanistic studies, a convergent theme regarding the importance of vocal practice in juvenile and adult songbirds emerges, providing a basis for linking these levels of analysis. By understanding vocal consistency at these levels, we gain an appreciation for the various dimensions of song control and plasticity and argue that genes regulating the function of basal ganglia circuits and sex steroid hormones could be sculpted by sexual selection. PMID:22189763

  20. Brain repair after stroke—a novel neurological model

    PubMed Central

    Small, Steven L.; Buccino, Giovanni; Solodkin, Ana

    2017-01-01

    Following stroke, patients are commonly left with debilitating motor and speech impairments. This article reviews the state of the art in neurological repair for stroke and proposes a new model for the future. We suggest that stroke treatment—from the time of the ictus itself to living with the consequences—must be fundamentally neurological, from limiting the extent of injury at the outset, to repairing the consequent damage. Our model links brain and behaviour by targeting brain circuits, and we illustrate the model though action observation treatment, which aims to enhance brain network connectivity. The model is based on the assumptions that the mechanisms of neural repair inherently involve cellular and circuit plasticity, that brain plasticity is a synaptic phenomenon that is largely stimulus-dependent, and that brain repair required both physical and behavioural interventions that are tailored to reorganize specific brain circuits. We review current approaches to brain repair after stroke and present our new model, and discuss the biological foundations, rationales, and data to support our novel approach to upper-extremity and language rehabilitation. We believe that by enhancing plasticity at the level of brain network interactions, this neurological model for brain repair could ultimately lead to a cure for stroke. PMID:24217509

  1. A Genetic RNAi Screen for IP3/Ca2+ Coupled GPCRs in Drosophila Identifies the PdfR as a Regulator of Insect Flight

    PubMed Central

    Agrawal, Tarjani; Sadaf, Sufia; Hasan, Gaiti

    2013-01-01

    Insect flight is regulated by various sensory inputs and neuromodulatory circuits which function in synchrony to control and fine-tune the final behavioral outcome. The cellular and molecular bases of flight neuromodulatory circuits are not well defined. In Drosophila melanogaster, it is known that neuronal IP3 receptor mediated Ca2+ signaling and store-operated Ca2+ entry (SOCE) are required for air-puff stimulated adult flight. However, G-protein coupled receptors (GPCRs) that activate intracellular Ca2+ signaling in the context of flight are unknown in Drosophila. We performed a genetic RNAi screen to identify GPCRs that regulate flight by activating the IP3 receptor. Among the 108 GPCRs screened, we discovered 5 IP3/Ca2+ linked GPCRs that are necessary for maintenance of air-puff stimulated flight. Analysis of their temporal requirement established that while some GPCRs are required only during flight circuit development, others are required both in pupal development as well as during adult flight. Interestingly, our study identified the Pigment Dispersing Factor Receptor (PdfR) as a regulator of flight circuit development and as a modulator of acute flight. From the analysis of PdfR expressing neurons relevant for flight and its well-defined roles in other behavioral paradigms, we propose that PdfR signaling functions systemically to integrate multiple sensory inputs and modulate downstream motor behavior. PMID:24098151

  2. IL-1β Enhances Wnt Signal by Inhibiting DKK1.

    PubMed

    Yoshida, Yusuke; Yamasaki, Satoshi; Oi, Katsuhiro; Kuranobu, Tatsuomi; Nojima, Takaki; Miyaki, Shigeru; Ida, Hiroaki; Sugiyama, Eiji

    2018-06-28

    Aberrant endochondral bone formation in the physis is a unique bone lesion in neonatal-onset multisystem inflammatory disease (NOMID), also called chronic infantile neurologic cutaneous articular (CINCA), the most severe of the cryopyrin-associated periodic syndrome (CAPS) diseases, which are interleukin-1β (IL-1β)-related monogenic autoinflammatory diseases. The wingless (Wnt) pathway plays an important role in osteoblast differentiation. In this study, we explored the potential role of IL-1β on the expression of WNT genes and the Wnt antagonist Dickkopf-1 (DKK1). The expression of WNT and DKK1 in fibroblast-like synoviocytes (FLS), which are articular resident cells, was quantified by quantitative PCR and enzyme-linked immunosorbent assay. Additionally, we used T cell factor (TCF) reporter assays to evaluate the activity of the canonical Wnt signal pathway in the presence or absence of the supernatant of cultured FLS treated with or without IL-1β and IL-6. Anti-DKK1 antibodies were used to neutralize DKK1. The expression of both canonical and non-canonical WNT genes as well as DKK1 was observed in FLS. The supernatant of cultured FLS suppressed the luciferase activity of the TCF reporter, and this effect was reduced by its pre-treatment with an anti-DKK1 antibody. Both IL-1β and IL-6 significantly reduced DKK1 production. Furthermore, the supernatant of FLS cultured with IL-1β or IL-6 showed a reduced inhibitory effect on Wnt signaling, compared with the supernatant of untreated FLS. These data suggest that IL-1β, like IL-6, dampens DKK1 production, and thereby promotes Wnt signal activation. Therefore, increased levels of IL-1β may contribute to the dysregulation of endochondral ossification in NOMID/CINCA.

  3. Reference Manual for the Ada Programming Language

    DTIC Science & Technology

    1983-01-01

    Convercions 4-21 4.7 Qualified Expresclions 4-24 4.8 Allocators 4-24 4.9 Static Expressions and Static Subtypes 4-26 , 4.10 Universal Expressions 4-27 5...record type.•: • 2 Access types allow the construction of linked data structures created by the evaluation of / allocators . They allow several...the following: A * An assignment (In assignment statements and Initializations), an allocator , a membership test, or a short-circuit control form, * A

  4. Optimization of interneuron function by direct coupling of cell migration and axonal targeting.

    PubMed

    Lim, Lynette; Pakan, Janelle M P; Selten, Martijn M; Marques-Smith, André; Llorca, Alfredo; Bae, Sung Eun; Rochefort, Nathalie L; Marín, Oscar

    2018-06-18

    Neural circuit assembly relies on the precise synchronization of developmental processes, such as cell migration and axon targeting, but the cell-autonomous mechanisms coordinating these events remain largely unknown. Here we found that different classes of interneurons use distinct routes of migration to reach the embryonic cerebral cortex. Somatostatin-expressing interneurons that migrate through the marginal zone develop into Martinotti cells, one of the most distinctive classes of cortical interneurons. For these cells, migration through the marginal zone is linked to the development of their characteristic layer 1 axonal arborization. Altering the normal migratory route of Martinotti cells by conditional deletion of Mafb-a gene that is preferentially expressed by these cells-cell-autonomously disrupts axonal development and impairs the function of these cells in vivo. Our results suggest that migration and axon targeting programs are coupled to optimize the assembly of inhibitory circuits in the cerebral cortex.

  5. Self-Oscillating Josephson Quantum Heat Engine

    NASA Astrophysics Data System (ADS)

    Marchegiani, G.; Virtanen, P.; Giazotto, F.; Campisi, M.

    2016-11-01

    The design of a mesoscopic self-oscillating heat engine that works thanks to purely quantum effects is presented. The proposed scheme is amenable to experimental implementation with current state-of-the-art nanotechnology and materials. One of the main features of the structure is its versatility: The engine can deliver work to a generic load without galvanic contact. This versatility makes it a promising building block for low-temperature on-chip energy-management applications. The heat engine consists of a circuit featuring a thermoelectric element based on a ferromagnetic insulator-superconductor tunnel junction and a Josephson weak link that realizes a purely quantum dc-ac converter. This makeup enables the contactless transfer of work to the load (a generic RL circuit). The performance of the heat engine is investigated as a function of the thermal gradient applied to the thermoelectric junction. Power up to 1 pW can be delivered to a load RL=10 Ω .

  6. Acousto-optic modulation and opto-acoustic gating in piezo-optomechanical circuits

    PubMed Central

    Balram, Krishna C.; Davanço, Marcelo I.; Ilic, B. Robert; Kyhm, Ji-Hoon; Song, Jin Dong; Srinivasan, Kartik

    2017-01-01

    Acoustic wave devices provide a promising chip-scale platform for efficiently coupling radio frequency (RF) and optical fields. Here, we use an integrated piezo-optomechanical circuit platform that exploits both the piezoelectric and photoelastic coupling mechanisms to link 2.4 GHz RF waves to 194 THz (1550 nm) optical waves, through coupling to propagating and localized 2.4 GHz acoustic waves. We demonstrate acousto-optic modulation, resonant in both the optical and mechanical domains, in which waveforms encoded on the RF carrier are mapped to the optical field. We also show opto-acoustic gating, in which the application of modulated optical pulses interferometrically gates the transmission of propagating acoustic pulses. The time-domain characteristics of this system under both pulsed RF and pulsed optical excitation are considered in the context of the different physical pathways involved in driving the acoustic waves, and modelled through the coupled mode equations of cavity optomechanics. PMID:28580373

  7. Single crystal CVD diamond membranes for betavoltaic cells

    NASA Astrophysics Data System (ADS)

    Delfaure, C.; Pomorski, M.; de Sanoit, J.; Bergonzo, P.; Saada, S.

    2016-06-01

    A single crystal diamond large area thin membrane was assembled as a p-doped/Intrinsic/Metal (PIM) structure and used in a betavoltaic configuration. When tested with a 20 keV electron beam from a high resolution scanning electron microscope, we measured an open circuit voltage (Voc) of 1.85 V, a charge collection efficiency (CCE) of 98%, a fill-factor of 80%, and a total conversion efficiency of 9.4%. These parameters are inherently linked to the diamond membrane PIM structure that allows full device depletion even at 0 V and are among the highest reported up to now for any other material tested for betavoltaic devices. It enables to drive a high short-circuit current Isc up to 7.12 μA, to reach a maximum power Pmax of 10.48 μW, a remarkable value demonstrating the high-benefit of diamond for the realization of long-life radioisotope based micro-batteries.

  8. Psychological Processing in Chronic Pain: A Neural Systems Approach

    PubMed Central

    Simons, Laura; Elman, Igor; Borsook, David

    2014-01-01

    Our understanding of chronic pain involves complex brain circuits that include sensory, emotional, cognitive and interoceptive processing. The feed-forward interactions between physical (e.g., trauma) and emotional pain and the consequences of altered psychological status on the expression of pain have made the evaluation and treatment of chronic pain a challenge in the clinic. By understanding the neural circuits involved in psychological processes, a mechanistic approach to the implementation of psychology-based treatments may be better understood. In this review we evaluate some of the principle processes that may be altered as a consequence of chronic pain in the context of localized and integrated neural networks. These changes are ongoing, vary in their magnitude, and their hierarchical manifestations, and may be temporally and sequentially altered by treatments, and all contribute to an overall pain phenotype. Furthermore, we link altered psychological processes to specific evidence-based treatments to put forth a model of pain neuroscience psychology. PMID:24374383

  9. The neurobiological link between compassion and love

    PubMed Central

    Esch, Tobias; Stefano, George B.

    2011-01-01

    Summary Love and compassion exert pleasant feelings and rewarding effects. Besides their emotional role and capacity to govern behavior, appetitive motivation, and a general ‘positive state’, even ‘spiritual’ at times, the behaviors shown in love and compassion clearly rely on neurobiological mechanisms and underlying molecular principles. These processes and pathways involve the brain’s limbic motivation and reward circuits, that is, a finely tuned and profound autoregulation. This capacity to self-regulate emotions, approach behaviors and even pair bonding, as well as social contact in general, i.e., love, attachment and compassion, can be highly effective in stress reduction, survival and overall health. Yet, molecular biology is the basis of interpersonal neurobiology, however, there is no answer to the question of what comes first or is more important: It is a cybernetic capacity and complex circuit of autoregulation that is clearly ‘amazing’. PMID:21358615

  10. System architecture of a gallium arsenide one-gigahertz digital IC tester

    NASA Technical Reports Server (NTRS)

    Fouts, Douglas J.; Johnson, John M.; Butner, Steven E.; Long, Stephen I.

    1987-01-01

    The design for a 1-GHz digital integrated circuit tester for the evaluation of custom GaAs chips and subsystems is discussed. Technology-related problems affecting the design of a GaAs computer are discussed, with emphasis on the problems introduced by long printed-circuit-board interconnect. High-speed interface modules provide a link between the low-speed microprocessor and the chip under test. Memory-multiplexer and memory-shift register architectures for the storage of test vectors are described in addition to an architecture for local data storage consisting of a long chain of GaAs shift registers. The tester is constructed around a VME system card cage and backplane, and very little high-speed interconnect exists between boards. The tester has a three part self-test consisting of a CPU board confidence test, a main memory confidence test, and a high-speed interface module functional test.

  11. A Fatigue Measuring Protocol for Wireless Body Area Sensor Networks.

    PubMed

    Akram, Sana; Javaid, Nadeem; Ahmad, Ashfaq; Khan, Zahoor Ali; Imran, Muhammad; Guizani, Mohsen; Hayat, Amir; Ilahi, Manzoor

    2015-12-01

    As players and soldiers preform strenuous exercises and do difficult and tiring duties, they are usually the common victims of muscular fatigue. Keeping this in mind, we propose FAtigue MEasurement (FAME) protocol for soccer players and soldiers using in-vivo sensors for Wireless Body Area Sensor Networks (WBASNs). In FAME, we introduce a composite parameter for fatigue measurement by setting a threshold level for each sensor. Whenever, any sensed data exceeds its threshold level, the players or soldiers are declared to be in a state of fatigue. Moreover, we use a vibration pad for the relaxation of fatigued muscles, and then utilize the vibrational energy by means of vibration detection circuit to recharge the in-vivo sensors. The induction circuit achieves about 68 % link efficiency. Simulation results show better performance of the proposed FAME protocol, in the chosen scenarios, as compared to an existing Wireless Soccer Team Monitoring (WSTM) protocol in terms of the selected metrics.

  12. Genes, Circuits, and Precision Therapies for Autism and Related Neurodevelopmental Disorders

    PubMed Central

    2016-01-01

    Research in genetics of neurodevelopmental disorders such as autism suggests that several hundred genes are likely risk factors for these disorders. This heterogeneity presents a challenge and an opportunity at the same time. While the exact identity of many of the genes remains to be discovered, genes identified to date encode for proteins that play roles in certain conserved pathways: protein synthesis, transcriptional/epigenetic regulation and synaptic signaling. Next generation of research in neurodevelopmental disorders needs to address the neural circuitry underlying the behavioral symptoms and co-morbidities, the cell types playing critical roles in these circuits and common intercellular signaling pathways that link diverse genes. Results from clinical trials have been mixed so far. Only when we are able to leverage the heterogeneity of neurodevelopmental disorders into precision medicine, will the mechanism-based therapeutics for these disorders start to unlock success. PMID:26472761

  13. Information processing in the vertebrate habenula.

    PubMed

    Fore, Stephanie; Palumbo, Fabrizio; Pelgrims, Robbrecht; Yaksi, Emre

    2018-06-01

    The habenula is a brain region that has gained increasing popularity over the recent years due to its role in processing value-related and experience-dependent information with a strong link to depression, addiction, sleep and social interactions. This small diencephalic nucleus is proposed to act as a multimodal hub or a switchboard, where inputs from different brain regions converge. These diverse inputs to the habenula carry information about the sensory world and the animal's internal state, such as reward expectation or mood. However, it is not clear how these diverse habenular inputs interact with each other and how such interactions contribute to the function of habenular circuits in regulating behavioral responses in various tasks and contexts. In this review, we aim to discuss how information processing in habenular circuits, can contribute to specific behavioral programs that are attributed to the habenula. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Neural mechanisms of movement planning: motor cortex and beyond.

    PubMed

    Svoboda, Karel; Li, Nuo

    2018-04-01

    Neurons in motor cortex and connected brain regions fire in anticipation of specific movements, long before movement occurs. This neural activity reflects internal processes by which the brain plans and executes volitional movements. The study of motor planning offers an opportunity to understand how the structure and dynamics of neural circuits support persistent internal states and how these states influence behavior. Recent advances in large-scale neural recordings are beginning to decipher the relationship of the dynamics of populations of neurons during motor planning and movements. New behavioral tasks in rodents, together with quantified perturbations, link dynamics in specific nodes of neural circuits to behavior. These studies reveal a neural network distributed across multiple brain regions that collectively supports motor planning. We review recent advances and highlight areas where further work is needed to achieve a deeper understanding of the mechanisms underlying motor planning and related cognitive processes. Copyright © 2017. Published by Elsevier Ltd.

  15. QPPM receiver for free-space laser communications

    NASA Technical Reports Server (NTRS)

    Budinger, J. M.; Mohamed, J. H.; Nagy, L. A.; Lizanich, P. J.; Mortensen, D. J.

    1994-01-01

    A prototype receiver developed at NASA Lewis Research Center for direct detection and demodulation of quaternary pulse position modulated (QPPM) optical carriers is described. The receiver enables dual-channel communications at 325-Megabits per second (Mbps) per channel. The optical components of the prototype receiver are briefly described. The electronic components, comprising the analog signal conditioning, slot clock recovery, matched filter and maximum likelihood data recovery circuits are described in more detail. A novel digital symbol clock recovery technique is presented as an alternative to conventional analog methods. Simulated link degradations including noise and pointing-error induced amplitude variations are applied. The bit-error-rate performance of the electronic portion of the prototype receiver under varying optical signal-to-noise power ratios is found to be within 1.5-dB of theory. Implementation of the receiver as a hybrid of analog and digital application specific integrated circuits is planned.

  16. Dielectric monitoring of carbon nanotube network formation in curing thermosetting nanocomposites

    NASA Astrophysics Data System (ADS)

    Battisti, A.; Skordos, A. A.; Partridge, I. K.

    2009-08-01

    This paper focuses on monitoring of carbon nanotube (CNT) network development during the cure of unsaturated polyester nanocomposites by means of electrical impedance spectroscopy. A phenomenological model of the dielectric response is developed using equivalent circuit analysis. The model comprises two parallel RC elements connected in series, each of them giving rise to a semicircular arc in impedance complex plane plots. An established inverse modelling methodology is utilized for the estimation of the parameters of the corresponding equivalent circuit. This allows a quantification of the evolution of two separate processes corresponding to the two parallel RC elements. The high frequency process, which is attributed to CNT aggregates, shows a monotonic decrease in characteristic time during the cure. In contrast, the low frequency process, which corresponds to inter-aggregate phenomena, shows a more complex behaviour explained by the interplay between conductive network development and the cross-linking of the polymer.

  17. Intergenerational neural mediators of early-life anxious temperament.

    PubMed

    Fox, Andrew S; Oler, Jonathan A; Shackman, Alexander J; Shelton, Steven E; Raveendran, Muthuswamy; McKay, D Reese; Converse, Alexander K; Alexander, Andrew; Davidson, Richard J; Blangero, John; Rogers, Jeffrey; Kalin, Ned H

    2015-07-21

    Understanding the heritability of neural systems linked to psychopathology is not sufficient to implicate them as intergenerational neural mediators. By closely examining how individual differences in neural phenotypes and psychopathology cosegregate as they fall through the family tree, we can identify the brain systems that underlie the parent-to-child transmission of psychopathology. Although research has identified genes and neural circuits that contribute to the risk of developing anxiety and depression, the specific neural systems that mediate the inborn risk for these debilitating disorders remain unknown. In a sample of 592 young rhesus monkeys that are part of an extended multigenerational pedigree, we demonstrate that metabolism within a tripartite prefrontal-limbic-midbrain circuit mediates some of the inborn risk for developing anxiety and depression. Importantly, although brain volume is highly heritable early in life, it is brain metabolism-not brain structure-that is the critical intermediary between genetics and the childhood risk to develop stress-related psychopathology.

  18. THE ROLE OF SEROTONIN IN RESPIRATORY FUNCTION AND DYSFUNCTION

    PubMed Central

    Hilaire, Gérard; Voituron, Nicolas; Menuet, Clément; Ichiyama, Ronaldo M.; Subramanian, Hari H.; Dutschmann, Mathias

    2010-01-01

    Serotonin (5-HT) is a neuro-modulator–transmitter influencing global brain function. Past and present findings illustrate a prominent role for 5-HT in the modulation of ponto-medullary autonomic circuits. 5-HT is also involved in the control of neurotrophic processes during pre- and postnatal development of neural circuits. The functional implications of 5-HT is particularly illustrated in the alterations to the serotonergic system, as seen in a wide range of neurological disorders. This article reviews the role of 5-HT in the development and control of respiratory networks in the ponto-medullary brainstem. The review further examines the role of 5-HT in breathing disorders occurring at different stages of life, in particular, the neonatal neurodevelopmental diseases such as Rett, sudden infant death and Prader-Willi syndromes, adult diseases such as sleep apnoea and mental illness linked to neurodegeneration. PMID:20801236

  19. Wired on sugar: the role of the CNS in the regulation of glucose homeostasis

    PubMed Central

    Grayson, Bernadette E.; Seeley, Randy J.; Sandoval, Darleen A.

    2014-01-01

    Obesity and type 2 diabetes mellitus (T2DM) — disorders of energy homeostasis and glucose homeostasis, respectively — are tightly linked and the incidences of both conditions are increasing in parallel. The CNS integrates information regarding peripheral nutrient and hormonal changes and processes this information to regulate energy homeostasis. Recent findings indicate that some of the neural circuits and mechanisms underlying energy balance are also essential for the regulation of glucose homeostasis. We propose that disruption of these overlapping pathways links the metabolic disturbances associated with obesity and T2DM. A better understanding of these converging mechanisms may lead to therapeutic strategies that target both T2DM and obesity. PMID:23232606

  20. Remote Neural Pendants In A Welding-Control System

    NASA Technical Reports Server (NTRS)

    Venable, Richard A.; Bucher, Joseph H.

    1995-01-01

    Neural network integrated circuits enhance functionalities of both remote terminals (called "pendants") and communication links, without necessitating installation of additional wires in links. Makes possible to incorporate many features into pendant, including real-time display of critical welding parameters and other process information, capability for communication between technician at pendant and host computer or technician elsewhere in system, and switches and potentiometers through which technician at pendant exerts remote control over such critical aspects of welding process as current, voltage, rate of travel, flow of gas, starting, and stopping. Other potential manufacturing applications include control of spray coating and of curing of composite materials. Potential nonmanufacturing uses include remote control of heating, air conditioning, and lighting in electrically noisy and otherwise hostile environments.

  1. Intelsat TDMA and its implementation in Australia

    NASA Astrophysics Data System (ADS)

    Howe, Stuart

    The developmental history and characteristics of the Intelsat digital communications network are surveyed, with a focus on the current implementation status in Australia. Topics addressed include the fundamental principles and advantages of a TDMA system, the hardware required for a TDMA traffic station, and the Intelsat Indian Ocean Primary satellite network. Detailed consideration is given to TDMA test equipment (burst-mode link analyzers, PCM DSI test sets, burst-power meters, burst negators, and reference burst generators), terminal integration with terrestrial and RF links (TWT sharing and equalization), equipment compatibility, and traffic. Plans call for 950 TDMA circuits by the end of 1990, representing about 36.5 percent of the traffic between Australia and Europe, Africa, India and Pakistan, and the Middle East.

  2. Design and Optimization of a 3-Coil Inductive Link for Efficient Wireless Power Transmission.

    PubMed

    Kiani, Mehdi; Jow, Uei-Ming; Ghovanloo, Maysam

    2011-07-14

    Inductive power transmission is widely used to energize implantable microelectronic devices (IMDs), recharge batteries, and energy harvesters. Power transfer efficiency (PTE) and power delivered to the load (PDL) are two key parameters in wireless links, which affect the energy source specifications, heat dissipation, power transmission range, and interference with other devices. To improve the PTE, a 4-coil inductive link has been recently proposed. Through a comprehensive circuit based analysis that can guide a design and optimization scheme, we have shown that despite achieving high PTE at larger coil separations, the 4-coil inductive links fail to achieve a high PDL. Instead, we have proposed a 3-coil inductive power transfer link with comparable PTE over its 4-coil counterpart at large coupling distances, which can also achieve high PDL. We have also devised an iterative design methodology that provides the optimal coil geometries in a 3-coil inductive power transfer link. Design examples of 2-, 3-, and 4-coil inductive links have been presented, and optimized for 13.56 MHz carrier frequency and 12 cm coupling distance, showing PTEs of 15%, 37%, and 35%, respectively. At this distance, the PDL of the proposed 3-coil inductive link is 1.5 and 59 times higher than its equivalent 2- and 4-coil links, respectively. For short coupling distances, however, 2-coil links remain the optimal choice when a high PDL is required, while 4-coil links are preferred when the driver has large output resistance or small power is needed. These results have been verified through simulations and measurements.

  3. Cross-linked Composite Gel Polymer Electrolyte using Mesoporous Methacrylate-Functionalized SiO2 Nanoparticles for Lithium-Ion Polymer Batteries

    PubMed Central

    Shin, Won-Kyung; Cho, Jinhyun; Kannan, Aravindaraj G.; Lee, Yoon-Sung; Kim, Dong-Won

    2016-01-01

    Liquid electrolytes composed of lithium salt in a mixture of organic solvents have been widely used for lithium-ion batteries. However, the high flammability of the organic solvents can lead to thermal runaway and explosions if the system is accidentally subjected to a short circuit or experiences local overheating. In this work, a cross-linked composite gel polymer electrolyte was prepared and applied to lithium-ion polymer cells as a safer and more reliable electrolyte. Mesoporous SiO2 nanoparticles containing reactive methacrylate groups as cross-linking sites were synthesized and dispersed into the fibrous polyacrylonitrile membrane. They directly reacted with gel electrolyte precursors containing tri(ethylene glycol) diacrylate, resulting in the formation of a cross-linked composite gel polymer electrolyte with high ionic conductivity and favorable interfacial characteristics. The mesoporous SiO2 particles also served as HF scavengers to reduce the HF content in the electrolyte at high temperature. As a result, the cycling performance of the lithium-ion polymer cells with cross-linked composite gel polymer electrolytes employing methacrylate-functionalized mesoporous SiO2 nanoparticles was remarkably improved at elevated temperatures. PMID:27189842

  4. Human APC sequesters beta-catenin even in the absence of GSK-3beta in a Drosophila model.

    PubMed

    Rao, P R; Makhijani, K; Shashidhara, L S

    2008-04-10

    There have been conflicting reports on the requirement of GSK-3beta-mediated phosphorylation of the tumor suppressor adenomatous polyposis coli (APC) vis-à-vis its ability to bind and degrade beta-catenin. Using a unique combination of loss of function for Shaggy/GSK-3beta and a gain of function for human APC in Drosophila, we show that misexpressed human APC (hAPC) can still sequester Armadillo/beta-catenin. In addition, human APC could suppress gain of Wnt/Wingless phenotypes associated with loss of Shaggy/GSK-3beta activity, suggesting that sequestered Armadillo/beta-catenin is non-functional. Based on these studies, we propose that binding per se of beta-catenin by APC does not require phosphorylation by GSK-3beta.

  5. Engineers Jim Murray and Joe Pahle prepare a deployable, inflatable wing technology demonstrator exp

    NASA Technical Reports Server (NTRS)

    2001-01-01

    Engineers Jim Murray and Joe Pahle prepare a deployable, inflatable wing technology demonstrator experiment flown by the NASA Dryden Flight Research Center, Edwards, California. The inflatable wing project represented a basic flight research effort by Dryden personnel. Three successful flights of the I2000 inflatable wing aircraft occurred. During the flights, the team air-launched the radio-controlled (R/C) I2000 from an R/C utility airplane at an altitude of 800-1000 feet. As the I2000 separated from the carrier aircraft, its inflatable wings 'popped-out,' deploying rapidly via an on-board nitrogen bottle. The aircraft remained stable as it transitioned from wingless to winged flight. The unpowered I2000 glided down to a smooth landing under complete control.

  6. The I2000, a deployable, inflatable wing technology demonstrator experiment aircraft, leaves the gro

    NASA Technical Reports Server (NTRS)

    2001-01-01

    The deployable, inflatable wing technology demonstrator experiment aircraft leaves the ground during a flight conducted by the NASA Dryden Flight Research Center, Edwards, California. The inflatable wing project represented a basic flight research effort by Dryden personnel. Three successful flights of the I2000 inflatable wing aircraft occurred. During the flights, the team air-launched the radio-controlled (R/C) I2000 from an R/C utility airplane at an altitude of 800-1000 feet. As the I2000 separated from the carrier aircraft, its inflatable wings 'popped-out,' deploying rapidly via an on-board nitrogen bottle. The aircraft remained stable as it transitioned from wingless to winged flight. The unpowered I2000 glided down to a smooth landing under complete control.

  7. Diverse microRNAs with convergent functions regulate tumorigenesis.

    PubMed

    Zhu, Min-Yan; Zhang, Wei; Yang, Tao

    2016-02-01

    MicroRNAs (miRNAs) regulate several biological processes, including tumorigenesis. In order to comprehend the roles of miRNAs in cancer, various screens were performed to investigate the changes in the expression levels of miRNAs that occur in different types of cancer. The present review focuses on the results of five recent screens, whereby a number of overlapping miRNAs were identified to be downregulated or differentially regulated, whereas no miRNAs were observed to be frequently upregulated. Furthermore, the majority of the miRNAs that were common to >1 screen were involved in signaling networks, including wingless-related integration site, receptor tyrosine kinase and transforming growth factor-β, or in cell cycle checkpoint control. The present review will discuss the aforementioned miRNAs implicated in cell cycle checkpoint control and signaling networks.

  8. Design and development of cell queuing, processing, and scheduling modules for the iPOINT input-buffered ATM testbed

    NASA Astrophysics Data System (ADS)

    Duan, Haoran

    1997-12-01

    This dissertation presents the concepts, principles, performance, and implementation of input queuing and cell-scheduling modules for the Illinois Pulsar-based Optical INTerconnect (iPOINT) input-buffered Asynchronous Transfer Mode (ATM) testbed. Input queuing (IQ) ATM switches are well suited to meet the requirements of current and future ultra-broadband ATM networks. The IQ structure imposes minimum memory bandwidth requirements for cell buffering, tolerates bursty traffic, and utilizes memory efficiently for multicast traffic. The lack of efficient cell queuing and scheduling solutions has been a major barrier to build high-performance, scalable IQ-based ATM switches. This dissertation proposes a new Three-Dimensional Queue (3DQ) and a novel Matrix Unit Cell Scheduler (MUCS) to remove this barrier. 3DQ uses a linked-list architecture based on Synchronous Random Access Memory (SRAM) to combine the individual advantages of per-virtual-circuit (per-VC) queuing, priority queuing, and N-destination queuing. It avoids Head of Line (HOL) blocking and provides per-VC Quality of Service (QoS) enforcement mechanisms. Computer simulation results verify the QoS capabilities of 3DQ. For multicast traffic, 3DQ provides efficient usage of cell buffering memory by storing multicast cells only once. Further, the multicast mechanism of 3DQ prevents a congested destination port from blocking other less- loaded ports. The 3DQ principle has been prototyped in the Illinois Input Queue (iiQueue) module. Using Field Programmable Gate Array (FPGA) devices, SRAM modules, and integrated on a Printed Circuit Board (PCB), iiQueue can process incoming traffic at 800 Mb/s. Using faster circuit technology, the same design is expected to operate at the OC-48 rate (2.5 Gb/s). MUCS resolves the output contention by evaluating the weight index of each candidate and selecting the heaviest. It achieves near-optimal scheduling and has a very short response time. The algorithm originates from a heuristic strategy that leads to 'socially optimal' solutions, yielding a maximum number of contention-free cells being scheduled. A novel mixed digital-analog circuit has been designed to implement the MUCS core functionality. The MUCS circuit maps the cell scheduling computation to the capacitor charging and discharging procedures that are conducted fully in parallel. The design has a uniform circuit structure, low interconnect counts, and low chip I/O counts. Using 2 μm CMOS technology, the design operates on a 100 MHz clock and finds a near-optimal solution within a linear processing time. The circuit has been verified at the transistor level by HSPICE simulation. During this research, a five-port IQ-based optoelectronic iPOINT ATM switch has been developed and demonstrated. It has been fully functional with an aggregate throughput of 800 Mb/s. The second-generation IQ-based switch is currently under development. Equipped with iiQueue modules and MUCS module, the new switch system will deliver a multi-gigabit aggregate throughput, eliminate HOL blocking, provide per-VC QoS, and achieve near-100% link bandwidth utilization. Complete documentation of input modules and trunk module for the existing testbed, and complete documentation of 3DQ, iiQueue, and MUCS for the second-generation testbed are given in this dissertation.

  9. Adaptive Topological Configuration of an Integrated Circuit/Packet-Switched Computer Network.

    DTIC Science & Technology

    1984-01-01

    Gitman et al. [45] state that there are basically two approaches to the integrated network design problem: (1) solve the link/capacity problem for...1972), 1385-1397. 33. Frank, H., and Gitman , I. Economic analysis of integrated voice and data networks: a case study. Proc. of IEEE 66 , 11 (Nov. 1978...1974), 1074-1079. 45. Gitman , I., Hsieh, W., and Occhiogrosso, B. J. Analysis and design of hybrid switching networks. IEEE Trans. on Comm. Com-29

  10. Power-efficient dual-rate optical transceiver.

    PubMed

    Zuo, Yongrong; Kiamiley, Fouad E; Wang, Xiaoqing; Gui, Ping; Ekman, Jeremy; Wang, Xingle; McFadden, Michael J; Haney, Michael W

    2005-11-20

    A dual-rate (2 Gbit/s and 100 Mbit/s) optical transceiver designed for power-efficient connections within and between modern high-speed digital systems is described. The transceiver can dynamically adjust its data rate according to performance requirements, allowing for power-on-demand operation. Dynamic power management permits energy saving and lowers device operating temperatures, improving the reliability and lifetime of optoelectronic-devices such as vertical-cavity surface-emitting lasers (VCSELs). To implement dual-rate functionality, we include in the transmitter and receiver circuits separate high-speed and low-power data path modules. The high-speed module is designed for gigabit operation to achieve high bandwidth. A simpler low-power module is designed for megabit data transmission with low power consumption. The transceiver is fabricated in a 0.5 microm silicon-on-sapphire complementary metal-oxide semiconductor. The VCSEL and photodetector devices are attached to the transceiver's integrated circuit by flip-chip bonding. A free-space optical link system is constructed to demonstrate correct dual-rate functionality. Experimental results show reliable link operation at 2 Gbit/s and 100 Mbit/s data transfer rates with approximately 104 and approximately 9 mW power consumption, respectively. The transceiver's switching time between these two data rates is demonstrated as 10 micros, which is limited by on-chip register reconfiguration time. Improvement of this switching time can be obtained by use of dedicated input-output pads for dual-rate control signals.

  11. Cenozoic motion between East and West Antarctica

    PubMed

    Cande; Stock; Muller; Ishihara

    2000-03-09

    The West Antarctic rift system is the result of late Mesozoic and Cenozoic extension between East and West Antarctica, and represents one of the largest active continental rift systems on Earth. But the timing and magnitude of the plate motions leading to the development of this rift system remain poorly known, because of a lack of magnetic anomaly and fracture zone constraints on seafloor spreading. Here we report on magnetic data, gravity data and swath bathymetry collected in several areas of the south Tasman Sea and northern Ross Sea. These results enable us to calculate mid-Cenozoic rotation parameters for East and West Antarctica. These rotations show that there was roughly 180 km of separation in the western Ross Sea embayment in Eocene and Oligocene time. This episode of extension provides a tectonic setting for several significant Cenozoic tectonic events in the Ross Sea embayment including the uplift of the Transantarctic Mountains and the deposition of large thicknesses of Oligocene sediments. Inclusion of this East-West Antarctic motion in the plate circuit linking the Australia, Antarctic and Pacific plates removes a puzzling gap between the Lord Howe rise and Campbell plateau found in previous early Tertiary reconstructions of the New Zealand region. Determination of this East-West Antarctic motion also resolves a long standing controversy regarding the contribution of deformation in this region to the global plate circuit linking the Pacific to the rest of the world.

  12. Specific cerebral perfusion patterns in three schizophrenia symptom dimensions.

    PubMed

    Stegmayer, Katharina; Strik, Werner; Federspiel, Andrea; Wiest, Roland; Bohlhalter, Stephan; Walther, Sebastian

    2017-12-01

    Dimensional concepts such as the Research Domain Criteria initiative have been proposed to disentangle the heterogeneity of schizophrenia. One model introduced three neurobiologically informed behavioral dimensions: language, affectivity and motor behavior. To study the brain-behavior associations of these three dimensions, we investigated whether current behavioral alterations were linked to resting state perfusion in distinct brain circuits in schizophrenia. In total, 47 patients with schizophrenia spectrum disorders and 44 healthy controls were included. Psychopathology was assessed with the Positive And Negative Syndrome Scale and the Bern Psychopathology scale (BPS). The BPS provides severity ratings of three behavioral dimensions (language, affectivity and motor). Patients were classified according to the severity of alterations (severe, mild, no) in each dimension. Whole brain resting state cerebral blood flow (CBF) was compared between patient subgroups and controls. Two symptom dimensions were associated with distinct CBF changes. Behavioral alterations in the language dimension were linked to increased CBF in Heschl's gyrus. Altered affectivity was related to increased CBF in amygdala. The ratings of motor behavior instead were not specifically associated with CBF. Investigating behavioral alterations in three schizophrenia symptom dimensions identified distinct regional CBF changes in the language and limbic brain circuits. The results demonstrate a hitherto unknown segregation of pathophysiological pathways underlying a limited number of specific symptom dimensions in schizophrenia. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

  13. A Hierarchical Generative Framework of Language Processing: Linking Language Perception, Interpretation, and Production Abnormalities in Schizophrenia

    PubMed Central

    Brown, Meredith; Kuperberg, Gina R.

    2015-01-01

    Language and thought dysfunction are central to the schizophrenia syndrome. They are evident in the major symptoms of psychosis itself, particularly as disorganized language output (positive thought disorder) and auditory verbal hallucinations (AVHs), and they also manifest as abnormalities in both high-level semantic and contextual processing and low-level perception. However, the literatures characterizing these abnormalities have largely been separate and have sometimes provided mutually exclusive accounts of aberrant language in schizophrenia. In this review, we propose that recent generative probabilistic frameworks of language processing can provide crucial insights that link these four lines of research. We first outline neural and cognitive evidence that real-time language comprehension and production normally involve internal generative circuits that propagate probabilistic predictions to perceptual cortices — predictions that are incrementally updated based on prediction error signals as new inputs are encountered. We then explain how disruptions to these circuits may compromise communicative abilities in schizophrenia by reducing the efficiency and robustness of both high-level language processing and low-level speech perception. We also argue that such disruptions may contribute to the phenomenology of thought-disordered speech and false perceptual inferences in the language system (i.e., AVHs). This perspective suggests a number of productive avenues for future research that may elucidate not only the mechanisms of language abnormalities in schizophrenia, but also promising directions for cognitive rehabilitation. PMID:26640435

  14. Packet based serial link realized in FPGA dedicated for high resolution infrared image transmission

    NASA Astrophysics Data System (ADS)

    Bieszczad, Grzegorz

    2015-05-01

    In article the external digital interface specially designed for thermographic camera built in Military University of Technology is described. The aim of article is to illustrate challenges encountered during design process of thermal vision camera especially related to infrared data processing and transmission. Article explains main requirements for interface to transfer Infra-Red or Video digital data and describes the solution which we elaborated based on Low Voltage Differential Signaling (LVDS) physical layer and signaling scheme. Elaborated link for image transmission is built using FPGA integrated circuit with built-in high speed serial transceivers achieving up to 2500Gbps throughput. Image transmission is realized using proprietary packet protocol. Transmission protocol engine was described in VHDL language and tested in FPGA hardware. The link is able to transmit 1280x1024@60Hz 24bit video data using one signal pair. Link was tested to transmit thermal-vision camera picture to remote monitor. Construction of dedicated video link allows to reduce power consumption compared to solutions with ASIC based encoders and decoders realizing video links like DVI or packed based Display Port, with simultaneous reduction of wires needed to establish link to one pair. Article describes functions of modules integrated in FPGA design realizing several functions like: synchronization to video source, video stream packeting, interfacing transceiver module and dynamic clock generation for video standard conversion.

  15. A Temperature-Responsive Network Links Cell Shape and Virulence Traits in a Primary Fungal Pathogen

    PubMed Central

    Beyhan, Sinem; Gutierrez, Matias; Voorhies, Mark; Sil, Anita

    2013-01-01

    Survival at host temperature is a critical trait for pathogenic microbes of humans. Thermally dimorphic fungal pathogens, including Histoplasma capsulatum, are soil fungi that undergo dramatic changes in cell shape and virulence gene expression in response to host temperature. How these organisms link changes in temperature to both morphologic development and expression of virulence traits is unknown. Here we elucidate a temperature-responsive transcriptional network in H. capsulatum, which switches from a filamentous form in the environment to a pathogenic yeast form at body temperature. The circuit is driven by three highly conserved factors, Ryp1, Ryp2, and Ryp3, that are required for yeast-phase growth at 37°C. Ryp factors belong to distinct families of proteins that control developmental transitions in fungi: Ryp1 is a member of the WOPR family of transcription factors, and Ryp2 and Ryp3 are both members of the Velvet family of proteins whose molecular function is unknown. Here we provide the first evidence that these WOPR and Velvet proteins interact, and that Velvet proteins associate with DNA to drive gene expression. Using genome-wide chromatin immunoprecipitation studies, we determine that Ryp1, Ryp2, and Ryp3 associate with a large common set of genomic loci that includes known virulence genes, indicating that the Ryp factors directly control genes required for pathogenicity in addition to their role in regulating cell morphology. We further dissect the Ryp regulatory circuit by determining that a fourth transcription factor, which we name Ryp4, is required for yeast-phase growth and gene expression, associates with DNA, and displays interdependent regulation with Ryp1, Ryp2, and Ryp3. Finally, we define cis-acting motifs that recruit the Ryp factors to their interwoven network of temperature-responsive target genes. Taken together, our results reveal a positive feedback circuit that directs a broad transcriptional switch between environmental and pathogenic states in response to temperature. PMID:23935449

  16. Space Weather Connections to Clouds and Climate

    NASA Astrophysics Data System (ADS)

    Tinsley, B. A.

    2004-12-01

    There is now a considerable amount of observational data and theoretical work pointing to a link between space weather and atmospheric electricity, and then between atmospheric electricity and cloud cover and precipitation, which ultimately affect climate and the biosphere. Studies so far have been largely confined to the Earth, but may be applicable to all planets with clouds in their atmospheres. The current density Jz, that is the return current flowing downward through clouds in the global circuit, is modulated by the galactic cosmic ray flux; by solar energetic particles; by the dawn-dusk polar cap potential difference; and by the precipitation of relativistic electrons from the radiation belts. The flow of Jz through clouds generates unipolar space charge, which is positive at cloud tops and negative at cloud base. This charge attaches to aerosol particles, and affects their interaction with other particles and droplets. Ultrafine aerosol particles are formed around ions and are preserved from scavenging on background aerosols, and preserved for growth by vapor deposition, by space charge at the bases and tops of layer clouds. There is electro-preservation of both ultrafines and of existing CCN that leads to increases in CCN concentration, and increases in cloud cover and reduction in both droplet size and precipitation by the `indirect aerosol effect'. For cold clouds and larger aerosol particles that act as ice forming nuclei, the rate of scavenging of the IFN by large supercooled droplets varies with space charge. Changes in space weather affect both ion production and Jz in planetary atmospheres. In addition, changes in cosmic ray flux affect conductivity within thunderclouds and may affect the output of the thundercloud generators in the global circuit. Thus all four processes, (a) ion-induced nucleation, (b) electro-preservation of leading to increases in CCN concentration and the indirect aerosol effect, (c) contact ice nucleation affecting the production of ices, (d) cosmic ray effects on the generators of the global circuit, are potential links between space weather and life on planets.

  17. Rocks, when Stressed, turn into a Battery that is Rechargeable

    NASA Astrophysics Data System (ADS)

    Lau, B. T.; Takeuchi, A. H.; Freund, F. T.

    2006-12-01

    Igneous rocks, when subjected to deviatory stresses, turn into a battery. We report on gabbro (Shanxi, China). We use steel pistons to load repeatedly ~10 cm3 in the center of 30 x 30 x 0.9 cm3 tiles, from 0 to 60 MPa, 1/3 failure strength, at 0.2 MPa/sec with 20-30 min at constant load. Instantly upon loading, a current begins to flow, increasing to 200-300 pA, equivalent to 30,000 to 50,000 A/km3. Under constant load the current continues to flow for at least 24 hrs with barely 10-20% reduction. During unloading the current stops but resumes during repetitive loading-unloading cycles for at least 22 times. One part of the current is carried by electrons. The electrons flow from the stressed rock into the steel pistons, through the external circuit to the edges of the tile. The other part is carried by holes. The holes flow inside the rock, from the stressed to the unstressed rock and to the edges of the tile. There they meet the electrons, thereby closing the circuit. Both types of charge carriers, electrons and holes, are associated with oxygen anions that changed their valence from 2- to 1- (peroxy). An O- among O2- represents a defect electron in the O2- sublattice, known as positive hole or p-hole for short. In unstressed rocks the O- exist in an electrically inactive form as O- pairs, chemically equivalent to peroxy links, O3X-OO-XO3 with X = Si4+, Al3+ etc. Deviatory stresses cause the peroxy links to break, allowing electrons from neighboring O2- to jump in and p-holes to jump out. The p-holes can spread into and through the unstressed rock using energy levels in the valence band. To observe sustained currents the battery circuit has to close.

  18. Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS.

    PubMed

    Silva, Mauro Sb; Prescott, Melanie; Campbell, Rebecca E

    2018-04-05

    Androgen excess is a hallmark of polycystic ovary syndrome (PCOS), a prevalent yet poorly understood endocrine disorder. Evidence from women and preclinical animal models suggests that elevated perinatal androgens can elicit PCOS onset in adulthood, implying androgen actions in both PCOS ontogeny and adult pathophysiology. Prenatally androgenized (PNA) mice exhibit a robust increase of progesterone-sensitive GABAergic inputs to gonadotropin-releasing hormone (GnRH) neurons implicated in the pathogenesis of PCOS. It is unclear when altered GABAergic wiring develops in the brain, and whether these central abnormalities are dependent upon adult androgen excess. Using GnRH-GFP-transgenic mice, we determined that increased GABA input to GnRH neurons occurs prior to androgen excess and the manifestation of reproductive impairments in PNA mice. These data suggest that brain circuit abnormalities precede the postpubertal development of PCOS traits. Despite the apparent developmental programming of circuit abnormalities, long-term blockade of androgen receptor signaling from early adulthood rescued normal GABAergic wiring onto GnRH neurons, improved ovarian morphology, and restored reproductive cycles in PNA mice. Therefore, androgen excess maintains changes in female brain wiring linked to PCOS features and the blockade of androgen receptor signaling reverses both the central and peripheral PNA-induced PCOS phenotype.

  19. Adrenomedullin increases the short-circuit current in the mouse seminal vesicle: actions on chloride secretion.

    PubMed

    Liao, S B; Cheung, K H; O, W S; Tang, Fai

    2014-08-01

    Adrenomedullin (ADM) may regulate seminal vesicle fluid secretion, and this may affect sperm quality. In this study, we investigated the effect of ADM on chloride secretion in the mouse seminal vesicle. The presence of ADM in mouse seminal vesicle was confirmed using immunostaining, and the molecular species was determined using gel filtration chromatography coupled with enzyme-linked assay for ADM. The effects of ADM on chloride secretion were studied by short-circuit current technique in a whole-mount preparation of mouse seminal vesicle in an Ussing chamber. The effects of specific ADM and calcitonin gene-related peptide (CGRP) receptor antagonists were investigated. Whether the ADM effect depended on the cAMP- and/or calcium-activated chloride channel was also studied using specific chloride channel blockers. The results showed that ADM was present in seminal vesicle epithelial cells. The major molecular species was precursor in the mouse seminal vesicle. ADM increased short-circuit current through the calcium-activated chloride channel in mouse seminal vesicle, and CGRP receptor was involved. We conclude that ADM may regulate chloride and fluid secretion from the seminal vesicle, which may affect the composition of the seminal plasma bathing the sperm and, hence, fertility. © 2014 by the Society for the Study of Reproduction, Inc.

  20. Adrenomedullin increases the short-circuit current in the rat prostate: Receptors, chloride channels, the effects of cAMP and calcium ions and implications on fluid secretion.

    PubMed

    Liao, S B; Cheung, K H; Cheung, M P L; Wong, P F; O, W S; Tang, F

    2014-05-01

    In this study, we have investigated the effects of adrenomedullin on chloride and fluid secretion in the rat prostate. The presence of adrenomedullin (ADM) in rat prostate was confirmed using immunostaining, and the molecular species was determined using gel filtration chromatography coupled with an enzyme-linked assay for ADM. The effects of ADM on fluid secretion were studied by short-circuit current technique in a whole mount preparation of the prostate in an Ussing chamber. The results indicated that the ADM level was higher in the ventral than the dorso-lateral prostate and the major molecular species was the active peptide. ADM increased the short-circuit current through both the cAMP- and calcium-activated chloride channels in the ventral lobe, but only through the calcium-activated channels in the dorso-lateral lobe. These stimulatory effects were blocked by the calcitonin gene-related peptide (CGRP) receptor antagonist, hCGRP8-37. We conclude that ADM may regulate prostatic fluid secretion through the chloride channels, which may affect the composition of the seminal plasma bathing the spermatozoa and hence fertility. © 2014 American Society of Andrology and European Academy of Andrology.

  1. Mechanosensation and Adaptive Motor Control in Insects.

    PubMed

    Tuthill, John C; Wilson, Rachel I

    2016-10-24

    The ability of animals to flexibly navigate through complex environments depends on the integration of sensory information with motor commands. The sensory modality most tightly linked to motor control is mechanosensation. Adaptive motor control depends critically on an animal's ability to respond to mechanical forces generated both within and outside the body. The compact neural circuits of insects provide appealing systems to investigate how mechanical cues guide locomotion in rugged environments. Here, we review our current understanding of mechanosensation in insects and its role in adaptive motor control. We first examine the detection and encoding of mechanical forces by primary mechanoreceptor neurons. We then discuss how central circuits integrate and transform mechanosensory information to guide locomotion. Because most studies in this field have been performed in locusts, cockroaches, crickets, and stick insects, the examples we cite here are drawn mainly from these 'big insects'. However, we also pay particular attention to the tiny fruit fly, Drosophila, where new tools are creating new opportunities, particularly for understanding central circuits. Our aim is to show how studies of big insects have yielded fundamental insights relevant to mechanosensation in all animals, and also to point out how the Drosophila toolkit can contribute to future progress in understanding mechanosensory processing. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. A two-layered diffusion model traces the dynamics of information processing in the valuation-and-choice circuit of decision making.

    PubMed

    Piu, Pietro; Fargnoli, Francesco; Innocenti, Alessandro; Rufa, Alessandra

    2014-01-01

    A circuit of evaluation and selection of the alternatives is considered a reliable model in neurobiology. The prominent contributions of the literature to this topic are reported. In this study, valuation and choice of a decisional process during Two-Alternative Forced-Choice (TAFC) task are represented as a two-layered network of computational cells, where information accrual and processing progress in nonlinear diffusion dynamics. The evolution of the response-to-stimulus map is thus modeled by two linked diffusive modules (2LDM) representing the neuronal populations involved in the valuation-and-decision circuit of decision making. Diffusion models are naturally appropriate for describing accumulation of evidence over the time. This allows the computation of the response times (RTs) in valuation and choice, under the hypothesis of ex-Wald distribution. A nonlinear transfer function integrates the activities of the two layers. The input-output map based on the infomax principle makes the 2LDM consistent with the reinforcement learning approach. Results from simulated likelihood time series indicate that 2LDM may account for the activity-dependent modulatory component of effective connectivity between the neuronal populations. Rhythmic fluctuations of the estimate gain functions in the delta-beta bands also support the compatibility of 2LDM with the neurobiology of DM.

  3. Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS

    PubMed Central

    Silva, Mauro S.B.; Prescott, Melanie; Campbell, Rebecca E.

    2018-01-01

    Androgen excess is a hallmark of polycystic ovary syndrome (PCOS), a prevalent yet poorly understood endocrine disorder. Evidence from women and preclinical animal models suggests that elevated perinatal androgens can elicit PCOS onset in adulthood, implying androgen actions in both PCOS ontogeny and adult pathophysiology. Prenatally androgenized (PNA) mice exhibit a robust increase of progesterone-sensitive GABAergic inputs to gonadotropin-releasing hormone (GnRH) neurons implicated in the pathogenesis of PCOS. It is unclear when altered GABAergic wiring develops in the brain, and whether these central abnormalities are dependent upon adult androgen excess. Using GnRH-GFP–transgenic mice, we determined that increased GABA input to GnRH neurons occurs prior to androgen excess and the manifestation of reproductive impairments in PNA mice. These data suggest that brain circuit abnormalities precede the postpubertal development of PCOS traits. Despite the apparent developmental programming of circuit abnormalities, long-term blockade of androgen receptor signaling from early adulthood rescued normal GABAergic wiring onto GnRH neurons, improved ovarian morphology, and restored reproductive cycles in PNA mice. Therefore, androgen excess maintains changes in female brain wiring linked to PCOS features and the blockade of androgen receptor signaling reverses both the central and peripheral PNA-induced PCOS phenotype. PMID:29618656

  4. Distribution of androgen receptor mRNA expression in vocal, auditory, and neuroendocrine circuits in a teleost fish.

    PubMed

    Forlano, Paul M; Marchaterre, Margaret; Deitcher, David L; Bass, Andrew H

    2010-02-15

    Across all major vertebrate groups, androgen receptors (ARs) have been identified in neural circuits that shape reproductive-related behaviors, including vocalization. The vocal control network of teleost fishes presents an archetypal example of how a vertebrate nervous system produces social, context-dependent sounds. We cloned a partial cDNA of AR that was used to generate specific probes to localize AR expression throughout the central nervous system of the vocal plainfin midshipman fish (Porichthys notatus). In the forebrain, AR mRNA is abundant in proposed homologs of the mammalian striatum and amygdala, and in anterior and posterior parvocellular and magnocellular nuclei of the preoptic area, nucleus preglomerulosus, and posterior, ventral and anterior tuberal nuclei of the hypothalamus. Many of these nuclei are part of the known vocal and auditory circuitry in midshipman. The midbrain periaqueductal gray, an essential link between forebrain and hindbrain vocal circuitry, and the lateral line recipient nucleus medialis in the rostral hindbrain also express abundant AR mRNA. In the caudal hindbrain-spinal vocal circuit, high AR mRNA is found in the vocal prepacemaker nucleus and along the dorsal periphery of the vocal motor nucleus congruent with the known pattern of expression of aromatase-containing glial cells. Additionally, abundant AR mRNA expression is shown for the first time in the inner ear of a vertebrate. The distribution of AR mRNA strongly supports the role of androgens as modulators of behaviorally defined vocal, auditory, and neuroendocrine circuits in teleost fish and vertebrates in general. 2009 Wiley-Liss, Inc.

  5. Impaired activity-dependent neural circuit assembly and refinement in autism spectrum disorder genetic models

    PubMed Central

    Doll, Caleb A.; Broadie, Kendal

    2014-01-01

    Early-use activity during circuit-specific critical periods refines brain circuitry by the coupled processes of eliminating inappropriate synapses and strengthening maintained synapses. We theorize these activity-dependent (A-D) developmental processes are specifically impaired in autism spectrum disorders (ASDs). ASD genetic models in both mouse and Drosophila have pioneered our insights into normal A-D neural circuit assembly and consolidation, and how these developmental mechanisms go awry in specific genetic conditions. The monogenic fragile X syndrome (FXS), a common cause of heritable ASD and intellectual disability, has been particularly well linked to defects in A-D critical period processes. The fragile X mental retardation protein (FMRP) is positively activity-regulated in expression and function, in turn regulates excitability and activity in a negative feedback loop, and appears to be required for the A-D remodeling of synaptic connectivity during early-use critical periods. The Drosophila FXS model has been shown to functionally conserve the roles of human FMRP in synaptogenesis, and has been centrally important in generating our current mechanistic understanding of the FXS disease state. Recent advances in Drosophila optogenetics, transgenic calcium reporters, highly-targeted transgenic drivers for individually-identified neurons, and a vastly improved connectome of the brain are now being combined to provide unparalleled opportunities to both manipulate and monitor A-D processes during critical period brain development in defined neural circuits. The field is now poised to exploit this new Drosophila transgenic toolbox for the systematic dissection of A-D mechanisms in normal versus ASD brain development, particularly utilizing the well-established Drosophila FXS disease model. PMID:24570656

  6. The human parental brain: In vivo neuroimaging

    PubMed Central

    Swain, James E.

    2015-01-01

    Interacting parenting thoughts and behaviors, supported by key brain circuits, critically shape human infants’ current and future behavior. Indeed, the parent–infant relationship provides infants with their first social environment, forming templates for what they can expect from others, how to interact with them and ultimately how they go on to themselves to be parents. This review concentrates on magnetic resonance imaging experiments of the human parent brain, which link brain physiology with parental thoughts and behaviors. After reviewing brain imaging techniques, certain social cognitive and affective concepts are reviewed, including empathy and trust—likely critical to parenting. Following that is a thorough study-by-study review of the state-of-the-art with respect to human neuroimaging studies of the parental brain—from parent brain responses to salient infant stimuli, including emotionally charged baby cries and brief visual stimuli to the latest structural brain studies. Taken together, this research suggests that networks of highly conserved hypothalamic–midbrain–limbic–paralimbic–cortical circuits act in concert to support parental brain responses to infants, including circuits for limbic emotion response and regulation. Thus, a model is presented in which infant stimuli activate sensory analysis brain regions, affect corticolimbic limbic circuits that regulate emotional response, motivation and reward related to their infant, ultimately organizing parenting impulses, thoughts and emotions into coordinated behaviors as a map for future studies. Finally, future directions towards integrated understanding of the brain basis of human parenting are outlined with profound implications for understanding and contributing to long term parent and infant mental health. PMID:21036196

  7. Serotonin's Complex Role in Alcoholism: Implications for Treatment and Future Research.

    PubMed

    Marcinkiewcz, Catherine A; Lowery-Gionta, Emily G; Kash, Thomas L

    2016-06-01

    Current pharmacological treatments for alcohol dependence have focused on reducing alcohol consumption, but to date there are few treatments that also address the negative affective symptoms during acute and protracted alcohol withdrawal which are often exacerbated in people with comorbid anxiety and depression. Selective serotonin reuptake inhibitors (SSRIs) are sometimes prescribed to ameliorate these symptoms but can exacerbate anxiety and cravings in a select group of patients. In this critical review, we discuss recent literature describing an association between alcohol dependence, the SERT linked polymorphic region (5-HTTLPR), and pharmacological response to SSRIs. Given the heterogeneity in responsiveness to serotonergic drugs across the spectrum of alcoholic subtypes, we assess the contribution of specific 5-HT circuits to discrete endophenotypes of alcohol dependence. 5-HT circuits play a distinctive role in reward, stress, and executive function which may account for the variation in response to serotonergic drugs. New optogenetic and chemogenetic methods for dissecting 5-HT circuits in alcohol dependence may provide clues leading to more effective pharmacotherapies. Although our current understanding of the role of 5-HT systems in alcohol dependence is incomplete, there is some evidence to suggest that 5-HT3 receptor antagonists are effective in people with the L/L genotype of the 5-HTTLPR polymorphism while SSRIs may be more beneficial to people with the S/L or S/S genotype. Studies that assess the impact of serotonin transporter polymorphisms on 5-HT circuit function and the subsequent development of alcohol use disorders will be an important step forward in treating alcohol dependence. Copyright © 2016 by the Research Society on Alcoholism.

  8. Merlin - Massively parallel heterogeneous computing

    NASA Technical Reports Server (NTRS)

    Wittie, Larry; Maples, Creve

    1989-01-01

    Hardware and software for Merlin, a new kind of massively parallel computing system, are described. Eight computers are linked as a 300-MIPS prototype to develop system software for a larger Merlin network with 16 to 64 nodes, totaling 600 to 3000 MIPS. These working prototypes help refine a mapped reflective memory technique that offers a new, very general way of linking many types of computer to form supercomputers. Processors share data selectively and rapidly on a word-by-word basis. Fast firmware virtual circuits are reconfigured to match topological needs of individual application programs. Merlin's low-latency memory-sharing interfaces solve many problems in the design of high-performance computing systems. The Merlin prototypes are intended to run parallel programs for scientific applications and to determine hardware and software needs for a future Teraflops Merlin network.

  9. Multiple Pathways Linking Racism to Health Outcomes

    PubMed Central

    Harrell, Camara Jules P.; Burford, Tanisha I.; Cage, Brandi N.; Nelson, Travette McNair; Shearon, Sheronda; Thompson, Adrian; Green, Steven

    2012-01-01

    This commentary discusses advances in the conceptual understanding of racism and selected research findings in the social neurosciences. The traditional stress and coping model holds that racism constitutes a source of aversive experiences that, when perceived by the individual, eventually lead to poor health outcomes. Current evidence points to additional psychophysiological pathways linking facets of racist environments with physiological reactions that contribute to disease. The alternative pathways emphasize prenatal experiences, subcortical emotional neural circuits, conscious and preconscious emotion regulation, perseverative cognitions, and negative affective states stemming from racist cognitive schemata. Recognition of these pathways challenges change agents to use an array of cognitive and self-controlling interventions in mitigating racism’s impact. Additionally, it charges policy makers to develop strategies that eliminate deep-seated structural aspects of racism in society. PMID:22518195

  10. Asymmetrical squaraines for high-performance small-molecule organic solar cells with a short circuit current of over 12 mA cm(-2).

    PubMed

    Chen, Yao; Zhu, Youqin; Yang, Daobin; Luo, Qian; Yang, Lin; Huang, Yan; Zhao, Suling; Lu, Zhiyun

    2015-04-11

    An asymmetrical squaraine dye (Py-3) with its two electron-donating aryl groups directly linked to the electron-withdrawing squaric acid core possesses an ideal bandgap of 1.33 eV, together with an intense and broad absorption band in the range 550-950 nm. Hence, the resulting solution-processed solar cells display an impressive Jsc of 12.03 mA cm(-2) and a PCE of 4.35%.

  11. On-board processing architectures for satellite B-ISDN services

    NASA Technical Reports Server (NTRS)

    Inukai, Thomas; Shyy, Dong-Jye; Faris, Faris

    1991-01-01

    Onboard baseband processing architectures for future satellite broadband integrated services digital networks (B-ISDN's) are addressed. To assess the feasibility of implementing satellite B-ISDN services, critical design issues, such as B-ISDN traffic characteristics, transmission link design, and a trade-off between onboard circuit and fast packet switching, are analyzed. Examples of the two types of switching mechanisms and potential onboard network control functions are presented. A sample network architecture is also included to illustrate a potential onboard processing system.

  12. On-board processing satellite network architectures for broadband ISDN

    NASA Technical Reports Server (NTRS)

    Inukai, Thomas; Faris, Faris; Shyy, Dong-Jye

    1992-01-01

    Onboard baseband processing architectures for future satellite broadband integrated services digital networks (B-ISDN's) are addressed. To assess the feasibility of implementing satellite B-ISDN services, critical design issues, such as B-ISDN traffic characteristics, transmission link design, and a trade-off between onboard circuit and fast packet switching, are analyzed. Examples of the two types of switching mechanisms and potential onboard network control functions are presented. A sample network architecture is also included to illustrate a potential onboard processing system.

  13. A Wire Antenna Designed for Space Wave Radiation Over the Earth Using a Genetic Algorithm

    DTIC Science & Technology

    1997-12-01

    are extended beyond that of connecting the wires in series. 1.6 Assumptions 1.6.1 Smooth Earth. It was not prudent for the research to account for an...and circuit grounds are connected in some manner. 1.7 Scope The research proposes a system antenna design, taking into account the link budget. The...1.10 Goals The purpose of the research is to conduct a thorough design approach taking into account all aspects of antenna design, to include the

  14. Cognitive-motor interactions of the basal ganglia in development

    PubMed Central

    Leisman, Gerry; Braun-Benjamin, Orit; Melillo, Robert

    2014-01-01

    Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human reasoning and adaptive function. The basal ganglia are key elements in the control of reward-based learning, sequencing, discrete elements that constitute a complete motor act, and cognitive function. Imaging studies of intact human subjects and electrophysiologic and tracer studies of the brains and behavior of other species confirm these findings. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. Neuronal activity within the basal ganglia associated with motor areas of the cerebral cortex is highly correlated with parameters of movement. Neuronal activity within the basal ganglia and cerebellar loops associated with the prefrontal cortex is related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Damage to the basal ganglia of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with non-motor areas of the cortex causes higher-order deficits. In this report, we review some of the anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to attention deficit/hyperactivity disorder (ADHD) with biomechanics and a discussion of retention of primitive reflexes being highly associated with the condition. PMID:24592214

  15. Towards a unified theory of neocortex: laminar cortical circuits for vision and cognition.

    PubMed

    Grossberg, Stephen

    2007-01-01

    A key goal of computational neuroscience is to link brain mechanisms to behavioral functions. The present article describes recent progress towards explaining how laminar neocortical circuits give rise to biological intelligence. These circuits embody two new and revolutionary computational paradigms: Complementary Computing and Laminar Computing. Circuit properties include a novel synthesis of feedforward and feedback processing, of digital and analog processing, and of preattentive and attentive processing. This synthesis clarifies the appeal of Bayesian approaches but has a far greater predictive range that naturally extends to self-organizing processes. Examples from vision and cognition are summarized. A LAMINART architecture unifies properties of visual development, learning, perceptual grouping, attention, and 3D vision. A key modeling theme is that the mechanisms which enable development and learning to occur in a stable way imply properties of adult behavior. It is noted how higher-order attentional constraints can influence multiple cortical regions, and how spatial and object attention work together to learn view-invariant object categories. In particular, a form-fitting spatial attentional shroud can allow an emerging view-invariant object category to remain active while multiple view categories are associated with it during sequences of saccadic eye movements. Finally, the chapter summarizes recent work on the LIST PARSE model of cognitive information processing by the laminar circuits of prefrontal cortex. LIST PARSE models the short-term storage of event sequences in working memory, their unitization through learning into sequence, or list, chunks, and their read-out in planned sequential performance that is under volitional control. LIST PARSE provides a laminar embodiment of Item and Order working memories, also called Competitive Queuing models, that have been supported by both psychophysical and neurobiological data. These examples show how variations of a common laminar cortical design can embody properties of visual and cognitive intelligence that seem, at least on the surface, to be mechanistically unrelated.

  16. Aphid Species and Population Dynamics Associated with Strawberry.

    PubMed

    Bernardi, D; Araujo, E S; Zawadneak, M A C; Botton, M; Mogor, A F; Garcia, M S

    2013-12-01

    Aphids are among the major pests associated with strawberries in Southern Brasil. In this study, we identified the main species that occur in strawberry fields in the states of Paraná and Rio Grande do Sul, Brasil. We also compared the effectiveness of different sampling methods and studied the population dynamics of aphid species during two strawberry crop cycles in the municipality of Pinhais, state of Paraná, Brasil. Chaetosiphon fragaefolii (Cockerell) and Aphis forbesi Weed were the main species associated with strawberry. The method of hit plant and the Möericke trap showed equal effectiveness to capture wingless and winged insects. The peak population of aphids in the state of Paraná occurred from September to November. This information can help producers to implement strategies to monitor and control the major aphid species that occur in strawberry culture.

  17. Structure of the kinase domain of Gilgamesh from Drosophila melanogaster

    PubMed Central

    Han, Ni; Chen, CuiCui; Shi, Zhubing; Cheng, Dianlin

    2014-01-01

    The CK1 family kinases regulate multiple cellular aspects and play important roles in Wnt/Wingless and Hedgehog signalling. The kinase domain of Drosophila Gilgamesh isoform I (Gilgamesh-I), a homologue of human CK1-γ, was purified and crystallized. Crystals of methylated Gilgamesh-I kinase domain with a D210A mutation diffracted to 2.85 Å resolution and belonged to space group P43212, with unit-cell parameters a = b = 52.025, c = 291.727 Å. The structure of Gilgamesh-I kinase domain, which was determined by molecular replacement, has conserved catalytic elements and an active conformation. Structural comparison indicates that an extended loop between the α1 helix and the β4 strand exists in the Gilgamesh-I kinase domain. This extended loop may regulate the activity and function of Gilgamesh-I. PMID:24699734

  18. Functional conservation of the human EXT1 tumor suppressor gene and its Drosophila homolog tout velu.

    PubMed

    Dasgupta, Ujjaini; Dixit, Bharat L; Rusch, Melissa; Selleck, Scott; The, Inge

    2007-08-01

    Heparan sulfate proteoglycans play a vital role in signaling of various growth factors in both Drosophila and vertebrates. In Drosophila, mutations in the tout velu (ttv) gene, a homolog of the mammalian EXT1 tumor suppressor gene, leads to abrogation of glycosaminoglycan (GAG) biosynthesis. This impairs distribution and signaling activities of various morphogens such as Hedgehog (Hh), Wingless (Wg), and Decapentaplegic (Dpp). Mutations in members of the exostosin (EXT) gene family lead to hereditary multiple exostosis in humans leading to bone outgrowths and tumors. In this study, we provide genetic and biochemical evidence that the human EXT1 (hEXT1) gene is conserved through species and can functionally complement the ttv mutation in Drosophila. The hEXT1 gene was able to rescue a ttv null mutant to adulthood and restore GAG biosynthesis.

  19. Chip-to-chip optical link by using optical wiring method

    NASA Astrophysics Data System (ADS)

    Cho, In-Kui; Ahn, Seoung Ho; Jeong, Myung-Yung; Rho, Byung Sup; Park, Hyo Hoon

    2008-01-01

    A practical optical link system was prepared with a transmitter (Tx) and receiver (Rx). The optical TRx module consisted of a metal optical bench, a module printed circuit board (PCB), a driver/receiver IC, a VCSEL/PD array, and an optical link block composed of plastic optical fiber (POF). For the optical interconnection between the light-sources and detectors, an optical wiring method has been proposed to enable easy assembly. This paper provides a method for optical interconnection between an optical Tx and an optical Rx, comprising the following steps: (a) forming a light source device, an optical detection device, and an optical transmission unit on a substrate (metal optical bench (MOB)); (b) preparing a flexible optical transmission-connection medium (optical wiring link) to optically connect the light source device formed on the substrate with the optical detection device; and (c) directly connecting one end of the surface-finished optical transmission connection medium with the light source device and the other end with the optical detection device. A chip-to-chip optical link system constructed with TRx modules was fabricated and the optical characteristics were measured. The results clearly demonstrate that the use of an optical wiring method can provide robust and cost-effective assembly for vertical-cavity surface-emitting lasers (VCSELs) and photodiodes (PDs). We successfully achieved a 5 Gb/s data transmission rate with this optical link.

  20. Single crystal CVD diamond membranes for betavoltaic cells

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

    Delfaure, C.; Pomorski, M., E-mail: michal.pomorski@cea.fr; Sanoit, J. de

    2016-06-20

    A single crystal diamond large area thin membrane was assembled as a p-doped/Intrinsic/Metal (PIM) structure and used in a betavoltaic configuration. When tested with a 20 keV electron beam from a high resolution scanning electron microscope, we measured an open circuit voltage (V{sub oc}) of 1.85 V, a charge collection efficiency (CCE) of 98%, a fill-factor of 80%, and a total conversion efficiency of 9.4%. These parameters are inherently linked to the diamond membrane PIM structure that allows full device depletion even at 0 V and are among the highest reported up to now for any other material tested for betavoltaic devices. Itmore » enables to drive a high short-circuit current I{sub sc} up to 7.12 μA, to reach a maximum power P{sub max} of 10.48 μW, a remarkable value demonstrating the high-benefit of diamond for the realization of long-life radioisotope based micro-batteries.« less

  1. On the Role of Glutamate in Presynaptic Development: Possible Contributions of Presynaptic NMDA Receptors.

    PubMed

    Fedder, Karlie N; Sabo, Shasta L

    2015-12-14

    Proper formation and maturation of synapses during development is a crucial step in building the functional neural circuits that underlie perception and behavior. It is well established that experience modifies circuit development. Therefore, understanding how synapse formation is controlled by synaptic activity is a key question in neuroscience. In this review, we focus on the regulation of excitatory presynaptic terminal development by glutamate, the predominant excitatory neurotransmitter in the brain. We discuss the evidence that NMDA receptor activation mediates these effects of glutamate and present the hypothesis that local activation of presynaptic NMDA receptors (preNMDARs) contributes to glutamate-dependent control of presynaptic development. Abnormal glutamate signaling and aberrant synapse development are both thought to contribute to the pathogenesis of a variety of neurodevelopmental disorders, including autism spectrum disorders, intellectual disability, epilepsy, anxiety, depression, and schizophrenia. Therefore, understanding how glutamate signaling and synapse development are linked is important for understanding the etiology of these diseases.

  2. Packaged Capacitive Pressure Sensor System for Aircraft Engine Health Monitoring

    NASA Technical Reports Server (NTRS)

    Scardelletti, Maximilian C.; Zorman, Christian A.

    2016-01-01

    This paper describes the development of a packaged silicon carbide (SiC) based MEMS pressure sensor system designed specifically for a conventional turbofan engine. The electronic circuit is based on a Clapp-type oscillator that incorporates a 6H-SiC MESFET, a SiCN MEMS capacitive pressure sensor, titanate MIM capacitors, wirewound inductors, and thick film resistors. The pressure sensor serves as the capacitor in the LC tank circuit, thereby linking pressure to the resonant frequency of the oscillator. The oscillator and DC bias circuitry were fabricated on an alumina substrate and secured inside a metal housing. The packaged sensing system reliably operates at 0 to 350 psi and 25 to 540C. The system has a pressure sensitivity of 6.8 x 10E-2 MHzpsi. The packaged system shows negligible difference in frequency response between 25 and 400C. The fully packaged sensor passed standard benchtop acceptance tests and was evaluated on a flight-worthy engine.

  3. Gq/5-HT2c receptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice.

    PubMed

    Spoida, Katharina; Masseck, Olivia A; Deneris, Evan S; Herlitze, Stefan

    2014-04-29

    Serotonin 2c receptors (5-HT2c-Rs) are drug targets for certain mental disorders, including schizophrenia, depression, and anxiety. 5-HT2c-Rs are expressed throughout the brain, making it difficult to link behavioral changes to circuit specific receptor expression. Various 5-HT-Rs, including 5-HT2c-Rs, are found in the dorsal raphe nucleus (DRN); however, the function of 5-HT2c-Rs and their influence on the serotonergic signals mediating mood disorders remain unclear. To investigate the role of 5-HT2c-Rs in the DRN in mice, we developed a melanopsin-based optogenetic probe for activation of Gq signals in cellular domains, where 5-HT2c-Rs are localized. Our results demonstrate that precise temporal control of Gq signals in 5-HT2c-R domains in GABAergic neurons upstream of 5-HT neurons provides negative feedback regulation of serotonergic firing to modulate anxiety-like behavior in mice.

  4. Gq/5-HT2c receptor signals activate a local GABAergic inhibitory feedback circuit to modulate serotonergic firing and anxiety in mice

    PubMed Central

    Spoida, Katharina; Masseck, Olivia A.; Deneris, Evan S.; Herlitze, Stefan

    2014-01-01

    Serotonin 2c receptors (5-HT2c-Rs) are drug targets for certain mental disorders, including schizophrenia, depression, and anxiety. 5-HT2c-Rs are expressed throughout the brain, making it difficult to link behavioral changes to circuit specific receptor expression. Various 5-HT-Rs, including 5-HT2c-Rs, are found in the dorsal raphe nucleus (DRN); however, the function of 5-HT2c-Rs and their influence on the serotonergic signals mediating mood disorders remain unclear. To investigate the role of 5-HT2c-Rs in the DRN in mice, we developed a melanopsin-based optogenetic probe for activation of Gq signals in cellular domains, where 5-HT2c-Rs are localized. Our results demonstrate that precise temporal control of Gq signals in 5-HT2c-R domains in GABAergic neurons upstream of 5-HT neurons provides negative feedback regulation of serotonergic firing to modulate anxiety-like behavior in mice. PMID:24733892

  5. Theoretical Comparison of Motional and Transformer EMF Device Damping Efficiency

    NASA Astrophysics Data System (ADS)

    GRAVES, K. E.; TONCICH, D.; IOVENITTI, P. G.

    2000-06-01

    In this paper, theoretical comparison between electromagnetic dampers based on a “motional emf” and “transformer emf” design is presented. Transformer emf devices are based on the generation of emf in a stationary circuit, in which the emf is generated by a time-varying magnetic field linking the circuit. Motional emf devices are based on the generation of emf due to a moving conductor within a stationary magnetic field. Both of these designs can be used as damping elements for applications such as semi-active and regenerative vehicle suspension systems. The findings herein are provided so as to evaluate the most efficient device for such applications. The analysis consists of comparing the damping coefficient of the electromagnetic devices for a given magnetic field and given volume of conducting material. It has been found that for a limited range of dimensions, the transformer emf devices can be more then 1·2 times as efficient as the motional emf devices. However, for most realistic situations, motional emf devices will have the highest efficiency.

  6. Internet of "printed" Things: low-cost fabrication of autonomous sensing nodes by inkjet printing

    NASA Astrophysics Data System (ADS)

    Kawahara, Yoshihiro

    2014-11-01

    "What if electronics devices are printed using an inkjet printer even at home?" "What if those devices no longer need a battery?" I will introduce two enabling technologies for the Internet of Things concept. 1. Instant Inkjet Circuits: A low cost, fast and accessible technology to support the rapid prototyping of electronic devices. We demonstrated that "sintering-free" silver nano particle ink with a commodity inkjet printer can be used to fabricate printed circuit board and high-frequency applications such as antennas and sensors. The technology is now commercialized by AgIC, Inc. 2. Wireless Power: Although large amounts of data can be exchanged over a wireless communication link, mobile devices are still tethered by power cables. We are trying to solve this problem by two different approaches: energy harvesting. A simple circuitry comprised of diodes and capacitor can convert ambient radio signals into DC current. Our research revealed the signals from TV tower located 6.5km apart could be used to feed 100 microwatts to power microcontrollers.

  7. Ultraflexible and tailorable all-solid-state supercapacitors using polyacrylamide-based hydrogel electrolyte with high ionic conductivity.

    PubMed

    Li, Huili; Lv, Tian; Li, Ning; Yao, Yao; Liu, Kai; Chen, Tao

    2017-11-30

    Hydrogels with high ionic conductivity consisting of a cross-linked polymer network swollen in water are very promising to be used as an electrolyte for all-solid-state supercapacitors. However, there are rather few flexible supercapacitors using ionic conducting hydrogel electrolytes reported to date. In this work, highly flexible and ionic conducting polyacrylamide hydrogels were synthesized through a simple approach. On using the ionic hydrogels as the electrolyte, the resulting supercapacitors not only exhibited a high specific capacitance but also showed a long self-discharge time (over 10 hours to the half of original open-circuit voltage) and a low leakage current. These newly-developed all-solid-state supercapacitors can be bent, knot, and kneaded for 5000 cycles without performance decay, suggesting excellent flexibility and mechanical stability. These all-solid-state supercapacitors can also be easily tailored into strip-like supercapacitors without a short circuit, which provides an efficient approach to fabricate wearable energy storage devices.

  8. INCREASES IN FUNCTIONAL CONNECTIVITY BETWEEN PREFRONTAL CORTEX AND STRIATUM DURING CATEGORY LEARNING

    PubMed Central

    Antzoulatos, Evan G.; Miller, Earl K.

    2014-01-01

    SUMMARY Functional connectivity between the prefrontal cortex (PFC) and striatum (STR) is thought critical for cognition, and has been linked to conditions like autism and schizophrenia. We recorded from multiple electrodes in PFC and STR while monkeys acquired new categories. Category learning was accompanied by an increase in beta-band synchronization of LFPs between, but not within, the PFC and STR. After learning, different pairs of PFC-STR electrodes showed stronger synchrony for one or the other category, suggesting category-specific functional circuits. This category-specific synchrony was also seen between PFC spikes and STR LFPs, but not the reverse, reflecting the direct monosynaptic connections from the PFC to STR. However, causal connectivity analyses suggested that the polysynaptic connections from STR to the PFC exerted a stronger overall influence. This supports models positing that the basal ganglia “train” the PFC. Category learning may depend on the formation of functional circuits between the PFC and STR. PMID:24930701

  9. Software-Reconfigurable Processors for Spacecraft

    NASA Technical Reports Server (NTRS)

    Farrington, Allen; Gray, Andrew; Bell, Bryan; Stanton, Valerie; Chong, Yong; Peters, Kenneth; Lee, Clement; Srinivasan, Jeffrey

    2005-01-01

    A report presents an overview of an architecture for a software-reconfigurable network data processor for a spacecraft engaged in scientific exploration. When executed on suitable electronic hardware, the software performs the functions of a physical layer (in effect, acts as a software radio in that it performs modulation, demodulation, pulse-shaping, error correction, coding, and decoding), a data-link layer, a network layer, a transport layer, and application-layer processing of scientific data. The software-reconfigurable network processor is undergoing development to enable rapid prototyping and rapid implementation of communication, navigation, and scientific signal-processing functions; to provide a long-lived communication infrastructure; and to provide greatly improved scientific-instrumentation and scientific-data-processing functions by enabling science-driven in-flight reconfiguration of computing resources devoted to these functions. This development is an extension of terrestrial radio and network developments (e.g., in the cellular-telephone industry) implemented in software running on such hardware as field-programmable gate arrays, digital signal processors, traditional digital circuits, and mixed-signal application-specific integrated circuits (ASICs).

  10. Statistical theory and applications of lock-in carrierographic image pixel brightness dependence on multi-crystalline Si solar cell efficiency and photovoltage

    NASA Astrophysics Data System (ADS)

    Mandelis, Andreas; Zhang, Yu; Melnikov, Alexander

    2012-09-01

    A solar cell lock-in carrierographic image generation theory based on the concept of non-equilibrium radiation chemical potential was developed. An optoelectronic diode expression was derived linking the emitted radiative recombination photon flux (current density), the solar conversion efficiency, and the external load resistance via the closed- and/or open-circuit photovoltage. The expression was shown to be of a structure similar to the conventional electrical photovoltaic I-V equation, thereby allowing the carrierographic image to be used in a quantitative statistical pixel brightness distribution analysis with outcome being the non-contacting measurement of mean values of these important parameters averaged over the entire illuminated solar cell surface. This is the optoelectronic equivalent of the electrical (contacting) measurement method using an external resistor circuit and the outputs of the solar cell electrode grid, the latter acting as an averaging distribution network over the surface. The statistical theory was confirmed using multi-crystalline Si solar cells.

  11. The Inner Nuclear Membrane Is a Metabolically Active Territory that Generates Nuclear Lipid Droplets.

    PubMed

    Romanauska, Anete; Köhler, Alwin

    2018-06-13

    The inner nuclear membrane (INM) encases the genome and is fused with the outer nuclear membrane (ONM) to form the nuclear envelope. The ONM is contiguous with the endoplasmic reticulum (ER), the main site of phospholipid synthesis. In contrast to the ER and ONM, evidence for a metabolic activity of the INM has been lacking. Here, we show that the INM is an adaptable membrane territory capable of lipid metabolism. S. cerevisiae cells target enzymes to the INM that can promote lipid storage. Lipid storage involves the synthesis of nuclear lipid droplets from the INM and is characterized by lipid exchange through Seipin-dependent membrane bridges. We identify the genetic circuit for nuclear lipid droplet synthesis and a role of these organelles in regulating this circuit by sequestration of a transcription factor. Our findings suggest a link between INM metabolism and genome regulation and have potential relevance for human lipodystrophy. Copyright © 2018 Elsevier Inc. All rights reserved.

  12. Development of Electromagnetically Actuated Vacuum Circuit Breaker for 72kV Rated Switchgear

    NASA Astrophysics Data System (ADS)

    Kim, Tae-Hyun; Tsukima, Mitsuru; Maruyama, Akihiko; Takahara, Osamu; Haruna, Kazushi; Yano, Tomotaka; Matsunaga, Toshihiro; Imamura, Kazuaki; Arioka, Masahiro; Takeuchi, Toshie

    A new electromagnetically actuated vacuum circuit breaker (VCB) has been developed for a 72kV rated switchgear. Each phase of this VCB has a plurality of compact electromagnetic actuators linked mechanically providing the required driving energy. The mechanical linkage working as a lever magnifies an actuator stroke to the required stroke of a 72kV rated vacuum interrupter. An electromagnetic analysis coupled with motion, which considers the mechanical linkage of the plural actuators, has been developed for designing the driving behavior of this VCB. Using this analytical method and a quality engineering method known as the Taguchi method, we have clarified effective parameters to reduce the time difference of the driving behavior for tolerance specifications. Moreover, analyzing the oscillatory behavior closing the contacts, a structure of this VCB has been designed to reduce the bounce duration. The developed new VCB has been confirmed that a time difference is short enough and bounce duration is reduced. This VCB is highly reliable against variations in manufacturing and environment.

  13. Sensory integration dynamics in a hierarchical network explains choice probabilities in cortical area MT

    PubMed Central

    Wimmer, Klaus; Compte, Albert; Roxin, Alex; Peixoto, Diogo; Renart, Alfonso; de la Rocha, Jaime

    2015-01-01

    Neuronal variability in sensory cortex predicts perceptual decisions. This relationship, termed choice probability (CP), can arise from sensory variability biasing behaviour and from top-down signals reflecting behaviour. To investigate the interaction of these mechanisms during the decision-making process, we use a hierarchical network model composed of reciprocally connected sensory and integration circuits. Consistent with monkey behaviour in a fixed-duration motion discrimination task, the model integrates sensory evidence transiently, giving rise to a decaying bottom-up CP component. However, the dynamics of the hierarchical loop recruits a concurrently rising top-down component, resulting in sustained CP. We compute the CP time-course of neurons in the medial temporal area (MT) and find an early transient component and a separate late contribution reflecting decision build-up. The stability of individual CPs and the dynamics of noise correlations further support this decomposition. Our model provides a unified understanding of the circuit dynamics linking neural and behavioural variability. PMID:25649611

  14. Modular implementation of a digital hardware design automation system

    NASA Astrophysics Data System (ADS)

    Masud, M.

    An automation system based on AHPL (A Hardware Programming Language) was developed. The project may be divided into three distinct phases: (1) Upgrading of AHPL to make it more universally applicable; (2) Implementation of a compiler for the language; and (3) illustration of how the compiler may be used to support several phases of design activities. Several new features were added to AHPL. These include: application-dependent parameters, mutliple clocks, asynchronous results, functional registers and primitive functions. The new language, called Universal AHPL, has been defined rigorously. The compiler design is modular. The parsing is done by an automatic parser generated from the SLR(1)BNF grammar of the language. The compiler produces two data bases from the AHPL description of a circuit. The first one is a tabular representation of the circuit, and the second one is a detailed interconnection linked list. The two data bases provide a means to interface the compiler to application-dependent CAD systems.

  15. A design procedure for the phase-controlled parallel-loaded resonant inverter

    NASA Technical Reports Server (NTRS)

    King, Roger J.

    1989-01-01

    High-frequency-link power conversion and distribution based on a resonant inverter (RI) has been recently proposed. The design of several topologies is reviewed, and a simple approximate design procedure is developed for the phase-controlled parallel-loaded RI. This design procedure seeks to ensure the benefits of resonant conversion and is verified by data from a laboratory 2.5 kVA, 20-kHz converter. A simple phasor analysis is introduced as a useful approximation for design purposes. The load is considered to be a linear impedance (or an ac current sink). The design procedure is verified using a 2.5-kVA 20-kHz RI. Also obtained are predictable worst-case ratings for each component of the resonant tank circuit and the inverter switches. For a given load VA requirement, below-resonance operation is found to result in a significantly lower tank VA requirement. Under transient conditions such as load short-circuit, a reversal of the expected commutation sequence is possible.

  16. MCTs and IGBTs - A comparison of performance in power electronic circuits

    NASA Technical Reports Server (NTRS)

    Sul, S. K.; Profumo, F.; Cho, G. H.; Lipo, T. A.

    1989-01-01

    There is a continuous demand for improvements in the quality of switching power devices, such as higher switching frequency, higher withstand voltage capability, larger current-handling capability, and lower conduction losses. However, for single-conduction-mechanism devices (SCRs, GTOs, BJTs, FETs), possessing all these features is probably unrealizable for physical reasons. An attractive solution appears to be double-mechanism devices, in which the features of both a minority carrier device (BJT or SCR) and a majority carrier device (MOSFET) are embedded. Both IGBTs (insulated-gate bipolar transistors) and MCTs (MOS-controlled thyristors) belong to this family of double-mechanism devices and promise to have a major impact on converter circuit signs. The authors deal with the major features of these two devices, pointing out those that are most critical to the design of converter topologies. In particular, the two devices have been tested both in a chopper and in two resonant link converter topologies, and the experimental results are reported.

  17. Parallel interconnect for a novel system approach to short distance high information transfer data links

    NASA Astrophysics Data System (ADS)

    Raskin, Glenn; Lebby, Michael S.; Carney, F.; Kazakia, M.; Schwartz, Daniel B.; Gaw, Craig A.

    1997-04-01

    The OPTOBUSTM family of products provides for high performance parallel interconnection utilizing optical links in a 10-bit wide bi-directional configuration. The link is architected to be 'transparent' in that it is totally asynchronous and dc coupled so that it can be treated as a perfect cable with extremely low skew and no losses. An optical link consists of two identical transceiver modules and a pair of connectorized 62.5 micrometer multi mode fiber ribbon cables. The OPTOBUSTM I link provides bi- directional functionality at 4 Gbps (400 Mbps per channel), while the OPTOBUSTM II link will offer the same capability at 8 Gbps (800 Mbps per channel). The transparent structure of the OPTOBUSTM links allow for an arbitrary data stream regardless of its structure. Both the OPTOBUSTM I and OPTOBUSTM II transceiver modules are packaged as partially populated 14 by 14 pin grid arrays (PGA) with optical receptacles on one side of the module. The modules themselves are composed of several elements; including passives, integrated circuits optoelectronic devices and optical interface units (OIUs) (which consist of polymer waveguides and a specially designed lead frame). The initial offering of the modules electrical interface utilizes differential CML. The CML line driver sinks 5 mA of current into one of two pins. When terminated with 50 ohm pull-up resistors tied to a voltage between VCC and VCC-2, the result is a differential swing of plus or minus 250 mV, capable of driving standard PECL I/Os. Future offerings of the OPTOBUSTM links will incorporate LVDS and PECL interfaces as well as CML. The integrated circuits are silicon based. For OPTOBUSTM I links, a 1.5 micrometer drawn emitter NPN bipolar process is used for the receiver and an enhanced 0.8 micrometer CMOS process for the laser driver. For OPTOBUSTM II links, a 0.8 micrometer drawn emitter NPN bipolar process is used for the receiver and the driver IC utilizes 0.8 micrometer BiCMOS technology. The OPTOBUSTM architecture uses AlGaAs vertical cavity surface emitting lasers (VCSELs) at 850 nm in conjunction with unique opto-electronic packaging concepts. Most laser based transmitter subsystems are incapable of carrying an arbitrary NRZ data stream at high data rates. The receiver subsystem utilizes a conventional GaAs PIN photo-detector. In parallel interconnect systems. The design must take into account the simultaneous switching noise from the neighboring systems. If not well controlled, the high density of the multiple interconnects can limit the sensitivity and therefore the performance of the system. The packaging approach of the VCSEL and PIN arrays allow for high bandwidths and provide the coupling mechanisms necessary to interface to the 62.5 micrometer multi mode fiber. To allow for extremely high electrical signals the OPTOBUSTM package utilizes a multilayer tape automated bonded (TAB) lead frame. The lead frame contains separate signal and ground layers. The ground layer successfully provides for a pseudo-coaxial environment (low inductance and effective signal coupling to the ground plane).

  18. Study of the generator/motor operation of induction machines in a high frequency link space power system

    NASA Technical Reports Server (NTRS)

    Lipo, Thomas A.; Sood, Pradeep K.

    1987-01-01

    Static power conversion systems have traditionally utilized dc current or voltage source links for converting power from one ac or dc form to another since it readily achieves the temporary energy storage required to decouple the input from the output. Such links, however, result in bulky dc capacitors and/or inductors and lead to relatively high losses in the converters due to stresses on the semiconductor switches. The feasibility of utilizing a high frequency sinusoidal voltage link to accomplish the energy storage and decoupling function is examined. In particular, a type of resonant six pulse bridge interface converter is proposed which utilizes zero voltage switching principles to minimize switching losses and uses an easy to implement technique for pulse density modulation to control the amplitude, frequency, and the waveshape of the synthesized low frequency voltage or current. Adaptation of the proposed topology for power conversion to single-phase ac and dc voltage or current outputs is shown to be straight forward. The feasibility of the proposed power circuit and control technique for both active and passive loads are verified by means of simulation and experiment.

  19. Implementation of Four-Phase Interleaved Balance Charger for Series-Connected Batteries with Power Factor Correction

    NASA Astrophysics Data System (ADS)

    Juan, Y. L.; Lee, Y. T.; Lee, Y. L.; Chen, L. L.; Huang, M. L.

    2017-11-01

    A four-phase interleaved balance charger for series-connected batteries with power factor correction is proposed in this dissertation. In the two phases of two buckboost converters, the rectified ac power is firstly converted to a dc link capacitor. In the other two phases of two flyback converters, the rectified ac power is directly converted to charge the corresponding batteries. Additionally, the energy on the leakage inductance of flyback converter is bypassed to the dc link capacitor. Then, a dual-output balance charging circuit is connected to the dc link to deliver the dc link power to charge two batteries in the series-connected batteries module. The constant-current/constant-voltage charging strategy is adopted. Finally, a prototype of the proposed charger with rated power 500 W is constructed. From the experimental results, the performance and validity of the proposed topology are verified. Compared to the conventional topology with passive RCD snubber, the efficiency of the proposed topology is improved about 3% and the voltage spike on the active switch is also reduced. The efficiency of the proposed charger is at least 83.6 % within the CC/CV charging progress.

  20. Altered reward anticipation: Potential explanation for weight gain in schizophrenia?

    PubMed

    Grimm, Oliver; Kaiser, Stefan; Plichta, Michael M; Tobler, Philippe N

    2017-04-01

    Obesity and weight gain are severe complications of mental illness, especially schizophrenia. They result from changes in lifestyle and nutrition, side effects of medication and other, less well-understood factors. Recent studies suggest that obesity and weight gain are linked to psychopathology. Specifically, severe psychopathology is associated with greater weight dysregulation, typically weight gain. However, our knowledge about the neuroscientific basis of weight gain in schizophrenia is currently limited. We propose that altered reward anticipation, which in turn is related to striatal dopaminergic dysregulation, may explain why obesity is more prevalent in individuals with mental illness. We review evidence that reward anticipation and weight change are linked by a core deficit in dopaminergic striatal circuits. Several lines of evidence, running from animal studies to preclinical and clinical studies, suggest that striatal dopaminergic neurotransmission is a major hub for the regulation of eating behavior and that dopamine links eating behavior to other motivated behavior. From this perspective, the present review outlines a unifying perspective on dopaminergic reward anticipation as a theoretical frame to link weight gain, medication effects and psychopathology. We derive important but open empirical questions and present perspectives for new therapeutic concepts. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. Two different ways for waveguides and optoelectronics components on top of C-MOS

    NASA Astrophysics Data System (ADS)

    Fedeli, J. M.; Jeannot, S.; Kostrzewa, M.; Di Cioccio, L.; Jousseaume, V.; Orobtchouk, R.; Maury, P.; Zussy, M.

    2006-02-01

    While fabrication of photonic components at the wafer level is a long standing goal of integrated optics, new applications such as optical interconnects are introducing new challenges for waveguides and optoelectronic component fabrication. Indeed, global interconnects are expected to face severe limitations in the near future. To face this problem, optical links on top of a CMOS circuits could be an alternative. The critical points to perform an optical link on a chip are firstly the realization of compact passive optical distribution and secondly the report of optoelectronic components for the sources and detectors. This paper presents two different approaches for the integration of both waveguides and optoelectronic components. In a first "total bonding" approach, waveguides have been elaborated using classical "Silicon On Insulators" technology and then reported using molecular bonding on top off Si wafers. The S0I substrate was then chemically etched, after what InP dies were moleculary bonded on top of the waveguides. With this approach, optical components with low loses and a good equilibrium are demonsrated. Using molecular bonding, InP dies were reported with no degradation of the optoelectronic properties of the films. In a second approach, using PECVD silicon nitride or amorphous silicon coupled to PECVD silicon oxide, basic optical components are demonstrated. This low temperature technology is compatible with a microelectronic Back End process, allowing an integration of the waveguides directly on top of CMOS circuits. InP dies can then be bonded on top of the waveguides.

  2. Procedures for Behavioral Experiments in Head-Fixed Mice

    PubMed Central

    Guo, Zengcai V.; Hires, S. Andrew; Li, Nuo; O'Connor, Daniel H.; Komiyama, Takaki; Ophir, Eran; Huber, Daniel; Bonardi, Claudia; Morandell, Karin; Gutnisky, Diego; Peron, Simon; Xu, Ning-long; Cox, James; Svoboda, Karel

    2014-01-01

    The mouse is an increasingly prominent model for the analysis of mammalian neuronal circuits. Neural circuits ultimately have to be probed during behaviors that engage the circuits. Linking circuit dynamics to behavior requires precise control of sensory stimuli and measurement of body movements. Head-fixation has been used for behavioral research, particularly in non-human primates, to facilitate precise stimulus control, behavioral monitoring and neural recording. However, choice-based, perceptual decision tasks by head-fixed mice have only recently been introduced. Training mice relies on motivating mice using water restriction. Here we describe procedures for head-fixation, water restriction and behavioral training for head-fixed mice, with a focus on active, whisker-based tactile behaviors. In these experiments mice had restricted access to water (typically 1 ml/day). After ten days of water restriction, body weight stabilized at approximately 80% of initial weight. At that point mice were trained to discriminate sensory stimuli using operant conditioning. Head-fixed mice reported stimuli by licking in go/no-go tasks and also using a forced choice paradigm using a dual lickport. In some cases mice learned to discriminate sensory stimuli in a few trials within the first behavioral session. Delay epochs lasting a second or more were used to separate sensation (e.g. tactile exploration) and action (i.e. licking). Mice performed a variety of perceptual decision tasks with high performance for hundreds of trials per behavioral session. Up to four months of continuous water restriction showed no adverse health effects. Behavioral performance correlated with the degree of water restriction, supporting the importance of controlling access to water. These behavioral paradigms can be combined with cellular resolution imaging, random access photostimulation, and whole cell recordings. PMID:24520413

  3. Brain Oscillations, Hypnosis, and Hypnotizability.

    PubMed

    Jensen, Mark P; Adachi, Tomonori; Hakimian, Shahin

    2015-01-01

    This article summarizes the state-of-science knowledge regarding the associations between hypnosis and brain oscillations. Brain oscillations represent the combined electrical activity of neuronal assemblies, usually measured as specific frequencies representing slower (delta, theta, alpha) and faster (beta, gamma) oscillations. Hypnosis has been most closely linked to power in the theta band and changes in gamma activity. These oscillations are thought to play a critical role in both the recording and recall of declarative memory and emotional limbic circuits. The authors propose that this role may be the mechanistic link between theta (and perhaps gamma) oscillations and hypnosis, specifically, that the increases in theta oscillations and changes in gamma activity observed with hypnosis may underlie some hypnotic responses. If these hypotheses are supported, they have important implications for both understanding the effects of hypnosis and for enhancing response to hypnotic treatments.

  4. Planning for growth in satellite systems - The Intelsat experience

    NASA Astrophysics Data System (ADS)

    Nadkarni, P.; Perillan, L.; Chasia, H.

    It is thought that the increase in conventional voice traffic will result primarily from growth on existing links rather than the establishment of new links. A steady growth of approximately 15% per annum is forecast over the next decade, for a requirement of more than 125,000 circuits, worldwide, by the early 1990s. It is noted that the transfer of services from a satellite to its successor is becoming increasingly complex with successive generations. Increases in the number of beams and beam interconnections, together with differences in coverages between successive satellites, have required totally new frequency plans and carrier assignments to be implemented as part of the operation transition. Attention is also given to the way that the investment in resources, technologies, and installed plant already in use exerts a strong influence on the alternatives for growth.

  5. Effects of supplemental training on fitness and aesthetic competence parameters in contemporary dance: a randomised controlled trial.

    PubMed

    Angioi, Manuela; Metsios, George; Twitchett, Emily A; Koutedakis, Yiannis; Wyon, Matthew

    2012-03-01

    Within aesthetic sports such as figure skating and rhythmic gymnastics, physical fitness has been shown to have positive benefits on performance outcomes. Presently the link between physical fitness and aesthetic contemporary dance performance has not been demonstrated within an intervention study. In this study, 24 females engaged in contemporary dance (age 27 ± 5.9 yrs; height 165.3 ± 4.8 cm; weight 59.2 ± 7.6 kg) were recruited and randomly assigned to either an exercise (n = 12) or a control group (n = 12). Three dancers withdrew during the study. The intervention group completed a 6-week conditioning programme comprising two 1-hr sessions of circuit and vibration training per week. The circuit training focused on local muscular endurance and aerobic conditioning and vibration training protocol concentrated on power. Repeated measures ANOVA revealed significant increases for the conditioning group in lower body muscular power (11%), upper body muscular endurance (22%), aerobic fitness (11%), and aesthetic competence (12%) (p < 0.05). The control group reported decreases in all the fitness parameters with the exception of aerobic fitness as well as a decrease in aesthetic competence (7%). A 6-week circuit and vibration training programme, which supplemented normal dance commitments, revealed significant increases in selected fitness components and a concomitant increase in aesthetic competence in contemporary professional and student dancers.

  6. Multicoil resonance-based parallel array for smart wireless power delivery.

    PubMed

    Mirbozorgi, S A; Sawan, M; Gosselin, B

    2013-01-01

    This paper presents a novel resonance-based multicoil structure as a smart power surface to wirelessly power up apparatus like mobile, animal headstage, implanted devices, etc. The proposed powering system is based on a 4-coil resonance-based inductive link, the resonance coil of which is formed by an array of several paralleled coils as a smart power transmitter. The power transmitter employs simple circuit connections and includes only one power driver circuit per multicoil resonance-based array, which enables higher power transfer efficiency and power delivery to the load. The power transmitted by the driver circuit is proportional to the load seen by the individual coil in the array. Thus, the transmitted power scales with respect to the load of the electric/electronic system to power up, and does not divide equally over every parallel coils that form the array. Instead, only the loaded coils of the parallel array transmit significant part of total transmitted power to the receiver. Such adaptive behavior enables superior power, size and cost efficiency then other solutions since it does not need to use complex detection circuitry to find the location of the load. The performance of the proposed structure is verified by measurement results. Natural load detection and covering 4 times bigger area than conventional topologies with a power transfer efficiency of 55% are the novelties of presented paper.

  7. The Circuit Theory Behind Coupled-Mode Magnetic Resonance-Based Wireless Power Transmission.

    PubMed

    Kiani, Mehdi; Ghovanloo, Maysam

    2012-09-01

    Inductive coupling is a viable scheme to wirelessly energize devices with a wide range of power requirements from nanowatts in radio frequency identification tags to milliwatts in implantable microelectronic devices, watts in mobile electronics, and kilowatts in electric cars. Several analytical methods for estimating the power transfer efficiency (PTE) across inductive power transmission links have been devised based on circuit and electromagnetic theories by electrical engineers and physicists, respectively. However, a direct side-by-side comparison between these two approaches is lacking. Here, we have analyzed the PTE of a pair of capacitively loaded inductors via reflected load theory (RLT) and compared it with a method known as coupled-mode theory (CMT). We have also derived PTE equations for multiple capacitively loaded inductors based on both RLT and CMT. We have proven that both methods basically result in the same set of equations in steady state and either method can be applied for short- or midrange coupling conditions. We have verified the accuracy of both methods through measurements, and also analyzed the transient response of a pair of capacitively loaded inductors. Our analysis shows that the CMT is only applicable to coils with high quality factor ( Q ) and large coupling distance. It simplifies the analysis by reducing the order of the differential equations by half compared to the circuit theory.

  8. Neural reuse of action perception circuits for language, concepts and communication.

    PubMed

    Pulvermüller, Friedemann

    2018-01-01

    Neurocognitive and neurolinguistics theories make explicit statements relating specialized cognitive and linguistic processes to specific brain loci. These linking hypotheses are in need of neurobiological justification and explanation. Recent mathematical models of human language mechanisms constrained by fundamental neuroscience principles and established knowledge about comparative neuroanatomy offer explanations for where, when and how language is processed in the human brain. In these models, network structure and connectivity along with action- and perception-induced correlation of neuronal activity co-determine neurocognitive mechanisms. Language learning leads to the formation of action perception circuits (APCs) with specific distributions across cortical areas. Cognitive and linguistic processes such as speech production, comprehension, verbal working memory and prediction are modelled by activity dynamics in these APCs, and combinatorial and communicative-interactive knowledge is organized in the dynamics within, and connections between APCs. The network models and, in particular, the concept of distributionally-specific circuits, can account for some previously not well understood facts about the cortical 'hubs' for semantic processing and the motor system's role in language understanding and speech sound recognition. A review of experimental data evaluates predictions of the APC model and alternative theories, also providing detailed discussion of some seemingly contradictory findings. Throughout, recent disputes about the role of mirror neurons and grounded cognition in language and communication are assessed critically. Copyright © 2017 The Author. Published by Elsevier Ltd.. All rights reserved.

  9. Altered structural and effective connectivity in anorexia and bulimia nervosa in circuits that regulate energy and reward homeostasis.

    PubMed

    Frank, G K W; Shott, M E; Riederer, J; Pryor, T L

    2016-11-01

    Anorexia and bulimia nervosa are severe eating disorders that share many behaviors. Structural and functional brain circuits could provide biological links that those disorders have in common. We recruited 77 young adult women, 26 healthy controls, 26 women with anorexia and 25 women with bulimia nervosa. Probabilistic tractography was used to map white matter connectivity strength across taste and food intake regulating brain circuits. An independent multisample greedy equivalence search algorithm tested effective connectivity between those regions during sucrose tasting. Anorexia and bulimia nervosa had greater structural connectivity in pathways between insula, orbitofrontal cortex and ventral striatum, but lower connectivity from orbitofrontal cortex and amygdala to the hypothalamus (P<0.05, corrected for comorbidity, medication and multiple comparisons). Functionally, in controls the hypothalamus drove ventral striatal activity, but in anorexia and bulimia nervosa effective connectivity was directed from anterior cingulate via ventral striatum to the hypothalamus. Across all groups, sweetness perception was predicted by connectivity strength in pathways connecting to the middle orbitofrontal cortex. This study provides evidence that white matter structural as well as effective connectivity within the energy-homeostasis and food reward-regulating circuitry is fundamentally different in anorexia and bulimia nervosa compared with that in controls. In eating disorders, anterior cingulate cognitive-emotional top down control could affect food reward and eating drive, override hypothalamic inputs to the ventral striatum and enable prolonged food restriction.

  10. Carbon Nanotube Devices for GHz to THz Applications

    NASA Astrophysics Data System (ADS)

    Burke, Peter

    2005-03-01

    In this talk I will present an overview of the high-frequency applications of carbon nanotubes, one realization of nano-electronic devices, and where the challenges and opportunities lie in this new field. Specifically, I will first discuss the passive RF circuit models of one-dimensional nanostructures as interconnects[1]. Next, I will discuss circuit models of the ac performance of active 1d transistor structures, leading to the prediction that THz cutoff frequencies should be possible[2]. We recently demonstrated the operation of nanotube transistors at 2.6 GHz[3]. Third, I discuss the radiation properties of 1d wires, which could form antennas linking the nanoworld to the macroworld[4]. This could completely remove the requirements for lithographically defined contacts to nanotube and nanowire devices, one of the greatest unsolved problems in nanotechnology. [1] P.J. Burke "An RF Circuit Model for Carbon Nanotubes" IEEE Transactions on Nanotechnology 2(1), 55-58 (2003). [2] P.J. Burke, ``AC Performance of Nanoelectronics: Towards a Ballistic THz Nanotube Transistor'' Solid State Electronics, 48(10), 1981-1986 (2004). [3] Shengdong Li, Zhen Yu, Sheng-Fen Yeng, W.C. Tang, Peter J. Burke, ``Carbon Nanotube Transistor Operation at 2.6 GHz'' Nano Letters, 4(4), 753-756 (2004). [4] Peter J. Burke, Shengdong Li, Zhen Yu ''Quantitative theory of nanowire and nanotube antenna performance,'' http://xxx.lanl.gov/abs/cond-mat/0408418cond-mat/0408418 (2004).

  11. The Circuit Theory Behind Coupled-Mode Magnetic Resonance-Based Wireless Power Transmission

    PubMed Central

    Kiani, Mehdi; Ghovanloo, Maysam

    2014-01-01

    Inductive coupling is a viable scheme to wirelessly energize devices with a wide range of power requirements from nanowatts in radio frequency identification tags to milliwatts in implantable microelectronic devices, watts in mobile electronics, and kilowatts in electric cars. Several analytical methods for estimating the power transfer efficiency (PTE) across inductive power transmission links have been devised based on circuit and electromagnetic theories by electrical engineers and physicists, respectively. However, a direct side-by-side comparison between these two approaches is lacking. Here, we have analyzed the PTE of a pair of capacitively loaded inductors via reflected load theory (RLT) and compared it with a method known as coupled-mode theory (CMT). We have also derived PTE equations for multiple capacitively loaded inductors based on both RLT and CMT. We have proven that both methods basically result in the same set of equations in steady state and either method can be applied for short- or midrange coupling conditions. We have verified the accuracy of both methods through measurements, and also analyzed the transient response of a pair of capacitively loaded inductors. Our analysis shows that the CMT is only applicable to coils with high quality factor (Q) and large coupling distance. It simplifies the analysis by reducing the order of the differential equations by half compared to the circuit theory. PMID:24683368

  12. An Implantable Wireless Neural Interface for Recording Cortical Circuit Dynamics in Moving Primates

    PubMed Central

    Borton, David A.; Yin, Ming; Aceros, Juan; Nurmikko, Arto

    2013-01-01

    Objective Neural interface technology suitable for clinical translation has the potential to significantly impact the lives of amputees, spinal cord injury victims, and those living with severe neuromotor disease. Such systems must be chronically safe, durable, and effective. Approach We have designed and implemented a neural interface microsystem, housed in a compact, subcutaneous, and hermetically sealed titanium enclosure. The implanted device interfaces the brain with a 510k-approved, 100-element silicon-based MEA via a custom hermetic feedthrough design. Full spectrum neural signals were amplified (0.1Hz to 7.8kHz, ×200 gain) and multiplexed by a custom application specific integrated circuit, digitized, and then packaged for transmission. The neural data (24 Mbps) was transmitted by a wireless data link carried on an frequency shift key modulated signal at 3.2GHz and 3.8GHz to a receiver 1 meter away by design as a point-to-point communication link for human clinical use. The system was powered by an embedded medical grade rechargeable Li-ion battery for 7-hour continuous operation between recharge via an inductive transcutaneous wireless power link at 2MHz. Main results Device verification and early validation was performed in both swine and non-human primate freely-moving animal models and showed that the wireless implant was electrically stable, effective in capturing and delivering broadband neural data, and safe for over one year of testing. In addition, we have used the multichannel data from these mobile animal models to demonstrate the ability to decode neural population dynamics associated with motor activity. Significance We have developed an implanted wireless broadband neural recording device evaluated in non-human primate and swine. The use of this new implantable neural interface technology can provide insight on how to advance human neuroprostheses beyond the present early clinical trials. Further, such tools enable mobile patient use, have the potential for wider diagnosis of neurological conditions, and will advance brain research. PMID:23428937

  13. The role of the central ghrelin system in reward from food and chemical drugs.

    PubMed

    Dickson, Suzanne L; Egecioglu, Emil; Landgren, Sara; Skibicka, Karolina P; Engel, Jörgen A; Jerlhag, Elisabet

    2011-06-20

    Here we review recent advances that identify a role for the central ghrelin signalling system in reward from both natural rewards (such as food) and artificial rewards (that include alcohol and drugs of abuse). Whereas ghrelin emerged as a stomach-derived hormone involved in energy balance, hunger and meal initiation via hypothalamic circuits, it now seems clear that it also has a role in motivated reward-driven behaviours via activation of the so-called "cholinergic-dopaminergic reward link". This reward link comprises a dopamine projection from the ventral tegmental area (VTA) to the nucleus accumbens together with a cholinergic input, arising primarily from the laterodorsal tegmental area. Ghrelin administration into the VTA or LDTg activates the "cholinergic-dopaminergic" reward link, suggesting that ghrelin may increase the incentive value of motivated behaviours such as reward-seeking behaviour ("wanting" or "incentive motivation"). Further, direct injection of ghrelin into the brain ventricles or into the VTA increases the consumption of rewarding foods as well as alcohol in mice and rats. Studies in rodents show beneficial effects of ghrelin receptor (GHS-R1A) antagonists to suppress the intake of palatable food, to reduce preference for caloric foods, to suppress food reward and motivated behaviour for food. They have also been shown to reduce alcohol consumption, suppress reward induced by alcohol, cocaine and amphetamine. Furthermore, variations in the GHS-R1A and pro-ghrelin genes have been associated with high alcohol consumption, smoking and increased weight gain in alcohol dependent individuals as well as with bulimia nervosa and obesity. Thus, the central ghrelin signalling system interfaces neurobiological circuits involved in reward from food as well as chemical drugs; agents that directly or indirectly suppress this system emerge as potential candidate drugs for suppressing problematic over-eating that leads to obesity as well as for the treatment of substance use disorder. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  14. Single-mode glass waveguide technology for optical interchip communication on board level

    NASA Astrophysics Data System (ADS)

    Brusberg, Lars; Neitz, Marcel; Schröder, Henning

    2012-01-01

    The large bandwidth demand in long-distance telecom networks lead to single-mode fiber interconnects as result of low dispersion, low loss and dense wavelength multiplexing possibilities. In contrast, multi-mode interconnects are suitable for much shorter lengths up to 300 meters and are promising for optical links between racks and on board level. Active optical cables based on multi-mode fiber links are at the market and research in multi-mode waveguide integration on board level is still going on. Compared to multi-mode, a single-mode waveguide has much more integration potential because of core diameters of around 20% of a multi-mode waveguide by a much larger bandwidth. But light coupling in single-mode waveguides is much more challenging because of lower coupling tolerances. Together with the silicon photonics technology, a single-mode waveguide technology on board-level will be the straight forward development goal for chip-to-chip optical interconnects integration. Such a hybrid packaging platform providing 3D optical single-mode links bridges the gap between novel photonic integrated circuits and the glass fiber based long-distance telecom networks. Following we introduce our 3D photonic packaging approach based on thin glass substrates with planar integrated optical single-mode waveguides for fiber-to-chip and chip-to-chip interconnects. This novel packaging approach merges micro-system packaging and glass integrated optics. It consists of a thin glass substrate with planar integrated singlemode waveguide circuits, optical mirrors and lenses providing an integration platform for photonic IC assembly and optical fiber interconnect. Thin glass is commercially available in panel and wafer formats and characterizes excellent optical and high-frequency properties. That makes it perfect for microsystem packaging. The paper presents recent results in single-mode waveguide technology on wafer level and waveguide characterization. Furthermore the integration in a hybrid packaging process and design issues are discussed.

  15. An implantable wireless neural interface for recording cortical circuit dynamics in moving primates

    NASA Astrophysics Data System (ADS)

    Borton, David A.; Yin, Ming; Aceros, Juan; Nurmikko, Arto

    2013-04-01

    Objective. Neural interface technology suitable for clinical translation has the potential to significantly impact the lives of amputees, spinal cord injury victims and those living with severe neuromotor disease. Such systems must be chronically safe, durable and effective. Approach. We have designed and implemented a neural interface microsystem, housed in a compact, subcutaneous and hermetically sealed titanium enclosure. The implanted device interfaces the brain with a 510k-approved, 100-element silicon-based microelectrode array via a custom hermetic feedthrough design. Full spectrum neural signals were amplified (0.1 Hz to 7.8 kHz, 200× gain) and multiplexed by a custom application specific integrated circuit, digitized and then packaged for transmission. The neural data (24 Mbps) were transmitted by a wireless data link carried on a frequency-shift-key-modulated signal at 3.2 and 3.8 GHz to a receiver 1 m away by design as a point-to-point communication link for human clinical use. The system was powered by an embedded medical grade rechargeable Li-ion battery for 7 h continuous operation between recharge via an inductive transcutaneous wireless power link at 2 MHz. Main results. Device verification and early validation were performed in both swine and non-human primate freely-moving animal models and showed that the wireless implant was electrically stable, effective in capturing and delivering broadband neural data, and safe for over one year of testing. In addition, we have used the multichannel data from these mobile animal models to demonstrate the ability to decode neural population dynamics associated with motor activity. Significance. We have developed an implanted wireless broadband neural recording device evaluated in non-human primate and swine. The use of this new implantable neural interface technology can provide insight into how to advance human neuroprostheses beyond the present early clinical trials. Further, such tools enable mobile patient use, have the potential for wider diagnosis of neurological conditions and will advance brain research.

  16. Extracting functionally feedforward networks from a population of spiking neurons

    PubMed Central

    Vincent, Kathleen; Tauskela, Joseph S.; Thivierge, Jean-Philippe

    2012-01-01

    Neuronal avalanches are a ubiquitous form of activity characterized by spontaneous bursts whose size distribution follows a power-law. Recent theoretical models have replicated power-law avalanches by assuming the presence of functionally feedforward connections (FFCs) in the underlying dynamics of the system. Accordingly, avalanches are generated by a feedforward chain of activation that persists despite being embedded in a larger, massively recurrent circuit. However, it is unclear to what extent networks of living neurons that exhibit power-law avalanches rely on FFCs. Here, we employed a computational approach to reconstruct the functional connectivity of cultured cortical neurons plated on multielectrode arrays (MEAs) and investigated whether pharmacologically induced alterations in avalanche dynamics are accompanied by changes in FFCs. This approach begins by extracting a functional network of directed links between pairs of neurons, and then evaluates the strength of FFCs using Schur decomposition. In a first step, we examined the ability of this approach to extract FFCs from simulated spiking neurons. The strength of FFCs obtained in strictly feedforward networks diminished monotonically as links were gradually rewired at random. Next, we estimated the FFCs of spontaneously active cortical neuron cultures in the presence of either a control medium, a GABAA receptor antagonist (PTX), or an AMPA receptor antagonist combined with an NMDA receptor antagonist (APV/DNQX). The distribution of avalanche sizes in these cultures was modulated by this pharmacology, with a shallower power-law under PTX (due to the prominence of larger avalanches) and a steeper power-law under APV/DNQX (due to avalanches recruiting fewer neurons) relative to control cultures. The strength of FFCs increased in networks after application of PTX, consistent with an amplification of feedforward activity during avalanches. Conversely, FFCs decreased after application of APV/DNQX, consistent with fading feedforward activation. The observed alterations in FFCs provide experimental support for recent theoretical work linking power-law avalanches to the feedforward organization of functional connections in local neuronal circuits. PMID:23091458

  17. Extracting functionally feedforward networks from a population of spiking neurons.

    PubMed

    Vincent, Kathleen; Tauskela, Joseph S; Thivierge, Jean-Philippe

    2012-01-01

    Neuronal avalanches are a ubiquitous form of activity characterized by spontaneous bursts whose size distribution follows a power-law. Recent theoretical models have replicated power-law avalanches by assuming the presence of functionally feedforward connections (FFCs) in the underlying dynamics of the system. Accordingly, avalanches are generated by a feedforward chain of activation that persists despite being embedded in a larger, massively recurrent circuit. However, it is unclear to what extent networks of living neurons that exhibit power-law avalanches rely on FFCs. Here, we employed a computational approach to reconstruct the functional connectivity of cultured cortical neurons plated on multielectrode arrays (MEAs) and investigated whether pharmacologically induced alterations in avalanche dynamics are accompanied by changes in FFCs. This approach begins by extracting a functional network of directed links between pairs of neurons, and then evaluates the strength of FFCs using Schur decomposition. In a first step, we examined the ability of this approach to extract FFCs from simulated spiking neurons. The strength of FFCs obtained in strictly feedforward networks diminished monotonically as links were gradually rewired at random. Next, we estimated the FFCs of spontaneously active cortical neuron cultures in the presence of either a control medium, a GABA(A) receptor antagonist (PTX), or an AMPA receptor antagonist combined with an NMDA receptor antagonist (APV/DNQX). The distribution of avalanche sizes in these cultures was modulated by this pharmacology, with a shallower power-law under PTX (due to the prominence of larger avalanches) and a steeper power-law under APV/DNQX (due to avalanches recruiting fewer neurons) relative to control cultures. The strength of FFCs increased in networks after application of PTX, consistent with an amplification of feedforward activity during avalanches. Conversely, FFCs decreased after application of APV/DNQX, consistent with fading feedforward activation. The observed alterations in FFCs provide experimental support for recent theoretical work linking power-law avalanches to the feedforward organization of functional connections in local neuronal circuits.

  18. Powering the High-Luminosity Triplets

    NASA Astrophysics Data System (ADS)

    Ballarino, A.; Burnet, J. P.

    The powering of the magnets in the LHC High-Luminosity Triplets requires production and transfer of more than 150 kA of DC current. High precision power converters will be adopted, and novel High Temperature Superconducting (HTS) current leads and MgB2 based transfer lines will provide the electrical link between the power converters and the magnets. This chapter gives an overview of the systems conceived in the framework of the LHC High-Luminosity upgrade for feeding the superconducting magnet circuits. The focus is on requirements, challenges and novel developments.

  19. Crosstalk in an FDM Laboratory Setup and the Athena X-IFU End-to-End Simulator

    NASA Astrophysics Data System (ADS)

    den Hartog, R.; Kirsch, C.; de Vries, C.; Akamatsu, H.; Dauser, T.; Peille, P.; Cucchetti, E.; Jackson, B.; Bandler, S.; Smith, S.; Wilms, J.

    2018-04-01

    The impact of various crosstalk mechanisms on the performance of the Athena X-IFU instrument has been assessed with detailed end-to-end simulations. For the crosstalk in the electrical circuit, a detailed model has been developed. In this contribution, we test this model against measurements made with an FDM laboratory setup and discuss the assumption of deterministic crosstalk in the context of the weak link effect in the detectors. We conclude that crosstalk levels predicted by the model are conservative with respect to the observed levels.

  20. VHDL simulation with access to transistor models

    NASA Technical Reports Server (NTRS)

    Gibson, J.

    1991-01-01

    Hardware description languages such as VHDL have evolved to aid in the design of systems with large numbers of elements and a wide range of electronic and logical abstractions. For high performance circuits, behavioral models may not be able to efficiently include enough detail to give designers confidence in a simulation's accuracy. One option is to provide a link between the VHDL environment and a transistor level simulation environment. The coupling of the Vantage Analysis Systems VHDL simulator and the NOVA simulator provides the combination of VHDL modeling and transistor modeling.

  1. Sharp wave/ripple network oscillations and learning-associated hippocampal maps.

    PubMed

    Csicsvari, Jozsef; Dupret, David

    2014-02-05

    Sharp wave/ripple (SWR, 150-250 Hz) hippocampal events have long been postulated to be involved in memory consolidation. However, more recent work has investigated SWRs that occur during active waking behaviour: findings that suggest that SWRs may also play a role in cell assembly strengthening or spatial working memory. Do such theories of SWR function apply to animal learning? This review discusses how general theories linking SWRs to memory-related function may explain circuit mechanisms related to rodent spatial learning and to the associated stabilization of new cognitive maps.

  2. Non-canonical WNT6/WNT10A signal factor expression in EBV+ post-transplant smooth muscle tumors.

    PubMed

    Teiken, Kristin; Kuehnel, Mark; Rehkaemper, Jan; Kreipe, Hans; Laenger, Florian; Hussein, Kais; Jonigk, Danny

    2018-01-01

    Post-transplant smooth muscle tumors (PTSMTs) are rare mesenchymal neoplasms which occur after solid organ or haematopoietic stem cell transplantation. PTSMT typically consist of Epstein-Barr-virus (EBV)+ smooth muscle-like cells and show an intermediate malignancy. Their main occurrences are visceral organs, especially the liver, but intracranial appearances are described and associated with a poor prognosis. EBV drives the growth of PTSMT; however, the underlying molecular mechanisms still remain unclear. Gene expression analysis of a set of morphologically similar tumors (leiomyomas, leiomyosarcomas, angioleiomyomas and endothelial haemangiomas) from patients without immunosuppression or EBV-association was performed. Our findings indicate that PTSMT's growth is driven by two factors of the wingless-type protein family: WNT6 and WNT10A. We are first to report that in PTSMTs, a non-canonical activation of WNT, independent of beta-catenin, drives tumor cell proliferation via MTOR/AKT1, MYC and Cyclin D2.

  3. Segregating Variation in the Polycomb Group Gene cramped Alters the Effect of Temperature on Multiple Traits

    PubMed Central

    Gibert, Jean-Michel; Karch, François; Schlötterer, Christian

    2011-01-01

    The phenotype produced by a given genotype can be strongly modulated by environmental conditions. Therefore, natural populations continuously adapt to environment heterogeneity to maintain optimal phenotypes. It generates a high genetic variation in environment-sensitive gene networks, which is thought to facilitate evolution. Here we analyze the chromatin regulator crm, identified as a candidate for adaptation of Drosophila melanogaster to northern latitudes. We show that crm contributes to environmental canalization. In particular, crm modulates the effect of temperature on a genomic region encoding Hedgehog and Wingless signaling effectors. crm affects this region through both constitutive heterochromatin and Polycomb silencing. Furthermore, we show that crm European and African natural variants shift the reaction norms of plastic traits. Interestingly, traits modulated by crm natural variants can differ markedly between Drosophila species, suggesting that temperature adaptation facilitates their evolution. PMID:21283785

  4. A century of paraphyly: a molecular phylogeny of katydids (Orthoptera: Tettigoniidae) supports multiple origins of leaf-like wings.

    PubMed

    Mugleston, Joseph D; Song, Hojun; Whiting, Michael F

    2013-12-01

    The phylogenetic relationships of Tettigoniidae (katydids and bush-crickets) were inferred using molecular sequence data. Six genes (18S rDNA, 28S rDNA, Cytochrome Oxidase II, Histone 3, Tubulin Alpha I, and Wingless) were sequenced for 135 ingroup taxa representing 16 of the 19 extant katydid subfamilies. Five subfamilies (Tettigoniinae, Pseudophyllinae, Mecopodinae, Meconematinae, and Listroscelidinae) were found to be paraphyletic under various tree reconstruction methods (Maximum Likelihood, Bayesisan Inference and Maximum Parsimony). Seven subfamilies - Conocephalinae, Hetrodinae, Hexacentrinae, Saginae, Phaneropterinae, Phyllophorinae, and Lipotactinae - were each recovered as well-supported monophyletic groups. We mapped the small and exposed thoracic auditory spiracle (a defining character of the subfamily Pseudophyllinae) and found it to be homoplasious. We also found the leaf-like wings of katydids have been derived independently in at least six lineages. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. E-21093

    NASA Image and Video Library

    1969-12-18

    The wingless, lifting body aircraft sitting on Rogers Dry Lake at what is now NASA's Dryden Flight Research Center, Edwards, California, from left to right are the X-24A, M2-F3 and the HL-10. The lifting body aircraft studied the feasibility of maneuvering and landing an aerodynamic craft designed for reentry from space. These lifting bodies were air launched by a B-52 mother ship, then flew powered by their own rocket engines before making an unpowered approach and landing. They helped validate the concept that a space shuttle could make accurate landings without power. The X-24A flew from April 17, 1969 to June 4, 1971. The M2-F3 flew from June 2, 1970 until December 20, 1972. The HL-10 flew from December 22, 1966 until July 17, 1970 and logged the highest and fastest records in the lifting body program.

  6. E-21115

    NASA Image and Video Library

    1969-12-18

    The wingless, lifting body aircraft sitting on Rogers Dry Lake at what is now NASA's Dryden Flight Research Center, Edwards, California, from left to right are the X-24A, M2-F3 and the HL-10. The lifting body aircraft studied the feasibility of maneuvering and landing an aerodynamic craft designed for reentry from space. These lifting bodies were air launched by a B-52 mother ship, then flew powered by their own rocket engines before making an unpowered approach and landing. They helped validate the concept that a space shuttle could make accurate landings without power. The X-24A flew from April 17, 1969 to June 4, 1971. The M2-F3 flew from June 2, 1970 until December 20, 1972. The HL-10 flew from December 22, 1966 until July 17, 1970 and logged the highest and fastest records in the lifting body program.

  7. EC69-2358

    NASA Image and Video Library

    1969-12-18

    The wingless, lifting body aircraft sitting on Rogers Dry Lake at what is now NASA's Dryden Flight Research Center, Edwards, California, from left to right are the X-24A, M2-F3 and the HL-10. The lifting body aircraft studied the feasibility of maneuvering and landing an aerodynamic craft designed for reentry from space. These lifting bodies were air launched by a B-52 mother ship, then flew powered by their own rocket engines before making an unpowered approach and landing. They helped validate the concept that a space shuttle could make accurate landings without power. The X-24A flew from April 17, 1969 to June 4, 1971. The M2-F3 flew from June 2, 1970 until December 21, 1971. The HL-10 flew from December 22, 1966 until July 17, 1970, and logged the highest and fastest records in the lifting body program.

  8. ECN-2359

    NASA Image and Video Library

    1969-12-18

    The wingless, lifting body aircraft sitting on Rogers Dry Lake at what is now NASA's Dryden Flight Research Center, Edwards, California, from left to right are the X-24A, M2-F3 and the HL-10. The lifting body aircraft studied the feasibility of maneuvering and landing an aerodynamic craft designed for reentry from space. These lifting bodies were air launched by a B-52 mother ship, then flew powered by their own rocket engines before making an unpowered approach and landing. They helped validate the concept that a space shuttle could make accurate landings without power. The X-24A flew from April 17, 1969 to June 4, 1971. The M2-F3 flew from June 2, 1970 until December 22, 1972. The HL-10 flew from December 22, 1966 until July 17, 1970, and logged the highest and fastest records in the lifting body program.

  9. The Crossroads of Synaptic Growth Signaling, Membrane Traffic and Neurological Disease: Insights from Drosophila.

    PubMed

    Deshpande, Mugdha; Rodal, Avital A

    2016-02-01

    Neurons require target-derived autocrine and paracrine growth factors to maintain proper identity, innervation, homeostasis and survival. Neuronal growth factor signaling is highly dependent on membrane traffic, both for the packaging and release of the growth factors themselves, and for regulation of intracellular signaling by their transmembrane receptors. Here, we review recent findings from the Drosophila larval neuromuscular junction (NMJ) that illustrate how specific steps of intracellular traffic and inter-organelle interactions impinge on signaling, particularly in the bone morphogenic protein, Wingless and c-Jun-activated kinase pathways, regulating elaboration and stability of NMJ arbors, construction of synapses and synaptic transmission and homeostasis. These membrane trafficking and signaling pathways have been implicated in human motor neuron diseases including amyotrophic lateral sclerosis and hereditary spastic paraplegia, highlighting their importance for neuronal health and survival. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  10. The integrative effects of population density, photoperiod, temperature, and host plant on the induction of alate aphids in Schizaphis graminum.

    PubMed

    An, Chunju; Fei, Xiaodong; Chen, Wenfeng; Zhao, Zhangwu

    2012-04-01

    The wheat aphid Schizaphis graminum (Rondani) displays wing dimorphism with both winged and wingless adult morphs. The winged morph is an adaptive microevolutionary response to undesirable environmental conditions, including undesirable population density, photoperiod, temperature, and host plant. Here we studied the integrative effects of population density, photoperiod, temperature, and host plant on the induction of alate aphids in S. graminum. The present results show that these four factors all play roles in inducing alate aphids in S. graminum but population density is the most important under almost all circumstances. In importance, population density is followed by photoperiod, host plant, and temperature, in that order. These results indicate that ambient environmental factors are highly important to stimulation of alate aphids in S. graminum, especially when population density reaches 64 individuals per leaf. © 2012 Wiley Periodicals, Inc.

  11. STAT, Wingless, and Nurf-38 determine the accuracy of regeneration after radiation damage in Drosophila.

    PubMed

    Verghese, Shilpi; Su, Tin Tin

    2017-10-01

    We report here a study of regeneration in Drosophila larval wing imaginal discs after damage by ionizing radiation. We detected faithful regeneration that restored a wing disc and abnormal regeneration that produced an extra wing disc. We describe a sequence of changes in cell number, location and fate that occur to produce an ectopic disc. We identified a group of cells that not only participate in ectopic disc formation but also recruit others to do so. STAT92E (Drosophila STAT3/5) and Nurf-38, which encodes a member of the Nucleosome Remodeling Factor complex, oppose each other in these cells to modulate the frequency of ectopic disc growth. The picture that emerges is one in which activities like STAT increase after radiation damage and fulfill essential roles in rebuilding the tissue. But such activities must be kept in check so that one and only one wing disc is regenerated.

  12. Signaling Molecules Governing Pluripotency and Early Lineage Commitments in Human Pluripotent Stem Cells

    PubMed Central

    Fathi, Ali; Eisa-Beygi, Shahram; Baharvand, Hossein

    2017-01-01

    Signaling in pluripotent stem cells is a complex and dynamic process involving multiple mediators, finely tuned to balancing pluripotency and differentiation states. Characterizing and modifying the necessary signaling pathways to attain desired cell types is required for stem-cell applications in various fields of regenerative medicine. These signals may help enhance the differentiation potential of pluripotent cells towards each of the embryonic lineages and enable us to achieve pure in vitro cultures of various cell types. This review provides a timely synthesis of recent advances into how maintenance of pluripotency in hPSCs is regulated by extrinsic cues, such as the fibroblast growth factor (FGF) and ACTIVIN signaling pathways, their interplay with other signaling pathways, namely, wingless- type MMTV integration site family (WNT) and mammalian target of rapamycin (mTOR), and the pathways governing the determination of multiple lineages. PMID:28670512

  13. Small molecule promotes β-catenin citrullination and inhibits Wnt signaling in cancer.

    PubMed

    Qu, Yi; Olsen, Jan Roger; Yuan, Xing; Cheng, Phil F; Levesque, Mitchell P; Brokstad, Karl A; Hoffman, Paul S; Oyan, Anne Margrete; Zhang, Weidong; Kalland, Karl-Henning; Ke, Xisong

    2018-01-01

    Wnt (wingless)/β-catenin signaling is critical for tumor progression and is frequently activated in colorectal cancer as a result of the mutation of adenomatous polyposis coli (APC); however, therapeutic agents targeting this pathway for clinical use are lacking. Here we report that nitazoxanide (NTZ), a clinically approved antiparasitic drug, efficiently inhibits Wnt signaling independent of APC. Using chemoproteomic approaches, we have identified peptidyl arginine deiminase 2 (PAD2) as the functional target of NTZ in Wnt inhibition. By targeting PAD2, NTZ increased the deamination (citrullination) and turnover of β-catenin in colon cancer cells. Replacement of arginine residues disrupted the transcriptional activity, and NTZ induced degradation of β-catenin. In Wnt-activated colon cancer cells, knockout of either PAD2 or β-catenin substantially increased resistance to NTZ treatment. Our data highlight the potential of NTZ as a modulator of β-catenin citrullination for the treatment of cancer patients with Wnt pathway mutations.

  14. A scale-free systems theory of motivation and addiction.

    PubMed

    Chambers, R Andrew; Bickel, Warren K; Potenza, Marc N

    2007-01-01

    Scale-free organizations, characterized by uneven distributions of linkages between nodal elements, describe the structure and function of many life-based complex systems developing under evolutionary pressures. We explore motivated behavior as a scale-free map toward a comprehensive translational theory of addiction. Motivational and behavioral repertoires are reframed as link and nodal element sets, respectively, comprising a scale-free structure. These sets are generated by semi-independent information-processing streams within cortical-striatal circuits that cooperatively provide decision-making and sequential processing functions necessary for traversing maps of motivational links connecting behavioral nodes. Dopamine modulation of cortical-striatal plasticity serves a central-hierarchical mechanism for survival-adaptive sculpting and development of motivational-behavioral repertoires by guiding a scale-free design. Drug-induced dopamine activity promotes drug taking as a highly connected behavioral hub at the expense of natural-adaptive motivational links and behavioral nodes. Conceptualizing addiction as pathological alteration of scale-free motivational-behavioral repertoires unifies neurobiological, neurocomputational and behavioral research while addressing addiction vulnerability in adolescence and psychiatric illness. This model may inform integrative research in defining more effective prevention and treatment strategies for addiction.

  15. Radio Links for the NASA ABTS

    NASA Technical Reports Server (NTRS)

    Jeutter, Dean C.

    1996-01-01

    The closed loop prototype has operational bi-directional wireless links. The Wideband PCM-FSK receiver has been designed and characterized. Now that both links function, communication performance can be addressed. For example, noise problems with the received outlink signal that caused the PC program to lockup were just recently revealed and minimized by software "enhancements" to the Windows based PC program. A similar problem with inlink communication was uncovered several days before this report: A noise spike or dropout (expected events in the animal Habitat) caused an interrupt to the implant microcontroller which halted outlink transmission. Recovery of outlink transmission did not reliably occur. The problem has been defined and implant software is being modified to better recognize noise from data by changing the timing associated with valid data packet identification and by better utilizing the error flags generated by the microcontroller's SCI circuits. Excellent inlink performance will also require improvements in the implant's receiver. The biggest performance improvement can be provided by antenna design for the Habitat. The quarter wavelength whip antennas used with the demo prototype inlink leave much to be desired.

  16. A Scale-Free Systems Theory of Motivation and Addiction

    PubMed Central

    Bickel, Warren K.; Potenza, Marc N.

    2007-01-01

    Scale-free organizations, characterized by uneven distributions of linkages between nodal elements, describe the structure and function of many life-based complex systems developing under evolutionary pressures. We explore motivated behavior as a scale-free map toward a comprehensive translational theory of addiction. Motivational and behavioral repertoires are reframed as link and nodal element sets, respectively, comprising a scale-free structure. These sets are generated by semi-independent information-processing streams within cortical-striatal circuits that cooperatively provide decision-making and sequential processing functions necessary for traversing maps of motivational links connecting behavioral nodes. Dopamine modulation of cortical-striatal plasticity serves a central-hierarchical mechanism for survival-adaptive sculpting and development of motivational-behavioral repertoires by guiding a scale-free design. Drug-induced dopamine activity promotes drug-taking as a highly connected behavioral hub at the expense of natural-adaptive motivational links and behavioral nodes. Conceptualizing addiction as pathological alteration of scale-free motivational-behavioral repertoires unifies neurobiological, neurocomputational and behavioral research while addressing addiction vulnerability in adolescence and psychiatric illness. This model may inform integrative research in defining more effective prevention and treatment strategies for addiction. PMID:17574673

  17. Optical link by using optical wiring method for reducing EMI

    NASA Astrophysics Data System (ADS)

    Cho, In-Kui; Kwon, Jong-Hwa; Choi, Sung-Woong; Bondarik, Alexander; Yun, Je-Hoon; Kim, Chang-Joo; Ahn, Seung-Beom; Jeong, Myung-Yung; Park, Hyo Hoon

    2008-12-01

    A practical optical link system was prepared with a transmitter (Tx) and receiver (Rx) for reducing EMI (electromagnetic interference). The optical TRx module consisted of a metal optical bench, a module printed circuit board (PCB), a driver/receiver IC, a VCSEL/PD array, and an optical link block composed of plastic optical fiber (POF). For the optical interconnection between the light-sources and detectors, an optical wiring method has been proposed to enable easy assembly. The key benefit of fiber optic link is the absence of electromagnetic interference (EMI) noise creation and susceptibility. This paper provides a method for optical interconnection between an optical Tx and an optical Rx, comprising the following steps: (i) forming a light source device, an optical detection device, and an optical transmission unit on a substrate (metal optical bench (MOB)); (ii) preparing a flexible optical transmission-connection medium (optical wiring link) to optically connect the light source device formed on the substrate with the optical detection device; and (iii) directly connecting one end of the surface-finished optical transmission connection medium with the light source device and the other end with the optical detection device. Electronic interconnections have uniquely electronic problems such as EMI, shorting, and ground loops. Since these problems only arise during transduction (electronics-to-optics or opticsto- electronics), the purely optical part and optical link(interconnection) is free of these problems. 1 An optical link system constructed with TRx modules was fabricated and the optical characteristics about data links and EMI levels were measured. The results clearly demonstrate that the use of an optical wiring method can provide robust and cost-effective assembly for reducing EMI of inter-chip interconnect. We successfully achieved a 4.5 Gb/s data transmission rate without EMI problems.

  18. Preparation of Power Distribution System for High Penetration of Renewable Energy Part I. Dynamic Voltage Restorer for Voltage Regulation Pat II. Distribution Circuit Modeling and Validation

    NASA Astrophysics Data System (ADS)

    Khoshkbar Sadigh, Arash

    Part I: Dynamic Voltage Restorer In the present power grids, voltage sags are recognized as a serious threat and a frequently occurring power-quality problem and have costly consequence such as sensitive loads tripping and production loss. Consequently, the demand for high power quality and voltage stability becomes a pressing issue. Dynamic voltage restorer (DVR), as a custom power device, is more effective and direct solutions for "restoring" the quality of voltage at its load-side terminals when the quality of voltage at its source-side terminals is disturbed. In the first part of this thesis, a DVR configuration with no need of bulky dc link capacitor or energy storage is proposed. This fact causes to reduce the size of the DVR and increase the reliability of the circuit. In addition, the proposed DVR topology is based on high-frequency isolation transformer resulting in the size reduction of transformer. The proposed DVR circuit, which is suitable for both low- and medium-voltage applications, is based on dc-ac converters connected in series to split the main dc link between the inputs of dc-ac converters. This feature makes it possible to use modular dc-ac converters and utilize low-voltage components in these converters whenever it is required to use DVR in medium-voltage application. The proposed configuration is tested under different conditions of load power factor and grid voltage harmonic. It has been shown that proposed DVR can compensate the voltage sag effectively and protect the sensitive loads. Following the proposition of the DVR topology, a fundamental voltage amplitude detection method which is applicable in both single/three-phase systems for DVR applications is proposed. The advantages of proposed method include application in distorted power grid with no need of any low-pass filter, precise and reliable detection, simple computation and implementation without using a phased locked loop and lookup table. The proposed method has been verified by simulation and experimental tests under various conditions considering all possible cases such as different amounts of voltage sag depth (VSD), different amounts of point-on-wave (POW) at which voltage sag occurs, harmonic distortion, line frequency variation, and phase jump (PJ). Furthermore, the ripple amount of fundamental voltage amplitude calculated by the proposed method and its error is analyzed considering the line frequency variation together with harmonic distortion. The best and worst detection time of proposed method were measured 1ms and 8.8ms, respectively. Finally, the proposed method has been compared with other voltage sag detection methods available in literature. Part 2: Power System Modeling for Renewable Energy Integration: As power distribution systems are evolving into more complex networks, electrical engineers have to rely on software tools to perform circuit analysis. There are dozens of powerful software tools available in the market to perform the power system studies. Although their main functions are similar, there are differences in features and formatting structures to suit specific applications. This creates challenges for transferring power system circuit models data (PSCMD) between different software and rebuilding the same circuit in the second software environment. The objective of this part of thesis is to develop a Unified Platform (UP) to facilitate transferring PSCMD among different software packages and relieve the challenges of the circuit model conversion process. UP uses a commonly available spreadsheet file with a defined format, for any home software to write data to and for any destination software to read data from, via a script-based application called PSCMD transfer application. The main considerations in developing the UP are to minimize manual intervention and import a one-line diagram into the destination software or export it from the source software, with all details to allow load flow, short circuit and other analyses. In this study, ETAP, OpenDSS, and GridLab-D are considered, and PSCMD transfer applications written in MATLAB have been developed for each of these to read the circuit model data provided in the UP spreadsheet. In order to test the developed PSCMD transfer applications, circuit model data of a test circuit and a power distribution circuit from Southern California Edison (SCE) - a utility company - both built in CYME, were exported into the spreadsheet file according to the UP format. Thereafter, circuit model data were imported successfully from the spreadsheet files into above mentioned software using the PSCMD transfer applications developed for each software. After the SCE studied circuit is transferred into OpenDSS software using the proposed UP scheme and developed application, it has been studied to investigate the impacts of large-scale solar energy penetration. The main challenge of solar energy integration into power grid is its intermittency (i.e., discontinuity of output power) nature due to cloud shading of photovoltaic panels which depends on weather conditions. In order to conduct this study, OpenDSS time-series simulation feature, which is required due to intermittency of solar energy, is utilized. In this study, the impacts of intermittency of solar energy penetration, especially high-variability points, on voltage fluctuation and operation of capacitor bank and voltage regulator is provided. In addition, the necessity to interpolate and resample unequally spaced time-series measurement data and convert them to equally spaced time-series data as well as the effect of resampling time-interval on the amount of error is discussed. Two applications are developed in Matlab to do interpolation and resampling as well as to calculate the amount of error for different resampling time-intervals to figure out the suitable resampling time-interval. Furthermore, an approach based on cumulative distribution, regarding the length for lines/cables types and the power rating for loads, is presented to prioritize which loads, lines and cables the meters should be installed at to have the most effect on model validation.

  19. Fragile X Mental Retardation Protein Restricts Small Dye Iontophoresis Entry into Central Neurons

    PubMed Central

    2017-01-01

    Fragile X mental retardation protein (FMRP) loss causes Fragile X syndrome (FXS), a major disorder characterized by autism, intellectual disability, hyperactivity, and seizures. FMRP is both an RNA- and channel-binding regulator, with critical roles in neural circuit formation and function. However, it remains unclear how these FMRP activities relate to each other and how dysfunction in their absence underlies FXS neurological symptoms. In testing circuit level defects in the Drosophila FXS model, we discovered a completely unexpected and highly robust neuronal dye iontophoresis phenotype in the well mapped giant fiber (GF) circuit. Controlled dye injection into the GF interneuron results in a dramatic increase in dye uptake in neurons lacking FMRP. Transgenic wild-type FMRP reintroduction rescues the mutant defect, demonstrating a specific FMRP requirement. This phenotype affects only small dyes, but is independent of dye charge polarity. Surprisingly, the elevated dye iontophoresis persists in shaking B mutants that eliminate gap junctions and dye coupling among GF circuit neurons. We therefore used a wide range of manipulations to investigate the dye uptake defect, including timed injection series, pharmacology and ion replacement, and optogenetic activity studies. The results show that FMRP strongly limits the rate of dye entry via a cytosolic mechanism. This study reveals an unexpected new phenotype in a physical property of central neurons lacking FMRP that could underlie aspects of FXS disruption of neural function. SIGNIFICANCE STATEMENT FXS is a leading heritable cause of intellectual disability and autism spectrum disorders. Although researchers established the causal link with FMRP loss >;25 years ago, studies continue to reveal diverse FMRP functions. The Drosophila FXS model is key to discovering new FMRP roles, because of its genetic malleability and individually identified neuron maps. Taking advantage of a well characterized Drosophila neural circuit, we discovered that neurons lacking FMRP take up dramatically more current-injected small dye. After examining many neuronal properties, we determined that this dye defect is cytoplasmic and occurs due to a highly elevated dye iontophoresis rate. We also report several new factors affecting neuron dye uptake. Understanding how FMRP regulates iontophoresis should reveal new molecular factors underpinning FXS dysfunction. PMID:28887386

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

    Tang, Jason D.; Schroeppel, Richard Crabtree; Robertson, Perry J.

    With the build-out of large transport networks utilizing optical technologies, more and more capacity is being made available. Innovations in Dense Wave Division Multiplexing (DWDM) and the elimination of optical-electrical-optical conversions have brought on advances in communication speeds as we move into 10 Gigabit Ethernet and above. Of course, there is a need to encrypt data on these optical links as the data traverses public and private network backbones. Unfortunately, as the communications infrastructure becomes increasingly optical, advances in encryption (done electronically) have failed to keep up. This project examines the use of optical logic for implementing encryption in themore » photonic domain to achieve the requisite encryption rates. This paper documents the innovations and advances of work first detailed in 'Photonic Encryption using All Optical Logic,' [1]. A discussion of underlying concepts can be found in SAND2003-4474. In order to realize photonic encryption designs, technology developed for electrical logic circuits must be translated to the photonic regime. This paper examines S-SEED devices and how discrete logic elements can be interconnected and cascaded to form an optical circuit. Because there is no known software that can model these devices at a circuit level, the functionality of S-SEED devices in an optical circuit was modeled in PSpice. PSpice allows modeling of the macro characteristics of the devices in context of a logic element as opposed to device level computational modeling. By representing light intensity as voltage, 'black box' models are generated that accurately represent the intensity response and logic levels in both technologies. By modeling the behavior at the systems level, one can incorporate systems design tools and a simulation environment to aid in the overall functional design. Each black box model takes certain parameters (reflectance, intensity, input response), and models the optical ripple and time delay characteristics. These 'black box' models are interconnected and cascaded in an encrypting/scrambling algorithm based on a study of candidate encryption algorithms. Demonstration circuits show how these logic elements can be used to form NAND, NOR, and XOR functions. This paper also presents functional analysis of a serial, low gate count demonstration algorithm suitable for scrambling/encryption using S-SEED devices.« less

  1. Flexible, Photopatterned, Colloidal CdSe Semiconductor Nanocrystal Integrated Circuits

    NASA Astrophysics Data System (ADS)

    Stinner, F. Scott

    As semiconductor manufacturing pushes towards smaller and faster transistors, a parallel goal exists to create transistors which are not nearly as small. These transistors are not intended to match the performance of traditional crystalline semiconductors; they are designed to be significantly lower in cost and manufactured using methods that can make them physically flexible for applications where form is more important than speed. One of the developing technologies for this application is semiconductor nanocrystals. We first explore methods to develop CdSe nanocrystal semiconducting "inks" into large-scale, high-speed integrated circuits. We demonstrate photopatterned transistors with mobilities of 10 cm2/Vs on Kapton substrates. We develop new methods for vertical interconnect access holes to demonstrate multi-device integrated circuits including inverting amplifiers with 7 kHz bandwidths, ring oscillators with <10 micros stage delays, and NAND and NOR logic gates. In order to produce higher performance and more consistent transistors, we develop a new hybrid procedure for processing the CdSe nanocrystals. This procedure produces transistors with repeatable performance exceeding 40 cm2/Vs when fabricated on silicon wafers and 16 cm 2/vs when fabricated as part of photopatterned integrated circuits on Kapton substrates. In order to demonstrate the full potential of these transistors, methods to create high-frequency oscillators were developed. These methods allow for transistors to operate at higher voltages as well as provide a means for wirebonding to the Kapton substrate, both of which are required for operating and probing high-frequency oscillators. Simulations of this system show the potential for operation at MHz frequencies. Demonstration of these transistors in this frequency range would open the door for development of CdSe integrated circuits for high-performance sensor, display, and audio applications. To develop further applications of electronics on flexible substrates, procedures are developed for the integration of polychromatic displays on polyethylene terephthalate (PET) substrates and a commercial near field communication (NFC) link. The device draws its power from the NFC transmitter common on smartphones and eliminates the need for a fixed battery. This allows for the mass deployment of flexible, interactive displays on product packaging.

  2. Effects of ion channel noise on neural circuits: an application to the respiratory pattern generator to investigate breathing variability.

    PubMed

    Yu, Haitao; Dhingra, Rishi R; Dick, Thomas E; Galán, Roberto F

    2017-01-01

    Neural activity generally displays irregular firing patterns even in circuits with apparently regular outputs, such as motor pattern generators, in which the output frequency fluctuates randomly around a mean value. This "circuit noise" is inherited from the random firing of single neurons, which emerges from stochastic ion channel gating (channel noise), spontaneous neurotransmitter release, and its diffusion and binding to synaptic receptors. Here we demonstrate how to expand conductance-based network models that are originally deterministic to include realistic, physiological noise, focusing on stochastic ion channel gating. We illustrate this procedure with a well-established conductance-based model of the respiratory pattern generator, which allows us to investigate how channel noise affects neural dynamics at the circuit level and, in particular, to understand the relationship between the respiratory pattern and its breath-to-breath variability. We show that as the channel number increases, the duration of inspiration and expiration varies, and so does the coefficient of variation of the breath-to-breath interval, which attains a minimum when the mean duration of expiration slightly exceeds that of inspiration. For small channel numbers, the variability of the expiratory phase dominates over that of the inspiratory phase, and vice versa for large channel numbers. Among the four different cell types in the respiratory pattern generator, pacemaker cells exhibit the highest sensitivity to channel noise. The model shows that suppressing input from the pons leads to longer inspiratory phases, a reduction in breathing frequency, and larger breath-to-breath variability, whereas enhanced input from the raphe nucleus increases breathing frequency without changing its pattern. A major source of noise in neuronal circuits is the "flickering" of ion currents passing through the neurons' membranes (channel noise), which cannot be suppressed experimentally. Computational simulations are therefore the best way to investigate the effects of this physiological noise by manipulating its level at will. We investigate the role of noise in the respiratory pattern generator and show that endogenous, breath-to-breath variability is tightly linked to the respiratory pattern. Copyright © 2017 the American Physiological Society.

  3. A Wnt1 regulated Frizzled-1/β-Catenin signaling pathway as a candidate regulatory circuit controlling mesencephalic dopaminergic neuron-astrocyte crosstalk: Therapeutical relevance for neuron survival and neuroprotection

    PubMed Central

    2011-01-01

    Background Dopamine-synthesizing (dopaminergic, DA) neurons in the ventral midbrain (VM) constitute a pivotal neuronal population controlling motor behaviors, cognitive and affective brain functions, which generation critically relies on the activation of Wingless-type MMTV integration site (Wnt)/β-catenin pathway in their progenitors. In Parkinson's disease, DA cell bodies within the substantia nigra pars compacta (SNpc) progressively degenerate, with causes and mechanisms poorly understood. Emerging evidence suggests that Wnt signaling via Frizzled (Fzd) receptors may play a role in different degenerative states, but little is known about Wnt signaling in the adult midbrain. Using in vitro and in vivo model systems of DA degeneration, along with functional studies in both intact and SN lesioned mice, we herein highlight an intrinsic Wnt1/Fzd-1/β-catenin tone critically contributing to the survival and protection of adult midbrain DA neurons. Results In vitro experiments identifie Fzd-1 receptor expression at a mRNA and protein levels in dopamine transporter (DAT) expressing neurons, and demonstrate the ability of exogenous Wnt1 to exert robust neuroprotective effects against Caspase-3 activation, the loss of tyrosine hydroxylase-positive (TH+) neurons and [3H] dopamine uptake induced by different DA-specific insults, including serum and growth factor deprivation, 6-hydroxydopamine and MPTP/MPP+. Co-culture of DA neurons with midbrain astrocytes phenocopies Wnt1 neuroprotective effects, whereas RNA interference-mediated knockdown of Wnt1 in midbrain astrocytes markedly reduces astrocyte-induced TH+ neuroprotection. Likewise, silencing β-catenin mRNA or knocking down Fzd-1 receptor expression in mesencephalic neurons counteract astrocyte-induced TH+ neuroprotection. In vivo experiments document Fzd-1 co-localization with TH+ neurons within the intact SNpc and blockade of Fzd/β-catenin signaling by unilateral infusion of a Fzd/β-catenin antagonist within the SN induces reactive astrocytosis and acutely inhibits TH+ neuron survival in ipsilateral SNpc, an effect efficiently prevented by pharmacological activation of β-catenin signaling within the SNpc. Conclusion These results defining a novel Wnt1/Fzd-1/β-catenin astrocyte-DA autoprotective loop provide a new mechanistic inside into the regulation of pro-survival processes, with potentially relevant consequences for drug design or drug action in Parkinson's disease. PMID:21752258

  4. Performance testing of a high frequency link converter for Space Station power distribution system

    NASA Technical Reports Server (NTRS)

    Sul, S. K.; Alan, I.; Lipo, T. A.

    1989-01-01

    The testing of a brassboard version of a 20-kHz high-frequency ac voltage link prototype converter dynamics for Space Station application is presented. The converter is based on a three-phase six-pulse bridge concept. The testing includes details of the operation of the converter when it is driving an induction machine source/load. By adapting a field orientation controller (FOC) to the converter, four-quadrant operation of the induction machine from the converter has been achieved. Circuit modifications carried out to improve the performance of the converter are described. The performance of two 400-Hz induction machines powered by the converter with simple V/f regulation mode is reported. The testing and performance results for the converter utilizing the FOC, which provides the capability for rapid torque changes, speed reversal, and four-quadrant operation, are reported.

  5. Stability Augmentation of Wind Farm using Variable Speed Permanent Magnet Synchronous Generator

    NASA Astrophysics Data System (ADS)

    Rosyadi, Marwan; Muyeen, S. M.; Takahashi, Rion; Tamura, Junji

    This paper presents a new control strategy of variable speed permanent magnet wind generator for stability augmentation of wind farm including fixed speed wind turbine with Induction Generator (IG). A new control scheme is developed for two levels back-to-back converters of Permanent Magnet Synchronous Generator (PMSG), by which both active and reactive powers delivered to the grid can be controlled easily. To avoid the converter damage, the DC link protection controller is also proposed in order to protect the dc link circuit during fault condition. To evaluate the control capability of the proposed controllers, simulations are performed on two model systems composed of wind farms connected to an infinite bus. From transient and steady state analyses by using PSCAD/EMTDC, it is concluded that the proposed control scheme is very effective to improve the stability of wind farm for severe network disturbance and randomly fluctuating wind speed.

  6. Engineering and Biology: Counsel for a Continued Relationship

    PubMed Central

    Levy, Arnon; Siegal, Mark L.; Soyer, Orkun S.; Wagner, Andreas

    2015-01-01

    Biologists frequently draw on ideas and terminology from engineering. Evolutionary systems biology—with its circuits, switches, and signal processing—is no exception. In parallel with the frequent links drawn between biology and engineering, there is ongoing criticism against this cross-fertilization, using the argument that over-simplistic metaphors from engineering are likely to mislead us as engineering is fundamentally different from biology. In this article, we clarify and reconfigure the link between biology and engineering, presenting it in a more favorable light. We do so by, first, arguing that critics operate with a narrow and incorrect notion of how engineering actually works, and of what the reliance on ideas from engineering entails. Second, we diagnose and diffuse one significant source of concern about appeals to engineering, namely that they are inherently and problematically metaphorical. We suggest that there is plenty of fertile ground left for a continued, healthy relationship between engineering and biology. PMID:26085824

  7. A Proposal for the Education based on the Information Technology in Technical High Schools, Linking Together Web Programming and Microcontroller

    NASA Astrophysics Data System (ADS)

    Shinozaki, Kenichi; Yanaru, Torao

    Recently, IT (Information Technology) have rapidly revolved and penetrated into the usual human life, with such as the household appliances and the mobile devices. Considering this strong change of social environment, what technology is introduced to satisfy the present educational needs and how to develop the teaching system is very important. Then in this paper, we describe the developed web-teaching material that links Xport, an embedded device server, with the control system using microcontroller technology. In the classes, we have implemented the lessons that utilize this system in the following subjects : programming technology, hardware technology, electronic circuit and practical training. Furthermore, because of high availability of the developed system through internet, it is also useful for the education on science and technical arts in general high schools or in junior high schools as well as in technical high schools.

  8. Learning to Link Visual Contours

    PubMed Central

    Li, Wu; Piëch, Valentin; Gilbert, Charles D.

    2008-01-01

    SUMMARY In complex visual scenes, linking related contour elements is important for object recognition. This process, thought to be stimulus driven and hard wired, has substrates in primary visual cortex (V1). Here, however, we find contour integration in V1 to depend strongly on perceptual learning and top-down influences that are specific to contour detection. In naive monkeys the information about contours embedded in complex backgrounds is absent in V1 neuronal responses, and is independent of the locus of spatial attention. Training animals to find embedded contours induces strong contour-related responses specific to the trained retinotopic region. These responses are most robust when animals perform the contour detection task, but disappear under anesthesia. Our findings suggest that top-down influences dynamically adapt neural circuits according to specific perceptual tasks. This may serve as a general neuronal mechanism of perceptual learning, and reflect top-down mediated changes in cortical states. PMID:18255036

  9. Brain Oscillations, Hypnosis, and Hypnotizability

    PubMed Central

    Jensen, Mark P.; Adachi, Tomonori; Hakimian, Shahin

    2014-01-01

    In this article, we summarize the state-of-science knowledge regarding the associations between hypnosis and brain oscillations. Brain oscillations represent the combined electrical activity of neuronal assemblies, and are usually measured as specific frequencies representing slower (delta, theta, alpha) and faster (beta, gamma) oscillations. Hypnosis has been most closely linked to power in the theta band and changes in gamma activity. These oscillations are thought to play a critical role in both the recording and recall of declarative memory and emotional limbic circuits. Here we propose that it is this role that may be the mechanistic link between theta (and perhaps gamma) oscillations and hypnosis; specifically that theta oscillations may facilitate, and that changes in gamma activity observed with hypnosis may underlie, some hypnotic responses. If these hypotheses are supported, they have important implications for both understanding the effects of hypnosis, and for enhancing response to hypnotic treatments. PMID:25792761

  10. Bosonic Confinement and Coherence in Disordered Nanodiamond Arrays.

    PubMed

    Zhang, Gufei; Samuely, Tomas; Du, Hongchu; Xu, Zheng; Liu, Liwang; Onufriienko, Oleksandr; May, Paul W; Vanacken, Johan; Szabó, Pavol; Kačmarčík, Jozef; Yuan, Haifeng; Samuely, Peter; Dunin-Borkowski, Rafal E; Hofkens, Johan; Moshchalkov, Victor V

    2017-11-28

    In the presence of disorder, superconductivity exhibits short-range characteristics linked to localized Cooper pairs which are responsible for anomalous phase transitions and the emergence of quantum states such as the bosonic insulating state. Complementary to well-studied homogeneously disordered superconductors, superconductor-normal hybrid arrays provide tunable realizations of the degree of granular disorder for studying anomalous quantum phase transitions. Here, we investigate the superconductor-bosonic dirty metal transition in disordered nanodiamond arrays as a function of the dispersion of intergrain spacing, which ranges from angstroms to micrometers. By monitoring the evolved superconducting gaps and diminished coherence peaks in the single-quasiparticle density of states, we link the destruction of the superconducting state and the emergence of bosonic dirty metallic state to breaking of the global phase coherence and persistence of the localized Cooper pairs. The observed resistive bosonic phase transitions are well modeled using a series-parallel circuit in the framework of bosonic confinement and coherence.

  11. Advantages of comparative studies in songbirds to understand the neural basis of sensorimotor integration.

    PubMed

    Murphy, Karagh; James, Logan S; Sakata, Jon T; Prather, Jonathan F

    2017-08-01

    Sensorimotor integration is the process through which the nervous system creates a link between motor commands and associated sensory feedback. This process allows for the acquisition and refinement of many behaviors, including learned communication behaviors such as speech and birdsong. Consequently, it is important to understand fundamental mechanisms of sensorimotor integration, and comparative analyses of this process can provide vital insight. Songbirds offer a powerful comparative model system to study how the nervous system links motor and sensory information for learning and control. This is because the acquisition, maintenance, and control of birdsong critically depend on sensory feedback. Furthermore, there is an incredible diversity of song organizations across songbird species, ranging from songs with simple, stereotyped sequences to songs with complex sequencing of vocal gestures, as well as a wide diversity of song repertoire sizes. Despite this diversity, the neural circuitry for song learning, control, and maintenance remains highly similar across species. Here, we highlight the utility of songbirds for the analysis of sensorimotor integration and the insights about mechanisms of sensorimotor integration gained by comparing different songbird species. Key conclusions from this comparative analysis are that variation in song sequence complexity seems to covary with the strength of feedback signals in sensorimotor circuits and that sensorimotor circuits contain distinct representations of elements in the vocal repertoire, possibly enabling evolutionary variation in repertoire sizes. We conclude our review by highlighting important areas of research that could benefit from increased comparative focus, with particular emphasis on the integration of new technologies. Copyright © 2017 the American Physiological Society.

  12. A facility for studying the carcinogenic and synergistic effects of radon daughters and other agents in rodents

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

    Strong, J.C.; Walsh, M.

    Although there is evidence to link lung cancer with radon exposures in miners, studies have not yet adequately demonstrated a link at domestic levels of exposure. Induction of cancer in animals after acute exposure to high levels of radon and radon daughters has been investigated by several laboratories. It is our intention to study the effects of radon and its daughters on rodents following both acute and chronic exposure. The studies will be extended to investigate the effects of other carcinogens in association with radon daughters. We will describe a facility in which rodents can be exposed continuously to radonmore » and its daughters for periods of up to several months. The facility consists of two exposure chambers with closed air circuits which are operated independently of each other. Aerosol generators provide controlled vector aerosols onto which radon daughters can attach. Particular attention has been paid to accurate measurements of the concentrations of radon gas and of individual radon daughters. Techniques have also been developed for measuring the {open_quotes}unattached{close_quotes} fraction, the activity size distribution of individual daughters, and the potential alpha energy. The environment within the facility will be adjusted to be comparable to that found in dwellings with regard to condensation nucleus concentration, {open_quotes}unattached{close_quotes} fraction, equilibrium factor, and activity size distribution. Other vapors and aerosols, such as tobacco smoke, can be introduced into one of the air circuits to study the combined effects of radiation and toxic chemical agents.« less

  13. Chip-to-chip interconnects based on 3D stacking of optoelectrical dies on Si

    NASA Astrophysics Data System (ADS)

    Duan, P.; Raz, O.; Smalbrugge, B. E.; Duis, J.; Dorren, H. J. S.

    2012-01-01

    We demonstrate a new approach to increase the optical interconnection bandwidth density by stacking the opto-electrical dies directly on the CMOS driver. The suggested implementation is aiming to provide a wafer scale process which will make the use of wire bonding redundant and will allow for impedance matched metallic wiring between the electronic driving circuit and its opto-electronic counter part. We suggest the use of a thick photoresist ramp between CMOS driver and opto-electrical dies surface as the bridge for supporting co-plannar waveguides (CPW) electrically plated with lithographic accuracy. In this way all three dimensions of the interconnecting metal layer, width, length and thickness can be completely controlled. In this 1st demonstration all processing is done on commercially available devices and products, and is compatible with CMOS processing technology. To test the applicability of CPW instead of wire bonds for interconnecting the CMOS circuit and opto-electronic chips, we have made test samples and tested their performance at speeds up to 10 Gbps. In this demonstration, a silicon substrate was used on which we evaporated gold co-planar waveguides (CPW) to mimic a wire on the driver. An optical link consisting of a VCSEL chip and a photodiode chip has been assembled and fully characterized using optical coupling into and out of a multimode fiber (MMF). A 10 Gb/s 27-1 NRZ PRBS signal transmitted from one chip to another chip was detected error free. A 4 dB receiver sensitivity penalty is measured for the integrated device compared to a commercial link.

  14. First report of Rickettsia raoultii and R. slovaca in Melophagus ovinus, the sheep ked.

    PubMed

    Liu, Dan; Wang, Yuan-Zhi; Zhang, Huan; Liu, Zhi-Qiang; Wureli, Ha-Zi; Wang, Shi-Wei; Tu, Chang-Chun; Chen, Chuang-Fu

    2016-11-25

    Melophagus ovinus (Diptera: Hippoboscidae), a hematophagous ectoparasite, is mainly found in Europe, Northwestern Africa, and Asia. This wingless fly infests sheep, rabbits, and red foxes, and causes inflammation, wool loss and skin damage. Furthermore, this parasite has been shown to transmit diseases, and plays a role as a vector. Herein, we investigated the presence of various Rickettsia species in M. ovinus. In this study, a total of 95 sheep keds were collected in Kuqa County and Alaer City southern region of Xinjiang Uygur Autonomous Region, northwestern China. First, collected sheep keds were identified on the species level using morphological keys and molecular methods based on a fragment of the 18S ribosomal DNA gene (18S rDNA). Thereafter, to assess the presence of rickettsial DNA in sheep keds, the DNA of individual samples was screened by PCR based on six Rickettsia-specific gene fragments originating from six genes: the 17-kilodalton antigen gene (17-kDa), 16S rRNA gene (rrs), surface cell antigen 4 gene (sca4), citrate synthase gene (gltA), and outer membrane protein A and B genes (ompA and ompB). The amplified products were confirmed by sequencing and BLAST analysis ( https://blast.ncbi.nlm.nih.gov/Blast.cgi?PROGRAM=blastn&PAGE_TYPE=BlastSearch&LINK_LOC=blasthome ). According to its morphology and results of molecular analysis, the species was identified as Melophagus ovinus, with 100% identity to M. ovinus from St. Kilda, Australia (FN666411). DNA of Rickettsia spp. were found in 12 M. ovinus samples (12.63%, 12/95). Rickettsia raoultii and R. slovaca were confirmed based on phylogenetic analysis, although the genetic markers of these two rickettsial agents amplified in this study showed molecular diversity. This is the first report of R. raoultii and R. slovaca DNA in M. ovinus. Rickettsia slovaca was found for the first time around the Taklimakan Desert located in China. This finding extends the geographical range of spotted fever group rickettsiae.

  15. WNT Stimulation Dissociates a Frizzled 4 Inactive-State Complex with Gα12/13.

    PubMed

    Arthofer, Elisa; Hot, Belma; Petersen, Julian; Strakova, Katerina; Jäger, Stefan; Grundmann, Manuel; Kostenis, Evi; Gutkind, J Silvio; Schulte, Gunnar

    2016-10-01

    Frizzleds (FZDs) are unconventional G protein-coupled receptors that belong to the class Frizzled. They are bound and activated by the Wingless/Int-1 lipoglycoprotein (WNT) family of secreted lipoglycoproteins. To date, mechanisms of signal initiation and FZD-G protein coupling remain poorly understood. Previously, we showed that FZD6 assembles with Gαi1/Gαq (but not with Gαs, Gαo and Ga12/13), and that these inactive-state complexes are dissociated by WNTs and regulated by the phosphoprotein Dishevelled (DVL). Here, we investigated the inactive-state assembly of heterotrimeric G proteins with FZD4, a receptor important in retinal vascular development and frequently mutated in Norrie disease or familial exudative vitreoretinopathy. Live-cell imaging experiments using fluorescence recovery after photobleaching show that human FZD4 assembles-in a DVL-independent manner-with Gα12/13 but not representatives of other heterotrimeric G protein subfamilies, such as Gαi1, Gαo, Gαs, and Gαq The FZD4-G protein complex dissociates upon stimulation with WNT-3A, WNT-5A, WNT-7A, and WNT-10B. In addition, WNT-induced dynamic mass redistribution changes in untransfected and, even more so, in FZD4 green fluorescent protein-transfected cells depend on Gα12/13 Furthermore, expression of FZD4 and Gα12 or Gα13 in human embryonic kidney 293 cells induces WNT-dependent membrane recruitment of p115-RHOGEF (RHO guanine nucleotide exchange factor, molecular weight 115 kDa), a direct target of Gα12/13 signaling, underlining the functionality of an FZD4-Gα12/13-RHO signaling axis. In summary, Gα12/13-mediated WNT/FZD4 signaling through p115-RHOGEF offers an intriguing and previously unappreciated mechanistic link of FZD4 signaling to cytoskeletal rearrangements and RHO signaling with implications for the regulation of angiogenesis during embryonic and tumor development. Copyright © 2016 by The American Society for Pharmacology and Experimental Therapeutics.

  16. WNT Stimulation Dissociates a Frizzled 4 Inactive-State Complex with Gα12/13

    PubMed Central

    Arthofer, Elisa; Hot, Belma; Petersen, Julian; Strakova, Katerina; Jäger, Stefan; Grundmann, Manuel; Kostenis, Evi; Gutkind, J. Silvio

    2016-01-01

    Frizzleds (FZDs) are unconventional G protein–coupled receptors that belong to the class Frizzled. They are bound and activated by the Wingless/Int-1 lipoglycoprotein (WNT) family of secreted lipoglycoproteins. To date, mechanisms of signal initiation and FZD–G protein coupling remain poorly understood. Previously, we showed that FZD6 assembles with Gαi1/Gαq (but not with Gαs, Gαo and Ga12/13), and that these inactive-state complexes are dissociated by WNTs and regulated by the phosphoprotein Dishevelled (DVL). Here, we investigated the inactive-state assembly of heterotrimeric G proteins with FZD4, a receptor important in retinal vascular development and frequently mutated in Norrie disease or familial exudative vitreoretinopathy. Live-cell imaging experiments using fluorescence recovery after photobleaching show that human FZD4 assembles—in a DVL-independent manner—with Gα12/13 but not representatives of other heterotrimeric G protein subfamilies, such as Gαi1, Gαo, Gαs, and Gαq. The FZD4–G protein complex dissociates upon stimulation with WNT-3A, WNT-5A, WNT-7A, and WNT-10B. In addition, WNT-induced dynamic mass redistribution changes in untransfected and, even more so, in FZD4 green fluorescent protein–transfected cells depend on Gα12/13. Furthermore, expression of FZD4 and Gα12 or Gα13 in human embryonic kidney 293 cells induces WNT-dependent membrane recruitment of p115-RHOGEF (RHO guanine nucleotide exchange factor, molecular weight 115 kDa), a direct target of Gα12/13 signaling, underlining the functionality of an FZD4-Gα12/13-RHO signaling axis. In summary, Gα12/13-mediated WNT/FZD4 signaling through p115-RHOGEF offers an intriguing and previously unappreciated mechanistic link of FZD4 signaling to cytoskeletal rearrangements and RHO signaling with implications for the regulation of angiogenesis during embryonic and tumor development. PMID:27458145

  17. Using NASA's GeneLab for VESGEN Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, P.; Weitzel, Alexander; Vyas, R. J.; Murray, M. C.; Vickerman, M. B.; Bhattacharya, S.; Wyatt, S. E.

    2016-01-01

    One fundamental requirement shared by humans with all higher terrestrial life forms, including other vertebrates, insects, and higher land plants, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. A unifying perspective is that vascular patterning offers a useful readout of molecular signaling that necessarily integrates these complex pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascularrelated changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the spatial and dynamic dimensions of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions. Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a Notch antagonist were analyzed by VESGEN. Other VESGEN research applications include the mouse retina, GI and coronary vessels, avian placental analogs and translational studies in the astronaut retina related to health challenges for long-duration missions.

  18. NASAs VESGEN: Systems Analysis of Vascular Phenotypes from Stress and Other Signaling Pathways Using GeneLab.

    NASA Technical Reports Server (NTRS)

    Parsons-Wingerter, Patricia A.; Weitzel, Alexander; Vyas, Ruchi J.; Murray, Matthew C.; Wyatt, Sarah E.

    2016-01-01

    One fundamental requirement shared by humans with all higher terrestrial life forms, including insect wings, higher land plants and other vertebrates, is a complex, fractally branching vascular system. NASA's VESsel GENeration Analysis (VESGEN) software maps and quantifies vascular trees, networks, and tree-network composites according to weighted physiological rules such as vessel connectivity, tapering and bifurcational branching. According to fluid dynamics, successful vascular transport requires a complex distributed system of highly regulated laminar flow. Microvascular branching rules within vertebrates, dicot leaves and the other organisms therefore display many similarities. One unifying perspective is that vascular patterning offers a useful readout that necessarily integrates complex molecular signaling pathways. VESGEN has elucidated changes in vascular pattern resulting from inflammatory, stress response, developmental and other signaling within numerous tissues and major model organisms studied for Space Biology. For a new VESGEN systems approach, we analyzed differential gene expression in leaves of Arabidopsis thaliana reported by GeneLab (GLDS-7) for spaceflight. Vascular-related changes in leaf gene expression were identified that can potentially be phenocopied by mutants in ground-based experiments. To link transcriptional, protein and other molecular change with phenotype, alterations in the Euclidean and dynamic dimensions (x,y,t) of vascular patterns for Arabidopsis leaves and other model species are being co-localized with signaling patterns of single molecular expression analyzed as information dimensions (i,j,k,...). Previously, Drosophila microarray data returned from space suggested significant changes in genes related to wing venation development that include EGF, Notch, Hedghog, Wingless and Dpp signaling. Phenotypes of increasingly abnormal ectopic wing venation in the (non-spaceflight) Drosophila wing generated by overexpression of a Notch antagonist were analyzed by VESGEN. Other VESGEN research applications include the mouse retina, GI and coronary vessels, avian placental analogs and translational studies in the astronaut retina related to health challenges for long-duration missions.

  19. Palaeo island-affinities revisited--biogeography and systematics of the Indo-Pacific genus Cethosia Fabricius (Lepidoptera: Nymphalidae).

    PubMed

    Müller, C J; Beheregaray, L B

    2010-10-01

    The Indo-Pacific is a very complex region encompassing several micro-continents with unique tectonic and geomorphologic histories. Unsurprisingly, the biogeographic history of Indo-Pacific biota is generally poorly known, especially that of organisms found in the heart of the region, the biodiversity hotspot known as Wallacea. Here, we explore the biogeographic history of the Indo-Pacific butterfly genus Cethosia using all known species and many distinctive subspecies. Cethosia butterflies span the Indo-Pacific tropics, including several lineages with localized endemism that are critically important when reconstructing biogeographic history of the Indo-Pacific and, in particular, of Wallacea. A phylogenetic hypothesis is proposed, based on sequences of the mitochondrial genes cytochrome oxidase subunit I (COI) and NADH dehydrogenase 5 (ND5), and the nuclear wingless gene. Both Maximum Parsimony and Bayesian analyses showed that the genus is monophyletic and consistently recovered seven, generally very well supported, clades, namely the cydippe, leschenault, biblis, nietneri, hypsea, penthesilea and cyane clades. Species group relationships are largely concordant with general morphology (i.e., wing pattern and colouration) and, based on the phylogeny, we propose a revised systematic classification at the species level. The evolution of the genus appears associated with the inferred geological history of the region, in particular with respect to the expanding Wallacea theory, whereby ancient connected terranes were fragmented during the mid Miocene to early Pliocene, approximately 14-3 Mya. Recent diversification events in Cethosia were likely promoted by climatic fluctuations during the Pliocene and, to a lesser extent, the Pleistocene. Our results support the view that, while dispersal has been important for Cethosia throughout much of the region, the high levels of island endemism and the essentially allopatric radiations recovered in Cethosia in Wallacea are better explained by vicariant processes linked to the history of formation of micro-continent and associated palaeo islands. Crown Copyright 2010. Published by Elsevier Inc. All rights reserved.

  20. Endothelial Dysfunction in Human Diabetes Is Mediated by Wnt5a-JNK Signaling.

    PubMed

    Bretón-Romero, Rosa; Feng, Bihua; Holbrook, Monika; Farb, Melissa G; Fetterman, Jessica L; Linder, Erika A; Berk, Brittany D; Masaki, Nobuyuki; Weisbrod, Robert M; Inagaki, Elica; Gokce, Noyan; Fuster, Jose J; Walsh, Kenneth; Hamburg, Naomi M

    2016-03-01

    Endothelial dysfunction is linked to insulin resistance, inflammatory activation, and increased cardiovascular risk in diabetes mellitus; however, the mechanisms remain incompletely understood. Recent studies have identified proinflammatory signaling of wingless-type family member (Wnt) 5a through c-jun N-terminal kinase (JNK) as a regulator of metabolic dysfunction with potential relevance to vascular function. We sought to gain evidence that increased activation of Wnt5a-JNK signaling contributes to impaired endothelial function in patients with diabetes mellitus. We measured flow-mediated dilation of the brachial artery and characterized freshly isolated endothelial cells by protein expression, eNOS activation, and nitric oxide production in 85 subjects with type 2 diabetes mellitus (n=42) and age- and sex-matched nondiabetic controls (n=43) and in human aortic endothelial cells treated with Wnt5a. Endothelial cells from patients with diabetes mellitus displayed 1.3-fold higher Wnt5a levels (P=0.01) along with 1.4-fold higher JNK activation (P<0.01) without a difference in total JNK levels. Higher JNK activation was associated with lower flow-mediated dilation, consistent with endothelial dysfunction (r=0.53, P=0.02). Inhibition of Wnt5a and JNK signaling restored insulin and A23187-mediated eNOS activation and improved nitric oxide production in endothelial cells from patients with diabetes mellitus. In endothelial cells from nondiabetic controls, rWnt5a treatment inhibited eNOS activation replicating the diabetic endothelial phenotype. In human aortic endothelial cells, Wnt5a-induced impairment of eNOS activation and nitric oxide production was reversed by Wnt5a and JNK inhibition. Our findings demonstrate that noncanonical Wnt5a signaling and JNK activity contribute to vascular insulin resistance and endothelial dysfunction and may represent a novel therapeutic opportunity to protect the vasculature in patients with diabetes mellitus. © 2016 American Heart Association, Inc.

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