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Sample records for genetically encoded optical

  1. Evaluating a genetically encoded optical sensor of neural activity using electrophysiology in intact adult fruit flies

    Directory of Open Access Journals (Sweden)

    Gilles Laurent

    2007-11-01

    Full Text Available Genetically encoded optical indicators hold the promise of enabling non-invasive monitoring of activity in identified neurons in behaving organisms. However, the interpretation of images of brain activity produced using such sensors is not straightforward. Several recent studies of sensory coding used G-CaMP 1.3-a calcium sensor-as an indicator of neural activity; some of these studies characterized the imaged neurons as having narrow tuning curves, a conclusion not always supported by parallel electrophysiological studies. To better understand the possible cause of these conflicting results, we performed simultaneous in vivo 2-photon imaging and electrophysiological recording of G-CaMP 1.3 expressing neurons in the antennal lobe (AL of intact fruitflies. We find that G-CaMP has a relatively high threshold, that its signal often fails to capture spiking response kinetics, and that it can miss even high instantaneous rates of activity if those are not sustained. While G-CaMP can be misleading, it is clearly useful for the identification of promising neural targets: when electrical activity is well above the sensor's detection threshold, its signal is fairly well correlated with mean firing rate and G-CaMP does not appear to alter significantly the responses of neurons that express it. The methods we present should enable any genetically encoded sensor, activator, or silencer to be evaluated in an intact neural circuit in vivo in Drosophila.

  2. Genetically encoded optical sensors for monitoring of intracellular chloride and chloride-selective channel activity

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    Piotr Bregestovski

    2009-12-01

    Full Text Available This review briefly discusses the main approaches for monitoring chloride (Cl−, the most abundant physiological anion. Noninvasive monitoring of intracellular Cl− ([Cl−]i is a challenging task owing to two main difficulties: (i the low transmembrane ratio for Cl−, approximately 10:1; and (ii the small driving force for Cl−, as the Cl− reversal potential (ECl is usually close to the resting potential of the cells. Thus, for reliable monitoring of intracellular Cl−, one has to use highly sensitive probes. From several methods for intracellular Cl− analysis, genetically encoded chloride indicators represent the most promising tools. Recent achievements in the development of genetically encoded chloride probes are based on the fact that yellow fluorescent protein (YFP exhibits Cl−-sensitivity. YFP-based probes have been successfully used for quantitative analysis of Cl− transport in different cells and for high-throughput screening of modulators of Cl−-selective channels. Development of a ratiometric genetically encoded probe, Clomeleon, has provided a tool for noninvasive estimation of intracellular Cl− concentrations. While the sensitivity of this protein to Cl− is low (EC50 about 160 mM, it has been successfully used for monitoring intracellular Cl− in different cell types. Recently a CFP–YFP-based probe with a relatively high sensitivity to Cl− (EC50 about 30 mM has been developed. This construct, termed Cl-Sensor, allows ratiometric monitoring using the fluorescence excitation ratio. Of particular interest are genetically encoded probes for monitoring of ion channel distribution and activity. A new molecular probe has been constructed by introducing into the cytoplasmic domain of the Cl−-selective glycine receptor (GlyR channel the CFP–YFP-based Cl-Sensor. This construct, termed BioSensor-GlyR, has been successfully expressed in cell lines. The new genetically encoded chloride probes offer means of screening

  3. A fully genetically encoded protein architecture for optical control of peptide ligand concentration

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    Schmidt, Daniel; Tillberg, Paul W.; Chen, Fei; Boyden, Edward S.

    2014-01-01

    Ion channels are among the most important proteins in biology, regulating the activity of excitable cells and changing in diseases. Ideally it would be possible to actuate endogenous ion channels, in a temporally precise and reversible manner, and without requiring chemical cofactors. Here we present a modular protein architecture for fully genetically encoded, light-modulated control of ligands that modulate ion channels of a targeted cell. Our reagent, which we call a lumitoxin, combines a photoswitch and an ion channel-blocking peptide toxin. Illumination causes the photoswitch to unfold, lowering the toxin's local concentration near the cell surface, and enabling the ion channel to function. We explore lumitoxin modularity by showing operation with peptide toxins that target different voltage-dependent K+ channels. The lumitoxin architecture may represent a new kind of modular protein-engineering strategy for designing light-activated proteins, and thus may enable development of novel tools for modulating cellular physiology.

  4. Combinatorial mutagenesis of the voltage-sensing domain enables the optical resolution of action potentials firing at 60 Hz by a genetically encoded fluorescent sensor of membrane potential.

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    Piao, Hong Hua; Rajakumar, Dhanarajan; Kang, Bok Eum; Kim, Eun Ha; Baker, Bradley J

    2015-01-07

    ArcLight is a genetically encoded fluorescent voltage sensor using the voltage-sensing domain of the voltage-sensing phosphatase from Ciona intestinalis that gives a large but slow-responding optical signal in response to changes in membrane potential (Jin et al., 2012). Fluorescent voltage sensors using the voltage-sensing domain from other species give faster yet weaker optical signals (Baker et al., 2012; Han et al., 2013). Sequence alignment of voltage-sensing phosphatases from different species revealed conserved polar and charged residues at 7 aa intervals in the S1-S3 transmembrane segments of the voltage-sensing domain, suggesting potential coil-coil interactions. The contribution of these residues to the voltage-induced optical signal was tested using a cassette mutagenesis screen by flanking each transmembrane segment with unique restriction sites to allow for the testing of individual mutations in each transmembrane segment, as well as combinations in all four transmembrane segments. Addition of a counter charge in S2 improved the kinetics of the optical response. A double mutation in the S4 domain dramatically reduced the slow component of the optical signal seen in ArcLight. Combining that double S4 mutant with the mutation in the S2 domain yielded a probe with kinetics voltage-sensing domain could potentially lead to fluorescent sensors capable of optically resolving neuronal inhibition and subthreshold synaptic activity.

  5. Genetically Encoded Sensors for Metabolites

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    Deuschle, Karen; Fehr, Marcus; Hilpert, Melanie; Lager, Ida; Lalonde, Sylvie; Looger, Loren L.; Okumoto, Sakiko; Persson, Jörgen; Schmidt, Anja; Frommer, Wolf B.

    2009-01-01

    Background Metabolomics, i.e., the multiparallel analysis of metabolite changes occurring in a cell or an organism, has become feasible with the development of highly efficient mass spectroscopic technologies. Functional genomics as a standard tool helped to identify the function of many of the genes that encode important transporters and metabolic enzymes over the past few years. Advanced expression systems and analysis technologies made it possible to study the biochemical properties of the corresponding proteins in great detail. We begin to understand the biological functions of the gene products by systematic analysis of mutants using systematic PTGS/RNAi, knockout and TILLING approaches. However, one crucial set of data especially relevant in the case of multicellular organisms is lacking: the knowledge of the spatial and temporal profiles of metabolite levels at cellular and subcellular levels. Methods We therefore developed genetically encoded nanosensors for several metabolites to provide a basic set of tools for the determination of cytosolic and subcellular metabolite levels in real time by using fluorescence microscopy. Results Prototypes of these sensors were successfully used in vitro and also in vivo, i.e., to measure sugar levels in fungal and animal cells. Conclusions One of the future goals will be to expand the set of sensors to a wider spectrum of substrates by using the natural spectrum of periplasmic binding proteins from bacteria and by computational design of proteins with altered binding pockets in conjunction with mutagenesis. This toolbox can then be applied for four-dimensional imaging of cells and tissues to elucidate the spatial and temporal distribution of metabolites as a discovery tool in functional genomics, as a tool for high-throughput, high-content screening for drugs, to test metabolic models, and to analyze the interplay of cells in a tissue or organ. PMID:15688353

  6. Toward Better Genetically Encoded Sensors of Membrane Potential.

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    Storace, Douglas; Sepehri Rad, Masoud; Kang, BokEum; Cohen, Lawrence B; Hughes, Thom; Baker, Bradley J

    2016-05-01

    Genetically encoded optical sensors of cell activity are powerful tools that can be targeted to specific cell types. This is especially important in neuroscience because individual brain regions can include a multitude of different cell types. Optical imaging allows for simultaneous recording from numerous neurons or brain regions. Optical signals of membrane potential are useful because membrane potential changes are a direct sign of both synaptic and action potentials. Here we describe recent improvements in the in vitro and in vivo signal size and kinetics of genetically encoded voltage indicators (GEVIs) and discuss their relationship to alternative sensors of neural activity.

  7. Optical recording of neuronal activity with a genetically-encoded calcium indicator in anesthetized and freely moving mice

    Directory of Open Access Journals (Sweden)

    Henry Lütcke

    2010-04-01

    Full Text Available Fluorescent calcium (Ca2+ indicator proteins (FCIPs are promising tools for functional imaging of cellular activity in living animals. However, they have still not reached their full potential for in vivo imaging of neuronal activity due to limitations in expression levels, dynamic range, and sensitivity for reporting action potentials. Here, we report that viral expression of the ratiometric Ca2+ sensor yellow cameleon 3.60 (YC3.60 in pyramidal neurons of mouse barrel cortex enables in vivo measurement of neuronal activity with high dynamic range and sensitivity across multiple spatial scales. By combining juxtacellular recordings and two-photon imaging in vitro and in vivo, we demonstrate that YC3.60 can resolve single action potential (AP-evoked Ca2+ transients and reliably reports bursts of APs with negligible saturation. Spontaneous and whisker-evoked Ca2+ transients were detected in individual apical dendrites and somata as well as in local neuronal populations. Moreover, bulk measurements using wide-field imaging or fiber-optics revealed sensory-evoked YC3.60 signals in large areas of the barrel field. Fiber-optic recordings in particular enabled measurements in awake, freely moving mice and revealed complex Ca2+ dynamics, possibly reflecting different behavior-related brain states. Viral expression of YC3.60 - in combination with various optical techniques - thus opens a multitude of opportunities for functional studies of the neural basis of animal behavior, from dendrites to the levels of local and large-scale neuronal populations.

  8. Dual optical recordings for action potentials and calcium handling in induced pluripotent stem cell models of cardiac arrhythmias using genetically encoded fluorescent indicators.

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    Song, LouJin; Awari, Daniel W; Han, Elizabeth Y; Uche-Anya, Eugenia; Park, Seon-Hye E; Yabe, Yoko A; Chung, Wendy K; Yazawa, Masayuki

    2015-05-01

    Reprogramming of human somatic cells to pluripotency has been used to investigate disease mechanisms and to identify potential therapeutics. However, the methods used for reprogramming, in vitro differentiation, and phenotyping are still complicated, expensive, and time-consuming. To address the limitations, we first optimized a protocol for reprogramming of human fibroblasts and keratinocytes into pluripotency using single lipofection and the episomal vectors in a 24-well plate format. This method allowed us to generate multiple lines of integration-free and feeder-free induced pluripotent stem cells (iPSCs) from seven patients with cardiac diseases and three controls. Second, we differentiated human iPSCs derived from patients with Timothy syndrome into cardiomyocytes using a monolayer differentiation method. We found that Timothy syndrome cardiomyocytes showed slower, irregular contractions and abnormal calcium handling compared with the controls. The results are consistent with previous reports using a retroviral method for reprogramming and an embryoid body-based method for cardiac differentiation. Third, we developed an efficient approach for recording the action potentials and calcium transients simultaneously in control and patient cardiomyocytes using genetically encoded fluorescent indicators, ArcLight and R-GECO1. The dual optical recordings enabled us to observe prolonged action potentials and abnormal calcium handling in Timothy syndrome cardiomyocytes. We confirmed that roscovitine rescued the phenotypes in Timothy syndrome cardiomyocytes and that these findings were consistent with previous studies using conventional electrophysiological recordings and calcium imaging with dyes. The approaches using our optimized methods and dual optical recordings will improve iPSC applicability for disease modeling to investigate mechanisms underlying cardiac arrhythmias and to test potential therapeutics.

  9. Monitoring activity in neural circuits with genetically encoded indicators

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    Gerard Joseph Broussard

    2014-12-01

    Full Text Available Recent developments in genetically encoded indicators of neural activity (GINAs have greatly advanced the field of systems neuroscience. As they are encoded by DNA, GINAs can be targeted to genetically defined cellular populations. Combined with fluorescence microscopy, most notably multi-photon imaging, GINAs allow chronic simultaneous optical recordings from large populations of neurons or glial cells in awake, behaving mammals, particularly rodents. This large-scale recording of neural activity at multiple temporal and spatial scales has greatly advanced our understanding of the dynamics of neural circuitry underlying behavior—a critical first step toward understanding the complexities of brain function, such as sensorimotor integration and learning.Here, we summarize the recent development and applications of the major classes of GINAs. In particular, we take an in-depth look at the design of available GINA families with a particular focus on genetically encoded calcium indicators, sensors probing synaptic activity, and genetically encoded voltage indicators. Using the family of the genetically encoded calcium indicator GCaMP as an example, we review established sensor optimization pipelines. We also discuss practical considerations for end users of GINAs about experimental methods including approaches for gene delivery, imaging system requirements, and data analysis techniques. With the growing toolbox of GINAs and with new microscopy techniques pushing beyond their current limits, the age of light can finally achieve the goal of broad and dense sampling of neuronal activity across time and brain structures to obtain a dynamic picture of brain function.

  10. Genetically Encoded Voltage Indicators in Circulation Research.

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    Kaestner, Lars; Tian, Qinghai; Kaiser, Elisabeth; Xian, Wenying; Müller, Andreas; Oberhofer, Martin; Ruppenthal, Sandra; Sinnecker, Daniel; Tsutsui, Hidekazu; Miyawaki, Atsushi; Moretti, Alessandra; Lipp, Peter

    2015-09-08

    Membrane potentials display the cellular status of non-excitable cells and mediate communication between excitable cells via action potentials. The use of genetically encoded biosensors employing fluorescent proteins allows a non-invasive biocompatible way to read out the membrane potential in cardiac myocytes and other cells of the circulation system. Although the approaches to design such biosensors date back to the time when the first fluorescent-protein based Förster Resonance Energy Transfer (FRET) sensors were constructed, it took 15 years before reliable sensors became readily available. Here, we review different developments of genetically encoded membrane potential sensors. Furthermore, it is shown how such sensors can be used in pharmacological screening applications as well as in circulation related basic biomedical research. Potentials and limitations will be discussed and perspectives of possible future developments will be provided.

  11. Genetically Encoded Voltage Indicators in Circulation Research

    Directory of Open Access Journals (Sweden)

    Lars Kaestner

    2015-09-01

    Full Text Available Membrane potentials display the cellular status of non-excitable cells and mediate communication between excitable cells via action potentials. The use of genetically encoded biosensors employing fluorescent proteins allows a non-invasive biocompatible way to read out the membrane potential in cardiac myocytes and other cells of the circulation system. Although the approaches to design such biosensors date back to the time when the first fluorescent-protein based Förster Resonance Energy Transfer (FRET sensors were constructed, it took 15 years before reliable sensors became readily available. Here, we review different developments of genetically encoded membrane potential sensors. Furthermore, it is shown how such sensors can be used in pharmacological screening applications as well as in circulation related basic biomedical research. Potentials and limitations will be discussed and perspectives of possible future developments will be provided.

  12. Digitally encoded all-optical sensor multiplexing

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    Pervez, Anjum

    1992-01-01

    A digital, all-optical temperature sensor design concept based on optical sampling and digital encoding is presented. The proposed sensor generates 2M binary digital codewords of length M bits. The codewords are generated serially and, therefore, only a single output fiber line is required. A multiplexing scheme, which minimizes the power requirement per sensor array and facilitates a cost-effective digit regeneration for remote monitoring over long distance, is presented. The sensor arrays are used as building blocks to configure large scale sensor networks based on LAN topologies.

  13. Optical position encoder based on four-section diffraction grating

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    Zherdev, A. Y.; Odinokov, S. B.; Lushnikov, D. S.; Markin, V. V.; Gurylev, O. A.; Shishova, M. V.

    2017-05-01

    Optical position encoder consists of movable coding grating and fixed analyzing grating. Light passing and diffracting through these two gratings creates interference signal on optical detector. Decoding of interference signal phase allows to determinate current position. Known optical position encoders use several accurate adjusted optical channels and detectors to gather several signals with different phase for higher encoder accuracy. We propose to use one optical channel with several-section analyzing diffraction grating for this purpose to simplify optical scheme and adjusting requirements. Optical scheme of position encoder based on four-section analyzing diffraction grating is developed and described in this paper.

  14. Mouse redox histology using genetically encoded probes.

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    Fujikawa, Yuuta; Roma, Leticia P; Sobotta, Mirko C; Rose, Adam J; Diaz, Mauricio Berriel; Locatelli, Giuseppe; Breckwoldt, Michael O; Misgeld, Thomas; Kerschensteiner, Martin; Herzig, Stephan; Müller-Decker, Karin; Dick, Tobias P

    2016-03-15

    Mapping the in vivo distribution of endogenous oxidants in animal tissues is of substantial biomedical interest. Numerous health-related factors, including diet, physical activity, infection, aging, toxins, or pharmacological intervention, may cause redox changes. Tools are needed to pinpoint redox state changes to particular organs, tissues, cell types, and subcellular organelles. We describe a procedure that preserves the in vivo redox state of genetically encoded redox biosensors within histological tissue sections, thus providing "redox maps" for any tissue and comparison of interest. We demonstrate the utility of the technique by visualizing endogenous redox differences and changes in the context of tumor growth, inflammation, embryonic development, and nutrient starvation. Copyright © 2016, American Association for the Advancement of Science.

  15. Method for high-speed Manchester encoded optical signal generation

    DEFF Research Database (Denmark)

    Zhang, Jianfeng; Chi, Nan; Holm-Nielsen, Pablo Villanueva

    2004-01-01

    A method for high-speed Manchester encoded optical signal generation is proposed and demonstrated with a specially configured electro-optical modulator. A 10 Gb/s Manchester encoded optical signal was generated, and its bit-error-ratio (BER) performance was evaluated.......A method for high-speed Manchester encoded optical signal generation is proposed and demonstrated with a specially configured electro-optical modulator. A 10 Gb/s Manchester encoded optical signal was generated, and its bit-error-ratio (BER) performance was evaluated....

  16. Optogenetic Monitoring of Synaptic Activity with Genetically Encoded Voltage Indicators

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    Nakajima, Ryuichi; Jung, Arong; Yoon, Bong-June; Baker, Bradley J.

    2016-01-01

    The age of genetically encoded voltage indicators (GEVIs) has matured to the point that changes in membrane potential can now be observed optically in vivo. Improving the signal size and speed of these voltage sensors has been the primary driving forces during this maturation process. As a result, there is a wide range of probes using different voltage detecting mechanisms and fluorescent reporters. As the use of these probes transitions from optically reporting membrane potential in single, cultured cells to imaging populations of cells in slice and/or in vivo, a new challenge emerges—optically resolving the different types of neuronal activity. While improvements in speed and signal size are still needed, optimizing the voltage range and the subcellular expression (i.e., soma only) of the probe are becoming more important. In this review, we will examine the ability of recently developed probes to report synaptic activity in slice and in vivo. The voltage-sensing fluorescent protein (VSFP) family of voltage sensors, ArcLight, ASAP-1, and the rhodopsin family of probes are all good at reporting changes in membrane potential, but all have difficulty distinguishing subthreshold depolarizations from action potentials and detecting neuronal inhibition when imaging populations of cells. Finally, we will offer a few possible ways to improve the optical resolution of the various types of neuronal activities. PMID:27547183

  17. Data-driven encoding for quantitative genetic trait prediction.

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    He, Dan; Wang, Zhanyong; Parida, Laxmi

    2015-01-01

    Given a set of biallelic molecular markers, such as SNPs, with genotype values on a collection of plant, animal or human samples, the goal of quantitative genetic trait prediction is to predict the quantitative trait values by simultaneously modeling all marker effects. Quantitative genetic trait prediction is usually represented as linear regression models which require quantitative encodings for the genotypes: the three distinct genotype values, corresponding to one heterozygous and two homozygous alleles, are usually coded as integers, and manipulated algebraically in the model. Further, epistasis between multiple markers is modeled as multiplication between the markers: it is unclear that the regression model continues to be effective under this. In this work we investigate the effects of encodings to the quantitative genetic trait prediction problem. We first showed that different encodings lead to different prediction accuracies, in many test cases. We then proposed a data-driven encoding strategy, where we encode the genotypes according to their distribution in the phenotypes and we allow each marker to have different encodings. We show in our experiments that this encoding strategy is able to improve the performance of the genetic trait prediction method and it is more helpful for the oligogenic traits, whose values rely on a relatively small set of markers. To the best of our knowledge, this is the first paper that discusses the effects of encodings to the genetic trait prediction problem.

  18. Negative base encoding in optical linear algebra processors

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    Perlee, C.; Casasent, D.

    1986-01-01

    In the digital multiplication by analog convolution algorithm, the bits of two encoded numbers are convolved to form the product of the two numbers in mixed binary representation; this output can be easily converted to binary. Attention is presently given to negative base encoding, treating base -2 initially, and then showing that the negative base system can be readily extended to any radix. In general, negative base encoding in optical linear algebra processors represents a more efficient technique than either sign magnitude or 2's complement encoding, when the additions of digitally encoded products are performed in parallel.

  19. Genetically-encoded biosensors for monitoring cellular stress in bioprocessing.

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    Polizzi, Karen M; Kontoravdi, Cleo

    2015-02-01

    With the current wealth of transcriptomic data, it is possible to design genetically-encoded biosensors for the detection of stress responses and apply these to high-throughput bioprocess development and monitoring of cellular health. Such biosensors can sense extrinsic factors such as nutrient or oxygen deprivation and shear stress, as well as intrinsic stress factors like oxidative damage and unfolded protein accumulation. Alongside, there have been developments in biosensing hardware and software applicable to the field of genetically-encoded biosensors in the near future. This review discusses the current state-of-the-art in biosensors for monitoring cultures during biological manufacturing and the future challenges for the field. Connecting the individual achievements into a coherent whole will enable the application of genetically-encoded biosensors in industry.

  20. Data Encoding using Periodic Nano-Optical Features

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    Vosoogh-Grayli, Siamack

    Successful trials have been made through a designed algorithm to quantize, compress and optically encode unsigned 8 bit integer values in the form of images using Nano optical features. The periodicity of the Nano-scale features (Nano-gratings) have been designed and investigated both theoretically and experimentally to create distinct states of variation (three on states and one off state). The use of easy to manufacture and machine readable encoded data in secured authentication media has been employed previously in bar-codes for bi-state (binary) models and in color barcodes for multiple state models. This work has focused on implementing 4 states of variation for unit information through periodic Nano-optical structures that separate an incident wavelength into distinct colors (variation states) in order to create an encoding system. Compared to barcodes and magnetic stripes in secured finite length storage media the proposed system encodes and stores more data. The benefits of multiple states of variation in an encoding unit are 1) increased numerically representable range 2) increased storage density and 3) decreased number of typical set elements for any ergodic or semi-ergodic source that emits these encoding units. A thorough investigation has targeted the effects of the use of multi-varied state Nano-optical features on data storage density and consequent data transmission rates. The results show that use of Nano-optical features for encoding data yields a data storage density of circa 800 Kbits/in2 via the implementation of commercially available high resolution flatbed scanner systems for readout. Such storage density is far greater than commercial finite length secured storage media such as Barcode family with maximum practical density of 1kbits/in2 and highest density magnetic stripe cards with maximum density circa 3 Kbits/in2. The numerically representable range of the proposed encoding unit for 4 states of variation is [0 255]. The number of

  1. Encoded diffractive optics for full-spectrum computational imaging

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    Heide, Felix; Fu, Qiang; Peng, Yifan; Heidrich, Wolfgang

    2016-09-01

    Diffractive optical elements can be realized as ultra-thin plates that offer significantly reduced footprint and weight compared to refractive elements. However, such elements introduce severe chromatic aberrations and are not variable, unless used in combination with other elements in a larger, reconfigurable optical system. We introduce numerically optimized encoded phase masks in which different optical parameters such as focus or zoom can be accessed through changes in the mechanical alignment of a ultra-thin stack of two or more masks. Our encoded diffractive designs are combined with a new computational approach for self-calibrating imaging (blind deconvolution) that can restore high-quality images several orders of magnitude faster than the state of the art without pre-calibration of the optical system. This co-design of optics and computation enables tunable, full-spectrum imaging using thin diffractive optics.

  2. Encoded diffractive optics for full-spectrum computational imaging

    KAUST Repository

    Heide, Felix

    2016-09-16

    Diffractive optical elements can be realized as ultra-thin plates that offer significantly reduced footprint and weight compared to refractive elements. However, such elements introduce severe chromatic aberrations and are not variable, unless used in combination with other elements in a larger, reconfigurable optical system. We introduce numerically optimized encoded phase masks in which different optical parameters such as focus or zoom can be accessed through changes in the mechanical alignment of a ultra-thin stack of two or more masks. Our encoded diffractive designs are combined with a new computational approach for self-calibrating imaging (blind deconvolution) that can restore high-quality images several orders of magnitude faster than the state of the art without pre-calibration of the optical system. This co-design of optics and computation enables tunable, full-spectrum imaging using thin diffractive optics.

  3. Genetically determined optic neuropathies

    DEFF Research Database (Denmark)

    Milea, Dan; Amati-Bonneau, Patrizia; Reynier, Pascal

    2010-01-01

    The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions.......The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions....

  4. Genetically determined optic neuropathies

    DEFF Research Database (Denmark)

    Milea, Dan; Amati-Bonneau, Patrizia; Reynier, Pascal

    2010-01-01

    The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions.......The present review focuses on recent advances in the knowledge of hereditary optic neuropathies resulting from retinal ganglion cell degeneration, mostly due to mitochondrial dysfunctions....

  5. Chronic imaging of cortical sensory map dynamics using a genetically encoded calcium indicator

    OpenAIRE

    Minderer, M; Liu, W.; Sumanovski, L. T.; Kügler, S; Helmchen, F; Margolis, D. J.

    2012-01-01

    Abstract  In vivo optical imaging can reveal the dynamics of large-scale cortical activity, but methods for chronic recording are limited. Here we present a technique for long-term investigation of cortical map dynamics using wide-field ratiometric fluorescence imaging of the genetically encoded calcium indicator (GECI) Yellow Cameleon 3.60. We find that wide-field GECI signals report sensory-evoked activity in anaesthetized mouse somatosensory cortex with high sensitivity and spatiotemporal ...

  6. Optical-spectrum-encoded analog-to-digital converter

    Institute of Scientific and Technical Information of China (English)

    LIAO Xiao-jun; YANG Ya-pei

    2007-01-01

    A novel optical-spectrum-encoded (OSE) analog-to-digital converter (ADC) is proposed in this letter. To simply exemplify the conversion idea, a 5-bit device structure consisted of Fabry-Perot interferometers (FPI) is analyzed and numerically simulated. The dependence of peak-transmission wavelength on modulation voltage in an electro-optical FPI and the dependence of transmitted power on incident light wavelength in an FPI are discussed and utilized to implement OSEADC.A linearly tunable mode-locked laser, as a voltage-wavelength transformer and a sampler, and chirped grating FPIs, as an encoder array, can be used to obtain much greater sampling rate and bit-resolution.

  7. Photoacoustic imaging using genetically encoded reporters: a review

    Science.gov (United States)

    Brunker, Joanna; Yao, Junjie; Laufer, Jan; Bohndiek, Sarah E.

    2017-07-01

    Genetically encoded contrast in photoacoustic imaging (PAI) is complementary to the intrinsic contrast provided by endogenous absorbing chromophores such as hemoglobin. The use of reporter genes expressing absorbing proteins opens the possibility of visualizing dynamic cellular and molecular processes. This is an enticing prospect but brings with it challenges and limitations associated with generating and detecting different types of reporters. The purpose of this review is to compare existing PAI reporters and signal detection strategies, thereby offering a practical guide, particularly for the nonbiologist, to choosing the most appropriate reporter for maximum sensitivity in the biological and technological system of interest.

  8. Recent Advances in Development of Genetically Encoded Fluorescent Sensors.

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    Sanford, Lynn; Palmer, Amy

    2017-01-01

    Genetically encoded fluorescent sensors are essential tools in modern biological research, and recent advances in fluorescent proteins (FPs) have expanded the scope of sensor design and implementation. In this review we compare different sensor platforms, including Förster resonance energy transfer (FRET) sensors, fluorescence-modulated single FP-based sensors, translocation sensors, complementation sensors, and dimerization-based sensors. We discuss elements of sensor design and engineering for each platform, including the incorporation of new types of FPs and sensor screening techniques. Finally, we summarize the wide range of sensors in the literature, exploring creative new sensor architectures suitable for different applications.

  9. Multi-DOF Incremental Optical Encoder with Laser Wavelength Compensation

    Directory of Open Access Journals (Sweden)

    Cha'o-Kuang Chen

    2013-09-01

    Full Text Available This study used a reflective diffraction grating as the medium to develop a multi-DOF incremental optical encoder for motion stage. The optical encoder can measure three angular displacements, roll, yaw and pitch of the motion stage simultaneously, as well as the horizontal straightness and linear displacement, summed to five DOF errors of motion stage by only using the positive and negative first-order diffracted light. The grating diffraction theory, Doppler effect, and optical interference technique were used. Two quadrant photodetectors were used to measure the changes in three-dimensional space of diffraction direction of diffracted light, in order to construct a multi-DOF incremental optical encoder. Considering the working stability of a laser diode and preventing the influence of the zeroth-order diffracted light returning to the laser diode, an additional optical isolation system was designed and a wavelength variation monitoring module was created. The compensation for the light source wavelength variation could be 0.001 nm. The multi-DOF verification results showed that the roll error is ±0.7/60 arcsec, the standard deviation is 0.025 arcsec; the yaw error is ±0.7/30 arcsec, the standard deviation is 0.05 arcsec; the pitch error is ±0.8/90 arcsec, the standard deviation is 0.18 arcsec, the horizontal straightness error is ±0.5/250 μm, the standard deviation is 0.05 μm and the linear displacement error is ±1/20000 μm, the standard deviation is 12 nm.

  10. Engineering Genetically-Encoded Mineralization and Magnetism via Directed Evolution.

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    Liu, Xueliang; Lopez, Paola A; Giessen, Tobias W; Giles, Michael; Way, Jeffrey C; Silver, Pamela A

    2016-11-29

    Genetically encoding the synthesis of functional nanomaterials such as magnetic nanoparticles enables sensitive and non-invasive biological sensing and control. Via directed evolution of the natural iron-sequestering ferritin protein, we discovered key mutations that lead to significantly enhanced cellular magnetism, resulting in increased physical attraction of ferritin-expressing cells to magnets and increased contrast for cellular magnetic resonance imaging (MRI). The magnetic mutants further demonstrate increased iron biomineralization measured by a novel fluorescent genetic sensor for intracellular free iron. In addition, we engineered Escherichia coli cells with multiple genomic knockouts to increase cellular accumulation of various metals. Lastly to explore further protein candidates for biomagnetism, we characterized members of the DUF892 family using the iron sensor and magnetic columns, confirming their intracellular iron sequestration that results in increased cellular magnetization.

  11. Measuring human ventilation for apnoea detection using an optical encoder.

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    Weinberg, G M; Webster, J G

    1998-08-01

    We have designed, built and tested a proof-of-concept system based on optical encoder technology for measuring adult or infant ventilation. It uses change in chest circumference to provide an indirect measure of ventilation. The Hewlett-Packard HEDS-9720 optical encoder senses displacement of its matching codestrip. It yields a resolution of 0.17 mm and is accurate to 0.008 mm over a 10 mm test distance. The encoder is mounted on a nylon web belt wrapped around the torso and responds to changes in circumference. Motion of the code strip during respiration is converted to direction of movement (inhalation or exhalation) as well as magnitude of circumference change. Use of two sensor bands, one on the chest and one on the abdomen, may allow detection of obstructive apnoea in which there is no air flow out of or into the subject despite respiratory movement. Applications of this technology include infant apnoea monitoring as well as long-term adult monitoring.

  12. Chronic imaging of cortical sensory map dynamics using a genetically encoded calcium indicator.

    Science.gov (United States)

    Minderer, Matthias; Liu, Wenrui; Sumanovski, Lazar T; Kügler, Sebastian; Helmchen, Fritjof; Margolis, David J

    2012-01-01

    In vivo optical imaging can reveal the dynamics of large-scale cortical activity, but methods for chronic recording are limited. Here we present a technique for long-term investigation of cortical map dynamics using wide-field ratiometric fluorescence imaging of the genetically encoded calcium indicator (GECI) Yellow Cameleon 3.60. We find that wide-field GECI signals report sensory-evoked activity in anaesthetized mouse somatosensory cortex with high sensitivity and spatiotemporal precision, and furthermore, can be measured repeatedly in separate imaging sessions over multiple weeks. This method opens new possibilities for the longitudinal study of stability and plasticity of cortical sensory representations.

  13. A method of developing frequency encoded multi-bit optical data comparator using semiconductor optical amplifier

    Science.gov (United States)

    Garai, Sisir Kumar

    2011-02-01

    Optical data comparator is the part and parcel of arithmetic and logical unit of any optical data processor and it is working as a building block in a larger optical circuit, as an optical switch in all optical header processing and optical packet switching based all optical telecommunications system. In this article the author proposes a method of developing an all optical single bit comparator unit and subsequently extending the proposal to develop a n-bit comparator exploiting the nonlinear rotation of the state of polarization of the probe beam in semiconductor optical amplifier (SOA). Here the dataset to be compared are taken in frequency encoded/decoded form throughout the communication. The major advantages of frequency encoding over all other conventional techniques are that as the frequency of any signal is fundamental one so it can preserve its identity throughout the communication of optical signal and minimizes the probability of bit error problem. For frequency routing purpose optical add/drop multiplexer (ADM) is used which not only route the pump beams properly but also to amplify the pump beams efficiently. Switching speed of 'MZI-SOA switch' as well as SOA based switches are very fast with good on-off contrast ratio and as a result it is possible to obtain very fast action of optical data comparator.

  14. Universal quantum computation using all-optical hybrid encoding

    Institute of Scientific and Technical Information of China (English)

    郭奇; 程留永; 王洪福; 张寿

    2015-01-01

    By employing displacement operations, single-photon subtractions, and weak cross-Kerr nonlinearity, we propose an alternative way of implementing several universal quantum logical gates for all-optical hybrid qubits encoded in both single-photon polarization state and coherent state. Since these schemes can be straightforwardly implemented only using local operations without teleportation procedure, therefore, less physical resources and simpler operations are required than the existing schemes. With the help of displacement operations, a large phase shift of the coherent state can be obtained via currently available tiny cross-Kerr nonlinearity. Thus, all of these schemes are nearly deterministic and feasible under current technology conditions, which makes them suitable for large-scale quantum computing.

  15. Fluorescent Proteins as Genetically Encoded FRET Biosensors in Life Sciences

    Science.gov (United States)

    Hochreiter, Bernhard; Pardo Garcia, Alan; Schmid, Johannes A.

    2015-01-01

    Fluorescence- or Förster resonance energy transfer (FRET) is a measurable physical energy transfer phenomenon between appropriate chromophores, when they are in sufficient proximity, usually within 10 nm. This feature has made them incredibly useful tools for many biomedical studies on molecular interactions. Furthermore, this principle is increasingly exploited for the design of biosensors, where two chromophores are linked with a sensory domain controlling their distance and thus the degree of FRET. The versatility of these FRET-biosensors made it possible to assess a vast amount of biological variables in a fast and standardized manner, allowing not only high-throughput studies but also sub-cellular measurements of biological processes. In this review, we aim at giving an overview over the recent advances in genetically encoded, fluorescent-protein based FRET-biosensors, as these represent the largest and most vividly growing group of FRET-based sensors. For easy understanding, we are grouping them into four categories, depending on their molecular mechanism. These are based on: (a) cleavage; (b) conformational-change; (c) mechanical force and (d) changes in the micro-environment. We also address the many issues and considerations that come with the development of FRET-based biosensors, as well as the possibilities that are available to measure them. PMID:26501285

  16. Fluorescent Proteins as Genetically Encoded FRET Biosensors in Life Sciences

    Directory of Open Access Journals (Sweden)

    Bernhard Hochreiter

    2015-10-01

    Full Text Available Fluorescence- or Förster resonance energy transfer (FRET is a measurable physical energy transfer phenomenon between appropriate chromophores, when they are in sufficient proximity, usually within 10 nm. This feature has made them incredibly useful tools for many biomedical studies on molecular interactions. Furthermore, this principle is increasingly exploited for the design of biosensors, where two chromophores are linked with a sensory domain controlling their distance and thus the degree of FRET. The versatility of these FRET-biosensors made it possible to assess a vast amount of biological variables in a fast and standardized manner, allowing not only high-throughput studies but also sub-cellular measurements of biological processes. In this review, we aim at giving an overview over the recent advances in genetically encoded, fluorescent-protein based FRET-biosensors, as these represent the largest and most vividly growing group of FRET-based sensors. For easy understanding, we are grouping them into four categories, depending on their molecular mechanism. These are based on: (a cleavage; (b conformational-change; (c mechanical force and (d changes in the micro-environment. We also address the many issues and considerations that come with the development of FRET-based biosensors, as well as the possibilities that are available to measure them.

  17. A genetically encoded, high-signal-to-noise maltose sensor

    Energy Technology Data Exchange (ETDEWEB)

    Marvin, Jonathan S.; Schreiter, Eric R.; Echevarría, Ileabett M.; Looger, Loren L. (Puerto Rico); (HHMI)

    2012-10-23

    We describe the generation of a family of high-signal-to-noise single-wavelength genetically encoded indicators for maltose. This was achieved by insertion of circularly permuted fluorescent proteins into a bacterial periplasmic binding protein (PBP), Escherichia coli maltodextrin-binding protein, resulting in a four-color family of maltose indicators. The sensors were iteratively optimized to have sufficient brightness and maltose-dependent fluorescence increases for imaging, under both one- and two-photon illumination. We demonstrate that maltose affinity of the sensors can be tuned in a fashion largely independent of the fluorescent readout mechanism. Using literature mutations, the binding specificity could be altered to moderate sucrose preference, but with a significant loss of affinity. We use the soluble sensors in individual E. coli bacteria to observe rapid maltose transport across the plasma membrane, and membrane fusion versions of the sensors on mammalian cells to visualize the addition of maltose to extracellular media. The PBP superfamily includes scaffolds specific for a number of analytes whose visualization would be critical to the reverse engineering of complex systems such as neural networks, biosynthetic pathways, and signal transduction cascades. We expect the methodology outlined here to be useful in the development of indicators for many such analytes.

  18. Fluorescent proteins as genetically encoded FRET biosensors in life sciences.

    Science.gov (United States)

    Hochreiter, Bernhard; Garcia, Alan Pardo; Schmid, Johannes A

    2015-10-16

    Fluorescence- or Förster resonance energy transfer (FRET) is a measurable physical energy transfer phenomenon between appropriate chromophores, when they are in sufficient proximity, usually within 10 nm. This feature has made them incredibly useful tools for many biomedical studies on molecular interactions. Furthermore, this principle is increasingly exploited for the design of biosensors, where two chromophores are linked with a sensory domain controlling their distance and thus the degree of FRET. The versatility of these FRET-biosensors made it possible to assess a vast amount of biological variables in a fast and standardized manner, allowing not only high-throughput studies but also sub-cellular measurements of biological processes. In this review, we aim at giving an overview over the recent advances in genetically encoded, fluorescent-protein based FRET-biosensors, as these represent the largest and most vividly growing group of FRET-based sensors. For easy understanding, we are grouping them into four categories, depending on their molecular mechanism. These are based on: (a) cleavage; (b) conformational-change; (c) mechanical force and (d) changes in the micro-environment. We also address the many issues and considerations that come with the development of FRET-based biosensors, as well as the possibilities that are available to measure them.

  19. Reversibly switchable photoacoustic tomography using a genetically encoded near-infrared phytochrome

    Science.gov (United States)

    Yao, Junjie; Kaberniuk, Andrii A.; Li, Lei; Shcherbakova, Daria M.; Zhang, Ruiying; Wang, Lidai; Li, Guo; Verkhusha, Vladislav V.; Wang, Lihong V.

    2016-03-01

    Optical imaging of genetically encoded probes has revolutionized biomedical studies by providing valuable information about targeted biological processes. Here, we report a novel imaging technique, termed reversibly switchable photoacoustic tomography (RS-PAT), which exhibits large penetration depth, high detection sensitivity, and super-resolution. RS-PAT combines advanced photoacoustic imaging techniques with, for the first time, a nonfluorescent photoswitchable bacterial phytochrome. This bacterial phytochrome is the most near-infrared shifted genetically encoded probe reported so far. Moreover, this bacterial phytochrome is reversibly photoconvertible between its far-red and near-infrared light absorption states. Taking maximum advantage of the powerful imaging capability of PAT and the unique photochemical properties of the phytochrome, RS-PAT has broken through both the optical diffusion limit for deep-tissue imaging and the optical diffraction limit for super-resolution photoacoustic microscopy. Specifically, with RS-PAT we have achieved an unprecedented detection sensitivity of ~2 μM, or as few as ~20 tumor cells, at a centimeter depth. Such high sensitivity is fully demonstrated in our study by monitoring tumor growth and metastasis at whole-body level with ~100 μm resolution. Moreover, our microscopic implementation of RS-PAT is capable of imaging mammalian cells with a sub-diffraction lateral resolution of ~140 nm and axial resolution of ~400 nm, which are respectively ~2-fold and ~75-fold finer than those of our conventional photoacoustic microscopy. Overall, RS-PAT is a new and promising imaging technology for studying biological processes at different length scales.

  20. Visualizing presynaptic calcium dynamics and vesicle fusion with a single genetically encoded reporter at individual synapses

    Directory of Open Access Journals (Sweden)

    Rachel E Jackson

    2016-07-01

    Full Text Available Synaptic transmission depends on the influx of calcium into the presynaptic compartment, which drives neurotransmitter release. Genetically encoded reporters are widely used tools to understand these processes, particularly pHluorin-based reporters that report vesicle exocytosis and endocytosis through pH dependent changes in fluorescence, and genetically encoded calcium indicators (GECIs that exhibit changes in fluorescence upon binding to calcium. The recent expansion of the color palette of available indicators has made it possible to image multiple probes simultaneously within a cell. We have constructed a single molecule reporter capable of concurrent imaging of both presynaptic calcium influx and exocytosis, by fusion of sypHy, the vesicle associated protein synaptophysin containing a GFP-based pHluorin sensor, with the red-shifted GECI R-GECO1. Due to the fixed stoichiometry of the two probes, the ratio of the two responses can also be measured, providing an all optical correlate of the calcium dependence of release. Here, we have characterized stimulus-evoked sypHy-RGECO responses of hippocampal synapses in vitro, exploring the effects of different stimulus strengths and frequencies as well as variations in external calcium concentrations. By combining live sypHy-RGECO imaging with post-hoc fixation and immunofluorescence, we have also investigated correlations between structural and functional properties of synapses.

  1. Genetically encoded norbornene directs site-specific cellular protein labelling via a rapid bioorthogonal reaction

    OpenAIRE

    Lang, Kathrin; Davis, Lloyd; Torres-Kolbus, Jessica; Chou, Chungjung; Deiters, Alexander; Chin, Jason W.

    2012-01-01

    The site-specific incorporation of bioorthogonal groups via genetic code expansion provides a powerful general strategy for site-specifically labelling proteins with any probe. However, the slow reactivity of the bioorthogonal functional groups that can be encoded genetically limits the utility of this strategy. We demonstrate the genetic encoding of a norbornene amino acid using the pyrrolysyl tRNA synthetase/tRNACUA pair in Escherichia coli and mammalian cells. We developed a series of tetr...

  2. Optical label encoding using electroabsorption modulators and investigation of chirp properties

    DEFF Research Database (Denmark)

    Xu, Lin; Chi, Nan; Oxenløwe, Leif Katsuo

    2003-01-01

    A novel scheme of optical label encoding by wavelength conversion based on electroabsorption modulators (EAMs) is reported. Based on the experimental observations, the chirp properties of the wavelength-converted signal are discussed and a wide dynamic range of the chirp α-parameter is found...... allowed. Compared with cross-gain modulation (XGM) in a semiconductor optical amplifier (SOA), the EAM has several advantages, which make it attractive for optical label encoding or other applications as a wavelength converter....

  3. Nonlinear inversion of potential-field data using a hybrid-encoding genetic algorithm

    Science.gov (United States)

    Chen, C.; Xia, J.; Liu, J.; Feng, G.

    2006-01-01

    Using a genetic algorithm to solve an inverse problem of complex nonlinear geophysical equations is advantageous because it does not require computer gradients of models or "good" initial models. The multi-point search of a genetic algorithm makes it easier to find the globally optimal solution while avoiding falling into a local extremum. As is the case in other optimization approaches, the search efficiency for a genetic algorithm is vital in finding desired solutions successfully in a multi-dimensional model space. A binary-encoding genetic algorithm is hardly ever used to resolve an optimization problem such as a simple geophysical inversion with only three unknowns. The encoding mechanism, genetic operators, and population size of the genetic algorithm greatly affect search processes in the evolution. It is clear that improved operators and proper population size promote the convergence. Nevertheless, not all genetic operations perform perfectly while searching under either a uniform binary or a decimal encoding system. With the binary encoding mechanism, the crossover scheme may produce more new individuals than with the decimal encoding. On the other hand, the mutation scheme in a decimal encoding system will create new genes larger in scope than those in the binary encoding. This paper discusses approaches of exploiting the search potential of genetic operations in the two encoding systems and presents an approach with a hybrid-encoding mechanism, multi-point crossover, and dynamic population size for geophysical inversion. We present a method that is based on the routine in which the mutation operation is conducted in the decimal code and multi-point crossover operation in the binary code. The mix-encoding algorithm is called the hybrid-encoding genetic algorithm (HEGA). HEGA provides better genes with a higher probability by a mutation operator and improves genetic algorithms in resolving complicated geophysical inverse problems. Another significant

  4. Genetic encoding of the post-translational modification 2-hydroxyisobutyryl-lysine

    OpenAIRE

    Knight, William A.; Cropp, T.Ashton

    2015-01-01

    We report the synthesis and genetic encoding of a recently discovered posttranslational modification, 2-hydroxyisobutryl-lysine, to the genetic code of E. coli. The production of homogeneous proteins containing this amino acid will facilitate the study of modification in full-length proteins.

  5. Genetically encoded tools: bridging the gap between neuronal identity and function.

    Science.gov (United States)

    Cho, Yong Ku

    2015-01-21

    Genetically encoded tools are positioned to serve a unique and critical role in bridging the gap between the genetic identity of neurons and their functional properties. However, the use of these tools is limited by our current understanding of cell-type identity. As we make technological advances that focus on capturing functional aspects of neurons such as connectivity, activity, and metabolic states, our understanding of neuronal identity will deepen and may enable the use of genetically encoded tools for modulating disease-specific circuits for therapeutic purposes.

  6. Spectrally encoded common-path fiber-optic-based parallel optical coherence tomography.

    Science.gov (United States)

    Lee, Kye-Sung; Hur, Hwan; Sung, Ha-Young; Kim, I Jong; Kim, Geon-Hee

    2016-09-15

    We demonstrate a fiber-optic-based parallel optical coherence tomography (OCT) using spectrally encoded extended illumination with a common-path handheld probe, where the flexibility and robustness of the system are significantly improved, which is critical in the clinical environment. To the best of our knowledge, we present the first parallel OCT based on fiber optics including a fiber coupler with a sensitivity of 94 dB, which is comparable to that of point-scanning OCT. We also investigated the effect of the phase stability of the fiber-based interferometry on the parallel OCT system by comparing the common-path OCT with two-arm OCT. Using the homemade common-path handheld probe based on a Mirau interferometer, the phase stability was 32 times better than that of the two-arm OCT. The axial resolution of the common-path OCT was measured as 5.1±0.3  μm. To demonstrate the in vivo imaging performance of the fiber-optic-based parallel OCT, human skin was imaged.

  7. DC-balanced line encoding for optical labeling scheme using orthogonal modulation

    DEFF Research Database (Denmark)

    Zhang, Jianfeng; Holm-Nielsen, Pablo Villanueva; Chi, Nan;

    2004-01-01

    It is shown both theoretically and experimentally that 8B/10B encoding is an efficient technique to mitigate the inherent modulation crosstalk in optical labeling scheme using orthogonal modulation....

  8. Implementation of an optical S-R flip-flop with polarization encoded light signal

    Institute of Scientific and Technical Information of China (English)

    Debajyoti; Samanta; Sourangshu; Mukhopadhyay

    2009-01-01

    A new method is proposed to implement an optical S-R flip-flop by polarization encoded light signal,necessary optical nonlinear material and half-wave plate.In this system the real time speed of operation can be achieved,and at the time of transmission the average power of a byte remains constant.This polarization encoded flip-flop can act as a memory cell.

  9. Digital ultrasonically encoded (DUE) optical focusing into random media

    CERN Document Server

    Tay, Jian Wei; Suzuki, Yuta; Wang, Lihong V

    2013-01-01

    Focusing light into opaque random or scattering media such as biological tissue is a much sought-after goal for biomedical applications such as photodynamic therapy, optical manipulation, and photostimulation. However, focusing with conventional lenses is restricted to one transport mean free path in scattering media, limiting both optical penetration depth and resolution. Focusing deeper is possible by using optical phase conjugation or wavefront shaping to compensate for the scattering. For practical applications, wavefront shaping offers the advantage of a robust optical system that is less sensitive to optical misalignment. Here, the phase of the incident light is spatially tailored using a phase-shifting array to pre-compensate for scattering. The challenge, then, is to determine the phase pattern which allows light to be optimally delivered to the target region. Optimization algorithms are typically employed for this purpose, with visible particles used as targets to generate feedback. However, using th...

  10. Investigating genetic loci that encode plant-derived paleoclimate proxies

    Science.gov (United States)

    Bender, A. L. D.; Suess, M.; Chitwood, D. H.; Bradley, A. S.

    2016-12-01

    Long chain (>C25) n-alkanes in sediments predominantly derive from terrestrial plant waxes. Hydrogen isotope ratios (δD) of leaf wax hydrocarbons correlate with δDH2O of precipitation and are commonly used as paleoclimate proxies. However, biological variability in the isotopic fractionations between water and plant materials also affects the n-alkane δD values. Correct interpretation of this paleoclimate proxy requires that we resolve genetic and environmental effects. Genetic variability underlying differences in leaf wax structure and isotopic composition can be quantitatively determined through the use of model organisms. Interfertile Solanum sect. Lycopersicon (tomato) species provide an ideal model species complex for this approach. We used a set of 76 precisely defined near-isogenic lines (introgression lines [ILs]) in which small genomic regions from the wild tomato relative Solanum pennellii have been introduced into the genome of the domestic tomato, S. lycopersicum. By characterizing quantitative traits of these ILs (leaf wax structure and isotopic composition), we can resolve the degree to which each trait is regulated by genetic versus environmental factors. We present data from two growth experiments conducted with all 76 ILs. In this study, we quantify leaf wax traits, including δD values, δ13C values, and structural metrics including the methylation index (a variable that describes the ratio of iso­- and anteiso- to n-alkanes). Among ILs, δD values vary by up to 35‰ and 60‰ for C31 and C33 n-alkanes, respectively. Many ILs have methylation indices that are discernably different from the parent domesticated tomato (p < 0.001), which suggests that methylation is a highly polygenic trait. This pattern is similar to the genetics that control leaf shape, another trait commonly used as a paleoclimate proxy. Based on our preliminary analysis, we propose candidate genes that control aspects of plant physiology that affect these quantitative

  11. The symmetric MSD encoder for one-step adder of ternary optical computer

    Science.gov (United States)

    Kai, Song; LiPing, Yan

    2016-08-01

    The symmetric Modified Signed-Digit (MSD) encoding is important for achieving the one-step MSD adder of Ternary Optical Computer (TOC). The paper described the symmetric MSD encoding algorithm in detail, and developed its truth table which has nine rows and nine columns. According to the truth table, the state table was developed, and the optical-path structure and circuit-implementation scheme of the symmetric MSD encoder (SME) for one-step adder of TOC were proposed. Finally, a series of experiments were designed and performed. The observed results of the experiments showed that the scheme to implement SME was correct, feasible and efficient.

  12. A genetically encoded biosensor for visualising hypoxia responses in vivo

    Science.gov (United States)

    Misra, Tvisha; Baccino-Calace, Martin; Meyenhofer, Felix; Rodriguez-Crespo, David; Akarsu, Hatice; Armenta-Calderón, Ricardo; Gorr, Thomas A.; Frei, Christian; Cantera, Rafael; Egger, Boris

    2017-01-01

    ABSTRACT Cells experience different oxygen concentrations depending on location, organismal developmental stage, and physiological or pathological conditions. Responses to reduced oxygen levels (hypoxia) rely on the conserved hypoxia-inducible factor 1 (HIF-1). Understanding the developmental and tissue-specific responses to changing oxygen levels has been limited by the lack of adequate tools for monitoring HIF-1 in vivo. To visualise and analyse HIF-1 dynamics in Drosophila, we used a hypoxia biosensor consisting of GFP fused to the oxygen-dependent degradation domain (ODD) of the HIF-1 homologue Sima. GFP-ODD responds to changing oxygen levels and to genetic manipulations of the hypoxia pathway, reflecting oxygen-dependent regulation of HIF-1 at the single-cell level. Ratiometric imaging of GFP-ODD and a red-fluorescent reference protein reveals tissue-specific differences in the cellular hypoxic status at ambient normoxia. Strikingly, cells in the larval brain show distinct hypoxic states that correlate with the distribution and relative densities of respiratory tubes. We present a set of genetic and image analysis tools that enable new approaches to map hypoxic microenvironments, to probe effects of perturbations on hypoxic signalling, and to identify new regulators of the hypoxia response. PMID:28011628

  13. Controlling Macromolecular Topology with Genetically Encoded SpyTag-SpyCatcher Chemistry

    OpenAIRE

    Zhang, Wen-Bin; Sun, Fei; Tirrell, David A.; Arnold, Frances H.

    2013-01-01

    Control of molecular topology constitutes a fundamental challenge in macromolecular chemistry. Here we describe the synthesis and characterization of artificial elastin-like proteins (ELPs) with unconventional nonlinear topologies including circular, tadpole, star, and H-shaped proteins using genetically encoded SpyTag–SpyCatcher chemistry. SpyTag is a short polypeptide that binds its protein partner SpyCatcher and forms isopeptide bonds under physiological conditions. Sequences encoding SpyT...

  14. Dual random phase encoding: a temporal approach for fiber optic applications.

    Science.gov (United States)

    Cuadrado-Laborde, Christian; Duchowicz, Ricardo; Torroba, Roberto; Sicre, Enrique E

    2008-04-10

    We analyze the dual random phase encoding technique in the temporal domain to evaluate its potential application for secure data transmission in fiber optic links. To take into account the optical fiber multiplexing capabilities, the noise content of the signal is restricted when multiple channels are transmitted over a single fiber optic link. We also discuss some mechanisms for producing encoded time-limited as well as bandwidth-limited signals and a comparison with another recently proposed technique is made. Numerical simulations have been carried out to analyze the system performance. The results indicate that this multiplexing encryption method could be a good alternative compared with other well-established methods.

  15. Exploration of genetically encoded voltage indicators based on a chimeric voltage sensing domain

    Directory of Open Access Journals (Sweden)

    Yukiko eMishina

    2014-09-01

    Full Text Available Deciphering how the brain generates cognitive function from patterns of electrical signals is one of the ultimate challenges in neuroscience. To this end, it would be highly desirable to monitor the activities of very large numbers of neurons while an animal engages in complex behaviours. Optical imaging of electrical activity using genetically encoded voltage indicators (GEVIs has the potential to meet this challenge. Currently prevalent GEVIs are based on the voltage-sensitive fluorescent protein (VSFP prototypical design or on the voltage dependent state transitions of microbial opsins.We recently introduced a new VSFP design in which the voltage-sensing domain (VSD is sandwiched between a FRET pair of fluorescent proteins (termed VSFP-Butterflies and also demonstrated a series of chimeric VSD in which portions of the VSD of Ciona intestinalis voltage-sensitive phosphatase (Ci-VSP are substituted by homologous portions of a voltage-gated potassium channel subunit. These chimeric VSD had faster sensing kinetics than that of the native Ci-VSD. Here, we describe a new set of VSFPs that combine chimeric VSD with the Butterfly structure. We show that these chimeric VSFP-Butterflies can report membrane voltage oscillations of up to 200 Hz in cultured cells and report sensory evoked cortical population responses in living mice. This class of GEVIs may be suitable for imaging of brain rhythms in behaving mammalians.

  16. Live cell monitoring of glycine betaine by FRET-based genetically encoded nanosensor.

    Science.gov (United States)

    Ahmad, Mohammad; Ameen, Seema; Siddiqi, Tariq Omar; Khan, Parvez; Ahmad, Altaf

    2016-12-15

    Glycine betaine (GB) is one of the key compatible solutes that accumulate in the cell at exceedingly high level under the conditions of high salinity. It plays a crucial role in the maintenance of osmolarity of the cell without affecting the physiological processes. Analysis of stress-induced physiological conditions in living cells, therefore, requires real-time monitoring of cellular GB level. Glycine Betaine Optical Sensor (GBOS), a genetically-encoded FRET-based nanosensor developed in this study, allows the real-time monitoring of GB levels inside living cells. This nanosensor has been developed by sandwiching GB binding protein (ProX) between the Förster resonance energy transfer (FRET) pair, the cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP). Conformational change in ProX, which was used as sensory domain, reported the change in the level of this compatible solute in in vitro and in vivo conditions. Binding of the GB to the sensory domain fetches close to both the fluorescent moieties that result in the form of increased FRET ratio. So, any change in the concentration of GB is correlated with change in FRET ratio. This sensor also reported the GB cellular dynamics in real-time in Escherichia coli cells after the addition of its precursor, choline. The GBOS was also expressed in yeast and mammalian cells to monitor the intracellular GB. Therefore, the GBOS represents a unique FRET-based nanosensor which allows the non-invasive ratiometric analysis of the GB in living cells.

  17. Double random fractional Fourier domain encoding for optical security

    Science.gov (United States)

    Unnikrishnan, G.; Singh, Kehar

    2000-11-01

    We propose a new optical encryption technique using the fractional Fourier transform. In this method, the data are encrypted to a stationary white noise by two statistically independent random phase masks in fractional Fourier domains. To decrypt the data correctly, one needs to specify the fractional domains in which the input plane, encryption plane, and output planes exist, in addition to the key used for encryption. The use of an anamorphic fractional Fourier transform for the encryption of 2D data is also discussed. We suggest an optical implementation of the proposed idea. Results of a numerical simulation to analyze the performance of the proposed method are presented.

  18. [Hereditary optic neuropathies: clinical and molecular genetic characteristics].

    Science.gov (United States)

    Khanakova, N A; Sheremet, N L; Loginova, A N; Chukhrova, A L; Poliakov, A V

    2013-01-01

    The article presents a review of literature on hereditary optic neuropathies: Leber mitochondrial hereditary optic neuropathy, autosomal dominant and autosomal recessive optic neuropathies, X-linked optic atrophy. Clinical and molecular genetic characteristics are covered. Isolated optic neuropathies, as well as hereditary optic disorders, being a part of a complex syndromic disease are described.

  19. Aerodynamic Shape Optimization Using A Real-Number-Encoded Genetic Algorithm

    Science.gov (United States)

    Holst, Terry L.; Pulliam, Thomas H.

    2001-01-01

    A new method for aerodynamic shape optimization using a genetic algorithm with real number encoding is presented. The algorithm is used to optimize three different problems, a simple hill climbing problem, a quasi-one-dimensional nozzle problem using an Euler equation solver and a three-dimensional transonic wing problem using a nonlinear potential solver. Results indicate that the genetic algorithm is easy to implement and extremely reliable, being relatively insensitive to design space noise.

  20. Enumerative Encoding of TMTR Codes for Optical Recording Channel

    Directory of Open Access Journals (Sweden)

    Tsai Hui-Feng

    2010-01-01

    Full Text Available We propose a new time-varying maximum transition run (TMTR code for DVD recording systems, which has a rate higher than the EFMPlus code and a lower power spectral density (PSD at low frequencies. An enumeration method for constructing the new TMTR code is presented. Computer simulations indicate that the proposed TMTR code outperforms the EFMPlus code in error performance when applied to partial response optical recording channels.

  1. Genetic Basis of Mitochondrial Optic Neuropathies.

    Science.gov (United States)

    Maresca, A; Caporali, L; Strobbe, D; Zanna, C; Malavolta, D; La Morgia, C; Valentino, M L; Carelli, V

    2014-01-01

    Over two decades have elapsed since the first mtDNA point mutation was associated with Leber's hereditary optic neuropathy (LHON) in 1988. We have subsequently witnessed a substantial understanding of the molecular basis of hereditary optic neuropathies, as well as of their clinical features and pathogenic mechanisms. It became clear that the large majority of genetic optic neuropathies have a primary or an indirect involvement of mitochondrial functions, justifying the definition of "mitochondrial optic neuropathies". Despite this progress many unsolved features remain to be understood, such as incomplete penetrance and variable clinical expressivity in LHON and dominant optic atrophy (DOA), gender prevalence in LHON, and complex gene/environment interactions in both LHON and DOA. The most recent advancement in our understanding of the molecular basis of mitochondrial optic neuropathies is the topic of this review. In particular, we analyze the role that mitochondrial biogenesis may play in the compensatory mechanisms that underlie incomplete penetrance and clinical expressivity, a scenario relevant for the possible design of future therapeutic approaches. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  2. Low-Cost Encoding Device for Optical Code Division Multiple Access System

    Directory of Open Access Journals (Sweden)

    Mohammad S. Ab-Rahman

    2009-01-01

    Full Text Available Problem statement: Instead of using Fiber Bragg Grating (FBG to develop the coded spectrums, which consist of expensive elements, the grating also are highly sensitive to environmental changes and this will contribute to the increment of capital and operational expenditures (CAPEX and OPEX. Approach: This study presented the development of low-cost 16-ports encoding device for Optical Code Division Multiple Access (OCDMA systems based on Arrayed Waveguide Grating (AWG devices and optical switches. The encoding device is one of the new technologies that used to transmit the coded data in the optical communication system by using AWG and optical switches. It provided a high security for data transmission due to all data will be transmitted in binary code form. The output signals from AWG were coded with a binary code that given to an optical switch before it signal modulate with the carrier and transmitted to the receiver. The 16-ports encoding device used 16 Double Pole Double Throw (DPDT toggle switches to control the polarization of voltage source from +5 V to -5 V for 16 optical switches. When +5 V was given, the optical switch will give code '1' and vice versa. Results: We found that the insertion loss, crosstalk, uniformity and Optical Signal-Noise-Ratio (OSNR for the developed prototype are Conclusion: We had successful developed the AWG-based OCDMA encoding device prototype and characterized using linearity testing and continuous signal testing. The developed prototype was expected to be applied in the optical communication system on Passive Optical Networks (PONs.

  3. All-optical subdiffraction multilevel data encoding onto azo-polymeric thin films

    Science.gov (United States)

    Savoini, Matteo; Biagioni, Paolo; Duò, Lamberto; Finazzi, Marco

    2009-03-01

    By exploiting photo-induced reorientation in azo-polymer thin films, we demonstrate all-optical polarization-encoded information storage with a scanning near-field optical microscope. In the writing routine, 5-level bits are created by associating different bit values to different birefringence directions, induced in the polymer after illumination with linearly polarized light. The reading routine is then performed by implementing polarization-modulation techniques on the same near-field microscope, in order to measure the encoded birefringence direction.

  4. A novel method of developing all optical frequency encoded Fredkin gates

    Science.gov (United States)

    Garai, Sisir Kumar

    2014-02-01

    All optical reversible logic gates have significant applications in the field of optics and optoelectronics for developing different sequential and combinational circuits of optical computing, optical signal processing and in multi-valued logic operations and quantum computing. Here the author proposes a method for developing all optical three-input-output Fredkin gate and modified Fredkin gate using frequency encoded data. For this purpose the author has exploited the properties of efficient frequency conversion and faster switching speed of semiconductor optical amplifiers. Simulation results of the three input-output Fredkin gate testifies to the feasibility of the proposed scheme. These Fredkin gates are universal logic gates, and can be used to develop different all-optical logic and data processors in communication network.

  5. Optogenetics Based Rat-Robot Control: Optical Stimulation Encodes "Stop" and "Escape" Commands.

    Science.gov (United States)

    Chen, SiCong; Zhou, Hong; Guo, SongChao; Zhang, JiaCheng; Qu, Yi; Feng, ZhouYan; Xu, KeDi; Zheng, XiaoXiang

    2015-08-01

    Electric brain stimulation is frequently used in bio-robot control. However, one possible limitation of electric stimulation is the resultant wide range of influences that may lead to unexpected side-effects. Although there has been prior research done towards optogenetics based brain activation, there has not been much development regarding the comparisons between electric and optical methods of brain activation. In this study, we first encode "Stop" and "Escape" commands by optical stimulation in the dorsal periaqueductal grey (dPAG). The rats behavioral comparisons are then noted down under these two methods. The dPAG neural activity recorded during optical stimulation suggests rate and temporal coding mechanisms in behavioral control. The behavioral comparisons show that rats exhibit anxiety under the "Stop" command conveyed through both optical and electric methods. However, rats are able to recover more quickly from freezing only under optical "Stop" command. Under "Escape" commands, also conveyed through optical means, the rat would move with lessened urgency but the results are more stable. Moreover, c-Fos study shows the optical stimulation activates restricted range in midbrain: the optical stimulation affected only dPAG and its downstreams but electric stimulation activates both the upstream and downstream circuits, in which the glutamatergic neurons are largely occupied and play important role in "Stop" and "Escape" behavior controls. We conclude that optical stimulation is more suited for encoding "Stop" and "Escape" commands for rat-robot control.

  6. Characterization of the Single Stranded DNA Binding Protein SsbB Encoded in the Gonoccocal Genetic Island

    NARCIS (Netherlands)

    Jain, Samta; Zweig, Maria; Peeters, Eveline; Siewering, Katja; Hackett, Kathleen T.; Dillard, Joseph P.; van der Does, Chris

    2012-01-01

    Background: Most strains of Neisseria gonorrhoeae carry a Gonococcal Genetic Island which encodes a type IV secretion system involved in the secretion of ssDNA. We characterize the GGI-encoded ssDNA binding protein, SsbB. Close homologs of SsbB are located within a conserved genetic cluster found in

  7. Low-Cost Encoding Device for Optical Code Division Multiple Access System

    OpenAIRE

    Mohammad S. Ab-Rahman; Boonchuan Ng; Norshilawati M. Ibrahim; Sahbudin Shaari

    2009-01-01

    Problem statement: Instead of using Fiber Bragg Grating (FBG) to develop the coded spectrums, which consist of expensive elements, the grating also are highly sensitive to environmental changes and this will contribute to the increment of capital and operational expenditures (CAPEX and OPEX). Approach: This study presented the development of low-cost 16-ports encoding device for Optical Code Division Multiple Access (OCDMA) systems based on Arrayed Waveguide Grating (AWG) devices and optical ...

  8. Reconfigurable optical quadrature amplitude modulation converter/encoder using a tunable complex coefficient optical tapped delay line.

    Science.gov (United States)

    Khaleghi, Salman; Chitgarha, Mohammad Reza; Yilmaz, Omer F; Tur, Moshe; Haney, Michael W; Langrock, Carsten; Fejer, Martin M; Willner, Alan E

    2013-05-15

    We experimentally demonstrate a reconfigurable optical converter/encoder for quadrature amplitude modulated (QAM) signals. The system utilizes nonlinear wavelength multicasting, conversion-dispersion delays, and simultaneous nonlinear multiplexing and sampling. We show baud rate tunability (31 and 20 Gbaud) and reconfigurable conversions from lower-order QAM signals to higher-order QAM signals (e.g., 64-QAM).

  9. Single logical qubit information encoding scheme with the minimal optical decoherence-free subsystem.

    Science.gov (United States)

    Dong, Li; Wang, Jun-Xi; Li, Qing-Yang; Shen, Hong-Zhi; Dong, Hai-Kuan; Xiu, Xiao-Ming; Gao, Ya-Jun

    2016-03-01

    We present a scheme for encoding single logical qubit information, which is immune to collective decoherence acting on Hilbert space spanned by the corresponding states. The scheme needs a spatial entanglement gate and a polarization entanglement gate, which are realized with the assistance of weak cross-Kerr nonlinear interaction between photons and coherent states via Kerr media. Under the condition of sufficient large phase shifts, single logical qubit information can be encoded into this minimal optical decoherence-free subsystem with near-unity fidelity. Together with the mature techniques of measurement and classical feed forward, simple linear optical elements are applied to complete the encoding task, which offers the feasibility of this scheme for protecting quantum information against decoherence.

  10. Encoding an Optical Signal using a Wireless Radio-Freqency Signal

    DEFF Research Database (Denmark)

    2011-01-01

    Source: US2012148252A The present invention provides a method for modulating an optical signal in a semiconductor device. A wireless radio frequency modulation signal is used to provide a time-dependent electric field in a semiconductor nanostructure region, which causes a change in the absorption...... in the semiconductor device. An optical signal propagating in the semiconductor device will be modulated in accordance with the properties of the wireless radio frequency modulation signal, thus providing a method for encoding information from a wireless radio frequency signal onto an optical carrier....

  11. Organoids and the genetically encoded self-assembly of embryonic stem cells.

    Science.gov (United States)

    Turner, David A; Baillie-Johnson, Peter; Martinez Arias, Alfonso

    2016-02-01

    Understanding the mechanisms of early embryonic patterning and the timely allocation of specific cells to embryonic regions and fates as well as their development into tissues and organs, is a fundamental problem in Developmental Biology. The classical explanation for this process had been built around the notion of positional information. Accordingly the programmed appearance of sources of Morphogens at localized positions within a field of cells directs their differentiation. Recently, the development of organs and tissues from unpatterned and initially identical stem cells (adult and embryonic) has challenged the need for positional information and even the integrity of the embryo, for pattern formation. Here we review the emerging area of organoid biology from the perspective of Developmental Biology. We argue that the events underlying the development of these systems are not purely linked to self-organization, as often suggested, but rather to a process of genetically encoded self-assembly where genetic programs encode and control the emergence of biological structures.

  12. Multi-Features Encoding and Selecting Based on Genetic Algorithm for Human Action Recognition from Video

    Directory of Open Access Journals (Sweden)

    Chenglong Yu

    2013-05-01

    Full Text Available In this study, we proposed multiple local features encoded for recognizing the human actions. The multiple local features were obtained from the simple feature description of human actions in video. The simple features are two kinds of important features, optical flow and edge, to represent the human perception for the video behavior. As the video information descriptors, optical flow and edge, which their computing speeds are very fast and their requirement of memory consumption is very low, can represent respectively the motion information and shape information. Furthermore, key local multi-features are extracted and encoded by GA in order to reduce the computational complexity of the algorithm. After then, the Multi-SVM classifier is applied to discriminate the human actions.

  13. Rapid Cellular Phenotyping of Human Pluripotent Stem Cell-Derived Cardiomyocytes using a Genetically Encoded Fluorescent Voltage Sensor

    Directory of Open Access Journals (Sweden)

    Jordan S. Leyton-Mange

    2014-02-01

    Full Text Available In addition to their promise in regenerative medicine, pluripotent stem cells have proved to be faithful models of many human diseases. In particular, patient-specific stem cell-derived cardiomyocytes recapitulate key features of several life-threatening cardiac arrhythmia syndromes. For both modeling and regenerative approaches, phenotyping of stem cell-derived tissues is critical. Cellular phenotyping has largely relied upon expression of lineage markers rather than physiologic attributes. This is especially true for cardiomyocytes, in part because electrophysiological recordings are labor intensive. Likewise, most optical voltage indicators suffer from phototoxicity, which damages cells and degrades signal quality. Here we present the use of a genetically encoded fluorescent voltage indicator, ArcLight, which we demonstrate can faithfully report transmembrane potentials in human stem cell-derived cardiomyocytes. We demonstrate the application of this fluorescent sensor in high-throughput, serial phenotyping of differentiating cardiomyocyte populations and in screening for drug-induced cardiotoxicity.

  14. Simultaneous demonstration on all-optical digital encoder and comparator at 40 Gb/s with semiconductor optical amplifiers.

    Science.gov (United States)

    Wang, Yang; Zhang, Xinliang; Dong, Jianji; Huang, Dexiu

    2007-11-12

    We proposed and experimental demonstrated all-optical two line-four line encoder and two bit-wise comparator of RZ data streams at 40Gb/s based on cross gain modulation (XGM) and four wave mixing (FWM) in three parallel SOAs. Five logic functions for digital encoder and comparator between two signals A and B: AB, AB, AB, AB and AOmicronB, were achieved simultaneously. The first three optical logics are realized based on XGM in SOAs, the fourth is realized with FWM, and the fifth is the mixing result of the first and the fourth. A detuning filter is employed to improve the output performance. The output extinction ratio (ER) for the XGM operation is above 10dB, and the ER for FWM operation is around 8 dB. Wide and clear eye patterns for the five logic outputs can be observed.

  15. Application of Hybrid Encoding Genetic Algorithm on Pickup and Delivery Traveling Salesman Problem with Traffic Conditions

    Directory of Open Access Journals (Sweden)

    S. Patvichaichod

    2011-01-01

    Full Text Available Problem statement: This study deals with the pickup and delivery traveling salesman problem with traffic conditions (PDTSPTW, an extension of the pickup and delivery traveling salesman problem (PDTSP where each customer to be served is associated with two quantities of product to be collected and delivered. Almost PDTSP problems uses distance between each point of customers as Euclidean Distance and are not concerned with other parameters to find minimal cost. Approach: The PDTSPTC concerns more parameters, such as street network and vehicle speed, which results it closer to the real world condition. The study also proposes the developed genetic algorithm called “Hybrid Encoding Genetic Algorithm (HEGA”. The concept is to combine binary encoding and integer encoding together, causing the in complexity of the algorithm structure and the ease of implementation. Results: the HEGA can save the travel cost about 26-57%. It is obviously seen that HEGA in the PDTSPTC test problems result the fast convergence that is about 12-43% and in all, the computational time is under 6 seconds. Conclusion: The HEGA performs quite well when testing a test problem. Computation times are small in all case. The PDTSPTC is closer to real-world conditions than PDTSP. This problem can be applied in logistics immediately if the distance of streets, traffic conditions (average vehicle speed in each street and vehicle conditions (fuel consumption rate and vehicle capacity are known.

  16. Incoherent optical correlators and phase encoding of identification codes for access control or authentication

    Science.gov (United States)

    Brasher, James D.; Johnson, Eric G.

    1997-09-01

    We show how phase-only filters can be used in incoherent optical correlators for security applications such as access control, identification, or authentication. As a specific example, a biometric signature, a fingerprint, is encoded in a phase-only representation. The phase encoding is accomplished with the method of generalized projections onto constraint sets implemented by an iterated Fourier transform algorithm. The operation of an incoherent optical security system using both a phase-only filter generated with the generalized projections algorithm and a phase-only matched filter is simulated. The results demonstrate that the selected access pattern was accepted while a false pattern was rejected by the security system and that better recognition and discrimination performance was attained with the phase-only filter produced by the generalized projections algorithm.

  17. Measurement of object structure from size-encoded images generated by optically-implemented Gabor filters.

    Science.gov (United States)

    Sierra, Heidy; Zheng, Jing-Yi; Rabin, Bryan; Boustany, Nada N

    2012-12-17

    We use optical Fourier processing based on two dimensional (2D) Gabor filters to obtain size-encoded images which depict with 20nm sensitivity to size while preserving a 0.36μm spatial resolution, the spatial distribution of structural features within transparent objects. The size of the object feature measured at each pixel in the encoded image is determined by the optimal Gabor filter period, S(max), that maximizes the scattering signal from that location in the object. We show that S(max) (in μm) depends linearly on feature size (also in μm) over a size range from 0.11μm to 2μm. This linear response remains largely unchanged when the refractive index ratio is varied and can be predicted from numerical simulations of Gabor-filtered light scattering. Pixel histograms of the size-encoded images of isolated spheres and diatoms were used to generate highly resolved size distributions ("size spectra") exhibiting sharp peaks characterizing the known major structural features within the studied objects. Dynamic signal associated with changes in selected feature sizes within living cells is also demonstrated. Taken together, our data suggest that a label-free, direct and objective measurement of sample structure is enabled by the size-encoded images and associated pixel histograms generated from a calibrated optical processing microscope based on Gabor filtering.

  18. Genetically encoded pH‐indicators reveal activity‐dependent cytosolic acidification of Drosophila motor nerve termini in vivo

    National Research Council Canada - National Science Library

    Rossano, Adam J; Chouhan, Amit K; Macleod, Gregory T

    2013-01-01

    .... •  At the fruit fly larval neuromuscular junction, fluorescent genetically encoded pH‐indicators (GEpHIs) revealed significant cytosolic acidification of presynaptic termini during nerve activity...

  19. Optimizing design of an optical encoder based on generalized grating imaging

    Science.gov (United States)

    Ye, Guoyong; Liu, Hongzhong; Shi, Yongsheng; Yin, Lei; Lu, Bingheng; Hui, Xiangyuan; Yang, Yulong

    2016-11-01

    The interpolation error of an optical encoder is largely determined by the imperfections in the electrical signals, such as amplitude error, phase-shift error, DC error and higher harmonic distortion. In this paper, an optimized optical encoder based on generalized grating imaging is presented. We first describe the basic principle and configuration of the optical encoder. To achieve four electrical signals with equal amplitudes, equal DC contents and accurate 90° electrically phase-shift, a photodiodes array is adopted as the photo-detector. The photodiodes array offers the advantage of single-field scanning. Then, to solve the remaining problem of higher harmonic distortion, a slit-width-modulated index grating is proposed to suppress the dominant third order and fifth order harmonics simultaneously, and the cell’s width of the photodiodes array is optimized to further reduce the fifth order harmonic. Experiments have been carried out to verify the theoretical results. The feasibility and effectiveness of the proposed optimizing methods have been confirmed from the experimental results.

  20. Drosophila domino Exhibits Genetic Interactions with a Wide Spectrum of Chromatin Protein-Encoding Loci.

    Science.gov (United States)

    Ellis, Kaitlyn; Friedman, Chloe; Yedvobnick, Barry

    2015-01-01

    The Drosophila domino gene encodes protein of the SWI2/SNF2 family that has widespread roles in transcription, replication, recombination and DNA repair. Here, the potential relationship of Domino protein to other chromatin-associated proteins has been investigated through a genetic interaction analysis. We scored for genetic modification of a domino wing margin phenotype through coexpression of RNAi directed against a set of previously characterized and more newly characterized chromatin-encoding loci. A set of other SWI2/SNF2 loci were also assayed for interaction with domino. Our results show that the majority of tested loci exhibit synergistic enhancement or suppression of the domino wing phenotype. Therefore, depression in domino function sensitizes the wing margin to alterations in the activity of numerous chromatin components. In several cases the genetic interactions are associated with changes in the level of cell death measured across the dorsal-ventral margin of the wing imaginal disc. These results highlight the broad realms of action of many chromatin proteins and suggest significant overlap with Domino function in fundamental cell processes, including cell proliferation, cell death and cell signaling.

  1. Genetic encoding of caged cysteine and caged homocysteine in bacterial and mammalian cells.

    Science.gov (United States)

    Uprety, Rajendra; Luo, Ji; Liu, Jihe; Naro, Yuta; Samanta, Subhas; Deiters, Alexander

    2014-08-18

    We report the genetic incorporation of caged cysteine and caged homocysteine into proteins in bacterial and mammalian cells. The genetic code of these cells was expanded with an engineered pyrrolysine tRNA/tRNA synthetase pair that accepts both light-activatable amino acids as substrates. Incorporation was validated by reporter assays, western blots, and mass spectrometry, and differences in incorporation efficiency were explained by molecular modeling of synthetase-amino acid interactions. As a proof-of-principle application, the genetic replacement of an active-site cysteine residue with a caged cysteine residue in Renilla luciferase led to a complete loss of enzyme activity; however, upon brief exposure to UV light, a >150-fold increase in enzymatic activity was observed, thus showcasing the applicability of the caged cysteine in live human cells. A simultaneously conducted genetic replacement with homocysteine yielded an enzyme with greatly reduced activity, thereby demonstrating the precise probing of a protein active site. These discoveries provide a new tool for the optochemical control of protein function in mammalian cells and expand the set of genetically encoded unnatural amino acids.

  2. StrigoQuant: A genetically encoded biosensor for quantifying strigolactone activity and specificity

    KAUST Repository

    Samodelov, S. L.

    2016-11-05

    Strigolactones are key regulators of plant development and interaction with symbiotic fungi; however, quantitative tools for strigolactone signaling analysis are lacking. We introduce a genetically encoded hormone biosensor used to analyze strigolactone-mediated processes, including the study of the components involved in the hormone perception/signaling complex and the structural specificity and sensitivity of natural and synthetic strigolactones in Arabidopsis, providing quantitative insights into the stereoselectivity of strigolactone perception. Given the high specificity, sensitivity, dynamic range of activity, modular construction, ease of implementation, and wide applicability, the biosensor StrigoQuant will be useful in unraveling multiple levels of strigolactone metabolic and signaling networks.

  3. Genetics Home Reference: septo-optic dysplasia

    Science.gov (United States)

    ... Conditions Genes Chromosomes & mtDNA Resources Help Me Understand Genetics Share: Email Facebook Twitter Home Health Conditions septo- ... my family? What is the prognosis of a genetic condition? Genetic and Rare Diseases Information Center Frequency ...

  4. pHlash: A New Genetically Encoded and Ratiometric Luminescence Sensor of Intracellular pH

    Science.gov (United States)

    Robertson, J. Brian; Johnson, Carl Hirschie

    2012-01-01

    We report the development of a genetically encodable and ratiometic pH probe named “pHlash” that utilizes Bioluminescence Resonance Energy Transfer (BRET) rather than fluorescence excitation. The pHlash sensor–composed of a donor luciferase that is genetically fused to a Venus fluorophore–exhibits pH dependence of its spectral emission in vitro. When expressed in either yeast or mammalian cells, pHlash reports basal pH and cytosolic acidification in vivo. Its spectral ratio response is H+ specific; neither Ca++, Mg++, Na+, nor K+ changes the spectral form of its luminescence emission. Moreover, it can be used to image pH in single cells. This is the first BRET-based sensor of H+ ions, and it should allow the approximation of pH in cytosolic and organellar compartments in applications where current pH probes are inadequate. PMID:22905204

  5. pHlash: a new genetically encoded and ratiometric luminescence sensor of intracellular pH.

    Directory of Open Access Journals (Sweden)

    Yunfei Zhang

    Full Text Available We report the development of a genetically encodable and ratiometic pH probe named "pHlash" that utilizes Bioluminescence Resonance Energy Transfer (BRET rather than fluorescence excitation. The pHlash sensor-composed of a donor luciferase that is genetically fused to a Venus fluorophore-exhibits pH dependence of its spectral emission in vitro. When expressed in either yeast or mammalian cells, pHlash reports basal pH and cytosolic acidification in vivo. Its spectral ratio response is H(+ specific; neither Ca(++, Mg(++, Na(+, nor K(+ changes the spectral form of its luminescence emission. Moreover, it can be used to image pH in single cells. This is the first BRET-based sensor of H(+ ions, and it should allow the approximation of pH in cytosolic and organellar compartments in applications where current pH probes are inadequate.

  6. Genetic control of encoding strategy in a food-sensing neural circuit

    Science.gov (United States)

    Diana, Giovanni; Patel, Dhaval S; Entchev, Eugeni V; Zhan, Mei; Lu, Hang; Ch'ng, QueeLim

    2017-01-01

    Neuroendocrine circuits encode environmental information via changes in gene expression and other biochemical activities to regulate physiological responses. Previously, we showed that daf-7 TGFβ and tph-1 tryptophan hydroxylase expression in specific neurons encode food abundance to modulate lifespan in Caenorhabditis elegans, and uncovered cross- and self-regulation among these genes (Entchev et al., 2015). Here, we now extend these findings by showing that these interactions between daf-7 and tph-1 regulate redundancy and synergy among neurons in food encoding through coordinated control of circuit-level signal and noise properties. Our analysis further shows that daf-7 and tph-1 contribute to most of the food-responsiveness in the modulation of lifespan. We applied a computational model to capture the general coding features of this system. This model agrees with our previous genetic analysis and highlights the consequences of redundancy and synergy during information transmission, suggesting a rationale for the regulation of these information processing features. DOI: http://dx.doi.org/10.7554/eLife.24040.001 PMID:28166866

  7. Inter-population differences in otolith morphology are genetically encoded in the killifish Aphanius fasciatus (Cyprinodontiformes

    Directory of Open Access Journals (Sweden)

    Ali Annabi

    2013-06-01

    Full Text Available Inter-population differences in otolith shape, morphology and chemistry have been used effectively as indicators for stock assessment or for recognizing environmental adaptation in fishes. However, the precise parameters that affect otolith morphology remain incompletely understood. Here we provide the first direct support for the hypothesis that inter-population differences in otolith morphology are genetically encoded. The study is based on otolith morphology and two mitochondrial markers (D-loop, 16S rRNA of three natural populations of Aphanius fasciatus (Teleostei: Cyprinodontidae from Southeast Tunisia. Otolith and genetic data yielded congruent tree topologies. Divergence of populations likely results from isolation events in the course of the Pleistocene sea level drops. We propose that otolith morphology is a valuable tool for resolving genetic diversity also within other teleost species, which may be important for ecosystem management and conservation of genetic diversity. As reconstructions of ancient teleost fish faunas are often solely based on fossil otoliths, our discoveries may also lead to a new approach to research in palaeontology.

  8. FRET-based genetically-encoded sensors for quantitative monitoring of metabolites.

    Science.gov (United States)

    Mohsin, Mohd; Ahmad, Altaf; Iqbal, Muhammad

    2015-10-01

    Neighboring cells in the same tissue can exist in different states of dynamic activities. After genomics, proteomics and metabolomics, fluxomics is now equally important for generating accurate quantitative information on the cellular and sub-cellular dynamics of ions and metabolite, which is critical for functional understanding of organisms. Various spectrometry techniques are used for monitoring ions and metabolites, although their temporal and spatial resolutions are limited. Discovery of the fluorescent proteins and their variants has revolutionized cell biology. Therefore, novel tools and methods targeting sub-cellular compartments need to be deployed in specific cells and targeted to sub-cellular compartments in order to quantify the target-molecule dynamics directly. We require tools that can measure cellular activities and protein dynamics with sub-cellular resolution. Biosensors based on fluorescence resonance energy transfer (FRET) are genetically encoded and hence can specifically target sub-cellular organelles by fusion to proteins or targetted sequences. Since last decade, FRET-based genetically encoded sensors for molecules involved in energy production, reactive oxygen species and secondary messengers have helped to unravel key aspects of cellular physiology. This review, describing the design and principles of sensors, presents a database of sensors for different analytes/processes, and illustrate examples of application in quantitative live cell imaging.

  9. Immobilization of aptamer-based molecular beacons onto optically-encoded micro-sized beads.

    Science.gov (United States)

    Jun, Bong-Hyun; Kim, Ji-Eun; Rho, Chul; Byun, Jang-Woong; Kim, Yo Han; Kang, Homan; Kim, Jong-Ho; Kang, Taegyu; Cho, Myung-Haing; Lee, Yoon-Sik

    2011-07-01

    This paper presents a method for the novel immobilization of aptamer-based molecular beacons (apta-beacons) onto optically-encoded micro-sized beads (apta-beacon beads). To immobilize apta-beacons onto flourescently-encoded micro-sized beads, core-shell type beads containing a fluorescent dye-encoded core and apta beacon-coupled shell were prepared. The fluorescent dye-encoded beads were prepared from TentaGel resins by coupling RITC to the amino groups of the core region, after partial protection of amino groups with Fmoc-OSu in a diffusion-controlled manner. After deprotection of the Fmoc-amino groups, FITC-coupled molecular beacons (MBs) were immobilized to the beads together with a quencher by covelent bonding. Briefly, aspartic acid (Asp) was coupled to the shell part of the beads. Then, the quencher was coupled to the N-terminal amino group of Asp and the MBs were coupled to the side chain carboxyl group. In a model study, thrombin was directly detected using this apta-beacon bead method. The thrombin-bound apta-beacon beads were easily recognized by the appearance of fluorescence without any further labeling step.

  10. Security enhanced multiple-image authentication based on cascaded optical interference and sparse phase mixed encoding

    Science.gov (United States)

    Wang, Qu; Alfalou, A.; Brosseau, C.

    2016-08-01

    An interference-based cascaded filtering method is proposed to perform multiple-image authentication. By using spatial phase mixed encoding technique and phase retrieval iteration in Fresnel transform domain, multiple original images are encoded in two phase-only cipher texts. Using correct keys in an interference-based configuration, one can only recover a noisy image without any secret information revealed. A cascaded phase-only filtering structure, instead of correlation methods, is applied to perform authentication where the decrypted image is converted into a pre-specified irregular pattern that functions as authentication criterion. The proposed structure can strengthen security greatly because authentication output strongly depends on the decrypted images and authentication keys. Moreover, the decryption and authentication procedures can be completed optically in a more compact way than previous methods. Simulation results have been given to prove the effectiveness of this proposal and evaluate its performance.

  11. Steganographic optical image encryption system based on reversible data hiding and double random phase encoding

    Science.gov (United States)

    Chuang, Cheng-Hung; Chen, Yen-Lin

    2013-02-01

    This study presents a steganographic optical image encryption system based on reversible data hiding and double random phase encoding (DRPE) techniques. Conventional optical image encryption systems can securely transmit valuable images using an encryption method for possible application in optical transmission systems. The steganographic optical image encryption system based on the DRPE technique has been investigated to hide secret data in encrypted images. However, the DRPE techniques vulnerable to attacks and many of the data hiding methods in the DRPE system can distort the decrypted images. The proposed system, based on reversible data hiding, uses a JBIG2 compression scheme to achieve lossless decrypted image quality and perform a prior encryption process. Thus, the DRPE technique enables a more secured optical encryption process. The proposed method extracts and compresses the bit planes of the original image using the lossless JBIG2 technique. The secret data are embedded in the remaining storage space. The RSA algorithm can cipher the compressed binary bits and secret data for advanced security. Experimental results show that the proposed system achieves a high data embedding capacity and lossless reconstruction of the original images.

  12. Fractional Fourier transform-based optical encryption with treble random phase-encoding

    Science.gov (United States)

    Xin, Yi; Tao, Ran; Wang, Yue

    2008-03-01

    We propose a new architecture of optical encryption technique using the fractional Fourier transform with three statistically independent random phase masks. Compared with the existing double-phase encoding method in the fractional Fourier-domain, the proposed extra phase mask in the last fractional Fourier domain makes the architecture symmetrical, and additive processing to the encrypted image can be turned into complex stationary white noise after decryption, and enlarge the key space without any degradation of its robustness to blind decryption. This property can be utilized to improve the quality of the recover image. Simulation results have verified the validity.

  13. Optical information authentication via compressed sensing and double random phase encoding

    Science.gov (United States)

    Chen, Junxin; Bao, Nan; Zhu, Zhi-liang

    2017-10-01

    This paper presents a novel information authentication scheme via compressed sensing and double random phase encoding. Two alternative architectures have been investigated, in which significantly compressed data with micro percentage is sufficient for authentication. At the decoder end, a noise-like image with no leakage of the plaintext is recovered and subsequently authenticated using a nonlinear optical correlation approach. The authentication effectiveness, noise resistance and security performance of the proposed scheme have been experimentally validated. This work was supported by the Fundamental Research Funds for the Central Universities (N162410002-4, N151904002), the National Natural Science Foundation of China (No. 61374178).

  14. Optical focusing inside scattering media with time-reversed ultrasound microbubble encoded (TRUME) light

    CERN Document Server

    Ruan, Haowen; Yang, Changhuei

    2015-01-01

    Focusing light inside scattering media in a freely addressable fashion is challenging, as the wavefront of the scattered light is highly disordered. Recently developed ultrasound-guided wavefront shaping methods are addressing this challenge, albeit with relatively low modulation efficiency and resolution limitations. In this paper, we present a new technique, time-reversed ultrasound microbubble encoded (TRUME) optical focusing, which is able to focus light with improved efficiency and sub-ultrasound wavelength resolution. This method ultrasonically destructs microbubbles, and measures the wavefront change to compute and render a suitable time-reversed wavefront solution for focusing. We demonstrate that the TRUME technique can create an optical focus at the site of bubble destruction with a size of ~2 microns. Due to the nonlinear pressure-to-destruction response, the TRUME technique can break the addressable focus resolution barrier imposed by the ultrasound focus. We experimentally demonstrate a 2-fold ad...

  15. Shining light on signaling and metabolic networks by genetically encoded biosensors

    Science.gov (United States)

    Lalonde, Sylvie; Ehrhardt, David W; Frommer, Wolf B

    2009-01-01

    Fluorescent labels have revolutionized cell biology. Signaling intermediates and metabolites can be measured in real time with subcellular spatial resolution. Most of these sensors are based on fluorescent proteins, and many report fluorescence resonance energy transfer. Because the biosensors are genetically encoded, a toolbox for addressing cell biological questions at the systems level is now available. Fluorescent biosensors are able to determine the localization of proteins and their dynamics, to reveal the cellular and subcellular localization of the respective interactions and activities, and to provide complementary data on the steady state levels of ions, metabolites, and signaling intermediates with high temporal and spatial resolution. They represent the basis for cell-based high-throughput assays that are necessary for a systems perspective on plant cell function. PMID:16188489

  16. Probing the Catalytic Charge-Relay System in Alanine Racemase with Genetically Encoded Histidine Mimetics.

    Science.gov (United States)

    Sharma, Vangmayee; Wang, Yane-Shih; Liu, Wenshe R

    2016-12-16

    Histidine is a unique amino acid with an imidazole side chain in which both of the nitrogen atoms are capable of serving as a proton donor and proton acceptor in hydrogen bonding interactions. In order to probe the functional role of histidine involved in hydrogen bonding networks, fine-tuning the hydrogen bonding potential of the imidazole side chain is required but not feasible through traditional mutagenesis methods. Here, we show that two close mimetics of histidine, 3-methyl-histidine and thiazole alanine, can be genetically encoded using engineered pyrrolysine incorporation machinery. Replacement of the three histidine residues predicted to be involved in an extended charge-relay system in alanine racemase with 3-methyl-histidine or thiazole alanine shows a dramatic loss in the enzyme's catalytic efficiency, implying the role of this extended charge-relay system in activating the active site residue Y265, a general acid/base catalyst in the enzyme.

  17. Statistical sulcal shape comparisons: application to the detection of genetic encoding of the central sulcus shape

    DEFF Research Database (Denmark)

    Le Goualher, G; Argenti, A.M.; Duyme, M

    2000-01-01

    Principal Component Analysis allows a quantitative description of shape variability with a restricted number of parameters (or modes) which can be used to quantify the difference between two shapes through the computation of a modal distance. A statistical test can then be applied to this set...... encoding. When applied to real data, this study highlighted genetic constraints on the shape of the central sulcus. We found from 10 pairs of monozygotic twins that the intrapair modal distance of the central sulcus was significantly smaller than the interpair modal distance, for both the left central...... sulcus (Z = -2.66; P definition of the central sulcus shape were confirmed by applying the same experiment to 10 pairs of normal young individuals (Z = -1.39; Z = -0.63, i.e., values not significant at the P

  18. Node ordinal encoded genetic algorithm for the optimal allocation of water resources

    Institute of Scientific and Technical Information of China (English)

    YANG Xiaohua; YANG Zhifeng; SHEN Zhenyao; LI Jianqiang

    2005-01-01

    A new method, node ordinal encoded genetic algorithm (NOEGA), is proposed for solving water resources optimal allocation problems, in which the capacity of water resources is split into a number of smaller parts so that successive operations can be overlapped. Our objective is to maximize the whole benefit function. To overcome the "dimensionality and algorithm complexity curse" while searching for solutions and looking for an optimal solution, the operations of one-point crossover operator, gene exchange operator, gene random operator, gene shift operator and node ordinal strings are established. It is proved to be an effective optimal method in searching for global solutions. The NOEGA does not need a diversity of initial population, and it does not have the problem of immature convergence. The results of two cases show that using NOEGA to solve the optimal allocation model is very efficient and robust. In addition, the algorithm complexity of NOEGA is discussed.

  19. Development and properties of genetically encoded pH sensors in plants.

    Directory of Open Access Journals (Sweden)

    Alexandre eMartinière

    2013-12-01

    Full Text Available Fluorescent proteins (FPs have given access to a large choice of live imaging techniques and has thereby profoundly modified our view of plant cells. Together with technological improvement of imaging, they have opened the possibility to monitor physico-chemical changes within cells. For this purpose, a new generation of fluorescent proteins has been engineered. For instance, pHluorin, a point mutated version of GFP, allows to get local pH estimates. In this paper, we will describe how genetically encoded sensors can be used to measure pH in the microenvironment of living tissues and subsequently discuss the role of pH in (i exocytosis, (ii ion uptake by plant roots, (iii cell growth and (iv protein trafficking.

  20. Lentivectors encoding immunosuppressive proteins genetically engineer pancreatic beta-cells to correct diabetes in allogeneic mice.

    Science.gov (United States)

    Kojaoghlanian, T; Joseph, A; Follenzi, A; Zheng, J H; Leiser, M; Fleischer, N; Horwitz, M S; DiLorenzo, T P; Goldstein, H

    2009-03-01

    The effectiveness of genetic engineering with lentivectors to protect transplanted cells from allogeneic rejection was examined using, as a model, type 1 diabetes treatment with beta-cell transplantation, whose widespread use has been limited by the requirement for sustained immunosuppressive treatment to prevent graft rejection. We examined whether lentivectors expressing select immunosuppressive proteins encoded by the adenoviral genome early region 3 (AdE3) would protect transplanted beta-cells from an alloimmune attack. The insulin-producing beta-cell line beta TC-tet (C3HeB/FeJ-derived) was transduced with lentiviruses encoding the AdE3 proteins gp19K and RID alpha/beta. The efficiency of lentiviral transduction of beta TC-tet cells exceeded 85%. Lentivector expression of gp19K decreased surface class I major histocompatibility complex expression by over 90%, whereas RID alpha/beta expression inhibited cytokine-induced Fas upregulation by over 75%. beta TC-tet cells transduced with gp19K and RID alpha/beta lentivectors, but not with a control lentivector, provided prolonged correction of hyperglycemia after transplantation into diabetic BALB/c severe combined immunodeficient mice reconstituted with allogeneic immune effector cells or into diabetic allogeneic BALB/c mice. Thus, genetic engineering of beta-cells using gp19K- and RID alpha/beta-expressing lentiviral vectors may provide an alternative that has the potential to eliminate or reduce treatment with the potent immunosuppressive agents necessary at present for prolonged engraftment with transplanted islets.

  1. Controlling enzyme inhibition using an expanded set of genetically encoded amino acids.

    Science.gov (United States)

    Zheng, Shun; Kwon, Inchan

    2013-09-01

    Enzyme inhibition plays an important role in drug development, metabolic pathway regulation, and biocatalysis with product inhibition. When an inhibitor has high structural similarities to the substrate of an enzyme, controlling inhibitor binding without affecting enzyme substrate binding is often challenging and requires fine-tuning of the active site. We hypothesize that an extended set of genetically encoded amino acids can be used to design an enzyme active site that reduces enzyme inhibitor binding without compromising substrate binding. As a model case, we chose murine dihydrofolate reductase (mDHFR), substrate dihydrofolate, and inhibitor methotrexate. Structural models of mDHFR variants containing non-natural amino acids complexed with each ligand were constructed to identify a key residue for inhibitor binding and non-natural amino acids to replace the key residue. Then, we discovered that replacing the key phenylalanine residue with two phenylalanine analogs (p-bromophenylalanine (pBrF) and L-2-naphthylalanine (2Nal)) enhances binding affinity toward the substrate dihydrofolate over the inhibitor by 4.0 and 5.8-fold, respectively. Such an enhanced selectivity is mainly due to a reduced inhibitor binding affinity by 2.1 and 4.3-fold, respectively. The catalytic efficiency of the mDHFR variant containing pBrF is comparable to that of wild-type mDHFR, whereas the mDHFR variant containing 2Nal exhibits a moderate decrease in the catalytic efficiency. The work described here clearly demonstrates the feasibility of selectively controlling enzyme inhibition using an expanded set of genetically encoded amino acids.

  2. Research on application of photoelectric rotary encoder in space optical remote sensor

    Science.gov (United States)

    Zheng, Jun; Qi, Shao-fan; Wang, Yuan-yuan; Zhang, Zhan-dong

    2016-11-01

    For space optical remote sensor, especially wide swath detecting sensor, the focusing control system for the focal plane should be well designed to obtain the best image quality. The crucial part of this system is the measuring instrument. For previous implements, the potentiometer, which is essentially a voltage divider, is usually introduced to conduct the position in feedback closed-loop control process system. However, the performances of both electro-mechanical and digital potentiometers is limited in accuracy, temperature coefficients, and scale range. To have a better performance of focal plane moving detection, this article presents a new measuring implement with photoelectric rotary encoder, which consists of the photoelectric conversion system and the signal process system. In this novel focusing control system, the photoelectric conversion system is fixed on main axis, which can transform the angle information into a certain analog signal. Through the signal process system, after analog-to-digital converting and data format processing of the certain analog signal, the focusing control system can receive the digital precision angle position which can be used to deduct the current moving position of the focal plane. For utilization of space optical remote sensor in aerospace areas, the reliability design of photoelectric rotary encoder system should be considered with highest priority. As mentioned above, this photoelectric digital precision angle measurement device is well designed for this real-time control and dynamic measurement system, because its characters of high resolution, high accuracy, long endurance, and easy to maintain.

  3. Optical multiple-image encryption based on phase encoding algorithm in the Fresnel transform domain

    Science.gov (United States)

    Huang, Jian-Ji; Hwang, Hone-Ene; Chen, Chun-Yuan; Chen, Ching-Mu

    2012-10-01

    A novel method of the optical multiple-image encryption based on the modified Gerchberg-Saxton algorithm (MGSA) is presented. This proposed method with an architecture of two adjacent phase only functions (POFs) in the Fresnel transform (FrT) domain that can extremely increase capacity of system for completely avoiding the crosstalk between the decrypted images. Each encrypted target image is separately encoded into a POF by using the MGSA which is with constraining the encrypted target image. Each created POF is then added to a prescribed fixed POF composed of a proposed MGSA-based phase encoding algorithm. Not only the wavelength and multiple-position parameters in the FrT domain as keys to increase system security, the created POFs are also served mutually as the encryption keys to decrypt target image based on cascading two POFs scheme. Compared with prior methods [23,24], the main advantages of this proposed encryption system is that it does not need any transformative lenses and that makes it very efficient and easy to implement optically. Simulation results show that this proposed encryption system can successfully achieve the multiple-image encryption with multiple-position keys, which is more advantageous in security than previous work [24] for its decryption process with only two POFs keys to accomplish this task.

  4. Optical position sensor based on a digital wavelength-encoding grating ruler

    Science.gov (United States)

    Wang, Yu; Chen, Huoyao; Liu, Zhengkun; Hong, Yilin

    2016-10-01

    A wavelength-encoding optical position sensor was designed in this study. The critical component of the sensor is its innovative digital encoding grating ruler (DEGR), which is a substrate on which several blazed grating units with different line densities are arranged parallel to one another following a certain order. Two types of multi-DEGR were designed. We obtained over 100,000 codes that significantly assisted in designing long-range and high-resolution position sensors by optimizing the coding algorithm. The wavelength signals generated by the multi-DEGR were demodulated using concave grating and several photosensitive elements. A 100-mm multi-DEGR with 1000 codes was successfully fabricated using the combined methods of direct laser writing and holographic technology. We described the principle of the sensor in detail and established the entire sensor system. A bench test was conducted to test the signal response of the sensor. Bench test results exhibited 100% accuracy of the signal response of the optical sensor and an excellent temperature performance within -55°C and 75°C.

  5. Research on the methods of optical image hiding based on double random phase encoding and digital holography

    Science.gov (United States)

    Xu, Hongsheng; Sang, Nong

    2011-12-01

    Optical information hiding system has many features such as high processing speed, high parallel, high encryption dimension and high speed of optical transformation and related operations, more advantages than digital method in some way. But it has not adequate security, and enough combination with techniques of digital image processing. So on basis of analyzing existing image hiding and analyzing techniques, we give out the idea. We should adopt idea of virtual optics on the way of all-digital simulation to do research of optical image hiding and analyzing methods based on optical image processing technique especially technique of double random phase encoding and digital holography.

  6. Depth-encoded synthetic aperture optical coherence tomography of biological tissues with extended focal depth.

    Science.gov (United States)

    Mo, Jianhua; de Groot, Mattijs; de Boer, Johannes F

    2015-02-23

    Optical coherence tomography (OCT) has proven to be able to provide three-dimensional (3D) volumetric images of scattering biological tissues for in vivo medical diagnostics. Unlike conventional optical microscopy, its depth-resolving ability (axial resolution) is exclusively determined by the laser source and therefore invariant over the full imaging depth. In contrast, its transverse resolution is determined by the objective's numerical aperture and the wavelength which is only approximately maintained over twice the Rayleigh range. However, the prevailing laser sources for OCT allow image depths of more than 5 mm which is considerably longer than the Rayleigh range. This limits high transverse resolution imaging with OCT. Previously, we reported a novel method to extend the depth-of-focus (DOF) of OCT imaging in Mo et al.Opt. Express 21, 10048 (2013)]. The approach is to create three different optical apertures via pupil segmentation with an annular phase plate. These three optical apertures produce three OCT images from the same sample, which are encoded to different depth positions in a single OCT B-scan. This allows for correcting the defocus-induced curvature of wave front in the pupil so as to improve the focus. As a consequence, the three images originating from those three optical apertures can be used to reconstruct a new image with an extended DOF. In this study, we successfully applied this method for the first time to both an artificial phantom and biological tissues over a four times larger depth range. The results demonstrate a significant DOF improvement, paving the way for 3D high resolution OCT imaging beyond the conventional Rayleigh range.

  7. Genetics Home Reference: Leber hereditary optic neuropathy

    Science.gov (United States)

    ... article on PubMed Central Yu-Wai-Man P, Griffiths PG, Hudson G, Chinnery PF. Inherited mitochondrial optic ... Institutes of Health National Library of Medicine Lister Hill National Center for Biomedical Communications 8600 Rockville Pike, ...

  8. Imaging activity in astrocytes and neurons with genetically encoded calcium indicators following in utero electroporation

    Directory of Open Access Journals (Sweden)

    J. Michael eGee

    2015-04-01

    Full Text Available Complex interactions between networks of astrocytes and neurons are beginning to be appreciated, but remain poorly understood. Transgenic mice expressing fluorescent protein reporters of cellular activity, such as the GCaMP family of genetically encoded calcium indicators, have been used to explore network behavior. However, in some cases, it may be desirable to use long-established rat models that closely mimic particular aspects of human conditions such as Parkinson’s disease and the development of epilepsy following status epilepticus. Methods for expressing reporter proteins in the rat brain are relatively limited. Transgenic rat technologies exist but are fairly immature. Viral-mediated expression is robust but unstable, requires invasive injections, and only works well for fairly small genes (< 5 kb. In utero electroporation offers a valuable alternative. IUE is a proven method for transfecting populations of astrocytes and neurons in the rat brain without the strict limitations on transgene size. We built a toolset of IUE plasmids carrying GCaMP variants 3, 6s or 6f driven by CAG and targeted to the cytosol or the plasma membrane. Because low baseline fluorescence of GCaMP can hinder identification of transfected cells, we included the option of co-expressing a cytosolic tdTomato protein. A binary system consisting of a plasmid carrying a piggyBac inverted terminal repeat-flanked CAG-GCaMP-IRES-tdTomato cassette and a separate plasmid encoding for expression of piggyBac transposase was employed to stably express GCaMP and tdTomato. The plasmids were co-electroporated on embryonic days 13.5-14.5 and astrocytic and neuronal activity was subsequently imaged in acute or cultured brain slices prepared from the cortex or hippocampus. Large spontaneous transients were detected in slices obtained from rats of varying ages up to 127 days. In this report, we demonstrate the utility of this toolset for interrogating astrocytic and neuronal

  9. Imaging the awake visual cortex with a genetically encoded voltage indicator.

    Science.gov (United States)

    Carandini, Matteo; Shimaoka, Daisuke; Rossi, L Federico; Sato, Tatsuo K; Benucci, Andrea; Knöpfel, Thomas

    2015-01-07

    Genetically encoded voltage indicators (GEVIs) promise to reveal the membrane potential of genetically targeted neuronal populations through noninvasive, chronic imaging of large portions of cortical space. Here we test a promising GEVI in mouse cortex during wakefulness, a challenging condition due to large hemodynamic activity, and we introduce a straightforward projection method to separate a signal dominated by membrane voltage from a signal dominated by hemodynamic activity. We expressed VSFP-Butterfly 1.2 plasmid in layer 2/3 pyramidal cells of visual cortex through electroporation in utero. We then used wide-field imaging with two cameras to measure both fluorophores of the indicator in response to visual stimuli. By taking weighted sums and differences of the two measurements, we obtained clear separation of hemodynamic and voltage signals. The hemodynamic signal showed strong heartbeat oscillations, superimposed on slow dynamics similar to blood oxygen level-dependent (BOLD) or "intrinsic" signals. The voltage signal had fast dynamics similar to neural responses measured electrically, and showed an orderly retinotopic mapping. We compared this voltage signal with calcium signals imaged in transgenic mice that express a calcium indicator (GCaMP3) throughout cortex. The voltage signal from VSFP had similar signal-to-noise ratios as the calcium signal, it was more immune to vascular artifacts, and it integrated over larger regions of visual space, which was consistent with its reporting mostly subthreshold activity rather than the spiking activity revealed by calcium signals. These results demonstrate that GEVIs provide a powerful tool to study the dynamics of neural populations at mesoscopic spatial scales in the awake cortex. Copyright © 2015 Carandini et al.

  10. Applications of genetically-encoded biosensors for the construction and control of biosynthetic pathways.

    Science.gov (United States)

    Michener, Joshua K; Thodey, Kate; Liang, Joe C; Smolke, Christina D

    2012-05-01

    Cells are filled with biosensors, molecular systems that measure the state of the cell and respond by regulating host processes. In much the same way that an engineer would monitor a chemical reactor, the cell uses these sensors to monitor changing intracellular environments and produce consistent behavior despite the variable environment. While natural systems derive a clear benefit from pathway regulation, past research efforts in engineering cellular metabolism have focused on introducing new pathways and removing existing pathway regulation. Synthetic biology is a rapidly growing field that focuses on the development of new tools that support the design, construction, and optimization of biological systems. Recent advances have been made in the design of genetically-encoded biosensors and the application of this class of molecular tools for optimizing and regulating heterologous pathways. Biosensors to cellular metabolites can be taken directly from natural systems, engineered from natural sensors, or constructed entirely in vitro. When linked to reporters, such as antibiotic resistance markers, these metabolite sensors can be used to report on pathway productivity, allowing high-throughput screening for pathway optimization. Future directions will focus on the application of biosensors to introduce feedback control into metabolic pathways, providing dynamic control strategies to increase the efficient use of cellular resources and pathway reliability.

  11. Imaging the response of the retina to electrical stimulation with genetically encoded calcium indicators.

    Science.gov (United States)

    Weitz, Andrew C; Behrend, Matthew R; Lee, Nan Sook; Klein, Ronald L; Chiodo, Vince A; Hauswirth, William W; Humayun, Mark S; Weiland, James D; Chow, Robert H

    2013-04-01

    Epiretinal implants for the blind are designed to stimulate surviving retinal neurons, thus bypassing the diseased photoreceptor layer. Single-unit or multielectrode recordings from isolated animal retina are commonly used to inform the design of these implants. However, such electrical recordings provide limited information about the spatial patterns of retinal activation. Calcium imaging overcomes this limitation, as imaging enables high spatial resolution mapping of retinal ganglion cell (RGC) activity as well as simultaneous recording from hundreds of RGCs. Prior experiments in amphibian retina have demonstrated proof of principle, yet experiments in mammalian retina have been hindered by the inability to load calcium indicators into mature mammalian RGCs. Here, we report a method for labeling the majority of ganglion cells in adult rat retina with genetically encoded calcium indicators, specifically GCaMP3 and GCaMP5G. Intravitreal injection of an adeno-associated viral vector targets ∼85% of ganglion cells with high specificity. Because of the large fluorescence signals provided by the GCaMP sensors, we can now for the first time visualize the response of the retina to electrical stimulation in real-time. Imaging transduced retinas mounted on multielectrode arrays reveals how stimulus pulse shape can dramatically affect the spatial extent of RGC activation, which has clear implications in prosthetic applications. Our method can be easily adapted to work with other fluorescent indicator proteins in both wild-type and transgenic mammals.

  12. Engineering genetically encoded nanosensors for real-time in vivo measurements of citrate concentrations.

    Directory of Open Access Journals (Sweden)

    Jennifer C Ewald

    Full Text Available Citrate is an intermediate in catabolic as well as biosynthetic pathways and is an important regulatory molecule in the control of glycolysis and lipid metabolism. Mass spectrometric and NMR based metabolomics allow measuring citrate concentrations, but only with limited spatial and temporal resolution. Methods are so far lacking to monitor citrate levels in real-time in-vivo. Here, we present a series of genetically encoded citrate sensors based on Förster resonance energy transfer (FRET. We screened databases for citrate-binding proteins and tested three candidates in vitro. The citrate binding domain of the Klebsiella pneumoniae histidine sensor kinase CitA, inserted between the FRET pair Venus/CFP, yielded a sensor highly specific for citrate. We optimized the peptide linkers to achieve maximal FRET change upon citrate binding. By modifying residues in the citrate binding pocket, we were able to construct seven sensors with different affinities spanning a concentration range of three orders of magnitude without losing specificity. In a first in vivo application we show that E. coli maintains the capacity to take up glucose or acetate within seconds even after long-term starvation.

  13. Flow Cytometry Enables Multiplexed Measurements of Genetically Encoded Intramolecular FRET Sensors Suitable for Screening.

    Science.gov (United States)

    Doucette, Jaimee; Zhao, Ziyan; Geyer, Rory J; Barra, Melanie M; Balunas, Marcy J; Zweifach, Adam

    2016-07-01

    Genetically encoded sensors based on intramolecular FRET between CFP and YFP are used extensively in cell biology research. Flow cytometry has been shown to offer a means to measure CFP-YFP FRET; we suspected it would provide a unique way to conduct multiplexed measurements from cells expressing different FRET sensors, which is difficult to do with microscopy, and that this could be used for screening. We confirmed that flow cytometry accurately measures FRET signals using cells transiently transfected with an ERK activity reporter, comparing responses measured with imaging and cytometry. We created polyclonal long-term transfectant lines, each expressing a different intramolecular FRET sensor, and devised a way to bar-code four distinct populations of cells. We demonstrated the feasibility of multiplexed measurements and determined that robust multiplexed measurements can be conducted in plate format. To validate the suitability of the method for screening, we measured responses from a plate of bacterial extracts that in unrelated experiments we had determined contained the protein kinase C (PKC)-activating compound teleocidin A-1. The multiplexed assay correctly identifying the teleocidin A-1-containing well. We propose that multiplexed cytometric FRET measurements will be useful for analyzing cellular function and for screening compound collections.

  14. Calcium Signaling throughout the Toxoplasma gondii Lytic Cycle: A STUDY USING GENETICALLY ENCODED CALCIUM INDICATORS.

    Science.gov (United States)

    Borges-Pereira, Lucas; Budu, Alexandre; McKnight, Ciara A; Moore, Christina A; Vella, Stephen A; Hortua Triana, Miryam A; Liu, Jing; Garcia, Celia R S; Pace, Douglas A; Moreno, Silvia N J

    2015-11-01

    Toxoplasma gondii is an obligate intracellular parasite that invades host cells, creating a parasitophorous vacuole where it communicates with the host cell cytosol through the parasitophorous vacuole membrane. The lytic cycle of the parasite starts with its exit from the host cell followed by gliding motility, conoid extrusion, attachment, and invasion of another host cell. Here, we report that Ca(2+) oscillations occur in the cytosol of the parasite during egress, gliding, and invasion, which are critical steps of the lytic cycle. Extracellular Ca(2+) enhances each one of these processes. We used tachyzoite clonal lines expressing genetically encoded calcium indicators combined with host cells expressing transiently expressed calcium indicators of different colors, and we measured Ca(2+) changes in both parasites and host simultaneously during egress. We demonstrated a link between cytosolic Ca(2+) oscillations in the host and in the parasite. Our approach also allowed us to measure two new features of motile parasites, which were enhanced by Ca(2+) influx. This is the first study showing, in real time, Ca(2+) signals preceding egress and their direct link with motility, an essential virulence trait.

  15. EPR Distance Measurements in Native Proteins with Genetically Encoded Spin Labels.

    Science.gov (United States)

    Schmidt, Moritz J; Fedoseev, Artem; Bücker, Dennis; Borbas, Julia; Peter, Christine; Drescher, Malte; Summerer, Daniel

    2015-12-18

    The genetic encoding of nitroxide amino acids in combination with electron paramagnetic resonance (EPR) distance measurements enables precise structural studies of native proteins, i.e. without the need for mutations to create unique reactive sites for chemical labeling and thus with minimal structural perturbation. We here report on in vitro DEER measurements in native E. coli thioredoxin (TRX) that establish the nitroxide amino acid SLK-1 as a spectroscopic probe that reports distances and conformational flexibilities in the enzyme with nonmutated catalytic centers that are not accessible by the use of the traditional methanethiosulfonate spin label (MTSSL). We generated a rotamer library for SLK-1 that in combination with molecular dynamics (MD) simulation enables predictions of distance distributions between two SLK-1 labels incorporated into a target protein. Toward a routine use of SLK-1 for EPR distance measurements in proteins and the advancement of the approach to intracellular environments, we study the stability of SLK-1 in E. coli cultures and lysates and establish guidelines for protein expression and purification that offer maximal nitroxide stability. These advancements and insights provide new perspectives for facile structural studies of native, endogenous proteins by EPR distance measurements.

  16. Probing Protein-Protein Interactions with Genetically Encoded Photoactivatable Cross-Linkers.

    Science.gov (United States)

    Cooley, Richard B; Sondermann, Holger

    2017-01-01

    Fundamental to all living organisms is the ability of proteins to interact with other biological molecules at the right time and location, with the proper affinity, and to do so reversibly. One well-established technique to study protein interactions is chemical cross-linking, a process in which proteins in close spatial proximity are covalently tethered together. An emerging technology that overcomes many limitations of traditional cross-linking methods is one in which photoactivatable cross-linking noncanonical amino acids are genetically encoded into a protein of interest using the cell's native translational machinery. These proteins can then be used to trap interacting biomolecules upon UV illumination. Here, we describe a method for the site-specific incorporation of photoactivatable cross-linking amino acids into fluorescently tagged proteins of interest in E. coli. Photo-cross-linking and analysis by SDS-PAGE using in-gel fluorescence detection, which provides rapid, highly sensitive, and specific detection of cross-linked adducts even in impure systems, are also described. An example expression and cross-linking experiment involving transmembrane signaling of a bacterial second messenger receptor system that controls biofilm formation is shown. All reagents needed to carry out these experiments are commercially available, and do not require special or unique technology to perform, making this method tractable to a broad community studying protein structure and function.

  17. Exploring dynamics of molybdate in living animal cells by a genetically encoded FRET nanosensor.

    Science.gov (United States)

    Nakanishi, Yoichi; Iida, Syuntaro; Ueoka-Nakanishi, Hanayo; Niimi, Tomoaki; Tomioka, Rie; Maeshima, Masayoshi

    2013-01-01

    Molybdenum (Mo) is an essential trace element for almost all living organisms including animals. Mo is used as a catalytic center of molybdo-enzymes for oxidation/reduction reactions of carbon, nitrogen, and sulfur metabolism. Whilst living cells are known to import inorganic molybdate oxyanion from the surrounding environment, the in vivo dynamics of cytosolic molybdate remain poorly understood as no appropriate indicator is available for this trace anion. We here describe a genetically encoded Förester-resonance-energy-transfer (FRET)-based nanosensor composed of CFP, YFP and the bacterial molybdate-sensor protein ModE. The nanosensor MolyProbe containing an optimized peptide-linker responded to nanomolar-range molybdate selectively, and increased YFP:CFP fluorescence intensity ratio by up to 109%. By introduction of the nanosensor, we have been able to successfully demonstrate the real-time dynamics of molybdate in living animal cells. Furthermore, time course analyses of the dynamics suggest that novel oxalate-sensitive- and sulfate-resistant- transporter(s) uptake molybdate in a model culture cell.

  18. A genetically encoded tag for correlated light and electron microscopy of intact cells, tissues, and organisms.

    Directory of Open Access Journals (Sweden)

    Xiaokun Shu

    2011-04-01

    Full Text Available Electron microscopy (EM achieves the highest spatial resolution in protein localization, but specific protein EM labeling has lacked generally applicable genetically encoded tags for in situ visualization in cells and tissues. Here we introduce "miniSOG" (for mini Singlet Oxygen Generator, a fluorescent flavoprotein engineered from Arabidopsis phototropin 2. MiniSOG contains 106 amino acids, less than half the size of Green Fluorescent Protein. Illumination of miniSOG generates sufficient singlet oxygen to locally catalyze the polymerization of diaminobenzidine into an osmiophilic reaction product resolvable by EM. MiniSOG fusions to many well-characterized proteins localize correctly in mammalian cells, intact nematodes, and rodents, enabling correlated fluorescence and EM from large volumes of tissue after strong aldehyde fixation, without the need for exogenous ligands, probes, or destructive permeabilizing detergents. MiniSOG permits high quality ultrastructural preservation and 3-dimensional protein localization via electron tomography or serial section block face scanning electron microscopy. EM shows that miniSOG-tagged SynCAM1 is presynaptic in cultured cortical neurons, whereas miniSOG-tagged SynCAM2 is postsynaptic in culture and in intact mice. Thus SynCAM1 and SynCAM2 could be heterophilic partners. MiniSOG may do for EM what Green Fluorescent Protein did for fluorescence microscopy.

  19. Imaging Membrane Potential with Two Types of Genetically Encoded Fluorescent Voltage Sensors.

    Science.gov (United States)

    Lee, Sungmoo; Piao, Hong Hua; Sepheri-Rad, Masoud; Jung, Arong; Sung, Uhna; Song, Yoon-Kyu; Baker, Bradley J

    2016-02-04

    Genetically encoded voltage indicators (GEVIs) have improved to the point where they are beginning to be useful for in vivo recordings. While the ultimate goal is to image neuronal activity in vivo, one must be able to image activity of a single cell to ensure successful in vivo preparations. This procedure will describe how to image membrane potential in a single cell to provide a foundation to eventually image in vivo. Here we describe methods for imaging GEVIs consisting of a voltage-sensing domain fused to either a single fluorescent protein (FP) or two fluorescent proteins capable of Förster resonance energy transfer (FRET) in vitro. Using an image splitter enables the projection of images created by two different wavelengths onto the same charge-coupled device (CCD) camera simultaneously. The image splitter positions a second filter cube in the light path. This second filter cube consists of a dichroic and two emission filters to separate the donor and acceptor fluorescent wavelengths depending on the FPs of the GEVI. This setup enables the simultaneous recording of both the acceptor and donor fluorescent partners while the membrane potential is manipulated via whole cell patch clamp configuration. When using a GEVI consisting of a single FP, the second filter cube can be removed allowing the mirrors in the image splitter to project a single image onto the CCD camera.

  20. Characterizing ligand-gated ion channel receptors with genetically encoded Ca2++ sensors.

    Directory of Open Access Journals (Sweden)

    John G Yamauchi

    Full Text Available We present a cell based system and experimental approach to characterize agonist and antagonist selectivity for ligand-gated ion channels (LGIC by developing sensor cells stably expressing a Ca(2+ permeable LGIC and a genetically encoded Förster (or fluorescence resonance energy transfer (FRET-based calcium sensor. In particular, we describe separate lines with human α7 and human α4β2 nicotinic acetylcholine receptors, mouse 5-HT(3A serotonin receptors and a chimera of human α7/mouse 5-HT(3A receptors. Complete concentration-response curves for agonists and Schild plots of antagonists were generated from these sensors and the results validate known pharmacology of the receptors tested. Concentration-response relations can be generated from either the initial rate or maximal amplitudes of FRET-signal. Although assaying at a medium throughput level, this pharmacological fluorescence detection technique employs a clonal line for stability and has versatility for screening laboratory generated congeners as agonists or antagonists on multiple subtypes of ligand-gated ion channels. The clonal sensor lines are also compatible with in vivo usage to measure indirectly receptor activation by endogenous neurotransmitters.

  1. Common genetic variation in the human CTF1 locus, encoding cardiotrophin-1, determines insulin sensitivity.

    Directory of Open Access Journals (Sweden)

    Stefan Z Lutz

    Full Text Available AIMS/HYPOTHESIS: Recently, cardiotrophin-1, a member of the interleukin-6 family of cytokines was described to protect beta-cells from apoptosis, to improve glucose-stimulated insulin secretion and insulin resistance, and to prevent streptozotocin-induced diabetes in mice. Here, we studied whether common single nucleotide polymorphisms (SNPs in the CTF1 locus, encoding cardiotrophin-1, influence insulin secretion and insulin sensitivity in humans. METHODS: We genotyped 1,771 German subjects for three CTF1 tagging SNPs (rs1046276, rs1458201, and rs8046707. The subjects were metabolically characterized by an oral glucose tolerance test. Subgroups underwent magnetic resonance (MR imaging/spectroscopy and hyperinsulinaemic-euglycaemic clamps. RESULTS: After appropriate adjustment, the minor allele of CTF1 SNP rs8046707 was significantly associated with decreased in vivo measures of insulin sensitivity. The other tested SNPs were not associated with OGTT-derived sensitivity parameters, nor did the three tested SNPs show any association with OGTT-derived parameters of insulin release. In the MR subgroup, SNP rs8046707 was nominally associated with lower visceral adipose tissue. Furthermore, the SNP rs1458201 showed a nominal association with increased VLDL levels. CONCLUSIONS: In conclusion, this study, even though preliminary and awaiting further confirmation by independent replication, provides first evidence that common genetic variation in CTF1 could contribute to insulin sensitivity in humans. Our SNP data indicate an insulin-desensitizing effect of cardiotrophin-1 and underline that cardiotrophin-1 represents an interesting target to influence insulin sensitivity.

  2. Genetically encoded Ca2+ indicators; expanded affinity range, color hue and compatibility with optogenetics

    Directory of Open Access Journals (Sweden)

    Takeharu eNagai

    2014-11-01

    Full Text Available Fluorescent protein-based indicators are invaluable tools for functional imaging of living cells and organisms. Genetically encoded calcium indicators (GECIs such as derivatives of yellow cameleons (YCs and GCaMPs/pericams (Miyawaki et al., 1997; Nakai et al., 2001; Nagai et al., 2001 are a highly advanced class of indicators. Continued efforts for improvement of the performance of GECIs have resulted in brighter indicators with better photo-stability and expanded dynamic range, thus improving the sensitivity of detection. Fine-tuning of other properties, including Ca2+ affinity and Hill constant, have also contributed to increase the detectability of Ca2+ dynamics. Emerging optogenetic technology has forced the spectrally compatible GECI color variants. In this opinion, we highlight the recent development of GECIs including photo-switchable Ca2+ indicators and bioluminescence-based Ca2+ indicator, mainly invented in our group, focusing especially on the parameters determining their performance in order to provide a guideline for the selection of appropriate GECI for a given experiment.

  3. Depth-Encoded Spectral Domain Phase Microscopy for Simultaneous Multi-Site Nanoscale Optical Measurements.

    Science.gov (United States)

    Hendargo, Hansford C; Bower, Bradley A; Reinstein, Alex S; Shepherd, Neal; Tao, Yuankai K; Izatt, Joseph A

    2011-09-01

    Spectral domain phase microscopy (SDPM) is an extension of spectral domain optical coherence tomography (SDOCT) that exploits the extraordinary phase stability of spectrometer-based systems with common-path geometry to resolve sub-wavelength displacements within a sample volume. This technique has been implemented for high resolution axial displacement and velocity measurements in biological samples, but since axial displacement information is acquired serially along the lateral dimension, it has been unable to measure fast temporal dynamics in extended samples. Depth-Encoded SDPM (DESDPM) uses multiple sample arms with unevenly spaced common path reference reflectors to multiplex independent SDPM signals from separate lateral positions on a sample simultaneously using a single interferometer, thereby reducing the time required to detect unique optical events to the integration period of the detector. Here, we introduce DESDPM and demonstrate the ability to acquire useful phase data concurrently at two laterally separated locations in a phantom sample as well as a biological preparation of spontaneously beating chick cardiomyocytes. DESDPM may be a useful tool for imaging fast cellular phenomena such as nervous conduction velocity or contractile motion.

  4. Optimization of multicast optical networks with genetic algorithm

    Science.gov (United States)

    Lv, Bo; Mao, Xiangqiao; Zhang, Feng; Qin, Xi; Lu, Dan; Chen, Ming; Chen, Yong; Cao, Jihong; Jian, Shuisheng

    2007-11-01

    In this letter, aiming to obtain the best multicast performance of optical network in which the video conference information is carried by specified wavelength, we extend the solutions of matrix games with the network coding theory and devise a new method to solve the complex problems of multicast network switching. In addition, an experimental optical network has been testified with best switching strategies by employing the novel numerical solution designed with an effective way of genetic algorithm. The result shows that optimal solutions with genetic algorithm are accordance with the ones with the traditional fictitious play method.

  5. Ultra-wideband fiber optical parametric amplifier for spectrally-encoded microscopy (Conference Presentation)

    Science.gov (United States)

    Wei, Xiaoming; Tan, Sisi; Mussot, Arnaud; Kudlinski, Alexandre; Tsia, Kevin K.; Wong, Kenneth

    2016-03-01

    Fiber optical parametric amplifier (FOPA) has gained its popularity in the telecommunication systems at the 1.5-um window for its gain, bandwidth etc. Unfortunately, its practical application at the bio-favorable window, i.e. 1.0 um, still requires substantial efforts. Thus, here we report a versatile all-fiber optical parametric amplifier for life-science (OPALS) at 1.0 um as an add-on module for optical imaging system. The parametric gain fiber (photonic-crystal fiber (PCF), 110 m in length) is specially designed to reduce the longitudinal dispersion fluctuation, which yields a superior figure of merit, i.e. a total insertion loss of ~2.5 dB and a nonlinear coefficient of 34 /(W•km). Our OPALS delivers a superior performance in terms of gain (~158,000), bandwidth (>100 nm) and gain flatness (Experimentally, we show that: 1) a wavelength-varying quasi-monochrome pump achieves a 52-dB gain and 160-nm bandwidth, but at the expense of a larger gain-spectrum ripple, i.e. a bell-shaped; 2) the birefringence of the parametric gain medium, i.e. PCF in this case, can be utilized to improve the gain-spectrum flatness of OPALS by 10.5 dB, meanwhile a 100-nm bandwidth can be guaranteed; 3) the gain-spectrum flatness of OPALS can be further flattened by using a high-speed wavelength-sweeping pump, which exhibits a 110-nm flat gain spectrum with ripple less than 3 dB. Finally, we employ this versatile all-fiber OPALS as an add-on module to enhance the sensitivity of a spectrally-encoded microscope by 47 dB over an ultra-wide spectral range.

  6. Genetic variability of Chlamydophila abortus strains assessed by PCR-RFLP analysis of polymorphic membrane protein-encoding genes.

    Science.gov (United States)

    Sait, Michelle; Clark, Ewan M; Wheelhouse, Nicholas; Spalding, Lucy; Livingstone, Morag; Sachse, Konrad; Markey, Bryan K; Magnino, Simone; Siarkou, Victoria I; Vretou, Evangelia; Caro, María R; Yaga, Raja; Lainson, F Alex; Smith, David G E; Wright, Frank; Longbottom, David

    2011-08-05

    This study used PCR-RFLP to investigate the genetic variability of pmp-encoding genes from fifty-two Chlamydophila abortus (C. abortus) strains originating from abortion cases from various geographical regions and host species. Six primer pairs were used to PCR-amplify DNA fragments encoding eighteen pmps. PCR products were digested using four restriction endonucleases and Bayesian methodologies were used to compare RFLP profiles and assign strains to a RFLP genotype. Strains could be assigned to 2 genotypes in the region encoding pmp18D, 3 genotypes in the regions encoding pmp1A-pmp2B, pmp3E-pmp6H and pmp11G-pmp15G, 4 genotypes in the region encoding pmp7G-pmp10G and 5 genotypes in the region encoding pmp16G-pmp17G. In all regions, the majority of strains (88.4-96.1%) had the same genotype as the reference strain S26/3. No correlation could be made between genotype, host species or geographical origin except for the two variant Greek strains, LLG and POS, which formed a discrete genotype in all pmp-encoding regions except pmp18D. Relative rates of evolution calculated for each pmp-encoding gene locus suggest that differing selective pressures and functional constraints may exist on C. abortus polymorphic membrane proteins. These findings suggest that although intraspecies heterogeneity of pmp-encoding genes in C. abortus is low, the sequence heterogeneity should be an important consideration when using pmps as the basis for novel diagnostics or vaccine development.

  7. Characterization of the single stranded DNA binding protein SsbB encoded in the Gonoccocal Genetic Island.

    Directory of Open Access Journals (Sweden)

    Samta Jain

    Full Text Available BACKGROUND: Most strains of Neisseria gonorrhoeae carry a Gonococcal Genetic Island which encodes a type IV secretion system involved in the secretion of ssDNA. We characterize the GGI-encoded ssDNA binding protein, SsbB. Close homologs of SsbB are located within a conserved genetic cluster found in genetic islands of different proteobacteria. This cluster encodes DNA-processing enzymes such as the ParA and ParB partitioning proteins, the TopB topoisomerase, and four conserved hypothetical proteins. The SsbB homologs found in these clusters form a family separated from other ssDNA binding proteins. METHODOLOGY/PRINCIPAL FINDINGS: In contrast to most other SSBs, SsbB did not complement the Escherichia coli ssb deletion mutant. Purified SsbB forms a stable tetramer. Electrophoretic mobility shift assays and fluorescence titration assays, as well as atomic force microscopy demonstrate that SsbB binds ssDNA specifically with high affinity. SsbB binds single-stranded DNA with minimal binding frames for one or two SsbB tetramers of 15 and 70 nucleotides. The binding mode was independent of increasing Mg(2+ or NaCl concentrations. No role of SsbB in ssDNA secretion or DNA uptake could be identified, but SsbB strongly stimulated Topoisomerase I activity. CONCLUSIONS/SIGNIFICANCE: We propose that these novel SsbBs play an unknown role in the maintenance of genetic islands.

  8. Genetically-encoded tools for cAMP probing and modulation in living systems.

    Directory of Open Access Journals (Sweden)

    Valeriy M Paramonov

    2015-09-01

    Full Text Available Intracellular 3'-5'-cyclic adenosine monophosphate (cAMP is one of the principal second messengers downstream of a manifold of signal transduction pathways, including the ones triggered by G protein-coupled receptors. Not surprisingly, biochemical assays for cAMP have been instrumental for basic research and drug discovery for decades, providing insights into cellular physiology and guiding pharmaceutical industry. However, despite impressive track record, the majority of conventional biochemical tools for cAMP probing share the same fundamental shortcoming - all the measurements require sample disruption for cAMP liberation. This common bottleneck, together with inherently low spatial resolution of measurements (as cAMP is typically analyzed in lysates of thousands of cells, underpin the ensuing limitations of the conventional cAMP assays: 1 genuine kinetic measurements of cAMP levels over time in a single given sample are unfeasible; 2 inability to obtain precise information on cAMP spatial distribution and transfer at subcellular levels, let alone the attempts to pinpoint dynamic interactions of cAMP and its effectors. At the same time, tremendous progress in synthetic biology over the recent years culminated in drastic refinement of our toolbox, allowing us not only to bypass the limitations of conventional assays, but to put intracellular cAMP life-span under tight control – something, that seemed scarcely attainable before. In this review article we discuss the main classes of modern genetically-encoded tools tailored for cAMP probing and modulation in living systems. We examine the capabilities and weaknesses of these different tools in the context of their operational characteristics and applicability to various experimental set-ups involving living cells, providing the guidance for rational selection of the best tools for particular needs.

  9. Visualization of glutamine transporter activities in living cells using genetically encoded glutamine sensors.

    Directory of Open Access Journals (Sweden)

    Katrin Gruenwald

    Full Text Available Glutamine plays a central role in the metabolism of critical biological molecules such as amino acids, proteins, neurotransmitters, and glutathione. Since glutamine metabolism is regulated through multiple enzymes and transporters, the cellular glutamine concentration is expected to be temporally dynamic. Moreover, differentiation in glutamine metabolism between cell types in the same tissue (e.g. neuronal and glial cells is often crucial for the proper function of the tissue as a whole, yet assessing cell-type specific activities of transporters and enzymes in such heterogenic tissue by physical fractionation is extremely challenging. Therefore, a method of reporting glutamine dynamics at the cellular level is highly desirable. Genetically encoded sensors can be targeted to a specific cell type, hence addressing this knowledge gap. Here we report the development of Föster Resonance Energy Transfer (FRET glutamine sensors based on improved cyan and yellow fluorescent proteins, monomeric Teal Fluorescent Protein (mTFP1 and venus. These sensors were found to be specific to glutamine, and stable to pH-changes within a physiological range. Using cos7 cells expressing the human glutamine transporter ASCT2 as a model, we demonstrate that the properties of the glutamine transporter can easily be analyzed with these sensors. The range of glutamine concentration change in a given cell can also be estimated using sensors with different affinities. Moreover, the mTFP1-venus FRET pair can be duplexed with another FRET pair, mAmetrine and tdTomato, opening up the possibility for real-time imaging of another molecule. These novel glutamine sensors will be useful tools to analyze specificities of glutamine metabolism at the single-cell level.

  10. Genetically encoded green fluorescent Ca2+ indicators with improved detectability for neuronal Ca2+ signals.

    Science.gov (United States)

    Ohkura, Masamichi; Sasaki, Takuya; Sadakari, Junko; Gengyo-Ando, Keiko; Kagawa-Nagamura, Yuko; Kobayashi, Chiaki; Ikegaya, Yuji; Nakai, Junichi

    2012-01-01

    Imaging the activities of individual neurons with genetically encoded Ca(2+) indicators (GECIs) is a promising method for understanding neuronal network functions. Here, we report GECIs with improved neuronal Ca(2+) signal detectability, termed G-CaMP6 and G-CaMP8. Compared to a series of existing G-CaMPs, G-CaMP6 showed fairly high sensitivity and rapid kinetics, both of which are suitable properties for detecting subtle and fast neuronal activities. G-CaMP8 showed a greater signal (F(max)/F(min) = 38) than G-CaMP6 and demonstrated kinetics similar to those of G-CaMP6. Both GECIs could detect individual spikes from pyramidal neurons of cultured hippocampal slices or acute cortical slices with 100% detection rates, demonstrating their superior performance to existing GECIs. Because G-CaMP6 showed a higher sensitivity and brighter baseline fluorescence than G-CaMP8 in a cellular environment, we applied G-CaMP6 for Ca(2+) imaging of dendritic spines, the putative postsynaptic sites. By expressing a G-CaMP6-actin fusion protein for the spines in hippocampal CA3 pyramidal neurons and electrically stimulating the granule cells of the dentate gyrus, which innervate CA3 pyramidal neurons, we found that sub-threshold stimulation triggered small Ca(2+) responses in a limited number of spines with a low response rate in active spines, whereas supra-threshold stimulation triggered large fluorescence responses in virtually all of the spines with a 100% activity rate.

  11. Genetically encoded calcium indicators for multi-color neural activity imaging and combination with optogenetics

    Directory of Open Access Journals (Sweden)

    Jasper eAkerboom

    2013-03-01

    Full Text Available Genetically encoded calcium indicators (GECIs are powerful tools for systems neuroscience. Here we describe red, single-wavelength GECIs, RCaMPs, engineered from circular permutation of the thermostable red fluorescent protein mRuby. High-resolution crystal structures of mRuby, the red sensor RCaMP, and the recently published red GECI R-GECO1 give insight into the chromophore environments of the Ca2+-bound state of the sensors and the engineered protein domain interfaces of the different indicators. We characterized the biophysical properties and performance of RCaMP sensors in vitro and in vivo in Caenorhabditis elegans, Drosophila larvae, and larval zebrafish. Further, we demonstrate 2-color calcium imaging both within the same cell (registering mitochondrial and somatic [Ca2+] and between two populations of cells: neurons and astrocytes. Finally, we perform integrated optogenetics experiments, wherein neural activation via channelrhodopsin-2 (ChR2 or a red-shifted variant, and activity imaging via RCaMP or GCaMP, are conducted simultaneously, with the ChR2/RCaMP pair providing independently addressable spectral channels. Using this paradigm, we measure calcium responses of naturalistic and ChR2-evoked muscle contractions in vivo in crawling C. elegans. We systematically compare the RCaMP sensors to R-GECO1, in terms of action potential-evoked fluorescence increases in neurons, photobleaching, and photoswitching. R-GECO1 displays higher Ca2+ affinity and larger dynamic range than RCaMP, but exhibits significant photoactivation with blue and green light, suggesting that integrated channelrhodopsin-based optogenetics using R-GECO1 may be subject to artifact. Finally, we create and test blue, cyan and yellow variants engineered from GCaMP by rational design. This engineered set of chromatic variants facilitates new experiments in functional imaging and optogenetics.

  12. Engineering of a Genetically Encodable Fluorescent Voltage Sensor Exploiting Fast Ci-VSP Voltage-Sensing Movements

    OpenAIRE

    Alicia Lundby; Hiroki Mutoh; Dimitar Dimitrov; Walther Akemann; Thomas Knöpfel

    2008-01-01

    Ci-VSP contains a voltage-sensing domain (VSD) homologous to that of voltage-gated potassium channels. Using charge displacement ('gating' current) measurements we show that voltage-sensing movements of this VSD can occur within 1 ms in mammalian membranes. Our analysis lead to development of a genetically encodable fluorescent protein voltage sensor (VSFP) in which the fast, voltage-dependent conformational changes of the Ci-VSP voltage sensor are transduced to similarly fast fluorescence re...

  13. Inhibition of Exotoxin Production by Mobile Genetic Element SCCmec-Encoded psm-mec RNA Is Conserved in Staphylococcal Species

    OpenAIRE

    Mariko Ikuo; Gentaro Nagano; Yuki Saito; Han Mao; Kazuhisa Sekimizu; Chikara Kaito

    2014-01-01

    Staphylococcal species acquire antibiotic resistance by incorporating the mobile-genetic element SCCmec. We previously found that SCCmec-encoded psm-mec RNA suppresses exotoxin production as a regulatory RNA, and the psm-mec translation product increases biofilm formation in Staphylococcus aureus. Here, we examined whether the regulatory role of psm-mec on host bacterial virulence properties is conserved among other staphylococcal species, S. epidermidis and S. haemolyticus, both of which are...

  14. Satellite range scheduling with the priority constraint: An improved genetic algorithm using a station ID encoding method

    Directory of Open Access Journals (Sweden)

    Li Yuqing

    2015-06-01

    Full Text Available Satellite range scheduling with the priority constraint is one of the most important problems in the field of satellite operation. This paper proposes a station coding based genetic algorithm to solve this problem, which adopts a new chromosome encoding method that arranges tasks according to the ground station ID. The new encoding method contributes to reducing the complexity in conflict checking and resolving, and helps to improve the ability to find optimal resolutions. Three different selection operators are designed to match the new encoding strategy, namely random selection, greedy selection, and roulette selection. To demonstrate the benefits of the improved genetic algorithm, a basic genetic algorithm is designed in which two cross operators are presented, a single-point crossover and a multi-point crossover. For the purpose of algorithm test and analysis, a problem-generating program is designed, which can simulate problems by modeling features encountered in real-world problems. Based on the problem generator, computational results and analysis are made and illustrated for the scheduling of multiple ground stations.

  15. Development of an automated fluorescence microscopy system for photomanipulation of genetically encoded photoactivatable proteins (optogenetics) in live cells.

    Science.gov (United States)

    Araki, Nobukazu; Ikeda, Yuka; Kato, Takuma; Kawai, Katsuhisa; Egami, Youhei; Miyake, Katsuya; Tsurumaki, Nobuhide; Yamaguchi, Mitsunari

    2014-06-01

    Photomanipulation of genetically encoded light-sensitive protein activity, also known as optogenetics, is one of the most innovative recent microscopy techniques in the fields of cell biology and neurobiology. Although photomanipulation is usually performed by diverting the photobleaching mode of a confocal laser microscope, photobleaching by the laser scanning unit is not always suitable for photoactivation. We have developed a simple automated wide-field fluorescence microscopy system for the photomanipulation of genetically encoded photoactivatable proteins in live cells. An electrically automated fluorescence microscope can be controlled through MetaMorph imaging software, making it possible to acquire time-lapse, multiwavelength images of live cells. Using the journal (macro recording) function of MetaMorph, we wrote a macro program to change the excitation filter for photoactivation and illumination area during the intervals of image acquisition. When this program was run on the wide-field fluorescence microscope, cells expressing genetically encoded photoactivatable Rac1, which is activated under blue light, showed morphological changes such as lamellipodial extension and cell surface ruffling in the illuminated region. Using software-based development, we successfully constructed a fully automated photoactivation microscopy system for a mercury lamp-based fluorescence microscope.

  16. Optical incremental rotary encoder in low-cost-design; Optischer inkrementaler Drehgeber in Low-Cost-Bauweise

    Energy Technology Data Exchange (ETDEWEB)

    Hopp, David; Pruss, Christof; Osten, Wolfgang [Stuttgart Univ. (Germany). Inst. fuer Technische Optik; Seybold, Jonathan; Mayer, Volker [Hans-Schickard-Gesellschaft, Stuttgart (DE). Inst. fuer Mikroaufbautechnik (IMAT); Kueck, Heinz [Hans-Schickard-Gesellschaft, Stuttgart (DE). Inst. fuer Mikroaufbautechnik (IMAT); Stuttgart Univ. (Germany). Inst. fuer Zeitmesstechnik, Fein- und Mikrotechnik

    2010-07-01

    We have developed a new concept for low-cost optical encoders to come up to meet the increasing demand for inexpensive rotary sensors. The principal idea is to use a micro patterned plastic disc with metal coating, as it is used for Compact Discs or DVDs. Such encoder discs can be manufactured by an efficient injection compression moulding process. With this well established technique it is possible to achieve highly precise micro patterns while running a cost effective process for high volume production. (orig.)

  17. Genetic characterization of psp encoding the DING protein in Pseudomonas fluorescens SBW25

    Directory of Open Access Journals (Sweden)

    Zhang Xue-Xian

    2007-12-01

    Full Text Available Abstract Background DING proteins constitute a conserved and broadly distributed set of proteins found in bacteria, fungi, plants and animals (including humans. Characterization of DING proteins from animal and plant tissues indicated ligand-binding ability suggesting a role for DING proteins in cell signaling and biomineralization. Surprisingly, the genes encoding DING proteins in eukaryotes have not been identified in the eukaryotic genome or EST databases. Recent discovery of a DING homologue (named Psp here in the genome of Pseudomonas fluorescens SBW25 provided a unique opportunity to investigate the physiological roles of DING proteins. P. fluorescens SBW25 is a model bacterium that can efficiently colonize plant surfaces and enhance plant health. In this report we genetically characterize Psp with a focus on conditions under which psp is expressed and the protein exported. Results Psp is closely related to the periplasmic Pi binding component of the ABC-type phosphate transporter system (Pst. psp is flanked by a gene cluster predicted to function as a type II protein secretion system (Hxc. Deletion analysis combined with chromosomally integrated 'lacZ fusions showed that both psp and pstC are induced by Pi limitation and that pstC is required for competitive growth of the bacterium in Pi limited medium. hxcR is not regulated by Pi limitation. Psp was detected (using anti-DING serum in the supernatant of wild-type culture but was greatly reduced in the supernatant of an isogenic strain carrying an hxcR mutation (ΔhxcR. A promoter fusion between hxcR and a promoterless copy of a gene ('dapB essential for growth in the plant environment showed that expression of hxcR is elevated during colonization of sugar beet seedlings. A similar analysis of psp showed that it is not induced in the plant environment. Conclusion Psp gene is expressed under conditions of Pi limitation. It is an exoprotein secreted mainly via the Hxc type II secretion

  18. Calibration and functional analysis of three genetically encoded Cl−/pH sensors

    Directory of Open Access Journals (Sweden)

    Marat eMukhtarov

    2013-04-01

    Full Text Available Monitoring of the intracellular concentrations of Cl− and H+ requires sensitive probes that allow reliable quantitative measurements without perturbation of cell functioning. For these purposes the most promising are genetically encoded fluorescent biosensors, which have become powerful tools for non-invasive intracellular monitoring of ions, molecules and enzymatic activity. A ratiometric CFP/YFP-based construct with a relatively good sensitivity to Cl− has been developed (Markova et al., 2008; Waseem et al., 2010. Recently, a combined Cl−/pH sensor (ClopHensor opened the way for simultaneous ratiometric measurement of these two ions (Arosio et al., 2010. ClopHensor was obtained by fusion of a red-fluorescent protein (DsRed-monomer to the E2GFP variant that contains a specific Cl−-binding site. This construct possesses pKa = 6.8 for H+ and Kd in the 40-50 mM range for Cl− at physiological pH (~7.3 As in the majority of cell types the intracellular Cl− concentration ([Cl−]i is about 10 mM, the development of sensors with higher sensitivity is highly desirable. Here we report the intracellular calibration and functional characterization of ClopHensor and its two derivatives: the membrane targeting PalmPalm-ClopHensor and the H148G/V224L mutant with improved Cl− affinity, reduced pH dependence and pKa shifted to more alkaline values. For functional analysis, constructs were expressed in CHO cells and [Cl−]i was changed by using pipettes with different Cl− concentrations during whole-cell recordings. Kd values for Cl− measured at 33°C and pH ~ 7.3 were, respectively, 39 mM, 47 mM and 21 mM for ClopHensor, PalmPalm-ClopHensor and the H148G/V224L mutant. PalmPalm-ClopHensor resolved responses to activation of Cl−-selective glycine receptor channels better than did ClopHensor. Our observations indicate that these different ClopHensor constructs are promising tools for non-invasive measurement of [Cl−]i in various living

  19. Resistance determinants and mobile genetic elements of an NDM-1-encoding Klebsiella pneumoniae strain.

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    Corey M Hudson

    Full Text Available Multidrug-resistant Enterobacteriaceae are emerging as a serious infectious disease challenge. These strains can accumulate many antibiotic resistance genes though horizontal transfer of genetic elements, those for β-lactamases being of particular concern. Some β-lactamases are active on a broad spectrum of β-lactams including the last-resort carbapenems. The gene for the broad-spectrum and carbapenem-active metallo-β-lactamase NDM-1 is rapidly spreading. We present the complete genome of Klebsiella pneumoniae ATCC BAA-2146, the first U.S. isolate found to encode NDM-1, and describe its repertoire of antibiotic-resistance genes and mutations, including genes for eight β-lactamases and 15 additional antibiotic-resistance enzymes. To elucidate the evolution of this rich repertoire, the mobile elements of the genome were characterized, including four plasmids with varying degrees of conservation and mosaicism and eleven chromosomal genomic islands. One island was identified by a novel phylogenomic approach, that further indicated the cps-lps polysaccharide synthesis locus, where operon translocation and fusion was noted. Unique plasmid segments and mosaic junctions were identified. Plasmid-borne blaCTX-M-15 was transposed recently to the chromosome by ISEcp1. None of the eleven full copies of IS26, the most frequent IS element in the genome, had the expected 8-bp direct repeat of the integration target sequence, suggesting that each copy underwent homologous recombination subsequent to its last transposition event. Comparative analysis likewise indicates IS26 as a frequent recombinational junction between plasmid ancestors, and also indicates a resolvase site. In one novel use of high-throughput sequencing, homologously recombinant subpopulations of the bacterial culture were detected. In a second novel use, circular transposition intermediates were detected for the novel insertion sequence ISKpn21 of the ISNCY family, suggesting that it uses

  20. A bio-inspired, computational model suggests velocity gradients of optic flow locally encode ordinal depth at surface borders and globally they encode self-motion.

    Science.gov (United States)

    Raudies, Florian; Ringbauer, Stefan; Neumann, Heiko

    2013-09-01

    Visual navigation requires the estimation of self-motion as well as the segmentation of objects from the background. We suggest a definition of local velocity gradients to compute types of self-motion, segment objects, and compute local properties of optical flow fields, such as divergence, curl, and shear. Such velocity gradients are computed as velocity differences measured locally tangent and normal to the direction of flow. Then these differences are rotated according to the local direction of flow to achieve independence of that direction. We propose a bio-inspired model for the computation of these velocity gradients for video sequences. Simulation results show that local gradients encode ordinal surface depth, assuming self-motion in a rigid scene or object motions in a nonrigid scene. For translational self-motion velocity, gradients can be used to distinguish between static and moving objects. The information about ordinal surface depth and self-motion can help steering control for visual navigation.

  1. Optical image cryptosystem using chaotic phase-amplitude masks encoding and least-data-driven decryption by compressive sensing

    Science.gov (United States)

    Lang, Jun; Zhang, Jing

    2015-03-01

    In our proposed optical image cryptosystem, two pairs of phase-amplitude masks are generated from the chaotic web map for image encryption in the 4f double random phase-amplitude encoding (DRPAE) system. Instead of transmitting the real keys and the enormous masks codes, only a few observed measurements intermittently chosen from the masks are delivered. Based on compressive sensing paradigm, we suitably refine the series expansions of web map equations to better reconstruct the underlying system. The parameters of the chaotic equations can be successfully calculated from observed measurements and then can be used to regenerate the correct random phase-amplitude masks for decrypting the encoded information. Numerical simulations have been performed to verify the proposed optical image cryptosystem. This cryptosystem can provide a new key management and distribution method. It has the advantages of sufficiently low occupation of the transmitted key codes and security improvement of information transmission without sending the real keys.

  2. Experimental Electrically Reconfigurable Time-Domain Spectral Amplitude Encoding/Decoding in an Optical Code Division Multiple Access System

    Science.gov (United States)

    Tainta, Santiago; Erro, María J.; Garde, María J.; Muriel, Miguel A.

    2013-11-01

    An electrically reconfigurable time-domain spectral amplitude encoding/decoding scheme is proposed herein. The setup is based on the concept of temporally pulse shaping dual to spatial arrangements. The transmitter is based on a short pulse source and uses two conjugate dispersive fiber gratings and an electro-optic intensity modulator placed in between. Proof of concept results are shown for an optical pulse train operating at 1.25 Gbps using codes from the Hadamard family with a length of eight chips. The system is electrically reconfigurable, compatible with fiber systems, and permits scalability in the size of the codes by modifying only the modulator velocity.

  3. Genetic optical design for a compressive sensing task

    Science.gov (United States)

    Horisaki, Ryoichi; Niihara, Takahiro; Tanida, Jun

    2016-07-01

    We present a sophisticated optical design method for reducing the number of photodetectors for a specific sensing task. The chosen design parameter is the point spread function, and the selected task is object recognition. The point spread function is optimized iteratively with a genetic algorithm for object recognition based on a neural network. In the experimental demonstration, binary classification of face and non-face datasets was performed with a single measurement using two photodetectors. A spatial light modulator operating in the amplitude modulation mode was provided in the imaging optics and was used to modulate the point spread function. In each generation of the genetic algorithm, the classification accuracy with a pattern displayed on the spatial light modulator was fed-back to the next generation to find better patterns. The proposed method increased the accuracy by about 30 % compared with a conventional imaging system in which the point spread function was the delta function. This approach is practically useful for compressing the cost, size, and observation time of optical sensors in specific applications, and robust for imperfections in optical elements.

  4. Genetic optical design for a compressive sensing task

    Science.gov (United States)

    Horisaki, Ryoichi; Niihara, Takahiro; Tanida, Jun

    2016-10-01

    We present a sophisticated optical design method for reducing the number of photodetectors for a specific sensing task. The chosen design parameter is the point spread function, and the selected task is object recognition. The point spread function is optimized iteratively with a genetic algorithm for object recognition based on a neural network. In the experimental demonstration, binary classification of face and non-face datasets was performed with a single measurement using two photodetectors. A spatial light modulator operating in the amplitude modulation mode was provided in the imaging optics and was used to modulate the point spread function. In each generation of the genetic algorithm, the classification accuracy with a pattern displayed on the spatial light modulator was fed-back to the next generation to find better patterns. The proposed method increased the accuracy by about 30 % compared with a conventional imaging system in which the point spread function was the delta function. This approach is practically useful for compressing the cost, size, and observation time of optical sensors in specific applications, and robust for imperfections in optical elements.

  5. A Fuzzy Genetic Algorithm Based on Binary Encoding for Solving Multidimensional Knapsack Problems

    Directory of Open Access Journals (Sweden)

    M. Jalali Varnamkhasti

    2012-01-01

    Full Text Available The fundamental problem in genetic algorithms is premature convergence, and it is strongly related to the loss of genetic diversity of the population. This study aims at proposing some techniques to tackle the premature convergence by controlling the population diversity. Firstly, a sexual selection mechanism which utilizes the mate chromosome during selection is used. The second technique focuses on controlling the genetic parameters by applying the fuzzy logic controller. Computational experiments are conducted on the proposed techniques and the results are compared with other genetic operators, heuristics, and local search algorithms commonly used for solving multidimensional 0/1 knapsack problems published in the literature.

  6. A strategy for genetic modification of the spike-encoding segment of human reovirus T3D for reovirus targeting.

    Science.gov (United States)

    van den Wollenberg, D J M; van den Hengel, S K; Dautzenberg, I J C; Cramer, S J; Kranenburg, O; Hoeben, R C

    2008-12-01

    Human Orthoreovirus Type 3 Dearing is not pathogenic to humans and has been evaluated clinically as an oncolytic agent. Its transduction efficiency and the tumor cell selectivity may be enhanced by incorporating ligands for alternative receptors. However, the genetic modification of reoviruses has been difficult, and genetic targeting of reoviruses has not been reported so far. Here we describe a technique for generating genetically targeted reoviruses. The propagation of wild-type reoviruses on cells expressing a modified sigma 1-encoding segment embedded in a conventional RNA polymerase II transcript leads to substitution of the wild-type genome segment by the modified version. This technique was used for generating reoviruses that are genetically targeted to an artificial receptor expressed on U118MG cells. These cells lack the junction adhesion molecule-1 and therefore resist infection by wild-type reoviruses. The targeted reoviruses were engineered to carry the ligand for this receptor at the C terminus of the sigma 1 spike protein. This demonstrates that the C terminus of the sigma 1 protein is a suitable locale for the insertion of oligopeptide ligands and that targeting of reoviruses is feasible. The genetically targeted viruses can be propagated using the modified U118MG cells as helper cells. This technique may be applicable for the improvement of human reoviruses as oncolytic agents.

  7. Interleukin-Encoding Adenoviral Vectors as Genetic Adjuvant for Vaccination against Retroviral Infection

    Science.gov (United States)

    Ohs, Inga; Windmann, Sonja; Wildner, Oliver; Dittmer, Ulf; Bayer, Wibke

    2013-01-01

    Interleukins (IL) are cytokines with stimulatory and modulatory functions in the immune system. In this study, we have chosen interleukins which are involved in the enhancement of TH2 responses and B cell functions to analyze their potential to improve a prophylactic adenovirus-based anti-retroviral vaccine with regard to antibody and virus-specific CD4+ T cell responses. Mice were vaccinated with an adenoviral vector which encodes and displays the Friend Virus (FV) surface envelope protein gp70 (Ad.pIXgp70) in combination with adenoviral vectors encoding the interleukins IL4, IL5, IL6, IL7 or IL23. Co-application of Ad.pIXgp70 with Ad.IL5, Ad.IL6 or Ad.IL23 resulted in improved protection with high control over FV-induced splenomegaly and reduced viral loads. Mice co-immunized with adenoviral vectors encoding IL5 or IL23 showed increased neutralizing antibody responses while mice co-immunized with Ad.IL6 or Ad.IL23 showed improved FV-specific CD4+ T cell responses compared to mice immunized with Ad.pIXgp70 alone. We show that the co-application of adenoviral vectors encoding specific interleukins is suitable to improve the vaccination efficacy of an anti-retroviral vaccine. Improved protection correlated with improved CD4+ T cell responses and especially with higher neutralizing antibody titers. The co-application of selected interleukin-encoding adenoviral vectors is a valuable tool for vaccination with regard to enhancement of antibody mediated immunity. PMID:24349306

  8. Interleukin-encoding adenoviral vectors as genetic adjuvant for vaccination against retroviral infection.

    Directory of Open Access Journals (Sweden)

    Inga Ohs

    Full Text Available Interleukins (IL are cytokines with stimulatory and modulatory functions in the immune system. In this study, we have chosen interleukins which are involved in the enhancement of TH2 responses and B cell functions to analyze their potential to improve a prophylactic adenovirus-based anti-retroviral vaccine with regard to antibody and virus-specific CD4(+ T cell responses. Mice were vaccinated with an adenoviral vector which encodes and displays the Friend Virus (FV surface envelope protein gp70 (Ad.pIXgp70 in combination with adenoviral vectors encoding the interleukins IL4, IL5, IL6, IL7 or IL23. Co-application of Ad.pIXgp70 with Ad.IL5, Ad.IL6 or Ad.IL23 resulted in improved protection with high control over FV-induced splenomegaly and reduced viral loads. Mice co-immunized with adenoviral vectors encoding IL5 or IL23 showed increased neutralizing antibody responses while mice co-immunized with Ad.IL6 or Ad.IL23 showed improved FV-specific CD4(+ T cell responses compared to mice immunized with Ad.pIXgp70 alone. We show that the co-application of adenoviral vectors encoding specific interleukins is suitable to improve the vaccination efficacy of an anti-retroviral vaccine. Improved protection correlated with improved CD4(+ T cell responses and especially with higher neutralizing antibody titers. The co-application of selected interleukin-encoding adenoviral vectors is a valuable tool for vaccination with regard to enhancement of antibody mediated immunity.

  9. Interleukin-encoding adenoviral vectors as genetic adjuvant for vaccination against retroviral infection.

    Science.gov (United States)

    Ohs, Inga; Windmann, Sonja; Wildner, Oliver; Dittmer, Ulf; Bayer, Wibke

    2013-01-01

    Interleukins (IL) are cytokines with stimulatory and modulatory functions in the immune system. In this study, we have chosen interleukins which are involved in the enhancement of TH2 responses and B cell functions to analyze their potential to improve a prophylactic adenovirus-based anti-retroviral vaccine with regard to antibody and virus-specific CD4(+) T cell responses. Mice were vaccinated with an adenoviral vector which encodes and displays the Friend Virus (FV) surface envelope protein gp70 (Ad.pIXgp70) in combination with adenoviral vectors encoding the interleukins IL4, IL5, IL6, IL7 or IL23. Co-application of Ad.pIXgp70 with Ad.IL5, Ad.IL6 or Ad.IL23 resulted in improved protection with high control over FV-induced splenomegaly and reduced viral loads. Mice co-immunized with adenoviral vectors encoding IL5 or IL23 showed increased neutralizing antibody responses while mice co-immunized with Ad.IL6 or Ad.IL23 showed improved FV-specific CD4(+) T cell responses compared to mice immunized with Ad.pIXgp70 alone. We show that the co-application of adenoviral vectors encoding specific interleukins is suitable to improve the vaccination efficacy of an anti-retroviral vaccine. Improved protection correlated with improved CD4(+) T cell responses and especially with higher neutralizing antibody titers. The co-application of selected interleukin-encoding adenoviral vectors is a valuable tool for vaccination with regard to enhancement of antibody mediated immunity.

  10. Fabrication of high-resolution reflective scale grating for an optical encoder using a patterned self-assembly process

    Science.gov (United States)

    Fan, Shanjin; Jiang, Weitao; Li, Xuan; Yu, Haoyu; Lei, Biao; Shi, Yongsheng; Yin, Lei; Chen, Bangdao; Liu, Hongzhong

    2016-07-01

    Steel tape scale grating of a reflective incremental linear encoder has a key impact on the measurement accuracy of the optical encoder. However, it is difficult for conventional manufacturing processes to fabricate scale grating with high-resolution grating strips, due to process and material problems. In this paper, self-assembly technology was employed to fabricate high-resolution steel tape scale grating for a reflective incremental linear encoder. Graphene oxide nanoparticles were adopted to form anti-reflective grating strips of steel tape scale grating. They were deposited in the tape, which had a hydrophobic and hydrophilic grating pattern when the dispersion of the nanoparticles evaporated. A standard lift-off process was employed to fabricate the hydrophobic grating strips on the steel tape. Simultaneously, the steel tape itself presents a hydrophilic property. The hydrophobic and hydrophilic grating pattern was thus obtained. In this study, octafluorocyclobutane was used to prepare the hydrophobic grating strips, due to its hydrophobic property. High-resolution graphene oxide steel tape scale grating with a pitch of 20 μm was obtained through the self-assembly process. The photoelectric signals of the optical encoder containing the graphene oxide scale grating and conventional scale grating were tested under the same conditions. Comparison test results showed that the graphene oxide scale grating has a better performance in its amplitude and harmonic components than that of the conventional steel tape scale. A comparison experiment of position errors was also conducted, demonstrating an improvement in the positioning error of the graphene oxide scale grating. The comparison results demonstrated the applicability of the proposed self-assembly process to fabricate high-resolution graphene oxide scale grating for a reflective incremental linear encoder.

  11. Engineering of a genetically encodable fluorescent voltage sensor exploiting fast Ci-VSP voltage-sensing movements

    DEFF Research Database (Denmark)

    Lundby, Alicia; Mutoh, Hiroki; Dimitrov, Dimitar

    2008-01-01

    Ci-VSP contains a voltage-sensing domain (VSD) homologous to that of voltage-gated potassium channels. Using charge displacement ('gating' current) measurements we show that voltage-sensing movements of this VSD can occur within 1 ms in mammalian membranes. Our analysis lead to development of a g...... of a genetically encodable fluorescent protein voltage sensor (VSFP) in which the fast, voltage-dependent conformational changes of the Ci-VSP voltage sensor are transduced to similarly fast fluorescence read-outs....

  12. Performance of an optical encoder based on a nondiffractive beam implemented with a specific photodetection integrated circuit and a diffractive optical element.

    Science.gov (United States)

    Quintián, Fernando Perez; Calarco, Nicolás; Lutenberg, Ariel; Lipovetzky, José

    2015-09-01

    In this paper, we study the incremental signal produced by an optical encoder based on a nondiffractive beam (NDB). The NDB is generated by means of a diffractive optical element (DOE). The detection system is composed by an application specific integrated circuit (ASIC) sensor. The sensor consists of an array of eight concentric annular photodiodes, each one provided with a programmable gain amplifier. In this way, the system is able to synthesize a nonuniform detectivity. The contrast, amplitude, and harmonic content of the sinusoidal output signal are analyzed. The influence of the cross talk among the annular photodiodes is placed in evidence through the dependence of the signal contrast on the wavelength.

  13. [Leber's hereditary optic neuropathy - phenotype, genetics, therapeutic options].

    Science.gov (United States)

    Gallenmüller, C; Klopstock, T

    2014-03-01

    Leber's hereditary optic neuropathy is a rare genetic disorder affecting the retinal ganglion cells leading to a persistent severe bilateral loss of visual acuity within weeks or months. Males are much more likely to be affected than females, disease onset in most cases takes place between age 15 and 35 years. The disease is caused by point mutations in the mitochondrial DNA. The penetrance of the disease is incomplete, i.e., not all mutation carriers develop clinical symptoms. The phenotype is relatively uniform, but age at onset, severity and prognosis may vary even within the same family. Environmental and endocrine factors, optic disc anatomy as well as mitochondrial and nuclear genetic factors are discussed to influence penetrance as well as interindividual and intrafamilial variability. However, only cigarette smoking and excessive alcohol consumption have been shown to trigger disease onset. The disease is characterised by a central visual field defect, impaired colour vision and fundoscopically a peripapillary microangiopathy in the acute phase. Most patients end up after some months with a severe visual loss below 0.1 and in most cases there is no significant improvement of visual acuity in the course. In rare cases patients experience a mostly partial visual recovery which depends on the type of mutation. For confirmation of the diagnosis a detailed ophthalmological examination with fundoscopy, family history and genetic analysis of the mitochondrial DNA is needed. To date, there is no proven causal therapy, but at early disease stages treatment with idebenone can be tried.

  14. Plant genetics. A Y-chromosome-encoded small RNA acts as a sex determinant in persimmons.

    Science.gov (United States)

    Akagi, Takashi; Henry, Isabelle M; Tao, Ryutaro; Comai, Luca

    2014-10-31

    In plants, multiple lineages have evolved sex chromosomes independently, providing a powerful comparative framework, but few specific determinants controlling the expression of a specific sex have been identified. We investigated sex determinants in the Caucasian persimmon, Diospyros lotus, a dioecious plant with heterogametic males (XY). Male-specific short nucleotide sequences were used to define a male-determining region. A combination of transcriptomics and evolutionary approaches detected a Y-specific sex-determinant candidate, OGI, that displays male-specific conservation among Diospyros species. OGI encodes a small RNA targeting the autosomal MeGI gene, a homeodomain transcription factor regulating anther fertility in a dosage-dependent fashion. This identification of a feminizing gene suppressed by a Y-chromosome-encoded small RNA contributes to our understanding of the evolution of sex chromosome systems in higher plants. Copyright © 2014, American Association for the Advancement of Science.

  15. Optically encoded nanoprobes using single walled carbon nanotube as the building scaffold for magnetic field guided cell imaging.

    Science.gov (United States)

    Wang, Hong; Wang, Zhuyuan; Ye, Minglang; Zong, Shenfei; Li, Mingyue; Chen, Peng; Ma, Xueqin; Cui, Yiping

    2014-02-01

    We construct a novel fluorescent, surface enhanced Raman scattering (SERS) encoded and magnetic nanoprobe for live cell imaging. To fabricate this nanoprobe, single walled carbon nanotube (SWNT) is used as the building scaffold while gold nanoparticles (Au NPs), superparamagnetic iron oxide nanoparticles (SPIONs) and quantum dots (QDs) are employed as the building blocks. Here, Au NPs serve as the SERS substrate and QDs act as the fluorescent agent. Au NPs and SPIONs are first adsorbed on the SWNT via electrostatic interactions. Then a silica layer is coated on the SWNT. Finally, QDs are attached on the silica shell. With such a structure, various optical signals can be readily encoded to the nanoprobe simply by using different Raman molecules and QDs with different emission wavelengths. Experimental results show that the as-prepared nanoprobe exhibits well fluorescence and SERS performance. Furthermore, in vitro experiments demonstrate that the nanoprobe can fulfill magnetic field guided fluorescence and SERS dual mode imaging of live cells. As a fascinating optical encoding material and a multifunctional nanoplatform, the presented nanoprobe holds genuine potential in future biosensing applications. © 2013 Published by Elsevier B.V.

  16. A comparative genomics study of genetic products potentially encoding ladderane lipid biosynthesis

    Directory of Open Access Journals (Sweden)

    Jetten Mike SM

    2009-02-01

    Full Text Available Abstract Background The fatty acids of anaerobic ammonium oxidizing (anammox bacteria contain linearly concatenated cyclobutane moieties, so far unique to biology. These moieties are under high ring strain and are synthesised by a presently unknown biosynthetic pathway. Results Gene clusters encoding enzymes of fatty acid biosynthesis in the anammox bacterium Kuenenia stuttgartiensis and 137 other organisms were analysed and compared in silico to gain further insight into the pathway of (ladderane fatty acid biosynthesis. In K. stuttgartiensis four large gene clusters encode fatty acid biosynthesis. Next to the regular enzyme complex needed for fatty acid biosynthesis (FASII, the presence of four putative S-adenosyl-methionine (SAM radical enzymes, two enzymes similar to phytoene desaturases and many divergent paralogues of β-ketoacyl-ACP synthase (fabF were unusual. Surprisingly, extensive synteny was observed with FASII gene clusters in the deltaproteobacterium Desulfotalea psychrophila. No ladderane lipids were detected in lipid extracts of this organism but we did find unusual polyunsaturated hydrocarbons (PUHC, not detected in K. stuttgartiensis. Conclusion We suggest that the unusual gene clusters of K. stuttgartiensis and D. psychrophila encode a novel pathway for anaerobic PUFA biosynthesis and that K. stuttgartiensis further processes PUFA into ladderane lipids, in similar fashion to the previously proposed route of ladderane lipid biosynthesis. However, the presence of divergent paralogues of fabF with radically different active site topologies may suggest an alternative pathway where ladderane moieties are synthesised externally and are recruited into the pathway of fatty acid biosynthesis. Reviewers This article was reviewed by Dr Michael Galperin (nominated by Prof E. Koonin, Dr Andrei Osterman and Dr Jeremy Selengut.

  17. Demonstration of an All-Optical 2-to-4 Level Encoder Based on an Optical Parametric Amplifier

    Directory of Open Access Journals (Sweden)

    Yu Liang

    2009-01-01

    Full Text Available We demonstrated a novel technique for all-optical 2-to-4 level amplitude-shift keying (ASK coding based on a fiber optical parametric amplifier. A 20-Gb/s signal is realized by multiplexing two 10-Gb/s data streams.

  18. Genetic analysis of a novel plasmid encoded durancin locus in Enterococcus durans 41D

    Science.gov (United States)

    Enterococcus durans is commonly found in the intestinal tract in humans and animals and several strains are known to produce bacteriocins. Durancin GL, a novel bacteriocin of Enterococcus durans 41D with antilisterial activity was isolated from artisanal cheese samples and its genetic determinants ...

  19. Molecular and genetic analysis of the gene encoding the Saccharomyces cerevisiae strand exchange protein Sep1.

    Science.gov (United States)

    Tishkoff, D X; Johnson, A W; Kolodner, R D

    1991-05-01

    Vegetatively grown Saccharomyces cerevisiae cells contain an activity that promotes a number of homologous pairing reactions. A major portion of this activity is due to strand exchange protein 1 (Sep1), which was originally purified as a 132,000-Mr species (R. Kolodner, D. H. Evans, and P. T. Morrison, Proc. Natl. Acad. Sci. USA 84:5560-5564, 1987). The gene encoding Sep1 was cloned, and analysis of the cloned gene revealed a 4,587-bp open reading frame capable of encoding a 175,000-Mr protein. The protein encoded by this open reading frame was overproduced and purified and had a relative molecular weight of approximately 160,000. The 160,000-Mr protein was at least as active in promoting homologous pairing as the original 132,000-Mr species, which has been shown to be a fragment of the intact 160,000-Mr Sep1 protein. The SEP1 gene mapped to chromosome VII within 20 kbp of RAD54. Three Tn10LUK insertion mutations in the SEP1 gene were characterized. sep1 mutants grew more slowly than wild-type cells, showed a two- to fivefold decrease in the rate of spontaneous mitotic recombination between his4 heteroalleles, and were delayed in their ability to return to growth after UV or gamma irradiation. Sporulation of sep1/sep1 diploids was defective, as indicated by both a 10- to 40-fold reduction in spore formation and reduced spore viability of approximately 50%. The majority of sep1/sep1 diploid cells arrested in meiosis after commitment to recombination but prior to the meiosis I cell division. Return-to-growth experiments showed that sep1/sep1 his4X/his4B diploids exhibited a five- to sixfold greater meiotic induction of His+ recombinants than did isogenic SEP1/SEP1 strains. sep1/sep1 mutants also showed an increased frequency of exchange between HIS4, LEU2, and MAT and a lack of positive interference between these markers compared with wild-type controls. The interaction between sep1, rad50, and spo13 mutations suggested that SEP1 acts in meiosis in a pathway that is

  20. Feasibility of two-way polarization encoded quantum communication in an optical fiber populated with telecom traffic

    CERN Document Server

    Xavier, G B; da Silva, T Ferreira; Temporao, G P; von der Weid, J P

    2009-01-01

    We experimentally show a two-way transmission of polarization encoded pseudo-single photons between two remote parties separated by a single 23 km optical fiber spool. Two optical classical channels are wavelength multiplexed in the same fiber and used as feedback to an active polarization drift compensation scheme. One of the classical channels contains a 10 Gb/s data stream simulating real telecom traffic. The feasibility of quantum communication is demonstrated in the fiber's two opposite directions of propagation over 6 hours of continuous operation, as well as a classical error rate in the data channel better than 1.0 x 10-9. The results are extended to show the estimated maximum transmission distance for the quantum signals based on the noise generated through Raman spontaneous scattering by up to 16 classical channels present in the fiber.

  1. Genetic diversity and population structure of genes encoding vaccine candidate antigens of Plasmodium vivax

    Directory of Open Access Journals (Sweden)

    Chenet Stella M

    2012-03-01

    Full Text Available Abstract Background A major concern in malaria vaccine development is genetic polymorphisms typically observed among Plasmodium isolates in different geographical areas across the world. Highly polymorphic regions have been observed in Plasmodium falciparum and Plasmodium vivax antigenic surface proteins such as Circumsporozoite protein (CSP, Duffy-binding protein (DBP, Merozoite surface protein-1 (MSP-1, Apical membrane antigen-1 (AMA-1 and Thrombospondin related anonymous protein (TRAP. Methods Genetic variability was assessed in important polymorphic regions of various vaccine candidate antigens in P. vivax among 106 isolates from the Amazon Region of Loreto, Peru. In addition, genetic diversity determined in Peruvian isolates was compared to population studies from various geographical locations worldwide. Results The structured diversity found in P. vivax populations did not show a geographic pattern and haplotypes from all gene candidates were distributed worldwide. In addition, evidence of balancing selection was found in polymorphic regions of the trap, dbp and ama-1 genes. Conclusions It is important to have a good representation of the haplotypes circulating worldwide when implementing a vaccine, regardless of the geographic region of deployment since selective pressure plays an important role in structuring antigen diversity.

  2. Design of 10Gbps optical encoder/decoder structure for FE-OCDMA system using SOA and opto-VLSI processors.

    Science.gov (United States)

    Aljada, Muhsen; Hwang, Seow; Alameh, Kamal

    2008-01-21

    In this paper we propose and experimentally demonstrate a reconfigurable 10Gbps frequency-encoded (1D) encoder/decoder structure for optical code division multiple access (OCDMA). The encoder is constructed using a single semiconductor optical amplifier (SOA) and 1D reflective Opto-VLSI processor. The SOA generates broadband amplified spontaneous emission that is dynamically sliced using digital phase holograms loaded onto the Opto-VLSI processor to generate 1D codewords. The selected wavelengths are injected back into the same SOA for amplifications. The decoder is constructed using single Opto-VLSI processor only. The encoded signal can successfully be retrieved at the decoder side only when the digital phase holograms of the encoder and the decoder are matched. The system performance is measured in terms of the auto-correlation and cross-correlation functions as well as the eye diagram.

  3. Method of implementing frequency-encoded NOT, OR and NOR logic operations using lithium niobate waveguide and reflecting semiconductor optical amplifiers

    Indian Academy of Sciences (India)

    Sisir Kumar Garai; Sourangshu Mukhopadhyay

    2009-11-01

    Optics has already proved its strong potentiality for the conduction of parallel logic, arithmetic and algebraic operations. In the last few decades several all-optical data processors were proposed. To implement these processors different data encoding/decoding techniques have been reported. In this context, polarization encoding technique, intensity-based encoding technique, tristate and quaternary logic operation, multivalued logic operations, symbolic substitution techniques etc. may be mentioned. Very recently, frequency encoding/decoding technique has drawn interest from the scientific community. Frequency is the fundamental character of any signal; and it remains unaltered in reflection, refraction, absorption etc. during the propagation and transmission of the signal. This is the most important advantage of frequency encoding technique over the conventional encoding techniques. In this communication the authors propose a new scheme for implementing NOT, OR and NOR logic operations. For this purpose co-propagating beams having different frequencies in C-band (1535–1560 nm) have been used for generating cascaded sum and difference frequency, exploiting the nonlinear response character of periodically poled LiNbO3 waveguide. The cross-gain modulation property of the semiconductor optical amplifier (SOA) and the wavelength conversion property of the reflecting semiconductor optical amplifiers (RSOA) are exploited here to implement the desired optical logic and arithmetic operations.

  4. Multiple-image encryption using polarized light encoding and the optical interference principle in the Fresnel-transform domain.

    Science.gov (United States)

    Wang, Qu; Guo, Qing; Zhou, Jinyun

    2013-12-20

    We propose a multiple-image encryption scheme, based on polarized light encoding and the interference principle of phase-only masks (POMs), in the Fresnel-transform (FrT) domain. In this scheme, each secret image is converted into an intensity image by polarized light encoding, where a random key image and a pixilated polarizer with random angles are employed as keys. The intensity encrypted images produced by different secret images are convolved together and then inverse Fresnel-transformed. Phase and amplitude truncations are used to generate the asymmetric decryption keys. The phase-truncated inverse FrT spectrum is sent into an interference-based encryption (IBE) system to analytically obtain two POMs. To reduce the transmission and storage load on the keys, the chaotic mapping method is employed to generate random distributions of keys for encryption and decryption. One can recover all secret images successfully only if the corresponding decryption keys, the mechanism of FrTs, and correct chaotic conditions are known. The inherent silhouette problem can be thoroughly resolved by polarized light encoding in this proposal, without using any time-consuming iterative methods. The entire encryption and decryption process can be realized digitally, or in combination with optical means. Numerical simulation results are presented to verify the effectiveness and performance of the proposed scheme.

  5. Real encoded genetic algorithm and response surface methodology to optimize production of an indolizidine alkaloid, swainsonine, from Metarhizium anisopliae.

    Science.gov (United States)

    Singh, Digar; Kaur, Gurvinder

    2013-09-01

    Response surface methodology (RSM) and artificial neural network-real encoded genetic algorithm (ANN-REGA) were employed to develop a process for fermentative swainsonine production from Metarhizium anisopliae (ARSEF 1724). The effect of finally screened process variables viz. inoculum size, oatmeal extract, glucose, and CaCl2 were investigated through central composite design and were further utilized for training sets in ANN with training and test R values of 0.99 and 0.94, respectively. ANN-REGA was finally employed to simulate the predictive swainsonine production with best evolved media composition. ANN-REGA predicted a more precise fermentation model with 103 % (shake flask) increase in alkaloid production compared to 75.62 % (shake flask) obtained with RSM model upon validation.

  6. Illumination of the Spatial Order of Intracellular pH by Genetically Encoded pH-Sensitive Sensors

    Directory of Open Access Journals (Sweden)

    Mojca Benčina

    2013-12-01

    Full Text Available Fluorescent proteins have been extensively used for engineering genetically encoded sensors that can monitor levels of ions, enzyme activities, redox potential, and metabolites. Certain fluorescent proteins possess specific pH-dependent spectroscopic features, and thus can be used as indicators of intracellular pH. Moreover, concatenated pH-sensitive proteins with target proteins pin the pH sensors to a definite location within the cell, compartment, or tissue. This study provides an overview of the continually expanding family of pH-sensitive fluorescent proteins that have become essential tools for studies of pH homeostasis and cell physiology. We describe and discuss the design of intensity-based and ratiometric pH sensors, their spectral properties and pH-dependency, as well as their performance. Finally, we illustrate some examples of the applications of pH sensors targeted at different subcellular compartments.

  7. Genetically Encoded Spy Peptide Fusion System to Detect Plasma Membrane-Localized Proteins In Vivo.

    Science.gov (United States)

    Bedbrook, Claire N; Kato, Mihoko; Ravindra Kumar, Sripriya; Lakshmanan, Anupama; Nath, Ravi D; Sun, Fei; Sternberg, Paul W; Arnold, Frances H; Gradinaru, Viviana

    2015-08-20

    Membrane proteins are the main gatekeepers of cellular state, especially in neurons, serving either to maintain homeostasis or instruct response to synaptic input or other external signals. Visualization of membrane protein localization and trafficking in live cells facilitates understanding the molecular basis of cellular dynamics. We describe here a method for specifically labeling the plasma membrane-localized fraction of heterologous membrane protein expression using channelrhodopsins as a case study. We show that the genetically encoded, covalent binding SpyTag and SpyCatcher pair from the Streptococcus pyogenes fibronectin-binding protein FbaB can selectively label membrane-localized proteins in living cells in culture and in vivo in Caenorhabditis elegans. The SpyTag/SpyCatcher covalent labeling method is highly specific, modular, and stable in living cells. We have used the binding pair to develop a channelrhodopsin membrane localization assay that is amenable to high-throughput screening for opsin discovery and engineering.

  8. Genuine genetic redundancy in maleylacetate-reductase-encoding genes involved in degradation of haloaromatic compounds by Cupriavidus necator JMP134.

    Science.gov (United States)

    Pérez-Pantoja, Danilo; Donoso, Raúl A; Sánchez, Miguel A; González, Bernardo

    2009-11-01

    Maleylacetate reductases (MAR) are required for biodegradation of several substituted aromatic compounds. To date, the functionality of two MAR-encoding genes (tfdF(I) and tfdF(II)) has been reported in Cupriavidus necator JMP134(pJP4), a known degrader of aromatic compounds. These two genes are located in tfd gene clusters involved in the turnover of 2,4-dichlorophenoxyacetate (2,4-D) and 3-chlorobenzoate (3-CB). The C. necator JMP134 genome comprises at least three other genes that putatively encode MAR (tcpD, hqoD and hxqD), but confirmation of their functionality and their role in the catabolism of haloaromatic compounds has not been assessed. RT-PCR expression analyses of C. necator JMP134 cells exposed to 2,4-D, 3-CB, 2,4,6-trichlorophenol (2,4,6-TCP) or 4-fluorobenzoate (4-FB) showed that tfdF(I) and tfdF(II) are induced by haloaromatics channelled to halocatechols as intermediates. In contrast, 2,4,6-TCP only induces tcpD, and any haloaromatic compounds tested did not induce hxqD and hqoD. However, the tcpD, hxqD and hqoD gene products showed MAR activity in cell extracts and provided the MAR function for 2,4-D catabolism when heterologously expressed in MAR-lacking strains. Growth tests for mutants of the five MAR-encoding genes in strain JMP134 showed that none of these genes is essential for degradation of the tested compounds. However, the role of tfdF(I)/tfdF(II) and tcpD genes in the expression of MAR activity during catabolism of 2,4-D and 2,4,6-TCP, respectively, was confirmed by enzyme activity tests in mutants. These results reveal a striking example of genetic redundancy in the degradation of aromatic compounds.

  9. Microsatellite-encoded domain in rodent Sry functions as a genetic capacitor to enable the rapid evolution of biological novelty.

    Science.gov (United States)

    Chen, Yen-Shan; Racca, Joseph D; Sequeira, Paul W; Phillips, Nelson B; Weiss, Michael A

    2013-08-13

    The male program of therian mammals is determined by Sry, a transcription factor encoded by the Y chromosome. Specific DNA binding is mediated by a high mobility group (HMG) box. Expression of Sry in the gonadal ridge activates a Sox9-dependent gene regulatory network leading to testis formation. A subset of Sry alleles in superfamily Muroidea (order Rodentia) is remarkable for insertion of an unstable DNA microsatellite, most commonly encoding (as in mice) a CAG repeat-associated glutamine-rich domain. We provide evidence, based on an embryonic pre-Sertoli cell line, that this domain functions at a threshold length as a genetic capacitor to facilitate accumulation of variation elsewhere in the protein, including the HMG box. The glutamine-rich domain compensates for otherwise deleterious substitutions in the box and absence of nonbox phosphorylation sites to ensure occupancy of DNA target sites. Such compensation enables activation of a male transcriptional program despite perturbations to the box. Whereas human SRY requires nucleocytoplasmic shuttling and coupled phosphorylation, mouse Sry contains a defective nuclear export signal analogous to a variant human SRY associated with inherited sex reversal. We propose that the rodent glutamine-rich domain has (i) fostered accumulation of cryptic intragenic variation and (ii) enabled unmasking of such variation due to DNA replicative slippage. This model highlights genomic contingency as a source of protein novelty at the edge of developmental ambiguity and may underlie emergence of non-Sry-dependent sex determination in the radiation of Muroidea.

  10. Genetic Structure Associated with blaOXA-18, Encoding a Clavulanic Acid-Inhibited Extended-Spectrum Oxacillinase▿

    Science.gov (United States)

    Naas, Thierry; Namdari, Fatemeh; Bogaerts, Pierre; Huang, Te-Din; Glupczynski, Youri; Nordmann, Patrice

    2008-01-01

    The genetic environment of the blaOXA-18 gene encoding a peculiar clavulanic acid-inhibitable Ambler class D extended-spectrum β-lactamase was determined from the prototype OXA-18-producing Pseudomonas aeruginosa MUS clinical isolate. An 8.2-kb genomic DNA fragment containing blaOXA-18 was cloned from P. aeruginosa MUS. Although most oxacillinases are located in integrons, blaOXA-18 lacked gene cassette-specific features. It was bracketed by two duplicated sequences containing ISCR19, a novel insertion sequence of the ISCR family of mobile elements; ΔintI1, a truncated integrase gene; and a truncated Δaac6′-Ib gene cassette. It is likely that ISCR19 was at the origin of the blaOXA-18 gene mobilization by a rolling-circle transposition event followed by homologous recombination. Furthermore, analysis of the cloned genomic DNA fragment revealed the presence of the integron-containing blaOXA-20 gene. Concomitantly, three P. aeruginosa clinical isolates, displaying a synergy image as determined by double-disk diffusion tests on cloxacillin-containing plates, were isolated from three patients hospitalized in different wards over a 9-month period at the Saint-Luc University hospital (Brussels, Belgium). These isolates were positive by PCR for blaOXA-18 and blaOXA-20 genes, genetically related to P. aeruginosa MUS as determined by pulsed-field gel electrophoresis, and carried the same blaOXA-18/blaOXA-20-associated genetic structures. This report characterized the genetic elements likely at the origin of blaOXA-18 gene mobilization in P. aeruginosa and suggests the spread of oxacillin-type extended-spectrum β-lactamases in P. aeruginosa at the Saint-Luc University hospital of Brussels, Belgium. PMID:18663027

  11. Experimental study of the use of multiband acousto-optic filters for spectral encoding / decoding the optical signals

    Science.gov (United States)

    Proklov, V. V.; Byshevski-Konopko, O. A.; Filatov, A. L.; Lugovskoi, A. V.; Pisarevsky, Yu V.

    2016-08-01

    A prototype of the acousto-optic (AO) decoder of optical signals is created on the base of the multiband AO filter. The joint work of the decoder with the developed previously AO coder has been verified experimentally. The main qualitative and quantitate characteristics of the spectral coding and decoding by Walsh sequences of the industrial LED radiation in the near infrared range are investigated. It is shown, that in the proposed data transmission system realization Signal-to-Interference Ratio (SIR) is not less than 13 dB.

  12. Focusing on optic tectum circuitry through the lens of genetics

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    Nevin Linda M

    2010-09-01

    Full Text Available Abstract The visual pathway is tasked with processing incoming signals from the retina and converting this information into adaptive behavior. Recent studies of the larval zebrafish tectum have begun to clarify how the 'micro-circuitry' of this highly organized midbrain structure filters visual input, which arrives in the superficial layers and directs motor output through efferent projections from its deep layers. The new emphasis has been on the specific function of neuronal cell types, which can now be reproducibly labeled, imaged and manipulated using genetic and optical techniques. Here, we discuss recent advances and emerging experimental approaches for studying tectal circuits as models for visual processing and sensorimotor transformation by the vertebrate brain.

  13. Live imaging in Drosophila: The optical and genetic toolkits.

    Science.gov (United States)

    Rebollo, Elena; Karkali, Katerina; Mangione, Federica; Martín-Blanco, Enrique

    2014-06-15

    Biological imaging based on light microscopy comes at the core of the methods that let us understanding morphology and its dynamics in synergy to the spatiotemporal distribution of cellular and molecular activities as the organism develops and becomes functional. Non-linear optical tools and superesolution methodologies are under constant development and their applications to live imaging of whole organisms keep improving as we speak. Genetically coded biosensors, multicolor clonal methods and optogenetics in different organisms and, in particular, in Drosophila follow equivalent paths. We anticipate a brilliant future for live imaging providing the roots for the holistic understanding, rather than for individual parts, of development and function at the whole-organism level.

  14. [Clinical and molecular genetic analysis of hereditary optic neuropathies].

    Science.gov (United States)

    Avetisov, S É; Sheremet, N L; Vorob'eva, O K; Eliseeva, É G; Chukhrova, A L; Loginova, A N; Khanakova, N A; Poliakov, A V

    2013-01-01

    DNA samples of 50 patients with optic neuropathy (ON) associated with congenital cataract were studied to find 3 major mt-DNA mutations (m.11778G>A, m.3460G>A, m.14484T>C), mutations in "hot" regions of OPA 1 gene (exons 8, 14, 15, 16, 18, 27, 28) and in the entire coding sequence of OPA3 gene for molecular genetic confirmation of diagnosis of hereditary Leber and autosomal dominant ON. Primary mutations of mtDNA responsible for hereditary Leber ON were found in 16 patients (32%). Pathogenic mutations of OPAl gene (c.869G>A and c. 2850delT) were identified in 2 patients (4%), these mutations were not found in the literature. OPA3 gene mutations were not revealed.

  15. Nanoporous hard data: optical encoding of information within nanoporous anodic alumina photonic crystals

    Science.gov (United States)

    Santos, Abel; Law, Cheryl Suwen; Pereira, Taj; Losic, Dusan

    2016-04-01

    Herein, we present a method for storing binary data within the spectral signature of nanoporous anodic alumina photonic crystals. A rationally designed multi-sinusoidal anodisation approach makes it possible to engineer the photonic stop band of nanoporous anodic alumina with precision. As a result, the transmission spectrum of these photonic nanostructures can be engineered to feature well-resolved and selectively positioned characteristic peaks across the UV-visible spectrum. Using this property, we implement an 8-bit binary code and assess the versatility and capability of this system by a series of experiments aiming to encode different information within the nanoporous anodic alumina photonic crystals. The obtained results reveal that the proposed nanosized platform is robust, chemically stable, versatile and has a set of unique properties for data storage, opening new opportunities for developing advanced nanophotonic tools for a wide range of applications, including sensing, photonic tagging, self-reporting drug releasing systems and secure encoding of information.Herein, we present a method for storing binary data within the spectral signature of nanoporous anodic alumina photonic crystals. A rationally designed multi-sinusoidal anodisation approach makes it possible to engineer the photonic stop band of nanoporous anodic alumina with precision. As a result, the transmission spectrum of these photonic nanostructures can be engineered to feature well-resolved and selectively positioned characteristic peaks across the UV-visible spectrum. Using this property, we implement an 8-bit binary code and assess the versatility and capability of this system by a series of experiments aiming to encode different information within the nanoporous anodic alumina photonic crystals. The obtained results reveal that the proposed nanosized platform is robust, chemically stable, versatile and has a set of unique properties for data storage, opening new opportunities for

  16. Assessing T lymphocyte function and differentiation by genetically encoded reporter systems.

    Science.gov (United States)

    Hoekstra, Mirjam E; Dijkgraaf, Feline E; Schumacher, Ton N; Rohr, Jan C

    2015-07-01

    Upon infection, antigen-specific T lymphocytes become activated, proliferate, differentiate, and acquire various effector functions. Much of our understanding of the molecular mechanisms underlying these processes derives from studies leveraging gene deletion, RNAi, and overexpression approaches. However, these perturbations do not inform on the regulation of gene activity under physiological conditions. Genetic reporter systems that couple biological events to detectable output signals are capable of providing this information. Here, we review the reporter approaches being currently used to investigate various aspects of T cell behavior, and discuss advantages and disadvantages inherent to different designs. We outline emerging applications based on recent advances in other fields, and highlight the potential of synthetic biology and genome engineering to address open questions in the field.

  17. Genetic variation in genes encoding airway epithelial potassium channels is associated with chronic rhinosinusitis in a pediatric population.

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    Michael T Purkey

    Full Text Available BACKGROUND: Apical potassium channels regulate ion transport in airway epithelial cells and influence air surface liquid (ASL hydration and mucociliary clearance (MCC. We sought to identify whether genetic variation within genes encoding airway potassium channels is associated with chronic rhinosinusitis (CRS. METHODS: Single nucleotide polymorphism (SNP genotypes for selected potassium channels were derived from data generated on the Illumnia HumanHap550 BeadChip or Illumina Human610-Quad BeadChip for 828 unrelated individuals diagnosed with CRS and 5,083 unrelated healthy controls from the Children's Hospital of Philadelphia (CHOP. Statistical analysis was performed with set-based tests using PLINK, and corrected for multiple testing. RESULTS: Set-based case control analysis revealed the gene KCNMA1 was associated with CRS in our Caucasian subset of the cohort (598 CRS cases and 3,489 controls; p = 0.022, based on 10,000 permutations. In addition there was borderline evidence that the gene KCNQ5 (p = 0.0704 was associated with the trait in our African American subset of the cohort (230 CRS cases and 1,594 controls. In addition to the top significant SNPs rs2917454 and rs6907229, imputation analysis uncovered additional genetic variants in KCNMA1 and in KCNQ5 that were associated with CRS. CONCLUSIONS: We have implicated two airway epithelial potassium channels as novel susceptibility loci in contributing to the pathogenesis of CRS.

  18. Generation of a genetically encoded marker of rod photoreceptor outer segment growth and renewal

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    John J. Willoughby

    2011-10-01

    Vertebrate photoreceptors are specialized light sensing neurons. The photoreceptor outer segment is a highly modified cilium where photons of light are transduced into a chemical and electrical signal. The outer segment has the typical cilary axoneme but, in addition, it has a large number of densely packed, stacked, intramembranous discs. The molecular and cellular mechanisms that contribute to vertebrate photoreceptor outer segment morphogenesis are still largely unknown. Unlike typical cilia, the outer segment is continuously regenerated or renewed throughout the life of the animal through the combined process of distal outer segment shedding and proximal outer segment growth. The process of outer segment renewal was discovered over forty years ago, but we still lack an understanding of how photoreceptors renew their outer segments and few, if any, molecular mechanisms that regulate outer segment growth or shedding have been described. Our lack of progress in understanding how photoreceptors renew their outer segments has been hampered by the difficulty in measuring rates of renewal. We have created a new method that uses heat-shock induction of a fluorescent protein that can be used to rapidly measure outer segment growth rates. We describe this method, the stable transgenic line we created, and the growth rates observed in larval and adult rod photoreceptors using this new method. This new method will allow us to begin to define the genetic and molecular mechanisms that regulate rod outer segment renewal, a crucial aspect of photoreceptor function and, possibly, viability.

  19. Optimization of a whole-cell biocatalyst by employing genetically encoded product sensors inside nanolitre reactors

    Science.gov (United States)

    Meyer, Andreas; Pellaux, René; Potot, Sébastien; Becker, Katja; Hohmann, Hans-Peter; Panke, Sven; Held, Martin

    2015-08-01

    Microcompartmentalization offers a high-throughput method for screening large numbers of biocatalysts generated from genetic libraries. Here we present a microcompartmentalization protocol for benchmarking the performance of whole-cell biocatalysts. Gel capsules served as nanolitre reactors (nLRs) for the cultivation and analysis of a library of Bacillus subtilis biocatalysts. The B. subtilis cells, which were co-confined with E. coli sensor cells inside the nLRs, converted the starting material cellobiose into the industrial product vitamin B2. Product formation triggered a sequence of reactions in the sensor cells: (1) conversion of B2 into flavin mononucleotide (FMN), (2) binding of FMN by a RNA riboswitch and (3) self-cleavage of RNA, which resulted in (4) the synthesis of a green fluorescent protein (GFP). The intensity of GFP fluorescence was then used to isolate B. subtilis variants that convert cellobiose into vitamin B2 with elevated efficiency. The underlying design principles of the assay are general and enable the development of similar protocols, which ultimately will speed up the optimization of whole-cell biocatalysts.

  20. Analog time-reversed ultrasonically encoded (TRUE) optical focusing inside scattering media with high power gain (Conference Presentation)

    Science.gov (United States)

    Ma, Cheng; Xu, Xiao; Wang, Lihong V.

    2016-03-01

    Focusing light deep inside scattering media plays a key role in such biomedical applications as high resolution optical imaging, control, and therapy. In recent years, wavefront shaping technologies have come a long way in controlling light propagation in complex media. A prominent example is time-reversed ultrasonically encoded (TRUE) focusing, which allows noninvasive introduction of "guide stars" inside biological tissue to guide light focusing. By measuring the optical wavefront emanating from an ultrasound focus created at the target location, TRUE determines the desired wavefront non-iteratively, and achieves focusing at the target position via a subsequent optical time reversal. Compared to digital counterparts that employ slow electronic spatial light modulators and cameras, analog TRUE focusing relies on nonlinear photorefractive crystals that inherently accommodate more spatial modes and eliminate the troublesome alignment and data transfer required by digital approaches. However, analog TRUE focusing suffers from its small gain, defined as the energy or power ratio between the focusing and probing beams in the focal volume. Here, by implementing a modified analog TRUE focusing scheme that squeezes the duration of the time-reversed photon packet below the carrier-recombination-limited hologram decay time of the crystal, we demonstrated a photon flux amplification much greater than unity at a preset focal voxel in between two scattering layers. Although the energy gain was still below unity, the unprecedented power gain will nevertheless benefit new biomedical applications.

  1. PEP1 of Arabis alpina is encoded by two overlapping genes that contribute to natural genetic variation in perennial flowering.

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    Maria C Albani

    Full Text Available Higher plants exhibit a variety of different life histories. Annual plants live for less than a year and after flowering produce seeds and senesce. By contrast perennials live for many years, dividing their life cycle into episodes of vegetative growth and flowering. Environmental cues control key check points in both life histories. Genes controlling responses to these cues exhibit natural genetic variation that has been studied most in short-lived annuals. We characterize natural genetic variation conferring differences in the perennial life cycle of Arabis alpina. Previously the accession Pajares was shown to flower after prolonged exposure to cold (vernalization and only for a limited period before returning to vegetative growth. We describe five accessions of A. alpina that do not require vernalization to flower and flower continuously. Genetic complementation showed that these accessions carry mutant alleles at PERPETUAL FLOWERING 1 (PEP1, which encodes a MADS box transcription factor orthologous to FLOWERING LOCUS C in the annual Arabidopsis thaliana. Each accession carries a different mutation at PEP1, suggesting that such variation has arisen independently many times. Characterization of these alleles demonstrated that in most accessions, including Pajares, the PEP1 locus contains a tandem arrangement of a full length and a partial PEP1 copy, which give rise to two full-length transcripts that are differentially expressed. This complexity contrasts with the single gene present in A. thaliana and might contribute to the more complex expression pattern of PEP1 that is associated with the perennial life-cycle. Our work demonstrates that natural accessions of A. alpina exhibit distinct life histories conferred by differences in PEP1 activity, and that continuous flowering forms have arisen multiple times by inactivation of the floral repressor PEP1. Similar phenotypic variation is found in other herbaceous perennial species, and our results

  2. The use of a genetic algorithm in optical thin film design and optimisation

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    Efrem K. Ejigu

    2010-07-01

    Full Text Available We used a genetic algorithm in the design and optimisation of optical thin films and present the effects of the choice of variables, refractive index and optical thickness, in both applications of this algorithm, in this paper. The Fourier transform optical thin film design method was used to create a starting population, which was later optimised by the genetic algorithm. In the genetic algorithm design application, the effect of the choice of variable was not distinct, as it depended on the type of design specification. In the genetic algorithm optimisation application, the choice of refractive index as a variable showed a better performance than that of optical thickness. The results of this study indicate that a genetic algorithm is more effective in the design application than in the optimisation application of optical thin film synthesis.

  3. Optical double image security using random phase fractional Fourier domain encoding and phase-retrieval algorithm

    Science.gov (United States)

    Rajput, Sudheesh K.; Nishchal, Naveen K.

    2017-04-01

    We propose a novel security scheme based on the double random phase fractional domain encoding (DRPE) and modified Gerchberg-Saxton (G-S) phase retrieval algorithm for securing two images simultaneously. Any one of the images to be encrypted is converted into a phase-only image using modified G-S algorithm and this function is used as a key for encrypting another image. The original images are retrieved employing the concept of known-plaintext attack and following the DRPE decryption steps with all correct keys. The proposed scheme is also used for encryption of two color images with the help of convolution theorem and phase-truncated fractional Fourier transform. With some modification, the scheme is extended for simultaneous encryption of gray-scale and color images. As a proof-of-concept, simulation results have been presented for securing two gray-scale images, two color images, and simultaneous gray-scale and color images.

  4. Optically encoded microspheres for high-throughput analysis of genes and proteins

    Science.gov (United States)

    Gao, Xiaohu; Han, Mingyong; Nie, Shuming

    2002-06-01

    We have developed a novel optical coding technology for massively parallel and high-throughput analysis of biological molecules. Its unprecedented multiplexing capability is based on the unique optical properties of semiconductor quantum dots (QDs) and the ability to incorporate multicolor QQs into small polymer beads at precisely controlled ratios. The use of 10 intensity levels and 6 colors could theoretically code one million nucleic acid or protein sequences. Imaging and spectroscopic studies indicate that the QD tagged beads are highly uniform and reproducible, yielding bead identification accuracies as high as 99.99 percent under favorable conditions. DNA hybridization results demonstrate that the coding and target signals can be simultaneously read at the single-bead level. This spectral coding technology is expected to open new opportunities in gene expression studies, high-throughput screening, and medical diagnosis.

  5. Analysis of All-Optical State Generator for "Encoding a Qubit in an Oscillator"

    Science.gov (United States)

    Policarpo, S. C.; Vasconcelos, H. M.

    2016-06-01

    The fault-tolerant quantum computation scheme proposed by Gottesman (Phys. Rev. A 64, 012310 (2001)) can be performed using relatively simple linear optical resources and provides a natural protection against arbitrary small errors. On the other hand, preparing the initial GKP states is a difficult task. A few proposals to generate GKP states have been done over the last years. Our objective here is to analyze the performance of a particular GKP generator that uses cat states, linear optical devices, squeezing, and homodyne detection. We use numerical simulations to study the behavior of the fidelity between the generated and the ideal states and show that the proposal in consideration is indeed a promising scheme.

  6. Enhanced intercarrier interference mitigation based on encoded bit-sequence distribution inside optical superchannels

    Science.gov (United States)

    Torres, Jhon James Granada; Soto, Ana María Cárdenas; González, Neil Guerrero

    2016-10-01

    In the context of gridless optical multicarrier systems, we propose a method for intercarrier interference (ICI) mitigation which allows bit error correction in scenarios of nonspectral flatness between the subcarriers composing the multicarrier system and sub-Nyquist carrier spacing. We propose a hybrid ICI mitigation technique which exploits the advantages of signal equalization at both levels: the physical level for any digital and analog pulse shaping, and the bit-data level and its ability to incorporate advanced correcting codes. The concatenation of these two complementary techniques consists of a nondata-aided equalizer applied to each optical subcarrier, and a hard-decision forward error correction applied to the sequence of bits distributed along the optical subcarriers regardless of prior subchannel quality assessment as performed in orthogonal frequency-division multiplexing modulations for the implementation of the bit-loading technique. The impact of the ICI is systematically evaluated in terms of bit-error-rate as a function of the carrier frequency spacing and the roll-off factor of the digital pulse-shaping filter for a simulated 3×32-Gbaud single-polarization quadrature phase shift keying Nyquist-wavelength division multiplexing system. After the ICI mitigation, a back-to-back error-free decoding was obtained for sub-Nyquist carrier spacings of 28.5 and 30 GHz and roll-off values of 0.1 and 0.4, respectively.

  7. Commensal E. coli as an Important Reservoir of Resistance Encoding Genetic Elements

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    Azam Mahmoudi-Aznaveh

    2013-11-01

    Full Text Available Background: Diarrheagenic E. coli is the most important cause of diarrhea in children and is a public health concern in developing countries. A major public problem is acquisition and transmission of antimicrobial resistance via mobile genetic elements including plasmids, conjugative transposons, and integrons which may occur through horizontal gene transfer. Objectives: The aim of this study was to investigate the distribution of class 1 and 2 integrons among commensal and enteropathogenic E. coli isolates and assess the role of commensal E. coli population as a reservoir in the acquisition and transmission of antimicrobial resistance. Materials and Methods: Swabs were collected directly from stool samples of the children with diarrhea admitted to three hospitals in Tehran, Iran during July 2012 through October 2012. Antimicrobial susceptibility testing and PCR analysis were performed for analysis of the resistance pattern and integron content of isolates. Results: A total of 20 enteropathogenic E.coli (identified as eae+stx1-stx2- and 20 commensal E.coli were selected for analysis. The resistance pattern in commensal and pathogenic E.coli was very similar. In both groups a high rate of resistance was seen to tetracycline, streptomycin, cotrimoxazole, nalidixic acid, and minocycline. Of 20 EPEC strains, 3 strains (15 % and 1 strain (5% had positive results for int and hep genes, respectively. Among 20 commensal, 65% (13 strains and 10% (2 strains had positive results for int and hep genes, respectively. Conclusions: The higher rate of class 1 integron occurrence among commensal population proposes the commensal intestinal organisms as a potential reservoir of mobile resistance gene elements which could transfer the resistance gene cassettes to other pathogenic and/or nonpathogenic organisms in the intestinal lumen at different occasions.

  8. Genetically encoded fluorescent probe to visualize intracellular phosphatidylinositol 3,5-bisphosphate localization and dynamics.

    Science.gov (United States)

    Li, Xinran; Wang, Xiang; Zhang, Xiaoli; Zhao, Mingkun; Tsang, Wai Lok; Zhang, Yanling; Yau, Richard Gar Wai; Weisman, Lois S; Xu, Haoxing

    2013-12-24

    Phosphatidylinositol 3,5-bisphosphate [PI(3,5)P2] is a low-abundance phosphoinositide presumed to be localized to endosomes and lysosomes, where it recruits cytoplasmic peripheral proteins and regulates endolysosome-localized membrane channel activity. Cells lacking PI(3,5)P2 exhibit lysosomal trafficking defects, and human mutations in the PI(3,5)P2-metabolizing enzymes cause lysosome-related diseases. The spatial and temporal dynamics of PI(3,5)P2, however, remain unclear due to the lack of a reliable detection method. Of the seven known phosphoinositides, only PI(3,5)P2 binds, in the low nanomolar range, to a cytoplasmic phosphoinositide-interacting domain (ML1N) to activate late endosome and lysosome (LEL)-localized transient receptor potential Mucolipin 1 (TRPML1) channels. Here, we report the generation and characterization of a PI(3,5)P2-specific probe, generated by the fusion of fluorescence tags to the tandem repeats of ML1N. The probe was mainly localized to the membranes of Lamp1-positive compartments, and the localization pattern was dynamically altered by either mutations in the probe, or by genetically or pharmacologically manipulating the cellular levels of PI(3,5)P2. Through the use of time-lapse live-cell imaging, we found that the localization of the PI(3,5)P2 probe was regulated by serum withdrawal/addition, undergoing rapid changes immediately before membrane fusion of two LELs. Our development of a PI(3,5)P2-specific probe may facilitate studies of both intracellular signal transduction and membrane trafficking in the endosomes and lysosomes.

  9. Multimodal swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography at 400 kHz

    Science.gov (United States)

    El-Haddad, Mohamed T.; Joos, Karen M.; Patel, Shriji N.; Tao, Yuankai K.

    2017-02-01

    Multimodal imaging systems that combine scanning laser ophthalmoscopy (SLO) and optical coherence tomography (OCT) have demonstrated the utility of concurrent en face and volumetric imaging for aiming, eye tracking, bulk motion compensation, mosaicking, and contrast enhancement. However, this additional functionality trades off with increased system complexity and cost because both SLO and OCT generally require dedicated light sources, galvanometer scanners, relay and imaging optics, detectors, and control and digitization electronics. We previously demonstrated multimodal ophthalmic imaging using swept-source spectrally encoded SLO and OCT (SS-SESLO-OCT). Here, we present system enhancements and a new optical design that increase our SS-SESLO-OCT data throughput by >7x and field-of-view (FOV) by >4x. A 200 kHz 1060 nm Axsun swept-source was optically buffered to 400 kHz sweep-rate, and SESLO and OCT were simultaneously digitized on dual input channels of a 4 GS/s digitizer at 1.2 GS/s per channel using a custom k-clock. We show in vivo human imaging of the anterior segment out to the limbus and retinal fundus over a >40° FOV. In addition, nine overlapping volumetric SS-SESLO-OCT volumes were acquired under video-rate SESLO preview and guidance. In post-processing, all nine SESLO images and en face projections of the corresponding OCT volumes were mosaicked to show widefield multimodal fundus imaging with a >80° FOV. Concurrent multimodal SS-SESLO-OCT may have applications in clinical diagnostic imaging by enabling aiming, image registration, and multi-field mosaicking and benefit intraoperative imaging by allowing for real-time surgical feedback, instrument tracking, and overlays of computationally extracted image-based surrogate biomarkers of disease.

  10. A genetically encoded FRET lactate sensor and its use to detect the Warburg effect in single cancer cells.

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    Alejandro San Martín

    Full Text Available Lactate is shuttled between and inside cells, playing metabolic and signaling roles in healthy tissues. Lactate is also a harbinger of altered metabolism and participates in the pathogenesis of inflammation, hypoxia/ischemia, neurodegeneration and cancer. Many tumor cells show high rates of lactate production in the presence of oxygen, a phenomenon known as the Warburg effect, which has diagnostic and possibly therapeutic implications. In this article we introduce Laconic, a genetically-encoded Forster Resonance Energy Transfer (FRET-based lactate sensor designed on the bacterial transcription factor LldR. Laconic quantified lactate from 1 µM to 10 mM and was not affected by glucose, pyruvate, acetate, betahydroxybutyrate, glutamate, citrate, α-ketoglutarate, succinate, malate or oxalacetate at concentrations found in mammalian cytosol. Expressed in astrocytes, HEK cells and T98G glioma cells, the sensor allowed dynamic estimation of lactate levels in single cells. Used in combination with a blocker of the monocarboxylate transporter MCT, the sensor was capable of discriminating whether a cell is a net lactate producer or a net lactate consumer. Application of the MCT-block protocol showed that the basal rate of lactate production is 3-5 fold higher in T98G glioma cells than in normal astrocytes. In contrast, the rate of lactate accumulation in response to mitochondrial inhibition with sodium azide was 10 times lower in glioma than in astrocytes, consistent with defective tumor metabolism. A ratio between the rate of lactate production and the rate of azide-induced lactate accumulation, which can be estimated reversibly and in single cells, was identified as a highly sensitive parameter of the Warburg effect, with values of 4.1 ± 0.5 for T98G glioma cells and 0.07 ± 0.007 for astrocytes. In summary, this article describes a genetically-encoded sensor for lactate and its use to measure lactate concentration, lactate flux, and the Warburg

  11. Optimal microscopic systems for long-term imaging of intracellular calcium using a ratiometric genetically-encoded calcium indicator.

    Science.gov (United States)

    Miyamoto, Akitoshi; Bannai, Hiroko; Michikawa, Takayuki; Mikoshiba, Katsuhiko

    2013-05-03

    Monitoring the pattern of intracellular Ca(2+) signals that control many diverse cellular processes is essential for understanding regulatory mechanisms of cellular functions. Various genetically encoded Ca(2+) indicators (GECIs) are used for monitoring intracellular Ca(2+) changes under several types of microscope systems. However, it has not yet been explored which microscopic system is ideal for long-term imaging of the spatiotemporal patterns of Ca(2+) signals using GECIs. We here compared the Ca(2+) signals reported by a fluorescence resonance energy transfer (FRET)-based ratiometric GECI, yellow cameleon 3.60 (YC3.60), stably expressed in DT40 B lymphocytes, using three different imaging systems. These systems included a wide-field fluorescent microscope, a multipoint scanning confocal system, and a single-point scanning confocal system. The degree of photobleaching and the signal-to-noise ratio of YC3.60 in DT40 cells were highly dependent on the fluorescence excitation method, although the total illumination energy was maintained at a constant level within each of the imaging systems. More strikingly, the Ca(2+) responses evoked by B-cell antigen receptor stimulation in YC3.60-expressing DT40 cells were different among the imaging systems, and markedly affected by the illumination power used. Our results suggest that optimization of the imaging system, including illumination and acquisition conditions, is crucial for accurate visualization of intracellular Ca(2+) signals.

  12. Use of genetically-encoded calcium indicators for live cell calcium imaging and localization in virus-infected cells.

    Science.gov (United States)

    Perry, Jacob L; Ramachandran, Nina K; Utama, Budi; Hyser, Joseph M

    2015-11-15

    Calcium signaling is a ubiquitous and versatile process involved in nearly every cellular process, and exploitation of host calcium signals is a common strategy used by viruses to facilitate replication and cause disease. Small molecule fluorescent calcium dyes have been used by many to examine changes in host cell calcium signaling and calcium channel activation during virus infections, but disadvantages of these dyes, including poor loading and poor long-term retention, complicate analysis of calcium imaging in virus-infected cells due to changes in cell physiology and membrane integrity. The recent expansion of genetically-encoded calcium indicators (GECIs), including blue and red-shifted color variants and variants with calcium affinities appropriate for calcium storage organelles like the endoplasmic reticulum (ER), make the use of GECIs an attractive alternative for calcium imaging in the context of virus infections. Here we describe the development and testing of cell lines stably expressing both green cytoplasmic (GCaMP5G and GCaMP6s) and red ER-targeted (RCEPIAer) GECIs. Using three viruses (rotavirus, poliovirus and respiratory syncytial virus) previously shown to disrupt host calcium homeostasis, we show the GECI cell lines can be used to detect simultaneous cytoplasmic and ER calcium signals. Further, we demonstrate the GECI expression has sufficient stability to enable long-term confocal imaging of both cytoplasmic and ER calcium during the course of virus infections.

  13. Imaging intracellular Ca²⁺ signals in striatal astrocytes from adult mice using genetically-encoded calcium indicators.

    Science.gov (United States)

    Jiang, Ruotian; Haustein, Martin D; Sofroniew, Michael V; Khakh, Baljit S

    2014-11-19

    Astrocytes display spontaneous intracellular Ca(2+) concentration fluctuations ([Ca(2+)]i) and in several settings respond to neuronal excitation with enhanced [Ca(2+)]i signals. It has been proposed that astrocytes in turn regulate neurons and blood vessels through calcium-dependent mechanisms, such as the release of signaling molecules. However, [Ca(2+)]i imaging in entire astrocytes has only recently become feasible with genetically encoded calcium indicators (GECIs) such as the GCaMP series. The use of GECIs in astrocytes now provides opportunities to study astrocyte [Ca(2+)]i signals in detail within model microcircuits such as the striatum, which is the largest nucleus of the basal ganglia. In the present report, detailed surgical methods to express GECIs in astrocytes in vivo, and confocal imaging approaches to record [Ca(2+)]i signals in striatal astrocytes in situ, are described. We highlight precautions, necessary controls and tests to determine if GECI expression is selective for astrocytes and to evaluate signs of overt astrocyte reactivity. We also describe brain slice and imaging conditions in detail that permit reliable [Ca(2+)]i imaging in striatal astrocytes in situ. The use of these approaches revealed the entire territories of single striatal astrocytes and spontaneous [Ca(2+)]i signals within their somata, branches and branchlets. The further use and expansion of these approaches in the striatum will allow for the detailed study of astrocyte [Ca(2+)]i signals in the striatal microcircuitry.

  14. Global connectivity of hub residues in Oncoprotein structures encodes genetic factors dictating personalized drug response to targeted Cancer therapy

    Science.gov (United States)

    Soundararajan, Venky; Aravamudan, Murali

    2014-12-01

    The efficacy and mechanisms of therapeutic action are largely described by atomic bonds and interactions local to drug binding sites. Here we introduce global connectivity analysis as a high-throughput computational assay of therapeutic action - inspired by the Google page rank algorithm that unearths most ``globally connected'' websites from the information-dense world wide web (WWW). We execute short timescale (30 ps) molecular dynamics simulations with high sampling frequency (0.01 ps), to identify amino acid residue hubs whose global connectivity dynamics are characteristic of the ligand or mutation associated with the target protein. We find that unexpected allosteric hubs - up to 20Å from the ATP binding site, but within 5Å of the phosphorylation site - encode the Gibbs free energy of inhibition (ΔGinhibition) for select protein kinase-targeted cancer therapeutics. We further find that clinically relevant somatic cancer mutations implicated in both drug resistance and personalized drug sensitivity can be predicted in a high-throughput fashion. Our results establish global connectivity analysis as a potent assay of protein functional modulation. This sets the stage for unearthing disease-causal exome mutations and motivates forecast of clinical drug response on a patient-by-patient basis. We suggest incorporation of structure-guided genetic inference assays into pharmaceutical and healthcare Oncology workflows.

  15. Inhibition of exotoxin production by mobile genetic element SCCmec-encoded psm-mec RNA is conserved in staphylococcal species.

    Science.gov (United States)

    Ikuo, Mariko; Nagano, Gentaro; Saito, Yuki; Mao, Han; Sekimizu, Kazuhisa; Kaito, Chikara

    2014-01-01

    Staphylococcal species acquire antibiotic resistance by incorporating the mobile-genetic element SCCmec. We previously found that SCCmec-encoded psm-mec RNA suppresses exotoxin production as a regulatory RNA, and the psm-mec translation product increases biofilm formation in Staphylococcus aureus. Here, we examined whether the regulatory role of psm-mec on host bacterial virulence properties is conserved among other staphylococcal species, S. epidermidis and S. haemolyticus, both of which are important causes of nosocomial infections. In S. epidermidis, introduction of psm-mec decreased the production of cytolytic toxins called phenol-soluble modulins (PSMs) and increased biofilm formation. Introduction of psm-mec with a stop-codon mutation that did not express PSM-mec protein but did express psm-mec RNA also decreased PSM production, but did not increase biofilm formation. Thus, the psm-mec RNA inhibits PSM production, whereas the PSM-mec protein increases biofilm formation in S. epidermidis. In S. haemolyticus, introduction of psm-mec decreased PSM production, but did not affect biofilm formation. The mutated psm-mec with a stop-codon also caused the same effect. Thus, the psm-mec RNA also inhibits PSM production in S. haemolyticus. These findings suggest that the inhibitory role of psm-mec RNA on exotoxin production is conserved among staphylococcal species, although the stimulating effect of the psm-mec gene on biofilm formation is not conserved.

  16. Redesign of genetically encoded biosensors for monitoring mitochondrial redox status in a broad range of model eukaryotes.

    Science.gov (United States)

    Albrecht, Simone C; Sobotta, Mirko C; Bausewein, Daniela; Aller, Isabel; Hell, Rüdiger; Dick, Tobias P; Meyer, Andreas J

    2014-03-01

    The development of genetically encoded redox biosensors has paved the way toward chemically specific, quantitative, dynamic, and compartment-specific redox measurements in cells and organisms. In particular, redox-sensitive green fluorescent proteins (roGFPs) have attracted major interest as tools to monitor biological redox changes in real time and in vivo. Most recently, the engineering of a redox relay that combines glutaredoxin (Grx) with roGFP2 as a translational fusion (Grx1-roGFP2) led to a biosensor for the glutathione redox potential (EGSH ). The expression of this probe in mitochondria is of particular interest as mitochondria are the major source of oxidants, and their redox status is closely connected to cell fate decisions. While Grx1-roGFP2 can be expressed in mammalian mitochondria, it fails to enter mitochondria in various nonmammalian model organisms. Here we report that inversion of domain order from Grx1-roGFP2 to roGFP2-Grx1 yields a biosensor with perfect mitochondrial targeting while fully maintaining its biosensor capabilities. The redesigned probe thus allows extending in vivo observations of mitochondrial redox homeostasis to important nonmammalian model organisms, particularly plants and insects.

  17. A genetic algorithm encoded with the structural information of amino acids and dipeptides for efficient conformational searches of oligopeptides.

    Science.gov (United States)

    Ru, Xiao; Song, Ce; Lin, Zijing

    2016-05-15

    The genetic algorithm (GA) is an intelligent approach for finding minima in a highly dimensional parametric space. However, the success of GA searches for low energy conformations of biomolecules is rather limited so far. Herein an improved GA scheme is proposed for the conformational search of oligopeptides. A systematic analysis of the backbone dihedral angles of conformations of amino acids (AAs) and dipeptides is performed. The structural information is used to design a new encoding scheme to improve the efficiency of GA search. Local geometry optimizations based on the energy calculations by the density functional theory are employed to safeguard the quality and reliability of the GA structures. The GA scheme is applied to the conformational searches of Lys, Arg, Met-Gly, Lys-Gly, and Phe-Gly-Gly representative of AAs, dipeptides, and tripeptides with complicated side chains. Comparison with the best literature results shows that the new GA method is both highly efficient and reliable by providing the most complete set of the low energy conformations. Moreover, the computational cost of the GA method increases only moderately with the complexity of the molecule. The GA scheme is valuable for the study of the conformations and properties of oligopeptides. © 2016 Wiley Periodicals, Inc.

  18. Genetically Encoded FRET-Sensor Based on Terbium Chelate and Red Fluorescent Protein for Detection of Caspase-3 Activity

    Directory of Open Access Journals (Sweden)

    Alexander S. Goryashchenko

    2015-07-01

    Full Text Available This article describes the genetically encoded caspase-3 FRET-sensor based on the terbium-binding peptide, cleavable linker with caspase-3 recognition site, and red fluorescent protein TagRFP. The engineered construction performs two induction-resonance energy transfer processes: from tryptophan of the terbium-binding peptide to Tb3+ and from sensitized Tb3+ to acceptor—the chromophore of TagRFP. Long-lived terbium-sensitized emission (microseconds, pulse excitation source, and time-resolved detection were utilized to eliminate directly excited TagRFP fluorescence and background cellular autofluorescence, which lasts a fraction of nanosecond, and thus to improve sensitivity of analyses. Furthermore the technique facilitates selective detection of fluorescence, induced by uncleaved acceptor emission. For the first time it was shown that fluorescence resonance energy transfer between sensitized terbium and TagRFP in the engineered construction can be studied via detection of microsecond TagRFP fluorescence intensities. The lifetime and distance distribution between donor and acceptor were calculated using molecular dynamics simulation. Using this data, quantum yield of terbium ions with binding peptide was estimated.

  19. A genetically encoded reporter for real-time imaging of cofilin-actin rods in living neurons.

    Directory of Open Access Journals (Sweden)

    Jianjie Mi

    Full Text Available Filament bundles (rods of cofilin and actin (1:1 form in neurites of stressed neurons where they inhibit synaptic function. Live-cell imaging of rod formation is hampered by the fact that overexpression of a chimera of wild type cofilin with a fluorescent protein causes formation of spontaneous and persistent rods, which is exacerbated by the photostress of imaging. The study of rod induction in living cells calls for a rod reporter that does not cause spontaneous rods. From a study in which single cofilin surface residues were mutated, we identified a mutant, cofilinR21Q, which when fused with monomeric Red Fluorescent Protein (mRFP and expressed several fold above endogenous cofilin, does not induce spontaneous rods even during the photostress of imaging. CofilinR21Q-mRFP only incorporates into rods when they form from endogenous proteins in stressed cells. In neurons, cofilinR21Q-mRFP reports on rods formed from endogenous cofilin and induced by all modes tested thus far. Rods have a half-life of 30-60 min upon removal of the inducer. Vesicle transport in neurites is arrested upon treatments that form rods and recovers as rods disappear. CofilinR21Q-mRFP is a genetically encoded rod reporter that is useful in live cell imaging studies of induced rod formation, including rod dynamics, and kinetics of rod elimination.

  20. Real-time determination of intracellular oxygen in bacteria using a genetically encoded FRET-based biosensor

    Directory of Open Access Journals (Sweden)

    Potzkei Janko

    2012-03-01

    Full Text Available Abstract Background Molecular oxygen (O2 is one of the key metabolites of all obligate and facultative aerobic pro- and eukaryotes. It plays a fundamental role in energy homeostasis whereas oxygen deprivation, in turn, broadly affects various physiological and pathophysiological processes. Therefore, real-time monitoring of cellular oxygen levels is basically a prerequisite for the analysis of hypoxia-induced processes in living cells and tissues. Results We developed a genetically encoded Förster resonance energy transfer (FRET-based biosensor allowing the observation of changing molecular oxygen concentrations inside living cells. This biosensor named FluBO (fluorescent protein-based biosensor for oxygen consists of the yellow fluorescent protein (YFP that is sensitive towards oxygen depletion and the hypoxia-tolerant flavin-binding fluorescent protein (FbFP. Since O2 is essential for the formation of the YFP chromophore, efficient FRET from the FbFP donor domain to the YFP acceptor domain only occurs in the presence but not in the absence of oxygen. The oxygen biosensor was used for continuous real-time monitoring of temporal changes of O2 levels in the cytoplasm of Escherichia coli cells during batch cultivation. Conclusions FluBO represents a unique FRET-based oxygen biosensor which allows the non-invasive ratiometric readout of cellular oxygen. Thus, FluBO can serve as a novel and powerful probe for investigating the occurrence of hypoxia and its effects on a variety of (pathophysiological processes in living cells.

  1. Genetically encoded pH-indicators reveal activity-dependent cytosolic acidification of Drosophila motor nerve termini in vivo.

    Science.gov (United States)

    Rossano, Adam J; Chouhan, Amit K; Macleod, Gregory T

    2013-04-01

    All biochemical processes, including those underlying synaptic function and plasticity, are pH sensitive. Cytosolic pH (pH(cyto)) shifts are known to accompany nerve activity in situ, but technological limitations have prevented characterization of such shifts in vivo. Genetically encoded pH-indicators (GEpHIs) allow for tissue-specific in vivo measurement of pH. We expressed three different GEpHIs in the cytosol of Drosophila larval motor neurons and observed substantial presynaptic acidification in nerve termini during nerve stimulation in situ. SuperEcliptic pHluorin was the most useful GEpHI for studying pH(cyto) shifts in this model system. We determined the resting pH of the nerve terminal cytosol to be 7.30 ± 0.02, and observed a decrease of 0.16 ± 0.01 pH units when the axon was stimulated at 40 Hz for 4 s. Realkalinization occurred upon cessation of stimulation with a time course of 20.54 ± 1.05 s (τ). The chemical pH-indicator 2,7-bis-(2-carboxyethyl)-5-(and-6)-carboxyfluorescein corroborated these changes in pH(cyto). Bicarbonate-derived buffering did not contribute to buffering of acid loads from short (≤ 4 s) trains of action potentials but did buffer slow (~60 s) acid loads. The magnitude of cytosolic acid transients correlated with cytosolic Ca(2+) increase upon stimulation, and partial inhibition of the plasma membrane Ca(2+)-ATPase, a Ca(2+)/H(+) exchanger, attenuated pH(cyto) shifts. Repeated stimulus trains mimicking motor patterns generated greater cytosolic acidification (~0.30 pH units). Imaging through the cuticle of intact larvae revealed spontaneous pH(cyto) shifts in presynaptic termini in vivo, similar to those seen in situ during fictive locomotion, indicating that presynaptic pH(cyto) shifts cannot be dismissed as artifacts of ex vivo preparations.

  2. Mobile genetic element SCCmec-encoded psm-mec RNA suppresses translation of agrA and attenuates MRSA virulence.

    Science.gov (United States)

    Kaito, Chikara; Saito, Yuki; Ikuo, Mariko; Omae, Yosuke; Mao, Han; Nagano, Gentaro; Fujiyuki, Tomoko; Numata, Shunsuke; Han, Xiao; Obata, Kazuaki; Hasegawa, Setsuo; Yamaguchi, Hiroki; Inokuchi, Koiti; Ito, Teruyo; Hiramatsu, Keiichi; Sekimizu, Kazuhisa

    2013-01-01

    Community acquired-methicillin resistant Staphylococcus aureus (CA-MRSA) is a socially problematic pathogen that infects healthy individuals, causing severe disease. CA-MRSA is more virulent than hospital associated-MRSA (HA-MRSA). The underlying mechanism for the high virulence of CA-MRSA is not known. The transcription product of the psm-mec gene, located in the mobile genetic element SCCmec of HA-MRSA, but not CA-MRSA, suppresses the expression of phenol-soluble modulin α (PSMα), a cytolytic toxin of S. aureus. Here we report that psm-mec RNA inhibits translation of the agrA gene encoding a positive transcription factor for the PSMα gene via specific binding to agrA mRNA. Furthermore, 25% of 325 clinical MRSA isolates had a mutation in the psm-mec promoter that attenuated transcription, and 9% of the strains had no psm-mec. In most of these psm-mec-mutated or psm-mec-deleted HA-MRSAs, PSMα expression was increased compared with strains carrying intact psm-mec, and some mutated strains produced high amounts of PSMα comparable with that of CA-MRSA. Deletion of psm-mec from HA-MRSA strains carrying intact psm-mec increased the expression of AgrA protein and PSMα, and virulence in mice. Thus, psm-mec RNA suppresses MRSA virulence via inhibition of agrA translation and the absence of psm-mec function in CA-MRSA causes its high virulence property.

  3. Fast-channel LSO detectors and fiber-optic encoding for excellent dual photon transmission measurements in PET

    Energy Technology Data Exchange (ETDEWEB)

    Jones, W.F.; Moyers, J.C.; Casey, M.E.; Watson, C.C.; Nutt, R. [CTI PET Systems, Inc., Knoxville, TN (United States)

    1999-08-01

    Improved attenuation correction remains critical to PET. Currently with dual photon rotating rod sources, benefits of windowing are limited by counting losses of detectors nearest the rods, the near detectors. With single photon sources, improved statistics are offset by a greater need for collimation and more complex emission background correction. Now, a dual photon point source array with fast-channel, near detectors improves on these earlier techniques -- here, adding transmission measurement to dual-head rotating PET. Arrays of collimated point sources are aligned axially and orbit the FOV. With each source is a dedicated near detector (LSO crystal). Crystals couple to photomultipliers (PMTs). As the crystals are not ``block`` encoded, pulse-processing time is reduced (to 120 ns). Reduced processing time lowers dead time and permits hotter sources. For improved axial sampling, larger arrays (21 sources/head) may be configured. To reduce costs, crystals couple fiber-optically into unique PMT pairs -- decreasing the total number of near-detector PMTs by 71%.

  4. Genetically encoded photocrosslinkers locate the high-affinity binding site of antidepressant drugs in the human serotonin transporter

    DEFF Research Database (Denmark)

    Rannversson, Hafsteinn; Andersen, Jacob; Hall, Lena Sørensen;

    2016-01-01

    Despite the well-established role of the human serotonin transporter (hSERT) in the treatment of depression, the molecular details of antidepressant drug binding are still not fully understood. Here we utilize amber codon suppression in a membrane-bound transporter protein to encode photocrosslin......Despite the well-established role of the human serotonin transporter (hSERT) in the treatment of depression, the molecular details of antidepressant drug binding are still not fully understood. Here we utilize amber codon suppression in a membrane-bound transporter protein to encode...

  5. A novel homologous dominant selection marker for genetic transformation of Penicillium chrysogenum: overexpression of squalene epoxidase-encoding ergA.

    Science.gov (United States)

    Sigl, Claudia; Handler, Monika; Sprenger, Georg; Kürnsteiner, Hubert; Zadra, Ivo

    2010-11-01

    Genetic engineering requires genetic selection markers. For generation of biosafe strains in industrial applications, homologous dominant selection markers allowing "self-cloning" are best suited but scarce. Here we describe a novel homologous dominant genetic selection system for the filamentous fungus Penicillium chrysogenum based on overexpression of the P. chrysogenum squalene epoxidase-encoding ergA gene, which confers resistance against terbinafine. Terbinafine (TRB) is a potent antifungal drug used in therapy of fungal infections. Overexpression of ergA was driven by the P. chrysogenum endoxylanase xylP promoter that is highly inducible by xylose. The suitability of the novel selection marker cassette for genetic manipulation was proven by its use for targeted deletion of the transcription factor nosA in P. chrysogenum. NosA-deficiency did not affect growth rates on solid or in liquid media, conidiation in light or darkness, and resistance to hydrogen peroxide. However, NosA-deficiency significantly decreased penicillin productivity. As TRB inhibits the growth of a variety of fungal species, this novel selection marker is expected to be suitable for genetic engineering of diverse fungal species.

  6. Identification of TENP as the Gene Encoding Chicken Egg White Ovoglobulin G2 and Demonstration of Its High Genetic Variability in Chickens.

    Science.gov (United States)

    Kinoshita, Keiji; Shimogiri, Takeshi; Ibrahim, Hisham R; Tsudzuki, Masaoki; Maeda, Yoshizane; Matsuda, Yoichi

    2016-01-01

    Ovoglobulin G2 (G2) has long been known as a major protein constituent of chicken egg white. However, little is known about the biochemical properties and biological functions of G2 because the gene encoding G2 has not been identified. Therefore, the identification of the gene encoding G2 and an analysis of its genetic variability is an important step toward the goal of understanding the biological functions of the G2 protein and its utility in poultry production. To identify and characterize the gene encoding G2, we separated G2 from egg white using electrophoresis on a non-denaturing polyacrylamide gel. Two polymorphic forms of G2 protein (G2A and G2B), with different mobilities (fast and slow respectively), were detected by staining. The protein band corresponding to G2B was electro-eluted from the native gel, re-electrophoresed under denaturing conditions and its N-terminal sequence was determined by Edman degradation following transfer onto a membrane. Sequencing of the 47 kDa G2B band revealed it to be identical to TENP (transiently expressed in neural precursors), also known as BPI fold-containing family B, member 2 (BPIFB2), a protein with strong homology to a bacterial permeability-increasing protein family (BPI) in mammals. Full-length chicken TENP cDNA sequences were determined for 78 individuals across 29 chicken breeds, lines, and populations, and consequently eleven non-synonymous substitutions were detected in the coding region. Of the eleven non-synonymous substitutions, A329G leading to Arg110Gln was completely associated with the noted differential electrophoretic mobility of G2. Specifically G2B, with a slower mobility is encoded by A329 (Arg110), whereas G2A, with a faster mobility, is encoded by G329 (Gln110). The sequence data, derived from the coding region, also revealed that the gene encoding G2 demonstrates significant genetic variability across different chicken breeds/lines/populations. These variants, and how they correlate with egg

  7. Simulating Visual Learning and Optical Illusions via a Network-Based Genetic Algorithm

    Science.gov (United States)

    Siu, Theodore; Vivar, Miguel; Shinbrot, Troy

    We present a neural network model that uses a genetic algorithm to identify spatial patterns. We show that the model both learns and reproduces common visual patterns and optical illusions. Surprisingly, we find that the illusions generated are a direct consequence of the network architecture used. We discuss the implications of our results and the insights that we gain on how humans fall for optical illusions

  8. Genetics and Molecular Biology of Epstein-Barr Virus-Encoded BART MicroRNA: A Paradigm for Viral Modulation of Host Immune Response Genes and Genome Stability

    Directory of Open Access Journals (Sweden)

    David H. Dreyfus

    2017-01-01

    Full Text Available Epstein-Barr virus, a ubiquitous human herpesvirus, is associated through epidemiologic evidence with common autoimmune syndromes and cancers. However, specific genetic mechanisms of pathogenesis have been difficult to identify. In this review, the author summarizes evidence that recently discovered noncoding RNAs termed microRNA encoded by Epstein-Barr virus BARF (BamHI A right frame termed BART (BamHI A right transcripts are modulators of human immune response genes and genome stability in infected and bystander cells. BART expression is apparently regulated by complex feedback loops with the host immune response regulatory NF-κB transcription factors. EBV-encoded BZLF-1 (ZEBRA protein could also regulate BART since ZEBRA contains a terminal region similar to ankyrin proteins such as IκBα that regulate host NF-κB. BALF-2 (BamHI A left frame transcript, a viral homologue of the immunoglobulin and T cell receptor gene recombinase RAG-1 (recombination-activating gene-1, may also be coregulated with BART since BALF-2 regulatory sequences are located near the BART locus. Viral-encoded microRNA and viral mRNA transferred to bystander cells through vesicles, defective viral particles, or other mechanisms suggest a new paradigm in which bystander or hit-and-run mechanisms enable the virus to transiently or chronically alter human immune response genes as well as the stability of the human genome.

  9. Towards PDT with Genetically Encoded Photosensitizer KillerRed: A Comparison of Continuous and Pulsed Laser Regimens in an Animal Tumor Model.

    Directory of Open Access Journals (Sweden)

    Marina Shirmanova

    Full Text Available The strong phototoxicity of the red fluorescent protein KillerRed allows it to be considered as a potential genetically encoded photosensitizer for the photodynamic therapy (PDT of cancer. The advantages of KillerRed over chemical photosensitizers are its expression in tumor cells transduced with the appropriate gene and direct killing of cells through precise damage to any desired cell compartment. The ability of KillerRed to affect cell division and to induce cell death has already been demonstrated in cancer cell lines in vitro and HeLa tumor xenografts in vivo. However, the further development of this approach for PDT requires optimization of the method of treatment. In this study we tested the continuous wave (593 nm and pulsed laser (584 nm, 10 Hz, 18 ns modes to achieve an antitumor effect. The research was implemented on CT26 subcutaneous mouse tumors expressing KillerRed in fusion with histone H2B. The results showed that the pulsed mode provided a higher rate of photobleaching of KillerRed without any temperature increase on the tumor surface. PDT with the continuous wave laser was ineffective against CT26 tumors in mice, whereas the pulsed laser induced pronounced histopathological changes and inhibition of tumor growth. Therefore, we selected an effective regimen for PDT when using the genetically encoded photosensitizer KillerRed and pulsed laser irradiation.

  10. Encoding of naturalistic optic flow by motion sensitive neurons of nucleus rotundus in the zebra finch (Taeniopygia guttata.

    Directory of Open Access Journals (Sweden)

    Dennis eEckmeier

    2013-09-01

    Full Text Available The retinal image changes that occur during locomotion, the optic flow, carry information about self-motion and the three-dimensional structure of the environment. Especially fast moving animals with only little binocular vision depend on these depth cues for manoeuvring. They actively control their gaze to facilitate perception of depth based on cues in the optic flow. In the visual system of birds, nucleus rotundus neurons were originally found to respond to object motion but not to background motion. However, when background and object were both moving, responses increase the more the direction and velocity of object and background motion on the retina differed. These properties may play a role in representing depth cues in the optic flow. We therefore investigated how neurons in nucleus rotundus respond to optic flow that contains depth cues. We presented simplified and naturalistic optic flow on a panoramic LED display while recording from single neurons in nucleus rotundus of anaesthetized zebra finches. Unlike most studies on motion vision in birds, our stimuli included depth information.We found extensive responses of motion selective neurons in nucleus rotundus to optic flow stimuli. Simplified stimuli revealed preferences for optic flow reflecting translational or rotational self-motion. Naturalistic optic flow stimuli elicited complex response modulations, but the presence of objects was signalled by only few neurons. The neurons that did respond to objects in the optic flow, however, show interesting properties.

  11. GENETIC ALGORITHM AND NEURAL NETWORK FOR OPTICAL CHARACTER RECOGNITION

    Directory of Open Access Journals (Sweden)

    Hendy Yeremia

    2013-01-01

    Full Text Available Computer system has been able to recognize writing as human brain does. The method mostly used for character recognition is the backpropagation network. Backpropagation network has been known for its accuracy because it allows itself to learn and improving itself thus it can achieve higher accuracy. On the other hand, backpropagation was less to be used because of its time length needed to train the network to achieve the best result possible. In this study, backpropagation network algorithm is combined with genetic algorithm to achieve both accuracy and training swiftness for recognizing alphabets. Genetic algorithm is used to define the best initial values for the network’s architecture and synapses’ weight thus within a shorter period of time, the network could achieve the best accuracy. The optimized backpropagation network has better accuracy and less training time than the standard backpropagation network. The accuracy in recognizing character differ by 10, 77%, with a success rate of 90, 77% for the optimized backpropagation and 80% accuracy for the standard backpropagation network. The training time needed for backpropagation learning phase improved significantly from 03 h, 14 min and 40 sec, a standard backpropagation training time, to 02 h 18 min and 1 sec for the optimized backpropagation network.

  12. A variant of Leber hereditary optic neuropathy characterized by recovery of vision and by an unusual mitochondrial genetic etiology

    Energy Technology Data Exchange (ETDEWEB)

    Mackey, D. (Royal Children' s Hospital, Melbourne (Australia)); Howell, N. (Univ. of Texas, Galveston (United States))

    1992-12-01

    The Tas2 and Vic2 Australian families are affected with a variant of Leber hereditary optic neuropathy (LHON). The risk of developing the optic neuropathy shows strict maternal inheritance, and the opthalmological changes in affected family members are characteristic of LHON. However, in contrast to the common form of the disease, members of these two families show a high frequency of vision recovery. To ascertain the mitochondrial genetic etiology of the LHON in these families, both (a) the nucleotide sequences of the seven mitochondrial genes encoding subunits of respiratory-chain complex I and (b) the mitochondrial cytochrome b gene were determined for representatives of both families. Neither family carries any of the previously identified primary mitochondrial LHON mutations: ND4/11778, ND1/3460, or ND1/4160. Instead, both LHON families carry multiple nucleotide changes in the mitochondrial complex I genes, which produce conservative amino acid changes. From the available sequence data, it is inferred that the Vic2 and Tas2 LHON families are phylogenetically related to each other and to a cluster of LHON families in which mutations in the mitochondrial cytochrome b gene have been hypothesized to play a primary etiological role. However, sequencing analysis establishes that the Vic2 and Tas2 LHON families do not carry these cytochrome b mutations. There are two hypotheses to account for the unusual mitochondrial genetic etiology of the LHON in the Tas2 and Vic2 LHON families. One possibility is that there is a primary LHON mutation within the mitochondrial genome but that it is at a site that was not included in the sequencing analyses. Alternatively, the disease in these families may result from the cumulative effects of multiple secondary LHON mutations that have less severe phenotypic consequences. 29 refs., 3 figs., 3 tabs.

  13. Clinical Findings and Genetic Expression Profiling of Three Pigmented Lesions of the Optic Nerve

    Directory of Open Access Journals (Sweden)

    Manuel A. de Alba

    2015-01-01

    Full Text Available Background. Optic disk melanocytoma is a primary tumor of the optic disk that represents a clinical diagnostic challenge due to its similarities with melanoma. Purpose. The authors present three cases in which genetic expression profiling was used to identify tumor prognosis of optic disk melanocytoma. Case Series. In two cases fine-needle aspiration biopsy was performed to obtain tissue through a transvitreal route into the apex of the tumor while the patient underwent pars plana vitrectomy, laser ablation, phacoemulsification with posterior chamber intraocular lens implantation, and intravitreal triamcinolone acetonide. In the other case the tissue was obtained after definite enucleation. Conclusion. Genetic expression profiling is a useful diagnostic tool for classification and can provide vital information to the ocular oncologist regarding prognosis.

  14. Separate and simultaneous generation of multioutputs in a polarization-encoded optical shadow-casting scheme: design of half- and full adders and subtractors.

    Science.gov (United States)

    Rizvi, R A; Zaheer, K; Zubairy, M S

    1988-12-15

    A design algorithm for separate and simultaneous generation of multioutputs in a polarization-encoded optical shadow-casting (POSC) scheme is presented. The logic unit truth table is converted into POSC logic equations for true and false logic. These are then solved consistently to obtain source plane, input pixel, and the decoding mask characteristics. The algorithm is used to design binary half-adder and half-subtractor and full adder and full subtractor to carry out all operations with a fixed source plane and a fixed decoding mask. The results have been verified experimentally.

  15. Study of Coding Image Acquisition System of Precise Absolute Optical Encoder%精密绝对光栅尺的编码采集系统研究

    Institute of Scientific and Technical Information of China (English)

    范朝龙; 王晗; 刘强; 陈新度

    2014-01-01

    通过对绝对光栅尺图像编码及解码原理的研究,完成了基于FPGA对绝对光栅尺编码图像软硬件采集系统的设计。在FPGA中实现基于SDRAM的控制模块,设计了CMOS摄像头的I2 C控制模块,建立了VGA输出显示模块,新增了 CMOS摄像头开窗扫瞄模块及灰度处理模块。整个模块的设计基于 Quartus II 9.0软件开发平台,使用 Verilog HDL 语言进行编程,在主控核心芯片EP2 C8 Q208 C8 N硬件平台上实现编码图像的采集,采集到的绝对编码数据传送给后端DSP解码得出绝对光栅尺的位移绝对位置。该系统实现了绝对位置的采码功能,同时保持了采码的可靠性,为绝对式光栅尺的开发研究提供了一条新的途径。%With studying of theory which is cording and decoding of image of absoluteoptical encoder, It have been designed that soft and hardware of Coding image acquisition system of absolute linear optical en-coder based on FPGA. It is have been completed on FPGA that controlling module based on SDRAM, and founded that I2 C controlling module of CMOS camera and designed that video display module of VGA out-put and newly increased that controlling module of window scanning of CMOS camera, and gray-scale pro-cessing module. All module have been designed onQuartus II 9. 0 that is software development platform, and have been assembled with Verilog HDL and have accomplished absolute coding image acquisition on hardware platform whose modle is EP2C8Q208C8N and that is main control chip. Images of the absolute encoding which is acquired is sent to DSP to decode and work out absolute position of moving of absoluteop-tical encoder. The system can accomplish acquisitionof absolute position and keep reliability of encoding ac-quisition, It provide a new approach to developing and studying of absoluteoptical encoder.

  16. Real-time and high-throughput analysis of mitochondrial metabolic states in living cells using genetically encoded NAD(+)/NADH sensors.

    Science.gov (United States)

    Zhao, Yuzheng; Yang, Yi

    2016-11-01

    Mitochondria are central organelles that regulate cellular bioenergetics, biosynthesis, and signaling processes. NADH, a key player in cell metabolism, is often considered as a marker of mitochondrial function. However, traditional methods for NADH measurements are either destructive or unable to distinguish between NADH and NADPH. In contrast to traditional methods, genetically encoded NADH sensors can be used for the real-time tracking and quantitative measurement of subcellular NADH levels in living cells. Therefore, these sensors provide innovative tools and address the limitations of current techniques. We herein summarize the properties of different types of recently developed NADH biosensors, discuss their advantages and disadvantages, and focus on the high-throughput analysis of mitochondrial function by using highly responsive NAD(+)/NADH sensors.

  17. Co-administration of a plasmid DNA encoding IL-15 improves long-term protection of a genetic vaccine against Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Christopher S Eickhoff

    Full Text Available BACKGROUND: Immunization of mice with the Trypanosoma cruzi trans-sialidase (TS gene using plasmid DNA, adenoviral vector, and CpG-adjuvanted protein delivery has proven highly immunogenic and provides protection against acute lethal challenge. However, long-term protection induced by TS DNA vaccines has not been reported. The goal of the present work was to test whether the co-administration of a plasmid encoding IL-15 (pIL-15 could improve the duration of protection achieved through genetic vaccination with plasmid encoding TS (pTS alone. METHODOLOGY: We immunized BALB/c mice with pTS in the presence or absence of pIL-15 and studied immune responses [with TS-specific IFN-γ ELISPOT, serum IgG ELISAs, intracellular cytokine staining (IFN-γ, TNF-α, and IL-2, tetramer staining, and CFSE dilution assays] and protection against lethal systemic challenge at 1 to 6 months post vaccination. Mice receiving pTS alone developed robust TS-specific IFN-γ responses and survived a lethal challenge given within the first 3 months following immunization. The addition of pIL-15 to pTS vaccination did not significantly alter T cell responses or protection during this early post-vaccination period. However, mice vaccinated with both pTS and pIL-15 challenged 6 months post-vaccination were significantly more protected against lethal T. cruzi challenges than mice vaccinated with pTS alone (P6 months post immunization. Also, these TS-specific T cells were better able to expand after in vitro re-stimulation. CONCLUSION: Addition of pIL-15 during genetic vaccination greatly improved long-term T cell survival, memory T cell expansion, and long-term protection against the important human parasite, T. cruzi.

  18. Improve the performance of orthogonal ASK/DPSK optical label switching by DC-balanced line encoding

    DEFF Research Database (Denmark)

    Chi, Nan; Xu, Lin; Zhang, J.;

    2006-01-01

    Orthogonal amplitude shift keying/differential phase-shift keying (ASK/DPSK) labeling is a promising approach to ultrahigh packet-rate routing and forwarding in the optical layer. However, the limitation on the payload extinction ratio (ER) is a detrimental effect for network scalability and tran......Orthogonal amplitude shift keying/differential phase-shift keying (ASK/DPSK) labeling is a promising approach to ultrahigh packet-rate routing and forwarding in the optical layer. However, the limitation on the payload extinction ratio (ER) is a detrimental effect for network scalability...... and transparency. This paper presents theoretical and experimental studies of ASK/DPSK labeling. It proposes that dc-balanced 8B10B coding can greatly improve ER tolerance, which in turn leads to better system performance. By using the 8B10B coding method, the paper demonstrates transmission and optical label...

  19. Demodulating the Response of Optical Fibre Long-Period Gratings: Genetic Algorithm Approach

    Institute of Scientific and Technical Information of China (English)

    P. S. André; R. A. Sá. Ferreira; C. M. L. Correia; H. Kalinowshy; XIN Xiang-Jun; J. L. Pinto

    2006-01-01

    @@ The extraction of the physical parameters of long period gratings from the spectral response is not an easy process. We present a demodulation technique to synthesize the physical parameters of a long period grating recorded in an optical fibre. The demodulation is achieved through the implementation of a genetic algorithm.The extracted parameters are in agreement with the typical values known for long period gratings.

  20. Combination encoding genetic algorithm for dynamic transmission network planning%动态输电网络规划的组合编码遗传算法

    Institute of Scientific and Technical Information of China (English)

    高元海; 王淳

    2013-01-01

    A combination encoding is proposed for handling the time decision variable in a dynamic transmission network planning (DTNP). The time decision variable is implied in the combination encoding, which converts the DTNP problem into a static programming problem. The encoding satisfies 1 to 1 mapping between the phenotype and genotype, and meets the consistency of phenotypic space distance and genotypic space distance, which ensure the search efficiency of genetic algorithm. Moreover, according to the characteristics of DTNP problem, some improvement measures are given for crossover operators, mutation mode, fitness function, penalty coefficient so as to enhance the performance of the genetic algorithm to solve DTNP problem. The proposed method is validated using a 19-node system, and results show that the optimal solution can be obtained within reasonable evolutionary generation.%  针对动态输电网络规划过程中需要考虑时间决策量的问题,提出了组合编码方式。组合编码方式将多阶段输电网络规划中的时间决策量隐含在编码中,从而使得多阶段的动态输电网络规划问题能够转换成静态规划问题进行求解。该编码方式满足表现型和基因型的1对1映射,及表现型空间与基因型空间距离上的一致性,从而保证了遗传算法的搜索效率。此外,针对动态输电网络规划的特点,对遗传算法的交叉算子、变异方式、适应度函数、惩罚系数等方面进行了改进,进一步改善了遗传算法求解多阶段输电网络规划问题的性能。以19节点系统为例对算法进行了验证,结果表明能够在较短的进化代数内得到问题的最优解。

  1. Genetic Algorithm Phase Retrieval for the Systematic Image-Based Optical Alignment Testbed

    Science.gov (United States)

    Taylor, Jaime; Rakoczy, John; Steincamp, James

    2003-01-01

    Phase retrieval requires calculation of the real-valued phase of the pupil fimction from the image intensity distribution and characteristics of an optical system. Genetic 'algorithms were used to solve two one-dimensional phase retrieval problem. A GA successfully estimated the coefficients of a polynomial expansion of the phase when the number of coefficients was correctly specified. A GA also successfully estimated the multiple p h e s of a segmented optical system analogous to the seven-mirror Systematic Image-Based Optical Alignment (SIBOA) testbed located at NASA s Marshall Space Flight Center. The SIBOA testbed was developed to investigate phase retrieval techniques. Tiphilt and piston motions of the mirrors accomplish phase corrections. A constant phase over each mirror can be achieved by an independent tip/tilt correction: the phase Conection term can then be factored out of the Discrete Fourier Tranform (DFT), greatly reducing computations.

  2. Partitioning of genetic variation between regulatory and coding gene segments: the predominance of software variation in genes encoding introvert proteins.

    Science.gov (United States)

    Mitchison, A

    1997-01-01

    In considering genetic variation in eukaryotes, a fundamental distinction can be made between variation in regulatory (software) and coding (hardware) gene segments. For quantitative traits the bulk of variation, particularly that near the population mean, appears to reside in regulatory segments. The main exceptions to this rule concern proteins which handle extrinsic substances, here termed extrovert proteins. The immune system includes an unusually large proportion of this exceptional category, but even so its chief source of variation may well be polymorphism in regulatory gene segments. The main evidence for this view emerges from genome scanning for quantitative trait loci (QTL), which in the case of the immune system points to a major contribution of pro-inflammatory cytokine genes. Further support comes from sequencing of major histocompatibility complex (Mhc) class II promoters, where a high level of polymorphism has been detected. These Mhc promoters appear to act, in part at least, by gating the back-signal from T cells into antigen-presenting cells. Both these forms of polymorphism are likely to be sustained by the need for flexibility in the immune response. Future work on promoter polymorphism is likely to benefit from the input from genome informatics.

  3. The physiological effects of deleting the mouse SLC30A8 gene encoding zinc transporter-8 are influenced by gender and genetic background.

    Directory of Open Access Journals (Sweden)

    Lynley D Pound

    Full Text Available The SLC30A8 gene encodes the islet-specific transporter ZnT-8, which is hypothesized to provide zinc for insulin-crystal formation. A polymorphic variant in SLC30A8 is associated with altered susceptibility to type 2 diabetes. Several groups have examined the effect of global Slc30a8 gene deletion but the results have been highly variable, perhaps due to the mixed 129SvEv/C57BL/6J genetic background of the mice studied. We therefore sought to remove the conflicting effect of 129SvEv-specific modifier genes.The impact of Slc30a8 deletion was examined in the context of the pure C57BL/6J genetic background.Male C57BL/6J Slc30a8 knockout (KO mice had normal fasting insulin levels and no change in glucose-stimulated insulin secretion (GSIS from isolated islets in marked contrast to the ∼50% and ∼35% decrease, respectively, in both parameters observed in male mixed genetic background Slc30a8 KO mice. This observation suggests that 129SvEv-specific modifier genes modulate the impact of Slc30a8 deletion. In contrast, female C57BL/6J Slc30a8 KO mice had reduced (∼20% fasting insulin levels, though this was not associated with a change in fasting blood glucose (FBG, or GSIS from isolated islets. This observation indicates that gender also modulates the impact of Slc30a8 deletion, though the physiological explanation as to why impaired insulin secretion is not accompanied by elevated FBG is unclear. Neither male nor female C57BL/6J Slc30a8 KO mice showed impaired glucose tolerance.Our data suggest that, despite a marked reduction in islet zinc content, the absence of ZnT-8 does not have a substantial impact on mouse physiology.

  4. Fluorescence-based characterization of genetically encoded peptides that fold in live cells: progress toward a generic hairpin scaffold

    Science.gov (United States)

    Cheng, Zihao; Campbell, Robert E.

    2007-02-01

    Binding proteins suitable for expression and high affinity molecular recognition in the cytoplasm or nucleus of live cells have numerous applications in the biological sciences. In an effort to add a new minimal motif to the growing repertoire of validated non-immunoglobulin binding proteins, we have undertaken the development of a generic protein scaffold based on a single β-hairpin that can fold efficiently in the cytoplasm. We have developed a method, based on the measurement of fluorescence resonance energy transfer (FRET) between a genetically fused cyan fluorescent protein (CFP) and yellow fluorescent protein (YFP), that allows the structural stability of recombinant β-hairpin peptides to be rapidly assessed both in vitro and in vivo. We have previously reported the validation of this method when applied to a 16mer tryptophan zipper β-hairpin. We now describe the use of this method to evaluate the potential of a designed 20mer β-hairpin peptide with a 3rd Trp/Trp cross-strand pair to function as a generic protein scaffold. Quantitative analysis of the FRET efficiency, resistance to proteolysis (assayed by loss of FRET), and circular dichroism spectra revealed that the 20mer peptide is significantly more tolerant of destabilizing mutations than the 16mer peptide. Furthermore, we experimentally demonstrate that the in vitro determined β-hairpin stabilities are well correlated with in vivo β-hairpin stabilities as determined by FRET measurements of colonies of live bacteria expressing the recombinant peptides flanked by CFP and YFP. Finally, we report on our progress to develop highly folded 24mer and 28mer β-hairpin peptides through the use of fluorescence-based library screening.

  5. A novel orthogonal modulation format of D8PSK/ASK with differential bi-phase encoding and its application in a label switching optical network

    Institute of Scientific and Technical Information of China (English)

    ZHANG Xing; ZHANG Xiao-lei; WANG Yong-jun; XIN Xiang-jun; YIN Xiao-li; LI Ling; ZHAO Ji-jun

    2012-01-01

    The principle of a novel orthogonal modulation format of differential 8-level phase-shift keying amplitude-shift keying (D8PSK/ASK) with differential bi-phase encoding (DBC) is introduced.Based on it,an optical labeling scheme,in which the payload is 100 Gbit/s D8PSK signal and the label is 10 Gbit/s DBC-ASK signal,is proposed and simulated.The results are compared with other current schemes,and the effects of transmission range,modulation extinction ratio (ER) and received power on system performance are analyzed,respectively.The results show that the spectrum efficiency and bit error rate (BER) are improved greatly,and when the modulation ER is increased to 11 dB,the balanced performance between the payload and label is achieved.

  6. Two-photon scanning microscopy of in vivo sensory responses of cortical neurons genetically encoded with a fluorescent voltage sensor in rat

    Directory of Open Access Journals (Sweden)

    Kurt F Ahrens

    2012-03-01

    Full Text Available A fluorescent voltage sensor protein Flare was created from a Kv1.4 potassium channel with YFP situated to report voltage-induced conformational changes in vivo. The RNA virus Sindbis introduced Flare into neurons in the binocular visual crescent in rat. Injection sites were selected based on intrinsic optical imaging. Expression of Flare occurred in the cell bodies and dendritic processes. Neurons imaged in vivo using two-photon scanning microscopy typically revealed the soma best, discernable against the background labeling of the neuropil. Somatic fluorescence changes were correlated with flashed visual stimuli; however, averaging was essential to observe these changes. This study demonstrates that the genetic modification of single neurons to express a fluorescent voltage sensor can be used to assess neuronal activity in vivo.

  7. Two-photon scanning microscopy of in vivo sensory responses of cortical neurons genetically encoded with a fluorescent voltage sensor in rat

    Science.gov (United States)

    Ahrens, Kurt F.; Heider, Barbara; Lee, Hanson; Isacoff, Ehud Y.; Siegel, Ralph M.

    2012-01-01

    A fluorescent voltage sensor protein “Flare” was created from a Kv1.4 potassium channel with YFP situated to report voltage-induced conformational changes in vivo. The RNA virus Sindbis introduced Flare into neurons in the binocular region of visual cortex in rat. Injection sites were selected based on intrinsic optical imaging. Expression of Flare occurred in the cell bodies and dendritic processes. Neurons imaged in vivo using two-photon scanning microscopy typically revealed the soma best, discernable against the background labeling of the neuropil. Somatic fluorescence changes were correlated with flashed visual stimuli; however, averaging was essential to observe these changes. This study demonstrates that the genetic modification of single neurons to express a fluorescent voltage sensor can be used to assess neuronal activity in vivo. PMID:22461770

  8. Genetic variability of Yersinia pestis isolates as predicted by PCR-based IS100 genotyping and analysis of structural genes encoding glycerol-3-phosphate dehydrogenase (glpD).

    Science.gov (United States)

    Motin, Vladimir L; Georgescu, Anca M; Elliott, Jeffrey M; Hu, Ping; Worsham, Patricia L; Ott, Linda L; Slezak, Tomas R; Sokhansanj, Bahrad A; Regala, Warren M; Brubaker, Robert R; Garcia, Emilio

    2002-02-01

    A PCR-based genotyping system that detects divergence of IS100 locations within the Yersinia pestis genome was used to characterize a large collection of isolates of different biovars and geographical origins. Using sequences derived from the glycerol-negative biovar orientalis strain CO92, a set of 27 locus-specific primers was designed to amplify fragments between the end of IS100 and its neighboring gene. Geographically diverse members of the orientalis biovar formed a homogeneous group with identical genotype with the exception of strains isolated in Indochina. In contrast, strains belonging to the glycerol-positive biovar antiqua showed a variety of fingerprinting profiles. Moreover, strains of the biovar medievalis (also glycerol positive) clustered together with the antiqua isolates originated from Southeast Asia, suggesting their close phylogenetic relationships. Interestingly, a Manchurian biovar antiqua strain Nicholisk 51 displayed a genotyping pattern typical of biovar orientalis isolates. Analysis of the glycerol pathway in Y. pestis suggested that a 93-bp deletion within the glpD gene encoding aerobic glycerol-3-phosphate dehydrogenase might account for the glycerol-negative phenotype of the orientalis biovar. The glpD gene of strain Nicholisk 51 did not possess this deletion, although it contained two nucleotide substitutions characteristic of the glpD version found exclusively in biovar orientalis strains. To account for this close relationship between biovar orientalis strains and the antiqua Nicholisk 51 isolate, we postulate that the latter represents a variant of this biovar with restored ability to ferment glycerol. The fact that such a genetic lesion might be repaired as part of the natural evolutionary process suggests the existence of genetic exchange between different Yersinia strains in nature. The relevance of this observation on the emergence of epidemic Y. pestis strains is discussed.

  9. Association of genetic variations of genes encoding thrombospondin, type 1, domain-containing 4 and 7A with low bone mineral density in Japanese women with osteoporosis.

    Science.gov (United States)

    Mori, Seijiro; Kou, Ikuyo; Sato, Hidenori; Emi, Mitsuru; Ito, Hideki; Hosoi, Takayuki; Ikegawa, Shiro

    2008-01-01

    Twins and family studies have shown that genetic factors are important determinants of bone mass. Important aspects of bone mineral density (BMD) regulation are endocrine systems, notably hormonal regulation of adrenal corticoids, as indicated by clinical knowledge of glucocorticoid-induced osteoporosis. Glucocorticoid is known to negatively regulate bone mass in vivo, and glucocorticoid increases thrombospondin messenger ribonucleic acid (mRNA) levels. We studied single nucleotide polymorphisms (SNPs) in genes encoding thrombospondin, type 1, domain-containing 4 and 7A (THSD4 and THSD7A) for possible association with lumbar and femoral BMD among 337 Japanese women with osteoporosis who participated in the BioBank Japan project. Genetic variations of THSD4 and THSD7A loci displayed significant association with lumbar and femoral BMD. Most significant correlation was observed for THSD7A SNP rs12673692 with lumbar BMD (P = 0.00017). Homozygous carriers of the major (G) allele had the highest BMD [0.886 +/- 0.011 g/cm2, mean +/- standard deviation (SD)], whereas heterozygous carriers were intermediate (0.872 +/- 0.013 g/cm2) and homozygous A-allele carriers had the lowest (0.753 +/- 0.023 g/cm2). THSD4 SNP rs10851839 also displayed strong association with lumbar BMD (P = 0.0092). In addition, both THSD7A and THSD4 displayed significant association with femoral BMD in a recessive model (P = 0.036 and P = 0.0046, respectively). Results suggest that variations of THSD7A and THSD4 loci may be important determinants of osteoporosis in Japanese women.

  10. Performance optimization of EDFA-Raman hybrid optical amplifier using genetic algorithm

    Science.gov (United States)

    Singh, Simranjit; Kaler, R. S.

    2015-05-01

    For the first time, a novel net gain analytical model of EDFA-Raman hybrid optical amplifier (HOA) is designed and optimized the various parameters using genetic algorithm. Our method has shown to be robust in the simultaneous analysis of multiple parameters, such as Raman length, EDFA length and its pump powers, to obtained highest possible gain. The optimized HOA is further investigated and characterized on system level in the scenario of 100×10 Gbps dense wavelength division multiplexed (DWDM) system with 25 GHz interval. With an optimized HOA, a flat gain of >18 dB is obtained from frequency region 187 to 189.5 THz with a gain variation of less than 1.35 dB without using any gain flattened technique. The obtained noise figure is also the lowest value (<2 dB/channel) ever reported for proposed hybrid optical amplifier at reduced channel spacing with acceptable bit error rate.

  11. Pitfalls in the molecular genetic diagnosis of Leber hereditary optic neuropathy (LHON)

    Energy Technology Data Exchange (ETDEWEB)

    Johns, D.R. (Beth Israel Hospital, Boston, MA (United States)); Neufeld, M.J. (Johns Hopkins Univ. School of Medicine, Baltimore, MD (United States))

    1993-10-01

    Pathogenetic mutations in mtDNA are found in the majority of patients with Leber hereditary optic neuropathy (LHON), and molecular genetic techniques to detect them are important for diagnosis. A false-positive molecular genetic error has adverse consequences for the diagnosis of this maternally inherited disease. The authors found a number of mtDNA polymorphisms that occur adjacent to known LHON-associated mutations and that confound their molecular genetic detection. These transition mutations occur at mtDNA nt 11779 (SfaNI site loss, 11778 mutation), nt 3459 (BsaHI site loss, 3460 mutation), nt 15258 (AccI site loss, 15257 mutation), nt 14485 (mismatch primer Sau3AI site loss, 14484 mutation), and nt 13707 (BstNI site loss, 13708 mutation). Molecular genetic detection of the most common pathogenetic mtDNA mutations in LHON, using a single restriction enzyme, may be confounded by adjacent polymorphisms that occur with a false-positive rate of 2%-7%. 19 refs.

  12. Engineering a genetically encoded competitive inhibitor of the KEAP1-NRF2 interaction via structure-based design and phage display.

    Science.gov (United States)

    Guntas, Gurkan; Lewis, Steven M; Mulvaney, Kathleen M; Cloer, Erica W; Tripathy, Ashutosh; Lane, Thomas R; Major, Michael B; Kuhlman, Brian

    2016-01-01

    In its basal state, KEAP1 binds the transcription factor NRF2 (Kd = 5 nM) and promotes its degradation by ubiquitylation. Changes in the redox environment lead to modification of key cysteines within KEAP1, resulting in NRF2 protein accumulation and the transcription of genes important for restoring the cellular redox state. Using phage display and a computational loop grafting protocol, we engineered a monobody (R1) that is a potent competitive inhibitor of the KEAP1-NRF2 interaction. R1 bound to KEAP1 with a Kd of 300 pM and in human cells freed NRF2 from KEAP1 resulting in activation of the NRF2 promoter. Unlike cysteine-reactive small molecules that lack protein specificity, R1 is a genetically encoded, reversible inhibitor designed specifically for KEAP1. R1 should prove useful for studying the role of the KEAP1-NRF2 interaction in several disease states. The structure-based phage display strategy employed here is a general approach for engineering high-affinity binders that compete with naturally occurring interactions.

  13. Color-Coded Batteries - Electro-Photonic Inverse Opal Materials for Enhanced Electrochemical Energy Storage and Optically Encoded Diagnostics.

    Science.gov (United States)

    O'Dwyer, Colm

    2016-07-01

    For consumer electronic devices, long-life, stable, and reasonably fast charging Li-ion batteries with good stable capacities are a necessity. For exciting and important advances in the materials that drive innovations in electrochemical energy storage (EES), modular thin-film solar cells, and wearable, flexible technology of the future, real-time analysis and indication of battery performance and health is crucial. Here, developments in color-coded assessment of battery material performance and diagnostics are described, and a vision for using electro-photonic inverse opal materials and all-optical probes to assess, characterize, and monitor the processes non-destructively in real time are outlined. By structuring any cathode or anode material in the form of a photonic crystal or as a 3D macroporous inverse opal, color-coded "chameleon" battery-strip electrodes may provide an amenable way to distinguish the type of process, the voltage, material and chemical phase changes, remaining capacity, cycle health, and state of charge or discharge of either existing or new materials in Li-ion or emerging alternative battery types, simply by monitoring its color change.

  14. Genetic diversity of EBV-encoded LMP1 in the Swiss HIV Cohort Study and implication for NF-Κb activation.

    Directory of Open Access Journals (Sweden)

    Emilie Zuercher

    Full Text Available Epstein-Barr virus (EBV is associated with several types of cancers including Hodgkin's lymphoma (HL and nasopharyngeal carcinoma (NPC. EBV-encoded latent membrane protein 1 (LMP1, a multifunctional oncoprotein, is a powerful activator of the transcription factor NF-κB, a property that is essential for EBV-transformed lymphoblastoid cell survival. Previous studies reported LMP1 sequence variations and induction of higher NF-κB activation levels compared to the prototype B95-8 LMP1 by some variants. Here we used biopsies of EBV-associated cancers and blood of individuals included in the Swiss HIV Cohort Study (SHCS to analyze LMP1 genetic diversity and impact of sequence variations on LMP1-mediated NF-κB activation potential. We found that a number of variants mediate higher NF-κB activation levels when compared to B95-8 LMP1 and mapped three single polymorphisms responsible for this phenotype: F106Y, I124V and F144I. F106Y was present in all LMP1 isolated in this study and its effect was variant dependent, suggesting that it was modulated by other polymorphisms. The two polymorphisms I124V and F144I were present in distinct phylogenetic groups and were linked with other specific polymorphisms nearby, I152L and D150A/L151I, respectively. The two sets of polymorphisms, I124V/I152L and F144I/D150A/L151I, which were markers of increased NF-κB activation in vitro, were not associated with EBV-associated HL in the SHCS. Taken together these results highlighted the importance of single polymorphisms for the modulation of LMP1 signaling activity and demonstrated that several groups of LMP1 variants, through distinct mutational paths, mediated enhanced NF-κB activation levels compared to B95-8 LMP1.

  15. Biosynthesis of the 22nd Genetically Encoded Amino Acid Pyrrolysine: Structure and Reaction Mechanism of PylC at 1.5Å Resolution

    KAUST Repository

    Quitterer, Felix

    2012-12-01

    The second step in the biosynthesis of the 22nd genetically encoded amino acid pyrrolysine (Pyl) is catalyzed by PylC that forms the pseudopeptide l-lysine-Nε-3R-methyl-d-ornithine. Here, we present six crystal structures of the monomeric active ligase in complex with substrates, reaction intermediates, and products including ATP, the non-hydrolyzable ATP analogue 5′-adenylyl-β-γ-imidodiphosphate, ADP, d-ornithine (d-Orn), l-lysine (Lys), phosphorylated d-Orn, l-lysine-Nε-d-ornithine, inorganic phosphate, carbonate, and Mg2 +. The overall structure of PylC reveals similarities to the superfamily of ATP-grasp enzymes; however, there exist unique structural and functional features for a topological control of successive substrate entry and product release. Furthermore, the presented high-resolution structures provide detailed insights into the reaction mechanism of isopeptide bond formation starting with phosphorylation of d-Orn by transfer of a phosphate moiety from activated ATP. The binding of Lys to the enzyme complex is then followed by an SN2 reaction resulting in l-lysine-Nε-d-ornithine and inorganic phosphate. Surprisingly, PylC harbors two adenine nucleotides bound at the active site, what has not been observed in any ATP-grasp protein analyzed to date. Whereas one ATP molecule is involved in catalysis, the second adenine nucleotide functions as a selective anchor for the C- and N-terminus of the Lys substrate and is responsible for protein stability as shown by mutagenesis. © 2012 Elsevier Ltd.

  16. Application of a genetically encoded biosensor for live cell imaging of L-valine production in pyruvate dehydrogenase complex-deficient Corynebacterium glutamicum strains.

    Science.gov (United States)

    Mustafi, Nurije; Grünberger, Alexander; Mahr, Regina; Helfrich, Stefan; Nöh, Katharina; Blombach, Bastian; Kohlheyer, Dietrich; Frunzke, Julia

    2014-01-01

    The majority of biotechnologically relevant metabolites do not impart a conspicuous phenotype to the producing cell. Consequently, the analysis of microbial metabolite production is still dominated by bulk techniques, which may obscure significant variation at the single-cell level. In this study, we have applied the recently developed Lrp-biosensor for monitoring of amino acid production in single cells of gradually engineered L-valine producing Corynebacterium glutamicum strains based on the pyruvate dehydrogenase complex-deficient (PDHC) strain C. glutamicum ΔaceE. Online monitoring of the sensor output (eYFP fluorescence) during batch cultivation proved the sensor's suitability for visualizing different production levels. In the following, we conducted live cell imaging studies on C. glutamicum sensor strains using microfluidic chip devices. As expected, the sensor output was higher in microcolonies of high-yield producers in comparison to the basic strain C. glutamicum ΔaceE. Microfluidic cultivation in minimal medium revealed a typical Gaussian distribution of single cell fluorescence during the production phase. Remarkably, low amounts of complex nutrients completely changed the observed phenotypic pattern of all strains, resulting in a phenotypic split of the population. Whereas some cells stopped growing and initiated L-valine production, others continued to grow or showed a delayed transition to production. Depending on the cultivation conditions, a considerable fraction of non-fluorescent cells was observed, suggesting a loss of metabolic activity. These studies demonstrate that genetically encoded biosensors are a valuable tool for monitoring single cell productivity and to study the phenotypic pattern of microbial production strains.

  17. Mapping the subcellular distribution of α-synuclein in neurons using genetically encoded probes for correlated light and electron microscopy: implications for Parkinson's disease pathogenesis.

    Science.gov (United States)

    Boassa, Daniela; Berlanga, Monica L; Yang, Mary Ann; Terada, Masako; Hu, Junru; Bushong, Eric A; Hwang, Minju; Masliah, Eliezer; George, Julia M; Ellisman, Mark H

    2013-02-06

    Modifications to the gene encoding human α-synuclein have been linked to the development of Parkinson's disease. The highly conserved structure of α-synuclein suggests a functional interaction with membranes, and several lines of evidence point to a role in vesicle-related processes within nerve terminals. Using recombinant fusions of human α-synuclein, including new genetic tags developed for correlated light microscopy and electron microscopy (the tetracysteine-biarsenical labeling system or the new fluorescent protein for electron microscopy, MiniSOG), we determined the distribution of α-synuclein when overexpressed in primary neurons at supramolecular and cellular scales in three dimensions (3D). We observed specific association of α-synuclein with a large and otherwise poorly characterized membranous organelle system of the presynaptic terminal, as well as with smaller vesicular structures within these boutons. Furthermore, α-synuclein was localized to multiple elements of the protein degradation pathway, including multivesicular bodies in the axons and lysosomes within neuronal cell bodies. Examination of synapses in brains of transgenic mice overexpressing human α-synuclein revealed alterations of the presynaptic endomembrane systems similar to our findings in cell culture. Three-dimensional electron tomographic analysis of enlarged presynaptic terminals in several brain areas revealed that these terminals were filled with membrane-bounded organelles, including tubulovesicular structures similar to what we observed in vitro. We propose that α-synuclein overexpression is associated with hypertrophy of membrane systems of the presynaptic terminal previously shown to have a role in vesicle recycling. Our data support the conclusion that α-synuclein is involved in processes associated with the sorting, channeling, packaging, and transport of synaptic material destined for degradation.

  18. Mapping the subcellular distribution of alpha-synuclein in neurons using genetically encoded probes for correlated light and electron microscopy: Implications for Parkinson’s disease pathogenesis

    Science.gov (United States)

    Boassa, D.; Berlanga, M.L.; Yang, M.-L.; Terada, M.; Hu, J.; Bushong, E.A.; Hwang, M.; Masliah, E.; George, J.M.; Ellisman, M.H.

    2013-01-01

    Modifications to the gene encoding human alpha-synuclein have been linked to development of Parkinson’s disease. The highly conserved structure of alpha-synuclein suggests a functional interaction with membranes, and several lines of evidence point to a role in vesicle-related processes within nerve terminals. Using recombinant fusions of human alpha-synuclein including new genetic tags developed for correlated LM and EM (the tetracysteine-biarsenical labeling system or the new fluorescent protein for EM, MiniSOG), we determined the distribution of alpha-synuclein when over-expressed in primary neurons at supramolecular and cellular scales, in three dimensions (3D). We observed specific association of alpha-synuclein with a large and otherwise poorly characterized membranous organelle system of the presynaptic terminal, as well as with smaller vesicular structures within these boutons. Furthermore, alpha-synuclein was localized to multiple elements of the protein degradation pathway, including multivesicular bodies in the axons and lysosomes within neuronal cell bodies. Examination of synapses in brains of transgenic mice over-expressing human alpha-synuclein revealed alterations of the presynaptic endomembrane systems similar to our findings in cell culture. 3D electron tomographic analysis of enlarged presynaptic terminals in several brain areas revealed that these terminals were filled with membrane-bounded organelles, including tubulo-vesicular structures similar to what observed in vitro. We propose that alpha-synuclein over-expression is associated with hypertrophy of membrane systems of the presynaptic terminal previously shown to have a role in vesicle recycling. Our data support the conclusion that alpha- synuclein is involved in processes associated with the sorting, channeling, packaging and transport of synaptic material destined for degradation. PMID:23392688

  19. Structural analysis of the PSD-95 cluster by electron tomography and CEMOVIS: a proposal for the application of the genetically encoded metallothionein tag.

    Science.gov (United States)

    Hirabayashi, Ai; Fukunaga, Yuko; Miyazawa, Atsuo

    2014-06-01

    Postsynaptic density-95 (PSD-95) accumulates at excitatory postsynapses and plays important roles in the clustering and anchoring of numerous proteins at the PSD. However, a detailed ultrastructural analysis of clusters exclusively consisting of PSD-95 has never been performed. Here, we employed a genetically encoded tag, three tandem repeats of metallothionein (3MT), to study the structure of PSD-95 clusters in cells by electron tomography and cryo-electron microscopy of vitreous sections. We also performed conventional transmission electron microscopy (TEM). Cultured hippocampal neurons expressing a fusion protein of PSD-95 coupled to 3MT (PDS-95-3MT) were incubated with CdCl2 to result in the formation of Cd-bound PSD-95-3MT. Two types of electron-dense deposits composed of Cd-bound PSD-95-3MT were observed in these cells by TEM, as reported previously. Electron tomography revealed the presence of membrane-shaped structures representing PSD-95 clusters at the PSD and an ellipsoidal structure located in the non-synaptic cytoplasm. By TEM, the PSD-95 clusters appeared to be composed of a number of dense cores. In frozen hydrated sections, these dense cores were also found beneath the postsynaptic membrane. Taken together, our findings suggest that dense cores of PSD-95 aggregate to form the larger clusters present in the PSD and the non-synaptic cytoplasm. © The Author 2014. Published by Oxford University Press on behalf of The Japanese Society of Microscopy. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  20. Reconstructing optical parameters from double-integrating-sphere measurements using a genetic algorithm

    Science.gov (United States)

    Böcklin, Christoph; Baumann, Dirk; Stuker, Florian; Klohs, Jan; Rudin, Markus; Fröhlich, Jürg

    2013-02-01

    For the reconstruction of physiological changes in specific tissue layers detected by optical techniques, the exact knowledge of the optical parameters μa, μs and g of different tissue types is of paramount importance. One approach to accurately determine these parameters for biological tissue or phantom material is to use a double-integrating-sphere measurement system. It offers a flexible way to measure various kinds of tissues, liquids and artificial phantom materials. Accurate measurements can be achieved by technical adjustments and calibration of the spheres using commercially available reflection and transmission standards. The determination For the reconstruction of physiological changes in specific tissue layers detected by optical techniques, the exact knowledge of the optical parameters μa, μs and g of different tissue types is of paramount importance. One approach to accurately determine these parameters for biological tissue or phantom material is to use a double-integrating-sphere measurement system. It offers a flexible way to measure various kinds of tissues, liquids and artificial phantom materials. Accurate measurements can be achieved by technical adjustments and calibration of the spheres using commercially available reflection and transmission standards. The determination of the optical parameters of a material is based on two separate steps. Firstly, the reflectance ρs, the total transmittance TsT and the unscattered transmittance TsC of the sample s are measured with the double-integrating-sphere setup. Secondly, the optical parameters μa, μs and g are reconstructed with an inverse search algorithm combined with an appropriate solver for the forward problem (calculating ρs, TsT and TsC from μa, μs and g) has to be applied. In this study a Genetic Algorithm is applied as search heuristic, since it offers the most flexible and general approach without requiring any foreknowledge of the fitness-landscape. Given the challenging

  1. Genetics

    Science.gov (United States)

    ... Inheritance; Heterozygous; Inheritance patterns; Heredity and disease; Heritable; Genetic markers ... The chromosomes are made up of strands of genetic information called DNA. Each chromosome contains sections of ...

  2. Optical highlighter molecules in neurobiology.

    Science.gov (United States)

    Datta, Sandeep Robert; Patterson, George H

    2012-02-01

    The development of advanced optical methods has played a key role in propelling progress in neurobiology. Genetically-encoded fluorescent molecules found in nature have enabled labeling of individual neurons to study their physiology and anatomy. Here we discuss the recent use of both native and synthetic optical highlighter proteins to address key problems in neurobiology, including questions relevant to synaptic function, neuroanatomy, and the organization of neural circuits.

  3. Robust Face Location and Tracking Using Optical Flow and Genetic Algorithms

    Institute of Scientific and Technical Information of China (English)

    WANG Yanjiang; YUAN Baozong

    2001-01-01

    This paper presents a new and robustapproach to the detection, localization and tracking ofa human face in image sequences. First, a fast algo-rithm based on the neighbor-point-reliability is pro-posed to calculate the optical flow, which is used toextract the motion region. Then the hair and thehead knowledges are used to locate the face area. Forface tracking, a new genetic algorithms-based dynamictemplate-matching method is applied to search thenew position of the face in each new video frame. Ex-perimental results show that the proposed face track-ing method is fast and robust to illumination, faceposes, facial expressions and image distractors suchas facial occlusion by hands.

  4. Femtosecond optical transfection as a tool for genetic manipulation of human embryonic stem cells

    Science.gov (United States)

    Torres-Mapa, M. L.; Gardner, J.; Bradburn, H.; King, J.; Dholakia, K.; Gunn-Moore, F.

    2013-03-01

    We demonstrate the use of femtosecond optical transfection for the genetic manipulation of human embryonic stem cells. Using a system with an SLM combined with a scanning mirror allows poration of both single-cell and colony-formed human embryonic stem cells in a rapid and targeted manner. In this work, we show successful transfection of plasmid DNA tagged with fluorescent reporters into human embryonic stem cells using three doses of focused femtosecond laser. A significant number of transfected cells retained their undifferentiated morphological feature of large nucleus with high nucleus to cytoplasmic ratio, 48h after photoporation. Furthermore, DNA constructs driven by different types of promoters were also successfully transfected into human embryonic stem cells using this technique.

  5. An optimal policy based on the genetic algorithm for the dynamic threshold of the optical network

    Science.gov (United States)

    Zhu, Hongying; Le, Zichun; Dong, Wen; Fu, Minglei

    2006-09-01

    The complete partitioning policy (CP) for the wavelength resource in optical networks is now widely focused on. The dynamic threshold is one of the ways to make CP policy more efficient. Furthermore, an optimized threshold will be better for reducing the blocking probability and improving the utilization of the wavelength resource. Hence, the genetic algorithm is selected as the optimal policy on virtue of its excellent global search performance for getting optimized value of the dynamic threshold. Moreover, a maximal threshold as the high limit for the dynamic threshold is needed to be decided for making wavelengths shared between different wavelength classes, because the class with higher priority can share its wavelengths with the lower one after its own call setups are satisfied. Therefore, a neural network predictor that can predict the number of the next call setup is designed on the basis of the genetic algorithm to solve this problem. The values of the dynamic threshold and the maximal threshold are calculated, and the simulation results show that they take good effect in reducing the blocking probability and improving the utilization of the wavelength resource.

  6. Image-guided feedback for ophthalmic microsurgery using multimodal intraoperative swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography

    Science.gov (United States)

    Li, Jianwei D.; Malone, Joseph D.; El-Haddad, Mohamed T.; Arquitola, Amber M.; Joos, Karen M.; Patel, Shriji N.; Tao, Yuankai K.

    2017-02-01

    Surgical interventions for ocular diseases involve manipulations of semi-transparent structures in the eye, but limited visualization of these tissue layers remains a critical barrier to developing novel surgical techniques and improving clinical outcomes. We addressed limitations in image-guided ophthalmic microsurgery by using microscope-integrated multimodal intraoperative swept-source spectrally encoded scanning laser ophthalmoscopy and optical coherence tomography (iSS-SESLO-OCT). We previously demonstrated in vivo human ophthalmic imaging using SS-SESLO-OCT, which enabled simultaneous acquisition of en face SESLO images with every OCT cross-section. Here, we integrated our new 400 kHz iSS-SESLO-OCT, which used a buffered Axsun 1060 nm swept-source, with a surgical microscope and TrueVision stereoscopic viewing system to provide image-based feedback. In vivo human imaging performance was demonstrated on a healthy volunteer, and simulated surgical maneuvers were performed in ex vivo porcine eyes. Denselysampled static volumes and volumes subsampled at 10 volumes-per-second were used to visualize tissue deformations and surgical dynamics during corneal sweeps, compressions, and dissections, and retinal sweeps, compressions, and elevations. En face SESLO images enabled orientation and co-registration with the widefield surgical microscope view while OCT imaging enabled depth-resolved visualization of surgical instrument positions relative to anatomic structures-of-interest. TrueVision heads-up display allowed for side-by-side viewing of the surgical field with SESLO and OCT previews for real-time feedback, and we demonstrated novel integrated segmentation overlays for augmented-reality surgical guidance. Integration of these complementary imaging modalities may benefit surgical outcomes by enabling real-time intraoperative visualization of surgical plans, instrument positions, tissue deformations, and image-based surrogate biomarkers correlated with completion of

  7. Partial Correction of Psoriasis upon Genetic Knock-Down of Human TNF-α by Lentivirus-Encoded shRNAs in a Xenograft Mouse Model

    DEFF Research Database (Denmark)

    Jakobsen, Maria; Stenderup, Karin; Rosada, Cecilia

    with lentiviral vectors encoding an irrelevant shRNA. In conclusion, our results demonstrate that lentiviral vector-encoded TNF- shRNAs have the potential to down-regulate TNF- production both in vitro and in vivo. Phenotypic changes in shRNA-treated psoriatic skin suggest that TNF- -encoding RNA is a valid......The proinflammatory cytokine Tumor Necrosis Factor alpha (TNF- ) is upregulated in inflammatory psoriatic skin. The increased level of TNF- protein is thought to cause keratinocyte hyperproliferation, leukocyte infiltration as well as growth and dilation of superficial blood vessels, which are all...... characteristics of human psoriasis skin. Blockade of TNF- function with specific inhibitors at the protein level has resulted in a rapid clinical improvement in psoriasis patients, demonstrating that TNF- inhibition offers a promising therapy of psoriasis. Whether TNF- -encoding RNA is a valid therapeutic target...

  8. Automated synthesis of both the topology and numerical parameters for seven patented optical lens systems using genetic programming

    Science.gov (United States)

    Jones, Lee W.; Al-Sakran, Sameer H.; Koza, John R.

    2005-08-01

    This paper describes how genetic programming was used as an automated invention machine to synthesize both the topology and numerical parameters for seven previously patented optical lens systems, including one aspherical system and one issued in the 21st-century. Two of the evolved optical lens systems infringe the claims of the patents and the others are novel solutions that satisfy the design goals stated in the patent. The automatic synthesis was done "from scratch"--that is, without starting from a pre-existing good design and without pre-specifying the number of lenses, the topological layout of the lenses, or the numerical parameters of the lenses. Genetic programming is a form of evolutionary computation used to automatically solve problems. It starts from a high-level statement of what needs to be done and progressively breeds a population of candidate individuals over many generations using the principle of Darwinian natural selection and genetic recombination. The paper describes how genetic programming created eyepieces that duplicated the functionality of seven previously patented lens systems. The seven designs were created in a substantially similar and routine way, suggesting that the use of genetic programming in the automated design of both the topology and numerical parameters for optical lens systems may have widespread utility.

  9. Genetic and biochemical analyses of chromosome and plasmid gene homologues encoding ICL and ArCP domains in Vibrio anguillarum strain 775.

    Science.gov (United States)

    Di Lorenzo, Manuela; Stork, Michiel; Crosa, Jorge H

    2011-08-01

    Anguibactin, the siderophore produced by Vibrio anguillarum 775 is synthesized from 2,3-dihydroxybenzoic acid (DHBA), cysteine and hydroxyhistamine via a nonribosomal peptide synthetase (NRPS) mechanism. Most of the genes encoding anguibactin biosynthetic proteins are harbored by the pJM1 plasmid. In this work we report the identification of a homologue of the plasmid-encoded angB on the chromosome of strain 775. The product of both genes harbor an isochorismate lyase (ICL) domain that converts isochorismic acid to 2,3-dihydro-2,3-dihydroxybenzoic acid, one of the steps of DHBA synthesis. We show in this work that both ICL domains are functional in the production of DHBA in V. anguillarum as well as in E. coli. Substitution by alanine of the aspartic acid residue in the active site of both ICL domains completely abolishes their isochorismate lyase activity in vivo. The two proteins also carry an aryl carrier protein (ArCP) domain. In contrast with the ICL domains only the plasmid encoded ArCP can participate in anguibactin production as determined by complementation analyses and site-directed mutagenesis in the active site of the plasmid encoded protein, S248A. The site-directed mutants, D37A in the ICL domain and S248A in the ArCP domain of the plasmid encoded AngB were also tested in vitro and clearly show the importance of each residue for the domain function and that each domain operates independently.

  10. Genetically encoded synthesis of protein-based polymers with precisely specified molecular weight and sequence by recursive directional ligation: examples from the elastin-like polypeptide system.

    Science.gov (United States)

    Meyer, Dan E; Chilkoti, Ashutosh

    2002-01-01

    We report a new strategy for the synthesis of genes encoding repetitive, protein-based polymers of specified sequence, chain length, and architecture. In this stepwise approach, which we term "recursive directional ligation" (RDL), short gene segments are seamlessly combined in tandem using recombinant DNA techniques. The resulting larger genes can then be recursively combined until a gene of a desired length is obtained. This approach is modular and can be used to combine genes encoding different polypeptide sequences. We used this method to synthesize three different libraries of elastin-like polypeptides (ELPs); each library encodes a unique ELP sequence with systematically varied molecular weights. We also combined two of these sequences to produce a block copolymer. Because the thermal properties of ELPs depend on their sequence and chain length, the synthesis of these polypeptides provides an example of the importance of precise control over these parameters that is afforded by RDL.

  11. Partial Correction of Psoriasis upon Genetic Knock-Down of Human TNF-α by Lentivirus-Encoded shRNAs in a Xenograft Mouse Model

    DEFF Research Database (Denmark)

    Jakobsen, Maria; Stenderup, Karin; Rosada, Cecilia

    reduced the amount of released TNF- more than 50% upon viral transduction, was selected for in vivo studies. In vivo studies were carried out in a xenograft mouse model in which human psoriatic plaques keratome skin biopsies were transplanted onto SCID mice. Initial studies using eGFP-encoding lentiviral...... vectors demonstrated efficient transduction of human psoriatic skin. Grafted psoriatic skin was exposed to viral vector-encoded TNF- shRNAs by a single intradermal injection of purified VSV-G-pseudotyped lentiviral vectors (150 l containing 46.4 ng p24/ l was injected at a single site). Biopsies were...

  12. Spectrally encoded confocal microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Tearney, G.J.; Webb, R.H.; Bouma, B.E. [Wellman Laboratories of Photomedicine, Massachusetts General Hospital, 50 Blossom Street, BAR 703, Boston, Massachusetts 02114 (United States)

    1998-08-01

    An endoscope-compatible, submicrometer-resolution scanning confocal microscopy imaging system is presented. This approach, spectrally encoded confocal microscopy (SECM), uses a quasi-monochromatic light source and a transmission diffraction grating to detect the reflectivity simultaneously at multiple points along a transverse line within the sample. Since this method does not require fast spatial scanning within the probe, the equipment can be miniaturized and incorporated into a catheter or endoscope. Confocal images of an electron microscope grid were acquired with SECM to demonstrate the feasibility of this technique. {copyright} {ital 1998} {ital Optical Society of America}

  13. Genetic and biochemical analyses of chromosome and plasmid gene homologues encoding ICL and ArCP domains in Vibrioanguillarum strain 775

    NARCIS (Netherlands)

    Di Lorenzo, M.; Stork, M.; Crosa, J.H.

    2011-01-01

    Anguibactin, the siderophore produced by Vibrio anguillarum 775 is synthesized from 2,3-dihydroxybenzoic acid (DHBA), cysteine and hydroxyhistamine via a nonribosomal peptide synthetase (NRPS) mechanism. Most of the genes encoding anguibactin biosynthetic proteins are harbored by the pJM1 plasmid. I

  14. Generation of Interleukin-2 Receptor Gamma Gene Knockout Pigs from Somatic Cells Genetically Modified by Zinc Finger Nuclease-Encoding mRNA

    Science.gov (United States)

    Watanabe, Masahito; Nakano, Kazuaki; Matsunari, Hitomi; Matsuda, Taisuke; Maehara, Miki; Kanai, Takahiro; Kobayashi, Mirina; Matsumura, Yukina; Sakai, Rieko; Kuramoto, Momoko; Hayashida, Gota; Asano, Yoshinori; Takayanagi, Shuko; Arai, Yoshikazu; Umeyama, Kazuhiro; Nagaya, Masaki; Hanazono, Yutaka; Nagashima, Hiroshi

    2013-01-01

    Zinc finger nuclease (ZFN) is a powerful tool for genome editing. ZFN-encoding plasmid DNA expression systems have been recently employed for the generation of gene knockout (KO) pigs, although one major limitation of this technology is the use of potentially harmful genome-integrating plasmid DNAs. Here we describe a simple, non-integrating strategy for generating KO pigs using ZFN-encoding mRNA. The interleukin-2 receptor gamma (IL2RG) gene was knocked out in porcine fetal fibroblasts using ZFN-encoding mRNAs, and IL2RG KO pigs were subsequently generated using these KO cells through somatic cell nuclear transfer (SCNT). The resulting IL2RG KO pigs completely lacked a thymus and were deficient in T and NK cells, similar to human X-linked SCID patients. Our findings demonstrate that the combination of ZFN-encoding mRNAs and SCNT provides a simple robust method for producing KO pigs without genomic integration. PMID:24130776

  15. Computational Intelligence and Its Encoding Mechanism

    Institute of Scientific and Technical Information of China (English)

    LIU Man-dan

    2004-01-01

    The origin and characteristics of computational intelligence, and several typical computational intelligence algorithms such as genetic algorithm and DNA computing are described, and the influence of evolution strategies and convergence properties on the encoding mechanism is discussed. A novel genetic algorithm based on degressive carry number encoding is then proposed. This algorithm uses degressive carry number encoding in the evolutionary process instead of commonly used fixed carry number. Finally a novel encoding mechanism and a new algorithm are proposed, which combine modern computational intelligence with the traditional Chinese methodology.

  16. Computational Intelligence and Its Encoding Mechanism

    Institute of Scientific and Technical Information of China (English)

    LIUMan-dan

    2004-01-01

    The origin and characteristics of computational intelligence, and several typical computational intelligence algorithms such as genetic algorithm and DNA computing are described, and the influence of evolution strategies and convergence properties on the encoding mechanism is discussed. A novel genetic algorithm based on degressive carry number encoding is then proposed. This algorithm uses degressive carry number encoding in the evolutionary process instead of commonly used fixed carry number. Finally a novel encoding mechanism and a new algorithm are proposed, which combine modem computational intelligence with the traditional Chinese methodology.

  17. Automated discovery of structural features of the optic nerve head on the basis of image and genetic data

    Science.gov (United States)

    Christopher, Mark; Tang, Li; Fingert, John H.; Scheetz, Todd E.; Abramoff, Michael D.

    2014-03-01

    Evaluation of optic nerve head (ONH) structure is a commonly used clinical technique for both diagnosis and monitoring of glaucoma. Glaucoma is associated with characteristic changes in the structure of the ONH. We present a method for computationally identifying ONH structural features using both imaging and genetic data from a large cohort of participants at risk for primary open angle glaucoma (POAG). Using 1054 participants from the Ocular Hypertension Treatment Study, ONH structure was measured by application of a stereo correspondence algorithm to stereo fundus images. In addition, the genotypes of several known POAG genetic risk factors were considered for each participant. ONH structural features were discovered using both a principal component analysis approach to identify the major modes of variance within structural measurements and a linear discriminant analysis approach to capture the relationship between genetic risk factors and ONH structure. The identified ONH structural features were evaluated based on the strength of their associations with genotype and development of POAG by the end of the OHTS study. ONH structural features with strong associations with genotype were identified for each of the genetic loci considered. Several identified ONH structural features were significantly associated (p genetic risk status was found to substantially increase performance of early POAG prediction. These results suggest incorporating both imaging and genetic data into ONH structural modeling significantly improves the ability to explain POAG-related changes to ONH structure.

  18. Distribution, Functional Expression, and Genetic Organization of Cif, a Phage-Encoded Type III-Secreted Effector from Enteropathogenic and Enterohemorrhagic Escherichia coli▿

    Science.gov (United States)

    Loukiadis, Estelle; Nobe, Rika; Herold, Sylvia; Tramuta, Clara; Ogura, Yoshitoshi; Ooka, Tadasuke; Morabito, Stefano; Kérourédan, Monique; Brugère, Hubert; Schmidt, Herbert; Hayashi, Tetsuya; Oswald, Eric

    2008-01-01

    Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) inject effector proteins into host cells via a type III secretion system encoded by the locus of enterocyte effacement (LEE). One of these effectors is Cif, encoded outside the LEE by a lambdoid prophage. In this study, we demonstrated that the Cif-encoding prophage of EPEC strain E22 is inducible and produces infectious phage particles. We investigated the distribution and functional expression of Cif in 5,049 E. coli strains of human, animal, and environmental origins. A total of 115 E. coli isolates from diverse origins and geographic locations carried cif. The presence of cif was tightly associated with the LEE, since all the cif-positive isolates were positive for the LEE. These results suggested that the Cif-encoding prophages have been widely disseminated within the natural population of E. coli but positively selected within the population of LEE-positive strains. Nonetheless, 66% of cif-positive E. coli strains did not induce a typical Cif-related phenotype in eukaryotic cells due to frameshift mutations or insertion of an IS element in the cif gene. The passenger region of the prophages carrying cif was highly variable and showed various combinations of IS elements and genes coding for other effectors such as nleB, nleC, nleH, nleG, espJ, and nleA/espI (some of which were also truncated). This diversity and the presence of nonfunctional effectors should be taken into account to assess EPEC and EHEC pathogenicity and tropism. PMID:17873042

  19. Distribution, functional expression, and genetic organization of Cif, a phage-encoded type III-secreted effector from enteropathogenic and enterohemorrhagic Escherichia coli.

    Science.gov (United States)

    Loukiadis, Estelle; Nobe, Rika; Herold, Sylvia; Tramuta, Clara; Ogura, Yoshitoshi; Ooka, Tadasuke; Morabito, Stefano; Kérourédan, Monique; Brugère, Hubert; Schmidt, Herbert; Hayashi, Tetsuya; Oswald, Eric

    2008-01-01

    Enteropathogenic Escherichia coli (EPEC) and enterohemorrhagic E. coli (EHEC) inject effector proteins into host cells via a type III secretion system encoded by the locus of enterocyte effacement (LEE). One of these effectors is Cif, encoded outside the LEE by a lambdoid prophage. In this study, we demonstrated that the Cif-encoding prophage of EPEC strain E22 is inducible and produces infectious phage particles. We investigated the distribution and functional expression of Cif in 5,049 E. coli strains of human, animal, and environmental origins. A total of 115 E. coli isolates from diverse origins and geographic locations carried cif. The presence of cif was tightly associated with the LEE, since all the cif-positive isolates were positive for the LEE. These results suggested that the Cif-encoding prophages have been widely disseminated within the natural population of E. coli but positively selected within the population of LEE-positive strains. Nonetheless, 66% of cif-positive E. coli strains did not induce a typical Cif-related phenotype in eukaryotic cells due to frameshift mutations or insertion of an IS element in the cif gene. The passenger region of the prophages carrying cif was highly variable and showed various combinations of IS elements and genes coding for other effectors such as nleB, nleC, nleH, nleG, espJ, and nleA/espI (some of which were also truncated). This diversity and the presence of nonfunctional effectors should be taken into account to assess EPEC and EHEC pathogenicity and tropism.

  20. High-performance genetically targetable optical neural silencing by light-driven proton pumps.

    Science.gov (United States)

    Chow, Brian Y; Han, Xue; Dobry, Allison S; Qian, Xiaofeng; Chuong, Amy S; Li, Mingjie; Henninger, Michael A; Belfort, Gabriel M; Lin, Yingxi; Monahan, Patrick E; Boyden, Edward S

    2010-01-07

    The ability to silence the activity of genetically specified neurons in a temporally precise fashion would provide the opportunity to investigate the causal role of specific cell classes in neural computations, behaviours and pathologies. Here we show that members of the class of light-driven outward proton pumps can mediate powerful, safe, multiple-colour silencing of neural activity. The gene archaerhodopsin-3 (Arch) from Halorubrum sodomense enables near-100% silencing of neurons in the awake brain when virally expressed in the mouse cortex and illuminated with yellow light. Arch mediates currents of several hundred picoamps at low light powers, and supports neural silencing currents approaching 900 pA at light powers easily achievable in vivo. Furthermore, Arch spontaneously recovers from light-dependent inactivation, unlike light-driven chloride pumps that enter long-lasting inactive states in response to light. These properties of Arch are appropriate to mediate the optical silencing of significant brain volumes over behaviourally relevant timescales. Arch function in neurons is well tolerated because pH excursions created by Arch illumination are minimized by self-limiting mechanisms to levels comparable to those mediated by channelrhodopsins or natural spike firing. To highlight how proton pump ecological and genomic diversity may support new innovation, we show that the blue-green light-drivable proton pump from the fungus Leptosphaeria maculans (Mac) can, when expressed in neurons, enable neural silencing by blue light, thus enabling alongside other developed reagents the potential for independent silencing of two neural populations by blue versus red light. Light-driven proton pumps thus represent a high-performance and extremely versatile class of 'optogenetic' voltage and ion modulator, which will broadly enable new neuroscientific, biological, neurological and psychiatric investigations.

  1. Associating optical measurements and estimating orbits of geocentric objects with a Genetic Algorithm: performance limitations.

    Science.gov (United States)

    Zittersteijn, Michiel; Schildknecht, Thomas; Vananti, Alessandro; Dolado Perez, Juan Carlos; Martinot, Vincent

    2016-07-01

    Currently several thousands of objects are being tracked in the MEO and GEO regions through optical means. With the advent of improved sensors and a heightened interest in the problem of space debris, it is expected that the number of tracked objects will grow by an order of magnitude in the near future. This research aims to provide a method that can treat the correlation and orbit determination problems simultaneously, and is able to efficiently process large data sets with minimal manual intervention. This problem is also known as the Multiple Target Tracking (MTT) problem. The complexity of the MTT problem is defined by its dimension S. Current research tends to focus on the S = 2 MTT problem. The reason for this is that for S = 2 the problem has a P-complexity. However, with S = 2 the decision to associate a set of observations is based on the minimum amount of information, in ambiguous situations (e.g. satellite clusters) this will lead to incorrect associations. The S > 2 MTT problem is an NP-hard combinatorial optimization problem. In previous work an Elitist Genetic Algorithm (EGA) was proposed as a method to approximately solve this problem. It was shown that the EGA is able to find a good approximate solution with a polynomial time complexity. The EGA relies on solving the Lambert problem in order to perform the necessary orbit determinations. This means that the algorithm is restricted to orbits that are described by Keplerian motion. The work presented in this paper focuses on the impact that this restriction has on the algorithm performance.

  2. Sequential amplitude divided angular multiplexing encoding optical system design for high power excimer laser system%连续分振幅式高功率准分子激光角多路编码光路设计

    Institute of Scientific and Technical Information of China (English)

    胡云; 王大辉; 赵学庆

    2016-01-01

    In high power excimer laser system, angular multiplexing technique is employed to achieve both high energy and narrow pulse output. In this article, angular multiplexing technique was introduced, and a multiplexing encoding method was presented. This method encoded seed beam in two steps by sequential amplitude splitting. The optical elements were arranged in rectangle arrays and piled by layers. A specific optical design was made for XeCl high power excimer laser system in this laboratory. This method of angular multiplexing encoding has advantages of compacted space, small encoding error, good compatibility with alignment and measurement, and is also easy to fabricate and assemble. This design is adopted in the system and performs well.%在高功率准分子激光系统中,一般采用光学角多路技术来获得高能量窄脉冲输出。文中介绍了角多路技术原理,提出了一种采用矩形阵列和空间层叠光路结构的连续分振幅两次编码方式,并针对该实验室的XeCl高功率准分子激光系统进行了具体的编码光路设计,给出了设计实例。该方法具有编码结构紧凑,编码精度高,与光路准直、激光参数测量系统等兼容性好,便于加工制作和安装调节等优点,目前已在系统中应用,效果良好。

  3. Reduced hippocampal activation during episodic encoding in middle-aged individuals at genetic risk of Alzheimer's Disease: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Torgerson Britta M

    2006-01-01

    Full Text Available Abstract Background The presence of the apolipoprotein E (APOE ε4 allele is a major risk factor for the development of Alzheimer's disease (AD, and has been associated with metabolic brain changes several years before the onset of typical AD symptoms. Functional MRI (fMRI is a brain imaging technique that has been used to demonstrate hippocampal activation during measurement of episodic encoding, but the effect of the ε4 allele on hippocampal activation has not been firmly established. Methods The present study examined the effects of APOE genotype on brain activation patterns in the medial temporal lobe (MTL during an episodic encoding task using a well-characterized novel item versus familiar item contrast in cognitively normal, middle-aged (mean = 54 years individuals who had at least one parent with AD. Results We found that ε3/4 heterozygotes displayed reduced activation in the hippocampus and MTL compared to ε3/3 homozygotes. There were no significant differences between the groups in age, education or neuropsychological functioning, suggesting that the altered brain activation seen in ε3/4 heterozygotes was not associated with impaired cognitive function. We also found that participants' ability to encode information on a neuropsychological measure of learning was associated with greater activation in the anterior MTL in the ε3/3 homozygotes, but not in the ε3/4 heterozygotes. Conclusion Together with previous studies reporting reduced glucose metabolism and AD-related neuropathology, this study provides convergent validity for the idea that the MTL exhibits functional decline associated with the APOE ε4 allele. Importantly, these changes were detected in the absence of meaningful neuropsychological differences between the groups. A focus of ongoing work in this laboratory is to determine if these findings are predictive of subsequent cognitive decline.

  4. The Association between Genetic Variations of CHI3L1, Levels of the Encoded Glycoprotein YKL-40 and the Lipid Profile in a Danish Population

    DEFF Research Database (Denmark)

    Thomsen, Stine Brinkløv; Rathcke, Camilla Noelle; Skaaby, Tea

    2012-01-01

    The inflammatory biomarker YKL-40 seems to play a role in atherosclerosis and is elevated in patients with obesity, cardiovascular disease and type 2 diabetes. Single nucleotide polymorphisms (SNPs) of the YKL-40 encoding gene, CHI3L1, are associated with inter-individual YKL-40 levels. One study...... of the differentiated lipid profile in a Danish general population....... has described an association between a promoter polymorphism of CHI3L1 and levels of low density lipoprotein. The objective of this study was to evaluate the influence of YKL-40 on lipid parameters by determining the association between polymorphisms of CHI3L1, serum YKL-40 and levels...

  5. Molecular analysis of the bacteriocin-encoding plasmid pDGL1 from Enterococcus durans and genetic characterization of the durancin locus

    Science.gov (United States)

    Enterococci constitute a significant component of lactic acid bacteria normally present in the intestinal microflora and include strains that produce bacteriocins. The genetic determinants for durancin GL in Enterococcus durans 41D were identified on the 8,347 bp plasmid pDGL1 by plasmid curing exp...

  6. Distribution and regulation of the mobile genetic element-encoded phenol-soluble modulin PSM-mec in methicillin-resistant Staphylococcus aureus.

    Science.gov (United States)

    Chatterjee, Som S; Chen, Liang; Joo, Hwang-Soo; Cheung, Gordon Y C; Kreiswirth, Barry N; Otto, Michael

    2011-01-01

    The phenol-soluble modulin PSM-mec is the only known staphylococcal toxin that is encoded on a mobile antibiotic resistance determinant, namely the staphylococcal cassette chromosome (SCC) element mec encoding resistance to methicillin. Here we show that the psm-mec gene is found frequently among methicillin-resistant Staphylococcus aureus (MRSA) strains of SCCmec types II, III, and VIII, and is a conserved part of the class A mec gene complex. Controlled expression of AgrA versus RNAIII in agr mutants of all 3 psm-mec-positive SCCmec types demonstrated that expression of psm-mec, which is highly variable, is controlled by AgrA in an RNAIII-independent manner. Furthermore, psm-mec isogenic deletion mutants showed only minor changes in PSMα peptide production and unchanged (or, as previously described, diminished) virulence compared to the corresponding wild-type strains in a mouse model of skin infection. This indicates that the recently reported regulatory impact of the psm-mec locus on MRSA virulence, which is opposite to that of the PSM-mec peptide and likely mediated by a regulatory RNA, is minor when analyzed in the original strain background. Our study gives new insight in the distribution, regulation, and role in virulence of the PSM-mec peptide and the psm-mec gene locus.

  7. Giardia intestinalis: conservation of the variant-specific surface protein VSP417-1 (TSA417) and identification of a divergent homologue encoded at a duplicated locus in genetic group II isolates.

    Science.gov (United States)

    Ey, P L; Darby, J M

    1998-11-01

    The stability of the gene encoding TSA417, a 72-kDa variant-specific surface protein (VSP) produced by trophozoites of Giardia intestinalis isolate WB-C6, was investigated in isolates of similar (Assemblage A / Group I) or distinct (Assemblage A / Group II) genotype. Using primers specific for the WB-C6 tsa417 gene, DNA amplified in polymerase chain reactions from genomic DNA indicated the presence, in every isolate, of an intact coding sequence possessing conserved restriction sites diagnostic for this locus (herein designated vsp417-1). Sequence analysis of the DNA amplified from the genomes of genetic Group I ("A-I") isolates revealed complete identity with the published WB-C6 tsa417 (vsp417-1(A-I)) sequence. Equivalent products, amplified from the genomes of genetic Group II ("A-II") isolates, similarly yielded an invariant and apparently allelic 2142-bp coding sequence (designated vsp417-1(A-II)) possessing 79% nucleotide identity with vsp417-1(A-I) and polymorphisms unique to Group II organisms. The encoded polypeptides (VSP417-1(A-I) and VSP417-1(A-II)) are identical at 75% of amino acid positions. Substitutions are concentrated within the N-terminal portions of the proteins, but the overall structure of VSP417-1 has changed little during the evolution of the Group I and Group II genotypes from their common clonal ancestor. An additional 0.7-kb DNA, representing a separate locus (vsp417-5) encoding a 22.3-kDa VSP, was amplified from genetic Group II genomes exclusively but only using particular primer combinations. The vsp417-5(A-II) gene exhibits >85% sequence identity with the 5' and 3' segments of vsp417-1(A-I) and vsp417-1(A-II) but it lacks a 1482-bp segment that comprises the central portion of the vsp417-1 locus. Excision of this segment seems to have occurred by intragenic recombination, possibly initiated by a stem loop formed between palindromic sequences which border the 1482-bp segment within vsp417-1 but which are contiguous in vsp417-5(A

  8. Genetics

    DEFF Research Database (Denmark)

    Christensen, Kaare; McGue, Matt

    2016-01-01

    The sequenced genomes of individuals aged ≥80 years, who were highly educated, self-referred volunteers and with no self-reported chronic diseases were compared to young controls. In these data, healthy ageing is a distinct phenotype from exceptional longevity and genetic factors that protect...

  9. Contrast improvement of continuous wave diffuse optical tomography reconstruction by hybrid approach using least square and genetic algorithm.

    Science.gov (United States)

    Patra, Rusha; Dutta, Pranab K

    2015-07-01

    Reconstruction of the absorption coefficient of tissue with good contrast is of key importance in functional diffuse optical imaging. A hybrid approach using model-based iterative image reconstruction and a genetic algorithm is proposed to enhance the contrast of the reconstructed image. The proposed method yields an observed contrast of 98.4%, mean square error of 0.638×10⁻³, and object centroid error of (0.001 to 0.22) mm. Experimental validation of the proposed method has also been provided with tissue-like phantoms which shows a significant improvement in image quality and thus establishes the potential of the method for functional diffuse optical tomography reconstruction with continuous wave setup. A case study of finger joint imaging is illustrated as well to show the prospect of the proposed method in clinical diagnosis. The method can also be applied to the concentration measurement of a region of interest in a turbid medium.

  10. An Encoder/Decoder Scheme of OCDMA Based on Waveguide

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    A new encoder/decoder scheme of OCDMA based on waveguide isproposed in this paper. The principle as well as the structure of waveguide encoder/decoder is given. It can be seen that all-optical OCDMA encoder/decoder can be realized by the proposed scheme of the waveguide encoder/decoder. It can also make the OCDMA encoder/decoder integrated easily and the access controlled easily. The system based on this scheme can work under the entirely asynchronous condition.

  11. Genetic Analysis Reveals a Hierarchy of Interactions between Polycystin-Encoding Genes and Genes Controlling Cilia Function during Left-Right Determination.

    Directory of Open Access Journals (Sweden)

    Daniel T Grimes

    2016-06-01

    Full Text Available During mammalian development, left-right (L-R asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This 'nodal flow' is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM. Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we characterize a Pkd1l1 mutant line in which Nodal is activated bilaterally, suggesting that PKD1L1 is not required for LPM Nodal pathway activation per se, but rather to restrict Nodal to the left side downstream of nodal flow. Epistasis analysis shows that Pkd1l1 acts as an upstream genetic repressor of Pkd2. This study therefore provides a genetic pathway for the early stages of L-R determination. Moreover, using a system in which cultured cells are supplied artificial flow, we demonstrate that PKD1L1 is sufficient to mediate a Ca2+ signaling response after flow stimulation. Finally, we show that an extracellular PKD domain within PKD1L1 is crucial for PKD1L1 function; as such, destabilizing the domain causes L-R defects in the mouse. Our demonstration that PKD1L1 protein can mediate a response to flow coheres with a mechanosensation model of flow sensation in which the force of fluid flow drives asymmetric gene expression in the embryo.

  12. Genetic Analysis Reveals a Hierarchy of Interactions between Polycystin-Encoding Genes and Genes Controlling Cilia Function during Left-Right Determination.

    Science.gov (United States)

    Grimes, Daniel T; Keynton, Jennifer L; Buenavista, Maria T; Jin, Xingjian; Patel, Saloni H; Kyosuke, Shinohara; Vibert, Jennifer; Williams, Debbie J; Hamada, Hiroshi; Hussain, Rohanah; Nauli, Surya M; Norris, Dominic P

    2016-06-01

    During mammalian development, left-right (L-R) asymmetry is established by a cilia-driven leftward fluid flow within a midline embryonic cavity called the node. This 'nodal flow' is detected by peripherally-located crown cells that each assemble a primary cilium which contain the putative Ca2+ channel PKD2. The interaction of flow and crown cell cilia promotes left side-specific expression of Nodal in the lateral plate mesoderm (LPM). Whilst the PKD2-interacting protein PKD1L1 has also been implicated in L-R patterning, the underlying mechanism by which flow is detected and the genetic relationship between Polycystin function and asymmetric gene expression remains unknown. Here, we characterize a Pkd1l1 mutant line in which Nodal is activated bilaterally, suggesting that PKD1L1 is not required for LPM Nodal pathway activation per se, but rather to restrict Nodal to the left side downstream of nodal flow. Epistasis analysis shows that Pkd1l1 acts as an upstream genetic repressor of Pkd2. This study therefore provides a genetic pathway for the early stages of L-R determination. Moreover, using a system in which cultured cells are supplied artificial flow, we demonstrate that PKD1L1 is sufficient to mediate a Ca2+ signaling response after flow stimulation. Finally, we show that an extracellular PKD domain within PKD1L1 is crucial for PKD1L1 function; as such, destabilizing the domain causes L-R defects in the mouse. Our demonstration that PKD1L1 protein can mediate a response to flow coheres with a mechanosensation model of flow sensation in which the force of fluid flow drives asymmetric gene expression in the embryo.

  13. A conserved genetic module that encodes the major virion components in both the coliphage T4 and the marine cyanophage S-PM2.

    Science.gov (United States)

    Hambly, E; Tétart, F; Desplats, C; Wilson, W H; Krisch, H M; Mann, N H

    2001-09-25

    Sequence analysis of a 10-kb region of the genome of the marine cyanomyovirus S-PM2 reveals a homology to coliphage T4 that extends as a contiguous block from gene (g)18 to g23. The order of the S-PM2 genes in this region is similar to that of T4, but there are insertions and deletions of small ORFs of unknown function. In T4, g18 codes for the tail sheath, g19, the tail tube, g20, the head portal protein, g21, the prohead core protein, g22, a scaffolding protein, and g23, the major capsid protein. Thus, the entire module that determines the structural components of the phage head and contractile tail is conserved between T4 and this cyanophage. The significant differences in the morphology of these phages must reflect the considerable divergence of the amino acid sequence of their homologous virion proteins, which uniformly exceeds 50%. We suggest that their enormous diversity in the sea could be a result of genetic shuffling between disparate phages mediated by such commonly shared modules. These conserved sequences could facilitate genetic exchange by providing partially homologous substrates for recombination between otherwise divergent phage genomes. Such a mechanism would thus expand the pool of phage genes accessible by recombination to all those phages that share common modules.

  14. Optics

    CERN Document Server

    Fincham, W H A

    2013-01-01

    Optics: Ninth Edition Optics: Ninth Edition covers the work necessary for the specialization in such subjects as ophthalmic optics, optical instruments and lens design. The text includes topics such as the propagation and behavior of light; reflection and refraction - their laws and how different media affect them; lenses - thick and thin, cylindrical and subcylindrical; photometry; dispersion and color; interference; and polarization. Also included are topics such as diffraction and holography; the limitation of beams in optical systems and its effects; and lens systems. The book is recommen

  15. A Preliminary Study of DBH (Encoding Dopamine Beta-Hydroxylase) Genetic Variation and Neural Correlates of Emotional and Motivational Processing in Individuals With and Without Pathological Gambling.

    Science.gov (United States)

    Yang, Bao-Zhu; Balodis, Iris M; Lacadie, Cheryl M; Xu, Jiansong; Potenza, Marc N

    2016-06-01

    Background and aims Corticostriatal-limbic neurocircuitry, emotional and motivational processing, dopaminergic and noradrenergic systems and genetic factors have all been implicated in pathological gambling (PG). However, allelic variants of genes influencing dopaminergic and noradrenergic neurotransmitters have not been investigated with respect to the neural correlates of emotional and motivational states in PG. Dopamine beta-hydroxylase (DBH) converts dopamine to norepinephrine; the T allele of a functional single-nucleotide polymorphism rs1611115 (C-1021T) in the DBH gene is associated with less DBH activity and has been linked to emotional processes and addiction. Here, we investigate the influence of rs1611115 on the neural correlates of emotional and motivational processing in PG and healthy comparison (HC) participants. Methods While undergoing functional magnetic resonance imaging, 18 PG and 25 HC participants, all European Americans, viewed gambling-, sad-, and cocaine-related videotapes. Analyses focused on brain activation differences related to DBH genotype (CC/T-carrier [i.e., CT and TT]) and condition (sad/gambling/cocaine). Results CC participants demonstrated greater recruitment of corticostriatal-limbic regions, relative to T-carriers. DBH variants were also associated with altered corticostriatal-limbic activations across the different videotape conditions, and this association appeared to be driven by greater activation in CC participants relative to T-carriers during the sad condition. CC relative to T-carrier subjects also reported greater subjective sadness to the sad videotapes. Conclusions Individual differences in genetic composition linked to aminergic function contribute significantly to emotional regulation across diagnostic groups and warrant further investigation in PG.

  16. Nucleotide sequence and molecular genetic analysis of the vaccinia virus HindIII N/M region encoding the genes responsible for resistance to alpha-amanitin.

    Science.gov (United States)

    Tamin, A; Villarreal, E C; Weinrich, S L; Hruby, D E

    1988-07-01

    The genomic location of the gene(s) which provides vaccinia virus (VV) alpha-amanitin-resistant mutants with a drug-resistant phenotype have been mapped to the HindIII N/M region of the genome by the use of marker rescue techniques [E. C. Villarreal and D. E. Hruby (1986) J. Virol. 57, 65-70]. Nucleotide sequencing of a 2356-bp HindIII-Sau3A fragment of the vaccinia virus genome encompassing this region reveals the presence of two complete leftward-reading open reading frames (ORFs, N2 and M1) and two incomplete ORFs (N1 and M2). By computer analysis the N2 and M1 ORFs would be predicted to encode soluble VV polypeptides with molecular weights of approximately 20 and 48 kDa, respectively. The N2 and M1 ORFs have extremely A-T-rich 5'-proximal sequences, consistent with previous data regarding the location and A-T-richness of viral early promoters. Likewise, the consensus signal believed to be involved in terminating VV early gene transcription, TTTTTNT, was evident at the 3'-boundary of both the N2 and M1 ORFs suggesting that these genes may be VV early genes. The in vivo transcriptional activity, orientation, and limits of these putative transcriptional units were investigated by Northern blot, nuclease S1, and primer extension analysis. Both N2- and M1-specific transcripts were detected in the cytoplasm of VV-infected cells, suggesting that these loci are bonafide viral genes. Time-course nuclease S1 experiments revealed that the N2 gene was transcribed exclusively prior to VV DNA replication. In contrast, the M1 gene was transcribed throughout infection, although different start sites were used at early versus late times postinfection. These results are discussed in relation to the drug-resistant phenotype and future experiments to identify the viral gene product responsible.

  17. Optics

    CERN Document Server

    Fincham, W H A

    2013-01-01

    Optics: Eighth Edition covers the work necessary for the specialization in such subjects as ophthalmic optics, optical instruments and lens design. The text includes topics such as the propagation and behavior of light; reflection and refraction - their laws and how different media affect them; lenses - thick and thin, cylindrical and subcylindrical; photometry; dispersion and color; interference; and polarization. Also included are topics such as diffraction and holography; the limitation of beams in optical systems and its effects; and lens systems. The book is recommended for engineering st

  18. Optical security system using jigsaw transforms of the second random phase mask and the encrypted image in a double random phase encoding system

    Science.gov (United States)

    Singh, Madan; Kumar, Arvind; Singh, Kehar

    2008-10-01

    In this paper, we have described a simple and secure double random phase encoding and decoding system to encrypt and decrypt a two-dimensional gray scale image. We have used jigsaw transforms of the second random phase mask and the encrypted image. The random phase mask placed in the Fourier plane is broken into independent non-overlapping segments by applying the jigsaw transform. To make the system more secure, a jigsaw transform on the encrypted image is also carried out. The encrypted image is also broken into independent non-overlapping segments. The jigsaw transform indices of random phase code and the encrypted image form the keys for the successful retrieval of the data. Encrypting with this technique makes it almost impossible to retrieve the image without using both the right keys. Results of computer simulation have been presented in support of the proposed idea. Mean square error (MSE) between the decrypted and the original image has also been calculated in support of the technique.

  19. Heat transfer analysis of unsteady graphene oxide nanofluid flow using a fuzzy identifier evolved by genetically encoded mutable smart bee algorithm

    Directory of Open Access Journals (Sweden)

    Mohammadreza Azimi

    2015-03-01

    Full Text Available In the current research, the unsteady two dimensional Graphene Oxide water based nanofluid heat transfer between two moving parallel plates is analyzed using an intelligent black-box identifier. The developed intelligent tool is known as evolvable evolutionary fuzzy inference system (EE-FIS which is based on the integration of low-level fuzzy programming and hyper-level evolutionary computing concepts. Here, the authors propose the use of a modified evolutionary algorithm (EA which is called hybrid genetic mutable smart bee algorithm (HGMSBA. The proposed HGMSBA is used to evolve both antecedent and consequent parts of fuzzy rule base. Besides, it tries to prune the rule base of fuzzy inference system (FIS to decrease its computational complexity and increase its interpretability. By considering the prediction error of the fuzzy identifier as the objective function of HGMSBA, an automatic soft interpolation machine is developed which can intuitively increase the robustness and accuracy of the final model. Here, HGMSBA-FIS is used to provide a nonlinear map between inputs, i.e. nanoparticles solid volume fraction (ϕ, Eckert number (Ec and a moving parameter which describes the movements of plates (S, and output, i.e. Nusselt number (Nu. Prior to proceeding with the modeling process, a comprehensive numerical comparative study is performed to investigate the potentials of the proposed model for nonlinear system identification. After demonstrating the efficacy of HGMSBA for training the FIS, the system is applied to the considered problem. Based on the obtained results, it can be inferred that the developed HGMSBA-FIS black-box identifier can be used as a very authentic tool with respect to accuracy and robustness. Besides, as the proposed black-box is not a physics-based identifier, it frees experts from the cumbersome mathematical formulations, and can be used for advanced real-time applications such as model-based control. The simulations

  20. Optimal Design of Dual-Pump Fibre-Optical Parametric Amplifiers with Dispersion Fluctuations Based on Hybrid Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    LIU Xue-Ming; LI Yan-He

    2005-01-01

    @@ Solutions of dual-pump fibre-optical parametric amplifiers (DP-FOPAs) with dispersion fluctuations are derived by using a matrix operator. Based on these solutions and a hybrid genetic algorithm, we have optimized threesection DP-FOPAs to increase the signal band and improve the gain uniformity. The optimizations demonstrate that when dispersion fluctuations are taken into account, the 44-nm signal band with the 0.37-dB ripple and over 14.8-dB gain can be obtained from the three-section DP-FOPA, instead of the lowest gain of ~13dB with the ripple of more than 15dB from the single-section DP-FOPA.

  1. Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population

    DEFF Research Database (Denmark)

    Rosenberg, Niels Thomas; Nørby, Søren; Schwartz, Marianne

    2016-01-01

    PURPOSE: In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012. METHODS: Affected individuals were identified from a nat...... of other European populations. The genealogic follow-up reveals a relatively high turnover among families with approximately 15 newly affected families per century and the dying out of earlier maternal lines....

  2. Biomimetic self-templating optical structures fabricated by genetically engineered M13 bacteriophage.

    Science.gov (United States)

    Kim, Won-Geun; Song, Hyerin; Kim, Chuntae; Moon, Jong-Sik; Kim, Kyujung; Lee, Seung-Wuk; Oh, Jin-Woo

    2016-11-15

    Here, we describe a highly sensitive and selective surface plasmon resonance sensor system by utilizing self-assembly of genetically engineered M13 bacteriophage. About 2700 copies of genetically expressed peptide copies give superior selectivity and sensitivity to M13 phage-based SPR sensor. Furthermore, the sensitivity of the M13 phage-based SPR sensor was enhanced due to the aligning of receptor matrix in specific direction. Incorporation of specific binding peptide (His Pro Gln: HPQ) gives M13 bacteriophage high selectivity for the streptavidin. Our M13 phage-based SPR sensor takes advantage of simplicity of self-assembly compared with relatively complex photolithography techniques or chemical conjugations. Additionally, designed structure which is composed of functionalized M13 bacteriophage can simultaneously improve the sensitivity and selectivity of SPR sensor evidently. By taking advantages of the genetic engineering and self-assembly, we propose the simple method for fabricating novel M13 phage-based SPR sensor system which has a high sensitivity and high selectivity. Copyright © 2016 Elsevier B.V. All rights reserved.

  3. Prevalence and Genetics of Leber Hereditary Optic Neuropathy in the Danish Population

    DEFF Research Database (Denmark)

    Rosenberg, Thomas; Nørby, Søren; Schwartz, Marianne

    2016-01-01

    PURPOSE: In Denmark, the occurrence of Leber hereditary optic neuropathy (LHON) has continuously been monitored since 1944. We provide here a summary of 70 years of data collection including registered lines and subjects by the end of 2012. METHODS: Affected individuals were identified from....... The number of live affected individuals with a verified mitochondrial DNA mutation was 104 on January 1, 2013, which translates to a prevalence rate of 1:54,000 in the Danish population. CONCLUSIONS: Haplogroup distribution as well as mutational spectrum of the Danish LHON cohort do not deviate from those...

  4. Characterization of genetically targeted neuron types in the zebrafish optic tectum

    Directory of Open Access Journals (Sweden)

    Estuardo eRobles

    2011-02-01

    Full Text Available The optically transparent larval zebrafish is ideally suited for in vivo analyses of neural circuitry controlling visually guided behaviors. However, there is a lack of information regarding specific cell types in the major retinorecipient brain region of the fish, the optic tectum. Here we report the characterization of three previously unidentified tectal cell types that are specifically labeled by dlx5/6 enhancer elements. In vivo laser scanning microscopy in conjunction with ex vivo array tomography revealed that these neurons differ in their morphologies, synaptic connectivity, and neurotransmitter phenotypes. The first type is an excitatory bistratified periventricular interneuron (bsPVIN that forms a dendritic arbor in the retinorecipient stratum fibrosum griseum et superficiale (SFGS and an axonal arbor in the stratum griseum centrale (SGC. The second type, a GABAergic nonstratified periventricular interneuron (nsPVIN, extends a bushy arbor containing both dendrites and axons into the SGC and the deepest sublayers of the SFGS. The third type is a GABAergic periventricular projection neuron (PVPN that extends a dendritic arbor into the SGC and a long axon to the torus semicircularis, medulla oblongata, and anterior hindbrain. Interestingly, the same axons form en passant synapses within the deepest neuropil layer of the tectum, the stratum album centrale. This approach revealed several novel aspects of tectal circuitry, including: (1 a glutamatergic mode of transmission from the superficial, retinorecipient neuropil layers to the deeper, output layers, (2 the presence of interneurons with mixed dendrite/axon arbors likely involved in local processing, and (3 a heretofore unknown GABAergic tectofugal projection to midbrain and hindbrain. These observations establish a framework for studying the morphological and functional differentiation of neural circuits in the zebrafish visual system.

  5. The Large Binocular Telescope azimuth and elevation encoder system

    Science.gov (United States)

    Ashby, David S.; Sargent, Tom; Cox, Dan; Rosato, Jerry; Brynnel, Joar G.

    2008-08-01

    A typical high-resolution encoder interpolator relies on careful mechanical alignment of the encoder read-heads and tight electrical tolerances of the signal processing electronics to ensure linearity. As the interpolation factor increases, maintaining these tight mechanical and electrical tolerances becomes impractical. The Large Binocular Telescope (LBT) is designed to utilize strip-type encoders on the main axes. Because of the very large scale of the telescope, the accumulative length of the azimuth and elevation encoder strips exceeds 80 meters, making optical tape prohibitively expensive. Consequently, the designers of the LBT incorporated the far less expensive Farrand Controls Inductosyn® linear strip encoder to encode the positions of the main axes and the instrument rotators. Since the cycle pitch of these encoders is very large compared to that of optical strip encoders, the interpolation factor must also be large in order to achieve the 0.005 arcsecond encoder resolution as specified. The authors present a description of the innovative DSP-based hardware / software solution that adaptively characterizes and removes common systematic cycle-to-cycle encoder interpolation errors. These errors can be caused by mechanical misalignment, encoder manufacturing flaws, variations in electrical gain, signal offset or cross-coupling of the encoder signals. Simulation data are presented to illustrate the performance of the interpolation algorithm, and telemetry data are presented to demonstrate the actual performance of the LBT main-axis encoder system.

  6. Treatment of hereditary optic neuropathies.

    Science.gov (United States)

    Newman, Nancy J

    2012-10-01

    The hereditary optic neuropathies are inherited disorders in which optic nerve dysfunction is a prominent feature in the phenotypic expression of disease. Optic neuropathy may be primarily an isolated finding, such as in Leber hereditary optic neuropathy and dominant optic atrophy, or part of a multisystem disorder. The pathophysiological mechanisms underlying the hereditary optic neuropathies involve mitochondrial dysfunction owing to mutations in mitochondrial or nuclear DNA that encodes proteins essential to mitochondrial function. Effective treatments are limited, and current management includes therapies directed at enhancing mitochondrial function and preventing oxidative damage, as well as genetic counselling, and supportive and symptomatic measures. New therapies, including gene therapy, are emerging via animal models and human clinical trials. Leber hereditary optic neuropathy, in particular, provides a unique model for testing promising treatments owing to its characteristic sequential bilateral involvement and the accessibility of target tissue within the eye. Lessons learned from treatment of the hereditary optic neuropathies may have therapeutic implications for other disorders of presumed mitochondrial dysfunction. In this Review, the natural history of the common inherited optic neuropathies, the presumed pathogenesis of several of these disorders, and the literature to date regarding potential therapies are summarized.

  7. Genetically encoded fluorescent coumarin amino acids

    Science.gov (United States)

    Wang, Jiangyun; Xie, Jianming; Schultz, Peter G.

    2010-10-05

    The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate the coumarin unnatural amino acid L-(7-hydroxycoumarin-4-yl) ethylglycine into proteins produced in eubacterial host cells such as E. coli. The invention provides, for example but not limited to, novel orthogonal synthetases, methods for identifying and making the novel synthetases, methods for producing proteins containing the unnatural amino acid L-(7-hydroxycoumarin-4-yl)ethylglycine and related translation systems.

  8. Genetically encoded fluorescent coumarin amino acids

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Jiangyun [San Diego, CA; Xie, Jianming [San Diego, CA; Schultz, Peter G [La Jolla, CA

    2012-06-05

    The invention relates to orthogonal pairs of tRNAs and aminoacyl-tRNA synthetases that can incorporate the coumarin unnatural amino acid L-(7-hydroxycoumarin-4-yl)ethylglycine into proteins produced in eubacterial host cells such as E. coli. The invention provides, for example but not limited to, novel orthogonal synthetases, methods for identifying and making the novel synthetases, methods for producing proteins containing the unnatural amino acid L-(7-hydroxycoumarin-4-yl)ethylglycine and related translation systems.

  9. Multiplexed modular genetic targeting of quantum dots.

    Science.gov (United States)

    Saurabh, Saumya; Beck, Lauren E; Maji, Suvrajit; Baty, Catherine J; Wang, Yi; Yan, Qi; Watkins, Simon C; Bruchez, Marcel P

    2014-11-25

    While DNA-directed nanotechnology is now a well-established platform for bioinspired nanoscale assembly in vitro, the direct targeting of various nanomaterials in living biological systems remains a significant challenge. Hybrid biological systems with integrated and targeted nanomaterials may have interesting and exploitable properties, so methods for targeting various nanomaterials to precise biological locations are required. Fluorescence imaging has benefited from the use of nanoparticles with superior optical properties compared to fluorescent organic dyes or fluorescent proteins. While single-particle tracking (SPT) in living cells with genetically encoded proteins is limited to very short trajectories, the high photon output of genetically targeted and multiplexed quantum dots (QDs) would enable long-trajectory analysis of multiple proteins. However, challenges with genetic targeting of QDs limit their application in these experiments. In this report, we establish a modular method for targeting QD nanoparticles selectively to multiple genetically encoded tags by precomplexing QD-streptavidin conjugates with cognate biotinylated hapten molecules. This approach enables labeling and SPT of multiple genetically encoded proteins on living cells at high speed and can label expressed proteins in the cytosol upon microinjection into living cells. While we demonstrate labeling with three distinct QD conjugates, the approach can be extended to other specific hapten-affinity molecule interactions and alternative nanoparticles, enabling precise directed targeting of nanoparticles in living biological systems.

  10. Monitoring cytosolic and ER Zn2+ in stimulated breast cancer cells using genetically encoded FRET sensors† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c5mt00257e Click here for additional data file.

    Science.gov (United States)

    Hessels, Anne M.; Taylor, Kathryn M.

    2016-01-01

    The Zn2+-specific ion channel ZIP7 has been implicated to play an important role in releasing Zn2+ from the ER. External stimulation of breast cancer cells has been proposed to induce phosphorylation of ZIP7 by CK2α, resulting in ZIP7-mediated Zn2+ release from the ER into the cytosol. Here, we examined whether changes in cytosolic and ER Zn2+ concentrations can be detected upon such external stimuli. Two previously developed FRET sensors for Zn2+, eZinCh-2 (K d = 1 nM at pH 7.1) and eCALWY-4 (K d = 0.63 nM at pH 7.1), were expressed in both the cytosol and the ER of wild-type MCF-7 and TamR cells. Treatment of MCF-7 and TamR cells with external Zn2+ and pyrithione, one of the previously used triggers, resulted in an immediate increase in free Zn2+ in both cytosol and ER, suggesting that Zn2+ was directly transferred across the cellular membranes by pyrithione. Cells treated with a second trigger, EGF/ionomycin, showed no changes in intracellular Zn2+ levels, neither in multicolor imaging experiments that allowed simultaneous imaging of cytosolic and ER Zn2+, nor in experiments in which cytosolic and ER Zn2+ were monitored separately. In contrast to previous work using small-molecule fluorescent dyes, these results indicate that EGF–ionomycin treatment does not result in significant changes in cytosolic Zn2+ levels as a result from Zn2+ release from the ER. These results underline the importance of using genetically encoded fluorescent sensors to complement and verify intracellular imaging experiments with synthetic fluorescent Zn2+ dyes. PMID:26739447

  11. Enhanced anti-tumor effect of a gene gun-delivered DNA vaccine encoding the human papillomavirus type 16 oncoproteins genetically fused to the herpes simplex virus glycoprotein D

    Directory of Open Access Journals (Sweden)

    M.O. Diniz

    2011-05-01

    Full Text Available Anti-cancer DNA vaccines have attracted growing interest as a simple and non-invasive method for both the treatment and prevention of tumors induced by human papillomaviruses. Nonetheless, the low immunogenicity of parenterally administered vaccines, particularly regarding the activation of cytotoxic CD8+ T cell responses, suggests that further improvements in both vaccine composition and administration routes are still required. In the present study, we report the immune responses and anti-tumor effects of a DNA vaccine (pgD-E7E6E5 expressing three proteins (E7, E6, and E5 of the human papillomavirus type 16 genetically fused to the glycoprotein D of the human herpes simplex virus type 1, which was administered to mice by the intradermal (id route using a gene gun. A single id dose of pgD-E7E6E5 (2 µg/dose induced a strong activation of E7-specific interferon-γ (INF-γ-producing CD8+ T cells and full prophylactic anti-tumor effects in the vaccinated mice. Three vaccine doses inhibited tumor growth in 70% of the mice with established tumors. In addition, a single vaccine dose consisting of the co-administration of pgD-E7E6E5 and the vector encoding interleukin-12 or granulocyte-macrophage colony-stimulating factor further enhanced the therapeutic anti-tumor effects and conferred protection to 60 and 50% of the vaccinated mice, respectively. In conclusion, id administration of pgD-E7E6E5 significantly enhanced the immunogenicity and anti-tumor effects of the DNA vaccine, representing a promising administration route for future clinical trials.

  12. 视神经炎的遗传学研究进展%Recent progress on genetics of optic neuritis

    Institute of Scientific and Technical Information of China (English)

    赵燕燕; 魏世辉

    2011-01-01

    视神经炎是一种神经眼科的常见疾病,严重威胁视力.目前其病因不明,但研究发现视神经炎伴有一定程度的家族性和遗传倾向.近年来,随着分子生物学技术和统计学方法的迅速发展,视神经炎的候选基因的关联研究取得了相当的进展,本文就目前与视神经炎相关的遗传学研究工作的最新进展加以阐述.%Optic neuritis (ON) is a common disorder of the neuro-ophthalmology,which harms patients vision seriously.However,there are a lot of controversy and confusion about its etiology.While ON has familial characteristic and the tendency of heredity to some extent. Recently,association studies have made considerable progress with the rapid development of molecular biology techniques and statistical methods.In this article,the latest progresses in genetics of ON are reviewed.

  13. Application of a genetic algorithm Elman network in temperature drift modeling for a fiber-optic gyroscope.

    Science.gov (United States)

    Chen, Xiyuan; Song, Rui; Shen, Chong; Zhang, Hong

    2014-09-10

    The fiber-optic gyroscope (FOG) has been widely used as a satellite and automobile attitude sensor in many industrial and defense fields such as navigation and positioning. Based on the fact that the FOG is sensitive to temperature variation, a novel (to our knowledge) error-processing technique for the FOG through a set of temperature experiment results and error analysis is presented. The method contains two parts: one is denoising, and the other is modeling and compensating. After the denoising part, a novel modeling method which is based on the dynamic modified Elman neural network (ENN) is proposed. In order to get the optimum parameters of the ENN, the genetic algorithm (GA) is applied and the optimization objective function was set as the difference between the predicted data and real data. The modeling and compensating results indicate that the drift caused by the varying temperature can be reduced and compensated effectively by the proposed model; the prediction accuracy of the GA-ENN is improved 20% over the ENN.

  14. Use of genetically encoded calcium indicators (GECIs combined with advanced motion tracking techniques to examine the behavior of neurons and glia in the enteric nervous system of the intact murine colon

    Directory of Open Access Journals (Sweden)

    Grant Willem Hennig

    2015-11-01

    Full Text Available Genetically encoded Ca2+ indicators (GECIs have been used extensively in many body systems to detect Ca2+ transients associated with neuronal activity. Their adoption in enteric neurobiology has been slower, although they offer many advantages in terms of selectivity, signal-to-noise and non-invasiveness. Our aims were to utilize a number of cell-specific promoters to express the Ca2+ indicator GCaMP3 in different classes of neurons and glia to determine their effectiveness in measuring activity in enteric neural networks during colonic motor behaviors. We developed several GCaMP3 mice: 1 Wnt1-GCaMP3, all enteric neurons and glia; 2 GFAP-GCaMP3, enteric glia; 3 nNOS-GaMP3, enteric nitrergic neurons, and 4 ChAT-GCaMP3, enteric cholinergic neurons. These mice allowed us to study the behavior of the enteric neurons in the intact colon maintained at a physiological temperature, especially during the colonic migrating motor complex (CMMC, using low power Ca2+ imaging. In this preliminary study, we observed neuronal and glial cell Ca2+ transients in specific cells in both the myenteric and submucous plexus in all of the transgenic mice variants. The number of cells that could be simultaneously imaged at low power (100-1000 active cells through the undissected gut required advanced motion tracking and analysis routines. The pattern of Ca2+ transients in myenteric neurons showed significant differences in response to spontaneous, oral or anal stimulation. Brief anal elongation or mucosal stimulation, which evokes a CMMC, were the most effective stimuli and elicited a powerful synchronized and prolonged burst of Ca2+ transients in many myenteric neurons, especially when compared with the same neurons during a spontaneous CMMC. In contrast, oral elongation, which normally inhibits CMMCs, appeared to suppress Ca2+ transients some of the neurons active during a spontaneous or an anally evoked CMMC. The activity in glial networks appeared to follow neural

  15. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

    Science.gov (United States)

    Springelkamp, Henriët; Iglesias, Adriana I; Mishra, Aniket; Höhn, René; Wojciechowski, Robert; Khawaja, Anthony P; Nag, Abhishek; Wang, Ya Xing; Wang, Jie Jin; Cuellar-Partida, Gabriel; Gibson, Jane; Bailey, Jessica N Cooke; Vithana, Eranga N; Gharahkhani, Puya; Boutin, Thibaud; Ramdas, Wishal D; Zeller, Tanja; Luben, Robert N; Yonova-Doing, Ekaterina; Viswanathan, Ananth C; Yazar, Seyhan; Cree, Angela J; Haines, Jonathan L; Koh, Jia Yu; Souzeau, Emmanuelle; Wilson, James F; Amin, Najaf; Müller, Christian; Venturini, Cristina; Kearns, Lisa S; Kang, Jae Hee; Tham, Yih Chung; Zhou, Tiger; van Leeuwen, Elisabeth M; Nickels, Stefan; Sanfilippo, Paul; Liao, Jiemin; van der Linde, Herma; Zhao, Wanting; van Koolwijk, Leonieke M E; Zheng, Li; Rivadeneira, Fernando; Baskaran, Mani; van der Lee, Sven J; Perera, Shamira; de Jong, Paulus T V M; Oostra, Ben A; Uitterlinden, André G; Fan, Qiao; Hofman, Albert; Tai, E-Shyong; Vingerling, Johannes R; Sim, Xueling; Wolfs, Roger C W; Teo, Yik Ying; Lemij, Hans G; Khor, Chiea Chuen; Willemsen, Rob; Lackner, Karl J; Aung, Tin; Jansonius, Nomdo M; Montgomery, Grant; Wild, Philipp S; Young, Terri L; Burdon, Kathryn P; Hysi, Pirro G; Pasquale, Louis R; Wong, Tien Yin; Klaver, Caroline C W; Hewitt, Alex W; Jonas, Jost B; Mitchell, Paul; Lotery, Andrew J; Foster, Paul J; Vitart, Veronique; Pfeiffer, Norbert; Craig, Jamie E; Mackey, David A; Hammond, Christopher J; Wiggs, Janey L; Cheng, Ching-Yu; van Duijn, Cornelia M; MacGregor, Stuart

    2017-01-15

    Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  16. The Role of Oxidative Stress in Diabetic Neuropathy: Generation of Free Radical Species in the Glycation Reaction and Gene Polymorphisms Encoding Antioxidant Enzymes to Genetic Susceptibility to Diabetic Neuropathy in Population of Type I Diabetic Patients.

    Science.gov (United States)

    Babizhayev, Mark A; Strokov, Igor A; Nosikov, Valery V; Savel'yeva, Ekaterina L; Sitnikov, Vladimir F; Yegorov, Yegor E; Lankin, Vadim Z

    2015-04-01

    pathway are detoxified by the glyoxalase system with reduced glutathione as co-factor. The concentration of reduced glutathione may be decreased by oxidative stress and by decreased in situ glutathione reductase activity in diabetes mellitus. Genetic variations within the antioxidant genes therefore could be implicated in the pathogenesis of DN. In this work, the supporting data about the association between the -262T > C polymorphism of the catalase (CAT) gene and DN were shown. The -262TT genotype of the CAT gene was significantly associated with higher erythrocyte catalase activity in blood of DN patients compared to the -262CC genotype (17.8 ± 2.7 × 10(4) IU/g Hb vs. 13.5 ± 3.2 × 10(4) IU/g Hb, P = 0.0022). The role of these factors in the development of diabetic complications and the prospective prevention of DN by supplementation in formulations of transglycating imidazole-containing peptide-based antioxidants (non-hydrolyzed carnosine, carcinine, n-acetylcarcinine) scavenging ROS in the glycation reaction, modifying the activity of enzymic and non-enzymic antioxidant defenses that participate in metabolic processes with ability of controlling at transcriptional levels the differential expression of several genes encoding antioxidant enzymes inherent to DN in Type I Diabetic patients, now deserve investigation.

  17. Optical image encryption topology.

    Science.gov (United States)

    Yong-Liang, Xiao; Xin, Zhou; Qiong-Hua, Wang; Sheng, Yuan; Yao-Yao, Chen

    2009-10-15

    Optical image encryption topology is proposed based on the principle of random-phase encoding. Various encryption topological units, involving peer-to-peer, ring, star, and tree topologies, can be realized by an optical 6f system. These topological units can be interconnected to constitute an optical image encryption network. The encryption and decryption can be performed in both digital and optical methods.

  18. Models of optical quantum computing

    Directory of Open Access Journals (Sweden)

    Krovi Hari

    2017-03-01

    Full Text Available I review some work on models of quantum computing, optical implementations of these models, as well as the associated computational power. In particular, we discuss the circuit model and cluster state implementations using quantum optics with various encodings such as dual rail encoding, Gottesman-Kitaev-Preskill encoding, and coherent state encoding. Then we discuss intermediate models of optical computing such as boson sampling and its variants. Finally, we review some recent work in optical implementations of adiabatic quantum computing and analog optical computing. We also provide a brief description of the relevant aspects from complexity theory needed to understand the results surveyed.

  19. Research on a novel orientation algorithm of single-ring absolute photoelectric shaft encoder

    Institute of Scientific and Technical Information of China (English)

    CHEN Yun

    2007-01-01

    A novel single-ring absolute optical shaft encoder is designed by studying the encoding principle of traditional absolute optical shaft encoder in this paper. The description of the orientation algorithm of the encoder is specified,and an example for explaining the orientation arithmetic is given,which indicates that the theory of the encoder works. The visual interface to acquire signals of CCD is shown with VB,which provides reliable foundation to process data. The effective factors of measurement precision of the encoder are analyzed.

  20. A three-photon microscope with adaptive optics for deep-tissue in vivo structural and functional brain imaging

    Science.gov (United States)

    Tao, Xiaodong; Lu, Ju; Lam, Tuwin; Rodriguez, Ramiro; Zuo, Yi; Kubby, Joel

    2017-02-01

    We developed a three-photon adaptive optics add-on to a commercial two-photon laser scanning microscope. We demonstrated its capability for structural and functional imaging of neurons labeled with genetically encoded red fluorescent proteins or calcium indicators deep in the living mouse brain with cellular and subcellular resolution.

  1. The Golden Ratio Encoder

    CERN Document Server

    Daubechies, I; Wang, Y; Yilmaz, Ö

    2008-01-01

    This paper proposes a novel Nyquist-rate analog-to-digital (A/D) conversion algorithm which achieves exponential accuracy in the bit-rate despite using imperfect components. The proposed algorithm is based on a robust implementation of a beta-encoder where the value of the base beta is equal to golden mean. It was previously shown that beta-encoders can be implemented in such a way that their exponential accuracy is robust against threshold offsets in the quantizer element. This paper extends this result by allowing for imperfect analog multipliers with imprecise gain values as well. A formal computational model for algorithmic encoders and a general test bed for evaluating their robustness is also proposed.

  2. The exome sequencing identified the mutation in YARS2 encoding the mitochondrial tyrosyl-tRNA synthetase as a nuclear modifier for the phenotypic manifestation of Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation.

    Science.gov (United States)

    Jiang, Pingping; Jin, Xiaofen; Peng, Yanyan; Wang, Meng; Liu, Hao; Liu, Xiaoling; Zhang, Zengjun; Ji, Yanchun; Zhang, Juanjuan; Liang, Min; Zhao, Fuxin; Sun, Yan-Hong; Zhang, Minglian; Zhou, Xiangtian; Chen, Ye; Mo, Jun Qin; Huang, Taosheng; Qu, Jia; Guan, Min-Xin

    2016-02-01

    Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disorder. Nuclear modifier genes are proposed to modify the phenotypic expression of LHON-associated mitochondrial DNA (mtDNA) mutations. By using an exome sequencing approach, we identified a LHON susceptibility allele (c.572G>T, p.191Gly>Val) in YARS2 gene encoding mitochondrial tyrosyl-tRNA synthetase, which interacts with m.11778G>A mutation to cause visual failure. We performed functional assays by using lymphoblastoid cell lines derived from members of Chinese families (asymptomatic individuals carrying m.11778G>A mutation, or both m.11778G>A and heterozygous p.191Gly>Val mutations and symptomatic subjects harboring m.11778G>A and homozygous p.191Gly>Val mutations) and controls lacking these mutations. The 191Gly>Val mutation reduced the YARS2 protein level in the mutant cells. The aminoacylated efficiency and steady-state level of tRNA(Tyr) were markedly decreased in the cell lines derived from patients both carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The failure in tRNA(Tyr) metabolism impaired mitochondrial translation, especially for polypeptides with high content of tyrosine codon such as ND4, ND5, ND6 and COX2 in cells lines carrying homozygous YARS2 p.191Gly>Val and m.11778G>A mutations. The YARS2 p.191Gly>Val mutation worsened the respiratory phenotypes associated with m.11778G>A mutation, especially reducing activities of complexes I and IV. The respiratory deficiency altered the efficiency of mitochondrial ATP synthesis and increased the production of reactive oxygen species. Thus, mutated YARS2 aggravates mitochondrial dysfunctions associated with the m.11778G>A mutation, exceeding the threshold for the expression of blindness phenotype. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between mtDNA mutation and mutated nuclear-modifier YARS2.

  3. Encoding complex values using two DLP spatial light modulators

    Science.gov (United States)

    Becker, Michael F.; Wu, Sih-Ying; Liang, Jinyang

    2013-03-01

    We present a method to encode complex values into three or four quantized complex values for wavefront modulation using two digital micromirror devices (DMDs). This encoding offers advantages to eliminate the twin image or suppress the zero order diffraction as well to improve hologram fidelity. The optical architecture utilizes a Michelson interferometer with a DMD in Littrow configuration replacing the mirrors to combine the two holograms with the desired phase shift. System performance was examined using numerical simulations and experimental measurements to explore different encoding methods for hologram reconstruction. Both ZOD and conjugate image suppression were demonstrated for different encoding schemes.

  4. Review of Random Phase Encoding in Volume Holographic Storage

    Directory of Open Access Journals (Sweden)

    Wei-Chia Su

    2012-09-01

    Full Text Available Random phase encoding is a unique technique for volume hologram which can be applied to various applications such as holographic multiplexing storage, image encryption, and optical sensing. In this review article, we first review and discuss diffraction selectivity of random phase encoding in volume holograms, which is the most important parameter related to multiplexing capacity of volume holographic storage. We then review an image encryption system based on random phase encoding. The alignment of phase key for decryption of the encoded image stored in holographic memory is analyzed and discussed. In the latter part of the review, an all-optical sensing system implemented by random phase encoding and holographic interconnection is presented.

  5. Negative Beta Encoder

    CERN Document Server

    Kohda, Tohru; Aihara, Kazuyuki

    2008-01-01

    A new class of analog-digital (A/D), digital-analog (D/A) converters as an alternative to conventional ones, called $\\beta$-encoder, has been shown to have exponential accuracy in the bit rates while possessing self-correction property for fluctuations of amplifier factor $\\beta$ and quantizer threshold $\

  6. DNA sequences encoding erythropoietin

    Energy Technology Data Exchange (ETDEWEB)

    Lin, F.K.

    1987-10-27

    A purified and isolated DNA sequence is described consisting essentially of a DNA sequence encoding a polypeptide having an amino acid sequence sufficiently duplicative of that of erythropoietin to allow possession of the biological property of causing bone marrow cells to increase production of reticulocytes and red blood cells, and to increase hemoglobin synthesis or iron uptake.

  7. Time-Encoded Imagers.

    Energy Technology Data Exchange (ETDEWEB)

    Marleau, Peter; Brubaker, Erik

    2014-11-01

    This report provides a short overview of the DNN R&D funded project, Time-Encoded Imagers. The project began in FY11 and concluded in FY14. The Project Description below provides the overall motivation and objectives for the project as well as a summary of programmatic direction. It is followed by a short description of each task and the resulting deliverables.

  8. Applications of Genetic Programming

    DEFF Research Database (Denmark)

    Gaunholt, Hans; Toma, Laura

    1996-01-01

    In this report a study of genetic programming (GP) has been performed with respect to a number of applications such as Symbolic function regression, Solving Symbolic Differential Equations, Image encoding, the ant problem etc.......In this report a study of genetic programming (GP) has been performed with respect to a number of applications such as Symbolic function regression, Solving Symbolic Differential Equations, Image encoding, the ant problem etc....

  9. Applications of Genetic Programming

    DEFF Research Database (Denmark)

    Gaunholt, Hans; Toma, Laura

    1996-01-01

    In this report a study of genetic programming (GP) has been performed with respect to a number of applications such as Symbolic function regression, Solving Symbolic Differential Equations, Image encoding, the ant problem etc.......In this report a study of genetic programming (GP) has been performed with respect to a number of applications such as Symbolic function regression, Solving Symbolic Differential Equations, Image encoding, the ant problem etc....

  10. On Derivations Of Genetic Algebras

    Science.gov (United States)

    Mukhamedov, Farrukh; Qaralleh, Izzat

    2014-11-01

    A genetic algebra is a (possibly non-associative) algebra used to model inheritance in genetics. In application of genetics this algebra often has a basis corresponding to genetically different gametes, and the structure constant of the algebra encode the probabilities of producing offspring of various types. In this paper, we find the connection between the genetic algebras and evolution algebras. Moreover, we prove the existence of nontrivial derivations of genetic algebras in dimension two.

  11. Optimization of unit commitment based on genetic algorithms

    Institute of Scientific and Technical Information of China (English)

    蔡兴国; 初壮

    2002-01-01

    How to solve unit commitment and load dispatch of power system by genetic algorithms is discussed in this paper. A combination encoding scheme of binary encoding and floating number encoding and corresponding genetic operators are developed. Meanwhile a contract mapping genetic algorithm is used to enhance traditional GA' s convergence. The result of a practical example shows that this algorithm is effective.

  12. Análisis de la Pérdida de Precisión en Codificadores Opticos Lineales por Deformación de la Retícula Grabada Analysis of the Precision Lost in Optical Linear Encoders as a Consequence of Reticule Deformation

    Directory of Open Access Journals (Sweden)

    Ignacio Alejandre

    2006-01-01

    Full Text Available Se analiza la pérdida de precisión en codificadores (encoders opticos lineales por deformación de la retícula grabada. Los encoders ópticos lineales basados en el efecto moiré de franja infinita incorporan una retícula grabada sobre la superficie de un vidrio. Las deformaciones que dicho vidrio puede experimentar influyen de forma directa en la homogeneidad de la retícula, bien con carácter local o de forma más extendida. Dichas deformaciones pueden ser producidas por montajes inapropiados o por la propia modificación de la estructura de la máquina, en la que el encoder va montado, en las condiciones de funcionamiento. En este trabajo se compara la pérdida de precisión que se produce en los dos estados más probables de flexión del vidrio. Los resultados muestran que en las dos situaciones analizadas la deformación de la retícula del vidrio correspondiente al caso de colocación de calzos traseros es unas tres veces mayor que la correspondiente al caso de colocación de calzos inferiores.An analysis is made of the loss of precision in optical linear encoders due to deformation of the engraved reticule. Optical linear encoders based on the moiré effect of infinite boundary incorporate a reticule etched on a glass surface. Potential deformations of this glass directly influence the homogeneity of the reticule, in a local or generalised character. These deformations can be caused by inappropriate assembly or as a consequence of modification by the structure of the machine in which the encoder is incorporated, during working conditions. This study compares the loss of precision which occurs under the most probable conditions of flexion of the glass. The results showed that in the two situations analyzed, the deformation of the glass from a rear position was three times greater in effect than that observed in the case of deformation from below.

  13. Genetic and Clinical Analyses of DOA and LHON in 304 Chinese Patients with Suspected Childhood-Onset Hereditary Optic Neuropathy

    Science.gov (United States)

    Xiao, Xueshan; Li, Shiqiang

    2017-01-01

    Leber hereditary optic neuropathy (LHON) and dominant optic atrophy (DOA), the most common forms of hereditary optic neuropathy, are easily confused, and it is difficult to distinguish one from the other in the clinic, especially in young children. The present study was designed to survey the mutation spectrum of common pathogenic genes (OPA1, OPA3 and mtDNA genes) and to analyze the genotype-phenotype characteristics of Chinese patients with suspected childhood-onset hereditary optic neuropathy. Genomic DNA and clinical data were collected from 304 unrelated Chinese probands with suspected hereditary optic neuropathy with an age of onset below 14 years. Sanger sequencing was used to screen variants in the coding and adjacent regions of OPA1, OPA3 and the three primary LHON-related mutation sites in mitochondrial DNA (mtDNA) (m.3460G>A, m.11778G>A and m.14484T>C). All patients underwent a complete ophthalmic examination and were compared with age-matched controls. We identified 89/304 (29.3%) primary mtDNA mutations related to LHON in 304 probands, including 76 mutations at m.11778 (76/89, 85.4% of all mtDNA mutations), four at m.3460 (4/89, 4.5%) and nine at m.14484 (9/89, 10.1%). This result was similar to the mutation frequency among Chinese patients with LHON of any age. Screening of OPA1 revealed 23 pathogenic variants, including 11 novel and 12 known pathogenic mutations. This study expanded the OPA1 mutation spectrum, and our results showed that OPA1 mutation is another common cause of childhood-onset hereditary optic neuropathy in Chinese pediatric patients, especially those with disease onset during preschool age. PMID:28081242

  14. Wavelength-encoded OCDMA system using opto-VLSI processors.

    Science.gov (United States)

    Aljada, Muhsen; Alameh, Kamal

    2007-07-01

    We propose and experimentally demonstrate a 2.5 Gbits/sper user wavelength-encoded optical code-division multiple-access encoder-decoder structure based on opto-VLSI processing. Each encoder and decoder is constructed using a single 1D opto-very-large-scale-integrated (VLSI) processor in conjunction with a fiber Bragg grating (FBG) array of different Bragg wavelengths. The FBG array spectrally and temporally slices the broadband input pulse into several components and the opto-VLSI processor generates codewords using digital phase holograms. System performance is measured in terms of the autocorrelation and cross-correlation functions as well as the eye diagram.

  15. Differentially-Enhanced Sideband Imaging via Radio-frequency Encoding

    CERN Document Server

    Fard, A M; Jalali, B

    2015-01-01

    We present a microscope paradigm that performs differential interference imaging with high sensitivity via optical amplification and radio-frequency (RF) heterodyne detection. This method, termed differentially-enhanced sideband imaging via radio-frequency encoding (DESIRE), uniquely exploits frequency-to-space mapping technique to encode the image of an object onto the RF sidebands of an illumination beam. As a proof-of-concept, we show validation experiment by implementing radio frequency (f = 15 GHz) phase modulation in conjunction with spectrally-encoded laser scanning technique to acquire one-dimensional image of a barcode-like object using a commercial RF spectrum analyzer.

  16. Genetics of stroke

    OpenAIRE

    Guo, Jin-Min; Liu, Ai-Jun; Su, Ding-Feng

    2010-01-01

    Stroke is the second most common cause of death and the most common cause of disability in developed countries. Stroke is a multi-factorial disease caused by a combination of environmental and genetic factors. Numerous epidemiologic studies have documented a significant genetic component in the occurrence of strokes. Genes encoding products involved in lipid metabolism, thrombosis, and inflammation are believed to be potential genetic factors for stroke. Although a large group of candidate ge...

  17. LHON and other optic nerve atrophies: the mitochondrial connection.

    Science.gov (United States)

    Howell, Neil

    2003-01-01

    The clinical, biochemical and genetic features of Leber's hereditary optic neuropathy (LHON) are reviewed. The etiology of LHON is complex, but the primary risk factor is a mutation in one of the seven mitochondrial genes that encode subunits of respiratory chain complex I. The pathogenesis of LHON is not yet understood, but one plausible model is that increased or altered mitochondrial ROS production renders the retinal ganglion cells vulnerable to apoptotic cell death. In addition to LHON, there are a large number of other optic nerve degenerative disorders including autosomal dominant optic atrophy, the toxic/nutritional optic neuropathies and glaucoma. A review of the recent scientific literature suggests that these disorders also involve mitochondrial dysfunction or altered mitochondrial signaling pathways in their pathogenesis. This mitochondrial link provides new avenues of experimental investigation to these major causes of loss of vision.

  18. All-optical control of neuronal function via optical delivery of light-sensitive proteins and optogenetic stimulation

    Science.gov (United States)

    Villalobos, Alex; Gu, Ling; Mohanty, Samarendra

    2012-02-01

    While pulsed laser beams have been used for stimulation of neurons, cellular specificity during optical stimulation is achieved by photo-sensitization of genetically-targeted cells by optogenetic means. However, till date, the process of optogenetic-sensitization primarily involves use of viral vectors. In rare occasions, electroporation has been used. Here, we report an all-optical method in which pulsed laser beam is used for delivery of genes, encoding optogenetic probes, to spatially-targeted cells, followed by optogenetic stimulation and optical detection of the activation process. Use of laser microbeam enabled highly precise spatially-patterned delivery of optogenes, as confirmed by expression of conjugated fluorescent protein. Light-activation of opsin-expressing cells was confirmed by calcium-imaging. The laser-assisted expression of optogenetic probes in spatially-targeted regions in combination with light-assisted activation and optical detection of neural activity will help in better understanding of the neuronal circuitry.

  19. Selecting Operations for Assembler Encoding

    Directory of Open Access Journals (Sweden)

    Tomasz Praczyk

    2010-04-01

    Full Text Available Assembler Encoding is a neuro-evolutionary method in which a neural network is represented in the form of a simple program called Assembler Encoding Program. The task of the program is to create the so-called Network Definition Matrix which maintains all the information necessary to construct the network. To generate Assembler Encoding Programs and the subsequent neural networks evolutionary techniques are used.
    The performance of Assembler Encoding strongly depends on operations used in Assembler Encoding Programs. To select the most effective operations, experiments in the optimization and the predator-prey problem were carried out. In the experiments, Assembler Encoding Programs equipped with different types of operations were tested. The results of the tests are presented at the end of the paper.

  20. Improved humoral and cellular immune responses against the gp120 V3 loop of HIV-1 following genetic immunization with a chimeric DNA vaccine encoding the V3 inserted into the hepatitis B surface antigen

    DEFF Research Database (Denmark)

    Fomsgaard, A; Nielsen, H V; Bryder, K

    1998-01-01

    with the HIV MN gp160 envelope plasmid induced a slow and low titred anti-MN V3 antibody response at 12 weeks post-inoculation (p.i.) and a late appearing (7 weeks), weak and variable CTL response. In contrast, DNA vaccination with the HBsAg-encoding plasmid induced a rapid and high titred anti-HBsAg antibody...... response and a uniform strong anti-HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V3/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks which peaked at 6-12 weeks and remained stable for at least 25 weeks. In addition, specific CTL......-2d-restricted cytotoxic T lymphocyte (CTL) epitope. In an attempt to improve the immunogenicity of V3 in DNA vaccines, a plasmid expressing MN V3 as a fusion protein with the highly immunogenic middle (pre-S2 + S) surface antigen of hepatitis B virus (HBsAg) was constructed. Epidermal inoculation...

  1. Improved humoral and cellular immune response against the gp120 V3 loop of HIV-1 following genetic immunization with a chimeric DNA vaccine encoding the V3 inserted into the hepatites B surface antigen

    DEFF Research Database (Denmark)

    Fomsgaard, A.; Nielsen, H.V.; Bryder, K.

    1998-01-01

    MN gp160 envelope plasmid induced a slow and low titred anti-MN V3 antibody response at 12 weeks post-inoculation (p.i.) and a late appearing (7 weeks), weak and variable CTL response. In contrast, DNA vaccination with the HBsAg-encoding plasmid induced a rapid and high titred anti-HBsAg antibody...... response and a uniform strong anti-HBs CTL response already 1 week p.i. in all mice. DNA vaccination with the chimeric MN V2/HBsAg plasmid elicited humoral responses against both viruses within 3-6 weeks which peaked at 6-12 weeks and remained stable for at least 25 weeks. In addition, specific CTL......-2d-restricted cytotoxic T lymphocyte (CTL) epitope. In an attempt to improve the immunogenicity of V3 in DNA vaccines, a plasmid expressing MN V3 as a fusion protein with the highly immunogenic middle (pre-S2+S) surface antigen of hepatitis B virus (HBsAg) was constructed. Epidermal inoculation...

  2. CONDENSED MATTER: ELECTRONIC STRUCTURE, ELECTRICAL, MAGNETIC, AND OPTICAL PROPERTIES: Frequency selective surface structure optimized by genetic algorithm

    Science.gov (United States)

    Lu, Jun; Wang, Jian-Bo; Sun, Guan-Cheng

    2009-04-01

    Frequency selective surface (FSS) is a two-dimensional periodic structure which has prominent characteristics of bandpass or bandblock when interacting with electromagnetic waves. In this paper, the thickness, the dielectric constant, the element graph and the arrangement periodicity of an FSS medium are investigated by Genetic Algorithm (GA) when an electromagnetic wave is incident on the FSS at a wide angle, and an optimized FSS structure and transmission characteristics are obtained. The results show that the optimized structure has better stability in relation to incident angle of electromagnetic wave and preserves the stability of centre frequency even at an incident angle as large as 80°, thereby laying the foundation for the application of FSS to curved surfaces at wide angles.

  3. Genetic evidence for host specificity in the adhesin-encoding genes hxaA of Helicobacter acinonyx, hnaA of H. nemestrinae and hpaA of H. pylori.

    Science.gov (United States)

    Evans, D G; Lampert, H C; Nakano, H; Eaton, K A; Burnens, A P; Bronsdon, M A; Evans, D J

    1995-09-22

    Gastric and non-gastric species of Helicobacter were examined for the presence of the adhesin-encoding gene, hpaA, from the human-associated gastric Helicobacter H. pylori (Hp), and for adhesin subunit protein HpaA. Amplification of a 375-bp internal DNA fragment of hpaA by PCR demonstrated the presence of the gene in Hp and in two closely related gastric Helicobacters, H. nemestrinae (Hn) and H. acinonyx (Hx), but not in the more distantly related H. felis (Hf) and H. mustelae (Hm). The non-gastric Helicobacters, H. canis (Hc), H. muridarum (Hr), H. fennelliae (He) and H. cinaedi (Hi), were all negative for hpaA. An immunoblot assay of water extracts with adhesin-specific antibody confirmed these results. The deduced amino acid (aa) sequences of Hp HpaA and Hn adhesin A (hereafter termed HnaA) are very similar, having identical receptor-binding motifs (rbm); also, the hemagglutination (HA) properties of Hn and Hp cells were indistinguishable. In contrast, the rbm of Hx adhesin A (hereafter termed HxaA), compared to that of Hp, contained a non-conservative aa substitution (Ile to Thr); also, there was variance in five consecutive aa from 10 to 14 residues upstream from the rbm. We conclude that these aa substitutions in HxaA are probably responsible for the difference in receptor recognition of this adhesin, as evidenced by the resistance of Hx HA to inhibition with N-acetylneuraminyl-alpha(2,3)-lactose. These results are consistent with the biological similarity between the natural host(s) of Hp and Hn; i.e., human and non-human primates, and the dissimilarity between these hosts and the feline host, the cheetah.

  4. Burst Encoding Mechanism for Low Delay and High Reliable Service in Optical Burst Switching Networks%光突发交换网络中面向低时延高可靠业务的突发编码机制

    Institute of Scientific and Technical Information of China (English)

    黄胜; 李佳良; 李根; 李玲霞; 刘焕淋

    2014-01-01

    为了保证光突发交换( OBS)网络中业务高可靠性的同时,降低突发的端到端的时延,提出了一种基于不规则重复积累( IRA)码的突发编码机制。对IRA码校验矩阵结构进行了一定的调整,得到一种能对突发进行在线编解码的在线不规则重复累积( OL-IRA)码。利用OL-IRA码对信息突发进行编码,以便用产生的冗余突发来恢复丢失的信息突发。仿真结果表明,OL-IRA码在保证恢复丢包能力的同时,也能明显缩短丢包恢复的时延。%In order to guarantee high reliable service in optical burst switching ( OBS ) networks and re-duce the end-to-end delay of bursts, an online burst encoding mechanism based on irregular repeat accu-mulate( IRA) codes was proposed. The parity-check matrix of IRA codes was adjusted into a special structure, and then an on line IRA ( OL-IRA) code which can encode and decode burst online was con-structed. Information data bursts are encoded by OL-IRA codes to recover lost bursts with redundant bursts. Simulations show that OL-IRA codes will guarantee the performance of burst loss recovery, and can also shorten the delay of burst loss recovery.

  5. PNA-encoded chemical libraries.

    Science.gov (United States)

    Zambaldo, Claudio; Barluenga, Sofia; Winssinger, Nicolas

    2015-06-01

    Peptide nucleic acid (PNA)-encoded chemical libraries along with DNA-encoded libraries have provided a powerful new paradigm for library synthesis and ligand discovery. PNA-encoding stands out for its compatibility with standard solid phase synthesis and the technology has been used to prepare libraries of peptides, heterocycles and glycoconjugates. Different screening formats have now been reported including selection-based and microarray-based methods that have yielded specific ligands against diverse target classes including membrane receptors, lectins and challenging targets such as Hsp70.

  6. Sin/cosine encoder interpolation methods: encoder to digital tracking converters for rate and position loop controllers

    Science.gov (United States)

    Jenkins, Steven T.; Hilkert, J. M.

    2008-04-01

    Pointing and tracking applications usually require relative gimbal angles to be measured for reporting and controlling the line-of-sight angular position. Depending on the application, angular resolution and/or accuracy might jointly or independently determine the angle transducer requirements. In the past decade, encoders have been increasingly taking the place of inductive devices where the measurement of angles over a wide range is required. This is primarily due to the fact that encoders are now achieving very high resolution in smaller sizes than was previously possible. These advances in resolution are primarily due to improved encoder disk and detector technology along with developments in interpolation techniques. Measurement accuracy, on the other hand, is primarily determined by mounting and bearing eccentricity as it is with all angular measurement devices. For very demanding accuracy requirements, some type of calibration of the assembled system may be the only solution, in which case transducer repeatability is paramount. This paper describes a unique encoder-to-digital tracking converter concept for improving interpolation of optical encoders. The new method relies on Fraunhofer diffraction models to correct the non-ideal sin/cos outputs of the encoder detectors. Diffraction model concepts are used in the interpolation filters to predict the phase of non-ideal sin and cosine encoder outputs. The new method also minimizes many of the open loop pre-processing requirements and assumptions that limit interpolation accuracy and rate loop noise performance in ratiometric tracking converter designs.

  7. Genetic Diversity of the fliC Genes Encoding the Flagellar Antigen H19 of Escherichia coli and Application to the Specific Identification of Enterohemorrhagic E. coli O121:H19.

    Science.gov (United States)

    Beutin, Lothar; Delannoy, Sabine; Fach, Patrick

    2015-06-15

    Enterohemorrhagic Escherichia coli (EHEC) O121:H19 belong to a specific clonal type distinct from other classical EHEC and major enteropathogenic E. coli groups and is regarded as one of the major EHEC serogroups involved in severe infections in humans. Sequencing of the fliC genes associated with the flagellar antigen H19 (fliCH19) revealed the genetic diversity of the fliCH19 gene sequences in E. coli. A cluster analysis of 12 fliCH19 sequences, 4 from O121 and 8 from non-O121 E. coli strains, revealed five different genotypes. All O121:H19 strains fell into one cluster, whereas a second cluster was formed by five non-O121:H19 strains. Cluster 1 and cluster 2 strains differ by 27 single nucleotide exchanges in their fliCH19 genes (98.5% homology). Based on allele discrimination of the fliCH19 genes, a real-time PCR test was designed for specific identification of EHEC O121:H19. The O121 fliCH19 PCR tested negative in 73 E. coli H19 strains that belonged to serogroups other than O121, including 28 different O groups, O-nontypeable H19, and O-rough:H19 strains. The O121 fliCH19 PCR reacted with all 16 tested O121:H19 strains and 1 O-rough:H19 strain which was positive for the O121 wzx gene. A cross-reaction was observed only with E. coli H32 strains which share sequence similarities in the target region of the O121 fliCH19 PCR. The combined use of O-antigen genotyping (O121 wzx) and the detection of O121 fliCH19 allele type contributes to improving the identification and molecular serotyping of EHEC O121:H19 motile and nonmotile strains and variants of these strains lacking stx genes.

  8. Genetically-Encoded Photocrosslinkers Determine the Biological Binding Site of Exendin-4 in the N-Terminal Domain of the Intact Human Glucagon-Like Peptide-1 Receptor (GLP-1R).

    Science.gov (United States)

    Koole, Cassandra; Reynolds, Christopher A; Mobarec, Juan C; Hick, Caroline; Sexton, Patrick M; Sakmar, Thomas P

    2017-03-10

    The glucagon-like peptide-1 receptor (GLP-1R) is a key therapeutic target in the management of type II diabetes mellitus, with actions including regulation of insulin biosynthesis and secretion, promotion of satiety and preservation of β-cell mass. Like most class B G protein-coupled receptors (GPCRs), there is limited knowledge linking biological activity of the GLP-1R with the molecular structure of an intact, full-length, functional receptor-ligand complex. In this study, we have utilized genetic code expansion to site-specifically incorporate the photoactive amino acid p-azido-L-phenylalanine (azF) into N-terminal residues of a full-length, functional human GLP-1R in mammalian cells. UV-mediated photolysis of azF was then carried out to induce targeted photocrosslinking to determine the proximity of the azido group in the mutant receptor with the peptide exendin-4. Crosslinking data were compared directly to the crystal structure of the isolated N-terminal extracellular domain (ECD) of the GLP-1R in complex with exendin(9-39), revealing both similarities as well as distinct differences in the mode of interaction. Generation of a molecular model to accommodate the photocrosslinking constraints highlights the potential influence of environmental conditions on the conformation of the receptor-peptide complex, including folding dynamics of the peptide and formation of dimeric and higher order oligomeric receptor multimers. These data demonstrate that crystal structures of isolated receptor regions may not give a complete reflection of peptide-receptor interactions, and should be combined with additional experimental constraints to reveal peptide-receptor interactions occurring in the dynamic, native, full-length receptor state.

  9. In vivo detection of exercised-induced ultrastructural changes in genetically-altered murine skeletal muscle using polarization-sensitive optical coherence tomography

    Science.gov (United States)

    Boppart, Stephen

    2006-02-01

    Skeletal muscle fibers are a known source of form birefringence in biological tissue. The birefringence present in skeletal muscle is associated with the ultrastructure of individual sarcomeres, specifically the arrangement of A-bands corresponding to the thick myosin filaments. Certain structural proteins that prevent damage and maintain the structural and functional health of the muscle fiber preserve the organization of the Abands in skeletal muscle. Therefore, the level of birefringence detected can estimate the health of the muscle as well as the damage incurred during exercise. Murine skeletal muscle from both genetically-altered (mdx) and normal (wild-type) specimens were imaged in vivo with a fiber-based PSOCT imaging system to quantitatively determine the level of birefringence present in the tissue before and after exercise. The mdx muscle lacks dystrophin, a structural protein that is mutated in Duchenne muscular dystrophy in humans. Muscle from these mdx mice exhibited a marked decrease in birefringence after exercise, whereas the wild-type muscle was highly birefringent before and after exercise. The quantitative results from this tissue optics study suggest for the first time that there is a distinct relationship between the degree of birefringence detected using PS-OCT and the sarcomeric ultrastructure present within skeletal muscle.

  10. System impairment compensation in coherent optical communications by using a bio-inspired detector based on artificial neural network and genetic algorithm

    Science.gov (United States)

    Wang, Danshi; Zhang, Min; Li, Ze; Song, Chuang; Fu, Meixia; Li, Jin; Chen, Xue

    2017-09-01

    A bio-inspired detector based on the artificial neural network (ANN) and genetic algorithm is proposed in the context of a coherent optical transmission system. The ANN is designed to mitigate 16-quadrature amplitude modulation system impairments, including linear impairment: Gaussian white noise, laser phase noise, in-phase/quadrature component imbalance, and nonlinear impairment: nonlinear phase. Without prior information or heuristic assumptions, the ANN, functioning as a machine learning algorithm, can learn and capture the characteristics of impairments from observed data. Numerical simulations were performed, and dispersion-shifted, dispersion-managed, and dispersion-unmanaged fiber links were investigated. The launch power dynamic range and maximum transmission distance for the bio-inspired method were 2.7 dBm and 240 km greater, respectively, than those of the maximum likelihood estimation algorithm. Moreover, the linewidth tolerance of the bio-inspired technique was 170 kHz greater than that of the k-means method, demonstrating its usability for digital signal processing in coherent systems.

  11. [Hereditary optic neuropathies].

    Science.gov (United States)

    Milea, D; Verny, C

    2012-10-01

    Hereditary optic neuropathies are a group of heterogeneous conditions affecting both optic nerves, with an autosomal dominant, autosomal recessive, X-related or mitochondrial transmission. The two most common non-syndromic hereditary optic neuropathies (Leber's hereditary optic neuropathy and autosomal dominant optic atrophy) are very different in their clinical presentation and their genetic transmission, leading however to a common, non-specific optic nerve atrophy. Beyond the optic atrophy-related visual loss, which is the clinical hallmark of this group of diseases, other associated neurological signs are increasingly recognized.

  12. Compressed Encoding for Rank Modulation

    CERN Document Server

    Gad, Eyal En; Jiang,; Bruck, Jehoshua

    2011-01-01

    Rank modulation has been recently proposed as a scheme for storing information in flash memories. While rank modulation has advantages in improving write speed and endurance, the current encoding approach is based on the "push to the top" operation that is not efficient in the general case. We propose a new encoding procedure where a cell level is raised to be higher than the minimal necessary subset - instead of all - of the other cell levels. This new procedure leads to a significantly more compressed (lower charge levels) encoding. We derive an upper bound for a family of codes that utilize the proposed encoding procedure, and consider code constructions that achieve that bound for several special cases.

  13. Cell encoding recombinant human erythropoietin

    Energy Technology Data Exchange (ETDEWEB)

    Beck, A.K.; Withy, R.M.; Zabrecky, J.R.; Masiello, N.C.

    1990-09-04

    This patent describes a C127 cell transformed with a recombinant DNA vector. It comprises: a DNA sequence encoding human erythropoietin, the transformed cell being capable of producing N-linked and O-linked glycosylated human erythropoietin.

  14. Self-Organising Stochastic Encoders

    CERN Document Server

    Luttrell, Stephen

    2010-01-01

    The processing of mega-dimensional data, such as images, scales linearly with image size only if fixed size processing windows are used. It would be very useful to be able to automate the process of sizing and interconnecting the processing windows. A stochastic encoder that is an extension of the standard Linde-Buzo-Gray vector quantiser, called a stochastic vector quantiser (SVQ), includes this required behaviour amongst its emergent properties, because it automatically splits the input space into statistically independent subspaces, which it then separately encodes. Various optimal SVQs have been obtained, both analytically and numerically. Analytic solutions which demonstrate how the input space is split into independent subspaces may be obtained when an SVQ is used to encode data that lives on a 2-torus (e.g. the superposition of a pair of uncorrelated sinusoids). Many numerical solutions have also been obtained, using both SVQs and chains of linked SVQs: (1) images of multiple independent targets (encod...

  15. Dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Lenaers Guy

    2012-07-01

    Full Text Available Abstract Definition of the disease Dominant Optic Atrophy (DOA is a neuro-ophthalmic condition characterized by a bilateral degeneration of the optic nerves, causing insidious visual loss, typically starting during the first decade of life. The disease affects primary the retinal ganglion cells (RGC and their axons forming the optic nerve, which transfer the visual information from the photoreceptors to the lateral geniculus in the brain. Epidemiology The prevalence of the disease varies from 1/10000 in Denmark due to a founder effect, to 1/30000 in the rest of the world. Clinical description DOA patients usually suffer of moderate visual loss, associated with central or paracentral visual field deficits and color vision defects. The severity of the disease is highly variable, the visual acuity ranging from normal to legal blindness. The ophthalmic examination discloses on fundoscopy isolated optic disc pallor or atrophy, related to the RGC death. About 20% of DOA patients harbour extraocular multi-systemic features, including neurosensory hearing loss, or less commonly chronic progressive external ophthalmoplegia, myopathy, peripheral neuropathy, multiple sclerosis-like illness, spastic paraplegia or cataracts. Aetiology Two genes (OPA1, OPA3 encoding inner mitochondrial membrane proteins and three loci (OPA4, OPA5, OPA8 are currently known for DOA. Additional loci and genes (OPA2, OPA6 and OPA7 are responsible for X-linked or recessive optic atrophy. All OPA genes yet identified encode mitochondrial proteins embedded in the inner membrane and ubiquitously expressed, as are the proteins mutated in the Leber Hereditary Optic Neuropathy. OPA1 mutations affect mitochondrial fusion, energy metabolism, control of apoptosis, calcium clearance and maintenance of mitochondrial genome integrity. OPA3 mutations only affect the energy metabolism and the control of apoptosis. Diagnosis Patients are usually diagnosed during their early childhood, because of

  16. Genetic Diversity of the fliC Genes Encoding the Flagellar Antigen H19 of Escherichia coli and Application to the Specific Identification of Enterohemorrhagic E. coli O121:H19

    Science.gov (United States)

    Beutin, Lothar; Delannoy, Sabine

    2015-01-01

    Enterohemorrhagic Escherichia coli (EHEC) O121:H19 belong to a specific clonal type distinct from other classical EHEC and major enteropathogenic E. coli groups and is regarded as one of the major EHEC serogroups involved in severe infections in humans. Sequencing of the fliC genes associated with the flagellar antigen H19 (fliCH19) revealed the genetic diversity of the fliCH19 gene sequences in E. coli. A cluster analysis of 12 fliCH19 sequences, 4 from O121 and 8 from non-O121 E. coli strains, revealed five different genotypes. All O121:H19 strains fell into one cluster, whereas a second cluster was formed by five non-O121:H19 strains. Cluster 1 and cluster 2 strains differ by 27 single nucleotide exchanges in their fliCH19 genes (98.5% homology). Based on allele discrimination of the fliCH19 genes, a real-time PCR test was designed for specific identification of EHEC O121:H19. The O121 fliCH19 PCR tested negative in 73 E. coli H19 strains that belonged to serogroups other than O121, including 28 different O groups, O-nontypeable H19, and O-rough:H19 strains. The O121 fliCH19 PCR reacted with all 16 tested O121:H19 strains and 1 O-rough:H19 strain which was positive for the O121 wzx gene. A cross-reaction was observed only with E. coli H32 strains which share sequence similarities in the target region of the O121 fliCH19 PCR. The combined use of O-antigen genotyping (O121 wzx) and the detection of O121 fliCH19 allele type contributes to improving the identification and molecular serotyping of EHEC O121:H19 motile and nonmotile strains and variants of these strains lacking stx genes. PMID:25862232

  17. Surfactant Protein-D-Encoding Gene Variant Polymorphisms Are Linked to Respiratory Outcome in Premature Infants

    DEFF Research Database (Denmark)

    Sorensen, Grith Lykke; Dahl, Marianne; Tan, Qihua

    2014-01-01

    OBJECTIVE: Associations between the genetic variation within or downstream of the surfactant protein-D-encoding gene (SFTPD), which encodes the collectin surfactant protein-D (SP-D) and may lead to respiratory distress syndrome or bronchopulmonary dysplasia, recently were reported. Our aim was to...

  18. Biomolecular screening with encoded porous-silicon photonic crystals

    Science.gov (United States)

    Cunin, Frédérique; Schmedake, Thomas A.; Link, Jamie R.; Li, Yang Yang; Koh, Jennifer; Bhatia, Sangeeta N.; Sailor, Michael J.

    2002-09-01

    Strategies to encode or label small particles or beads for use in high-throughput screening and bioassay applications focus on either spatially differentiated, on-chip arrays or random distributions of encoded beads. Attempts to encode large numbers of polymeric, metallic or glass beads in random arrays or in fluid suspension have used a variety of entities to provide coded elements (bits)-fluorescent molecules, molecules with specific vibrational signatures, quantum dots, or discrete metallic layers. Here we report a method for optically encoding micrometre-sized nanostructured particles of porous silicon. We generate multilayered porous films in crystalline silicon using a periodic electrochemical etch. This results in photonic crystals with well-resolved and narrow optical reflectivity features, whose wavelengths are determined by the etching parameters. Millions of possible codes can be prepared this way. Micrometre-sized particles are then produced by ultrasonic fracture, mechanical grinding or by lithographic means. A simple antibody-based bioassay using fluorescently tagged proteins demonstrates the encoding strategy in biologically relevant media.

  19. Ultrasonically encoded photoacoustic flowgraphy in biological tissue

    Science.gov (United States)

    Wang, Lidai; Xia, Jun; Yao, Junjie; Maslov, Konstantin I.; Wang, Lihong V.

    2014-01-01

    Blood flow speed is an important functional parameter. Doppler ultrasound flowmetry lacks sufficient sensitivity to slow blood flow (several to tens of millimeters per second) in deep tissue. To address this challenge, we developed ultrasonically encoded photoacoustic flowgraphy combining ultrasonic thermal tagging with photoacoustic imaging. Focused ultrasound generates a confined heat source in acoustically absorptive fluid. Thermal waves propagate with the flow and are directly visualized in pseudo color using photoacoustic computed tomography. The Doppler shift is employed to calculate the flow speed. This method requires only acoustic and optical absorption, and thus is applicable to continuous fluid. A blood flow speed as low as 0.24 mm·s−1 was successfully measured. Deep blood flow imaging was experimentally demonstrated under 5-mm-thick chicken breast tissue. PMID:24289689

  20. Ultrasonically encoded photoacoustic flowgraphy in biological tissue.

    Science.gov (United States)

    Wang, Lidai; Xia, Jun; Yao, Junjie; Maslov, Konstantin I; Wang, Lihong V

    2013-11-15

    Blood flow speed is an important functional parameter. Doppler ultrasound flowmetry lacks sufficient sensitivity to slow blood flow (several to tens of millimeters per second) in deep tissue. To address this challenge, we developed ultrasonically encoded photoacoustic flowgraphy combining ultrasonic thermal tagging with photoacoustic imaging. Focused ultrasound generates a confined heat source in acoustically absorptive fluid. Thermal waves propagate with the flow and are directly visualized in pseudo color using photoacoustic computed tomography. The Doppler shift is employed to calculate the flow speed. This method requires only acoustic and optical absorption, and thus is applicable to continuous fluid. A blood flow speed as low as 0.24  mm·s(-1)} was successfully measured. Deep blood flow imaging was experimentally demonstrated under 5-mm-thick chicken breast tissue.

  1. Multidimensionally encoded magnetic resonance imaging.

    Science.gov (United States)

    Lin, Fa-Hsuan

    2013-07-01

    Magnetic resonance imaging (MRI) typically achieves spatial encoding by measuring the projection of a q-dimensional object over q-dimensional spatial bases created by linear spatial encoding magnetic fields (SEMs). Recently, imaging strategies using nonlinear SEMs have demonstrated potential advantages for reconstructing images with higher spatiotemporal resolution and reducing peripheral nerve stimulation. In practice, nonlinear SEMs and linear SEMs can be used jointly to further improve the image reconstruction performance. Here, we propose the multidimensionally encoded (MDE) MRI to map a q-dimensional object onto a p-dimensional encoding space where p > q. MDE MRI is a theoretical framework linking imaging strategies using linear and nonlinear SEMs. Using a system of eight surface SEM coils with an eight-channel radiofrequency coil array, we demonstrate the five-dimensional MDE MRI for a two-dimensional object as a further generalization of PatLoc imaging and O-space imaging. We also present a method of optimizing spatial bases in MDE MRI. Results show that MDE MRI with a higher dimensional encoding space can reconstruct images more efficiently and with a smaller reconstruction error when the k-space sampling distribution and the number of samples are controlled.

  2. Genetic basis of chronic pancreatitis

    NARCIS (Netherlands)

    Jansen, JBMJ; Morsche, RT; van Goor, Harry; Drenth, JPH

    2002-01-01

    Background: Pancreatitis has a proven genetic basis in a minority of patients. Methods: Review of the literature on genetics of pancreatitis. Results: Ever since the discovery that in most patients with hereditary pancreatitis a mutation in the gene encoding for cationic trypsinogen (R122H) was

  3. Genetic basis of chronic pancreatitis

    NARCIS (Netherlands)

    Jansen, JBMJ; Morsche, RT; van Goor, Harry; Drenth, JPH

    2002-01-01

    Background: Pancreatitis has a proven genetic basis in a minority of patients. Methods: Review of the literature on genetics of pancreatitis. Results: Ever since the discovery that in most patients with hereditary pancreatitis a mutation in the gene encoding for cationic trypsinogen (R122H) was foun

  4. Virally encoded 7TM receptors

    DEFF Research Database (Denmark)

    Rosenkilde, M M; Waldhoer, M; Lüttichau, H R

    2001-01-01

    A number of herpes- and poxviruses encode 7TM G-protein coupled receptors most of which clearly are derived from their host chemokine system as well as induce high expression of certain 7TM receptors in the infected cells. The receptors appear to be exploited by the virus for either immune evasion...... in various parts of the viral life cyclus. Most of the receptors encoded by human pathogenic virus are still orphan receptors, i.e. the endogenous ligand is unknown. In the few cases where it has been possible to characterize these receptors pharmacologically, they have been found to bind a broad spectrum...... expression of this single gene in certain lymphocyte cell lineages leads to the development of lesions which are remarkably similar to Kaposi's sarcoma, a human herpesvirus 8 associated disease. Thus, this and other virally encoded 7TM receptors appear to be attractive future drug targets....

  5. Synaptic encoding of temporal contiguity

    Directory of Open Access Journals (Sweden)

    Srdjan eOstojic

    2013-04-01

    Full Text Available Often we need to perform tasks in an environment that changes stochastically. In these situations it is important to learn the statistics of sequences of events in order to predict the future and the outcome of our actions. The statistical description of many of these sequences can be reduced to the set of probabilities that a particular event follows another event (temporal contiguity. Under these conditions, it is important to encode and store in our memory these transition probabilities. Here we show that for a large class of synaptic plasticity models, the distribution of synaptic strengths encodes transitions probabilities. Specifically, when the synaptic dynamics depend on pairs of contiguous events and the synapses can remember multiple instances of the transitions, then the average synaptic weights are a monotonic function of the transition probabilities. The synaptic weights converge to the distribution encoding the probabilities also when the correlations between consecutive synaptic modifications are considered. We studied how this distribution depends on the number of synaptic states for a specific model of a multi-state synapse with hard bounds. In the case of bistable synapses, the average synaptic weights are a smooth function of the transition probabilities and the accuracy of the encoding depends on the learning rate. As the number of synaptic states increases, the average synaptic weights become a step function of the transition probabilities. We finally show that the information stored in the synaptic weights can be read out by a simple rate-based neural network. Our study shows that synapses encode transition probabilities under general assumptions and this indicates that temporal contiguity is likely to be encoded and harnessed in almost every neural circuit in the brain.

  6. Heterogeneidade genética em atrofia óptica autossômica dominante Genetic heterogeneity in autosomal dominant optic atrophy

    Directory of Open Access Journals (Sweden)

    Juliana Maria Ferraz Sallum

    2002-08-01

    locus para esta doença.Purpose: Autosomal dominant optic atrophy is a hereditary optic neuropathy characterized by progressive visual loss in childhood, color vision anomalies, visual field defects and temporal pallor of the optic disc. This disease has been mapped to a 1.4 cM interval in chromosome 3q28-29 between markers D3S3669 and D3S3562. One family was mapped to chromosome 18q12.2-12.3. Linkage analysis in three families with autosomal dominant optic atrophy with polymorphic DNA markers for chromosome 3q28-29 and 18q12.2-12.3. Methods: 57 individuals from three families underwent ophthalmological examination. Genomic DNA was extracted from blood samples. Linkage analysis was performed between the disease and 11 polymorphic markers around 3q28-qter and 18q12.2-12.3. Polymerase chain reaction (PCR fragments sizes were identified in a scanner gel using a 373 DNA sequencer. These numbers were used as alleles for pedigree analysis. The lod scores were calculated using the MLINK program. Results: All three families presented optic atrophy with autosomal dominant pattern of inheritance, variable expression and high penetrance. Two families were linked to 3q28-29 markers. A maximal lod score of 3.56, at a recombination fraction of zero, was obtained using the marker D3S3669 in one family. The linkage area was defined in a 2 cM interval by haplotype analysis between markers D3S2418 and D3S1305, because patients III.4 and III.14 showed crossing-overs. The third family was not linked to 3q28-29 neither to 18q12.2-12.3. Conclusions: There is genetic heterogeneity in autosomal dominant optic atrophy, because the third family did not map to any known locus. And a third locus for this disease may exist.

  7. Optics/Optical Diagnostics Laboratory

    Data.gov (United States)

    Federal Laboratory Consortium — The Optics/Optical Diagnostics Laboratory supports graduate instruction in optics, optical and laser diagnostics and electro-optics. The optics laboratory provides...

  8. Genetic elements of plant viruses as tools for genetic engineering.

    OpenAIRE

    Mushegian, A R; Shepherd, R J

    1995-01-01

    Viruses have developed successful strategies for propagation at the expense of their host cells. Efficient gene expression, genome multiplication, and invasion of the host are enabled by virus-encoded genetic elements, many of which are well characterized. Sequences derived from plant DNA and RNA viruses can be used to control expression of other genes in vivo. The main groups of plant virus genetic elements useful in genetic engineering are reviewed, including the signals for DNA-dependent a...

  9. Genetically Engineered Cyanobacteria

    Science.gov (United States)

    Zhou, Ruanbao (Inventor); Gibbons, William (Inventor)

    2015-01-01

    The disclosed embodiments provide cyanobacteria spp. that have been genetically engineered to have increased production of carbon-based products of interest. These genetically engineered hosts efficiently convert carbon dioxide and light into carbon-based products of interest such as long chained hydrocarbons. Several constructs containing polynucleotides encoding enzymes active in the metabolic pathways of cyanobacteria are disclosed. In many instances, the cyanobacteria strains have been further genetically modified to optimize production of the carbon-based products of interest. The optimization includes both up-regulation and down-regulation of particular genes.

  10. [Cerebrotendinous xanthomatosis: physiopathology, clinical manifestations and genetics].

    Science.gov (United States)

    Preiss, Yudith; Santos, José L; Smalley, Susan V; Maiz, Alberto

    2014-05-01

    Cerebrotendinous xanthomatosis (CTX) is a rare autosomal recessive disease, caused by genetic deficiency of the 27-hydroxylase enzyme (encoded by CYP27A1). It plays a key role in cholesterol metabolism, especially in bile acid synthesis and in the 25-hydroxylation of vitamin D3 in the liver. Its deficiency causes reduced bile acid synthesis and tissue accumulation of cholestanol. Clinical manifestations are related to the presence of cholestanol deposits and include tendon xanthomas, premature cataracts, chronic diarrhea, progressive neurologic impairment and less frequently coronary heart disease, early onset osteoporosis and abnormalities in the optic disk and retina. An early diagnosis and treatment with quenodeoxycholic acid may prevent further complications, mainly neurological manifestations. This review summarizes cholesterol metabolism related to bile acid synthesis, physiopathology, biochemistry and treatment of cerebrotendinous xanthomatosis.

  11. Atmospheric effects on Quaternary polarization encoding for free space communication

    Science.gov (United States)

    Soorat, Ram; Vudayagiri, Ashok

    2016-10-01

    We have simulated atmospheric effects such as fog and smoke in laboratory environment to simulate depolarisation due to atmospheric effects during a free space optical communi- cation. This has been used to study noise in two components of quaternary encoding for polarization shift keying. Individual components of a Quaternary encoding, such as vertical and horizontal as well as 45$^\\circ$ and 135$^\\circ$ , are tested separately and indicates that the depo- larization effects are different for these two situation. However, due to a differential method used to extract information bits, the protocol shows extremely low bit error rates. The information obtained is useful during deployment of a fully functional Quaternary encoded PolSK scheme in free space.

  12. Genetically encoded biosensors based on engineered fluorescent proteins.

    Science.gov (United States)

    Frommer, Wolf B; Davidson, Michael W; Campbell, Robert E

    2009-10-01

    Fluorescent proteins have revolutionized cell biology by allowing researchers to non-invasively peer into the inner workings of cells and organisms. While the most common applications of fluorescent proteins are to image expression, localization, and dynamics of protein chimeras, there is a growing interest in using fluorescent proteins to create biosensors for minimally invasive imaging of concentrations of ions and small molecules, the activity of enzymes, and changes in the conformation of proteins in living cells. This tutorial review provides an overview of the progress made in the development of fluorescent protein-based biosensors to date.

  13. A genetically encoded fluorescent probe in mammalian cells.

    Science.gov (United States)

    Chatterjee, Abhishek; Guo, Jiantao; Lee, Hyun Soo; Schultz, Peter G

    2013-08-28

    Fluorescent reporters are useful in vitro and in vivo probes of protein structure, function, and localization. Here we report that the fluorescent amino acid, 3-(6-acetylnaphthalen-2-ylamino)-2-aminopropanoic acid (Anap), can be site-specifically incorporated into proteins in mammalian cells in response to the TAG codon with high efficiency using an orthogonal amber suppressor tRNA/aminoacyl-tRNA synthetase (aaRS) pair. We further demonstrate that Anap can be used to image the subcellular localization of proteins in live mammalian cells. The small size of Anap, its environment-sensitive fluorescence, and the ability to introduce Anap at specific sites in the proteome by simple mutagenesis make it a unique and valuable tool in eukaryotic cell biology.

  14. Detection of cortical optical changes during seizure activity using optical coherence tomography (Conference Presentation)

    Science.gov (United States)

    Ornelas, Danielle; Hasan, Md.; Gonzalez, Oscar; Krishnan, Giri; Szu, Jenny I.; Myers, Timothy; Hirota, Koji; Bazhenov, Maxim; Binder, Devin K.; Park, Boris H.

    2017-02-01

    Electrophysiology has remained the gold standard of neural activity detection but its resolution and high susceptibility to noise and motion artifact limit its efficiency. Imaging techniques, including fMRI, intrinsic optical imaging, and diffuse optical imaging, have been used to detect neural activity, but rely on indirect measurements such as changes in blood flow. Fluorescence-based techniques, including genetically encoded indicators, are powerful techniques, but require introduction of an exogenous fluorophore. A more direct optical imaging technique is optical coherence tomography (OCT), a label-free, high resolution, and minimally invasive imaging technique that can produce depth-resolved cross-sectional and 3D images. In this study, we sought to examine non-vascular depth-dependent optical changes directly related to neural activity. We used an OCT system centered at 1310 nm to search for changes in an ex vivo brain slice preparation and an in vivo model during 4-AP induced seizure onset and propagation with respect to electrical recording. By utilizing Doppler OCT and the depth-dependency of the attenuation coefficient, we demonstrate the ability to locate and remove the optical effects of vasculature within the upper regions of the cortex from in vivo attenuation calculations. The results of this study show a non-vascular decrease in intensity and attenuation in ex vivo and in vivo seizure models, respectively. Regions exhibiting decreased optical changes show significant temporal correlation to regions of increased electrical activity during seizure. This study allows for a thorough and biologically relevant analysis of the optical signature of seizure activity both ex vivo and in vivo using OCT.

  15. Holistic random encoding for imaging through multimode fibers.

    Science.gov (United States)

    Jang, Hwanchol; Yoon, Changhyeong; Chung, Euiheon; Choi, Wonshik; Lee, Heung-No

    2015-03-01

    The input numerical aperture (NA) of multimode fiber (MMF) can be effectively increased by placing turbid media at the input end of the MMF. This provides the potential for high-resolution imaging through the MMF. While the input NA is increased, the number of propagation modes in the MMF and hence the output NA remains the same. This makes the image reconstruction process underdetermined and may limit the quality of the image reconstruction. In this paper, we aim to improve the signal to noise ratio (SNR) of the image reconstruction in imaging through MMF. We notice that turbid media placed in the input of the MMF transforms the incoming waves into a better format for information transmission and information extraction. We call this transformation as holistic random (HR) encoding of turbid media. By exploiting the HR encoding, we make a considerable improvement on the SNR of the image reconstruction. For efficient utilization of the HR encoding, we employ sparse representation (SR), a relatively new signal reconstruction framework when it is provided with a HR encoded signal. This study shows for the first time to our knowledge the benefit of utilizing the HR encoding of turbid media for recovery in the optically underdetermined systems where the output NA of it is smaller than the input NA for imaging through MMF.

  16. Encoding information into precipitation structures

    Science.gov (United States)

    Martens, Kirsten; Bena, Ioana; Droz, Michel; Rácz, Zoltan

    2008-12-01

    Material design at submicron scales would be profoundly affected if the formation of precipitation patterns could be easily controlled. It would allow the direct building of bulk structures, in contrast to traditional techniques which consist of removing material in order to create patterns. Here, we discuss an extension of our recent proposal of using electrical currents to control precipitation bands which emerge in the wake of reaction fronts in A+ + B- → C reaction-diffusion processes. Our main result, based on simulating the reaction-diffusion-precipitation equations, is that the dynamics of the charged agents can be guided by an appropriately designed time-dependent electric current so that, in addition to the control of the band spacing, the width of the precipitation bands can also be tuned. This makes straightforward the encoding of information into precipitation patterns and, as an amusing example, we demonstrate the feasibility by showing how to encode a musical rhythm.

  17. Geometric Hyperplanes: Desargues Encodes Doily

    CERN Document Server

    Saniga, Metod

    2011-01-01

    It is shown that the structure of the generalized quadrangle of order two is fully encoded in the properties of the Desargues configuration. A point of the quadrangle is represented by a geometric hyperplane of the Desargues configuration and its line by a set of three hyperplanes such that one of them is the complement of the symmetric difference of the remaining two and they all share a pair of non-collinear points.

  18. Vector Encoding in Biochemical Networks

    Science.gov (United States)

    Potter, Garrett; Sun, Bo

    Encoding of environmental cues via biochemical signaling pathways is of vital importance in the transmission of information for cells in a network. The current literature assumes a single cell state is used to encode information, however, recent research suggests the optimal strategy utilizes a vector of cell states sampled at various time points. To elucidate the optimal sampling strategy for vector encoding, we take an information theoretic approach and determine the mutual information of the calcium signaling dynamics obtained from fibroblast cells perturbed with different concentrations of ATP. Specifically, we analyze the sampling strategies under the cases of fixed and non-fixed vector dimension as well as the efficiency of these strategies. Our results show that sampling with greater frequency is optimal in the case of non-fixed vector dimension but that, in general, a lower sampling frequency is best from both a fixed vector dimension and efficiency standpoint. Further, we find the use of a simple modified Ornstein-Uhlenbeck process as a model qualitatively captures many of our experimental results suggesting that sampling in biochemical networks is based on a few basic components.

  19. Genetic Discrimination

    Science.gov (United States)

    ... in Genetics Archive Regulation of Genetic Tests Genetic Discrimination Overview Many Americans fear that participating in research ... I) and employment (Title II). Read more Genetic Discrimination and Other Laws Genetic Discrimination and Other Laws ...

  20. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

    NARCIS (Netherlands)

    Springelkamp, H. (Henriët); Iglesias, A.I. (Adriana); Mishra, A. (Aniket); Höhn, R. (René); Wojciechowski, R. (Robert); Khawaja, A.P. (Anthony); Nag, A. (Abhishek); Wang, Y.X. (Ya Xing); Wang, J.J. (Jie Jin); Cuellar-Partida, G. (Gabriel); Gibson, J. (Jane); Cooke Bailey, J.N. (Jessica); Vithana, E.N. (Eranga); Gharahkhani, P. (Puya); Boutin, T. (Thibaud); Ramdas, W.D. (Wishal); Zeller, T. (Tanja); Luben, R.N. (Robert); Yonova-Doing, E. (Ekaterina); Viswanathan, A.C. (Ananth); Yazar, S. (Seyhan); Cree, A.J. (Angela); Haines, J.L. (Jonathan); Koh, J.Y. (Jia Yu); Souzeau, E. (Emmanuelle); Wilson, J.F. (James); Amin, N. (Najaf); Müller, C. (Christian); Venturini, C. (Cristina); Kearns, L.S. (Lisa); Hee Kang, J. (Jae); Consortium, N. (Neighborhood); Tham, Y.C. (Yih Chung); Zhou, T. (Tiger); van Leeuwen, E.M. (Elisabeth); Nickels, S. (Stefan); Sanfilippo, P. (Paul); Liao, J. (Jiemin); Linde, H.V. (Herma van der); Zhao, W. (Wanting); van Koolwijk, L.M. (Leonieke); Zheng, L. (Li); Rivadeneira, F. (Fernando); Baskaran, M. (Mani); van der Lee, S.J. (Sven); Perera, S. (Shamira); de Jong, P.T. (Paulus); Oostra, B.A. (Ben); Uitterlinden, A.G. (André); Fan, Q. (Qiao); Hofman, A. (Albert); Shyong Tai, E. (E-); Vingerling, J.R. (Johannes); Sim, X. (Xueling); Wolfs, R.C. (Roger); Teo, Y.Y. (Yik Ying); Lemij, H.G. (Hans); Khor, C.C. (Chiea Chuen); Willemsen, R. (Rob); Lackner, K.J. (Karl); Aung, T. (Tin); Jansonius, N.M. (Nomdo); Montgomery, G. (Grant); Wild, P.S. (Philipp); Young, T.L. (Terri); Burdon, K.P. (Kathryn); Hysi, P.G. (Pirro); Pasquale, L.R. (Louis); Wong, T.Y. (Tien Yin); Klaver, C.C. (Caroline); Hewitt, A.W. (Alex); Jonas, J.B. (Jost); Mitchell, P. (Paul); Lotery, A.J. (Andrew); Foster, P.J. (Paul); Vitart, V. (Veronique); Pfeiffer, N. (Norbert); Craig, J.E. (Jamie); Mackey, D.A. (David); Hammond, C.J. (Christopher); Wiggs, J.L. (Janey); Cheng, C.Y. (Ching-Yu); van Duijn, C.M. (Cornelia); MacGregor, S. (Stuart)

    2017-01-01

    textabstractPrimary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increase risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We

  1. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics

    NARCIS (Netherlands)

    Springelkamp, Henriët; Iglesias, Adriana I; Mishra, Aniket; Höhn, René; Wojciechowski, Robert; Khawaja, Anthony P; Nag, Abhishek; Wang, Ya Xing; Wang, Jie Jin; Cuellar-Partida, Gabriel; Gibson, Jane; Cooke Bailey, Jessica N; Vithana, Eranga N; Gharahkhani, Puya; Boutin, Thibaud; Ramdas, Wishal D; Zeller, Tanja; Luben, Robert N; Yonova-Doing, Ekaterina; Viswanathan, Ananth C; Yazar, Seyhan; Cree, Angela J; Haines, Jonathan L; Koh, Jia Yu; Souzeau, Emmanuelle; Wilson, James F; Amin, Najaf; Müller, Christian; Venturini, Cristina; Kearns, Lisa S; Hee Kang, Jae; Consortium, Neighborhood; Tham, Yih Chung; Zhou, Tiger; van Leeuwen, Elisabeth M; Nickels, Stefan; Sanfilippo, Paul; Liao, Jiemin; Linde, Herma van der; Zhao, Wanting; van Koolwijk, Leonieke M E; Zheng, Li; Rivadeneira, Fernando; Baskaran, Mani; van der Lee, Sven J; Perera, Shamira; de Jong, Paulus T V M; Oostra, Ben A; Uitterlinden, André G; Fan, Qiao; Hofman, Albert; Shyong Tai, E-; Vingerling, Johannes R; Sim, Xueling; Wolfs, Roger C W; Teo, Yik Ying; Lemij, Hans G; Khor, Chiea Chuen; Willemsen, Rob; Lackner, Karl J; Aung, Tin; Jansonius, Nomdo M; Montgomery, Grant; Wild, Philipp S; Young, Terri L; Burdon, Kathryn P; Hysi, Pirro G; Pasquale, Louis R; Wong, Tien Yin; Klaver, Caroline C W; Hewitt, Alex W; Jonas, Jost B; Mitchell, Paul; Lotery, Andrew J; Foster, Paul J; Vitart, Veronique; Pfeiffer, Norbert; Craig, Jamie E; Mackey, David A; Hammond, Christopher J; Wiggs, Janey L; Cheng, Ching-Yu; van Duijn, Cornelia M; MacGregor, Stuart

    2017-01-01

    Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increase risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a

  2. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics

    NARCIS (Netherlands)

    Springelkamp, H.; Iglesias, A.I.; Mishra, A; Hohn, R.; Wojciechowski, R.; Khawaja, A.P.; Nag, A.; Wang, Y.X.; Wang, J.J.; Cuellar-Partida, G.; Gibson, J.; Bailey, J.N.; Vithana, E.N.; Gharahkhani, P.; Boutin, T.; Ramdas, W.D.; Zeller, T.; Luben, R.N.; Yonova-Doing, E.; Viswanathan, A.C.; Yazar, S.; Cree, A.J.; Haines, J.L.; Koh, J.Y.; Souzeau, E.; Wilson, J.F.; Amin, N.; Muller, C.; Venturini, C.; Kearns, L.S.; Kang, J.H.; Tham, Y.C.; Zhou, T.; Leeuwen, E.M. van; Nickels, S.; Sanfilippo, P.; Liao, J.; Linde, H. van der; Zhao, W.; Koolwijk, L.M. van; Zheng, L.; Rivadeneira, F.; Baskaran, M.; Lee, S.J. van der; Perera, S.; Jong, P.T.; Oostra, B.A.; Uitterlinden, A.G.; Fan, Q.; Hofman, A.; Tai, E.S.; Vingerling, J.R.; Sim, X.; Wolfs, R.C.; Teo, Y.Y.; Lemij, H.G.; Khor, C.C.; Willemsen, R.; Lackner, K.J.; Aung, T.; Jansonius, N.M.; Montgomery, G.; Wild, P.S.; Young, T.L.; Burdon, K.P.; Hysi, P.G.; Pasquale, L.R.; Wong, T.Y.; Klaver, C.C.W.; Hewitt, A.W.; Jonas, J.B.; Mitchell, P.; Lotery, A.J.; Foster, P.J.; Vitart, V.; Pfeiffer, N.; Craig, J.E.; Mackey, D.A.; Hammond, C.J.; Wiggs, J.L.; Cheng, C.Y.; Duijn, C.M. van; MacGregor, S.

    2017-01-01

    Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a

  3. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics

    NARCIS (Netherlands)

    Springelkamp, Henriët; Iglesias, Adriana I; Mishra, Aniket; Höhn, René; Wojciechowski, Robert; Khawaja, Anthony P; Nag, Abhishek; Wang, Ya Xing; Wang, Jie Jin; Cuellar-Partida, Gabriel; Gibson, Jane; Cooke Bailey, Jessica N; Vithana, Eranga N; Gharahkhani, Puya; Boutin, Thibaud; Ramdas, Wishal D; Zeller, Tanja; Luben, Robert N; Yonova-Doing, Ekaterina; Viswanathan, Ananth C; Yazar, Seyhan; Cree, Angela J; Haines, Jonathan L; Koh, Jia Yu; Souzeau, Emmanuelle; Wilson, James F; Amin, Najaf; Müller, Christian; Venturini, Cristina; Kearns, Lisa S; Hee Kang, Jae; Consortium, Neighborhood; Tham, Yih Chung; Zhou, Tiger; van Leeuwen, Elisabeth M; Nickels, Stefan; Sanfilippo, Paul; Liao, Jiemin; Linde, Herma van der; Zhao, Wanting; van Koolwijk, Leonieke M E; Zheng, Li; Rivadeneira, Fernando; Baskaran, Mani; van der Lee, Sven J; Perera, Shamira; de Jong, Paulus T V M; Oostra, Ben A; Uitterlinden, André G; Fan, Qiao; Hofman, Albert; Shyong Tai, E-; Vingerling, Johannes R; Sim, Xueling; Wolfs, Roger C W; Teo, Yik Ying; Lemij, Hans G; Khor, Chiea Chuen; Willemsen, Rob; Lackner, Karl J; Aung, Tin; Jansonius, Nomdo M; Montgomery, Grant; Wild, Philipp S; Young, Terri L; Burdon, Kathryn P; Hysi, Pirro G; Pasquale, Louis R; Wong, Tien Yin; Klaver, Caroline C W; Hewitt, Alex W; Jonas, Jost B; Mitchell, Paul; Lotery, Andrew J; Foster, Paul J; Vitart, Veronique; Pfeiffer, Norbert; Craig, Jamie E; Mackey, David A; Hammond, Christopher J; Wiggs, Janey L; Cheng, Ching-Yu; van Duijn, Cornelia M; MacGregor, Stuart

    2017-01-01

    Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increase risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genom

  4. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

    NARCIS (Netherlands)

    Springelkamp, H. (Henriët); Iglesias, A.I. (Adriana); Mishra, A. (Aniket); Höhn, R. (René); Wojciechowski, R. (Robert); Khawaja, A.P. (Anthony); Nag, A. (Abhishek); Wang, Y.X. (Ya Xing); Wang, J.J. (Jie Jin); Cuellar-Partida, G. (Gabriel); Gibson, J. (Jane); Cooke Bailey, J.N. (Jessica); Vithana, E.N. (Eranga); Gharahkhani, P. (Puya); Boutin, T. (Thibaud); Ramdas, W.D. (Wishal); Zeller, T. (Tanja); Luben, R.N. (Robert); Yonova-Doing, E. (Ekaterina); Viswanathan, A.C. (Ananth); Yazar, S. (Seyhan); Cree, A.J. (Angela); Haines, J.L. (Jonathan); Koh, J.Y. (Jia Yu); Souzeau, E. (Emmanuelle); Wilson, J.F. (James); Amin, N. (Najaf); Müller, C. (Christian); Venturini, C. (Cristina); Kearns, L.S. (Lisa); Hee Kang, J. (Jae); Consortium, N. (Neighborhood); Tham, Y.C. (Yih Chung); Zhou, T. (Tiger); van Leeuwen, E.M. (Elisabeth); Nickels, S. (Stefan); Sanfilippo, P. (Paul); Liao, J. (Jiemin); Linde, H.V. (Herma van der); Zhao, W. (Wanting); van Koolwijk, L.M. (Leonieke); Zheng, L. (Li); Rivadeneira, F. (Fernando); Baskaran, M. (Mani); van der Lee, S.J. (Sven); Perera, S. (Shamira); de Jong, P.T. (Paulus); Oostra, B.A. (Ben); Uitterlinden, A.G. (André); Fan, Q. (Qiao); Hofman, A. (Albert); Shyong Tai, E. (E-); Vingerling, J.R. (Johannes); Sim, X. (Xueling); Wolfs, R.C. (Roger); Teo, Y.Y. (Yik Ying); Lemij, H.G. (Hans); Khor, C.C. (Chiea Chuen); Willemsen, R. (Rob); Lackner, K.J. (Karl); Aung, T. (Tin); Jansonius, N.M. (Nomdo); Montgomery, G. (Grant); Wild, P.S. (Philipp); Young, T.L. (Terri); Burdon, K.P. (Kathryn); Hysi, P.G. (Pirro); Pasquale, L.R. (Louis); Wong, T.Y. (Tien Yin); Klaver, C.C. (Caroline); Hewitt, A.W. (Alex); Jonas, J.B. (Jost); Mitchell, P. (Paul); Lotery, A.J. (Andrew); Foster, P.J. (Paul); Vitart, V. (Veronique); Pfeiffer, N. (Norbert); Craig, J.E. (Jamie); Mackey, D.A. (David); Hammond, C.J. (Christopher); Wiggs, J.L. (Janey); Cheng, C.Y. (Ching-Yu); van Duijn, C.M. (Cornelia); MacGregor, S. (Stuart)

    2017-01-01

    textabstractPrimary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increase risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We condu

  5. Research on encoding multi-gray-scale phase hologram and wavefront reconstruction.

    Science.gov (United States)

    Zhang, Hongxin; Zhou, Hao; Li, Jingyao; Qiao, Yujing; Gao, Wei

    2016-04-01

    Application of computer-generated holography for wavefront generation is beneficial for optical interferometry and 3D image display. However, there is a noticeable encoding error in computer-generated holograms, which is encoded by using the object's wavefront function in a computer. The encoding error will be transmitted and amplified during fabrication of a hologram, which can cause a reconstructed error in the generated wavefront. A correction method of encoding errors based on the least-squares fitting is proposed. A validating experiment is completed by using a liquid crystal spatial light modulator to reconstruct a group of paraboloid wavefronts. The results show that encoding errors increase the reconstructed error of a wavefront less than optical system errors, and the root-mean-square value drops 0.022λ after the correction of the encoding error, but it falls 0.092λ after the correction of optical system errors. The total error has been reduced by 0.114λ. This research is helpful for prediction of encoding errors and improvement of wavefront reconstruction accuracy.

  6. Power calculation of linear and angular incremental encoders

    Science.gov (United States)

    Prokofev, Aleksandr V.; Timofeev, Aleksandr N.; Mednikov, Sergey V.; Sycheva, Elena A.

    2016-04-01

    Automation technology is constantly expanding its role in improving the efficiency of manufacturing and testing processes in all branches of industry. More than ever before, the mechanical movements of linear slides, rotary tables, robot arms, actuators, etc. are numerically controlled. Linear and angular incremental photoelectric encoders measure mechanical motion and transmit the measured values back to the control unit. The capabilities of these systems are undergoing continual development in terms of their resolution, accuracy and reliability, their measuring ranges, and maximum speeds. This article discusses the method of power calculation of linear and angular incremental photoelectric encoders, to find the optimum parameters for its components, such as light emitters, photo-detectors, linear and angular scales, optical components etc. It analyzes methods and devices that permit high resolutions in the order of 0.001 mm or 0.001°, as well as large measuring lengths of over 100 mm. In linear and angular incremental photoelectric encoders optical beam is usually formulated by a condenser lens passes through the measuring unit changes its value depending on the movement of a scanning head or measuring raster. Past light beam is converting into an electrical signal by the photo-detecter's block for processing in the electrical block. Therefore, for calculating the energy source is a value of the desired value of the optical signal at the input of the photo-detecter's block, which reliably recorded and processed in the electronic unit of linear and angular incremental optoelectronic encoders. Automation technology is constantly expanding its role in improving the efficiency of manufacturing and testing processes in all branches of industry. More than ever before, the mechanical movements of linear slides, rotary tables, robot arms, actuators, etc. are numerically controlled. Linear and angular incremental photoelectric encoders measure mechanical motion and

  7. Loss Tolerant Optical Qubits

    CERN Document Server

    Ralph, T C; Gilchrist, A; Gilchrist, Alexei

    2005-01-01

    We present a linear optics quantum computation scheme that employs a new encoding approach that incrementally adds qubits and is tolerant to photon loss errors. The scheme employs a circuit model but uses techniques from cluster state computation and achieves comparable resource usage. To illustrate our techniques we describe a quantum memory which is fault tolerant to photon loss.

  8. New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics.

    OpenAIRE

    Springelkamp, H.; Iglesias, A. I.; A.; Mishra; Höhn, R; Wojciechowski, R.; Khawaja, A.P. (Anthony); Nag, A.; Wang, Y.X.; Wang, J. J.; Cuellar-Partida, G.; Gibson, J.; Cooke Bailey, J.N. (Jessica); Vithana, E. N.; Gharahkhani, P.; Boutin, T.

    2017-01-01

    textabstractPrimary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increase risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) re...

  9. Hall effect encoding of brushless dc motors

    Science.gov (United States)

    Berard, C. A.; Furia, T. J.; Goldberg, E. A.; Greene, R. C.

    1970-01-01

    Encoding mechanism integral to the motor and using the permanent magnets embedded in the rotor eliminates the need for external devices to encode information relating the position and velocity of the rotating member.

  10. Genetic Control of Potassium Channels.

    Science.gov (United States)

    Amin, Ahmad S; Wilde, Arthur A M

    2016-06-01

    Approximately 80 genes in the human genome code for pore-forming subunits of potassium (K(+)) channels. Rare variants (mutations) in K(+) channel-encoding genes may cause heritable arrhythmia syndromes. Not all rare variants in K(+) channel-encoding genes are necessarily disease-causing mutations. Common variants in K(+) channel-encoding genes are increasingly recognized as modifiers of phenotype in heritable arrhythmia syndromes and in the general population. Although difficult, distinguishing pathogenic variants from benign variants is of utmost importance to avoid false designations of genetic variants as disease-causing mutations.

  11. Amplifying genetic logic gates.

    Science.gov (United States)

    Bonnet, Jerome; Yin, Peter; Ortiz, Monica E; Subsoontorn, Pakpoom; Endy, Drew

    2013-05-03

    Organisms must process information encoded via developmental and environmental signals to survive and reproduce. Researchers have also engineered synthetic genetic logic to realize simpler, independent control of biological processes. We developed a three-terminal device architecture, termed the transcriptor, that uses bacteriophage serine integrases to control the flow of RNA polymerase along DNA. Integrase-mediated inversion or deletion of DNA encoding transcription terminators or a promoter modulates transcription rates. We realized permanent amplifying AND, NAND, OR, XOR, NOR, and XNOR gates actuated across common control signal ranges and sequential logic supporting autonomous cell-cell communication of DNA encoding distinct logic-gate states. The single-layer digital logic architecture developed here enables engineering of amplifying logic gates to control transcription rates within and across diverse organisms.

  12. Tape measuring system using linear encoder and digital camera

    Science.gov (United States)

    Eom, Tae Bong; Jeong, Don Young; Kim, Myung Soon; Kim, Jae Wan; Kim, Jong Ahn

    2013-04-01

    We have designed and constructed the calibration system of line standards such as tape and rule for the secondary calibration laboratories. The system consists of the main body with linear stage and linear encoder, the optical microscope with digital camera, and the computer. The base of the system is a aluminum profile with 2.9 m length, 0.09 m height and 0.18 m width. The linear stage and the linear encoder are fixed on the aluminum profile. The micro-stage driven by micrometer is fixed on the carriage of the long linear stage, and the optical microscope with digital camera and the tablet PC are on the this stage. The linear encoder counts the moving distance of the linear stage with resolution of 1 μm and its counting value is transferred to the tablet PC. The image of the scale mark of the tape is captured by the CCD camera of optical microscope and transferred to the PC through USB interface. The computer automatically determines the center of the scale mark by image processing technique and at the same time reads the moving distance of the linear stage. As a result, the computer can calculate the interval between the scale marks of the tape. In order to achieve the high accuracy, the linear encoder should be calibrated using the laser interferometer or the rigid steel rule. This calibration data of the linear encoder is stored at the computer and the computer corrects the reading value of the linear encoder. In order to determine the center of the scale mark, we use three different algorithms. First, the image profile over specified threshold level is fitted in even order polynomial and the axis of the polynomial is used as the center of the line. Second, the left side and right side areas at the center of the image profile are calculated so that two areas are same. Third, the left and right edges of the image profile are determined at every intensity level of the image and the center of the graduation is calculated as an average of the centers of the left

  13. [Neurons that encode sound direction].

    Science.gov (United States)

    Peña, J L

    In the auditory system, the inner ear breaks down complex signals into their spectral components, and encodes the amplitude and phase of each. In order to infer sound direction in space, a computation on each frequency component of the sound must be performed. Space specific neurons in the owl s inferior colliculus respond only to sounds coming from a particular direction and represent the results of this computation. The interaural time difference (ITD) and interaural level difference (ILD define the auditory space for the owl and are processed in separate neural pathways. The parallel pathways that process these cues merge in the external nucleus of the inferior colliculus where the space specific neurons are selective to combinations of ITD and ILD. How do inputs from the two sources interact to produce combination selectivity to ITD ILD pairs? A multiplication of postsynaptic potentials tuned to ITD and ILD can account for the subthreshold responses of these neurons to ITD ILD pairs. Examples of multiplication by neurons or neural circuits are scarce, but many computational models assume the existence of this basic operation. The owl s auditory system uses such operation to create a 2 dimensional map of auditory space. The map of space in the owl s auditory system shows important similarities with representations of space in the cerebral cortex and other sensory systems. In encoding space or other stimulus features, individual neurons appear to possess analogous functional properties related to the synthesis of high order receptive fields.

  14. Successful Scene Encoding in Presymptomatic Early-Onset Alzheimer's Disease.

    Science.gov (United States)

    Quiroz, Yakeel T; Willment, Kim Celone; Castrillon, Gabriel; Muniz, Martha; Lopera, Francisco; Budson, Andrew; Stern, Chantal E

    2015-01-01

    Brain regions critical to episodic memory are altered during the preclinical stages of Alzheimer's disease (AD). However, reliable means of identifying cognitively-normal individuals at higher risk to develop AD have not been established. To examine whether functional MRI can detect early functional changes associated with scene encoding in a group of presymptomatic presenilin-1 (PSEN1) E280A mutation carriers. Participants were 39 young, cognitively-normal individuals from an autosomal dominant early-onset AD kindred, located in Antioquia, Colombia. Participants performed a functional MRI scene encoding task and a post-scan subsequent memory test. PSEN1 mutation carriers exhibited hyperactivation within medial temporal lobe regions (hippocampus,parahippocampal formation) during successful scene encoding compared to age-matched non-carriers. Hyperactivation in medial temporal lobe regions during scene encoding is seen in individuals genetically-determined to develop AD years before their clinical onset. Our findings will guide future research with the ultimate goal of using functional neuroimaging in the early detection of preclinical AD.

  15. Efficient production of optically pure D-lactic acid from raw corn starch by using a genetically modified L-lactate dehydrogenase gene-deficient and alpha-amylase-secreting Lactobacillus plantarum strain.

    Science.gov (United States)

    Okano, Kenji; Zhang, Qiao; Shinkawa, Satoru; Yoshida, Shogo; Tanaka, Tsutomu; Fukuda, Hideki; Kondo, Akihiko

    2009-01-01

    In order to achieve direct and efficient fermentation of optically pure D-lactic acid from raw corn starch, we constructed L-lactate dehydrogenase gene (ldhL1)-deficient Lactobacillus plantarum and introduced a plasmid encoding Streptococcus bovis 148 alpha-amylase (AmyA). The resulting strain produced only D-lactic acid from glucose and successfully expressed amyA. With the aid of secreting AmyA, direct D-lactic acid fermentation from raw corn starch was accomplished. After 48 h of fermentation, 73.2 g/liter of lactic acid was produced with a high yield (0.85 g per g of consumed sugar) and an optical purity of 99.6%. Moreover, a strain replacing the ldhL1 gene with an amyA-secreting expression cassette was constructed. Using this strain, direct D-lactic acid fermentation from raw corn starch was accomplished in the absence of selective pressure by antibiotics. This is the first report of direct D-lactic acid fermentation from raw starch.

  16. Generalized non-separable two-dimensional Dammann encoding method

    Science.gov (United States)

    Yu, Junjie; Zhou, Changhe; Zhu, Linwei; Lu, Yancong; Wu, Jun; Jia, Wei

    2017-01-01

    We generalize for the first time, to the best of our knowledge, the Dammann encoding method into non-separable two-dimensional (2D) structures for designing various pure-phase Dammann encoding gratings (DEGs). For examples, three types of non-separable 2D DEGs, including non-separable binary Dammann vortex gratings, non-separable binary distorted Dammann gratings, and non-separable continuous-phase cubic gratings, are designed theoretically and demonstrated experimentally. Correspondingly, it is shown that 2D square arrays of optical vortices with topological charges proportional to the diffraction orders, focus spots shifting along both transversal and axial directions with equal spacings, and Airy-like beams with controllable orientation for each beam, are generated in symmetry or asymmetry by these three DEGs, respectively. Also, it is shown that a more complex-shaped array of modulated beams could be achieved by this non-separable 2D Dammann encoding method, which will be a big challenge for those conventional separable 2D Dammann encoding gratings. Furthermore, the diffractive efficiency of the gratings can be improved around ∼10% when the non-separable structure is applied, compared with their conventional separable counterparts. Such improvement in the efficiency should be of high significance for some specific applications.

  17. Quantum-dots-encoded-microbeads based molecularly imprinted polymer.

    Science.gov (United States)

    Liu, Yixi; Liu, Le; He, Yonghong; He, Qinghua; Ma, Hui

    2016-03-15

    Quantum dots encoded microbeads have various advantages such as large surface area, superb optical properties and the ability of multiplexing. Molecularly imprinted polymer that can mimic the natural recognition entities has high affinity and selectivity for the specific analyte. Here, the concept of utilizing the quantum dots encoded microbeads as the supporting material and the polydopamine as the functional monomer to form the core-shell molecular imprinted polymer was proposed for the first time. The resulted imprinted polymer can provide various merits: polymerization can complete in aqueous environment; fabrication procedure is facile and universal; the obvious economic advantage; the thickness of the imprinting layer is highly controllable; polydopamine coating can improve the biocompatibility of the quantum dot encoded microbeads. The rabbit IgG binding and flow cytometer experiment result showed the distinct advantages of this strategy: cost-saving, facile and fast preparation procedure. Most importantly, the ability for the multichannel detection, which makes the imprinted polydopamine modified encoded-beads very attractive in protein pre-concentration, recognition, separation and biosensing. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. Optic glioma

    Science.gov (United States)

    Glioma - optic; Optic nerve glioma; Juvenile pilocytic astrocytoma; Brain cancer - optic glioma ... Optic gliomas are rare. The cause of optic gliomas is unknown. Most optic gliomas are slow-growing ...

  19. New Genetics

    Science.gov (United States)

    ... Home > Science Education > The New Genetics The New Genetics Living Laboratories Classroom Poster Order a Free Copy ... Piece to a Century-Old Evolutionary Puzzle Computing Genetics Model Organisms RNA Interference The New Genetics is ...

  20. Molecular mechanisms for protein-encoded inheritance.

    Science.gov (United States)

    Wiltzius, Jed J W; Landau, Meytal; Nelson, Rebecca; Sawaya, Michael R; Apostol, Marcin I; Goldschmidt, Lukasz; Soriaga, Angela B; Cascio, Duilio; Rajashankar, Kanagalaghatta; Eisenberg, David

    2009-09-01

    In prion inheritance and transmission, strains are phenotypic variants encoded by protein 'conformations'. However, it is unclear how a protein conformation can be stable enough to endure transmission between cells or organisms. Here we describe new polymorphic crystal structures of segments of prion and other amyloid proteins, which offer two structural mechanisms for the encoding of prion strains. In packing polymorphism, prion strains are encoded by alternative packing arrangements (polymorphs) of beta-sheets formed by the same segment of a protein; in segmental polymorphism, prion strains are encoded by distinct beta-sheets built from different segments of a protein. Both forms of polymorphism can produce enduring conformations capable of encoding strains. These molecular mechanisms for transfer of protein-encoded information into prion strains share features with the familiar mechanism for transfer of nucleic acid-encoded information into microbial strains, including sequence specificity and recognition by noncovalent bonds.

  1. Molecular mechanisms for protein-encoded inheritance

    Energy Technology Data Exchange (ETDEWEB)

    Wiltzius, Jed J.W.; Landau, Meytal; Nelson, Rebecca; Sawaya, Michael R.; Apostol, Marcin I.; Goldschmidt, Lukasz; Soriaga, Angela B.; Cascio, Duilio; Rajashankar, Kanagalaghatta; Eisenberg, David; (Cornell); (HHMI)

    2009-12-01

    In prion inheritance and transmission, strains are phenotypic variants encoded by protein 'conformations'. However, it is unclear how a protein conformation can be stable enough to endure transmission between cells or organisms. Here we describe new polymorphic crystal structures of segments of prion and other amyloid proteins, which offer two structural mechanisms for the encoding of prion strains. In packing polymorphism, prion strains are encoded by alternative packing arrangements (polymorphs) of {beta}-sheets formed by the same segment of a protein; in segmental polymorphism, prion strains are encoded by distinct {beta}-sheets built from different segments of a protein. Both forms of polymorphism can produce enduring conformations capable of encoding strains. These molecular mechanisms for transfer of protein-encoded information into prion strains share features with the familiar mechanism for transfer of nucleic acid-encoded information into microbial strains, including sequence specificity and recognition by noncovalent bonds.

  2. Dynamical encoding of cursive handwriting.

    Science.gov (United States)

    Singer, Y; Tishby, N

    1994-01-01

    A model-based approach to on-line cursive handwriting analysis and recognition is presented and evaluated. In this model, on-line handwriting is considered as a modulation of a simple cycloidal pen motion, described by two coupled oscillations with a constant linear drift along the line of the writing. By slow modulations of the amplitudes and phase lags of the two oscillators, a general pen trajectory can be efficiently encoded. These parameters are then quantized into a small number of values without altering the writing intelligibility. A general procedure for the estimation and quantization of these cycloidal motion parameters for arbitrary handwriting is presented. The result is a discrete motor control representation of the continuous pen motion, via the quantized levels of the model parameters. This motor control representation enables successful word spotting and matching of cursive scripts. Our experiments clearly indicate the potential of this dynamic representation for complete cursive handwriting recognition.

  3. Biomolecule-to-fluorescent-color encoder: modulation of fluorescence emission via DNA structural changes.

    Science.gov (United States)

    Nishimura, Takahiro; Ogura, Yusuke; Yamada, Kenji; Ohno, Yuko; Tanida, Jun

    2014-07-01

    A biomolecule-to-fluorescent-color (B/F) encoder for optical readout of biomolecular information is proposed. In the B/F encoder, a set of fluorescence wavelengths and their intensity levels are used for coding of a biomolecular signal. A hybridization chain reaction of hairpin DNAs labeled with fluorescent reporters was performed to generate the fluorescence color codes. The fluorescence is modulated via fluorescence resonance energy transfer, which is controlled by DNA structural changes. The results demonstrate that fluorescent color codes can be configured based on two wavelengths and five intensities using the B/F encoder, and the assigned codes can be retrieved via fluorescence measurements.

  4. Design of 4 to 2 line encoder using lithium niobate based Mach Zehnder Interferometers for high speed communication

    Science.gov (United States)

    Pal, Amrindra; Kumar, Santosh; Sharma, Sandeep; Raghuwanshi, Sanjeev K.

    2016-04-01

    Encoder is a device that allows placing digital information from many inputs to many outputs. Any application of combinational logic circuit can be implemented by using encoder and external gates. In this paper, 4 to 2 line encoder is proposed using electro-optic effect inside lithium-niobate based Mach-Zehnder interferometers (MZIs). The MZI structures have powerful capability to switching an optical input signal to a desired output port. The paper constitutes a mathematical description of the proposed device and thereafter simulation using MATLAB. The study is verified using beam propagation method (BPM).

  5. Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia

    NARCIS (Netherlands)

    DeVries, DD; Went, LN; Bruyn, GW; Scholte, HR; Hofstra, RMW; Bolhuis, PA; vanOost, BA

    1996-01-01

    A rare form of Leber hereditary optic neuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA

  6. Antifungal activity of a virally encoded gene in transgenic wheat.

    Science.gov (United States)

    Clausen, M; Kräuter, R; Schachermayr, G; Potrykus, I; Sautter, C

    2000-04-01

    The cDNA encoding the antifungal protein KP4 from Ustilago maydis-infecting virus was inserted behind the ubiquitin promoter of maize and genetically transferred to wheat varieties particularly susceptible to stinking smut (Tilletia tritici) disease. The transgene was integrated and inherited over several generations. Of seven transgenic lines, three showed antifungal activity against U. maydis. The antifungal activity correlated with the presence of the KP4 transgene. KP4-transgenic, soil-grown wheat plants exhibit increased endogenous resistance against stinking smut.

  7. [Mutations in the gene encoding filaggrin cause ichthyosis vulgaris].

    Science.gov (United States)

    Prasad, Sumangali Chandra; Rasmussen, Kirsten; Bygum, Anette

    2011-02-14

    Ichthyosis vulgaris is a common genetic skin disorder with an estimated prevalence of 1:250 caused by mutations in the gene encoding filaggrin. This disorder manifests itself within the first year of life and is clinically characterized by dry, scaly skin, keratosis pilaris, palmar hyperlinearity and atopic manifestations. Patients with a severe phenotype are homozygous or compound heterozygous for the mutations, whereas heterozygous patients show mild disease, suggesting semidominant inheritance with incomplete penetrance. We present a patient with classic severe ichthyosis vulgaris, atopic eczema and two loss-of-function mutations.

  8. NMDA receptors and memory encoding.

    Science.gov (United States)

    Morris, Richard G M

    2013-11-01

    It is humbling to think that 30 years have passed since the paper by Collingridge, Kehl and McLennan showing that one of Jeff Watkins most interesting compounds, R-2-amino-5-phosphonopentanoate (d-AP5), blocked the induction of long-term potentiation in vitro at synapses from area CA3 of the hippocampus to CA1 without apparent effect on baseline synaptic transmission (Collingridge et al., 1983). This dissociation was one of the key triggers for an explosion of interest in glutamate receptors, and much has been discovered since that collectively contributes to our contemporary understanding of glutamatergic synapses - their biophysics and subunit composition, of the agonists and antagonists acting on them, and their diverse functions in different networks of the brain and spinal cord. It can be fairly said that Collingridge et al.'s (1983) observation was the stimulus that has led, on the one hand, to structural biological work at the atomic scale describing the key features of NMDA receptors that enables their coincidence function to happen; and, on the other, to work with whole animals investigating the contributions that calcium signalling via this receptor can have on rhythmical activities controlled by spinal circuits, memory encoding in the hippocampus (the topic of this article), visual cortical plasticity, sensitization in pain, and other functions. In this article, I lay out how my then interest in long-term potentiation (LTP) as a model of memory enabled me to recognise the importance of Collingridge et al.'s discovery - and how I and my colleagues endeavoured to take things forward in the area of learning and memory. This is in some respects a personal story, and I tell it as such. The idea that NMDA receptor activation is essential for memory encoding, though not for storage, took time to develop and to be accepted. Along the way, there have been confusions, challenges, and surprises surrounding the idea that activation of NMDA receptors can

  9. A new genetic representation for quadratic assignment problem

    Directory of Open Access Journals (Sweden)

    Kratica Jozef

    2011-01-01

    Full Text Available In this paper, we propose a new genetic encoding for well known Quadratic Assignment Problem (QAP. The new encoding schemes are implemented with appropriate objective function and modified genetic operators. The numerical experiments were carried out on the standard QAPLIB data sets known from the literature. The presented results show that in all cases proposed genetic algorithm reached known optimal solutions in reasonable time.

  10. Genetic biomarkers in hypertrophic cardiomyopathy.

    Science.gov (United States)

    Coats, Caroline J; Elliott, Perry M

    2013-08-01

    Hypertrophic cardiomyopathy is a common inherited heart muscle disorder associated with sudden cardiac death, arrhythmias and heart failure. Genetic mutations can be identified in approximately 60% of patients; these are commonest in genes that encode proteins of the cardiac sarcomere. Similar to other Mendelian diseases these mutations are characterized by incomplete penetrance and variable clinical expression. Our knowledge of this genetic diversity is rapidly evolving as high-throughput DNA sequencing technology is now used to characterize an individual patient's disease. In addition, the genomic basis of several multisystem diseases associated with a hypertrophic cardiomyopathy phenotype has been elucidated. Genetic biomarkers can be helpful in making an accurate diagnosis and in identifying relatives at risk of developing the condition. In the clinical setting, genetic testing and genetic screening should be used pragmatically with appropriate counseling. Here we review the current role of genetic biomarkers in hypertrophic cardiomyopathy, highlight recent progress in the field and discuss future challenges.

  11. Expanding the eukaryotic genetic code

    Energy Technology Data Exchange (ETDEWEB)

    Chin, Jason W.; Cropp, T. Ashton; Anderson, J. Christopher; Schultz, Peter G.

    2017-02-28

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  12. Molecular Genetics of Mitochondrial Disorders

    Science.gov (United States)

    Wong, Lee-Jun C.

    2010-01-01

    Mitochondrial respiratory chain (RC) disorders (RCDs) are a group of genetically and clinically heterogeneous diseases because of the fact that protein components of the RC are encoded by both mitochondrial and nuclear genomes and are essential in all cells. In addition, the biogenesis, structure, and function of mitochondria, including DNA…

  13. Expanding the eukaryotic genetic code

    Science.gov (United States)

    Chin, Jason W.; Cropp, T. Ashton; Anderson, J. Christopher; Schultz, Peter G.

    2013-01-22

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, orthogonal pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.

  14. METHOD AND MODULE FOR OPTICAL SUBCARRIER LABELLING

    DEFF Research Database (Denmark)

    2004-01-01

    ) transmitters. The payload and the label are encoded independently on optical carrier and subcarrier signals respectively, using electro-optical modulators. The invention applies single or double sideband carrier-suppressed modulation to generate subcarrier signals for encoding of the label. Thereby the payload......The present invention relates to optical labelling in WDM networks, in that it provides a method and a module to be used in subcarrier label generation and switching in network edge nodes and core switch nodes. The methods and modules are typically employed in Optical Subcarrier Multiplexing (OSCM...

  15. Learning Intelligent Genetic Algorithms Using Japanese Nonograms

    Science.gov (United States)

    Tsai, Jinn-Tsong; Chou, Ping-Yi; Fang, Jia-Cen

    2012-01-01

    An intelligent genetic algorithm (IGA) is proposed to solve Japanese nonograms and is used as a method in a university course to learn evolutionary algorithms. The IGA combines the global exploration capabilities of a canonical genetic algorithm (CGA) with effective condensed encoding, improved fitness function, and modified crossover and…

  16. Learning Intelligent Genetic Algorithms Using Japanese Nonograms

    Science.gov (United States)

    Tsai, Jinn-Tsong; Chou, Ping-Yi; Fang, Jia-Cen

    2012-01-01

    An intelligent genetic algorithm (IGA) is proposed to solve Japanese nonograms and is used as a method in a university course to learn evolutionary algorithms. The IGA combines the global exploration capabilities of a canonical genetic algorithm (CGA) with effective condensed encoding, improved fitness function, and modified crossover and…

  17. Novelty's effect on memory encoding.

    Science.gov (United States)

    Rangel-Gomez, Mauricio; Janenaite, Sigita; Meeter, Martijn

    2015-07-01

    It is often thought that novelty benefits memory formation. However, support for this idea mostly comes from paradigms that are open to alternative explanations. In the present study we manipulated novelty in a word-learning task through task-irrelevant background images. These background images were either standard (presented repeatedly), or novel (presented only once). Two types of background images were used: Landscape pictures and fractals. EEG was also recorded during encoding. Contrary to the idea that novelty aids memory formation, memory performance was not affected by the novelty of the background. In the evoked response potentials, we found evidence of distracting effects of novelty: both the N1 and P3b components were smaller to words studied with novel backgrounds, and the amplitude of the N2b component correlated negatively with subsequent retrieval. We conclude that although evidence from other studies does suggest benefits on a longer time scale, novelty has no instantaneous benefits for learning. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. [Immunoglobulin genes encoding antibodies directed to oncodevelopmental carbohydrate antigens].

    Science.gov (United States)

    Zenita, K; Yago, K; Fujimoto, E; Kannagi, R

    1990-07-01

    We investigated the immunoglobulin genes which encode the variable region of the monoclonal antibodies directed to the onco-developmental carbohydrate antigens such SSEA-1, fucosyl SSEA-1, SSEA-3 and SSEA-4. The VH region of these antibodies was preferentially encoded by the gene members of the X24, VH7183 and Q52 families, the families which are known to be located at the 3'-end region of the murine germ line VH gene. This result is interesting particularly when considering that the members of the 3'-end VH families are known to be preferentially expressed in embryonic B lymphocytes by an intrinsic genetic program. The comparative study of the nucleic acid sequences of mRNAs encoding these antibodies and the sequences of the corresponding germ line VH genes disclosed that the sequences encoding the antibodies contain no mutation from the germ line VH genes, or contain only a few somatic mutations, which are thought to be insignificant for the reactivity of the antibodies to the nominal antigens. These results imply that some of the embryonic B lymphocytes that express the unmutated germ line VH genes of the 3'-end families can be reactive with embryonic carbohydrate antigens, albeit rearranged with appropriate D-JH gene segments, and coupled with proper light chains. The VH region of the syngenic monoclonal anti-idiotypic antibodies directed to these anti-carbohydrate antibodies were also encoded preferentially by the members of the 3'-end VH families. We propose here that a part of the virgin embryonic B lymphocytes, which express the antibody encoded by the gene members of the 3'-end VH families at the cell surface, will be stimulated by the embryonic carbohydrate antigens which are abundantly present in the internal milieu of the embryo. The clonally expanded B lymphocytes, in turn, will facilitate the proliferation of other populations of embryonic B lymphocytes expressing the corresponding anti-idiotypic antibodies, which are also encoded by the gene members

  19. [Genetics of migraine].

    Science.gov (United States)

    Ducros, A

    2013-05-01

    The aim of genetic studies in migraine is to identify key proteins in order to better understand the molecular mechanisms of this frequent but still incompletely understood condition. This review describes the current knowledge in the field of migraine genetics. Migraine genes have been, and still are, difficult to identify. The more common varieties of migraine are characterized by a high prevalence in the general population, and a high phenotypic variability. In the absence of any objective diagnosis marker, the status for genetic studies is established only clinically. The first breakthrough was permitted by the study of familial hemiplegic migraine, a variety of migraine with motor aura. This rare condition has a monogenic, autosomal dominant mode of inheritance, thus enabling genetic studies. The three first genes, identified from 1996 to 2005, all encode ion-channel transporters: a neuronal calcium channel (CACNA1A, FHM1), a glial sodium/potassium pump (ATP1A2, FHM2) and a neuronal sodium channel (SCN1A, FHM3). Study of cellular and animal models have shown that mutations in CACNA1A and ATP1A2 facilitated the initiation of cortical spreading depression waves, the mechanism underlying the migraine aura, and most likely increased neuronal excitability with an excess of glutamatergic neurotransmission. In 2012, PRRT2 has been identified as the fourth FHM gene, and encodes an axonal protein associated to the exocytosis complex. In the 1990s, family and twin studies showed that the more common varieties of migraine (migraine without aura and migraine with typical aura) were polygenic, with an overall heritability nearing 50 %. These genetic factors interact with environmental factors. The initial attempts to identify migraine genes by candidate gene approaches or by linkage studies were deceiving. Since 2010, three large genome-wide association studies (GWAS) have identified six genetic variants associated with migraine. Each variant has only a modest

  20. Encoder designed to work in harsh environments

    Energy Technology Data Exchange (ETDEWEB)

    Toop, L.

    2007-05-15

    Dynapar has developed the Acuro AX71 absolute encoder for use on offshore or land-based oil rig operations. It provides feedback on the operation of automated systems such as draw works, racking systems, rotary tables and top drives. By ensuring that automated systems function properly, this encoder responds to a need by the oil and gas industry to keep workers safe and improve efficiency, particularly for operations in rugged situations. The encoder provides feedback from motor systems to controllers, giving information about position and speed of downhole drill bits. This newly developed encoder is better than commonly used incremental encoders which are not precise in strong electrical noise environments. Rather, the absolute encoder uses a different method of reporting to the controller. A digital signal is transmitted constantly as the device operates. It is less susceptible to noise issues. It is highly accurate, tolerant of noise and is not affected by power outages. However, the absolute encoder is generally more delicate in drilling applications with high ambient temperatures and shock levels. Dynapar addressed this issue by developing compact stainless steel housing that is useful for corrosion resistance in marine applications. The AX71 absolute encoder can withstand up to 100 G of mechanical shock and ambient temperatures of up to 60 degrees C. The encoder is ATEX certified without barriers, and offers the high resolution feedback of 4,000 counts of multiturn rotation and 16,000 counts of position. 1 fig.

  1. Encoding of High Frequencies Improves with Maturation of Action Potential Generation in Cultured Neocortical Neurons

    Science.gov (United States)

    Nikitin, Evgeny S.; Bal, Natalia V.; Malyshev, Aleksey; Ierusalimsky, Victor N.; Spivak, Yulia; Balaban, Pavel M.; Volgushev, Maxim

    2017-01-01

    The ability of neocortical neurons to detect and encode rapid changes at their inputs is crucial for basic neuronal computations, such as coincidence detection, precise synchronization of activity and spike-timing dependent plasticity. Indeed, populations of cortical neurons can respond to subtle changes of the input very fast, on a millisecond time scale. Theoretical studies and model simulations linked the encoding abilities of neuronal populations to the fast onset dynamics of action potentials (APs). Experimental results support this idea, however mechanisms of fast onset of APs in cortical neurons remain elusive. Studies in neuronal cultures, that are allowing for accurate control over conditions of growth and microenvironment during the development of neurons and provide better access to the spike initiation zone, may help to shed light on mechanisms of AP generation and encoding. Here we characterize properties of AP encoding in neocortical neurons grown for 11–25 days in culture. We show that encoding of high frequencies improves upon culture maturation, which is accompanied by the development of passive electrophysiological properties and AP generation. The onset of APs becomes faster with culture maturation. Statistical analysis using correlations and linear model approaches identified the onset dynamics of APs as a major predictor of age-dependent changes of encoding. Encoding of high frequencies strongly correlated also with the input resistance of neurons. Finally, we show that maturation of encoding properties of neurons in cultures is similar to the maturation of encoding in neurons studied in slices. These results show that maturation of AP generators and encoding is, to a large extent, determined genetically and takes place even without normal micro-environment and activity of the whole brain in vivo. This establishes neuronal cultures as a valid experimental model for studying mechanisms of AP generation and encoding, and their maturation. PMID

  2. Demonstration of 20-Gbit/s high-speed Bessel beam encoding/decoding link with adaptive turbulence compensation.

    Science.gov (United States)

    Chen, Shi; Li, Shuhui; Zhao, Yifan; Liu, Jun; Zhu, Long; Wang, Andong; Du, Jing; Shen, Li; Wang, Jian

    2016-10-15

    By mapping traditional amplitude modulation to spatial modulation and employing adaptive optics compensation technique, we propose and experimentally demonstrate a high-speed Bessel beam encoding/decoding free-space optical link through atmospheric turbulence. The Bessel beam encoding/decoding speed is not limited by the conventional slow switching response of a spatial light modulator (SLM) but is fully determined by the modulation rate of an intensity modulator, which easily supports tens of gigabits per second modulation and resultant encoding/decoding. We use an SLM loaded with a pseudorandom phase mask to emulate atmospheric turbulence in the laboratory environment. An adaptive optics closed loop is used to sense the phase distortion of an extra probe Gaussian beam and then compensate the distorted Bessel beams. A 20-Gbit/s Bessel beam encoding/decoding link with adaptive turbulence compensation is demonstrated in the experiment, showing favorable operation performance.

  3. Coherent ultrafast measurement of time-bin encoded photons

    CERN Document Server

    Donohue, John M; Lavoie, Jonathan; Resch, Kevin J

    2013-01-01

    Time-bin encoding is a robust form of optical quantum information, especially for transmission in optical fibers. To read out the information, the separation of the time bins must be larger than the detector time resolution, typically on the order of nanoseconds for photon counters. In the present work, we demonstrate a technique using a nonlinear interaction between chirped entangled time-bin photons and shaped laser pulses to perform projective measurements on arbitrary time-bin states with picosecond-scale separations. We demonstrate a tomographically-complete set of time-bin qubit projective measurements and show the fidelity of operations is sufficiently high to violate the CHSH-Bell inequality by more than 6 standard deviations.

  4. Genetic algorithms

    Science.gov (United States)

    Wang, Lui; Bayer, Steven E.

    1991-01-01

    Genetic algorithms are mathematical, highly parallel, adaptive search procedures (i.e., problem solving methods) based loosely on the processes of natural genetics and Darwinian survival of the fittest. Basic genetic algorithms concepts are introduced, genetic algorithm applications are introduced, and results are presented from a project to develop a software tool that will enable the widespread use of genetic algorithm technology.

  5. Genetic Mapping

    Science.gov (United States)

    ... Fact Sheets Fact Sheets En Español: Mapeo Genético Genetic Mapping What is genetic mapping? How do researchers create ... genetic map? What are genetic markers? What is genetic mapping? Among the main goals of the Human Genome ...

  6. Time encoded multicolor fluorescence detection in a microfluidic flow cytometer.

    Science.gov (United States)

    Martini, Joerg; Recht, Michael I; Huck, Malte; Bern, Marshall W; Johnson, Noble M; Kiesel, Peter

    2012-12-07

    We describe an optical detection technique that delivers high signal-to-noise discrimination to enable a multi-parameter flow cytometer that combines high performance, robustness, compactness and low cost. The enabling technique is termed "spatially modulated detection" and generates a time-dependent signal as a continuously fluorescing (bio-) particle traverses an optical transmission pattern along the fluidic channel. Correlating the detected signal with the expected transmission pattern achieves high discrimination of the particle signal from background noise. Additionally, the particle speed and its fluorescence emission characteristics are deduced from the correlation analysis. Our method uses a large excitation/emission volume along the fluidic channel in order to increase the total flux of fluorescence light that originates from a particle while requiring minimal optical alignment. Despite the large excitation/detection volume, the mask pattern enables a high spatial resolution in the micron range. This allows for detection and characterization of particles with a separation (in flow direction) comparable to the dimension of individual particles. In addition, the concept is intrinsically tolerant of non-encoded background fluorescence originating from fluorescent components in solution, fluorescing components of the chamber and contaminants on its surface. The optical detection technique is illustrated with experimental results of multicolor detection with a single large area detector by filtering fluorescence emission of different particles through a patterned color mask. Thereby the particles' fluorescence emission spectrum is encoded in a time dependent intensity signal and color information can be extracted from the correlation analysis. The multicolor detection technique is demonstrated by differentiation of micro-beads loaded with PE (Phycoerythrin) and PE-Cy5 that are excited at 532 nm.

  7. Optical Implementation of Quantum Orienteering

    Science.gov (United States)

    Jeffrey, Evan R.; Altepeter, Joseph B.; Colci, Madalina; Kwiat, Paul G.

    2006-04-01

    We present results from an optical implementation of quantum orienteering, a protocol for communicating directions in space using quantum bits. We show how different types of measurements and encodings can be used to increase the communication efficiency. In particular, if Alice and Bob use two spin-1/2 particles for communication and employ joint measurements, they do better than is possible with local operations and classical communication. Furthermore, by using oppositely oriented spins, the achievable communication efficiency is further increased. Finally, we discuss the limitations of an optical approach: our results highlight the usually overlooked nonequivalence of different physical encodings of quantum bits.

  8. Operation-based Encoding and Neighborhood Search Genetic Algorithm for Job Shop Scheduling Optimization%基于工序编码和邻域搜索策略的遗传算法优化作业车间调度

    Institute of Scientific and Technical Information of China (English)

    赵诗奎; 方水良

    2013-01-01

    For the job shop scheduling optimization problem,population initialization method and neighborhood search mechanism of its solution genetic algorithm are studied.To improve the quality of the initial population,heuristic initialization method that combining active scheduling,non-delay scheduling with heuristic rules is adopted.Neighborhood structure is constructed based on the critical path.Neighborhood search moving of the key operations is carried out based on operation-based encoding to avoid infeasible solutions and chromosome testing-repair work.Different neighborhood moving for the first,inside and last operations of the operation block is defined respectively.Based on the active decoded gantt chart,to standardize the chromosome by the operation start time,and get the chromosome that the operation's position order is in accordance with the actual processing order on machines.For the expansion of the range of operation neighborhood search,the right moving is operated on the gantt chart,and to standardize the chromosome reversely by the operation completion time.Neighborhood search is implemented on the two standardized chromosome individuals obtained by forward and reverse standardization.Benchmark problems are applied to test the proposed algorithm,and effectiveress is verified.%针对作业车间调度优化问题,研究对其进行求解的遗传算法的种群初始方法和邻域搜索机制.为提高初始种群的质量,采用主动调度、无延迟调度与启发式规则相结合的启发式方法初始群体;基于关键路径构造邻域结构,将关键工序的邻域搜索移动与基于工序的编码方式相结合,避免不可行解的产生以及染色体的检测修复等工作;对工序块的块首、块内和块尾工序分别定义了不同的邻域移动操作.基于主动解码得到的甘特图,根据工序的开工时间,正向标准化染色体,使染色体中的工序位置顺序与机器上的工序实际加工顺序一致.为扩

  9. 结核分枝杆菌102株临床分离株的磷脂酶C编码基因多态性%Genetic diversity of phospholipase C-encoding genes among 102 clinical isolates of Mycobacterium tuberculosis

    Institute of Scientific and Technical Information of China (English)

    王兆芬; Michael R.Barer

    2011-01-01

    Objective To explore and analyze genetic mutations of phospholipase C (PLC)-encoding genes plcABCD among clinical isolates of Mycobacterium tuberculosis and to provide scientific basis for understanding virulence and pathogenesis of Mycobacterium tuberculosis. Methods A total of 102 isolates from patients with active tuberculosis were identified. Bacterial DNA was extracted. All plcABCD genes were amplified by polymerase chain reaction (PCR) and checked for deletions or mutations by agarose gel electrophoresis. Results According to presence or absence of plcABCD genes, 102 isolates were divided into 13 genotypes. Thirty-one (30.39%) isolates were plc wild genotype with all plcABCD genes; 71(69. 61%) isolates were plc mutant type with different plc gene deletions. Of 71 plc mutant isolates, 48 missed only one of four plc genes, 14 had deletions of 2 plc genes, 8 were triple mutants and 1 was quadruple mutant. There were 61 (59. 80%) isolates with plcD gene mutation, while the mutation rates of plcA, plcB and plcC genes were lower, which were 15. 69%(16/102), 9. 80%(10/102) and 16. 67%(17/ 102), respectively. Conclusion This study shows great diversity in plcABCD genes among clinical isolates of Mycobacterium tuberculosis, with the most common of plcD.%目的 分析临床分离的结核分枝杆菌中磷脂酶C(PLC)编码基因plcABCD的突变情况,以进一步了解结核分枝杆菌的致病力.方法 102株菌株均分离于结核病患者并准确鉴定.增菌后提取DNA,并对plcABCD 4个基因同时扩增,扩增产物经电泳后分析基因的突变或缺失.结果 根据plcABCD 4个基因的存在或缺失情况,102株菌可以分为13个基因型,其中31株含有完整的plcABCD所有基因.为plc野生株,占30.39%;71株菌有不同plc基因的缺失,为plc突变株,突变率为69.61%.71株突变型菌株中,只缺失任意1个plc基因的有48株,发生任意2个plc基因缺失或突变的共有14株,发生任意3个plc基因缺失或突变的共有8株

  10. RMI1/NCE4, a suppressor of genome instability, encodes a member of the RecQ helicase/Topo III complex

    NARCIS (Netherlands)

    Chang, M; Bellaoui, M; Zhang, CY; Desai, R; Morozov, P; Delgado-Cruzata, L; Rothstein, R; Freyer, GA; Boone, C; Brown, GW

    2005-01-01

    SGS1 encodes a DNA helicase whose homologues in human cells include the BLM, WRN, and RECQ4 genes, mutations in which lead to cancer-predisposition syndromes. Clustering of synthetic genetic interactions identified by large-scale genetic network analysis revealed that the genetic interaction profile

  11. Genetic Counseling

    Science.gov (United States)

    Genetic counseling provides information and support to people who have, or may be at risk for, genetic disorders. A ... meets with you to discuss genetic risks. The counseling may be for yourself or a family member. ...

  12. [Leber's hereditary optic neuropathy].

    Science.gov (United States)

    Leo-Kottler, B; Wissinger, B

    2011-12-01

    Leber's hereditary optic neuropathy (LHON) is a rare disease primarily affecting the retinal ganglion cells. In most cases patients with LHON develop permanent visual loss with a large central scotoma in the visual field of both eyes. The optic disc becomes partially or completely pale. At the onset of the disease many patients are considered to suffer from an optic neuritis and are treated under the diagnostic and therapeutic regimen of optic neuritis. LHON is mostly only considered when high dose cortisone therapy fails to be effective or the second eye is affected. Thereafter, molecular genetic analysis will prove LHON in these cases. Detailed anamnesis including pedigree analysis in combination with observance of the peripapillary microangiopathic alterations at the fundus will help to speed up the diagnosis of LHON, but even after exact clinical and molecular genetic diagnosis of LHON some aspects of the disease still remain a mystery today.

  13. Improved Quantum Genetic Algorithm in Application of Scheduling Engineering Personnel

    Directory of Open Access Journals (Sweden)

    Huaixiao Wang

    2014-01-01

    Full Text Available To verify the availability of the improved quantum genetic algorithm in solving the scheduling engineering personnel problem, the following work has been carried out: the characteristics of the scheduling engineering personnel problem are analyzed, the quantum encoding method is proposed, and an improved quantum genetic algorithm is applied to address the issue. Taking the low efficiency and the bad performance of the conventional quantum genetic algorithm into account, a universal improved quantum genetic algorithm is introduced to solve the scheduling engineering personnel problem. Finally, the examples are applied to verify the effectiveness and superiority of the improved quantum genetic algorithm and the rationality of the encoding method.

  14. Cellular encoding for interactive evolutionary robotics

    NARCIS (Netherlands)

    Gruau, F.C.; Quatramaran, K.

    1996-01-01

    This work reports experiments in interactive evolutionary robotics. The goal is to evolve an Artificial Neural Network (ANN) to control the locomotion of an 8-legged robot. The ANNs are encoded using a cellular developmental process called cellular encoding. In a previous work similar experiments ha

  15. A METHOD OF SHAPE ENCODING AND RETRIEVAL

    Institute of Scientific and Technical Information of China (English)

    Huang Xianglin; Song Lei; Shen Lansun

    2002-01-01

    A method of shape encoding and retrieval is proposed in this letter, which uses centripetal code to encode shape and extracts shape's convex for retrieval. For the rotation invariance and translation invariance of the centripetal code and the normalization of convex,the proposed retrieval method is similarity transform resistant, Experimental results confirm this capability.

  16. 基于量子遗传算法的光电干扰资源优化分配研究%Optimization Assignment Model for Electro-optic Jamming Resources Based on Quantum Genetic Algorithms

    Institute of Scientific and Technical Information of China (English)

    吴涛; 王迅

    2011-01-01

    Combining the principle of the target assignment for the defense strategy in an electro-optic information system,A model for the optimization assignment of jamming resources is established.The solution and steps are presented by using the quantum genetic algorithms.With the example simulation,it succeeds in obtaining an optimum assignment scheme for jamming resources.The simulation shows that the proposed solution superiors to the genetic algorithms and is a valid methods to the solution of the model for the optimization assignment of jamming resources.%结合光电信息系统作战运筹中目标分配原则,建立了干扰资源优化分配模型。给出了基于量子遗传算法的模型求解方法及步骤,并进行了实例仿真,得出了最佳干扰资源分配方案。仿真结果表明,该方法优于遗传算法,对于求解干扰资源优化分配模型是有效、可行的。

  17. Optical quantum computing.

    Science.gov (United States)

    O'Brien, Jeremy L

    2007-12-07

    In 2001, all-optical quantum computing became feasible with the discovery that scalable quantum computing is possible using only single-photon sources, linear optical elements, and single-photon detectors. Although it was in principle scalable, the massive resource overhead made the scheme practically daunting. However, several simplifications were followed by proof-of-principle demonstrations, and recent approaches based on cluster states or error encoding have dramatically reduced this worrying resource overhead, making an all-optical architecture a serious contender for the ultimate goal of a large-scale quantum computer. Key challenges will be the realization of high-efficiency sources of indistinguishable single photons, low-loss, scalable optical circuits, high-efficiency single-photon detectors, and low-loss interfacing of these components.

  18. Nucleases Encoded by Integraded Elements CJIE2 and CJIE4 Inhibit Natural Transformation of Campylobacter Jejuni

    NARCIS (Netherlands)

    Gaasbeek, E.J.; Wagenaar, J.A.; Guilhabert, M.R.; Putten, van J.P.; Parker, C.T.; Wal, van der F.J.

    2010-01-01

    The species Campylobacter jejuni is naturally competent for DNA uptake; nevertheless, nonnaturally transformable strains do exist. For a subset of strains we previously showed that a periplasmic DNase, encoded by dns, inhibits natural transformation in C. jejuni. In the present study, genetic factor

  19. The Arabic Diatessaron Project: Digitalizing, Encoding, Lemmatization

    Directory of Open Access Journals (Sweden)

    Giuliano Lancioni

    2016-04-01

    Full Text Available The Arabic Diatessaron Project (henceforth ADP is an international research project in Digital Humanities that aims to collect, digitalise and encode all known manuscripts of the Arabic Diatessaron (henceforth AD, a text that has been relatively neglected in scholarly research. ADP’s final goal is to provide a number of tools that can enable scholars to effectively query, compare and investigate all known variants of the text that will be encoded as far as possible in compliance with the Text Encoding Initiative (TEI guidelines. The paper addresses a number of issues involved in the process of digitalising manuscripts included in the two existing editions (Ciasca 1888 and Marmardji 1935, adding variants in unedited manuscripts, encoding and lemmatising the text. Issues involved in the design of the ADP include presentation of variants, choice of the standard text, applicability of TEI guidelines, automatic translation between different encodings, cross-edition concordances and principles of lemmatisation.

  20. On the optimization of fiber Bragg grating optical sensor using genetic algorithm to monitor the strain of civil structure with high sensitivity

    Science.gov (United States)

    Kaur, Gurpreet; Kaler, Rajinder Singh; Kwatra, Naveen

    2016-08-01

    The effect of strain on civil structures is experimentally studied using fiber Bragg grating (FBG). The genetic algorithm is implemented to optimize the multiple parameters (Poisson's ratio, photoelastic coefficient P11, and photoelastic coefficient P12) of the proposed sensor. The optimized results helped in increasing the sensitivity in terms of wavelength shift. It is observed that the proposed FBG provides maximum wavelength shift of 38.16 nm with Poisson's ratio of 1.94, photoelastic coefficient P11 of 1.994, and photoelastic coefficient P12 of 1.8103.

  1. A model for visual memory encoding.

    Directory of Open Access Journals (Sweden)

    Rodolphe Nenert

    Full Text Available Memory encoding engages multiple concurrent and sequential processes. While the individual processes involved in successful encoding have been examined in many studies, a sequence of events and the importance of modules associated with memory encoding has not been established. For this reason, we sought to perform a comprehensive examination of the network for memory encoding using data driven methods and to determine the directionality of the information flow in order to build a viable model of visual memory encoding. Forty healthy controls ages 19-59 performed a visual scene encoding task. FMRI data were preprocessed using SPM8 and then processed using independent component analysis (ICA with the reliability of the identified components confirmed using ICASSO as implemented in GIFT. The directionality of the information flow was examined using Granger causality analyses (GCA. All participants performed the fMRI task well above the chance level (>90% correct on both active and control conditions and the post-fMRI testing recall revealed correct memory encoding at 86.33 ± 5.83%. ICA identified involvement of components of five different networks in the process of memory encoding, and the GCA allowed for the directionality of the information flow to be assessed, from visual cortex via ventral stream to the attention network and then to the default mode network (DMN. Two additional networks involved in this process were the cerebellar and the auditory-insular network. This study provides evidence that successful visual memory encoding is dependent on multiple modules that are part of other networks that are only indirectly related to the main process. This model may help to identify the node(s of the network that are affected by a specific disease processes and explain the presence of memory encoding difficulties in patients in whom focal or global network dysfunction exists.

  2. A model for visual memory encoding.

    Science.gov (United States)

    Nenert, Rodolphe; Allendorfer, Jane B; Szaflarski, Jerzy P

    2014-01-01

    Memory encoding engages multiple concurrent and sequential processes. While the individual processes involved in successful encoding have been examined in many studies, a sequence of events and the importance of modules associated with memory encoding has not been established. For this reason, we sought to perform a comprehensive examination of the network for memory encoding using data driven methods and to determine the directionality of the information flow in order to build a viable model of visual memory encoding. Forty healthy controls ages 19-59 performed a visual scene encoding task. FMRI data were preprocessed using SPM8 and then processed using independent component analysis (ICA) with the reliability of the identified components confirmed using ICASSO as implemented in GIFT. The directionality of the information flow was examined using Granger causality analyses (GCA). All participants performed the fMRI task well above the chance level (>90% correct on both active and control conditions) and the post-fMRI testing recall revealed correct memory encoding at 86.33 ± 5.83%. ICA identified involvement of components of five different networks in the process of memory encoding, and the GCA allowed for the directionality of the information flow to be assessed, from visual cortex via ventral stream to the attention network and then to the default mode network (DMN). Two additional networks involved in this process were the cerebellar and the auditory-insular network. This study provides evidence that successful visual memory encoding is dependent on multiple modules that are part of other networks that are only indirectly related to the main process. This model may help to identify the node(s) of the network that are affected by a specific disease processes and explain the presence of memory encoding difficulties in patients in whom focal or global network dysfunction exists.

  3. An Encoding Technique for Multiobjective Evolutionary Algorithms Applied to Power Distribution System Reconfiguration

    Directory of Open Access Journals (Sweden)

    J. L. Guardado

    2014-01-01

    Full Text Available Network reconfiguration is an alternative to reduce power losses and optimize the operation of power distribution systems. In this paper, an encoding scheme for evolutionary algorithms is proposed in order to search efficiently for the Pareto-optimal solutions during the reconfiguration of power distribution systems considering multiobjective optimization. The encoding scheme is based on the edge window decoder (EWD technique, which was embedded in the Strength Pareto Evolutionary Algorithm 2 (SPEA2 and the Nondominated Sorting Genetic Algorithm II (NSGA-II. The effectiveness of the encoding scheme was proved by solving a test problem for which the true Pareto-optimal solutions are known in advance. In order to prove the practicability of the encoding scheme, a real distribution system was used to find the near Pareto-optimal solutions for different objective functions to optimize.

  4. An encoding technique for multiobjective evolutionary algorithms applied to power distribution system reconfiguration.

    Science.gov (United States)

    Guardado, J L; Rivas-Davalos, F; Torres, J; Maximov, S; Melgoza, E

    2014-01-01

    Network reconfiguration is an alternative to reduce power losses and optimize the operation of power distribution systems. In this paper, an encoding scheme for evolutionary algorithms is proposed in order to search efficiently for the Pareto-optimal solutions during the reconfiguration of power distribution systems considering multiobjective optimization. The encoding scheme is based on the edge window decoder (EWD) technique, which was embedded in the Strength Pareto Evolutionary Algorithm 2 (SPEA2) and the Nondominated Sorting Genetic Algorithm II (NSGA-II). The effectiveness of the encoding scheme was proved by solving a test problem for which the true Pareto-optimal solutions are known in advance. In order to prove the practicability of the encoding scheme, a real distribution system was used to find the near Pareto-optimal solutions for different objective functions to optimize.

  5. Genetics for the ophthalmologist

    Directory of Open Access Journals (Sweden)

    Karthikeyan A Sadagopan

    2012-01-01

    Full Text Available The eye has played a major role in human genomics including gene therapy. It is the fourth most common organ system after integument (skin, hair and nails, nervous system, and musculoskeletal system to be involved in genetic disorders. The eye is involved in single gene disorders and those caused by multifactorial etiology. Retinoblastoma was the first human cancer gene to be cloned. Leber hereditary optic neuropathy was the first mitochondrial disorder described. X-Linked red-green color deficiency was the first X-linked disorder described. The eye, unlike any other body organ, allows directly visualization of genetic phenomena such as skewed X-inactivation in the fundus of a female carrier of ocular albinism. Basic concepts of genetics and their application to clinical ophthalmological practice are important not only in making a precise diagnosis and appropriate referral, but also in management and genetic counseling.

  6. Multiplexing encoding method for full-color dynamic 3D holographic display.

    Science.gov (United States)

    Xue, Gaolei; Liu, Juan; Li, Xin; Jia, Jia; Zhang, Zhao; Hu, Bin; Wang, Yongtian

    2014-07-28

    The multiplexing encoding method is proposed and demonstrated for reconstructing colorful images accurately by using single phase-only spatial light modulator (SLM). It will encode the light waves at different wavelengths into one pure-phase hologram at the same time based on the analytic formulas. The three-dimensional (3D) images can be reconstructed clearly when the light waves at different wavelengths are incident into the encoding hologram. Numerical simulations and optical experiments for 2D and 3D colorful images are performed. The results show that the colorful reconstructed images with high quality are achieved successfully. The proposed multiplexing method is a simple and fast encoding approach and the size of the system is small and compact. It is expected to be used for realizing full-color 3D holographic display in future.

  7. Genetic and biochemical impairment of mitochondrial complex I activity in a family with Leber hereditary optic neuropathy and hereditary spastic dystonia

    Energy Technology Data Exchange (ETDEWEB)

    De Vries, D.D.; Oost, B.A. van [Univ. Hospital Nijmegen (Netherlands); Went, L.N.; Bruyn, G.W. [Univ. of Leiden (Netherlands)] [and others

    1996-04-01

    A rare form of Leber hereditary optic neuropathy (LHON) that is associated with hereditary spastic dystonia has been studied in a large Dutch family. Neuropathy and ophthalmological lesions were present together in some family members, whereas only one type of abnormality was found in others. mtDNA mutations previously reported in LHON were not present. Sequence analysis of the protein-coding mitochondrial genes revealed two previously unreported mtDNA mutations. A heteroplasmic A{yields}G transition at nucleotide position 11696 in the ND4 gene resulted in the substitution of an isoleucine for valine at amino acid position 312. A second mutation, a homoplasmic T{yields}A transition at nucleotide position 14596 in the ND6 gene, resulted in the substitution of a methionine for the isoleucine at amino acid residue 26. Biochemical analysis of a muscle biopsy revealed a severe complex I deficiency, providing a link between these unique mtDNA mutations and this rare, complex phenotype including Leber optic neuropathy. 80 refs., 2 figs., 3 tabs.

  8. Leber遗传性视神经病变分子遗传学研究进展%Molecule Genetic Research Advances of Leber's Hereditary Optic Neuropathy

    Institute of Scientific and Technical Information of China (English)

    赵福新; 管敏鑫

    2008-01-01

    Leber hereditary optic neuropathy(LHON)is a maternally inherited disorder leading to rapid,painless,bilateral loss of central vision.Point mutation of mitochondrial DNA(mtDNA)results in LHON.This paper makes a brief introduction of primary,secondary mutations and other mutations,and elucidates the role of nuclear modified gene;haplogroup and surroundings factor(smoking,alcohol,etc.)in the penetrance and phenotypic expression of the LHON,respectively.%Leber遗传性视神经病变(Leber hereditary optic neuropathy,LHON)是一种导致双眼快速的、无痛性的中心视力丧失的母系遗传性疾病.主要是由线粒体DNA(mitochondrial DNA,mtDNA)发生点突变所致.本文主要介绍LHON原发性、继发性和其他相关位点突变,阐述核修饰基因、mtDNA单体型及环境因素(吸烟、饮酒等)对LHON外显率和发病严重程度的影响.

  9. dlx and sp6-9 Control optic cup regeneration in a prototypic eye.

    Directory of Open Access Journals (Sweden)

    Sylvain W Lapan

    2011-08-01

    Full Text Available Optic cups are a structural feature of diverse eyes, from simple pit eyes to camera eyes of vertebrates and cephalopods. We used the planarian prototypic eye as a model to study the genetic control of optic cup formation and regeneration. We identified two genes encoding transcription factors, sp6-9 and dlx, that were expressed in the eye specifically in the optic cup and not the photoreceptor neurons. RNAi of these genes prevented formation of visible optic cups during regeneration. Planarian regeneration requires an adult proliferative cell population with stem cell-like properties called the neoblasts. We found that optic cup formation occurred only after migration of progressively differentiating progenitor cells from the neoblast population. The eye regeneration defect caused by dlx and sp6-9 RNAi can be explained by a failure to generate these early optic cup progenitors. Dlx and Sp6-9 genes function as a module during the development of diverse animal appendages, including vertebrate and insect limbs. Our work reveals a novel function for this gene pair in the development of a fundamental eye component, and it utilizes these genes to demonstrate a mechanism for total organ regeneration in which extensive cell movement separates new cell specification from organ morphogenesis.

  10. Biochemical evidence for a mitochondrial genetic modifier in the phenotypic manifestation of Leber's hereditary optic neuropathy-associated mitochondrial DNA mutation.

    Science.gov (United States)

    Jiang, Pingping; Liang, Min; Zhang, Chaofan; Zhao, Xiaoxu; He, Qiufen; Cui, Limei; Liu, Xiaoling; Sun, Yan-Hong; Fu, Qun; Ji, Yanchun; Bai, Yidong; Huang, Taosheng; Guan, Min-Xin

    2016-08-15

    Leber's hereditary optic neuropathy (LHON) is the most common mitochondrial disease. Mitochondrial modifiers are proposed to modify the phenotypic expression of primary LHON-associated mitochondrial DNA (mtDNA) mutations. In this study, we demonstrated that the LHON susceptibility allele (m.14502T > C, p. 58I > V) in the ND6 gene modulated the phenotypic expression of primary LHON-associated m.11778G > A mutation. Twenty-two Han Chinese pedigrees carrying m.14502T > C and m.11778G > A mutations exhibited significantly higher penetrance of optic neuropathy than those carrying only m.11778G > A mutation. We performed functional assays using the cybrid cell models, generated by fusing mtDNA-less ρ(o) cells with enucleated cells from LHON patients carrying both m.11778G > A and m.14502T > C mutations, only m.14502T > C or m.11778G > A mutation and a control belonging to the same mtDNA haplogroup. These cybrids cell lines bearing m.14502T > C mutation exhibited mild effects on mitochondrial functions compared with those carrying only m.11778G > A mutation. However, more severe mitochondrial dysfunctions were observed in cell lines bearing both m.14502T > C and m.11778G > A mutations than those carrying only m.11778G > A or m.14502T > C mutation. In particular, the m.14502T > C mutation altered assemble of complex I, thereby aggravating the respiratory phenotypes associated with m.11778G > A mutation, resulted in a more defective complex I. Furthermore, more reductions in the levels of mitochondrial ATP and increasing production of reactive oxygen species were also observed in mutant cells bearing both m.14502T > C and m.11778G > A mutation than those carrying only 11778G > A mutation. Our findings provided new insights into the pathophysiology of LHON that were manifested by interaction between primary and secondary mtDNA mutations.

  11. Initial Photophysical Characterization of the Proteorhodopsin Optical Proton Sensor (PROPS

    Directory of Open Access Journals (Sweden)

    Jay eNadeau

    2015-09-01

    Full Text Available Fluorescence is not frequently used as a tool for investigating the photocycles of rhodopsins, largely because of the low quantum yield of the retinal chromophore. However, a new class of genetically encoded voltage sensors is based upon rhodopsins and their fluorescence. The first such sensor reported in the literature was the proteorhodopsin optical proton sensor (PROPS, which is capable of indicating membrane voltage changes in bacteria by means of changes in fluorescence. However, the properties of this fluorescence, such as its lifetime decay components and its origin in the protein photocycle, remain unknown. This paper reports steady-state and nanoscale time-resolved emission of this protein expressed in two strains of Escherichia coli, before and after membrane depolarization. The voltage-dependence of a particularly long lifetime component is established. Additional work to improve quantum yields and improve the general utility of PROPS is suggested.

  12. Cellobiohydrolase variants and polynucleotides encoding same

    Energy Technology Data Exchange (ETDEWEB)

    Wogulis, Mark

    2017-04-04

    The present invention relates to variants of a parent cellobiohydrolase II. The present invention also relates to polynucleotides encoding the variants; nucleic acid constructs, vectors, and host cells comprising the polynucleotides; and methods of using the variants.

  13. Chemical Space of DNA-Encoded Libraries.

    Science.gov (United States)

    Franzini, Raphael M; Randolph, Cassie

    2016-07-28

    In recent years, DNA-encoded chemical libraries (DECLs) have attracted considerable attention as a potential discovery tool in drug development. Screening encoded libraries may offer advantages over conventional hit discovery approaches and has the potential to complement such methods in pharmaceutical research. As a result of the increased application of encoded libraries in drug discovery, a growing number of hit compounds are emerging in scientific literature. In this review we evaluate reported encoded library-derived structures and identify general trends of these compounds in relation to library design parameters. We in particular emphasize the combinatorial nature of these libraries. Generally, the reported molecules demonstrate the ability of this technology to afford hits suitable for further lead development, and on the basis of them, we derive guidelines for DECL design.

  14. Clustering of polarization-encoded images.

    Science.gov (United States)

    Zallat, Jihad; Collet, Christophe; Takakura, Yoshitate

    2004-01-10

    Polarization-encoded imaging consists of the distributed measurements of polarization parameters for each pixel of an image. We address clustering of multidimensional polarization-encoded images. The spatial coherence of polarization information is considered. Two methods of analysis are proposed: polarization contrast enhancement and a more-sophisticated image-processing algorithm based on a Markovian model. The proposed algorithms are applied and validated with two different Mueller images acquired by a fully polarimetric imaging system.

  15. Using XML to encode TMA DES metadata

    Directory of Open Access Journals (Sweden)

    Oliver Lyttleton

    2011-01-01

    Full Text Available Background: The Tissue Microarray Data Exchange Specification (TMA DES is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. Materials and Methods: We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. Results: We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. Conclusions: All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs.

  16. Using XML to encode TMA DES metadata.

    Science.gov (United States)

    Lyttleton, Oliver; Wright, Alexander; Treanor, Darren; Lewis, Paul

    2011-01-01

    The Tissue Microarray Data Exchange Specification (TMA DES) is an XML specification for encoding TMA experiment data. While TMA DES data is encoded in XML, the files that describe its syntax, structure, and semantics are not. The DTD format is used to describe the syntax and structure of TMA DES, and the ISO 11179 format is used to define the semantics of TMA DES. However, XML Schema can be used in place of DTDs, and another XML encoded format, RDF, can be used in place of ISO 11179. Encoding all TMA DES data and metadata in XML would simplify the development and usage of programs which validate and parse TMA DES data. XML Schema has advantages over DTDs such as support for data types, and a more powerful means of specifying constraints on data values. An advantage of RDF encoded in XML over ISO 11179 is that XML defines rules for encoding data, whereas ISO 11179 does not. We created an XML Schema version of the TMA DES DTD. We wrote a program that converted ISO 11179 definitions to RDF encoded in XML, and used it to convert the TMA DES ISO 11179 definitions to RDF. We validated a sample TMA DES XML file that was supplied with the publication that originally specified TMA DES using our XML Schema. We successfully validated the RDF produced by our ISO 11179 converter with the W3C RDF validation service. All TMA DES data could be encoded using XML, which simplifies its processing. XML Schema allows datatypes and valid value ranges to be specified for CDEs, which enables a wider range of error checking to be performed using XML Schemas than could be performed using DTDs.

  17. Multiplex immunoassay for persistent organic pollutants in tilapia: Comparison of imaging- and flow cytometry-based platforms using spectrally encoded paramagnetic microspheres

    Science.gov (United States)

    Recent developments in spectrally encoded microspheres (SEMs)-based technologies provide high multiplexing possibilities. Most SEMs-based assays required a flow cytometer with sophisticated fluidics and optics. The new imaging superparamagnetic SEMs-based platform transports SEMs with considerably ...

  18. Neurally Encoding Time for Olfactory Navigation.

    Directory of Open Access Journals (Sweden)

    In Jun Park

    2016-01-01

    Full Text Available Accurately encoding time is one of the fundamental challenges faced by the nervous system in mediating behavior. We recently reported that some animals have a specialized population of rhythmically active neurons in their olfactory organs with the potential to peripherally encode temporal information about odor encounters. If these neurons do indeed encode the timing of odor arrivals, it should be possible to demonstrate that this capacity has some functional significance. Here we show how this sensory input can profoundly influence an animal's ability to locate the source of odor cues in realistic turbulent environments-a common task faced by species that rely on olfactory cues for navigation. Using detailed data from a turbulent plume created in the laboratory, we reconstruct the spatiotemporal behavior of a real odor field. We use recurrence theory to show that information about position relative to the source of the odor plume is embedded in the timing between odor pulses. Then, using a parameterized computational model, we show how an animal can use populations of rhythmically active neurons to capture and encode this temporal information in real time, and use it to efficiently navigate to an odor source. Our results demonstrate that the capacity to accurately encode temporal information about sensory cues may be crucial for efficient olfactory navigation. More generally, our results suggest a mechanism for extracting and encoding temporal information from the sensory environment that could have broad utility for neural information processing.

  19. Current View on Phytoplasma Genomes and Encoded Metabolism

    Directory of Open Access Journals (Sweden)

    Michael Kube

    2012-01-01

    Full Text Available Phytoplasmas are specialised bacteria that are obligate parasites of plant phloem tissue and insects. These bacteria have resisted all attempts of cell-free cultivation. Genome research is of particular importance to analyse the genetic endowment of such bacteria. Here we review the gene content of the four completely sequenced ‘Candidatus Phytoplasma’ genomes that include those of ‘Ca. P. asteris’ strains OY-M and AY-WB, ‘Ca. P. australiense,’ and ‘Ca. P. mali’. These genomes are characterized by chromosome condensation resulting in sizes below 900 kb and a G + C content of less than 28%. Evolutionary adaption of the phytoplasmas to nutrient-rich environments resulted in losses of genetic modules and increased host dependency highlighted by the transport systems and limited metabolic repertoire. On the other hand, duplication and integration events enlarged the chromosomes and contribute to genome instability. Present differences in the content of membrane and secreted proteins reflect the host adaptation in the phytoplasma strains. General differences are obvious between different phylogenetic subgroups. ‘Ca. P. mali’ is separated from the other strains by its deviating chromosome organization, the genetic repertoire for recombination and excision repair of nucleotides or the loss of the complete energy-yielding part of the glycolysis. Apart from these differences, comparative analysis exemplified that all four phytoplasmas are likely to encode an alternative pathway to generate pyruvate and ATP.

  20. Remotely operated compact underwater temporally encoded imager: CUTEI

    Science.gov (United States)

    Alley, Derek; Cochenour, Brandon; Mullen, Linda

    2016-05-01

    Remotely operated vehicles (ROVs) typically use traditional optical imaging systems, such as cameras, for high resolution imaging. Cameras are effective in clear water, but have extremely poor performance in degraded visual environments (DVEs) such as turbid coastal waters and harbors. This is due to the multiple scattering of the light from the particulates and organic matter in the water. Laser-based sensors have been developed to enhance optical imaging in DVEs1,3,4,5,6. However, since conventional approaches require that the illuminator and receiver be located on the same platform, the size, weight, and power (SWaP) requirements are incompatible with small ROVs. Researchers at NAVAIR have developed a low cost optical imager utilizing a bistatic geometry where the illuminator and receiver are mounted on separate, smaller platforms. The illuminator steers a modulated laser beam with a microelectromechanical system (MEMS) scanner to sequentially illuminate an underwater object. A distant receiver collects the object reflected laser light and reconstructs the imagery. Communications information, including a synchronization sequence, is encoded onto the modulation which is used by the receiver to build the image. The SWaP of the illuminator's components have been optimized and integrated into a modified version of the OpenROV, a miniature, commercial off-the-shelf ROV. This paper reports on the efforts to reduce the SWaP of the modulated illuminator and the results of testing this system in a laboratory water tank environment.

  1. Leber遗传性视神经病变的遗传学进展%Genetic research progrees in Leber hereditary optic neuropathy

    Institute of Scientific and Technical Information of China (English)

    贺江梅; 郑梅玲

    2006-01-01

    1871年德国眼科医生Theodor Leber首次描述了一种遗传性眼病,主要表现为双眼急性或亚急性中心视力下降。多累及青年男性,随后便将此病命名为Leber遗传性视神经病变(Leber hereditary optic neuropathy,LHON)。现已证实该病为母系遗传性疾病,其主要病因是线粒体DNA(mitochondrial DNA,mtDNA)某些位点发生突变,是一种最为常见的线粒体遗传病。尽管现在对此病已进行了深入研究。但有很多方面尚需进一步讨论,例如:有关LHON突变基因位点的研究、LHON的不完全外显性、LHON的遗传种族差异性以及突变位点与临床表现和预后的关系等,本文就这几方面进行综述。

  2. Fiber optic sensors for military, industrial and commercial applications

    Science.gov (United States)

    James, K. A.; Quick, W. H.; Strahan, V. H.

    1978-01-01

    Four examples of specific fiber optic sensor system designs, each of which demonstrates a different optical modulation format, are described. The birefrigent temperature transducer illustrates direct digital signal modulation. The temperature/pressure dependent semiconductor filter illustrates high-pass optical wavelength signal encoding. The coupled polarized-mode transducer shows how a solid-state sensor can produce narrow-bandpass optical wavelength signal encoding. The luminescent temperature sensor illustrates a way to construct a solid state sensor in order to produce pulse width modulation of an optical signal.

  3. Riboswitch-based sensor in low optical background

    Science.gov (United States)

    Harbaugh, Svetlana V.; Davidson, Molly E.; Chushak, Yaroslav G.; Kelley-Loughnane, Nancy; Stone, Morley O.

    2008-08-01

    Riboswitches are a type of natural genetic control element that use untranslated sequence in the RNA to recognize and bind to small molecules that regulate expression of that gene. Creation of synthetic riboswitches to novel ligands depends on the ability to screen for analyte binding sensitivity and specificity. In our work, we have coupled a synthetic riboswitch to an optical reporter assay based on fluorescence resonance energy transfer (FRET) between two genetically-coded fluorescent proteins. Specifically, a theophylline-sensitive riboswitch was placed upstream of the Tobacco Etch Virus (TEV) protease coding sequence, and a FRET-based construct, BFP-eGFP or eGFP-REACh, was linked by a peptide encoding the recognition sequence for TEV protease. Cells expressing the riboswitch showed a marked optical difference in fluorescence emission in the presence of theophylline. However, the BFP-eGFP FRET pair posses significant optical background that reduces the sensitivity of a FRET-based assay. To improve the optical assay, we designed a nonfluorescent yellow fluorescent protein (YFP) mutant called REACh (for Resonance Energy-Accepting Chromoprotein) as the FRET acceptor for eGFP. The advantage of using an eGFP-REACh pair is the elimination of acceptor fluorescence which leads to an improved detection of FRET via better signal-to-noise ratio. The EGFP-REACh fusion protein was constructed with the TEV protease cleavage site; thus upon TEV translation, cleavage occurs diminishing REACh quenching and increasing eGFP emission resulting in a 4.5-fold improvement in assay sensitivity.

  4. The expanded genetic alphabet.

    Science.gov (United States)

    Malyshev, Denis A; Romesberg, Floyd E

    2015-10-05

    All biological information, since the last common ancestor of all life on Earth, has been encoded by a genetic alphabet consisting of only four nucleotides that form two base pairs. Long-standing efforts to develop two synthetic nucleotides that form a third, unnatural base pair (UBP) have recently yielded three promising candidates, one based on alternative hydrogen bonding, and two based on hydrophobic and packing forces. All three of these UBPs are replicated and transcribed with remarkable efficiency and fidelity, and the latter two thus demonstrate that hydrogen bonding is not unique in its ability to underlie the storage and retrieval of genetic information. This Review highlights these recent developments as well as the applications enabled by the UBPs, including the expansion of the evolution process to include new functionality and the creation of semi-synthetic life that stores increased information.

  5. Genetics Home Reference: myoclonic epilepsy with ragged-red fibers

    Science.gov (United States)

    ... Encyclopedia: Lipoma Encyclopedia: Optic nerve atrophy Encyclopedia: Peripheral Neuropathy Health Topic: Dementia Health Topic: Epilepsy Health Topic: Genetic Brain Disorders Health Topic: Mitochondrial Diseases Genetic and Rare Diseases Information Center (1 ...

  6. Visually Improved Image Compression by Combining EZW Encoding with Texture Modeling using Huffman Encoder

    Directory of Open Access Journals (Sweden)

    Vinay U. Kale

    2010-05-01

    Full Text Available This paper proposes a technique for image compression which uses the Wavelet-based Image/Texture Coding Hybrid (WITCH scheme [1] in combination with Huffman encoder. It implements a hybrid coding approach, while nevertheless preserving the features of progressive and lossless coding. The hybrid scheme was designed to encode the structural image information by Embedded Zerotree Wavelet (EZW encoding algorithm [2] and the stochastic texture in a model-based manner and this encoded data is then compressed using Huffman encoder. The scheme proposed here achieves superior subjective quality while increasing the compression ratio by more than a factor of three or even four. With this technique, it is possible to achieve compression ratios as high as 10 to 12 but with some minor distortions in the encoded image.

  7. Molecular Genetics in Glaucoma

    OpenAIRE

    Liu, Yutao; Allingham, R Rand

    2011-01-01

    Glaucoma is a family of diseases whose pathology is defined by the progressive loss of retinal ganglion cells. Clinically, glaucoma presents as a distinctive optic neuropathy with associated visual field loss. Primary open-angle glaucoma (POAG), chronic angle closure glaucoma (ACG), and exfoliation glaucoma (XFG) are the most prevalent forms of glaucoma globally and are the most common causes of glaucoma-related blindness worldwide. A host of genetic and environmental factors contribute to gl...

  8. Dynamic array of dark optical traps

    DEFF Research Database (Denmark)

    Daria, V.R.; Rodrigo, P.J.; Glückstad, J.

    2004-01-01

    A dynamic array of dark optical traps is generated for simultaneous trapping and arbitrary manipulation of multiple low-index microstructures. The dynamic intensity patterns forming the dark optical trap arrays are generated using a nearly loss-less phase-to-intensity conversion of a phase-encode...... optical traps for simultaneous manipulation of hollow "air-filled" glass microspheres suspended in an aqueous medium. (C) 2004 American Institute of Physics....

  9. Experimental generation of optical coherence lattices

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Yahong; Cai, Yangjian, E-mail: serpo@dal.ca, E-mail: yangjiancai@suda.edu.cn [College of Physics, Optoelectronics and Energy and Collaborative Innovation Center of Suzhou Nano Science and Technology, Soochow University, Suzhou 215006 (China); Key Lab of Advanced Optical Manufacturing Technologies of Jiangsu Province and Key Lab of Modern Optical Technologies of Education Ministry of China, Soochow University, Suzhou 215006 (China); Ponomarenko, Sergey A., E-mail: serpo@dal.ca, E-mail: yangjiancai@suda.edu.cn [Department of Electrical and Computer Engineering, Dalhousie University, Halifax, Nova Scotia B3J 2X4 (Canada)

    2016-08-08

    We report experimental generation and measurement of recently introduced optical coherence lattices. The presented optical coherence lattice realization technique hinges on a superposition of mutually uncorrelated partially coherent Schell-model beams with tailored coherence properties. We show theoretically that information can be encoded into and, in principle, recovered from the lattice degree of coherence. Our results can find applications to image transmission and optical encryption.

  10. DNA-encoded chemical libraries: foundations and applications in lead discovery.

    Science.gov (United States)

    Zimmermann, Gunther; Neri, Dario

    2016-11-01

    DNA-encoded chemical libraries have emerged as a powerful tool for hit identification in the pharmaceutical industry and in academia. Similar to biological display techniques (such as phage display technology), DNA-encoded chemical libraries contain a link between the displayed chemical building block and an amplifiable genetic barcode on DNA. Using routine procedures, libraries containing millions to billions of compounds can be easily produced within a few weeks. The resulting compound libraries are screened in a single test tube against proteins of pharmaceutical interest and hits can be identified by PCR amplification of DNA barcodes and subsequent high-throughput sequencing.

  11. Multichannel compressive sensing MRI using noiselet encoding.

    Directory of Open Access Journals (Sweden)

    Kamlesh Pawar

    Full Text Available The incoherence between measurement and sparsifying transform matrices and the restricted isometry property (RIP of measurement matrix are two of the key factors in determining the performance of compressive sensing (CS. In CS-MRI, the randomly under-sampled Fourier matrix is used as the measurement matrix and the wavelet transform is usually used as sparsifying transform matrix. However, the incoherence between the randomly under-sampled Fourier matrix and the wavelet matrix is not optimal, which can deteriorate the performance of CS-MRI. Using the mathematical result that noiselets are maximally incoherent with wavelets, this paper introduces the noiselet unitary bases as the measurement matrix to improve the incoherence and RIP in CS-MRI. Based on an empirical RIP analysis that compares the multichannel noiselet and multichannel Fourier measurement matrices in CS-MRI, we propose a multichannel compressive sensing (MCS framework to take the advantage of multichannel data acquisition used in MRI scanners. Simulations are presented in the MCS framework to compare the performance of noiselet encoding reconstructions and Fourier encoding reconstructions at different acceleration factors. The comparisons indicate that multichannel noiselet measurement matrix has better RIP than that of its Fourier counterpart, and that noiselet encoded MCS-MRI outperforms Fourier encoded MCS-MRI in preserving image resolution and can achieve higher acceleration factors. To demonstrate the feasibility of the proposed noiselet encoding scheme, a pulse sequences with tailored spatially selective RF excitation pulses was designed and implemented on a 3T scanner to acquire the data in the noiselet domain from a phantom and a human brain. The results indicate that noislet encoding preserves image resolution better than Fouirer encoding.

  12. Multichannel compressive sensing MRI using noiselet encoding.

    Science.gov (United States)

    Pawar, Kamlesh; Egan, Gary; Zhang, Jingxin

    2015-01-01

    The incoherence between measurement and sparsifying transform matrices and the restricted isometry property (RIP) of measurement matrix are two of the key factors in determining the performance of compressive sensing (CS). In CS-MRI, the randomly under-sampled Fourier matrix is used as the measurement matrix and the wavelet transform is usually used as sparsifying transform matrix. However, the incoherence between the randomly under-sampled Fourier matrix and the wavelet matrix is not optimal, which can deteriorate the performance of CS-MRI. Using the mathematical result that noiselets are maximally incoherent with wavelets, this paper introduces the noiselet unitary bases as the measurement matrix to improve the incoherence and RIP in CS-MRI. Based on an empirical RIP analysis that compares the multichannel noiselet and multichannel Fourier measurement matrices in CS-MRI, we propose a multichannel compressive sensing (MCS) framework to take the advantage of multichannel data acquisition used in MRI scanners. Simulations are presented in the MCS framework to compare the performance of noiselet encoding reconstructions and Fourier encoding reconstructions at different acceleration factors. The comparisons indicate that multichannel noiselet measurement matrix has better RIP than that of its Fourier counterpart, and that noiselet encoded MCS-MRI outperforms Fourier encoded MCS-MRI in preserving image resolution and can achieve higher acceleration factors. To demonstrate the feasibility of the proposed noiselet encoding scheme, a pulse sequences with tailored spatially selective RF excitation pulses was designed and implemented on a 3T scanner to acquire the data in the noiselet domain from a phantom and a human brain. The results indicate that noislet encoding preserves image resolution better than Fouirer encoding.

  13. An encyclopedia of mouse DNA elements (Mouse ENCODE).

    Science.gov (United States)

    Stamatoyannopoulos, John A; Snyder, Michael; Hardison, Ross; Ren, Bing; Gingeras, Thomas; Gilbert, David M; Groudine, Mark; Bender, Michael; Kaul, Rajinder; Canfield, Theresa; Giste, Erica; Johnson, Audra; Zhang, Mia; Balasundaram, Gayathri; Byron, Rachel; Roach, Vaughan; Sabo, Peter J; Sandstrom, Richard; Stehling, A Sandra; Thurman, Robert E; Weissman, Sherman M; Cayting, Philip; Hariharan, Manoj; Lian, Jin; Cheng, Yong; Landt, Stephen G; Ma, Zhihai; Wold, Barbara J; Dekker, Job; Crawford, Gregory E; Keller, Cheryl A; Wu, Weisheng; Morrissey, Christopher; Kumar, Swathi A; Mishra, Tejaswini; Jain, Deepti; Byrska-Bishop, Marta; Blankenberg, Daniel; Lajoie, Bryan R; Jain, Gaurav; Sanyal, Amartya; Chen, Kaun-Bei; Denas, Olgert; Taylor, James; Blobel, Gerd A; Weiss, Mitchell J; Pimkin, Max; Deng, Wulan; Marinov, Georgi K; Williams, Brian A; Fisher-Aylor, Katherine I; Desalvo, Gilberto; Kiralusha, Anthony; Trout, Diane; Amrhein, Henry; Mortazavi, Ali; Edsall, Lee; McCleary, David; Kuan, Samantha; Shen, Yin; Yue, Feng; Ye, Zhen; Davis, Carrie A; Zaleski, Chris; Jha, Sonali; Xue, Chenghai; Dobin, Alex; Lin, Wei; Fastuca, Meagan; Wang, Huaien; Guigo, Roderic; Djebali, Sarah; Lagarde, Julien; Ryba, Tyrone; Sasaki, Takayo; Malladi, Venkat S; Cline, Melissa S; Kirkup, Vanessa M; Learned, Katrina; Rosenbloom, Kate R; Kent, W James; Feingold, Elise A; Good, Peter J; Pazin, Michael; Lowdon, Rebecca F; Adams, Leslie B

    2012-08-13

    To complement the human Encyclopedia of DNA Elements (ENCODE) project and to enable a broad range of mouse genomics efforts, the Mouse ENCODE Consortium is applying the same experimental pipelines developed for human ENCODE to annotate the mouse genome.

  14. Genetic Disorders

    Science.gov (United States)

    ... This can cause a medical condition called a genetic disorder. You can inherit a gene mutation from ... during your lifetime. There are three types of genetic disorders: Single-gene disorders, where a mutation affects ...

  15. Genetic modification and genetic determinism.

    Science.gov (United States)

    Resnik, David B; Vorhaus, Daniel B

    2006-06-26

    In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound. Serious discussion of the morality of genetic modification, and the development of sound science policy, should be driven by arguments that address the actual consequences of genetic modification for individuals and society, not by ones propped up by false or misleading biological assumptions.

  16. Virus-Encoded microRNAs: Future Therapeutic Targets?

    Institute of Scientific and Technical Information of China (English)

    Peng Qi; Jinxiang Han; Yanqin Lu; Chuanxi Wang; Fanfeng Bu

    2006-01-01

    The discovery of microRNAs (miRNAs) is a remarkable breakthrough in the field of molecular genetics, as miRNAs are key actors which regulate gene expression in diverse cellular processes from unicellular yeast to human. The recent discovery of virus-encoded miRNAs indicates that viruses also use this fundamental mode of gene regulation. Research into viral miRNAs function demonstrates that some miRNAs play an important role in regulating both the viral life cycle and the interaction between viruses and their hosts. The first in vivo "antagomir" study provides an exciting first step towards miRNA therapy, and the potential for ultimately designing molecular medicines based on the modulation of miRNAs seems good.

  17. Genetic variation in KCNA5

    DEFF Research Database (Denmark)

    Christophersen, Ingrid E; Olesen, Morten S; Liang, Bo

    2012-01-01

    (Kur). Three studies have identified loss-of-function mutations in KCNA5 in patients with idiopathic AF. We hypothesized that early-onset lone AF is associated with high prevalence of genetic variants in KCNA5 and KCNAB2.Methods and resultsThe coding sequences of KCNA5 and KCNAB2 were sequenced in 307 patients......AimsGenetic factors may be important in the development of atrial fibrillation (AF) in the young. KCNA5 encodes the potassium channel a-subunit K(V)1.5, which underlies the voltage-gated atrial-specific potassium current I(Kur). KCNAB2 encodes K(V)ß2, a ß-subunit of K(V)1.5, which increases I...

  18. Genotype-phenotype correlations in Leber hereditary optic neuropathy.

    Science.gov (United States)

    Tońska, Katarzyna; Kodroń, Agata; Bartnik, Ewa

    2010-01-01

    Leber hereditary optic neuropathy (LHON), acute or subacute vision loss due to retinal ganglion cell death which in the long run leads to optic nerve atrophy is one of the most widely studied maternally inherited diseases caused by mutations in mitochondrial DNA. Although three common mutations, 11778G>A, 14484T>C or 3460G>A are responsible for over 90% of cases and affect genes encoding complex I subunits of the respiratory chain, their influence on bioenergetic properties of the cell is marginal and cannot fully explain the pathology of the disease. The following chain of events was proposed, based on biochemical and anatomical properties of retinal ganglion cells whose axons form the optic nerve: mitochondrial DNA mutations increase reactive oxygen species production in these sensitive cells, leading to caspase-independent apoptosis. As LHON is characterized by low penetrance and sex bias (men are affected about 5 times more frequently than women) the participation of the other factors-genetic and environmental-beside mtDNA mutations was studied. Mitochondrial haplogroups and smoking are some of the factors involved in the complex etiology of this disease.

  19. Encoding high-order cylindrically polarized light beams.

    Science.gov (United States)

    Moreno, Ignacio; Davis, Jeffrey A; Cottrell, Don M; Donoso, Ramiro

    2014-08-20

    In this work we present a setup for the experimental production of cylindrically polarized beams, as well as other variations of polarized light beams. The optical system uses a single transmissive phase-only spatial light modulator, which is used to apply different spatial phase modulation to two output collinear R and L circularly polarized components. Different cylindrically polarized light beams can be obtained by applying different phase shifts to these two circularly polarized components. The system is very efficient since modulation is directly applied to the light beam (as opposed to other common methods operating in the first order of encoded diffraction gratings). Different variations to the cylindrically polarized light beams are also reported, obtained by adding linear or quadratic relative phase shifts between the two circular polarization components of the light beam. Experimental results are provided in all cases.

  20. Imaging Genetics

    Science.gov (United States)

    Munoz, Karen E.; Hyde, Luke W.; Hariri, Ahmad R.

    2009-01-01

    Imaging genetics is an experimental strategy that integrates molecular genetics and neuroimaging technology to examine biological mechanisms that mediate differences in behavior and the risks for psychiatric disorder. The basic principles in imaging genetics and the development of the field are discussed.

  1. Genetic principles.

    Science.gov (United States)

    Abuelo, D

    1987-01-01

    The author discusses the basic principles of genetics, including the classification of genetic disorders and a consideration of the rules and mechanisms of inheritance. The most common pitfalls in clinical genetic diagnosis are described, with emphasis on the problem of the negative or misleading family history.

  2. Imaging Genetics

    Science.gov (United States)

    Munoz, Karen E.; Hyde, Luke W.; Hariri, Ahmad R.

    2009-01-01

    Imaging genetics is an experimental strategy that integrates molecular genetics and neuroimaging technology to examine biological mechanisms that mediate differences in behavior and the risks for psychiatric disorder. The basic principles in imaging genetics and the development of the field are discussed.

  3. Genetics of alcoholism.

    Science.gov (United States)

    Edenberg, Howard J; Foroud, Tatiana

    2014-01-01

    Multiple lines of evidence strongly indicate that genetic factors contribute to the risk for alcohol use disorders (AUD). There is substantial heterogeneity in AUD, which complicates studies seeking to identify specific genetic factors. To identify these genetic effects, several different alcohol-related phenotypes have been analyzed, including diagnosis and quantitative measures related to AUDs. Study designs have used candidate gene analyses, genetic linkage studies, genomewide association studies (GWAS), and analyses of rare variants. Two genes that encode enzymes of alcohol metabolism have the strongest effect on AUD: aldehyde dehydrogenase 2 and alcohol dehydrogenase 1B each has strongly protective variants that reduce risk, with odds ratios approximately 0.2-0.4. A number of other genes important in AUD have been identified and replicated, including GABRA2 and alcohol dehydrogenases 1B and 4. GWAS have identified additional candidates. Rare variants are likely also to play a role; studies of these are just beginning. A multifaceted approach to gene identification, targeting both rare and common variations and assembling much larger datasets for meta-analyses, is critical for identifying the key genes and pathways important in AUD.

  4. Expression of genes encoding extracellular matrix proteins: a macroarray study.

    Science.gov (United States)

    Futyma, Konrad; Miotła, Paweł; Różyńska, Krystyna; Zdunek, Małgorzata; Semczuk, Andrzej; Rechberger, Tomasz; Wojcierowski, Jacek

    2014-12-01

    Endometrial cancer (EC) is one of the most common gynecological malignancies in Poland, with well-established risk factors. Genetic instability and molecular alterations responsible for endometrial carcinogenesis have been systematically investigated. The aim of the present study was to investigate, by means of cDNA macroarrays, the expression profiles of genes encoding extracellular matrix (ECM) proteins in ECs. Tissue specimens were collected during surgical procedures from 40 patients with EC, and control tissue was collected from 9 patients with uterine leiomyomas. RNA was isolated and RT-PCR with radioisotope-labeled cDNA was performed. The levels of ECM protein gene expression in normal endometrial tissues were compared to the expression of these genes in EC specimens. Statistically significant differences in gene expression, stratified by clinical stage of the ECs, were detected for aggrecan, vitronectin, tenascin R, nidogen and two collagen proteins: type VIII chain α1 and type XI chain α2. All of these proteins were overexpressed in stage III endometrial carcinomas compared to levels in stage I and II uterine neoplasms. In conclusion, increased expression of genes encoding ECM proteins may play an important role in facilitating accelerated disease progression of human ECs.

  5. Absolute multi-pole encoder with a simple structure based on an improved gray code to enhance the resolution

    Institute of Scientific and Technical Information of China (English)

    LIU Yong; HAO Shuang-hui; HAO Ming-hui

    2009-01-01

    We developed a novel absolute multi-pole encoder structure to improve the resolution of the multi-pole encoder, realize absolute output and reduce the manufacturing cost of the encoder. The structure includes two ring alnicos defined as index track and sub-division track, respectively. The index track is magnetized based on the improved gray code, with linear halls placed around the track evenly. The outputs of linear halls show the region the rotor belongs to. The sub-division track is magnetized to N-S-N-S (north-south-north-south), and the number of N-S pole pairs is determined by the index track. Three linear hall sensors with an air-gap of 2 mm are used to translate the magnetic filed to voltage signals. The relative offset in a single N-S is obtained through look-up. The magnetic encoder is calibrated using a higher-resolution incremental optical encoder. The pulse output from the optical encoder and hall signals from the magnetic encoder are sampled at the same time and transmitted to a computer, and the relation between them is calculated, and stored in the FLASH of MCU (micro controller unit) for look-up. In the working state, the absolute angle is derived by looking-up with hall signals. The structure is simple and the manufacturing cost is very low and suitable for mass production.

  6. 自适应遗传算法的数据中继卫星光网络资源调度算法%Scheduling algorithm for data relay satellite optical network based on self-adaptive genetic algorithm

    Institute of Scientific and Technical Information of China (English)

    赵卫虎; 赵静; 赵尚弘; 李勇军; 董毅; 李轩

    2015-01-01

    According to the resources, missions and restraints of the data relay satellite optical network, a scheduling algorithm based on improved self-adaptive genetic algorithm was put forwarded. Considering the multi-relay satellite, multi-window, multi-optical-antenna and multi-mission PRI, the model was established. The missions were scheduled by the scheduling operates: the ascertainment of current mission scheduling time and the refreshment of latter mission time-window. The whole weight of the scheduled missions was set as the cost value and the scheduling schemes were optimized by the self-adaptive genetic algorithm. The simulation scene including 3 relay satellites, 12 user satellites, 6 antennas and 60 missions, the result reveals that the algorithm obtains satisfactory results in both time and optimization which is suitable in multi-user, multi-mission and multi-optical-antenna recourse scheduling.%以数据中继卫星光网络系统资源、任务和约束条件为参量,以任务对资源的选择为优化对象,提出了一种基于自适应遗传算法的数据中继卫星光网络资源调度算法。综合考虑多中继星、多时间窗口、多光学天线以及任务优先级要求,建立调度模型;采用“当前任务调度时间的确定”和“后续任务可见时间窗口的更新”的调度操作,对不同资源的任务集合进行调度安排并实现了可见时间窗口的动态更新,获得调度任务的总权值并将其作为参量计算适应度值,最后通过改进的自适应遗传算法对不同调度方案进行寻优。以3颗中继星、12颗用户星,6个光天线,60个任务为条件设置了仿真场景,仿真结果表明该算法在收敛速度、调度效率方面具有优势,适应于多任务、多天线的数据中继卫星光网络系统资源调度。

  7. Optical processing

    Science.gov (United States)

    Gustafson, S. C.

    1985-12-01

    The technical contributions were as follows: (1) Optical parallel 2-D neighborhood processor and optical processor assessment technique; (2) High accuracy with moderately accurate components and optical fredkin gate architectures; (3) Integrated optical threshold computing, pipelined polynomial processor, and all optical analog/digital converter; (4) Adaptive optical associative memory model with attention; (5) Effectiveness of parallelism and connectivity in optical computers; (6) Optical systolic array processing using an integrated acoustooptic module; (7) Optical threshold elements and networks, holographic threshold processors, adaptive matched spatial filtering, and coherence theory in optical computing; (8) Time-varying optical processing for sub-pixel targets, optical Kalman filtering, and adaptive matched filtering; (9) Optical degrees of freedom, ultra short optical pulses, number representations, content-addressable-memory processors, and integrated optical Givens rotation devices; (10) Optical J-K flip flop analysis and interfacing for optical computers; (11) Matrix multiplication algorithms and limits of incoherent optical computers; (12) Architecture for machine vision with sensor fusion, pattern recognition functions, and neural net implementations; (13) Optical computing algorithms, architectures, and components; and (14) Dynamic optical interconnections, advantages and architectures.

  8. Nonlinear Inversion of Potential-Field Data Using an Improved Genetic Algorithm

    Institute of Scientific and Technical Information of China (English)

    Feng Gangding; Chen Chao

    2004-01-01

    The genetic algorithm is useful for solving an inversion of complex nonlinear geophysical equations. The multi-point search of the genetic algorithm makes it easier to find a globally optimal solution and avoid falling into a local extremum. The search efficiency of the genetic algorithm is a key to producing successful solutions in a huge multi-parameter model space. The encoding mechanism of the genetic algorithm affects the searching processes in the evolution. Not all genetic operations perform perfectly in a search under either a binary or decimal encoding system. As such, a standard genetic algorithm (SGA) is sometimes unable to resolve an optimization problem such as a simple geophysical inversion. With the binary encoding system the operation of the crossover may produce more new individuals. The decimal encoding system, on the other hand, makes the mutation generate more new genes. This paper discusses approaches of exploiting the search potentials of genetic operations with different encoding systems and presents a hybrid-encoding mechanism for the genetic algorithm. This is referred to as the hybrid-encoding genetic algorithm (HEGA). The method is based on the routine in which the mutation operation is executed in decimal code and other operations in binary code. HEGA guarantees the birth of better genes by mutation processing with a high probability, so that it is beneficial for resolving the inversions of complicated problems. Synthetic and real-world examples demonstrate the advantages of using HEGA in the inversion of potential-field data.

  9. RNA chaperones encoded by RNA viruses

    Institute of Scientific and Technical Information of China (English)

    Jie Yang; Hongjie Xia; Qi Qian; Xi Zhou

    2015-01-01

    RNAs are functionally diverse macromolecules whose proper functions rely strictly upon their correct tertiary structures. However, because of their high structural flexibility, correct folding of RNAs is challenging and slow. Therefore, cells and viruses encode a variety of RNA remodeling proteins, including helicases and RNA chaperones. In RNA viruses, these proteins are believed to play pivotal roles in all the processes involving viral RNAs during the life cycle. RNA helicases have been studied extensively for decades, whereas RNA chaperones, particularly virus-encoded RNA chaperones, are often overlooked. This review describes the activities of RNA chaperones encoded by RNA viruses, particularly the ones identified and characterized in recent years, and the functions of these proteins in different steps of viral life cycles, and presents an overview of this unique group of proteins.

  10. Challenges in Decomposing Encodings of Verification Problems

    Directory of Open Access Journals (Sweden)

    Peter Schrammel

    2016-07-01

    Full Text Available Modern program verifiers use logic-based encodings of the verification problem that are discharged by a back end reasoning engine. However, instances of such encodings for large programs can quickly overwhelm these back end solvers. Hence, we need techniques to make the solving process scale to large systems, such as partitioning (divide-and-conquer and abstraction. In recent work, we showed how decomposing the formula encoding of a termination analysis can significantly increase efficiency. The analysis generates a sequence of logical formulas with existentially quantified predicates that are solved by a synthesis-based program analysis engine. However, decomposition introduces abstractions in addition to those required for finding the unknown predicates in the formula, and can hence deteriorate precision. We discuss the challenges associated with such decompositions and their interdependencies with the solving process.

  11. An information theoretic characterisation of auditory encoding.

    Directory of Open Access Journals (Sweden)

    Tobias Overath

    2007-10-01

    Full Text Available The entropy metric derived from information theory provides a means to quantify the amount of information transmitted in acoustic streams like speech or music. By systematically varying the entropy of pitch sequences, we sought brain areas where neural activity and energetic demands increase as a function of entropy. Such a relationship is predicted to occur in an efficient encoding mechanism that uses less computational resource when less information is present in the signal: we specifically tested the hypothesis that such a relationship is present in the planum temporale (PT. In two convergent functional MRI studies, we demonstrated this relationship in PT for encoding, while furthermore showing that a distributed fronto-parietal network for retrieval of acoustic information is independent of entropy. The results establish PT as an efficient neural engine that demands less computational resource to encode redundant signals than those with high information content.

  12. Cluster parallel rendering based on encoded mesh

    Institute of Scientific and Technical Information of China (English)

    QIN Ai-hong; XIONG Hua; PENG Hao-yu; LIU Zhen; SHI Jiao-ying

    2006-01-01

    Use of compressed mesh in parallel rendering architecture is still an unexplored area, the main challenge of which is to partition and sort the encoded mesh in compression-domain. This paper presents a mesh compression scheme PRMC (Parallel Rendering based Mesh Compression) supplying encoded meshes that can be partitioned and sorted in parallel rendering system even in encoded-domain. First, we segment the mesh into submeshes and clip the submeshes' boundary into Runs, and then piecewise compress the submeshes and Runs respectively. With the help of several auxiliary index tables, compressed submeshes and Runs can serve as rendering primitives in parallel rendering system. Based on PRMC, we design and implement a parallel rendering architecture. Compared with uncompressed representation, experimental results showed that PRMC meshes applied in cluster parallel rendering system can dramatically reduce the communication requirement.

  13. Genetic modification and genetic determinism

    OpenAIRE

    Vorhaus Daniel B; Resnik David B

    2006-01-01

    Abstract In this article we examine four objections to the genetic modification of human beings: the freedom argument, the giftedness argument, the authenticity argument, and the uniqueness argument. We then demonstrate that each of these arguments against genetic modification assumes a strong version of genetic determinism. Since these strong deterministic assumptions are false, the arguments against genetic modification, which assume and depend upon these assumptions, are therefore unsound....

  14. Pacifist's guide to optical computers

    Science.gov (United States)

    Caulfield, H. John

    1991-11-01

    Optical algebraic processors can perform complex calculations in parallel and at high speeds. However, they commonly suffer from a low analog accuracy which hinders their widespread application. Error detection and correction codes provide one technique for improving the accuracy of optical algebraic processors. The use of these codes would allow some of the errors that may occur during a computation to be detected and possibly corrected. This paper describes the results of various computer simulations of optical matrix-vector multipliers employing error-correction codes. It discusses the application of convolutional codes to optical matrix-vector multipliers along with several block codes. Both binary and nonbinary codes are not employing error-correction codes. Also, the type of noise, whether signal-independent or signal-dependent, has a significant effect on the performance of a matrix-vector multiplier employing an error code. The encoding and decoding operations required for the error codes can be performed optically.

  15. Enhanced double patterning decomposition using lines encoding

    Directory of Open Access Journals (Sweden)

    Khaled M. Soradi

    2016-09-01

    Full Text Available Double patterning photolithography (DPL is considered one of the best solutions used for enabling 32 nm/22 nm technology. In this paper, we propose a new technique for double patterning post decomposition conflict resolution. The algorithm is based on lines positions encoding followed by code pattern matching. Experimental results show that the usage of encoded patterns decreases the time needed for pattern matching and increases the matching accuracy. The overall manual problem solution time is reduced to about 1%.

  16. Fidelity enhancement by logical qubit encoding.

    Science.gov (United States)

    Henry, Michael K; Ramanathan, Chandrasekhar; Hodges, Jonathan S; Ryan, Colm A; Ditty, Michael J; Laflamme, Raymond; Cory, David G

    2007-11-30

    We demonstrate coherent control of two logical qubits encoded in a decoherence free subspace (DFS) of four dipolar-coupled protons in an NMR quantum information processor. A pseudopure fiducial state is created in the DFS, and a unitary logical qubit entangling operator evolves the system to a logical Bell state. The four-spin molecule is partially aligned by a liquid crystal solvent, which introduces strong dipolar couplings among the spins. Although the system Hamiltonian is never fully specified, we demonstrate high fidelity control over the logical degrees of freedom. In fact, the DFS encoding leads to higher fidelity control than is available in the full four-spin Hilbert space.

  17. A novel mutation of AFG3L2 might cause dominant optic atrophy in patients with mild intellectual disability

    Directory of Open Access Journals (Sweden)

    Majida eCharif

    2015-10-01

    Full Text Available Dominant optic neuropathies causing fiber loss in the optic nerve are among the most frequent inherited mitochondrial diseases. In most genetically resolved cases, the disease is associated to a mutation in OPA1, which encodes an inner mitochondrial dynamin involved in network fusion, cristae structure and mitochondrial genome maintenance. OPA1 cleavage is regulated by two m-AAA proteases, SPG7 and AFG3L2, which are respectively involved in Spastic Paraplegia 7 and Spino-Cerebellar Ataxia 28. Here, we identified a novel mutation c.1402C>T in AFG3L2, modifying the arginine 468 in cysteine in an evolutionary highly conserved arginine-finger motif, in a family with optic atrophy and mild intellectual disability. Ophthalmic examinations disclosed a loss of retinal nerve fibers on the temporal and nasal sides of the optic disk and a red-green dyschromatopsia. Thus, our results suggest that neuro-ophthalmological symptom as optic atrophy might be associated with AFG3L2 mutations, and should prompt the screening of this gene in patients with isolated and syndromic inherited optic neuropathies.

  18. Atmospheric effects on Quaternary polarization encoding for free space communication, laboratory simulation

    CERN Document Server

    Soorat, Ram

    2015-01-01

    We have simulated atmospheric effects such as fog and smoke in laboratory environment to simulate depolarisation due to atmospheric effects during a free space optical communi- cation. This has been used to study noise in two components of quaternary encoding for polarization shift keying. Individual components of a Quaternary encoding, such as vertical and horizontal as well as 45$^\\circ$ and 135$^\\circ$ , are tested separately and indicates that the depo- larization effects are different for these two situation. However, due to a differential method used to extract information bits, the protocol shows extremely low bit error rates. The information obtained is useful during deployment of a fully functional Quaternary encoded PolSK scheme in free space.

  19. Optical Diagnostics in Medicine

    Science.gov (United States)

    Iftimia, Nicusor

    2003-03-01

    Light has a unique potential for non-invasive tissue diagnosis. The relatively short wavelength of light allows imaging of tissue at the resolution of histopathology. While strong multiple scattering of light in tissue makes attainment of this resolution difficult for thick tissues, most pathology emanates from epithelial surfaces. Therefore, high-resolution diagnosis of many important diseases may be achieved by transmitting light to the surface of interest. The recent fiber-optic implementation of technologies that reject multiple scattering, such as confocal microscopy and optical low coherence interferometry, have brought us one step closer to realizing non-invasive imaging of architectural and cellular features of tissue. Optical coherence tomography (OCT) can produce high-resolution cross-sectional images of biological structures. Clinical OCT studies conducted in the gastrointestinal tract and cardiovascular system have shown that OCT is capable of providing images of the architectural (> 20 µm) microanatomy of a variety of epithelial tissues, including the layered structure of squamous epithelium and arterial vessels. Fine Needle Aspiration- Low Coherence Interferometry (FNA-LCI) is another optical diagnostics technique, which is a suitable solution to increase the effectiveness of the FNA procedures. LCI is capable of measuring depth resolved (axial, z) tissue structure, birefringence, flow (Doppler shift), and spectra at a resolution of several microns. Since LCI systems are fiber-optic based, LCI probes may easily fit within the bore of a fine gauge needle, allowing diagnostic information to be obtained directly from the FNA biopsy site. Fiber optic spectrally encoded confocal microscopy (SECM) is a new confocal microscopy method, which eliminates the need for rapid beam scanning within the optical probe. This advance enables confocal microscopy to be performed through small diameter probes and will allow assessment of internal human tissues in vivo at

  20. Genetic and molecular aspects of spinocerebellar ataxias

    OpenAIRE

    Honti, Viktor; Vécsei, László

    2005-01-01

    The group of spinocerebellar ataxias (SCAs) includes more than 20 subgroups based only on genetic research. The “ataxia genes” are autosomal; the “disease-alleles” are dominant, and many of them, but not all, encode a protein with an abnormally long polyglutamine domain. In DNA, this domain can be detected as an elongated CAG repeat region, which is the basis of genetic diagnostics. The polyglutamine tails often tend to aggregate and form inclusions. In some cases, protein–protein interaction...

  1. Encoded Archival Description as a Halfway Technology

    Science.gov (United States)

    Dow, Elizabeth H.

    2009-01-01

    In the mid 1990s, Encoded Archival Description (EAD) appeared as a revolutionary technology for publishing archival finding aids on the Web. The author explores whether or not, given the advent of Web 2.0, the archival community should abandon EAD and look for something to replace it. (Contains 18 notes.)

  2. 47 CFR 11.32 - EAS Encoder.

    Science.gov (United States)

    2010-10-01

    ... codes shall be retained even with the power removed. (7) Indicator. An aural or visible means that it... levels of the mark or space frequencies. (9) Attention Signal generator. The encoder must provide an attention signal that complies with the following: (i) Tone Frequencies. The audio tones shall have...

  3. Encoding and Decoding Procedures for Arrangements

    Directory of Open Access Journals (Sweden)

    Alexander A. Babaev

    2012-05-01

    Full Text Available This article discusses an algorithm based on the encoding procedure for representing a set of arrangement elements as a single number. Also the author provides the procedure for the inverse transformation of the code into arrangement elements. In addition the Article includes recommendations on the use of the above procedures in combinatorial algorithms of optimization.

  4. Design Primer for Reed-Solomon Encoders

    Science.gov (United States)

    Perlman, M.; Lee, J. J.

    1985-01-01

    Design and operation of Reed-Solomon (RS) encoders discussed in document prepared as instruction manual for computer designers and others in dataprocessing field. Conventional and Berlekamp architectures compared. Engineers who equip computer memory chips with burst-error and dropout detection and correction find report especially useful.

  5. How Attention Modulates Encoding of Dynamic Stimuli

    Science.gov (United States)

    Oren, Noga; Shapira-Lichter, Irit; Lerner, Yulia; Tarrasch, Ricardo; Hendler, Talma; Giladi, Nir; Ash, Elissa L.

    2016-01-01

    When encoding a real-life, continuous stimulus, the same neural circuits support processing and integration of prior as well as new incoming information. This ongoing interplay is modulated by attention, and is evident in regions such as the prefrontal cortex section of the task positive network (TPN), and in the posterior cingulate cortex (PCC), a hub of the default mode network (DMN). Yet the exact nature of such modulation is still unclear. To investigate this issue, we utilized an fMRI task that employed movies as the encoded stimuli and manipulated attentional load via an easy or hard secondary task that was performed simultaneously with encoding. Results showed increased intersubject correlation (inter-SC) levels when encoding movies in a condition of high, as compared to low attentional load. This was evident in bilateral ventrolateral and dorsomedial prefrontal cortices and the dorsal PCC (dPCC). These regions became more attuned to the combination of the movie and the secondary task as the attentional demand of the latter increased. Activation analyses revealed that at higher load the prefrontal TPN regions were more activated, whereas the dPCC was more deactivated. Attentional load also influenced connectivity within and between the networks. At high load the dPCC was anti-correlated to the prefrontal regions, which were more functionally coherent amongst themselves. Finally and critically, greater inter-SC in the dPCC at high load during encoding predicted lower memory strength when that information was retrieved. This association between inter-SC levels and memory strength suggest that as attentional demands increased, the dPCC was more attuned to the secondary task at the expense of the encoded stimulus, thus weakening memory for the encoded stimulus. Together, our findings show that attentional load modulated the function of core TPN and DMN regions. Furthermore, the observed relationship between memory strength and the modulation of the dPCC points

  6. Encoding and decoding spatio-temporal information for super-resolution microscopy.

    Science.gov (United States)

    Lanzanò, Luca; Coto Hernández, Iván; Castello, Marco; Gratton, Enrico; Diaspro, Alberto; Vicidomini, Giuseppe

    2015-04-02

    The challenge of increasing the spatial resolution of an optical microscope beyond the diffraction limit can be reduced to a spectroscopy task by proper manipulation of the molecular states. The nanoscale spatial distribution of the molecules inside the detection volume of a scanning microscope can be encoded within the fluorescence dynamics and decoded by resolving the signal into its dynamics components. Here we present a robust and general method to decode this information using phasor analysis. As an example of the application of this method, we optically generate spatially controlled gradients in the fluorescence lifetime by stimulated emission. Spatial resolution can be increased indefinitely by increasing the number of resolved dynamics components up to a maximum determined by the amount of noise. We demonstrate that the proposed method provides nanoscale imaging of subcellular structures, opening new routes in super-resolution microscopy based on the encoding/decoding of spatial information through manipulation of molecular dynamics.

  7. An optical encryption scheme that uses polarization of coherent light

    OpenAIRE

    Gopinathan, Unnikrishnan; David S. Monaghan; Naughton, Thomas J.; Sheridan, John T.

    2005-01-01

    We demonstrate an optical system that encodes two dimensional data as different polarization states. The encrypted image is recorded using a digital holographic setup and the decryption is done numerically.

  8. Manipulating time-bin qubits with fiber optics components

    OpenAIRE

    Bussieres, Felix; Soudagar, Yasaman; Berlin, Guido; Lacroix, Suzanne; Godbout, Nicolas

    2006-01-01

    We propose two experimental schemes to implement arbitrary unitary single qubit operations on single photons encoded in time-bin qubits. Both schemes require fiber optics components that are available with current technology.

  9. Intra-Channel Nonlinear Effect on Optical PPM Pulse Transmission

    Institute of Scientific and Technical Information of China (English)

    Sun; Linghao; Jarmo; Takala

    2003-01-01

    PPM encoded Gaussian pulse sequence shows more immunity than non-PPM schemes on optical fiber intra-channel nonlinearity and demonstrated by a numerical study of IXPM and IFWM effects deploying on 100Gb/s single channelsystem.

  10. Amygdala neurons differentially encode motivation and reinforcement.

    Science.gov (United States)

    Tye, Kay M; Janak, Patricia H

    2007-04-11

    Lesion studies demonstrate that the basolateral amygdala complex (BLA) is important for assigning motivational significance to sensory stimuli, but little is known about how this information is encoded. We used in vivo electrophysiology procedures to investigate how the amygdala encodes motivating and reinforcing properties of cues that induce reinstatement of reward-seeking behavior. Two groups of rats were trained to respond to a sucrose reward. The "paired" group was trained with a reward-predictive cue, whereas the "unpaired" group was trained with a randomly presented cue. Both groups underwent identical extinction and reinstatement procedures during which the reward was withheld. The proportion of neurons that were phasically cue responsive during reinstatement was significantly higher in the paired group (46 of 100) than in the unpaired group (8 of 112). Cues that induce reward-seeking behavior can do so by acting as incentives or reinforcers. Distinct populations of neurons responded to the cue in trials in which the cue acted as an incentive, triggering a motivated reward-seeking state, or as a reinforcer, supporting continued instrumental responding. The incentive motivation-encoding population of neurons (34 of 46 cue-responsive neurons; 74%) extinguished in temporal agreement with a decrease in the rate of instrumental responding. The conditioned reinforcement-encoding population of neurons (12 of 46 cue-responsive neurons; 26%) maintained their response for the duration of cue-reinforced instrumental responding. These data demonstrate that separate populations of cue-responsive neurons in the BLA encode the motivating or reinforcing properties of a cue previously associated with a reward.

  11. Analogue Encoding of Physicochemical Properties of Proteins in their Cognate Messenger RNAs

    OpenAIRE

    Polyansky, Anton A; Hlevnjak, Mario; Zagrovic, Bojan

    2013-01-01

    Being related by the genetic code, mRNAs and their cognate proteins exhibit mutually interdependent compositions, which implies the possibility of a direct connection between their general physicochemical properties. Here we probe the general potential of the cell to encode information about proteins in the average characteristics of their cognate mRNAs and decode it in a ribosome-independent manner. We show that average protein hydrophobicity, calculated from either sequences or 3D structure...

  12. On the Role of PDZ Domain-Encoding Genes in Drosophila Border Cell Migration

    OpenAIRE

    Aranjuez, George; Kudlaty, Elizabeth; Longworth, Michelle S; McDonald, Jocelyn A.

    2012-01-01

    Cells often move as collective groups during normal embryonic development and wound healing, although the mechanisms governing this type of migration are poorly understood. The Drosophila melanogaster border cells migrate as a cluster during late oogenesis and serve as a powerful in vivo genetic model for collective cell migration. To discover new genes that participate in border cell migration, 64 out of 66 genes that encode PDZ domain-containing proteins were systematically targeted by in v...

  13. Genetic barcodes

    Energy Technology Data Exchange (ETDEWEB)

    Weier, Heinz -Ulrich G

    2015-08-04

    Herein are described multicolor FISH probe sets termed "genetic barcodes" targeting several cancer or disease-related loci to assess gene rearrangements and copy number changes in tumor cells. Two, three or more different fluorophores are used to detect the genetic barcode sections thus permitting unique labeling and multilocus analysis in individual cell nuclei. Gene specific barcodes can be generated and combined to provide both numerical and structural genetic information for these and other pertinent disease associated genes.

  14. Features of mtDNA mutation patterns in European pedigrees and sporadic cases with leber hereditary optic neuropathy

    Energy Technology Data Exchange (ETDEWEB)

    Obermaier-Kusser, B.; Schubring, S.; Paprotta, A.; Meitinger, T.; Jaksch, M.; Gerbitz, K.D. [Univ. of Munich (Germany); Lorenz, B. [Univ. of Rogensburgh (Germany); Zerres, K. [Univ. of Bonn (Germany); Meire, F. [Univ. of Ghent (Belgium); Cochaux, P. [Univ. of Brussels (Belgium)] [and others

    1994-11-01

    Leber hereditary optic neuropathy (LHON) is maternally transmitted and is characterized by bilateral loss of central vision in young adults as a result of optic nerve degeneration. Fifteen transition mutations located in different genes for the mitochondrially encoded subunits of respiratory chain complexes have been associated thus far with the disease. Genetic studies have led to the classification of the pathogenic significance of these different mutations. However, more research is required to determine the causality of the mutations and the penetrance of the disease. The present study compares studies of populations of different ethnic origins, namely European LHON pedigrees and sporadic cases, in order to elucidate the pathogenic mechanisms involved. 21 refs., 2 figs., 1 tab.

  15. Random codon re-encoding induces stable reduction of replicative fitness of Chikungunya virus in primate and mosquito cells.

    Directory of Open Access Journals (Sweden)

    Antoine Nougairede

    2013-02-01

    Full Text Available Large-scale codon re-encoding represents a powerful method of attenuating viruses to generate safe and cost-effective vaccines. In contrast to specific approaches of codon re-encoding which modify genome-scale properties, we evaluated the effects of random codon re-encoding on the re-emerging human pathogen Chikungunya virus (CHIKV, and assessed the stability of the resultant viruses during serial in cellulo passage. Using different combinations of three 1.4 kb randomly re-encoded regions located throughout the CHIKV genome six codon re-encoded viruses were obtained. Introducing a large number of slightly deleterious synonymous mutations reduced the replicative fitness of CHIKV in both primate and arthropod cells, demonstrating the impact of synonymous mutations on fitness. Decrease of replicative fitness correlated with the extent of re-encoding, an observation that may assist in the modulation of viral attenuation. The wild-type and two re-encoded viruses were passaged 50 times either in primate or insect cells, or in each cell line alternately. These viruses were analyzed using detailed fitness assays, complete genome sequences and the analysis of intra-population genetic diversity. The response to codon re-encoding and adaptation to culture conditions occurred simultaneously, resulting in significant replicative fitness increases for both re-encoded and wild type viruses. Importantly, however, the most re-encoded virus failed to recover its replicative fitness. Evolution of these viruses in response to codon re-encoding was largely characterized by the emergence of both synonymous and non-synonymous mutations, sometimes located in genomic regions other than those involving re-encoding, and multiple convergent and compensatory mutations. However, there was a striking absence of codon reversion (<0.4%. Finally, multiple mutations were rapidly fixed in primate cells, whereas mosquito cells acted as a brake on evolution. In conclusion, random

  16. Micron-sized surface enhanced Raman scattering reporter/fluorescence probe encoded colloidal microspheres for sensitive DNA detection.

    Science.gov (United States)

    You, Lijun; Li, Ruimin; Dong, Xu; Wang, Fang; Guo, Jia; Wang, Changchun

    2017-02-15

    A new type of optical probes, featuring surface enhanced Raman scattering (SERS) and fluorescence spectra dual-mode encoding, has been reported in this article. Based on the uniform micrometer-sized melamine resin/Ag nanoparticles (MRM/Ag-NPs) composite microspheres, the SERS reporters and fluorescent probes were successfully fixed onto the different layers of the MEM/Ag-NPs microspheres, which supported the sensitive DNA detecton. The two spectroscopic methods commonly considered to be contradictive to each other, yet the optical signals were separable in the experiments. The dual-encoding strategy and single microsphere detecton method put the number of available independent codes to be rough the multiple of those available in the two optical detection channels, which increases far more rapidly than the summation of the two channels. As a proof of cencept, the utility of this dual spectrum mode SERS-fluoresecence encoded microsphere (SFEM) was demonstrated in a specific DNA detection using complimentary ssDNA functionalized magnetic beads as the DNA capturing and separation agents. Excellent encoding results were demonstrated from the decoding of the SERS and fluorescence signals of the SFEM. The method appears to be general in scope and we expect that the SERS-fluoresecence encoded microspheres system is applicable to multiplex bioassays of a variety of biomolecules.

  17. Genetics of osteoporosis

    Energy Technology Data Exchange (ETDEWEB)

    Urano, Tomohiko [Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655 (Japan); Inoue, Satoshi, E-mail: INOUE-GER@h.u-tokyo.ac.jp [Department of Geriatric Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655 (Japan); Department of Anti-Aging Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo 113-8655 (Japan); Division of Gene Regulation and Signal Transduction, Research Center for Genomic Medicine, Saitama Medical University, Saitama (Japan)

    2014-09-19

    Highlights: • Single-nucleotide polymorphisms (SNPs) associated with osteoporosis were identified. • SNPs mapped close to or within VDR and ESR1 are associated with bone mineral density. • WNT signaling pathway plays a pivotal role in regulating bone mineral density. • Genetic studies will be useful for identification of new therapeutic targets. - Abstract: Osteoporosis is a skeletal disease characterized by low bone mineral density (BMD) and microarchitectural deterioration of bone tissue, which increases susceptibility to fractures. BMD is a complex quantitative trait with normal distribution and seems to be genetically controlled (in 50–90% of the cases), according to studies on twins and families. Over the last 20 years, candidate gene approach and genome-wide association studies (GWAS) have identified single-nucleotide polymorphisms (SNPs) that are associated with low BMD, osteoporosis, and osteoporotic fractures. These SNPs have been mapped close to or within genes including those encoding nuclear receptors and WNT-β-catenin signaling proteins. Understanding the genetics of osteoporosis will help identify novel candidates for diagnostic and therapeutic targets.

  18. Genetics of Congenital Cataract.

    Science.gov (United States)

    Pichi, Francesco; Lembo, Andrea; Serafino, Massimiliano; Nucci, Paolo

    2016-01-01

    Congenital cataract is a type of cataract that presents at birth or during early childhood, and it is one of the most easily treatable causes of visual impairment and blindness during infancy, with an estimated prevalence of 1-6 cases per 10,000 live births. Approximately 50% of all congenital cataract cases may have a genetic cause, and such cases are quite heterogeneous. Although congenital nuclear cataract can be caused by multiple factors, genetic mutation remains the most common cause. All three types of Mendelian inheritance have been reported for cataract; however, autosomal dominant transmission seems to be the most frequent. The transparency and high refractive index of the lens are achieved by the precise architecture of fiber cells and homeostasis of the lens proteins in terms of their concentrations, stabilities, and supramolecular organization. Research on hereditary congenital cataract has led to the identification of several classes of candidate genes that encode proteins such crystallins, lens-specific connexins, aquaporin, cytoskeletal structural proteins, and developmental regulators. In this review, we highlight the identified genetic mutations that account for congenital nuclear cataract.

  19. An Optical Tri-valued Computing System

    Directory of Open Access Journals (Sweden)

    Junjie Peng

    2014-03-01

    Full Text Available A new optical computing experimental system is presented. Designed based on tri-valued logic, the system is built as a photoelectric hybrid computer system which is much advantageous over its electronic counterparts. Say, the tri-valued logic of the system guarantees that it is more powerful in information processing than that of systems with binary logic. And the optical characteristic of the system makes it be much capable in huge data processing than that of the electronic computers. The optical computing system includes two parts, electronic part and optical part. The electronic part consists of a PC and two embedded systems which are used for data input/output, monitor, synchronous control, user data combination and separation and so on. The optical part includes three components. They are optical encoder, logic calculator and decoder. It mainly answers for encoding the users' requests into tri-valued optical information, computing and processing the requests, decoding the tri-valued optical information to binary electronic information and so forth. Experiment results show that the system is quite right in optical information processing which demonstrates the feasibility and correctness of the optical computing system.

  20. Unnatural reactive amino acid genetic code additions

    Science.gov (United States)

    Deiters, Alexander; Cropp, Ashton T; Chin, Jason W; Anderson, Christopher J; Schultz, Peter G

    2013-05-21

    This invention provides compositions and methods for producing translational components that expand the number of genetically encoded amino acids in eukaryotic cells. The components include orthogonal tRNAs, orthogonal aminoacyl-tRNA synthetases, pairs of tRNAs/synthetases and unnatural amino acids. Proteins and methods of producing proteins with unnatural amino acids in eukaryotic cells are also provided.