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Sample records for induces selective time

  1. Transitions induced by cross-correlated bounded noises and time delay in a genotype selection model

    NASA Astrophysics Data System (ADS)

    Liu, Pei; Ning, Li Juan

    2016-01-01

    We present a numerical investigation of occurrence of transitions in a genotype selection model with time delay, where two bounded noises are cross-correlated. Stationary probability distribution (SPD) function is obtained. It is found that: the multiplicative bounded noise can facilitate the gene separation and it plays a constructive role in the genetic selection progress, while the additive bounded noise suppresses the gene separation. The strong correlation between noises gives a big chance to one type haploid out of the group. Besides, what is more interesting is that the correlation time τ can induce a new transitions (i.e., the curve of the SPD changes from unimodal to bimodal, and then to four peaks as the correlation time τ increases).

  2. Artifacts Induced by Selective Blanking of Time-Domain Data in Fourier Transform Mass Spectrometry

    NASA Astrophysics Data System (ADS)

    Xian, Feng; Valeja, Santosh G.; Beu, Steve C.; Hendrickson, Christopher L.; Marshall, Alan G.

    2013-11-01

    Fourier transform mass spectrometry (FTMS) of the isolated isotopic distribution for a highly charged biomolecule produces time-domain signal containing large amplitude signal "beats" separated by extended periods of much lower signal magnitude. Signal-to-noise ratio for data sampled between beats is low because of destructive interference of the signals induced by members of the isotopic distribution. Selective blanking of the data between beats has been used to increase spectral signal-to-noise ratio. However, blanking also eliminates signal components and, thus, can potentially distort the resulting FT spectrum. Here, we simulate the time-domain signal from a truncated isotopic distribution for a single charge state of an antibody. Comparison of the FT spectra produced with or without blanking and with or without added noise clearly show that blanking does not improve mass accuracy and introduces spurious peaks at both ends of the isotopic distribution (thereby making it more difficult to identify posttranslational modifications and/or adducts). Although the artifacts are reduced by use of multiple Gaussian (rather than square wave) windowing, blanking appears to offer no advantages for identifying true peaks or for mass measurement.

  3. Selection of charge methods for lithium ion batteries by considering diffusion induced stress and charge time

    NASA Astrophysics Data System (ADS)

    Lu, Bo; Song, Yicheng; Zhang, Junqian

    2016-07-01

    This article demonstrates the design of charging strategies for lithium ion batteries with considering the balance between diffusion induced stress and total charge time for two- and three-stage charge methods. For the two-stage galvanostatic-potentiostatic charge method the low mechanical stress can be achieved without increasing total charge time by switching the galvanostatic to the potentiostatic at the time moment when the lithium concentration at the surface of particles reaches the limit cbarsurf = 0 . A three-stage method, which consists of an initial galvanostatic stage of high current, a galvanostatic stage of low current and a potentiostatic ending stage, is suggested. Employing the initial galvanostatic stage of high current is helpful not only in accelerating the charge process, but also in controlling the mechanical stress once the electrical current and time duration of the initial galvanostatic stage are properly designed.

  4. Selective Reaction Times and Intelligence.

    ERIC Educational Resources Information Center

    Neubauer, Aljoscha C.

    1990-01-01

    The relationship between psychometric intelligence and 2 selective reaction time (RT) tasks was determined for 81 university students (27 males and 54 females). Results generally support the paradigm of W. E. Hick (1952). Some surprising findings are discussed with respect to the specific demands of selective RT tasks. (SLD)

  5. Selection of suitable reference genes for quantitative real-time PCR in apoptosis-induced MCF-7 breast cancer cells.

    PubMed

    Ferreira, Eloise; Cronjé, Marianne J

    2012-02-01

    Apoptosis is induced in MCF-7 breast cancer cells following treatment with salicylic acid (20 mM), either in the presence or absence of a heat shock (42°C for 30 min). In order to study the alterations of apoptotic genes with quantitative real-time PCR (qPCR), suitable genes with unchanged expression following the treatments is required for normalizing the gene expression levels. In this study, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), β-actin (ACTB), Histone H2A (HIST), constitutively expressed heat shock protein 70 (HSC70) and tyrosine 3-monooxygenase/trytophan 5 monooxygenase activation protein, 14-3-3 (YWHAZ) were evaluated as appropriate reference genes. Analysis of gene expression data with one-way ANOVA, geNorm and NormFinder identified HIST and YWHAZ as the least affected during the induction of apoptosis by the different treatments, and is the most suitable gene-pair for normalization during qPCR analysis in MCF-7 breast cancer cells undergoing apoptosis following treatment with SA and/or HS.

  6. Effects of polychlorinated biphenyls and nutritional restriction on barbituate-induced sleeping times and selected blood characteristics in raccoons (Procyon lotor)

    SciTech Connect

    Montz, W.E.; Card, W.C.; Kirkpatrick, R.L.

    1982-05-01

    Hepatic microsomal enzyme activity was induced in wild-trapped raccoons (Procyon lotor) and selected blood characteristics were measured in an effort to detect responses due to PCB ingestion, nutritional restriction, and their interactions. Barbiturate-induced sleeping times were used as an index of hepatic microsomal activity because they have been used reliably by other workers. Blood characteristics examined in the study were nonesterified fatty acids (NEFA), cholesterol, and three ketone bodies (D-(-)-3-hydroxybutyrate, acetoacetate, and acetone). Results show a reduction in sleeping times, elevated NEFA and D-(-)-3-hydroxybutyrate concentrations, and lower cholesterol concentrations in PCB-treated groups. A highly significant interaction between PCB treatment and nutritional restriction was observed in acetoacetate concentrations. (JMT)

  7. Fisheries-induced disruptive selection.

    PubMed

    Landi, Pietro; Hui, Cang; Dieckmann, Ulf

    2015-01-21

    Commercial harvesting is recognized to induce adaptive responses of life-history traits in fish populations, in particular by shifting the age and size at maturation through directional selection. In addition to such evolution of a target stock, the corresponding fishery itself may adapt, in terms of fishing policy, technological progress, fleet dynamics, and adaptive harvest. The aim of this study is to assess how the interplay between natural and artificial selection, in the simplest setting in which a fishery and a target stock coevolve, can lead to disruptive selection, which in turn may cause trait diversification. To this end, we build an eco-evolutionary model for a size-structured population, in which both the stock׳s maturation schedule and the fishery׳s harvest rate are adaptive, while fishing may be subject to a selective policy based on fish size and/or maturity stage. Using numerical bifurcation analysis, we study how the potential for disruptive selection changes with fishing policy, fishing mortality, harvest specialization, life-history tradeoffs associated with early maturation, and other demographic and environmental parameters. We report the following findings. First, fisheries-induced disruptive selection is readily caused by commonly used fishing policies, and occurs even for policies that are not specific for fish size or maturity, provided that the harvest is sufficiently adaptive and large individuals are targeted intensively. Second, disruptive selection is more likely in stocks in which the selective pressure for early maturation is naturally strong, provided life-history tradeoffs are sufficiently consequential. Third, when a fish stock is overexploited, fisheries targeting only large individuals might slightly increase sustainable yield by causing trait diversification (even though the resultant yield always remains lower than the maximum sustainable yield that could be obtained under low fishing mortality, without causing disruptive

  8. Models of blockage-induced selectivity

    NASA Astrophysics Data System (ADS)

    Barré, C.; Talbot, J.

    2017-04-01

    We examine blockage-induced selectivity in a particulate stream flowing through a channel. Each component of the mixture is characterized by the transit time, τ, necessary to pass through the channel. The model is motivated by filtration and other processes involving blockage. The transit time distribution of exiting particles depends on the entering particle distribution, \\psi(τ) , the intensity, λ, of the entering stream, and the blocking rule. With the simple rule that a blockage occurs whenever two particles are present in the channel, the properties of the exiting stream are directly related to the Laplace transform of the entering distribution, \\tilde\\psi(λ) . For any entering distribution, the exiting stream is enriched in faster moving components. The selectivity of a species in a binary mixture can be mapped to a thermodynamic system, namely a hard rod mixture at a given pressure and temperature that can model the adsorption of gas mixtures in nanopores. We also examine an alternative rule according to which blocking only occurs if a faster moving particle catches up to a slower one in the channel. The selectivity is quantitatively different compared to the simple blocking rule. In a binary mixture the majority component in the entering stream is further enhanced in the exiting stream, independently of the transit times.

  9. In vivo real-time two-photon microscopic imaging of platelet aggregation induced by selective laser irradiation to the endothelium created in the beta-actin-green fluorescent protein transgenic mice.

    PubMed

    Koike, Yuhki; Tanaka, Koji; Okugawa, Yoshinaga; Morimoto, Yuhki; Toiyama, Yuji; Uchida, Keiichi; Miki, Chikao; Mizoguchi, Akira; Kusunoki, Masato

    2011-08-01

    Although thrombus formation in vivo has recently been reported, all previous laser induced thrombus models have been associated with vessel wall disruption. This study aimed to evaluate in vivo real-time platelet aggregation after selective endothelial injury, and to visualize thrombus formation without disruption and swelling of the arterial intima induced by two-photon laser irradiation. Cecal arteriole thrombi were created in beta-actin-green fluorescent protein transgenic mice by selective endothelial injury using two-photon laser-scanning microscopy (TPLSM). The in vivo real-time process of thrombus formation was assessed. Anticoagulant drug efficiency for thrombi was also analyzed in detail. TPLSM allowed visualization of microvessel components from the arterial smooth muscle to the intimal layer. Immediately after selective laser irradiation of the intimal layer, platelet adhesion and aggregation were seen only at the area of injury of the intimal layer after forming linear adhesions downstream of the injured area. When shear stress was overcome, thrombus formation began at the downstream edge of the injured area. Thrombus volume plateaued approximately 60 min after laser irradiation. The thrombolytic effects of anticoagulant drugs were precisely assessed; therefore, our model appears the most advanced model in point of real-time imaging of pathophysiological processes in vivo currently reported. In vivo real-time imaging of thrombus formation can be achieved using TPLSM in combination with an organ stabilizing system. The high magnification and resolution of TPLSM allows investigation of the mechanisms of thrombus formation along with assessment of antithrombotic drug efficacy with little interexperimental variation.

  10. Cytokines induce selective granulocyte chemotactic responses.

    PubMed

    Bittleman, D B; Erger, R A; Casale, T B

    1996-02-01

    Neutrophils, eosinophils and cytokines are important in allergic airway inflammatory responses. However, it is unclear how cytokines selectively influence neutrophils versus eosinophils to migrate to an inflammatory site. The cytokines, transforming growth factor-beta1 (TGF-beta1), interleukin (IL)-1alpha, IL-5, IL-8, granulocyte macrophage-colony stimulating factor (GM-CSF) and tumor necrosis factor-alpha (TNF-alpha), are released subsequent to allergic reactions and affect both neutrophil and eosinophil functions. We studied whether these cytokines differed in capacity to induce human neutrophil versus eosinophil migration through naked filters and human umbilical vein endothelial cell (HUVEC) and human pulmonary type II-like epithelial (A549) cell monolayers grown on filters. Dose-response experiments using all barriers were performed for each granulocyte and cytokine. TGF-beta1 did not induce granulocyte migration. IL-5 induced eosinophil migration only through naked filters. IL-1alpha stimulated neutrophil migration through cellular barriers, but not through naked filters. TNF-alpha and GM-CSF induced neutrophil and eosinophil migration through filters, but only neutrophil migration through cellular monolayers. Only IL-8 induced significant neutrophil and eosinophil migration; however, there were clear-cut differences between the neutrophilotactic and eosinophilotactic responses through all barriers employed. Thus, our data show that these cytokines induce distinct chemotactic responses for neutrophils versus eosinophils. Moreover, by using relevant cellular barriers versus naked filters, our data better examines the capability of these cytokines to induce selective granulocyte migration to an inflammatory site in lung diseases such as asthma.

  11. Estimating fisheries-induced selection: traditional gear selectivity research meets fisheries-induced evolution.

    PubMed

    Kuparinen, Anna; Kuikka, Sakari; Merilä, Juha

    2009-05-01

    The study of fisheries-induced evolution is a research field which is becoming recognized both as an important and interesting problem in applied evolution, as well as a practical management problem in fisheries. Much of the research in fisheries-induced evolution has focussed on quantifying and proving that an evolutionary response has taken place, but less effort has been invested on the actual processes and traits underlying capture of a fish by a fishing gear. This knowledge is not only needed to understand possible phenotypic selection associated to fishing but also to help to device sustainable fisheries and management strategies. Here, we draw attention to the existing knowledge about selectivity of fishing gears and outline the ways in which this information could be utilized in the context of fisheries-induced evolution. To these ends, we will introduce a mathematical framework commonly applied to quantify fishing gear selectivity, illustrate the link between gear selectivity and the change in the distribution of phenotypes induced by fishing, review what is known about selectivity of commonly used fishing gears, and discuss how this knowledge could be applied to improve attempts to predict evolutionary impacts of fishing.

  12. Estimating fisheries-induced selection: traditional gear selectivity research meets fisheries-induced evolution

    PubMed Central

    Kuparinen, Anna; Kuikka, Sakari; Merilä, Juha

    2009-01-01

    The study of fisheries-induced evolution is a research field which is becoming recognized both as an important and interesting problem in applied evolution, as well as a practical management problem in fisheries. Much of the research in fisheries-induced evolution has focussed on quantifying and proving that an evolutionary response has taken place, but less effort has been invested on the actual processes and traits underlying capture of a fish by a fishing gear. This knowledge is not only needed to understand possible phenotypic selection associated to fishing but also to help to device sustainable fisheries and management strategies. Here, we draw attention to the existing knowledge about selectivity of fishing gears and outline the ways in which this information could be utilized in the context of fisheries-induced evolution. To these ends, we will introduce a mathematical framework commonly applied to quantify fishing gear selectivity, illustrate the link between gear selectivity and the change in the distribution of phenotypes induced by fishing, review what is known about selectivity of commonly used fishing gears, and discuss how this knowledge could be applied to improve attempts to predict evolutionary impacts of fishing. PMID:25567864

  13. Optoacoustic real-time dosimetry for selective retina treatment.

    PubMed

    Schuele, Georg; Elsner, Hanno; Framme, Carsten; Roider, Johann; Birngruber, Reginald; Brinkmann, Ralf

    2005-01-01

    The selective retina treatment (SRT) targets retinal diseases associated with disorders in the retinal pigment epithelium (RPE). Due to the ophthalmoscopic invisibility of the laser-induced RPE effects, we investigate a noninvasive optoacoustic real-time dosimetry system. In vitro porcine RPE is irradiated with a Nd:YLF laser (527 nm, 1.7-micros pulse duration, 5 to 40 microJ, 30 pulses, 100-Hz repetition rate). Generated acoustic transients are measured with a piezoelectric transducer. During 27 patient treatments, the acoustic transients are measured with a transducer embedded in an ophthalmic contact lens. After treatment, RPE damage is visualized by fluorescein angiographic leakage. Below the RPE damage threshold, the optoacoustic transients show no pulse-to-pulse fluctuations within a laser pulse train. Above threshold, fluctuations of the individual transients among each other are observed. If optoacoustic pulse-to-pulse fluctuations are present, RPE leakage is observed in fluorescein angiography. In 96% of the irradiated areas, RPE leakage correlated with the optoacoustic defined threshold value. A noninvasive optoacoustic real-time dosimetry for SRT is developed and proved in vitro and during patient treatment. It detects the ophthalmoscopically invisible laser-induced damage of RPE cells and overcomes practical limitations of SRT for use in private practice.

  14. Time variation of some selected topics in bioethical publications.

    PubMed

    Cohen, C; Vianna, J A R; Battistella, L R; Massad, E

    2008-02-01

    To analyse the time variation of topics in bioethical publications as a proxy of the relative importance. We searched the Medline database for bioethics publications using the words "ethics or bioethics", and for 360 specific topics publications, associating Medical Subject Heading topic descriptors to those words. We calculated the ratio of bioethics publications to the total publications of Medline, and the ratio of each topic publications to the total bioethics publications, for five-year intervals, from 1970 to 2004. We calculated the time variation of ratios, dividing the difference between the highest and lowest ratio of each topic by its highest ratio. Four topics were described, selected to illustrate different patterns of variation: "Induced Abortion", "Conflict of Interest", "Acquired Immunodeficiency Syndrome", "Medical Education." The ratio of bioethics publications to total Medline publications increased from 0.003 to 0.012. The variation of the topic's ratios was higher than 0.7 for 68% of the topics. The Induced Abortion ratios decreased from 0.12 to 0.02. Conflict of Interest ratios increased from zero to 0.07. The Acquired Immunodeficiency Syndrome ratios were nearly zero in the first three intervals, had a peak of 0.06 during 1985-9, followed by a decrease to 0.01. Medical Education ratios varied few, from 0.04 to 0.03. There was an increase of bioethical publications in the Medline database. The topics in bioethics literature have an important time variation. Some factors were suggested to explain this variation: current legal cases, resolution of the issue, saturation of a discussion and epidemiologic importance.

  15. Allostery in the lac operon: population selection or induced dissociation?

    PubMed

    Sharp, Kim A

    2011-11-01

    Allostery, the modulation of function of a protein at one site by the binding of a ligand at a different site, is a property of many proteins. Two kinetically distinct models have been proposed: i) The induced fit model in which the ligand binds to the protein and then induces the conformational change. ii) The population selection model, in which the protein spontaneously undergoes a conformational change, which is then 'captured' by the ligand. Using measured kinetic constants for the lac repressor the contribution of population selection vs. induced dissociation is quantified by simulating the kinetics of allostery. At very low inducer concentration, both mechanisms contribute significantly. Total induction, though, is small under these conditions. At increasing levels of induction the induced dissociation mechanism soon dominates, first due to binding of one inducer, and then from two inducers binding.

  16. Selective Nitrations: Laser-Induced Nitrations

    DTIC Science & Technology

    1989-01-01

    Produt Mol Thermalt Laser-Induced Propane Nitrornethane 22.0 (32.3) 32 Nitroethane 16.6 (24I.2) 17 1-nitropropane 13.2 (2 4. 2) 15 2-nitropropane 48.2...Alrich Library of FT-IR Spectra, Ed. 1, Charles J. Pouchert (1985, Alrich Chemical Company, Inc., Milwaukee, WI), p. 397. 11. Norton, R. H. and Beer , R

  17. Selective fishing induces density-dependent growth

    PubMed Central

    Svedäng, Henrik; Hornborg, Sara

    2014-01-01

    Over the last decades, views on fisheries management have oscillated between alarm and trust in management progress. The predominant policy for remedying the world fishing crisis aims at maximum sustainable yield (MSY) by adjusting gear selectivity and fishing effort. Here we report a case study on how striving for higher yields from the Eastern Baltic cod stock by increasing selectivity has become exceedingly detrimental for its productivity. Although there is a successive increase in numbers of undersized fish, growth potential is severely reduced, and fishing mortality in fishable size has increased. Once density-dependent growth is introduced, the process is self-enforcing as long as the recruitment remains stable. Our findings suggest that policies focusing on maximum yield while targeting greater sizes are risky and should instead prioritize catch rates over yield. Disregarding the underlying population structure may jeopardize stock productivity, with dire consequences for the fishing industry and ecosystem structure and function. PMID:24920387

  18. Selective fishing induces density-dependent growth.

    PubMed

    Svedäng, Henrik; Hornborg, Sara

    2014-06-12

    Over the last decades, views on fisheries management have oscillated between alarm and trust in management progress. The predominant policy for remedying the world fishing crisis aims at maximum sustainable yield (MSY) by adjusting gear selectivity and fishing effort. Here we report a case study on how striving for higher yields from the Eastern Baltic cod stock by increasing selectivity has become exceedingly detrimental for its productivity. Although there is a successive increase in numbers of undersized fish, growth potential is severely reduced, and fishing mortality in fishable size has increased. Once density-dependent growth is introduced, the process is self-enforcing as long as the recruitment remains stable. Our findings suggest that policies focusing on maximum yield while targeting greater sizes are risky and should instead prioritize catch rates over yield. Disregarding the underlying population structure may jeopardize stock productivity, with dire consequences for the fishing industry and ecosystem structure and function.

  19. Real-time selective sequencing using nanopore technology

    PubMed Central

    Loose, Matthew; Malla, Sunir; Stout, Michael

    2016-01-01

    The Oxford Nanopore MinION sequences DNA by sensing changes in electrical current flow in real-time as molecules traverse nanopores. Optionally, the voltage across specific nanopores can be reversed, ejecting the DNA molecule. This enables “Read Until”, the selection of specific DNA molecules for sequencing. We use dynamic time warping to match reads to reference, selecting regions of small genomes, individual amplicons, or normalization of the amplicon set. This first demonstration of direct selection of specific DNA molecules in real-time enables many novel future applications. PMID:27454285

  20. Clines Induced by Variable Selection and Migration.

    DTIC Science & Technology

    1980-09-01

    population genetics , equation (1.1) has been used in models designed to describe certain phenomena in ecology [12). We suppose that f(0) = f(1) = 0...In terms of the example from population genetics , b histahiiitv means we are in the underdominant case, i.e., si > 0 and I~!i s2 > 0. Arain in the...369. 8. W. H. Fleming, A selection-mioration nmodel in population genetics , J. Math. Biol. 2, (1975) 219-233. 9. J. 9. S. Haldane, The theory of a

  1. A novel “correlated ion and neutral time of flight” method: Event-by-event detection of neutral and charged fragments in collision induced dissociation of mass selected ions

    SciTech Connect

    Teyssier, C.; Fillol, R.; Abdoul-Carime, H.; Farizon, B.; Farizon, M.

    2014-01-15

    A new tandem mass spectrometry (MS/MS) method based on time of flight measurements performed on an event-by-event detection technique is presented. This “correlated ion and neutral time of flight” method allows to explore Collision Induced Dissociation (CID) fragmentation processes by directly identifying not only all ions and neutral fragments produced but also their arrival time correlations within each single fragmentation event from a dissociating molecular ion. This constitutes a new step in the characterization of molecular ions. The method will be illustrated here for a prototypical case involving CID of protonated water clusters H{sup +}(H{sub 2}O){sub n=1–5} upon collisions with argon atoms.

  2. Onboard Run-Time Goal Selection for Autonomous Operations

    NASA Technical Reports Server (NTRS)

    Rabideau, Gregg; Chien, Steve; McLaren, David

    2010-01-01

    We describe an efficient, online goal selection algorithm for use onboard spacecraft and its use for selecting goals at runtime. Our focus is on the re-planning that must be performed in a timely manner on the embedded system where computational resources are limited. In particular, our algorithm generates near optimal solutions to problems with fully specified goal requests that oversubscribe available resources but have no temporal flexibility. By using a fast, incremental algorithm, goal selection can be postponed in a "just-in-time" fashion allowing requests to be changed or added at the last minute. This enables shorter response cycles and greater autonomy for the system under control.

  3. Onboard Run-Time Goal Selection for Autonomous Operations

    NASA Technical Reports Server (NTRS)

    Rabideau, Gregg; Chien, Steve; McLaren, David

    2010-01-01

    We describe an efficient, online goal selection algorithm for use onboard spacecraft and its use for selecting goals at runtime. Our focus is on the re-planning that must be performed in a timely manner on the embedded system where computational resources are limited. In particular, our algorithm generates near optimal solutions to problems with fully specified goal requests that oversubscribe available resources but have no temporal flexibility. By using a fast, incremental algorithm, goal selection can be postponed in a "just-in-time" fashion allowing requests to be changed or added at the last minute. This enables shorter response cycles and greater autonomy for the system under control.

  4. Utilizing Response Time Distributions for Item Selection in CAT

    ERIC Educational Resources Information Center

    Fan, Zhewen; Wang, Chun; Chang, Hua-Hua; Douglas, Jeffrey

    2012-01-01

    Traditional methods for item selection in computerized adaptive testing only focus on item information without taking into consideration the time required to answer an item. As a result, some examinees may receive a set of items that take a very long time to finish, and information is not accrued as efficiently as possible. The authors propose two…

  5. Utilizing Response Time Distributions for Item Selection in CAT

    ERIC Educational Resources Information Center

    Fan, Zhewen; Wang, Chun; Chang, Hua-Hua; Douglas, Jeffrey

    2012-01-01

    Traditional methods for item selection in computerized adaptive testing only focus on item information without taking into consideration the time required to answer an item. As a result, some examinees may receive a set of items that take a very long time to finish, and information is not accrued as efficiently as possible. The authors propose two…

  6. Sexual selection gradients change over time in a simultaneous hermaphrodite

    PubMed Central

    Hoffer, Jeroen NA; Mariën, Janine; Ellers, Jacintha; Koene, Joris M

    2017-01-01

    Sexual selection is generally predicted to act more strongly on males than on females. The Darwin-Bateman paradigm predicts that this should also hold for hermaphrodites. However, measuring this strength of selection is less straightforward when both sexual functions are performed throughout the organism’s lifetime. Besides, quantifications of sexual selection are usually done during a short time window, while many animals store sperm and are long-lived. To explore whether the chosen time frame affects estimated measures of sexual selection, we recorded mating success and reproductive success over time, using a simultaneous hermaphrodite. Our results show that male sexual selection gradients are consistently positive. However, an individual’s female mating success seems to negatively affect its own male reproductive success, an effect that only becomes visible several weeks into the experiment, highlighting that the time frame is crucial for the quantification and interpretation of sexual selection measures, an insight that applies to any iteroparous mating system. DOI: http://dx.doi.org/10.7554/eLife.25139.001 PMID:28613158

  7. Time resolved ion beam induced charge collection

    SciTech Connect

    SEXTON,FREDERICK W.; WALSH,DAVID S.; DOYLE,BARNEY L.; DODD,PAUL E.

    2000-04-01

    Under this effort, a new method for studying the single event upset (SEU) in microelectronics has been developed and demonstrated. Called TRIBICC, for Time Resolved Ion Beam Induced Charge Collection, this technique measures the transient charge-collection waveform from a single heavy-ion strike with a {minus}.03db bandwidth of 5 GHz. Bandwidth can be expanded up to 15 GHz (with 5 ps sampling windows) by using an FFT-based off-line waveform renormalization technique developed at Sandia. The theoretical time resolution of the digitized waveform is 24 ps with data re-normalization and 70 ps without re-normalization. To preserve the high bandwidth from IC to the digitizing oscilloscope, individual test structures are assembled in custom high-frequency fixtures. A leading-edge digitized waveform is stored with the corresponding ion beam position at each point in a two-dimensional raster scan. The resulting data cube contains a spatial charge distribution map of up to 4,096 traces of charge (Q) collected as a function of time. These two dimensional traces of Q(t) can cover a period as short as 5 ns with up to 1,024 points per trace. This tool overcomes limitations observed in previous multi-shot techniques due to the displacement damage effects of multiple ion strikes that changed the signal of interest during its measurement. This system is the first demonstration of a single-ion transient measurement capability coupled with spatial mapping of fast transients.

  8. Time domain para hydrogen induced polarization.

    PubMed

    Ratajczyk, Tomasz; Gutmann, Torsten; Dillenberger, Sonja; Abdulhussaein, Safaa; Frydel, Jaroslaw; Breitzke, Hergen; Bommerich, Ute; Trantzschel, Thomas; Bernarding, Johannes; Magusin, Pieter C M M; Buntkowsky, Gerd

    2012-01-01

    Para hydrogen induced polarization (PHIP) is a powerful hyperpolarization technique, which increases the NMR sensitivity by several orders of magnitude. However the hyperpolarized signal is created as an anti-phase signal, which necessitates high magnetic field homogeneity and spectral resolution in the conventional PHIP schemes. This hampers the application of PHIP enhancement in many fields, as for example in food science, materials science or MRI, where low B(0)-fields or low B(0)-homogeneity do decrease spectral resolution, leading to potential extinction if in-phase and anti-phase hyperpolarization signals cannot be resolved. Herein, we demonstrate that the echo sequence (45°-τ-180°-τ) enables the acquisition of low resolution PHIP enhanced liquid state NMR signals of phenylpropiolic acid derivatives and phenylacetylene at a low cost low-resolution 0.54 T spectrometer. As low field TD-spectrometers are commonly used in industry or biomedicine for the relaxometry of oil-water mixtures, food, nano-particles, or other systems, we compare two variants of para-hydrogen induced polarization with data-evaluation in the time domain (TD-PHIP). In both TD-ALTADENA and the TD-PASADENA strong spin echoes could be detected under conditions when usually no anti-phase signals can be measured due to the lack of resolution. The results suggest that the time-domain detection of PHIP-enhanced signals opens up new application areas for low-field PHIP-hyperpolarization, such as non-invasive compound detection or new contrast agents and biomarkers in low-field Magnetic Resonance Imaging (MRI). Finally, solid-state NMR calculations are presented, which show that the solid echo (90y-τ-90x-τ) version of the TD-ALTADENA experiment is able to convert up to 10% of the PHIP signal into visible magnetization.

  9. Selective attention to temporal features on nested time scales.

    PubMed

    Henry, Molly J; Herrmann, Björn; Obleser, Jonas

    2015-02-01

    Meaningful auditory stimuli such as speech and music often vary simultaneously along multiple time scales. Thus, listeners must selectively attend to, and selectively ignore, separate but intertwined temporal features. The current study aimed to identify and characterize the neural network specifically involved in this feature-selective attention to time. We used a novel paradigm where listeners judged either the duration or modulation rate of auditory stimuli, and in which the stimulation, working memory demands, response requirements, and task difficulty were held constant. A first analysis identified all brain regions where individual brain activation patterns were correlated with individual behavioral performance patterns, which thus supported temporal judgments generically. A second analysis then isolated those brain regions that specifically regulated selective attention to temporal features: Neural responses in a bilateral fronto-parietal network including insular cortex and basal ganglia decreased with degree of change of the attended temporal feature. Critically, response patterns in these regions were inverted when the task required selectively ignoring this feature. The results demonstrate how the neural analysis of complex acoustic stimuli with multiple temporal features depends on a fronto-parietal network that simultaneously regulates the selective gain for attended and ignored temporal features. © The Author 2013. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Method for production of sorghum hybrids with selected flowering times

    DOEpatents

    Mullet, John E.; Rooney, William L.

    2016-08-30

    Methods and composition for the production of sorghum hybrids with selected and different flowering times are provided. In accordance with the invention, a substantially continual and high-yield harvest of sorghum is provided. Improved methods of seed production are also provided.

  11. Resource Selection Using Execution and Queue Wait Time Predictions

    NASA Technical Reports Server (NTRS)

    Warren, Smith; Wong, Parkson; Biegel, Bryan A. (Technical Monitor)

    2002-01-01

    Computational grids provide users with many possible places to execute their applications. We wish to help users select where to run their applications by providing predictions of the execution times of applications on space shared parallel computers and predictions of when scheduling systems for such parallel computers will start applications. Our predictions are based on instance based learning techniques and simulations of scheduling algorithms. We find that our execution time prediction techniques have an average error of 37 percent of the execution times for trace data recorded from SGI Origins at NASA Ames Research Center and that this error is 67 percent lower than the error of user estimates. We also find that the error when predicting how long applications will wait in scheduling queues is 95 percent of mean queue wait times when using our execution time predictions and this is 57 percent lower than if we use user execution time estimates.

  12. A time domain frequency-selective multivariate Granger causality approach.

    PubMed

    Leistritz, Lutz; Witte, Herbert

    2016-08-01

    The investigation of effective connectivity is one of the major topics in computational neuroscience to understand the interaction between spatially distributed neuronal units of the brain. Thus, a wide variety of methods has been developed during the last decades to investigate functional and effective connectivity in multivariate systems. Their spectrum ranges from model-based to model-free approaches with a clear separation into time and frequency range methods. We present in this simulation study a novel time domain approach based on Granger's principle of predictability, which allows frequency-selective considerations of directed interactions. It is based on a comparison of prediction errors of multivariate autoregressive models fitted to systematically modified time series. These modifications are based on signal decompositions, which enable a targeted cancellation of specific signal components with specific spectral properties. Depending on the embedded signal decomposition method, a frequency-selective or data-driven signal-adaptive Granger Causality Index may be derived.

  13. Selecting Variables for the Time Domain Spectroscopic Survey

    NASA Astrophysics Data System (ADS)

    Morganson, Eric; TDSS; SDSS; Pan-STARRS1

    2014-01-01

    The Time Domain Spectroscopic Survey is an eBOSS subprogram that will obtain spectroscopy for 400,000 objects that vary more than 0.1 magnitudes. 100,000 of these objects will be unique to TDSS and 300,000 will be shared with other subprograms. We use a combination of Pan-STARRS1 and SDSS photometry to select a sample of variables that is 95% pure and 60% complete. This sample is obtained with three dimension Kernel Density Analysis. Our data and method are particularly effective at selecting long term variables, and more than 300,000 of our variables will be quasars.

  14. A new way to integrate selection when both demography and selection gradients vary over time

    PubMed Central

    HORVITZ, CAROL C.; COULSON, TIM; TULJAPURKAR, SHRIPAD; SCHEMSKE, DOUGLAS W.

    2013-01-01

    When both selection and demography vary over time, how can the long-run expected strength of selection on quantitative traits be measured? There are two basic steps in the proposed new analysis: one relates trait values to fitness components and the other relates fitness components to total fitness. We used one population projection matrix for each state of the environment together with a model of environmental dynamics, defining total fitness as the stochastic growth rate. We multiplied environment-specific, stage-specific mean-standardized selection gradients by environment-specific, stage-specific elasticities of the stochastic growth rate, summing over all relevant life history and environmental paths. Our two example traits were floral tube length in a rainforest herb and the timing of birth in Red Deer. For each species, we constructed two models of environmental dynamics, including one based on historical climate records. We found that total integrated selection, as well as the relative contributions of life-history pathways and environments, varied with environmental dynamics. Temporal patterning in the environment has selective consequences. Linking models of environmental change to relevant short term data on demography and selection may permit estimation of the force of selection over the long-term in variable environments. PMID:25089083

  15. Quantum mechanics of time travel through post-selected teleportation

    NASA Astrophysics Data System (ADS)

    Lloyd, Seth; Maccone, Lorenzo; Garcia-Patron, Raul; Giovannetti, Vittorio; Shikano, Yutaka

    2011-07-01

    This paper discusses the quantum mechanics of closed-timelike curves (CTCs) and of other potential methods for time travel. We analyze a specific proposal for such quantum time travel, the quantum description of CTCs based on post-selected teleportation (P-CTCs). We compare the theory of P-CTCs to previously proposed quantum theories of time travel: the theory is inequivalent to Deutsch’s theory of CTCs, but it is consistent with path-integral approaches (which are the best suited for analyzing quantum-field theory in curved space-time). We derive the dynamical equations that a chronology-respecting system interacting with a CTC will experience. We discuss the possibility of time travel in the absence of general-relativistic closed-timelike curves, and investigate the implications of P-CTCs for enhancing the power of computation.

  16. Epistasis-Induced Evolutionary Plateaus in Selection Responses.

    PubMed

    Le Rouzic, Arnaud; Álvarez-Castro, José M

    2016-12-01

    Understanding and predicting evolution is a central challenge in both population and quantitative genetics. The amount of genetic variance for quantitative traits available in a population conditions the particular way in which this population will (or will not) evolve under natural or artificial selection. Here, we explore the potential of gene-gene interactions (epistasis) to induce evolutionary plateaus at which evolutionary change virtually collapses for a number of generations, followed by the release of previously cryptic genetic variation. First, we demonstrate theoretically that a wide range of epistatic interactions has the potential to generate temporary decelerations in the course of response to selection. Second, we perform simulations to show that such microevolutionary plateaus may occur in selection responses under empirically based assumptions. Finally, we show that such events can be traced in artificial selection experiments, thus providing further empirical evidence for this phenomenon.

  17. Real-time fiber selection using the Wii remote

    NASA Astrophysics Data System (ADS)

    Klein, Jan; Scholl, Mike; Köhn, Alexander; Hahn, Horst K.

    2010-02-01

    In the last few years, fiber tracking tools have become popular in clinical contexts, e.g., for pre- and intraoperative neurosurgical planning. The efficient, intuitive, and reproducible selection of fiber bundles still constitutes one of the main issues. In this paper, we present a framework for a real-time selection of axonal fiber bundles using a Wii remote control, a wireless controller for Nintendo's gaming console. It enables the user to select fiber bundles without any other input devices. To achieve a smooth interaction, we propose a novel spacepartitioning data structure for efficient 3D range queries in a data set consisting of precomputed fibers. The data structure which is adapted to the special geometry of fiber tracts allows for queries that are many times faster compared with previous state-of-the-art approaches. In order to extract reliably fibers for further processing, e.g., for quantification purposes or comparisons with preoperatively tracked fibers, we developed an expectationmaximization clustering algorithm that can refine the range queries. Our initial experiments have shown that white matter fiber bundles can be reliably selected within a few seconds by the Wii, which has been placed in a sterile plastic bag to simulate usage under surgical conditions.

  18. The time course of attention: selection is transient.

    PubMed

    Wilschut, Anna; Theeuwes, Jan; Olivers, Christian N L

    2011-01-01

    The time course of attention has often been investigated using a spatial cuing task. However, attention likely consists of multiple components, such as selectivity (resolving competition) and orienting (spatial shifting). Here we sought to investigate the time course of the selective aspect of attention, using a cuing task that did not require spatial shifting. In several experiments, targets were always presented at central fixation, and were preceded by a cue at different cue-target intervals. The selection component of attention was investigated by manipulating the presence of distractors. Regardless of the presence of distractors, an initial rapid performance enhancement was found that reached its maximum at around 100 ms post cue onset. Subsequently, when the target was the only item in the display, performance was sustained, but when the target was accompanied by irrelevant distractor items, performance declined. This temporal pattern matches closely with the transient attention response that has been found in spatial cuing studies, and shows that the selectivity aspect of attention is transient.

  19. Selective excitation of vibrational states by shaping of light-induced potentials

    PubMed

    Sola; Chang; Santamaria; Malinovsky; Krause

    2000-11-13

    In this Letter we describe a method for population transfer using intense, ultrafast laser pulses. The selectivity is accomplished by careful shaping of light-induced potentials (LIPs). Creation and control of the LIPs is accomplished by choosing pairs of pulses with proper frequency detunings and time delays. As an example, selective population transfer is demonstrated for a three-state model of the sodium dimer.

  20. THz-Pulse-Induced Selective Catalytic CO Oxidation on Ru.

    PubMed

    LaRue, Jerry L; Katayama, Tetsuo; Lindenberg, Aaron; Fisher, Alan S; Öström, Henrik; Nilsson, Anders; Ogasawara, Hirohito

    2015-07-17

    We demonstrate the use of intense, quasi-half-cycle THz pulses, with an associated electric field component comparable to intramolecular electric fields, to direct the reaction coordinate of a chemical reaction by stimulating the nuclear motions of the reactants. Using a strong electric field from a THz pulse generated via coherent transition radiation from an ultrashort electron bunch, we present evidence that CO oxidation on Ru(0001) is selectively induced, while not promoting the thermally induced CO desorption process. The reaction is initiated by the motion of the O atoms on the surface driven by the electric field component of the THz pulse, rather than thermal heating of the surface.

  1. GPS time transfer with implementation of selective availability

    NASA Technical Reports Server (NTRS)

    Allan, David W.; Granveaud, Michel P.; Klepczynski, William J.; Lewandowski, Wlodzimierz W.

    1990-01-01

    The international community of time metrology is facing a major challenge with the Selective Availability (SA) degradation of GPS satellite signals. At present there are 6 Block 1 satellites and 8 Block 2 satellites operating. According to the policy of the U.S. Department of Defence the Block 1 satellite signals will not be degraded, but these satellites are old with a finite life. The Block 2 satellites, which have all been launched since 1988, were subject to Selective Availability from March 25, 1990. The effect of SA should be to limit precision to about 100 meters for navigation and 167 ns for timing. A study was conducted in order to understand the nature of the actual introduced degradation, and to elaborate the means of removing the effects of this degradation on time transfer. This study concerns the time extraction from GPS satellites at NIST, USNO and Paris Observatory, and the comparison of atomic clocks between these laboratories by common view approach. The results show that when using the data taken over several days the time extraction can be achieved with uncertainty of a few tens of nanoseconds, while strict common-view has removed entirely the effects of SA during the periods under study.

  2. THE TIME DOMAIN SPECTROSCOPIC SURVEY: VARIABLE SELECTION AND ANTICIPATED RESULTS

    SciTech Connect

    Morganson, Eric; Green, Paul J.; Anderson, Scott F.; Ruan, John J.; Myers, Adam D.; Eracleous, Michael; Brandt, William Nielsen; Kelly, Brandon; Badenes, Carlos; Bañados, Eduardo; Blanton, Michael R.; Bershady, Matthew A.; Borissova, Jura; Burgett, William S.; Chambers, Kenneth; and others

    2015-06-20

    We present the selection algorithm and anticipated results for the Time Domain Spectroscopic Survey (TDSS). TDSS is an Sloan Digital Sky Survey (SDSS)-IV Extended Baryon Oscillation Spectroscopic Survey (eBOSS) subproject that will provide initial identification spectra of approximately 220,000 luminosity-variable objects (variable stars and active galactic nuclei across 7500 deg{sup 2} selected from a combination of SDSS and multi-epoch Pan-STARRS1 photometry. TDSS will be the largest spectroscopic survey to explicitly target variable objects, avoiding pre-selection on the basis of colors or detailed modeling of specific variability characteristics. Kernel Density Estimate analysis of our target population performed on SDSS Stripe 82 data suggests our target sample will be 95% pure (meaning 95% of objects we select have genuine luminosity variability of a few magnitudes or more). Our final spectroscopic sample will contain roughly 135,000 quasars and 85,000 stellar variables, approximately 4000 of which will be RR Lyrae stars which may be used as outer Milky Way probes. The variability-selected quasar population has a smoother redshift distribution than a color-selected sample, and variability measurements similar to those we develop here may be used to make more uniform quasar samples in large surveys. The stellar variable targets are distributed fairly uniformly across color space, indicating that TDSS will obtain spectra for a wide variety of stellar variables including pulsating variables, stars with significant chromospheric activity, cataclysmic variables, and eclipsing binaries. TDSS will serve as a pathfinder mission to identify and characterize the multitude of variable objects that will be detected photometrically in even larger variability surveys such as Large Synoptic Survey Telescope.

  3. The Time Domain Spectroscopic Survey: Variable Selection and Anticipated Results

    NASA Astrophysics Data System (ADS)

    Morganson, Eric; Green, Paul J.; Anderson, Scott F.; Ruan, John J.; Myers, Adam D.; Eracleous, Michael; Kelly, Brandon; Badenes, Carlos; Bañados, Eduardo; Blanton, Michael R.; Bershady, Matthew A.; Borissova, Jura; Brandt, William Nielsen; Burgett, William S.; Chambers, Kenneth; Draper, Peter W.; Davenport, James R. A.; Flewelling, Heather; Garnavich, Peter; Hawley, Suzanne L.; Hodapp, Klaus W.; Isler, Jedidah C.; Kaiser, Nick; Kinemuchi, Karen; Kudritzki, Rolf P.; Metcalfe, Nigel; Morgan, Jeffrey S.; Pâris, Isabelle; Parvizi, Mahmoud; Poleski, Radosław; Price, Paul A.; Salvato, Mara; Shanks, Tom; Schlafly, Eddie F.; Schneider, Donald P.; Shen, Yue; Stassun, Keivan; Tonry, John T.; Walter, Fabian; Waters, Chris Z.

    2015-06-01

    We present the selection algorithm and anticipated results for the Time Domain Spectroscopic Survey (TDSS). TDSS is an Sloan Digital Sky Survey (SDSS)-IV Extended Baryon Oscillation Spectroscopic Survey (eBOSS) subproject that will provide initial identification spectra of approximately 220,000 luminosity-variable objects (variable stars and active galactic nuclei across 7500 deg2 selected from a combination of SDSS and multi-epoch Pan-STARRS1 photometry. TDSS will be the largest spectroscopic survey to explicitly target variable objects, avoiding pre-selection on the basis of colors or detailed modeling of specific variability characteristics. Kernel Density Estimate analysis of our target population performed on SDSS Stripe 82 data suggests our target sample will be 95% pure (meaning 95% of objects we select have genuine luminosity variability of a few magnitudes or more). Our final spectroscopic sample will contain roughly 135,000 quasars and 85,000 stellar variables, approximately 4000 of which will be RR Lyrae stars which may be used as outer Milky Way probes. The variability-selected quasar population has a smoother redshift distribution than a color-selected sample, and variability measurements similar to those we develop here may be used to make more uniform quasar samples in large surveys. The stellar variable targets are distributed fairly uniformly across color space, indicating that TDSS will obtain spectra for a wide variety of stellar variables including pulsating variables, stars with significant chromospheric activity, cataclysmic variables, and eclipsing binaries. TDSS will serve as a pathfinder mission to identify and characterize the multitude of variable objects that will be detected photometrically in even larger variability surveys such as Large Synoptic Survey Telescope.

  4. Cuprous oxide nanoparticles selectively induce apoptosis of tumor cells

    PubMed Central

    Wang, Ye; Zi, Xiao-Yuan; Su, Juan; Zhang, Hong-Xia; Zhang, Xin-Rong; Zhu, Hai-Ying; Li, Jian-Xiu; Yin, Meng; Yang, Feng; Hu, Yi-Ping

    2012-01-01

    In the rapid development of nanoscience and nanotechnology, many researchers have discovered that metal oxide nanoparticles have very useful pharmacological effects. Cuprous oxide nanoparticles (CONPs) can selectively induce apoptosis and suppress the proliferation of tumor cells, showing great potential as a clinical cancer therapy. Treatment with CONPs caused a G1/G0 cell cycle arrest in tumor cells. Furthermore, CONPs enclosed in vesicles entered, or were taken up by mitochondria, which damaged their membranes, thereby inducing apoptosis. CONPs can also produce reactive oxygen species (ROS) and initiate lipid peroxidation of the liposomal membrane, thereby regulating many signaling pathways and influencing the vital movements of cells. Our results demonstrate that CONPs have selective cytotoxicity towards tumor cells, and indicate that CONPs might be a potential nanomedicine for cancer therapy. PMID:22679374

  5. Transmit alternate laser selection with time diversity for FSO communications.

    PubMed

    García-Zambrana, Antonio; Boluda-Ruiz, Rubén; Castillo-Vázquez, Carmen; Castillo-Vázquez, Beatriz

    2014-10-06

    In this paper, a new transmit alternate laser selection (TALS) scheme for FSO communication systems using intensity modulation and direct detection (IM/DD) over atmospheric turbulence and misalignment fading channels is presented when limited time diversity is available in the turbulent channel. Assuming channel state information (CSI) at the transmitter and receiver and a time diversity order (TDO) limited, we propose the transmit diversity technique based on the rotating selection of TDO out of the available L lasers corresponding to the optical paths with greater values of scintillation. Implementing repetition coding with blocks of TDO information bits, each information bit will be retransmitted TDO times using the TDO largest order statistics in an alternating way. Closed-form asymptotic bit error-rate (BER) expressions are derived when the irradiance of the transmitted optical beam is susceptible to moderate-to-strong turbulence conditions, following a gamma-gamma (GG) distribution, and pointing error effects, following a misalignment fading model where the effect of beam width, detector size and jitter variance is considered. Fully exploiting the potential time-diversity TDO available in the turbulent channel, a significant diversity gain is achieved, providing a diversity order of (2L + 1 - TDO)TDO/2.

  6. Selectively fired, tubing-conveyed perforating guns save rig time

    SciTech Connect

    Snider, P.M. ); Bond, P.L. )

    1993-07-19

    Selective firing of tubing-conveyed perforating (TCP) guns during drill stem tests (DSTs) added flexibility and saved costs for Marathon Oil Co. As an example, in the Garland field in Wyoming, the guns allowed perforating multiple zones in one trip. This saved 1 1/2--2 days/well in rig time and $25,000--30,000/well in electric wire line and DST tool charges. For international offshore operations, savings of $200,000/well appear possible. Savings result not only from perforating multiple zones, but also from arbitrarily setting firing patterns with or without zone isolation. The paper describes the testing of equipment, the design of the guns, firing heads, crossover assembly, pressure isolation sub, control line, and select-fire sub, and applications for the guns.

  7. Visual analytics for model selection in time series analysis.

    PubMed

    Bögl, Markus; Aigner, Wolfgang; Filzmoser, Peter; Lammarsch, Tim; Miksch, Silvia; Rind, Alexander

    2013-12-01

    Model selection in time series analysis is a challenging task for domain experts in many application areas such as epidemiology, economy, or environmental sciences. The methodology used for this task demands a close combination of human judgement and automated computation. However, statistical software tools do not adequately support this combination through interactive visual interfaces. We propose a Visual Analytics process to guide domain experts in this task. For this purpose, we developed the TiMoVA prototype that implements this process based on user stories and iterative expert feedback on user experience. The prototype was evaluated by usage scenarios with an example dataset from epidemiology and interviews with two external domain experts in statistics. The insights from the experts' feedback and the usage scenarios show that TiMoVA is able to support domain experts in model selection tasks through interactive visual interfaces with short feedback cycles.

  8. Light-inducible pigmentation in Portulaca callus; selection of a high betalain producing cell line.

    PubMed

    Kishima, Y; Nozaki, K; Akashi, R; Adachi, T

    1991-09-01

    We have established a unique betalain pigmentation system in callus cultures that originated from seedlings of Portulaca sp. 'Jewel'. Within three different 'Jewel' lines examined, one line (JR) was clearly superior with regard to callus growth rate and pigment formation. Furthermore, after ten cycles of selection of deeply colored callus patches, the selected clones contained on an average four times the amount of betalain as compared to the non-selected mother line. The colorization was induced by light, but disappeared in the dark. Pigment synthesis was detectable within 30 h after irradiation and showed positive correlation with irradiation periods.

  9. Laser-induced selective copper plating of polypropylene surface

    NASA Astrophysics Data System (ADS)

    Ratautas, K.; Gedvilas, M.; Stankevičiene, I.; JagminienÄ--, A.; Norkus, E.; Li Pira, N.; Sinopoli, S.; Emanuele, U.; Račiukaitis, G.

    2016-03-01

    Laser writing for selective plating of electro-conductive lines for electronics has several significant advantages, compared to conventional printed circuit board technology. Firstly, this method is faster and cheaper at the prototyping stage. Secondly, material consumption is reduced, because it works selectively. However, the biggest merit of this method is potentiality to produce moulded interconnect device, enabling to create electronics on complex 3D surfaces, thus saving space, materials and cost of production. There are two basic techniques of laser writing for selective plating on plastics: the laser-induced selective activation (LISA) and laser direct structuring (LDS). In the LISA method, pure plastics without any dopant (filler) can be used. In the LDS method, special fillers are mixed in the polymer matrix. These fillers are activated during laser writing process, and, in the next processing step, the laser modified area can be selectively plated with metals. In this work, both methods of the laser writing for the selective plating of polymers were investigated and compared. For LDS approach, new material: polypropylene with carbon-based additives was tested using picosecond and nanosecond laser pulses. Different laser processing parameters (laser pulse energy, scanning speed, the number of scans, pulse durations, wavelength and overlapping of scanned lines) were applied in order to find out the optimal regime of activation. Areal selectivity tests showed a high plating resolution. The narrowest width of a copper-plated line was less than 23 μm. Finally, our material was applied to the prototype of the electronic circuit board on a 2D surface.

  10. Emotion and Time Perception: Effects of Film-Induced Mood

    PubMed Central

    Droit-Volet, Sylvie; Fayolle, Sophie L.; Gil, Sandrine

    2011-01-01

    Previous research into emotion and time perception has been designed to study the time perception of emotional events themselves (e.g., facial expression). Our aim was to investigate the effect of emotions per se on the subsequent time judgment of a neutral, non-affective event. In the present study, the participants were presented with films inducing a specific mood and were subsequently given a temporal bisection task. More precisely, the participants were given two temporal bisection tasks, one before and the other after viewing the emotional film. Three emotional films were tested: one eliciting fear, another sadness, and a neutral control film. In addition, the direct mood experience was assessed using the Brief Mood Introspective Scale that was administered to the participants at the beginning and the end of the session. The results showed that the perception of time did not change after viewing either the neutral control films or the sad films although the participants reported being sadder and less aroused after than before watching the sad film clips. In contrast, the stimulus durations were judged longer after than before viewing the frightening films that were judged to increase the emotion of fear and arousal level. In combination with findings from previous studies, our data suggest that the selective lengthening effect after watching frightening films was mediated by an effect of arousal on the speed of the internal clock system. PMID:21886610

  11. Time perception, attention, and memory: a selective review.

    PubMed

    Block, Richard A; Gruber, Ronald P

    2014-06-01

    This article provides a selective review of time perception research, mainly focusing on the authors' research. Aspects of psychological time include simultaneity, successiveness, temporal order, and duration judgments. In contrast to findings at interstimulus intervals or durations less than 3.0-5.0 s, there is little evidence for an "across-senses" effect of perceptual modality (visual vs. auditory) at longer intervals or durations. In addition, the flow of time (events) is a pervasive perceptual illusion, and we review evidence on that. Some temporal information is encoded All rights reserved. relatively automatically into memory: People can judge time-related attributes such as recency, frequency, temporal order, and duration of events. Duration judgments in prospective and retrospective paradigms reveal differences between them, as well as variables that moderate the processes involved. An attentional-gate model is needed to account for prospective judgments, and a contextual-change model is needed to account for retrospective judgments. Copyright © 2013 Elsevier B.V. All rights reserved.

  12. Selective equal-spin Andreev reflections induced by Majorana fermions.

    PubMed

    He, James J; Ng, T K; Lee, Patrick A; Law, K T

    2014-01-24

    In this work, we find that Majorana fermions induce selective equal spin Andreev reflections (SESARs), in which incoming electrons with certain spin polarization in the lead are reflected as counterpropagating holes with the same spin. The spin polarization direction of the electrons of this Andreev reflected channel is selected by the Majorana fermions. Moreover, electrons with opposite spin polarization are always reflected as electrons with unchanged spin. As a result, the charge current in the lead is spin polarized. Therefore, a topological superconductor which supports Majorana fermions can be used as a novel device to create fully spin-polarized currents in paramagnetic leads. We point out that SESARs can also be used to detect Majorana fermions in topological superconductors.

  13. Magnetically induced spreading and pattern selection in thin ferrofluid drops.

    PubMed

    Chen, Ching-Yao; Wu, W-L; Miranda, José A

    2010-11-01

    We report an experimental study of a fingering pattern formation which occurs during the spreading of an immiscible thin ferrofluid drop subjected to a radial magnetic field. Our results indicate that this ferrohydrodynamic system works as a magnetic analog of conventional spin coating, where centrifugal driving is replaced with a magnetic body force induced by the radial applied field. In this context, a magnetically tunable pattern selection mechanism is proposed in which the shape and number of the arising fingered structures can be properly controlled.

  14. Continuous time limits of the utterance selection model

    NASA Astrophysics Data System (ADS)

    Michaud, Jérôme

    2017-02-01

    In this paper we derive alternative continuous time limits of the utterance selection model (USM) for language change [G. J. Baxter et al., Phys. Rev. E 73, 046118 (2006), 10.1103/PhysRevE.73.046118]. This is motivated by the fact that the Fokker-Planck continuous time limit derived in the original version of the USM is only valid for a small range of parameters. We investigate the consequences of relaxing these constraints on parameters. Using the normal approximation of the multinomial approximation, we derive a continuous time limit of the USM in the form of a weak-noise stochastic differential equation. We argue that this weak noise, not captured by the Kramers-Moyal expansion, cannot be neglected. We then propose a coarse-graining procedure, which takes the form of a stochastic version of the heterogeneous mean field approximation. This approximation groups the behavior of nodes of the same degree, reducing the complexity of the problem. With the help of this approximation, we study in detail two simple families of networks: the regular networks and the star-shaped networks. The analysis reveals and quantifies a finite-size effect of the dynamics. If we increase the size of the network by keeping all the other parameters constant, we transition from a state where conventions emerge to a state where no convention emerges. Furthermore, we show that the degree of a node acts as a time scale. For heterogeneous networks such as star-shaped networks, the time scale difference can become very large, leading to a noisier behavior of highly connected nodes.

  15. Continuous time limits of the utterance selection model.

    PubMed

    Michaud, Jérôme

    2017-02-01

    In this paper we derive alternative continuous time limits of the utterance selection model (USM) for language change [G. J. Baxter et al., Phys. Rev. E 73, 046118 (2006)PLEEE81539-375510.1103/PhysRevE.73.046118]. This is motivated by the fact that the Fokker-Planck continuous time limit derived in the original version of the USM is only valid for a small range of parameters. We investigate the consequences of relaxing these constraints on parameters. Using the normal approximation of the multinomial approximation, we derive a continuous time limit of the USM in the form of a weak-noise stochastic differential equation. We argue that this weak noise, not captured by the Kramers-Moyal expansion, cannot be neglected. We then propose a coarse-graining procedure, which takes the form of a stochastic version of the heterogeneous mean field approximation. This approximation groups the behavior of nodes of the same degree, reducing the complexity of the problem. With the help of this approximation, we study in detail two simple families of networks: the regular networks and the star-shaped networks. The analysis reveals and quantifies a finite-size effect of the dynamics. If we increase the size of the network by keeping all the other parameters constant, we transition from a state where conventions emerge to a state where no convention emerges. Furthermore, we show that the degree of a node acts as a time scale. For heterogeneous networks such as star-shaped networks, the time scale difference can become very large, leading to a noisier behavior of highly connected nodes.

  16. Real-time flavour tagging selection in ATLAS

    NASA Astrophysics Data System (ADS)

    Bertella, Claudia

    2015-12-01

    In high-energy physics experiments, online selection is crucial to the identification of the few interesting collisions from the large data volume processed. In the overall ATLAS trigger strategy, b-jet triggers are designed to identify heavy-flavor content in real-time and, in particular, provide the only option to efficiently record events with fully hadronic final states containing b-jets. In doing so, two different, but related, challenges are faced. The physics goal is to optimise as far as possible the rejection for light jets from QCD processes, while retaining a high efficiency on selecting jets from beauty, while maintaining affordable trigger rates without raising jet energy thresholds. This poses a challenging computing task, as charged tracks and their corresponding vertices must be reconstructed and analysed for each jet above the desired threshold, regardless of the increasingly harsh pile-up conditions. The performance of b-jet triggers during the LHC Run I data-taking campaigns is presented, together with an overview of the new online b-tagging strategy and algorithms, designed to face the above mentioned challenges, which will be adopted during Run II.

  17. Selective endosomal microautophagy is starvation-inducible in Drosophila

    PubMed Central

    Mukherjee, Anindita; Patel, Bindi; Koga, Hiroshi; Cuervo, Ana Maria; Jenny, Andreas

    2016-01-01

    ABSTRACT Autophagy delivers cytosolic components to lysosomes for degradation and is thus essential for cellular homeostasis and to cope with different stressors. As such, autophagy counteracts various human diseases and its reduction leads to aging-like phenotypes. Macroautophagy (MA) can selectively degrade organelles or aggregated proteins, whereas selective degradation of single proteins has only been described for chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI). These 2 autophagic pathways are specific for proteins containing KFERQ-related targeting motifs. Using a KFERQ-tagged fluorescent biosensor, we have identified an eMI-like pathway in Drosophila melanogaster. We show that this biosensor localizes to late endosomes and lysosomes upon prolonged starvation in a KFERQ- and Hsc70-4- dependent manner. Furthermore, fly eMI requires endosomal multivesicular body formation mediated by ESCRT complex components. Importantly, induction of Drosophila eMI requires longer starvation than the induction of MA and is independent of the critical MA genes atg5, atg7, and atg12. Furthermore, inhibition of Tor signaling induces eMI in flies under nutrient rich conditions, and, as eMI in Drosophila also requires atg1 and atg13, our data suggest that these genes may have a novel, additional role in regulating eMI in flies. Overall, our data provide the first evidence for a novel, starvation-inducible, catabolic process resembling endosomal microautophagy in the Drosophila fat body. PMID:27487474

  18. Selective endosomal microautophagy is starvation-inducible in Drosophila.

    PubMed

    Mukherjee, Anindita; Patel, Bindi; Koga, Hiroshi; Cuervo, Ana Maria; Jenny, Andreas

    2016-11-01

    Autophagy delivers cytosolic components to lysosomes for degradation and is thus essential for cellular homeostasis and to cope with different stressors. As such, autophagy counteracts various human diseases and its reduction leads to aging-like phenotypes. Macroautophagy (MA) can selectively degrade organelles or aggregated proteins, whereas selective degradation of single proteins has only been described for chaperone-mediated autophagy (CMA) and endosomal microautophagy (eMI). These 2 autophagic pathways are specific for proteins containing KFERQ-related targeting motifs. Using a KFERQ-tagged fluorescent biosensor, we have identified an eMI-like pathway in Drosophila melanogaster. We show that this biosensor localizes to late endosomes and lysosomes upon prolonged starvation in a KFERQ- and Hsc70-4- dependent manner. Furthermore, fly eMI requires endosomal multivesicular body formation mediated by ESCRT complex components. Importantly, induction of Drosophila eMI requires longer starvation than the induction of MA and is independent of the critical MA genes atg5, atg7, and atg12. Furthermore, inhibition of Tor signaling induces eMI in flies under nutrient rich conditions, and, as eMI in Drosophila also requires atg1 and atg13, our data suggest that these genes may have a novel, additional role in regulating eMI in flies. Overall, our data provide the first evidence for a novel, starvation-inducible, catabolic process resembling endosomal microautophagy in the Drosophila fat body.

  19. Human-induced evolution caused by unnatural selection through harvest of wild animals.

    PubMed

    Allendorf, Fred W; Hard, Jeffrey J

    2009-06-16

    Human harvest of phenotypically desirable animals from wild populations imposes selection that can reduce the frequencies of those desirable phenotypes. Hunting and fishing contrast with agricultural and aquacultural practices in which the most desirable animals are typically bred with the specific goal of increasing the frequency of desirable phenotypes. We consider the potential effects of harvest on the genetics and sustainability of wild populations. We also consider how harvesting could affect the mating system and thereby modify sexual selection in a way that might affect recruitment. Determining whether phenotypic changes in harvested populations are due to evolution, rather than phenotypic plasticity or environmental variation, has been problematic. Nevertheless, it is likely that some undesirable changes observed over time in exploited populations (e.g., reduced body size, earlier sexual maturity, reduced antler size, etc.) are due to selection against desirable phenotypes-a process we call "unnatural" selection. Evolution brought about by human harvest might greatly increase the time required for over-harvested populations to recover once harvest is curtailed because harvesting often creates strong selection differentials, whereas curtailing harvest will often result in less intense selection in the opposing direction. We strongly encourage those responsible for managing harvested wild populations to take into account possible selective effects of harvest management and to implement monitoring programs to detect exploitation-induced selection before it seriously impacts viability.

  20. Human-induced evolution caused by unnatural selection through harvest of wild animals

    PubMed Central

    Allendorf, Fred W.; Hard, Jeffrey J.

    2009-01-01

    Human harvest of phenotypically desirable animals from wild populations imposes selection that can reduce the frequencies of those desirable phenotypes. Hunting and fishing contrast with agricultural and aquacultural practices in which the most desirable animals are typically bred with the specific goal of increasing the frequency of desirable phenotypes. We consider the potential effects of harvest on the genetics and sustainability of wild populations. We also consider how harvesting could affect the mating system and thereby modify sexual selection in a way that might affect recruitment. Determining whether phenotypic changes in harvested populations are due to evolution, rather than phenotypic plasticity or environmental variation, has been problematic. Nevertheless, it is likely that some undesirable changes observed over time in exploited populations (e.g., reduced body size, earlier sexual maturity, reduced antler size, etc.) are due to selection against desirable phenotypes—a process we call “unnatural” selection. Evolution brought about by human harvest might greatly increase the time required for over-harvested populations to recover once harvest is curtailed because harvesting often creates strong selection differentials, whereas curtailing harvest will often result in less intense selection in the opposing direction. We strongly encourage those responsible for managing harvested wild populations to take into account possible selective effects of harvest management and to implement monitoring programs to detect exploitation-induced selection before it seriously impacts viability. PMID:19528656

  1. Selective Induced Altered Coccidians to Immunize and Prevent Enteritis

    PubMed Central

    2016-01-01

    Microbiomic flora in digestive tract is pivotal to the state of our health and disease. Antibiotics affect GI, control composition of microbiome, and shift equilibrium from health into disease status. Coccidiosis causes gastrointestinal inflammation. Antibiotic additives contaminate animal products and enter food chain, consumed by humans with possible allergic, antibiotic resistance and enigmatic side effects. Purposed study induced nonpathogenic, immunogenic organisms to protect against disease and abolish antibiotics' use in food animals and side effects in man. Diverse species of Coccidia were used as model. Immature organisms were treated with serial purification procedure prior to developmental stages to obtain altered strains. Chicks received oral gavage immunized with serial low doses of normal or altered organisms or sham treatment and were challenged with high infective normal organisms to compare pathogenicity and immunogenicity. Mature induced altered forms of E. tenella and E. necatrix lacked developmental stage of “sporocysts” and contained free sporozoites. In contrast, E. maxima progressed to normal forms or did not mature at all. Animals that received altered forms were considerably protected with higher weight gain and antibody titers against challenge infection compared to those that received normal organisms (p < 0.05). This is the first report to induce selected protective altered organisms for possible preventive measures to minimize antibiotic use in food animals. PMID:27721824

  2. Selective use of a reserved mechanism for inducing calcium oscillations.

    PubMed

    Ma, Chun Yan; Chen, Chun Ying; Cui, Zong Jie

    2004-12-01

    Concentration-dependent transformation of hormone- and neurotransmitter-induced calcium oscillation is a common phenomenon in diverse types of cells especially of the secretory type. The rodent submandibular acinar cells are an exception to this rule, which show elevated plateau increase in intracellular calcium under all stimulatory concentrations of both norepinephrine and acetylcholine. However, under depolarized state this cell type could also show a variation of periodic calcium changes. This reserved mechanism of calcium oscillation is jump-started by depolarization only with muscarinic cholinergic stimulation, but not with adrenergic stimulation. This latter effect is attributable to alpha receptor activation, not due to simultaneous activation of alpha and beta receptors, with beta receptor activation only serving to enhance the magnitude. These data suggest that this reserved mechanism for inducing calcium oscillation can be selectively used only by specific receptor-signaling pathways, and may therefore partly explain the long-known differences between secretion induced by sympathetic and parasympathetic stimulation in the submandibular gland.

  3. Dopamine selectively sensitizes dopaminergic neurons to rotenone-induced apoptosis.

    PubMed

    Ahmadi, Ferogh A; Grammatopoulos, Tom N; Poczobutt, Andy M; Jones, Susan M; Snell, Laurence D; Das, Mita; Zawada, W Michael

    2008-05-01

    Among various types of neurons affected in Parkinson's disease, dopamine (DA) neurons of the substantia nigra undergo the most pronounced degeneration. Products of DA oxidation and consequent cellular damage have been hypothesized to contribute to neuronal death. To examine whether elevated intracellular DA will selectively predispose the dopaminergic subpopulation of nigral neurons to damage by an oxidative insult, we first cultured rat primary mesencephalic cells in the presence of rotenone to elevate reactive oxygen species. Although MAP2(+) neurons were more sensitive to rotenone-induced toxicity than type 1 astrocytes, rotenone affected equally both DA (TH(+)) neurons and MAP2(+) neurons. In contrast, when intracellular DA concentration was elevated, DA neurons became selectively sensitized to rotenone. Raising intracellular DA levels in primary DA neurons resulted in dopaminergic neuron death in the presence of subtoxic concentrations of rotenone. Furthermore, mitochondrial superoxide dismutase mimetic, manganese (III) meso-tetrakis (4-benzoic acid) porphyrin, blocked activation of caspase-3, and consequent cell death. Our results demonstrate that an inhibitor of mitochondrial complex I and increased cytosolic DA may cooperatively lead to conditions of elevated oxidative stress and thereby promote selective demise of dopaminergic neurons.

  4. Inducing self-selected human engagement in robotic locomotion training.

    PubMed

    Collins, Steven H; Jackson, Rachel W

    2013-06-01

    Stroke leads to severe mobility impairments for millions of individuals each year. Functional outcomes can be improved through manual treadmill therapy, but high costs limit patient exposure and, thereby, outcomes. Robotic gait training could increase the viable duration and frequency of training sessions, but robotic approaches employed thus far have been less effective than manual therapy. These shortcomings may relate to subconscious energy-minimizing drives, which might cause patients to engage less actively in therapy when provided with corrective robotic assistance. We have devised a new method for gait rehabilitation that harnesses, rather than fights, least-effort tendencies. Therapeutic goals, such as increased use of the paretic limb, are made easier than the patient's nominal gait through selective assistance from a robotic platform. We performed a pilot test on a healthy subject (N = 1) in which altered self-selected stride length was induced using a tethered robotic ankle-foot orthosis. The subject first walked on a treadmill while wearing the orthosis with and without assistance at unaltered and voluntarily altered stride length. Voluntarily increasing stride length by 5% increased metabolic energy cost by 4%. Robotic assistance decreased energy cost at both unaltered and voluntarily increased stride lengths, by 6% and 8% respectively. We then performed a test in which the robotic system continually monitored stride length and provided more assistance if the subject's stride length approached a target increase. This adaptive assistance protocol caused the subject to slowly adjust their gait patterns towards the target, leading to a 4% increase in stride length. Metabolic energy consumption was simultaneously reduced by 5%. These results suggest that selective-assistance protocols based on targets relevant to rehabilitation might lead patients to self-select desirable gait patterns during robotic gait training sessions, possibly facilitating better

  5. Non-gated laser-induced breakdown spectroscopy in bulk water by position-selective detection

    SciTech Connect

    Tian, Ye; Xue, Boyang; Song, Jiaojian; Lu, Yuan; Zheng, Ronger

    2015-09-14

    Temporal and spatial evolutions of the laser-induced plasma in bulk water are investigated using fast imaging and emission spectroscopic techniques. By tightly focusing a single-pulse nanosecond Nd: YAG laser beam into the bulk water, we generate a strongly expanded plasma with high reproducibility. Such a strong expanding plasma enables us to obtain well-resolved spectral lines by means of position-selective detection; hence, the time-gated detector becomes abdicable. The present results suggest not only a possible non-gated approach for underwater laser-induced breakdown spectroscopy but also give an insight into the plasma generation and expansion in bulk water.

  6. Chiral-selective chemistry induced by spin-polarized secondary electrons from a magnetic substrate.

    PubMed

    Rosenberg, R A; Abu Haija, M; Ryan, P J

    2008-10-24

    We demonstrate for the first time that low-energy spin-polarized secondary electrons, produced by irradiation of a magnetic substrate, can induce chiral-selective chemistry. Our approach was to perform detailed measurements of the reaction rate for x-ray induced, secondary electron photolysis of a model chiral compound, (R)- or (S)-2-butanol, adsorbed on a magnetized Permalloy substrate. The results showed that there is an enhancement of approximately 10% in the rate of CO bond cleavage that depends on the chirality of the molecule and the spin polarization of the substrate secondary electrons.

  7. Four decades of opposing natural and human-induced artificial selection acting on Windermere pike (Esox lucius).

    PubMed

    Carlson, Stephanie M; Edeline, Eric; Asbjørn Vøllestad, L; Haugen, Thrond O; Winfield, Ian J; Fletcher, Janice M; Ben James, J; Stenseth, Nils Chr

    2007-06-01

    The ability of natural selection to drive local adaptation has been appreciated ever since Darwin. Whether human impacts can impede the adaptive process has received less attention. We tested this hypothesis by quantifying natural selection and harvest selection acting on a freshwater fish (pike) over four decades. Across the time series, directional natural selection tended to favour large individuals whereas the fishery targeted large individuals. Moreover, non-linear natural selection tended to favour intermediate sized fish whereas the fishery targeted intermediate sized fish because the smallest and largest individuals were often not captured. Thus, our results unequivocally demonstrate that natural selection and fishery selection often acted in opposite directions within this natural system. Moreover, the two selective factors combined to produce reduced fitness overall and stronger stabilizing selection relative to natural selection acting alone. The long-term ramifications of such human-induced modifications to adaptive landscapes are currently unknown and certainly warrant further investigation.

  8. Metal intercalation-induced selective adatom mass transport on graphene

    DOE PAGES

    Liu, Xiaojie; Wang, Cai -Zhuang; Hupalo, Myron; ...

    2016-03-29

    Recent experiments indicate that metal intercalation is a very effective method to manipulate the graphene-adatom interaction and control metal nanostructure formation on graphene. A key question is mass transport, i.e., how atoms deposited uniformly on graphene populate different areas depending on the local intercalation. Using first-principles calculations, we show that partially intercalated graphene, with a mixture of intercalated and pristine areas, can induce an alternating electric field because of the spatial variations in electron doping, and thus, an oscillatory electrostatic potential. As a result, this alternating field can change normal stochastic adatom diffusion to biased diffusion, leading to selective massmore » transport and consequent nucleation, on either the intercalated or pristine areas, depending on the charge state of the adatoms.« less

  9. Metal intercalation-induced selective adatom mass transport on graphene

    SciTech Connect

    Liu, Xiaojie; Wang, Cai -Zhuang; Hupalo, Myron; Lin, Hai -Qing; Ho, Kai -Ming; Thiel, Patricia A.; Tringides, Michael C.

    2016-03-29

    Recent experiments indicate that metal intercalation is a very effective method to manipulate the graphene-adatom interaction and control metal nanostructure formation on graphene. A key question is mass transport, i.e., how atoms deposited uniformly on graphene populate different areas depending on the local intercalation. Using first-principles calculations, we show that partially intercalated graphene, with a mixture of intercalated and pristine areas, can induce an alternating electric field because of the spatial variations in electron doping, and thus, an oscillatory electrostatic potential. As a result, this alternating field can change normal stochastic adatom diffusion to biased diffusion, leading to selective mass transport and consequent nucleation, on either the intercalated or pristine areas, depending on the charge state of the adatoms.

  10. Electric Field Induced Selective Disordering in Lamellar Block Copolymers

    SciTech Connect

    Ruppel, Markus A; Pester, Christian W; Langner, Karol M; Sevink, Geert; Schoberth, Heiko; Schmidt, Kristin; Urban, Volker S; Mays, Jimmy; Boker, Alexander

    2013-01-01

    External electric fields align nanostructured block copolymers by either rotation of grains or nucleation and growth depending on how strongly the chemically distinct block copolymer components are segregated. In close vicinity to the orderdisorder transition, theory and simulations suggest a third mechanism: selective disordering. We present a time-resolved small-angle X-ray scattering study that demonstrates how an electric field can indeed selectively disintegrate ill-aligned lamellae in a lyotropic block copolymer solution, while lamellae with interfaces oriented parallel to the applied field prevail. The present study adds an additional mechanism to the experimentally corroborated suite of mechanistic pathways, by which nanostructured block copolymers can align with an electric field. Our results further unveil the benefit of electric field assisted annealing for mitigating orientational disorder and topological defects in block copolymer mesophases, both in close vicinity to the orderdisorder transition and well below it.

  11. Electric field induced selective disordering in lamellar block copolymers.

    PubMed

    Ruppel, Markus; Pester, Christian W; Langner, Karol M; Sevink, Geert J A; Schoberth, Heiko G; Schmidt, Kristin; Urban, Volker S; Mays, Jimmy W; Böker, Alexander

    2013-05-28

    External electric fields align nanostructured block copolymers by either rotation of grains or nucleation and growth depending on how strongly the chemically distinct block copolymer components are segregated. In close vicinity to the order-disorder transition, theory and simulations suggest a third mechanism: selective disordering. We present a time-resolved small-angle X-ray scattering study that demonstrates how an electric field can indeed selectively disintegrate ill-aligned lamellae in a lyotropic block copolymer solution, while lamellae with interfaces oriented parallel to the applied field prevail. The present study adds an additional mechanism to the experimentally corroborated suite of mechanistic pathways, by which nanostructured block copolymers can align with an electric field. Our results further unveil the benefit of electric field assisted annealing for mitigating orientational disorder and topological defects in block copolymer mesophases, both in close vicinity to the order-disorder transition and well below it.

  12. Polystyrene nanoparticle exposure induces ion-selective pores in lipid bilayers

    PubMed Central

    Negoda, Alexander; Kim, Kwang-Jin; Crandall, Edward D.; Worden, Robert M.

    2014-01-01

    A diverse range of molecular interactions can occur between engineered nanomaterials (ENM) and biomembranes, some of which could lead to toxic outcomes following human exposure to ENM. In this study, we adapted electrophysiology methods to investigate the ability of 20 nm polystyrene nanoparticles (PNP) to induce pores in model bilayer lipid membranes (BLM) that mimic biomembranes. PNP charge was varied using PNP decorated with either positive (amidine) groups or negative (carboxyl) groups, and BLM charge was varied using dioleoyl phospholipids having cationic (ethylphosphocholine), zwitterionic (phosphocholine), or anionic (phosphatidic acid) headgroups. Both positive and negative PNP induced BLM pores for all lipid compositions studied, as evidenced by current spikes and integral conductance. Stable PNP-induced pores exhibited ion selectivity, with the highest selectivity for K+ (PK/PCl ~ 8.3) observed when both the PNP and lipids were negatively charged, and the highest selectivity for Cl− (PK/PCl ~ 0.2) observed when both the PNP and lipids were positively charged. This trend is consistent with the finding that selectivity for an ion in channel proteins is imparted by oppositely charged functional groups within the channel’s filter region. The PK/PCl value was unaffected by the voltage-ramp method, the pore conductance, or the side of the BLM to which the PNP were applied. These results demonstrate for the first time that PNP can induce ion-selective pores in BLM, and that the degree of ion selectivity is influenced synergistically by the charges of both the lipid headgroups and functional groups on the PNP. PMID:23747366

  13. Gravitational time dilation induced decoherence in spontaneous emission

    NASA Astrophysics Data System (ADS)

    Xie, Dong; Xu, Chunling; Wang, An Min

    2017-08-01

    We investigate decoherence of quantum superpositions induced by gravitational time dilation and spontaneous emission between two atomic levels. It has been shown that gravitational time dilation can be a universal decoherence source by Pikovski et al. Here, we consider the decoherence induced by the gravitational time dilation only in the situation of spontaneous emission. We obtain the analytical results of the coherence of particle’s position state. Then, we obtain that the coherence of particle’s position state depends on reference frame because the time dilation changes the distinguishability of emitted photons from two positions of particle in different reference frames. For observing the decoherence effect induced by the gravitational time dilation, time-delayed feedback can be utilized to increase the decoherence of particle’s superposition state.

  14. Factors associated with induced abortion at selected hospitals in the Volta Region, Ghana

    PubMed Central

    Klutsey, Ellen Eyi; Ankomah, Augustine

    2014-01-01

    Background Induced abortion rates remained persistently high in the Volta Region of Ghana in the 5 years from 2006 to 2011. Some hospitals, both rural and urban, report induced abortion-related complications as one of the top ten conditions in hospital admissions. This study explored demographic and other factors associated with induced abortion, and also assessed awareness of abortion-related complications among women of reproductive age in the Volta Region. Methods A quantitative, hospital-based, unmatched case-control study was performed. The Volta Region was stratified into two health administration zones, ie, north and south. For each zone, hospitals were stratified into government and private hospitals. Employing simple random sampling, one private and three government hospitals were selected from each zone. This study is therefore based on eight hospitals, ie, six government hospitals and two private hospitals. Results Marital status, employment status, number of total pregnancies, and knowledge about contraception were found to be associated with induced abortion. Multiple logistic regression showed a 4% reduction in the odds of induced abortion in married women compared with women who were single (odds ratio [OR] 0.11, 95% confidence interval [CI] 0.07–0.22). Unemployed women of reproductive age were found to be 0.35 times less likely to seek induced abortion compared with their employed counterparts (OR 0.35, CI 0.19–0.65). It was also observed that women with their second pregnancies were 3.8 times more likely to seek induced abortion and women with more than two pregnancies were 6.6 times more likely to do so (OR 3.81, CI 1.94–7.49 and OR 6.58, CI 2.58–16.79, respectively). Women with no knowledge of contraceptive methods were 4.6 times likely to seek induced abortion (OR 4.64, CI 1.39–15.4). Compared with women who had not had induced abortion, women with a high number of pregnancies and no contraceptive knowledge were more likely to have

  15. Factors associated with induced abortion at selected hospitals in the Volta Region, Ghana.

    PubMed

    Klutsey, Ellen Eyi; Ankomah, Augustine

    2014-01-01

    Induced abortion rates remained persistently high in the Volta Region of Ghana in the 5 years from 2006 to 2011. Some hospitals, both rural and urban, report induced abortion-related complications as one of the top ten conditions in hospital admissions. This study explored demographic and other factors associated with induced abortion, and also assessed awareness of abortion-related complications among women of reproductive age in the Volta Region. A quantitative, hospital-based, unmatched case-control study was performed. The Volta Region was stratified into two health administration zones, ie, north and south. For each zone, hospitals were stratified into government and private hospitals. Employing simple random sampling, one private and three government hospitals were selected from each zone. This study is therefore based on eight hospitals, ie, six government hospitals and two private hospitals. Marital status, employment status, number of total pregnancies, and knowledge about contraception were found to be associated with induced abortion. Multiple logistic regression showed a 4% reduction in the odds of induced abortion in married women compared with women who were single (odds ratio [OR] 0.11, 95% confidence interval [CI] 0.07-0.22). Unemployed women of reproductive age were found to be 0.35 times less likely to seek induced abortion compared with their employed counterparts (OR 0.35, CI 0.19-0.65). It was also observed that women with their second pregnancies were 3.8 times more likely to seek induced abortion and women with more than two pregnancies were 6.6 times more likely to do so (OR 3.81, CI 1.94-7.49 and OR 6.58, CI 2.58-16.79, respectively). Women with no knowledge of contraceptive methods were 4.6 times likely to seek induced abortion (OR 4.64, CI 1.39-15.4). Compared with women who had not had induced abortion, women with a high number of pregnancies and no contraceptive knowledge were more likely to have induced abortion. It was found that lack

  16. Determining the Capacity of Time-Based Selection

    ERIC Educational Resources Information Center

    Watson, Derrick G.; Kunar, Melina A.

    2012-01-01

    In visual search, a set of distractor items can be suppressed from future selection if they are presented (previewed) before a second set of search items arrive. This "visual marking" mechanism provides a top-down way of prioritizing the selection of new stimuli, at the expense of old stimuli already in the field (Watson & Humphreys,…

  17. Adaptive real time selection for quantum key distribution in lossy and turbulent free-space channels

    NASA Astrophysics Data System (ADS)

    Vallone, Giuseppe; Marangon, Davide G.; Canale, Matteo; Savorgnan, Ilaria; Bacco, Davide; Barbieri, Mauro; Calimani, Simon; Barbieri, Cesare; Laurenti, Nicola; Villoresi, Paolo

    2015-04-01

    The unconditional security in the creation of cryptographic keys obtained by quantum key distribution (QKD) protocols will induce a quantum leap in free-space communication privacy in the same way that we are beginning to realize secure optical fiber connections. However, free-space channels, in particular those with long links and the presence of atmospheric turbulence, are affected by losses, fluctuating transmissivity, and background light that impair the conditions for secure QKD. Here we introduce a method to contrast the atmospheric turbulence in QKD experiments. Our adaptive real time selection (ARTS) technique at the receiver is based on the selection of the intervals with higher channel transmissivity. We demonstrate, using data from the Canary Island 143-km free-space link, that conditions with unacceptable average quantum bit error rate which would prevent the generation of a secure key can be used once parsed according to the instantaneous scintillation using the ARTS technique.

  18. Effects of hyperbaric nitrogen-induced narcosis on response-selection processes.

    PubMed

    Meckler, Cédric; Blatteau, Jean-Eric; Hasbroucq, Thierry; Schmid, Bruno; Risso, Jean-Jacques; Vidal, Franck

    2014-01-01

    Certain underwater circumstances carry risk of inert gas narcosis. Impairment of sensorimotor information processing due to narcosis, induced by normobaric nitrous oxide or high partial nitrogen pressure, has been broadly evidenced, by a lengthening of the reaction time (RT). However, the locus of this effect remains a matter of debate. We examined whether inert gas narcosis affects the response-selection stage of sensorimotor information processing. We compared an air normobaric condition with a hyperbaric condition in which 10 subjects were subjected to 6 absolute atmospheres of 8.33% O2 Nitrox. In both conditions, subjects performed a between-hand choice-RT task in which we explicitly manipulated the stimulus-response association rule. The effect of this manipulation (which is supposed to affect response-selection processes) was modified by inert gas narcosis. It is concluded, therefore, that response selection processes are among the loci involved in the effect of inert gas narcosis on information processing.

  19. Noise-induced transition in human reaction times

    NASA Astrophysics Data System (ADS)

    Medina, José M.; Díaz, José A.

    2016-09-01

    The human reaction/response time can be defined as the time elapsed from the onset of stimulus presentation until a response occurs in many sensory and cognitive processes. A reaction time model based on Piéron’s law is investigated. The model shows a noise-induced transition in the moments of reaction time distributions due to the presence of strong additive noise. The model also demonstrates that reaction times do not follow fluctuation scaling between the mean and the variance but follow a generalized version between the skewness and the kurtosis. The results indicate that noise-induced transitions in the moments govern fluctuations in sensory-motor transformations and open an insight into the macroscopic effects of noise in human perception and action. The conditions that lead to extreme reaction times are discussed based on the transfer of information in neurons.

  20. The timing of induced resistance and induced susceptibility in the soybean-Mexican bean beetle system.

    PubMed

    Underwood, Nora C

    1998-04-01

    Induced plant responses to herbivory have been demonstrated in many systems. It has been suggested that the timing of these responses may influence the impact of induced resistance on herbivore populations, and may affect the evolution of induced defenses. This study used a bioassay to characterize the time course of systemic induced responses to Mexican bean beetle herbivory in four genotypes of soybeans. The results suggest that the time course of induced responses in this system is more complex than most previous studies have indicated. Herbivory provoked both rapid induced resistance and subsequent induced susceptibility to beetle feeding. All four genotypes of soybean induced significant resistance to beetle damage (beetles preferred undamaged to damaged plants) by 3 days after damage. By 15 days after damage, this resistance had decayed (beetles showed no preference for undamaged over damaged plants), and by 20 days after damage, all four genotypes exhibited significant induced susceptibility (beetles preferred previously damaged plants over undamaged plants). The magnitude of induced resistance in each genotype correlated strongly with the magnitude of induced susceptibility in that genotype.

  1. Timing behavior in streptozotocin-induced diabetic rats.

    PubMed

    Orduña, Vladimir; Hong, Enrique; Bouzas, Arturo

    2011-10-10

    There is evidence of deterioration of spatial cognition in streptozotocin (STZ)-induced diabetic rats. Here, we evaluate a possible dissociation in the cognitive deficits due to diabetes by examining another crucial aspect of animal cognition: temporal perception. Timing behavior and temporal memory were evaluated in STZ-induced diabetic rats employing two timing tasks: the peak-interval procedure, with its Gap variant, and the interval bisection task. A spatial memory task, rewarded alternation in the T-maze, was also evaluated to explore spatial cognition. The two timing tasks employed coincide in the finding of a normal timing performance in STZ-induced diabetic rats. The peak-interval procedure provided results that suggest that the timing behavior is equally accurate and precise than in control subjects; in the Gap procedure, an equal change in peak time in both groups indicates that temporal working memory is also intact. In the interval bisection task, we analyzed the acquisition of a temporal discrimination and the sensitivity to changes in the duration of the stimulus; no differences were found in either the acquisition process or the sensitivity index. In contrast, in the rewarded alternation task, STZ-induced diabetic rats exhibited a significant deficit in spatial cognition. The cognitive processes involved in timing behavior and temporal memory are not deteriorated as a consequence of diabetes; the cognitive deficits associated to diabetes thus seem to be restricted to the spatial domain.

  2. Artificial selection on chill-coma recovery time in Drosophila melanogaster: Direct and correlated responses to selection.

    PubMed

    Gerken, Alison R; Mackay, Trudy F C; Morgan, Theodore J

    2016-07-01

    Artificial selection can be used to create populations with extreme phenotypic responses to environmental stressors. When artificial selection is applied to a single component of a stress response, this selection may result in correlated responses in other stress responses, a phenomenon called cross-tolerance, which is ultimately controlled by the genetic correlations among traits. We selected for extreme responses to cold tolerance by selecting for chill-coma recovery time from a single temperate population of Drosophila melanogaster. Chill-coma recovery time is a common metric of low, but non-lethal, cold temperature tolerance. Replicated divergent artificial selection was applied to a genetically variable base population for 31 generations, resulting in two cold resistant, two cold susceptible, and two unselected control lines. To quantify the relationship between selection on chill-coma recovery and other metrics of thermal performance, we also measured survivorship after acute cold exposure, survivorship after chronic cold exposure, survivorship after cold exposure following a pre-treatment period (rapid cold hardening), starvation tolerance, and heat tolerance. We find that chill-coma recovery time is heritable within this population and that there is an asymmetric response to increased and decreased chill-coma recovery time. Surprisingly, we found no cross-tolerances between selection on chill-coma recovery time and the other environmental stress response traits. These results suggest that although artificial selection has dramatically altered chill-coma recovery time, the correlated response to selection on other stress response phenotypes has been negligible. The lack of a correlated response suggests that chill-coma recovery time in these selection lines is likely genetically independent from measures of cold survivorship tested here.

  3. A time-gating scintillation detector for the measurement of laser-induced fast neutrons

    SciTech Connect

    Lee, Sungman; Park, Sangsoon; Yea, Kwon-hae; Cha, Hyungki

    2009-06-15

    A time-gating scintillation detector, in which a fast high voltage switch is used for gating a channel photomultiplier, was developed for a measurement of laser-induced fast neutrons. The x rays generated from the intense femtosecond laser and the solid target interactions were suppressed selectively and a time-of-flight signal of a laser-generated fast neutron was measured effectively. The detector was used successfully to measure the neutron yield of a femtosecond, deuterated, polystyrene plasma.

  4. Continuum model for chiral induced spin selectivity in helical molecules

    SciTech Connect

    Medina, Ernesto; González-Arraga, Luis A.; Finkelstein-Shapiro, Daniel; Mujica, Vladimiro; Berche, Bertrand

    2015-05-21

    A minimal model is exactly solved for electron spin transport on a helix. Electron transport is assumed to be supported by well oriented p{sub z} type orbitals on base molecules forming a staircase of definite chirality. In a tight binding interpretation, the spin-orbit coupling (SOC) opens up an effective π{sub z} − π{sub z} coupling via interbase p{sub x,y} − p{sub z} hopping, introducing spin coupled transport. The resulting continuum model spectrum shows two Kramers doublet transport channels with a gap proportional to the SOC. Each doubly degenerate channel satisfies time reversal symmetry; nevertheless, a bias chooses a transport direction and thus selects for spin orientation. The model predicts (i) which spin orientation is selected depending on chirality and bias, (ii) changes in spin preference as a function of input Fermi level and (iii) back-scattering suppression protected by the SO gap. We compute the spin current with a definite helicity and find it to be proportional to the torsion of the chiral structure and the non-adiabatic Aharonov-Anandan phase. To describe room temperature transport, we assume that the total transmission is the result of a product of coherent steps.

  5. A Selected Annotated Bibliography on Work Time Options.

    ERIC Educational Resources Information Center

    Ivantcho, Barbara

    This annotated bibliography is divided into three sections. Section I contains annotations of general publications on work time options. Section II presents resources on flexitime and the compressed work week. In Section III are found resources related to these reduced work time options: permanent part-time employment, job sharing, voluntary…

  6. The Timing of Verb Selection in Japanese Sentence Production

    ERIC Educational Resources Information Center

    Momma, Shota; Slevc, L. Robert; Phillips, Colin

    2016-01-01

    Many influential models of sentence production (e.g., Bock & Levelt, 1994; Kempen & Hoenkamp, 1987; Levelt, 1989) emphasize the central role of verbs in structural encoding, and thus predict that verbs should be selected early in sentence formulation, possibly even before the phonological encoding of the first constituent (Ferreira, 2000).…

  7. Selective visual scaling of time-scale processes facilitates broadband learning of isometric force frequency tracking.

    PubMed

    King, Adam C; Newell, Karl M

    2015-10-01

    The experiment investigated the effect of selectively augmenting faster time scales of visual feedback information on the learning and transfer of continuous isometric force tracking tasks to test the generality of the self-organization of 1/f properties of force output. Three experimental groups tracked an irregular target pattern either under a standard fixed gain condition or with selectively enhancement in the visual feedback display of intermediate (4-8 Hz) or high (8-12 Hz) frequency components of the force output. All groups reduced tracking error over practice, with the error lowest in the intermediate scaling condition followed by the high scaling and fixed gain conditions, respectively. Selective visual scaling induced persistent changes across the frequency spectrum, with the strongest effect in the intermediate scaling condition and positive transfer to novel feedback displays. The findings reveal an interdependence of the timescales in the learning and transfer of isometric force output frequency structures consistent with 1/f process models of the time scales of motor output variability.

  8. Mechanism of selective inhibition of the inducible isoform of prostaglandin G/H synthase.

    PubMed Central

    Copeland, R A; Williams, J M; Giannaras, J; Nurnberg, S; Covington, M; Pinto, D; Pick, S; Trzaskos, J M

    1994-01-01

    Selective inhibition of the inducible isoform of prostaglandin G/H synthase (cyclooxygenase-2; COX2; EC 1.14.99.1) can be achieved with compounds of the general form of aryl methyl sulfonyls and aryl methyl sulfonamides. DuP 697 and NS-398 are representative examples of these compounds. Both inhibit the constitute (COX1) and inducible (COX2) isoforms of the enzyme with equal potency shortly after mixing, but their potencies increase with time for COX2 selectively. This time-dependent inhibition follows first-order kinetics, and the rate constant for inactivation of COX2 is dose dependent for both compounds. Kinetic analysis allows us to determine KI and kinact (the maximal rate of inactivation) for each inhibitor. The potency of both compounds is substrate concentration dependent, as expected for time-dependent competitive inhibitors. COX2 that has been incubated with these inhibitors, and then extensively dialyzed against buffer, shows no recovery of enzyme activity, while complete recovery of activity is seen for COX1. Thus, these inhibitors irreversibly inactivate COX2 with time, while showing minimal reversible inhibition of COX1. We isolated these inhibitors after long incubation with excess enzyme and subsequent denaturation of the enzyme. Both inhibitors showed no loss of potency resulting from interactions with COX2, suggesting that inhibition is not mediated by covalent modification of the enzyme. These data suggest that binding of these inhibitors to COX2 induces a slow structural transition of the enzyme that results in its selective inactivation. PMID:7972034

  9. Polarization selectivity of charge localization induced by a 7-fs nearly single-cycle light field in an organic metal

    NASA Astrophysics Data System (ADS)

    Kawakami, Y.; Yoneyama, Y.; Amano, T.; Itoh, H.; Yamamoto, K.; Nakamura, Y.; Kishida, H.; Sasaki, T.; Ishihara, S.; Tanaka, Y.; Yonemitsu, K.; Iwai, S.

    2017-05-01

    Polarization selectivity of light-field-induced charge localization was investigated in an organic metal α -(BEDT-TTF ) 2I3 with a triangular lattice. Dependences of transient reflectivity spectra on polarizations of the 7-fs pump and probe lights indicate that a short-range charge order (CO) is induced efficiently from the metallic phase for the pump polarization perpendicular to the 1010-type CO axis. A numerical solution of a time-dependent Schrödinger equation clarified that the 1010 CO is induced by field-induced re-distribution of charges cooperating with competing intersite Coulomb repulsions in the triangular lattice.

  10. Long-time observation of meteor induced layers with ionosonde

    NASA Astrophysics Data System (ADS)

    Yusupov, Kamil; Akchurin, Adel

    2016-07-01

    It is considered that the main theory explaining appearance of sporadic E is the theory of wind shear, which means (includes) the presence and movement of nodes converging tidal wind through the height region of the most frequent occurrence Es (120-140km) [Mathew et. all, 1998]. However, the appearance of intense layers, following its name, are sporadic, and such variability cannot to explain by the influence of tidal waves only. Another indication inconsistency theory of wind shear is the appearance of so-called transient Es layers [Maruiama, 2003]. The distinctive feature of this trace is the high critical frequency (> 5 MHz), a constant height, weak amplitude, all trace semitransparent and short lifetime [Maruiama et. all, 2003 and 2008 and references there]. Because of duration, such layer is opposite to the traditional persistent Es layer, which we do not consider in this paper. Various researchers have used different terms for such spontaneous Es, it is meteor echo, meteor induced Es, spontaneously formed sporadic Es patches resulting of the Fresnel scattering from a region of enhanced plasma density along the meteor trail, transitory Es and transient Es. Since the term transient Es is unstable, to avoid confusion, we will stick to this term. Since meteor echo is not fully satisfy this term by some parameter, we will describe the properties of transient Es based on the ionogram properties and not from physics of its origin. We used data from our ionosonde with one-minute ionogram repetition rate for 2010-2014 years. For processing performed a method are using to select beatings and the ionosphere reflectivity of the layers by means A-, H-and AΣ-map [Akchurin, 2011; Yusupov, 2014]. This maps allow to collect transient Es appearance over a long-time. Such statistics comparison with meteor showers activity showed good agreement. It shows the presence of the transient Es formation mechanism, which coupling with meteors.

  11. Time-variant Catchment Transit Time Distribution and StorAge Selection Functions in Neighbouring Catchments

    NASA Astrophysics Data System (ADS)

    Klaus, J.; Rodriguez, N. B.; McGuire, K. J.

    2016-12-01

    The understanding of the catchment functions of storage, mixing, and release is a major research challenge as their behavior is fundamental for understanding water quality and flow quantity and timing. Generally, the complexity of the flow paths and associated mixing processes is still a major hindrance to a thorough understanding of catchment functions. Catchment transit time distributions can be used as an integrative descriptor of catchment functions. Here we aim to understand these fundamental catchment functions in four neighboring catchments of the HJA Experimental Forest in Oregon, USA. The areas of the four catchments (WS2, WS3, WS9, WS10) range from 0.085 to 1.011 km2. The catchments are fully forested with Douglas fir, western hemlock, and western redcedar dominating the lower elevations, and noble fir, Pacific silver fir, Douglas fir dominating higher elevations. Geology is dominated by volcaniclastics, covering 68% to 99% of the catchments. We employed a two storage conceptual model in each catchment for stream flow and transport modeling. We used solutions of the Master Equation to determine transit time distributions. We assumed randomly sampled/fully mixed conditions in each storage to model 18Oxygen in stream flow over a two year period. For example, modeling results for WS10 yielded a Nash-Sutcliffe efficiency (NSE) of 0.84 for stream flow of and a NSE of 0.7 for the (volume weighted) 18O in stream flow. Furthermore, we derived the master transit time distribution (mttd) for the catchments. Eventually we investigated the landscape controls (topography, geology, morphology) on mttd and the dynamics of storage selection functions of each catchment.

  12. Select timely data and local benchmarks to profile MDs.

    PubMed

    1999-03-01

    DATA BENCHMARKS: Seeking an effective way to let their physicians know their costs were too high and LOS too long, managers at two New York health care organizations began profiling the physicians by using data the physicians themselves deemed most appropriate. Find out what data they selected. And review samples of the reports they prepare for their physicians. It's all part of a new book from the publisher of CRR.

  13. The timing of selection at the human FOXP2 gene.

    PubMed

    Coop, Graham; Bullaughey, Kevin; Luca, Francesca; Przeworski, Molly

    2008-07-01

    Krause J, Lalueza-Fox C, Orlando L, et al. recently examined patterns of genetic variation at FOXP2 in 2 Neanderthals. This gene is of particular interest because it is involved in speech and language and was previously shown to harbor the signature of recent positive selection. The authors found the same 2 amino acid substitutions in Neanderthals as in modern humans. Assuming that these sites were the targets of selection and no interbreeding between the 2 groups, they concluded that selection at FOXP2 occurred before the populations split, over 300 thousand years ago. Here, we show that the data are unlikely under this scenario but may instead be consistent with low rates of gene flow between modern humans and Neanderthals. We also collect additional data and introduce a modeling framework to estimate levels of modern human contamination of the Neanderthal samples. We find that, depending on the assumptions, additional control experiments may be needed to rule out contamination at FOXP2.

  14. The Timing of Selection at the Human FOXP2 Gene

    PubMed Central

    Bullaughey, Kevin; Luca, Francesca; Przeworski, Molly

    2008-01-01

    Krause J, Lalueza-Fox C, Orlando L, et al. recently examined patterns of genetic variation at FOXP2 in 2 Neanderthals. This gene is of particular interest because it is involved in speech and language and was previously shown to harbor the signature of recent positive selection. The authors found the same 2 amino acid substitutions in Neanderthals as in modern humans. Assuming that these sites were the targets of selection and no interbreeding between the 2 groups, they concluded that selection at FOXP2 occurred before the populations split, over 300 thousand years ago. Here, we show that the data are unlikely under this scenario but may instead be consistent with low rates of gene flow between modern humans and Neanderthals. We also collect additional data and introduce a modeling framework to estimate levels of modern human contamination of the Neanderthal samples. We find that, depending on the assumptions, additional control experiments may be needed to rule out contamination at FOXP2. PMID:18413354

  15. Manufacturing time operators: Covariance, selection criteria, and examples

    SciTech Connect

    Hegerfeldt, G. C.; Muga, J. G.; Munoz, J.

    2010-07-15

    We provide the most general forms of covariant and normalized time operators and their probability densities, with applications to quantum clocks, the time of arrival, and Lyapunov quantum operators. Examples are discussed of the profusion of possible operators and their physical meaning. Criteria to define unique, optimal operators for specific cases are given.

  16. Comparative Time Chart of Selected Chemical Discoveries and Achievements

    ERIC Educational Resources Information Center

    Uzzell, P. S.

    1977-01-01

    This article chronologically outlines discoveries and achievements made in the field of Chemistry from Ancient times to 1900. These events are classified into three categories: physical, inorganic, and organic chemistry. The approximate dates, scientists, and their countries of origin for each event are included in the time chart. (MA)

  17. Pressure-overload-induced heart failure induces a selective reduction in glucose oxidation at physiological afterload.

    PubMed

    Zhabyeyev, Pavel; Gandhi, Manoj; Mori, Jun; Basu, Ratnadeep; Kassiri, Zamaneh; Clanachan, Alexander; Lopaschuk, Gary D; Oudit, Gavin Y

    2013-03-15

    Development of heart failure is known to be associated with changes in energy substrate metabolism. Information on the changes in energy substrate metabolism that occur in heart failure is limited and results vary depending on the methods employed. Our aim is to characterize the changes in energy substrate metabolism associated with pressure overload and ischaemia-reperfusion (I/R) injury. We used transverse aortic constriction (TAC) in mice to induce pressure overload-induced heart failure. Metabolic rates were measured in isolated working hearts perfused at physiological afterload (80 mmHg) using (3)H- or (14)C-labelled substrates. As a result of pressure-overload injury, murine hearts exhibited: (i) hypertrophy, systolic, and diastolic dysfunctions; (ii) reduction in LV work, (iii) reduced rates of glucose and lactate oxidations, with no change in glycolysis or fatty acid oxidation and a small decrease in triacylglycerol oxidation, and (iv) increased phosphorylation of AMPK and a reduction in malonyl-CoA levels. Sham hearts produced more acetyl CoA from carbohydrates than from fats, whereas TAC hearts showed a reverse trend. I/R in sham group produced a metabolic switch analogous to the TAC-induced shift to fatty acid oxidation, whereas I/R in TAC hearts greatly exacerbated the existing imbalance, and was associated with a poorer recovery during reperfusion. Pressure overload-induced heart failure and I/R shift the preference of substrate oxidation from glucose and lactate to fatty acid due to a selective reduction in carbohydrate oxidation. Normalizing the balance between metabolic substrate utilization may alleviate pressure-overload-induced heart failure and ischaemia.

  18. Time-resolved aluminium laser-induced plasma temperature measurements

    NASA Astrophysics Data System (ADS)

    Surmick, D. M.; Parigger, C. G.

    2014-11-01

    We seek to characterize the temperature decay of laser-induced plasma near the surface of an aluminium target from laser-induced breakdown spectroscopy measurements of aluminium alloy sample. Laser-induced plasma are initiated by tightly focussing 1064 nm, nanosecond pulsed Nd:YAG laser radiation. Temperatures are inferred from aluminium monoxide spectra viewed at systematically varied time delays by comparing experimental spectra to theoretical calculations with a Nelder Mead algorithm. The temperatures are found to decay from 5173 ± 270 to 3862 ± 46 Kelvin from 10 to 100 μs time delays following optical breakdown. The temperature profile along the plasma height is also inferred from spatially resolved spectral measurements and the electron number density is inferred from Stark broadened Hβ spectra.

  19. Estimating selection through male fitness: three complementary methods illuminate the nature and causes of selection on flowering time.

    PubMed

    Austen, Emily J; Weis, Arthur E

    2016-02-24

    Our understanding of selection through male fitness is limited by the resource demands and indirect nature of the best available genetic techniques. Applying complementary, independent approaches to this problem can help clarify evolution through male function. We applied three methods to estimate selection on flowering time through male fitness in experimental populations of the annual plant Brassica rapa: (i) an analysis of mating opportunity based on flower production schedules, (ii) genetic paternity analysis, and (iii) a novel approach based on principles of experimental evolution. Selection differentials estimated by the first method disagreed with those estimated by the other two, indicating that mating opportunity was not the principal driver of selection on flowering time. The genetic and experimental evolution methods exhibited striking agreement overall, but a slight discrepancy between the two suggested that negative environmental covariance between age at flowering and male fitness may have contributed to phenotypic selection. Together, the three methods enriched our understanding of selection on flowering time, from mating opportunity to phenotypic selection to evolutionary response. The novel experimental evolution method may provide a means of examining selection through male fitness when genetic paternity analysis is not possible.

  20. Estimating selection through male fitness: three complementary methods illuminate the nature and causes of selection on flowering time

    PubMed Central

    Austen, Emily J.; Weis, Arthur E.

    2016-01-01

    Our understanding of selection through male fitness is limited by the resource demands and indirect nature of the best available genetic techniques. Applying complementary, independent approaches to this problem can help clarify evolution through male function. We applied three methods to estimate selection on flowering time through male fitness in experimental populations of the annual plant Brassica rapa: (i) an analysis of mating opportunity based on flower production schedules, (ii) genetic paternity analysis, and (iii) a novel approach based on principles of experimental evolution. Selection differentials estimated by the first method disagreed with those estimated by the other two, indicating that mating opportunity was not the principal driver of selection on flowering time. The genetic and experimental evolution methods exhibited striking agreement overall, but a slight discrepancy between the two suggested that negative environmental covariance between age at flowering and male fitness may have contributed to phenotypic selection. Together, the three methods enriched our understanding of selection on flowering time, from mating opportunity to phenotypic selection to evolutionary response. The novel experimental evolution method may provide a means of examining selection through male fitness when genetic paternity analysis is not possible. PMID:26911957

  1. Excitation emission and time-resolved fluorescence spectroscopy of selected varnishes used in historical musical instruments.

    PubMed

    Nevin, Austin; Echard, Jean-Philippe; Thoury, Mathieu; Comelli, Daniela; Valentini, Gianluca; Cubeddu, Rinaldo

    2009-11-15

    The analysis of various varnishes from different origins, which are commonly found on historical musical instruments was carried out for the first time with both fluorescence excitation emission spectroscopy and laser-induced time-resolved fluorescence spectroscopy. Samples studied include varnishes prepared using shellac, and selected diterpenoid and triterpenoid resins from plants, and mixtures of these materials. Fluorescence excitation emission spectra have been collected from films of naturally aged varnishes. In parallel, time-resolved fluorescence spectroscopy of varnishes provides means for discriminating between short- (less than 2.0 ns) and long-lived (greater than 7.5 ns) fluorescence emissions in each of these complex materials. Results suggest that complementary use of the two non destructive techniques allows a better understanding of the main fluorophores responsible for the emission in shellac, and further provides means for distinguishing the main classes of other varnishes based on differences in fluorescence lifetime behaviour. Spectrofluorimetric data and time resolved spectra presented here may form the basis for the interpretation of results from future in situ fluorescence examination and time resolved fluorescence imaging of varnished musical instruments.

  2. Time Adaptation Shows Duration Selectivity in the Human Parietal Cortex

    PubMed Central

    Hayashi, Masamichi J.; Ditye, Thomas; Harada, Tokiko; Hashiguchi, Maho; Sadato, Norihiro; Carlson, Synnöve; Walsh, Vincent; Kanai, Ryota

    2015-01-01

    Although psychological and computational models of time estimation have postulated the existence of neural representations tuned for specific durations, empirical evidence of this notion has been lacking. Here, using a functional magnetic resonance imaging (fMRI) adaptation paradigm, we show that the inferior parietal lobule (IPL) (corresponding to the supramarginal gyrus) exhibited reduction in neural activity due to adaptation when a visual stimulus of the same duration was repeatedly presented. Adaptation was strongest when stimuli of identical durations were repeated, and it gradually decreased as the difference between the reference and test durations increased. This tuning property generalized across a broad range of durations, indicating the presence of general time-representation mechanisms in the IPL. Furthermore, adaptation was observed irrespective of the subject’s attention to time. Repetition of a nontemporal aspect of the stimulus (i.e., shape) did not produce neural adaptation in the IPL. These results provide neural evidence for duration-tuned representations in the human brain. PMID:26378440

  3. Fabrication of chemical templates via selective laser-induced desorption of hexadecanethiol self-assembled monolayers

    NASA Astrophysics Data System (ADS)

    Schröter, Anja; Mathieu, Mareike; Franzka, Steffen; Feydt, Jürgen; Irsen, Stephan; Hartmann, Nils

    2013-08-01

    A nonlinear photothermal laser patterning technique for rapid fabrication of chemical templates is demonstrated. Hexadecanethiol monolayers on Au-coated Si substrates are processed at λ = 532 nm, a 1/e2 spot diameter of d=2.8 μm and ambient conditions. Local laser irradiation at high laser powers and short irradiation times in the micro-/millisecond range induces desorption of thiol molecules. The laser-depleted areas are backfilled with mercaptohexadecanoic acid in order to build up chemical templates. Atomic force microscopy, scanning electron microscopy and scanning Auger electron spectroscopy are used for characterization of these templates. In agreement with a selective laser process, the results indicate the formation of flat chemical patterns with well-defined boundaries. Complementary condensation experiments demonstrate the functionality of the patterns as hydrophilic/hydrophobic templates. In particular, upon decreasing the temperature below the dew point, selective formation of water droplets on the backfilled areas is observed.

  4. Time- and space-resolved selective multipair creation

    NASA Astrophysics Data System (ADS)

    Lv, Q. Z.; Bauke, Heiko

    2017-09-01

    The simultaneous creation of multiple electron-positron pairs by localized strong electric fields is studied by utilizing a time- and space-resolved quantum field theory approach. It is demonstrated that the number of simultaneously created pairs equals the number of the potential's supercritical quasibound states in the Dirac sea. This means it can be controlled by tuning the potential parameters. Furthermore, the energy of the created particles corresponds to the energy of the supercritical quasibound states. The simultaneously created electrons and positrons are statistically correlated, which is reflected in the spatial distribution and the momentum distribution of these particles and antiparticles.

  5. Field site selection: getting it right first time around

    PubMed Central

    Malcolm, Colin A; El Sayed, Badria; Babiker, Ahmed; Girod, Romain; Fontenille, Didier; Knols, Bart GJ; Nugud, Abdel Hameed; Benedict, Mark Q

    2009-01-01

    The selection of suitable field sites for integrated control of Anopheles mosquitoes using the sterile insect technique (SIT) requires consideration of the full gamut of factors facing most proposed control strategies, but four criteria identify an ideal site: 1) a single malaria vector, 2) an unstructured, relatively low density target population, 3) isolation of the target population and 4) actual or potential malaria incidence. Such a site can exist in a diverse range of situations or can be created. Two contrasting SIT field sites are examined here: the desert-flanked Dongola Reach of the Nile River in Northern State, Sudan, where malaria is endemic, and the island of La Reunion, where autochthonous malaria is rare but risk is persistent. The single malaria-transmitting vector at both sites is Anopheles arabiensis. In Sudan, the target area is a narrow 500 km corridor stretching from the rocky terrain at the Fourth Cataract - just above the new Merowe Dam, to the northernmost edge of the species range, close to Egypt. Vector distribution and temporal changes in density depend on the Nile level, ambient temperature and human activities. On La Reunion, the An. arabiensis population is coastal, limited and divided into three areas by altitude and exposure to the trade winds on the east coast. Mosquito vectors for other diseases are an issue at both sites, but of primary importance on La Reunion due to the recent chikungunya epidemic. The similarities and differences between these two sites in terms of suitability are discussed in the context of area-wide integrated vector management incorporating the SIT. PMID:19917079

  6. Field site selection: getting it right first time around.

    PubMed

    Malcolm, Colin A; El Sayed, Badria; Babiker, Ahmed; Girod, Romain; Fontenille, Didier; Knols, Bart G J; Nugud, Abdel Hameed; Benedict, Mark Q

    2009-11-16

    The selection of suitable field sites for integrated control of Anopheles mosquitoes using the sterile insect technique (SIT) requires consideration of the full gamut of factors facing most proposed control strategies, but four criteria identify an ideal site: 1) a single malaria vector, 2) an unstructured, relatively low density target population, 3) isolation of the target population and 4) actual or potential malaria incidence. Such a site can exist in a diverse range of situations or can be created. Two contrasting SIT field sites are examined here: the desert-flanked Dongola Reach of the Nile River in Northern State, Sudan, where malaria is endemic, and the island of La Reunion, where autochthonous malaria is rare but risk is persistent. The single malaria-transmitting vector at both sites is Anopheles arabiensis. In Sudan, the target area is a narrow 500 km corridor stretching from the rocky terrain at the Fourth Cataract--just above the new Merowe Dam, to the northernmost edge of the species range, close to Egypt. Vector distribution and temporal changes in density depend on the Nile level, ambient temperature and human activities. On La Reunion, the An. arabiensis population is coastal, limited and divided into three areas by altitude and exposure to the trade winds on the east coast. Mosquito vectors for other diseases are an issue at both sites, but of primary importance on La Reunion due to the recent chikungunya epidemic. The similarities and differences between these two sites in terms of suitability are discussed in the context of area-wide integrated vector management incorporating the SIT.

  7. Transfer and the Part-Time Student: The Gulf Separating Community Colleges and Selective Universities

    ERIC Educational Resources Information Center

    Handel, Stephen J.

    2009-01-01

    When representatives from community colleges and selective four-year institutions gather, there is no greater flashpoint than the topic of part-time enrollment. This issue--that students coming from an institution comprising mostly part-time students should be enabled to transfer to selective four-year institutions in which full-time enrollment is…

  8. Transfer and the Part-Time Student: The Gulf Separating Community Colleges and Selective Universities

    ERIC Educational Resources Information Center

    Handel, Stephen J.

    2009-01-01

    When representatives from community colleges and selective four-year institutions gather, there is no greater flashpoint than the topic of part-time enrollment. This issue--that students coming from an institution comprising mostly part-time students should be enabled to transfer to selective four-year institutions in which full-time enrollment is…

  9. Study of selected phenotype switching strategies in time varying environment

    NASA Astrophysics Data System (ADS)

    Horvath, Denis; Brutovsky, Branislav

    2016-03-01

    Population heterogeneity plays an important role across many research, as well as the real-world, problems. The population heterogeneity relates to the ability of a population to cope with an environment change (or uncertainty) preventing its extinction. However, this ability is not always desirable as can be exemplified by an intratumor heterogeneity which positively correlates with the development of resistance to therapy. Causation of population heterogeneity is therefore in biology and medicine an intensively studied topic. In this paper the evolution of a specific strategy of population diversification, the phenotype switching, is studied at a conceptual level. The presented simulation model studies evolution of a large population of asexual organisms in a time-varying environment represented by a stochastic Markov process. Each organism disposes with a stochastic or nonlinear deterministic switching strategy realized by discrete-time models with evolvable parameters. We demonstrate that under rapidly varying exogenous conditions organisms operate in the vicinity of the bet-hedging strategy, while the deterministic patterns become relevant as the environmental variations are less frequent. Statistical characterization of the steady state regimes of the populations is done using the Hellinger and Kullback-Leibler functional distances and the Hamming distance.

  10. Developmental Trajectories of Regulating Attentional Selection Over Time

    PubMed Central

    Heim, Sabine; Keil, Andreas

    2012-01-01

    Adaptive behavior in learning environments requires both the maintenance of an attentional focus on a task-set and suppression of distracting stimuli. This may be especially difficult when the competing information is more appealing than the target event. The aptitude to “pay attention” and resist distraction has often been noted as an important prerequisite of successful acquisition of intellectual abilities in children. This focused review draws on research that highlights interindividual differences in the temporal dynamics of attentional engagement and disengagement under competition, and their relation with age and cognitive/academic skills. Although basic strategies of attention control are present in very young children, the more refined ability to manage attentional resources over time in an economic and adaptive fashion appears during early school years, dramatically improves until the early teen years, and continues to develop into late adolescence. Across studies, parameters of attention control over time predict specific aspects of academic performance, rather than general intellectual ability. We conclude that the ability to strategically regulate the dynamic allocation of attention at rapid rates may represent an important element of cognitive and academic development. PMID:22905028

  11. Developmental trajectories of regulating attentional selection over time.

    PubMed

    Heim, Sabine; Keil, Andreas

    2012-01-01

    Adaptive behavior in learning environments requires both the maintenance of an attentional focus on a task-set and suppression of distracting stimuli. This may be especially difficult when the competing information is more appealing than the target event. The aptitude to "pay attention" and resist distraction has often been noted as an important prerequisite of successful acquisition of intellectual abilities in children. This focused review draws on research that highlights interindividual differences in the temporal dynamics of attentional engagement and disengagement under competition, and their relation with age and cognitive/academic skills. Although basic strategies of attention control are present in very young children, the more refined ability to manage attentional resources over time in an economic and adaptive fashion appears during early school years, dramatically improves until the early teen years, and continues to develop into late adolescence. Across studies, parameters of attention control over time predict specific aspects of academic performance, rather than general intellectual ability. We conclude that the ability to strategically regulate the dynamic allocation of attention at rapid rates may represent an important element of cognitive and academic development.

  12. Selective Serotonin Reuptake Inhibitor-Induced Sexual Dysfunction in Adolescents: A Review.

    ERIC Educational Resources Information Center

    Scharko, Alexander M.

    2004-01-01

    Objective: To review the existing literature on selective serotonin reuptake inhibitor (SSRI)-induced sexual dysfunction in adolescents. Method: A literature review of SSRI-induced adverse effects in adolescents focusing on sexual dysfunction was done. Nonsexual SSRI-induced adverse effects were compared in adult and pediatric populations.…

  13. Visible light-induced ion-selective optodes based on a metastable photoacid for cation detection.

    PubMed

    Patel, Parth K; Chumbimuni-Torres, Karin Y

    2016-01-07

    A new platform of ion-selective optodes is presented here to detect cations under thermodynamic equilibrium via ratiometric analysis. This novel platform utilizes a 'one of a kind' visible light-induced metastable photoacid as a reference ion indicator to achieve activatable and controllable sensors. These ion-selective optodes were studied in terms of their stability, sensitivity, selectivity, and theoretical aspects.

  14. UV radiation induced surface modulation time evolution in polymeric materials

    NASA Astrophysics Data System (ADS)

    Apostol, I.; Apostol, D.; Damian, V.; Iordache, I.; Hurduc, N.; Sava, I.; Sacarescu, L.; Stoica, I.

    2010-11-01

    The reorganization processes at submicron level of the polymeric materials have been investigated because of their applications in optoelectronics and bio-science. We have obtained surface relief modulation in single step processing on the photo resist and polysiloxane films. But for technical applications the time evolution and stability of the induced surface structure is an important parameter and is a problem to be discussed. In case of single step surface relief formation on polymeric materials the process is connected with the photochromic behavior of the materials. As it is known the UV light induced effects on the material structure are reversible under the action of visible light, but with different speeds. In this report is analyzed the time evolution of the surface modulation obtained under the action of the UV light for azopolymers with different structures.

  15. Timing of Initiation of RRT and Modality Selection

    PubMed Central

    2015-01-01

    There is no shortage of studies and registry data examining outcomes of patients on dialysis and those with a renal transplant. However, recently, there has been a greater focus on the events leading up to the institution of kidney replacement therapy. Associative data suggest that early and consistent predialysis care leads to better outcomes, including greater take-on to home-based therapy, diminished use of tunneled venous hemodialysis catheters, and improved early and even late survival. What transpires during predialysis visits is also important. Simple dissemination of facts to the unprepared patient is unlikely to be effective in moving the patient and family along in the process of the series of choices that have to be made around therapy. A more flexible and circumspect approach is needed, including recognizing when the patient is or is not ready for change. There seems to be no optimal timing of dialysis start that can be applied to the ESRD population as a whole, although the pendulum seems to be swinging back toward symptom-based rather than eGFR-based starts. PMID:25762523

  16. Inducible and Selective Erasure of Memories in the Mouse Brain via Chemical-Genetic Manipulation

    PubMed Central

    Cao, Xiaohua; Wang, Huimin; Mei, Bing; An, Shuming; Yin, Liang; Wang, L. Phillip; Tsien, Joe Z.

    2010-01-01

    SUMMARY Rapid and selective erasures of certain types of memories in the brain would be desirable under certain clinical circumstances. By employing an inducible and reversible chemical-genetic technique, we find that transient αCaMKII overexpression at the time of recall impairs the retrieval of both newly formed one-hour object recognition memory and fear memories, as well as 1-month-old fear memories. Systematic analyses suggest that excessive αCaMKII activity-induced recall deficits are not caused by disrupting the retrieval access to the stored information but are, rather, due to the active erasure of the stored memories. Further experiments show that the recall-induced erasure of fear memories is highly restricted to the memory being retrieved while leaving other memories intact. Therefore, our study reveals a molecular genetic paradigm through which a given memory, such as new or old fear memory, can be rapidly and specifically erased in a controlled and inducible manner in the brain. PMID:18957226

  17. Real-time monitoring of cisplatin-induced cell death.

    PubMed

    Alborzinia, Hamed; Can, Suzan; Holenya, Pavlo; Scholl, Catharina; Lederer, Elke; Kitanovic, Igor; Wölfl, Stefan

    2011-01-01

    Since the discovery of cisplatin more than 40 years ago and its clinical introduction in the 1970s an enormous amount of research has gone into elucidating the mechanism of action of cisplatin on tumor cells. With a novel cell biosensor chip system allowing continuous monitoring of respiration, glycolysis, and impedance we followed cisplatin treatment of different cancer cell lines in real-time. Our measurements reveal a first effect on respiration, in all cisplatin treated cell lines, followed with a significant delay by interference with glycolysis in HT-29, HCT-116, HepG2, and MCF-7 cells but not in the cisplatin-resistant cell line MDA-MB-231. Most strikingly, cell death started in all cisplatin-sensitive cell lines within 8 to 11 h of treatment, indicating a clear time frame from exposure, first response to cisplatin lesions, to cell fate decision. The time points of most significant changes were selected for more detailed analysis of cisplatin response in the breast cancer cell line MCF-7. Phosphorylation of selected signal transduction mediators connected with cellular proliferation, as well as changes in gene expression, were analyzed in samples obtained directly from sensor chips at the time points when changes in glycolysis and impedance occurred. Our online cell biosensor measurements reveal for the first time the time scale of metabolic response until onset of cell death under cisplatin treatment, which is in good agreement with models of p53-mediated cell fate decision.

  18. Setipiprant, a selective CRTH2 antagonist, reduces allergen-induced airway responses in allergic asthmatics.

    PubMed

    Diamant, Z; Sidharta, P N; Singh, D; O'Connor, B J; Zuiker, R; Leaker, B R; Silkey, M; Dingemanse, J

    2014-08-01

    CRTH2 is a G-protein-coupled receptor on T helper2 cells that mediates pro-inflammatory effects of prostaglandin D2 in allergic responses. To investigate the tolerability and pharmacokinetics of setipiprant (ACT-129968), a selective orally active CRTH2 antagonist, in allergic asthmatics and to assess the protective effects of multiple doses of this drug against allergen-induced airway responses. In this 3-centre, double-blinded, placebo-controlled, cross-over study, 18 allergic asthmatic males were randomized to setipiprant 1000 mg or matching placebo b.i.d. for 5 consecutive days. Study periods were separated by a washout of ≥ 3 weeks. On study day 4, subjects underwent a standardized allergen challenge and airway response was recorded by FEV1 until 10 h post-allergen. Airway responsiveness to methacholine and exhaled nitric oxide (eNO) were measured pre- and post-dosing. The effects of both treatments on the allergen-induced airway responses were compared by a paired Student's t-test. Fifteen subjects completed the study per-protocol and were included in the analysis. Overall, setipiprant was well tolerated and no clinically relevant adverse events occurred. Trough plasma concentrations showed a high inter-subject variability. Compared with placebo, setipiprant significantly reduced the allergen-induced late asthmatic response (LAR), inhibiting the area under the response vs. time curve (AUC(3-10 h) ) by on average 25.6% (P = 0.006) and significantly protected against the allergen-induced airway hyperresponsiveness (AHR) to methacholine (P = 0.0029). There was no difference in the early asthmatic response (EAR) or in allergen-induced changes in eNO between treatments. Setipiprant at multiple oral doses was well tolerated and reduced both the allergen-induced LAR and the associated AHR in allergic asthmatics. Our findings confirm that CRTH2 may be a promising target for the treatment of allergic disorders. © 2014 John Wiley & Sons Ltd.

  19. An Examination of Program Selection Criteria for Part-Time MBA Students

    ERIC Educational Resources Information Center

    Colburn, Michael; Fox, Daniel E.; Westerfelt, Debra Kay

    2011-01-01

    Prospective graduate students select a graduate program as a result of a multifaceted decision-making process. This study examines the selection criteria that part-time MBA students used in selecting a program at a private university. Further, it analyzes the methods by which the students first learned of the MBA program. The authors posed the…

  20. An Examination of Program Selection Criteria for Part-Time MBA Students

    ERIC Educational Resources Information Center

    Colburn, Michael; Fox, Daniel E.; Westerfelt, Debra Kay

    2011-01-01

    Prospective graduate students select a graduate program as a result of a multifaceted decision-making process. This study examines the selection criteria that part-time MBA students used in selecting a program at a private university. Further, it analyzes the methods by which the students first learned of the MBA program. The authors posed the…

  1. Aberrant Time to Most Recent Common Ancestor as a Signature of Natural Selection.

    PubMed

    Hunter-Zinck, Haley; Clark, Andrew G

    2015-10-01

    Natural selection inference methods often target one mode of selection of a particular age and strength. However, detecting multiple modes simultaneously, or with atypical representations, would be advantageous for understanding a population's evolutionary history. We have developed an anomaly detection algorithm using distributions of pairwise time to most recent common ancestor (TMRCA) to simultaneously detect multiple modes of natural selection in whole-genome sequences. As natural selection distorts local genealogies in distinct ways, the method uses pairwise TMRCA distributions, which approximate genealogies at a nonrecombining locus, to detect distortions without targeting a specific mode of selection. We evaluate the performance of our method, TSel, for both positive and balancing selection over different time-scales and selection strengths and compare TSel's performance with that of other methods. We then apply TSel to the Complete Genomics diversity panel, a set of human whole-genome sequences, and recover loci previously inferred to be under positive or balancing selection.

  2. Effect of previous induced abortions on postabortion contraception selection.

    PubMed

    Keene, Melissa; Roston, Alicia; Keith, Louis; Patel, Ashlesha

    2015-05-01

    The objective was to compare contraceptive method selection in women undergoing their first pregnancy termination versus women undergoing repeat pregnancy termination in an urban abortion clinic. We hypothesized that women undergoing repeat abortions will select highly effective contraceptives (intrauterine device, subdermal implant, tubal ligation) more often than patients undergoing their first abortion. We conducted a retrospective analysis of all women undergoing first-trimester surgical abortion at John H. Stroger, Jr., Hospital of Cook County from October 1, 2009, to October 31, 2011. We compared contraceptive method selection in the postabortion period after receipt of contraceptive counseling for 7466 women, stratifying women by history of no prior abortion versus one or more abortions. Of the 7466 women, 48.6% (3625) had no history of previous abortion. After controlling for age, race and number of living children, women with a history of abortion were more likely to select a highly effective method [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.06-1.33]. Most significantly, having living children was the strongest predictor of a highly effective method with an OR of 3.17 (95% CI 2.69-3.75). In women having a first-trimester abortion, the factors most predictive of selecting a highly effective method for postabortion contraception include history of previous abortion and having living children. The latter holds true independent of abortion history. This paper is unique in its ability to demonstrate the high interest in highly effective contraceptive selection in high-risk, low-income women with prior abortion history. Efforts to integrate provision of highly effective methods of contraception for postabortion care are essential for the reduction of future unintended pregnancies. Copyright © 2015 Elsevier Inc. All rights reserved.

  3. CREB Selectively Controls Learning-Induced Structural Remodeling of Neurons

    ERIC Educational Resources Information Center

    Middei, Silvia; Spalloni, Alida; Longone, Patrizia; Pittenger, Christopher; O'Mara, Shane M.; Marie, Helene; Ammassari-Teule, Martine

    2012-01-01

    The modulation of synaptic strength associated with learning is post-synaptically regulated by changes in density and shape of dendritic spines. The transcription factor CREB (cAMP response element binding protein) is required for memory formation and in vitro dendritic spine rearrangements, but its role in learning-induced remodeling of neurons…

  4. CREB Selectively Controls Learning-Induced Structural Remodeling of Neurons

    ERIC Educational Resources Information Center

    Middei, Silvia; Spalloni, Alida; Longone, Patrizia; Pittenger, Christopher; O'Mara, Shane M.; Marie, Helene; Ammassari-Teule, Martine

    2012-01-01

    The modulation of synaptic strength associated with learning is post-synaptically regulated by changes in density and shape of dendritic spines. The transcription factor CREB (cAMP response element binding protein) is required for memory formation and in vitro dendritic spine rearrangements, but its role in learning-induced remodeling of neurons…

  5. Parity-time-symmetry enhanced optomechanically-induced-transparency

    PubMed Central

    Li, Wenlin; Jiang, Yunfeng; Li, Chong; Song, Heshan

    2016-01-01

    We propose and analyze a scheme to enhance optomechanically-induced-transparency (OMIT) based on parity-time-symmetric optomechanical system. Our results predict that an OMIT window which does not exist originally can appear in weak optomechanical coupling and driving system via coupling an auxiliary active cavity with optical gain. This phenomenon is quite different from these reported in previous works in which the gain is considered just to damage OMIT phenomenon even leads to electromagnetically induced absorption or inverted-OMIT. Such enhanced OMIT effects are ascribed to the additional gain which can increase photon number in cavity without reducing effective decay. We also discuss the scheme feasibility by analyzing recent experiment parameters. Our work provide a promising platform for the coherent manipulation and slow light operation, which has potential applications for quantum information processing and quantum optical device. PMID:27489193

  6. Earthquake Interevent Time Distribution for Induced Micro-, Nano-, and Picoseismicity

    NASA Astrophysics Data System (ADS)

    Davidsen, Jörn; Kwiatek, Grzegorz

    2013-02-01

    We examine the temporal statistics of micro-, nano-, and picoseismicity induced by mining as well as by long-term fluid injection. Specifically, we analyze catalogs of seismic events recorded at the Mponeng deep gold mine, South Africa, and at the German deep drilling site. We show that the distribution of time intervals between successive earthquakes is form invariant between the different catalogs. In particular, the distribution can be described by the same scaling function recently established for tectonic seismicity and acoustic emissions from laboratory rock fracture. Thus, our findings bridge the energy gap between those two cases and provide clear evidence that these temporal features of seismicity are independent of the energy scales of the events and whether they are of tectonic or induced origin.

  7. Earthquake interevent time distribution for induced micro-, nano-, and picoseismicity.

    PubMed

    Davidsen, Jörn; Kwiatek, Grzegorz

    2013-02-08

    We examine the temporal statistics of micro-, nano-, and picoseismicity induced by mining as well as by long-term fluid injection. Specifically, we analyze catalogs of seismic events recorded at the Mponeng deep gold mine, South Africa, and at the German deep drilling site. We show that the distribution of time intervals between successive earthquakes is form invariant between the different catalogs. In particular, the distribution can be described by the same scaling function recently established for tectonic seismicity and acoustic emissions from laboratory rock fracture. Thus, our findings bridge the energy gap between those two cases and provide clear evidence that these temporal features of seismicity are independent of the energy scales of the events and whether they are of tectonic or induced origin.

  8. A comparison of selection at list time and time-stratified sampling for estimating suspended sediment loads

    Treesearch

    Robert B. Thomas; Jack Lewis

    1993-01-01

    Time-stratified sampling of sediment for estimating suspended load is introduced and compared to selection at list time (SALT) sampling. Both methods provide unbiased estimates of load and variance. The magnitude of the variance of the two methods is compared using five storm populations of suspended sediment flux derived from turbidity data. Under like conditions,...

  9. Selected time delay data, phase 3. [computerized simulation of time lag of teleoperators for communication satellites

    NASA Technical Reports Server (NTRS)

    Walsh, J. R.; Wetherington, R. D.

    1975-01-01

    The results of a study on time delays in communication systems applicable to the teleoperator program are presented. Time delay data for 11 specific orbits of interest are shown. These data can be used in the MSFC teleoperator simulator to investigate the effect of time delays in the communications link on the teleoperator control functions.

  10. Selected pharmaceutical excipient prevent isoniazid and rifampicin induced hepatotoxicity.

    PubMed

    Shih, Tung-Yuan; Ho, Shan-Chu; Hsiong, Cheng-Huei; Huang, Tien-Yu; Hu, Oliver Yoa-Pu

    2013-07-01

    The incidence of isoniazid (INH)- and rifampicin (RIF)-induced abnormal liver enzyme activity is 27% but only 19% with INH alone. Cytochrome P450 2E1 (CYP2E1) is thought to contribute to the synergistic effects of RIF and INH. Pharmaceutical excipients are inactive ingredients that are added to a pharmaceutical compound. The purpose of this study was to screen excipients for CYP2E1 inhibition and identify whether the screened excipients prevented INH/RIF-induced hepatotoxicity. Fifty-five known pharmaceutical excipients were screened for CYP2E1 inhibition. The hepatotoxic doses of INH and RIF were 50 and 100 mg/kg/day, respectively. Hepatotoxicity was assessed by the galactose single point (GSP) method (a US Food and Drug Administration (FDA) recommended quantitative liver function test), liver histopathology, malondialdehyde (MDA) assay, and measurement of aspartate aminotransferase (AST) and alanine aminotransferase (ALT) activity. We chose the CYP2E1-specific substrate chlorzoxazone to assess CYP2E1 activity in animal and human. Mannitol inhibited CYP2E1 activity by 54% in mice with INH/RIF-induced hepatotoxicity (p < 0.005). Serum AST, ALT and GSP levels were significantly increased 3.8- to 7.8-fold in these mice (p < 0.005), and these levels could be lowered by mannitol. Mannitol significantly alleviated the depletion of hepatic glutathione (GSH) and partially reversed the increase in MDA formation in mice treated with INH/RIF (p < 0.005). Mannitol also decreased CYP2E1 activity by 58% in humans (p < 0.005). Furthermore, an antituberculosis (TB) efficacy assay revealed that mannitol did not affect the anti-TB effects of INH/RIF. Mannitol, an FDA-approved excipient, was found to be a CYP2E1 inhibitor. Mannitol may be a useful adjuvant for drugs that induce hepatotoxicity through CYP2E1, such as INH and RIF.

  11. Sequence selectivity of macrolide-induced translational attenuation

    PubMed Central

    Davis, Amber R.; Gohara, David W.; Yap, Mee-Ngan F.

    2014-01-01

    The prevailing “plug-in-the-bottle” model suggests that macrolide antibiotics inhibit translation by binding inside the ribosome tunnel and indiscriminately arresting the elongation of every nascent polypeptide after the synthesis of six to eight amino acids. To test this model, we performed a genome-wide analysis of translation in azithromycin-treated Staphylococcus aureus. In contrast to earlier predictions, we found that the macrolide does not preferentially induce ribosome stalling near the 5′ end of mRNAs, but rather acts at specific stalling sites that are scattered throughout the entire coding region. These sites are highly enriched in prolines and charged residues and are strikingly similar to other ligand-independent ribosome stalling motifs. Interestingly, the addition of structurally related macrolides had dramatically different effects on stalling efficiency. Our data suggest that ribosome stalling can occur at a surprisingly large number of low-complexity motifs in a fashion that depends only on a few arrest-inducing residues and the presence of a small molecule inducer. PMID:25313041

  12. Sequence selectivity of macrolide-induced translational attenuation.

    PubMed

    Davis, Amber R; Gohara, David W; Yap, Mee-Ngan F

    2014-10-28

    The prevailing "plug-in-the-bottle" model suggests that macrolide antibiotics inhibit translation by binding inside the ribosome tunnel and indiscriminately arresting the elongation of every nascent polypeptide after the synthesis of six to eight amino acids. To test this model, we performed a genome-wide analysis of translation in azithromycin-treated Staphylococcus aureus. In contrast to earlier predictions, we found that the macrolide does not preferentially induce ribosome stalling near the 5' end of mRNAs, but rather acts at specific stalling sites that are scattered throughout the entire coding region. These sites are highly enriched in prolines and charged residues and are strikingly similar to other ligand-independent ribosome stalling motifs. Interestingly, the addition of structurally related macrolides had dramatically different effects on stalling efficiency. Our data suggest that ribosome stalling can occur at a surprisingly large number of low-complexity motifs in a fashion that depends only on a few arrest-inducing residues and the presence of a small molecule inducer.

  13. Method for selectively orienting induced fractures in subterranean earth formations

    DOEpatents

    Shuck, Lowell Z.

    1977-02-01

    The orientation of hydraulically-induced fractures in relatively deep subterranean earth formations is normally confined to vertical projections along a plane parallel to the maximum naturally occurring (tectonic) compressive stress field. It was found that this plane of maximum compressive stress may be negated and, in effect, re-oriented in a plane projecting generally orthogonal to the original tectonic stress plane by injecting liquid at a sufficiently high pressure into a wellbore fracture oriented in a plane parallel to the plane of tectonic stress for the purpose of stressing the surrounding earth formation in a plane generally orthogonal to the plane of tectonic stress. With the plane of maximum compressive stress re-oriented due to the presence of the induced compressive stress, liquid under pressure is injected into a second wellbore disposed within the zone influenced by the induced compressive stress but at a location in the earth formation laterally spaced from the fracture in the first wellbore for effecting a fracture in the second wellbore along a plane generally orthogonal to the fracture in the first wellbore.

  14. Parasite Exposure Drives Selective Evolution of Constitutive versus Inducible Defense.

    PubMed

    Westra, Edze R; van Houte, Stineke; Oyesiku-Blakemore, Sam; Makin, Ben; Broniewski, Jenny M; Best, Alex; Bondy-Denomy, Joseph; Davidson, Alan; Boots, Mike; Buckling, Angus

    2015-04-20

    In the face of infectious disease, organisms evolved a range of defense mechanisms, with a clear distinction between those that are constitutive (always active) and those that are inducible (elicited by parasites). Both defense strategies have evolved from each other, but we lack an understanding of the conditions that favor one strategy over the other. While it is hard to generalize about their degree of protection, it is possible to make generalizations about their associated fitness costs, which are commonly detected. By definition, constitutive defenses are always "on," and are therefore associated with a fixed cost, independent of parasite exposure. Inducible defenses, on the other hand, may lack costs in the absence of parasites but become costly when defense is elicited through processes such as immunopathology. Bacteria can evolve constitutive defense against phage by modification/masking of surface receptors, which is often associated with reduced fitness in the absence of phage. Bacteria can also evolve inducible defense using the CRISPR-Cas (clustered regularly interspaced short palindromic repeat, CRISPR associated) immune system, which is typically elicited upon infection. CRISPR-Cas functions by integrating phage sequences into CRISPR loci on the host genome. Upon re-infection, CRISPR transcripts guide cleavage of phage genomes. In nature, both mechanisms are important. Using a general theoretical model and experimental evolution, we tease apart the mechanism that drives their evolution and show that infection risk determines the relative investment in the two arms of defense. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Selective cytoprotective effect of histamine on doxorubicin-induced hepatic and cardiac toxicity in animal models

    PubMed Central

    Lamas, DJMartinel; Nicoud, MB; Sterle, HA; Carabajal, E; Tesan, F; Perazzo, JC; Cremaschi, GA; Rivera, ES; Medina, VA

    2015-01-01

    The aim of the present work was to evaluate the potential protective effect of histamine on Doxorubicin (Dox)-induced hepatic and cardiac toxicity in different rodent species and in a triple-negative breast tumor-bearing mice model. Male Sprague Dawley rats and Balb/c mice were divided into four groups: control (received saline), histamine (5 mg/kg for rats and 1 mg/kg for mice, daily subcutaneous injection starting 24 h before treatment with Dox), Dox (2 mg/kg, intraperitoneally injected three times a week for 2 weeks) and Dox+histamine (received both treatments). Tissue toxicity was evaluated by histopathological studies and oxidative stress and biochemical parameters. The combined effect of histamine and Dox was also investigated in vitro and in vivo in human MDA-MB-231 triple-negative breast cancer model. Heart and liver of Dox-treated animals displayed severe histological damage, loss of tissue weight, increased TBARS levels and DNA damage along with an augment in serum creatine kinase-myocardial band. Pretreatment with histamine prevented Dox-induced tissue events producing a significant preservation of the integrity of both rat and mouse myocardium and liver, through the reduction of Dox-induced oxidative stress and apoptosis. Histamine treatment preserved anti-tumor activity of Dox, exhibiting differential cytotoxicity and increasing the Dox-induced inhibition of breast tumor growth. Findings provide preclinical evidence indicating that histamine could be a promising candidate as a selective cytoprotective agent for the treatment of Dox-induced cardiac and hepatic toxicity, and encourage the translation to clinical practice. PMID:27551485

  16. Selective-resputtering-induced perpendicular magnetic anisotropy in amorphous TbFe films.

    PubMed

    Harris, V G; Pokhil, T

    2001-08-06

    Perpendicular magnetic anisotropy energy in rf magnetron sputtered amorphous TbFe films is measured to increase exponentially with pair-order anisotropy induced by the selective resputtering of surface adatoms during film growth.

  17. Performance of the disease risk score in a cohort study with policy-induced selection bias.

    PubMed

    Tadrous, Mina; Mamdani, Muhammad M; Juurlink, David N; Krahn, Murray D; Lévesque, Linda E; Cadarette, Suzanne M

    2015-11-01

    To examine the performance of the disease risk score (DRS) in a cohort study with evidence of policy-induced selection bias. We examined two cohorts of new users of bisphosphonates. Estimates for 1-year hip fracture rates between agents using DRS, exposure propensity scores and traditional multivariable analysis were compared. The results for the cohort with no evidence of policy-induced selection bias showed little variation across analyses (-4.1-2.0%). Analysis of the cohort with evidence of policy-induced selection bias showed greater variation (-13.5-8.1%), with the greatest difference seen with DRS analyses. Our findings suggest that caution may be warranted when using DRS methods in cohort studies with policy-induced selection bias, further research is needed.

  18. Selective inhibition of human inducible nitric oxide synthase by S-alkyl-L-isothiocitrulline-containing dipeptides

    PubMed Central

    Park, Jung-Min; Higuchi, Tsunehiko; Kikuchi, Kazuya; Urano, Yasuteru; Hori, Hiroyuki; Nishino, Takeshi; Aoki, Junken; Inoue, Keizo; Nagano, Tetsuo

    2001-01-01

    The aim of this study was to investigate the structure-activity relationship of S-alkyl-L-isothiocitrulline-containing dipeptides towards three partially purified recombinant human nitric oxide synthase (NOS) isozymes, as well as the effects of these compounds on cytokine-induced NO production by human DLD-1 cells.In an in vitro assay, S-methyl-L-isothiocitrulline (L-MIT) was slightly selective for human neuronal NOS (nNOS) over the inducible (iNOS) or endothelial (eNOS) isozyme, but the combination of a hydrophobic L-amino acid (L-Phe, L-Leu or L-Trp) with L-MIT dramatically altered the inhibition pattern to give selective iNOS inhibitors. Introduction of a hydroxy, nitro, amino or methoxy group at the para position of the aromatic ring of L-MIT-L-Phe (MILF) decreased the selectivity and inhibitory potency. A longer or larger S-alkyl group also decreased the selectivity and potency. Dixon analysis showed that all of the dipeptides were competitive inhibitors of the three isoforms of human NOS. The enzymatic time course curves indicated that MILF was a slow binding inhibitor of human iNOS.These results suggest that the human NOS isozymes have different-sized cavities in the binding site near the position to which the C-terminal of L-arginine binds, and the cavity of iNOS is hydrophobic. Interestingly, L-MIT-D-Phe (MIDF) showed little inhibitory activity or selectivity, suggesting that the cavity of human iNOS is located in a well-defined direction from the α carbon atom.NO production in cytokine-stimulated human DLD-1 cells was measured with a fluorescent indicator, DAF-FM. MILF, L-MIT-L-Trp(-CHO) (MILW) and L-MIT-L-Tyr (MILY) showed more potent activity than L-MIT in this whole-cell assay.Thus, S-alkyl-L-isothiocitrulline-containing dipeptides are selective inhibitors of human iNOS, and work efficiently in cell-based assay. PMID:11309260

  19. Selective inhibition of human inducible nitric oxide synthase by S-alkyl-L-isothiocitrulline-containing dipeptides.

    PubMed

    Park, J M; Higuchi, T; Kikuchi, K; Urano, Y; Hori, H; Nishino, T; Aoki, J; Inoue, K; Nagano, T

    2001-04-01

    The aim of this study was to investigate the structure-activity relationship of S-alkyl-L-isothiocitrulline-containing dipeptides towards three partially purified recombinant human nitric oxide synthase (NOS) isozymes, as well as the effects of these compounds on cytokine-induced NO production by human DLD-1 cells. In an in vitro assay, S-methyl-L-isothiocitrulline (L-MIT) was slightly selective for human neuronal NOS (nNOS) over the inducible (iNOS) or endothelial (eNOS) isozyme, but the combination of a hydrophobic L-amino acid (L-Phe, L-Leu or L-Trp) with L-MIT dramatically altered the inhibition pattern to give selective iNOS inhibitors. Introduction of a hydroxy, nitro, amino or methoxy group at the para position of the aromatic ring of L-MIT-L-Phe (MILF) decreased the selectivity and inhibitory potency. A longer or larger S-alkyl group also decreased the selectivity and potency. Dixon analysis showed that all of the dipeptides were competitive inhibitors of the three isoforms of human NOS. The enzymatic time course curves indicated that MILF was a slow binding inhibitor of human iNOS. These results suggest that the human NOS isozymes have different-sized cavities in the binding site near the position to which the C-terminal of L-arginine binds, and the cavity of iNOS is hydrophobic. Interestingly, L-MIT-D-Phe (MIDF) showed little inhibitory activity or selectivity, suggesting that the cavity of human iNOS is located in a well-defined direction from the alpha carbon atom. NO production in cytokine-stimulated human DLD-1 cells was measured with a fluorescent indicator, DAF-FM. MILF, L-MIT-L-Trp(-CHO) (MILW) and L-MIT-L-Tyr (MILY) showed more potent activity than L-MIT in this whole-cell assay. Thus, S-alkyl-L-isothiocitrulline-containing dipeptides are selective inhibitors of human iNOS, and work efficiently in cell-based assay.

  20. Exploring the influential factors in incident clearance time: Disentangling causation from self-selection bias.

    PubMed

    Ding, Chuan; Ma, Xiaolei; Wang, Yinhai; Wang, Yunpeng

    2015-12-01

    Understanding the relationships between influential factors and incident clearance time is crucial to make effective countermeasures for incident management agencies. Although there have been a certain number of achievements on incident clearance time modeling, limited effort is made to investigate the relative role of incident response time and its self-selection in influencing the clearance time. To fill this gap, this study uses the endogenous switching model to explore the influential factors in incident clearance time, and aims to disentangle causation from self-selection bias caused by response process. Under the joint two-stage model framework, the binary probit model and switching regression model are formulated for both incident response time and clearance time, respectively. Based on the freeway incident data collected in Washington State, full information maximum likelihood (FIML) method is utilized to estimate the endogenous switching model parameters. Significant factors affecting incident response time and clearance time can be identified, including incident, temporal, geographical, environmental, traffic and operational attributes. The estimate results reveal the influential effects of incident, temporal, geographical, environmental, traffic and operational factors on incident response time and clearance time. In addition, the causality of incident response time itself and its self-selection correction on incident clearance time are found to be indispensable. These findings suggest that the causal effect of response time on incident clearance time will be overestimated if the self-selection bias is not considered.

  1. Selective cell targeting and lineage tracing of human induced pluripotent stem cells using recombinant avian retroviruses.

    PubMed

    Hildebrand, Laura; Seemann, Petra; Kurtz, Andreas; Hecht, Jochen; Contzen, Jörg; Gossen, Manfred; Stachelscheid, Harald

    2015-12-01

    Human induced pluripotent stem cells (hiPSC) differentiate into multiple cell types. Selective cell targeting is often needed for analyzing gene function by overexpressing proteins in a distinct population of hiPSC-derived cell types and for monitoring cell fate in response to stimuli. However, to date, this has not been possible, as commonly used viruses enter the hiPSC via ubiquitously expressed receptors. Here, we report for the first time the application of a heterologous avian receptor, the tumor virus receptor A (TVA), to selectively transduce TVA(+) cells in a mixed cell population. Expression of the TVA surface receptor via genetic engineering renders cells susceptible for infection by avian leucosis virus (ALV). We generated hiPSC lines with this stably integrated, ectopic TVA receptor gene that expressed the receptor while retaining pluripotency. The undifferentiated hiPSC(TVA+) as well as their differentiating progeny could be infected by recombinant ALV (so-called RCAS virus) with high efficiency. Due to incomplete receptor blocking, even sequential infection of differentiating or undifferentiated TVA(+) cells was possible. In conclusion, the TVA/RCAS system provides an efficient and gentle gene transfer system for hiPSC and extends our possibilities for selective cell targeting and lineage tracing studies.

  2. Debye decomposition of time-lapse spectral induced polarisation data

    NASA Astrophysics Data System (ADS)

    Weigand, M.; Kemna, A.

    2016-01-01

    Spectral induced polarisation (SIP) measurements capture the low-frequency electrical properties of soils and rocks and provide a non-invasive means to access lithological, hydrogeological, and geochemical properties of the subsurface. The Debye decomposition (DD) approach is now increasingly being used to analyse SIP signatures in terms of relaxation time distributions due to its flexibility regarding the shape of the spectra. Imaging and time-lapse (monitoring) SIP measurements, capturing SIP variations in space and time, respectively, are now more and more conducted and lead to a drastic increase in the number of spectra considered, which prompts the need for robust and reliable DD tools to extract quantitative parameters from such data. We here present an implementation of the DD method for the analysis of a series of SIP data sets which are expected to only smoothly change in terms of spectral behaviour, such as encountered in many time-lapse applications where measurement geometry does not change. The routine is based on a non-linear least-squares inversion scheme with smoothness constraints on the spectral variation and in addition from one spectrum of the series to the next to deal with the inherent ill-posedness and non-uniqueness of the problem. By means of synthetic examples with typical SIP characteristics we elucidate the influence of the number and range of considered relaxation times on the inversion results. The source code of the presented routines is provided under an open source licence as a basis for further applications and developments.

  3. Bilateral activation of the abdominal muscles induces longer reaction time.

    PubMed

    Tsao, Henry; Overs, Michelle E; Wu, Jennifer C-Y; Galea, Mary P; Hodges, Paul W

    2008-05-01

    Bilateral deficit is the increase in reaction time during bilateral activation compared to unilateral activation. This has been reported extensively for the limb muscles and is argued to be due to concurrent inhibition through transcallosal pathways. Unlike the limb muscles, the axial muscles are commonly activated bilaterally during functional tasks and have bilateral projections to their motoneurones. Thus it is reasonable to hypothesise that there will be no bilateral deficit for these muscles. Recordings of electromyographic (EMG) activity were made using surface electrodes placed bilaterally over the abdominal muscles in eight healthy right-handed subjects. Subjects performed either right or left pelvic elevation (unilateral abdominal activation), or posterior pelvic tilt (bilateral abdominal activation) "as fast as possible" in response to an auditory tone. Movements were performed as either a simple or choice reaction time task. Bilateral activation induced significantly longer reaction time than unilateral activation, and was observed during both simple and choice reaction time tasks. The results demonstrate that reaction time is delayed during bilateral activation of the abdominal muscles. These findings suggest that bilateral deficit is present for the axial muscles. This could be mediated through inhibition at various levels of the nervous system or variations in postural demand.

  4. Quantifying Airborne Induced Polarization effects in helicopter time domain electromagnetics

    NASA Astrophysics Data System (ADS)

    Macnae, James

    2016-12-01

    This paper derives the Airborne Induced Polarization (AIP) response of an airborne electromagnetic (AEM) system to a horizontal, thin sheet conductor. A vertical component double-dipole approximates helicopter systems with towed concentric horizontal transmitter and receiver loops in frequency- or time-domain. In time domain, the AIP effect typically shows up as late-time negative data with amplitude 4 to 5 orders of magnitude smaller than the early-time peak of the positive AEM responses. Because of limited bandwidth from the short sample time after the decay of inductive responses, accurate extraction of intrinsic AIP parameters other than a minimum chargeability is almost impossible. Modelling further suggests that AIP effects in double-dipole AEM systems can only be reliably detected from polarizable material in the top few tens of metres. A titanium mineral exploration case history from the Lac Brûlé area, Quebec, Canada illustrates strong spatial coherence of AIP minimum chargeability estimates and their independence from other effects such as conductivity and magnetic susceptibility.

  5. Selective response of various brain cell types during neurodegeneration induced by mild impairment of oxidative metabolism.

    PubMed

    Ke, Zun-Ji; Gibson, Gary E

    2004-01-01

    Age-related neurodegenerative diseases are characterized by selective neuron loss, glial activation, inflammation and abnormalities in oxidative metabolism. Thiamine deficiency (TD) is a model of neurodegeneration induced by impairment of oxidative metabolism. TD produces a time-dependent, selective neuronal death in specific brain regions, while other cell types are either activated or unaffected. TD-induced neurodegeneration occurs first in a small, well-defined brain region, the submedial thalamic nucleus (SmTN). This discrete localization permits careful analysis of the relationship between neuronal loss and the response of other cell types. The temporal analysis of the changes in the region in combination with the use of transgenic mice permits testing of proposed mechanisms of how the interaction of neurons with other cell types produces neurodegeneration. Loss of neurons and elevation in markers of neurodegeneration are accompanied by changes in microglia including increased redox active iron, the induction of nitric oxide synthase (NOS) and hemeoxygenase-1, a marker of oxidative stress. Endothelial cells also show changes in early stages of TD including induction of intracellular adhesion molecule-1 (ICAM-1) and endothelial NOS. The number of degranulating mast cells also increases in early stages of TD. Alterations in astrocytes and neutrophils occur at later stages of TD. Studies with transgenic knockouts indicate that the endothelial cell changes are particularly important. We hypothesize that TD-induced abnormalities in oxidative metabolism promote release of neuronal inflammatory signals that activate microglia, astrocytes and endothelial cells. Although at early stages the responses of non-neuronal cells may be neuroprotective, at late phases they lead to entry of peripheral inflammatory cells into the brain and promote neurodegeneration.

  6. A Small Molecule Inhibitor Selectively Induces Apoptosis in Cells Transformed by High Risk Human Papilloma Viruses

    PubMed Central

    Lee, Min S.; Qi, Huilin; Chaniewski, Susan; Zheng, Xiaofan; Farr, Glen A.; Esposito, Kim; Harden, David; Lei, Ming; Schweizer, Liang; Friborg, Jacques; Agler, Michele; McPhee, Fiona; Gentles, Robert; Beno, Brett R.; Chupak, Lou; Mason, Stephen

    2016-01-01

    A phenotypic high-throughput cell culture screen was performed to identify compounds that prevented proliferation of the human Papilloma virus type 16 (HPV-16) transformed cell line Ca Ski. A series of quinoxaline compounds exemplified by Compound 1 was identified. Testing against a panel of cell lines demonstrated that Compound 1 selectively inhibited replication of all HPV-16, HPV-18, and HPV-31 transformed cell lines tested with 50% Inhibitory Concentration (IC50) values of 2 to 8 μM relative to IC50 values of 28 to 73 μM in HPV-negative cell lines. Treatment with Compound 1 resulted in a cascade of multiple apoptotic events, including selective activation of effector caspases 3 and 7, fragmentation of cellular DNA, and PARP (poly(ADP-ribose) polymerase) cleavage in HPV-positive cells relative to HPV-negative cells. Unregulated proliferation of HPV transformed cells is dependent on the viral oncogenes, E6 and E7. Treatment with Compound 1 resulted in a decrease in HPV E7 protein in Ca Ski cells. However, the timing of this reduction relative to other effects of compound treatment suggests that this was a consequence, rather than a cause, of the apoptotic cascade. Likewise, compound treatment resulted in no obvious effects on the E6- and E7- mediated down regulation of p53 and Rb, or their downstream effectors, p21 or PCNA. Further investigation of apoptotic signals induced by Compound 1 revealed cleavage of Caspase-8 in HPV-positive cells as early as 2 hours post-treatment, suggesting the compound initiates apoptosis through the extrinsic, death receptor-mediated, pathway of cell death. These studies provide proof of concept that cells transformed by oncogenic Papillomaviruses can be selectively induced to undergo apoptosis by compound treatment. PMID:27280728

  7. Time-Resolved Aluminum Monoxide Emission Measurements in Laser-Induced Plasma

    NASA Astrophysics Data System (ADS)

    Surmick, David; Parigger, Christian

    2014-03-01

    Laser-induced plasmas are useful for diagnostic applications in a wide variety of fields. One application is the creation of laser-induced plasmas on the surface of an aluminum sample to simulate an aluminized flame. In this study, aluminum monoxide emissions are measured to characterize the temperature along the laser-induced plasma as a function of time delay following laser-induced optical breakdown. The breakdown event is achieved by focusing 1064 nanometer laser radiation from an Nd:YAG laser onto the surface of an aluminum sample. Light from the plasma is dispersed with the use of a Czerny-Turner spectrograph, and time resolved emission spectra are recorded with an intensified, gated detector. Temperatures are inferred from the diatomic molecular emissions by fitting the experimentally collected to theoretically calculated spectra using a Nelder-Mead algorithm. For computation of synthetic spectra we utilize accurate line strengths for selected AlO molecular bands. Atomic emissions from aluminum are also investigated in our study of laser-induced plasma.

  8. Timing as a sexually selected trait: the right mate at the right moment.

    PubMed

    Hau, Michaela; Dominoni, Davide; Casagrande, Stefania; Buck, C Loren; Wagner, Gabriela; Hazlerigg, David; Greives, Timothy; Hut, Roelof A

    2017-11-19

    Sexual selection favours the expression of traits in one sex that attract members of the opposite sex for mating. The nature of sexually selected traits such as vocalization, colour and ornamentation, their fitness benefits as well as their costs have received ample attention in field and laboratory studies. However, sexually selected traits may not always be expressed: coloration and ornaments often follow a seasonal pattern and behaviours may be displayed only at specific times of the day. Despite the widely recognized differences in the daily and seasonal timing of traits and their consequences for reproductive success, the actions of sexual selection on the temporal organization of traits has received only scant attention. Drawing on selected examples from bird and mammal studies, here we summarize the current evidence for the daily and seasonal timing of traits. We highlight that molecular advances in chronobiology have opened exciting new opportunities for identifying the genetic targets that sexual selection may act on to shape the timing of trait expression. Furthermore, known genetic links between daily and seasonal timing mechanisms lead to the hypothesis that selection on one timescale may simultaneously also affect the other. We emphasize that studies on the timing of sexual displays of both males and females from wild populations will be invaluable for understanding the nature of sexual selection and its potential to act on differences within and between the sexes in timing. Molecular approaches will be important for pinpointing genetic components of biological rhythms that are targeted by sexual selection, and to clarify whether these represent core or peripheral components of endogenous clocks. Finally, we call for a renewed integration of the fields of evolution, behavioural ecology and chronobiology to tackle the exciting question of how sexual selection contributes to the evolution of biological clocks.This article is part of the themed issue

  9. Stress, Time Pressure, Strategy Selection and Math Anxiety in Mathematics: A Review of the Literature.

    PubMed

    Caviola, Sara; Carey, Emma; Mammarella, Irene C; Szucs, Denes

    2017-01-01

    We review how stress induction, time pressure manipulations and math anxiety can interfere with or modulate selection of problem-solving strategies (henceforth "strategy selection") in arithmetical tasks. Nineteen relevant articles were identified, which contain references to strategy selection and time limit (or time manipulations), with some also discussing emotional aspects in mathematical outcomes. Few of these take cognitive processes such as working memory or executive functions into consideration. We conclude that due to the sparsity of available literature our questions can only be partially answered and currently there is not much evidence of clear associations. We identify major gaps in knowledge and raise a series of open questions to guide further research.

  10. Selective Serotonin–norepinephrine Reuptake Inhibitors-induced Takotsubo Cardiomyopathy

    PubMed Central

    Vasudev, Rahul; Rampal, Upamanyu; Patel, Hiten; Patel, Kunal; Bikkina, Mahesh; Shamoon, Fayez

    2016-01-01

    Context: Takotsubo translates to “octopus pot” in Japanese. Takotsubo cardiomyopathy (TTC) is characterized by a transient regional systolic dysfunction of the left ventricle. Catecholamine excess is the one most studied and favored theories explaining the pathophysiology of TTC. Case Report: We present the case of a 52-year-old Hispanic female admitted for venlafaxine-induced TTC with a review literature on all the cases of Serotonin–norepinephrine reuptake inhibitors (SNRI)-associated TTC published so far. Conclusion: SNRI inhibit the reuptake of catecholamines into the presynaptic neuron, resulting in a net gain in the concentration of epinephrine and serotonin in the neuronal synapses and causing iatrogenic catecholamine excess, ultimately leading to TTC. PMID:27583240

  11. Capture and real-time display of selected Space Shuttle reentry data

    NASA Technical Reports Server (NTRS)

    Chiles, H. R.

    1983-01-01

    Because the flight planning for the orbital flight test (OFT) flights of the NASA Space Shuttle required several months, there was very little time to analyze data from one flight before it was necessary to start final planning for the next flight. Real-time and selected immediate postflight data display of the reentry data minimized the postflight computer analysis time required so that the rigid time restraints imposed by the program could be met. This paper describes the methods used to decommutate and provide real-time and immediate postflight data display of selected Space Shuttle reentry data.

  12. Selective inhibition of microglia-mediated neuroinflammation mitigates radiation-induced cognitive impairment.

    PubMed

    Jenrow, Kenneth A; Brown, Stephen L; Lapanowski, Karen; Naei, Hoda; Kolozsvary, Andrew; Kim, Jae Ho

    2013-05-01

    Cognitive impairment precipitated by irradiation of normal brain tissue is commonly associated with radiation therapy for treatment of brain cancer, and typically manifests more than 6 months after radiation exposure. The risks of cognitive impairment are of particular concern for an increasing number of long-term cancer survivors. There is presently no effective means of preventing or mitigating this debilitating condition. Neuroinflammation mediated by activated microglial cytokines has been implicated in the pathogenesis of radiation-induced cognitive impairment in animal models, including the disruption of neurogenesis and activity-induced gene expression in the hippocampus. These pathologies evolve rapidly and are associated with relatively subtle cognitive impairment at 2 months postirradiation. However, recent reports suggest that more profound cognitive impairment develops at later post-irradiation time points, perhaps reflecting a gradual loss of responsiveness within the hippocampus by the disruption of neurogenesis. We hypothesized that inhibiting neuroinflammation using MW01-2-151SRM (MW-151), a selective inhibitor of proinflammatory cytokine production, might mitigate these deleterious radiation effects by preserving/restoring hippocampal neurogenesis. MW-151 therapy was initiated 24 h after 10 Gy whole-brain irradiation (WBI) administered as a single fraction and maintained for 28 days thereafter. Proinflammatory activated microglia in the dentate gyrus were assayed at 2 and 9 months post-WBI. Cell proliferation and neurogenesis in the dentate gyrus were assayed at 2 months post-WBI, whereas novel object recognition and long-term potentiation were assayed at 6 and 9 months post-WBI, respectively. MW-151 mitigated radiation-induced neuroinflammation at both early and late time points post-WBI, selectively mitigated the deleterious effects of irradiation on hippocampal neurogenesis, and potently mitigated radiation-induced deficits of novel object

  13. Flexibility of inorganic tennis ball structures inducing anion selectivity.

    PubMed

    Kim, Ki-Hyun; Park, Jung Su; Kang, Tae Yi; Oh, Kyungeun; Seo, Mi-Sook; Sohn, Youn Soo; Jun, Moo-Jin; Nam, Wonwoo; Kim, Kwan Mook

    2006-09-18

    Inorganic tennis balls (ITBs), [[{Pt(betmp)(dach)}(2)Cu](2)(X)][X](3) (in which X=ClO(4) (-) (3), NO(3) (-) (4), Cl(-) (5) and Br(-) (6); dach=trans-1,2-diaminocyclohexane and betmp=bisethylthiomethylidenepropanedioate) and [[{Pt(dteym)(dach)}(2)Cu](2)(PF(6))][PF(6)](3) (7; dteym=1,3-dithiepane-2-ylidenemalonate), were prepared as crystals. Investigation of their X-ray crystal structures revealed that shapes of the cavities in ITBs show significant distortions that depend on the properties of the encapsulated anions. The CuCu* distance was observed to be longest in 7 and shortest in 5, the difference between them being 2.05 A. The flexibility of cavity structures of ITBs makes it possible to encapsulate various anions inside the cavity, while their distortions may be a reason for the difference in the encapsulating ability for anions, that is, anion selectivity. Especially, the distortions observed in 7 are so severe that the encapsulating ability of the cavity for PF(6) (-) is very low compared to other anions. The shapes of ITBs with ClO(4) (-) and BF(4) (-) ions inside their cavities are very similar; however, ClO(4) (-) is encapsulated by the cavity better than BF(4) (-), which is explicable by the difference of metal-anion interactions. This structural study on ITBs gives a clue to the origin of the anion selectivity of the cavity in ITBs previously investigated by (19)F NMR spectroscopy of the ITBs in methanol.

  14. Quantum to classical transition induced by gravitational time dilation

    NASA Astrophysics Data System (ADS)

    Sokolov, Boris; Vilja, Iiro; Maniscalco, Sabrina

    2017-07-01

    We study the loss of quantumness caused by time dilation [I. Pikovski, M. Zych, F. Costa, and Č. Brukner, Nat. Phys. 11, 668 (2015), 10.1038/nphys3366] for a Schrödinger cat state. We give a holistic view of the quantum to classical transition by comparing the dynamics of several nonclassicality indicators, such as the Wigner function interference fringe, the negativity of the Wigner function, the nonclassical depth, the Vogel criterion, and the Klyshko criterion. Our results show that only two of these indicators depend critically on the size of the cat, namely, on how macroscopic the superposition is. Finally we compare the gravitation-induced decoherence times to the typical decoherence times due to classical noise originating from the unavoidable statistical fluctuations in the characteristic parameters of the system [J. Trapani, M. Bina, S. Maniscalco, and M. G. A. Paris, Phys. Rev. A 91, 022113 (2015), 10.1103/PhysRevA.91.022113]. We show that the experimental observation of decoherence due to time dilation imposes severe limitations on the allowed levels of classical noise in the experiments.

  15. A nonlinear correlation function for selecting the delay time in dynamical reconstructions

    NASA Astrophysics Data System (ADS)

    Aguirre, Luis Antonio

    1995-02-01

    Numerical results discussed in this paper suggest that a function which detects nonlinear correlations in time series usually indicates shorter correlation times than the linear autocorrelation function which is often used for this purpose. The nonlinear correlation function can also detect changes in the data which cannot be distinguished by the linear counterpart. This affects a number of approaches for the selection of the delay time used in the reconstruction of nonlinear dynamics from a single time series based on time delay coordinates.

  16. Undecylprodigiosin selectively induces apoptosis in human breast carcinoma cells independent of p53

    SciTech Connect

    Ho, T.-F.; Ma, C.-J.; Lu, C.-H.; Tsai, Yo-Ting; Wei, Y.-H.; Chang, J.-S.; Lai, J.-K.; Cheuh, Pin-Ju; Yeh, C.-T.; Tang, P.-C.; Jingua, T.C.; Ko, J.-L.; Liu, F.-S.; Yen, H.E.

    2007-12-15

    Undecylprodigiosin (UP) is a bacterial bioactive metabolite produced by Streptomyces and Serratia. In this study, we explored the anticancer effect of UP. Human breast carcinoma cell lines BT-20, MCF-7, MDA-MB-231 and T47D and one nonmalignant human breast epithelial cell line, MCF-10A, were tested in this study. We found that UP exerted a potent cytotoxicity against all breast carcinoma cell lines in a dose- and time-dependent manner. In contrast, UP showed limited toxicity to MCF-10A cells, indicating UP's cytotoxic effect is selective for malignant cells. UP's cytotoxic effect was due to apoptosis, as confirmed by positive TUNEL signals, annexin V-binding, caspase 9 activation and PARP cleavage. Notably, UP-induced apoptosis was blocked by the pan-caspase inhibitor z-VAD.fmk, further indicating the involvement of caspase activity. Moreover, UP caused a marked decrease of the levels of antiapoptotic BCL-X{sub L}, Survivin and XIAP while enhancing the levels of proapoptotic BIK, BIM, MCL-1S and NOXA, consequently favoring induction of apoptosis. Additionally, we found that cells with functional p53 (MCF-7, T47D) or mutant p53 (BT-20, MDA-MB-231) were both susceptible to UP's cytotoxicity. Importantly, UP was able to induce apoptosis in MCF-7 cells with p53 knockdown by RNA interference, confirming the dispensability of p53 in UP-induced apoptosis. Overall, our results establish that UP induces p53-independent apoptosis in breast carcinoma cells with no marked toxicity to nonmalignant cells, raising the possibility of its use as a new chemotherapeutic drug for breast cancer irrespective of p53 status.

  17. 76 FR 46840 - Time Extension To Accept Proposals, Select One Lessee, and Contract for Hydroelectric Power...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-03

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF THE INTERIOR Bureau of Reclamation Time Extension To Accept Proposals, Select One Lessee, and Contract for... proposals detailed in the Notice of Intent to Accept Proposals, Select One Lessee, and Contract...

  18. β-Cyclodextrin/glycyrrhizic acid functionalised quantum dots selectively enter hepatic cells and induce apoptosis.

    PubMed

    Zhao, Mei-Xia; Ji, Liang-Nian; Mao, Zong-Wan

    2012-02-06

    The use of active components from important medical herbs has proved effective in treating various cancers. Glycyrrhizic acid (GA) is one of the many interesting triterpenoic acids with anticancerogenic potential, and is known to trigger apoptosis in hepatocarcinoma cells. In this study we combined quantum dots (QDs) with GA in the presence of β-cyclodextrin (β-CD), and prepared β-CD/GA-functionalised QDs, which led to improved antitumor activity and induced apoptosis in hepatocarcinoma cells. These compounds showed a better selectivity for hepatic cells compared to HeLa and ECV-304 cells. Hoechst and annexin V-FITC staining and mitochondrial membrane potential (MMP) experiments proved an apoptotic effect of these compounds on HepG2 cells. At the same time, transmission electron microscopy (TEM) showed obvious features of apoptosis, for example, irregularities of nuclear shapes, mitochondria swelling, clumping and peripheral chromatin condensation, zeiosis or blebbing of the plasma membrane and formation of apoptotic bodies. It is notable that β-CD/GA-functionalised QDs showed effective cell growth inhibition by triggering G0/G1 phase arrest and inducing apoptosis through an reactive oxygen species mediated mitochondrial dysfunction pathway. β-CD/GA-functionalised QDs primarily induced apoptotic response in a time- and dose-dependent manner, but little apoptosis appeared with L-Cys-β-CD-functionalised QDs or GA alone. These studies suggest that β-CD/GA-functionalised QDs have therapeutic potential against cancer. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  19. Ferrocifen derivatives that induce senescence in cancer cells: selected examples.

    PubMed

    Bruyère, Céline; Mathieu, Véronique; Vessières, Anne; Pigeon, Pascal; Top, Siden; Jaouen, Gérard; Kiss, Robert

    2014-12-01

    Platinum coordination complexes represent an important class of anti-tumor agents. Due to recognized drawbacks, research into other types of metallodrugs has been diversified with the aim of finding new chemical entities with alternative mechanisms of action to overcome classical chemoresistance. P5 and DP1, two closely related ferrocenyl complexes bearing a similar ferrocenyl-ene-phenyl motif and displaying marked differences in their conformations and oxidation state versatility, were assayed in cancer cell models characterized by various sensitivities to pro-apoptotic stimuli. P5 and DP1 exert growth inhibitory effects between 0.5 and 10 μM against glioma and melanoma cells including pluripotent stem-like cells. These effects are due, at least partly, to senescence induction with typical SA-β-galactosidase staining and senescence-associated secretory phenotype (SASP) as measured by the secretion of IL-1α, IL-1β, IL-6, IL-8 and TNF-α. Regulation of these cytokines' secretion may be related to AP-1 and other transcription factors unrelated to senescence. An in vivo graft of B16F10 cells after in vitro pre-incubation with DP1 or P5 led to increased survival in mice. In conclusion, P5 and DP1 ferrocenyl complexes induce senescence in various cancer cell models associated with distinct sensitivity to pro-apoptotic stimuli.

  20. Inducing superconductivity in Weyl semimetal microstructures by selective ion sputtering.

    PubMed

    Bachmann, Maja D; Nair, Nityan; Flicker, Felix; Ilan, Roni; Meng, Tobias; Ghimire, Nirmal J; Bauer, Eric D; Ronning, Filip; Analytis, James G; Moll, Philip J W

    2017-05-01

    By introducing a superconducting gap in Weyl or Dirac semimetals, the superconducting state inherits the nontrivial topology of their electronic structure. As a result, Weyl superconductors are expected to host exotic phenomena, such as nonzero-momentum pairing due to their chiral node structure, or zero-energy Majorana modes at the surface. These are of fundamental interest to improve our understanding of correlated topological systems, and, moreover, practical applications in phase-coherent devices and quantum applications have been proposed. Proximity-induced superconductivity promises to allow these experiments on nonsuperconducting Weyl semimetals. We show a new route to reliably fabricate superconducting microstructures from the nonsuperconducting Weyl semimetal NbAs under ion irradiation. The significant difference in the surface binding energy of Nb and As leads to a natural enrichment of Nb at the surface during ion milling, forming a superconducting surface layer (Tc ~ 3.5 K). Being formed from the target crystal itself, the ideal contact between the superconductor and the bulk may enable an effective gapping of the Weyl nodes in the bulk because of the proximity effect. Simple ion irradiation may thus serve as a powerful tool for the fabrication of topological quantum devices from monoarsenides, even on an industrial scale.

  1. Inducing superconductivity in Weyl semimetal microstructures by selective ion sputtering

    PubMed Central

    Bachmann, Maja D.; Nair, Nityan; Flicker, Felix; Ilan, Roni; Meng, Tobias; Ghimire, Nirmal J.; Bauer, Eric D.; Ronning, Filip; Analytis, James G.; Moll, Philip J. W.

    2017-01-01

    By introducing a superconducting gap in Weyl or Dirac semimetals, the superconducting state inherits the nontrivial topology of their electronic structure. As a result, Weyl superconductors are expected to host exotic phenomena, such as nonzero-momentum pairing due to their chiral node structure, or zero-energy Majorana modes at the surface. These are of fundamental interest to improve our understanding of correlated topological systems, and, moreover, practical applications in phase-coherent devices and quantum applications have been proposed. Proximity-induced superconductivity promises to allow these experiments on nonsuperconducting Weyl semimetals. We show a new route to reliably fabricate superconducting microstructures from the nonsuperconducting Weyl semimetal NbAs under ion irradiation. The significant difference in the surface binding energy of Nb and As leads to a natural enrichment of Nb at the surface during ion milling, forming a superconducting surface layer (Tc ~ 3.5 K). Being formed from the target crystal itself, the ideal contact between the superconductor and the bulk may enable an effective gapping of the Weyl nodes in the bulk because of the proximity effect. Simple ion irradiation may thus serve as a powerful tool for the fabrication of topological quantum devices from monoarsenides, even on an industrial scale. PMID:28560340

  2. Selective HDAC6 inhibition prevents TNF-α-induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema.

    PubMed

    Yu, Jinyan; Ma, Zhongsen; Shetty, Sreerama; Ma, Mengshi; Fu, Jian

    2016-07-01

    Lung endothelial damage contributes to the pathogenesis of acute lung injury. New strategies against lung endothelial barrier dysfunction may provide therapeutic benefits against lung vascular injury. Cell-cell junctions and microtubule cytoskeleton are basic components in maintaining endothelial barrier integrity. HDAC6, a deacetylase primarily localized in the cytoplasm, has been reported to modulate nonnuclear protein function through deacetylation. Both α-tubulin and β-catenin are substrates for HDAC6. Here, we examined the effects of tubastatin A, a highly selective HDAC6 inhibitor, on TNF-α induced lung endothelial cell barrier disruption and endotoxin-induced pulmonary edema. Selective HDAC6 inhibition by tubastatin A blocked TNF-α-induced lung endothelial cell hyperpermeability, which was associated with increased α-tubulin acetylation and microtubule stability. Tubastatin A pretreatment inhibited TNF-α-induced endothelial cell contraction and actin stress fiber formation with reduced myosin light chain phosphorylation. Selective HDAC6 inhibition by tubastatin A also induced β-catenin acetylation in human lung endothelial cells, which was associated with increased membrane localization of β-catenin and stabilization of adherens junctions. HDAC6 knockdown by small interfering RNA also prevented TNF-α-induced barrier dysfunction and increased α-tubulin and β-catenin acetylation in endothelial cells. Furthermore, in a mouse model of endotoxemia, tubastatin A was able to prevent endotoxin-induced deacetylation of α-tubulin and β-catenin in lung tissues, which was associated with reduced pulmonary edema. Collectively, our data indicate that selective HDAC6 inhibition by tubastatin A is a potent approach against lung endothelial barrier dysfunction.

  3. Selective impairment in the recognition of anger induced by diazepam.

    PubMed

    Blair, R J; Curran, H V

    1999-12-01

    Facial expressions appear to be processed by at least partially separable neuro-cognitive systems. Given this functional specialization of expression processing, it is plausible that these neurocognitive systems may also be dissociable pharmacologically. The present study therefore compared the effects of diazepam (15 mg) with placebo upon the ability to recognize emotional expressions. A double blind, independent group design was used to compare the effects of diazepam and matched placebo in 32 healthy volunteers. Participants were presented morphed facial expression stimuli following a paradigm developed for use with patients with brain damage and asked to name one of the six basic emotions (sadness, happiness, anger, disgust, fear and surprise). Diazepam selectively impaired subjects' ability to recognize angry expressions but did not affect recognition of any other emotional expression. The findings are interpreted as providing further support for the suggestion that there are dissociable systems responsible for processing emotional expressions. It is suggested that these findings may have implications for understanding paradoxical aggression sometimes elicited by benzodiazepines.

  4. Within-plant variation in reproductive investment: consequences for selection on flowering time.

    PubMed

    Austen, E J; Forrest, J R K; Weis, A E

    2015-01-01

    Variation among the leaves, flowers or fruit produced by a plant is often regarded as a nuisance to the experimenter and an impediment to selection. Here, we suggest that within-plant variation can drive selection on other plant-level traits. We examine within-plant variation in floral sex allocation and in fruit set and predict that such variation generates variation in male success among plants, thereby driving selection on flowering time. We tested this prediction in a simulation model estimating selection on flowering time through male fitness when floral sex allocation and/or fruit set vary directionally among flowers on plants. We parameterized the model through a quantitative literature survey of within-plant change in sex allocation. As predicted, within-plant variation in floral sex allocation and in fruit set probability can generate selection on flowering time through male fitness. Declining fruit set from first to last flowers on plants, as occurs in many species, selected for early flowering onset through male fitness. This result was robust to self-incompatibility and to varying returns on male versus female investment. Selection caused by declining fruit set was strong enough to reverse the selection for late flowering that can be caused by intrafloral protandry. Our model provides testable predictions regarding selection on flowering time through male fitness. The model also establishes the intriguing possibility that within-plant variation may influence selection on other traits, regardless of whether that variation is under selection itself. © 2014 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2014 European Society For Evolutionary Biology.

  5. Optomechanically induced absorption in parity-time-symmetric optomechanical systems

    NASA Astrophysics Data System (ADS)

    Zhang, X. Y.; Guo, Y. Q.; Pei, P.; Yi, X. X.

    2017-06-01

    We explore the optomechanically induced absorption (OMIA) in a parity-time- (PT -) symmetric optomechanical system (OMS). By numerically calculating the Lyapunov exponents, we find out the stability border of the PT -symmetric OMS. The results show that in the PT -symmetric phase the system can be either stable or unstable depending on the coupling constant and the decay rate. In the PT -symmetric broken phase the system can have a stable state only for small gain rates. By calculating the transmission rate of the probe field, we find that there is an inverted optomechanically induced transparency (OMIT) at δ =-ωM and an OMIA at δ =ωM for the PT -symmetric optomechanical system. At each side of δ =-ωM there is an absorption window due to the resonance absorption of the two generated supermodes. Comparing with the case of optomechanics coupled to a passive cavity, we find that the active cavity can enhance the resonance absorption. The absorption rate at δ =ωM increases as the coupling strength between the two cavities increases. Our work provides us with a promising platform for controlling light propagation and light manipulation in terms of PT symmetry, which might have potential applications in quantum information processing and quantum optical devices.

  6. Correlation-induced Time Delay in Atomic Photoionization

    NASA Astrophysics Data System (ADS)

    Keating, David A.; Manson, Steven T.; Deshmukh, Pranawa C.; Kheifets, Anatoli S.

    2016-05-01

    Interchannel coupling has been seen to result in structures in the photoionization cross sections of outer shell electrons in the vicinity of inner-shell thresholds, a result which leads us to ask if the same would be true for the time delay of outer shell electrons near inner-shell thresholds. Using the relativistic-random-phase approximation (RRPA) methodology, a theoretical study of neon, argon, krypton, and xenon were performed to search for these correlation-induced effects. Calculations were performed both with coupling and without coupling to verify that the structures found in the time delay were in fact due to interchannel coupling. Using this method to study the effects of interchannel coupling reveals how much of an impact the coupling has on the time delay, in some cases over a broad energy range. In cases where the spin-orbit doublets' respective thresholds are far enough apart, effects can be found in the j = l + 1/2channels due to interchannel coupling with the j = l-1/2 channels. These structures are purely a relativistic effect and are related to spin-obit activated interchannel coupling effects. Work supported by DOE, Office of Chemical Sciences, DST (India), and the Australian Research Council.

  7. Time-reversal-breaking induced quantum spin Hall effect.

    PubMed

    Luo, Wei; Shao, D X; Deng, Ming-Xun; Deng, W Y; Sheng, L

    2017-02-21

    We show that quantum spin Hall (QSH) effect does not occur in a square lattice model due to cancellation of the intrinsic spin-orbit coupling coming from different hopping paths. However, we show that QSH effect can be induced by the presence of staggered magnetic fluxes alternating directions square by square. When the resulting Peierls phase takes a special value , the system has a composite symmetry ΘΡ- with Θ the time-reversal operator and Ρ- transforming the Peierls phase from γ to γ - , which protects the gapless edge states. Once the phase deviates from , the edge states open a gap, as the composite symmetry is broken. We further investigate the effect of a Zeeman field on the QSH state, and find that the edge states remain gapless for . This indicates that the QSH effect is immune to the magnetic perturbation.

  8. Time-reversal-breaking induced quantum spin Hall effect

    NASA Astrophysics Data System (ADS)

    Luo, Wei; Shao, D. X.; Deng, Ming-Xun; Deng, W. Y.; Sheng, L.

    2017-02-01

    We show that quantum spin Hall (QSH) effect does not occur in a square lattice model due to cancellation of the intrinsic spin-orbit coupling coming from different hopping paths. However, we show that QSH effect can be induced by the presence of staggered magnetic fluxes alternating directions square by square. When the resulting Peierls phase takes a special value , the system has a composite symmetry ΘΡ- with Θ the time-reversal operator and Ρ- transforming the Peierls phase from γ to γ - , which protects the gapless edge states. Once the phase deviates from , the edge states open a gap, as the composite symmetry is broken. We further investigate the effect of a Zeeman field on the QSH state, and find that the edge states remain gapless for . This indicates that the QSH effect is immune to the magnetic perturbation.

  9. Time-reversal-breaking induced quantum spin Hall effect

    PubMed Central

    Luo, Wei; Shao, D. X.; Deng, Ming-Xun; Deng, W. Y.; Sheng, L.

    2017-01-01

    We show that quantum spin Hall (QSH) effect does not occur in a square lattice model due to cancellation of the intrinsic spin-orbit coupling coming from different hopping paths. However, we show that QSH effect can be induced by the presence of staggered magnetic fluxes alternating directions square by square. When the resulting Peierls phase takes a special value , the system has a composite symmetry ΘΡ− with Θ the time-reversal operator and Ρ− transforming the Peierls phase from γ to γ − , which protects the gapless edge states. Once the phase deviates from , the edge states open a gap, as the composite symmetry is broken. We further investigate the effect of a Zeeman field on the QSH state, and find that the edge states remain gapless for . This indicates that the QSH effect is immune to the magnetic perturbation. PMID:28220858

  10. Fishery-induced selection on an Alpine whitefish: quantifying genetic and environmental effects on individual growth rate

    PubMed Central

    Nusslé, Sébastien; Bornand, Christophe N; Wedekind, Claus

    2009-01-01

    Size-selective fishing, environmental changes and reproductive strategies are expected to affect life-history traits such as the individual growth rate. The relative contribution of these factors is not clear, particularly whether size-selective fishing can have a substantial impact on the genetics and hence on the evolution of individual growth rates in wild populations. We analysed a 25-year monitoring survey of an isolated population of the Alpine whitefish Coregonus palaea. We determined the selection differentials on growth rate, the actual change of growth rate over time and indicators of reproductive strategies that may potentially change over time. The selection differential can be reliably estimated in our study population because almost all the fish are harvested within their first years of life, i.e. few fish escape fishing mortality. We found a marked decline in average adult growth rate over the 25 years and a significant selection differential for adult growth, but no evidence for any linear change in reproductive strategies over time. Assuming that the heritability of growth in this whitefish corresponds to what was found in other salmonids, about a third of the observed decline in growth rate would be linked to fishery-induced evolution. Size-selective fishing seems to affect substantially the genetics of individual growth in our study population. PMID:25567861

  11. Fishery-induced selection on an Alpine whitefish: quantifying genetic and environmental effects on individual growth rate.

    PubMed

    Nusslé, Sébastien; Bornand, Christophe N; Wedekind, Claus

    2009-05-01

    Size-selective fishing, environmental changes and reproductive strategies are expected to affect life-history traits such as the individual growth rate. The relative contribution of these factors is not clear, particularly whether size-selective fishing can have a substantial impact on the genetics and hence on the evolution of individual growth rates in wild populations. We analysed a 25-year monitoring survey of an isolated population of the Alpine whitefish Coregonus palaea. We determined the selection differentials on growth rate, the actual change of growth rate over time and indicators of reproductive strategies that may potentially change over time. The selection differential can be reliably estimated in our study population because almost all the fish are harvested within their first years of life, i.e. few fish escape fishing mortality. We found a marked decline in average adult growth rate over the 25 years and a significant selection differential for adult growth, but no evidence for any linear change in reproductive strategies over time. Assuming that the heritability of growth in this whitefish corresponds to what was found in other salmonids, about a third of the observed decline in growth rate would be linked to fishery-induced evolution. Size-selective fishing seems to affect substantially the genetics of individual growth in our study population.

  12. Harvest-induced phenotypic selection in an island population of moose, Alces alces.

    PubMed

    Kvalnes, Thomas; Saether, Bernt-Erik; Haanes, Hallvard; Røed, Knut H; Engen, Steinar; Solberg, Erling J

    2016-07-01

    Empirical evidence strongly indicates that human exploitation has frequently led to rapid evolutionary changes in wild populations, yet the mechanisms involved are often poorly understood. Here, we applied a recently developed demographic framework for analyzing selection to data from a 20-year study of a wild population of moose, Alces alces. In this population, a genetic pedigree has been established all the way back to founders. We demonstrate harvest-induced directional selection for delayed birth dates in males and reduced body mass as calf in females. During the study period, birth date was delayed by 0.81 days per year for both sexes, whereas no significant changes occurred in calf body mass. Quantitative genetic analyses indicated that both traits harbored significant additive genetic variance. These results show that selective harvesting can induce strong selection that oppose natural selection. This may cause evolution of less favorable phenotypes that become maladaptive once harvesting ceases.

  13. Unidirectional invisibility induced by parity-time symmetric circuit.

    PubMed

    Lv, Bo; Fu, Jiahui; Wu, Bian; Li, Rujiang; Zeng, Qingsheng; Yin, Xinhua; Wu, Qun; Gao, Lei; Chen, Wan; Wang, Zhefei; Liang, Zhiming; Li, Ao; Ma, Ruyu

    2017-01-18

    Parity-time (PT) symmetric structures present the unidirectional invisibility at the spontaneous PT-symmetry breaking point. In this paper, we propose a PT-symmetric circuit consisting of a resistor and a microwave tunnel diode (TD) which represent the attenuation and amplification, respectively. Based on the scattering matrix method, the circuit can exhibit an ideal unidirectional performance at the spontaneous PT-symmetry breaking point by tuning the transmission lines between the lumped elements. Additionally, the resistance of the reactance component can alter the bandwidth of the unidirectional invisibility flexibly. Furthermore, the electromagnetic simulation for the proposed circuit validates the unidirectional invisibility and the synchronization with the input energy well. Our work not only provides an unidirectional invisible circuit based on PT-symmetry, but also proposes a potential solution for the extremely selective filter or cloaking applications.

  14. Unidirectional invisibility induced by parity-time symmetric circuit

    PubMed Central

    Lv, Bo; Fu, Jiahui; Wu, Bian; Li, Rujiang; Zeng, Qingsheng; Yin, Xinhua; Wu, Qun; Gao, Lei; Chen, Wan; Wang, Zhefei; Liang, Zhiming; Li, Ao; Ma, Ruyu

    2017-01-01

    Parity-time (PT) symmetric structures present the unidirectional invisibility at the spontaneous PT-symmetry breaking point. In this paper, we propose a PT-symmetric circuit consisting of a resistor and a microwave tunnel diode (TD) which represent the attenuation and amplification, respectively. Based on the scattering matrix method, the circuit can exhibit an ideal unidirectional performance at the spontaneous PT-symmetry breaking point by tuning the transmission lines between the lumped elements. Additionally, the resistance of the reactance component can alter the bandwidth of the unidirectional invisibility flexibly. Furthermore, the electromagnetic simulation for the proposed circuit validates the unidirectional invisibility and the synchronization with the input energy well. Our work not only provides an unidirectional invisible circuit based on PT-symmetry, but also proposes a potential solution for the extremely selective filter or cloaking applications. PMID:28098258

  15. Unidirectional invisibility induced by parity-time symmetric circuit

    NASA Astrophysics Data System (ADS)

    Lv, Bo; Fu, Jiahui; Wu, Bian; Li, Rujiang; Zeng, Qingsheng; Yin, Xinhua; Wu, Qun; Gao, Lei; Chen, Wan; Wang, Zhefei; Liang, Zhiming; Li, Ao; Ma, Ruyu

    2017-01-01

    Parity-time (PT) symmetric structures present the unidirectional invisibility at the spontaneous PT-symmetry breaking point. In this paper, we propose a PT-symmetric circuit consisting of a resistor and a microwave tunnel diode (TD) which represent the attenuation and amplification, respectively. Based on the scattering matrix method, the circuit can exhibit an ideal unidirectional performance at the spontaneous PT-symmetry breaking point by tuning the transmission lines between the lumped elements. Additionally, the resistance of the reactance component can alter the bandwidth of the unidirectional invisibility flexibly. Furthermore, the electromagnetic simulation for the proposed circuit validates the unidirectional invisibility and the synchronization with the input energy well. Our work not only provides an unidirectional invisible circuit based on PT-symmetry, but also proposes a potential solution for the extremely selective filter or cloaking applications.

  16. SEASAT: A satellite scatterometer illumination times of selected in situ sites

    NASA Technical Reports Server (NTRS)

    Schroeder, L. C.; Goodridge, D. R.; Boberly, J. C.; Hughes, J. K.; Sweet, J. L.

    1982-01-01

    A list of times that the SEASAT A Satellite Scatterometer (SASS) illuminated from directly above or directly abeam, selected surface sites where in situ winds were measured is provided. The list is ordered by the Greenwich Mean Time (GMT) of the midpoint of the illumination period (hit time) for a given surface site. The site identification, the orbit number and the direction from the subtrack in which the truth lies are provided. The accuracy of these times depends in part upon the ascending node times, which are estimated to be within +.1 sec, and on the illumination time relative to the ascending node, which is estimated to be within +6 seconds. The uncertainties in the times provided were judged to be sufficiently small to allow efficient and accurate extraction of SASS and in situ data at the selected surface sites. The list contains approximately six thousand hit times from 61 geographically dispersed sites.

  17. Mechanisms and time course of menthol-induced cutaneous vasodilation.

    PubMed

    Craighead, Daniel H; McCartney, Nathaniel B; Tumlinson, James H; Alexander, Lacy M

    2017-03-01

    Menthol is a vasoactive compound that is widely used in topical analgesic agents. Menthol induces cutaneous vasodilation, however the underlying mechanisms are unknown. Determining the rates of appearance and clearance of menthol in the skin is important for optimizing topical treatment formulation and dosing. The purpose of this study was to determine the mechanisms contributing to menthol-mediated cutaneous vasodilation and to establish a time course for menthol appearance/clearance in the skin. Ten young (23±1years, 5 males 5 females) subjects participated in two protocols. In study 1, four intradermal microdialysis fibers were perfused with increasing doses of menthol (0.1-500mM) and inhibitors for nitric oxide (NO), endothelium derived hyperpolarizing factors (EDHFs), and sensory nerves. Skin blood flow was measured with laser Doppler flowmetry and normalized to %CVCmax. In study 2, two intradermal microdialysis fibers were perfused with lactated Ringer's solution. 0.017mL·cm(-2) of a 4% menthol gel was placed over each fiber. 5μL samples of dialysate from the microdialysis fibers were collected every 30min and analyzed for the presence of menthol with high performance gas chromatography/mass spectrometry. Skin blood flow (laser speckle contrast imaging) and subjective ratings of menthol sensation were simultaneously obtained with dialysate samples. In study 1, menthol induced cutaneous vasodilation at all doses ≥100mM (all p<0.05). However, inhibition of either NO, EDHFs, or sensory nerves fully inhibited menthol-mediated vasodilation (all p>0.05). In study 2, significant menthol was detected in dialysate 30min post menthol application (0.89ng, p=0.0002). Relative to baseline, cutaneous vasodilation was elevated from minutes 15-45 and ratings of menthol sensation were elevated from minute 5-60 post menthol application (all p<0.05). Menthol induces cutaneous vasodilation in the skin through multiple vasodilator pathways, including NO, EDHF, and sensory

  18. Protective effects of mercaptoethylguanidine, a selective inhibitor of inducible nitric oxide synthase, in ligature-induced periodontitis in the rat

    PubMed Central

    Lohinai, Zsolt; Benedek, Péter; Fehér, Erzsébet; Györfi, Adrienn; Rosivall, László; Fazekas, Árpád; Salzman, Andrew L; Szabó, Csaba

    1998-01-01

    Excessive production of nitric oxide (NO), and the generation of peroxynitrite have been implicated in various proinflammatory conditions. In the present study, using mercaptoethylguanidine (MEG), a selective inhibitor of iNOS and a peroxynitrite scavenger, we investigated the role of iNOS and peroxynitrite in a rat model of periodontitis.Periodontitis was produced in rat by a ligature of 2/0 braided silk placed around the cervix of the lower left 1st molar. Animals were then divided into two groups: one group of rats was treated with MEG (30 mg kg−1, i.p., 4 times per day for 8 days), animals in the other group received vehicle. At day 8, the gingivomucosal tissue encircling the mandibular 1st molars was removed on both sides from ligated and sham operated animals for inducible nitric oxide synthase (iNOS) activity assay and for immunocytochemistry with anti-iNOS serum. Plasma extravasation was measured with the Evans blue technique. Alveolar bone loss was measured with a videomicroscopy.Ligation caused a significant, more than 3 fold increase in the gingival iNOS activity, whereas it did not affect iNOS activity on the contralateral side, when compared to sham-operated animals. Immunohistochemical analysis revealed iNOS-positive macrophages, lymphocytes and PMNs in the connective tissue and immunoreactive basal layers of epithelium on side of the ligature, and only a few iNOS-reactive connective tissue cells on the contralateral side. Ligation significantly increased Evans blue extravasation in gingivomucosal tissue and alveolar bone destruction compared to the contralateral side. MEG treatment significantly reduced the plasma extravasation and bone destruction.The present results demonstrated that ligature-induced periodontitis increases local NO production and that MEG treatment protects against the associated extravasation and bone destruction. Based on the present data, we propose that enhanced formation of NO and peroxynitrite plays a significant role

  19. Nondestructive nanofabrication on Si(100) surface by tribochemistry-induced selective etching

    PubMed Central

    Guo, Jian; Yu, Bingjun; Chen, Lei; Qian, Linmao

    2015-01-01

    A tribochemistry-induced selective etching approach is proposed for the first time to produce silicon nanostructures without lattice damage. With a ~1 nm thick SiOx film as etching mask grown on Si(100) surface (Si(100)/SiOx) by wet-oxidation technique, nano-trenches can be produced through the removal of local SiOx mask by a SiO2 tip in humid air and the post-etching of the exposed Si in potassium hydroxide (KOH) solution. The material removal of SiOx mask and Si under low load is dominated by the tribochemical reaction at the interface between SiO2 tip and Si/SiOx sample, where the contact pressure is much lower than the critical pressure for initial yield of Si. High resolution transmission electron microscope (HRTEM) observation indicates that neither the material removal induced by tribochemical reaction nor the wet etching in KOH solution leads to lattice damage of the fabricated nanostructures. The proposed approach points out a new route in nondestructive nanofabrication. PMID:26559014

  20. Selective inhibition of inducible cyclooxygenase 2 in vivo is antiinflammatory and nonulcerogenic.

    PubMed Central

    Masferrer, J L; Zweifel, B S; Manning, P T; Hauser, S D; Leahy, K M; Smith, W G; Isakson, P C; Seibert, K

    1994-01-01

    We have examined the role of cyclooxygenase 2 (COX-2) in a model of inflammation in vivo. Carrageenan administration to the subcutaneous rat air pouch induces a rapid inflammatory response characterized by high levels of prostaglandins (PGs) and leukotrienes in the fluid exudate. The time course of the induction of COX-2 mRNA and protein coincided with the production of PGs in the pouch tissue and cellular infiltrate. Carrageenan-induced COX-2 immunoreactivity was localized to macrophages obtained from the fluid exudate as well as to the inner surface layer of cells within the pouch lining. Dexamethasone inhibited both COX-2 expression and PG synthesis in the fluid exudate but failed to inhibit PG synthesis in the stomach. Furthermore, NS-398, a selective COX-2 inhibitor, and indomethacin, a nonselective COX-1/COX-2 inhibitor, blocked proinflammatory PG synthesis in the air pouch. In contrast, only indomethacin blocked gastric PG and, additionally, produced gastric lesions. These results suggest that inhibitors of COX-2 are potent antiinflammatory agents which do not produce the typical side effects (e.g., gastric ulcers) associated with the nonselective, COX-1-directed antiinflammatory drugs. Images PMID:8159730

  1. Nondestructive nanofabrication on Si(100) surface by tribochemistry-induced selective etching

    NASA Astrophysics Data System (ADS)

    Guo, Jian; Yu, Bingjun; Chen, Lei; Qian, Linmao

    2015-11-01

    A tribochemistry-induced selective etching approach is proposed for the first time to produce silicon nanostructures without lattice damage. With a ~1 nm thick SiOx film as etching mask grown on Si(100) surface (Si(100)/SiOx) by wet-oxidation technique, nano-trenches can be produced through the removal of local SiOx mask by a SiO2 tip in humid air and the post-etching of the exposed Si in potassium hydroxide (KOH) solution. The material removal of SiOx mask and Si under low load is dominated by the tribochemical reaction at the interface between SiO2 tip and Si/SiOx sample, where the contact pressure is much lower than the critical pressure for initial yield of Si. High resolution transmission electron microscope (HRTEM) observation indicates that neither the material removal induced by tribochemical reaction nor the wet etching in KOH solution leads to lattice damage of the fabricated nanostructures. The proposed approach points out a new route in nondestructive nanofabrication.

  2. A novel caspase 8 selective small molecule potentiates TRAIL-induced cell death.

    PubMed

    Bucur, Octavian; Gaidos, Gabriel; Yatawara, Achani; Pennarun, Bodvael; Rupasinghe, Chamila; Roux, Jérémie; Andrei, Stefan; Guo, Bingqian; Panaitiu, Alexandra; Pellegrini, Maria; Mierke, Dale F; Khosravi-Far, Roya

    2015-05-11

    Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, but not alone. The molecule was identified through an in silico chemical screen for compounds with affinity for the caspase 8 homodimer's interface. The compound was experimentally validated to directly bind caspase 8, and to promote caspase 8 activation and cell death in single living cells or population of cells, upon TRAIL stimulation. Our approach is a proof-of-concept strategy leading to the discovery of a novel small molecule that not only stimulates TRAIL-induced apoptosis in cancer cells, but may also provide insights into the structure-function relationship of caspase 8 homodimers as putative targets in cancer.

  3. A novel caspase 8 selective small molecule potentiates TRAIL-induced cell death

    PubMed Central

    Bucur, Octavian; Gaidos, Gabriel; Yatawara, Achani; Pennarun, Bodvael; Rupasinghe, Chamila; Roux, Jérémie; Andrei, Stefan; Guo, Bingqian; Panaitiu, Alexandra; Pellegrini, Maria; Mierke, Dale F.; Khosravi-Far, Roya

    2015-01-01

    Recombinant soluble TRAIL and agonistic antibodies against TRAIL receptors (DR4 and DR5) are currently being created for clinical cancer therapy, due to their selective killing of cancer cells and high safety characteristics. However, resistance to TRAIL and other targeted therapies is an important issue facing current cancer research field. An attractive strategy to sensitize resistant malignancies to TRAIL-induced cell death is the design of small molecules that target and promote caspase 8 activation. For the first time, we describe the discovery and characterization of a small molecule that directly binds caspase 8 and enhances its activation when combined with TRAIL, but not alone. The molecule was identified through an in silico chemical screen for compounds with affinity for the caspase 8 homodimer’s interface. The compound was experimentally validated to directly bind caspase 8, and to promote caspase 8 activation and cell death in single living cells or population of cells, upon TRAIL stimulation. Our approach is a proof-of-concept strategy leading to the discovery of a novel small molecule that not only stimulates TRAIL-induced apoptosis in cancer cells, but may also provide insights into the structure-function relationship of caspase 8 homodimers as putative targets in cancer. PMID:25962125

  4. A modelling framework for the analysis of artificial-selection time series.

    PubMed

    Le Rouzic, Arnaud; Houle, David; Hansen, Thomas F

    2011-04-01

    Artificial-selection experiments constitute an important source of empirical information for breeders, geneticists and evolutionary biologists. Selected characters can generally be shifted far from their initial state, sometimes beyond what is usually considered as typical inter-specific divergence. A careful analysis of the data collected during such experiments may thus reveal the dynamical properties of the genetic architecture that underlies the trait under selection. Here, we propose a statistical framework describing the dynamics of selection-response time series. We highlight how both phenomenological models (which do not make assumptions on the nature of genetic phenomena) and mechanistic models (explaining the temporal trends in terms of e.g. mutations, epistasis or canalization) can be used to understand and interpret artificial-selection data. The practical use of the models and their implementation in a software package are demonstrated through the analysis of a selection experiment on the shape of the wing in Drosophila melanogaster.

  5. Bayesian inference of selection in a heterogeneous environment from genetic time-series data.

    PubMed

    Gompert, Zachariah

    2016-01-01

    Evolutionary geneticists have sought to characterize the causes and molecular targets of selection in natural populations for many years. Although this research programme has been somewhat successful, most statistical methods employed were designed to detect consistent, weak to moderate selection. In contrast, phenotypic studies in nature show that selection varies in time and that individual bouts of selection can be strong. Measurements of the genomic consequences of such fluctuating selection could help test and refine hypotheses concerning the causes of ecological specialization and the maintenance of genetic variation in populations. Herein, I proposed a Bayesian nonhomogeneous hidden Markov model to estimate effective population sizes and quantify variable selection in heterogeneous environments from genetic time-series data. The model is described and then evaluated using a series of simulated data, including cases where selection occurs on a trait with a simple or polygenic molecular basis. The proposed method accurately distinguished neutral loci from non-neutral loci under strong selection, but not from those under weak selection. Selection coefficients were accurately estimated when selection was constant or when the fitness values of genotypes varied linearly with the environment, but these estimates were less accurate when fitness was polygenic or the relationship between the environment and the fitness of genotypes was nonlinear. Past studies of temporal evolutionary dynamics in laboratory populations have been remarkably successful. The proposed method makes similar analyses of genetic time-series data from natural populations more feasible and thereby could help answer fundamental questions about the causes and consequences of evolution in the wild.

  6. Easy-to-use strategy for reference gene selection in quantitative real-time PCR experiments.

    PubMed

    Klenke, Stefanie; Renckhoff, Kristina; Engler, Andrea; Peters, Jürgen; Frey, Ulrich H

    2016-12-01

    Real-time PCR is an indispensable technique for mRNA expression analysis but conclusions depend on appropriate reference gene selection. However, while reference gene selection has been a topic of publications, this issue is often disregarded when measuring target mRNA expression. Therefore, we (1) evaluated the frequency of appropriate reference gene selection, (2) suggest an easy-to-use tool for least variability reference gene selection, (3) demonstrate application of this tool, and (4) show effects on target gene expression profiles. All 2015 published articles in Naunyn-Schmiedeberg's Archives of Pharmacology were screened for the use of quantitative real-time PCR analysis and selection of reference genes. Target gene expression (Vegfa, Grk2, Sirt4, and Timp3) in H9c2 cells was analyzed following various interventions (hypoxia, hyperglycemia, and/or isoflurane exposure with and without subsequent hypoxia) in relation to putative reference genes (Actb, Gapdh, B2m, Sdha, and Rplp1) using the least variability method vs. an arbitrarily selected but established reference gene. In the vast majority (18 of 21) of papers, no information was provided regarding selection of an appropriate reference gene. In only 1 of 21 papers, a method of appropriate reference gene selection was described and in 2 papers reference gene selection remains unclear. The method of reference gene selection had major impact on interpretation of target gene expression. With hypoxia, for instance, the least variability gene was Rplp1 and target gene expression (Vefga) heavily showed a 2-fold up-regulation (p = 0.022) but no change (p = 0.3) when arbitrarily using Gapdh. Frequency of appropriate reference gene selection in this journal is low, and we propose our strategy for reference gene selection as an easy tool for proper target gene expression.

  7. Cocaine-induced c-Fos expression in rats selectively bred for high or low saccharin intake and in rats selected for high or low impulsivity.

    PubMed

    Regier, Paul S; Carroll, Marilyn E; Meisel, Robert L

    2012-08-01

    Sweet preference and impulsivity are predictors of cocaine self-administration; however, no research has been conducted to investigate neuronal activation in key brain reward areas after first time exposure to cocaine in rats that differ in their propensity for cocaine-seeking and -taking behavior. In this study we used rats that had been selectively bred for high vs. low saccharin intake and rats selected for high vs. low impulsivity for food. The goal of this study was to investigate whether there are differences of c-Fos reactivity between high and low phenotypes and determine whether these differences are similar between the two animal models. A group of rats was bred for high or low saccharin intake. Another group of rats was selected as high or low impulsive based on performance in a delay-discounting task. Subsequently, rats were given an acute injection of cocaine or saline and then c-Fos expression was observed and analyzed in several brain regions. The low reward-seeking phenotypes showed higher cocaine-induced c-Fos expression in several of these regions. Low saccharin preferring rats showed higher cocaine-induced c-Fos expression in the nucleus accumbens shell, and low impulsive rats showed higher cocaine-induced c-Fos expression in the orbitofrontal cortex and cingulate gyrus 1 area. In addition, both low impulsive and low saccharin rats had higher cocaine-induced c-Fos in the dorsal medial and dorsal lateral caudate putamen. The results indicate that individual differences in neuronal reactivity exist prior to chronic exposure to drugs of abuse. Furthermore, similar differences between the two animal models may be indicative of a common mechanism underlying vulnerability to drugs of abuse. Copyright © 2012 Elsevier B.V. All rights reserved.

  8. Cocaine-induced c-Fos expression in rats selectively bred for high or low saccharin intake and in rats selected for high or low impulsivity

    PubMed Central

    Carroll, Marilyn E.; Meisel, Robert L.

    2013-01-01

    Sweet preference and impulsivity are predictors of cocaine self-administration; however no research has been conducted to investigate neuronal activation in key brain reward areas after first time exposure to cocaine in rats that differ in their propensity for cocaine-seeking and – taking behavior. In this study we used rats that that been selectively bred for high vs. low saccharin intake and rats selected for high vs. low impulsivity for food. The goal of this study was to investigate whether there are differences of c-Fos reactivity between high and low phenotypes and determine whether these differences are similar between the two animal models. A group of rats was bred for either high or low saccharin intake. Another group of rats was selected as high or low impulsive based on performance in a delay-discounting task. Subsequently, rats were given an acute injection of cocaine or saline and then c-Fos expression was observed and analyzed in several brain regions. The low reward-seeking phenotypes showed higher cocaine-induced c-Fos expression in several of these regions. Low saccharin preferring rats showed higher cocaine-induced c-Fos expression in the nucleus accumbens shell, and low impulsive rats showed higher cocaine-induced c-Fos expression in the orbitofrontal cortex and cingulate gyrus 1 area. In addition, both low impulsive and low saccharin rats had higher cocaine-induced c-Fos in the dorsal medial and dorsal lateral caudate putamen. The results indicate that individual differences in neuronal reactivity exist prior to chronic exposure to drugs of abuse. Furthermore, similar differences between the two animal models may be indicative of a common mechanism underlying vulnerability to drugs of abuse. PMID:22613730

  9. Model selection and change detection for a time-varying mean in process monitoring

    NASA Astrophysics Data System (ADS)

    Burr, Tom; Hamada, Michael S.; Ticknor, Larry; Weaver, Brian

    2014-07-01

    Process monitoring (PM) for nuclear safeguards sometimes requires estimation of thresholds corresponding to small false alarm rates. Threshold estimation is an old topic; however, because possible new roles for PM are being evaluated in nuclear safeguards, it is timely to consider modern model selection options in the context of alarm threshold estimation. One of the possible new PM roles involves PM residuals, where a residual is defined as residual=data-prediction. This paper briefly reviews alarm threshold estimation, introduces model selection options, and considers several assumptions regarding the data-generating mechanism for PM residuals. Four PM examples from nuclear safeguards are included. One example involves frequent by-batch material balance closures where a dissolution vessel has time-varying efficiency, leading to time-varying material holdup. Another example involves periodic partial cleanout of in-process inventory, leading to challenging structure in the time series of PM residuals. Our main focus is model selection to select a defensible model for normal behavior with a time-varying mean in a PM residual stream. We use approximate Bayesian computation to perform the model selection and parameter estimation for normal behavior. We then describe a simple lag-one-differencing option similar to that used to monitor non-stationary times series to monitor for off-normal behavior.

  10. [Embryo selection in IVF/ICSI cycles using time-lapse microscopy and the clinical outcomes].

    PubMed

    Chen, Minghao; Huang, Jun; Zhong, Ying; Quan, Song

    2015-12-01

    To compare the clinical outcomes of embryos selected using time-lapse microscopy and traditional morphological method in IVF/ICSI cycles and evaluate the clinical value of time-lapse microscopy in early embryo monitoring and selection. e retrospectively analyzed the clinical data of 139 IVF/ICSI cycles with embryo selection based on time-lapse monitoring (TLM group, n=68) and traditional morphological method (control group, n=71). The βHCG-positive rate, clinical pregnancy rate and embryo implantation rate were compared between the 2 groups. Subgroup analysis was performed in view of female patients age and the fertilization type. The βHCG-positive rate, clinical pregnancy rate and implantation rate were 66.2%, 61.8% and 47.1% in TLM group, significantly higher than those in the control group (47.9%, 43.7% and 30.3%, respectively; P<0.05). Compared with patients below 30 years of age, patients aged between 31 and 35 years benefited more from time-lapse monitoring with improved clinical outcomes. time-lapse monitoring significantly increased the βHCG-positive rate, clinical pregnancy rate and implantation rate for patients undergoing IVF cycles, but not for those undergoing ICSI or TESA cycles. Compared with those selected using traditional morphological method, the embryos selected with time-lapse microscopy have better clinical outcomes, especially in older patients (31-35 years of age) and in IVF cycles.

  11. The causes of selection on flowering time through male fitness in a hermaphroditic annual plant.

    PubMed

    Austen, Emily J; Weis, Arthur E

    2016-01-01

    Flowering is a key life-history event whose timing almost certainly affects both male and female fitness, but tests of selection on flowering time through male fitness are few. Such selection may arise from direct effects of flowering time, and indirect effects through covariance between flowering time and the environment experienced during reproduction. To isolate these intrinsically correlated associations, we staggered planting dates of Brassica rapa families with known flowering times, creating populations in which age at flowering (i.e., flowering time genotype) and Julian date of flowering (i.e., flowering time environment) were positively, negatively, or uncorrelated. Genetic paternity analysis revealed that male fitness was not strongly influenced by seasonal environmental changes. Instead, when age and date were uncorrelated, selection through male fitness strongly favored young age at flowering. Strategic sampling offspring for paternity analysis rejected covariance between sire age at flowering and dam quality as the cause of this selection. Results instead suggest a negative association between age at flowering and pollen competitive ability. The manipulation also revealed that, at least in B. rapa, the often-observed correlation between flowering time and flowering duration is environmental, not genetic, in origin. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

  12. Development of target protein-selective degradation inducer for protein knockdown.

    PubMed

    Itoh, Yukihiro; Ishikawa, Minoru; Kitaguchi, Risa; Sato, Shinichi; Naito, Mikihiko; Hashimoto, Yuichi

    2011-05-15

    Our previous technique for inducing selective degradation of target proteins with ester-type SNIPER (Specific and Nongenetic Inhibitor-of-apoptosis-proteins (IAPs)-dependent Protein ERaser) degrades both the target proteins and IAPs. Here, we designed a small-molecular amide-type SNIPER to overcome this issue. As proof of concept, we synthesized and biologically evaluated an amide-type SNIPER which induces selective degradation of cellular retinoic acid binding protein II (CRABP-II), but not IAPs. Such small-molecular, amide-type SNIPERs that induce target protein-selective degradation without affecting IAPs should be effective tools to study the biological roles of target proteins in living cells.

  13. Advancements in time-resolved x-ray laser induced time-of-flight photoelectron spectroscopy

    SciTech Connect

    Nelson, A J; Dunn, J; Widmann, K; Ao, T; Ping, Y; Hunter, J; Ng, A

    2005-07-28

    Time-resolved soft x-ray photoelectron spectroscopy is used to probe the non-steady-state evolution of the valence band electronic structure of laser heated ultra-thin (50 nm) metal foils and bulk semiconductors. Single-shot soft x-ray laser induced time-of-flight photoelectron spectroscopy with picosecond time resolution was used in combination with optical measurements of the disassembly dynamics that have shown the existence of a metastable liquid phase in fs-laser heated metal foils persisting 4-5 ps. This metastable phase is studied using a 527 nm wavelength 400 fs laser pulse containing 0.3-2.5 mJ laser energy focused in a large 500 x 700 {micro}m{sup 2} spot to create heated conditions of 0.2-1.8 x 10{sup 12} W cm{sup -2} intensity. The unique LLNL COMET compact tabletop soft x-ray laser source provided the necessary high photon flux, highly monoenergetic, picosecond pulse duration, and coherence for observing the evolution of changes in the valence band electronic structure of laser heated metals and semiconductors with picosecond time resolution. This work demonstrates the continuing development of a powerful new technique for probing reaction dynamics and changes of local order on surfaces on their fundamental timescales including phenomena such as non-thermal melting, chemical bond formation, intermediate reaction steps, and the existence of transient reaction products.

  14. Advancements in time-resolved x-ray laser induced time-of-flight photoelectron spectroscopy

    NASA Astrophysics Data System (ADS)

    Nelson, A. J.; Dunn, J.; Widmann, K.; Ao, T.; Ping, Y.; Hunter, J.; Ng, A.

    2005-09-01

    Time-resolved soft x-ray photoelectron spectroscopy is used to probe the non-steady-state evolution of the valence band electronic structure of laser heated ultra-thin (50 nm) metal foils and bulk semiconductors. Single-shot soft x-ray laser induced time-of-flight photoelectron spectroscopy with picosecond time resolution was used in combination with optical measurements of the disassembly dynamics that have shown the existence of a metastable liquid phase in fs-laser heated metal foils persisting 4-5 ps. This metastable phase is studied using a 527 nm wavelength 400 fs laser pulse containing 0.3 - 2.5 mJ laser energy focused in a large 500 × 700 μm2 spot to create heated conditions of 0.2 - 1.8 × 1012 W cm-2 intensity. The unique LLNL COMET compact tabletop soft x-ray laser source provided the necessary high photon flux, highly monoenergetic, picosecond pulse duration, and coherence for observing the evolution of changes in the valence band electronic structure of laser heated metals and semiconductors with picosecond time resolution. This work demonstrates the continuing development of a powerful new technique for probing reaction dynamics and changes of local order on surfaces on their fundamental timescales including phenomena such as non-thermal melting, chemical bond formation, intermediate reaction steps, and the existence of transient reaction products.

  15. Methylmercury induces the expression of TNF-α selectively in the brain of mice

    PubMed Central

    Iwai-Shimada, Miyuki; Takahashi, Tsutomu; Kim, Min-Seok; Fujimura, Masatake; Ito, Hitoyasu; Toyama, Takashi; Naganuma, Akira; Hwang, Gi-Wook

    2016-01-01

    Methylmercury selectively damages the central nervous system (CNS). The tumor necrosis factor (TNF) superfamily includes representative cytokines that participate in the inflammatory response as well as cell survival, and apoptosis. In this study, we found that administration of methylmercury selectively induced TNF-α expression in the brain of mice. Although the accumulated mercury concentration in the liver and kidneys was greater than in the brain, TNF-α expression was induced to a greater extent in brain. Thus, it is possible that there may exist a selective mechanism by which methylmercury induces TNF-α expression in the brain. We also found that TNF-α expression was induced by methylmercury in C17.2 cells (mouse neural stem cells) and NF-κB may participate as a transcription factor in that induction. Further, we showed that the addition of TNF-α antagonist (WP9QY) reduced the toxicity of methylmercury to C17.2 cells. In contrast, the addition of recombinant TNF-α to the culture medium decreased the cell viability. We suggest that TNF-α may play a part in the selective damage of the CNS by methylmercury. Furthermore, our results indicate that the higher TNF-α expression induced by methylmercury maybe the cause of cell death, as TNF-α binds to its receptor after being released extracellularly. PMID:27910896

  16. Divergent selection on flowering time contributes to local adaptation in Mimulus guttatus populations.

    PubMed

    Hall, Megan C; Willis, John H

    2006-12-01

    The timing of when to initiate reproduction is an important transition in any organism's life cycle. There is much variation in flowering time among populations, but we do not know to what degree this variation contributes to local adaptation. Here we use a reciprocal transplant experiment to examine the presence of divergent natural selection for flowering time and local adaptation between two distinct populations of Mimulus guttatus. We plant both parents and hybrids (to tease apart differences in suites of associated parental traits) between these two populations into each of the two native environments and measure floral, vegetative, life-history, and fitness characters to assess which traits are under selection at each site. Analysis of fitness components indicates that each of these plant populations is locally adapted. We obtain striking evidence for divergent natural selection on date of first flower production at these two sites. Early flowering is favored at the montane site, which is inhabited by annual plants and characterized by dry soils in midsummer, whereas intermediate (though later) flowering dates are selectively favored at the temperate coastal site, which is inhabited by perennial plants and is almost continually moist. Divergent selection on flowering time contributes to local adaptation between these two populations of M. guttatus, suggesting that genetic differentiation in the timing of reproduction may also serve as a partial reproductive isolating barrier to gene flow among populations.

  17. Selective apoptosis-inducing activity of crinum-type Amaryllidaceae alkaloids.

    PubMed

    McNulty, James; Nair, Jerald J; Codina, Carles; Bastida, Jaume; Pandey, Siyaram; Gerasimoff, Jenny; Griffin, Carly

    2007-04-01

    The selective apoptosis-inducing activity of Amaryllidaceae alkaloids belonging to the crinane-type is reported. A mini-library of natural and synthetic crinane alkaloids was assembled. Biological screening indicated crinamine 4 and haemanthamine 9 to be potent inducers of apoptosis in tumour cells at micromolar concentrations. Structure-activity relationships demonstrated the requirement for both an alpha-C2 bridge and a free hydroxyl at the C-11 position as pharmacophoric requirements for this activity.

  18. Compound Selectivity and Target Residence Time of Kinase Inhibitors Studied with Surface Plasmon Resonance.

    PubMed

    Willemsen-Seegers, Nicole; Uitdehaag, Joost C M; Prinsen, Martine B W; de Vetter, Judith R F; de Man, Jos; Sawa, Masaaki; Kawase, Yusuke; Buijsman, Rogier C; Zaman, Guido J R

    2017-02-17

    Target residence time (τ) has been suggested to be a better predictor of the biological activity of kinase inhibitors than inhibitory potency (IC50) in enzyme assays. Surface plasmon resonance binding assays for 46 human protein and lipid kinases were developed. The association and dissociation constants of 80 kinase inhibitor interactions were determined. τ and equilibrium affinity constants (KD) were calculated to determine kinetic selectivity. Comparison of τ and KD or IC50 values revealed a strikingly different view on the selectivity of several kinase inhibitors, including the multi-kinase inhibitor ponatinib, which was tested on 10 different kinases. In addition, known pan-Aurora inhibitors resided much longer on Aurora B than on Aurora A, despite having comparable affinity for Aurora A and B. Furthermore, the γ/δ-selective PI3K inhibitor duvelisib and the δ-selective drug idelalisib had similar 20-fold selectivity for δ- over γ-isoform but duvelisib resided much longer on both targets.

  19. Temperature-induced labelling of Fluo-3 AM selectively yields brighter nucleus in adherent cells.

    PubMed

    Meng, Guixian; Pan, Leiting; Li, Cunbo; Hu, Fen; Shi, Xuechen; Lee, Imshik; Drevenšek-Olenik, Irena; Zhang, Xinzheng; Xu, Jingjun

    2014-01-17

    Fluo-3 is widely used to study cell calcium. Two traditional approaches: (1) direct injection and (2) Fluo-3 acetoxymethyl ester (AM) loading, often bring conflicting results in cytoplasmic calcium ([Ca(2+)]c) and nuclear calcium ([Ca(2+)]n) imaging. AM loading usually yields a darker nucleus than in cytoplasm, while direct injection always induces a brighter nucleus which is more responsive to [Ca(2+)]n detection. In this work, we detailedly investigated the effects of loading and de-esterification temperatures on the fluorescence intensity of Fluo-3 in response to [Ca(2+)]n and [Ca(2+)]c in adherent cells, including osteoblast, HeLa and BV2 cells. Interestingly, it showed that fluorescence intensity of nucleus in osteoblast cells was about two times larger than that of cytoplasm when cells were loaded with Fluo-3 AM at 4 °C and allowed a subsequent step for de-esterification at 20 °C. Brighter nuclei were also acquired in HeLa and BV2 cells using the same experimental condition. Furthermore, loading time and adhesion quality of cells had effect on fluorescence intensity. Taken together, cold loading and room temperature de-esterification treatment of Fluo-3 AM selectively yielded brighter nucleus in adherent cells. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Lysophosphatidic acid induces cell migration through the selective activation of Akt1

    PubMed Central

    Kim, Eun Kyoung; Yun, Sung Ji; Do, Kee Hun; Kim, Min Sung; Cho, Mong; Suh, Dong-Soo; Kim, Chi Dae; Kim, Jae Ho; Birnbaum, Morris J.

    2008-01-01

    Akt plays pivotal roles in many physiological responses including growth, proliferation, survival, metabolism, and migration. In the current studies, we have evaluated the isoform-specific role of akt in lysophosphatidic acid (LPA)-induced cell migration. Ascites from ovarian cancer patients (AOCP) induced mouse embryo fibroblast (MEF) cell migration in a dose-dependent manner. On the other hand, ascites from liver cirrhosis patients (ALCP) did not induce MEF cell migration. AOCP-induced MEF cell migration was completely blocked by pre-treatment of cells with LPA receptor antagonist, Ki16425. Both LPA- and AOCP-induced MEF cell migration was completely attenuated by PI3K inhibitor, LY294002. Furthermore, cells lacking Akt1 displayed defect in LPA-induced cell migration. Re-expression of Akt1 in DKO (Akt1-/-Akt2-/-) cells restored LPA-induced cell migration, whereas re-expression of Akt2 in DKO cells could not restore the LPA-induced cell migration. Finally, Akt1 was selectively phosphorylated by LPA and AOCP stimulation. These results suggest that LPA is a major factor responsible for AOCP-induced cell migration and signaling specificity of Akt1 may dictate LPA-induced cell migration. PMID:18779657

  1. Laser photo-induced dissociation using tandem time-of-flight mass spectrometry

    PubMed

    Quiniou; Yates; Langridge-Smith

    2000-01-01

    A novel tandem time-of-flight (TOF) mass spectrometer has been developed for studying the photo-induced dissociation of large molecules and elemental clusters. It consists of a linear first stage TOF analyser for primary mass separation and precursor ion selection, and a second orthogonal reflecting field TOF analyser for product ion analysis. The instrument is equipped with a large volume throughput molecular beam source chamber allowing the production of jet-cooled molecules and molecular clusters, as well as elemental clusters, using either a pulsed laser vaporisation source (LVS) or a pulsed are cluster ion source (PACIS). A second differentially pumped chamber can be used with effusive sources, or for infrared laser desorption of large molecules, followed by laser ionisation. These primary ions can then be irradiated with a second, high energy laser to induce photodissociation. Detailed information about the fragmentation mechanisms can be deduced from the product ion mass spectra. Preliminary results on the photo-induced dissociation (PID) of the molecule ion of aniline at 266 nm are presented. In this case the molecule ions were generated via two-photon laser ionisation at 266 nm using an effusive source. Results for the collision-induced dissociation (CID) of the aniline molecule ion, using a commercial mass spectrometer equipped with an atmospheric pressure electrospray ionisation interface, are also presented. Copyright 2000 John Wiley & Sons, Ltd.

  2. Conflicting selection on the timing of germination in a natural population of Arabidopsis thaliana.

    PubMed

    Akiyama, R; Ågren, J

    2014-01-01

    The timing of germination is a key life-history trait that may strongly influence plant fitness and that sets the stage for selection on traits expressed later in the life cycle. In seasonal environments, the period favourable for germination and the total length of the growing season are limited. The optimal timing of germination may therefore be governed by conflicting selection through survival and fecundity. We conducted a field experiment to examine the effects of timing of germination on survival, fecundity and overall fitness in a natural population of the annual herb Arabidopsis thaliana in north-central Sweden. Seedlings were transplanted at three different times in late summer and in autumn covering the period of seed germination in the study population. Early germination was associated with low seedling survival, but also with high survival and fecundity among established plants. The advantages of germinating early more than balanced the disadvantage and selection favoured early germination. The results suggest that low survival among early germinating seeds is the main force opposing the evolution of earlier germination and that the optimal timing of germination should vary in space and time as a function of the direction and strength of selection acting during different life-history stages.

  3. Conditioned taste aversion induced by motion is prevented by selective vagotomy in the rat

    NASA Technical Reports Server (NTRS)

    Fox, Robert A.; Mckenna, Susan

    1991-01-01

    The role of the vagus nerve in motion-induced conditioned taste aversion (CTA) was studied in hooded rats. Animals with complete, selective gastric vagotomy failed to form conditioned taste aversion after multiple conditioning sessions in which the conditioned stimulus (a cider vinegar solution) was drunk immediately before a 30-min exposure to vertical axis rotation at 150 deg/s. Results are discussed with reference to the use of CTA as a measure of motion-induced 'sickness' or gastrointestinal disturbance, and because motion-induced CTA requires that both the vagus nerve and the vestibular apparatus be intact, in light of the possible convergence of vegal and vestibular functions.

  4. Directional selection for flowering time leads to adaptive evolution in Raphanus raphanistrum (Wild radish).

    PubMed

    Ashworth, Michael B; Walsh, Michael J; Flower, Ken C; Vila-Aiub, Martin M; Powles, Stephen B

    2016-04-01

    Herbicides have been the primary tool for controlling large populations of yield depleting weeds from agro-ecosystems, resulting in the evolution of widespread herbicide resistance. In response, nonherbicidal techniques have been developed which intercept weed seeds at harvest before they enter the soil seed bank. However, the efficiency of these techniques allows an intense selection for any trait that enables weeds to evade collection, with early-flowering ecotypes considered likely to result in early seed shedding. Using a field-collected wild radish population, five recurrent generations were selected for early maturity and three generations for late maturity. Phenology associated with flowering time and growth traits were measured. Our results demonstrate the adaptive capacity of wild radish to halve its time to flowering following five generations of early-flowering selection. Early-maturing phenotypes had reduced height and biomass at maturity, leading to less competitive, more prostrate growth forms. Following three generations of late-flowering selection, wild radish doubled its time to flowering time leading to increased biomass and flowering height at maturity. This study demonstrates the potential for the rapid evolution in growth traits in response to highly effective seed collection techniques that imposed a selection on weed populations within agro-ecosystems at harvest.

  5. Observation of Doppler-free electromagnetically induced transparency in atoms selected optically with specific velocity

    SciTech Connect

    Yu, Hoon; Kim, Kwan Su; Kim, Jung Dong; Lee, Hyun Kyung; Kim, Jung Bog

    2011-11-15

    We observed an electromagnetically induced transparency signal in a four-level system with optically selected rubidium atoms at specific velocities in a room-temperature vaporized cell. Since the atoms behave like cold atoms in the selected atomic view, the observed signals coincide with a trapped atomic system. According to this result, we can observe Doppler-free signals, which correspond from 1.2 to 1.0 K in a Doppler-broadened medium. And the selected atoms have velocity components of {+-}(131 {+-} 3) MHz per wave number. Our experimental results can provide insight for research in cold media.

  6. Strain-induced selective growth in 1.5% temper-rolled Fe;1%Si.

    PubMed

    Bennett, Tricia A; Kalu, Peter N; Rollett, Anthony D

    2011-06-01

    Strain-induced selective growth was investigated in a 1.5% temper-rolled Fe∼1%Si alloy using the electron backscatter diffraction (EBSD) technique. The EBSD technique was used to quantify the presence of orientation spreads within grains and to show that this particular case of selective growth can be directly related to differences in stored energy as reflected in the geometrically necessary dislocation content. The differences in stored energy were sufficient to give rise to selective growth as evidenced by bi-modal grain sizes.

  7. Selective antagonism of isolation-induced aggression in mice by diazepam following chronic administration.

    PubMed

    Malick, J B

    1978-04-01

    Benzodiazepines are non-selective (i.e., they only inhibit aggression at doses producing concurrent neuromuscular impairment) antagonists of isolation-induced aggression in mice following acute administration. However, in the present study diazepam was shown to be a selective antagonist of fighting in isolated mice following chronic administration for 5 days. When administered chronically, selective tolerance rapidly developed to the general CNS depression produced by diazepam whereas the antifighting activity was not diminished and, in fact, tended to be enhanced following multiple drug administrations. Thus, the antagonism of fighting in isolated mice by diazepam does not appear to be due solely to general CNS depressant properties.

  8. Influence of dosing times on cisplatin-induced peripheral neuropathy in rats.

    PubMed

    Seto, Yoshihiro; Okazaki, Fumiyasu; Horikawa, Keiji; Zhang, Jing; Sasaki, Hitoshi; To, Hideto

    2016-09-27

    Although cis-diamminedichloro-platinum (CDDP) exhibits strong therapeutic effects in cancer chemotherapy, its adverse effects such as peripheral neuropathy, nephropathy, and vomiting are dose-limiting factors. Previous studies reported that chronotherapy decreased CDDP-induced nephropathy and vomiting. In the present study, we investigated the influence of dosing times on CDDP-induced peripheral neuropathy in rats. CDDP (4 mg/kg) was administered intravenously at 5:00 or 17:00 every 7 days for 4 weeks to male Sprague-Dawley rats, and saline was given to the control group. To assess the dosing time dependency of peripheral neuropathy, von-Frey test and hot-plate test were performed. In order to estimate hypoalgesia, the hot-plate test was performed in rats administered CDDP weekly for 4 weeks. On day 28, the withdrawal latency to thermal stimulation was significantly prolonged in the 17:00-treated group than in the control and 5:00-treated groups. When the von-Frey test was performed to assess mechanical allodynia, the withdrawal threshold was significantly lower in the 5:00 and 17:00-treated groups than in the control group on day 6 after the first CDDP dose. The 5:00-treated group maintained allodynia throughout the experiment with the repeated administration of CDDP, whereas the 17:00-treated group deteriorated from allodynia to hypoalgesia. It was revealed that the severe of CDDP-induced peripheral neuropathy was inhibited in the 5:00-treated group, whereas CDDP-treated groups exhibited mechanical allodynia. These results suggested that the selection of an optimal dosing time ameliorated CDDP-induced peripheral neuropathy.

  9. Selecting the most appropriate time points to profile in high-throughput studies

    PubMed Central

    Kleyman, Michael; Sefer, Emre; Nicola, Teodora; Espinoza, Celia; Chhabra, Divya; Hagood, James S; Kaminski, Naftali; Ambalavanan, Namasivayam; Bar-Joseph, Ziv

    2017-01-01

    Biological systems are increasingly being studied by high throughput profiling of molecular data over time. Determining the set of time points to sample in studies that profile several different types of molecular data is still challenging. Here we present the Time Point Selection (TPS) method that solves this combinatorial problem in a principled and practical way. TPS utilizes expression data from a small set of genes sampled at a high rate. As we show by applying TPS to study mouse lung development, the points selected by TPS can be used to reconstruct an accurate representation for the expression values of the non selected points. Further, even though the selection is only based on gene expression, these points are also appropriate for representing a much larger set of protein, miRNA and DNA methylation changes over time. TPS can thus serve as a key design strategy for high throughput time series experiments. Supporting Website: www.sb.cs.cmu.edu/TPS DOI: http://dx.doi.org/10.7554/eLife.18541.001 PMID:28124972

  10. Effect of individual thinking styles on item selection during study time allocation.

    PubMed

    Jia, Xiaoyu; Li, Weijian; Cao, Liren; Li, Ping; Shi, Meiling; Wang, Jingjing; Cao, Wei; Li, Xinyu

    2016-03-14

    The influence of individual differences on learners' study time allocation has been emphasised in recent studies; however, little is known about the role of individual thinking styles (analytical versus intuitive). In the present study, we explored the influence of individual thinking styles on learners' application of agenda-based and habitual processes when selecting the first item during a study-time allocation task. A 3-item cognitive reflection test (CRT) was used to determine individuals' degree of cognitive reliance on intuitive versus analytical cognitive processing. Significant correlations between CRT scores and the choices of first item selection were observed in both Experiment 1a (study time was 5 seconds per triplet) and Experiment 1b (study time was 20 seconds per triplet). Furthermore, analytical decision makers constructed a value-based agenda (prioritised high-reward items), whereas intuitive decision makers relied more upon habitual responding (selected items from the leftmost of the array). The findings of Experiment 1a were replicated in Experiment 2 notwithstanding ruling out the possible effects from individual intelligence and working memory capacity. Overall, the individual thinking style plays an important role on learners' study time allocation and the predictive ability of CRT is reliable in learners' item selection strategy.

  11. Induced defences alter the strength and direction of natural selection on reproductive traits in common milkweed.

    PubMed

    Thompson, K A; Cory, K A; Johnson, M T J

    2017-06-01

    Evolutionary biologists have long sought to understand the ecological processes that generate plant reproductive diversity. Recent evidence indicates that constitutive antiherbivore defences can alter natural selection on reproductive traits, but it is unclear whether induced defences will have the same effect and whether reduced foliar damage in defended plants is the cause of this pattern. In a factorial field experiment using common milkweed, Asclepias syriaca L., we induced plant defences using jasmonic acid (JA) and imposed foliar damage using scissors. We found that JA-induced plants experienced selection for more inflorescences that were smaller in size (fewer flowers), whereas control plants only experienced a trend towards selection for larger inflorescences (more flowers); all effects were independent of foliar damage. Our results demonstrate that induced defences can alter both the strength and direction of selection on reproductive traits, and suggest that antiherbivore defences may promote the evolution of plant reproductive diversity. © 2017 European Society For Evolutionary Biology. Journal of Evolutionary Biology © 2017 European Society For Evolutionary Biology.

  12. High-speed energy efficient selective removal of large area copper layer by laser induced delamination

    NASA Astrophysics Data System (ADS)

    Kmetec, Blaž; Kovačič, Drago; Možina, Janez; Podobnik, Boštjan

    2009-07-01

    An indirect laser-induced method for selective removal of large copper areas from a printed circuit board is theoretically and experimentally investigated. The results show that the threshold condition for the process involves phase transition of the epoxy-based substrate resin. Optimal parameters for maximizing process speed are found and discussed.

  13. Evaluation of the AIRS near-real-time channel selection for application to numerical weather prediction

    NASA Astrophysics Data System (ADS)

    Fourrié, Nadia; Thépaut, Jean-Noël

    2003-07-01

    The Atmospheric Infrared Sounder (AIRS) on board the National Aeronautics and Space Administration (NASA) Earth Observing System (EOS) Aqua satellite provides 2378 channels for each field of view of the instrument. As it is neither feasible nor efficient to assimilate all the channels in a numerical weather-prediction system, a policy of channel selection has to be designed in this context. This paper attempts to assess the optimality of the selection of the AIRS radiance channels that are made available to the scientific community in near real time (hereafter called AIRS NRT) by the National Oceanic and Atmospheric Administration (NOAA) National Environmental Satellite Data and Information Service. This assessment is done by comparing this channel selection with a method preserving the information content of the instrument, the so-called 'global' method. It turns out that although the selected channels are different and the information content as measured by the entropy reduction (ER) and the degrees of freedom for signal (DFS) is slightly smaller for the AIRS NRT channel set than for the 'global' set, both channel selections give similar results in terms of analysis error for temperature, humidity and ozone. The robustness of the results is then evaluated by varying the range of input parameters to the channel-selection scheme, in particular the atmospheric training dataset on which the channel selection is based, and the background-error covariance matrix. It is found that the performance of the 'global' channel selection is sensitive to the training dataset, while the AIRS NRT channel selection remains robust, even, to some extent, for the retrieval of key analysis-error structures. Altogether, the 'manually selected' AIRS NRT channels provide a good compromise between robustness and quality.

  14. Effects of a novel selective androgen receptor modulator on dexamethasone-induced and hypogonadism-induced muscle atrophy.

    PubMed

    Jones, Amanda; Hwang, Dong-Jin; Narayanan, Ramesh; Miller, Duane D; Dalton, James T

    2010-08-01

    Glucocorticoids are the most widely used antiinflammatory drugs in the world. However, prolonged use of glucocorticoids results in undesirable side effects such as muscle wasting, osteoporosis, and diabetes. Skeletal muscle wasting, which currently has no approved therapy, is a debilitating condition resulting from either reduced muscle protein synthesis or increased degradation. The imbalance in protein synthesis could occur from increased expression and function of muscle-specific ubiquitin ligases, muscle atrophy F-box (MAFbx)/atrogin-1 and muscle ring finger 1 (MuRF1), or decreased function of the IGF-I and phosphatidylinositol-3 kinase/Akt kinase pathways. We examined the effects of a nonsteroidal tissue selective androgen receptor modulator (SARM) and testosterone on glucocorticoid-induced muscle atrophy and castration-induced muscle atrophy. The SARM and testosterone propionate blocked the dexamethasone-induced dephosphorylation of Akt and other proteins involved in protein synthesis, including Forkhead box O (FoxO). Dexamethasone caused a significant up-regulation in the expression of ubiquitin ligases, but testosterone propionate and SARM administration blocked this effect by phosphorylating FoxO. Castration induced rapid myopathy of the levator ani muscle, accompanied by up-regulation of MAFbx and MuRF1 and down-regulation of IGF-I, all of which was attenuated by a SARM. The results suggest that levator ani atrophy caused by hypogonadism may be the result of loss of IGF-I stimulation, whereas that caused by glucocorticoid treatment relies almost solely on up-regulation of MAFbx and MuRF1. Our studies provide the first evidence that glucocorticoid- and hypogonadism-induced muscle atrophy are mediated by distinct but overlapping mechanisms and that SARMs may provide a more effective and selective pharmacological approach to prevent glucocorticoid-induced muscle loss than steroidal androgen therapy.

  15. Comment: On the consequences of sexual selection for fisheries-induced evolution.

    PubMed

    Urbach, Davnah; Cotton, Samuel

    2008-11-01

    It is becoming increasingly recognized that fishing (and other forms of nonrandom harvesting) can have profound evolutionary consequences for life history traits. A recent and welcome publication provided the first description of how sexual selection might influence the outcome of fisheries-induced evolution (FIE). One of the main conclusions was that if sexual selection generates a positive relationship between body size and reproductive success, increased fishing pressure on large individuals causes stronger selection for smaller body size. Here, we re-evaluate the sexual selection interpretation of the relationship between body size and reproductive success, and suggest it may in fact be representative of a more general case of pure natural selection. The consequences of sexual selection on FIE are likely to be complicated and dynamic, and we provide additional perspectives to these new and exciting results. Selection differentials and trait variance are considered, with density-dependent and genetic effects on the strength and the direction of sexual selection given particular attention. We hope that our additional views on the role of sexual selection in FIE will encourage more theoretical and empirical work into this important application of evolutionary biology.

  16. How to Distinguish Conformational Selection and Induced Fit Based on Chemical Relaxation Rates

    PubMed Central

    2016-01-01

    Protein binding often involves conformational changes. Important questions are whether a conformational change occurs prior to a binding event (‘conformational selection’) or after a binding event (‘induced fit’), and how conformational transition rates can be obtained from experiments. In this article, we present general results for the chemical relaxation rates of conformational-selection and induced-fit binding processes that hold for all concentrations of proteins and ligands and, thus, go beyond the standard pseudo-first-order approximation of large ligand concentration. These results allow to distinguish conformational-selection from induced-fit processes—also in cases in which such a distinction is not possible under pseudo-first-order conditions—and to extract conformational transition rates of proteins from chemical relaxation data. PMID:27636092

  17. Adaptation-induced modification of motion selectivity tuning in visual tectal neurons of adult zebrafish

    PubMed Central

    Lucks, Valerie; Kurtz, Rafael; Engelmann, Jacob

    2015-01-01

    In the developing brain, training-induced emergence of direction selectivity and plasticity of orientation tuning appear to be widespread phenomena. These are found in the visual pathway across different classes of vertebrates. Moreover, short-term plasticity of orientation tuning in the adult brain has been demonstrated in several species of mammals. However, it is unclear whether neuronal orientation and direction selectivity in nonmammalian species remains modifiable through short-term plasticity in the fully developed brain. To address this question, we analyzed motion tuning of neurons in the optic tectum of adult zebrafish by calcium imaging. In total, orientation and direction selectivity was enhanced by adaptation, responses of previously orientation-selective neurons were sharpened, and even adaptation-induced emergence of selectivity in previously nonselective neurons was observed in some cases. The different observed effects are mainly based on the relative distance between the previously preferred and the adaptation direction. In those neurons in which a shift of the preferred orientation or direction was induced by adaptation, repulsive shifts (i.e., away from the adapter) were more prevalent than attractive shifts. A further novel finding for visually induced adaptation that emerged from our study was that repulsive and attractive shifts can occur within one brain area, even with uniform stimuli. The type of shift being induced also depends on the difference between the adapting and the initially preferred stimulus direction. Our data indicate that, even within the fully developed optic tectum, short-term plasticity might have an important role in adjusting neuronal tuning functions to current stimulus conditions. PMID:26378206

  18. Time-spatial Labeling Inversion Pulse (Time-SLIP) with Pencil Beam Pulse: A Selective Labeling Technique for Observing Cerebrospinal Fluid Flow Dynamics.

    PubMed

    Shibukawa, Shuhei; Miyati, Tosiaki; Niwa, Tetsu; Matsumae, Mitsunori; Ogino, Tetsuo; Horie, Tomohiko; Imai, Yutaka; Muro, Isao

    2017-08-24

    We assessed labeling region selectivity on time-spatial labeling inversion pulse (Time-SLIP) with pencil beam pulse (PB Time-SLIP) for the use of visualizing cerebrospinal fluid (CSF) flow dynamics. We compared the selectivity of labeling to the third and fourth ventricles between PB Time-SLIP and conventional Time-SLIP (cTime-SLIP) in eight volunteers and one patient using a 1.5T magnetic resonance imaging (MRI). PB Time-SLIP provided more selective labeling in CSF than cTime-SLIP, particularly in complex anatomical regions.

  19. Route selection for double-balloon endoscopy, based on capsule transit time, in obscure gastrointestinal bleeding.

    PubMed

    Nakamura, Masanao; Ohmiya, Naoki; Shirai, Osamu; Takenaka, Hiroyuki; Morishima, Kenji; Miyahara, Ryoji; Ando, Takafumi; Watanabe, Osamu; Kawashima, Hiroki; Itoh, Akihiro; Hirooka, Yoshiki; Goto, Hidemi

    2010-06-01

    Double-balloon endoscopy (DBE) utilizes both oral and anal routes. The proper selection of the initial route is important for more rapid management of obscure gastrointestinal bleeding (OGIB). The aim of this retrospective study was to clarify the accuracy of the transit time of video capsule endoscopy (VCE) to the lesion as a predictive indicator for the decision on the initial DBE route. Of 172 patients who underwent both DBE and VCE, 65 who were diagnosed with small-intestinal hemorrhagic lesions by both means were enrolled. The relation between VCE transit time to the lesion and the DBE route by which the lesion was discovered was analyzed, distinguishing between 46 complete and 19 incomplete VCEs. Among the 46 patients with a complete VCE, the transit time and position of the lesion were strongly correlated. The best cutoff values for route selection by the VCE transit time from capsule intake and from the duodenal bulb to the lesion, determined using a receiver operating characteristic (ROC) curve, were 60% and 50%, respectively, of the transit time to the cecum. At that point, the accuracy of route selection was 90% and 94%, respectively. Positions shown by VCE for ileal lesions tended to be more proximal than those shown by surgery. In the 19 patients with incomplete VCEs, the best cutoff for transit time was 180 min from the duodenal bulb. The VCE transit time was useful for determining the route for DBE in OGIB. This parameter was most accurate when the cutoff value for the selection was half of the small-bowel transit time in the complete VCE examination.

  20. Moving attention - Evidence for time-invariant shifts of visual selective attention

    NASA Technical Reports Server (NTRS)

    Remington, R.; Pierce, L.

    1984-01-01

    Two experiments measured the time to shift spatial selective attention across the visual field to targets 2 or 10 deg from central fixation. A central arrow cued the most likely target location. The direction of attention was inferred from reaction times to expected, unexpected, and neutral locations. The development of a spatial attentional set with time was examined by presenting target probes at varying times after the cue. There were no effects of distance on the time course of the attentional set. Reaction times for far locations were slower than for near, but the effects of attention were evident by 150 msec in both cases. Spatial attention does not shift with a characteristic, fixed velocity. Rather, velocity is proportional to distance, resulting in a movement time that is invariant over the distances tested.

  1. Moving attention - Evidence for time-invariant shifts of visual selective attention

    NASA Technical Reports Server (NTRS)

    Remington, R.; Pierce, L.

    1984-01-01

    Two experiments measured the time to shift spatial selective attention across the visual field to targets 2 or 10 deg from central fixation. A central arrow cued the most likely target location. The direction of attention was inferred from reaction times to expected, unexpected, and neutral locations. The development of a spatial attentional set with time was examined by presenting target probes at varying times after the cue. There were no effects of distance on the time course of the attentional set. Reaction times for far locations were slower than for near, but the effects of attention were evident by 150 msec in both cases. Spatial attention does not shift with a characteristic, fixed velocity. Rather, velocity is proportional to distance, resulting in a movement time that is invariant over the distances tested.

  2. First successful pregnancies following embryo selection using Time-lapse technology in Iran: Case report

    PubMed Central

    Faramarzi, Azita; Khalili, Mohammad Ali; Soleimani, Mehrdad

    2015-01-01

    Background: Embryo selection is a vital part of in vitro fertilization (IVF) programs, with morphology-based grading systems having been widely used for decades. Time-lapse imaging combined with embryo morph kinetics may proffer a non-invasive means for improving embryo selection. We report the first ongoing and chemical pregnancies using Time-lapse embryo scope to select best embryos for transfer in Iran. Cases: A case with tubal factor infertility was admitted to IVF program with normozoospermia. After ovarian hyper stimulation, 6 COCs were retrieved and inseminated with 25,000 progressive sperms/ oocyte. Five zygotes were placed individually into the micro wells of equilibrated embryo scope dish for Time-lapse observation, and incubated at 37°C, 5% CO2. On day 3, single embryo transfer (SET) took place based on kinetic parameters of the embryos. Clinical pregnancy was confirmed 7 weeks after SET. The second case with history of previous ICSI failure was admitted with azoospermia. Nine MII oocytes underwent ICSI, and incubated in Time-lapse facilities. The rest of procedures were followed as described for case 1. Chemical pregnancy was confirmed 15 days after SET. Conclusion: This approach opens a way to select best embryo non-invasively for SET; thus, increasing implantation, while reducing multiple pregnancy complications. PMID:26131014

  3. Time-Delayed Two-Step Selective Laser Photodamage of Dye-Biomolecule Complexes

    NASA Astrophysics Data System (ADS)

    Andreoni, A.; Cubeddu, R.; de Silvestri, S.; Laporta, P.; Svelto, O.

    1980-08-01

    A scheme is proposed for laser-selective photodamage of biological molecules, based on time-delayed two-step photoionization of a dye molecule bound to the biomolecule. The validity of the scheme is experimentally demonstrated in the case of the dye Proflavine, bound to synthetic polynucleotides.

  4. Estimating Allele Age and Selection Coefficient from Time-Serial Data

    PubMed Central

    Malaspinas, Anna-Sapfo; Malaspinas, Orestis; Evans, Steven N.; Slatkin, Montgomery

    2012-01-01

    Recent advances in sequencing technologies have made available an ever-increasing amount of ancient genomic data. In particular, it is now possible to target specific single nucleotide polymorphisms in several samples at different time points. Such time-series data are also available in the context of experimental or viral evolution. Time-series data should allow for a more precise inference of population genetic parameters and to test hypotheses about the recent action of natural selection. In this manuscript, we develop a likelihood method to jointly estimate the selection coefficient and the age of an allele from time-serial data. Our method can be used for allele frequencies sampled from a single diallelic locus. The transition probabilities are calculated by approximating the standard diffusion equation of the Wright–Fisher model with a one-step process. We show that our method produces unbiased estimates. The accuracy of the method is tested via simulations. Finally, the utility of the method is illustrated with an application to several loci encoding coat color in horses, a pattern that has previously been linked with domestication. Importantly, given our ability to estimate the age of the allele, it is possible to gain traction on the important problem of distinguishing selection on new mutations from selection on standing variation. In this coat color example for instance, we estimate the age of this allele, which is found to predate domestication. PMID:22851647

  5. Evaluation of Select Sensors for Real-Time Monitoring of Escherichia coli in Water Distribution Systems▿

    PubMed Central

    Miles, Syreeta L.; Sinclair, Ryan G.; Riley, Mark R.; Pepper, Ian L.

    2011-01-01

    This study evaluated real-time sensing of Escherichia coli as a microbial contaminant in water distribution systems. Most sensors responded to increased E. coli concentrations, showing that select sensors can detect microbial water quality changes and be utilized as part of a contaminant warning system. PMID:21357435

  6. ShapeSelectForest: a new r package for modeling landsat time series

    Treesearch

    Mary Meyer; Xiyue Liao; Gretchen Moisen; Elizabeth. Freeman

    2015-01-01

    We present a new R package called ShapeSelectForest recently posted to the Comprehensive R Archival Network. The package was developed to fit nonparametric shape-restricted regression splines to time series of Landsat imagery for the purpose of modeling, mapping, and monitoring annual forest disturbance dynamics over nearly three decades. For each pixel and spectral...

  7. Estimating allele age and selection coefficient from time-serial data.

    PubMed

    Malaspinas, Anna-Sapfo; Malaspinas, Orestis; Evans, Steven N; Slatkin, Montgomery

    2012-10-01

    Recent advances in sequencing technologies have made available an ever-increasing amount of ancient genomic data. In particular, it is now possible to target specific single nucleotide polymorphisms in several samples at different time points. Such time-series data are also available in the context of experimental or viral evolution. Time-series data should allow for a more precise inference of population genetic parameters and to test hypotheses about the recent action of natural selection. In this manuscript, we develop a likelihood method to jointly estimate the selection coefficient and the age of an allele from time-serial data. Our method can be used for allele frequencies sampled from a single diallelic locus. The transition probabilities are calculated by approximating the standard diffusion equation of the Wright-Fisher model with a one-step process. We show that our method produces unbiased estimates. The accuracy of the method is tested via simulations. Finally, the utility of the method is illustrated with an application to several loci encoding coat color in horses, a pattern that has previously been linked with domestication. Importantly, given our ability to estimate the age of the allele, it is possible to gain traction on the important problem of distinguishing selection on new mutations from selection on standing variation. In this coat color example for instance, we estimate the age of this allele, which is found to predate domestication.

  8. Plant breeding with genomic selection: potential gain per unit time and cost

    USDA-ARS?s Scientific Manuscript database

    Advancements in genotyping are rapidly decreasing marker costs and increasing genome coverage. This is facilitating the use of marker-assisted selection (MAS) in plant breeding. Commonly employed MAS strategies, however, are not well suited for complex traits, requiring extra time for field-based ph...

  9. Selection bias due to parity-conditioning in studies of time trends in fertility.

    PubMed

    Sallmén, Markku; Bonde, Jens Peter; Lindbohm, Marja-Liisa; Kristensen, Petter

    2015-01-01

    Studies of couple fertility over time have often examined study populations with broad age ranges at a cross-section of time. An increase in fertility has been observed in studies that followed episodes of fertility events either prospectively among nulliparous women or retrospectively among parous women. Fertility has a biological effect on parity. If defined at a cross-section of time, parity will also be affected by year of birth, and thus becomes a collider. Conditioning (stratifying, restricting, or adjusting) on a collider may cause selection bias in the studied association. A study with prospective follow-up was taken as the model to assess the validity of fertility studies. We demonstrate the potential for selection bias using causal graphs and nationwide birth statistics and other demographic data. We tested the existence of parity-conditioning bias in data including both parous and nulliparous women. We also used a simulation approach to assess the strength of the bias in populations with prior at-risk cycles. Finally, we evaluated the potential for selection bias due to conditioning on parity in various sampling frames. Analyses indicate that the observed increase in fertility over time can be entirely explained by selection bias due to parity-conditioning. Heterogeneity in fertility and differential success in prior at-risk cycles are the ultimate factors behind the selection bias. The potential for selection bias due to parity-conditioning varies by sampling frame. A prospective multidecade study with representative sampling of birth cohorts and follow-up from menarche to menopause would bypass the described bias.

  10. Light-induced hetero-Diels-Alder cycloaddition: a facile and selective photoclick reaction.

    PubMed

    Arumugam, Selvanathan; Popik, Vladimir V

    2011-04-13

    2-Napthoquinone-3-methides (oNQMs) generated by efficient photodehydration (Φ=0.2) of 3-(hydroxymethyl)-2-naphthol undergo facile hetero-Diels-Alder addition (k(D-A)∼ 4×10(4) M(-1) s(-1)) to electron-rich polarized olefins in an aqueous solution. The resulting photostable benzo[g]chromans are produced in high to quantitative yield. The unreacted oNQM is rapidly hydrated (k(H2O) ∼145 s(-1)) to regenerate the starting diol. This competition between hydration and cycloaddition makes oNQMs highly selective, since only vinyl ethers and enamines are reactive enough to form the Diels-Alder adduct in an aqueous solution; no cycloaddition was observed with other types of alkenes. To achieve photolabeling or photoligation of two substrates, one is derivatized with a vinyl ether moiety, while 3-(hydroxymethyl)-2-naphthol is attached to the other via an appropriate linker. The light-induced Diels-Alder "click" strategy permits the formation of either a permanent or hydrolytically labile linkage. Rapid kinetics of this photoclick reaction (k=4×10(4) M(-1) s(-1)) is useful for time-resolved applications. The short lifetime (τ ∼7 ms in H(2)O) of the active form of the photoclick reagent prevents its migration from the site of irradiation, thus, allowing for spatial control of the ligation or labeling.

  11. SEM-induced shrinkage and site-selective modification of single-crystal silicon nanopores

    NASA Astrophysics Data System (ADS)

    Chen, Qi; Wang, Yifan; Deng, Tao; Liu, Zewen

    2017-07-01

    Solid-state nanopores with feature sizes around 5 nm play a critical role in bio-sensing fields, especially in single molecule detection and sequencing of DNA, RNA and proteins. In this paper we present a systematic study on shrinkage and site-selective modification of single-crystal silicon nanopores with a conventional scanning electron microscope (SEM). Square nanopores with measurable sizes as small as 8 nm × 8 nm and rectangle nanopores with feature sizes (the smaller one between length and width) down to 5 nm have been obtained, using the SEM-induced shrinkage technique. The analysis of energy dispersive x-ray spectroscopy and the recovery of the pore size and morphology reveal that the grown material along with the edge of the nanopore is the result of deposition of hydrocarbon compounds, without structural damage during the shrinking process. A simplified model for pore shrinkage has been developed based on observation of the cross-sectional morphology of the shrunk nanopore. The main factors impacting on the task of controllably shrinking the nanopores, such as the accelerating voltage, spot size, scanned area of e-beam, and the initial pore size have been discussed. It is found that single-crystal silicon nanopores shrink linearly with time under localized irradiation by SEM e-beam in all cases, and the pore shrinkage rate is inversely proportional to the initial equivalent diameter of the pore under the same e-beam conditions.

  12. Fabrication mechanism of friction-induced selective etching on Si(100) surface

    PubMed Central

    2012-01-01

    As a maskless nanofabrication technique, friction-induced selective etching can easily produce nanopatterns on a Si(100) surface. Experimental results indicated that the height of the nanopatterns increased with the KOH etching time, while their width increased with the scratching load. It has also found that a contact pressure of 6.3 GPa is enough to fabricate a mask layer on the Si(100) surface. To understand the mechanism involved, the cross-sectional microstructure of a scratched area was examined, and the mask ability of the tip-disturbed silicon layer was studied. Transmission electron microscope observation and scanning Auger nanoprobe analysis suggested that the scratched area was covered by a thin superficial oxidation layer followed by a thick distorted (amorphous and deformed) layer in the subsurface. After the surface oxidation layer was removed by HF etching, the residual amorphous and deformed silicon layer on the scratched area can still serve as an etching mask in KOH solution. The results may help to develop a low-destructive, low-cost, and flexible nanofabrication technique suitable for machining of micro-mold and prototype fabrication in micro-systems. PMID:22356699

  13. Aspirin-induced post-gingivectomy haemorrhage: a timely reminder.

    PubMed

    Thomason, J M; Seymour, R A; Murphy, P; Brigham, K M; Jones, P

    1997-02-01

    A case report is described of significant aspirin-induced haemorrhage following a gingivectory procedure in an organ transplant patient. Aspirin-induced platelet impairment secondary to low-dose aspirin was implicated as the cause of the haemorrhage. Haemostasis was eventually achieved after platelet transfusion. The case illustrates the problems that can arise when carrying out gingival surgery on patients medicated with low-dose aspirin.

  14. Selective Rac1 inhibition protects renal tubular epithelial cells from oxalate-induced NADPH oxidase-mediated oxidative cell injury

    PubMed Central

    Thamilselvan, Vijayalakshmi; Menon, Mani

    2013-01-01

    Oxalate-induced oxidative cell injury is one of the major mechanisms implicated in calcium oxalate nucleation, aggregation and growth of kidney stones. We previously demonstrated that oxalate-induced NADPH oxidase-derived free radicals play a significant role in renal injury. Since NADPH oxidase activation requires several regulatory proteins, the primary goal of this study was to characterize the role of Rac GTPase in oxalate-induced NADPH oxidase-mediated oxidative injury in renal epithelial cells. Our results show that oxalate significantly increased membrane translocation of Rac1 and NADPH oxidase activity of renal epithelial cells in a time-dependent manner. We found that NSC23766, a selective inhibitor of Rac1, blocked oxalate-induced membrane translocation of Rac1 and NADPH oxidase activity. In the absence of Rac1 inhibitor, oxalate exposure significantly increased hydrogen peroxide formation and LDH release in renal epithelial cells. In contrast, Rac1 inhibitor pretreatment, significantly decreased oxalate-induced hydrogen peroxide production and LDH release. Furthermore, PKC α and δ inhibitor, oxalate exposure did not increase Rac1 protein translocation, suggesting that PKC resides upstream from Rac1 in the pathway that regulates NADPH oxidase. In conclusion, our data demonstrate for the first time that Rac1-dependent activation of NADPH oxidase might be a crucial mechanism responsible for oxalate-induced oxidative renal cell injury. These findings suggest that Rac1 signaling plays a key role in oxalate-induced renal injury, and may serve as a potential therapeutic target to prevent calcium oxalate crystal deposition in stone formers and reduce recurrence. PMID:21814770

  15. A method for real-time visual stimulus selection in the study of cortical object perception

    PubMed Central

    Leeds, Daniel D.; Tarr, Michael J.

    2016-01-01

    The properties utilized by visual object perception in the mid- and high-level ventral visual pathway are poorly understood. To better establish and explore possible models of these properties, we adopt a data-driven approach in which we repeatedly interrogate neural units using functional Magnetic Resonance Imaging (fMRI) to establish each unit’s image selectivity. This approach to imaging necessitates a search through a broad space of stimulus properties using a limited number of samples. To more quickly identify the complex visual features underlying human cortical object perception, we implemented a new functional magnetic resonance imaging protocol in which visual stimuli are selected in real-time based on BOLD responses to recently shown images. Two variations of this protocol were developed, one relying on natural object stimuli and a second based on synthetic object stimuli, both embedded in feature spaces based on the complex visual properties of the objects. During fMRI scanning, we continuously controlled stimulus selection in the context of a real-time search through these image spaces in order to maximize neural responses across predetermined 1 cm3 brain regions. Elsewhere we have reported the patterns of cortical selectivity revealed by this approach (Leeds 2014). In contrast, here our objective is to present more detailed methods and explore the technical and biological factors influencing the behavior of our real-time stimulus search. We observe that: 1) Searches converged more reliably when exploring a more precisely parameterized space of synthetic objects; 2) Real-time estimation of cortical responses to stimuli are reasonably consistent; 3) Search behavior was acceptably robust to delays in stimulus displays and subject motion effects. Overall, our results indicate that real-time fMRI methods may provide a valuable platform for continuing study of localized neural selectivity, both for visual object representation and beyond. PMID:26973168

  16. A method for real-time visual stimulus selection in the study of cortical object perception.

    PubMed

    Leeds, Daniel D; Tarr, Michael J

    2016-06-01

    The properties utilized by visual object perception in the mid- and high-level ventral visual pathway are poorly understood. To better establish and explore possible models of these properties, we adopt a data-driven approach in which we repeatedly interrogate neural units using functional Magnetic Resonance Imaging (fMRI) to establish each unit's image selectivity. This approach to imaging necessitates a search through a broad space of stimulus properties using a limited number of samples. To more quickly identify the complex visual features underlying human cortical object perception, we implemented a new functional magnetic resonance imaging protocol in which visual stimuli are selected in real-time based on BOLD responses to recently shown images. Two variations of this protocol were developed, one relying on natural object stimuli and a second based on synthetic object stimuli, both embedded in feature spaces based on the complex visual properties of the objects. During fMRI scanning, we continuously controlled stimulus selection in the context of a real-time search through these image spaces in order to maximize neural responses across pre-determined 1cm(3) rain regions. Elsewhere we have reported the patterns of cortical selectivity revealed by this approach (Leeds et al., 2014). In contrast, here our objective is to present more detailed methods and explore the technical and biological factors influencing the behavior of our real-time stimulus search. We observe that: 1) Searches converged more reliably when exploring a more precisely parameterized space of synthetic objects; 2) real-time estimation of cortical responses to stimuli is reasonably consistent; 3) search behavior was acceptably robust to delays in stimulus displays and subject motion effects. Overall, our results indicate that real-time fMRI methods may provide a valuable platform for continuing study of localized neural selectivity, both for visual object representation and beyond.

  17. Functional selectivity and time-dependence of μ-opioid receptor desensitization at nerve terminals in the mouse ventral tegmental area

    PubMed Central

    Lowe, J D; Bailey, C P

    2015-01-01

    BACKGROUND AND PURPOSE The majority of studies examining desensitization of the μ-opioid receptor (MOR) have examined those located at cell bodies. However, MORs are extensively expressed at nerve terminals throughout the mammalian nervous system. This study is designed to investigate agonist-induced MOR desensitization at nerve terminals in the mouse ventral tegmental area (VTA). EXPERIMENTAL APPROACH MOR function was measured in mature mouse brain slices containing the VTA using whole-cell patch-clamp electrophysiology. Presynaptic MOR function was isolated from postsynaptic function and the functional selectivity, time-dependence and mechanisms of agonist-induced MOR desensitization were examined. KEY RESULTS MORs located at GABAergic nerve terminals in the VTA were completely resistant to rapid desensitization induced by the high-efficacy agonists DAMGO and Met-enkephalin. MORs located postsynaptically on GABAergic cell bodies readily underwent rapid desensitization in response to DAMGO. However, after prolonged (>7 h) treatment with Met-enkephalin, profound homologous MOR desensitization was observed. Morphine could induce rapid MOR desensitization at nerve terminals when PKC was activated. CONCLUSIONS AND IMPLICATIONS Agonist-induced MOR desensitization in GABAergic neurons in the VTA is compartment-selective as well as agonist-selective. When MORs are located at cell bodies, higher-efficacy agonists induce greater levels of rapid desensitization than lower-efficacy agonists. However, the converse is true at nerve terminals where agonists that induce MOR desensitization via PKC are capable of rapid agonist-induced desensitization while higher-efficacy agonists are not. MOR desensitization induced by higher-efficacy agonists at nerve terminals only takes place after prolonged receptor activation. LINKED ARTICLES This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http

  18. The value in rushing: Memory and selectivity when short on time.

    PubMed

    Middlebrooks, Catherine D; Murayama, Kou; Castel, Alan D

    2016-10-01

    While being short on time can certainly limit what one remembers, are there always such costs? The current study investigates the impact of time constraints on selective memory and the self-regulated study of valuable information. Participants studied lists of words ranging in value from 1-10 points, with the goal being to maximize their score during recall. Half of the participants studied these words at a constant presentation rate of either 1 s or 5s. The other half of participants studied under both rates, either fast (1s) during the first several lists and then slow (5s) during later lists, or vice versa. Study was then self-paced during a final segment of lists for all participants to determine how people regulate their study time after experiencing different presentation rates during study. While participants recalled more words overall when studying at a 5-second rate, there were no significant differences in terms of value-based recall, with all participants demonstrating better recall for higher-valued words and similar patterns of selectivity, regardless of study time or prior timing experience. Self-paced study was also value-based, with participants spending more time studying high-value words than low-value. Thus, while being short on time may have impaired memory overall, participants' attention to item value during study was not differentially impacted by the fast and slow timing rates. Overall, these findings offer further insight regarding the influence that timing schedules and task experience have on how people selectively focus on valuable information.

  19. Quantifying selection in evolving populations using time-resolved genetic data

    NASA Astrophysics Data System (ADS)

    Illingworth, Christopher J. R.; Mustonen, Ville

    2013-01-01

    Methods which uncover the molecular basis of the adaptive evolution of a population address some important biological questions. For example, the problem of identifying genetic variants which underlie drug resistance, a question of importance for the treatment of pathogens, and of cancer, can be understood as a matter of inferring selection. One difficulty in the inference of variants under positive selection is the potential complexity of the underlying evolutionary dynamics, which may involve an interplay between several contributing processes, including mutation, recombination and genetic drift. A source of progress may be found in modern sequencing technologies, which confer an increasing ability to gather information about evolving populations, granting a window into these complex processes. One particularly interesting development is the ability to follow evolution as it happens, by whole-genome sequencing of an evolving population at multiple time points. We here discuss how to use time-resolved sequence data to draw inferences about the evolutionary dynamics of a population under study. We begin by reviewing our earlier analysis of a yeast selection experiment, in which we used a deterministic evolutionary framework to identify alleles under selection for heat tolerance, and to quantify the selection acting upon them. Considering further the use of advanced intercross lines to measure selection, we here extend this framework to cover scenarios of simultaneous recombination and selection, and of two driver alleles with multiple linked neutral, or passenger, alleles, where the driver pair evolves under an epistatic fitness landscape. We conclude by discussing the limitations of the approach presented and outlining future challenges for such methodologies.

  20. Time-Dependent Tree-Structured Survival Analysis with Unbiased Variable Selection through Permutation Tests

    PubMed Central

    Wallace, M. L.

    2014-01-01

    Incorporating time-dependent covariates into tree-structured survival analysis (TSSA) may result in more accurate prognostic models than if only baseline values are used. Available time-dependent TSSA methods exhaustively test every binary split on every covariate; however, this approach may result in selection bias towards covariates with more observed values. We present a method that uses unbiased significance levels from newly proposed permutation tests to select the time-dependent or baseline covariate with the strongest relationship with the survival outcome. The specific splitting value is identified using only the selected covariate. Simulation results show that the proposed time-dependent TSSA method produces tree models of equal or greater accuracy as compared to baseline TSSA models, even with high censoring rates and large within-subject variability in the time-dependent covariate. To illustrate, the proposed method is applied to data from a cohort of bipolar youth to identify subgroups at risk for self-injurious behavior. PMID:25043382

  1. Stress, Time Pressure, Strategy Selection and Math Anxiety in Mathematics: A Review of the Literature

    PubMed Central

    Caviola, Sara; Carey, Emma; Mammarella, Irene C.; Szucs, Denes

    2017-01-01

    We review how stress induction, time pressure manipulations and math anxiety can interfere with or modulate selection of problem-solving strategies (henceforth “strategy selection”) in arithmetical tasks. Nineteen relevant articles were identified, which contain references to strategy selection and time limit (or time manipulations), with some also discussing emotional aspects in mathematical outcomes. Few of these take cognitive processes such as working memory or executive functions into consideration. We conclude that due to the sparsity of available literature our questions can only be partially answered and currently there is not much evidence of clear associations. We identify major gaps in knowledge and raise a series of open questions to guide further research. PMID:28919870

  2. Enantiomer-Selective Photo-Induced Reaction of Protonated Tryptophan with Disaccharides in the Gas Phase.

    PubMed

    Doan, Thuc N; Fujihara, Akimasa

    2017-07-08

    In order to investigate chemical evolution in interstellar molecular clouds, enantiomer-selective photo-induced chemical reactions between an amino acid and disaccharides in the gas phase were examined using a tandem mass spectrometer containing an electrospray ionization source and a cold ion trap. Ultraviolet photodissociation mass spectra of cold gas-phase noncovalent complexes of protonated tryptophan (Trp) enantiomers with disaccharides consisting of two D-glucose units, such as D-maltose or D-cellobiose, were obtained by photoexcitation of the indole ring of Trp. NH2CHCOOH loss via cleavage of the Cα-Cβ bond in Trp induced by hydrogen atom transfer from the NH3(+) group of a protonated Trp was observed in a noncovalent heterochiral H(+)(L-Trp)(D-maltose) complex. In contrast, a photo-induced chemical reaction forming the product ion with m/z 282 occurs in homochiral H(+)(D-Trp)(D-maltose). For D-cellobiose, both NH2CHCOOH elimination and the m/z 282 product ion were observed, and no enantiomer-selective phenomena occurred. The m/z 282 product ion indicates that the photo-induced C-glycosylation, which links D-glucose residues to the indole moiety of Trp via a C-C bond, can occur in cold gas-phase noncovalent complexes, and its enantiomer-selectivity depends on the structure of the disaccharide.

  3. Enantiomer-Selective Photo-Induced Reaction of Protonated Tryptophan with Disaccharides in the Gas Phase

    NASA Astrophysics Data System (ADS)

    Doan, Thuc N.; Fujihara, Akimasa

    2017-07-01

    In order to investigate chemical evolution in interstellar molecular clouds, enantiomer-selective photo-induced chemical reactions between an amino acid and disaccharides in the gas phase were examined using a tandem mass spectrometer containing an electrospray ionization source and a cold ion trap. Ultraviolet photodissociation mass spectra of cold gas-phase noncovalent complexes of protonated tryptophan (Trp) enantiomers with disaccharides consisting of two uc(d)-glucose units, such as uc(d)-maltose or uc(d)-cellobiose, were obtained by photoexcitation of the indole ring of Trp. NH2CHCOOH loss via cleavage of the Cα-Cβ bond in Trp induced by hydrogen atom transfer from the NH3 + group of a protonated Trp was observed in a noncovalent heterochiral H+(uc(l)-Trp)(uc(d)-maltose) complex. In contrast, a photo-induced chemical reaction forming the product ion with m/z 282 occurs in homochiral H+(uc(d)-Trp)(uc(d)-maltose). For uc(d)-cellobiose, both NH2CHCOOH elimination and the m/z 282 product ion were observed, and no enantiomer-selective phenomena occurred. The m/z 282 product ion indicates that the photo-induced C-glycosylation, which links uc(d)-glucose residues to the indole moiety of Trp via a C-C bond, can occur in cold gas-phase noncovalent complexes, and its enantiomer-selectivity depends on the structure of the disaccharide.

  4. A Universal Scaling Law Determines Time Reversibility and Steady State of Substitutions under Selection

    PubMed Central

    Manhart, Michael; Haldane, Allan

    2012-01-01

    Monomorphic loci evolve through a series of substitutions on a fitness landscape. Understanding how mutation, selection, and genetic drift drive this process, and uncovering the structure of the fitness landscape from genomic data are two major goals of evolutionary theory. Population genetics models of the substitution process have traditionally focused on the weak-selection regime, which is accurately described by diffusion theory. Predictions in this regime can be considered universal in the sense that many population models exhibit equivalent behavior in the diffusion limit. However, a growing number of experimental studies suggest that strong selection plays a key role in some systems, and thus there is a need to understand universal properties of models without a priori assumptions about selection strength. Here we study time reversibility in a general substitution model of a monomorphic haploid population. We show that for any time-reversible population model, such as the Moran process, substitution rates obey an exact scaling law. For several other irreversible models, such as the simple Wright-Fisher process and its extensions, the scaling law is accurate up to selection strengths that are well outside the diffusion regime. Time reversibility gives rise to a power-law expression for the steady-state distribution of populations on an arbitrary fitness landscape. The steady-state behavior is dominated by weak selection and is thus adequately described by the diffusion approximation, which guarantees universality of the steady-state formula and its applicability to the problem of reconstructing fitness landscapes from DNA or protein sequence data. PMID:22838027

  5. Integrating fossil preservation biases in the selection of calibrations for molecular divergence time estimation.

    PubMed

    Dornburg, Alex; Beaulieu, Jeremy M; Oliver, Jeffrey C; Near, Thomas J

    2011-07-01

    The selection of fossil data to use as calibration age priors in molecular divergence time estimates inherently links neontological methods with paleontological theory. However, few neontological studies have taken into account the possibility of a taphonomic bias in the fossil record when developing approaches to fossil calibration selection. The Sppil-Rongis effect may bias the first appearance of a lineage toward the recent causing most objective calibration selection approaches to erroneously exclude appropriate calibrations or to incorporate multiple calibrations that are too young to accurately represent the divergence times of target lineages. Using turtles as a case study, we develop a Bayesian extension to the fossil selection approach developed by Marshall (2008. A simple method for bracketing absolute divergence times on molecular phylogenies using multiple fossil calibrations points. Am. Nat. 171:726-742) that takes into account this taphonomic bias. Our method has the advantage of identifying calibrations that may bias age estimates to be too recent while incorporating uncertainty in phylogenetic parameter estimates such as tree topology and branch lengths. Additionally, this method is easily adapted to assess the consistency of potential calibrations to any one calibration in the candidate pool.

  6. Selective Na+/Ca2+ exchanger inhibition prevents Ca2+ overload-induced triggered arrhythmias

    PubMed Central

    Nagy, Norbert; Kormos, Anita; Kohajda, Zsófia; Szebeni, Áron; Szepesi, Judit; Pollesello, Piero; Levijoki, Jouko; Acsai, Károly; Virág, László; Nánási, Péter P; Papp, Julius Gy; Varró, András; Tóth, András

    2014-01-01

    Background and Purpose Augmented Na+/Ca2+ exchanger (NCX) activity may play a crucial role in cardiac arrhythmogenesis; however, data regarding the anti-arrhythmic efficacy of NCX inhibition are debatable. Feasible explanations could be the unsatisfactory selectivity of NCX inhibitors and/or the dependence of the experimental model on the degree of Ca2+i overload. Hence, we used NCX inhibitors SEA0400 and the more selective ORM10103 to evaluate the efficacy of NCX inhibition against arrhythmogenic Ca2+i rise in conditions when [Ca2+]i was augmented via activation of the late sodium current (INaL) or inhibition of the Na+/K+ pump. Experimental Approach Action potentials (APs) were recorded from canine papillary muscles and Purkinje fibres by microelectrodes. NCX current (INCX) was determined in ventricular cardiomyocytes utilizing the whole-cell patch clamp technique. Ca2+i transients (CaTs) were monitored with a Ca2+-sensitive fluorescent dye, Fluo-4. Key Results Enhanced INaL increased the Ca2+ load and AP duration (APD). SEA0400 and ORM10103 suppressed INCX and prevented/reversed the anemone toxin II (ATX-II)-induced [Ca2+]i rise without influencing APD, CaT or cell shortening, or affecting the ATX-II-induced increased APD. ORM10103 significantly decreased the number of strophanthidin-induced spontaneous diastolic Ca2+ release events; however, SEA0400 failed to restrict the veratridine-induced augmentation in Purkinje-ventricle APD dispersion. Conclusions and Implications Selective NCX inhibition – presumably by blocking revINCX (reverse mode NCX current) – is effective against arrhythmogenesis caused by [Na+]i-induced [Ca2+]i elevation, without influencing the AP waveform. Therefore, selective INCX inhibition, by significantly reducing the arrhythmogenic trigger activity caused by the perturbed Ca2+i handling, should be considered as a promising anti-arrhythmic therapeutic strategy. PMID:25073832

  7. Stable Epigenetic Variants Selected from an Induced Hypomethylated Fragaria vesca Population.

    PubMed

    Xu, Jihua; Tanino, Karen K; Robinson, Stephen J

    2016-01-01

    Epigenetic inheritance was transmitted through selection over five generations of extreme early, but not late flowering time phenotypic lines in Fragaria vesca. Epigenetic variation was initially artificially induced using the DNA demethylation reagent 5-azacytidine (5-azaC). It is the first report to explore epigenetic variant selection and phenotypic trait inheritance in strawberry. Transmission frequency of these traits was determined across generations. The early flowering (EF4) and late stolon (LS) phenotypic traits were successfully transmitted across five and three generations through meiosis, respectively. Stable mitotic transmission of the early flowering phenotype was also demonstrated using clonal daughters derived from the 4th Generation (S4) mother plant. In order to further explore the DNA methylation patterns underlying the early flowering trait, the standard MSAP method using isoschizomers Hpa II/Msp I, and newly modified MSAP method using isoschizomers Tfi I/Pfe I which detected DNA methylation at CG, CHG, CHH sites were used in two early flowering lines, EF lines 1 (P2) and EF lines 2 (P3), and control lines (P1). A significant reduction in the number of fully-methylated bands was detected in P2 and P3 when compared to P1 using the novel MSAP method. In the standard MSAP, the symmetric CG and CHG methylation was maintained over generations in the early flowering lines based on the clustering in P2 and P3, the novel MSAP approach revealed the asymmetric CHH methylation pattern was not maintained over generations. This study provides evidence of stable selection of phenotypic traits, particularly early flowering through both meiosis and mitosis, which is meaningful to both breeding programs and commercial horticulture. The maintenance in CG and CHG methylation over generations suggests the early flowering phenotype might be related to DNA methylation alterations at the CG or CHG sites. Finally, this work provides a new approach for studying the role

  8. Stable Epigenetic Variants Selected from an Induced Hypomethylated Fragaria vesca Population

    PubMed Central

    Xu, Jihua; Tanino, Karen K.; Robinson, Stephen J.

    2016-01-01

    Epigenetic inheritance was transmitted through selection over five generations of extreme early, but not late flowering time phenotypic lines in Fragaria vesca. Epigenetic variation was initially artificially induced using the DNA demethylation reagent 5-azacytidine (5-azaC). It is the first report to explore epigenetic variant selection and phenotypic trait inheritance in strawberry. Transmission frequency of these traits was determined across generations. The early flowering (EF4) and late stolon (LS) phenotypic traits were successfully transmitted across five and three generations through meiosis, respectively. Stable mitotic transmission of the early flowering phenotype was also demonstrated using clonal daughters derived from the 4th Generation (S4) mother plant. In order to further explore the DNA methylation patterns underlying the early flowering trait, the standard MSAP method using isoschizomers Hpa II/Msp I, and newly modified MSAP method using isoschizomers Tfi I/Pfe I which detected DNA methylation at CG, CHG, CHH sites were used in two early flowering lines, EF lines 1 (P2) and EF lines 2 (P3), and control lines (P1). A significant reduction in the number of fully-methylated bands was detected in P2 and P3 when compared to P1 using the novel MSAP method. In the standard MSAP, the symmetric CG and CHG methylation was maintained over generations in the early flowering lines based on the clustering in P2 and P3, the novel MSAP approach revealed the asymmetric CHH methylation pattern was not maintained over generations. This study provides evidence of stable selection of phenotypic traits, particularly early flowering through both meiosis and mitosis, which is meaningful to both breeding programs and commercial horticulture. The maintenance in CG and CHG methylation over generations suggests the early flowering phenotype might be related to DNA methylation alterations at the CG or CHG sites. Finally, this work provides a new approach for studying the role

  9. Collective effectiveness in the XV de France: selections and time matter.

    PubMed

    Sedeaud, Adrien; Saulière, Guillaume; Marquet, Laurie-Anne; Del Vecchio, Scott; Bar-Hen, Avner; Toussaint, Jean-François

    2017-03-13

    The aim of this study was to quantify the impact of selections and shared selections in the rugby union. Players' names, positions, and number of selections were collected for all XV de France's games (1906-2014). Every team's percentage of renewal of workforce was calculated for backs and forwards. During the 1987-2014 period, all second row forwards (locks), halfbacks, and centres' shared selections (number of times when two players have competed together) were recreated. The Best vs. Rest method was applied to these remodelled dyads. They were analysed and compared with surrounding teammates as well as opponents. Head coaches similarly change their workforce for upcoming matches after winning or losing (around 30%), but losing teams renew significantly more positions in their line-ups. The recreated halfbacks, locks, and centres reveal a common pattern. Whether victorious or not, the 'renewed couples' victory percentage will congregate towards the XV de France's victory percentage. For all the best recreated couples, the cumulated number of selections for forwards' is always higher than the ones part of less efficient teams: 231.3 ± 80 vs. 212.9 ± 91 selections for locks' teammates (Effect sizes (ES) small, possibly positive, 54.8%). In best recreated couples, number 8's are significantly more experienced than their counterparts in less efficient pairs (ES small, likely positive, 76.3%). The XV de France's collective effectiveness relies on a balance between stability and workforce renewal, which allows the building of specific position interactions and builds on experimented forwards packs. Selections and shared selections are serious collective performance parameters associated with performance.

  10. Selective Activation of the Prostaglandin E2 Circuit in Chronic Injury-Induced Pathologic Angiogenesis

    PubMed Central

    Liclican, Elvira L.; Nguyen, Van; Sullivan, Aaron B.

    2010-01-01

    Purpose. Cyclooxygenase (COX)-derived prostaglandin E2 (PGE2) is a prevalent and established mediator of inflammation and pain in numerous tissues and diseases. Distribution and expression of the four PGE2 receptors (EP1-EP4) can dictate whether PGE2 exerts an anti-inflammatory or a proinflammatory and/or a proangiogenic effect. The role and mechanism of endogenous PGE2 in the cornea, and the regulation of EP expression during a dynamic and complex inflammatory/reparative response remain to be clearly defined. Methods. Chronic or acute self-resolving inflammation was induced in mice by corneal suture or epithelial abrasion, respectively. Reepithelialization was monitored by fluorescein staining and neovascularization quantified by CD31/PECAM-1 immunofluorescence. PGE2 formation was analyzed by lipidomics and polymorphonuclear leukocyte (PMN) infiltration quantified by myeloperoxidase activity. Expression of EPs and inflammatory/angiogenic mediators was assessed by real-time PCR and immunohistochemistry. Mice eyes were treated with PGE2 (100 ng topically, three times a day) for up to 7 days. Results. COX-2, EP-2, and EP-4 expression was upregulated with chronic inflammation that correlated with increased corneal PGE2 formation and marked neovascularization. In contrast, acute abrasion injury did not alter PGE2 or EP levels. PGE2 treatment amplified PMN infiltration and the angiogenic response to chronic inflammation but did not affect wound healing or PMN infiltration after epithelial abrasion. Exacerbated inflammatory neovascularization with PGE2 treatment was independent of the VEGF circuit but was associated with a significant induction of the eotaxin-CCR3 axis. Conclusions. These findings place the corneal PGE2 circuit as an endogenous mediator of inflammatory neovascularization rather than general inflammation and demonstrate that chronic inflammation selectively regulates this circuit at the level of biosynthetic enzyme and receptor expression. PMID:20610836

  11. Photodynamic therapy induces selective extravasation of macromolecules: Insights using intravital microscopy.

    PubMed

    Debefve, E; Cheng, C; Schaefer, S C; Yan, H; Ballini, J-P; van den Bergh, H; Lehr, H-A; Ruffieux, C; Ris, H-B; Krueger, T

    2010-01-21

    Photodynamic therapy (PDT) with Visudyne acts by direct cellular phototoxicity and/or by an indirect vascular-mediated effect. Here, we demonstrate that the vessel integrity interruption by PDT can promote the extravasation of a macromolecular agent in normal tissue. To obtain extravasation in normal tissue PDT conditions were one order of magnitude more intensive than the ones in tissue containing neovessels reported in the literature. Fluorescein isothiocyanate dextran (FITC-D, 2000 kDa), a macromolecular agent, was intravenously injected 10 min before (LK0 group, n=14) or 2h (LK2 group, n=16) after Visudyne-mediated PDT in nude mice bearing a dorsal skin fold chamber. Control animals had no PDT (CTRL group, n=8). The extravasation of FITC-D from blood vessels in striated muscle tissue was observed in both groups in real-time for up to 2500 s after injection. We also monitored PDT-induced leukocyte rolling in vivo and assessed, by histology, the corresponding inflammatory reaction score in the dorsal skin fold chambers. In all animals, at the applied PDT conditions, FITC-D extravasation was significantly enhanced in the PDT-treated areas as compared to the surrounding non-treated areas (p<0.0001). There was no FITC-D leakage in the control animals. Animals from the LK0 group had significantly less FITC-D extravasation than those from the LK2 group (p=0.0002). In the LK0 group FITC-D leakage correlated significantly with the inflammation (p<0.001). At the selected conditions, Visudyne-mediated PDT promotes vascular leakage and FITC-D extravasation into the interstitial space of normal tissue. The intensity of vascular leakage depends on the time interval between PDT and FITC-D injection. This concept could be used to locally modulate the delivery of macromolecules in vivo. Copyright 2009 Elsevier B.V. All rights reserved.

  12. Temperature-induced labelling of Fluo-3 AM selectively yields brighter nucleus in adherent cells

    SciTech Connect

    Meng, Guixian; Pan, Leiting; Li, Cunbo; Hu, Fen; Shi, Xuechen; Lee, Imshik; Drevenšek-Olenik, Irena; Zhang, Xinzheng; Xu, Jingjun

    2014-01-17

    Highlights: •We detailedly examine temperature effects of Fluo-3 AM labelling in adherent cells. •4 °C Loading and 20 °C de-esterification of Fluo-3 AM yields brighter nuclei. •Brighter nuclei labelling by Fluo-3 AM also depends on cell adhesion quality. •A qualitative model of the brighter nucleus is proposed. -- Abstract: Fluo-3 is widely used to study cell calcium. Two traditional approaches: (1) direct injection and (2) Fluo-3 acetoxymethyl ester (AM) loading, often bring conflicting results in cytoplasmic calcium ([Ca{sup 2+}]{sub c}) and nuclear calcium ([Ca{sup 2+}]{sub n}) imaging. AM loading usually yields a darker nucleus than in cytoplasm, while direct injection always induces a brighter nucleus which is more responsive to [Ca{sup 2+}]{sub n} detection. In this work, we detailedly investigated the effects of loading and de-esterification temperatures on the fluorescence intensity of Fluo-3 in response to [Ca{sup 2+}]{sub n} and [Ca{sup 2+}]{sub c} in adherent cells, including osteoblast, HeLa and BV2 cells. Interestingly, it showed that fluorescence intensity of nucleus in osteoblast cells was about two times larger than that of cytoplasm when cells were loaded with Fluo-3 AM at 4 °C and allowed a subsequent step for de-esterification at 20 °C. Brighter nuclei were also acquired in HeLa and BV2 cells using the same experimental condition. Furthermore, loading time and adhesion quality of cells had effect on fluorescence intensity. Taken together, cold loading and room temperature de-esterification treatment of Fluo-3 AM selectively yielded brighter nucleus in adherent cells.

  13. Selective heart rate reduction with ivabradine slows ischaemia-induced electrophysiological changes and reduces ischaemia–reperfusion-induced ventricular arrhythmias

    PubMed Central

    Ng, Fu Siong; Shadi, Iqbal T.; Peters, Nicholas S.; Lyon, Alexander R.

    2013-01-01

    Heart rates during ischaemia and reperfusion are possible determinants of reperfusion arrhythmias. We used ivabradine, a selective If current inhibitor, to assess the effects of heart rate reduction (HRR) during ischaemia–reperfusion on reperfusion ventricular arrhythmias and assessed potential anti-arrhythmic mechanisms by optical mapping. Five groups of rat hearts were subjected to regional ischaemia by left anterior descending artery occlusion for 8 min followed by 10 min of reperfusion: (1) Control n = 10; (2) 1 μM of ivabradine perfusion n = 10; (3) 1 μM of ivabradine + 5 Hz atrial pacing throughout ischaemia–reperfusion n = 5; (4) 1 μM of ivabradine + 5 Hz pacing only at reperfusion; (5) 100 μM of ivabradine was used as a 1 ml bolus upon reperfusion. For optical mapping, 10 hearts (ivabradine n = 5; 5 Hz pacing n = 5) were subjected to global ischaemia whilst transmembrane voltage transients were recorded. Epicardial activation was mapped, and the rate of development of ischaemia-induced electrophysiological changes was assessed. HRR observed in the ivabradine group during both ischaemia (195 ± 11 bpm vs. control 272 ± 14 bpm, p < 0.05) and at reperfusion (168 ± 13 bpm vs. 276 ± 14 bpm, p < 0.05) was associated with reduced reperfusion ventricular fibrillation (VF) incidence (20% vs. 90%, p < 0.05). Pacing throughout ischaemia–reperfusion abolished the protective effects of ivabradine (100% VF), whereas pacing at reperfusion only partially attenuated this effect (40% VF). Ivabradine, given as a bolus at reperfusion, did not significantly affect VF incidence (80% VF). Optical mapping experiments showed a delay to ischaemia-induced conduction slowing (time to 50% conduction slowing: 10.2 ± 1.3 min vs. 5.1 ± 0.7 min, p < 0.05) and to loss of electrical excitability in ivabradine-perfused hearts (27.7 ± 4.3 min vs. 14.5 ± 0.6 min, p < 0.05). Ivabradine administered throughout ischaemia

  14. Effects of furosemide on the racing times of horses with exercise-induced pulmonary hemorrhage.

    PubMed

    Soma, L R; Laster, L; Oppenlander, F; Barr-Alderfer, V

    1985-04-01

    In 3 groups of horses with exercise-induced pulmonary hemorrhage (EIPH), comparisons of racing times and finishing positions were made between the 5 races before the horses were given furosemide and 5 races after furosemide administration. The horses were grouped according to 3 methods used to diagnose EIPH: group 1, observation of hemorrhage at the nostrils within 1 hour after a workout or race; group 2, observation of pulmonary hemorrhage only by endoscopic examination after a race or workout; and group 3, observation of hemorrhage at the nostrils during a race or immediately after a race. Group 4 horses were randomly selected horses running during the study period and were not given furosemide. The statistical method was analysis of covariance and the dependent variable was horses' time per distance. The study compared the 4 groups of horses, using the estimated value of the horses (less than or equal to +10,000 or greater than +10,000), and the horses' interaction in races 1 through 5 before and races 6 through 10 after furosemide treatment. The horses' times were adjusted by the relevant covariates, distance, track variant, and winning time per distance. Significant changes in horses' time per distance were not noticed when comparing values from races 1 through 5 with those in races 6 through 10 in group 1 horses.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Ondansetron, a selective 5-HT3 antagonist, antagonizes methamphetamine-induced anorexia in mice.

    PubMed

    Ginawi, O T; Al-Majed, A A; Al-Suwailem, A K

    2005-03-01

    Effects of some selective serotonergic (5-HT) antagonists on methamphetamine-induced anorexia were investigated in male mice. The least possible dose of methamphetamine alone that caused significant anorectic activity was 11 micromolkg(-1), i.p. (2 mgkg(-1)). Various doses of some selective serotonergic receptor antagonists were administered half an hour before the above mentioned dose of methamphetamine. Methiothepin potentiated, whereas NAN-190, methysergide, mianserin and ondansetron antagonized methamphetamine-induced anorectic activity. The least possible doses of these antagonists which modified methamphetamine-induced anorexia were as follows: methiothepin (1.1 micromolkg(-1), i.p.), NAN-190 (4.2 micromolkg(-1), i.p.), methysergide (2.1 micromolkg(-1), i.p.), mianserin (3.3 micromolkg(-1), i.p.) and ondansetron (0.003 micromolkg(-1), i.p.). The serotonergic antagonists at the above mentioned doses did not modify the food intake of animals not treated with methamphetamine, except for methiothepin, which produced a significant reduction, and mianserin, which produced a significant increase in food intake. The results of the present study indicated that the anorectic activity induced by methamphetamine is related to the interactions of methamphetamine with 5-HT receptor. Since a very small dose (0.003 micromolkg(-1)) of ondansetron (the 5-HT(3) antagonist), as compared with the other antagonists used in this study, antagonized the anorexia induced by methamphetamine, the 5-HT(3) receptor is likely to be the site for this interaction.

  16. Space-Time Areal Mixture Model: Relabeling Algorithm and Model Selection Issues.

    PubMed

    Hossain, M M; Lawson, A B; Cai, B; Choi, J; Liu, J; Kirby, R S

    2014-03-01

    With the growing popularity of spatial mixture models in cluster analysis, model selection criteria have become an established tool in the search for parsimony. However, the label-switching problem is often inherent in Bayesian implementation of mixture models and a variety of relabeling algorithms have been proposed. We use a space-time mixture of Poisson regression models with homogeneous covariate effects to illustrate that the best model selected by using model selection criteria does not always support the model that is chosen by the optimal relabeling algorithm. The results are illustrated for real and simulated datasets. The objective is to make the reader aware that if the purpose of statistical modeling is to identify clusters, applying a relabeling algorithm to the model with the best fit may not generate the optimal relabeling.

  17. Population dynamics under selection and mutation: Long-time behavior for differential equations in measure spaces

    NASA Astrophysics Data System (ADS)

    Ackleh, Azmy S.; Cleveland, John; Thieme, Horst R.

    2016-07-01

    We study the long-time behavior of solutions to a measure-valued selection-mutation model that we formulated in [14]. We establish permanence results for the full model, and we study the limiting behavior even when there is more than one strategy of a given fitness; a case that arises in applications. We show that for the pure selection case the solution of the dynamical system converges to a Dirac measure centered at the fittest strategy class provided that the support of the initial measure contains a fittest strategy; thus we term this Dirac measure an Asymptotically Stable Strategy. We also show that when the strategy space is discrete, the selection-mutation model with small mutation has a locally asymptotically stable equilibrium that attracts all initial conditions that are positive at the fittest strategy.

  18. Precise Spatially Selective Photothermolysis Using Modulated Femtosecond Lasers and Real-time Multimodal Microscopy Monitoring

    PubMed Central

    Huang, Yimei; Lui, Harvey; Zhao, Jianhua; Wu, Zhenguo; Zeng, Haishan

    2017-01-01

    The successful application of lasers in the treatment of skin diseases and cosmetic surgery is largely based on the principle of conventional selective photothermolysis which relies strongly on the difference in the absorption between the therapeutic target and its surroundings. However, when the differentiation in absorption is not sufficient, collateral damage would occur due to indiscriminate and nonspecific tissue heating. To deal with such cases, we introduce a novel spatially selective photothermolysis method based on multiphoton absorption in which the radiant energy of a tightly focused near-infrared femtosecond laser beam can be directed spatially by aiming the laser focal point to the target of interest. We construct a multimodal optical microscope to perform and monitor the spatially selective photothermolysis. We demonstrate that precise alteration of the targeted tissue is achieved while leaving surrounding tissue intact by choosing appropriate femtosecond laser exposure with multimodal optical microscopy monitoring in real time. PMID:28255346

  19. Forward-in-Time, Spatially Explicit Modeling Software to Simulate Genetic Lineages Under Selection

    PubMed Central

    Currat, Mathias; Gerbault, Pascale; Di, Da; Nunes, José M.; Sanchez-Mazas, Alicia

    2015-01-01

    SELECTOR is a software package for studying the evolution of multiallelic genes under balancing or positive selection while simulating complex evolutionary scenarios that integrate demographic growth and migration in a spatially explicit population framework. Parameters can be varied both in space and time to account for geographical, environmental, and cultural heterogeneity. SELECTOR can be used within an approximate Bayesian computation estimation framework. We first describe the principles of SELECTOR and validate the algorithms by comparing its outputs for simple models with theoretical expectations. Then, we show how it can be used to investigate genetic differentiation of loci under balancing selection in interconnected demes with spatially heterogeneous gene flow. We identify situations in which balancing selection reduces genetic differentiation between population groups compared with neutrality and explain conflicting outcomes observed for human leukocyte antigen loci. These results and three previously published applications demonstrate that SELECTOR is efficient and robust for building insight into human settlement history and evolution. PMID:26949332

  20. Positron Annihilation Induced Auger Electron Spectroscopy of Inner Shell Transitions Using Time-Of Technique

    NASA Astrophysics Data System (ADS)

    Xie, Shuping; Jiang, Neng; Weiss, A. H.

    2003-03-01

    Positron annihilation induced Auger electron spectroscopy (PAES) has been shown to have unique advantages over conventional electron collision induced Auger techniques, including the ability to eliminate the secondary electron background and selectively probe the top-most atomic layer on the sample surface. Here we report on the development of a new time-of-flight (TOF) spectrometer which combines features high efficiency magnetic transport and parrallel energy measurment with high resolution by using an innovative timing method. The new TOF-PAES system, was used to make the first quantitative comparative measurements of the Auger intensities associated with the annihilation of positrons with the deep core levels (1s) of S KLL (180eV), C KLL (270eV), N KLL (360eV), and O KLL (510eV). Experimental results of Auger probabilities at outer core level (3s, 3P) of Cu M2,3VV (60eV), M1VV (105eV) are compared with the theoretical value of Jensen and Weiss. Quantitatively study the surface adsorbate process on Cu is performed and concentration changes of surface components are obtained. These results demonstrate that TOF-PAES can be used to obtain quantitative,top-layer specific, information from chemically important elements including those with relatively deep core levels (e.g. C and O).

  1. Detecting Selection on Temporal and Spatial Scales: A Genomic Time-Series Assessment of Selective Responses to Devil Facial Tumor Disease.

    PubMed

    Brüniche-Olsen, Anna; Austin, Jeremy J; Jones, Menna E; Holland, Barbara R; Burridge, Christopher P

    2016-01-01

    Detecting loci under selection is an important task in evolutionary biology. In conservation genetics detecting selection is key to investigating adaptation to the spread of infectious disease. Loci under selection can be detected on a spatial scale, accounting for differences in demographic history among populations, or on a temporal scale, tracing changes in allele frequencies over time. Here we use these two approaches to investigate selective responses to the spread of an infectious cancer--devil facial tumor disease (DFTD)--that since 1996 has ravaged the Tasmanian devil (Sarcophilus harrisii). Using time-series 'restriction site associated DNA' (RAD) markers from populations pre- and post DFTD arrival, and DFTD free populations, we infer loci under selection due to DFTD and investigate signatures of selection that are incongruent among methods, populations, and times. The lack of congruence among populations influenced by DFTD with respect to inferred loci under selection, and the direction of that selection, fail to implicate a consistent selective role for DFTD. Instead genetic drift is more likely driving the observed allele frequency changes over time. Our study illustrates the importance of applying methods with different performance optima e.g. accounting for population structure and background selection, and assessing congruence of the results.

  2. Detecting Selection on Temporal and Spatial Scales: A Genomic Time-Series Assessment of Selective Responses to Devil Facial Tumor Disease

    PubMed Central

    Brüniche-Olsen, Anna; Austin, Jeremy J.; Jones, Menna E.; Holland, Barbara R.; Burridge, Christopher P.

    2016-01-01

    Detecting loci under selection is an important task in evolutionary biology. In conservation genetics detecting selection is key to investigating adaptation to the spread of infectious disease. Loci under selection can be detected on a spatial scale, accounting for differences in demographic history among populations, or on a temporal scale, tracing changes in allele frequencies over time. Here we use these two approaches to investigate selective responses to the spread of an infectious cancer—devil facial tumor disease (DFTD)—that since 1996 has ravaged the Tasmanian devil (Sarcophilus harrisii). Using time-series ‘restriction site associated DNA’ (RAD) markers from populations pre- and post DFTD arrival, and DFTD free populations, we infer loci under selection due to DFTD and investigate signatures of selection that are incongruent among methods, populations, and times. The lack of congruence among populations influenced by DFTD with respect to inferred loci under selection, and the direction of that selection, fail to implicate a consistent selective role for DFTD. Instead genetic drift is more likely driving the observed allele frequency changes over time. Our study illustrates the importance of applying methods with different performance optima e.g. accounting for population structure and background selection, and assessing congruence of the results. PMID:26930198

  3. Ticks per thought or thoughts per tick? A selective review of time perception with hints on future research.

    PubMed

    Gorea, Andrei

    2011-12-01

    The last decade underwent a revival of interest in the perception of time and duration. The present short essay does not compete with the many other recent reviews and books on this topic. Instead, it is meant to emphasize the notion that humans (and most likely other animals) have at their disposal more than one time measuring device and to propose that they use these devices jointly to appraise the passage of time. One possible consequence of this conjecture is that the same physical duration can be judged differently depending on the reference 'clock' used in any such judgment. As this view has not yet been tested empirically, several experimental manipulations susceptible to directly test it are suggested. Before, are summarized a number of its latent precursors, namely the relativity of perceived duration, current trends in modeling time perception and its neural and pharmacological substrate, the experimental literature supporting the existence of multiple 'clocks' and a selected number of experimental manipulations known to induce time perception illusions which together with many others are putatively accountable in terms of alternative clock readings. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Selective gastrointestinal uptake of ALA and its benefits for laserlight-induced fluorescence diagnostics (LIFD) and photodynamic therapy (PDT)

    NASA Astrophysics Data System (ADS)

    Pressmar, Jochen; Stern, Josef; Boehm, J.; Kohl, B.; Gahlen, Johannes

    1997-12-01

    LIFD and PDT are based on the selective uptake of photosensitizers resp. the selective metabolism of their precursors in malignant tissue. Excitation with laserlight results in fluorescence or phototoxic reactions which can be used for the detection or destruction of colorectal carcinoma and dysplasia. General photosensibilization resulting in an increased photosensitivity of the whole body represents the main side and necessitates avoidance of daylight for days up to weeks. Local application of (delta) - aminolevulinic acid (ALA) may reduce systemic uptake. Rats with DMH induced colorectal cancer were photosensitized for LIFD by oral, intravenous or local application of ALA. Urine concentrations of ALA and porphobilinogen (PBG) representing systemic photosensibilization were determined by two-column chromatography. Local colon application of ALA not only increases the quality of LIFD of colorectal cancer, it also provokes three times lower concentrations of PBG in comparison to oral or intravenous administration and reduces in consequence general photosensibilization.

  5. Time-selective windowing technique in free-field microphone reciprocity calibration.

    PubMed

    Kwon, Hyu-Sang; Cho, Wan-Ho; Suh, Sang-Joon

    2013-07-01

    Time-selective windowing techniques, which effectively remove multi-path noise, have been widely utilized for reciprocity calibration of microphone there are still limitations imposed by overlapping signals, particularly at low frequencies and for high Q microphones. Based on a fast Fourier transform analysis, the leakage due to a limited frequency range makes the overlap problem worse, not be perfectly separated. Instead of using conventional low-pass filters that are designed to have a flat response in the frequency range of interest, in this study, a filter with a Dolph-Chebyshev window shape was proposed because it has low sidelobe levels. After removing multi-path noise with a time-selective window, an inverse filter should be applied to compensate for distortion created by the applied filter. The method suggested in this paper extends the possible frequency range of free-field reciprocity calibration to frequencies below 2 kHz.

  6. Imaging multicellular specimens with real-time optimized tiling light-sheet selective plane illumination microscopy

    PubMed Central

    Fu, Qinyi; Martin, Benjamin L.; Matus, David Q.; Gao, Liang

    2016-01-01

    Despite the progress made in selective plane illumination microscopy, high-resolution 3D live imaging of multicellular specimens remains challenging. Tiling light-sheet selective plane illumination microscopy (TLS-SPIM) with real-time light-sheet optimization was developed to respond to the challenge. It improves the 3D imaging ability of SPIM in resolving complex structures and optimizes SPIM live imaging performance by using a real-time adjustable tiling light sheet and creating a flexible compromise between spatial and temporal resolution. We demonstrate the 3D live imaging ability of TLS-SPIM by imaging cellular and subcellular behaviours in live C. elegans and zebrafish embryos, and show how TLS-SPIM can facilitate cell biology research in multicellular specimens by studying left-right symmetry breaking behaviour of C. elegans embryos. PMID:27004937

  7. On studentising and blocklength selection for the bootstrap on time series.

    PubMed

    Peifer, M; Schelter, B; Guschlbauer, B; Hellwig, B; Lücking, C H; Timmer, J

    2005-06-01

    For independent data, non-parametric bootstrap is realised by resampling the data with replacement. This approach fails for dependent data such as time series. If the data generating process is at least stationary and mixing, the blockwise bootstrap by drawing subsamples or blocks of the data saves the concept. For the blockwise bootstrap a blocklength has to be selected. We propose a method for selecting the optimal blocklength. To improve the finite size properties of the blockwise bootstrap, studentised statistics is considered. If the statistic can be represented as a smooth function model this studentisation can be approximated efficiently. The studentised blockwise bootstrap method is applied for testing hypotheses on medical time series.

  8. Structure-selection techniques applied to continuous-time nonlinear models

    NASA Astrophysics Data System (ADS)

    Aguirre, Luis A.; Freitas, Ubiratan S.; Letellier, Christophe; Maquet, Jean

    2001-10-01

    This paper addresses the problem of choosing the multinomials that should compose a polynomial mathematical model starting from data. The mathematical representation used is a nonlinear differential equation of the polynomial type. Some approaches that have been used in the context of discrete-time models are adapted and applied to continuous-time models. Two examples are included to illustrate the main ideas. Models obtained with and without structure selection are compared using topological analysis. The main differences between structure-selected models and complete structure models are: (i) the former are more parsimonious than the latter, (ii) a predefined fixed-point configuration can be guaranteed for the former, and (iii) the former set of models produce attractors that are topologically closer to the original attractor than those produced by the complete structure models.

  9. Effect of Inducers, Incubation Time and Heme Concentration on IC(50) Value Variation in Anti-heme Crystallization Assay.

    PubMed

    Nhien, Nguyen Thanh Thuy; Huy, Nguyen Tien; Uyen, Dinh Thanh; Deharo, Eric; Hoa, Pham Thi Le; Hirayama, Kenji; Harada, Shigeharu; Kamei, Kaeko

    2011-12-01

    Heme detoxification through crystallization into hemozoin has been suggested as a good target for the development of screening assays for new antimalarials. However, comparisons among the data obtained from different experiments are difficult, and the IC(50) values (the concentrations of drug that are required to inhibit 50% of hemozoin formation) for the same drug vary widely. We studied the effects of changes in heme concentration (precursor of β-hematin), incubation time and three inducers (SDS, Tween 20 and linoleic acid) on the IC(50) of some antimalarials (chloroquine, quinine, amodiaquine, and clotrimazole). The results showed that increasing both inducer concentration and incubation time raised the IC(50) of selected antimalarials. Any change in those factors caused the IC(50) value to vary. Standardization of assay conditions is, therefore, necessary to increase reproducibility and reduce discrepancies in assay performance. Considering all of the variables, the best choice of inducers is in the order of SDS > Tween 20 > linoleic acid.

  10. Selective breeding for magnitude of methamphetamine-induced sensitization alters methamphetamine consumption

    PubMed Central

    Scibelli, Angela C.; McKinnon, Carrie S.; Reed, Cheryl; Burkhart-Kasch, Sue; Li, Na; Baba, Harue; Wheeler, Jeanna M.

    2012-01-01

    Rationale Genetically determined differences in susceptibility to drug-induced sensitization could be related to risk for drug consumption. Objectives Studies were performed to determine whether selective breeding could be used to create lines of mice with different magnitudes of locomotor sensitization to methamphetamine (MA). MA sensitization (MASENS) lines were also examined for genetically correlated responses to MA. Methods Beginning with the F2 cross of C57BL/6J and DBA/2J strains, mice were tested for locomotor sensitization to repeated injections of 1 mg/kg MA and bred based on magnitude of sensitization. Five selected offspring generations were tested. All generations were also tested for MA consumption, and some were tested for dose-dependent locomotor-stimulant responses to MA, consumption of saccharin, quinine, and potassium chloride as a measure of taste sensitivity, and MA clearance after acute and repeated MA. Results Selective breeding resulted in creation of two lines [MA high sensitization (MAHSENS) and MA low sensitization (MALSENS)] that differed in magnitude of MA-induced sensitization. Initially, greater MA consumption in MAHSENS mice reversed over the course of selection so that MALSENS mice consumed more MA. MAHSENS mice exhibited greater sensitivity to the acute stimulant effects of MA, but there were no significant differences between the lines in MA clearance from blood. Conclusions Genetic factors influence magnitude of MA-induced locomotor sensitization and some of the genes involved in magnitude of this response also influence MA sensitivity and consumption. Genetic factors leading to greater MA-induced sensitization may serve a protective role against high levels of MA consumption. PMID:21088960

  11. Selective Real-time Detection of Gaseous Nerve Agent Simulants Using Multiwavelength Photoacoustics

    DTIC Science & Technology

    2012-08-15

    Selective real-time detection of gaseous nerve agent simulants using multiwavelength photoacoustics Kristan P. Gurton,* Melvin Felton, and Richard...concentrations. The technique is based on a modified version of conventional laser photoacoustic (PA) spectroscopy, in which optical absorption is typically...spec- troscopic approach [1–4]. One of the more direct methods to implement in prac- tice (without sacrificing sensitivity) is laser photoacoustic

  12. Plasmoelectronic sensor for real-time on-chip wavelength selective biosensing

    NASA Astrophysics Data System (ADS)

    Cheney, Alec; Chen, Borui; Zhang, Tianmu; Thomay, Tim; Cartwright, Alexander

    2017-02-01

    Using resistive losses induced by optically excited surface plasmons has shown promise as a CMOS-compatible plasmonic light detector. Increased electron scattering introduced by surface plasmons in an applied current results in a measurable decrease in electrical conductance of a grating, allowing a purely electronic readout of surface plasmon excitation. Accordingly, because of its plasmonic nature, such a detector is dependent on both the wavelength and polarization of incident light with a response time limited by the surface plasmon lifetime. Our ultrafast measurements with electronic read-out indicate that the response time of this detector is on the order of 1ps. Thus such a detector would enable time-resolved biomedical applications such as real-time monitoring of protein structural dynamics for pharmacological applications and research.

  13. Time-frequency based feature selection for discrimination of non-stationary biosignals

    NASA Astrophysics Data System (ADS)

    D Martínez-Vargas, Juan; I Godino-Llorente, Juan; Castellanos-Dominguez, Germán

    2012-12-01

    This research proposes a generic methodology for dimensionality reduction upon time-frequency representations applied to the classification of different types of biosignals. The methodology directly deals with the highly redundant and irrelevant data contained in these representations, combining a first stage of irrelevant data removal by variable selection, with a second stage of redundancy reduction using methods based on linear transformations. The study addresses two techniques that provided a similar performance: the first one is based on the selection of a set of the most relevant time-frequency points, whereas the second one selects the most relevant frequency bands. The first methodology needs a lower quantity of components, leading to a lower feature space; but the second improves the capture of the time-varying dynamics of the signal, and therefore provides a more stable performance. In order to evaluate the generalization capabilities of the methodology proposed it has been applied to two types of biosignals with different kinds of non-stationary behaviors: electroencephalographic and phonocardiographic biosignals. Even when these two databases contain samples with different degrees of complexity and a wide variety of characterizing patterns, the results demonstrate a good accuracy for the detection of pathologies, over 98 %.The results open the possibility to extrapolate the methodology to the study of other biosignals.

  14. Luminescent trimethoprim-polyaminocarboxylate lanthanide complex conjugates for selective protein labeling and time-resolved bioassays

    PubMed Central

    Reddy, D. Rajasekhar; Pedró Rosa, Laura E.; Miller, Lawrence W.

    2011-01-01

    Labeling proteins with long-lifetime emitting lanthanide (III) chelate reporters enables sensitive, time-resolved luminescence bioaffinity assays. Heterodimers of trimethoprim (TMP) covalently linked to various cs124-sensitized, polyaminocarboxylate chelates stably retain lanthanide ions and exhibit quantum yields of europium emission up to 20% in water. A time-resolved, luminescence resonance energy transfer (LRET) assay showed that TMP-polyaminocarboxylates bind to Escherichia coli dihydrofolate reductase (eDHFR) fusion proteins with nanomolar affinity in purified solutions and in bacterial lysates. The ability to selectively impart terbium or europium luminescence to fusion proteins in complex physiological mixtures bypasses the need for specific antibodies and simplifies sample preparation. PMID:21619068

  15. Long-lifetime Martian orbit selection using a time-dependent model of the Martian atmosphere

    NASA Technical Reports Server (NTRS)

    Culp, R. D.; Stewart, A. I.; Chow, C.-C.; Uphoff, C.

    1984-01-01

    A mathematical model of the time-dependent Martian atmosphere has been developed in order to accurately calculate the effects of aerodynamic drag on a low altitude satellite. The time-dependent properties of the model include solar activity effects, dust storm effects, seasonal and diurnal variations, and annual motion effects. Position effects are accounted for through Martian latitude and longitude. Expected values of mass density, temperature, scale height, and the estimated standard deviation of the mass density are provided. An example of the use of the model in selecting an orbit for the Mars Geochemical/Climatology Orbiter is given.

  16. Requirement for Cell Dispersion Prior to Selection of Induced Azaguanine-Resistant Colonies of Chinese Hamster Cells

    PubMed Central

    Myhr, B. C.; DiPaolo, J. A.

    1975-01-01

    With V79 Chinese hamster cell cultures treated with a mutagen, the maximum frequency of colonies resistant to 8-azaguanine (AZG) was attained when the cells were dispersed after a suitable expression time before adding the selection medium. V79–4 cells were exposed to 500 µM MMS, 7 µM AFAA, or 10 µM MNNG and allowed to multiply before being reseeded at 4 x 104 cells/60 mm dish and selected with 10 µg/ml AZG. Maximum frequencies of 4 x 10-5, 4 x 10-4, and 2.4 x 10-3 were obtained about 100, 130, and 200 hrs after exposure to MMS, AFAA, and MNNG, respectively. The maximum frequencies following MMS or MNNG treatments were about 10-fold greater than those obtained when induction and selection of AZG-resistant colonies were performed in the same culture dish. The reseeding of treated cells eliminated the possibility of metabolic cooperation within mosaic colonies of wild-type and mutant cells and achieved expression of the induced changes before intercolony crossfeeding reduced the frequency of resistant colonies.—AZG-resistant colonies were selected in medium containing dialyzed fetal bovine serum, and the selection medium was replaced at least twice. Both serum dialysis and selection medium replacement were necessary for consistent achievement of background frequencies of resistant colonies near 10-6. Reconstruction experiments with AZG-resistant V79 lines showed that the efficiency of recovery of resistant cells in the selection medium was constant over a range of 0–20 colonies observed/dish. A mixed population of V79 and AZG-resistant cells was also correctly analyzed by the procedure used in mutagenesis studies. PMID:1093934

  17. Environmentally induced changes in correlated responses to selection reveal variable pleiotropy across a complex genetic network.

    PubMed

    Sikkink, Kristin L; Reynolds, Rose M; Cresko, William A; Phillips, Patrick C

    2015-05-01

    Selection in novel environments can lead to a coordinated evolutionary response across a suite of characters. Environmental conditions can also potentially induce changes in the genetic architecture of complex traits, which in turn could alter the pattern of the multivariate response to selection. We describe a factorial selection experiment using the nematode Caenorhabditis remanei in which two different stress-related phenotypes (heat and oxidative stress resistance) were selected under three different environmental conditions. The pattern of covariation in the evolutionary response between phenotypes or across environments differed depending on the environment in which selection occurred, including asymmetrical responses to selection in some cases. These results indicate that variation in pleiotropy across the stress response network is highly sensitive to the external environment. Our findings highlight the complexity of the interaction between genes and environment that influences the ability of organisms to acclimate to novel environments. They also make clear the need to identify the underlying genetic basis of genetic correlations in order understand how patterns of pleiotropy are distributed across complex genetic networks.

  18. ENVIRONMENTALLY INDUCED CHANGES IN CORRELATED RESPONSES TO SELECTION REVEAL VARIABLE PLEIOTROPY ACROSS A COMPLEX GENETIC NETWORK

    PubMed Central

    Sikkink, Kristin L.; Reynolds, Rose M.; Cresko, William A.; Phillips, Patrick C.

    2017-01-01

    Selection in novel environments can lead to a coordinated evolutionary response across a suite of characters. Environmental conditions can also potentially induce changes in the genetic architecture of complex traits, which in turn could alter the pattern of the multivariate response to selection. We describe a factorial selection experiment using the nematode Caenorhabditis remanei in which two different stress-related phenotypes (heat and oxidative stress resistance) were selected under three different environmental conditions. The pattern of covariation in the evolutionary response between phenotypes or across environments differed depending on the environment in which selection occurred, including asymmetrical responses to selection in some cases. These results indicate that variation in pleiotropy across the stress response network is highly sensitive to the external environment. Our findings highlight the complexity of the interaction between genes and environment that influences the ability of organisms to acclimate to novel environments. They also make clear the need to identify the underlying genetic basis of genetic correlations in order understand how patterns of pleiotropy are distributed across complex genetic networks. PMID:25809411

  19. Health-Care Waste Treatment Technology Selection Using the Interval 2-Tuple Induced TOPSIS Method

    PubMed Central

    Lu, Chao; You, Jian-Xin; Liu, Hu-Chen; Li, Ping

    2016-01-01

    Health-care waste (HCW) management is a major challenge for municipalities, particularly in the cities of developing nations. Selecting the best treatment technology for HCW can be regarded as a complex multi-criteria decision making (MCDM) issue involving a number of alternatives and multiple evaluation criteria. In addition, decision makers tend to express their personal assessments via multi-granularity linguistic term sets because of different backgrounds and knowledge, some of which may be imprecise, uncertain and incomplete. Therefore, the main objective of this study is to propose a new hybrid decision making approach combining interval 2-tuple induced distance operators with the technique for order preference by similarity to an ideal solution (TOPSIS) for tackling HCW treatment technology selection problems with linguistic information. The proposed interval 2-tuple induced TOPSIS (ITI-TOPSIS) can not only model the uncertainty and diversity of the assessment information given by decision makers, but also reflect the complex attitudinal characters of decision makers and provide much more complete information for the selection of the optimum disposal alternative. Finally, an empirical example in Shanghai, China is provided to illustrate the proposed decision making method, and results show that the ITI-TOPSIS proposed in this paper can solve the problem of HCW treatment technology selection effectively. PMID:27271652

  20. Health-Care Waste Treatment Technology Selection Using the Interval 2-Tuple Induced TOPSIS Method.

    PubMed

    Lu, Chao; You, Jian-Xin; Liu, Hu-Chen; Li, Ping

    2016-06-04

    Health-care waste (HCW) management is a major challenge for municipalities, particularly in the cities of developing nations. Selecting the best treatment technology for HCW can be regarded as a complex multi-criteria decision making (MCDM) issue involving a number of alternatives and multiple evaluation criteria. In addition, decision makers tend to express their personal assessments via multi-granularity linguistic term sets because of different backgrounds and knowledge, some of which may be imprecise, uncertain and incomplete. Therefore, the main objective of this study is to propose a new hybrid decision making approach combining interval 2-tuple induced distance operators with the technique for order preference by similarity to an ideal solution (TOPSIS) for tackling HCW treatment technology selection problems with linguistic information. The proposed interval 2-tuple induced TOPSIS (ITI-TOPSIS) can not only model the uncertainty and diversity of the assessment information given by decision makers, but also reflect the complex attitudinal characters of decision makers and provide much more complete information for the selection of the optimum disposal alternative. Finally, an empirical example in Shanghai, China is provided to illustrate the proposed decision making method, and results show that the ITI-TOPSIS proposed in this paper can solve the problem of HCW treatment technology selection effectively.

  1. Selective Sirt2 inhibition by ligand-induced rearrangement of the active site.

    PubMed

    Rumpf, Tobias; Schiedel, Matthias; Karaman, Berin; Roessler, Claudia; North, Brian J; Lehotzky, Attila; Oláh, Judit; Ladwein, Kathrin I; Schmidtkunz, Karin; Gajer, Markus; Pannek, Martin; Steegborn, Clemens; Sinclair, David A; Gerhardt, Stefan; Ovádi, Judit; Schutkowski, Mike; Sippl, Wolfgang; Einsle, Oliver; Jung, Manfred

    2015-02-12

    Sirtuins are a highly conserved class of NAD(+)-dependent lysine deacylases. The human isotype Sirt2 has been implicated in the pathogenesis of cancer, inflammation and neurodegeneration, which makes the modulation of Sirt2 activity a promising strategy for pharmaceutical intervention. A rational basis for the development of optimized Sirt2 inhibitors is lacking so far. Here we present high-resolution structures of human Sirt2 in complex with highly selective drug-like inhibitors that show a unique inhibitory mechanism. Potency and the unprecedented Sirt2 selectivity are based on a ligand-induced structural rearrangement of the active site unveiling a yet-unexploited binding pocket. Application of the most potent Sirtuin-rearranging ligand, termed SirReal2, leads to tubulin hyperacetylation in HeLa cells and induces destabilization of the checkpoint protein BubR1, consistent with Sirt2 inhibition in vivo. Our structural insights into this unique mechanism of selective sirtuin inhibition provide the basis for further inhibitor development and selective tools for sirtuin biology.

  2. Selective inhibitors of the FK506-binding protein 51 by induced fit.

    PubMed

    Gaali, Steffen; Kirschner, Alexander; Cuboni, Serena; Hartmann, Jakob; Kozany, Christian; Balsevich, Georgia; Namendorf, Christian; Fernandez-Vizarra, Paula; Sippel, Claudia; Zannas, Anthony S; Draenert, Rika; Binder, Elisabeth B; Almeida, Osborne F X; Rühter, Gerd; Uhr, Manfred; Schmidt, Mathias V; Touma, Chadi; Bracher, Andreas; Hausch, Felix

    2015-01-01

    The FK506-binding protein 51 (FKBP51, encoded by the FKBP5 gene) is an established risk factor for stress-related psychiatric disorders such as major depression. Drug discovery for FKBP51 has been hampered by the inability to pharmacologically differentiate against the structurally similar but functional opposing homolog FKBP52, and all known FKBP ligands are unselective. Here, we report the discovery of the potent and highly selective inhibitors of FKBP51, SAFit1 and SAFit2. This new class of ligands achieves selectivity for FKBP51 by an induced-fit mechanism that is much less favorable for FKBP52. By using these ligands, we demonstrate that selective inhibition of FKBP51 enhances neurite elongation in neuronal cultures and improves neuroendocrine feedback and stress-coping behavior in mice. Our findings provide the structural and functional basis for the development of mechanistically new antidepressants.

  3. Pyrithione Zn selectively inhibits hypoxia-inducible factor prolyl hydroxylase PHD3.

    PubMed

    Na, Yu-Ran; Woo, Dustin J; Kim, So Yeon; Yang, Eun Gyeong

    2016-04-01

    Increasing evidence emphasizes the role of the hypoxia-inducible factor (HIF) prolyl hydroxylase (PHD) isoforms in regulating non-HIF substrates, but isoform selective PHD inhibitors under physiological conditions have not yet been reported. Here we have identified pyrithione Zn (PZ) as a potent, isoform-selective PHD3 inhibitor. The IC50 value of PZ was determined as 0.98 μM for PHD3, while it did not show any inhibitory activity toward full length and truncated PHD2 up to 1 mM. The selective efficacy of PZ was further demonstrated at the cellular level by observing inhibition of the PHD3-dependent DNA damage response pathway without stabilization of HIF-1α.

  4. Resveratrol prevents rapamycin-induced upregulation of autophagy and selectively induces apoptosis in TSC2-deficient cells.

    PubMed

    Alayev, Anya; Sun, Yang; Snyder, Rose B; Berger, Sara Malka; Yu, Jane J; Holz, Marina K

    2014-01-01

    The mammalian/mechanistic target of rapamycin complex 1 (mTORC1) signaling pathway is hyperactivated in a variety of cancers and disorders, including lymphangioleiomyomatosis (LAM) and tuberous sclerosis complex (TSC), which are characterized by mutations in tumor suppressors TSC1 or TSC2. The concern with the use of mTORC1 inhibitors, such as rapamycin or its analogs (rapalogs), is that they cause upregulation of autophagy and suppress the negative feedback loop to Akt, which promotes cell survival, causing the therapy to be only partially effective, and relapse occurs upon cessation of treatment. In this study, we investigate the use of rapamycin in combination with resveratrol, a naturally occurring polyphenol, in TSC2-deficient cells. We tested whether such combination would prevent rapamycin-induced upregulation of autophagy and shift the cell fate toward apoptosis. We found that this combination treatment blocked rapamycin-induced upregulation of autophagy and restored inhibition of Akt. Interestingly, the combination of rapamycin and resveratrol selectively promoted apoptosis of TSC2-deficient cells. Thus, the addition of resveratrol to rapamycin treatment may be a promising option for selective and targeted therapy for diseases with TSC loss and mTORC1 hyperactivation.

  5. Selective aldosterone blockade prevents angiotensin II/salt-induced vascular inflammation in the rat heart.

    PubMed

    Rocha, Ricardo; Martin-Berger, Cynthia L; Yang, Pochang; Scherrer, Rachel; Delyani, John; McMahon, Ellen

    2002-12-01

    We studied the role of aldosterone (aldo) in myocardial injury in a model of angiotensin (Ang) II-hypertension. Wistar rats were given 1% NaCl (salt) to drink and randomized into one of the following groups (n = 10; treatment, 21 d): 1) vehicle control (VEH); 2) Ang II infusion (25 ng/min, sc); 3) Ang II infusion plus the selective aldo blocker, eplerenone (epl, 100 mg/kg.d, orally); 4) Ang II infusion in adrenalectomized (ADX) rats; and 5) Ang II infusion in ADX rats with aldo treatment (20 micro g/kg.d, sc). ADX rats received also dexamethasone (12 micro g/kg.d, sc). Systolic blood pressure increased with time in all treatment groups except the VEH group (VEH, 136 +/- 6; Ang II/NaCl, 203 +/- 12; Ang II/NaCl/epl, 196 +/- 10; Ang II/NaCl/ADX, 181 +/- 7; Ang II/NaCl/ADX/aldo, 236 +/- 8 mm Hg). Despite similar levels of hypertension, epl and ADX attenuated the increase in heart weight/body weight induced by Ang II. Histological examination of the hearts evidenced myocardial and vascular injury in the Ang II/salt (7 of 10 hearts with damage, P < 0.05 vs. VEH) and Ang II/salt/ADX/aldo groups (10 of 10 hearts with damage, P < 0.05). Injury included arterial fibrinoid necrosis, perivascular inflammation (primarily macrophages), and focal infarctions. Vascular lesions were associated with expression of the inflammatory mediators cyclooxygenase 2 (COX-2) and osteopontin in the media of coronary arteries. Myocardial injury, COX-2, and osteopontin expression were markedly attenuated by epl treatment (1 of 10 hearts with damage, P < 0.05 vs. Ang II/salt) and adrenalectomy (2 of 10 hearts with damage, P < 0.05 vs. Ang II/salt). Our data indicate that aldo plays a major role in Ang II-induced vascular inflammation in the heart and implicate COX-2 and osteopontin as potential mediators of the damage.

  6. Trait Associations across Evolutionary Time within a Drosophila Phylogeny: Correlated Selection or Genetic Constraint?

    PubMed Central

    Kellermann, Vanessa; Overgaard, Johannes; Loeschcke, Volker; Kristensen, Torsten Nygaard; Hoffmann, Ary A.

    2013-01-01

    Traits do not evolve independently. To understand how trait changes under selection might constrain adaptive changes, phenotypic and genetic correlations are typically considered within species, but these capture constraints across a few generations rather than evolutionary time. For longer-term constraints, comparisons are needed across species but associations may arise because of correlated selection pressures rather than genetic interactions. Implementing a unique approach, we use known patterns of selection to separate likely trait correlations arising due to correlated selection from those reflecting genetic constraints. We examined the evolution of stress resistance in >90 Drosophila species adapted to a range of environments, while controlling for phylogeny. Initially we examined the role of climate and phylogeny in shaping the evolution of starvation and body size, two traits previously not examined in this context. Following correction for phylogeny only a weak relationship between climate and starvation resistance was detected, while all of the variation in the relationship between body size and climate could be attributed to phylogeny. Species were divided into three environmental groups (hot and dry, hot and wet, cold) with the expectation that, if genetic correlations underpin trait correlations, these would persist irrespective of the environment, whereas selection-driven evolution should produce correlations dependent on the environment. We found positive associations between most traits in hot and dry environments coupled with high trait means. In contrast few trait correlations were observed in hot/wet and cold environments. These results suggest trait associations are primarily driven by correlated selection rather than genetic interactions, highlighting that such interactions are unlikely to limit evolution of stress resistance. PMID:24015206

  7. Timing and direction selectivity of subthalamic and pallidal neurons in patients with Parkinson disease.

    PubMed

    Williams, Ziv M; Neimat, Joseph S; Cosgrove, G Rees; Eskandar, Emad N

    2005-05-01

    Current models of basal ganglia function suggest that some manifestations of Parkinson disease (PD) arise from abnormal activity and decreased selectivity of neurons in the subthalamic nucleus (STN) and globus pallidus internus (Gpi). Our goal was to examine the timing and direction selectivity of neuronal activity relative to visually guided movements in the STN and Gpi of patients with PD. Recordings were made from 152 neurons in the STN and 33 neurons in the Gpi of awake subjects undergoing surgery for PD. Corresponding EMG data were obtained for half the cells. We employed a structured behavioral task in which the subjects used a joystick to guide a cursor to one of four targets displayed on a monitor. Each direction was tested over multiple trials. Movement-related modulation of STN activity began on average 264+/-10 ms before movement initiation and 92+/-13 ms before initial EMG activity, while modulation of Gpi activity began 204+/-21 ms before overt movement initiation. In the STN, 40% of cells demonstrated perimovement activity, and of these 64% were directionally selective. In Gpi, 45% of cells showed perimovement activity of which 80% were selective. In both nuclei, directionally selective cells had significantly lower baseline firing rates than nonselective cells (41+/-5 vs 59+/-4 spikes/s in STN, and 50+/-9 vs 74+/-15 spikes/s in Gpi). These results suggest that STN activity occurs earlier than previously reported, and that higher neuronal firing rates maybe associated with decreased direction selectivity in PD patients.

  8. Living With Limited Time: Socioemotional Selectivity Theory in the Context of Health Adversity

    PubMed Central

    Sullivan-Singh, Sarah J.; Stanton, Annette L.; Low, Carissa A.

    2016-01-01

    The current research was designed to test the applicability of socioemotional selectivity theory (SST; Carstensen, 2006), a life span theory that posits that perceived time remaining in life (time perspective) is a critical determinant of motivation, to individuals who face foreshortened futures (limited time perspective) due to life-limiting medical illness. In Study 1, we investigated whether life goals and biases in attention and memory for valenced emotional stimuli differed between women living with metastatic breast cancer (n = 113; theoretically living under greater limited time perspective than peers without cancer) and similarly aged women without a cancer diagnosis (n = 50; theoretically living under greater expansive time perspective than peers with cancer) in accordance with SST. As hypothesized, metastatic group goals reflected greater emphasis on limited versus expansive time perspective relative to comparison group goals. Hypotheses regarding biases in attention and memory were not supported. Study 2 followed metastatic group participants over 3 months and revealed that, consistent with hypotheses, whereas limited time perspective goals predicted decreased intrusive thoughts about cancer, expansive time perspective goals predicted decreased perceived cancer-related benefits. Together, these studies suggest that SST is a useful lens through which to view some components of motivation and psychological adjustment among individuals confronting medically foreshortened futures. PMID:25984789

  9. Directional selection by fisheries and the timing of sockeye salmon (Oncorhynchus nerka) migrations.

    PubMed

    Quinn, Thomas P; Hodgson, Sayre; Flynn, Lucy; Hilborn, Ray; Rogers, Donald E

    2007-04-01

    The timing of migration from feeding to breeding areas is a critical link between the growth and survival of adult animals, their reproduction, and the fitness of their progeny. Commercial fisheries often catch a large fraction of the migrants (e.g., salmon), and exploitation rates can vary systematically over the fishing season. We examined daily records of sockeye salmon (Oncorhynchus nerka) in the Egegik and Ugashik management districts in Bristol Bay, Alaska (USA), for evidence of such temporally selective fishing. In recent years, the early migrants have experienced lower fishing rates than later migrants, especially in the Egegik district, and the median migration date of the fish escaping the fisheries has been getting progressively earlier in both districts. Moreover, the overall runs (catch and escapement) in the Egegik district and, to a lesser extent the Ugashik district, have been getting earlier, as predicted in response to the selection on timing. The trends in timing were not correlated with sea surface temperature in the region of the North Pacific Ocean where the salmon tend to concentrate, but the trends in the two districts were correlated with each other, indicating that there may be some common environmental influence in addition to the effect of selection. Despite the selection, both groups of salmon have remained productive. We hypothesize that this resilience may result from representation of all component populations among the early and late migrants, so that the fisheries have not eliminated entire populations, and from density-dependent processes that may have helped maintain the productivity of these salmon populations.

  10. Minimal microwave anisotrophy from perturbations induced at late times

    NASA Technical Reports Server (NTRS)

    Jaffe, Andrew H.; Stebbins, Albert; Frieman, Joshua A.

    1994-01-01

    Aside from primordial gravitational instability of the cosmological fluid, various mechanisms have been proposed to generate large-scale structure at relatively late times, including, e.g., 'late-time' cosmological phase transitions. In these scenarios, it is envisioned that the universe is nearly homogeneous at the times of last scattering and that perturbations grow rapidly sometimes after the primordial plasma recombines. On this basis, it was suggested that large inhomogeneities could be generated while leaving relatively little imprint on the cosmic microwave background (MBR) anisotropy. In this paper, we calculate the minimal anisotropies possible in any 'late-time' scenario for structure formation, given the level of inhomogeneity observed at present. Since the growth of the inhomogeneity involves time-varying gravitational fields, these scenarios inevitably generate significant MBR anisotropy via the Sachs-Wolfe effect. Moreover, we show that the large-angle MBR anisotropy produced by the rapid post-recombination growth of inhomogeneity is generally greater than that produced by the same inhomogeneity growth via gravitational instability. In 'realistic' scenarios one can decrease the anisotropy compared to models with primordial adiabatic fluctuations, but only on very small angular scales. The value of any particular measure of the anisotropy can be made small in late-time models, but only by making the time-dependence of the gravitational field sufficiently 'pathological'.

  11. Selective Inducible Nitric Oxide Synthase Inhibitor Reversed Zinc Chloride-Induced Spatial Memory Impairment via Increasing Cholinergic Marker Expression.

    PubMed

    Tabrizian, Kaveh; Azami, Kian; Belaran, Maryam; Soodi, Maliheh; Abdi, Khosrou; Fanoudi, Sahar; Sanati, Mehdi; Mottaghi Dastjerdi, Negar; Soltany Rezaee-Rad, Mohammad; Sharifzadeh, Mohammad

    2016-10-01

    Zinc, an essential micronutrient and biochemical element of the human body, plays structural, catalytic, and regulatory roles in numerous physiological functions. In the current study, the effects of a pretraining oral administration of zinc chloride (10, 25, and 50 mg/kg) for 14 consecutive days and post-training bilateral intra-hippocampal infusion of 1400W as a selective inducible nitric oxide synthase (iNOS) inhibitor (10, 50, and 100 μM/side), alone and in combination, on the spatial memory retention in Morris water maze (MWM) were investigated. Animals were trained for 4 days and tested 48 h after completion of training. Also, the molecular effects of these compounds on the expression of choline acetyltransferase (ChAT), as a cholinergic marker in the CA1 region of the hippocampus and medial septal area (MSA), were evaluated. Behavioral and molecular findings of this study showed that a 2-week oral administration of zinc chloride (50 mg/kg) impaired spatial memory retention in MWM and decreased ChAT expression. Immunohistochemical analysis of post-training bilateral intra-hippocampal infusion of 1400W revealed a significant increase in ChAT immunoreactivity. Furthermore, post-training bilateral intra-hippocampal infusion of 1400W into the CA1 region of the hippocampus reversed zinc chloride-induced spatial memory impairment in MWM and significantly increased ChAT expression in comparison with zinc chloride-treated animals. Taken together, these results emphasize the role of selective iNOS inhibitors in reversing zinc chloride-induced spatial memory deficits via modulation of cholinergic marker expression.

  12. Gallic acid as a selective anticancer agent that induces apoptosis in SMMC-7721 human hepatocellular carcinoma cells.

    PubMed

    Sun, Guojun; Zhang, Shuqin; Xie, Yanru; Zhang, Ziyu; Zhao, Wenjing

    2016-01-01

    Gallic acid (3,4,5-trihydroxybenzoic acid; GA) is a naturally occurring plant polyphenol, isolated from water caltrop, which has been reported to exert anticancer effects. The present study investigated the antiproliferative effects of GA on the HepG2 and SMMC-7721 human hepatocellular carcinoma (HCC) cell lines using MTT and colony formation assays. In particular, the underlying mechanism of GA-induced apoptosis in SMMC-7721 cells was studied in vitro by flow cytometry and western blotting. The results of the present study indicated that GA was capable of inhibiting the proliferation of HepG2 and SMMC-7721 cells in a time- and dose-dependent manner, as well as inducing the apoptosis of SMMC-7721 cells. GA induced caspase-3, caspase-9 and reactive oxygen species activity, elevated the expression of apoptosis regulator Bcl-2-like protein 4 and reduced the mitochondrial membrane potential in SMMC-7721 cells. When compared with HL-7702 normal human hepatocytes, GA demonstrated selective toxicity for HCC cells. In conclusion, GA is able to induce apoptosis in SMMC-7721 cells in vitro via mitochondrial-mediated pathways, and may possess the potential to be a novel therapeutic compound for use in the treatment of HCC.

  13. Real time measurement of cytoplasmic ions with ion-selective microelectrodes.

    PubMed

    Miller, Anthony J

    2013-01-01

    Ion-selective microelectrodes can be used to report intracellular ion concentrations. The ion-selective barrels of microelectrodes are filled with a sensor cocktail containing several different components including an ion-selective molecule, sensor or exchanger, a solvent or plasticizer, lipophilic cation/anion additives, and a matrix to solidify the membrane. For many ions, the readymade membrane cocktail can be purchased, but the individual chemical components can be bought from suppliers and mixing the cocktail saves money. For commercially available liquid membrane cocktails the membrane matrix is often not included. For plants a matrix is essential for intracellular impalements because without it cell turgor will displace the liquid membrane from the electrode tip, giving decreased or even lost sensitivity. The matrix frequently used is a high molecular weight poly(vinyl chloride). This addition increases the electrical resistance of the electrode, slowing the response time of the electrode. The use of multi-barreled electrodes enables the identification of the cellular compartment. For example, the inclusion of a pH-selective electrode enables the cytoplasm and vacuole to be distinguished.

  14. Time-dependent phenomena in the potential response of ion-selective electrodes treated by the Nernst-Planck-Poisson model. 1. Intramembrane processes and selectivity.

    PubMed

    Lingenfelter, Peter; Bedlechowicz-Sliwakowska, Iwona; Sokalski, Tomasz; Maj-Zurawska, Magdalena; Lewenstam, Andrzej

    2006-10-01

    The variability of selectivity coefficients, resulting from potential changes over time and the concentration ratio of primary to interfering ions, impedes many practical applications of ion-selective electrodes (ISEs). Existing theoretical interpretations of ISE selectivity are restricted by severe assumptions, such as steady state and electroneutrality, which hinder theorizing on this problem. For this reason, for the first time, the Nernst-Planck-Poisson equations are used to predict and visualize the selectivity variability over time and the concentration ratio. Special emphasis is placed on the non-Nernstian response in the measurements with liquid-ion-exchanger- and neutral-carrier-based ISEs. The conditions under which measured selectivity coefficients are true (unbiased) are demonstrated.

  15. Initial tsunami source estimation by inversion with an intelligent selection of model parameters and time delays

    NASA Astrophysics Data System (ADS)

    Mulia, Iyan E.; Asano, Toshiyuki

    2016-01-01

    We propose a method for accurately estimating the initial tsunami source. Our technique is independent of the earthquake parameters, because we only use recorded tsunami waveforms and an auxiliary basis function, instead of a fault model. We first use the measured waveforms to roughly identify the source area using backward propagated travel times, and then infer the initial sea surface deformation through inversion analysis. A computational intelligence approach based on a genetic algorithm combined with a pattern search was used to select appropriate least squares model parameters and time delays. The proposed method significantly reduced the number of parameters and suppressed the negative effect of regularization schemes that decreased the plausibility of the model. Furthermore, the stochastic approach for deriving the time delays is a more flexible strategy for simulating actual phenomena that occur in nature. The selected parameters and time delays increased the accuracy, and the model's ability to reveal the underlying physics associated with the tsunami-generating processes. In this paper, we applied the method to the 2011 Tohoku-Oki tsunami event and examined its effectiveness by comparing the results to those using the conventional method.

  16. Genome-wide Selective Sweeps in Natural Bacterial Populations Revealed by Time-series Metagenomics

    SciTech Connect

    Chan, Leong-Keat; Bendall, Matthew L.; Malfatti, Stephanie; Schwientek, Patrick; Tremblay, Julien; Schackwitz, Wendy; Martin, Joel; Pati, Amrita; Bushnell, Brian; Foster, Brian; Kang, Dongwan; Tringe, Susannah G.; Bertilsson, Stefan; Moran, Mary Ann; Shade, Ashley; Newton, Ryan J.; Stevens, Sarah; McMcahon, Katherine D.; Mamlstrom, Rex R.

    2014-05-12

    Multiple evolutionary models have been proposed to explain the formation of genetically and ecologically distinct bacterial groups. Time-series metagenomics enables direct observation of evolutionary processes in natural populations, and if applied over a sufficiently long time frame, this approach could capture events such as gene-specific or genome-wide selective sweeps. Direct observations of either process could help resolve how distinct groups form in natural microbial assemblages. Here, from a three-year metagenomic study of a freshwater lake, we explore changes in single nucleotide polymorphism (SNP) frequencies and patterns of gene gain and loss in populations of Chlorobiaceae and Methylophilaceae. SNP analyses revealed substantial genetic heterogeneity within these populations, although the degree of heterogeneity varied considerably among closely related, co-occurring Methylophilaceae populations. SNP allele frequencies, as well as the relative abundance of certain genes, changed dramatically over time in each population. Interestingly, SNP diversity was purged at nearly every genome position in one of the Chlorobiaceae populations over the course of three years, while at the same time multiple genes either swept through or were swept from this population. These patterns were consistent with a genome-wide selective sweep, a process predicted by the ecotype model? of diversification, but not previously observed in natural populations.

  17. Genome-wide Selective Sweeps in Natural Bacterial Populations Revealed by Time-series Metagenomics

    SciTech Connect

    Chan, Leong-Keat; Bendall, Matthew L.; Malfatti, Stephanie; Schwientek, Patrick; Tremblay, Julien; Schackwitz, Wendy; Martin, Joel; Pati, Amrita; Bushnell, Brian; Foster, Brian; Kang, Dongwan; Tringe, Susannah G.; Bertilsson, Stefan; Moran, Mary Ann; Shade, Ashley; Newton, Ryan J.; Stevens, Sarah; McMahon, Katherine D.; Malmstrom, Rex R.

    2014-06-18

    Multiple evolutionary models have been proposed to explain the formation of genetically and ecologically distinct bacterial groups. Time-series metagenomics enables direct observation of evolutionary processes in natural populations, and if applied over a sufficiently long time frame, this approach could capture events such as gene-specific or genome-wide selective sweeps. Direct observations of either process could help resolve how distinct groups form in natural microbial assemblages. Here, from a three-year metagenomic study of a freshwater lake, we explore changes in single nucleotide polymorphism (SNP) frequencies and patterns of gene gain and loss in populations of Chlorobiaceae and Methylophilaceae. SNP analyses revealed substantial genetic heterogeneity within these populations, although the degree of heterogeneity varied considerably among closely related, co-occurring Methylophilaceae populations. SNP allele frequencies, as well as the relative abundance of certain genes, changed dramatically over time in each population. Interestingly, SNP diversity was purged at nearly every genome position in one of the Chlorobiaceae populations over the course of three years, while at the same time multiple genes either swept through or were swept from this population. These patterns were consistent with a genome-wide selective sweep, a process predicted by the ‘ecotype model’ of diversification, but not previously observed in natural populations.

  18. Real-time gesture recognition by learning and selective control of visual interest points.

    PubMed

    Kirishima, Toshiyuki; Sato, Kosuke; Chihara, Kunihiro

    2005-03-01

    For the real-time recognition of unspecified gestures by an arbitrary person, a comprehensive framework is presented that addresses two important problems in gesture recognition systems: selective attention and processing frame rate. To address the first problem, we propose the Quadruple Visual Interest Point Strategy. No assumptions are made with regard to scale or rotation of visual features, which are computed from dynamically changing regions of interest in a given image sequence. In this paper, each of the visual features is referred to as a visual interest point, to which a probability density function is assigned, and the selection is carried out. To address the second problem, we developed a selective control method to equip the recognition system with self-load monitoring and controlling functionality. Through evaluation experiments, we show that our approach provides robust recognition with respect to such factors as type of clothing, type of gesture, extent of motion trajectories, and individual differences in motion characteristics. In order to indicate the real-time performance and utility aspects of our approach, a gesture video system is developed that demonstrates full video-rate interaction with displayed image objects.

  19. Action recognition based on a selective sampling strategy for real-time video surveillance

    NASA Astrophysics Data System (ADS)

    Zhang, Bo; Zhang, Hong; Yuan, Ding

    2015-12-01

    Action recognition is a very challenging task in the field of real-time video surveillance. The traditional models on action recognition are constructed of Spatial-temporal features and Bag-of-Feature representations. Based on this model, current research work tends to introduce dense sampling to achieve better performance. However, such approaches are computationally intractable when dealing with large video dataset. Hence, there are some recent works focused on feature reduction to speed up the algorithm without reducing accuracy. In this paper, we proposed a novel selective feature sampling strategy on action recognition. Firstly, the optical flow field is estimated throughout the input video. And then the sparse FAST (Features from Accelerated Segment Test) points are selected within the motion regions detected by using the optical flows on the temporally down-sampled image sequences. The selective features, sparse FAST points, are the seeds to generate the 3D patches. Consequently, the simplified LPM (Local Part Model) which greatly speeds up the model is formed via 3D patches. Moreover, MBHs (Motion Boundary Histograms) calculated by optical flows are also adopted in the framework to further improve the efficiency. Experimental results on UCF50 dataset and our artificial dataset show that our method could reach more real-time effect and achieve a higher accuracy compared with the other competitive methods published recently.

  20. Autostereoscopic display concept with time-sequential wavelength-selective filter-barrier

    NASA Astrophysics Data System (ADS)

    Jurk, Silvio; Kuhlmey, Mathias; Bartmann, Roland; Duckstein, Bernd; de la Barré, René

    2016-03-01

    A spatially multiplexed autostereoscopic 3D display design with a strip barrier consisting of RGB-color filters is presented. The wavelength selective filter barrier emits the light from a display area larger than that of common autostereoscopic barrier displays. However, such construction is still used rather rarely. The time sequential operation mode is a supplemental option. Wavelength selective filter barrier arrangements exhibit characteristics different from common barrier displays with similar barrier pitch and ascent. In particular these constructions show strong angular luminance dependency under barrier inclination specified by correspondent slant angle. In time sequential implementation it is important to avoid that quick eye or eyelid movement lead to visible color artifacts. Those circumstances limit the possibility to find well working and usable display designs superior to usual barrier displays. The newly introduced design is usable as a multi user display as well as a single user system with user adaptive control. In case of tracked single user mode the adaption in x-z-direction is continuously. The design has been modelled with simulation software developed for that purpose. The modelling of wavelength-selective barriers was used to calculate the light ray distribution properties of that arrangement. For the experimental verification of the image separation and evaluation of image quality, commercially available display components were combined for a display demonstrator.

  1. Improving the time efficiency of the Fourier synthesis method for slice selection in magnetic resonance imaging.

    PubMed

    Tahayori, B; Khaneja, N; Johnston, L A; Farrell, P M; Mareels, I M Y

    2016-01-01

    The design of slice selective pulses for magnetic resonance imaging can be cast as an optimal control problem. The Fourier synthesis method is an existing approach to solve these optimal control problems. In this method the gradient field as well as the excitation field are switched rapidly and their amplitudes are calculated based on a Fourier series expansion. Here, we provide a novel insight into the Fourier synthesis method via representing the Bloch equation in spherical coordinates. Based on the spherical Bloch equation, we propose an alternative sequence of pulses that can be used for slice selection which is more time efficient compared to the original method. Simulation results demonstrate that while the performance of both methods is approximately the same, the required time for the proposed sequence of pulses is half of the original sequence of pulses. Furthermore, the slice selectivity of both sequences of pulses changes with radio frequency field inhomogeneities in a similar way. We also introduce a measure, referred to as gradient complexity, to compare the performance of both sequences of pulses. This measure indicates that for a desired level of uniformity in the excited slice, the gradient complexity for the proposed sequence of pulses is less than the original sequence. Copyright © 2015 Associazione Italiana di Fisica Medica. Published by Elsevier Ltd. All rights reserved.

  2. Non-Selective Cation Channels Mediate Chloroquine-Induced Relaxation in Precontracted Mouse Airway Smooth Muscle

    PubMed Central

    Li, Wen-Er; Ma, Yun-Fei; Chen, Weiwei; Zhai, Kui; Qin, Gangjian; Guo, Donglin; Zheng, Yun-Min; Wang, Yong-Xiao; Shen, Jin-Hua; Ji, Guangju; Liu, Qing-Hua

    2014-01-01

    Bitter tastants can induce relaxation in precontracted airway smooth muscle by activating big-conductance potassium channels (BKs) or by inactivating voltage-dependent L-type Ca2+ channels (VDLCCs). In this study, a new pathway for bitter tastant-induced relaxation was defined and investigated. We found nifedipine-insensitive and bitter tastant chloroquine-sensitive relaxation in epithelium-denuded mouse tracheal rings (TRs) precontracted with acetylcholine (ACH). In the presence of nifedipine (10 µM), ACH induced cytosolic Ca2+ elevation and cell shortening in single airway smooth muscle cells (ASMCs), and these changes were inhibited by chloroquine. In TRs, ACH triggered a transient contraction under Ca2+-free conditions, and, following a restoration of Ca2+, a strong contraction occurred, which was inhibited by chloroquine. Moreover, the ACH-activated whole-cell and single channel currents of non-selective cation channels (NSCCs) were blocked by chloroquine. Pyrazole 3 (Pyr3), an inhibitor of transient receptor potential C3 (TRPC3) channels, partially inhibited ACH-induced contraction, intracellular Ca2+ elevation, and NSCC currents. These results demonstrate that NSCCs play a role in bitter tastant-induced relaxation in precontracted airway smooth muscle. PMID:24992312

  3. Maternal exposures in the National Birth Defects Prevention Study: Time trends of selected exposures.

    PubMed

    Dawson, April L; Razzaghi, Hilda; Arth, Annelise; Canfield, Mark A; Parker, Samantha E; Reefhuis, Jennita

    2015-08-01

    Our objective was to describe time trends in selected pregnancy exposures in the National Birth Defects Prevention Study (NBDPS). We analyzed data from the NBDPS, a multi-site case-control study of major birth defects, for mothers of live-born infants without birth defects (controls), with an expected date of delivery (EDD) from 1998 to 2011. Mothers from the 10 participating centers across the United States were interviewed by phone between 6 weeks and 2 years after the EDD. We focused on maternal race/ethnicity and five maternal risk factors: obesity, use of folic acid-containing multivitamins, opioid analgesics, selective serotonin reuptake inhibitors, and loratadine because of their prevalence of use and some reports of associations with major birth defects. Prevalence time trends were examined using the Kendall's τβ test statistic. The exposure trend analysis included 11,724 control mothers with EDDs from 1998 to 2011. We observed a significant increase in obesity prevalence among control mothers, as well as use of selective serotonin reuptake inhibitors and loratadine. We also observed an increase in periconceptional use of folic acid-containing multivitamins. Some of the time trends varied by race/ethnicity. No remarkable trend in the overall use of opioid analgesics was observed. The racial/ethnic distribution of mothers changed slightly during the study period. Long-term, population-based case-control studies continue to be an effective way to assess exposure-birth defects associations and provide guidance to health care providers. However, investigators examining rare outcomes covering many years of data collection need to be cognizant of time trends in exposures. © 2015 Wiley Periodicals, Inc.

  4. Caesarean delivery before 39 weeks associated with selecting an auspicious time for birth in Taiwan.

    PubMed

    Chu, Kuei-Hui; Lee, Yu-Hsiang; Tai, Chen-Jei; Lin, Yu-Hung; Huang, Chiu-Mieh; Chien, Li-Yin

    2015-09-01

    Caesarean delivery before 39 weeks of gestation increases the risk of morbidity among infants. Taiwan has one of the highest caesarean rates in the world, but little attention has been paid to this issue. This study aimed to describe the rate of caesarean delivery before 39 weeks gestation among women who did not have labour signs and had a non-emergency caesarean delivery in Taiwan and to examine whether the phenomenon was associated with the Chinese cultural practice of selecting an auspicious time for birth. We recruited women at 15-28 weeks of pregnancy at 5 hospitals in northern Taiwan and followed them at 4 or 5 weeks after delivery using structured questionnaires. This analysis included 150 primiparous mothers with a singleton pregnancy who had a non-emergency caesarean delivery without the presence of labour signs. Ninety-three of these women (62.0%) had caesarean deliveries before 39 weeks of gestation. Logistic regression analysis showed that women who had selected an auspicious time for delivery (OR=2.82, 95% CI: 1.15-6.95) and delivered in medical centres (OR=5.26, 95% CI: 2.25-12.26) were more likely to deliver before 39 weeks of gestation. Non-emergency caesarean delivery before 39 weeks of gestation was common among the study women, and was related to the Chinese cultural practice of selecting an auspicious time for birth. Further studies are needed to examine the risks and benefits associated with timing of caesarean delivery in Taiwan in order to generate a consensus among obstetricians and give pregnant women appropriate information. Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.

  5. Assessment of exercise-induced minor muscle lesions: the accuracy of Cyriax's diagnosis by selective tension paradigm.

    PubMed

    Franklin, M E; Conner-Kerr, T; Chamness, M; Chenier, T C; Kelly, R R; Hodge, T

    1996-09-01

    The Cyriax selective tension assessment paradigm is commonly used by clinicians for the diagnosis of soft tissue lesions; however, studies have not demonstrated that it is a valid method. The purpose of this study was to examine the construct validity of the active motion, passive motion, resisted movement, and palpation components of the Cyriax selective tension diagnosis paradigm in subjects with an exercise-induced minor hamstring muscle lesion. Nine female subjects with a mean age of 23.6 years (SD = 4.7) and a mass of 57.3 kg (SD = 10.7) performed two sets of 20 maximal eccentric isokinetic knee flexor contractions designed to induce a minor muscle lesion of the hamstrings. Active range of motion, passive range of motion, knee extension end-feel pain relative to resistance sequence, knee flexor isometric strength, pain perception during knee flexor resisted movement testing, and palpation pain of the hamstrings were assessed at 0, 5, 2, 12, 24, 48, and 72 hours postexercise and compared with Cyriax's hypothesized selective tension paradigm results. Consistent with Cyriax's paradigm, passive range of motion remained unchanged, and perceived pain of the hamstrings increased with resistance testing at 12, 24, 48, and 72 hours postexercise when compared with baseline. In addition, palpation pain of the hamstrings was significantly elevated at 48 and 72 hours after exercise (p < 0.05). In contrast of Cyriax's paradigm, active range of motion was significantly reduced over time (p < 0.05), with the least amount of motion compared to baseline (85%) occurring at 48 hours postexercise. Further, resisted movement testing found significant knee flexor isometric strength reductions over time (p < 0.05), with the greatest reductions (33%) occurring at 48 hours postexercise. According to Cyriax, when a minor muscle lesion is tested, it should be strong and painful; however, none of the postexercise time frames exhibited results that were strong and painful. This study

  6. Space-time wiring specificity supports direction selectivity in the retina

    PubMed Central

    Zlateski, Aleksandar; Lee, Kisuk; Richardson, Mark; Turaga, Srinivas C.; Purcaro, Michael; Balkam, Matthew; Robinson, Amy; Behabadi, Bardia F.; Campos, Michael; Denk, Winfried; Seung, H. Sebastian

    2014-01-01

    How does the mammalian retina detect motion? This classic problem in visual neuroscience has remained unsolved for 50 years. In search of clues, we reconstructed Off-type starburst amacrine cells (SACs) and bipolar cells (BCs) in serial electron microscopic images with help from EyeWire, an online community of “citizen neuroscientists.” Based on quantitative analyses of contact area and branch depth in the retina, we found evidence that one BC type prefers to wire with a SAC dendrite near the SAC soma, while another BC type prefers to wire far from the soma. The near type is known to lag the far type in time of visual response. A mathematical model shows how such “space-time wiring specificity” could endow SAC dendrites with receptive fields that are oriented in space-time and therefore respond selectively to stimuli that move in the outward direction from the soma. PMID:24805243

  7. Space-time wiring specificity supports direction selectivity in the retina.

    PubMed

    Kim, Jinseop S; Greene, Matthew J; Zlateski, Aleksandar; Lee, Kisuk; Richardson, Mark; Turaga, Srinivas C; Purcaro, Michael; Balkam, Matthew; Robinson, Amy; Behabadi, Bardia F; Campos, Michael; Denk, Winfried; Seung, H Sebastian

    2014-05-15

    How does the mammalian retina detect motion? This classic problem in visual neuroscience has remained unsolved for 50 years. In search of clues, here we reconstruct Off-type starburst amacrine cells (SACs) and bipolar cells (BCs) in serial electron microscopic images with help from EyeWire, an online community of 'citizen neuroscientists'. On the basis of quantitative analyses of contact area and branch depth in the retina, we find evidence that one BC type prefers to wire with a SAC dendrite near the SAC soma, whereas another BC type prefers to wire far from the soma. The near type is known to lag the far type in time of visual response. A mathematical model shows how such 'space-time wiring specificity' could endow SAC dendrites with receptive fields that are oriented in space-time and therefore respond selectively to stimuli that move in the outward direction from the soma.

  8. Real-time Microseismic Processing for Induced Seismicity Hazard Detection

    SciTech Connect

    Matzel, Eric M.

    2016-10-31

    Induced seismicity is inherently associated with underground fluid injections. If fluids are injected in proximity to a pre-existing fault or fracture system, the resulting elevated pressures can trigger dynamic earthquake slip, which could both damage surface structures and create new migration pathways. The goal of this research is to develop a fundamentally better approach to geological site characterization and early hazard detection. We combine innovative techniques for analyzing microseismic data with a physics-based inversion model to forecast microseismic cloud evolution. The key challenge is that faults at risk of slipping are often too small to detect during the site characterization phase. Our objective is to devise fast-running methodologies that will allow field operators to respond quickly to changing subsurface conditions.

  9. Chronic Nicotine Attenuates Phencyclidine-Induced Impulsivity in a Mouse Serial Reaction Time Task

    PubMed Central

    Scott, Daniel; Taylor, Jane R.

    2013-01-01

    Schizophrenia is a disorder characterized by positive, negative, and cognitive symptoms. While positive symptoms can be effectively treated with typical antipsychotic medication, which generally affects the dopaminergic system, negative and cognitive symptoms, including attentional deficits and impulsive behavior, are less sensitive to standard treatments. It has further been well documented that schizophrenic patients use tobacco products at a rate much higher than the general population, and this persists despite treatment. It has been argued this behavior may be a form of self-medication, to alleviate some symptoms of schizophrenia. It has further been posited that prefrontal glutamatergic hypofunction may underlie some aspects of schizophrenia, and in accordance with this model, systemic phencyclidine has been used to model the disease. We employed a modified 5-choice serial reaction time test, a paradigm that is often used to investigate many of the treatment-resistant symptoms of schizophrenia including impulsivity, selective attention, and sustained attention/cognitive vigilance, to determine the medicinal effects of nicotine. We demonstrate that chronic oral, but not acute injections of, nicotine can selectively attenuate phencyclidine-induced increases in impulsivity without affecting other measures of attention. This suggests that nicotine use by schizophrenics may provide some relief of distinct symptoms that involve impulsive behaviors. PMID:24239695

  10. Continuous-Time Mean-Variance Portfolio Selection: A Stochastic LQ Framework

    SciTech Connect

    Zhou, X.Y.; Li, D. dli@se.cuhk.edu.hk

    2000-07-01

    This paper is concerned with a continuous-time mean-variance portfolio selection model that is formulated as a bicriteria optimization problem. The objective is to maximize the expected terminal return and minimize the variance of the terminal wealth. By putting weights on the two criteria one obtains a single objective stochastic control problem which is however not in the standard form due to the variance term involved. It is shown that this nonstandard problem can be 'embedded' into a class of auxiliary stochastic linear-quadratic (LQ) problems. The stochastic LQ control model proves to be an appropriate and effective framework to study the mean-variance problem in light of the recent development on general stochastic LQ problems with indefinite control weighting matrices. This gives rise to the efficient frontier in a closed form for the original portfolio selection problem.

  11. In vivo Target Residence Time and Kinetic Selectivity: The Association Rate Constant as Determinant.

    PubMed

    de Witte, Wilhelmus E A; Danhof, Meindert; van der Graaf, Piet H; de Lange, Elizabeth C M

    2016-10-01

    It is generally accepted that, in conjunction with pharmacokinetics, the first-order rate constant of target dissociation is a major determinant of the time course and duration of in vivo target occupancy. Here we show that the second-order rate constant of target association can be equally important. On the basis of the commonly used mathematical models for drug-target binding, it is shown that a high target association rate constant can increase the (local) concentration of the drug, which decreases the rate of decline of target occupancy. The increased drug concentration can also lead to increased off-target binding and decreased selectivity. Therefore, the kinetics of both target association and dissociation need to be taken into account in the selection of drug candidates with optimal pharmacodynamic properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Selection of Spectral Data for Classification of Steels Using Laser-Induced Breakdown Spectroscopy

    NASA Astrophysics Data System (ADS)

    Kong, Haiyang; Sun, Lanxiang; Hu, Jingtao; Xin, Yong; Cong, Zhibo

    2015-11-01

    Principal component analysis (PCA) combined with artificial neural networks was used to classify the spectra of 27 steel samples acquired using laser-induced breakdown spectroscopy. Three methods of spectral data selection, selecting all the peak lines of the spectra, selecting intensive spectral partitions and the whole spectra, were utilized to compare the influence of different inputs of PCA on the classification of steels. Three intensive partitions were selected based on experience and prior knowledge to compare the classification, as the partitions can obtain the best results compared to all peak lines and the whole spectra. We also used two test data sets, mean spectra after being averaged and raw spectra without any pretreatment, to verify the results of the classification. The results of this comprehensive comparison show that a back propagation network trained using the principal components of appropriate, carefully selected spectral partitions can obtain the best results. A perfect result with 100% classification accuracy can be achieved using the intensive spectral partitions ranging of 357-367 nm. supported by the National High Technology Research and Development Program of China (863 Program) (No. 2012AA040608), National Natural Science Foundation of China (Nos. 61473279, 61004131) and the Development of Scientific Research Equipment Program of Chinese Academy of Sciences (No. YZ201247)

  13. Clinical outcomes following selection of human preimplantation embryos with time-lapse monitoring: a systematic review.

    PubMed

    Kaser, Daniel J; Racowsky, Catherine

    2014-01-01

    Time-lapse monitoring (TLM) has emerged as a novel technology to perform semi-quantitative evaluation of embryo morphology and developmental kinetics in assisted reproduction. While this method has already been introduced into clinical practice in many laboratories, it is unclear whether it adds value to conventional morphology. Most studies only report blastocyst formation as the primary end-point. The aim of this systematic review is to provide a critical evaluation of the available studies that report clinical outcomes following embryo selection with TLM. A literature search in MEDLINE, Cochrane CENTRAL and ISI Web of Knowledge Science Citation Index was performed to identify studies that assess the clinical utility of kinetic markers for non-invasive selection of human embryos with high implantation potential. Only studies published before 31 December 2013 in the English language that report rates of implantation, clinical pregnancy or live birth were included. Two hundred and fifty-one studies were identified by database search and reference list review; only 13 met eligibility criteria and were included in this analysis. The following morphokinetic parameters were assessed: pronuclear dynamics and morphology (n = 3), duration of first cytokinesis and reappearance of nuclei after cleavage (n = 3), time to various cleavage stages (n = 5), duration of various cleavage stages (n = 6), duration of cleavage cycles and mitotic synchronicity (n = 6), and time to morula, blastocyst and hatching (n = 4). Five studies used combined parameter grading to generate a cumulative score, and two studies retrospectively compared implantation rates following embryo selection by conventional morphology alone or with the addition of a hierarchal time-lapse classification. While several studies suggest higher implantation rates for fast-cleaving embryos and those with a timely duration (i.e. all time points within the defined ranges) of the 2-cell and 3-cell stages, no single

  14. Magnetic field-induced modification of selection rules for Rb D 2 line monitored by selective reflection from a vapor nanocell

    NASA Astrophysics Data System (ADS)

    Klinger, Emmanuel; Sargsyan, Armen; Tonoyan, Ara; Hakhumyan, Grant; Papoyan, Aram; Leroy, Claude; Sarkisyan, David

    2017-08-01

    Magnetic field-induced giant modification of the probabilities of five transitions of 5 S 1 / 2, F g = 2 → 5 P 3 / 2, F e = 4 of 85Rb and three transitions of 5 S 1 / 2, F g = 1 → 5 P 3 / 2, F e = 3 of 87Rb forbidden by selection rules for zero magnetic field has been observed experimentally and described theoretically for the first time. For the case of excitation with circularly-polarized ( σ +) laser radiation, the probability of F g = 2, m F = - 2 → F e = 4, m F = - 1 transition becomes the largest among the seventeen transitions of 85Rb F g = 2 → F e = 1,2,3,4 group, and the probability of F g = 1, m F = - 1 → F e = 3, m F = 0 transition becomes the largest among the nine transitions of 87Rb F g = 1 → F e = 0,1,2,3 group, in a wide range of magnetic field 200-1000 G. Complete frequency separation of individual Zeeman components was obtained by implementation of derivative selective reflection technique with a 300 nm-thick nanocell filled with Rb, allowing formation of narrow optical resonances. Possible applications are addressed. The theoretical model is well consistent with the experimental results.

  15. Induced Time-Reversal Symmetry Breaking Observed in Microwave Billiards

    SciTech Connect

    Dietz, B.; Friedrich, T.; Miski-Oglu, M.; Richter, A.; Schaefer, F.; Harney, H. L.; Weidenmueller, H. A.

    2007-02-16

    Using reciprocity, we investigate the breaking of time-reversal (T) symmetry due to a ferrite embedded in a flat microwave billiard. Transmission spectra of isolated single resonances are not sensitive to T violation, whereas those of pairs of nearly degenerate resonances do depend on the direction of time. For their theoretical description a scattering matrix model from nuclear physics is used. The T-violating matrix elements of the effective Hamiltonian for the microwave billiard with the embedded ferrite are determined experimentally as functions of the magnetization of the ferrite.

  16. Vacuum radiation induced by time dependent electric field

    NASA Astrophysics Data System (ADS)

    Zhang, Bo; Zhang, Zhi-meng; Hong, Wei; He, Shu-Kai; Teng, Jian; Gu, Yu-qiu

    2017-04-01

    Many predictions of new phenomena given by strong field quantum electrodynamics (SFQED) will be tested on next generation multi-petawatt laser facilities in the near future. These new phenomena are basis to understand physics in extremely strong electromagnetic fields therefore have attracted wide research interest. Here we discuss a new SFQED phenomenon that is named as vacuum radiation. In vacuum radiation, a virtual electron loop obtain energy from time dependent external electric field and radiate an entangled photon pair. Features of vacuum radiation in a locally time dependent electric field including spectrum, characteristic temperature, production rate and power are given.

  17. Time fractional capital-induced labor migration model

    NASA Astrophysics Data System (ADS)

    Ali Balcı, Mehmet

    2017-07-01

    In this study we present a new model of neoclassical economic growth by considering that workers move from regions with lower density of capital to regions with higher density of capital. Since the labor migration and capital flow involves self-similarities in long range time, we use the fractional order derivatives for the time variable. To solve this model we proposed Variational Iteration Method, and studied numerically labor migration flow data from Turkey along with other countries throughout the period of 1966-2014.

  18. Induced time-reversal symmetry breaking observed in microwave billiards.

    PubMed

    Dietz, B; Friedrich, T; Harney, H L; Miski-Oglu, M; Richter, A; Schäfer, F; Weidenmüller, H A

    2007-02-16

    Using reciprocity, we investigate the breaking of time-reversal (T) symmetry due to a ferrite embedded in a flat microwave billiard. Transmission spectra of isolated single resonances are not sensitive to T violation, whereas those of pairs of nearly degenerate resonances do depend on the direction of time. For their theoretical description a scattering matrix model from nuclear physics is used. The T-violating matrix elements of the effective Hamiltonian for the microwave billiard with the embedded ferrite are determined experimentally as functions of the magnetization of the ferrite.

  19. Effect of selected water temperatures used in Mycoplasma gallisepticum vaccine reconstitution on titer at selected time intervals

    USDA-ARS?s Scientific Manuscript database

    Numerous methods are currently used throughout the poultry industry for the administration of vaccines. Each utilizes water for vaccine reconstitution and/or administration, including two of the three commercially available live Mycoplasma gallisepticum (MG) vaccines. Selected water temperatures w...

  20. Cocaine-induced locomotor activity in rats selectively bred for low and high voluntary running behavior.

    PubMed

    Brown, Jacob D; Green, Caroline L; Arthur, Ian M; Booth, Frank W; Miller, Dennis K

    2015-02-01

    The rewarding effects of physical activity and abused drugs are caused by stimulation of similar brain pathways. Low (LVR) and high (HVR) voluntary running lines were developed by selectively breeding Wistar rats on running distance performance on postnatal days 28-34. We hypothesized that LVR rats would be more sensitive to the locomotor-activating effects of cocaine than HVR rats due to their lower motivation for wheel running. We investigated how selection for LVR or HVR behavior affects inherited activity responses: (a) open field activity levels, (b) habituation to an open field environment, and (c) the locomotor response to cocaine. Open field activity was measured for 80 min on three successive days (days 1-3). Data from the first 20 min were analyzed to determine novelty-induced locomotor activity (day 1) and the habituation to the environment (days 1-3). On day 3, rats were acclimated to the chamber for 20 min and then received saline or cocaine (10, 20, or 30 mg/kg) injection. Dopamine transporter (DAT) protein in the nucleus accumbens was measured via Western blot. Selecting for low and high voluntary running behavior co-selects for differences in inherent (HVR > LVR) and cocaine-induced (LVR > HVR) locomotor activity levels. The differences in the selected behavioral measures do not appear to correlate with DAT protein levels. LVR and HVR rats are an intriguing physical activity model for studying the interactions between genes related to the motivation to run, to use drugs of abuse, and to exhibit locomotor activity.

  1. Time-resolved photoluminescence for evaluating laser-induced damage during dielectric stack ablation in silicon solar cells

    NASA Astrophysics Data System (ADS)

    Parola, Stéphanie; Blanc-Pélissier, Danièle; Barbos, Corina; Le Coz, Marine; Poulain, Gilles; Lemiti, Mustapha

    2016-06-01

    Selective laser ablation of dielectric layers on crystalline silicon wafers was investigated for solar cell fabrication. Laser processing was performed on Al2O3, and bi-layers Al2O3/SiNX:H with a nanosecond UV laser at various energy densities ranging from 0.4 to 2 J cm-2. Ablation threshold was correlated to the simulated temperature at the interface between the dielectric coatings and the silicon substrate. Laser-induced damage to the silicon substrate was evaluated by time-resolved photoluminescence. The minority carrier lifetime deduced from time-resolved photoluminescence was related to the depth of the heat affected zone in the substrate.

  2. Nest site selection and induced response in a dominant arboreal ant species.

    PubMed

    Dejean, Alain; Grangier, Julien; Leroy, Céline; Orivel, Jerôme; Gibernau, Marc

    2008-09-01

    It is well known that arboreal ants, both territorially dominant species and plant ants (e.g., species associated with myrmecophytes or plants housing them in hollow structures), protect their host trees from defoliators. Nevertheless, the presence of an induced defense, suggested by the fact that the workers discovering a leaf wound recruit nestmates, is only known for plant ants. Based on the results from a field study, we show here (1) that colonies of Azteca chartifex, a territorially dominant, neotropical arboreal ant species, mostly selected Goupia glabra (Goupiaceae) trees in which to build their principal carton nests and (2) that plant signals induced workers to recruit nestmates, which patrol the leaves, likely providing the plant with a biotic defense. Furthermore, the number of recruited workers was clearly higher on G. glabra, their most frequently selected host tree species, than on other tree species. These results show that contrary to what was previously believed, induced responses are also found in territorially dominant arboreal ants and so are not limited to the specific associations between myrmecophytes and plant ants.

  3. Current approaches to prevent NSAID-induced gastropathy – COX selectivity and beyond

    PubMed Central

    Becker, Jan C; Domschke, Wolfram; Pohle, Thorsten

    2004-01-01

    Gastrointestinal (GI) toxicity associated with nonsteroidal anti-inflammatory drugs (NSAIDs) is still an important medical and socio-economic problem – despite recent pharmaceutical advances. To prevent NSAID-induced gastropathy, three strategies are followed in clinical routine: (i) coprescription of a gastroprotective drug, (ii) use of selective COX-2 inhibitors, and (iii) eradication of Helicobacter pylori. Proton pump inhibitors are the comedication of choice as they effectively reduce gastrointestinal adverse events of NSAIDs and are safe even in long-term use. Co-medication with vitamin C has only been little studied in the prevention of NSAID-induced gastropathy. Apart from scavenging free radicals it is able to induce haeme-oxgenase 1 in gastric cells, a protective enzyme with antioxidant and vasodilative properties. Final results of the celecoxib outcome study (CLASS study) attenuated the initial enthusiasm about the GI safety of selective COX-2 inhibitors, especially in patients concomitantly taking aspirin for cardiovascular prophylaxis. Helicobacter pylori increases the risk for ulcers particularly in NSAID-naive patients and therefore eradication is recommended prior to long-term NSAID therapy at least in patients at high risk. New classes of COX-inhibitors are currently evaluated in clinical studies with very promising results: NSAIDs combined with a nitric oxide releasing moiety (NO-NSAID) and dual inhibitors of COX and 5-LOX. These drugs offer extended anti-inflammatory potency while sparing gastric mucosa. PMID:15563357

  4. Maskless and low-destructive nanofabrication on quartz by friction-induced selective etching

    NASA Astrophysics Data System (ADS)

    Song, Chenfei; Li, Xiaoying; Cui, Shuxun; Dong, Hanshan; Yu, Bingjun; Qian, Linmao

    2013-03-01

    A low-destructive friction-induced nanofabrication method is proposed to produce three-dimensional nanostructures on a quartz surface. Without any template, nanofabrication can be achieved by low-destructive scanning on a target area and post-etching in a KOH solution. Various nanostructures, such as slopes, hierarchical stages and chessboard-like patterns, can be fabricated on the quartz surface. Although the rise of etching temperature can improve fabrication efficiency, fabrication depth is dependent only upon contact pressure and scanning cycles. With the increase of contact pressure during scanning, selective etching thickness of the scanned area increases from 0 to 2.9 nm before the yield of the quartz surface and then tends to stabilise after the appearance of a wear. Refabrication on existing nanostructures can be realised to produce deeper structures on the quartz surface. Based on Arrhenius fitting of the etching rate and transmission electron microscopy characterization of the nanostructure, fabrication mechanism could be attributed to the selective etching of the friction-induced amorphous layer on the quartz surface. As a maskless and low-destructive technique, the proposed friction-induced method will open up new possibilities for further nanofabrication.

  5. Engineered cellular gene-replacement platform for selective and inducible proteolytic profiling

    PubMed Central

    Morgan, Charles W.; Diaz, Juan E.; Zeitlin, Samantha G.; Gray, Daniel C.; Wells, James A.

    2015-01-01

    Cellular demolition during apoptosis is completed by executioner caspases, that selectively cleave more than 1,500 proteins but whose individual roles are challenging to assess. Here, we used an optimized site-specific and inducible protease to examine the role of a classic apoptotic node, the caspase-activated DNase (CAD). CAD is activated when caspases cleave its endogenous inhibitor ICAD, resulting in the characteristic DNA laddering of apoptosis. We describe a posttranscriptional gene replacement (PTGR) approach where endogenous biallelic ICAD is knocked down and simultaneously replaced with an engineered allele that is susceptible to inducible cleavage by tobacco etch virus protease. Remarkably, selective activation of CAD alone does not induce cell death, although hallmarks of DNA damage are detected in human cancer cell lines. Our data strongly support that the highly cooperative action of CAD and inhibition of DNA repair systems are critical for the DNA laddering phenotype in apoptosis. Furthermore, the PTGR approach provides a general means for replacing wild-type protein function with a precisely engineered mutant at the transcriptional level that should be useful for cell engineering studies. PMID:26106156

  6. Maskless and low-destructive nanofabrication on quartz by friction-induced selective etching

    PubMed Central

    2013-01-01

    A low-destructive friction-induced nanofabrication method is proposed to produce three-dimensional nanostructures on a quartz surface. Without any template, nanofabrication can be achieved by low-destructive scanning on a target area and post-etching in a KOH solution. Various nanostructures, such as slopes, hierarchical stages and chessboard-like patterns, can be fabricated on the quartz surface. Although the rise of etching temperature can improve fabrication efficiency, fabrication depth is dependent only upon contact pressure and scanning cycles. With the increase of contact pressure during scanning, selective etching thickness of the scanned area increases from 0 to 2.9 nm before the yield of the quartz surface and then tends to stabilise after the appearance of a wear. Refabrication on existing nanostructures can be realised to produce deeper structures on the quartz surface. Based on Arrhenius fitting of the etching rate and transmission electron microscopy characterization of the nanostructure, fabrication mechanism could be attributed to the selective etching of the friction-induced amorphous layer on the quartz surface. As a maskless and low-destructive technique, the proposed friction-induced method will open up new possibilities for further nanofabrication. PMID:23531381

  7. Selective differentiation and proliferation of hematopoietic cells induced by recombinant human interleukins.

    PubMed Central

    Saito, H; Hatake, K; Dvorak, A M; Leiferman, K M; Donnenberg, A D; Arai, N; Ishizaka, K; Ishizaka, T

    1988-01-01

    Effects of recombinant human interleukins on hematopoiesis were explored by using suspension cultures of mononuclear cells of human umbilical-cord blood and bone marrow. The results showed that interleukin 5 induced the selective differentiation and proliferation of eosinophils. After 3 weeks in culture with interleukin 5, essentially all nonadherent cells in both bone marrow and cord blood cell cultures became eosinophilic myelocytes. Culture of the same cells with interleukin 4 resulted in the selective growth of OKT3+ lymphocytes. However, OKT3+ cells did not develop if the bone marrow cells were depleted of OKT3+/OKT11+ cells prior to the culture, indicating that interleukin 4 induced the proliferation of a subpopulation of resting T cells present in cord blood and bone marrow cell preparations. In suspension cultures of bone marrow cells and cord blood cells grown in the presence of interleukin 3, basophilic, eosinophilic, and neutrophilic myelocytes and macrophages developed within 2 weeks. By 3 weeks, however, the majority of nonadherent cells became eosinophilic myelocytes. In contrast to mouse bone marrow cell cultures, neither interleukin 3 nor a combination of interleukins 3 and 4 induced the differentiation of mast cells in human bone marrow or cord blood cell cultures. Images PMID:3258425

  8. Nest site selection and induced response in a dominant arboreal ant species

    NASA Astrophysics Data System (ADS)

    Dejean, Alain; Grangier, Julien; Leroy, Céline; Orivel, Jerôme; Gibernau, Marc

    2008-09-01

    It is well known that arboreal ants, both territorially dominant species and plant ants (e.g., species associated with myrmecophytes or plants housing them in hollow structures), protect their host trees from defoliators. Nevertheless, the presence of an induced defense, suggested by the fact that the workers discovering a leaf wound recruit nestmates, is only known for plant ants. Based on the results from a field study, we show here (1) that colonies of Azteca chartifex, a territorially dominant, neotropical arboreal ant species, mostly selected Goupia glabra (Goupiaceae) trees in which to build their principal carton nests and (2) that plant signals induced workers to recruit nestmates, which patrol the leaves, likely providing the plant with a biotic defense. Furthermore, the number of recruited workers was clearly higher on G. glabra, their most frequently selected host tree species, than on other tree species. These results show that contrary to what was previously believed, induced responses are also found in territorially dominant arboreal ants and so are not limited to the specific associations between myrmecophytes and plant ants.

  9. Selective Attrition and Intraindividual Variability in Response Time Moderate Cognitive Change

    PubMed Central

    Yao, Christie; Stawski, Robert S.; Hultsch, David F.; MacDonald, Stuart W.S.

    2016-01-01

    Objectives Selection of a developmental time metric is useful for understanding causal processes that underlie aging-related cognitive change, and for the identification of potential moderators of cognitive decline. Building on research suggesting that time to attrition is a metric sensitive to non-normative influences of aging (e.g., subclinical health conditions), we examined reason for attrition and intraindividual variability (IIV) in reaction time as predictors of cognitive performance. Method Three-hundred and four community dwelling older adults (64-92 years) completed annual assessments in a longitudinal study. IIV was calculated from baseline performance on reaction time tasks. Multilevel models were fit to examine patterns and predictors of cognitive change. Results We show that time to attrition was associated with cognitive decline. Greater IIV was associated with declines on executive functioning and episodic memory measures. Attrition due to personal health reasons was also associated with decreased executive functioning compared to individuals who remained in study. Discussion These findings suggest that time to attrition is a useful metric for representing cognitive change, and reason for attrition and IIV are predictive of non-normative influences that may underlie instances of cognitive loss in older adults. PMID:26647008

  10. The Effects of Time on Task in Response Selection - An ERP Study of Mental Fatigue

    PubMed Central

    Möckel, Tina; Beste, Christian; Wascher, Edmund

    2015-01-01

    Long lasting involvement in a cognitive task leads to mental fatigue. Substantial efforts have been undertaken to understand this phenomenon. However, it has been demonstrated that some changes with time on task are not only related to mental fatigue. The present study intends to clarify these effects of time on task unrelated to mental fatigue on response selection processes at the behavioural and electrophysiological level (using event-related potentials, ERPs). Participants had to perform a Simon task for more than 3 hours and rated their experienced mental fatigue and motivation to continue with the task at several time points during the experiment. The results show that at the beginning of the experiment some unspecific modulations of training and adaptation are evident. With time on task participants’ ability to resolve response conflict appears to become impaired. The results reveal that time on task effects cannot be completely explained by mental fatigue. Instead, it seems that an interplay of adaptation at the beginning and motivational effects in the course of a task modulate performance and neurophysiological parameters. In future studies it will be important to account for the relative contribution of adaptation and motivation parameters when time on task effects are investigated. PMID:26054837

  11. The Effects of Time on Task in Response Selection--An ERP Study of Mental Fatigue.

    PubMed

    Möckel, Tina; Beste, Christian; Wascher, Edmund

    2015-06-09

    Long lasting involvement in a cognitive task leads to mental fatigue. Substantial efforts have been undertaken to understand this phenomenon. However, it has been demonstrated that some changes with time on task are not only related to mental fatigue. The present study intends to clarify these effects of time on task unrelated to mental fatigue on response selection processes at the behavioural and electrophysiological level (using event-related potentials, ERPs). Participants had to perform a Simon task for more than 3 hours and rated their experienced mental fatigue and motivation to continue with the task at several time points during the experiment. The results show that at the beginning of the experiment some unspecific modulations of training and adaptation are evident. With time on task participants' ability to resolve response conflict appears to become impaired. The results reveal that time on task effects cannot be completely explained by mental fatigue. Instead, it seems that an interplay of adaptation at the beginning and motivational effects in the course of a task modulate performance and neurophysiological parameters. In future studies it will be important to account for the relative contribution of adaptation and motivation parameters when time on task effects are investigated.

  12. Primary gamma ray selection in a hybrid timing/imaging Cherenkov array

    NASA Astrophysics Data System (ADS)

    Postnikov, E. B.; Grinyuk, A. A.; Kuzmichev, L. A.; Sveshnikova, L. G.

    2017-06-01

    This work is a methodical study on hybrid reconstruction techniques for hybrid imaging/timing Cherenkov observations. This type of hybrid array is to be realized at the gamma-observatory TAIGA intended for very high energy gamma-ray astronomy (> 30 TeV). It aims at combining the cost-effective timing-array technique with imaging telescopes. Hybrid operation of both of these techniques can lead to a relatively cheap way of development of a large area array. The joint approach of gamma event selection was investigated on both types of simulated data: the image parameters from the telescopes, and the shower parameters reconstructed from the timing array. The optimal set of imaging parameters and shower parameters to be combined is revealed. The cosmic ray background suppression factor depending on distance and energy is calculated. The optimal selection technique leads to cosmic ray background suppression of about 2 orders of magnitude on distances up to 450 m for energies greater than 50 TeV.

  13. Electromagnetic field redistribution induced selective plasmon driven surface catalysis in metal nanowire-film systems

    PubMed Central

    Pan, Liang; Huang, Yingzhou; Yang, Yanna; Xiong, Wen; Chen, Guo; Su, Xun; Wei, Hua; Wang, Shuxia; Wen, Weijia

    2015-01-01

    For the novel interpretation of Raman spectrum from molecule at metal surface, the plasmon driven surface catalysis (PDSC) reactions have become an interesting topic in the research field of surface enhanced Raman scattering (SERS). In this work, the selective PDSC reactions of p,p’-dimercaptoazobenzene (DMAB) produced from para-aminothiophenol (PATP) or 4-nitrobenzenethiol (4NBT) were demonstrated in the Ag nanowires dimer-Au film systems. The different SERS spectra collected at individual part and adjacent part of the same nanowire-film system pointed out the importance of the electromagnetic field redistribution induced by image charge on film in this selective surface catalysis, which was confirmed by the simulated electromagnetic simulated electro- magnetic field distributions. Our result indicated this electromagnetic field redistribution induced selective surface catalysis was largely affected by the polarization and wavelength of incident light but slightly by the difference in diameters between two nanowires. Our work provides a further understanding of PDSC reaction in metal nanostructure and could be a deep support for the researches on surface catalysis and surface analysis. PMID:26601698

  14. Selective flow-induced vesicle rupture to sort by membrane mechanical properties

    NASA Astrophysics Data System (ADS)

    Pommella, Angelo; Brooks, Nicholas J.; Seddon, John M.; Garbin, Valeria

    2015-08-01

    Vesicle and cell rupture caused by large viscous stresses in ultrasonication is central to biomedical and bioprocessing applications. The flow-induced opening of lipid membranes can be exploited to deliver drugs into cells, or to recover products from cells, provided that it can be obtained in a controlled fashion. Here we demonstrate that differences in lipid membrane and vesicle properties can enable selective flow-induced vesicle break-up. We obtained vesicle populations with different membrane properties by using different lipids (SOPC, DOPC, or POPC) and lipid:cholesterol mixtures (SOPC:chol and DOPC:chol). We subjected vesicles to large deformations in the acoustic microstreaming flow generated by ultrasound-driven microbubbles. By simultaneously deforming vesicles with different properties in the same flow, we determined the conditions in which rupture is selective with respect to the membrane stretching elasticity. We also investigated the effect of vesicle radius and excess area on the threshold for rupture, and identified conditions for robust selectivity based solely on the mechanical properties of the membrane. Our work should enable new sorting mechanisms based on the difference in membrane composition and mechanical properties between different vesicles, capsules, or cells.

  15. Electromagnetic field redistribution induced selective plasmon driven surface catalysis in metal nanowire-film systems

    NASA Astrophysics Data System (ADS)

    Pan, Liang; Huang, Yingzhou; Yang, Yanna; Xiong, Wen; Chen, Guo; Su, Xun; Wei, Hua; Wang, Shuxia; Wen, Weijia

    2015-11-01

    For the novel interpretation of Raman spectrum from molecule at metal surface, the plasmon driven surface catalysis (PDSC) reactions have become an interesting topic in the research field of surface enhanced Raman scattering (SERS). In this work, the selective PDSC reactions of p,p’-dimercaptoazobenzene (DMAB) produced from para-aminothiophenol (PATP) or 4-nitrobenzenethiol (4NBT) were demonstrated in the Ag nanowires dimer-Au film systems. The different SERS spectra collected at individual part and adjacent part of the same nanowire-film system pointed out the importance of the electromagnetic field redistribution induced by image charge on film in this selective surface catalysis, which was confirmed by the simulated electromagnetic simulated electro- magnetic field distributions. Our result indicated this electromagnetic field redistribution induced selective surface catalysis was largely affected by the polarization and wavelength of incident light but slightly by the difference in diameters between two nanowires. Our work provides a further understanding of PDSC reaction in metal nanostructure and could be a deep support for the researches on surface catalysis and surface analysis.

  16. Nanofabrication on monocrystalline silicon through friction-induced selective etching of Si3N4 mask.

    PubMed

    Guo, Jian; Yu, Bingjun; Wang, Xiaodong; Qian, Linmao

    2014-01-01

    A new fabrication method is proposed to produce nanostructures on monocrystalline silicon based on the friction-induced selective etching of its Si3N4 mask. With low-pressure chemical vapor deposition (LPCVD) Si3N4 film as etching mask on Si(100) surface, the fabrication can be realized by nanoscratching on the Si3N4 mask and post-etching in hydrofluoric acid (HF) and potassium hydroxide (KOH) solution in sequence. Scanning Auger nanoprobe analysis indicated that the HF solution could selectively etch the scratched Si3N4 mask and then provide the gap for post-etching of silicon substrate in KOH solution. Experimental results suggested that the fabrication depth increased with the increase of the scratching load or KOH etching period. Because of the excellent masking ability of the Si3N4 film, the maximum fabrication depth of nanostructure on silicon can reach several microns. Compared to the traditional friction-induced selective etching technique, the present method can fabricate structures with lesser damage and deeper depths. Since the proposed method has been demonstrated to be a less destructive and flexible way to fabricate a large-area texture structure, it will provide new opportunities for Si-based nanofabrication.

  17. Nanofabrication on monocrystalline silicon through friction-induced selective etching of Si3N4 mask

    PubMed Central

    2014-01-01

    A new fabrication method is proposed to produce nanostructures on monocrystalline silicon based on the friction-induced selective etching of its Si3N4 mask. With low-pressure chemical vapor deposition (LPCVD) Si3N4 film as etching mask on Si(100) surface, the fabrication can be realized by nanoscratching on the Si3N4 mask and post-etching in hydrofluoric acid (HF) and potassium hydroxide (KOH) solution in sequence. Scanning Auger nanoprobe analysis indicated that the HF solution could selectively etch the scratched Si3N4 mask and then provide the gap for post-etching of silicon substrate in KOH solution. Experimental results suggested that the fabrication depth increased with the increase of the scratching load or KOH etching period. Because of the excellent masking ability of the Si3N4 film, the maximum fabrication depth of nanostructure on silicon can reach several microns. Compared to the traditional friction-induced selective etching technique, the present method can fabricate structures with lesser damage and deeper depths. Since the proposed method has been demonstrated to be a less destructive and flexible way to fabricate a large-area texture structure, it will provide new opportunities for Si-based nanofabrication. PMID:24940174

  18. The effects of celecoxib, a COX-2 selective inhibitor, on acute inflammation induced in irradiated rats.

    PubMed

    Khayyal, M T; El-Ghazaly, Mona A; El-Hazek, R M; Nada, A S

    2009-10-01

    The potential value of selective and non-selective COX-2 inhibitors in preventing some of the biochemical changes induced by ionizing radiation was studied in rats exposed to carrageenan-induced paw edema and 6-day-old air pouch models. The animals were exposed to different exposure levels of gamma-radiation, namely either to single doses of 2 and 7.5 Gy or a fractionated dose level of 7.5 Gy delivered as 0.5 Gy twice weekly for 7.5 weeks. The inflammatory response produced by carrageenan in irradiated rats was markedly higher than that induced in non-irradiated animals, and depended on the extent of irradiation. Celecoxib, a selective COX-2 inhibitor, in doses of 3, 5, 10, and 15 mg/kg was effective in reducing paw edema in irradiated and non-irradiated rats in a dose-dependent manner as well as diclofenac (3 mg/kg), a non-selective COX inhibitor. Irradiation of animals before the induction of the air pouch by an acute dose of 2 Gy led to a significant increase in leukocytic count, as well as in the level of interleukin-6 (IL-6), interleukin-1beta (IL-1beta), tumor necrosis factor-alpha (TNF-alpha), LTB(4), PGE(2) (as an index of COX-2 activity), TXB(2) (as an index of COX-1 activity), and the plasma level of MDA. This increase in level of these parameters was more marked than that observed in the non-irradiated animals subjected to the inflammagen. The blood GSH level was not affected by the dose of irradiation used, whereas superoxide dismutase (SOD) activity was suppressed. In many respects, celecoxib (5 mg/kg) was as potent as diclofenac in decreasing the elevated levels of IL-6, IL-1beta, TNF-alpha, LTB(4), PGE(2), but lacked any significant effect on TXB(2) level. Since it is mostly selective for COX-2 with a rare effect on COX-1 enzyme, both drugs at the selected dose levels showed no effect on level of MDA, GSH, and SOD activity.

  19. A time course analysis of satiety-induced instrumental outcome devaluation.

    PubMed

    Parkes, Shauna L; Marchand, Alain R; Ferreira, Guillaume; Coutureau, Etienne

    2016-12-01

    Sensory-specific satiety is commonly used in studies of decision making to selectively devalue a food reward. Devaluation is reflected in an immediate reduction in the subsequent intake of the food and in the performance of actions that gain access to that food. Despite its frequent use, the lasting effects of satiety-induced devaluation on instrumental actions are unknown. Here, we examined the time course and contextual dependency of sensory-specific satiety-induced devaluation on instrumental responding and consumption. Rats were trained to perform two instrumental actions for two distinct food rewards. Then, one of the instrumental outcomes was provided ad libitum for 1 hour in separate feeding cages and the effect of this devaluation was assessed 0, 2, or 5 hours after satiation. At a delay of 0 or 2 hours, both intake and instrumental responding were sensitive to the satiety treatment. That is, rats consumed less of the devalued outcome and responded less for the devalued outcome than for the valued outcome. By contrast, after 5 hours, rats showed sensitivity to devaluation in consumption but not in instrumental responding. Strikingly, sensitivity to devaluation was restored for the instrumental response after a 5 hour delay when devaluation was performed in the instrumental context. These results indicate that, in rats, specific satiety-induced devaluation endures and is context-independent for up to 2 hours post-satiation. At longer delays, the impact of sensory-specific satiety on instrumental responding is context-dependent, suggesting that contextual cues may be required for the value of specific outcomes to control instrumental responding.

  20. Model Estimation and Selection towardsUnconstrained Real-Time Tracking and Mapping.

    PubMed

    Gauglitz, Steffen; Sweeney, Chris; Ventura, Jonathan; Turk, Matthew; Höllerer, Tobias

    2014-06-01

    We present an approach and prototype implementation to initialization-free real-time tracking and mapping that supports any type of camera motion in 3D environments, that is, parallax-inducing as well as rotation-only motions. Our approach effectively behaves like a keyframe-based Simultaneous Localization and Mapping system or a panorama tracking and mapping system, depending on the camera movement. It seamlessly switches between the two modes and is thus able to track and map through arbitrary sequences of parallax-inducing and rotation-only camera movements. The system integrates both model-based and model-free tracking, automatically choosing between the two depending on the situation, and subsequently uses the "Geometric Robust Information Criterion" to decide whether the current camera motion can best be represented as a parallax-inducing motion or a rotation-only motion. It continues to collect and map data after tracking failure by creating separate tracks which are later merged if they are found to overlap. This is in contrast to most existing tracking and mapping systems, which suspend tracking and mapping and thus discard valuable data until relocalization with respect to the initial map is successful. We tested our prototype implementation on a variety of video sequences, successfully tracking through different camera motions and fully automatically building combinations of panoramas and 3D structure.

  1. Meditation-induced states predict attentional control over time.

    PubMed

    Colzato, Lorenza S; Sellaro, Roberta; Samara, Iliana; Baas, Matthijs; Hommel, Bernhard

    2015-12-01

    Meditation is becoming an increasingly popular topic for scientific research and various effects of extensive meditation practice (ranging from weeks to several years) on cognitive processes have been demonstrated. Here we show that extensive practice may not be necessary to achieve those effects. Healthy adult non-meditators underwent a brief single session of either focused attention meditation (FAM), which is assumed to increase top-down control, or open monitoring meditation (OMM), which is assumed to weaken top-down control, before performing an Attentional Blink (AB) task - which assesses the efficiency of allocating attention over time. The size of the AB was considerably smaller after OMM than after FAM, which suggests that engaging in meditation immediately creates a cognitive-control state that has a specific impact on how people allocate their attention over time. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Inducing and Probing Attosecond-Time-Scale Electronic Wavefunction Beating

    NASA Astrophysics Data System (ADS)

    Ott, Christian; Raith, Philipp; Pfeifer, Thomas

    2010-03-01

    Much of the current interest in the field of ultrafast science focuses on the observation of attosecond dynamics of electronic wavepackets. These experiments typically require attosecond pulses either for pumping or probing such dynamics and/or are limited to observing electronic states embedded in the ionization continuum of atoms. Here, we present numerical evidence---based on solutions of the time-dependent Schr"odinger equation for a 1-dimensional model atom---that a pump--probe scheme with two few-cycle femtosecond laser pulses provides interferometric access to sub-femtosecond electron wavepacket dynamics. Both continuum- and bound-state electronic wavepacket interference can be simultaneously observed by recording and analyzing time-delay dependent interferences in the ATI spectrum of an atom. Both dipole-allowed and forbidden electronic transition information can be extracted from the data, making this approach a versatile and comprehensive spectroscopic method for probing the bound electronic level structure of an atom.

  3. Ultrafast nuclear dynamics in halomethanes studied with time-resolved Coulomb explosion imaging and channel-selective Fourier spectroscopy

    NASA Astrophysics Data System (ADS)

    Malakar, Y.; Kaderiya, B.; Pearson, W. L.; Ziaee, F.; Kanaka Raju, P.; Zohrabi, M.; Jensen, K.; Rajput, J.; Ben-Itzhak, I.; Rolles, D.; Rudenko, A.

    2016-05-01

    Halomethanes have recently attracted considerable attention since they often serve as prototype systems for laser-controlled chemistry (e.g., selective bond breaking or concerted elimination reactions), and are important molecules in atmospheric chemistry. Here we combine a femtosecond laser pump-probe setup with coincident 3D ion momentum imaging apparatus to study strong-field induced nuclear dynamics in methane and several of its halogenated derivatives (CH3 I, CH2 I2, CH2 ICl). We apply a time-resolved Coulomb explosion imaging technique to map the nuclear motion on both, bound and continuum potential surfaces, disentangle different fragmentation pathways and, for halogenated molecules, observe clear signatures of vibrational wave packets in neutral or ionized states. Channel-selective and kinetic-energy resolved Fourier analysis of these data allows for unique identification of different electronic states and vibrational modes responsible for a particular structure. Supported by the Chemical Sciences, Geosciences, and Biosciences Division, Office of Basic Energy Sciences, Office of Science, U. S. DOE. K. R. P. and W. L. P. supported by NSF Award No. IIA-143049. K.J. supported by the NSF-REU Grant No. PHYS-1461251.

  4. Blockade of 5-HT2 Receptor Selectively Prevents MDMA-Induced Verbal Memory Impairment

    PubMed Central

    van Wel, J H P; Kuypers, K P C; Theunissen, E L; Bosker, W M; Bakker, K; Ramaekers, J G

    2011-01-01

    3,4-Methylenedioxymethamphetamine (MDMA) or ‘ecstasy' has been associated with memory deficits during abstinence and intoxication. The human neuropharmacology of MDMA-induced memory impairment is unknown. This study investigated the role of 5-HT2A and 5-HT1A receptors in MDMA-induced memory impairment. Ketanserin is a 5-HT2A receptor blocker and pindolol a 5-HT1A receptor blocker. It was hypothesized that pretreatment with ketanserin and pindolol would protect against MDMA-induced memory impairment. Subjects (N=17) participated in a double-blind, placebo-controlled, within-subject design involving six experimental conditions consisting of pretreatment (T1) and treatment (T2). T1 preceded T2 by 30 min. T1–T2 combinations were: placebo–placebo, pindolol 20 mg–placebo, ketanserin 50 mg–placebo, placebo–MDMA 75 mg, pindolol 20 mg–MDMA 75 mg, and ketanserin 50 mg–MDMA 75 mg. Memory function was assessed at Tmax of MDMA by means of a word-learning task (WLT), a spatial memory task and a prospective memory task. MDMA significantly impaired performance in all memory tasks. Pretreatment with a 5-HT2A receptor blocker selectively interacted with subsequent MDMA treatment and prevented MDMA-induced impairment in the WLT, but not in the spatial and prospective memory task. Pretreatment with a 5-HT1A blocker did not affect MDMA-induced memory impairment in any of the tasks. Together, the results demonstrate that MDMA-induced impairment of verbal memory as measured in the WLT is mediated by 5-HT2A receptor stimulation. PMID:21562484

  5. Vascular dysfunction induced by hypochlorite is improved by the selective phosphodiesterase-5-inhibitor vardenafil.

    PubMed

    Radovits, Tamás; Arif, Rawa; Bömicke, Timo; Korkmaz, Sevil; Barnucz, Enikő; Karck, Matthias; Merkely, Béla; Szabó, Gábor

    2013-06-15

    Reactive oxygen species, such as hypochlorite induce oxidative stress, which impairs nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signalling and leads to vascular dysfunction. It has been proposed, that elevated cGMP-levels may contribute to an effective cytoprotection against oxidative stress. We investigated the effects of vardenafil, a selective inhibitor of the cGMP-degrading phosphodiesterase-5 enzyme on vascular dysfunction induced by hypochlorite. In organ bath experiments for isometric tension, we investigated the endothelium-dependent and endothelium-independent vasorelaxation of isolated rat aortic rings using cumulative concentrations of acetylcholine and sodium nitroprusside (SNP). Vascular dysfunction was induced by exposing rings to hypochlorite (100-400 µM). In the treatment groups, rats were pretreated with vardenafil (30 and 300 µg/kg i.v.). Immunohistochemical analysis was performed for the oxidative stress markers nitrotyrosine, poly(ADP-ribose) and for apoptosis inducing factor (AIF). Exposure to hypochlorite resulted in a marked impairment of acetylcholine-induced endothelium-dependent vasorelaxation of aortic rings. Pretreatment with vardenafil led to improved endothelial function as reflected by the higher maximal vasorelaxation (Rmax) to acetylcholine. Regarding endothelium-independent vasorelaxation, hypochlorite exposure led to a left-shift of SNP concentration-response curves in the vardenafil groups without any alterations of the Rmax. In the hypochlorite groups immunohistochemical analysis showed enhanced poly(ADP-ribose)-formation and nuclear translocation of AIF, which were prevented by vardenafil-pretreatment. Our results support the view that cytoprotective effects of PDE-5-inhibitors on the endothelium may underlie the improved endothelial function, however, a slight sensitisation of vascular smooth muscle to NO was also confirmed. PDE-5-inhibition may represent a potential therapy approach for treating vascular

  6. Stress within a Restricted Time Window Selectively Affects the Persistence of Long-Term Memory

    PubMed Central

    Fang, Qin; Chai, Ning; Zhao, Li-Yan; Xue, Yan-Xue; Luo, Yi-Xiao; Jian, Min; Han, Ying; Shi, Hai-Shui; Lu, Lin; Wu, Ping; Wang, Ji-Shi

    2013-01-01

    The effects of stress on emotional memory are distinct and depend on the stages of memory. Memory undergoes consolidation and reconsolidation after acquisition and retrieval, respectively. Stress facilitates the consolidation but disrupts the reconsolidation of emotional memory. Previous research on the effects of stress on memory have focused on long-term memory (LTM) formation (tested 24 h later), but the effects of stress on the persistence of LTM (tested at least 1 week later) are unclear. Recent findings indicated that the persistence of LTM requires late-phase protein synthesis in the dorsal hippocampus. The present study investigated the effect of stress (i.e., cold water stress) during the late phase after the acquisition and retrieval of contextual fear memory in rats. We found that stress and corticosterone administration during the late phase (12 h) after acquisition, referred to as late consolidation, selectively enhanced the persistence of LTM, whereas stress during the late phase (12 h) after retrieval, referred to as late reconsolidation, selectively disrupted the restabilized persistence of LTM. Moreover, the effects of stress on the persistence of LTM were blocked by the corticosterone synthesis inhibitor metyrapone, which was administered before stress, suggesting that the glucocorticoid system is involved in the effects of stress on the persistence of LTM. We conclude that stress within a restricted time window after acquisition or retrieval selectively affects the persistence of LTM and depends on the glucocorticoid system. PMID:23544051

  7. [Indications of lung transplantation: Patients selection, timing of listing, and choice of procedure].

    PubMed

    Morisse Pradier, H; Sénéchal, A; Philit, F; Tronc, F; Maury, J-M; Grima, R; Flamens, C; Paulus, S; Neidecker, J; Mornex, J-F

    2016-02-01

    Lung transplantation (LT) is now considered as an excellent treatment option for selected patients with end-stage pulmonary diseases, such as COPD, cystic fibrosis, idiopathic pulmonary fibrosis, and pulmonary arterial hypertension. The 2 goals of LT are to provide a survival benefit and to improve quality of life. The 3-step decision process leading to LT is discussed in this review. The first step is the selection of candidates, which requires a careful examination in order to check absolute and relative contraindications. The second step is the timing of listing for LT; it requires the knowledge of disease-specific prognostic factors available in international guidelines, and discussed in this paper. The third step is the choice of procedure: indications of heart-lung, single-lung, and bilateral-lung transplantation are described. In conclusion, this document provides guidelines to help pulmonologists in the referral and selection processes of candidates for transplantation in order to optimize the outcome of LT. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

  8. Born at the Wrong Time: Selection Bias in the NHL Draft

    PubMed Central

    Deaner, Robert O.; Lowen, Aaron; Cobley, Stephen

    2013-01-01

    Relative age effects (RAEs) occur when those who are relatively older for their age group are more likely to succeed. RAEs occur reliably in some educational and athletic contexts, yet the causal mechanisms remain unclear. Here we provide the first direct test of one mechanism, selection bias, which can be defined as evaluators granting fewer opportunities to relatively younger individuals than is warranted by their latent ability. Because RAEs are well-established in hockey, we analyzed National Hockey League (NHL) drafts from 1980 to 2006. Compared to those born in the first quarter (i.e., January–March), those born in the third and fourth quarters were drafted more than 40 slots later than their productivity warranted, and they were roughly twice as likely to reach career benchmarks, such as 400 games played or 200 points scored. This selection bias in drafting did not decrease over time, apparently continues to occur, and reduces the playing opportunities of relatively younger players. This bias is remarkable because it is exhibited by professional decision makers evaluating adults in a context where RAEs have been widely publicized. Thus, selection bias based on relative age may be pervasive. PMID:23460902

  9. Selective deficiency in collagen-induced platelet aggregation during L-asparaginase therapy.

    PubMed

    Shapiro, R S; Gerrard, J M; Ramsay, N K; Nesbit, M E; Coccia, P F; Stoddard, S F; Plow, E F; White, J G; Krivit, W

    1980-01-01

    Platelet aggregation studies were performed on 10 pediatric patients with acute lymphoblastic leukemia (ALL) receiving induction therapy with vincristine, prednisone, and L-asparaginase. An isolated abnormality in platelet aggregation in response to collagen was found in all patients during the course of therapy. Platelet aggregation in response to collagen normalized following the discontinuation of L-asparaginase, while patients were still on vincristine and prednisone. In contrast to the abnormal collagen response, platelet aggregation induced by epinephrine, arachidonic acid, adenosine diphosphate (ADP), and thrombin were normal both during and following therapy. In the one patient with a normal platelet count before therapy, aggregation induced by all agents was normal. This selective abnormality in collagen aggregation therefore appears to result from therapy, with the use of L-asparaginase in particular being implicated.

  10. Transformation of diatom Phaeodactylum tricornutum by electroporation and establishment of inducible selection marker.

    PubMed

    Niu, Ying-Fang; Yang, Zhi-Kai; Zhang, Meng-Han; Zhu, Cong-Cong; Yang, Wei-Dong; Liu, Jie-Sheng; Li, Hong-Ye

    2012-06-01

    Diatoms are important primary producers in the marine ecosystem. Currently it is difficult to genetically transform diatoms due to the technical limitations of existing methods. The promoter/terminator of the nitrate reductase gene of the model diatom Phaeodactylum tricornutum was cloned and used to drive chloramphenicol acetyltransferase (CAT) reporter gene expression. The construct was transferred by electroporation into P. tricornutum grown in medium lacking silicon. CAT expression was induced in transformed diatoms in the presence of nitrate, enabling growth in selective medium, and was repressed when ammonium was the only nitrogen source. Expression of CAT transcript and protein were demonstrated by RT-PCR and Western blot analysis, respectively. Our study is the first to report a successful genetic transformation of diatom by electroporation in an economical and efficient manner and provides a tightly regulated inducible gene expression system for diatom.

  11. Neighbourhood selection for local modelling and prediction of hydrological time series

    NASA Astrophysics Data System (ADS)

    Jayawardena, A. W.; Li, W. K.; Xu, P.

    2002-02-01

    The prediction of a time series using the dynamical systems approach requires the knowledge of three parameters; the time delay, the embedding dimension and the number of nearest neighbours. In this paper, a new criterion, based on the generalized degrees of freedom, for the selection of the number of nearest neighbours needed for a better local model for time series prediction is presented. The validity of the proposed method is examined using time series, which are known to be chaotic under certain initial conditions (Lorenz map, Henon map and Logistic map), and real hydro meteorological time series (discharge data from Chao Phraya river in Thailand, Mekong river in Thailand and Laos, and sea surface temperature anomaly data). The predicted results are compared with observations, and with similar predictions obtained by using arbitrarily fixed numbers of neighbours. The results indicate superior predictive capability as measured by the mean square errors and coefficients of variation by the proposed approach when compared with the traditional approach of using a fixed number of neighbours.

  12. Superfamily phenomena and motifs of networks induced from time series

    PubMed Central

    Xu, Xiaoke; Zhang, Jie; Small, Michael

    2008-01-01

    We introduce a transformation from time series to complex networks and then study the relative frequency of different subgraphs within that network. The distribution of subgraphs can be used to distinguish between and to characterize different types of continuous dynamics: periodic, chaotic, and periodic with noise. Moreover, although the general types of dynamics generate networks belonging to the same superfamily of networks, specific dynamical systems generate characteristic dynamics. When applied to discrete (map-like) data this technique distinguishes chaotic maps, hyperchaotic maps, and noise data. PMID:19064916

  13. Selective induction of integrin beta1 by hypoxia-inducible factor: implications for wound healing.

    PubMed

    Keely, Simon; Glover, Louise E; MacManus, Christopher F; Campbell, Eric L; Scully, Melanie M; Furuta, Glenn T; Colgan, Sean P

    2009-05-01

    Because of localized vascular damage and increased tissue oxygen demand, wound healing occurs in a relatively hypoxic microenvironment. These features are particularly relevant to wound healing and fibrosis in chronic inflammatory conditions, such as Crohn's disease and ulcerative colitis. In these studies, we sought to identify the contribution of hypoxia to mechanisms of wound repair in a model of the intestinal submucosa. Initial studies revealed that hypoxia promotes wound healing, as modeled by an increase in intestinal fibroblast-mediated collagen gel contraction. Guided by results from transcriptional profiling, we identified the selective induction of fibroblast integrin beta1 (ITGB1) by hypoxia. Further analysis revealed that hypoxia, as well as pharmacological activators of hypoxia-inducible factor (HIF), induce fibroblast beta1 integrin mRNA, protein, and function by as much as 4-fold. Cloning and analysis of the beta1 integrin gene promoter revealed a 10 +/- 0.8-fold increase in promoter activity in response to hypoxia, and subsequent studies identified a functional DNA binding region for HIF in the ITGB1 gene promoter. Mutational analysis of the HIF binding site within the ITGB1 promoter resulted in a significant loss of ITGB1 hypoxia-inducibility. As proof of principle, studies in a murine model of colitis revealed a correlation between colitic disease severity and tissue ITGB1 expression (R(2)=0.80). Taken together, these results demonstrate that hypoxia induces fibroblast ITGB1 expression and function by transcriptional mechanisms dependent on HIF.

  14. The synthetic purine reversine selectively induces cell death of cancer cells.

    PubMed

    Piccoli, Marco; Palazzolo, Giacomo; Conforti, Erika; Lamorte, Giuseppe; Papini, Nadia; Creo, Pasquale; Fania, Chiara; Scaringi, Raffaella; Bergante, Sonia; Tringali, Cristina; Roncoroni, Leda; Mazzoleni, Stefania; Doneda, Luisa; Galli, Rossella; Venerando, Bruno; Tettamanti, Guido; Gelfi, Cecilia; Anastasia, Luigi

    2012-10-01

    The synthetic purine reversine has been shown to possess a dual activity as it promotes the de-differentiation of adult cells, including fibroblasts, into stem-cell-like progenitors, but it also induces cell growth arrest and ultimately cell death of cancer cells, suggesting its possible application as an anti-cancer agent. Aim of this study was to investigate the mechanism underneath reversine selectivity in inducing cell death of cancer cells by a comparative analysis of its effects on several tumor cells and normal dermal fibroblasts. We found that reversine is lethal for all cancer cells studied as it induces cell endoreplication, a process that malignant cells cannot effectively oppose due to aberrations in cell cycle checkpoints. On the other hand, normal cells, like dermal fibroblasts, can control reversine activity by blocking the cell cycle, entering a reversible quiescent state. However, they can be induced to become sensitive to the molecule when key cell cycle proteins, e.g., p53, are silenced. Copyright © 2012 Wiley Periodicals, Inc.

  15. UV-induced changes in antioxidant capacities of selected carotenoids toward lecithin in aqueous solution

    NASA Astrophysics Data System (ADS)

    Cvetkovic, Dragan; Markovic, Dejan

    2008-01-01

    Antioxidant action of four selected carotenoids (two carotenes, β-carotene and lycopene, and two xanthophylls, lutein and neoxanthin) on UV-induced lecithin lipid peroxidation in aqueous solution has been studied by thiobarbituric acid (TBA) test. TBA test is based on absorbance measurements of complex formed between malondialdehyde, secondary product of lipid peroxidation and thiobarbituric acid, at 532 nm. The antioxidant capacities of investigated carotenoids appeared to be strongly affected by UV-action. High energy input of the involved UV-photons plays major governing role, though a certain impact of the carotenoid structures cannot be neglected. The results suggest a minor remained contribution of selected carotenoids to prevention of lecithin peroxidation in the studied system as a result of UV-irradiation.

  16. Selection of motor programs for suppressing food intake and inducing locomotion in the Drosophila brain.

    PubMed

    Schoofs, Andreas; Hückesfeld, Sebastian; Schlegel, Philipp; Miroschnikow, Anton; Peters, Marc; Zeymer, Malou; Spieß, Roland; Chiang, Ann-Shyn; Pankratz, Michael J

    2014-06-01

    Central mechanisms by which specific motor programs are selected to achieve meaningful behaviors are not well understood. Using electrophysiological recordings from pharyngeal nerves upon central activation of neurotransmitter-expressing cells, we show that distinct neuronal ensembles can regulate different feeding motor programs. In behavioral and electrophysiological experiments, activation of 20 neurons in the brain expressing the neuropeptide hugin, a homolog of mammalian neuromedin U, simultaneously suppressed the motor program for food intake while inducing the motor program for locomotion. Decreasing hugin neuropeptide levels in the neurons by RNAi prevented this action. Reducing the level of hugin neuronal activity alone did not have any effect on feeding or locomotion motor programs. Furthermore, use of promoter-specific constructs that labeled subsets of hugin neurons demonstrated that initiation of locomotion can be separated from modulation of its motor pattern. These results provide insights into a neural mechanism of how opposing motor programs can be selected in order to coordinate feeding and locomotive behaviors.

  17. Time takes space: selective effects of multitasking on concurrent spatial processing.

    PubMed

    Mäntylä, Timo; Coni, Valentina; Kubik, Veit; Todorov, Ivo; Del Missier, Fabio

    2017-03-18

    Many everyday activities require coordination and monitoring of complex relations of future goals and deadlines. Cognitive offloading may provide an efficient strategy for reducing control demands by representing future goals and deadlines as a pattern of spatial relations. We tested the hypothesis that multiple-task monitoring involves time-to-space transformational processes, and that these spatial effects are selective with greater demands on coordinate (metric) than categorical (nonmetric) spatial relation processing. Participants completed a multitasking session in which they monitored four series of deadlines, running on different time scales, while making concurrent coordinate or categorical spatial judgments. We expected and found that multitasking taxes concurrent coordinate, but not categorical, spatial processing. Furthermore, males showed a better multitasking performance than females. These findings provide novel experimental evidence for the hypothesis that efficient multitasking involves metric relational processing.

  18. Deuterium enrichment by selective photo-induced dissociation of an organic carbonyl compound

    DOEpatents

    Marling, John B.

    1981-01-01

    A method for producing a deuterium enriched material by photoinduced dissociation which uses as the working material a gas phase photolytically dissociable organic carbonyl compound containing at least one hydrogen atom bonded to an atom which is adjacent to a carbonyl group and consisting of molecules wherein said hydrogen atom is present as deuterium and molecules wherein said hydrogen atom is present as another isotope of hydrogen. The organic carbonyl compound is subjected to intense infrared radiation at a preselected wavelength to selectively excite and thereby induce dissociation of the deuterium containing species to yield a deuterium enriched stable molecular product. Undissociated carbonyl compound, depleted in deuterium, is preferably redeuterated for reuse.

  19. Avoidance of fisheries-induced evolution: management implications for catch selectivity and limit reference points.

    PubMed

    Hutchings, Jeffrey A

    2009-08-01

    I examined how the fitness (r) associated with early- and late-maturing genotypes varies with fishing mortality (F) and age-/size-specific probability of capture. Life-history data on Newfoundland's northern Atlantic cod (Gadus morhua) allowed for the estimation of r for individuals maturing at 4 and 7 year in the absence of fishing. Catch selectivity data associated with four types of fishing gear (trap, gillnet, handline, otter trawl) were then incorporated to examine how r varied with gear type and with F. The resulting fitness functions were then used to estimate the F above which selection would favour early (4 year) rather than delayed (7 year) maturity. This evolutionarily-sensitive threshold, F evol, identifies a limit reference point somewhat similar to those used to define overfishing (e.g., F msy, F 0.1). Over-exploitation of northern cod resulted in fishing mortalities considerably greater than those required to effect evolutionary change. Selection for early maturity is reduced by the dome-shaped selectivities characteristic of fixed gears such as handlines (the greater the leptokurtosis, the lower the probability of a selection response) and enhanced by the knife-edged selectivities of bottom trawls. Strategies to minimize genetic change are consistent with traditional management objectives (e.g., yield maximization, population increase). Compliance with harvest control rules guided by evolutionarily-sensitive limit reference points, which may be achieved by adherence to traditional reference points such as F msy and F 0.1, should be sufficient to minimize the probability of fisheries-induced evolution for commercially exploited species.

  20. Avoidance of fisheries-induced evolution: management implications for catch selectivity and limit reference points

    PubMed Central

    Hutchings, Jeffrey A

    2009-01-01

    I examined how the fitness (r) associated with early- and late-maturing genotypes varies with fishing mortality (F) and age-/size-specific probability of capture. Life-history data on Newfoundland's northern Atlantic cod (Gadus morhua) allowed for the estimation of r for individuals maturing at 4 and 7 year in the absence of fishing. Catch selectivity data associated with four types of fishing gear (trap, gillnet, handline, otter trawl) were then incorporated to examine how r varied with gear type and with F. The resulting fitness functions were then used to estimate the F above which selection would favour early (4 year) rather than delayed (7 year) maturity. This evolutionarily-sensitive threshold, Fevol, identifies a limit reference point somewhat similar to those used to define overfishing (e.g., Fmsy, F0.1). Over-exploitation of northern cod resulted in fishing mortalities considerably greater than those required to effect evolutionary change. Selection for early maturity is reduced by the dome-shaped selectivities characteristic of fixed gears such as handlines (the greater the leptokurtosis, the lower the probability of a selection response) and enhanced by the knife-edged selectivities of bottom trawls. Strategies to minimize genetic change are consistent with traditional management objectives (e.g., yield maximization, population increase). Compliance with harvest control rules guided by evolutionarily-sensitive limit reference points, which may be achieved by adherence to traditional reference points such as Fmsy and F0.1, should be sufficient to minimize the probability of fisheries-induced evolution for commercially exploited species. PMID:25567884

  1. Recognition of Time-Compressed and Natural Speech with Selective Temporal Enhancements by Young and Elderly Listeners

    ERIC Educational Resources Information Center

    Gordon-Salant, Sandra; Fitzgibbons, Peter J.; Friedman, Sarah A.

    2007-01-01

    Purpose: The goal of this experiment was to determine whether selective slowing of speech segments improves recognition performance by young and elderly listeners. The hypotheses were (a) the benefits of time expansion occur for rapid speech but not for natural-rate speech, (b) selective time expansion of consonants produces greater score…

  2. Recognition of Time-Compressed and Natural Speech with Selective Temporal Enhancements by Young and Elderly Listeners

    ERIC Educational Resources Information Center

    Gordon-Salant, Sandra; Fitzgibbons, Peter J.; Friedman, Sarah A.

    2007-01-01

    Purpose: The goal of this experiment was to determine whether selective slowing of speech segments improves recognition performance by young and elderly listeners. The hypotheses were (a) the benefits of time expansion occur for rapid speech but not for natural-rate speech, (b) selective time expansion of consonants produces greater score…

  3. Positive selection of T-lymphocytes induced by intrathymic injection of a thymic epithelial cell line

    PubMed Central

    Vukmanović, Stanislav; Grandea, Andres G.; Faas, Susan J.; Knowles, Barbara B.; Bevan, Michael J.

    2009-01-01

    Tlymphocytes recognize antigens as peptide fragments associated with molecules encoded by the major histocompatibility complex (MHC) and expressed on the surface of antigen-presenting cells1. In the thymus, T cells bearing αβ receptors that react with the MHC molecules expressed by radioresistant stromal elements are positively selected for maturation2–5. In (A × B → A) bone marrow chimaeras, T cells restricted to the MHC-A haplotype are positively selected, whereas MHC-B-reactive thymocytes are not. We investigated whether the introduction of particular thymic stromal elements bearing MHC-B molecules could alter the fate of B-reactive T cells in these (A × B → A) chimaeras. Thymic epithelial cell (TEC) lines expressing H-2b were introduced by intrathymic injection into (H-2b/s → H2S) bone marrow chimaeras and we measured their ability to generate H-2b-restricted cytotoxic T-lymphocytes (CTLs). We report here that one TEC line, 427.1, was able positively to select CTLs specific for influenza and vesicular stomatitis virus antigens in association with class I H–2b molecules. In addition, line 427.1 can process cytoplasmic proteins for presentation to H–2Kb- and H-2Db-restricted CTLs. Thus, a TEC line capable of normal class I MHC antigen processing and presentation in vitro can induce positive selection after intrathymic injection. PMID:1331804

  4. Selection of single chain variable fragments specific for the human-inducible costimulator using ribosome display.

    PubMed

    Pan, Yangbin; Mao, Weiping; Liu, Xuanxuan; Xu, Chong; He, Zhijuan; Wang, Wenqian; Yan, Hao

    2012-11-01

    We applied a ribosome display technique to a mouse single chain variable fragment (scFv) library to select scFvs specific for the inducible costimulator (ICOS). mRNA was isolated from the spleens of BALB/c mice immunized with ICOS protein. Heavy and κ chain genes (VH and κ) were amplified separately by reverse transcriptase polymerase chain reaction, and the anti-ICOS VH/κ chain ribosome display library was constructed with a special flexible linker by overlap extension PCR. The VH/κ chain library was transcribed and translated in vitro using a rabbit reticulocyte lysate system. Then, antibody-ribosome-mRNA complexes were produced and panned against ICOS protein under appropriate conditions. However, in order to isolate specific scFvs for ICOS, negative selection using CD28 was carried out before three rounds of positive selection on ICOS. After three rounds of panning, the selected scFv DNAs were cloned into pET43.1a and detected by SDS-PAGE. Then, enzyme-linked immunosorbent assay showed that we successfully constructed a native ribosome display library, and among seven clones, clone 5 had the highest affinity for the ICOS and low for the CD28. Anti-ICOS scFvs are assessed for binding specificity and affinity and may provide the potential for development of the humanized and acute and chronic allograft rejection.

  5. Direct numerical simulation of current-induced convection near an ion-selective surface

    NASA Astrophysics Data System (ADS)

    Druzgalski, Clara; Andersen, Mathias B.; Mani, Ali

    2012-11-01

    Understanding fundamentals of electrokinetic transport and fluid flow phenomena near ion-selective surfaces provides insight to improve systems such as electrodialysis for water deionization. The work of Rubinstein and Zaltzman [e.g. Phys Rev E 62, 2238 (2000)] have clarified qualitative aspects of how development of current-induced space-charge layers near ion-selective surfaces can lead to the onset of electro-osmotic instabilities. We expand on this work through multidimensional numerical simulation of the full nonlinear Poisson-Nernst-Planck and Navier-Stokes equations with ideally selective membrane boundary conditions. Our numerical scheme is optimized by exploiting the periodicity in the system parallel to the ion-selective surface, using a spectral method in these coordinates. In the wall normal direction a finite difference approach accurately captures the strongly nonlinear nested boundary layer structure. Our numerical scheme fully resolves the concentration profiles throughout the system including the numerically stiff electric double layer and extended space charge layer. Our simulations enable prediction of the full continuous current versus voltage curves showing overlimiting current without resorting to any adjustable parameter.

  6. Maternal exposures in the National Birth Defects Prevention Study: time trends of selected exposures

    PubMed Central

    Dawson, April L.; Razzaghi, Hilda; Arth, Annelise; Canfield, Mark A.; Parker, Samantha E.; Reefhuis, Jennita

    2015-01-01

    Background Our objective was to describe time trends in selected pregnancy exposures in the National Birth Defects Prevention Study (NBDPS). Methods We analyzed data from the NBDPS, a multi-site case-control study of major birth defects, for mothers of live-born infants without birth defects (controls), with an expected date of delivery (EDD) from 1998 –2011. Mothers from the 10 participating centers across the United States were interviewed by phone between six weeks and two years after the EDD. We focused on maternal race/ethnicity and five maternal risk factors: obesity, use of folic acid-containing multivitamins, opioid analgesics, selective serotonin reuptake inhibitors (SSRIs), and loratadine because of their prevalence of use and some reports of associations with major birth defects. Prevalence time trends were examined using the Kendall’s τβ test statistic. Results The exposure trend analysis included 11,724 control mothers with EDDs from 1998–2011. We observed a significant increase in obesity prevalence among control mothers, as well as use of SSRIs and loratadine. We also observed an increase in periconceptional use of folic acid-containing multivitamins. Some of the time trends varied by race/ethnicity. No remarkable trend in the overall use of opioid analgesics was observed. The racial/ethnic distribution of mothers changed slightly during the study period. Conclusions Long-term, population-based case-control studies continue to be an effective way to assess exposure-birth defects associations and provide guidance to health care providers. However, investigators examining rare outcomes covering many years of data collection need to be cognizant of time trends in exposures. PMID:25884728

  7. Predicting bacterial resistance using the time inside the mutant selection window: possibilities and limitations.

    PubMed

    Firsov, Alexander A; Portnoy, Yury A; Strukova, Elena N; Shlykova, Darya S; Zinner, Stephen H

    2014-10-01

    The time inside the mutant selection window (TMSW) has been shown to be less predictive of selection of fluoroquinolone-resistant bacteria than the ratio of the area under the concentration-time curve to minimum inhibitory concentration (AUC/MIC). To explore the different predictive powers of TMSW and AUC/MIC, enrichment of ciprofloxacin-resistant mutants of four Escherichia coli strains was studied in an in vitro dynamic model at widely ranging TMSW values. Each organism was exposed to twice-daily ciprofloxacin for 3 days. Peak antibiotic concentrations were simulated to be close to the MIC, between the MIC and the mutant prevention concentration (MPC), and above the MPC, with TMSW varying from 0% to 100% of the dosing interval. Amplification of resistant mutants was monitored by plating on medium with 8× MIC of the antibiotic. For each organism, TMSW plots of the area under the bacterial mutant concentration-time curve (AUBCM) exhibited a hysteresis loop: at a given TMSW that corresponds to the points on the ascending portion of the bell-shaped AUBCM-AUC/MIC curve [when the time above the MPC (T>MPC) was zero], the AUBCM was greater than at the same TMSW related to the descending portion (T>MPC>0). A sigmoid function fits these separate data sets well for combined data with the four organisms (r(2)=0.81 and 0.92, respectively), in contrast to fitting the whole data pool while ignoring the AUC/MIC-resistance relationship (r(2)=0.61). These data allow the appropriate use of TMSW as a predictor of bacterial resistance.

  8. Selective 6OHDA-induced destruction of mesolimbic dopamine neurons: abolition of psychostimulant-induced locomotor activity in rats.

    PubMed

    Kelly, P H; Iversen, S D

    1976-11-01

    Selective large scale destruction of mesolimbic dopamine-containing terminals is produced by bilateral injection of 8 mug of 6-hydroxydopamine (6OHDA) into the nucleus accumbens septi (NAS) of rats pretreated with pargyline and desipramine (DMI). The DMI prevents the destruction of the noradrenergic innervation of the forebrain normally produced by the NAS 6OHDA lesion, without affecting the destruction of dopamine-containing neurons. The locomotor stimulation produced by the psychostimulants d-amphetamine (1.5 mg/kg) and cocaine (20 mg/kg) is blocked in rats with selective destruction of the mesolimbic dopamine system. In contrast the locomotor stimulation produced by the directly acting dopamine agonist apomorphine (1.0 mg/kg) is enhanced, which may indicate supersensitivity of the denervated dopamine receptors. These results lend further support to the view that psychostimulant-induced locomotr stimulation in rats results from effects on mesolimbic dopamine neurons. In addition, the protection by DMI of noradrenergic neurons from the toxic effects of 6OHDA is evidence that 6OHDA, as used here, destroys catecholamine neurons mainly by an uptake-dependent specific mechanism.

  9. Adaptation through genetic time travel? Fluctuating selection can drive the evolution of bacterial transformation.

    PubMed

    Engelstädter, Jan; Moradigaravand, Danesh

    2014-01-22

    Natural transformation is a process whereby bacteria actively take up DNA from the surrounding environment and incorporate it into their genome. Natural transformation is widespread in bacteria, but its evolutionary significance is still debated. Here, we hypothesize that transformation may confer a fitness advantage in changing environments through a process we term 'genetic time travel': by taking up old genes that were retained in the environment, the bacteria may revert to a past genotypic state that proves advantageous in the present or a future environment. We scrutinize our hypothesis by means of a mathematical model involving two bacterial types (transforming and non-transforming), a single locus under natural selection and a free DNA pool. The two bacterial types were competed in environments with changing selection regimes. We demonstrate that for a wide range of parameter values for the DNA turnover rate, the transformation rate and the frequency of environmental change, the transforming type outcompetes the non-transforming type. We discuss the empirical plausibility of our hypothesis, as well as its relationship to other hypotheses for the evolution of transformation in bacteria and sex more generally, speculating that 'genetic time travel' may also be relevant in eukaryotes that undergo horizontal gene transfer.

  10. Dependence of the Crossing Time on the Sequence Length in a Diploid Discrete-Time Mutation-Selection Model for a Finite Population

    NASA Astrophysics Data System (ADS)

    Gill, Wonpyong

    This study examined the crossing time in the diploid discrete-time mutation-selection model in a finite population for a range of dominance parameters and selective advantages by switching on a diploid, asymmetric, bridged landscape, from an initial state, a steady state in a diploid, bridged landscape. The dependence of the crossing time on the sequence length was examined for a fixed extension parameter, which was defined as the mean Hamming distance from the optimal allele of the initial steady state divided by the sequence length. The boundary between the deterministic and stochastic regions in the diploid discrete-time mutation-selection model was characterized using the same formula as that in the haploid discrete-time mutation-selection model. The crossing time in a finite population with various population sizes, dominance parameters and selective advantages began to deviate from the crossing time for an infinite population at the critical sequence length. The crossing time for a finite population in the stochastic region was found to be an exponentially increasing function of the sequence length, whose rate was unchanged, regardless of changes in the population size, dominance parameter and selective advantage with a fixed extension parameter. This work was supported by a 2-Year Research Grant of Pusan National University.

  11. Real-time observation of liposome bursting induced by acetonitrile.

    PubMed

    Yoshida, Kazunari; Horii, Keitaro; Fujii, Yasuhiro; Nishio, Izumi

    2014-10-06

    We show the bursting process of dioleoylphosphatidylcholine (DOPC) liposomes in response to the addition of acetonitrile, a small toxic molecule widely used in the fields of chemistry and industry. The percentage of destroyed liposomes is reduced upon decreasing the acetonitrile fraction in the aqueous solution and vesicle bursting is not observed at volume ratios of 4:6 and below. This indicates that a high fraction of acetonitrile causes the bursting of liposomes, and it is proposed that this occurs through insertion of the molecules into outer leaflet of the lipid bilayer. The elapsed time between initial addition of acetonitrile and liposome bursting at each vesicle is also measured and demonstrated to be dependent on the volume fraction of acetonitrile and the vesicle size.

  12. Spin-orbit torque induced spike-timing dependent plasticity

    SciTech Connect

    Sengupta, Abhronil Al Azim, Zubair; Fong, Xuanyao; Roy, Kaushik

    2015-03-02

    Nanoelectronic devices that mimic the functionality of synapses are a crucial requirement for performing cortical simulations of the brain. In this work, we propose a ferromagnet-heavy metal heterostructure that employs spin-orbit torque to implement spike-timing dependent plasticity. The proposed device offers the advantage of decoupled spike transmission and programming current paths, thereby leading to reliable operation during online learning. Possible arrangement of such devices in a crosspoint architecture can pave the way for ultra-dense neural networks. Simulation studies indicate that the device has the potential of achieving pico-Joule level energy consumption (maximum 2 pJ per synaptic event) which is comparable to the energy consumption for synaptic events in biological synapses.

  13. Automated selection of brain regions for real-time fMRI brain-computer interfaces

    NASA Astrophysics Data System (ADS)

    Lührs, Michael; Sorger, Bettina; Goebel, Rainer; Esposito, Fabrizio

    2017-02-01

    Objective. Brain-computer interfaces (BCIs) implemented with real-time functional magnetic resonance imaging (rt-fMRI) use fMRI time-courses from predefined regions of interest (ROIs). To reach best performances, localizer experiments and on-site expert supervision are required for ROI definition. To automate this step, we developed two unsupervised computational techniques based on the general linear model (GLM) and independent component analysis (ICA) of rt-fMRI data, and compared their performances on a communication BCI. Approach. 3 T fMRI data of six volunteers were re-analyzed in simulated real-time. During a localizer run, participants performed three mental tasks following visual cues. During two communication runs, a letter-spelling display guided the subjects to freely encode letters by performing one of the mental tasks with a specific timing. GLM- and ICA-based procedures were used to decode each letter, respectively using compact ROIs and whole-brain distributed spatio-temporal patterns of fMRI activity, automatically defined from subject-specific or group-level maps. Main results. Letter-decoding performances were comparable to supervised methods. In combination with a similarity-based criterion, GLM- and ICA-based approaches successfully decoded more than 80% (average) of the letters. Subject-specific maps yielded optimal performances. Significance. Automated solutions for ROI selection may help accelerating the translation of rt-fMRI BCIs from research to clinical applications.

  14. Magnetic-field-induced diameter-selective synthesis of single-walled carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Su, Yanjie; Zhang, Yaozhong; Wei, Hao; Zhang, Liling; Zhao, Jiang; Yang, Zhi; Zhang, Yafei

    2012-02-01

    We report a facile and scalable approach to synthesize single-walled carbon nanotubes (SWNTs) with selected diameter distribution by applying a magnetic field perpendicular to the electric field in the arc plasma region. It is found that this magnetic field-induced diameter-selectivity strategy enables the control of the SWNTs with different diameter distributions in different regions, and the diameter-selective efficiency could be enhanced by modifying the direction of magnetic field. Our results indicate that the motions of the catalysts with different particle sizes, positive carbon ions and electrons are significantly influenced by the magnetic field and electromagnetic force, resulting in the different nucleation and growth processes of SWNTs due to the collective interactions between the magnetic field and arc plasma. This approach would enable a viable route towards the synthesis of SWNTs with desired diameter through the tuning of arc parameters in the arc discharge process.We report a facile and scalable approach to synthesize single-walled carbon nanotubes (SWNTs) with selected diameter distribution by applying a magnetic field perpendicular to the electric field in the arc plasma region. It is found that this magnetic field-induced diameter-selectivity strategy enables the control of the SWNTs with different diameter distributions in different regions, and the diameter-selective efficiency could be enhanced by modifying the direction of magnetic field. Our results indicate that the motions of the catalysts with different particle sizes, positive carbon ions and electrons are significantly influenced by the magnetic field and electromagnetic force, resulting in the different nucleation and growth processes of SWNTs due to the collective interactions between the magnetic field and arc plasma. This approach would enable a viable route towards the synthesis of SWNTs with desired diameter through the tuning of arc parameters in the arc discharge process

  15. Selective Light-Induced Patterning of Carbon Nanotube/Silver Nanoparticle Composite To Produce Extremely Flexible Conductive Electrodes.

    PubMed

    Kim, Inhyuk; Woo, Kyoohee; Zhong, Zhaoyang; Lee, Eonseok; Kang, Dongwoo; Jeong, Sunho; Choi, Young-Man; Jang, Yunseok; Kwon, Sin; Moon, Jooho

    2017-02-22

    Recently, highly flexible conductive features have been widely demanded for the development of various electronic applications, such as foldable displays, deformable lighting, disposable sensors, and flexible batteries. Herein, we report for the first time a selective photonic sintering-derived, highly reliable patterning approach for creating extremely flexible carbon nanotube (CNT)/silver nanoparticle (Ag NP) composite electrodes that can tolerate severe bending (20 000 cycles at a bending radius of 1 mm). The incorporation of CNTs into a Ag NP film can enhance not only the mechanical stability of electrodes but also the photonic-sintering efficiency when the composite is irradiated by intense pulsed light (IPL). Composite electrodes were patterned on various plastic substrates by a three-step process comprising coating, selective IPL irradiation, and wiping. A composite film selectively exposed to IPL could not be easily wiped from the substrate, because interfusion induced strong adhesion to the underlying polymer substrate. In contrast, a nonirradiated film adhered weakly to the substrate and was easily removed, enabling highly flexible patterned electrodes. The potential of our flexible electrode patterns was clearly demonstrated by fabricating a light-emitting diode circuit and a flexible transparent heater with unimpaired functionality under bending, rolling, and folding.

  16. The effect of sine-Wiener noises on transition in a genotype selection model with time delays

    NASA Astrophysics Data System (ADS)

    Ning, Li Juan; Liu, Pei

    2016-09-01

    A genotype selection system interplay with sine-Wiener noises and time delays is investigated. Stationary probability distribution function is obtained by numerical simulations. Results show that the multiplicative bounded noise can facilitate the gene separation, while the additive bounded noise suppresses the gene separation. Besides, local time delays α and β, being in gene transformation and gene heredity progress respectively, play opposite roles in the gene selection process. What is more interesting is that there is no transition during the process of gene select when time delays α = β (i.e., the system is subjected to global time delay).

  17. The effect of sine-Wiener noises on transition in a genotype selection model with time delays

    NASA Astrophysics Data System (ADS)

    Juan Ning, Li; Liu, Pei

    2016-09-01

    A genotype selection system interplay with sine-Wiener noises and time delays is investigated. Stationary probability distribution function is obtained by numerical simulations. Results show that the multiplicative bounded noise can facilitate the gene separation, while the additive bounded noise suppresses the gene separation. Besides, local time delays α and β, being in gene transformation and gene heredity progress respectively, play opposite roles in the gene selection process. What is more interesting is that there is no transition during the process of gene select when time delays α = β (i.e., the system is subjected to global time delay).

  18. Phenotypic Selection Exerted by a Seed Predator Is Replicated in Space and Time and among Prey Species.

    PubMed

    Benkman, Craig W; Mezquida, Eduardo T

    2015-11-01

    Although consistent phenotypic selection arising from biotic interactions is thought to be the primary cause of adaptive diversification, studies documenting such selection are relatively few. Here we analyze 12 episodes of phenotypic selection exerted by a predispersal seed predator, the red crossbill (Loxia curvirostra complex), on five species of pines (Pinus). We find that even though the intensity of selection for some traits increased with the strength of the interaction (i.e., proportion of seeds eaten), the relative strength of selection exerted by crossbills on cone and seed traits is replicated across space and time and among species. Such selection (1) can account for repeated patterns of conifer cone evolution and escalation in seed defenses with time and (2) suggests that variation in selection is less the result of variation intrinsic to pairwise biotic interactions than, for example, variation in relative densities of the interacting species, community context, and abiotic factors.

  19. Observational selection biases in time-delay strong lensing and their impact on cosmography

    NASA Astrophysics Data System (ADS)

    Collett, Thomas E.; Cunnington, Steven D.

    2016-11-01

    Inferring cosmological parameters from time-delay strong lenses requires a significant investment of telescope time; it is therefore tempting to focus on the systems with the brightest sources, the highest image multiplicities and the widest image separations. We investigate if this selection bias can influence the properties of the lenses studied and the cosmological parameters inferred. Using an ellipsoidal power-law deflector population, we build a sample of double- and quadruple-image systems. Assuming reasonable thresholds on image separation and flux, based on current lens monitoring campaigns, we find that the typical density profile slopes of monitorable lenses are significantly shallower than the input ensemble. From a sample of quads, we find that this selection function can introduce a 3.5 per cent bias on the inferred time-delay distances if the properties of the input ensemble are (incorrectly) used as priors on the lens model. This bias remains at the 2.4 per cent level when high-resolution imaging of the quasar host is used to precisely infer the properties of individual lenses. We also investigate if the lines of sight for monitorable strong lenses are biased. The expectation value for the line-of-sight convergence is increased by 0.009 (0.004) for quads (doubles) implying a 0.9 per cent (0.4 per cent) bias on H0. We therefore conclude that whilst the properties of typical quasar lenses and their lines of sight do deviate from the global population, the total magnitude of this effect is likely to be a subdominant effect for current analyses, but has the potential to be a major systematic for samples of ˜25 or more lenses.

  20. Basis for sensitive and selective time-delayed luminescence detection of hydroxyl radical by lanthanide complexes.

    PubMed

    Peterson, Katie L; Margherio, Maximilian J; Doan, Phi; Wilke, Kyle T; Pierre, Valérie C

    2013-08-19

    Molecular probes for the detection of hydroxyl radical (HO•) by time-delayed luminescence spectroscopy directly in water at neutral pH with high sensitivity and selectivity are presented. The bimolecular probes consist of a lanthanide complex with open coordination sites and a reactive pre-antenna composed of an aromatic acid or amide; the latter binds to and sensitizes terbium emission upon hydroxylation by HO•. These probes exhibit long luminescence lifetimes compatible with time-delayed measurements that remove interfering background fluorescence from the sample. Six different reactive pre-antenna (benzoate, benzamide, isophthalate, isophthalamide, trimesate, and trimesamide) and two different terbium complexes [Tb-(1,4,7,10-tetraazacyclododecane-1,4,7-tris(acetic acid)) (Tb-DO3A) and Tb-(1,4,7,10-tetraazacyclododecane-1,7-bis(acetic acid)) (Tb-DO2A)] were evaluated. Of these the trimesamide/Tb-DO3A system enables the most sensitive detection of HO• with an about 1000-fold increase in metal-centered time-delayed emission upon hydroxylation of the pre-antenna to 2-hydroxytrimesamide. Excellent selectivity for both the trimesamide/Tb-DO3A and trimesate/Tb-DO3A systems over other reactive oxygen and nitrogen species are observed. Notably, the increase in metal-centered luminescence intensity is not associated with a decrease in the hydration number (q) of Tb-DO3A, suggesting that the antenna is interacting with the lanthanide via a second sphere coordination environment or that coordination by the antenna occurs by displacement of one or more of the carboxylate arms of DO3A. Formation of a weak ternary complex Tb-DO3A•hydroxytrimesamide was confirmed by temperature-dependent titration and a decrease in K(app) with increasing temperature.

  1. Single-molecule FRET unveils induced-fit mechanism for substrate selectivity in flap endonuclease 1

    PubMed Central

    Rashid, Fahad; Harris, Paul D; Zaher, Manal S; Sobhy, Mohamed A; Joudeh, Luay I; Yan, Chunli; Piwonski, Hubert; Tsutakawa, Susan E; Ivanov, Ivaylo; Tainer, John A; Habuchi, Satoshi; Hamdan, Samir M

    2017-01-01

    Human flap endonuclease 1 (FEN1) and related structure-specific 5’nucleases precisely identify and incise aberrant DNA structures during replication, repair and recombination to avoid genomic instability. Yet, it is unclear how the 5’nuclease mechanisms of DNA distortion and protein ordering robustly mediate efficient and accurate substrate recognition and catalytic selectivity. Here, single-molecule sub-millisecond and millisecond analyses of FEN1 reveal a protein-DNA induced-fit mechanism that efficiently verifies substrate and suppresses off-target cleavage. FEN1 sculpts DNA with diffusion-limited kinetics to test DNA substrate. This DNA distortion mutually ‘locks’ protein and DNA conformation and enables substrate verification with extreme precision. Strikingly, FEN1 never misses cleavage of its cognate substrate while blocking probable formation of catalytically competent interactions with noncognate substrates and fostering their pre-incision dissociation. These findings establish FEN1 has practically perfect precision and that separate control of induced-fit substrate recognition sets up the catalytic selectivity of the nuclease active site for genome stability. DOI: http://dx.doi.org/10.7554/eLife.21884.001 PMID:28230529

  2. Memory modulation in the classroom: selective enhancement of college examination performance by arousal induced after lecture.

    PubMed

    Nielson, Kristy A; Arentsen, Timothy J

    2012-07-01

    Laboratory studies examining moderate physiological or emotional arousal induced after learning indicate that it enhances memory consolidation. Yet, no studies have yet examined this effect in an applied context. As such, arousal was induced after a college lecture and its selective effects were examined on later exam performance. Participants were divided into two groups who either watched a neutral video clip (n=66) or an arousing video clip (n=70) after lecture in a psychology course. The final examination occurred two weeks after the experimental manipulation. Only performance on the group of final exam items that covered material from the manipulated lecture were significantly different between groups. Other metrics, such as the midterm examination and the total final examination score, did not differ between groups. The results indicate that post-lecture arousal selectively increased the later retrieval of lecture material, despite the availability of the material for study before and after the manipulation. The results reinforce the role of post-learning arousal on memory consolidation processes, expanding the literature to include a real-world learning context.

  3. Single-molecule FRET unveils induced-fit mechanism for substrate selectivity in flap endonuclease 1

    DOE PAGES

    Rashid, Fahad; Harris, Paul D.; Zaher, Manal S.; ...

    2017-02-23

    Human flap endonuclease 1 (FEN1) and related structure-specific 5’nucleases precisely identify and incise aberrant DNA structures during replication, repair and recombination to avoid genomic instability. Yet, it is unclear how the 5’nuclease mechanisms of DNA distortion and protein ordering robustly mediate efficient and accurate substrate recognition and catalytic selectivity. Here, single-molecule sub-millisecond and millisecond analyses of FEN1 reveal a protein-DNA induced-fit mechanism that efficiently verifies substrate and suppresses off-target cleavage. FEN1 sculpts DNA with diffusion-limited kinetics to test DNA substrate. This DNA distortion mutually ‘locks’ protein and DNA conformation and enables substrate verification with extreme precision. Strikingly, FEN1 never missesmore » cleavage of its cognate substrate while blocking probable formation of catalytically competent interactions with noncognate substrates and fostering their pre-incision dissociation. These findings establish FEN1 has practically perfect precision and that separate control of induced-fit substrate recognition sets up the catalytic selectivity of the nuclease active site for genome stability.« less

  4. Conformational selection or induced fit: a flux description of reaction mechanism.

    PubMed

    Hammes, Gordon G; Chang, Yu-Chu; Oas, Terrence G

    2009-08-18

    The mechanism of ligand binding coupled to conformational changes in macromolecules has recently attracted considerable interest. The 2 limiting cases are the "induced fit" mechanism (binding first) or "conformational selection" (conformational change first). Described here are the criteria by which the sequence of events can be determined quantitatively. The relative importance of the 2 pathways is determined not by comparing rate constants (a common misconception) but instead by comparing the flux through each pathway. The simple rules for calculating flux in multistep mechanisms are described and then applied to 2 examples from the literature, neither of which has previously been analyzed using the concept of flux. The first example is the mechanism of conformational change in the binding of NADPH to dihydrofolate reductase. The second example is the mechanism of flavodoxin folding coupled to binding of its cofactor, flavin mononucleotide. In both cases, the mechanism switches from being dominated by the conformational selection pathway at low ligand concentration to induced fit at high ligand concentration. Over a wide range of conditions, a significant fraction of the flux occurs through both pathways. Such a mixed mechanism likely will be discovered for many cases of coupled conformational change and ligand binding when kinetic data are analyzed by using a flux-based approach.

  5. alpha7 Nicotinic acetylcholine receptor knockout selectively enhances ethanol-, but not beta-amyloid-induced neurotoxicity.

    PubMed

    de Fiebre, Nancyellen C; de Fiebre, Christopher M

    2005-01-03

    The alpha7 subtype of nicotinic acetylcholine receptor (nAChR) has been implicated as a potential site of action for two neurotoxins, ethanol and the Alzheimer's disease related peptide, beta-amyloid. Here, we utilized primary neuronal cultures of cerebral cortex from alpha7 nAChR null mutant mice to examine the role of this receptor in modulating the neurotoxic properties of subchronic, "binge" ethanol and beta-amyloid. Knockout of the alpha7 nAChR gene selectively enhanced ethanol-induced neurotoxicity in a gene dosage-related fashion. Susceptibility of cultures to beta-amyloid induced toxicity, however, was unaffected by alpha7 nAChR gene null mutation. Further, beta-amyloid did not inhibit the binding of the highly alpha7-selective radioligand, [(125)I]alpha-bungarotoxin. On the other hand, in studies in Xenopus oocytes ethanol efficaciously inhibited alpha7 nAChR function. These data suggest that alpha7 nAChRs modulate the neurotoxic effects of binge ethanol, but not the neurotoxicity produced by beta-amyloid. It is hypothesized that inhibition of alpha7 nAChRs by ethanol provides partial protection against the neurotoxic properties of subchronic ethanol.

  6. The marine cytotoxin portimine is a potent and selective inducer of apoptosis.

    PubMed

    Cuddihy, Sarah L; Drake, Sarah; Harwood, D Tim; Selwood, Andrew I; McNabb, Paul S; Hampton, Mark B

    2016-12-01

    Portimine is a recently discovered member of a class of marine micro-algal toxins called cyclic imines. In dramatic contrast to related compounds in this toxin class, portimine has very low acute toxicity to mice but is highly cytotoxic to cultured cells. In this study we show that portimine kills human Jurkat T-lymphoma cells and mouse embryonic fibroblasts (MEFs), with LC50 values of 6 and 2.5 nM respectively. Treated cells displayed rapid caspase activation and phosphatidylserine exposure, indicative of apoptotic cell death. Jurkat cells overexpressing the anti-apoptotic protein Bcl-2 or Bax/Bak knockout MEFs were completely protected from portimine. This protection was apparent even at high concentrations of portimine, with no evidence of necrotic cell death, indicating that portimine is a selective chemical inducer of apoptosis. Treatment of the Bcl-2-overexpressing cells with both portimine and the Bcl-2 inhibitor ABT-737 proved a powerful combination, causing >90 % death. We conclude that portimine is one of the most potent naturally derived inducers of apoptosis to be discovered, and it displays strong selectivity for the induction of apoptotic pathways.

  7. Melatonin, a novel selective ATF-6 inhibitor, induces human hepatoma cell apoptosis through COX-2 downregulation.

    PubMed

    Bu, Li-Jia; Yu, Han-Qing; Fan, Lu-Lu; Li, Xiao-Qiu; Wang, Fang; Liu, Jia-Tao; Zhong, Fei; Zhang, Cong-Jun; Wei, Wei; Wang, Hua; Sun, Guo-Ping

    2017-02-14

    To clarify the mechanisms involved in the critical endoplasmic reticulum (ER) stress initiating unfolded protein response pathway modified by melatonin. Hepatoma cells, HepG2, were cultured in vitro. Flow cytometry and TUNEL assay were used to measure HepG2 cell apoptosis. Western blotting and quantitative reverse transcription-polymerase chain reaction methods were used to determine the protein and messenger RNA levels of ER stress and apoptosis related genes' expression, respectively. Tissue microarray construction from patients was verified by immunohistochemical analysis. In the present study, we first identified that melatonin selectively blocked activating transcription factor 6 (ATF-6) and then inhibited cyclooxygenase-2 (COX-2) expression, leading to enhanced liver cancer cell apoptosis under ER stress condition. Dramatically increased CCAAT-enhancer-binding protein homologous protein level, suppressed COX-2 and decreased Bcl-2/Bax ratio by melatonin or ATF-6 siRNA contributed the enhanced HepG2 cell apoptosis under tunicamycin (an ER stress inducer) stimulation. In clinical hepatocellular carcinoma patients, the close relationship between ATF-6 and COX-2 was further confirmed. These findings indicate that melatonin as a novel selective ATF-6 inhibitor can sensitize human hepatoma cells to ER stress inducing apoptosis.

  8. Melatonin, a novel selective ATF-6 inhibitor, induces human hepatoma cell apoptosis through COX-2 downregulation

    PubMed Central

    Bu, Li-Jia; Yu, Han-Qing; Fan, Lu-Lu; Li, Xiao-Qiu; Wang, Fang; Liu, Jia-Tao; Zhong, Fei; Zhang, Cong-Jun; Wei, Wei; Wang, Hua; Sun, Guo-Ping

    2017-01-01

    AIM To clarify the mechanisms involved in the critical endoplasmic reticulum (ER) stress initiating unfolded protein response pathway modified by melatonin. METHODS Hepatoma cells, HepG2, were cultured in vitro. Flow cytometry and TUNEL assay were used to measure HepG2 cell apoptosis. Western blotting and quantitative reverse transcription-polymerase chain reaction methods were used to determine the protein and messenger RNA levels of ER stress and apoptosis related genes’ expression, respectively. Tissue microarray construction from patients was verified by immunohistochemical analysis. RESULTS In the present study, we first identified that melatonin selectively blocked activating transcription factor 6 (ATF-6) and then inhibited cyclooxygenase-2 (COX-2) expression, leading to enhanced liver cancer cell apoptosis under ER stress condition. Dramatically increased CCAAT-enhancer-binding protein homologous protein level, suppressed COX-2 and decreased Bcl-2/Bax ratio by melatonin or ATF-6 siRNA contributed the enhanced HepG2 cell apoptosis under tunicamycin (an ER stress inducer) stimulation. In clinical hepatocellular carcinoma patients, the close relationship between ATF-6 and COX-2 was further confirmed. CONCLUSION These findings indicate that melatonin as a novel selective ATF-6 inhibitor can sensitize human hepatoma cells to ER stress inducing apoptosis. PMID:28246472

  9. Trichostatin A selectively suppresses the cold-induced transcription of the ZmDREB1 gene in maize.

    PubMed

    Hu, Yong; Zhang, Lu; Zhao, Lin; Li, Jun; He, Shibin; Zhou, Kun; Yang, Fei; Huang, Min; Jiang, Li; Li, Lijia

    2011-01-01

    Post-translational modifications of histone proteins play a crucial role in responding to environmental stresses. Histone deacetylases (HDACs) catalyze the removal of an acetyl group from histones and are generally believed to be a transcriptional repressor. In this paper, we report that cold treatment highly induces the up-regulation of HDACs, leading to global deacetylation of histones H3 and H4. Treatment of maize with the HDAC inhibitor trichostatin A (TSA) under cold stress conditions strongly inhibits induction of the maize cold-responsive genes ZmDREB1 and ZmCOR413. However, up-regulation of the ZmICE1 gene in response to cold stress is less affected. The expression of drought and salt induced genes, ZmDBF1 and rab17, is almost unaffected by TSA treatment. Thus, these observations show that HDACs may selectively activate transcription. The time course of TSA effects on the expression of ZmDREB1 and ZmCOR413 genes indicates that HDACs appear to directly activate the ZmDREB1 gene, which in turn modulates ZmCOR413 expression. After cold treatment, histone hyperacetylation and DNA demethylation occurs in the ICE1 binding region, accompanied by an increase in accessibility to micrococcal nuclease (MNase). The two regions adjacent to the ICE1 binding site remain hypoacetylated and methylated. However, during cold acclimation, TSA treatment increases the acetylation status and accessibility of MNase and decreases DNA methylation at these two regions. However, TSA treatment does not affect histone hyperacetylation and DNA methylation levels at the ICE1 binding regions of the ZmDREB1 gene. Altogether, our findings indicate that HDACs positively regulate the expression of the cold-induced ZmDREB1 gene through histone modification and chromatin conformational changes and that this activation is both gene and site selective.

  10. Quantum Mode Selectivity of Plasmon-Induced Water Splitting on Gold Nanoparticles.

    PubMed

    Yan, Lei; Wang, Fangwei; Meng, Sheng

    2016-05-24

    Plasmon induced water splitting is a promising research area with the potential for efficient conversion of solar to chemical energy, yet its atomic mechanism is not well understood. Here, ultrafast electron-nuclear dynamics of water splitting on gold nanoparticles upon exposure to femtosecond laser pulses was directly simulated using real time time-dependent density functional theory (TDDFT). Strong correlation between laser intensity, hot electron transfer, and reaction rates has been identified. The rate of water splitting is dependent not only on respective optical absorption strength, but also on the quantum oscillation mode of plasmonic excitation. Odd modes are more efficient than even modes, owing to faster decaying into hot electrons whose energy matches well the antibonding orbital of water. This finding suggests photocatalytic activity can be manipulated by adjusting the energy level of plasmon-induced hot carriers, through altering the cluster size and laser parameter, to better overlap adsorbate unoccupied level in plasmon-assisted photochemistry.

  11. Medial prefrontal theta oscillations track the time course of interference during selective memory retrieval.

    PubMed

    Ferreira, Catarina S; Marful, Alejandra; Staudigl, Tobias; Bajo, Teresa; Hanslmayr, Simon

    2014-04-01

    Memory retrieval is often challenged by other irrelevant competing memories that cause interference. This phenomenon is typically studied with the retrieval practice paradigm in which a category cue (e.g., Fruits) is presented together with an item-specific cue (e.g., Or::). Presentation of the category cue usually induces interference by reactivating competing memories (e.g., Banana, Apple, etc.), which is thought to be solved by means of inhibition, leading to retrieval-induced forgetting of these competing memories. Previous studies associated interference with an increase in medial prefrontal theta band (4-8 Hz) oscillations, but these studies could not disentangle the interference from the inhibition processes. We here used a retrieval practice procedure in which the category cue was presented before the item-specific cue to disentangle the interference from the inhibition signal. Furthermore, a competitive retrieval condition was contrasted with a noncompetitive condition. At a behavioral level, retrieval-induced forgetting was found in the competitive but not in the noncompetitive condition. At a neural level, presentation of the category cue elicited higher levels of theta power in the competitive condition, when compared with the noncompetitive retrieval condition. Importantly, this difference was localized to the ACC, which has been associated with the detection and mediation of interference. Additionally, theta power decreased upon presentation of the item-specific cue, and this difference was related to later forgetting. Our results therefore disentangle, for the first time, interference and inhibition in episodic memory retrieval and suggest that theta oscillations track the fine-grained temporal dynamics of interference during competitive memory retrieval.

  12. Selective prostacyclin receptor agonism augments glucocorticoid-induced gene expression in human bronchial epithelial cells.

    PubMed

    Wilson, Sylvia M; Shen, Pamela; Rider, Christopher F; Traves, Suzanne L; Proud, David; Newton, Robert; Giembycz, Mark A

    2009-11-15

    Prostacyclin receptor (IP-receptor) agonists display anti-inflammatory and antiviral activity in cell-based assays and in preclinical models of asthma and chronic obstructive pulmonary disease. In this study, we have extended these observations by demonstrating that IP-receptor activation also can enhance the ability of glucocorticoids to induce genes with anti-inflammatory activity. BEAS-2B bronchial epithelial cells stably transfected with a glucocorticoid response element (GRE) luciferase reporter were activated in a concentration-dependent manner by the glucocorticoid dexamethasone. An IP-receptor agonist, taprostene, increased cAMP in these cells and augmented luciferase expression at all concentrations of dexamethasone examined. Analysis of the concentration-response relationship that described this effect showed that taprostene increased the magnitude of transcription without affecting the potency of dexamethasone and was, thus, steroid-sparing in this simple system. RO3244794, an IP-receptor antagonist, and oligonucleotides that selectively silenced the IP-receptor gene, PTGIR, abolished these effects of taprostene. Infection of BEAS-2B GRE reporter cells with an adenovirus vector encoding a highly selective inhibitor of cAMP-dependent protein kinase (PKA) also prevented taprostene from enhancing GRE-dependent transcription. In BEAS-2B cells and primary cultures of human airway epithelial cells, taprostene and dexamethasone interacted either additively or cooperatively in the expression of three glucocorticoid-inducible genes (GILZ, MKP-1, and p57(kip2)) that have anti-inflammatory potential. Collectively, these data show that IP-receptor agonists can augment the ability of glucocorticoids to induce anti-inflammatory genes in human airway epithelial cells by activating a cAMP/PKA-dependent mechanism. This observation may have clinical relevance in the treatment of airway inflammatory diseases that are either refractory or respond suboptimally to

  13. Selective white matter pathology induces a specific impairment in spatial working memory.

    PubMed

    Coltman, Robin; Spain, Aisling; Tsenkina, Yanina; Fowler, Jill H; Smith, Jessica; Scullion, Gillian; Allerhand, Mike; Scott, Fiona; Kalaria, Rajesh N; Ihara, Masafumi; Daumas, Stephanie; Deary, Ian J; Wood, Emma; McCulloch, James; Horsburgh, Karen

    2011-12-01

    The integrity of the white matter is critical in regulating efficient neuronal communication and maintaining cognitive function. Damage to brain white matter putatively contributes to age-related cognitive decline. There is a growing interest in animal models from which the mechanistic basis of white matter pathology in aging can be elucidated but to date there has been a lack of systematic behavior and pathology in the same mice. Anatomically widespread, diffuse white matter damage was induced, in 3 different cohorts of C57Bl/6J mice, by chronic hypoperfusion produced by bilateral carotid stenosis. A comprehensive assessment of spatial memory (spatial reference learning and memory; cohort 1) and serial spatial learning and memory (cohort 2) using the water maze, and spatial working memory (cohort 3) using the 8-arm radial arm maze, was conducted. In parallel, a systematic assessment of white matter components (myelin, axon, glia) was conducted using immunohistochemical markers (myelin-associated glycoprotein [MAG], degraded myelin basic protein [dMBP], anti-amyloid precursor protein [APP], anti-ionized calcium-binding adapter molecule [Iba-1]). Ischemic neuronal perikarya damage, assessed using histology (hematoxylin and eosin; H&E), was absent in all shams but was present in some hypoperfused mice (2/11 in cohort 1, 4/14 in cohort 2, and 17/24 in cohort 3). All animals with neuronal perikaryal damage were excluded from further study. Diffuse white matter damage occurred, throughout the brain, in all hypoperfused mice in each cohort and was essentially absent in sham-operated controls. There was a selective impairment in spatial working memory, with all other measures of spatial memory remaining intact, in hypoperfused mice with selective white matter damage. The results demonstrate that diffuse white matter pathology, in the absence of gray matter damage, induces a selective impairment of spatial working memory. This highlights the importance of assessing

  14. Novel Analogue of Colchicine Induces Selective Pro-Death Autophagy and Necrosis in Human Cancer Cells

    PubMed Central

    Larocque, Kristen; Ovadje, Pamela; Djurdjevic, Sinisa; Mehdi, Mariam; Green, James; Pandey, Siyaram

    2014-01-01

    Colchicine, a natural product of Colchicum autumnae currently used for gout treatment, is a tubulin targeting compound which inhibits microtubule formation by targeting fast dividing cells. This tubulin-targeting property has lead researchers to investigate the potential of colchicine and analogs as possible cancer therapies. One major study conducted on an analogue of allocolchicine, ZD 6126, was halted in phase 2 clinical trials due to severe cardio-toxicity associated with treatment. This study involves the development and testing of novel allocolchicine analogues that hold non-toxic anti-cancer properties. Currently we have synthesized and evaluated the anti-cancer activities of two analogues; N-acetyl-O-methylcolchinol (NSC 51046 or NCME), which is structurally similar to ZD 6126, and (S)-3,8,9,10-tetramethoxyallocolchicine (Green 1), which is a novel derivative of allocolchicine that is isomeric in the A ring. NSC 51046 was found to be non-selective as it induced apoptosis in both BxPC-3 and PANC-1 pancreatic cancer cells and in normal human fibroblasts. Interestingly, we found that Green 1 was able to modestly induce pro-death autophagy in these pancreatic cancer cells and E6-1 leukemia cells but not in normal human fibroblasts. Unlike colchicine and NSC 51046, Green 1 does not appear to affect tubulin polymerization indicating that it has a different molecular target. Green 1 also caused increased reactive oxygen species (ROS) production in mitochondria isolated from pancreatic cancer cells. Furthermore, in vivo studies revealed that Green 1 was well tolerated in mice. Our findings suggest that a small change in the structure of colchicine has apparently changed the mechanism of action and lead to improved selectivity. This may lead to better selective treatments in cancer therapy. PMID:24466327

  15. Evaluating Varied Label Designs for Use with Medical Devices: Optimized Labels Outperform Existing Labels in the Correct Selection of Devices and Time to Select

    PubMed Central

    Seo, Do Chan; Ladoni, Moslem; Brunk, Eric; Becker, Mark W.

    2016-01-01

    Purpose Effective standardization of medical device labels requires objective study of varied designs. Insufficient empirical evidence exists regarding how practitioners utilize and view labeling. Objective Measure the effect of graphic elements (boxing information, grouping information, symbol use and color-coding) to optimize a label for comparison with those typical of commercial medical devices. Design Participants viewed 54 trials on a computer screen. Trials were comprised of two labels that were identical with regard to graphics, but differed in one aspect of information (e.g., one had latex, the other did not). Participants were instructed to select the label along a given criteria (e.g., latex containing) as quickly as possible. Dependent variables were binary (correct selection) and continuous (time to correct selection). Participants Eighty-nine healthcare professionals were recruited at Association of Surgical Technologists (AST) conferences, and using a targeted e-mail of AST members. Results Symbol presence, color coding and grouping critical pieces of information all significantly improved selection rates and sped time to correct selection (α = 0.05). Conversely, when critical information was graphically boxed, probability of correct selection and time to selection were impaired (α = 0.05). Subsequently, responses from trials containing optimal treatments (color coded, critical information grouped with symbols) were compared to two labels created based on a review of those commercially available. Optimal labels yielded a significant positive benefit regarding the probability of correct choice ((P<0.0001) LSM; UCL, LCL: 97.3%; 98.4%, 95.5%)), as compared to the two labels we created based on commercial designs (92.0%; 94.7%, 87.9% and 89.8%; 93.0%, 85.3%) and time to selection. Conclusions Our study provides data regarding design factors, namely: color coding, symbol use and grouping of critical information that can be used to significantly enhance

  16. FACS identifies unique cocaine-induced gene regulation in selectively activated adult striatal neurons

    PubMed Central

    Guez-Barber, Danielle; Fanous, Sanya; Golden, Sam A.; Schrama, Regina; Koya, Eisuke; Stern, Anna L.; Bossert, Jennifer M.; Harvey, Brandon K.; Picciotto, Marina R.; Hope, Bruce T.

    2011-01-01

    Numerous studies with the neural activity marker Fos indicate that cocaine activates only a small proportion of sparsely distributed striatal neurons. Until now, efficient methods were not available to assess neuroadaptations induced specifically within these activated neurons. We used fluorescence-activated cell sorting (FACS) to purify striatal neurons activated during cocaine-induced locomotion in naïve and cocaine-sensitized cfos-lacZ transgenic rats. Activated neurons were labeled with an antibody against β-galactosidase, the protein product of the lacZ gene. Cocaine induced a unique gene expression profile selectively in the small proportion of activated neurons that was not observed in the non-activated majority of neurons. These genes included altered levels of the immediate early genes arc, fosB, and nr4a3, as well as genes involved in p38 MAPK signaling and cell-type specificity. We propose that this FACS method can be used to study molecular neuroadaptations in specific neurons encoding the behavioral effects of abused drugs and other learned behaviors. PMID:21411666

  17. A PPARδ-selective antagonist ameliorates IMQ-induced psoriasis-like inflammation in mice.

    PubMed

    Wang, Xuguo; Hao, Yangyang; Wang, Xiaohuan; Wang, Lumei; Chen, Yongchun; Sun, Jun; Hu, Jinhong

    2016-11-01

    PPARδ is highly expressed in skin, especially keratinocytes, and its expression is increased in psoriatic lesions. However, the potential role of PPARδ in the pathogenesis of psoriasis remains undefined. Mice treated with Imiquimod (IMQ) to induce psoriasis can be used to evaluate the pathogenesis of psoriasis, and this model has become one of the most important in vivo research tools for research on the disease. In the current study, we showed that PPARδ was highly expressed in the skin of IMQ-induced psoriasis mice. To further understand the impact of PPARδ in psoriasis, we used these mice in a series of experiments to evaluate the pathogenesis of psoriasis. We found that PPARδ was highly expressed in both psoriatic lesions and normal skin in IMQ-induced psoriasis mice. Furthermore, the expression of PPARδ-relevant lipases was also significantly increased. The PPARδ-selective antagonist GSK3787 ameliorated the observed inflammation in the skin of the experimental mice. Based on these results, PPARδ may be a potential target for the effective treatment of psoriasis. Copyright © 2016 Elsevier B.V. All rights reserved.

  18. Thymic involution perturbs negative selection leading to autoreactive T cells that induce chronic inflammation.

    PubMed

    Coder, Brandon D; Wang, Hongjun; Ruan, Linhui; Su, Dong-Ming

    2015-06-15

    Thymic involution and the subsequent amplified release of autoreactive T cells increase the susceptibility toward developing autoimmunity, but whether they induce chronic inflammation with advanced age remains unclear. The presence of chronic low-level proinflammatory factors in elderly individuals (termed inflammaging) is a significant risk factor for morbidity and mortality in virtually every chronic age-related disease. To determine how thymic involution leads to the persistent release and activation of autoreactive T cells capable of inducing inflammaging, we used a Foxn1 conditional knockout mouse model that induces accelerated thymic involution while maintaining a young periphery. We found that thymic involution leads to T cell activation shortly after thymic egress, which is accompanied by a chronic inflammatory phenotype consisting of cellular infiltration into non-lymphoid tissues, increased TNF-α production, and elevated serum IL-6. Autoreactive T cell clones were detected in the periphery of Foxn1 conditional knockout mice. A failure of negative selection, facilitated by decreased expression of Aire rather than impaired regulatory T cell generation, led to autoreactive T cell generation. Furthermore, the young environment can reverse age-related regulatory T cell accumulation in naturally aged mice, but not inflammatory infiltration. Taken together, these findings identify thymic involution and the persistent activation of autoreactive T cells as a contributing source of chronic inflammation (inflammaging).

  19. Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

    1995-01-01

    Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

  20. Supraspinal-selective TRPV1 desensitization induced by intracerebroventricular treatment with resiniferatoxin.

    PubMed

    Fukushima, Akihiro; Mamada, Kizuku; Iimura, Aki; Ono, Hideki

    2017-09-29

    The transient receptor potential vanilloid type 1 (TRPV1) is a thermosensitive cation channel that triggers heat pain in the periphery. Long-term desensitization of TRPV1, which can be induced by excess amounts of agonists, has been a method for investigating the physiological relevance of TRPV1-containing neuronal circuits, and desensitization induced by various routes of administration, including systemic, intrathecal and intraganglionic, has been demonstrated in rodents. In the present study, we examined the effect of intracerebroventricular (i.c.v.) treatment with an ultrapotent TRPV1 agonist, resiniferatoxin (RTX), on nociception and the analgesic effect of acetaminophen, which is known to mediate the activation of central TRPV1. I.c.v. administration of RTX a week before the test did not affect the licking/biting response to intraplantar injection of RTX (RTX test), suggesting that such i.c.v. treatment spares the function of TRPV1 at the hindpaw. Mice that had been i.c.v.-administered RTX also exhibited normal nociceptive responses in the formalin test and the tail pressure test, but acetaminophen failed to induce analgesia in those mice in any of the tests. These results suggest that i.c.v. administration of RTX leads to brain-selective TRPV1 desensitization in mice.

  1. Skeletal unloading induces selective resistance to the anabolic actions of growth hormone on bone

    NASA Technical Reports Server (NTRS)

    Halloran, B. P.; Bikle, D. D.; Harris, J.; Autry, C. P.; Currier, P. A.; Tanner, S.; Patterson-Buckendahl, P.; Morey-Holton, E.

    1995-01-01

    Loss of skeletal weight bearing or physical unloading of bone in the growing animal inhibits bone formation and induces a bone mineral deficit. To determine whether the inhibition of bone formation induced by skeletal unloading in the growing animal is a consequence of diminished sensitivity to growth hormone (GH) we studied the effects of skeletal unloading in young hypophysectomized rats treated with GH (0, 50, 500 micrograms/100 g body weight/day). Skeletal unloading reduced serum osteocalcin, impaired uptake of 3H-proline into bone, decreased proximal tibial mass, and diminished periosteal bone formation at the tibiofibular junction. When compared with animals receiving excipient alone, GH administration increased bone mass in all animals. The responses in serum osteocalcin, uptake of 3H-proline and 45Ca into the proximal tibia, and proximal tibial mass in non-weight bearing animals were equal to those in weight bearing animals. The responses in trabecular bone volume in the proximal tibia and bone formation at the tibiofibular junction to GH, however, were reduced significantly by skeletal unloading. Bone unloading prevented completely the increase in metaphyseal trabecular bone normally induced by GH and severely dampened the stimulatory effect (158% vs. 313%, p < 0.002) of GH on periosteal bone formation. These results suggest that while GH can stimulate the overall accumulation of bone mineral in both weight bearing and non-weight bearing animals, skeletal unloading selectively impairs the response of trabecular bone and periosteal bone formation to the anabolic actions of GH.

  2. Time of travel of solutes in Buffalo Bayou and selected tributaries, Houston, Texas, August 1999

    USGS Publications Warehouse

    East, Jeffery W.; Schaer, Jasper D.

    2000-01-01

    The U.S. Geological Survey (USGS), in cooperation with the U.S. Environmental Protection Agency, conducted a time-of-travel study in the Buffalo Bayou watershed during low flow in August 1999. The study was done as part of the U.S. Environmental Protection Agency Environmental Monitoring for Public Access and Community Tracking (EMPACT) program. The EMPACT program was designed for the U.S. Environmental Protection Agency to work with communities to “make timely, accurate, and understandable environmental information available to millions of people in the largest metropolitan areas across the country.” (U.S. Environmental Protection Agency, 2000). Buffalo Bayou, located in Houston, Texas, was chosen as a pilot project because it is a frequently used recreational water source, it has many water-treatment facilities located along its stream segments, and it has a history of water-quality problems (Houston-Galveston Area Council, 2000). One component of the pilot project is to develop a water-quality simulation model that can be used to assess the effects of noncompliance events on Buffalo Bayou. Because accurate estimates of time of travel during low flow are required to develop the model, the time of travel of solutes in Buffalo Bayou and selected tributaries was determined using dye tracing methods. The study was conducted during low flow in a 38.7-mile reach of Buffalo Bayou, a 9.6-mile reach of Whiteoak Bayou, a 5.9-mile reach of Mason Creek, and a 6.6-mile reach of Bear Creek. Efforts to determine the time of travel in a 7.5-mile reach of Horsepen Creek were unsuccessful. This report explains the approach used to conduct the study and presents the results of the study

  3. SHORT DISSIPATION TIMES OF PROTO-PLANETARY DISKS: AN ARTIFACT OF SELECTION EFFECTS?

    SciTech Connect

    Pfalzner, Susanne; Steinhausen, Manuel; Menten, Karl

    2014-10-01

    The frequency of disks around young stars, a key parameter for understanding planet formation, is most readily determined in young stellar clusters where many relatively coeval stars are located in close proximity. Observational studies seem to show that the disk frequency decreases rapidly with cluster age with <10% of cluster stars retaining their disks for longer than 2-6 Myr. Given that at least half of all stars in the field seem to harbor one or more planets, this would imply extremely fast disk dispersal and rapid planet growth. Here we question the validity of this constraint by demonstrating that the short disk dissipation times inferred to date might have been heavily underestimated by selection effects. Critically, for ages >3 Myr only stars that originally populated the densest areas of very populous clusters, which are prone to disk erosion, are actually considered. This tiny sample may not be representative of the majority of stars. In fact, the higher disk fractions in co-moving groups indicate that it is likely that over 30% of all field stars retain their disks well beyond 10 Myr, leaving ample time for planet growth. Equally, our solar system, with a likely formation time >10 Myr, need no longer be an exception but in fact typical of planetary systems.

  4. Classifying Human Voices by Using Hybrid SFX Time-Series Preprocessing and Ensemble Feature Selection

    PubMed Central

    Wong, Raymond

    2013-01-01

    Voice biometrics is one kind of physiological characteristics whose voice is different for each individual person. Due to this uniqueness, voice classification has found useful applications in classifying speakers' gender, mother tongue or ethnicity (accent), emotion states, identity verification, verbal command control, and so forth. In this paper, we adopt a new preprocessing method named Statistical Feature Extraction (SFX) for extracting important features in training a classification model, based on piecewise transformation treating an audio waveform as a time-series. Using SFX we can faithfully remodel statistical characteristics of the time-series; together with spectral analysis, a substantial amount of features are extracted in combination. An ensemble is utilized in selecting only the influential features to be used in classification model induction. We focus on the comparison of effects of various popular data mining algorithms on multiple datasets. Our experiment consists of classification tests over four typical categories of human voice data, namely, Female and Male, Emotional Speech, Speaker Identification, and Language Recognition. The experiments yield encouraging results supporting the fact that heuristically choosing significant features from both time and frequency domains indeed produces better performance in voice classification than traditional signal processing techniques alone, like wavelets and LPC-to-CC. PMID:24288684

  5. Time constant of round superconducting structures determined from the time development of the induced magnetic field

    NASA Astrophysics Data System (ADS)

    Takács, S.

    2016-12-01

    It is shown that evaluating the time development of the penetrated magnetic field into the superconductors can be used for the determination of time constant for round structures, too. The calculations are very similar to those used for the flat structures. The method is very simple, both by the practical realization of the experiment and by the evaluation of the time evolution of the penetrated magnetic field above the superconductor. The procedure uses an exponential decrease of the applied magnetic field, which can be easily performed by discharging an external circuit. By determining the position of the maximum of the difference between the penetrated field induction and the applied magnetic field induction, the corresponding time constant can be evaluated by a very simple equation, which is calculated in the paper. The results are very similar to the previous calculations, obtained for the flat superconducting cables. In addition, it is suggested that knowing the time constant of superconducting structures could be in many cases more important both for research aspects and for practical applications.

  6. Double Point Source W-phase Inversion: Real-time Implementation and Automated Model Selection

    NASA Astrophysics Data System (ADS)

    Nealy, J. L.; Hayes, G. P.

    2015-12-01

    Rapid and accurate characterization of an earthquake source is an extremely important and ever-evolving field of research. Within this field, source inversion of the W-phase has recently been shown to be an effective technique, which can be efficiently implemented in real-time. An extension to the W-phase source inversion is presented in which two point sources are derived to better characterize complex earthquakes. A single source inversion followed by a double point source inversion with centroid locations fixed at the single source solution location can be efficiently run as part of earthquake monitoring network operational procedures. In order to determine the most appropriate solution, i.e., whether an earthquake is most appropriately described by a single source or a double source, an Akaike information criterion (AIC) test is performed. Analyses of all earthquakes of magnitude 7.5 and greater occurring since January 2000 were performed with extended analyses of the September 29, 2009 magnitude 8.1 Samoa and the April 19, 2014 magnitude 7.5 Papua New Guinea earthquakes. The AIC test is shown to be able to accurately select the most appropriate model and the selected W-phase inversion is shown to yield reliable solutions that match previously published analyses of the same events.

  7. Double point source W-phase inversion: Real-time implementation and automated model selection

    NASA Astrophysics Data System (ADS)

    Nealy, Jennifer L.; Hayes, Gavin P.

    2015-12-01

    Rapid and accurate characterization of an earthquake source is an extremely important and ever evolving field of research. Within this field, source inversion of the W-phase has recently been shown to be an effective technique, which can be efficiently implemented in real-time. An extension to the W-phase source inversion is presented in which two point sources are derived to better characterize complex earthquakes. A single source inversion followed by a double point source inversion with centroid locations fixed at the single source solution location can be efficiently run as part of earthquake monitoring network operational procedures. In order to determine the most appropriate solution, i.e., whether an earthquake is most appropriately described by a single source or a double source, an Akaike information criterion (AIC) test is performed. Analyses of all earthquakes of magnitude 7.5 and greater occurring since January 2000 were performed with extended analyses of the September 29, 2009 magnitude 8.1 Samoa earthquake and the April 19, 2014 magnitude 7.5 Papua New Guinea earthquake. The AIC test is shown to be able to accurately select the most appropriate model and the selected W-phase inversion is shown to yield reliable solutions that match published analyses of the same events.

  8. Selection of Reference Genes for Real-Time Quantitative PCR in Pinus massoniana Post Nematode Inoculation.

    PubMed

    Wei, Yongcheng; Liu, Qinghua; Dong, Hongyu; Zhou, Zhichun; Hao, Yanping; Chen, Xuelian; Xu, Liuyi

    2016-01-01

    Pinus massoniaia Lamb has gained more and more attention as the most important tree species for timber and forestation in South China. Gene expression studies are of great importance to identify new and elite cultivars. Real-time quantitative PCR, a highly sensitive and specific method, is commonly used in the analysis of gene expression. The appropriate reference genes must be employed to normalize the calculation program for ascertaining repeatable and significant results. Herein, eleven housekeeping genes were evaluated during different stages of P. massoniana post nematode inoculation in this study. Three statistical approaches such as geNorm, NormFinder and BestKeeper were selected to analyze the stability of candidate genes. The results indicated that U2af and β-TUB were the most stable reference genes. These two genes could be used for the normalization in most of the experiments of P. massoniana, while Histone and AK were the least stable ones. In addition, EF expressed at the lowest average Ct value was the most abundant candidate gene. As an important gene associated with defense mechanisms, ABC transporter was analyzed by qRT-PCR, and the results were used to confirm the reliability of two genes. The selected reference genes in the present study will be conducive to future gene expression normalized by qRT-PCR in P. massoniana.

  9. Selection of Reference Genes for Real-Time Quantitative PCR in Pinus massoniana Post Nematode Inoculation

    PubMed Central

    Wei, Yongcheng; Liu, Qinghua; Dong, Hongyu; Zhou, Zhichun; Hao, Yanping; Chen, Xuelian; Xu, Liuyi

    2016-01-01

    Pinus massoniaia Lamb has gained more and more attention as the most important tree species for timber and forestation in South China. Gene expression studies are of great importance to identify new and elite cultivars. Real-time quantitative PCR, a highly sensitive and specific method, is commonly used in the analysis of gene expression. The appropriate reference genes must be employed to normalize the calculation program for ascertaining repeatable and significant results. Herein, eleven housekeeping genes were evaluated during different stages of P. massoniana post nematode inoculation in this study. Three statistical approaches such as geNorm, NormFinder and BestKeeper were selected to analyze the stability of candidate genes. The results indicated that U2af and β-TUB were the most stable reference genes. These two genes could be used for the normalization in most of the experiments of P. massoniana, while Histone and AK were the least stable ones. In addition, EF expressed at the lowest average Ct value was the most abundant candidate gene. As an important gene associated with defense mechanisms, ABC transporter was analyzed by qRT-PCR, and the results were used to confirm the reliability of two genes. The selected reference genes in the present study will be conducive to future gene expression normalized by qRT-PCR in P. massoniana. PMID:26800152

  10. Sensitive and selective real-time electrochemical monitoring of DNA repair (Presentation Recording)

    NASA Astrophysics Data System (ADS)

    Slinker, Jason D.; McWilliams, Marc; Anka, Fadwa; Balkus, Kenneth

    2015-10-01

    Unrepaired DNA damage can lead to mutation, cancer, and death of cells or organisms. However, due to the subtlety of DNA damage, it is difficult to sense the repair of damage products with high selectivity and sensitivity. Here, we show sensitive and selective electrochemical sensing of the repair activity of 8-oxoguanine and uracil glycosylases within DNA monolayers on gold by multiplexed analysis with silicon chips and low-cost electrospun nanofibers. Our approach involves comparing the electrochemical signal of redox probe modified monolayers containing the defect versus the rational control of defect-free monolayers. We find sequence-specific sensitivity thresholds on the order of femtomoles of proteins and dynamic ranges of over two orders of magnitude for each target. For 8-oxoguanine repair, temperature-dependent kinetics are extracted, showing exponential signal loss with time constants of seconds. Electrospun fibers are shown to behave similarly to conventional gold-on-silicon devices, showing the potential of these low-cost devices for sensing applications.

  11. Double point source W-phase inversion: Real-time implementation and automated model selection

    USGS Publications Warehouse

    Nealy, Jennifer; Hayes, Gavin

    2015-01-01

    Rapid and accurate characterization of an earthquake source is an extremely important and ever evolving field of research. Within this field, source inversion of the W-phase has recently been shown to be an effective technique, which can be efficiently implemented in real-time. An extension to the W-phase source inversion is presented in which two point sources are derived to better characterize complex earthquakes. A single source inversion followed by a double point source inversion with centroid locations fixed at the single source solution location can be efficiently run as part of earthquake monitoring network operational procedures. In order to determine the most appropriate solution, i.e., whether an earthquake is most appropriately described by a single source or a double source, an Akaike information criterion (AIC) test is performed. Analyses of all earthquakes of magnitude 7.5 and greater occurring since January 2000 were performed with extended analyses of the September 29, 2009 magnitude 8.1 Samoa earthquake and the April 19, 2014 magnitude 7.5 Papua New Guinea earthquake. The AIC test is shown to be able to accurately select the most appropriate model and the selected W-phase inversion is shown to yield reliable solutions that match published analyses of the same events.

  12. Recommendations for appropriate activated partial thromboplastin time reagent selection and utilization.

    PubMed

    Fritsma, George A; Dembitzer, Francine R; Randhawa, Ankush; Marques, Marisa B; Van Cott, Elizabeth M; Adcock-Funk, Dorothy; Peerschke, Ellinor I

    2012-06-01

    The activated partial thromboplastin time (aPTT) is widely used as a screening coagulation test and for monitoring unfractionated heparin therapy. Various commercial reagents are available, with different performance characteristics, particularly responsiveness to the lupus anticoagulant (LA). Because aPTT reagent selection significantly affects the interpretation of results, we reviewed College of American Pathologists proficiency testing data involving approximately 4,000 coagulation laboratories, and conducted a survey of coagulation laboratories (n = 93) using The Fritsma Factor hemostasis Web site to determine the basis for aPTT reagent selection. The data demonstrate that for routine aPTT testing, most laboratories use reagents with high/moderate responsiveness to LA. Significant misunderstanding was apparent regarding the use of appropriate aPTT reagent for routine testing and LA identification. We recommend aPTT reagents with low LA responsiveness to screen for coagulation factor deficiencies and heparin monitoring, and suggest continued education of laboratory professionals and reagent manufacturers about appropriate aPTT reagent use.

  13. Detection of Salmonella spp. in veterinary samples by combining selective enrichment and real-time PCR.

    PubMed

    Goodman, Laura B; McDonough, Patrick L; Anderson, Renee R; Franklin-Guild, Rebecca J; Ryan, James R; Perkins, Gillian A; Thachil, Anil J; Glaser, Amy L; Thompson, Belinda S

    2017-08-01

    Rapid screening for enteric bacterial pathogens in clinical environments is essential for biosecurity. Salmonella found in veterinary hospitals, particularly Salmonella enterica serovar Dublin, can pose unique challenges for culture and testing because of its poor growth. Multiple Salmonella serovars including Dublin are emerging threats to public health given increasing prevalence and antimicrobial resistance. We adapted an automated food testing method to veterinary samples and evaluated the performance of the method in a variety of matrices including environmental samples ( n = 81), tissues ( n = 52), feces ( n = 148), and feed ( n = 29). A commercial kit was chosen as the basis for this approach in view of extensive performance characterizations published by multiple independent organizations. A workflow was established for efficiently and accurately testing veterinary matrices and environmental samples by use of real-time PCR after selective enrichment in Rappaport-Vassiliadis soya (RVS) medium. Using this method, the detection limit for S. Dublin improved by 100-fold over subculture on selective agars (eosin-methylene blue, brilliant green, and xylose-lysine-deoxycholate). Overall, the procedure was effective in detecting Salmonella spp. and provided next-day results.

  14. Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates

    PubMed Central

    Furman, Adam C.; Kujawa, Sharon G.

    2013-01-01

    Acoustic overexposure can cause a permanent loss of auditory nerve fibers without destroying cochlear sensory cells, despite complete recovery of cochlear thresholds (Kujawa and Liberman 2009), as measured by gross neural potentials such as the auditory brainstem response (ABR). To address this nominal paradox, we recorded responses from single auditory nerve fibers in guinea pigs exposed to this type of neuropathic noise (4- to 8-kHz octave band at 106 dB SPL for 2 h). Two weeks postexposure, ABR thresholds had recovered to normal, while suprathreshold ABR amplitudes were reduced. Both thresholds and amplitudes of distortion-product otoacoustic emissions fully recovered, suggesting recovery of hair cell function. Loss of up to 30% of auditory-nerve synapses on inner hair cells was confirmed by confocal analysis of the cochlear sensory epithelium immunostained for pre- and postsynaptic markers. In single fiber recordings, at 2 wk postexposure, frequency tuning, dynamic range, postonset adaptation, first-spike latency and its variance, and other basic properties of auditory nerve response were all completely normal in the remaining fibers. The only physiological abnormality was a change in population statistics suggesting a selective loss of fibers with low- and medium-spontaneous rates. Selective loss of these high-threshold fibers would explain how ABR thresholds can recover despite such significant noise-induced neuropathy. A selective loss of high-threshold fibers may contribute to the problems of hearing in noisy environments that characterize the aging auditory system. PMID:23596328

  15. Tumor-selective mitochondrial network collapse induced by atmospheric gas plasma-activated medium.

    PubMed

    Saito, Kosuke; Asai, Tomohiko; Fujiwara, Kyoko; Sahara, Junki; Koguchi, Haruhisa; Fukuda, Noboru; Suzuki-Karasaki, Miki; Soma, Masayoshi; Suzuki-Karasaki, Yoshihiro

    2016-04-12

    Non-thermal atmospheric gas plasma (AGP) exhibits cytotoxicity against malignant cells with minimal cytotoxicity toward normal cells. However, the mechanisms of its tumor-selective cytotoxicity remain unclear. Here we report that AGP-activated medium increases caspase-independent cell death and mitochondrial network collapse in a panel of human cancer cells, but not in non-transformed cells. AGP irradiation stimulated reactive oxygen species (ROS) generation in AGP-activated medium, and in turn the resulting stable ROS, most likely hydrogen peroxide (H2O2), activated intracellular ROS generation and mitochondrial ROS (mROS) accumulation. Culture in AGP-activated medium resulted in cell death and excessive mitochondrial fragmentation and clustering, and these responses were inhibited by ROS scavengers. AGP-activated medium also increased dynamin-related protein 1-dependent mitochondrial fission in a tumor-specific manner, and H2O2 administration showed similar effects. Moreover, the vulnerability of tumor cells to mitochondrial network collapse appeared to result from their higher sensitivity to mROS accumulation induced by AGP-activated medium or H2O2. The present findings expand our previous observations on death receptor-mediated tumor-selective cell killing and reinforce the importance of mitochondrial network remodeling as a powerful target for tumor-selective cancer treatment.

  16. Tumor-selective mitochondrial network collapse induced by atmospheric gas plasma-activated medium

    PubMed Central

    Saito, Kosuke; Asai, Tomohiko; Fujiwara, Kyoko; Sahara, Junki; Koguchi, Haruhisa; Fukuda, Noboru; Suzuki-Karasaki, Miki; Soma, Masayoshi; Suzuki-Karasaki, Yoshihiro

    2016-01-01

    Non-thermal atmospheric gas plasma (AGP) exhibits cytotoxicity against malignant cells with minimal cytotoxicity toward normal cells. However, the mechanisms of its tumor-selective cytotoxicity remain unclear. Here we report that AGP-activated medium increases caspase-independent cell death and mitochondrial network collapse in a panel of human cancer cells, but not in non-transformed cells. AGP irradiation stimulated reactive oxygen species (ROS) generation in AGP-activated medium, and in turn the resulting stable ROS, most likely hydrogen peroxide (H2O2), activated intracellular ROS generation and mitochondrial ROS (mROS) accumulation. Culture in AGP-activated medium resulted in cell death and excessive mitochondrial fragmentation and clustering, and these responses were inhibited by ROS scavengers. AGP-activated medium also increased dynamin-related protein 1-dependent mitochondrial fission in a tumor-specific manner, and H2O2 administration showed similar effects. Moreover, the vulnerability of tumor cells to mitochondrial network collapse appeared to result from their higher sensitivity to mROS accumulation induced by AGP-activated medium or H2O2. The present findings expand our previous observations on death receptor-mediated tumor-selective cell killing and reinforce the importance of mitochondrial network remodeling as a powerful target for tumor-selective cancer treatment. PMID:26942565

  17. Preferential and non-selective cyclooxygenase inhibitors reduce inflammation during lipopolysaccharide-induced synovitis.

    PubMed

    Morton, Alison J; Campbell, Nigel B; Gayle, J'mai M; Redding, W Rich; Blikslager, Anthony T

    2005-04-01

    Synovitis in horses is frequently treated by administration of non-steroidal anti-inflammatory drugs (NSAIDs), which inhibit cyclooxygenase isoforms (COX-1 and COX-2). Constitutively expressed COX-1 is involved in physiologic functions such as maintenance of gastric mucosal integrity, whereas COX-2 is up-regulated at sites of inflammation. Thus, COX-2 inhibitors reduce inflammation with reduced gastrointestinal side effects as compared to non-selective COX inhibitors. The objective of the present study was to compare the anti-inflammatory effects of the preferential COX-2 inhibitor etodolac with the non-selective COX inhibitor phenylbutazone in horses with lipopolysaccharide (LPS)-induced synovitis. Three groups of horses (n=6) received no treatment, phenylbutazone (4.4 mg/kg, IV, q12h), or etodolac (23 mg/kg, IV, q12h), respectively, 2-h following injection of LPS into one middle carpal joint. Synovial fluid was analyzed for white blood cell (WBC) count, and TXB2 and PGE2 levels. Phenylbutazone and etodolac significantly reduced WBC count 6 and 24-h following injection of LPS compared to untreated horses. In addition, both drugs significantly reduced PGE2 levels (P<0.05) 6-h following LPS injection, whereas the probable COX-1 prostanoid TXB2 was significantly reduced by phenylbutazone (P<0.05), but not etodolac. Etodolac may serve as a more selective anti-inflammatory agent than phenylbutazone for treatment of equine synovitis.

  18. Bond selectivity in electron-induced reaction due to directed recoil on an anisotropic substrate

    NASA Astrophysics Data System (ADS)

    Anggara, Kelvin; Huang, Kai; Leung, Lydie; Chatterjee, Avisek; Cheng, Fang; Polanyi, John C.

    2016-12-01

    Bond-selective reaction is central to heterogeneous catalysis. In heterogeneous catalysis, selectivity is found to depend on the chemical nature and morphology of the substrate. Here, however, we show a high degree of bond selectivity dependent only on adsorbate bond alignment. The system studied is the electron-induced reaction of meta-diiodobenzene physisorbed on Cu(110). Of the adsorbate's C-I bonds, C-I aligned `Along' the copper row dissociates in 99.3% of the cases giving surface reaction, whereas C-I bond aligned `Across' the rows dissociates in only 0.7% of the cases. A two-electronic-state molecular dynamics model attributes reaction to an initial transition to a repulsive state of an Along C-I, followed by directed recoil of C towards a Cu atom of the same row, forming C-Cu. A similar impulse on an Across C-I gives directed C that, moving across rows, does not encounter a Cu atom and hence exhibits markedly less reaction.

  19. Microbially induced selective flotation of sphalerite from galena using mineral-adapted strains of Bacillus megaterium.

    PubMed

    Vasanthakumar, B; Ravishankar, H; Subramanian, S

    2013-12-01

    The selective flotation of sphalerite from a sphalerite-galena mineral mixture has been achieved using cells and extracellular secretions of Bacillus megaterium after adaptation to the chosen minerals. The extracellular secretions obtained after thermolysis of bacterial cells adapted to sphalerite yield the highest flotation recovery of sphalerite with a selectivity index value of 24.5, in comparison to the other cellular and extra-cellular bio-reagents studied. The protein profile for the unadapted and mineral-adapted cells has been found to differ distinctly, attesting to variation in the yield and nature of extra-cellular polymeric substances (EPS). The changes induced in the bacterial cell wall components after adaptation to sphalerite or galena with respect to the contents of phosphate, uronic acid and acetylated sugars of B. megaterium have been quantified. The role of the dissolved metal ions from the minerals as well as that of the constituents of extracellular secretions in modulating the surface charge of the bacterial cells as well as the minerals under study has been confirmed using various enzymatic treatments of the bacterial cells. It has been demonstrated that the induction of additional molecular weight protein fractions as well as the higher amount of extracellular proteins and phosphate secreted after adaptation to sphalerite vis-à-vis galena are contributory factors for the selective separation of sphalerite from galena.

  20. Carbon induced selective regulation of cobalt-based Fischer-Tropsch catalysts by ethylene treatment.

    PubMed

    Zhai, Peng; Chen, Pei-Pei; Xie, Jinglin; Liu, Jin-Xun; Zhao, Huabo; Lin, Lili; Zhao, Bo; Su, Hai-Yan; Zhu, Qingjun; Li, Wei-Xue; Ma, Ding

    2017-02-10

    Various carbonaceous species were controllably deposited on Co/Al2O3 catalysts using ethylene as carbon source during the activation process for Fischer-Tropsch synthesis (FTS). Atomic, polymeric and graphitic carbon were distinguished by Raman spectroscopy, thermoanalysis and temperature programmed hydrogenation. Significant changes occurred in both the catalytic activity and selectivity toward hydrocarbon products after ethylene treatment. The activity decreased along with an increase in CH4 selectivity, at the expense of a remarkable decrease of heavy hydrocarbon production, resulting in enhanced selectivity for the gasoline fraction. In situ XPS experiments show the possible electron transfer from cobalt to carbon and the blockage of metallic cobalt sites, which is responsible for the deactivation of the catalyst. DFT calculations reveal that the activation barrier (Ea) of methane formation decreases by 0.61 eV on the carbon-absorbed Co(111) surface, whereas the Ea of the CH + CH coupling reaction changes unnoticeably. Hydrogenation of CHx to methane becomes the preferable route among the elementary reactions on the Co(111) surface, leading to dramatic changes in the product distribution. Detailed coke-induced deactivation mechanisms of Co-based catalysts during FTS are discussed.

  1. A zinc-binding site by negative selection induces metallodrug susceptibility in an essential chaperonin

    PubMed Central

    Cun, Shujian; Sun, Hongzhe

    2010-01-01

    GroES is an indispensable chaperonin virtually found throughout all life forms. Consequently, mutations of this protein must be critically scrutinized by natural selection. Nevertheless, the homolog from a potentially virulent gastric pathogen, Helicobacter pylori, strikingly features a histidine/cysteine-rich C terminus that shares no significant homology with other family members. Additionally, three more (H45, C51, and C53) are uniquely present in its apical domain. The statistical analyses show that these residues may have originated from negative selection, presumably driven by either dependent or independent amino acid mutations. In the absence of the C-terminal metal-binding domain, the mutant protein still exhibits a substantial capacity for zinc binding in vivo. The biochemical properties of site-directed mutants indicate that H45, C51, and C53 make up an oxidation-sensitive zinc-binding site that may donate the bound metal to a zinc acceptor. Of interest, bismuth antiulcer drugs strongly bind at this site (Kd of approximately 7 × 10-26 M), replacing the bound zinc and consequently inducing the disruption of the quaternary structure. Because biological features by negative selection are usually inert to change during evolution, this study sheds light on a promising field whereby medicines can be designed or improved to specifically target the residues that uniquely evolved in pathogenic proteins so as to retard the emergence of drug resistance. PMID:20194796

  2. Inhomogeneity-induced timing jitter of superconducting nanowire single-photon detectors

    NASA Astrophysics Data System (ADS)

    Cheng, Yuhao; Gu, Chao; Hu, Xiaolong

    2017-08-01

    We show that the distributed electronic and geometric inhomogeneity of a superconducting nanowire induces timing jitter of the resulting single-photon detector and this timing jitter could be further exacerbated by localized constrictions. Due to the distributed inhomogeneity, photons absorbed at different locations of the nanowire generate hotspots that "sense" different local properties of the nanowire during the electro-thermal evolutions and thereby produce varying time delays. The localized constrictions limit the bias current, slow down the Joule-heating process, and consequently increase the average time delays and the inhomogeneity-induced timing jitter. We combine the Monte-Carlo method and the electro-thermal simulation to illustrate the inhomogeneity-induced timing jitter.

  3. Extraordinary reflection and transmission with direction dependent wavelength selectivity based on parity-time-symmetric multilayers

    SciTech Connect

    Ding, Shulin; Wang, Guo Ping

    2015-01-14

    In this paper, we present a kind of periodical ternary parity-time (PT) -symmetric multilayers to realize nearly 100% reflectance and transmittance simultaneously when light is incident from a certain direction. This extraordinary reflection and transmission is original from unidirectional Bragg reflection of PT-symmetric systems as the symmetry spontaneous breaking happens at PT thresholds. The extra energy involved in reflection and transmission lights is obtained from pumping light to the gain regions of the structure. Moreover, we find that our PT-symmetric structure shows direction dependent wavelength selectivity. When the illumination light is incident from two opposite directions into the multilayer structure, such extraordinary reflection and transmission appear at visible and near-infrared wavelengths, respectively. Such distinguishing properties may provide these structures with attractive applications as beam splitters, laser mirrors, narrow band filters, and multiband PT-symmetric optical devices.

  4. The negative compatibility effect: unconscious inhibition influences reaction time and response selection.

    PubMed

    Klapp, Stuart T; Hinkley, Leighton B

    2002-06-01

    In the negative compatibility effect (NCE) a masked prime arrow, pointing left or right, is followed by an unmasked (visible) target arrow. The task is to press the left or right switch corresponding to the visible arrow. Surprisingly, reaction time is longer (slowed) when the prime and target indicate the same, rather than different, responses. By contrast, the effect of an unmasked prime is positive-opposite to the NCE. This indicates that the NCE is not attributable to incomplete masking; to the extent that the prime is visible, the NCE would be reduced by this positive influence. Thus, the NCE appears to result from unconscious processing of the prime and, in that sense, may be a form of subliminal perception. Additional findings show that the NCE is due to inhibition of a response code, that it is automatic in that it occurs even if the information in the prime and target could be ignored, and that it also influences response selection.

  5. Control of selectivity in heterogeneous catalysis by tuning nanoparticle properties and reactor residence time

    NASA Astrophysics Data System (ADS)

    Gross, Elad; Liu, Jack Hung-Chang; Toste, F. Dean; Somorjai, Gabor A.

    2012-11-01

    A combination of the advantages of homogeneous and heterogeneous catalysis could enable the development of sustainable catalysts with novel reactivity and selectivity. Although heterogeneous catalysts are often recycled more easily than their homogeneous counterparts, they can be difficult to apply in traditional organic reactions and modification of their properties towards a desired reactivity is, at best, complex. In contrast, tuning the properties of homogeneous catalysts by, for example, modifying the ligands that coordinate a metal centre is better understood. Here, using olefin cyclopropanation reactions catalysed by dendrimer-encapsulated Au nanoclusters as examples, we demonstrate that changing the dendrimer properties allows the catalytic reactivity to be tuned in a similar fashion to ligand modification in a homogeneous catalyst. Furthermore, we show that these heterogeneous catalysts employed in a fixed-bed flow reactor allow fine control over the residence time of the reactants and thus enables the control over product distribution in a way that is not easily available for homogeneous catalysts.

  6. On the non-stationarity of financial time series: impact on optimal portfolio selection

    NASA Astrophysics Data System (ADS)

    Livan, Giacomo; Inoue, Jun-ichi; Scalas, Enrico

    2012-07-01

    We investigate the possible drawbacks of employing the standard Pearson estimator to measure correlation coefficients between financial stocks in the presence of non-stationary behavior, and we provide empirical evidence against the well-established common knowledge that using longer price time series provides better, more accurate, correlation estimates. Then, we investigate the possible consequences of instabilities in empirical correlation coefficient measurements on optimal portfolio selection. We rely on previously published works which provide a framework allowing us to take into account possible risk underestimations due to the non-optimality of the portfolio weights being used in order to distinguish such non-optimality effects from risk underestimations genuinely due to non-stationarities. We interpret such results in terms of instabilities in some spectral properties of portfolio correlation matrices.

  7. Measuring JHH values with a selective constant-time 2D NMR protocol

    NASA Astrophysics Data System (ADS)

    Lin, Liangjie; Wei, Zhiliang; Lin, Yanqin; Chen, Zhong

    2016-11-01

    Proton-proton scalar couplings play important roles in molecule structure elucidation. However, measurements of JHH values in complex coupled spin systems remain challenging. In this study, we develop a selective constant-time (SECT) 2D NMR protocol with which scalar coupling networks involving chosen protons can be revealed, and corresponding JHH values can be measured through doublets along the F1 dimension. All JHH values within a network of n fully coupled protons can be separately determined with (n - 1) SECT experiments. Additionally, the proposed pulse sequence possesses satisfactory sensitivity and handy implementation. Therefore, it will interest scientists who intend to address structural analyzes of molecules with overcrowded spectra, and may greatly facilitate the applications of scalar-coupling constants in molecule structure studies.

  8. Control of selectivity in heterogeneous catalysis by tuning nanoparticle properties and reactor residence time.

    PubMed

    Gross, Elad; Liu, Jack Hung-Chang; Toste, F Dean; Somorjai, Gabor A

    2012-11-01

    A combination of the advantages of homogeneous and heterogeneous catalysis could enable the development of sustainable catalysts with novel reactivity and selectivity. Although heterogeneous catalysts are often recycled more easily than their homogeneous counterparts, they can be difficult to apply in traditional organic reactions and modification of their properties towards a desired reactivity is, at best, complex. In contrast, tuning the properties of homogeneous catalysts by, for example, modifying the ligands that coordinate a metal centre is better understood. Here, using olefin cyclopropanation reactions catalysed by dendrimer-encapsulated Au nanoclusters as examples, we demonstrate that changing the dendrimer properties allows the catalytic reactivity to be tuned in a similar fashion to ligand modification in a homogeneous catalyst. Furthermore, we show that these heterogeneous catalysts employed in a fixed-bed flow reactor allow fine control over the residence time of the reactants and thus enables the control over product distribution in a way that is not easily available for homogeneous catalysts.

  9. Emergence of drug tolerance in cancer cell populations: an evolutionary outcome of selection, nongenetic instability, and stress-induced adaptation.

    PubMed

    Chisholm, Rebecca H; Lorenzi, Tommaso; Lorz, Alexander; Larsen, Annette K; de Almeida, Luís Neves; Escargueil, Alexandre; Clairambault, Jean

    2015-03-15

    In recent experiments on isogenetic cancer cell lines, it was observed that exposure to high doses of anticancer drugs can induce the emergence of a subpopulation of weakly proliferative and drug-tolerant cells, which display markers associated with stem cell-like cancer cells. After a period of time, some of the surviving cells were observed to change their phenotype to resume normal proliferation and eventually repopulate the sample. Furthermore, the drug-tolerant cells could be drug resensitized following drug washout. Here, we propose a theoretical mechanism for the transient emergence of such drug tolerance. In this framework, we formulate an individual-based model and an integro-differential equation model of reversible phenotypic evolution in a cell population exposed to cytotoxic drugs. The outcomes of both models suggest that nongenetic instability, stress-induced adaptation, selection, and the interplay between these mechanisms can push an actively proliferating cell population to transition into a weakly proliferative and drug-tolerant state. Hence, the cell population experiences much less stress in the presence of the drugs and, in the long run, reacquires a proliferative phenotype, due to phenotypic fluctuations and selection pressure. These mechanisms can also reverse epigenetic drug tolerance following drug washout. Our study highlights how the transient appearance of the weakly proliferative and drug-tolerant cells is related to the use of high-dose therapy. Furthermore, we show how stem-like characteristics can act to stabilize the transient, weakly proliferative, and drug-tolerant subpopulation for a longer time window. Finally, using our models as in silico laboratories, we propose new testable hypotheses that could help uncover general principles underlying the emergence of cancer drug tolerance.

  10. Selective cerebral perfusion: real-time evidence of brain oxygen and energy metabolism preservation.

    PubMed

    Salazar, Jorge D; Coleman, Ryan D; Griffith, Stephen; McNeil, Jeffrey D; Steigelman, Megan; Young, Haven; Hensler, Bart; Dixon, Patricia; Calhoon, John; Serrano, Faridis; DiGeronimo, Robert

    2009-07-01

    Deep hypothermic circulatory arrest (DHCA) is commonly used for complex cardiac operations in children, often with selective cerebral perfusion (SCP). Little data exist concerning the real-time effects of DHCA with or without SCP on cerebral metabolism. Our objective was to better define these effects, focusing on brain oxygenation and energy metabolism. Piglets undergoing cardiopulmonary bypass were assigned to either 60 minutes of DHCA at 18 degrees C (n = 9) or DHCA with SCP at 18 degrees C (n = 8), using pH-stat management. SCP was administered at 10 mL/kg/min. A cerebral microdialysis catheter was implanted into the cortex for monitoring of cellular ischemia and energy stores. Cerebral oxygen tension and intracranial pressure also were monitored. After DHCA with or without SCP, animals were recovered for 4 hours off cardiopulmonary bypass. With SCP, brain oxygen tension was preserved in contrast to DHCA alone (p < 0.01). Deep hypothermic circulatory arrest was associated with marked elevations of lactate (p < 0.01), glycerol (p < 0.01), and the lactate to pyruvate ratio (p < 0.001), as well as profound depletion of the energy substrates glucose (p < 0.001) and pyruvate (p < 0.001). These changes persisted well into recovery. With SCP, no significant cerebral microdialysis changes were observed. A strong correlation was demonstrated between cerebral oxygen levels and cerebral microdialysis markers (p < 0.001). Selective cerebral perfusion preserves cerebral oxygenation and attenuates derangements in cerebral metabolism associated with DHCA. Cerebral microdialysis provides real-time metabolic feedback that correlates with changes in brain tissue oxygenation. This model enables further study and refinement of strategies aiming to limit brain injury in children requiring complex cardiac operations.

  11. Breakdown of selection-mediated correlation between development time and clock period.

    PubMed

    Yadav, Pankaj; Sharma, Vijay Kumar

    2014-04-22

    Previously we have reported that selection for faster pre-adult development in fruit flies speeded-up development by ~29-h and shortened the clock period (τ) by ~0.5h, which suggests that development time and τ are correlated. Since it is known that τ is altered following exposure to light/dark (LD) cycles, we asked whether this correlation persists in the faster developing (FD) and control (BD) flies by examining the τ of the activity/rest rhythm and its difference between the two stocks following exposure to a variety of cyclic conditions. We assayed the activity/rest behavior of FD and BD flies under DD, following a week-long exposure to (a) LD cycles of 10:10h, 12:12h and 14:14h, or (b) LD12:12h with different light intensities (10, 100 and 1000lx), or (c) 12:12h warm/cold (WC) cycles of 25:18°C (WC1) and 29:25°C (WC2), or (d) WC1 or WC2, in-phase or out-of-phase with LD. The results revealed that both LD and WC altered the τ of FD and BD flies, and considerably reduced the selection-mediated difference between the two stocks. LD10:10 caused more severe after-effects on τ compared to LD12:12 and LD14:14. Among the WC cycles, WC1 which had a higher contrast caused period shortening. Irrespective of the phase relationship, imposition of LD cycles on WC cycles made no difference to the extent of after-effects; however, interestingly there was a reversal in the trend, in that, now WC2 with LD caused most drastic reduction in τ. These results suggest that cyclic environments modulate the circadian organization of Drosophila melanogaster altering the selection-mediated correlation between pre-adult development time and clock period. Copyright © 2014 Elsevier Inc. All rights reserved.

  12. Antioxidant defense in quiescent cells determines selectivity of electron transport chain inhibition-induced cell death.

    PubMed

    Blecha, Jan; Novais, Silvia Magalhaes; Rohlenova, Katerina; Novotna, Eliska; Lettlova, Sandra; Schmitt, Sabine; Zischka, Hans; Neuzil, Jiri; Rohlena, Jakub

    2017-07-31

    Mitochondrial electron transport chain (ETC) targeting shows a great promise in cancer therapy. It is particularly effective in tumors with high ETC activity where ETC-derived reactive oxygen species (ROS) are efficiently induced. Why modern ETC-targeted compounds are tolerated on the organismal level remains unclear. As most somatic cells are in non-proliferative state, the features associated with the ETC in quiescence could account for some of the specificity observed. Here we report that quiescent cells, despite increased utilization of the ETC and enhanced supercomplex assembly, are less susceptible to cell death induced by ETC disruption when glucose is not limiting. Mechanistically, this is mediated by the increased detoxification of ETC-derived ROS by mitochondrial antioxidant defense, principally by the superoxide dismutase 2 - thioredoxin axis. In contrast, under conditions of glucose limitation, cell death is induced preferentially in quiescent cells and is correlated with intracellular ATP depletion but not with ROS. This is related to the inability of quiescent cells to compensate for the lost mitochondrial ATP production by the upregulation of glucose uptake. Hence, elevated ROS, not the loss of mitochondrially-generated ATP, are responsible for cell death induction by ETC disruption in ample nutrients condition, e.g. in well perfused healthy tissues, where antioxidant defense imparts specificity. However, in conditions of limited glucose, e.g. in poorly perfused tumors, ETC disruption causes rapid depletion of cellular ATP, optimizing impact towards tumor-associated dormant cells. In summary, we propose that antioxidant defense in quiescent cells is aided by local glucose limitations to ensure selectivity of ETC inhibition-induced cell death. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. Host-Selective Toxins of Pyrenophora tritici-repentis Induce Common Responses Associated with Host Susceptibility

    PubMed Central

    Pandelova, Iovanna; Figueroa, Melania; Wilhelm, Larry J.; Manning, Viola A.; Mankaney, Aakash N.; Mockler, Todd C.; Ciuffetti, Lynda M.

    2012-01-01

    Pyrenophora tritici-repentis (Ptr), a necrotrophic fungus and the causal agent of tan spot of wheat, produces one or a combination of host-selective toxins (HSTs) necessary for disease development. The two most studied toxins produced by Ptr, Ptr ToxA (ToxA) and Ptr ToxB (ToxB), are proteins that cause necrotic or chlorotic symptoms respectively. Investigation of host responses induced by HSTs provides better insight into the nature of the host susceptibility. Microarray analysis of ToxA has provided evidence that it can elicit responses similar to those associated with defense. In order to evaluate whether there are consistent host responses associated with susceptibility, a similar analysis of ToxB-induced changes in the same sensitive cultivar was conducted. Comparative analysis of ToxA- and ToxB-induced transcriptional changes showed that similar groups of genes encoding WRKY transcription factors, RLKs, PRs, components of the phenylpropanoid and jasmonic acid pathways are activated. ROS accumulation and photosystem dysfunction proved to be common mechanism-of-action for these toxins. Despite similarities in defense responses, transcriptional and biochemical responses as well as symptom development occur more rapidly for ToxA compared to ToxB, which could be explained by differences in perception as well as by differences in activation of a specific process, for example, ethylene biosynthesis in ToxA treatment. Results of this study suggest that perception of HSTs will result in activation of defense responses as part of a susceptible interaction and further supports the hypothesis that necrotrophic fungi exploit defense responses in order to induce cell death. PMID:22792250

  14. The atypical antipsychotic clozapine selectively inhibits interleukin 8 (IL-8)-induced neutrophil chemotaxis.

    PubMed

    Capannolo, Marta; Fasciani, Irene; Romeo, Stefania; Aloisi, Gabriella; Rossi, Mario; Bellio, Pierangelo; Celenza, Giuseppe; Cinque, Benedetta; Cifone, Maria Grazia; Scarselli, Marco; Maggio, Roberto

    2015-03-01

    Clozapine is the most effective antipsychotic to date, but its benefits are counterbalanced by the risk of severe hematological effects. In this study, we analyzed whether clozapine inhibits polymorphonuclear (PMN) leukocyte chemotaxis. We found that clozapine, within the therapeutic concentration range, potently and selectively inhibits PMN chemotaxis induced by interleukin 8 (IL-8), a chemokine inducing neutrophil migration. The effect was not due to its action at dopamine, serotonin and muscarinic receptors, or to a direct antagonism to IL-8 receptors. Furthermore, clozapine did not inhibit PMN chemotaxis by its presumed toxic mechanism. In fact, after an overnight incubation in cell culture, the drug did not increase the physiological PMN apoptosis. An interference of clozapine with the autocrine release of leukotriene B4 (LTB4), a secondary chemoattractant secreted by neutrophils in response to the primary chemoattractant IL-8, was hypothesized. In agreement with this hypothesis, clozapine attenuated the IL-8-induced release of LTB4 in PMNs. A series of experiments with an antagonist of the LTB4 receptor, U75302, and an inhibitor of LTB4 synthesis, zileuton, provided support to this conjecture. Intriguingly MK-571, an inhibitor of the multi-drug resistance protein MRP4, playing a pivotal role in effluxing LTB4, completely blocked PMN chemotaxis induced by IL-8, but gave conflicting results when tested for its ability to reduce LTB4 release, increasing LTB4 efflux by itself but reducing the release when in combination with IL-8. The reduction of PMN chemotaxis due to clozapine could predispose patients to infections. Whether this effect is a prelude to clozapine agranulocytosis requires further investigation.

  15. Lipophilic but not hydrophilic statins selectively induce cell death in gynaecological cancers expressing high levels of HMGCoA reductase.

    PubMed

    Kato, S; Smalley, S; Sadarangani, A; Chen-Lin, K; Oliva, B; Brañes, J; Carvajal, J; Gejman, R; Owen, G I; Cuello, M

    2010-05-01

    Recent reports have suggested that statins induce cell death in certain epithelial cancers and that patients taking statins to reduce cholesterol levels possess lower cancer incidence. However, little is known about the mechanisms of action of different statins or the effects of these statins in gynaecological malignancies. The apoptotic potential of two lipophilic statins (lovastatin and simvastatin) and one hydrophilic statin (pravastatin) was assessed in cancer cell lines (ovarian, endometrial and cervical) and primary cultured cancerous and normal tissues. Cell viability was studied by MTS assays and apoptosis was confirmed by Western blotting of PARP and flow cytometry. The expressions of key apoptotic cascade proteins were analysed. Our results demonstrate that both lovastatin and simvastatin, but not pravastatin, selectively induced cell death in dose- and time-dependent manner in ovarian, endometrial and cervical cancers. Little or no toxicity was observed with any statin on normal cells. Lipophilic statins induced activation of caspase-8 and -9; BID cleavage, cytochrome C release and PARP cleavage. Statin-sensitive cancers expressed high levels of HMG-CoA reductase compared with resistant cultures. The effect of lipophilic statins was dependent on inhibition of enzymatic activity of HMG-CoA reductase since mevalonate pre-incubation almost completely abrogated the apoptotic effect. Moreover, the apoptotic effect involved the inhibition of synthesis of geranylgeranyl pyrophosphate rather than farnesyl pyrophosphate. In conclusion, lipophilic but not hydrophilic statins induce cell death through activation of extrinsic and intrinsic apoptotic cascades in cancerous cells from the human female genital tract, which express high levels of HMG-CoA reductase. These results promote further investigation in the use of lipophilic statins as anticancer agents in gynaecological malignancies.

  16. Lipophilic but not hydrophilic statins selectively induce cell death in gynaecological cancers expressing high levels of HMGCoA reductase

    PubMed Central

    Kato, S; Smalley, S; Sadarangani, A; Chen-Lin, K; Oliva, B; Brañes, J; Carvajal, J; Gejman, R; Owen, G I; Cuello, M

    2010-01-01

    Abstract Recent reports have suggested that statins induce cell death in certain epithelial cancers and that patients taking statins to reduce cholesterol levels possess lower cancer incidence. However, little is known about the mechanisms of action of different statins or the effects of these statins in gynaecological malignancies. The apoptotic potential of two lipophilic statins (lovastatin and simvastatin) and one hydrophilic statin (pravastatin) was assessed in cancer cell lines (ovarian, endometrial and cervical) and primary cultured cancerous and normal tissues. Cell viability was studied by MTS assays and apoptosis was confirmed by Western blotting of PARP and flow cytometry. The expressions of key apoptotic cascade proteins were analysed. Our results demonstrate that both lovastatin and simvastatin, but not pravastatin, selectively induced cell death in dose- and time-dependent manner in ovarian, endometrial and cervical cancers. Little or no toxicity was observed with any statin on normal cells. Lipophilic statins induced activation of caspase-8 and -9; BID cleavage, cytochrome C release and PARP cleavage. Statin-sensitive cancers expressed high levels of HMG-CoA reductase compared with resistant cultures. The effect of lipophilic statins was dependent on inhibition of enzymatic activity of HMG-CoA reductase since mevalonate pre-incubation almost completely abrogated the apoptotic effect. Moreover, the apoptotic effect involved the inhibition of synthesis of geranylgeranyl pyrophosphate rather than farnesyl pyrophosphate. In conclusion, lipophilic but not hydrophilic statins induce cell death through activation of extrinsic and intrinsic apoptotic cascades in cancerous cells from the human female genital tract, which express high levels of HMG-CoA reductase. These results promote further investigation in the use of lipophilic statins as anticancer agents in gynaecological malignancies. PMID:19432822

  17. Age-related slowing of response selection and production in a visual choice reaction time task

    PubMed Central

    Woods, David L.; Wyma, John M.; Yund, E. William; Herron, Timothy J.; Reed, Bruce

    2015-01-01

    Aging is associated with delayed processing in choice reaction time (CRT) tasks, but the processing stages most impacted by aging have not been clearly identified. Here, we analyzed CRT latencies in a computerized serial visual feature-conjunction task. Participants responded to a target letter (probability 40%) by pressing one mouse button, and responded to distractor letters differing either in color, shape, or both features from the target (probabilities 20% each) by pressing the other mouse button. Stimuli were presented randomly to the left and right visual fields and stimulus onset asynchronies (SOAs) were adaptively reduced following correct responses using a staircase procedure. In Experiment 1, we tested 1466 participants who ranged in age from 18 to 65 years. CRT latencies increased significantly with age (r = 0.47, 2.80 ms/year). Central processing time (CPT), isolated by subtracting simple reaction times (SRT) (obtained in a companion experiment performed on the same day) from CRT latencies, accounted for more than 80% of age-related CRT slowing, with most of the remaining increase in latency due to slowed motor responses. Participants were faster and more accurate when the stimulus location was spatially compatible with the mouse button used for responding, and this effect increased slightly with age. Participants took longer to respond to distractors with target color or shape than to distractors with no target features. However, the additional time needed to discriminate the more target-like distractors did not increase with age. In Experiment 2, we replicated the findings of Experiment 1 in a second population of 178 participants (ages 18–82 years). CRT latencies did not differ significantly in the two experiments, and similar effects of age, distractor similarity, and stimulus-response spatial compatibility were found. The results suggest that the age-related slowing in visual CRT latencies is largely due to delays in response selection and

  18. Bifurcations Induced in a Bistable Oscillator via Joint Noises and Time Delay

    NASA Astrophysics Data System (ADS)

    Fu, Jin; Sun, Zhongkui; Xiao, Yuzhu; Xu, Wei

    2016-06-01

    In this paper, noise-induced and delay-induced bifurcations in a bistable Duffing-van der Pol (DVP) oscillator under time delay and joint noises are discussed theoretically and numerically. Based on the qualitative changes of the plane phase, delay-induced bifurcations are investigated in the deterministic case. However, in the stochastic case, the response of the system is a stochastic non-Markovian process owing to the existence of noise and time delay. Then, methods have been employed to derive the stationary probability density function (PDF) of the amplitude of the response. Accordingly, stochastic P-bifurcations can be observed with the variations in the qualitative behavior of the stationary PDF for amplitude. Furthermore, results from both theoretical analyses and numerical simulations best demonstrate the appearance of noise-induced and delay-induced bifurcations, which are in good agreement.

  19. Structure-activity relationship of 9-methylstreptimidone, a compound that induces apoptosis selectively in adult T-cell leukemia cells.

    PubMed

    Takeiri, Masatoshi; Ota, Eisuke; Nishiyama, Shigeru; Kiyota, Hiromasa; Umezawa, Kazuo

    2012-01-01

    We previously reported that 9-methylstreptimidone, a piperidine compound isolated from a culture filtrate of Streptomyces, induces apoptosis selectively in adult T-cell leukemia cells. It was screened for a compound that inhibits LPS-induced NF-kappaB and NO production in mouse macrophages. However, 9-methystreptimidone is poorly obtained from the producing microorganism and difficult to synthesize. Therefore, in the present research, we studied the structure-activity relationship to look for new selective inhibitors. We found that the structure of the unsaturated hydrophobic portion of 9-methylstreptimidone was essential for the inhibition of LPS-induced NO production. Among the 9-methylstreptimidone-related compounds tested, (+/-)-4,alpha-diepi-streptovitacin A inhibited NO production in macrophage-like cells as potently as 9-methylstreptimidone and without cellular toxicity. Moreover, this compound selectively induced apoptosis in adult T-cell leukemia MT-1 cells.

  20. Cardiovascular control and time domain Granger causality: insights from selective autonomic blockade.

    PubMed

    Porta, Alberto; Castiglioni, Paolo; Di Rienzo, Marco; Bassani, Tito; Bari, Vlasta; Faes, Luca; Nollo, Giandomenico; Cividjan, Andrei; Quintin, Luc

    2013-08-28

    We studied causal relations among heart period (HP), systolic arterial pressure (SAP) and respiration (R) according to the definition of Granger causality in the time domain. Autonomic pharmacological challenges were used to alter the complexity of cardiovascular control. Atropine (AT), propranolol and clonidine (CL) were administered to block muscarinic receptors, β-adrenergic receptors and centrally sympathetic outflow, respectively. We found that: (i) at baseline, HP and SAP interacted in a closed loop with a dominant causal direction from HP to SAP; (ii) pharmacological blockades did not alter the bidirectional closed-loop interactions between HP and SAP, but AT reduced the dominance of the causal direction from HP to SAP; (iii) at baseline, bidirectional interactions between HP and R were frequently found; (iv) the closed-loop relation between HP and R was unmodified by the administration of drugs; (v) at baseline, unidirectional interactions from R to SAP were often found; and (vi) while AT induced frequently an uncoupling between R and SAP, CL favoured bidirectional interactions. These results prove that time domain measures of Granger causality can contribute to the description of cardiovascular control by suggesting the temporal direction of the interactions and by separating different causality schemes (e.g. closed loop versus unidirectional relations).

  1. Vortex-crossing-induced timing jitter of superconducting nanowire single-photon detectors

    NASA Astrophysics Data System (ADS)

    Wu, Hao; Gu, Chao; Cheng, Yuhao; Hu, Xiaolong

    2017-08-01

    We investigate the timing properties of single-photon-triggered vortex (or anti-vortex) crossing in a current-biased superconducting nanowire and find that the time delays caused in the vortex-crossing process vary with the transverse positions on the nanowire where the photons are absorbed. The position-dependent time delays indicate that the vortex-crossing process induces timing jitter of a superconducting nanowire single-photon detector (SNSPD). The magnitude of this timing jitter further depends on various parameters, including the polarization of the incident photon, the bias current, and the width of the nanowire. This vortex-crossing-induced timing jitter might represent the lower bound of the timing jitter of the SNSPD and fundamentally limit its time-resolving capability.

  2. Ultra-sensitive and selective NH3 room temperature gas sensing induced by manganese-doped titanium dioxide nanoparticles.

    PubMed

    Tshabalala, Zamaswazi P; Shingange, Katekani; Cummings, Franscious R; Ntwaeaborwa, Odireleng M; Mhlongo, Gugu H; Motaung, David E

    2017-10-15

    The study of the fabrication of ultra-high sensitive and selective room temperature ammonia (NH3) and nitrogen dioxide (NO2) gas sensors remains an important scientific challenge in the gas sensing field. This is motivated by their harmful impact on the human health and environment. Therefore, herein, we report for the first time on the gas sensing properties of TiO2 nanoparticles doped with various concentrations of manganese (Mn) (1.0, 1.5, 2.0, 2.5 and 3.0mol.% presented as S1, S2, S3, S4 and S5, respectively), synthesized using hydrothermal method. Structural analyses showed that both undoped and Mn-doped TiO2 crystallized in tetragonal phases. Optical studies revealed that the Mn doped TiO2 nanoparticles have enhanced UV→Vis emission with a broad shoulder at 540nm, signifying induced defects by substituting Ti(4+) ions with Mn(2+). The X-ray photoelectron spectroscopy and the electron paramagnetic resonance studies revealed the presence of Ti(3+) and singly ionized oxygen vacancies in both pure and Mn doped TiO2 nanoparticles. Additionally, a hyperfine split due to Mn(2+) ferromagnetic ordering was observed, confirming incorporation of Mn ions into the lattice sites. The sensitivity, selectivity, operating temperature, and response-recovery times were thoroughly evaluated according to the alteration in the materials electrical resistance in the presence of the target gases. Gas sensing studies showed that Mn(2+) doped on the TiO2 surface improved the NH3 sensing performance in terms of response, sensitivity and selectivity. The S1 sensing material revealed higher sensitivity of 127.39 at 20 ppm NH3 gas. The sensing mechanism towards NH3 gas is also proposed. Copyright © 2017 Elsevier Inc. All rights reserved.

  3. Time-dependent inhibition of CYP3A4 by sertraline, a selective serotonin reuptake inhibitor.

    PubMed

    Masubuchi, Yasuhiro; Kawaguchi, Yuki

    2013-11-01

    Drug-drug interactions associated with selective serotonin reuptake inhibitors (SSRIs) are widely known. A major interaction by SSRIs is the inhibition of cytochrome P450 (P450)-mediated hepatic drug metabolism. The SSRI, sertraline, is also reported to increase the blood concentration of co-administered drugs. The potency of sertraline directly to inhibit hepatic drug metabolism is relatively weak compared with the other SSRIs, implying that additional mechanisms are involved in the interactions. The study examined whether sertraline produces time-dependent inhibition of CYP3A4 and/or other P450 enzymes. Incubation of human liver microsomes with sertraline in the presence of NADPH resulted in marked decreases in testosterone 6β-hydroxylation activities, indicating that sertraline metabolism leads to CYP3A4 inactivation. This inactivation required NADPH and was not protected by glutathione. No significant inactivation was observed for other P450 enzymes. Spectroscopic evaluation revealed that microsomes with and without sertraline in the presence of NADPH gave a Soret peak at 455 nm, suggesting the formation of metabolic intermediate (MI) complexes of sertraline metabolite(s) with the reduced form of P450. This is the first report indicating that sertraline produced time-dependent inhibition of CYP3A4, which may be associated with MI complex formation. Copyright © 2013 John Wiley & Sons, Ltd.

  4. The Galex Time Domain Survey. I. Selection And Classification of Over a Thousand Ultraviolet Variable Sources

    NASA Technical Reports Server (NTRS)

    Gezari, S.; Martin, D. C.; Forster, K.; Neill, J. D.; Huber, M.; Heckman, T.; Bianchi, L.; Morrissey, P.; Neff, S. G.; Seibert, M.; hide

    2013-01-01

    We present the selection and classification of over a thousand ultraviolet (UV) variable sources discovered in approximately 40 deg(exp 2) of GALEX Time Domain Survey (TDS) NUV images observed with a cadence of 2 days and a baseline of observations of approximately 3 years. The GALEX TDS fields were designed to be in spatial and temporal coordination with the Pan-STARRS1 Medium Deep Survey, which provides deep optical imaging and simultaneous optical transient detections via image differencing. We characterize the GALEX photometric errors empirically as a function of mean magnitude, and select sources that vary at the 5 sigma level in at least one epoch. We measure the statistical properties of the UV variability, including the structure function on timescales of days and years. We report classifications for the GALEX TDS sample using a combination of optical host colors and morphology, UV light curve characteristics, and matches to archival X-ray, and spectroscopy catalogs. We classify 62% of the sources as active galaxies (358 quasars and 305 active galactic nuclei), and 10% as variable stars (including 37 RR Lyrae, 53 M dwarf flare stars, and 2 cataclysmic variables). We detect a large-amplitude tail in the UV variability distribution for M-dwarf flare stars and RR Lyrae, reaching up to absolute value(?m) = 4.6 mag and 2.9 mag, respectively. The mean amplitude of the structure function for quasars on year timescales is five times larger than observed at optical wavelengths. The remaining unclassified sources include UV-bright extragalactic transients, two of which have been spectroscopically confirmed to be a young core-collapse supernova and a flare from the tidal disruption of a star by dormant supermassive black hole. We calculate a surface density for variable sources in the UV with NUV less than 23 mag and absolute value(?m) greater than 0.2 mag of approximately 8.0, 7.7, and 1.8 deg(exp -2) for quasars, active galactic nuclei, and RR Lyrae stars

  5. THE GALEX TIME DOMAIN SURVEY. I. SELECTION AND CLASSIFICATION OF OVER A THOUSAND ULTRAVIOLET VARIABLE SOURCES

    SciTech Connect

    Gezari, S.; Martin, D. C.; Forster, K.; Neill, J. D.; Morrissey, P.; Wyder, T. K.; Huber, M.; Burgett, W. S.; Chambers, K. C.; Kaiser, N.; Magnier, E. A.; Tonry, J. L.; Heckman, T.; Bianchi, L.; Neff, S. G.; Seibert, M.; Schiminovich, D.; Price, P. A.

    2013-03-20

    We present the selection and classification of over a thousand ultraviolet (UV) variable sources discovered in {approx}40 deg{sup 2} of GALEX Time Domain Survey (TDS) NUV images observed with a cadence of 2 days and a baseline of observations of {approx}3 years. The GALEX TDS fields were designed to be in spatial and temporal coordination with the Pan-STARRS1 Medium Deep Survey, which provides deep optical imaging and simultaneous optical transient detections via image differencing. We characterize the GALEX photometric errors empirically as a function of mean magnitude, and select sources that vary at the 5{sigma} level in at least one epoch. We measure the statistical properties of the UV variability, including the structure function on timescales of days and years. We report classifications for the GALEX TDS sample using a combination of optical host colors and morphology, UV light curve characteristics, and matches to archival X-ray, and spectroscopy catalogs. We classify 62% of the sources as active galaxies (358 quasars and 305 active galactic nuclei), and 10% as variable stars (including 37 RR Lyrae, 53 M dwarf flare stars, and 2 cataclysmic variables). We detect a large-amplitude tail in the UV variability distribution for M-dwarf flare stars and RR Lyrae, reaching up to |{Delta}m| = 4.6 mag and 2.9 mag, respectively. The mean amplitude of the structure function for quasars on year timescales is five times larger than observed at optical wavelengths. The remaining unclassified sources include UV-bright extragalactic transients, two of which have been spectroscopically confirmed to be a young core-collapse supernova and a flare from the tidal disruption of a star by dormant supermassive black hole. We calculate a surface density for variable sources in the UV with NUV < 23 mag and |{Delta}m| > 0.2 mag of {approx}8.0, 7.7, and 1.8 deg{sup -2} for quasars, active galactic nuclei, and RR Lyrae stars, respectively. We also calculate a surface density rate in the

  6. Effects of Selection and Training on Unit-Level Performance over Time: A Latent Growth Modeling Approach

    ERIC Educational Resources Information Center

    Van Iddekinge, Chad H.; Ferris, Gerald R.; Perrewe, Pamela L.; Perryman, Alexa A.; Blass, Fred R.; Heetderks, Thomas D.

    2009-01-01

    Surprisingly few data exist concerning whether and how utilization of job-related selection and training procedures affects different aspects of unit or organizational performance over time. The authors used longitudinal data from a large fast-food organization (N = 861 units) to examine how change in use of selection and training relates to…

  7. Effects of Selection and Training on Unit-Level Performance over Time: A Latent Growth Modeling Approach

    ERIC Educational Resources Information Center

    Van Iddekinge, Chad H.; Ferris, Gerald R.; Perrewe, Pamela L.; Perryman, Alexa A.; Blass, Fred R.; Heetderks, Thomas D.

    2009-01-01

    Surprisingly few data exist concerning whether and how utilization of job-related selection and training procedures affects different aspects of unit or organizational performance over time. The authors used longitudinal data from a large fast-food organization (N = 861 units) to examine how change in use of selection and training relates to…

  8. Time gating for energy selection and scatter rejection: High-energy pulsed neutron imaging at LANSCE

    NASA Astrophysics Data System (ADS)

    Swift, Alicia; Schirato, Richard; McKigney, Edward; Hunter, James; Temple, Brian

    2015-09-01

    The Los Alamos Neutron Science Center (LANSCE) is a linear accelerator in Los Alamos, New Mexico that accelerates a proton beam to 800 MeV, which then produces spallation neutron beams. Flight path FP15R uses a tungsten target to generate neutrons of energy ranging from several hundred keV to ~600 MeV. The beam structure has micropulses of sub-ns width and period of 1.784 ns, and macropulses of 625 μs width and frequency of either 50 Hz or 100 Hz. This corresponds to 347 micropulses per macropulse, or 1.74 x 104 micropulses per second when operating at 50 Hz. Using a very fast, cooled ICCD camera (Princeton Instruments PI-Max 4), gated images of various objects were obtained on FP15R in January 2015. Objects imaged included blocks of lead and borated polyethylene; a tungsten sphere; and a tungsten, polyethylene, and steel cylinder. Images were obtained in 36 min or less, with some in as little as 6 min. This is novel because the gate widths (some as narrow as 10 ns) were selected to reject scatter and other signal not of interest (e.g. the gamma flash that precedes the neutron pulse), which has not been demonstrated at energies above 14 MeV. This proof-of-principle experiment shows that time gating is possible above 14MeV and is useful for selecting neutron energy and reducing scatter, thus forming clearer images. Future work (simulation and experimental) is being undertaken to improve camera shielding and system design and to precisely determine optical properties of the imaging system.

  9. A selectable system for mutation detection in the Big Blue lacI transgenic mouse system: what happens to the mutational spectra over time.

    PubMed

    Knöll, A; Jacobson, D P; Nishino, H; Kretz, P L; Short, J M; Sommer, S S

    1996-06-10

    Transgenic animals offer a powerful tool to study the mechanisms of spontaneous and induced mutagenesis in vivo. Herein we used a test version of a growth selectable assay to obtain spontaneous mutants in a lacI target transgene recovered from lacI transgenic B6C3F1 mice (Big Blue). This selection system may have certain advantages relative to the more established plaque screening system for mutation detection because: (1) the plating density of the phage is up to 60 times higher in the selectable assay, reducing the number of plates needed to be screened for a comparable amount of mutants; and (2) the mutant frequency obtained from the selectable assay is higher compared to the plaque assay, possibly due to a higher sensitivity for weaker mutants. However, the longer incubation time of the growth selectable assay might allow E. coli host derived mutants to appear. To address this issue, we investigated the sequence changes in the amino-terminal domain of the lacI gene of 405 mutants derived from the liver, spleen, brain, germ cells and skin of five untreated 6-week-old mice. The mutant colonies were isolated after 60, 84, 108 and 150 h of incubation under growth selectable conditions. Tissue-specific differences in the mutational pattern obtained after 60 and 84 h disappear after a longer time of incubation, possibly due to an increasing contribution of E. coli derived mutants. The evolving selectable systems offer the potential to increase screening efficiency, but the results suggest caution in interpreting data from this system because repair by E. coli of DNA lesions or mismatched heteroduplexes either originating in mouse in vivo or produced by ex vivo manipulation as well as de novo mutations in E. coli might contribute significantly to the observed mutational spectra at each timepoint.

  10. Selection of a cutoff value for real-time polymerase chain reaction results to fit a diagnostic purpose: analytical and epidemiologic approaches.

    PubMed

    Caraguel, Charles G B; Stryhn, Henrik; Gagné, Nellie; Dohoo, Ian R; Hammell, K Larry

    2011-01-01

    Diagnostic laboratories frequently select a subjective cutoff value for real-time amplification assays, above which a threshold cycle (Ct) value is deemed false. Commonly, higher Ct values are interpreted as amplification or fluorescence artifacts, or cross contaminations. Although the implementation of Ct cutoff might be reasonable, its justification and selection should be based on evidence. The current article reviewed evidence-based strategies to select Ct cutoffs grouped in analytical and epidemiologic approaches. Analytical strategies use criteria gathered during the assay development and include fluorescence threshold, reaction end-cycle, limit of detection, and artifact investigation. Variability in amplification efficacy across test runs may induce some instability in an intended Ct cutoff and requires some standardization or normalization procedures. Epidemiologic strategies use criteria based on either the probability or the cost of a false test result associated with a specified cutoff. Cutoffs, depending on the intended purpose of the test, can be selected graphically to minimize the probability of either false-positive or false-negative results by using two-graph receiver operating characteristics curves. The assay's diagnostic sensitivity and specificity may vary with the tested population, thus, the estimated two-graph receiver operating characteristics curve is population dependent and should be established for the targeted population. Although the selection of a cutoff based on misclassification cost depends on infection prevalence, the selection based on predictive values does not. To optimize the test average diagnostic performance, the Ct cutoff should be selected when diagnostic odds ratio is maximal. Epidemiologic approaches were illustrated by selecting Ct cutoffs for a real-time assay for Infectious salmon anemia virus.

  11. Selection of reference genes for gene expression studies in virus-infected monocots using quantitative real-time PCR.

    PubMed

    Zhang, Kun; Niu, Shaofang; Di, Dianping; Shi, Lindan; Liu, Deshui; Cao, Xiuling; Miao, Hongqin; Wang, Xianbing; Han, Chenggui; Yu, Jialin; Li, Dawei; Zhang, Yongliang

    2013-10-10

    Both genome-wide transcriptomic surveys of the mRNA expression profiles and virus-induced gene silencing-based molecular studies of target gene during virus-plant interaction involve the precise estimation of the transcript abundance. Quantitative real-time PCR (qPCR) is the most widely adopted technique for mRNA quantification. In order to obtain reliable quantification of transcripts, identification of the best reference genes forms the basis of the preliminary work. Nevertheless, the stability of internal controls in virus-infected monocots needs to be fully explored. In this work, the suitability of ten housekeeping genes (ACT, EF1α, FBOX, GAPDH, GTPB, PP2A, SAND, TUBβ, UBC18 and UK) for potential use as reference genes in qPCR were investigated in five different monocot plants (Brachypodium, barley, sorghum, wheat and maize) under infection with different viruses including Barley stripe mosaic virus (BSMV), Brome mosaic virus (BMV), Rice black-streaked dwarf virus (RBSDV) and Sugarcane mosaic virus (SCMV). By using three different algorithms, the most appropriate reference genes or their combinations were identified for different experimental sets and their effectiveness for the normalisation of expression studies were further validated by quantitative analysis of a well-studied PR-1 gene. These results facilitate the selection of desirable reference genes for more accurate gene expression studies in virus-infected monocots.

  12. Selected scorpion toxin exposures induce cytokine release in human peripheral blood mononuclear cells.

    PubMed

    Corzo, Gerardo; Espino-Solis, Gerardo Pavel

    2017-03-01

    A cytokine screening on human peripheral blood mononuclear cells (PBMCs) stimulated with selected scorpion toxins (ScTx's) was performed in order to evaluate their effect on human immune cells. The ScTx's chosen for this report were three typical buthid scorpion venom peptides, one with lethal effects on mammals Centruroides suffussus suffusus toxin II (CssII), another, with lethal effects on insects and crustaceans Centruroides noxius toxin 5 (Cn5), and one more without lethal effects Tityus discrepans toxin (Discrepin). A Luminex multiplex analysis was performed in order to determine the amounts chemokines and cytokines IL-1β, IL-2, IL-4, IL-5, IL-6, IL-10, IL-12-p40, IL-13, interferon alpha (IFN-α), interferon gamma (IFN-γ), tumor necrosis factor alpha TNF-α, and interferon-inducible protein-10 (IP-10) secreted from human PBMCs exposed to these toxins. Although, the ScTx Cn5 is not lethal for mammals, it was able to induce the secretion of cytokines IL-1β, IL-6, and TNF-α, IL-10 and IP-10 in comparison to the lethal CssII, which was able to induce only IP-10 secretion. Discrepin also was able to induce only IP-10. Interestingly, only low amounts of interferons α and β were induced in the presence of the ScTx's assayed. In a synergic experiment, the combination of Discrepin and Cn5 displayed considerable reverse effects on induction of IL-1β, IL-6, IL-10 and TNF-α, but they had a slight synergic effect on IP-10 cytokine production in comparison with the single effect obtained with the Cn5 alone. Thus, the results obtained suggest that the profile of secreted cytokines promoted by ScTx Cn5 is highly related with a cytokine storm event, and also it suggests that the mammalian lethal neurotoxins are not solely responsible of the scorpion envenomation symptomatology. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Digitized pressure-time records, selected nuclear events. Technical report, 1 September 1982-1 April 1986

    SciTech Connect

    McMullan, F.W.; Bryant, E.J.

    1986-04-30

    Pressure-time records are presented for selected atmospheric nuclear events. The records were extracted from published test reports, digitized, and given uniform pressure-time scales for a given event and a given range to permit easier comparison. Data include p-t, q-t, p(tot)-t, Mach No-t, and Impulse-t as appropriate. Selected data were scaled to 1 kT.

  14. Complex Chromosomal Rearrangements Mediated by Break-Induced Replication Involve Structure-Selective Endonucleases

    PubMed Central

    Pardo, Benjamin; Aguilera, Andrés

    2012-01-01

    DNA double-strand break (DSB) repair occurring in repeated DNA sequences often leads to the generation of chromosomal rearrangements. Homologous recombination normally ensures a faithful repair of DSBs through a mechanism that transfers the genetic information of an intact donor template to the broken molecule. When only one DSB end shares homology to the donor template, conventional gene conversion fails to occur and repair can be channeled to a recombination-dependent replication pathway termed break-induced replication (BIR), which is prone to produce chromosome non-reciprocal translocations (NRTs), a classical feature of numerous human cancers. Using a newly designed substrate for the analysis of DSB–induced chromosomal translocations, we show that Mus81 and Yen1 structure-selective endonucleases (SSEs) promote BIR, thus causing NRTs. We propose that Mus81 and Yen1 are recruited at the strand invasion intermediate to allow the establishment of a replication fork, which is required to complete BIR. Replication template switching during BIR, a feature of this pathway, engenders complex chromosomal rearrangements when using repeated DNA sequences dispersed over the genome. We demonstrate here that Mus81 and Yen1, together with Slx4, also promote template switching during BIR. Altogether, our study provides evidence for a role of SSEs at multiple steps during BIR, thus participating in the destabilization of the genome by generating complex chromosomal rearrangements. PMID:23071463

  15. Potentiation of opioid-induced conditioned place preference by the selective serotonin reuptake inhibitor fluoxetine.

    PubMed

    Subhan, F; Pache, D M; Sewell, R D

    2000-02-25

    The ability of the selective serotonin reuptake inhibitor, fluoxetine, to modify the effects of morphine, N-((S)-2-benzyl-3[(S) 2-amino-4-methylthio)butyldithio-]-1-oxopropyl)-L-alanine benzylester (RB 120; mixed inhibitor of enkephalin metabolism), and 4-¿[2-[[3-(1H-indol-3-yl))-2-methyl-1-oxo-2-[[(tricyclo[3,3,1,1] dec-2-yloxy) carbonyl] amino¿ propyl] amino]-1-phenylethyl] amino¿-4-oxo-[R-(R*,R*)]-butanoate N-methyl-D-glucamine (CI 988; cholecystokinin receptor subtype [CCK(2)] antagonist), was assessed using conditioned place preference. RB 120 and morphine both induced significant, dose-dependent conditioned place preference, whilst CI 988 failed to elicit conditioned place preference. A subthreshold dose of fluoxetine (2.5 mg/kg) potentiated the morphine submaximal response. Notably, the combination of a subthreshold dose of fluoxetine (2.5 mg/kg) with RB 120 (5 mg/kg) or CI 988 (3 mg/kg) was devoid of any significant conditioned place preference properties. Fluoxetine may act via enhanced serotonergic activity to modulate enkephalinergic tone. Agents that increase enkephalinergic tone more directly such as RB 120 and CI 988, at submaximal doses, did not induce conditioned place preference when co-administered with fluoxetine. These data suggest that fluoxetine, in combination with CI 988 or RB 120, might prove to be a beneficial treatment strategy for opioid drug addiction, though further studies are necessary.

  16. Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells.

    PubMed

    Lu, Desheng; Choi, Michael Y; Yu, Jian; Castro, Januario E; Kipps, Thomas J; Carson, Dennis A

    2011-08-09

    Salinomycin, an antibiotic potassium ionophore, has been reported recently to act as a selective breast cancer stem cell inhibitor, but the biochemical basis for its anticancer effects is not clear. The Wnt/β-catenin signal transduction pathway plays a central role in stem cell development, and its aberrant activation can cause cancer. In this study, we identified salinomycin as a potent inhibitor of the Wnt signaling cascade. In Wnt-transfected HEK293 cells, salinomycin blocked the phosphorylation of the Wnt coreceptor lipoprotein receptor related protein 6 (LRP6) and induced its degradation. Nigericin, another potassium ionophore with activity against cancer stem cells, exerted similar effects. In otherwise unmanipulated chronic lymphocytic leukemia cells with constitutive Wnt activation nanomolar concentrations of salinomycin down-regulated the expression of Wnt target genes such as LEF1, cyclin D1, and fibronectin, depressed LRP6 levels, and limited cell survival. Normal human peripheral blood lymphocytes resisted salinomycin toxicity. These results indicate that ionic changes induced by salinomycin and related drugs inhibit proximal Wnt signaling by interfering with LPR6 phosphorylation, and thus impair the survival of cells that depend on Wnt signaling at the plasma membrane.

  17. Salinomycin inhibits Wnt signaling and selectively induces apoptosis in chronic lymphocytic leukemia cells

    PubMed Central

    Lu, Desheng; Choi, Michael Y.; Yu, Jian; Castro, Januario E.; Kipps, Thomas J.; Carson, Dennis A.

    2011-01-01

    Salinomycin, an antibiotic potassium ionophore, has been reported recently to act as a selective breast cancer stem cell inhibitor, but the biochemical basis for its anticancer effects is not clear. The Wnt/β-catenin signal transduction pathway plays a central role in stem cell development, and its aberrant activation can cause cancer. In this study, we identified salinomycin as a potent inhibitor of the Wnt signaling cascade. In Wnt-transfected HEK293 cells, salinomycin blocked the phosphorylation of the Wnt coreceptor lipoprotein receptor related protein 6 (LRP6) and induced its degradation. Nigericin, another potassium ionophore with activity against cancer stem cells, exerted similar effects. In otherwise unmanipulated chronic lymphocytic leukemia cells with constitutive Wnt activation nanomolar concentrations of salinomycin down-regulated the expression of Wnt target genes such as LEF1, cyclin D1, and fibronectin, depressed LRP6 levels, and limited cell survival. Normal human peripheral blood lymphocytes resisted salinomycin toxicity. These results indicate that ionic changes induced by salinomycin and related drugs inhibit proximal Wnt signaling by interfering with LPR6 phosphorylation, and thus impair the survival of cells that depend on Wnt signaling at the plasma membrane. PMID:21788521

  18. Evaluation of region selective bilirubin-induced brain damage as a basis for a pharmacological treatment

    PubMed Central

    Dal Ben, Matteo; Bottin, Cristina; Zanconati, Fabrizio; Tiribelli, Claudio; Gazzin, Silvia

    2017-01-01

    The neurologic manifestations of neonatal hyperbilirubinemia in the central nervous system (CNS) exhibit high variations in the severity and appearance of motor, auditory and cognitive symptoms, which is suggestive of a still unexplained selective topography of bilirubin-induced damage. By applying the organotypic brain culture (OBC: preserving in vitro the cellular complexity, connection and architecture of the in vivo brain) technique to study hyperbilirubinemia, we mapped the regional target of bilirubin-induced damage, demonstrated a multifactorial toxic action of bilirubin, and used this information to evaluate the efficacy of drugs applicable to newborns to protect the brain. OBCs from 8-day-old rat pups showed a 2–13 fold higher sensitivity to bilirubin damage than 2-day-old preparations. The hippocampus, inferior colliculus and cerebral cortex were the only brain regions affected, presenting a mixed inflammatory-oxidative mechanism. Glutamate excitotoxicity was appreciable in only the hippocampus and inferior colliculus. Single drug treatment (indomethacin, curcumin, MgCl2) significantly improved cell viability in all regions, while the combined (cocktail) administration of the three drugs almost completely prevented damage in the most affected area (hippocampus). Our data may supports an innovative (complementary to phototherapy) approach for directly protecting the newborn brain from bilirubin neurotoxicity. PMID:28102362

  19. The sesquiterpene lactone parthenolide induces selective apoptosis of B-chronic lymphocytic leukemia cells in vitro.

    PubMed

    Steele, A J; Jones, D T; Ganeshaguru, K; Duke, V M; Yogashangary, B C; North, J M; Lowdell, M W; Kottaridis, P D; Mehta, A B; Prentice, A G; Hoffbrand, A V; Wickremasinghe, R G

    2006-06-01

    We have studied the in vitro actions of the sesquiterpene lactone parthenolide (PTL) on cells isolated from patients with chronic lymphocytic leukemia (CLL). Dye reduction viability assays showed that the median LD(50) for PTL was 6.2 muM (n=78). Fifteen of these isolates were relatively resistant to the conventional agent chlorambucil but retained sensitivity to PTL. Brief exposures to PTL (1-3 h) were sufficient to induce caspase activation and commitment to cell death. Chronic lymphocytic leukemia cells were more sensitive towards PTL than were normal T lymphocytes or CD34(+) haematopoietic progenitor cells. The mechanism of cell killing was via PTL-induced generation of reactive oxygen species, resulting in turn in a proapoptotic Bax conformational change, release of mitochondrial cytochrome c and caspase activation. Parthenolide also decreased nuclear levels of the antiapoptotic transcription factor nuclear factor-kappa B and diminished phosphorylation of its negative regulator IkappaB. Killing of CLL cells by PTL was apparently independent of p53 induction. This is the first report showing the relative selectivity of PTL towards CLL cells. The data here warrant further investigation of this class of natural product as potential therapeutic agents for CLL.

  20. Selective nitrations. Volume 2: The laser-induced nitration of three cycloalkanes

    NASA Astrophysics Data System (ADS)

    Stanley, Ann E.; Bonicamp, Judith M.; Godbey, Susan E.; Ludwick, Larry M.

    1993-03-01

    The army uses nitrated compounds as explosives and propellants. There is a special need for propellants with the chemical composition necessary to burn exactly with high energy production, but with a minimum of side products which create smoke. Laser-induced chemistry possesses the potential to drive some reactions in an efficient and selective manner, and may be useful in driving nitration reactions toward specific products. Reported here are the results of several successful attempts to laser-induce the reactions of nitrogen oxides with three cycloalkanes. Specifically, the tunable, continuous wave, carbon dioxide infrared laser was used to drive the reaction between the nitrogen dioxide and cyclopropane, cyclobutane, and cyclopentane under a variety of reaction conditions. The spectrochemical analyses of the product mixtures are presented here. In addition to nitrocycloalkanes, other products resulting were either from ring cleavage, or from nitration or oxidation of ring fragments. By examining the effects of various reaction conditions on the product arrays, it was possible to find optimum conditions for producing the nitrocycloalkanes while minimizing side products.

  1. Bile acids induce apoptosis selectively in androgen-dependent and -independent prostate cancer cells

    PubMed Central

    Goldberg, Alexander A.; Titorenko, Vladimir I.; Beach, Adam

    2013-01-01

    Prostate cancer is a prevalent age-related disease in North America, accounting for about 15% of all diagnosed cancers. We have previously identified lithocholic acid (LCA) as a potential chemotherapeutic compound that selectively kills neuroblastoma cells while sparing normal human neurons. Now, we report that LCA inhibits the proliferation of androgen-dependent (AD) LNCaP prostate cancer cells and that LCA is the most potent bile acid with respect to inducing apoptosis in LNCaP as well as androgen-independent (AI) PC-3 cells, without killing RWPE-1 immortalized normal prostate epithelial cells. In LNCaP and PC-3 cells, LCA triggered the extrinsic pathway of apoptosis and cell death induced by LCA was partially dependent on the activation of caspase-8 and -3. Moreover, LCA increased cleavage of Bid and Bax, down-regulation of Bcl-2, permeabilization of the mitochondrial outer membrane and activation of caspase-9. The cytotoxic actions of LCA occurred despite the inability of this bile acid to enter the prostate cancer cells with about 98% of the nominal test concentrations present in the extracellular culture medium. With our findings, we provide evidence to support a mechanism of action underlying the broad anticancer activity of LCA in various human tissues. PMID:23940835

  2. Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors.

    PubMed

    Murga, Matilde; Campaner, Stefano; Lopez-Contreras, Andres J; Toledo, Luis I; Soria, Rebeca; Montaña, Maria F; Artista, Luana D'; Schleker, Thomas; Guerra, Carmen; Garcia, Elena; Barbacid, Mariano; Hidalgo, Manuel; Amati, Bruno; Fernandez-Capetillo, Oscar

    2011-11-27

    Oncogene-induced replicative stress activates an Atr- and Chk1-dependent response, which has been proposed to be widespread in tumors. We explored whether the presence of replicative stress could be exploited for the selective elimination of cancer cells. To this end, we evaluated the impact of targeting the replicative stress-response on cancer development. In mice (Mus musculus), the reduced levels of Atr found on a mouse model of the Atr-Seckel syndrome completely prevented the development of Myc-induced lymphomas or pancreatic tumors, both of which showed abundant levels of replicative stress. Moreover, Chk1 inhibitors were highly effective in killing Myc-driven lymphomas. By contrast, pancreatic adenocarcinomas initiated by K-Ras(G12V) showed no detectable evidence of replicative stress and were nonresponsive to this therapy. Besides its impact on cancer, Myc overexpression aggravated the phenotypes of Atr-Seckel mice, revealing that oncogenes can modulate the severity of replicative stress-associated diseases.

  3. Mechanism of melanoma cells selective apoptosis induced by a photoactive NADPH analogue

    PubMed Central

    Rouaud, Florian; Boucher, Jean-Luc; Slama-Schwok, Anny; Rocchi, Stéphane

    2016-01-01

    Melanoma is one of the most lethal cancers when it reaches a metastatic stage. Despite the spectacular achievements of targeted therapies (BRAF inhibitors) or immuno-therapies (anti-CTLA4 or anti-PD1), most patients with melanoma will need additional treatments. Here we used a photoactive NADPH analogue called NS1 to induce cell death by inhibition of NADPH oxidases NOX in melanoma cells, including melanoma cells isolated from patients. In contrast, healthy melanocytes growth was unaffected by NS1 treatment. NS1 established an early Endoplasmic Reticulum stress by the early release of calcium mediated by (a) calcium-dependent redox-sensitive ion channel(s). These events initiated autophagy and apoptosis in all tested melanoma cells independently of their mutational status. The autophagy promoted by NS1 was incomplete. The autophagic flux was blocked at late stage events, consistent with the accumulation of p62, and a close localization of LC3 with NS1 associated with NS1 inhibition of NOX1 in autophagosomes. This hypothesis of a specific incomplete autophagy and apoptosis driven by NS1 was comforted by the use of siRNAs and pharmacological inhibitors blocking different processes. This study highlights the potential therapeutic interest of NS1 inducing cell death by triggering a selective ER stress and incomplete autophagy in melanoma cells harbouring wt and BRAF mutation. PMID:27756874

  4. Built-in microscale electrostatic fields induced by anatase–rutile-phase transition in selective areas promote osteogenesis

    PubMed Central

    Ning, Chengyun; Yu, Peng; Zhu, Ye; Yao, Mengyu; Zhu, Xiaojing; Wang, Xiaolan; Lin, Zefeng; Li, Weiping; Wang, Shuangying; Tan, Guoxin; Zhang, Yu; Wang, Yingjun; Mao, Chuanbin

    2016-01-01

    Bone has a built-in electric field because of the presence of piezoelectric collagen. To date, only externally applied electric fields have been used to direct cell behavior; however, these fields are not safe or practical for in vivo use. In this work, for the first time, we use a periodic microscale electric field (MEF) built into a titanium implant to induce osteogenesis. Such a MEF is generated by the periodic organization of a junction made of two parallel semiconducting TiO2 zones: anatase and rutile with lower and higher electron densities, respectively. The junctions were formed through anatase–rutile-phase transition in selective areas using laser irradiation on the implants. The in vitro and in vivo studies confirmed that the built-in MEF was an efficient electrical cue for inducing osteogenic differentiation in the absence of osteogenic supplements and promoted bone regeneration around the implants. Our work opens up a new avenue toward bone repair and regeneration using built-in MEF. PMID:27818718

  5. Full time directional versus user selectable microphone modes in hearing aids.

    PubMed

    Ricketts, Todd; Henry, Paula; Gnewikow, David

    2003-10-01

    The purpose of this experiment was to systematically examine hearing aid benefit as measured by speech recognition and self-assessment methods across omnidirectional and directional hearing aid modes. These data were used to compare directional benefit as measured by speech recognition in the laboratory to hearing aid wearer's perceptions of benefit in everyday environments across full-time directional, full-time omnidirectional, and user selectable directional fittings. Identification of possible listening situations that resulted in different self reported hearing aid benefit as a function of microphone type was a secondary objective of this experiment. Fifteen adults with symmetrical, sloping sensorineural hearing loss were fitted bilaterally with in-the-ear (ITE) directional hearing aids. Measures of hearing aid benefit included the Profile of Hearing Aid Benefit (PHAB), the Connected Sentence Test (CST), the Hearing in Noise Test (HINT), and a daily use log. Additionally, two new subscales were developed for administration with the PHAB. These subscales were developed to specifically address situations in which directional hearing aids may provide different degrees of benefit than omnidirectional hearing aids. Participants completed these measures in three conditions: omnidirectional only (O), directional only with low-frequency gain compensation (D), and user-selectable directional/omnidirectional (DO). Results from the speech intelligibility in noise testing indicated significantly more hearing aid benefit in directional modes than omnidirectional. PHAB results indicated more benefit on the background noise subscale (BN) in the DO condition than in the O condition; however, this directional advantage was not present for the D condition. Although the reliability of the newly proposed subscales is as yet unknown, the data were interpreted as revealing a directional advantage in situations where the signal of interest was in front of the participant and a

  6. Selective and protracted effect of nifedipine on fear memory extinction correlates with induced stress response.

    PubMed

    Waltereit, Robert; Mannhardt, Sönke; Nescholta, Sabine; Maser-Gluth, Christiane; Bartsch, Dusan

    2008-05-01

    Memory extinction, defined as a decrease of a conditioned response as a function of a non-reinforced conditioned stimulus presentation, has high biological and clinical relevance. Extinction is not a passive reversing or erasing of the plasticity associated with acquisition, but a novel, active learning process. Nifedipine blocks L-type voltage gated calcium channels (LVGCC) and has been shown previously to selectively interfere with the extinction, but not the acquisition, of fear memory. We studied here the effect of retrograde and anterograde shifts of nifedipine application, with respect to an extinction training, on the extinction of fear conditioning. Subcutaneous injection of 30 mg/kg nifedipine, at least up to 4 h before the extinction session, significantly impaired extinction, as did intraperitoneal injection of 15 mg/kg nifedipine, at least up to 2 h before extinction training. However, the injection of nifedipine also induced a strong and protracted stress response. The pharmacokinetics of nifedipine suggest that it was mainly this stress response that triggered the specific inhibition of extinction, not the blockade of LVGCC in the brain. Our results support recent findings that stress selectively interferes with the extinction, but not the acquisition, of fear memory. They also indicate that a pharmacological approach is not sufficient to study the role of brain LVGCC in learning and memory. Further research using specific genetically modified animals is necessary to delineate the role of LVGCC in fear memory extinction.

  7. Selective lowering of synapsins induced by oligomeric α-synuclein exacerbates memory deficits.

    PubMed

    Larson, Megan E; Greimel, Susan J; Amar, Fatou; LaCroix, Michael; Boyle, Gabriel; Sherman, Mathew A; Schley, Hallie; Miel, Camille; Schneider, Julie A; Kayed, Rakez; Benfenati, Fabio; Lee, Michael K; Bennett, David A; Lesné, Sylvain E

    2017-06-06

    Mounting evidence indicates that soluble oligomeric forms of amyloid proteins linked to neurodegenerative disorders, such as amyloid-β (Aβ), tau, or α-synuclein (αSyn) might be the major deleterious species for neuronal function in these diseases. Here, we found an abnormal accumulation of oligomeric αSyn species in AD brains by custom ELISA, size-exclusion chromatography, and nondenaturing/denaturing immunoblotting techniques. Importantly, the abundance of αSyn oligomers in human brain tissue correlated with cognitive impairment and reductions in synapsin expression. By overexpressing WT human αSyn in an AD mouse model, we artificially enhanced αSyn oligomerization. These bigenic mice displayed exacerbated Aβ-induced cognitive deficits and a selective decrease in synapsins. Following isolation of various soluble αSyn assemblies from transgenic mice, we found that in vitro delivery of exogenous oligomeric αSyn but not monomeric αSyn was causing a lowering in synapsin-I/II protein abundance. For a particular αSyn oligomer, these changes were either dependent or independent on endogenous αSyn expression. Finally, at a molecular level, the expression of synapsin genes SYN1 and SYN2 was down-regulated in vivo and in vitro by αSyn oligomers, which decreased two transcription factors, cAMP response element binding and Nurr1, controlling synapsin gene promoter activity. Overall, our results demonstrate that endogenous αSyn oligomers can impair memory by selectively lowering synapsin expression.

  8. Tuning a strain-induced orbital selective Mott transition in epitaxial VO2

    NASA Astrophysics Data System (ADS)

    Mukherjee, Shantanu; Quackenbush, N. F.; Paik, H.; Schlueter, C.; Lee, T.-L.; Schlom, D. G.; Piper, L. F. J.; Lee, Wei-Cheng

    2016-06-01

    We present evidence of strain-induced modulation of electron correlation effects and increased orbital anisotropy in the rutile phase of epitaxial VO2/TiO2 films from hard x-ray photoelectron spectroscopy and soft V L-edge x-ray absorption spectroscopy, respectively. By using the U(1) slave spin formalism, we further argue that the observed anisotropic correlation effects can be understood by a model of orbital selective Mott transition at a filling that is noninteger but close to the half filling. Because the overlaps of wave functions between d orbitals are modified by the strain, orbital-dependent renormalizations of the bandwidths and the onsite energy occur. These renormalizations generally result in different occupation numbers in different orbitals. We find that if the system has a noninteger filling number near the half filling such as for VO2, certain orbitals could reach an occupation number closer to half filling under the strain, resulting in a strong reduction in the quasiparticle weight Zα of that orbital. Our work demonstrates that such an orbital selective Mott transition, defined as the case with Zα=0 in some but not all orbitals, could be accessed by epitaxial-strain engineering of correlated electron systems.

  9. Selective and protracted effect of nifedipine on fear memory extinction correlates with induced stress response

    PubMed Central

    Waltereit, Robert; Mannhardt, Sönke; Nescholta, Sabine; Maser-Gluth, Christiane; Bartsch, Dusan

    2008-01-01

    Memory extinction, defined as a decrease of a conditioned response as a function of a non-reinforced conditioned stimulus presentation, has high biological and clinical relevance. Extinction is not a passive reversing or erasing of the plasticity associated with acquisition, but a novel, active learning process. Nifedipine blocks L-type voltage gated calcium channels (LVGCC) and has been shown previously to selectively interfere with the extinction, but not the acquisition, of fear memory. We studied here the effect of retrograde and anterograde shifts of nifedipine application, with respect to an extinction training, on the extinction of fear conditioning. Subcutaneous injection of 30 mg/kg nifedipine, at least up to 4 h before the extinction session, significantly impaired extinction, as did intraperitoneal injection of 15 mg/kg nifedipine, at least up to 2 h before extinction training. However, the injection of nifedipine also induced a strong and protracted stress response. The pharmacokinetics of nifedipine suggest that it was mainly this stress response that triggered the specific inhibition of extinction, not the blockade of LVGCC in the brain. Our results support recent findings that stress selectively interferes with the extinction, but not the acquisition, of fear memory. They also indicate that a pharmacological approach is not sufficient to study the role of brain LVGCC in learning and memory. Further research using specific genetically modified animals is necessary to delineate the role of LVGCC in fear memory extinction. PMID:18441293

  10. Insensitivity to pain induced by a potent selective closed-state Nav1.7 inhibitor.

    PubMed

    Flinspach, M; Xu, Q; Piekarz, A D; Fellows, R; Hagan, R; Gibbs, A; Liu, Y; Neff, R A; Freedman, J; Eckert, W A; Zhou, M; Bonesteel, R; Pennington, M W; Eddinger, K A; Yaksh, T L; Hunter, M; Swanson, R V; Wickenden, A D

    2017-01-03

    Pain places a devastating burden on patients and society and current pain therapeutics exhibit limitations in efficacy, unwanted side effects and the potential for drug abuse and diversion. Although genetic evidence has clearly demonstrated that the voltage-gated sodium channel, Nav1.7, is critical to pain sensation in mammals, pharmacological inhibitors of Nav1.7 have not yet fully recapitulated the dramatic analgesia observed in Nav1.7-null subjects. Using the tarantula venom-peptide ProTX-II as a scaffold, we engineered a library of over 1500 venom-derived peptides and identified JNJ63955918 as a potent, highly selective, closed-state Nav1.7 blocking peptide. Here we show that JNJ63955918 induces a pharmacological insensitivity to pain that closely recapitulates key features of the Nav1.7-null phenotype seen in mice and humans. Our findings demonstrate that a high degree of selectivity, coupled with a closed-state dependent mechanism of action is required for strong efficacy and indicate that peptides such as JNJ63955918 and other suitably optimized Nav1.7 inhibitors may represent viable non-opioid alternatives for the pharmacological treatment of severe pain.

  11. Insensitivity to pain induced by a potent selective closed-state Nav1.7 inhibitor

    PubMed Central

    Flinspach, M.; Xu, Q.; Piekarz, A. D.; Fellows, R.; Hagan, R.; Gibbs, A.; Liu, Y.; Neff, R. A.; Freedman, J.; Eckert, W. A.; Zhou, M.; Bonesteel, R.; Pennington, M. W.; Eddinger, K. A.; Yaksh, T. L.; Hunter, M.; Swanson, R. V.; Wickenden, A. D.

    2017-01-01

    Pain places a devastating burden on patients and society and current pain therapeutics exhibit limitations in efficacy, unwanted side effects and the potential for drug abuse and diversion. Although genetic evidence has clearly demonstrated that the voltage-gated sodium channel, Nav1.7, is critical to pain sensation in mammals, pharmacological inhibitors of Nav1.7 have not yet fully recapitulated the dramatic analgesia observed in Nav1.7-null subjects. Using the tarantula venom-peptide ProTX-II as a scaffold, we engineered a library of over 1500 venom-derived peptides and identified JNJ63955918 as a potent, highly selective, closed-state Nav1.7 blocking peptide. Here we show that JNJ63955918 induces a pharmacological insensitivity to pain that closely recapitulates key features of the Nav1.7-null phenotype seen in mice and humans. Our findings demonstrate that a high degree of selectivity, coupled with a closed-state dependent mechanism of action is required for strong efficacy and indicate that peptides such as JNJ63955918 and other suitably optimized Nav1.7 inhibitors may represent viable non-opioid alternatives for the pharmacological treatment of severe pain. PMID:28045073

  12. Selection of Motor Programs for Suppressing Food Intake and Inducing Locomotion in the Drosophila Brain

    PubMed Central

    Schoofs, Andreas; Hückesfeld, Sebastian; Schlegel, Philipp; Miroschnikow, Anton; Peters, Marc; Zeymer, Malou; Spieß, Roland; Chiang, Ann-Shyn; Pankratz, Michael J.

    2014-01-01

    Central mechanisms by which specific motor programs are selected to achieve meaningful behaviors are not well understood. Using electrophysiological recordings from pharyngeal nerves upon central activation of neurotransmitter-expressing cells, we show that distinct neuronal ensembles can regulate different feeding motor programs. In behavioral and electrophysiological experiments, activation of 20 neurons in the brain expressing the neuropeptide hugin, a homolog of mammalian neuromedin U, simultaneously suppressed the motor program for food intake while inducing the motor program for locomotion. Decreasing hugin neuropeptide levels in the neurons by RNAi prevented this action. Reducing the level of hugin neuronal activity alone did not have any effect on feeding or locomotion motor programs. Furthermore, use of promoter-specific constructs that labeled subsets of hugin neurons demonstrated that initiation of locomotion can be separated from modulation of its motor pattern. These results provide insights into a neural mechanism of how opposing motor programs can be selected in order to coordinate feeding and locomotive behaviors. PMID:24960360

  13. Laser-induced selective metallization of polypropylene doped with multiwall carbon nanotubes

    NASA Astrophysics Data System (ADS)

    Ratautas, Karolis; Gedvilas, Mindaugas; Stankevičiene, Ina; Jagminienė, Aldona; Norkus, Eugenijus; Pira, Nello Li; Sinopoli, Stefano; Račiukaitis, Gediminas

    2017-08-01

    Moulded interconnect devices (MID) offer the material, weight and cost saving by integration electronic circuits directly into polymeric components used in automotive and other consumer products. Lasers are used to write circuits directly by modifying the surface of polymers followed by an electroless metal plating. A new composite material - the polypropylene doped with multiwall carbon nanotubes was developed for the laser-induced selective metallization. Mechanism of surface activation by laser irradiation was investigated in details utilising pico- and nanoseconds lasers. Deposition of copper was performed in the autocatalytic electroless plating bath. The laser-activated polymer surfaces have been studied using the Raman spectroscopy and scanning electron microscope (SEM). Microscopic images revealed that surface becomes active only after its melting by a laser. Alterations in the Raman spectra of the D and G bands indicated the clustering of carbon additives in the composite material. Optimal laser parameters for the surface activation were found by measuring a sheet resistance of the finally metal-plated samples. A spatially selective copper plating was achieved with the smallest conductor line width of 22 μm at the laser scanning speed of 3 m/s and the pulse repetition rate of 100 kHz. Finally, the technique was validated by making functional electronic circuits by this MID approach.

  14. Polarity-Induced Selective Area Epitaxy of GaN Nanowires.

    PubMed

    de Souza Schiaber, Ziani; Calabrese, Gabriele; Kong, Xiang; Trampert, Achim; Jenichen, Bernd; Dias da Silva, José Humberto; Geelhaar, Lutz; Brandt, Oliver; Fernández-Garrido, Sergio

    2017-01-11

    We present a conceptually novel approach to achieve selective area epitaxy of GaN nanowires. The approach is based on the fact that these nanostructures do not form in plasma-assisted molecular beam epitaxy on structurally and chemically uniform cation-polar substrates. By in situ depositing and nitridating Si on a Ga-polar GaN film, we locally reverse the polarity to induce the selective area epitaxy of N-polar GaN nanowires. We show that the nanowire number density can be controlled over several orders of magnitude by varying the amount of predeposited Si. Using this growth approach, we demonstrate the synthesis of single-crystalline and uncoalesced nanowires with diameters as small as 20 nm. The achievement of nanowire number densities low enough to prevent the shadowing of the nanowire sidewalls from the impinging fluxes paves the way for the realization of homogeneous core-shell heterostructures without the need of using ex situ prepatterned substrates.

  15. EEG-based recognition of video-induced emotions: selecting subject-independent feature set.

    PubMed

    Kortelainen, Jukka; Seppänen, Tapio

    2013-01-01

    Emotions are fundamental for everyday life affecting our communication, learning, perception, and decision making. Including emotions into the human-computer interaction (HCI) could be seen as a significant step forward offering a great potential for developing advanced future technologies. While the electrical activity of the brain is affected by emotions, offers electroencephalogram (EEG) an interesting channel to improve the HCI. In this paper, the selection of subject-independent feature set for EEG-based emotion recognition is studied. We investigate the effect of different feature sets in classifying person's arousal and valence while watching videos with emotional content. The classification performance is optimized by applying a sequential forward floating search algorithm for feature selection. The best classification rate (65.1% for arousal and 63.0% for valence) is obtained with a feature set containing power spectral features from the frequency band of 1-32 Hz. The proposed approach substantially improves the classification rate reported in the literature. In future, further analysis of the video-induced EEG changes including the topographical differences in the spectral features is needed.

  16. The Ebola virus matrix protein VP40 selectively induces vesiculation from phosphatidylserine-enriched membranes.

    PubMed

    Soni, Smita P; Stahelin, Robert V

    2014-11-28

    Ebola virus is from the Filoviridae family of viruses and is one of the most virulent pathogens known with ∼ 60% clinical fatality. The Ebola virus negative sense RNA genome encodes seven proteins including viral matrix protein 40 (VP40), which is the most abundant protein found in the virions. Within infected cells VP40 localizes at the inner leaflet of the plasma membrane (PM), binds lipids, and regulates formation of new virus particles. Expression of VP40 in mammalian cells is sufficient to form virus-like particles that are nearly indistinguishable from the authentic virions. However, how VP40 interacts with the PM and forms virus-like particles is for the most part unknown. To investigate VP40 lipid specificity in a model of viral egress we employed giant unilamellar vesicles with different lipid compositions. The results demonstrate VP40 selectively induces vesiculation from membranes containing phosphatidylserine (PS) at concentrations of PS that are representative of the PM inner leaflet content. The formation of intraluminal vesicles was not significantly detected in the presence of other important PM lipids including cholesterol and polyvalent phosphoinositides, further demonstrating PS selectivity. Taken together, these studies suggest that PM phosphatidylserine may be an important component of Ebola virus budding and that VP40 may be able to mediate PM scission.

  17. Maskless micro/nanofabrication on GaAs surface by friction-induced selective etching

    PubMed Central

    2014-01-01

    In the present study, a friction-induced selective etching method was developed to produce nanostructures on GaAs surface. Without any resist mask, the nanofabrication can be achieved by scratching and post-etching in sulfuric acid solution. The effects of the applied normal load and etching period on the formation of the nanostructure were studied. Results showed that the height of the nanostructure increased with the normal load or the etching period. XPS and Raman detection demonstrated that residual compressive stress and lattice densification were probably the main reason for selective etching, which eventually led to the protrusive nanostructures from the scratched area on the GaAs surface. Through a homemade multi-probe instrument, the capability of this fabrication method was demonstrated by producing various nanostructures on the GaAs surface, such as linear array, intersecting parallel, surface mesas, and special letters. In summary, the proposed method provided a straightforward and more maneuverable micro/nanofabrication method on the GaAs surface. PMID:24495647

  18. Investigation of the effect of the hyperparameter optimization and the time lag selection in time series forecasting using machine learning algorithms

    NASA Astrophysics Data System (ADS)

    Papacharalampous, Georgia; Tyralis, Hristos; Koutsoyiannis, Demetris

    2017-04-01

    The hyperparameter optimization and the time lag selection are considered to be of great importance in time series forecasting using machine learning (ML) algorithms. To investigate their effect on the ML forecasting performance we conduct several large-scale simulation experiments. Within each of the latter we compare 12 methods on 2 000 simulated time series from the family of Autoregressive Fractionally Integrated Moving Average (ARFIMA) models. The methods are defined by the set {ML algorithm, hyperparameter selection procedure, time lags}. We compare three ML algorithms, i.e. Neural Networks (NN), Random Forests (RF) and Support Vector Machines (SVM), two procedures for hyperparameter selection i.e. predefined hyperparameters or defined after optimization and two regression matrices (using time lag 1 or 1, …, 21). After splitting each simulated time series into a fitting and a testing set, we fit the models to the former set and compare their performance on the latter one. We quantify the methods' performance using several metrics proposed in the literature and benchmark methods. Furthermore, we conduct a sensitivity analysis on the length of the fitting set to examine how it affects the robustness of our results. The findings indicate that the hyperparameter optimization mostly has a small effect on the forecasting performance. This is particularly important, because the hyperparameter optimization is computationally intensive. On the other hand, the time lag selection seems to mostly significantly affect the methods performance when using the NN algorithm, while we observe a similar behaviour for the RF algorithm albeit to a smaller extent.