Science.gov

Sample records for induces selective time

  1. 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.

  2. Dose and Time-Dependent Selective Neurotoxicity Induced by Mephedrone in Mice

    PubMed Central

    Martínez-Clemente, José; López-Arnau, Raúl; Abad, Sonia; Pubill, David; Escubedo, Elena; Camarasa, Jorge

    2014-01-01

    Mephedrone is a drug of abuse marketed as ‘bath salts". There are discrepancies concerning its long-term effects. We have investigated the neurotoxicity of mephedrone in mice following different exposition schedules. Schedule 1: four doses of 50 mg/kg. Schedule 2: four doses of 25 mg/kg. Schedule 3: three daily doses of 25 mg/kg, for two consecutive days. All schedules induced, in some animals, an aggressive behavior and hyperthermia as well as a decrease in weight gain. Mephedrone (schedule 1) induced dopaminergic and serotoninergic neurotoxicity that persisted 7 days after exposition. At a lower dose (schedule 2) only a transient dopaminergic injury was found. In the weekend consumption pattern (schedule 3), mephedrone induced dopamine and serotonin transporter loss that was accompanied by a decrease in tyrosine hydroxylase and tryptophan hydroxylase 2 expression one week after exposition. Also, mephedrone induced a depressive-like behavior, as well as a reduction in striatal D2 density, suggesting higher susceptibility to addictive drugs. In cultured cortical neurons, mephedrone induced a concentration-dependent cytotoxic effect. Using repeated doses for 2 days in an elevated ambient temperature we evidenced a loss of frontal cortex dopaminergic and hippocampal serotoninergic neuronal markers that suggest injuries at nerve endings. PMID:24892744

  3. 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)

  4. Minima Times of Selected Eclipsing Binaries

    NASA Astrophysics Data System (ADS)

    Parimucha, S.; Dubovsky, P.; Kudak, V.; Perig, V.

    2016-05-01

    We present 221 CCD minima times of the 76 selected eclipsing binaries obtained during 2013-2016 at Observatory at Kolonica Saddle in Slovakia and Observatory of Laboratory of Space Research, Uzhhorod National University in Ukraine

  5. Mammary tumors induce select cognitive impairments.

    PubMed

    Pyter, Leah M; Cochrane, Sally F; Ouwenga, Rebecca L; Patel, Priyesh N; Pineros, Vanessa; Prendergast, Brian J

    2010-08-01

    Cancer, in addition to many other chronic diseases, is associated with serious and problematic behavioral symptoms, including cognitive impairments. In humans, various factors likely contribute to cancer-associated cognitive deficits including disease awareness and chemotherapy; however, the endogenous biological factors arising from tumor development may also play a causal role. In the present study, rats with mammary tumors exhibited impaired spatial reference memory on a radial arm maze and amnesia for familiar objects in an object recognition memory test. In contrast, their performance in the Morris water maze and in fear conditioning tests was comparable to that of controls. These select cognitive impairments were accompanied by elevations in hippocampal interleukin-1beta mRNA expression, but were not associated with decreases in hippocampal brain-derived neurotrophic factor gene expression. Together the results indicate that peripheral tumors alone are sufficient to induce increases in hippocampal cytokine expression and select deficits in hippocampal-dependent memory tasks. PMID:20188817

  6. Time of travel of selected Arkansas streams

    USGS Publications Warehouse

    Lamb, T.E.

    1982-01-01

    Between 1971 and 1981, time-of-travel and dispersion measurements were made in 15 streams in Arkansas. Most of the streams studied were at or near base flow. Graphs are presented for predicting traveltime of solutes in segments of the streams studied. The relationship of time of passage and peak unit concentration to traveltime is presented for two of the streams. Examples of use and application of the data are given. (USGS)

  7. Opposing selection and environmental variation modify optimal timing of breeding.

    PubMed

    Tarwater, Corey E; Beissinger, Steven R

    2013-09-17

    Studies of evolution in wild populations often find that the heritable phenotypic traits of individuals producing the most offspring do not increase proportionally in the population. This paradox may arise when phenotypic traits influence both fecundity and viability and when there is a tradeoff between these fitness components, leading to opposing selection. Such tradeoffs are the foundation of life history theory, but they are rarely investigated in selection studies. Timing of breeding is a classic example of a heritable trait under directional selection that does not result in an evolutionary response. Using a 22-y study of a tropical parrot, we show that opposing viability and fecundity selection on the timing of breeding is common and affects optimal breeding date, defined by maximization of fitness. After accounting for sampling error, the directions of viability (positive) and fecundity (negative) selection were consistent, but the magnitude of selection fluctuated among years. Environmental conditions (rainfall and breeding density) primarily and breeding experience secondarily modified selection, shifting optimal timing among individuals and years. In contrast to other studies, viability selection was as strong as fecundity selection, late-born juveniles had greater survival than early-born juveniles, and breeding later in the year increased fitness under opposing selection. Our findings provide support for life history tradeoffs influencing selection on phenotypic traits, highlight the need to unify selection and life history theory, and illustrate the importance of monitoring survival as well as reproduction for understanding phenological responses to climate change. PMID:24003118

  8. Selective fishing induces density-dependent growth.

    PubMed

    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

  9. 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.

  10. 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.

  11. 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…

  12. Using Response Times for Item Selection in Adaptive Testing

    ERIC Educational Resources Information Center

    van der Linden, Wim J.

    2008-01-01

    Response times on items can be used to improve item selection in adaptive testing provided that a probabilistic model for their distribution is available. In this research, the author used a hierarchical modeling framework with separate first-level models for the responses and response times and a second-level model for the distribution of the…

  13. 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.

  14. Identification and real-time expression analysis of selected Toxoplasma gondii in-vivo induced antigens recognized by IgG and IgM in sera of acute toxoplasmosis patients

    PubMed Central

    2013-01-01

    Background Toxoplasma gondii is an obligate intracellular zoonotic parasite of the phylum Apicomplexa which infects a wide range of warm-blooded animals, including humans. In this study in-vivo induced antigens of this parasite was investigated using in-vivo induced antigen technology (IVIAT) and pooled sera from patients with serological evidence of acute infection. Methods The pooled sera was first pre-absorbed against three different preparations of antigens from in-vitro-grown cells of each T. gondii and E. coli XL1-Blue MRF’, subsequently it was used to screen T. gondii cDNA phage expression library. Positive clones from each group were subjected to quantitative real-time PCR expression analysis on mRNA of in-vivo and in-vitro grown parasites. Results A total of 29 reactive clones from each IgM and IgG immunoscreenings were found to have high homology to T. gondii genes. Quantitative real-time PCR expression analysis showed that 20 IgM-detected genes and 11 IgG-detected genes were up-regulated in-vivo relative to their expression levels in-vitro. These included genes encoding micronemes, sterol-regulatory element binding protein site, SRS34A, MIC2-associated protein M2AP, nucleoredoxin, protein phosphatase 2C and several hypothetical proteins. A hypothetical protein (GenBank accession no. 7899266) detected by IgG had the highest in-vivo over in-vitro fold change of 499.86; while another up-regulated hypothetical protein (GenBank accession no. 7898829) recognized by IgM showed high sensitivity (90%) and moderate specificity (70%) in detecting T. gondii antibodies when tested with 20 individual serum samples. Conclusion The highly up-regulated genes and the corresponding proteins, in particular the hypothetical proteins, may be useful in further studies on understanding the disease pathogenesis and as potential vaccine candidates. PMID:23800344

  15. Laser induced alignment of state-selected CH3I.

    PubMed

    He, Lanhai; Bulthuis, Jaap; Luo, Sizuo; Wang, Jia; Lu, Chunjing; Stolte, Steven; Ding, Dajun; Roeterdink, Wim G

    2015-10-01

    Hexapole state selection is used to prepare CH3I molecules in the |JKM〉 = |1±1∓1〉 state. The molecules are aligned in a strong 800 nm laser field, which is linearly polarised perpendicular to the weak static extraction field E of the time of flight setup. The molecules are subsequently ionised by a second time delayed probe laser pulse. It will be shown that in this geometry at high enough laser intensities the Newton sphere has sufficient symmetry to apply the inverse Abel transformation to reconstruct the three dimensional distribution from the projected ion image. The laser induced controllable alignment was found to have the upper and lower extreme values of 〈P2(cos θ)〉 = 0.7 for the aligned molecule and -0.1 for the anti-aligned molecule, coupled to 〈P4(cos θ)〉 between 0.3 and 0.0. The method to extract the alignment parameters 〈P2(cos θ)〉 and 〈P4(cos θ)〉 directly from the velocity map ion images will be discussed. PMID:26314900

  16. Chiral Selective Chemistry Induced by Natural Selection of Spin-Polarized Electrons.

    PubMed

    Rosenberg, Richard A; Mishra, Debabrata; Naaman, Ron

    2015-06-15

    The search to understand the origin of homochirality in nature has been ongoing since the time of Pasteur. Previous work has shown that DNA can act as a spin filter for low-energy electrons and that spin-polarized secondary electrons produced by X-ray irradiation of a magnetic substrate can induce chiral selective chemistry. In the present work it is demonstrated that secondary electrons from a substrate that are transmitted through a chiral overlayer cause enantiomeric selective chemistry in an adsorbed adlayer. We determine the quantum yields (QYs) for dissociation of (R)- or (S)-epichlorohydrin adsorbed on a chiral self-assembled layer of DNA on gold and on bare gold (for control). The results show that there is a significant difference in the QYs between the two enantiomers when adsorbed on DNA, but none when they are adsorbed on bare Au. We propose that the effect results from natural spin filtering effects cause by the chiral monolayer. PMID:25950284

  17. 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. PMID:23978652

  18. 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.

  19. From Induced Seismicity to Direct Time-Dependent Seismic Hazard

    NASA Astrophysics Data System (ADS)

    Convertito, V.; Maercklin, N.; Sharma, N.; Zollo, A.

    2012-12-01

    The growing installation of industrial facilities for subsurface exploration worldwide requires continuous refinements in understanding both the mechanisms by which seismicity is induced by field operations and the related seismic hazard. Particularly in proximity of densely populated areas, induced low-to-moderate magnitude seismicity characterized by high-frequency content can be clearly felt by the surrounding inhabitants and, in some cases, may produce damage. In this respect we propose a technique for time-dependent probabilistic seismic hazard analysis to be used in geothermal fields as a monitoring tool for the effects of on-going field operations. The technique integrates the observed features of the seismicity induced by fluid injection and extraction with a local ground-motion prediction equation. The result of the analysis is the time-evolving probability of exceedance of peak ground acceleration (PGA), which can be compared with selected critical values to manage field operations. To evaluate the reliability of the proposed technique, we applied it to data collected in The Geysers geothermal field in northern California between 1 September 2007 and 15 November 2010. We show that the period considered the seismic hazard at The Geysers was variable in time and space, which is a consequence of the field operations and the variation of both seismicity rate and b-value. We conclude that, for the exposure period taken into account (i.e., two months), as a conservative limit, PGA values corresponding to the lowest probability of exceedance (e.g., 30%) must not be exceeded to ensure safe field operations. We suggest testing the proposed technique at other geothermal areas or in regions where seismicity is induced, for example, by hydrocarbon exploitation or carbon dioxide storage.

  20. 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.

  1. Identifying Signatures of Selection in Genetic Time Series

    PubMed Central

    Feder, Alison F.; Kryazhimskiy, Sergey; Plotkin, Joshua B.

    2014-01-01

    Both genetic drift and natural selection cause the frequencies of alleles in a population to vary over time. Discriminating between these two evolutionary forces, based on a time series of samples from a population, remains an outstanding problem with increasing relevance to modern data sets. Even in the idealized situation when the sampled locus is independent of all other loci, this problem is difficult to solve, especially when the size of the population from which the samples are drawn is unknown. A standard χ2-based likelihood-ratio test was previously proposed to address this problem. Here we show that the χ2-test of selection substantially underestimates the probability of type I error, leading to more false positives than indicated by its P-value, especially at stringent P-values. We introduce two methods to correct this bias. The empirical likelihood-ratio test (ELRT) rejects neutrality when the likelihood-ratio statistic falls in the tail of the empirical distribution obtained under the most likely neutral population size. The frequency increment test (FIT) rejects neutrality if the distribution of normalized allele-frequency increments exhibits a mean that deviates significantly from zero. We characterize the statistical power of these two tests for selection, and we apply them to three experimental data sets. We demonstrate that both ELRT and FIT have power to detect selection in practical parameter regimes, such as those encountered in microbial evolution experiments. Our analysis applies to a single diallelic locus, assumed independent of all other loci, which is most relevant to full-genome selection scans in sexual organisms, and also to evolution experiments in asexual organisms as long as clonal interference is weak. Different techniques will be required to detect selection in time series of cosegregating linked loci. PMID:24318534

  2. 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. PMID:26230806

  3. 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.

  4. GPS time transfer with implementation of selective availability

    NASA Astrophysics Data System (ADS)

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

    1990-05-01

    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.

  5. 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.

  6. Cell selectivity to laser-induced photoacoustic injury of skin.

    PubMed

    Yashima, Y; McAuliffe, D J; Flotte, T J

    1990-01-01

    Cell selectivity to photoacoustic injury induced by argon-fluoride excimer laser (193 nm) was studied. Rats were irradiated through air or water and a 2.5 mm aperture. The laser was adjusted to deliver 150 mJ/cm2 at the skin surface with 12 and 24 pulses. Immediate damage was assessed by transmission electron microscopy. Cell selectivity was observed in dermis and epidermis. Fibroblasts showed alteration of nuclear chromatin and cytoplasmic organelles, while some of the migratory cells adjacent to fibroblasts did not. Similar difference of damage was observed between keratinocytes and Langerhans cells in epidermis. Considering the relationship between cells and their microenvironment in tissue, this selectivity may be due to the difference of acoustical coupling of propagation of acoustic waves rather than to differential sensitivity of the cells to damage. PMID:2345477

  7. Bayesian Inference of Natural Selection from Allele Frequency Time Series.

    PubMed

    Schraiber, Joshua G; Evans, Steven N; Slatkin, Montgomery

    2016-05-01

    The advent of accessible ancient DNA technology now allows the direct ascertainment of allele frequencies in ancestral populations, thereby enabling the use of allele frequency time series to detect and estimate natural selection. Such direct observations of allele frequency dynamics are expected to be more powerful than inferences made using patterns of linked neutral variation obtained from modern individuals. We developed a Bayesian method to make use of allele frequency time series data and infer the parameters of general diploid selection, along with allele age, in nonequilibrium populations. We introduce a novel path augmentation approach, in which we use Markov chain Monte Carlo to integrate over the space of allele frequency trajectories consistent with the observed data. Using simulations, we show that this approach has good power to estimate selection coefficients and allele age. Moreover, when applying our approach to data on horse coat color, we find that ignoring a relevant demographic history can significantly bias the results of inference. Our approach is made available in a C++ software package. PMID:27010022

  8. 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.

  9. Preimplantation Mouse Embryo Selection Guided by Light-Induced Dielectrophoresis

    PubMed Central

    Valley, Justin K.; Swinton, Paul; Boscardin, W. John; Lue, Tom F.; Rinaudo, Paolo F.; Wu, Ming C.; Garcia, Maurice M.

    2010-01-01

    Selection of optimal quality embryos for in vitro fertilization (IVF) transfer is critical to successful live birth outcomes. Currently, embryos are chosen based on subjective assessment of morphologic developmental maturity. A non-invasive means to quantitatively measure an embryo's developmental maturity would reduce the variability introduced by the current standard. We present a method that exploits the scaling electrical properties of pre-transfer embryos to quantitatively discern embryo developmental maturity using light-induced dielectrophoresis (DEP). We show that an embryo's DEP response is highly correlated with its developmental stage. Uniquely, this technique allows one to select, in sequence and under blinded conditions, the most developmentally mature embryos among a mixed cohort of morphologically indistinguishable embryos cultured in optimized and sub-optimal culture media. Following assay, embryos continue to develop normally in vitro. Light-induced dielectrophoresis provides a non-invasive, quantitative, and reproducible means to select embryos for applications including IVF transfer and embryonic stem cell harvest. PMID:20405021

  10. TRACING GALAXIES THROUGH COSMIC TIME WITH NUMBER DENSITY SELECTION

    SciTech Connect

    Leja, Joel; Van Dokkum, Pieter; Franx, Marijn

    2013-03-20

    A central challenge in observational studies of galaxy formation is how to associate progenitor galaxies with their descendants at lower redshifts. One promising approach is to link galaxies at fixed number density rather than fixed luminosity or mass. This method is effective if stellar mass rank order is broadly conserved through cosmic time. In this paper, we use the Guo et al. semi-analytical model to analyze under what circumstances this assumption is valid in the context of a cosmological simulation. Specifically, we select progenitor galaxies at a constant number density and compare the stellar mass evolution of their descendants to the evolution at a constant number density. The median stellar mass of the descendants increases by a factor of four (0.6 dex) from z = 3 to z = 0. Constant number density selection reproduces this to within 40% (0.15 dex) over a wide range of number densities. We show that the discrepancy primarily results from scatter in the stellar mass growth rates and merging. After applying simple, observationally based corrections for these processes, the discrepancy is reduced to 12% (0.05 dex). We conclude that number density selection can be used to predict the median descendant mass of high-redshift progenitor galaxies. The main uncertainty in this study is that semi-analytical models do not reproduce the observed mass evolution of galaxies, which makes the quantitative aggregate effects of star formation, merging, and quenching on the rank order of galaxies somewhat uncertain.

  11. Targeting Mitochondria with Avocatin B Induces Selective Leukemia Cell Death.

    PubMed

    Lee, Eric A; Angka, Leonard; Rota, Sarah-Grace; Hanlon, Thomas; Mitchell, Andrew; Hurren, Rose; Wang, Xiao Ming; Gronda, Marcela; Boyaci, Ezel; Bojko, Barbara; Minden, Mark; Sriskanthadevan, Shrivani; Datti, Alessandro; Wrana, Jeffery L; Edginton, Andrea; Pawliszyn, Janusz; Joseph, Jamie W; Quadrilatero, Joe; Schimmer, Aaron D; Spagnuolo, Paul A

    2015-06-15

    Treatment regimens for acute myeloid leukemia (AML) continue to offer weak clinical outcomes. Through a high-throughput cell-based screen, we identified avocatin B, a lipid derived from avocado fruit, as a novel compound with cytotoxic activity in AML. Avocatin B reduced human primary AML cell viability without effect on normal peripheral blood stem cells. Functional stem cell assays demonstrated selectivity toward AML progenitor and stem cells without effects on normal hematopoietic stem cells. Mechanistic investigations indicated that cytotoxicity relied on mitochondrial localization, as cells lacking functional mitochondria or CPT1, the enzyme that facilitates mitochondria lipid transport, were insensitive to avocatin B. Furthermore, avocatin B inhibited fatty acid oxidation and decreased NADPH levels, resulting in ROS-dependent leukemia cell death characterized by the release of mitochondrial proteins, apoptosis-inducing factor, and cytochrome c. This study reveals a novel strategy for selective leukemia cell eradication based on a specific difference in mitochondrial function. PMID:26077472

  12. Conformational selection or induced fit? 50 years of debate resolved

    PubMed Central

    Edelstein, Stuart

    2011-01-01

    Exactly 50 years ago, biochemists raised the question of the mechanism of the conformational change that mediates “allosteric” interactions between regulatory sites and biologically active sites in regulatory/receptor proteins. Do the different conformations involved already exist spontaneously in the absence of the regulatory ligands (Monod-Wyman-Changeux), such that the complementary protein conformation would be selected to mediate signal transduction, or do particular ligands induce the receptor to adopt the conformation best suited to them (Koshland-Nemethy-Filmer—induced fit)? This is not just a central question for biophysics, it also has enormous importance for drug design. Recent advances in techniques have allowed detailed experimental and theoretical comparisons with the formal models of both scenarios. Also, it has been shown that mutated receptors can adopt constitutively active confirmations in the absence of ligand. There have also been demonstrations that the atomic resolution structures of the same protein are essentially the same whether ligand is bound or not. These and other advances in past decades have produced a situation where the vast majority of the data using different categories of regulatory proteins (including regulatory enzymes, ligand-gated ion channels, G protein-coupled receptors, and nuclear receptors) support the conformational selection scheme of signal transduction. PMID:21941598

  13. 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

  14. 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.

  15. 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.

  16. 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. PMID:17498150

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

    DOE PAGESBeta

    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 massmore » transport and consequent nucleation, on either the intercalated or pristine areas, depending on the charge state of the adatoms.« less

  18. Single molecule insights on conformational selection and induced fit mechanism.

    PubMed

    Hatzakis, Nikos S

    2014-02-01

    Biomolecular interactions regulate a plethora of vital cellular processes, including signal transduction, metabolism, catalysis and gene regulation. Regulation is encoded in the molecular properties of the constituent proteins; distinct conformations correspond to different functional outcomes. To describe the molecular basis of this behavior, two main mechanisms have been advanced: 'induced fit' and 'conformational selection'. Our understanding of these models relies primarily on NMR, computational studies and kinetic measurements. These techniques report the average behavior of a large ensemble of unsynchronized molecules, often masking intrinsic dynamic behavior of proteins and biologically significant transient intermediates. Single molecule measurements are emerging as a powerful tool for characterizing protein function. They offer the direct observation and quantification of the activity, abundance and lifetime of multiple states and transient intermediates in the energy landscape, that are typically averaged out in non-synchronized ensemble measurements. Here we survey new insights from single molecule studies that advance our understanding of the molecular mechanisms underlying biomolecular recognition. PMID:24342874

  19. 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

  20. Timing of induced resistance in a clonal plant network.

    PubMed

    Gómez, Sara; van Dijk, William; Stuefer, Josef F

    2010-05-01

    After local herbivory, plants can activate defense traits both at the damaged site and in undamaged plant parts such as in connected ramets of clonal plants. Since defense induction has costs, a mismatch in time and space between defense activation and herbivore feeding might result in negative consequences for plant fitness. A short time lag between attack and defense activation is important to ensure efficient protection of the plant. Additionally, the duration of induced defense production once the attack has stopped is also relevant in assessing the cost-benefit balance of inducible defenses, which will depend on the absence or presence of subsequent attacks. In this study we quantified the timing of induced responses in ramet networks of the stoloniferous herb Trifolium repens after local damage by Mamestra brassicae larvae. We studied the activation time of systemic defense induction in undamaged ramets and the decay time of the response after local attack. Undamaged ramets became defense-induced 38-51 h after the initial attack. Defense induction was measured as a reduction in leaf palatability. Defense induction lasted at least 28 days, and there was strong genotypic variation in the duration of this response. Ramets formed after the initial attack were also defense-induced, implying that induced defense can extend to new ramet generations, thereby contributing to protection of plant tissue that is both very vulnerable to herbivores and most valuable in terms of future plant growth and fitness. PMID:20522188

  1. On selection of the optimal data time interval for real-time hydrological forecasting

    NASA Astrophysics Data System (ADS)

    Liu, J.; Han, D.

    2013-09-01

    With the advancement in modern telemetry and communication technologies, hydrological data can be collected with an increasingly higher sampling rate. An important issue deserving attention from the hydrological community is which suitable time interval of the model input data should be chosen in hydrological forecasting. Such a problem has long been recognised in the control engineering community but is a largely ignored topic in operational applications of hydrological forecasting. In this study, the intrinsic properties of rainfall-runoff data with different time intervals are first investigated from the perspectives of the sampling theorem and the information loss using the discrete wavelet transform tool. It is found that rainfall signals with very high sampling rates may not always improve the accuracy of rainfall-runoff modelling due to the catchment low-pass-filtering effect. To further investigate the impact of a data time interval in real-time forecasting, a real-time forecasting system is constructed by incorporating the probability distributed model (PDM) with a real-time updating scheme, the autoregressive moving-average (ARMA) model. Case studies are then carried out on four UK catchments with different concentration times for real-time flow forecasting using data with different time intervals of 15, 30, 45, 60, 90 and 120 min. A positive relation is found between the forecast lead time and the optimal choice of the data time interval, which is also highly dependent on the catchment concentration time. Finally, based on the conclusions from the case studies, a hypothetical pattern is proposed in three-dimensional coordinates to describe the general impact of the data time interval and to provide implications of the selection of the optimal time interval in real-time hydrological forecasting. Although nowadays most operational hydrological systems still have low data sampling rates (daily or hourly), the future is that higher sampling rates will become

  2. The nest site lottery: how selectively neutral density dependent growth suppression induces frequency dependent selection.

    PubMed

    Argasinski, K; Broom, M

    2013-12-01

    Modern developments in population dynamics emphasize the role of the turnover of individuals. In the new approaches stable population size is a dynamic equilibrium between different mortality and fecundity factors instead of an arbitrary fixed carrying capacity. The latest replicator dynamics models assume that regulation of the population size acts through feedback driven by density dependent juvenile mortality. Here, we consider a simplified model to extract the properties of this approach. We show that at the stable population size, the structure of the frequency dependent evolutionary game emerges. Turnover of individuals induces a lottery mechanism where for each nest site released by a dead adult individual a single newborn is drawn from the pool of newborn candidates. This frequency dependent selection leads towards the strategy maximizing the number of newborns per adult death. However, multiple strategies can maximize this value. Among them, the strategy with the greatest mortality (which implies the greatest instantaneous growth rate) is selected. This result is important for the discussion about universal fitness measures and which parameters are maximized by natural selection. This is related to the fitness measures R0 and r, because the number of newborns per single dead individual equals the lifetime production of newborn R0 in models without aging. We thus have a two-stage procedure, instead of a single fitness measure, which is a combination of R0 and r. According to the nest site lottery mechanism, at stable population size, selection favors strategies with the greatest r, i.e. those with the highest turnover, from those with the greatest R0. PMID:24071631

  3. 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, 1997).…

  4. 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.

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

    PubMed

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

    2009-06-01

    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. PMID:19566199

  6. Photo-SRM: laser-induced dissociation improves detection selectivity of Selected Reaction Monitoring mode.

    PubMed

    Enjalbert, Quentin; Simon, Romain; Salvador, Arnaud; Antoine, Rodolphe; Redon, Sébastien; Ayhan, Mehmet Menaf; Darbour, Florence; Chambert, Stéphane; Bretonnière, Yann; Dugourd, Philippe; Lemoine, Jérôme

    2011-11-30

    Selected Reaction Monitoring (SRM) carried out on triple-quadrupole mass spectrometers coupled to liquid chromatography has been a reference method to develop quantitative analysis of small molecules in biological or environmental matrices for years and is currently emerging as a promising tool in clinical proteomic. However, sensitive assays in complex matrices are often hampered by the presence of co-eluted compounds that share redundant transitions with the target species. On-the-fly better selection of the precursor ion by high-field asymmetric waveform ion mobility spectrometry (FAIMS) or increased quadrupole resolution is one way to escape from interferences. In the present work we document the potential interest of substituting classical gas-collision activation mode by laser-induced dissociation in the visible wavelength range to improve the specificity of the fragmentation step. Optimization of the laser beam pathway across the different quadrupoles to ensure high photo-dissociation yield in Q2 without detectable fragmentation in Q1 was assessed with sucrose tagged with a push-pull chromophore. Next, the proof of concept that photo-SRM ensures more specific detection than does conventional collision-induced dissociation (CID)-based SRM was carried out with oxytocin peptide. Oxytocin was derivatized by the thiol-reactive QSY® 7 C(5)-maleimide quencher on cysteine residues to shift its absorption property into the visible range. Photo-SRM chromatograms of tagged oxytocin spiked in whole human plasma digest showed better detection specificity and sensitivity than CID, that resulted in extended calibration curve linearity. We anticipate that photo-SRM might significantly improve the limit of quantification of classical SRM-based assays targeting cysteine-containing peptides. PMID:22002689

  7. Time-dependent induced potentials in convoy electron emission

    NASA Astrophysics Data System (ADS)

    Acuña, G. P.; Miraglia, J. E.

    2006-11-01

    We study the time-dependent induced potentials at the convoy electron position due to the self-interaction with a metal surface and to the shock wave created by the positive hole (vacancy) left. The time evolution of these potentials are calculated using the linear response theory. Results obtained are fitted with simple functions. We find that those two potentials nearly cancel each other in the first ten atomic units of time.

  8. The timing of verb selection in Japanese sentence production.

    PubMed

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

    2016-05-01

    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). However, the most direct experimental test of this hypothesis (Schriefers, Teruel, & Meinshausen, 1998) found no evidence for advance verb selection in verb-final (subject-verb and subject-object-verb) utterances in German. The current study, based on a multiword picture-word interference task (Meyer, 1996; Schriefers et al., 1998), demonstrates that in Japanese, a strongly verb-final language, verbs are indeed planned in advance, but selectively before object noun articulation and not before subject noun articulation. This contrasting pattern of advance verb selection may reconcile the motivation for advance verb selection in structural encoding while explaining the previous failures to demonstrate it. Potential mechanisms that might underlie this contrasting pattern of advance verb selection are discussed. (PsycINFO Database Record PMID:26569434

  9. Resource Selection Using Execution and Queue Wait Time Predictions

    NASA Technical Reports Server (NTRS)

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

    2001-01-01

    We developed techniques to predict application execution times for instance-based learning with an average error of 33% of average run time. We developed techniques to predict queue wait times that included a simulation of scheduling algorithms and execution time predictions. We implemented these techniques for the NAS Origin cluster.

  10. 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.

  11. 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.

  12. 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. PMID:27264892

  13. 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. PMID:26041272

  14. Effects of selective and non-selective endothelin receptor blockade on ET-1-induced pressor response in the hamster.

    PubMed

    Honoré, Jean-Claude; Fecteau, Marie-Hélène; Wessale, Jerry L; D'Orléans-Juste, Pedro

    2004-11-01

    In order to assess the physiological balance existing between vasoconstrictor and vasodilator endothelin-B receptor actions associated with their dual locations (i.e. on vascular smooth muscle and endothelial cells), we investigated the effects of selective and non-selective endothelin receptor antagonists on endothelin-1-induced increase in blood pressure. Atrasentan (a selective endothelin-A receptor antagonist; 6 mg/kg) and A-192621 (a selective endothelin-B receptor antagonist; 0.03, 0.3, or 30 mg/kg) were administered intravenously to anaesthetized Syrian Golden hamsters, alone or in combination, to induce respectively selective or non-selective receptor antagonism. Atrasentan partially blocked the blood pressure response induced by endothelin-1 (0.5 nmol/kg), whereas a selective endothelin-B receptor antagonism potentiated this response, independently of the dose of A-192621. Interestingly, combination of the very low dose of A-192621 (which selectively blocked putatively endothelium-located endothelin-B receptors) with atrasentan, suppressed the protective effect previously observed with atrasentan alone. Nevertheless, combination of atrasentan with the two highest doses of A-192621 tested, dose-dependently reduced the response triggered by endothelin-1. Our results suggest that endothelial endothelin-B receptors are important to control the vascular reactivity to endothelin-1. Furthermore, our data suggest that the efficacy of a non-selective endothelin-A/ endothelin-B receptor antagonist relies upon its potency to block endothelin-B receptors in the hamster. PMID:15838362

  15. Leisure-Time Activities in Selected Nursing Homes.

    ERIC Educational Resources Information Center

    Tague, Jean Ruth

    This study sought to identify leisure interests and participation patterns of residents over 65 in selected nursing homes in Los Angeles County, California, together with general and professional beliefs of nursing home administrators and authorities on aging as to leisure activities for aged nursing home patients. Interviews were held with 107…

  16. 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).…

  17. Behavioral destabilization induced by the selective serotonin reuptake inhibitor fluoxetine

    PubMed Central

    2011-01-01

    Background Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat mood and anxiety disorders. However, neuronal bases for both beneficial and adverse effects of SSRIs remain poorly understood. We have recently shown that the SSRI fluoxetine can reverse the state of maturation of hippocampal granule cells in adult mice. The granule cell "dematuration" is induced in a large population of granule cells, and greatly changes functional and physiological properties of these cells. Here we show that this unique form of neuronal plasticity is correlated with a distinct change in behavior of mice. Results We chronically treated adult male mice with fluoxetine, and examined its effect on several forms of behavior of mice. During fluoxetine treatments, mice showed a marked increase in day-to-day fluctuations of home cage activity levels that was characterized by occasional switching between hypoactivity and hyperactivity within a few days. This destabilized cage activity was accompanied by increased anxiety-related behaviors and could be observed up to 4 weeks after withdrawal from fluoxetine. As reported previously, the granule cell dematuration by fluoxetine includes a reduction of synaptic facilitation at the granule cell output, mossy fiber, synapse to the juvenile level. Mossy fiber synaptic facilitation examined electrophysiologically in acute hippocampal slices also remained suppressed after fluoxetine withdrawal and significantly correlated with the fluctuation of cage activity levels in individual mice. Furthermore, in mice lacking the 5-HT4 receptor, in which the granule cell dematuration has been shown to be attenuated, fluoxetine had no significant effect on the fluctuation of cage activity levels. Conclusions Our results demonstrate that the SSRI fluoxetine can induce marked day-to-day changes in activity levels of mice in the familiar environment, and that the dematuration of the hippocampal granule cells is closely associated with the

  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. Surface-induced selection during in situ photoswitching at the solid/liquid interface.

    PubMed

    Bonacchi, Sara; El Garah, Mohamed; Ciesielski, Artur; Herder, Martin; Conti, Simone; Cecchini, Marco; Hecht, Stefan; Samorì, Paolo

    2015-04-13

    Here we report for the first time a submolecularly resolved scanning tunneling microscopy (STM) study at the solid/liquid interface of the in situ reversible interconversion between two isomers of a diarylethene photoswitch, that is, open and closed form, self-assembled on a graphite surface. Prolonged irradiation with UV light led to the in situ irreversible formation of another isomer as by-product of the reaction, which due to its preferential physisorption accumulates at the surface. By making use of a simple yet powerful thermodynamic model we provide a quantitative description for the observed surface-induced selection of one isomeric form. PMID:25728405

  20. [Billroth and his time; selected passages from his letters].

    PubMed

    Budernik, A

    1986-04-18

    Billroth's life and work are illustrated by selected excerpts from his letters written to outstanding personalities and colleagues. Not only his medical activities, but also his initiative in the planning of the Rudolfinerhaus hospital, and the reconstruction of his own department and the building of the Medical Association house in the Frankgasse are described. In addition, his love of music and his deep friendship with Johannes Brahms are demonstrated by these letters. PMID:3521104

  1. 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.

  2. Systemically induced plant volatiles emitted at the time of "danger".

    PubMed

    Mattiacci, L; Rocca, B A; Scascighini, N; D'Alessandro, M; Hern, A; Dorn, S

    2001-11-01

    Feeding by Pieris brassicae caterpillars on the lower leaves of Brussels sprouts (Brassica oleracea var. gemmifera) plants triggers the release of volatiles from upper leaves. The volatiles are attractive for a natural antagonist of the herbivore, the parasitoid Cotesia glomerata. Parasitoids are attracted only if additional damage is inflicted on the systemically induced upper leaves and only after at least three days of herbivore feeding on the lower leaves. Upon termination of caterpillar feeding, the systemic signal is emitted for a maximum of one more day. Systemic induction did not occur at low levels of herbivore infestation. Systemically induced leaves emitted green leaf volatiles, cyclic monoterpenoids, and sesquiterpenes. GC-MS profiles of systemically induced and herbivore-infested leaves did not differ for most compounds, although herbivore infested plants did emit higher amounts of green leaf volatiles. Emission of systemically induced volatiles in Brussels sprouts might function as an induced defense that is activated only when needed, i.e., at the time of caterpillar attack. This way, plants may adopt a flexible management of inducible defensive resources to minimize costs of defense and to maximize fitness in response to unpredictable herbivore attack. PMID:11817078

  3. Time-intensity trading functions for selected pure tones.

    PubMed

    Young, L L

    1976-03-01

    A substantial number of investigations have examined the ability of the auditory system to trade time for intensity on a lateralization task. Most of these investigations, however, have employed clicks and noise bursts as stimuli with interaural disparities between onset times. Consequently, there is a lack of quantitative data for time-intensity trades where pure tones that had identical onset times but disparate phase were employed as signals. For this reason we employed sinusoids ranging from 200 to 2000 Hz and determined the extent to which the intensity of one signal must be decreased to achieve a midline image when interaural phase disparities of 0 degrees to 360 degrees were imposed between the binaural signals in 30 degree increments. The time-intensity trading functions yielded in this experiment demonstrate that (1) not unexpectedly, the largest time-intensity trades were accomplished for the lower frequencies; (2) the maximum time-intensity trade for each frequency occurred at interaural phase disparities of 90 degrees and 270 degrees; and (3) when the low-frequency tones were 180 degrees out of phase, essentially the same intraaural intensity relationship was required to achieve midline as was needed for the 0 degree interaural phase condition. PMID:1271802

  4. Selective enhancement of topologically induced interface states in a dielectric resonator chain

    PubMed Central

    Poli, Charles; Bellec, Matthieu; Kuhl, Ulrich; Mortessagne, Fabrice; Schomerus, Henning

    2015-01-01

    The recent realization of topological phases in insulators and superconductors has advanced the search for robust quantum technologies. The prospect to implement the underlying topological features controllably has given incentive to explore optical platforms for analogous realizations. Here we realize a topologically induced defect state in a chain of dielectric microwave resonators and show that the functionality of the system can be enhanced by supplementing topological protection with non-hermitian symmetries that do not have an electronic counterpart. We draw on a characteristic topological feature of the defect state, namely, that it breaks a sublattice symmetry. This isolates the state from losses that respect parity-time symmetry, which enhances its visibility relative to all other states both in the frequency and in the time domain. This mode selection mechanism naturally carries over to a wide range of topological and parity-time symmetric optical platforms, including couplers, rectifiers and lasers. PMID:25833814

  5. 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. PMID:26911957

  6. [Discrimination of Crude Oil Samples Using Laser-Induced Time-Resolved Fluorescence Spectroscopy].

    PubMed

    Han, Xiao-shuang; Liu, De-qing; Luan, Xiao-ning; Guo, Jin-jia; Liu, Yong-xin; Zheng, Rong-er

    2016-02-01

    The Laser-induced fluorescence spectra combined with pattern recognition method has been widely applied in discrimination of different spilled oil, such as diesel, gasoline, and crude oil. However, traditional three-dimension fluorescence analysis method, which is not adapted to requirement of field detection, is limited to laboratory investigatio ns. The development of oil identification method for field detection is significant to quick response and operation of oil spill. In this paper, a new method based on laser-induced time-resolved fluorescence combined with support vector machine (SVM) model was introduced to discriminate crude oil samples. In this method, time-resolved spectra data was descended into two dimensions with selecting appropriate range in time and wavelength domains respectively to form a SVM data base. It is found that the classification accurate rate increased with an appropriate selection. With a selected range from 54 to 74 ns in time domain, the classification accurate rate has been increased from 83.3% (without selection) to 88.1%. With a selected wavelength range of 387.00~608.87 nm, the classification accurate rate of suspect oil was improved from 84% (without selection) to 100%. Since the detection delay of fluorescence lidar fluctuates due to wave and platform swing, the identification method with optimizing in both time and wavelength domains could offer a better flexibility for field applications. It is hoped that the developed method could provide some useful reference with data reduction for classification of suspect crude oil in the future development. PMID:27209747

  7. Timing determines dexamethasone and rituximab induced synergistic cell death.

    PubMed

    Adem, Jemal; Eray, Mine; Eeva, Jonna; Nuutinen, Ulla; Pelkonen, Jukka

    2016-07-01

    Dysregulation of cell death signaling pathways in many cell types such as B lymphocytes (B-cells) can lead to cancer, for example to B-cell lymphomas. Rituximab (RTX) and glucocorticoids such as dexamethasone (Dex) are widely used to treat hematological malignancies including B-cell lymphomas. Although the combination of Dex and RTX improves the treatment outcome of lymphoma patients, most lymphomas remain incurable diseases. Therefore, a detailed investigation of Dex- and RTX-induced signaling might provide new insights into the therapeutic benefits of these drugs. In this paper, we describe Dex- and RTX-induced signaling pathways and their downstream target proteins/cells. In addition, we also overview how the signaling initiated by Dex and RTX modulate the outcome of Dex- and RTX-mediated cell death in lymphoma cells. The combination of Dex and RTX results in massive cell death in lymphoma cells. However, pretreatment of lymphoma cells or mononuclear cytotoxic cells with Dex followed by RTX leads to a decrease in apoptosis or it impairs antibody-dependent cellular cytotoxicity (ADCC). RTX-mediated ADCC is impaired by Dex-induced depletion of cytotoxic cells, whereas RTX-mediated short-term ERK1/2 activation decreases Dex-induced apoptosis. Therefore, the timing of the combination of Dex and RTX is a determining factor for the synergistic effect of these cell death inducing agents. PMID:27290654

  8. Real-Time PCR-Coupled CE-SELEX for DNA Aptamer Selection

    PubMed Central

    Ruff, Patrick; Pai, Rekha B.; Storici, Francesca

    2012-01-01

    Aptamers are short nucleic acid or peptide sequences capable of binding to a target molecule with high specificity and affinity. Also known as “artificial antibodies,” aptamers provide many advantages over antibodies. One of the major hurdles to aptamer isolation is the initial time and effort needed for selection. The systematic evolution of ligands by exponential enrichment (SELEX) is the traditional procedure for generating aptamers, but this process is lengthy and requires a large quantity of target and starting aptamer library. A relatively new procedure for generating aptamers using capillary electrophoresis (CE), known as CE-SELEX, is faster and more efficient than SELEX but requires laser-induced fluorescence (LIF) to detect the aptamer-target complexes. Here, we implemented an alternative system without LIF using real-time- (RT-) PCR to indirectly measure aptamer-target complexes. In three rounds of selection, as opposed to ten or more rounds common in SELEX protocols, a specific aptamer for bovine serum albumin (BSA) was obtained. The specificity of the aptamer to BSA was confirmed by electrophoretic mobility shift assays (EMSAs), an unlabeled competitor assay, and by a supershift assay. The system used here provides a cost effective and a highly efficient means of generating aptamers. PMID:27335672

  9. 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.…

  10. Time-Resolved Electron Diffraction from Selectively Aligned Molecules

    SciTech Connect

    Reckenthaeler, Peter; Krausz, Ferenc; Centurion, Martin; Fuss, Werner; Trushin, Sergei A.; Fill, Ernst E.

    2009-05-29

    We experimentally demonstrate ultrafast electron diffraction from transiently aligned molecules in the absence of external (aligning) fields. A sample of aligned molecules is generated through photodissociation with femtosecond laser pulses, and the diffraction pattern is captured by probing the sample with picosecond electron pulses shortly after dissociation - before molecular rotation causes the alignment to vanish. In our experiments the alignment decays with a time constant of 2.6{+-}1.2 ps.

  11. 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

  12. 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…

  13. Real-time object tracking via online discriminative feature selection.

    PubMed

    Zhang, Kaihua; Zhang, Lei; Yang, Ming-Hsuan

    2013-12-01

    Most tracking-by-detection algorithms train discriminative classifiers to separate target objects from their surrounding background. In this setting, noisy samples are likely to be included when they are not properly sampled, thereby causing visual drift. The multiple instance learning (MIL) paradigm has been recently applied to alleviate this problem. However, important prior information of instance labels and the most correct positive instance (i.e., the tracking result in the current frame) can be exploited using a novel formulation much simpler than an MIL approach. In this paper, we show that integrating such prior information into a supervised learning algorithm can handle visual drift more effectively and efficiently than the existing MIL tracker. We present an online discriminative feature selection algorithm that optimizes the objective function in the steepest ascent direction with respect to the positive samples while in the steepest descent direction with respect to the negative ones. Therefore, the trained classifier directly couples its score with the importance of samples, leading to a more robust and efficient tracker. Numerous experimental evaluations with state-of-the-art algorithms on challenging sequences demonstrate the merits of the proposed algorithm. PMID:23955750

  14. Fluorescence spectroscopy in probing spontaneous and induced aggregation amongst size-selective gold nanoclusters

    NASA Astrophysics Data System (ADS)

    Rahman, Dewan S.; Ghosh, Sujit Kumar

    2014-06-01

    Gold nanoparticles have been synthesized by borohydride reduction using poly(N-vinyl 2-pyrrolidone) as the stabilizing agent in aqueous medium in the size regime of 1-5 nm. Aggregation amongst these polymer-stabilized gold nanoparticles has been accomplished by the controlled addition of hydrazine or aggregation may occur spontaneously (devoid of any chemicals) that is ubiquitous to nanoparticulate systems. Now, fluorescencein isothiocyanate (FITC), a prototype molecular probe has been employed in understanding the physical principles of aggregation phenomenon of the size-selective gold nanoparticles undergoing spontaneous and induced-aggregation under stipulated conditions. It is seen that there is enhancement of fluorescence intensity of FITC in the presence of both spontaneously and induced-aggregated gold nanoclusters as compared to free FITC. Interestingly, it is observed that the fluorescence sensitivity is able to distinguish seven different sizes of the gold nanoparticles in the aggregates and maximum enhancement of intensity arises at higher concentration with increase in size of gold particles within the aggregates. With increase in concentration of gold nanoparticle aggregates, the intensity increases, initially, reaches a maximum at a threshold concentration and then, gradually decreases in the presence of both spontaneously and induced-aggregated gold particles. However, the salient feature of physical significance is that the maximum enhancement of intensity with time has remained almost same for induced-aggregated gold while decreases exponentially with spontaneously aggregated gold particles.

  15. 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

    2009-01-01

    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

  16. 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

  17. 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

  18. 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.

  19. 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. PMID:22905028

  20. Dissecting protein-induced DNA looping dynamics in real time

    PubMed Central

    Laurens, Niels; Bellamy, Stuart R. W.; Harms, August F.; Kovacheva, Yana S.; Halford, Stephen E.; Wuite, Gijs J. L.

    2009-01-01

    Many proteins that interact with DNA perform or enhance their specific functions by binding simultaneously to multiple target sites, thereby inducing a loop in the DNA. The dynamics and energies involved in this loop formation influence the reaction mechanism. Tethered particle motion has proven a powerful technique to study in real time protein-induced DNA looping dynamics while minimally perturbing the DNA–protein interactions. In addition, it permits many single-molecule experiments to be performed in parallel. Using as a model system the tetrameric Type II restriction enzyme SfiI, that binds two copies of its recognition site, we show here that we can determine the DNA–protein association and dissociation steps as well as the actual process of protein-induced loop capture and release on a single DNA molecule. The result of these experiments is a quantitative reaction scheme for DNA looping by SfiI that is rigorously compared to detailed biochemical studies of SfiI looping dynamics. We also present novel methods for data analysis and compare and discuss these with existing methods. The general applicability of the introduced techniques will further enhance tethered particle motion as a tool to follow DNA–protein dynamics in real time. PMID:19586932

  1. 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

  2. Timing of Initiation of RRT and Modality Selection.

    PubMed

    Bargman, Joanne M

    2015-06-01

    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

  3. SELECTIVE AND NON-SELECTIVE METALLOPROTEINASE INHIBITORS REDUCE IL-1-INDUCED CARTILAGE DEGRADATION AND LOSS OF MECHANICAL PROPERTIES

    PubMed Central

    Wilson, Christopher G.; Palmer, Ashley W.; Zuo, Fengrong; Eugui, Elsie; Wilson, Stacy; Mackenzie, Rebecca; Sandy, John D.; Levenston, Marc E.

    2015-01-01

    Articular cartilage undergoes matrix degradation and loss of mechanical properties when stimulated with proinflammatory cytokines such as interleukin-1 (IL-1). Aggrecanases and matrix metalloproteinases (MMPs) are thought to be principal downstream effectors of cytokine-induced matrix catabolism, and aggrecanase- or MMP-selective inhibitors reduce or block matrix destruction in several model systems. The objective of this study was to use metalloproteinase inhibitors to perturb IL-1-induced matrix catabolism in bovine cartilage explants and examine their effects on changes in tissue compression and shear properties. Explanted tissue was stimulated with IL-1 for up to 24 days in the absence or presence of inhibitors which were aggrecanase-selective, MMP-selective, or non-selective. Analysis of conditioned media and explant digests revealed that aggrecanase-mediated aggrecanolysis was delayed to varying extents with all inhibitor treatments, but that aggrecan release persisted. Collagen degradation was abrogated by MMP- and non-selective inhibitors and reduced by the aggrecanase inhibitor. The inhibitors delayed but did not reduce loss of the equilibrium compression modulus, whereas the loss of dynamic compression and shear moduli was delayed and reduced. The data suggest that non-metalloproteinase mechanisms participate in IL-1-induced matrix degradation and loss of tissue material properties. PMID:17174540

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

    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.

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

    PubMed

    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

  7. Denoising time-domain induced polarisation data using wavelet techniques

    NASA Astrophysics Data System (ADS)

    Deo, Ravin N.; Cull, James P.

    2016-05-01

    Time-domain induced polarisation (TDIP) methods are routinely used for near-surface evaluations in quasi-urban environments harbouring networks of buried civil infrastructure. A conventional technique for improving signal to noise ratio in such environments is by using analogue or digital low-pass filtering followed by stacking and rectification. However, this induces large distortions in the processed data. In this study, we have conducted the first application of wavelet based denoising techniques for processing raw TDIP data. Our investigation included laboratory and field measurements to better understand the advantages and limitations of this technique. It was found that distortions arising from conventional filtering can be significantly avoided with the use of wavelet based denoising techniques. With recent advances in full-waveform acquisition and analysis, incorporation of wavelet denoising techniques can further enhance surveying capabilities. In this work, we present the rationale for utilising wavelet denoising methods and discuss some important implications, which can positively influence TDIP methods.

  8. Select forms of tumor cell apoptosis induce dendritic cell maturation.

    PubMed

    Demaria, Sandra; Santori, Fabio R; Ng, Bruce; Liebes, Leonard; Formenti, Silvia C; Vukmanovic, Stanislav

    2005-03-01

    Dendritic cells (DC) play a crucial role in initiating immune responses to tumors. DC can efficiently present antigens from apoptotic tumor cells, but apoptotic cells are thought to lack the inflammatory signals required to induce DC maturation. Here, we show that apoptosis of 67NR mouse carcinoma cells via the Fas (CD95) pathway or induced by the anticancer drug bortezomib (PS-341) but not by ultraviolet irradiation is associated with the production of maturation signals for DC. These data have important implications for the effects of chemotherapy on antitumor immunity in solid and hematologic malignancies. PMID:15569694

  9. 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…

  10. 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

  11. 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.

  12. 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

  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. 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. PMID:11309260

  15. 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

  16. 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.

  17. Time-resolved electric-field-induced second harmonic

    NASA Astrophysics Data System (ADS)

    Meshulam, Guilia; Berkovic, Garry; Kotler, Zvi

    2001-12-01

    One limitation of using electric field induced second harmonic (EFISH) to determine the molecular first hyperpolarizability (beta) of nonlinear optical molecules lies in the fact that part of the second harmonic signal comes from the second hyperpolarizability (gamma) produced by mixing two optical fields with the DC field. In analyzing EFISH results, the second hyperpolarizability contribution of the studied molecules is generally neglected. We present a modified time resolved EFISH technique that allows us, in a single experiment, to determine separately the beta and the gamma contributions. We study para-nitro aniline dissolved in Glycerol, a highly viscous solvent, and apply the DC field via a high voltage pulse with a fast rise time of approximately 40 nsec. As a result, the orientation of the molecules under the applied electric field is slow relative to the build-up of the field, enabling us to directly measure only the DC induced second harmonic (gamma contribution), at the beginning of the HV pulse. The pure beta contribution is determined from the difference between this signal and the conventional EFISH signal at the plateau of the HV pulse. Our result confirm that the gamma contribution is indeed less than 10% of the total.

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

    PubMed

    Sheaffer, Amy K; 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

  19. 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

  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. PMID:26373988

  1. A Locked Nucleic Acid Probe Based on Selective Salt-Induced Effect Detects Single Nucleotide Polymorphisms

    PubMed Central

    Zhang, Jing; Wu, Huizhe; Chen, Qiuchen; Zhao, Pengfei; Zhao, Haishan; Yao, Weifan; Wei, Minjie

    2015-01-01

    Detection of single based genetic mutation by using oligonucleotide probes is one of the common methods of detecting single nucleotide polymorphisms at known loci. In this paper, we demonstrated a hybridization system which included a buffer solution that produced selective salt-induced effect and a locked nucleic acid modified 12 nt oligonucleotide probe. The hybridization system is suitable for hybridization under room temperature. By using magnetic nanoparticles as carriers for PCR products, the SNPs (MDR1 C3435T/A) from 45 volunteers were analyzed, and the results were consistent with the results from pyrophosphoric acid sequencing. The method presented in this paper differs from the traditional method of using molecular beacons to detect SNPs in that it is suitable for research institutions lacking real-time quantitative PCR detecting systems, to detect PCR products at room temperature. PMID:26347880

  2. Neuronal polarity selection by topography-induced focal adhesion control.

    PubMed

    Ferrari, Aldo; Cecchini, Marco; Serresi, Michela; Faraci, Paolo; Pisignano, Dario; Beltram, Fabio

    2010-06-01

    Interaction between differentiating neurons and the extracellular environment guides the establishment of cell polarity during nervous system development. Developing neurons read the physical properties of the local substrate in a contact-dependent manner and retrieve essential guidance cues. In previous works we demonstrated that PC12 cell interaction with nanogratings (alternating lines of ridges and grooves of submicron size) promotes bipolarity and alignment to the substrate topography. Here, we investigate the role of focal adhesions, cell contractility, and actin dynamics in this process. Exploiting nanoimprint lithography techniques and a cyclic olefin copolymer, we engineered biocompatible nanostructured substrates designed for high-resolution live-cell microscopy. Our results reveal that neuronal polarization and contact guidance are based on a geometrical constraint of focal adhesions resulting in an angular modulation of their maturation and persistence. We report on ROCK1/2-myosin-II pathway activity and demonstrate that ROCK-mediated contractility contributes to polarity selection during neuronal differentiation. Importantly, the selection process confined the generation of actin-supported membrane protrusions and the initiation of new neurites at the poles. Maintenance of the established polarity was independent from NGF stimulation. Altogether our results imply that focal adhesions and cell contractility stably link the topographical configuration of the extracellular environment to a corresponding neuronal polarity state. PMID:20304485

  3. An integrated analysis of phenotypic selection on insect body size and development time.

    PubMed

    Eck, Daniel J; Shaw, Ruth G; Geyer, Charles J; Kingsolver, Joel G

    2015-09-01

    Most studies of phenotypic selection do not estimate selection or fitness surfaces for multiple components of fitness within a unified statistical framework. This makes it difficult or impossible to assess how selection operates on traits through variation in multiple components of fitness. We describe a new generation of aster models that can evaluate phenotypic selection by accounting for timing of life-history transitions and their effect on population growth rate, in addition to survival and reproductive output. We use this approach to estimate selection on body size and development time for a field population of the herbivorous insect, Manduca sexta (Lepidoptera: Sphingidae). Estimated fitness surfaces revealed strong and significant directional selection favoring both larger adult size (via effects on egg counts) and more rapid rates of early larval development (via effects on larval survival). Incorporating the timing of reproduction and its influence on population growth rate into the analysis resulted in larger values for size in early larval development at which fitness is maximized, and weaker selection on size in early larval development. These results illustrate how the interplay of different components of fitness can influence selection on size and development time. This integrated modeling framework can be readily applied to studies of phenotypic selection via multiple fitness components in other systems. PMID:26257167

  4. 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

  5. Optimal Selection of Parameters for Nonuniform Embedding of Chaotic Time Series Using Ant Colony Optimization.

    PubMed

    Shen, Meie; Chen, Wei-Neng; Zhang, Jun; Chung, Henry Shu-Hung; Kaynak, Okyay

    2013-04-01

    The optimal selection of parameters for time-delay embedding is crucial to the analysis and the forecasting of chaotic time series. Although various parameter selection techniques have been developed for conventional uniform embedding methods, the study of parameter selection for nonuniform embedding is progressed at a slow pace. In nonuniform embedding, which enables different dimensions to have different time delays, the selection of time delays for different dimensions presents a difficult optimization problem with combinatorial explosion. To solve this problem efficiently, this paper proposes an ant colony optimization (ACO) approach. Taking advantage of the characteristic of incremental solution construction of the ACO, the proposed ACO for nonuniform embedding (ACO-NE) divides the solution construction procedure into two phases, i.e., selection of embedding dimension and selection of time delays. In this way, both the embedding dimension and the time delays can be optimized, along with the search process of the algorithm. To accelerate search speed, we extract useful information from the original time series to define heuristics to guide the search direction of ants. Three geometry- or model-based criteria are used to test the performance of the algorithm. The optimal embeddings found by the algorithm are also applied in time-series forecasting. Experimental results show that the ACO-NE is able to yield good embedding solutions from both the viewpoints of optimization performance and prediction accuracy. PMID:23144038

  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. Optomechanically-induced transparency in parity-time-symmetric microresonators.

    PubMed

    Jing, H; Özdemir, Şahin K; Geng, Z; Zhang, Jing; Lü, Xin-You; Peng, Bo; Yang, Lan; Nori, Franco

    2015-01-01

    Optomechanically-induced transparency (OMIT) and the associated slowing of light provide the basis for storing photons in nanoscale devices. Here we study OMIT in parity-time (PT)-symmetric microresonators with a tunable gain-to-loss ratio. This system features a sideband-reversed, non-amplifying transparency, i.e., an inverted-OMIT. When the gain-to-loss ratio is varied, the system exhibits a transition from a PT-symmetric phase to a broken-PT-symmetric phase. This PT-phase transition results in the reversal of the pump and gain dependence of the transmission rates. Moreover, we show that by tuning the pump power at a fixed gain-to-loss ratio, or the gain-to-loss ratio at a fixed pump power, one can switch from slow to fast light and vice versa. These findings provide new tools for controlling light propagation using nanofabricated phononic devices. PMID:26169253

  8. 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

    ... notice was originally published in the Federal Register on April 20, 2011 (76 FR 22143). The due date was... 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...

  9. Radiation-induced lung damage: dose-time-fractionation considerations.

    PubMed

    Van Dyk, J; Mah, K; Keane, T J

    1989-01-01

    The comparison of different dose-time-fractionation schedules requires the use of an isoeffect formula. In recent years, the NSD isoeffect formula has been heavily criticized. In this report, we consider an isoeffect formula which is specifically developed for radiation-induced lung damage. The formula is based on the linear-quadratic model and includes a factor for overall treatment time. The proposed procedures allow for the simultaneous derivation of an alpha/beta ratio and a gamma/beta time factor. From animal data in the literature, the derived alpha/beta and gamma/beta ratios for acute lung damage are 5.0 +/- 1.0 Gy and 2.7 +/- 1.4 Gy2/day respectively, while for late damage the suggested values are 2.0 Gy and 0.0 Gy2/day. Data from two clinical studies, one prospective and the other retrospective, were also analysed and corresponding alpha/beta and gamma/beta ratios were determined. For the prospective clinical study, with a limited range of doses per fraction, the resultant alpha/beta and gamma/beta ratios were 0.9 +/- 2.6 Gy and 2.6 +/- 2.5 Gy2/day. The combination of the retrospective and prospective data yielded alpha/beta and gamma/beta ratios of 3.3 +/- 1.5 Gy and 2.4 +/- 1.5 Gy2/day, respectively. One potential advantage of this isoeffect formalism is that it might possibly be applied to both acute and late lung damage. The results of this formulation for acute lung damage indicate that time-dependent effects such as slow repair or proliferation might be more important in determining isoeffect doses than previously predicted by the estimated single dose (ED) formula. Although we present this as an alternative approach, we would caution against its clinical use until its applicability has been confirmed by additional clinical data. PMID:2928557

  10. Statistical Inference of Selection and Divergence from a Time-Dependent Poisson Random Field Model

    PubMed Central

    Amei, Amei; Sawyer, Stanley

    2012-01-01

    We apply a recently developed time-dependent Poisson random field model to aligned DNA sequences from two related biological species to estimate selection coefficients and divergence time. We use Markov chain Monte Carlo methods to estimate species divergence time and selection coefficients for each locus. The model assumes that the selective effects of non-synonymous mutations are normally distributed across genetic loci but constant within loci, and synonymous mutations are selectively neutral. In contrast with previous models, we do not assume that the individual species are at population equilibrium after divergence. Using a data set of 91 genes in two Drosophila species, D. melanogaster and D. simulans, we estimate the species divergence time (or 1.68 million years, assuming the haploid effective population size years) and a mean selection coefficient per generation . Although the average selection coefficient is positive, the magnitude of the selection is quite small. Results from numerical simulations are also presented as an accuracy check for the time-dependent model. PMID:22509300

  11. Role and Mechanism of Microglial Activation in Iron-Induced Selective and Progressive Dopaminergic Neurodegeneration

    PubMed Central

    Yan, Zhao-fen; Gao, Jun-hua; Sun, Li; Huang, Xi-yan; Liu, Zhuo; Yu, Shu-yang; Cao, Chen-Jie; Zuo, Li-jun; Chen, Ze-Jie; Hu, Yang; Wang, Fang; Hong, Jau-shyong; Wang, Xiao-min

    2016-01-01

    Parkinson’s disease (PD) patients have excessive iron depositions in substantia nigra (SN). Neuroinflammation characterized by microglial activation is pivotal for dopaminergic neurodegeneration in PD. However, the role and mechanism of microglial activation in iron-induced dopaminergic neurodegeneration in SN remain unclear yet. This study aimed to investigate the role and mechanism of microglial β-nicotinamide adenine dinucleotide phosphate oxidase 2 (NOX2) activation in iron-induced selective and progressive dopaminergic neurodegeneration. Multiple primary midbrain cultures from rat, NOX2+/+ and NOX2−/− mice were used. Dopaminergic neurons, total neurons, and microglia were visualized by immunostainings. Cell viability was measured by MTT assay. Superoxide (O2·−) and intracellular reactive oxygen species (iROS) were determined by measuring SOD-inhibitable reduction of tetrazolium salt WST-1 and DCFH-DA assay. mRNA and protein were detected by real-time PCR and Western blot. Iron induces selective and progressive dopaminergic neurotoxicity in rat neuron–microglia–astroglia cultures and microglial activation potentiates the neurotoxicity. Activated microglia produce a magnitude of O2·− and iROS, and display morphological alteration. NOX2 inhibitor diphenylene iodonium protects against iron-elicited dopaminergic neurotoxicity through decreasing microglial O2·− generation, and NOX2−/− mice are resistant to the neurotoxicity by reducing microglial O2·− production, indicating that iron-elicited dopaminergic neurotoxicity is dependent of NOX2, a O2·−-generating enzyme. NOX2 activation is indicated by the increased mRNA and protein levels of subunits P47 and gp91. Molecules relevant to NOX2 activation include PKC-σ, P38, ERK1/2, JNK, and NF-ΚBP65 as their mRNA and protein levels are enhanced by NOX2 activation. Iron causes selective and progressive dopaminergic neurodegeneration, and microglial NOX2 activation potentiates the

  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. PMID:27174031

  13. Statin-induced muscle necrosis in the rat: distribution, development, and fibre selectivity.

    PubMed

    Westwood, F Russell; Bigley, Alison; Randall, Kevin; Marsden, Alan M; Scott, Robert C

    2005-01-01

    Simvastatin and cerivastatin have been used to investigate the development of statin-induced muscle necrosis in the rat. This was similar for both statins and was treatment-duration dependent, only occurring after 10 days had elapsed even if the dose was increased, and still occurring after this time when dosing was terminated earlier as a result of morbidity. It was then widespread and affected all areas of the muscular system. However, even when myotoxicity was severe, particular individual muscles and some types of fibres within affected muscles were spared consistently. Fibre typing of spared muscles and of acutely necrotic fibres within affected muscles indicated a differential fibre sensitivity to statin-induced muscle necrosis. The fibres showed a necrotic response to statin administration that matched their oxidative/glycolytic metabolic nature: Least sensitive --> I < - > IIA < - > IID < - > IIB <-- most sensitive. Type I and IIB fibres represent metabolic extremes of a continuum of metabolic properties through the fibre types with type I fibres most oxidative in metabolism and type IIB fibres most glycolytic. In addition, in some (nonnecrotic) glycolytic fibres from muscles showing early multifocal single fibre necrosis the only subcellular alterations present in isolation of any other changes were mitochondrial. These changes were characterised by an increased incidence of vacuolation and the formation of myelinoid vesicular bodies that accumulated in the subsarcolemmal areas. These findings suggest an important early involvement of mitochondria in selective glycolytic muscle fibre necrosis following inhibition of the enzyme HMG-CoA reductase. PMID:15902968

  14. A distant cis acting intronic element induces site-selective RNA editing.

    PubMed

    Daniel, Chammiran; Venø, Morten T; Ekdahl, Ylva; Kjems, Jørgen; Öhman, Marie

    2012-10-01

    Transcripts have been found to be site selectively edited from adenosine-to-inosine (A-to-I) in the mammalian brain, mostly in genes involved in neurotransmission. While A-to-I editing occurs at double-stranded structures, other structural requirements are largely unknown. We have investigated the requirements for editing at the I/M site in the Gabra-3 transcript of the GABA(A) receptor. We identify an evolutionarily conserved intronic duplex, 150 nt downstream of the exonic hairpin where the I/M site resides, which is required for its editing. This is the first time a distant RNA structure has been shown to be important for A-to-I editing. We demonstrate that the element also can induce editing in related but normally not edited RNA sequences. In human, thousands of genes are edited in duplexes formed by inverted repeats in non-coding regions. It is likely that numerous such duplexes can induce editing of coding regions throughout the transcriptome. PMID:22848101

  15. A distant cis acting intronic element induces site-selective RNA editing

    PubMed Central

    Daniel, Chammiran; Venø, Morten T.; Ekdahl, Ylva; Kjems, Jørgen; Öhman, Marie

    2012-01-01

    Transcripts have been found to be site selectively edited from adenosine-to-inosine (A-to-I) in the mammalian brain, mostly in genes involved in neurotransmission. While A-to-I editing occurs at double-stranded structures, other structural requirements are largely unknown. We have investigated the requirements for editing at the I/M site in the Gabra-3 transcript of the GABAA receptor. We identify an evolutionarily conserved intronic duplex, 150 nt downstream of the exonic hairpin where the I/M site resides, which is required for its editing. This is the first time a distant RNA structure has been shown to be important for A-to-I editing. We demonstrate that the element also can induce editing in related but normally not edited RNA sequences. In human, thousands of genes are edited in duplexes formed by inverted repeats in non-coding regions. It is likely that numerous such duplexes can induce editing of coding regions throughout the transcriptome. PMID:22848101

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

    PubMed

    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

  17. 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

  18. 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.

  19. 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

  20. Strain-induced time-reversal odd superconductivity in graphene

    NASA Astrophysics Data System (ADS)

    Juricic, Vladimir; Roy, Bitan

    2014-03-01

    I will discuss the possibility of realizing a time-reversal-symmetry breaking superconducting state that exhibits an f + is pairing symmetry in strained graphene. Although the underlying attractive interactions need to be sufficiently strong and comparable in pristine graphene to support such pairing state, I will argue that strain can be conducive for its formation even for weak interactions. I will show that quantum-critical behavior near the transition is controlled by a fermionic multicritical point, characterized by various critical exponents computed in the framework of an ɛ-expansion near four spacetime dimensions. I will then discuss the scaling of the superconducting gap with the strain-induced axial pseudo-magnetic field. Furthermore, a vortex in this mixed superconducting state hosts a pair of Majorana fermions supporting a quartet of insulating and superconducting orders, among which quantum spin Hall topological insulator. Finally, I will mention some experimental signatures of this f + is time-reversal odd superconductor. These findings suggest that strained graphene could provide a platform for the realization of exotic superconducting states of Dirac fermions. VJ is supported by the Netherlands Organization for Scientific Research (NWO).

  1. Directional versus Stabilizing Selection for Developmental Time in Natural and Laboratory Populations of Flour Beetles.

    PubMed

    Dawson, P S

    1975-08-01

    Artificial selection for fast development is successful in long-established laboratory populations of Tribolium, but not in strains recently derived from natural populations. It is shown that selection against fast development in dense, synchronized cultures operates through cannibalism of early pupae by larvae. Since standard husbandry procedures for laboratory strains involve the periodic creation of dense, synchronized cultures, it is suggested that these populations are subjected to stabilizing selection for intermediate developmental time. Natural populations, on the other hand, are probably subjected to directional selection for rapid development. PMID:17248688

  2. 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.

  3. Computational design of a time-dependent histone deacetylase 2 selective inhibitor.

    PubMed

    Zhou, Jingwei; Li, Min; Chen, Nanhao; Wang, Shenglong; Luo, Hai-Bin; Zhang, Yingkai; Wu, Ruibo

    2015-03-20

    Development of isoform-selective histone deacetylase (HDAC) inhibitors is of great biological and medical interest. Among 11 zinc-dependent HDAC isoforms, it is particularly challenging to achieve isoform inhibition selectivity between HDAC1 and HDAC2 due to their very high structural similarities. In this work, by developing and applying a novel de novo reaction-mechanism-based inhibitor design strategy to exploit the reactivity difference, we have discovered the first HDAC2-selective inhibitor, β-hydroxymethyl chalcone. Our bioassay experiments show that this new compound has a unique time-dependent selective inhibition on HDAC2, leading to about 20-fold isoform-selectivity against HDAC1. Furthermore, our ab initio QM/MM molecular dynamics simulations, a state-of-the-art approach to study reactions in biological systems, have elucidated how the β-hydroxymethyl chalcone can achieve the distinct time-dependent inhibition toward HDAC2. PMID:25546141

  4. Vessel-selective, non-contrast enhanced, time-resolved MR angiography with vessel-selective arterial spin labeling technique (CINEMA-SELECT) in intracranial arteries.

    PubMed

    Nakamura, Masanobu; Yoneyama, Masami; Tabuchi, Takashi; Takemura, Atsushi; Obara, Makoto; Tatsuno, Satoshi; Sawano, Seishi

    2013-07-01

    We demonstrate the feasibility of the vessel-selective, non-contrast, time-resolved magnetic resonance angiography (MRA) technique, "contrast inherent inflow enhanced multi-phase angiography combining vessel-selective arterial spin labeling technique (CINEMA-SELECT)". This sequence consists of two major techniques: pulsed star labeling of arterial regions (PULSAR) and Look-Locker sampling. We hypothesize that this technique allows selective labeling of single intracranial arteries, consisting of high-resolution four-dimensional data with a wide coverage of the brain. In this study, a new vessel-selective, time-resolved angiographic technique is demonstrated that can produce individual angiograms non-invasively by labeling the principal arterial vessels proximal to the circle of Willis. Clear vessel delineation is achieved, and the separation of the three vessels is evident in healthy volunteers. This technique could play an important role in the assessment of the structure and hemodynamics of intracranial arteries without the use of contrast agents. PMID:23475783

  5. Acute Stress Induces Selective Alterations in Cost/Benefit Decision-Making

    PubMed Central

    Shafiei, Naghmeh; Gray, Megan; Viau, Victor; Floresco, Stan B

    2012-01-01

    Acute stress can exert beneficial or detrimental effects on different forms of cognition. In the present study, we assessed the effects of acute restraint stress on different forms of cost/benefit decision-making, and some of the hormonal and neurochemical mechanisms that may underlie these effects. Effort-based decision-making was assessed where rats chose between a low effort/reward (1 press=2 pellets) or high effort/reward option (4 pellets), with the effort requirement increasing over 4 blocks of trials (2, 5, 10, and 20 lever presses). Restraint stress for 1 h decreased preference for the more costly reward and induced longer choice latencies. Control experiments revealed that the effects on decision-making were not mediated by general reductions in motivation or preference for larger rewards. In contrast, acute stress did not affect delay-discounting, when rats chose between a small/immediate vs larger/delayed reward. The effects of stress on decision-making were not mimicked by treatment with physiological doses of corticosterone (1–3 mg/kg). Blockade of dopamine receptors with flupenthixol (0.25 mg/kg) before restraint did not attenuate stress-induced effects on effort-related choice, but abolished effects on choice latencies. These data suggest that acute stress interferes somewhat selectively with cost/benefit evaluations concerning effort costs. These effects do not appear to be mediated solely by enhanced glucocorticoid activity, whereas dopaminergic activation may contribute to increased deliberation times induced by stress. These findings may provide insight into impairments in decision-making and anergia associated with stress-related disorders, such as depression. PMID:22569506

  6. 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.

  7. Spatial and Functional Selectivity of Peripheral Nerve Signal Recording With the Transversal Intrafascicular Multichannel Electrode (TIME).

    PubMed

    Badia, Jordi; Raspopovic, Stanisa; Carpaneto, Jacopo; Micera, Silvestro; Navarro, Xavier

    2016-01-01

    The selection of suitable peripheral nerve electrodes for biomedical applications implies a trade-off between invasiveness and selectivity. The optimal design should provide the highest selectivity for targeting a large number of nerve fascicles with the least invasiveness and potential damage to the nerve. The transverse intrafascicular multichannel electrode (TIME), transversally inserted in the peripheral nerve, has been shown to be useful for the selective activation of subsets of axons, both at inter- and intra-fascicular levels, in the small sciatic nerve of the rat. In this study we assessed the capabilities of TIME for the selective recording of neural activity, considering the topographical selectivity and the distinction of neural signals corresponding to different sensory types. Topographical recording selectivity was proved by the differential recording of CNAPs from different subsets of nerve fibers, such as those innervating toes 2 and 4 of the hindpaw of the rat. Neural signals elicited by sensory stimuli applied to the rat paw were successfully recorded. Signal processing allowed distinguishing three different types of sensory stimuli such as tactile, proprioceptive and nociceptive ones with high performance. These findings further support the suitability of TIMEs for neuroprosthetic applications, by exploiting the transversal topographical structure of the peripheral nerves. PMID:26087496

  8. 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. PMID:26596860

  9. Stress-induced neuroinflammatory priming is time of day dependent.

    PubMed

    Fonken, Laura K; Weber, Michael D; Daut, Rachel A; Kitt, Meagan M; Frank, Matthew G; Watkins, Linda R; Maier, Steven F

    2016-04-01

    Circadian rhythms are endogenous cycles of physiology and behavior that align with the daily rotation of the planet and resulting light-dark cycle. The circadian system ensures homeostatic balance and regulates many aspects of physiology, including the stress response and susceptibility to and/or severity of stress-related sequelae. Both acute and chronic stressors amplify neuroinflammatory responses to a subsequent immune challenge, however it is not known whether circadian timing of the stressor regulates the priming response. Here, we test whether stress-induced neuroinflammatory priming is regulated by the circadian system. As has been previously shown, exposure to 100 inescapable tails shocks (IS) increased hippocampal cytokines following a subsequent inflammatory challenge. However, this effect was limited to animals that experienced the stressor during the light phase. Rats exposed to stress during the dark phase did not alter inflammatory potential following lipopolysaccharide (LPS) challenge. To determine whether microglia might be involved in diurnal differences in neuroinflammatory priming, microglia were isolated 24h after stress that occurred either during the middle of the light or dark phase. Only microglia isolated from animals stressed during the light phase demonstrated an exaggerated inflammatory response when treated ex vivo with LPS. To determine possible circadian dependency of microglia responsiveness to glucocorticoids - the likely proximal mediator for stress associated neuroinflammatory priming - microglia were isolated during the middle of the light or dark phase and treated ex vivo with corticosterone. Glucocorticoids treatment downregulated CX3CR1 and CD200R, two genes involved in microglial inflammatory "off" signaling; however, there was no effect of time of day on expression of either gene. Importantly, while absolute concentrations of corticosterone were comparable following IS during the light and dark phase, the magnitude of

  10. Selective inhibition of the hypoxia-inducible factor prolyl hydroxylase PHD3 by Zn(II).

    PubMed

    Na, Yu-Ran; Woo, Dustin J; Choo, Hyunah; Chung, Hak Suk; Yang, Eun Gyeong

    2015-07-01

    We report herein that Zn(II) selectively inhibits the hypoxia-inducible factor prolyl hydroxylase PHD3 over PHD2, and does not compete with Fe(II). Independent of the oligomer formation induced by Zn(II), inhibition of the activity of PHD3 by Zn(II) involves Cys42 and Cys52 residues distantly located from the active site. PMID:26051901

  11. 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.

  12. Real time chemical detection using species selective thin films and waveguide Zeeman interferometry

    SciTech Connect

    Grace, K.M.; Shrouf, K.; Honkanen, S.

    1998-12-01

    The authors present a chemical sensor scheme based on selective sensing surfaces and highly sensitive integrated optical transduction methods. Using self-assembly techniques, species selective thin-films are covalently attached to the surface of Si{sub 3}N{sub 4} channel waveguides to produce robust sensor elements. Exposure to targeted analytes results in the selective absorption of these molecules onto the waveguide surface causing a change in the effective index of the guided modes. These relative changes in effective index between TE and TM modes are precisely measured using Zeeman interferometry. Measurements demonstrate reversible, real time sensing of volatile organic compounds at ppm levels.

  13. 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.

  14. 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. PMID:27099626

  15. Selective glucocorticoid receptor translational isoforms reveal glucocorticoid-induced apoptotic transcriptomes

    PubMed Central

    Wu, I; Shin, S C; Cao, Y; Bender, I K; Jafari, N; Feng, G; Lin, S; Cidlowski, J A; Schleimer, R P; Lu, N Z

    2013-01-01

    Induction of T-cell apoptosis contributes to the anti-inflammatory and antineoplastic benefits of glucocorticoids. The glucocorticoid receptor (GR) translational isoforms have distinct proapoptotic activities in osteosarcoma cells. Here we determined whether GR isoforms selectively induce apoptosis in Jurkat T lymphoblastic leukemia cells. Jurkat cells stably expressing individual GR isoforms were generated and treated with vehicle or dexamethasone (DEX). DEX induced apoptosis in cells expressing the GR-A, -B, or -C, but not the GR-D, isoform. cDNA microarray analyses of cells sensitive (GR-C3) and insensitive (GR-D3) to DEX revealed glucocorticoid-induced proapoptotic transcriptomes. Genes that were regulated by the proapoptotic GR-C3, but not by the GR-D3, isoform likely contributed to glucocorticoid-induced apoptosis. The identified genes include those that are directly involved in apoptosis and those that facilitate cell killing. Chromatin immunoprecipitation assays demonstrated that distinct chromatin modification abilities may underlie the distinct functions of GR isoforms. Interestingly, all GR isoforms, including the GR-D3 isoform, suppressed mitogen-stimulated cytokines. Furthermore, the GR-C isoforms were selectively upregulated in mitogen-activated primary T cells and DEX treatment induced GR-C target genes in activated T cells. Cell-specific expressions and functions of GR isoforms may help to explain the tissue- and individual-selective actions of glucocorticoids and may provide a basis for developing improved glucocorticoids. PMID:23303127

  16. Selective glucocorticoid receptor translational isoforms reveal glucocorticoid-induced apoptotic transcriptomes.

    PubMed

    Wu, I; Shin, S C; Cao, Y; Bender, I K; Jafari, N; Feng, G; Lin, S; Cidlowski, J A; Schleimer, R P; Lu, N Z

    2013-01-01

    Induction of T-cell apoptosis contributes to the anti-inflammatory and antineoplastic benefits of glucocorticoids. The glucocorticoid receptor (GR) translational isoforms have distinct proapoptotic activities in osteosarcoma cells. Here we determined whether GR isoforms selectively induce apoptosis in Jurkat T lymphoblastic leukemia cells. Jurkat cells stably expressing individual GR isoforms were generated and treated with vehicle or dexamethasone (DEX). DEX induced apoptosis in cells expressing the GR-A, -B, or -C, but not the GR-D, isoform. cDNA microarray analyses of cells sensitive (GR-C3) and insensitive (GR-D3) to DEX revealed glucocorticoid-induced proapoptotic transcriptomes. Genes that were regulated by the proapoptotic GR-C3, but not by the GR-D3, isoform likely contributed to glucocorticoid-induced apoptosis. The identified genes include those that are directly involved in apoptosis and those that facilitate cell killing. Chromatin immunoprecipitation assays demonstrated that distinct chromatin modification abilities may underlie the distinct functions of GR isoforms. Interestingly, all GR isoforms, including the GR-D3 isoform, suppressed mitogen-stimulated cytokines. Furthermore, the GR-C isoforms were selectively upregulated in mitogen-activated primary T cells and DEX treatment induced GR-C target genes in activated T cells. Cell-specific expressions and functions of GR isoforms may help to explain the tissue- and individual-selective actions of glucocorticoids and may provide a basis for developing improved glucocorticoids. PMID:23303127

  17. The detection and identification of selected lube base oil using terahertz time-domain spectroscopy

    NASA Astrophysics Data System (ADS)

    Lu, Tian; Zhou, Qing-li; Jin, Bin; Zhao, Kun; Zhao, Song-qing; Zhang, Cun-lin

    2009-07-01

    Using the terahertz time-domain spectroscopy (THz-TDS), the frequency-dependent absorption coefficient(s) and refractive index (indices) of selected lube base oil (LBO) were extracted in the spectral range of 0.3-1.6 THz. The selected LBO was also characterized by near-infrared spectrum. The experimental results reveal that LBO is more sensitive in the THz range than near-infrared, and the different viscosity index of LBO can be identified according to their different spectral features in THz range. Due to better repeatability, shorter testing time, and easy operation, THz- TDS can be used as a complementary for identifying the chemical composition of LBO.

  18. Influence of time and length size feature selections for human activity sequences recognition.

    PubMed

    Fang, Hongqing; Chen, Long; Srinivasan, Raghavendiran

    2014-01-01

    In this paper, Viterbi algorithm based on a hidden Markov model is applied to recognize activity sequences from observed sensors events. Alternative features selections of time feature values of sensors events and activity length size feature values are tested, respectively, and then the results of activity sequences recognition performances of Viterbi algorithm are evaluated. The results show that the selection of larger time feature values of sensor events and/or smaller activity length size feature values will generate relatively better results on the activity sequences recognition performances. PMID:24075148

  19. Selective thermal desorption of ultrathin aluminum oxide layers induced by electron beams

    SciTech Connect

    Kundu, Manisha; Miyata, Noriyuki; Ichikawa, Masakazu

    2001-08-06

    The mechanism of electron-beam-induced selective thermal desorption of ultrathin aluminum-oxide layer ({approx}0.4 nm) on Si(001) surface was investigated by using scanning reflection electron microscopy, reflection high-energy electron diffraction, and Auger electron spectroscopy. We found that the change in the aluminum-oxide layer composition induced by electron-stimulated oxygen desorption accounted for the selective thermal desorption of the oxide layer. A systematic increase in the vacuum-annealing temperature to 500{sup o}C, 600{sup o}C and 720{sup o}C resulted in the formation of three-dimensional metal aluminum clusters, desorption of these clusters, and creation of a nanometer-scale clean Si(001)-2 x 1 open window in the selected electron-beam-irradiated area. {copyright} 2001 American Institute of Physics.

  20. Resource competition induces heterogeneity and can increase cohort survivorship: selection-event duration matters.

    PubMed

    Gosselin, Jennifer L; Anderson, James J

    2013-12-01

    Determining when resource competition increases survivorship can reveal processes underlying population dynamics and reinforce the importance of heterogeneity among individuals in conservation. We ran an experiment mimicking the effects of competition in a growing season on survivorship during a selection event (e.g., overwinter starvation, drought). Using a model fish species (Poecilia reticulata), we studied how food availability and competition affect mass in a treatment stage, and subsequently survivorship in a challenge stage of increased temperature and starvation. The post-treatment mean mass was strongly related to the mean time to mortality and mass at mortality at all levels of competition. However, competition increased variance in mass and extended the right tail of the survivorship curve, resulting in a greater number of individuals alive beyond a critical temporal threshold ([Formula: see text]) than without competition. To realize the benefits from previously experienced competition, the duration of the challenge ([Formula: see text]) following the competition must exceed the critical threshold [Formula: see text] (i.e., competition increases survivorship when [Formula: see text]). Furthermore, this benefit was equivalent to increasing food availability by 20 % in a group without competition in our experiment. The relationship of [Formula: see text] to treatment and challenge conditions was modeled by characterizing mortality through mass loss in terms of the stochastic rate of loss of vitality (individual's survival capacity). In essence, when the duration of a selection event exceeds [Formula: see text], competition-induced heterogeneity buffers against mortality through overcompensation processes among individuals of a cohort. Overall, our study demonstrates an approach to quantify how early life stage heterogeneity affects survivorship. PMID:23912261

  1. Detecting and Quantifying Changing Selection Intensities from Time-Sampled Polymorphism Data

    PubMed Central

    Shim, Hyunjin; Laurent, Stefan; Matuszewski, Sebastian; Foll, Matthieu; Jensen, Jeffrey D.

    2016-01-01

    During his well-known debate with Fisher regarding the phenotypic dataset of Panaxia dominula, Wright suggested fluctuating selection as a potential explanation for the observed change in allele frequencies. This model has since been invoked in a number of analyses, with the focus of discussion centering mainly on random or oscillatory fluctuations of selection intensities. Here, we present a novel method to consider nonrandom changes in selection intensities using Wright-Fisher approximate Bayesian (ABC)-based approaches, in order to detect and evaluate a change in selection strength from time-sampled data. This novel method jointly estimates the position of a change point as well as the strength of both corresponding selection coefficients (and dominance for diploid cases) from the allele trajectory. The simulation studies of this method reveal the combinations of parameter ranges and input values that optimize performance, thus indicating optimal experimental design strategies. We apply this approach to both the historical dataset of P. dominula in order to shed light on this historical debate, as well as to whole-genome time-serial data from influenza virus in order to identify sites with changing selection intensities in response to drug treatment. PMID:26869618

  2. Detecting and Quantifying Changing Selection Intensities from Time-Sampled Polymorphism Data.

    PubMed

    Shim, Hyunjin; Laurent, Stefan; Matuszewski, Sebastian; Foll, Matthieu; Jensen, Jeffrey D

    2016-01-01

    During his well-known debate with Fisher regarding the phenotypic dataset of Panaxia dominula, Wright suggested fluctuating selection as a potential explanation for the observed change in allele frequencies. This model has since been invoked in a number of analyses, with the focus of discussion centering mainly on random or oscillatory fluctuations of selection intensities. Here, we present a novel method to consider nonrandom changes in selection intensities using Wright-Fisher approximate Bayesian (ABC)-based approaches, in order to detect and evaluate a change in selection strength from time-sampled data. This novel method jointly estimates the position of a change point as well as the strength of both corresponding selection coefficients (and dominance for diploid cases) from the allele trajectory. The simulation studies of this method reveal the combinations of parameter ranges and input values that optimize performance, thus indicating optimal experimental design strategies. We apply this approach to both the historical dataset of P. dominula in order to shed light on this historical debate, as well as to whole-genome time-serial data from influenza virus in order to identify sites with changing selection intensities in response to drug treatment. PMID:26869618

  3. 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

  4. 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.

  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. Evaluation of select sensors for real-time monitoring of Escherichia coli in water distribution systems.

    PubMed

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

    2011-04-01

    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

  7. 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

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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. Inducible nitric oxide synthase (NOS2) expressed in septic patients is nitrated on selected tyrosine residues: implications for enzymic activity.

    PubMed Central

    Lanone, Sophie; Manivet, Philippe; Callebert, Jacques; Launay, Jean-Marie; Payen, Didier; Aubier, Michel; Boczkowski, Jorge; Mebazaa, Alexandre

    2002-01-01

    Tyrosine nitration is a post-translational protein modification with potentially significant biological implications. In the present study we demonstrate, for the first time, that tyrosine residues of human inducible nitric oxide synthase (NOS2) can be nitrated by peroxynitrite in vitro, leading to a decreased activity. Moreover, we show that NOS2 expressed in a skeletal muscle from septic patients is nitrated on selective tyrosine residues belonging to a canonic sequence. This phenomenon could be an endogenous mechanism of in vivo modulation of NOS2 enzymic activity. PMID:12097137

  10. Length of time in tissue culture can affect the selected glyphosate resistance mechanism.

    PubMed

    Papanikou, Efstratia; Brotherton, Jeffrey E; Widholm, Jack M

    2004-02-01

    Usually, stepwise selection of plant suspension cultures with gradually increasing concentrations of the herbicide glyphosate results in the amplification of the target enzyme 5-enolpyruvylshikimate-3-phosphate synthase (EPSPS; EC 2.5.1.19) gene that leads to resistance by increasing EPSPS mRNA and enzyme activity. We show that glyphosate selection with newly initiated suspension cultures can produce resistant lines with resistance mechanisms other than gene amplification and that usually as the cultures age gene amplification becomes the predominant mechanism. Gene amplification did not occur in 3 lines selected from 5-month-old Datura innoxia Mill. cultures but did occur in all 10 lines selected after 52 months. Selection with Nicotiana tabacum L. (tobacco) less than 5 months old produced 2 lines out of 24 with no EPSPS amplification while all 17 lines selected from older cultures contained amplified genes. Lines selected from the oldest culture (35 years) also exhibited amplification of several different genes, indicating the expression of different EPSPS genes or an enhanced gene amplification incidence. None of the 15 lines selected from 2 different 5-month-old Daucus carota L. (carrot) lines exhibited amplification while amplification led to the resistance of all 7 lines selected from one of the original carrot lines (DHL) after 3 years. However, the other line (Car4) was exceptional and produced only non-amplified lines (9 of 9) after 8 years in culture. These results show that plant tissue cultures change with time in culture and that several different new mechanisms can result in glyphosate resistance. PMID:14566562

  11. Uranium and nitrate remote sensing in the nuclear fuel cycle by time-resolved laser-induced fluorescence

    NASA Astrophysics Data System (ADS)

    Moulin, Christophe; Couston, Laurent; Decambox, Pierre; Mauchien, Patrick; Pouyat, Dominique

    1994-12-01

    Time-Resolved Laser-Induced Fluorescence has been used for uranium and nitrate remote sensing in the nuclear fuel cycle. Advantages of this technique are aside sensitivity and selectivity, its ability to perform remote measurements via fiber optics and optode. Uranium is usually determined by the standard addition method but by applying a fluorescence model taking into account complexation and absorption phenomena, it is possible to directly determine uranium concentration. Nitrate concentration is determined after spectral deconvolution of the uranium fluorescence spectrum.

  12. 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. PMID

  13. 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

  14. 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.

  15. Selective regulation of neurosteroid biosynthesis under ketamine-induced apoptosis of cortical neurons in vitro.

    PubMed

    Li, Jianli; Yu, Yang; Wang, Bei; Wu, Honghai; Xue, Gai; Hou, Yanning

    2016-02-01

    Numerous studies have suggested that ketamine administration can induce neuroapoptosis in primary cultured cortical neurons. Neurosteroids modulate neuronal function and serve important roles in the central nervous system, however the role of neurosteroids in neuroapoptosis induced by ketamine remains to be elucidated. The present study aimed to explore whether neurosteroidogenesis was a pivotal mechanism for neuroprotection against ketamine-induced neuroapoptosis, and whether it may be selectively regulated under ketamine-induced neuroapoptosis conditions in primary cultured cortical neurons. To study this hypothesis, the effect of ketamine exposure on neurosteroidogenesis in primary cultured cortical neurons was investigated. Cholesterol, a substrate involved in the synthesis of neurosteroids, was added to the culture medium, and neurosteroids were quantified using high-performance liquid chromatography-tandem mass spectrometry analysis. The data demonstrated that cholesterol blocked ketamine-induced neuroapoptosis by promoting the synthesis of various neurosteroids, and the pathway of neurosteroid testosterone conversion into estradiol was inhibited by ketamine exposure. These data suggest that endogenous neurosteroids biosynthesis is critical for neuroprotection against ketamine-induced neuroapoptosis and inhibiting the biosynthesis of neuroprotective-neurosteroid estradiol is of notable importance for ketamine-induced neuroapoptosis. PMID:26709052

  16. Selective regulation of neurosteroid biosynthesis under ketamine-induced apoptosis of cortical neurons in vitro

    PubMed Central

    LI, JIANLI; YU, YANG; WANG, BEI; WU, HONGHAI; XUE, GAI; HOU, YANNING

    2016-01-01

    Numerous studies have suggested that ketamine administration can induce neuroapoptosis in primary cultured cortical neurons. Neurosteroids modulate neuronal function and serve important roles in the central nervous system, however the role of neurosteroids in neuroapoptosis induced by ketamine remains to be elucidated. The present study aimed to explore whether neurosteroidogenesis was a pivotal mechanism for neuroprotection against ketamine-induced neuroapoptosis, and whether it may be selectively regulated under ketamine-induced neuroapoptosis conditions in primary cultured cortical neurons. To study this hypothesis, the effect of ketamine exposure on neurosteroidogenesis in primary cultured cortical neurons was investigated. Cholesterol, a substrate involved in the synthesis of neurosteroids, was added to the culture medium, and neurosteroids were quantified using high-performance liquid chromatography-tandem mass spectrometry analysis. The data demonstrated that cholesterol blocked ketamine-induced neuroapoptosis by promoting the synthesis of various neurosteroids, and the pathway of neurosteroid testosterone conversion into estradiol was inhibited by ketamine exposure. These data suggest that endogenous neurosteroids biosynthesis is critical for neuroprotection against ketamine-induced neuroapoptosis and inhibiting the biosynthesis of neuroprotective-neurosteroid estradiol is of notable importance for ketamine-induced neuroapoptosis. PMID:26709052

  17. 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.

  18. Coevolution of strategy-selection time scale and cooperation in spatial prisoner's dilemma game

    NASA Astrophysics Data System (ADS)

    Rong, Zhihai; Wu, Zhi-Xi; Chen, Guanrong

    2013-06-01

    In this paper, we investigate a networked prisoner's dilemma game where individuals' strategy-selection time scale evolves based on their historical learning information. We show that the more times the current strategy of an individual is learnt by his neighbors, the longer time he will stick on the successful behavior by adaptively adjusting the lifetime of the adopted strategy. Through characterizing the extent of success of the individuals with normalized payoffs, we show that properly using the learned information can form a positive feedback mechanism between cooperative behavior and its lifetime, which can boost cooperation on square lattices and scale-free networks.

  19. Continuous-Time Mean-Variance Portfolio Selection with Random Horizon

    SciTech Connect

    Yu, Zhiyong

    2013-12-15

    This paper examines the continuous-time mean-variance optimal portfolio selection problem with random market parameters and random time horizon. Treating this problem as a linearly constrained stochastic linear-quadratic optimal control problem, I explicitly derive the efficient portfolios and efficient frontier in closed forms based on the solutions of two backward stochastic differential equations. Some related issues such as a minimum variance portfolio and a mutual fund theorem are also addressed. All the results are markedly different from those in the problem with deterministic exit time. A key part of my analysis involves proving the global solvability of a stochastic Riccati equation, which is interesting in its own right.

  20. EFFECT OF OZONE ON DRUG-INDUCED SLEEPING TIME IN MICE PRETREATED WITH MIXED-FUNCTION OXIDASE INDUCERS AND INHIBITORS

    EPA Science Inventory

    Studies were conducted to investigate the effect of ozone in prolonging pentobarbital (PEN)-induced sleeping time (S.T.). Since ozone is a common air pollutant, an ozone-induced alteration of mechanisms of drug action could have public health implications. It was shown that a 5-h...

  1. Temperature-Dependent Nanofabrication on Silicon by Friction-Induced Selective Etching.

    PubMed

    Jin, Chenning; Yu, Bingjun; Xiao, Chen; Chen, Lei; Qian, Linmao

    2016-12-01

    Friction-induced selective etching provides a convenient and practical way for fabricating protrusive nanostructures. A further understanding of this method is very important for establishing a controllable nanofabrication process. In this study, the effect of etching temperature on the formation of protrusive hillocks and surface properties of the etched silicon surface was investigated. It is found that the height of the hillock produced by selective etching increases with the etching temperature before the collapse of the hillock. The temperature-dependent selective etching rate can be fitted well by the Arrhenius equation. The etching at higher temperature can cause rougher silicon surface with a little lower elastic modulus and hardness. The contact angle of the etched silicon surface decreases with the etching temperature. It is also noted that no obvious contamination can be detected on silicon surface after etching at different temperatures. As a result, the optimized condition for the selective etching was addressed. The present study provides a new insight into the control and application of friction-induced selective nanofabrication. PMID:27119157

  2. Natural selection underlies apparent stress-induced mutagenesis in a bacteriophage infection model.

    PubMed

    Yosef, Ido; Edgar, Rotem; Levy, Asaf; Amitai, Gil; Sorek, Rotem; Munitz, Ariel; Qimron, Udi

    2016-01-01

    The emergence of mutations following growth-limiting conditions underlies bacterial drug resistance, viral escape from the immune system and fundamental evolution-driven events. Intriguingly, whether mutations are induced by growth limitation conditions or are randomly generated during growth and then selected by growth limitation conditions remains an open question(1). Here, we show that bacteriophage T7 undergoes apparent stress-induced mutagenesis when selected for improved recognition of its host's receptor. In our unique experimental set-up, the growth limitation condition is physically and temporally separated from mutagenesis: growth limitation occurs while phage DNA is outside the host, and spontaneous mutations occur during phage DNA replication inside the host. We show that the selected beneficial mutations are not pre-existing and that the initial slow phage growth is enabled by the phage particle's low-efficiency DNA injection into the host. Thus, the phage particle allows phage populations to initially extend their host range without mutagenesis by virtue of residual recognition of the host receptor. Mutations appear during non-selective intracellular replication, and the frequency of mutant phages increases by natural selection acting on free phages, which are not capable of mutagenesis. PMID:27572836

  3. Difference-NMR techniques for selection of components on the basis of relaxation times

    NASA Astrophysics Data System (ADS)

    Harris, Douglas J.; de Azevedo, Eduardo R.; Bonagamba, Tito J.

    2003-05-01

    This work describes a numerical methodology to obtain more efficient relaxation filters to selectively retain or remove components based on relaxation times. The procedure uses linear combinations of spectra with various recycle or filter delays to obtain components that are both quantitative and pure. Modulation profiles are calculated assuming exponential relaxation behavior. The method is general and can be applied to a wide range of solution or solid-state NMR experiments including direct-polarization (DP), or filtered cross-polarization (CP) spectra. 13C NMR experiments on isotactic poly(1-butene) and dimethyl sulfone showed the utility of the technique for selectively suppressing peaks.

  4. On Large Time Behavior and Selection Principle for a Diffusive Carr-Penrose Model

    NASA Astrophysics Data System (ADS)

    Conlon, Joseph G.; Dabkowski, Michael; Wu, Jingchen

    2016-04-01

    This paper is concerned with the study of a diffusive perturbation of the linear LSW model introduced by Carr and Penrose. A main subject of interest is to understand how the presence of diffusion acts as a selection principle, which singles out a particular self-similar solution of the linear LSW model as determining the large time behavior of the diffusive model. A selection principle is rigorously proven for a model which is a semiclassical approximation to the diffusive model. Upper bounds on the rate of coarsening are also obtained for the full diffusive model.

  5. EXTRAPULMONARY EFFECTS OF NO2 AS REFLECTED BY PENTOBARBITAL-INDUCED SLEEPING TIME IN MICE

    EPA Science Inventory

    The influence of nitrogen dioxide (NO2) on pentobarbital(PEN)-induced sleeping time (S.T.) was investigated in mice. Acute exposure to concentrations as low as 470 micrograms NO2/cu m (0.25 ppm) caused a significant increase in PEN-induced S.T. No significant effects on PEN-induc...

  6. Time dependent measurements of induced fission for SNM interrogation

    NASA Astrophysics Data System (ADS)

    Beck, A.; Israelashvili, I.; Wengrowicz, U.; Caspi, E. N.; Yaar, I.; Osovizki, A.; Ocherashvili, A.; Rennhofer, H.; Pedersen, B.; Crochemore, J.-M.; Roesgen, E.

    2013-08-01

    Gammas from induced fissions were measured and separated into prompt and delayed particles. To this end, a dedicated detector was realized, based on a plastic scintillator, a wavelength shifter fiber and a silicon photomultiplier (SiPM). Results are presented from the interrogation of Special Nuclear Materials (SNM), employing a pulsed neutron generator in the PUNITA graphite moderator incorporating the above detector assembly. The detector response is presented, as well as the sensitivities for prompt and delayed processes within the same experimental setup.

  7. Aggregation-induced fabrication of fluorescent organic nanorings: selective biosensing of cysteine and application to molecular logic gate.

    PubMed

    Mati, Soumya Sundar; Chall, Sayantani; Bhattacharya, Subhash Chandra

    2015-05-12

    Self-aggregation behavior in aqueous medium of four naphthalimide derivatives has exhibited substitution-dependent, unusual, aggregation induced emission enhancement (AIEE) phenomena. Absorption, emission, and time-resolved study initially indicated the formation of J-type fluorescent organic nanoaggregates (FONs). Simultaneous applications of infrared spectroscopy, theoretical studies, and dynamic light scattering (DLS) measurements explored the underlying mechanism of such substitution-selective aggregation of a chloro-naphthalimide organic molecule. Furthermore, transmission electron microscopy (TEM) visually confirmed the formation of ring like FONs with average size of 7.5-9.5 nm. Additionally, naphthalimide FONs also exhibited selective and specific cysteine amino acid sensing property. The specific behavior of NPCl aggregation toward amino acids was also employed as a molecular logic gate in information technology (IT). PMID:25893428

  8. Site-selective nanoscale-polymerization of pyrrole on gold nanoparticles via plasmon induced charge separation

    NASA Astrophysics Data System (ADS)

    Takahashi, Y.; Furukawa, Y.; Ishida, T.; Yamada, S.

    2016-04-01

    We proposed a nanoscale oxidative polymerization method which enables site-selective deposition on the surface of gold nanoparticles (AuNPs) combined with TiO2 by using plasmon induced charge separation (PICS) under visible-to-near infrared (IR) light irradiation. The method also revealed that the anodic site of PICS was located at the surface of AuNPs.We proposed a nanoscale oxidative polymerization method which enables site-selective deposition on the surface of gold nanoparticles (AuNPs) combined with TiO2 by using plasmon induced charge separation (PICS) under visible-to-near infrared (IR) light irradiation. The method also revealed that the anodic site of PICS was located at the surface of AuNPs. Electronic supplementary information (ESI) available. See DOI: 10.1039/c6nr01531j

  9. 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. PMID:25221430

  10. 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

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

    PubMed Central

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

    2014-01-01

    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. PMID:25221430

  12. 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.

  13. Motor commands induce time compression for tactile stimuli.

    PubMed

    Tomassini, Alice; Gori, Monica; Baud-Bovy, Gabriel; Sandini, Giulio; Morrone, Maria Concetta

    2014-07-01

    Saccades cause compression of visual space around the saccadic target, and also a compression of time, both phenomena thought to be related to the problem of maintaining saccadic stability (Morrone et al., 2005; Burr and Morrone, 2011). Interestingly, similar phenomena occur at the time of hand movements, when tactile stimuli are systematically mislocalized in the direction of the movement (Dassonville, 1995; Watanabe et al., 2009). In this study, we measured whether hand movements also cause an alteration of the perceived timing of tactile signals. Human participants compared the temporal separation between two pairs of tactile taps while moving their right hand in response to an auditory cue. The first pair of tactile taps was presented at variable times with respect to movement with a fixed onset asynchrony of 150 ms. Two seconds after test presentation, when the hand was stationary, the second pair of taps was delivered with a variable temporal separation. Tactile stimuli could be delivered to either the right moving or left stationary hand. When the tactile stimuli were presented to the motor effector just before and during movement, their perceived temporal separation was reduced. The time compression was effector-specific, as perceived time was veridical for the left stationary hand. The results indicate that time intervals are compressed around the time of hand movements. As for vision, the mislocalizations of time and space for touch stimuli may be consequences of a mechanism attempting to achieve perceptual stability during tactile exploration of objects, suggesting common strategies within different sensorimotor systems. PMID:24990936

  14. Selective inducible nitric oxide synthase inhibition attenuates organ dysfunction and elevated endothelin levels in LPS-induced DIC model rats.

    PubMed

    Asakura, H; Asamura, R; Ontachi, Y; Hayashi, T; Yamazaki, M; Morishita, E; Miyamoto, K-I; Nakao, S

    2005-05-01

    We examined the role of nitric oxide (NO) produced by an inducible isoform of NO synthase (iNOS) using N[6]-(iminoethyl)-lysine (L-NIL), a selective iNOS inhibitor, in the rat model of lipopolysaccharide (LPS)-induced disseminated intravascular coagulation (DIC) and investigated changes in organ function, plasma levels of NOX (metabolites of NO) and endothelin. We induced experimental DIC by the sustained infusion of 30 mg kg(-1) LPS for 4 h via the tail vein. We then investigated the effect of L-NIL (6 mg kg(-1), from - 0.5 to 4 h) on LPS-induced DIC. Blood was withdrawn at 4 and 8 h, and all four groups (LPS with or without L-NIL at 4 and 8 h) consisted of eight rats. Three of the animals in the 8-h LPS group died, and we examined blood samples from five rats in this group. None of the other rats died. The LPS-induced elevation of creatinine, alanine aminotransferase, glomerular fibrin deposition and plasminogen activator inhibitor was significantly suppressed by L-NIL coadministration, although L-NIL did not affect the platelet count, fibrinogen concentration or the level of thrombin-antithrombin complex. Moreover, plasma levels of the D-dimer that reflect the lysis of cross-linked fibrin were significantly increased by L-NIL coadministration in the LPS-induced DIC model. Plasma levels of NOX and endothelin were obviously increased by LPS infusion. However, both levels were significantly suppressed in the LPS + L-NIL group, when compared with the LPS group. Although mean arterial pressure (MAP) was significantly decreased between 2 and 8 h compared with the control in the LPS group, this depression was significantly attenuated in the LPS + L-NIL group. Our results suggest that NO induced by iNOS contributes to hypotension (depressed MAP), the progression of hepatic and renal dysfunction, microthrombus deposition and elevated endothelin levels in the rat model of LPS-induced DIC. PMID:15869603

  15. 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. PMID:26930198

  16. 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

  17. Myricetin Selectively Induces Apoptosis on Cancerous Hepatocytes by Directly Targeting Their Mitochondria.

    PubMed

    Seydi, Enayatollah; Rasekh, Hamid Reza; Salimi, Ahmad; Mohsenifar, Zhaleh; Pourahmad, Jalal

    2016-09-01

    Hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. In patients for whom HCC could not be detected early, current treatments show poor tolerance and low efficacy. So, alternative therapies with good efficacy are urgently needed. The aim of this research was to evaluate the selective apoptotic effects of myricetin (MYR), a flavonoid compound, on hepatocytes and mitochondria obtained from the liver of HCC rats. In this study, HCC induced by diethylnitrosamine (DEN), as an initiator, and 2-acetylaminofluorene (2-AAF), as a promoter. To confirm the HCC induction, serum levels of alpha-fetoprotein (AFP), AST, AST and ALP and histopathological changes in the liver tissue were evaluated. Rat liver hepatocytes and mitochondria for evaluation of the selective cytotoxic effects of MYR were isolated, and mitochondrial and cellular parameters related to apoptosis signalling were then determined. Our results showed that MYR was able to induce cytotoxicity only in hepatocytes from the HCC but not from the untreated control group. Besides, MYR (12.5, 25 and 50 μM) induced a considerable increase in reactive oxygen species (ROS) level, mitochondrial swelling, mitochondrial membrane permeabilization (MMP) and cytochrome c release only in cancerous but not in untreated normal hepatocyte mitochondria. MYR selectively increased caspase-3 activation and apoptotic phenotypes in HCC, but not untreated normal hepatocytes. Finally, our finding underlines MYR as a promising therapeutic candidate against HCC and recommends the compound for further studies. PMID:26919160

  18. The Steppengrille (Gryllus spec./assimilis): selective filters and signal mismatch on two time scales.

    PubMed

    Rothbart, Matti Michael; Hennig, Ralf Matthias

    2012-01-01

    In Europe, several species of crickets are available commercially as pet food. Here we investigated the calling song and phonotactic selectivity for sound patterns on the short and long time scales for one such a cricket, Gryllus spec., available as "Gryllus assimilis", the Steppengrille, originally from Ecuador. The calling song consisted of short chirps (2-3 pulses, carrier frequency: 5.0 kHz) emitted with a pulse period of 30.2 ms and chirp rate of 0.43 per second. Females exhibited high selectivity on both time scales. The preference for pulse period peaked at 33 ms which was higher then the pulse period produced by males. Two consecutive pulses per chirp at the correct pulse period were already sufficient for positive phonotaxis. The preference for the chirp pattern was limited by selectivity for small chirp duty cycles and for chirp periods between 200 ms and 500 ms. The long chirp period of the songs of males was unattractive to females. On both time scales a mismatch between the song signal of the males and the preference of females was observed. The variability of song parameters as quantified by the coefficient of variation was below 50% for all temporal measures. Hence, there was not a strong indication for directional selection on song parameters by females which could account for the observed mismatch. The divergence of the chirp period and female preference may originate from a founder effect, when the Steppengrille was cultured. Alternatively the mismatch was a result of selection pressures exerted by commercial breeders on low singing activity, to satisfy customers with softly singing crickets. In the latter case the prominent divergence between male song and female preference was the result of domestication and may serve as an example of rapid evolution of song traits in acoustic communication systems. PMID:22970154

  19. The Steppengrille (Gryllus spec./assimilis): Selective Filters and Signal Mismatch on Two Time Scales

    PubMed Central

    Rothbart, Matti Michael; Hennig, Ralf Matthias

    2012-01-01

    In Europe, several species of crickets are available commercially as pet food. Here we investigated the calling song and phonotactic selectivity for sound patterns on the short and long time scales for one such a cricket, Gryllus spec., available as “Gryllus assimilis”, the Steppengrille, originally from Ecuador. The calling song consisted of short chirps (2–3 pulses, carrier frequency: 5.0 kHz) emitted with a pulse period of 30.2 ms and chirp rate of 0.43 per second. Females exhibited high selectivity on both time scales. The preference for pulse period peaked at 33 ms which was higher then the pulse period produced by males. Two consecutive pulses per chirp at the correct pulse period were already sufficient for positive phonotaxis. The preference for the chirp pattern was limited by selectivity for small chirp duty cycles and for chirp periods between 200 ms and 500 ms. The long chirp period of the songs of males was unattractive to females. On both time scales a mismatch between the song signal of the males and the preference of females was observed. The variability of song parameters as quantified by the coefficient of variation was below 50% for all temporal measures. Hence, there was not a strong indication for directional selection on song parameters by females which could account for the observed mismatch. The divergence of the chirp period and female preference may originate from a founder effect, when the Steppengrille was cultured. Alternatively the mismatch was a result of selection pressures exerted by commercial breeders on low singing activity, to satisfy customers with softly singing crickets. In the latter case the prominent divergence between male song and female preference was the result of domestication and may serve as an example of rapid evolution of song traits in acoustic communication systems. PMID:22970154

  20. Reference gene selection for gene expression studies in lily using quantitative real-time PCR.

    PubMed

    Zhang, M F; Liu, Q; Jia, G X

    2016-01-01

    Quantitative real-time polymerase chain reaction (qRT-PCR) is an important technology used to analyze gene-expression levels. Reference genes, which are assumed to be expressed consistently across various developmental stages and in different tissues, were selected for expression level analysis. Using digital gene expression technology, we selected nine reference genes (18S, EF, CYCOL, SAND, GAPDH, ACTIN, BHLH, TIP, and Clathrin) as candidate reference genes for further study. Using three different analysis methods (GeNorm, NormFinder, and BestKeeper), a total of 144 lily (Lilium x formolongi "Raizan 3") samples were analyzed. The samples were collected from four different tissues under various developmental stages. In addition, leaves treated with different plant hormones were collected and analyzed. The data showed that the stability of the nine reference genes differed among samples, but TIP, EF, Clathrin, and BHLH could be identified as the most stable genes overall. In addition, the relative expression level of LfFT in different lily tissues with the competence to flower was also analyzed to verify the selected reference genes. This study constitutes an important source for selecting reference genes when analyzing the expression patterns of flowering time and floral development regulation genes in lily cultivars. PMID:27173307

  1. A NOVEL SPECTRAL METHOD FOR INFERRING GENERAL DIPLOID SELECTION FROM TIME SERIES GENETIC DATA

    PubMed Central

    Steinrücken, Matthias; Bhaskar, Anand; Song, Yun S.

    2014-01-01

    The increased availability of time series genetic variation data from experimental evolution studies and ancient DNA samples has created new opportunities to identify genomic regions under selective pressure and to estimate their associated fitness parameters. However, it is a challenging problem to compute the likelihood of non-neutral models for the population allele frequency dynamics, given the observed temporal DNA data. Here, we develop a novel spectral algorithm to analytically and efficiently integrate over all possible frequency trajectories between consecutive time points. This advance circumvents the limitations of existing methods which require fine-tuning the discretization of the population allele frequency space when numerically approximating requisite integrals. Furthermore, our method is flexible enough to handle general diploid models of selection where the heterozygote and homozygote fitness parameters can take any values, while previous methods focused on only a few restricted models of selection. We demonstrate the utility of our method on simulated data and also apply it to analyze ancient DNA data from genetic loci associated with coat coloration in horses. In contrast to previous studies, our exploration of the full fitness parameter space reveals that a heterozygote-advantage form of balancing selection may have been acting on these loci. PMID:25598858

  2. Time-shared experiments for efficient assignment of triple-selectively labeled proteins

    PubMed Central

    Löhr, Frank; Laguerre, Aisha; Bock, Christoph; Reckel, Sina; Connolly, Peter J.; Abdul-Manan, Norzehan; Tumulka, Franz; Abele, Rupert; Moore, Jonathan M.; Dötsch, Volker

    2014-01-01

    Combinatorial triple-selective labeling facilitates the NMR assignment process for proteins that are subject to signal overlap and insufficient signal-to-noise in standard triple-resonance experiments. Aiming at maximum amino-acid type and sequence-specific information, the method represents a trade-off between the number of selectively labeled samples that have to be prepared and the number of spectra to be recorded per sample. In order to address the demand of long measurement times, we here propose pulse sequences in which individual phase-shifted transients are stored separately and recombined later to produce several 2D HN(CX) type spectra that are usually acquired sequentially. Sign encoding by the phases of 13C 90° pulses allows to either select or discriminate against 13C’ or 13Cα spins coupled to 15N. As a result, 1H-15N correlation maps of the various isotopomeric species present in triple-selectively labeled proteins are deconvoluted which in turn reduces problems due to spectral overlap. The new methods are demonstrated with four different membrane proteins with rotational correlation times ranging from 18 to 52 ns. PMID:25442777

  3. Time course of shape and category selectivity revealed by EEG rapid adaptation.

    PubMed

    Scholl, Clara A; Jiang, Xiong; Martin, Jacob G; Riesenhuber, Maximilian

    2014-02-01

    A hallmark of human cognition is the ability to rapidly assign meaning to sensory stimuli. It has been suggested that this fast visual object categorization ability is accomplished by a feedforward processing hierarchy consisting of shape-selective neurons in occipito-temporal cortex that feed into task circuits in frontal cortex computing conceptual category membership. We performed an EEG rapid adaptation study to test this hypothesis. Participants were trained to categorize novel stimuli generated with a morphing system that precisely controlled both stimulus shape and category membership. We subsequently performed EEG recordings while participants performed a category matching task on pairs of successively presented stimuli. We used space-time cluster analysis to identify channels and latencies exhibiting selective neural responses. Neural signals before 200 msec on posterior channels demonstrated a release from adaptation for shape changes, irrespective of category membership, compatible with a shape- but not explicitly category-selective neural representation. A subsequent cluster with anterior topography appeared after 200 msec and exhibited release from adaptation consistent with explicit categorization. These signals were subsequently modulated by perceptual uncertainty starting around 300 msec. The degree of category selectivity of the anterior signals was strongly predictive of behavioral performance. We also observed a posterior category-selective signal after 300 msec exhibiting significant functional connectivity with the initial anterior category-selective signal. In summary, our study supports the proposition that perceptual categorization is accomplished by the brain within a quarter second through a largely feedforward process culminating in frontal areas, followed by later category-selective signals in posterior regions. PMID:24001003

  4. 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

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

    PubMed Central

    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. PMID:24304514

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

    PubMed Central

    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

    2015-01-01

    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. PMID:25672491

  7. The response of correlated traits following cessation of fishery-induced selection

    PubMed Central

    Salinas, Santiago; Perez, Kestrel O; Duffy, Tara A; Sabatino, Stephen J; Hice, Lyndie A; Munch, Stephan B; Conover, David O

    2012-01-01

    The application of evolutionary principles to the management of fisheries has gained considerable attention recently. Harvesting of fish may apply directional or disruptive selection to key life-history traits, and evidence for fishery-induced evolution is growing. The traits that are directly selected upon are often correlated (genetically or phenotypically) with a suite of interrelated physiological, behavioral, and morphological characters. A question that has received comparatively little attention is whether or not, after cessation of fishery-induced selection, these correlated traits revert back to previous states. Here, we empirically examine this question. In experiments with the Atlantic silverside, Menidia menidia, we applied size-selective culling for five generations and then maintained the lines a further five generations under random harvesting. We found that some traits do return to preharvesting levels (e.g., larval viability), some partially recover (e.g., egg volume, size-at-hatch), and others show no sign of change (e.g., food consumption rate, vertebral number). Such correlations among characters could, in theory, greatly accelerate or decelerate the recovery of fish populations. These results may explain why some fish stocks fail to recover after fishing pressure is relaxed. PMID:23144653

  8. 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

    2016-01-01

    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

  9. 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

  10. Highly selective fluorogenic multianalyte biosensors constructed via enzyme-catalyzed coupling and aggregation-induced emission.

    PubMed

    Wang, Xiaorui; Hu, Jinming; Zhang, Guoying; Liu, Shiyong

    2014-07-16

    The development of a highly selective and fast responsive fluorogenic biosensor for diverse analytes ranging from bioactive small molecules to specific antigens is highly desirable but remains a considerable challenge. We herein propose a new approach by integrating substrate-selective enzymatic reactions with fluorogens exhibiting aggregation-induced emission feature. Tyrosine-functionalized tetraphenylethene, TPE-Tyr, molecularly dissolves in aqueous media with negligible fluorescence emission; upon addition of horseradish peroxidase (HRP) and H2O2, effective cross-linking occurs due to HRP-catalyzed oxidative coupling of tyrosine moieties in TPE-Tyr. This leads to fluorescence emission turn-on and fast detection of H2O2 with high sensitivity and selectivity. As a validation of the new strategy's generality, we further configure it into the biosensor design for glucose through cascade enzymatic reactions and for pathologically relevant antigens (e.g., human carcinoembryonic antigen) by combining with the ELISA kit. PMID:24983204

  11. Magnetic-field-induced diameter-selective synthesis of single-walled carbon nanotubes.

    PubMed

    Su, Yanjie; Zhang, Yaozhong; Wei, Hao; Zhang, Liling; Zhao, Jiang; Yang, Zhi; Zhang, Yafei

    2012-03-01

    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. PMID:22301844

  12. 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. PMID:26940742

  13. Time-dependent ion selectivity in capacitive charging of porous electrodes.

    PubMed

    Zhao, R; van Soestbergen, M; Rijnaarts, H H M; van der Wal, A; Bazant, M Z; Biesheuvel, P M

    2012-10-15

    In a combined experimental and theoretical study, we show that capacitive charging of porous electrodes in multicomponent electrolytes may lead to the phenomenon of time-dependent ion selectivity of the electrical double layers (EDLs) in the electrodes. This effect is found in experiments on capacitive deionization of water containing NaCl/CaCl(2) mixtures, when the concentration of Na(+) ions in the water is five times the Ca(2+)-ion concentration. In this experiment, after applying a voltage difference between two porous carbon electrodes, first the majority monovalent Na(+) cations are preferentially adsorbed in the EDLs, and later, they are gradually replaced by the minority, divalent Ca(2+) cations. In a process where this ion adsorption step is followed by washing the electrode with freshwater under open-circuit conditions, and subsequent release of the ions while the cell is short-circuited, a product stream is obtained which is significantly enriched in divalent ions. Repeating this process three times by taking the product concentrations of one run as the feed concentrations for the next, a final increase in the Ca(2+)/Na(+)-ratio of a factor of 300 is achieved. The phenomenon of time-dependent ion selectivity of EDLs cannot be explained by linear response theory. Therefore, a nonlinear time-dependent analysis of capacitive charging is performed for both porous and flat electrodes. Both models attribute time-dependent ion selectivity to the interplay between the transport resistance for the ions in the aqueous solution outside the EDL, and the voltage-dependent ion adsorption capacity of the EDLs. Exact analytical expressions are presented for the excess ion adsorption in planar EDLs (Gouy-Chapman theory) for mixtures containing both monovalent and divalent cations. PMID:22819395

  14. Survivin selective inhibitor YM155 promotes cisplatin‑induced apoptosis in embryonal rhabdomyosarcoma.

    PubMed

    Ueno, Takehisa; Uehara, Shuichiro; Nakahata, Kengo; Okuyama, Hiroomi

    2016-05-01

    Survivin, a member of the inhibitor of apoptosis protein family, functions as a key regulator of programmed cell death. YM155 is a small molecule that selectively inhibits survivin. We investigated the effect of YM155 on survivin suppression in the human rhabdomyosarcoma (RMS) cell line RD. The efficacy of YM155 in combination with cisplatin was also determined in a xenograft model. The effect of YM155 on survivin expression in the RD cell line was examined at both mRNA and protein levels using real-time PCR and western blot analysis. RD cells were cultured with various concentrations of YM155, then cisplatin was added to the medium and the anti-proliferation response was determined. Cell growth was evaluated by WST-8 assay. Finally, the efficacy of YM155 combined with cisplatin was examined in an established xenograft model. Survivin mRNA levels in the RD cell line were decreased to 72 and 24% at 24 and 48 h, respectively, after 10 nM of YM155 was added. YM155 also decreased the levels of survivin protein. YM155 treatment (10 nM) inhibited cell proliferation of RD in a dose-dependent manner in vitro, with 58% of cells viable at 48 h. When cultured with 10 nM of YM155 and 10 µM cisplatin, RD cells demonstrated only 25% of the growth observed when cultured with cisplatin alone. YM155 in combination with cisplatin significantly inhibited tumor growth by 13% compared with control (P<0.0001) in RD xenograft tumors. YM155 increased the sensitivity of cisplatin by suppressing survivin in the embryonal RMS cell line RD. Further studies should investigate the use of YM155 as an apoptosis inducer, either alone or in combination with cisplatin, for the treatment of malignant RMS. PMID:26983495

  15. Reusable light-emitting-diode induced chemiluminescence aptasensor for highly sensitive and selective detection of riboflavin.

    PubMed

    Xu, Shuxia; Zhang, Xinfeng; Liu, Weiwei; Sun, Yonghua; Zhang, Heliang

    2013-05-15

    A novel reusable chemiluminescence aptasensor was developed based on aptamer recognition coupled with light-emitting-diode induced chemiluminescence (LED-CL) detection. The sensing approach was based on the design that the model analyte riboflavin (Rf) in sample solutions was captured by the immobilized aptamers and then eluted simply with alkaline luminol solution to catalyze the CL reaction between luminol and dissolved oxygen under high power LED irradiation. This design allowed a very simple (branch-free) flow way for the CL sensing system. The CL intensity versus the Rf concentration was linear in the range from 0.03 to 5ngmL(-1) with a limit of detection (LOD) down low to 8pgmL(-1). Without renewing the aptamer, the relative standard deviation (RSD) for seven consecutive detections is 2.33%; the sensor also showed good stability without performance deterioration after >100 times use. Up to 10000-fold of K(+), Na(+), Ca(2+), Mg(2+), and Fe(3+), 5000-fold for glucose and bovine serum albumin, 1000-fold of uric acid, 1500-fold of ascorbic acid (added with Fe(3+)), 100-fold of flavin mononucleotide and 200-fold of flavin adenine dinucleotide caused no significant interference with the determination of 0.5ngmL(-1) Rf. The sensor was applied for analysis of Rf in urine and food samples with the recovery of 94-103%. The advantages of reusability, simplicity, high sensitivity and selectivity provided by the LED-CL aptasensor will make it a good alternative tool for biological and food analysis. PMID:23298628

  16. INFLUENCE OF OZONE ON PENTOBARBITAL-INDUCED SLEEPING TIME IN MICE, RATS, AND HAMSTERS

    EPA Science Inventory

    Prior studies have shown that ozone (O3) increases pentobarbital (PEN)-induced sleeping time (S.T.) in female mice, rats, and hamsters. To investigate some potential mechanisms producing these effects, the authors measured zoxazolamine-induced paralysis time and thiopental- and h...

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

    PubMed Central

    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. PMID:26870182

  18. Exercise induced sympathetic influences do not change interatrial conduction times in VDD and DDD pacing.

    PubMed

    Ismer, B; Von Knorre, G H; Voss, W; Grille, W; Klenke, G; Pulya, K; Koglek, W; Suntinger, A; Luessow, H

    1996-11-01

    Using telemetry, right atrial electrogram (RA), and marker channel of atrial sense events (MA) in combination with the left atrial electrogram (LA), recorded by a filtered bipolar esophageal lead, interatrial conduction during submaximal exercise and at rest was examined in 46 DDD pacemaker patients. The RA-LA and MA-LA conduction times measured in the presence of atrial sensing (VDD) as well as the conduction time SA-LA from atrial stimulus (SA) to LA, determined during atrial pacing (DDD) were found to be individual constants independent of exercise induced sympathetic influences. Thus, having determined an optimal mechanical interval (LA-LV)mech/opt from left atrium to ventricle by other methods, the optimal AV delay for DDD as well as for VDD operation can be calculated by the sum of the appropriate interatrial conduction time (SA-LA, respectively MA-LA) and the (LA-LV)mech/opt interval. Due to the constant SA-LA and MA-LA, the difference between these two values (AV delay correction interval) is a constant as well, which remains unchanged during exercise. Therefore, in selecting the rate responsive AV delay, only hemodynamic and not electrophysiological measurements need to be considered. PMID:8945041

  19. Hesperetin, a Selective Phosphodiesterase 4 Inhibitor, Effectively Suppresses Ovalbumin-Induced Airway Hyperresponsiveness without Influencing Xylazine/Ketamine-Induced Anesthesia

    PubMed Central

    Shih, Chung-Hung; Lin, Ling-Hung; Hsu, Hsin-Te; Wang, Kuo-Hsien; Lai, Chi-Yin; Chen, Chien-Ming; Ko, Wun-Chang

    2012-01-01

    Hesperetin, a selective phosphodiesterase (PDE)4 inhibitor, is present in the traditional Chinese medicine, “Chen Pi.” Therefore, we were interested in investigating its effects on ovalbumin- (OVA-) induced airway hyperresponsiveness, and clarifying its rationale for ameliorating asthma and chronic obstructive pulmonary disease (COPD). Hesperetin was revealed to have a therapeutic (PDE4H/PDE4L) ratio of >11. Hesperetin (10 ~ 30 μmol/kg, intraperitoneally (i.p.)) dose-dependently and significantly attenuated the airway hyperresponsiveness induced by methacholine. It also significantly suppressed the increases in total inflammatory cells, macrophages, lymphocytes, neutrophils, and eosinophils, and levels of cytokines, including interleukin (IL)-2, IL-4, IL-5, interferon-γ, and tumor necrosis factor-α in bronchoalveolar lavage fluid (BALF). It dose-dependently and significantly suppressed total and OVA-specific immunoglobulin E levels in the BALF and serum. However, hesperetin did not influence xylazine/ketamine-induced anesthesia, suggesting that hesperetin has few or no emetic effects. In conclusion, the rationales for ameliorating allergic asthma and COPD by hesperetin are anti-inflammation, immunoregulation, and bronchodilation. PMID:22454667

  20. Recirculating photonic filter: a wavelength-selective time delay for optically controlled phased-array antenna

    NASA Astrophysics Data System (ADS)

    Yegnanarayanan, Siva; Trinh, Paul D.; Jalali, Bahram

    1996-11-01

    A wavelength-selective photonic time delay filter is proposed and demonstrated. The device consists of an optical phased-array waveguide grating in a recirculating feedback configuration. It can function as a true-time-delay generator for squint-free beam steering in optically- controlled phased-array antennas. As the photonic filter uses the optical carrier wavelength to select the desired time delay, a one-to-one map is established between the optical carrier wavelength and the desired antenna direction, thus eliminating complex switching networks required to select the appropriate delay line. The proposed device can also function as the encoder/decoder in wavelength-CDMA. The concept uses a waveguide prism in a symmetric feedback (recirculating) configuration. The modulated optical carrier is steered by the waveguide prism to the appropriate integrated delay line depending on the carrier wavelength. The signal is delayed and is fed back into the symmetric input port. The prism then focuses the delayed beam into the common output port. Thus three sequential operations are performed: (1) wavelength demultiplexing, (2) time delay, and (3) wavelength multiplexing. It is important to note that the recirculating photonic filter has no 1/N loss; all the power at a given wavelength is diffracted into the output port. Furthermore, high resolution (6 - 8 bits) can be obtained in a compact integrated device. A prototype regular recirculating photonic filter true-time delay device was realized using a 8-channel arrayed-waveguide grating demultiplexer and external (off-chip) fiber delay lines. The grating was fabricated in the silica waveguide technology with 0.8 nm channel spacing (FSR equals 6.4 nm) and operating in the 1.5 micrometers wavelength range. Light from an external cavity tunable laser was rf modulated at 10 - 40 MHz and was coupled into the arrayed waveguide grating chip and time/phase measurements were performed sing a digital oscilloscope. Feedback delay

  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. Living with limited time: Socioemotional selectivity theory in the context of health adversity.

    PubMed

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

    2015-06-01

    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

  3. 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

  4. Salinomycin induces selective cytotoxicity to MCF-7 mammosphere cells through targeting the Hedgehog signaling pathway.

    PubMed

    Fu, Ying-Zi; Yan, Yuan-Yuan; He, Miao; Xiao, Qing-Huan; Yao, Wei-Fan; Zhao, Lin; Wu, Hui-Zhe; Yu, Zhao-Jin; Zhou, Ming-Yi; Lv, Mu-Tian; Zhang, Shan-Shan; Chen, Jian-Jun; Wei, Min-Jie

    2016-02-01

    Breast cancer stem cells (BCSCs) are believed to be responsible for tumor chemoresistance, recurrence, and metastasis formation. Salinomycin (SAL), a carboxylic polyether ionophore, has been reported to act as a selective breast CSC inhibitor. However, the molecular mechanisms underlying SAL-induced cytotoxicity on BCSCs remain unclear. The Hedgehog (Hh) signaling pathway plays an important role in CSC maintenance and carcinogenesis. Here, we investigated whether SAL induces cytotoxicity on BCSCs through targeting Hh pathway. In the present study, we cultured breast cancer MCF-7 cells in suspension in serum-free medium to obtain breast CSC-enriched MCF-7 mammospheres (MCF-7 MS). MCF-7 MS cells possessed typical BCSC properties, such as CD44+CD24-/low phenotype, high expression of OCT4 (a stem cell marker), increased colony-forming ability, strong migration and invasion capabilities, differentiation potential, and strong tumorigenicity in xenografted mice. SAL exhibited selective cytotoxicity to MCF-7 MS cells relative to MCF-7 cells. The Hh pathway was highly activated in BCSC-enriched MCF-7 MS cells and SAL inhibited Hh signaling activation by downregulating the expression of critical components of the Hh pathway such as PTCH, SMO, Gli1, and Gli2, and subsequently repressing the expression of their essential downstream targets including C-myc, Bcl-2, and Snail (but not cyclin D1). Conversely, Shh-induced Hh signaling activation could largely reverse SAL-mediated inhibitory effects. These findings suggest that SAL-induced selective cytotoxicity against MCF-7 MS cells is associated with the inhibition of Hh signaling activation and the expression of downstream targets and the Hh pathway is an important player and a possible drug target in the pathogenesis of BCSCs. PMID:26718029

  5. Space-time metrical fluctuations induced by cosmic turbulence

    NASA Technical Reports Server (NTRS)

    Rosen, G.

    1980-01-01

    For a stochastic stress-energy tensor associated with cosmic turbulence, it is observed that Einstein's equations imply fluctuations in the space-time metric tensor. Such metrical fluctuations are shown to engender modified values for the average effective proper density and total pressure and thus to alter the solutions to the Friedman equations.

  6. 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.

  7. 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.

  8. 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.

  9. 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)

  10. 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.

  11. 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.

  12. Control of laser induced reactions in solids using selected photon energies and pulse pairs

    NASA Astrophysics Data System (ADS)

    Hess, Wayne; Joly, Alan; Beck, Kenneth; Gerrity, Daniel; Dickinson, J. Thomas; Sushko, Peter; Shluger, Alexander

    2002-03-01

    Laser control of reaction dynamics is an intensely studied area of chemical physics. Sophisticated quantum and optimal control schemes have been developed to overcome difficulties associated with rapid energy redistribution from laser-prepared initial states. Experiment and theory have demonstrated how specific product pathways can be selected by irradiation with one or more laser beams. Although most laser control research has focused on small gas-phase molecules, product and quantum state control of laser desorption from solids is possible using delayed pulse pairs, selected pulse duration or by judicious choice of laser wavelength. Theory indicates that it is possible to excite the surface of ionic crystals, over the bulk, using tunable laser sources.[1] We recently demonstrated control of ion emission from MgO surfaces[2] using femtosecond pulse pairs and nearly exclusive emission of hyperthermal Br (2P3/2) from laser excited KBr.[3] Here, we explore the mechanism of laser desorption in experiments using delayed pulse pairs and tunable single pulses. The first laser pulse induces formation of transient species and the second pulse then excites the intermediate state to induce desorption of selected species or quantum states. Selective desorption raises the intriguing prospect of selective surface modification. The principles described here should be extendable to other alkali halides and metal oxides. References: [1] A.L. Shluger, P.V. Sushko, and L.N. Kantorovich, Phys. Rev. B. 59, (1999) 2417. [2] K.M. Beck, A.G. Joly, and W.P. Hess, Sur. Sci. 451, 166 (2000). [3] W. P. Hess, A. G. Joly, K. M. Beck, D. P. Gerrity, P. V. Sushko, and A. L. Shluger, J. Chem. Phys. 115, 9463 (2001).

  13. 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. PMID:26320866

  14. 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.

  15. 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.

  16. 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

  17. Selective flow-induced vesicle rupture to sort by membrane mechanical properties

    PubMed Central

    Pommella, Angelo; Brooks, Nicholas J.; Seddon, John M.; Garbin, Valeria

    2015-01-01

    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. PMID:26302783

  18. 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

  19. 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

  20. Electromagnetic field redistribution induced selective plasmon driven surface catalysis in metal nanowire-film systems.

    PubMed

    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

  1. Approach for Selection of Rayleigh Damping Parameters Used for Time History Analysis

    SciTech Connect

    R. E. Spears; S. R. Jensen

    2012-12-01

    Nonlinearities, whether geometric or material, need to be addressed in seismic analysis. One good analysis method that can address these nonlinearities is direct time integration with Rayleigh damping. Modal damping is the damping typically specified in seismic analysis Codes and Standards. Modal damping is constant for all frequencies where Rayleigh damping varies with frequency. An approach is proposed here for selection of Rayleigh damping coefficients to be used in seismic analyses that is consistent with given Modal damping. The approach uses the difference between the modal damping response and the Rayleigh damping response along with effective mass properties of the model being evaluated to match overall system response levels. This paper provides a simple example problem to demonstrate the approach. It also provides results for a finite element model representing an existing piping system. Displacement, acceleration, and stress results are compared from model runs using modal damping and model runs using Rayleigh damping with coefficients selected using the proposed method.

  2. Methods to characterize selective sweeps using time serial samples: an ancient DNA perspective.

    PubMed

    Malaspinas, Anna-Sapfo

    2016-01-01

    With hundreds of ancient genomes becoming available this year, ancient DNA research has now entered the genomics era. Utilizing the temporal aspect of these new data, we can now address fundamental evolutionary questions such as the characterization of selection processes shaping the genomes. The temporal dimension in the data has spurred the development in the last 10 years of new methods allowing the detection of loci evolving non-neutrally but also the inference of selection coefficients across genomes capitalizing on these time serial data. To guide empirically oriented researchers towards the statistical approach most appropriate for their data, this article reviews several of those methods, discussing their underlying assumptions and the parameter ranges for which they have been developed. While I discuss some methods developed for experimental evolution, the main focus is ancient DNA. PMID:26613371

  3. Developing and Selecting Auditory Warnings for a Real-Time Behavioral Intervention

    PubMed Central

    Bellettiere, John; Hughes, Suzanne C.; Liles, Sandy; Boman-Davis, Marie; Klepeis, Neil; Blumberg, Elaine; Mills, Jeff; Berardi, Vincent; Obayashi, Saori; Allen, T. Tracy; Hovell, Melbourne F.

    2015-01-01

    Real-time sensing and computing technologies are increasingly used in the delivery of real-time health behavior interventions. Auditory signals play a critical role in many of these interventions, impacting not only behavioral response but also treatment adherence and participant retention. Yet, few behavioral interventions that employ auditory feedback report the characteristics of sounds used and even fewer design signals specifically for their intervention. This paper describes a four-step process used in developing and selecting auditory warnings for a behavioral trial designed to reduce indoor secondhand smoke exposure. In step one, relevant information was gathered from ergonomic and behavioral science literature to assist a panel of research assistants in developing criteria for intervention-specific auditory feedback. In step two, multiple sounds were identified through internet searches and modified in accordance with the developed criteria, and two sounds were selected that best met those criteria. In step three, a survey was conducted among 64 persons from the primary sampling frame of the larger behavioral trial to compare the relative aversiveness of sounds, determine respondents' reported behavioral reactions to those signals, and assess participant's preference between sounds. In the final step, survey results were used to select the appropriate sound for auditory warnings. Ultimately, a single-tone pulse, 500 milliseconds (ms) in length that repeats every 270 ms for 3 cycles was chosen for the behavioral trial. The methods described herein represent one example of steps that can be followed to develop and select auditory feedback tailored for a given behavioral intervention. PMID:25745633

  4. Effect of selected water temperatures used in Mycoplasma gallisepticum vaccine reconstitution on titer at selected time intervals

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  5. Selective activation of a putative reinforcement signal conditions cued interval timing in primary visual cortex

    PubMed Central

    Liu, Cheng-Hang; Coleman, Jason E.; Davoudi, Heydar; Zhang, Kechen; Hussain Shuler, Marshall G.

    2015-01-01

    Summary As a consequence of conditioning visual cues with delayed reward, cue-evoked neural activity that predicts the time of expected future reward emerges in the primary visual cortex (V1). We hypothesized that this reward timing activity is engendered by a reinforcement signal conveying reward acquisition to V1. In lieu of behavioral conditioning, we assessed in vivo whether selective activation of either basal forebrain (BF) or cholinergic innervation is sufficient to condition cued interval timing activity. Substituting for actual reward, optogenetic activation of BF or cholinergic input within V1 at fixed delays following visual stimulation entrains neural responses that mimic behaviorally-conditioned reward timing activity. Optogenetically-conditioned neural responses express cue-evoked temporal intervals that correspond to the conditioning intervals, are bidirectionally modifiable, display experience-dependent refinement, and exhibit a scale invariance to the encoded delay. Our results demonstrate that the activation of BF or cholinergic input within V1is sufficient to encode cued interval timing activity, and indicate that V1 itself is a substrate for associative learning that may inform the timing of visually-cued behaviors. PMID:26004763

  6. Size-selective sorting in bubble streaming flows: Particle migration on fast time scales

    NASA Astrophysics Data System (ADS)

    Thameem, Raqeeb; Rallabandi, Bhargav; Hilgenfeldt, Sascha

    2015-11-01

    Steady streaming from ultrasonically driven microbubbles is an increasingly popular technique in microfluidics because such devices are easily manufactured and generate powerful and highly controllable flows. Combining streaming and Poiseuille transport flows allows for passive size-sensitive sorting at particle sizes and selectivities much smaller than the bubble radius. The crucial particle deflection and separation takes place over very small times (milliseconds) and length scales (20-30 microns) and can be rationalized using a simplified geometric mechanism. A quantitative theoretical description is achieved through the application of recent results on three-dimensional streaming flow field contributions. To develop a more fundamental understanding of the particle dynamics, we use high-speed photography of trajectories in polydisperse particle suspensions, recording the particle motion on the time scale of the bubble oscillation. Our data reveal the dependence of particle displacement on driving phase, particle size, oscillatory flow speed, and streaming speed. With this information, the effective repulsive force exerted by the bubble on the particle can be quantified, showing for the first time how fast, selective particle migration is effected in a streaming flow. We acknowledge support by the National Science Foundation under grant number CBET-1236141.

  7. Subtype selective NMDA receptor antagonists induce recovery of synapses lost following exposure to HIV-1 Tat

    PubMed Central

    Shin, AH; Kim, HJ; Thayer, SA

    2012-01-01

    BACKGROUND AND PURPOSE Neurocognitive disorders afflict approximately 20% of HIV-infected patients. HIV-1-infected cells in the brain shed viral proteins such as transactivator of transcription (Tat). Tat elicits cell death and synapse loss via processes initiated by NMDA receptor activation but mediated by separate downstream signalling pathways. Subunit selective NMDA receptor antagonists may differentially modulate survival relative to synaptic changes. EXPERIMENTAL APPROACH Tat-evoked cell death was quantified by measuring propidium iodide uptake into rat hippocampal neurons in culture. The effects of Tat on synaptic changes were measured using an imaging-based assay that quantified clusters of the scaffolding protein postsynaptic density 95 fused to green fluorescent protein. KEY RESULTS Dizocilpine, a non-competitive NMDA receptor antagonist, inhibited Tat-induced synapse loss, subsequent synapse recovery and Tat-induced cell death with comparable potencies. Memantine (10 µM) and ifenprodil (10 µM), which preferentially inhibit GluN2B-containing NMDA receptors, protected from Tat-induced cell death with no effect on synapse loss. Surprisingly, memantine and ifenprodil induced synapse recovery in the presence of Tat. In contrast, the GluN2A-prefering antagonist TCN201 prevented synapse loss and recovery with no effect on cell death. CONCLUSIONS AND IMPLICATIONS Synapse loss is a protective mechanism that enables the cell to cope with excess excitatory input. Thus, memantine and ifenprodil are promising neuroprotective drugs because they spare synaptic changes and promote survival. These GluN2B-preferring drugs induced recovery from Tat-evoked synapse loss, suggesting that synaptic pharmacology changed during the neurotoxic process. NMDA receptor subtypes differentially participate in the adaptation and death induced by excitotoxic insult. PMID:22142193

  8. Laser-Induced Selectivity for Dimerization Versus Polymerization of Butadiene Under Pressure

    NASA Astrophysics Data System (ADS)

    Citroni, Margherita; Ceppatelli, Matteo; Bini, Roberto; Schettino, Vincenzo

    2002-03-01

    The pressure-induced chemical reaction of liquid butadiene was studied by Fourier transform infrared spectroscopy in a diamond anvil cell. Dimerization was found to occur above 0.7 gigapascal, giving vinylcyclohexene according to a cyclo-addiction reaction and only a trace amount of polybutadiene forms. By irradiating the high-pressure sample with a few milliwatts of the 488-nanometer argon+ laser line, the dimerization was completely inhibited, and the rapid formation of pure trans-polybutadiene was observed. The use of different excitation wavelength allows us to emphasize the selectivity of the process and to identify the active role of the 21Ag state in this pressure- and laser-induced chemical reaction.

  9. 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.

  10. Time of travel of solutes in selected reaches of the Sandusky River Basin, Ohio, 1972 and 1973

    USGS Publications Warehouse

    Westfall, Arthur O.

    1976-01-01

    A time of travel study of a 106-mile (171-kilometer) reach of the Sandusky River and a 39-mile (63-kilometer) reach of Tymochtee Creek was made to determine the time required for water released from Killdeer Reservoir on Tymochtee Creek to reach selected downstream points. In general, two dye sample runs were made through each subreach to define the time-discharge relation for approximating travel times at selected discharges within the measured range, and time-discharge graphs are presented for 38 subreaches. Graphs of dye dispersion and variation in relation to time are given for three selected sampling sites. For estimating travel time and velocities between points in the study reach, tables for selected flow durations are given. Duration curves of daily discharge for four index stations are presented to indicate the lo-flow characteristics and for use in shaping downward extensions of the time-discharge curves.

  11. In vivo selective cytoskeleton dynamics quantification in interphase cells induced by pulsed ultraviolet laser nanosurgery.

    PubMed

    Colombelli, Julien; Reynaud, Emmanuel G; Rietdorf, Jens; Pepperkok, Rainer; Stelzer, Ernst H K

    2005-12-01

    We report on the manipulation of intracellular filaments using a nanosurgery system based on a subnanosecond pulsed UV laser optimized for the localized severing of biological polymers. By inducing artificial catastrophe of selected microtubules (MTs), we perform shrinkage-rate measurements in interphase Ptk-2 cells throughout the entire cell. We quantify the impact of two labeling methods and three fluorescent markers, showing a 25% faster depolymerization with Alexa-488 tubulin compared with Rhodamine and yellow fluorescent protein (YFP) tubulins and a 20% higher variability induced by microinjection compared with stable transfection. Using EB3-GFP as a tip marker, we establish a new protocol to measure shrinkage rate, growth rate and rescue frequency simultaneously with high temporal and spatial specificity in live cells. As our analysis shows, laser-induced MT dynamics are physiologically relevant. The high statistical efficiency that the method offers in terms of numbers of measured events and therefore reduced standard deviations represents an important quantitative improvement in the measurement of dynamic instability parameters in vivo. We extend the application of the method by demonstrating induced dynamic behavior of actin-stress fibers after severing. This new method enables the quantitative investigation of cytoskeleton dynamics in a local confinement. PMID:16262721

  12. Spin-orbit torque induced spike-timing dependent plasticity

    NASA Astrophysics Data System (ADS)

    Sengupta, Abhronil; Al Azim, Zubair; Fong, Xuanyao; Roy, Kaushik

    2015-03-01

    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. Valproic Acid Induced Hyperammonemia in a Long Time Treated Patient

    PubMed Central

    Seide, Margaret; Stern, Robert G.

    2016-01-01

    We report a case of a patient who had been on long time valproic acid for treatment of bipolar affective disorder. While being an inpatient, serology ammonia level testing revealed a very high ammonia level despite being asymptomatic. Dual therapy of carnitine and lactulose was provided to the patient for treatment of the hyperammonemia. It should also be noted that, during this treatment, valproic acid was not stopped. Consequently, this case illustrates that patients can present asymptomatically despite very high ammonia levels and hyperammonemia can occur in chronic valproic acid despite not increasing the dose of the medication and psychiatrists do not need to discontinue valproic acid in the presence of elevated levels of ammonia if the patient shows no signs of encephalopathy or delirium. PMID:27516916

  14. 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.

  15. Valproic Acid Induced Hyperammonemia in a Long Time Treated Patient.

    PubMed

    Aiyer, Rohit; Seide, Margaret; Stern, Robert G

    2016-01-01

    We report a case of a patient who had been on long time valproic acid for treatment of bipolar affective disorder. While being an inpatient, serology ammonia level testing revealed a very high ammonia level despite being asymptomatic. Dual therapy of carnitine and lactulose was provided to the patient for treatment of the hyperammonemia. It should also be noted that, during this treatment, valproic acid was not stopped. Consequently, this case illustrates that patients can present asymptomatically despite very high ammonia levels and hyperammonemia can occur in chronic valproic acid despite not increasing the dose of the medication and psychiatrists do not need to discontinue valproic acid in the presence of elevated levels of ammonia if the patient shows no signs of encephalopathy or delirium. PMID:27516916

  16. 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.

  17. Induced fit, conformational selection and independent dynamic segments: an extended view of binding events

    PubMed Central

    Csermely, Peter; Palotai, Robin; Nussinov, Ruth

    2010-01-01

    Single molecule and NMR measurements of protein dynamics increasingly uncover the complexity of binding scenarios. Here we describe an extended conformational selection model which embraces a repertoire of selection and adjustment processes. Induced fit can be viewed as a subset of this repertoire, whose contribution is affected by the bond-types stabilizing the interaction and the differences between the interacting partners. We argue that protein segments whose dynamics are distinct from the rest of the protein (‘discrete breathers’) can govern conformational transitions and allosteric propagation that accompany binding processes, and as such might be more sensitive to mutational events. Additionally, we highlight the dynamic complexity of binding scenarios as they relate to events such as aggregation and signalling, and the crowded cellular environment. PMID:20541943

  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. Photoactivatable aggregation-induced emission fluorophores with multiple-color fluorescence and wavelength-selective activation.

    PubMed

    Peng, Lu; Zheng, Yue; Wang, Xiaoyan; Tong, Aijun; Xiang, Yu

    2015-03-01

    Photoactivatable (caged) fluorophores are widely used in chemistry, materials, and biology. However, the development of such molecules exhibiting photoactivable solid-state fluorescence is still challenging due to the aggregation-caused quenching (ACQ) effect of most fluorophores in their aggregate or solid states. In this work, we developed caged salicylaldehyde hydrazone derivatives, which are of aggregation-induced emission (AIE) characteristics upon light irradiation, as efficient photoactivatable solid-state fluorophores. These compounds displayed multiple-color emissions and ratiometric (photochromic) fluorescence switches upon wavelength-selective photoactivation, and were successfully applied for photopatterning and photoactivatable cell imaging in a multiple-color and stepwise manner. PMID:25644036

  20. Temperature-induced shifts in selective pressure at a critical developmental transition.

    PubMed

    Gagliano, Monica; McCormick, Mark I; Meekan, Mark G

    2007-05-01

    Selective mortality within a population, based on the phenotype of individuals, is the foundation of the theory of natural selection. We examined temperature-induced shifts in the relationships among early life history traits and survivorship over the embryonic and larval stages of a tropical damselfish, Pomacentrus amboinensis. Our experiments show that temperature determines the intensity of selective mortality, and that this changes with ontogeny. The size of energy stores determined survival through to hatching, after which egg size became a good indicator of fitness as predicted by theoretical models. Yet, the benefits associated with egg size were not uniform among test temperatures. Initial egg size positively influenced larval survival at control temperature (29 degrees C). However, this embryonic trait had no effect on post-hatching longevity of individuals reared at the higher (31 degrees C) and lower (25 degrees C) end of the temperature range. Overall, our findings indicate that the outcome of selective mortality is strongly dependent on the interaction between environment conditions and intrinsic developmental schedules. PMID:17242907

  1. 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.

  2. 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

  3. Selective translocation of protein kinase C-delta in PC12 cells during nerve growth factor-induced neuritogenesis.

    PubMed Central

    O'Driscoll, K R; Teng, K K; Fabbro, D; Greene, L A; Weinstein, I B

    1995-01-01

    The specific intracellular signals initiated by nerve growth factor (NGF) that lead to neurite formation in PC12 rat pheochromocytoma cells are as of yet unclear. Protein kinase C-delta (PKC delta) is translocated from the soluble to the particulate subcellular fraction during NGF-induced-neuritogenesis; however, this does not occur after treatment with the epidermal growth factor, which is mitogenic but does not induce neurite formation. PC12 cells also contain both Ca(2+)-sensitive and Ca(2+)-independent PKC enzymatic activities, and express mRNA and immunoreactive proteins corresponding to the PKC isoforms alpha, beta, delta, epsilon, and zeta. There are transient decreases in the levels of immunoreactive PKCs alpha, beta, and epsilon after 1-3 days of NGF treatment, and after 7 days there is a 2.5-fold increase in the level of PKC alpha, and a 1.8-fold increase in total cellular PKC activity. NGF-induced PC12 cell neuritogenesis is enhanced by 12-O-tetradecanoyl phorbol-13-acetate (TPA) in a TPA dose- and time-dependent manner, and this differentiation coincides with abrogation of the down-regulation of PKC delta and other PKC isoforms, when the cells are treated with TPA. Thus a selective activation of PKC delta may play a role in neuritogenic signals in PC12 cells. Images PMID:7626808

  4. 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.

  5. 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…

  6. Ultra-small time-delay estimation via a weak measurement technique with post-selection

    NASA Astrophysics Data System (ADS)

    Fang, Chen; Huang, Jing-Zheng; Yu, Yang; Li, Qinzheng; Zeng, Guihua

    2016-09-01

    Weak measurement is a novel technique for parameter estimation with higher precision. In this paper we develop a general theory for the parameter estimation based on a weak measurement technique with arbitrary post-selection. The weak-value amplification model and the joint weak measurement model are two special cases in our theory. Applying the developed theory, time-delay estimation is investigated in both theory and experiments. The experimental results show that when the time delay is ultra-small, the joint weak measurement scheme outperforms the weak-value amplification scheme, and is robust against not only misalignment errors but also the wavelength dependence of the optical components. These results are consistent with theoretical predictions that have not been previously verified by any experiment.

  7. 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.

  8. Source Selection for Real-time User Intent Recognition towards Volitional Control of Artificial Legs

    PubMed Central

    Zhang, Fan; Huang, He

    2013-01-01

    Various types of data sources have been used to recognize user intent for volitional control of powered artificial legs. However, there is still a debate on what exact data sources are necessary for accurately and responsively recognizing the user's intended tasks. Motivated by this widely interested question, in this study we aimed to (1) investigate the usefulness of different data sources commonly suggested for user intent recognition and (2) determine an informative set of data sources for volitional control of prosthetic legs. The studied data sources included eight surface electromyography (EMG) signals from the residual thigh muscles of transfemoral (TF) amputees, ground reaction forces/moments from a prosthetic pylon, and kinematic measurements from the residual thigh and prosthetic knee. We then ranked included data sources based on the usefulness for user intent recognition and selected a reduced number of data sources that ensured accurate recognition of the user's intended task by using three source selection algorithms. The results showed that EMG signals and ground reaction forces/moments were more informative than prosthesis kinematics. Nine to eleven of all the initial data sources were sufficient to maintain 95% accuracy for recognizing the studied seven tasks without missing additional task transitions in real time. The selected data sources produced consistent system performance across two experimental days for four recruited TF amputee subjects, indicating the potential robustness of the selected data sources. Finally, based on the study results, we suggested a protocol for determining the informative data sources and sensor configurations for future development of volitional control of powered artificial legs. PMID:25055369

  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. PMID:21811564

  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. PMID:27127849

  11. 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.

  12. Selection and investigation of sites for the disposal of radioactive wastes in hydraulically induced subsurface fractures

    SciTech Connect

    Sun, R.J.

    1982-01-01

    Injection of intermediate-level radioactive wastes (specific activity of less than 6 x 10/sup 3/ ..mu..Ci/mL, consisting mainly of radionuclides, such as strontium and cesium, having half-lives of less than 50 years) mixed with cement into a thick shale formation is a promising and feasible disposal method. Hydraulic fracturing provides openings in the shale to accommodate the wastes. Ion exchange and radionuclide-adsorption materials can be added to the grout during mixing to further increase the radionuclide-retaining capacity of the grout. After solidification of the grout, the injected wastes become an integral part of the shale formation, and therefore the wastes will remain at depth and in place as long as the injection zone is not subjected to erosion and dissolution. Problems concerning safety of the disposal method are (1) the potential for inducing vertical fractures, (2) phase separation during and after the injections, (3) the reliability of methods for determining the orientation of induced fractures, (4) the possibility of triggering earthquakes, and (5) radionuclides being leached and transported by ground water. Theoretical considerations about inducing nearly horizontal bedding-plane fractures in shale are discussed, as are field procedures for site selection, safety, and the monitoring and operation of radioactive waste disposal. Case histories are used as examples to demonstrate the application of the theory and techniques of field operations. (JMT)

  13. Selection and investigation of sites for the disposal of radioactive wastes in hydraulically induced subsurface fractures

    SciTech Connect

    Sun, R.J.

    1982-01-01

    Injection of intermediate-level radioactive wastes (specific activity of less than 6 x 10/sup 3/..mu..Ci/mL, consisting mainly of radionuclides, such as strontium and cesium, having half-lives of less than 50 years) mixed with cement into a thick shale formation is a promising and feasible disposal method. Hydraulic fracturing provides openings in the shale to accommodate the wastes. Ion exchange and radionuclide-adsorption materials can be added to the grout during mixing to further increase the radionuclide-retaining capacity of the grout. After solidification of the grout, the injected wastes become an integral part of the shale formation, and therefore the wastes will remain at depth and in place as long as the injection zone is not subjected to erosion or dissolution. Problems concerning safety of the disposal method are: (1) the potential for inducing vertical fractures, (2) phase separation during and after the injections, (3) the reliability of methods for determining the orientation of induced fractures, (4) the possibility of triggering earthquakes, and (5) radionuclides being leached and transported by ground water. Theoretical considerations about inducing nearly horizontal bedding-plane fractures in shale are discussed, as are field procedures for site selection, safety, and the monitoring and operation of radioactive waste disposal. Case histories are used as examples to demonstrate the application of the theory and techniques of field operations.

  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. 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.

  16. Diversity of actions of GnRHs mediated by ligand-induced selective signaling

    PubMed Central

    Millar, Robert P.; Pawson, Adam J.; Morgan, Kevin; Rissman, Emilie F.; Lu, Zhi-Liang

    2009-01-01

    Geoffrey Wingfield Harris’ demonstration of hypothalamic hormones regulating pituitary function led to their structural identification and therapeutic utilization in a wide spectrum of diseases. Amongst these, Gonadotropin Releasing Hormone (GnRH) and its analogs are widely employed in modulating gonadotropin and sex steroid secretion to treat infertility, precocious puberty and many hormone-dependent diseases including endometriosis, uterine fibroids and prostatic cancer. While these effects are all mediated via modulation of the pituitary gonadotrope GnRH receptor and the Gq signaling pathway, it has become increasingly apparent that GnRH regulates many extrapituitary cells in the nervous system and periphery. This review focuses on two such examples, namely GnRH analog effects on reproductive behaviors and GnRH analog effects on the inhibition of cancer cell growth. For both effects the relative activities of a range of GnRH analogs is distinctly different from their effects on the pituitary gonadotrope and different signaling pathways are utilized. As there is only a single functional GnRH receptor type in man we have proposed that the GnRH receptor can assume different conformations which have different selectivity for GnRH analogs and intracellular signaling proteins complexes. This ligand-induced selective-signaling recruits certain pathways while by-passing others and has implications in developing more selective GnRH analogs for highly specific therapeutic intervention. PMID:17976709

  17. Noise-induced cochlear neuropathy is selective for fibers with low spontaneous rates.

    PubMed

    Furman, Adam C; Kujawa, Sharon G; Liberman, M Charles

    2013-08-01

    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

  18. 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

  19. 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. PMID:26942565

  20. Lysosomotropic agents selectively potentiate thrombin-induced acid hydrolase secretion from platelets.

    PubMed Central

    Van Oost, B A; Smith, J B; Holmsen, H; Vladutiu, G D

    1985-01-01

    Thrombin induces partial secretion (up to 60%) of beta-N-acetyl-D-hexosaminidase (EC 3.2.1.52) from untreated platelets. Preincubation of platelets with 10 mM NH4Cl for up to 2 hr resulted in a time-dependent and marked stimulation of thrombin-induced secretion of both this enzyme and other acid glycosidases from platelets. The enhancement of the thrombin-induced secretion was not due to cell lysis, and NH4Cl alone did not cause leakage of lysosomal enzymes into the medium. The effect could be reversed by reincubating the platelets in NH4Cl-free medium. Stimulation of thrombin-induced secretion also was produced by a series of aliphatic primary amines from methylamine to butylamine, and by micromolar concentrations of chloroquine. The effect of weak bases on platelets appeared to be quite specific for enhancing lysosomal enzyme secretion. Thrombin-induced secretion of adenine nucleotides from dense granules and of beta-thromboglobulin from alpha granules was slightly enhanced by NH4Cl but was slightly inhibited by methylamine. The only direct effect of the weak bases on platelets was the displacement of serotonin from dense granules. Accumulation of weak bases in acidic pools in the platelets (e.g., lysosomes) might, therefore, be responsible for the enhanced secretion of lysosomal enzymes. By using controlled digitonin-induced platelet lysis, it was found that preincubation of platelets with NH4Cl lowered the digitonin concentration required for enzyme solubilization. We suggest that loading of lysosomes with weak bases dissociates already bound enzyme inside the lysosomes, resulting in a more effective discharge upon stimulation by thrombin. PMID:3157989

  1. Spike-timing dependent plasticity in a transistor-selected resistive switching memory

    NASA Astrophysics Data System (ADS)

    Ambrogio, S.; Balatti, S.; Nardi, F.; Facchinetti, S.; Ielmini, D.

    2013-09-01

    In a neural network, neuron computation is achieved through the summation of input signals fed by synaptic connections. The synaptic activity (weight) is dictated by the synchronous firing of neurons, inducing potentiation/depression of the synaptic connection. This learning function can be supported by the resistive switching memory (RRAM), which changes its resistance depending on the amplitude, the pulse width and the bias polarity of the applied signal. This work shows a new synapse circuit comprising a MOS transistor as a selector and a RRAM as a variable resistance, displaying spike-timing dependent plasticity (STDP) similar to the one originally experienced in biological neural networks. We demonstrate long-term potentiation and long-term depression by simulations with an analytical model of resistive switching. Finally, the experimental demonstration of the new STDP scheme is presented.

  2. Spike-timing dependent plasticity in a transistor-selected resistive switching memory.

    PubMed

    Ambrogio, S; Balatti, S; Nardi, F; Facchinetti, S; Ielmini, D

    2013-09-27

    In a neural network, neuron computation is achieved through the summation of input signals fed by synaptic connections. The synaptic activity (weight) is dictated by the synchronous firing of neurons, inducing potentiation/depression of the synaptic connection. This learning function can be supported by the resistive switching memory (RRAM), which changes its resistance depending on the amplitude, the pulse width and the bias polarity of the applied signal. This work shows a new synapse circuit comprising a MOS transistor as a selector and a RRAM as a variable resistance, displaying spike-timing dependent plasticity (STDP) similar to the one originally experienced in biological neural networks. We demonstrate long-term potentiation and long-term depression by simulations with an analytical model of resistive switching. Finally, the experimental demonstration of the new STDP scheme is presented. PMID:23999495

  3. 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

  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. 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.

  6. Selection of fluorescent DNA dyes for real-time LAMP with portable and simple optics.

    PubMed

    Seyrig, Gregoire; Stedtfeld, Robert D; Tourlousse, Dieter M; Ahmad, Farhan; Towery, Keara; Cupples, Alison M; Tiedje, James M; Hashsham, Syed A

    2015-12-01

    Loop-mediated isothermal amplification (LAMP) is increasingly used for point-of-care nucleic acid based diagnostics. LAMP can be monitored in real-time by measuring the increase in fluorescence of DNA binding dyes. However, there is little information comparing the effect of various fluorescent dyes on signal to noise ratio (SNR) or threshold time (Tt). This information is critical for implementation with field deployable diagnostic tools that require small, low power consumption, robust, and inexpensive optical components with reagent saving low volume reactions. In this study, SNR and Tt during real-time LAMP was evaluated with eleven fluorescent dyes. Of all dyes tested, SYTO-82, SYTO-84, and SYTOX Orange resulted in the shortest Tt, and SYTO-81 had the widest range of working concentrations. The optimized protocol detected 10 genome copies of Mycobacterium tuberculosis in less than 10 min, 10 copies of Giardia intestinalis in ~20 min, and 10 copies of Staphylococcus aureus or Salmonella enterica in less than 15 min. Results demonstrate that reaction efficiency depends on both dye type and concentration and the selected polymerase. The optimized protocol was evaluated in the Gene-Z™ device, a hand-held battery operated platform characterized via simple and low cost optics, and a multiple assay microfluidic chip with micron volume reaction wells. Compared to the more conventional intercalating dye (SYBR Green), reliable amplification was only observed in the Gene-Z™ when using higher concentrations of SYTO-81. PMID:26554941

  7. 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

  8. 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.

  9. 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.

  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. 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

  12. 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.

  13. 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.

  14. The timing of face selectivity and attentional modulation in visual processing.

    PubMed

    Okazaki, Y; Abrahamyan, A; Stevens, C J; Ioannides, A A

    2008-04-01

    Despite the complete imprint of a visual scene on the retina, the brain selects particular items for further processing. However, there is considerable debate about when and where the first attentional effects take hold in the cortex. We examined the timing of face specificity and attentional influences in the primary/secondary visual cortex (V1/V2) and in the fusiform gyrus (FG) in two experiments using magnetoencephalography (MEG). In experiment 1, using a passive viewing task, we identified three components in response to "Face," "Hand," and "Shoe" stimuli bilaterally in the FG: M(FG)100, M(FG)170, and M(FG)200-all showing a stronger preference for faces. The timing of these three activations of the FG is consistent with earlier studies claiming distinct stages of processing of visual stimuli in the first 300 ms. In experiment 2, subjects performed a gender-discrimination task on either faces or hands, drawing attention to only one of the two object categories. In addition to the previously identified three components in FG, here we found object-selective attentional enhancement first appearing in V1/V2 at around 170 ms, and then in FG at around 200 ms, i.e. concurrent with the third component. No attentional effects were evident on the first or second magnetoencephalography components. These findings may indicate that the visual input for an object is first encoded and matched to an attended "cue" object held in mind. When the attended and encoded objects match, a third stage involving attentive processing is enhanced. PMID:18355971

  15. Age-related slowing of response selection and production in a visual choice reaction time task.

    PubMed

    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

  16. 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

  17. Remote time-resolved filament-induced breakdown spectroscopy of biological materials

    NASA Astrophysics Data System (ADS)

    Xu, H. L.; Liu, W.; Chin, S. L.

    2006-05-01

    We report, for what we believe to be the first time, on the feasibility of remote time-resolved filament-induced breakdown spectroscopy (FIBS) of biological materials. The fluorescence from egg white and yeast powder, induced by femtosecond laser pulse filamentation in air, was detected in the backward direction with targets located 3.5 m away from the detection system. The remarkably distinct spectra of egg white and yeast allow us to propose that this technique, time-resolved FIBS, could be potentially useful for remote detection and identification of harmful biological agents.

  18. Moiré induced organization of size-selected Pt clusters soft landed on epitaxial graphene

    PubMed Central

    Linas, Sébastien; Jean, Fabien; Zhou, Tao; Albin, Clément; Renaud, Gilles; Bardotti, Laurent; Tournus, Florent

    2015-01-01

    Two-dimensional hexagonal arrays of Pt nanoparticles (1.5 nm diameter) have been obtained by deposition of preformed and size selected Pt nanoparticles on graphene. This original self-organization is induced, at room temperature, by the 2D periodic undulation (the moiré pattern) of graphene epitaxially grown on the Ir(111) surface. By means of complementary techniques (scanning tunneling microscopy, grazing incidence X ray scattering), the Pt clusters shapes and organization are characterized and the structural evolution during annealing is investigated. The soft-landed clusters remain quasi-spherical and a large proportion appears to be pinned on specific moiré sites. The quantitative determination of the proportion of organized clusters reveals that the obtained hexagonal array of the almost spherical nanoparticles is stable up to 650 K, which is an indication of a strong cluster-surface interaction. PMID:26278787

  19. Two-Photon-Induced Selective Decarboxylation of Aspartic Acids D85 and D212 in Bacteriorhodopsin.

    PubMed

    Imhof, Martin; Rhinow, Daniel; Linne, Uwe; Hampp, Norbert

    2012-10-18

    The interest in microbial opsins stems from their photophysical properties, which are superior to most organic dyes. Microbial rhodopsins like bacteriorhodopsin (BR) from Halobacterium salinarum have an astonishingly high cross-section for two-photon-absorption (TPA), which is of great interest for technological applications such as data storage. Irradiation of BR with intense laser pulses at 532 nm leads to formation of a bathochromic photoproduct, which is further converted to a photochemical species absorbing in the UV range. As demonstrated earlier, the photochemical conversions are induced by resonant TPA. However, the molecular basis of these conversions remained unresolved. In this work we use mass spectroscopy to demonstrate that TPA of BR leads to selective decarboxylation of two aspartic acids in the vicinity of the retinal chromphore. These photochemical conversions are the basis of permanent two-photon data storage in BR and are of critical importance for application of microbial opsins in optogenetics. PMID:26292239

  20. Spectral selective radio frequency emissions from laser induced breakdown of target materials

    SciTech Connect

    Vinoth Kumar, L.; Manikanta, E.; Leela, Ch.; Prem Kiran, P.

    2014-08-11

    The radio frequency emissions scanned over broad spectral range (30 MHz–1 GHz) from single shot nanosecond (7 ns) and picosecond (30 ps) laser induced breakdown (LIB) of different target materials (atmospheric air, aluminum, and copper) are presented. The dominant emissions from ns-LIB, compared to those from the ps-LIB, indicate the presence and importance of atomic and molecular clusters in the plasma. The dynamics of laser pulse-matter interaction and the properties of the target materials were found to play an important role in determining the plasma parameters which subsequently determine the emissions. Thus, with a particular laser and target material, the emissions were observed to be spectral selective. The radiation detection capability was observed to be relatively higher, when the polarization of the input laser and the antenna is same.

  1. Shape selection in Landsat time series: a tool for monitoring forest dynamics.

    PubMed

    Moisen, Gretchen G; Meyer, Mary C; Schroeder, Todd A; Liao, Xiyue; Schleeweis, Karen G; Freeman, Elizabeth A; Toney, Chris

    2016-10-01

    We present a new methodology for fitting 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 band or index of choice in temporal Landsat data, our method delivers a smoothed rendition of the trajectory constrained to behave in an ecologically sensible manner, reflecting one of seven possible 'shapes'. It also provides parameters summarizing the patterns of each change including year of onset, duration, magnitude, and pre- and postchange rates of growth or recovery. Through a case study featuring fire, harvest, and bark beetle outbreak, we illustrate how resultant fitted values and parameters can be fed into empirical models to map disturbance causal agent and tree canopy cover changes coincident with disturbance events through time. We provide our code in the r package ShapeSelectForest on the Comprehensive R Archival Network and describe our computational approaches for running the method over large geographic areas. We also discuss how this methodology is currently being used for forest disturbance and attribute mapping across the conterminous United States. PMID:27185612

  2. 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…

  3. The GALEX Time Domain Survey. I. Selection and Classification of Over a Thousand Ultraviolet Variable Sources

    NASA Astrophysics Data System (ADS)

    Gezari, S.; Martin, D. C.; Forster, K.; Neill, J. D.; Huber, M.; Heckman, T.; Bianchi, L.; Morrissey, P.; Neff, S. G.; Seibert, M.; Schiminovich, D.; Wyder, T. K.; Burgett, W. S.; Chambers, K. C.; Kaiser, N.; Magnier, E. A.; Price, P. A.; Tonry, J. L.

    2013-03-01

    We present the selection and classification of over a thousand ultraviolet (UV) variable sources discovered in ~40 deg2 of GALEX Time Domain Survey (TDS) NUV images observed with a cadence of 2 days and a baseline of observations of ~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 5σ 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 |Δm| = 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 |Δm| > 0.2 mag of ~8.0, 7.7, and 1.8 deg-2 for quasars, active galactic nuclei, and RR Lyrae stars, respectively. We also calculate a surface density rate in the UV for transient sources, using the effective

  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.; Schiminovich, D.; Wyder, T. K.; Burgett, W. S.; Chambers, K. C.; Kaiser, N.; Magnier, E. A.; Price, P. A.; Tonry, J. L.

    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. Inter event times of fluid induced earthquakes suggest their Poisson nature

    NASA Astrophysics Data System (ADS)

    Langenbruch, C.; Dinske, C.; Shapiro, S. A.

    2011-11-01

    We analyze the inter event time distribution of fluid-injection-induced earthquakes for six catalogs collected at geothermal injection sites at Soultz-sous-Forêts and Basel. We find that the distribution of waiting times during phases of constant seismicity rate coincides with the exponential distribution of the homogeneous Poisson process (HPP). We analyze the waiting times for the complete event catalogs and find that, as for naturally occurring earthquakes, injection induced earthquakes are distributed according to a non homogeneous Poisson process in time. Moreover, the process of event occurrence in the injection volume domain is a HPP. These results indicate that fluid-injection-induced earthquakes are directly triggered by the loading induced by the fluid injection. We also consider the spatial distance between events and perform a nearest neighbor analysis in the time-space-magnitude domain. Our analysis including a comparison to a synthetic catalog created according to the ETAS model reveals no signs of causal relationships between events. Therefore, coupling effects between events are very weak. The Poisson model seems to be a very good approximation of fluid induced seismicity.

  7. Conformational Changes in Thiazole-2-carboxylic Acid Selectively Induced by Excitation with Narrowband Near-IR and UV Light.

    PubMed

    Halasa, Anna; Reva, Igor; Lapinski, Leszek; Nowak, Maciej J; Fausto, Rui

    2016-04-01

    Conformers and photoinduced conformational transformations were studied for monomers of thiazole-2-carboxylic acid (TCA). The matrix-isolation technique and excitations with narrowband near-IR and UV light, tuned in an optical parametric oscillator, were used for this purpose. Form I, with the carboxylic moiety in the trans orientation and with the hydrogen atom of the OH group directed toward the nitrogen atom of the ring, was the most abundant in low-temperature argon or nitrogen matrixes. Conformer II, differing from I by 180° rotation of the OH group around the C-O bond, was also trapped in the matrixes, but in much smaller amount. The abundance of form II was experimentally determined as ∼6% of the total amount of TCA molecules. Selective excitation of I with narrowband near-IR laser light resulted in I → II transformation. This near-IR-induced conformational change was photoreversible: form II converted back to I upon selective excitation of II with near-IR light of different wavelength. Conformational conversions of I into II, or vice versa, were also induced in TCA monomers by narrowband UV excitations at 300 nm (for I → II transformation) and at 305 nm (for II → I transformation). A spontaneous conversion of photogenerated II into the most stable form I was observed for the compound trapped in the matrix at 15 K and kept in the dark. This process was very slow; the estimated half-life time of conformer II was longer than 50 h. Finally, TCA was shown to thermally decompose at room temperature, yielding CO2 and thiazole. PMID:26986193

  8. Schedule-induced Polydipsia in Lines of Rats Selectively Bred for High and Low Ethanol Preference

    PubMed Central

    Gilpin, N. W.; Badia-Elder, N. E.; Elder, R. L.; Stewart, R. B.

    2008-01-01

    Ethanol drinking was assessed in the P/NP, HAD1/LAD1, and HAD2/LAD2 lines of rats under environmental conditions that produce schedule-induced polydipsia. Female rats (n = 8/line), maintained at 85% of free-feeding body weights, underwent daily 1-h sessions during which 45-mg food pellets were delivered every 60 s. Water, 2, 4, 8, 16, or 32% w/v ethanol solution was available from a single bottle for 8 consecutive sessions at each concentration, with blood-ethanol levels (BELs) determined after selected sessions. P and HAD2 rats drank more water and ethanol than their non-preferring counterparts, while HAD1 and LAD1 rats did not differ. Ethanol intake and BELs were positively correlated (r = 0.75) across lines. Finally, rats were allowed 14 daily choice sessions with 8% ethanol and water concurrently available. Water intake generally exceeded ethanol intake in all lines, while P rats drank similar amounts of both fluids. These line differences indicate pleiotropic effects of genes that mediate ethanol intake and schedule-induced behaviors. PMID:18780177

  9. Exploiting oncogene-induced replicative stress for the selective killing of Myc-driven tumors

    PubMed Central

    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

    2016-01-01

    Oncogene-induced replicative stress activates an Atr- and Chk1-dependent response, which has been proposed to be widespread in tumors. We here 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, 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 show abundant levels of replicative stress. Moreover, Chk1 inhibitors are very effective in killing Myc-driven lymphomas. In contrast, pancreatic adenocarcinomas initiated by K-RasG12V show no detectable evidence of replicative stress and are non-responsive to this therapy. Besides cancer, Myc overexpression aggravated the phenotypes of Atr-Seckel mice, revealing that oncogenes can modulate the severity of replicative stress-associated diseases. PMID:22120667

  10. Herbivore-induced plant volatiles mediate host selection by a root herbivore.

    PubMed

    Robert, Christelle A M; Erb, Matthias; Duployer, Marianne; Zwahlen, Claudia; Doyen, Gwladys R; Turlings, Ted C J

    2012-06-01

    In response to herbivore attack, plants mobilize chemical defenses and release distinct bouquets of volatiles. Aboveground herbivores are known to use changes in leaf volatile patterns to make foraging decisions, but it remains unclear whether belowground herbivores also use volatiles to select suitable host plants. We therefore investigated how above- and belowground infestation affects the performance of the root feeder Diabrotica virgifera virgifera, and whether the larvae of this specialized beetle are able to use volatile cues to assess from a distance whether a potential host plant is already under herbivore attack. Diabrotica virgifera larvae showed stronger growth on roots previously attacked by conspecific larvae, but performed more poorly on roots of plants whose leaves had been attacked by larvae of the moth Spodoptera littoralis. Fittingly, D. virgifera larvae were attracted to plants that were infested with conspecifics, whereas they avoided plants that were attacked by S. littoralis. We identified (E)-β-caryophyllene, which is induced by D. virgifera, and ethylene, which is suppressed by S. littoralis, as two signals used by D. virgifera larvae to locate plants that are most suitable for their development. Our study demonstrates that soil-dwelling insects can use herbivore-induced changes in root volatile emissions to identify suitable host plants. PMID:22486361

  11. Effect of domperidone-induced hyperprolactinemia on selected immune parameters in healthy women.

    PubMed

    Rovenský, J; Buc, M; Lojda, Z; Ruzicková, M; Blazícková, S; Rauová, L; Mistina, T; Vigas, M; Lackovic, V

    1995-01-01

    Domperidone, anti-emetic drug, given to healthy female volunteers, induced an elevation of plasma prolactin (PRL) concentration with the peak in 1-4 h. The release of prolactin had a transient stimulating effect on theophylline sensitive T lymphocytes and on concanavalin A induced mitogenic activity, suggesting an enhanced activity of T suppressor lymphocytes. The relative number of CD4+ lymphocytes decreased markedly one hour after domperidone administration and returned to normal values within 2 h (that means 3 h after taking the drug). The number of lymphocytes positive for dipeptidyl peptidase IV exhibited similar transient increase and normalization of activity. No change was observed in the number of CD8+ lymphocytes. The production of interferon by leukocytes treated with Newcastle disease virus was found to be significantly increased 2 h after domperidone administration. The results suggest that prolactin can selectively stimulate some functions of cellular immunity as well as the release of cytokines (IFN). The present study may contribute to the understanding of the role of the immune system in endogenous hyperprolactinemia. PMID:8744700

  12. The effect of selective 5-hydroxytryptamine uptake inhibitors on 5-methoxy-N,N-dimethyltryptamine-induced ejaculation in the rat.

    PubMed Central

    Rényi, L.

    1986-01-01

    The ejaculatory response and the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (3 mg kg-1 i.p.) were studied following acute and repeated treatment of rats with the selective uptake inhibitors of 5-HT, fluoxetine, zimeldine, alaproclate, and citalopram. The oral doses used were based on the respective ED50 values for uptake inhibition. Acute doses of fluoxetine and zimeldine significantly reduced the ejaculatory response when given 48 h before 5-MeODMT. This blockade was prevented by treatment of the rats with the postsynaptic 5-HT receptor antagonist methergoline. An acute dose of fluoxetine given 7 and 14 days before 5-MeODMT significantly enhanced the ejaculatory response. On day 24, the response returned to the control level. Repeated treatment every second day (5 times over 9 days and 10 times over 19 days) with fluoxetine caused a longer blockade of the ejaculatory response and the sensitization of the response came later than after an acute dose. Parallel with the ejaculatory response three other components of the 5-HT behavioural syndrome also decreased significantly. Acute doses of alaproclate and citalopram significantly blocked the ejaculatory response at 1 h, but they failed to affect the response at any other time point after either acute or repeated treatment. Neither did these drugs attentuate the 5-HT syndrome. It is concluded that acute and repeated treatment of rats with different selective 5-HT uptake inhibitors does not produce a common alteration in 5-HT2-receptor functions. PMID:2939912

  13. The effect of selective 5-hydroxytryptamine uptake inhibitors on 5-methoxy-N,N-dimethyltryptamine-induced ejaculation in the rat.

    PubMed

    Rényi, L

    1986-04-01

    The ejaculatory response and the 5-hydroxytryptamine (5-HT) behavioural syndrome induced by 5-methoxy-N,N-dimethyltryptamine (5-MeODMT) (3 mg kg-1 i.p.) were studied following acute and repeated treatment of rats with the selective uptake inhibitors of 5-HT, fluoxetine, zimeldine, alaproclate, and citalopram. The oral doses used were based on the respective ED50 values for uptake inhibition. Acute doses of fluoxetine and zimeldine significantly reduced the ejaculatory response when given 48 h before 5-MeODMT. This blockade was prevented by treatment of the rats with the postsynaptic 5-HT receptor antagonist methergoline. An acute dose of fluoxetine given 7 and 14 days before 5-MeODMT significantly enhanced the ejaculatory response. On day 24, the response returned to the control level. Repeated treatment every second day (5 times over 9 days and 10 times over 19 days) with fluoxetine caused a longer blockade of the ejaculatory response and the sensitization of the response came later than after an acute dose. Parallel with the ejaculatory response three other components of the 5-HT behavioural syndrome also decreased significantly. Acute doses of alaproclate and citalopram significantly blocked the ejaculatory response at 1 h, but they failed to affect the response at any other time point after either acute or repeated treatment. Neither did these drugs attentuate the 5-HT syndrome. It is concluded that acute and repeated treatment of rats with different selective 5-HT uptake inhibitors does not produce a common alteration in 5-HT2-receptor functions. PMID:2939912

  14. Site selection and investigation for subsurface disposal of radioactive wastes in hydraulically induced fractures

    SciTech Connect

    Sun, R.J.

    1980-01-01

    Injection into a thick shale formation of intermediate-level radioactive wastes (specific activity of less than 6 x 10/sup 3/ ..mu..Ci/ml consisting mainly of radionuclides such as strontium and cesium with half-lives of less than 50 years) mixed with cement is a promising and feasible disposal method. Hydraulic fracturing provides openings in the shale to accommodate the wastes. Ion exchange and radionuclide adsorption materials can be added to the grout during mixing to further increase the radionuclide retaining capacity of the grout. After solidification of the grout, the injected wastes become an integral part of the shale formation and thus the wastes will remain at depth and in place as long as the injection zone is not subjected to erosion or dissolution. Problems concerning safety of the disposal method are: (1) potential of inducing vertical fractures; (2) phase separation during and after injections; (3) reliability of methods for determining orientation of induced fractures; (4) possibility of triggering earthquakes; and (5) radionuclides leaching and transporting by ground water. Waste injections are made in multiple-layer injection stages in an injection well. After the first series of injections are made at the greatest depth, the well is plugged by cement at the injection depth. The depth of the second series of injections is located at a suitable distance above the first injection depth. The repeated use of the injection well distributes the cost of construction of injection and monitoring wells over many injections, thereby making hydraulic fracturing and grout injection economically attractive as a method for disposal of radioactive wastes. Theoretical considerations of inducing nearly horizontal bedding-plane fractures in shale and field procedures for site selection, safety, monitoring and operation of radioactive waste disposal are discussed. Case histories are used as examples to demonstrate the theoretical applications and field operations.

  15. Trialkyltin Rexinoid-X Receptor Agonists Selectively Potentiate Thyroid Hormone Induced Programs of Xenopus laevis Metamorphosis.

    PubMed

    Mengeling, Brenda J; Murk, Albertinka J; Furlow, J David

    2016-07-01

    The trialkyltins tributyltin (TBT) and triphenyltin (TPT) can function as rexinoid-X receptor (RXR) agonists. We recently showed that RXR agonists can alter thyroid hormone (TH) signaling in a mammalian pituitary TH-responsive reporter cell line, GH3.TRE-Luc. The prevalence of TBT and TPT in the environment prompted us to test whether they could also affect TH signaling. Both trialkyltins induced the integrated luciferase reporter alone and potentiated TH activation at low doses. Trimethyltin, which is not an RXR agonist, did not. We turned to a simple, robust, and specific in vivo model system of TH action: metamorphosis of Xenopus laevis, the African clawed frog. Using a precocious metamorphosis assay, we found that 1nM TBT and TPT, but not trimethyltin, greatly potentiated the effect of TH treatment on resorption phenotypes of the tail, which is lost at metamorphosis, and in the head, which undergoes extensive remodeling including gill loss. Consistent with these responses, TH-induced caspase-3 activation in the tail was enhanced by cotreatment with TBT. Induction of a transgenic reporter gene and endogenous collagenase 3 (mmp13) and fibroblast-activating protein-α (fap) genes were not induced by TBT alone, but TH induction was significantly potentiated by TBT. However, induction of other TH receptor target genes such as TRβ and deiodinase 3 by TH were not affected by TBT cotreatment. These data indicate that trialkyltins that can function as RXR agonists can selectively potentiate gene expression and resultant morphological programs directed by TH signaling in vivo. PMID:27167774

  16. Clustering and training set selection methods for improving the accuracy of quantitative laser induced breakdown spectroscopy

    NASA Astrophysics Data System (ADS)

    Anderson, Ryan B.; Bell, James F., III; Wiens, Roger C.; Morris, Richard V.; Clegg, Samuel M.

    2012-04-01

    We investigated five clustering and training set selection methods to improve the accuracy of quantitative chemical analysis of geologic samples by laser induced breakdown spectroscopy (LIBS) using partial least squares (PLS) regression. The LIBS spectra were previously acquired for 195 rock slabs and 31 pressed powder geostandards under 7 Torr CO2 at a stand-off distance of 7 m at 17 mJ per pulse to simulate the operational conditions of the ChemCam LIBS instrument on the Mars Science Laboratory Curiosity rover. The clustering and training set selection methods, which do not require prior knowledge of the chemical composition of the test-set samples, are based on grouping similar spectra and selecting appropriate training spectra for the partial least squares (PLS2) model. These methods were: (1) hierarchical clustering of the full set of training spectra and selection of a subset for use in training; (2) k-means clustering of all spectra and generation of PLS2 models based on the training samples within each cluster; (3) iterative use of PLS2 to predict sample composition and k-means clustering of the predicted compositions to subdivide the groups of spectra; (4) soft independent modeling of class analogy (SIMCA) classification of spectra, and generation of PLS2 models based on the training samples within each class; (5) use of Bayesian information criteria (BIC) to determine an optimal number of clusters and generation of PLS2 models based on the training samples within each cluster. The iterative method and the k-means method using 5 clusters showed the best performance, improving the absolute quadrature root mean squared error (RMSE) by ~ 3 wt.%. The statistical significance of these improvements was ~ 85%. Our results show that although clustering methods can modestly improve results, a large and diverse training set is the most reliable way to improve the accuracy of quantitative LIBS. In particular, additional sulfate standards and specifically fabricated

  17. 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. PMID:24960360

  18. Velocity-selective electromagnetically-induced-transparency measurements of potassium Rydberg states

    NASA Astrophysics Data System (ADS)

    Xu, Wenchao; DeMarco, Brian

    2016-01-01

    We demonstrate a velocity selection scheme that mitigates suppression of electromagnetically induced transparency (EIT) by Doppler shifts for coupling wavelengths larger than the probe wavelength. An optical pumping beam counterpropagating with the EIT probe beam transfers atoms between hyperfine states in a velocity-selective fashion. Measurement of the transmitted probe beam synchronous with chopping of the optical pumping beam enables a Doppler-free EIT signal to be detected. Transition frequencies between 5 P1 /2 and n S1 /2 states for n =26 , 27, and 28 in 39K are obtained via EIT spectroscopy in a heated vapor cell with a probe beam stabilized to the 4 S1 /2→5 P1 /2 transition. Using previous high-resolution measurements of the 4 S1 /2→n S1 /2 transitions, we make a determination of the absolute frequency of the 4 S1 /2→5 P1 /2 transition. Our measurement is shifted by 560 MHz from the currently accepted value with a twofold improvement in uncertainty. These measurements will enable novel experiments with Rydberg-dressed ultracold Fermi gases composed of 40K atoms.

  19. Pyrvinium selectively induces apoptosis of lymphoma cells through impairing mitochondrial functions and JAK2/STAT5.

    PubMed

    Xiao, Meifang; Zhang, Liming; Zhou, Yizheng; Rajoria, Pasupati; Wang, Changfu

    2016-01-15

    Targeting mitochondrial respiration has emerged as an attractive therapeutic strategy in blood cancer due to their unique metabolic dependencies. In this study, we show that pyrvinium, a FDA-approved anthelmintic drug, selectively targets lymphoma T-cells though inhibition of mitochondrial functions and JAK2/STAT5. Pyrvinium induces apoptosis of malignant T-cell line Jurkat and primary T-cells from lymphoma patients while sparing T-cells from healthy donors. Increased level of active caspase-3 and decreased levels of Bcl-2 and Mcl-1 were also observed in Jurkat and lymphoma T-cells but not normal T-cells treated with pyrvinium. In addition, pyrvinium impairs mitochondrial functions by inhibit mitochondrial respiration, suppressing mitochondrial respiratory complex I activity, increasing ROS and decreasing ATP levels. However, the effects of pyrvinium were abolished in mitochondrial respiration-deficient Jurkat ρ(0) cells, confirming that pyrvinium acts on lymphoma T-cells via targeting mitochondrial respiration. We further show that lymphoma T-cells derived from patients depend more on mitochondrial respiration than normal T-cells, and this explains the selective toxicity of pyrvinium in lymphoma versus normal T-cells. Finally, we demonstrate that pyrvinium also suppresses JAK2/STAT5 signaling pathway in Jurkat cells. Our study suggests that pyrvinium is a useful addition to T-cell lymphoma treatment, and emphasizes the potential therapeutic value of the differences in the mitochondrial characteristics between malignant and normal T-cells in blood cancer. PMID:26707639

  20. Maskless micro/nanofabrication on GaAs surface by friction-induced selective etching

    NASA Astrophysics Data System (ADS)

    Tang, Peng; Yu, Bingjun; Guo, Jian; Song, Chenfei; Qian, Linmao

    2014-02-01

    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.

  1. Maskless micro/nanofabrication on GaAs surface by friction-induced selective etching.

    PubMed

    Tang, Peng; Yu, Bingjun; Guo, Jian; Song, Chenfei; Qian, Linmao

    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

  2. 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

  3. 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. PMID:18441293

  4. 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

  5. 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.

  6. An inexpensive technique for the time resolved laser induced plasma spectroscopy

    NASA Astrophysics Data System (ADS)

    Ahmed, Rizwan; Ahmed, Nasar; Iqbal, J.; Aslam Baig, M.

    2016-08-01

    We present an efficient and inexpensive method for calculating the time resolved emission spectrum from the time integrated spectrum by monitoring the time evolution of neutral and singly ionized species in the laser produced plasma. To validate our assertion of extracting time resolved information from the time integrated spectrum, the time evolution data of the Cu II line at 481.29 nm and the molecular bands of AlO in the wavelength region (450-550 nm) have been studied. The plasma parameters were also estimated from the time resolved and time integrated spectra. A comparison of the results clearly reveals that the time resolved information about the plasma parameters can be extracted from the spectra registered with a time integrated spectrograph. Our proposed method will make the laser induced plasma spectroscopy robust and a low cost technique which is attractive for industry and environmental monitoring.

  7. Time-dependent effects of rapamycin on consolidation of predator stress-induced hyperarousal.

    PubMed

    Fifield, Kathleen; Hebert, Mark; Williams, Kimberly; Linehan, Victoria; Whiteman, Jesse D; Mac Callum, Phillip; Blundell, Jacqueline

    2015-06-01

    Previous studies have indicated that rapamycin, a potent inhibitor of the mammalian target of rapamycin (mTOR) pathway, blocks consolidation of shock-induced associative fear memories. Moreover, rapamycin's block of associative fear memories is time-dependent. It is unknown, however, if rapamycin blocks consolidation of predator stress-induced non-associative fear memories. Furthermore, the temporal pattern of mTOR activation following predator stress is unknown. Thus, the goal of the current studies was to determine if rapamycin blocks consolidation of predator stress-induced fear memories and if so, whether rapamycin's effect is time-dependent. Male rats were injected systemically with rapamycin at various time points following predator stress. Predator stress involves an acute, unprotected exposure of a rat to a cat, which causes long-lasting non-associative fear memories manifested as generalized hyperarousal and increased anxiety-like behaviour. We show that rapamycin injected immediately after predator stress blocked consolidation of stress-induced startle. However, rapamycin injected 9, 24 or 48h post predator stress potentiated stress-induced startle. Consistent with shock-induced associative fear memories, we show that mTOR signalling is essential for consolidation of predator stress-induced hyperarousal. However, unlike shock-induced fear memories, a second, persistent, late phase mTOR-dependent process following predator stress actually dampens startle. Consistent with previous findings, our data support the potential role for rapamycin in treatment of stress related disorders such as posttraumatic stress disorder. However, our data suggest timing of rapamycin administration is critical. PMID:25746515

  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. 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.

  10. Nucleic acid determinants for selective deamination of DNA over RNA by activation-induced deaminase.

    PubMed

    Nabel, Christopher S; Lee, Jae W; Wang, Laura C; Kohli, Rahul M

    2013-08-27

    Activation-induced deaminase (AID), a member of the larger AID/APOBEC family, is the key catalyst in initiating antibody somatic hypermutation and class-switch recombination. The DNA deamination model accounting for AID's functional role posits that AID deaminates genomic deoxycytosine bases within the immunoglobulin locus, activating downstream repair pathways that result in antibody maturation. Although this model is well supported, the molecular basis for AID's selectivity for DNA over RNA remains an open and pressing question, reflecting a broader need to elucidate how AID/APOBEC enzymes engage their substrates. To address these questions, we have synthesized a series of chimeric nucleic acid substrates and characterized their reactivity with AID. These chimeric substrates feature targeted variations at the 2'-position of nucleotide sugars, allowing us to interrogate the steric and conformational basis for nucleic acid selectivity. We demonstrate that modifications to the target nucleotide can significantly alter AID's reactivity. Strikingly, within a substrate that is otherwise DNA, a single RNA-like 2'-hydroxyl substitution at the target cytosine is sufficient to compromise deamination. Alternatively, modifications that favor a DNA-like conformation (or sugar pucker) are compatible with deamination. AID's closely related homolog APOBEC1 is similarly sensitive to RNA-like substitutions at the target cytosine. Inversely, with unreactive 2'-fluoro-RNA substrates, AID's deaminase activity was rescued by introducing a trinucleotide DNA patch spanning the target cytosine and two nucleotides upstream. These data suggest a role for nucleotide sugar pucker in explaining the molecular basis for AID's DNA selectivity and, more generally, suggest how other nucleic acid-modifying enzymes may distinguish DNA from RNA. PMID:23942124

  11. Optimizing the salt-induced activation of enzymes in organic solvents: effects of lyophilization time and water content.

    PubMed

    Ru, M T; Dordick, J S; Reimer, J A; Clark, D S

    1999-04-20

    The addition of simple inorganic salts to aqueous enzyme solutions prior to lyophilization results in a dramatic activation of the dried powder in organic media relative to enzyme with no added salt. Activation of both the serine protease subtilisin Carlsberg and lipase from Mucor javanicus resulting from lyophilization in the presence of KCl was highly sensitive to the lyophilization time and water content of the sample. Specifically, for a preparation containing 98% (w/w) KCl, 1% (w/w) phosphate buffer, and 1% (w/w) enzyme, varying the lyophilization time showed a direct correlation between water content and activity up to an optimum, beyond which the activity decreased with increasing lyophilization time. The catalytic efficiency in hexane varied as much as 13-fold for subtilisin Carlsberg and 11-fold for lipase depending on the lyophilization time. This dependence was apparently a consequence of including the salt, as a similar result was not observed for the enzyme freeze-dried without KCl. In the case of subtilisin Carlsberg, the salt-induced optimum value of kcat/Km for transesterification in hexane was over 20,000-fold higher than that for salt-free enzyme, a substantial improvement over the previously reported enhancement of 3750-fold (Khmelnitsky, 1994). As was found previously for pure enzyme, the salt-activated enzyme exhibited greatest activity when lyophilized from a solution of pH equal to the pH for optimal activity in water. The active-site content of the lyophilized enzyme samples also depended upon lyophilization time and inclusion of salt, with opposite trends in this dependence observed for the solvents hexane and tetrahydrofuran. Finally, substrate selectivity experiments suggested that mechanism(s) other than selective partitioning of substrate into the enzyme-salt matrix are responsible for salt-induced activation of enzymes in organic solvents. PMID:10099600

  12. Optimizing the salt-induced activation of enzymes in organic solvents: Effects of lyophilization time and water content

    SciTech Connect

    Ru, M.T.; Reimer, J.A.; Clark, D.S.; Dordick, J.S.

    1999-04-20

    The addition of simple inorganic salts to aqueous enzyme solutions prior to lyophilization results in a dramatic activation of the dried powder in organic media relative to enzyme with no added salt. Activation of both the serine protease subtilisin Carlsberg and lipase from Mucor javanicus resulting from lyophilization in the presence of KCl was highly sensitive to the lyophilization time and water content of the sample. Specifically, for a preparation containing 98% (w/w) KCl, 1% (w/w) phosphate buffer, and 1% (w/w) enzyme, varying the lyophilization time showed a direct correlation between water content and activity up to an optimum, beyond which the activity decreased with increasing lyophilization time. The catalytic efficiency in hexane varied as much as 13-fold for subtilisin Carlsberg and 11-fold for lipase depending on the lyophilization time. This dependence was apparently a consequence of including the salt, as a similar result was not observed for the enzyme freeze-dried without KCl. In the case of subtilisin Carlsberg, the salt-induced optimum value of k{sub cat}/K{sub m} for transesterification in hexane was over 20,000-fold higher than that for salt-free enzyme, a substantial improvement over the previously reported enhancement of 3750-fold. As was found previously for pure enzyme, the salt-activated enzyme exhibited greatest activity when lyophilized from a solution of pH equal to the pH for optimal activity in water. The active-site content of the lyophilized enzyme samples also depended upon lyophilization time and inclusion of salt, with opposite trends in this dependence observed for the solvents hexane and tetrahydrofuran. Finally, substrate selectivity experiments suggested that mechanism(s) other than selective partitioning of substrate into the enzyme-salt matrix are responsible for salt-induced activation of enzymes in organic solvents.

  13. Maitotoxin-induced cell death cascade in bovine aortic endothelial cells: divalent cation specificity and selectivity.

    PubMed

    Wisnoskey, Brian J; Estacion, Mark; Schilling, William P

    2004-08-01

    The maitotoxin (MTX)-induced cell death cascade in bovine aortic endothelial cells (BAECs), a model for Ca(2+) overload-induced toxicity, reflects three sequential changes in plasmalemmal permeability. MTX initially activates Ca(2+)-permeable, nonselective cation channels (CaNSC) and causes a massive increase in cytosolic free Ca(2+) concentration ([Ca(2+)](i)). This is followed by the opening of large endogenous cytolytic/oncotic pores (COP) that allow molecules <800 Da to enter the cell. The cells then lyse not by rupture of the plasmalemma but through the activation of a "death" channel that lets large proteins (e.g., 140-160 kDa) leave the cell. These changes in permeability are accompanied by the formation of membrane blebs. In this study, we took advantage of the well-known differences in affinity of various Ca(2+)-binding proteins for Ca(2+) and Sr(2+) vs. Ba(2+) to probe their involvement in each phase of the cell death cascade. Using fluorescence techniques at the cell population level (cuvette-based) and at the single-cell level (time-lapse videomicroscopy), we found that the replacement of Ca(2+) with either Sr(2+) or Ba(2+) delayed both MTX-induced activation of COP, as indicated by the uptake of ethidium bromide, and subsequent cell lysis, as indicated by the uptake of propidium iodide or the release of cell-associated green fluorescent protein. MTX-induced responses were mimicked by ionomycin and were significantly delayed in BAPTA-loaded cells. Experiments at the single-cell level revealed that Ba(2+) not only delayed the time to cell lysis but also caused desynchronization of the lytic phase. Last, membrane blebs, which were numerous and spherical in Ca(2+)-containing solutions, were poorly defined and greatly reduced in number in the presence of Ba(2+). Taken together, these results suggest that intracellular high-affinity Ca(2+)-binding proteins are involved in the MTX-induced changes in plasmalemmal permeability that are responsible for cell

  14. The optimal timing of stimulation to induce long-lasting positive effects on episodic memory in physiological aging.

    PubMed

    Manenti, Rosa; Sandrini, Marco; Brambilla, Michela; Cotelli, Maria

    2016-09-15

    Episodic memory displays the largest degree of age-related decline. A noninvasive brain stimulation technique that can be used to modulate memory in physiological aging is transcranial Direct Current Stimulation (tDCS). However, an aspect that has not been adequately investigated in previous studies is the optimal timing of stimulation to induce long-lasting positive effects on episodic memory function. Our previous studies showed episodic memory enhancement in older adults when anodal tDCS was applied over the left lateral prefrontal cortex during encoding or after memory consolidation with or without a contextual reminder. Here we directly compared the two studies to explore which of the tDCS protocols would induce longer-lasting positive effects on episodic memory function in older adults. In addition, we aimed to determine whether subjective memory complaints would be related to the changes in memory performance (forgetting) induced by tDCS, a relevant issue in aging research since individuals with subjective memory complaints seem to be at higher risk of later memory decline. The results showed that anodal tDCS applied after consolidation with a contextual reminder induced longer-lasting positive effects on episodic memory, conceivably through reconsolidation, than anodal tDCS during encoding. Furthermore, we reported, providing new data, a moderate negative correlation between subjective memory complaints and forgetting when anodal tDCS was applied after consolidation with a contextual reminder. This study sheds light on the best-suited timing of stimulation to induce long-lasting positive effects on memory function and might help the clinicians to select the most effective tDCS protocol to prevent memory decline. PMID:27185737

  15. Responses of selected birch (Betula pendula Roth) clones to ozone change over time.

    PubMed

    Oksanen, E.

    2003-06-01

    A long-term free air ozone fumigation experiment was conducted to study changes in physiological ozone responses during tree ontogeny and exposure time in ozone sensitive and tolerant clones of European white birch (Betula pendula Roth), originated from south and central Finland. The trees were grown in soil in natural microclimatic conditions under ambient ozone (control) and 1.4-1.7 x ambient (elevated) ozone from May 1996 to October 2001, and were measured for stem and foliage growth, net photosynthesis, stomatal conductance, stomatal density, visible injuries, foliar starch content and bud formation. After 6 years of exposure, the magnitude of ozone-induced growth reductions in the sensitive clone was 12-48% (significant difference), levels similar or greater than those reported earlier for 2- and 3-year-old saplings undergoing shorter exposures. In the tolerant clone, growth of these larger trees was reduced by 1-38% (significant difference in stem volume), although the saplings had previously been unaffected. In both clones, ozone stress led to significantly reduced leaf-level net photosynthesis but significantly increased stomatal conductance rates during the late summer, resulting in a lower carbon gain for bud formation and the onset of visible foliar injuries. Increasing ozone sensitivity with duration of exposure was explained by a change in growth form (relatively reduced foliage mass), a lower photosynthesis to stomatal conductance ratio during the late summer, and deleterious carry-over effects arising from the reduced number of over-wintering buds. PMID:12803615

  16. Dynamics of Time Delay-Induced Multiple Synchronous Behaviors in Inhibitory Coupled Neurons

    PubMed Central

    Gu, Huaguang; Zhao, Zhiguo

    2015-01-01

    The inhibitory synapse can induce synchronous behaviors different from the anti-phase synchronous behaviors, which have been reported in recent studies. In the present paper, synchronous behaviors are investigated in the motif model composed of reciprocal inhibitory coupled neurons with endogenous bursting and time delay. When coupling strength is weak, synchronous behavior appears at a single interval of time delay within a bursting period. When coupling strength is strong, multiple synchronous behaviors appear at different intervals of time delay within a bursting period. The different bursting patterns of synchronous behaviors, and time delays and coupling strengths that can induce the synchronous bursting patterns can be well interpreted by the dynamics of the endogenous bursting pattern of isolated neuron, which is acquired by the fast-slow dissection method, combined with the inhibitory coupling current. For an isolated neuron, when a negative impulsive current with suitable strength is applied at different phases of the bursting, multiple different bursting patterns can be induced. For a neuron in the motif, the inhibitory coupling current, of which the application time and strength is modulated by time delay and coupling strength, can cause single or multiple synchronous firing patterns like the negative impulsive current when time delay and coupling strength is suitable. The difference compared to the previously reported multiple synchronous behaviors that appear at time delays wider than a period of the endogenous firing is discussed. The results present novel examples of synchronous behaviors in the neuronal network with inhibitory synapses and provide a reasonable explanation. PMID:26394224

  17. TRIASSIC: the Time-Resolved Industrial Alpha-Source Scanning Induced Current microscope

    NASA Astrophysics Data System (ADS)

    Pallone, Arthur

    Time-resolved ion beam induced current (TRIBIC) microscopy yields useful information such as carrier mobility and lifetimes in semiconductors and defect locations in devices; however, traditional TRIBIC uses large, expensive particle accelerators that require specialized training to operate and maintain. The time-resolved industrial alpha-source scanning induced current (TRIASSIC) microscope transforms TRIBIC by replacing the particle accelerator facility with an affordable, tabletop instrument suitable for use in research and education at smaller colleges and universities. I will discuss the development of, successes with, setbacks to and future directions for TRIASSIC.

  18. Selective and potent Akt inhibition triggers anti-myeloma activities and enhances fatal endoplasmic reticulum stress induced by proteasome inhibition

    PubMed Central

    Mimura, Naoya; Hideshima, Teru; Shimomura, Toshiyasu; Suzuki, Rikio; Ohguchi, Hiroto; Rizq, Ola; Kikuchi, Shohei; Yoshida, Yasuhiro; Cottini, Francesca; Jakubikova, Jana; Cirstea, Diana; Gorgun, Gullu; Minami, Jiro; Tai, Yu-Tzu; Richardson, Paul G.; Utsugi, Teruhiro; Iwama, Atsushi; Anderson, Kenneth C.

    2014-01-01

    The PI3K/Akt pathway plays a crucial role in the pathogenesis of multiple myeloma (MM) in the bone marrow (BM) milieu. However, efficacy of selective and potent Akt inhibition has not yet been fully elucidated. In this study, we therefore examined the biologic impact of selective and potent Akt inhibition by a novel allosteric inhibitor TAS-117. TAS-117 induced significant growth inhibition, associated with downregulation of phosphorylated Akt (p-Akt), selectively in MM cell lines with high baseline p-Akt. Cytotoxicity of TAS-117 was also observed in patients MM cells, but not in normal peripheral blood mononuclear cells. Importantly, TAS-117 induced significant cytotoxicity in MM cells even in the presence of BM stromal cells, associated with inhibition of IL-6 secretion. Oral administration of TAS-117 significantly inhibited human MM cell growth in murine xenograft models. TAS-117 triggered apoptosis and autophagy, as well as induction of endoplasmic reticulum (ER) stress response with minimal expression of CHOP, a fatal ER-stress marker. Importantly, TAS-117 enhanced bortezomib-induced cytotoxicity, associated with increased CHOP and PARP cleavage and blockade of bortezomib-induced p-Akt, suggesting that TAS-117 augments bortezomib-induced ER stress and apoptotic signaling. Carfilzomib-induced cytotoxicity was similarly enhanced by TAS-117. Importantly, TAS-117 enhanced bortezomib-induced cytotoxicity in vivo, associated with prolonged host survival. Our results show that selective and potent Akt inhibition by TAS-117 triggers anti-MM activities in vitro and in vivo, as well as enhances cytotoxicity of proteasome inhibition, providing the preclinical framework for clinical evaluation of selective Akt inhibitors, alone and in combination with proteasome inhibitors in MM. PMID:24934808

  19. Selective and potent Akt inhibition triggers anti-myeloma activities and enhances fatal endoplasmic reticulum stress induced by proteasome inhibition.

    PubMed

    Mimura, Naoya; Hideshima, Teru; Shimomura, Toshiyasu; Suzuki, Rikio; Ohguchi, Hiroto; Rizq, Ola; Kikuchi, Shohei; Yoshida, Yasuhiro; Cottini, Francesca; Jakubikova, Jana; Cirstea, Diana; Gorgun, Gullu; Minami, Jiro; Tai, Yu-Tzu; Richardson, Paul G; Utsugi, Teruhiro; Iwama, Atsushi; Anderson, Kenneth C

    2014-08-15

    The PI3K/Akt pathway plays a crucial role in the pathogenesis of multiple myeloma (MM) in the bone marrow (BM) milieu. However, efficacy of selective and potent Akt inhibition has not yet been fully elucidated. In this study, we, therefore, examined the biologic impact of selective and potent Akt inhibition by a novel allosteric inhibitor TAS-117. TAS-117 induced significant growth inhibition, associated with downregulation of phosphorylated Akt (p-Akt), selectively in MM cell lines with high baseline p-Akt. Cytotoxicity of TAS-117 was also observed in patient MM cells, but not in normal peripheral blood mononuclear cells. Importantly, TAS-117 induced significant cytotoxicity in MM cells even in the presence of BM stromal cells, associated with inhibition of IL6 secretion. Oral administration of TAS-117 significantly inhibited human MM cell growth in murine xenograft models. TAS-117 triggered apoptosis and autophagy, as well as induction of endoplasmic reticulum (ER) stress response with minimal expression of C/EBP homologous protein (CHOP), a fatal ER stress marker. Importantly, TAS-117 enhanced bortezomib-induced cytotoxicity, associated with increased CHOP and PARP cleavage and blockade of bortezomib-induced p-Akt, suggesting that TAS-117 augments bortezomib-induced ER stress and apoptotic signaling. Carfilzomib-induced cytotoxicity was similarly enhanced by TAS-117. Importantly, TAS-117 enhanced bortezomib-induced cytotoxicity in vivo, associated with prolonged host survival. Our results show that selective and potent Akt inhibition by TAS-117 triggers anti-MM activities in vitro and in vivo, as well as enhances cytotoxicity of proteasome inhibition, providing the preclinical framework for clinical evaluation of selective Akt inhibitors, alone and in combination with proteasome inhibitors in MM. PMID:24934808

  20. Novel space-time trellis codes for free-space optical communications using transmit laser selection.

    PubMed

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

    2015-09-21

    In this paper, the deployment of novel space-time trellis codes (STTCs) with transmit laser selection (TLS) for free-space optical (FSO) communication systems using intensity modulation and direct detection (IM/DD) over atmospheric turbulence and misalignment fading channels is presented. Combining TLS and STTC with rate 1 bit/(s · Hz), a new code design criterion based on the use of the largest order statistics is here proposed for multiple-input/single-output (MISO) FSO systems in order to improve the diversity order gain by properly chosing the transmit lasers out of the available L lasers. Based on a pairwise error probability (PEP) analysis, closed-form asymptotic bit error-rate (BER) expressions in the range from low to high signal-to-noise ratio (SNR) 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. Obtained results show diversity orders of 2L and 3L when simple two-state and four-state STTCs are considered, respectively. Simulation results are further demonstrated to confirm the analytical results. PMID:26406626

  1. 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. PMID:23089871

  2. Approach towards sensor placement, selection and fusion for real-time condition monitoring of precision machines

    NASA Astrophysics Data System (ADS)

    Er, Poi Voon; Teo, Chek Sing; Tan, Kok Kiong

    2016-02-01

    Moving mechanical parts in a machine will inevitably generate vibration profiles reflecting its operating conditions. Vibration profile analysis is a useful tool for real-time condition monitoring to avoid loss of performance and unwanted machine downtime. In this paper, we propose and validate an approach for sensor placement, selection and fusion for continuous machine condition monitoring. The main idea is to use a minimal series of sensors mounted at key locations of a machine to measure and infer the actual vibration spectrum at a critical point where it is not suitable to mount a sensor. The locations for sensors' mountings which are subsequently used for vibration inference are identified based on sensitivity calibration at these locations moderated with normalized Fisher Information (NFI) associated with the measurement quality of the sensor at that location. Each of the identified sensor placement location is associated with one or more sensitive frequencies for which it ranks top in terms of the moderated sensitivities calibrated. A set of Radial Basis Function (RBF), each of them associated with a range of sensitive frequencies, is used to infer the vibration at the critical point for that frequency. The overall vibration spectrum of the critical point is then fused from these components. A comprehensive set of experimental results for validation of the proposed approach is provided in the paper.

  3. Time-dependent wave selection for information processing in excitable media

    NASA Astrophysics Data System (ADS)

    Stevens, William M.; Adamatzky, Andrew; Jahan, Ishrat; Costello, Ben de Lacy

    2012-06-01

    We demonstrate an improved technique for implementing logic circuits in light-sensitive chemical excitable media. The technique makes use of the constant-speed propagation of waves along defined channels in an excitable medium based on the Belousov-Zhabotinsky reaction, along with the mutual annihilation of colliding waves. What distinguishes this work from previous work in this area is that regions where channels meet at a junction can periodically alternate between permitting the propagation of waves and blocking them. These valvelike areas are used to select waves based on the length of time that it takes waves to propagate from one valve to another. In an experimental implementation, the channels that make up the circuit layout are projected by a digital projector connected to a computer. Excitable channels are projected as dark areas and unexcitable regions as light areas. Valves alternate between dark and light: Every valve has the same period and phase, with a 50% duty cycle. This scheme can be used to make logic gates based on combinations of or and and-not operations, with few geometrical constraints. Because there are few geometrical constraints, compact circuits can be implemented. Experimental results from an implementation of a four-bit input, two-bit output integer square root circuit are given.

  4. Unilateral deactivation of macaque dorsolateral prefrontal cortex induces biases in stimulus selection.

    PubMed

    Johnston, Kevin; Lomber, Stephen G; Everling, Stefan

    2016-03-01

    Following unilateral brain injury, patients are often unable to detect a stimulus presented in the contralesional field when another is presented simultaneously ipsilesionally. This phenomenon has been referred to as extinction and has been conceptualized as a deficit in selective attention. Although most commonly observed following damage to posterior parietal areas, extinction has been observed following lesions of prefrontal cortex (PFC) in both humans and nonhuman primates. To date, most studies in nonhuman primates have examined lesions of multiple PFC subregions, including the frontal eye fields (FEF). Theoretical accounts of attentional disturbances from human patients, however, also implicate other PFC areas, including the middle frontal gyrus. Here, we investigated the effects of deactivating PFC areas anterior to the FEF on stimulus selection using a free-choice task. Macaque monkeys were presented with two peripheral stimuli appearing either simultaneously, or at varying stimulus onset asynchronies, and their performance was evaluated during unilateral cryogenic deactivation of part of dorsolateral prefrontal cortex or the cortex lining the caudal principal sulcus, the likely homologue of the human middle frontal gyrus. A decreased proportion of saccades was made to stimuli presented in the hemifield contralateral to the deactivated PFC. We also observed increases in reaction times to contralateral stimuli and decreases for stimuli presented in the hemifield ipsilateral to the deactivated hemisphere. In both cases, these results were greatest when both PFC subregions were deactivated. These findings demonstrate that selection biases result from PFC deactivation and support a role of dorsolateral prefrontal subregions anterior to FEF in stimulus selection. PMID:26792881

  5. Different Effects of Three Selected Lactobacillus Strains in Dextran Sulfate Sodium-Induced Colitis in BALB/c Mice

    PubMed Central

    Cui, Yi; Wei, Hongyun; Lu, Fanggen; Liu, Xiaowei; Liu, Deliang; Gu, Li; Ouyang, Chunhui

    2016-01-01

    Aim To analyze the changes of different Lactobacillus species in ulcerative colitis patients and to further assess the therapeutic effects of selected Lactobacillus strains on dextran sulfate sodium (DSS)-induced experimental colitis in BALB/c mice. Methods Forty-five active ulcerative colitis (UC) patients and 45 population-based healthy controls were enrolled. Polymerase chain reaction (PCR) amplification and real-time PCR were performed for qualitative and quantitative analyses, respectively, of the Lactobacillus species in UC patients. Three Lactobacillus strains from three species were selected to assess the therapeutic effects on experimental colitis. Sixty 8-week-old BALB/c mice were divided into six groups. The five groups that had received DSS were administered normal saline, mesalazine, L. fermentum CCTCC M206110 strain, L. crispatus CCTCC M206119 strain, or L. plantarum NCIMB8826 strain. We assessed the severity of colitis based on disease activity index (DAI), body weight loss, colon length, and histologic damage. Results The detection rate of four of the 11 Lactobacillus species decreased significantly (P < 0.05), and the detection rate of two of the 11 Lactobacillus species increased significantly (P < 0.05) in UC patients. Relative quantitative analysis revealed that eight Lactobacillus species declined significantly in UC patients (P < 0.05), while three Lactobacillus species increased significantly (P < 0.05). The CCTCC M206110 treatment group had less weight loss and colon length shortening, lower DAI scores, and lower histologic scores (P < 0.05), while the CCTCC M206119 treatment group had greater weight loss and colon length shortening, higher histologic scores, and more severe inflammatory infiltration (P < 0.05). NCIMB8826 improved weight loss and colon length shortening (P < 0.05) with no significant influence on DAI and histologic damage in the colitis model. Conclusions Administration of an L. crispatus CCTCC M206119 supplement aggravated

  6. A Selective Orexin-1 Receptor Antagonist Attenuates Stress-Induced Hyperarousal without Hypnotic Effects

    PubMed Central

    Yun, Sujin; Johnson, Philip L.; Shekhar, Anantha; Fitz, Stephanie D.; Shireman, Brock T.; Lebold, Terry P.; Nepomuceno, Diane; Lord, Brian; Wennerholm, Michelle; Shelton, Jonathan; Carruthers, Nicholas; Lovenberg, Timothy; Dugovic, Christine

    2015-01-01

    Orexins (OXs) are peptides produced by perifornical (PeF) and lateral hypothalamic neurons that exert a prominent role in arousal-related processes, including stress. A critical role for the orexin-1 receptor (OX1R) in complex emotional behavior is emerging, such as overactivation of the OX1R pathway being associated with panic or anxiety states. Here we characterize a brain-penetrant, selective, and high-affinity OX1R antagonist, compound 56 [N-({3-[(3-ethoxy-6-methylpyridin-2-yl)carbonyl]-3-azabicyclo[4.1.0]hept-4-yl}methyl)-5-(trifluoromethyl)pyrimidin-2-amine]. Ex vivo receptor binding studies demonstrated that, after subcutaneous administration, compound 56 crossed the blood-brain barrier and occupied OX1Rs in the rat brain at lower doses than standard OX1R antagonists GSK-1059865 [5-bromo-N-({1-[(3-fluoro-2-methoxyphenyl)carbonyl]-5-methylpiperidin-2-yl}methyl)pyridin-2-amine], SB-334867 [1-(2-methyl-1,3-benzoxazol-6-yl)-3-(1,5-naphthyridin-4-yl)urea], and SB-408124 [1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea]. Although compound 56 did not alter spontaneous sleep in rats and in wild-type mice, its administration in orexin-2 receptor knockout mice selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. In a rat model of psychological stress induced by cage exchange, the OX1R antagonist prevented the prolongation of sleep onset without affecting sleep duration. In a rat model of panic vulnerability (involving disinhibition of the PeF OX region) to threatening internal state changes (i.e., intravenous sodium lactate infusion), compound 56 attenuated sodium lactate–induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. In conclusion, OX1R antagonism represents a novel therapeutic strategy for the treatment of various psychiatric disorders associated with stress or hyperarousal states. PMID:25583879

  7. A selective orexin-1 receptor antagonist attenuates stress-induced hyperarousal without hypnotic effects.

    PubMed

    Bonaventure, Pascal; Yun, Sujin; Johnson, Philip L; Shekhar, Anantha; Fitz, Stephanie D; Shireman, Brock T; Lebold, Terry P; Nepomuceno, Diane; Lord, Brian; Wennerholm, Michelle; Shelton, Jonathan; Carruthers, Nicholas; Lovenberg, Timothy; Dugovic, Christine

    2015-03-01

    Orexins (OXs) are peptides produced by perifornical (PeF) and lateral hypothalamic neurons that exert a prominent role in arousal-related processes, including stress. A critical role for the orexin-1 receptor (OX1R) in complex emotional behavior is emerging, such as overactivation of the OX1R pathway being associated with panic or anxiety states. Here we characterize a brain-penetrant, selective, and high-affinity OX1R antagonist, compound 56 [N-({3-[(3-ethoxy-6-methylpyridin-2-yl)carbonyl]-3-azabicyclo[4.1.0]hept-4-yl}methyl)-5-(trifluoromethyl)pyrimidin-2-amine]. Ex vivo receptor binding studies demonstrated that, after subcutaneous administration, compound 56 crossed the blood-brain barrier and occupied OX1Rs in the rat brain at lower doses than standard OX1R antagonists GSK-1059865 [5-bromo-N-({1-[(3-fluoro-2-methoxyphenyl)carbonyl]-5-methylpiperidin-2-yl}methyl)pyridin-2-amine], SB-334867 [1-(2-methyl-1,3-benzoxazol-6-yl)-3-(1,5-naphthyridin-4-yl)urea], and SB-408124 [1-(6,8-difluoro-2-methylquinolin-4-yl)-3-[4-(dimethylamino)phenyl]urea]. Although compound 56 did not alter spontaneous sleep in rats and in wild-type mice, its administration in orexin-2 receptor knockout mice selectively promoted rapid eye movement sleep, demonstrating target engagement and specific OX1R blockade. In a rat model of psychological stress induced by cage exchange, the OX1R antagonist prevented the prolongation of sleep onset without affecting sleep duration. In a rat model of panic vulnerability (involving disinhibition of the PeF OX region) to threatening internal state changes (i.e., intravenous sodium lactate infusion), compound 56 attenuated sodium lactate-induced panic-like behaviors and cardiovascular responses without altering baseline locomotor or autonomic activity. In conclusion, OX1R antagonism represents a novel therapeutic strategy for the treatment of various psychiatric disorders associated with stress or hyperarousal states. PMID:25583879

  8. Photothermolysis by laser-induced microbubbles generated around gold nanorod clusters selectively formed in leukemia cells

    NASA Astrophysics Data System (ADS)

    Lapotko, Dmitri; Lukianova-Hleb, Ekaterina; Zhdanok, Sergei; Rostro, Betty; Simonette, Rebecca; Hafner, Jason; Konopleva, Marina; Andreeff, Michael; Conjusteau, Andre; Oraevsky, Alexander

    2008-02-01

    In an effort of developing clinical LANTCET (laser-activated nano-thermolysis as cell elimination technology) we achieved selective destruction of individual tumor cells through laser generation of vapor microbubbles around clusters of light absorbing gold nanorods (GNR) selectively formed in target tumor cells. Among all gold nanoparticles, nanorods offer the highest optical absorption in the near-infrared. We applied covalent conjugates of gold nanorods with targeting vectors such as monoclonal antibodies CD33 (specific for Acute Myeloid Leukemia), while GNR conjugates with polyethylene-glycol (PEG) were used as nonspecific targeting control. GNR clusters were formed inside the tumor cells at 37 °C due to endocytosis of large concentration of nanorods accumulated on the surface of tumor cells targeted at 4 °C. Formation of GNR clusters significantly reduces the threshold of tumor cell damage making LANTCET safe for normal cells. Appearance of GNR clusters was verified directly with optical resonance scattering microscopy. LANTCET was performed in vitro with living cells of (1) model myeloid K562 cells (CD33 positive), (2) primary human bone marrow CD33-positive blast cells from patients diagnosed with acute myeloid leukemia. Laser-induced microbubbles were generated and detected with a photothermal microscope equipped with a tunable Ti-Sa pulsed laser. GNT cluster formation caused a 100-fold decrease in the threshold optical fluence for laser microbubble generation in tumor cells compared with that in normal cells under the same targeting and irradiation conditions. Combining imaging based on resonance optical scattering with photothermal imaging of microbubbles, we developed a method for detection, image-guided treatment and monitoring of LANTCET. Pilot experiments were performed in flow mode bringing LANTCET closer to reality of clinical procedure of purging tumor cells from bone marrow grafts.

  9. Time delay induced different synchronization patterns in repulsively coupled chaotic oscillators

    NASA Astrophysics Data System (ADS)

    Yao, Chenggui; Yi, Ming; Shuai, Jianwei

    2013-09-01

    Time delayed coupling plays a crucial role in determining the system's dynamics. We here report that the time delay induces transition from the asynchronous state to the complete synchronization (CS) state in the repulsively coupled chaotic oscillators. In particular, by changing the coupling strength or time delay, various types of synchronous patterns, including CS, antiphase CS, antiphase synchronization (ANS), and phase synchronization, can be generated. In the transition regions between different synchronous patterns, bistable synchronous oscillators can be observed. Furthermore, we show that the time-delay-induced phase flip bifurcation is of key importance for the emergence of CS. All these findings may light on our understanding of neuronal synchronization and information processing in the brain.

  10. Effects of Spring Temperatures on the Strength of Selection on Timing of Reproduction in a Long-Distance Migratory Bird

    PubMed Central

    Visser, Marcel E.; Gienapp, Phillip; Husby, Arild; Morrisey, Michael; de la Hera, Iván; Pulido, Francisco; Both, Christiaan

    2015-01-01

    Climate change has differentially affected the timing of seasonal events for interacting trophic levels, and this has often led to increased selection on seasonal timing. Yet, the environmental variables driving this selection have rarely been identified, limiting our ability to predict future ecological impacts of climate change. Using a dataset spanning 31 years from a natural population of pied flycatchers (Ficedula hypoleuca), we show that directional selection on timing of reproduction intensified in the first two decades (1980–2000) but weakened during the last decade (2001–2010). Against expectation, this pattern could not be explained by the temporal variation in the phenological mismatch with food abundance. We therefore explored an alternative hypothesis that selection on timing was affected by conditions individuals experience when arriving in spring at the breeding grounds: arriving early in cold conditions may reduce survival. First, we show that in female recruits, spring arrival date in the first breeding year correlates positively with hatch date; hence, early-hatched individuals experience colder conditions at arrival than late-hatched individuals. Second, we show that when temperatures at arrival in the recruitment year were high, early-hatched young had a higher recruitment probability than when temperatures were low. We interpret this as a potential cost of arriving early in colder years, and climate warming may have reduced this cost. We thus show that higher temperatures in the arrival year of recruits were associated with stronger selection for early reproduction in the years these birds were born. As arrival temperatures in the beginning of the study increased, but recently declined again, directional selection on timing of reproduction showed a nonlinear change. We demonstrate that environmental conditions with a lag of up to two years can alter selection on phenological traits in natural populations, something that has important

  11. Effects of spring temperatures on the strength of selection on timing of reproduction in a long-distance migratory bird.

    PubMed

    Visser, Marcel E; Gienapp, Phillip; Husby, Arild; Morrisey, Michael; de la Hera, Iván; Pulido, Francisco; Both, Christiaan

    2015-04-01

    Climate change has differentially affected the timing of seasonal events for interacting trophic levels, and this has often led to increased selection on seasonal timing. Yet, the environmental variables driving this selection have rarely been identified, limiting our ability to predict future ecological impacts of climate change. Using a dataset spanning 31 years from a natural population of pied flycatchers (Ficedula hypoleuca), we show that directional selection on timing of reproduction intensified in the first two decades (1980-2000) but weakened during the last decade (2001-2010). Against expectation, this pattern could not be explained by the temporal variation in the phenological mismatch with food abundance. We therefore explored an alternative hypothesis that selection on timing was affected by conditions individuals experience when arriving in spring at the breeding grounds: arriving early in cold conditions may reduce survival. First, we show that in female recruits, spring arrival date in the first breeding year correlates positively with hatch date; hence, early-hatched individuals experience colder conditions at arrival than late-hatched individuals. Second, we show that when temperatures at arrival in the recruitment year were high, early-hatched young had a higher recruitment probability than when temperatures were low. We interpret this as a potential cost of arriving early in colder years, and climate warming may have reduced this cost. We thus show that higher temperatures in the arrival year of recruits were associated with stronger selection for early reproduction in the years these birds were born. As arrival temperatures in the beginning of the study increased, but recently declined again, directional selection on timing of reproduction showed a nonlinear change. We demonstrate that environmental conditions with a lag of up to two years can alter selection on phenological traits in natural populations, something that has important

  12. The multiple time step r-RESPA procedure and polarizable potentials based on induced dipole moments

    NASA Astrophysics Data System (ADS)

    Masella, Michel

    In the present study, we present an accelerating scheme based on the reversible multiple time step r-RESPA method to be used in molecular dynamics simulations with polarizable potentials based on induced dipole moments. Even if the induced dipoles are estimated with an iterative self-consistent procedure, this scheme significantly reduces the CPU time needed to perform a molecular dynamics simulation, up to a factor 2, as compared to the Car-Parrinello method where additional dynamical variables are introduced for the treatment of the induced dipoles. The tests show that stable and reliable molecular dynamics trajectories can be generated with that scheme, and that the physical properties derived from the trajectories are equivalent to those computed with the classical all atom iterative approach and the Car-Parrinello one.

  13. Timing the second birth: fecundability models for selected race and age groups in Hawaii.

    PubMed

    Swanson, D A

    1986-12-01

    This article tests exponential models for fecundability for use in predicting the timing of the second birth in a non-contracepting population, using data from Hawaii for reference. The paper begins with an extensive review of the literature on mathematical models for birth intervals. The most common problem with prior studies is that the reference data are often biased with uncontrolled parameters such as maternal age, abortion history, lactation practice and pregnancy planning. Pertinent bias in the present data is evaluated. The principal tool used here is an exponential distribution, maximum-likelihood method, involving partial differential equations. The model was constructed by subjecting it to 3 steps: 1) it was tested for exponentiality with a Gail-Gastwirth test that does not depend upon an unknown parameter; 2) the reciprocal of the mean second birth interval was calculated for each group that passed the first test; 3) the estimated frequencies were tested against observed by the chi-squared goodness of fit test. The results are tabulated as separate racial groups, combined races, and age groups. Fecundabilities varied widely by age within all races. For all races, rates were .07045, .03423 and .02777 for ages 20-24, 25-29, and 30-34. Thus the results suggest that fecundability rates are largely determined by age related factors associated with coital frequency, rather than by racial or physiological variations. Other factors potentially influencing fecundability in actual data or models are discussed, such as period effects, the "intendedness" of pregnancy, types of non-live birth intervals, lactation, induced and spontaneous abortion, and differences in pre- and post-demographic transition populations. Finally appendices are added discussing cohort size bias, presenting data set documentation and evaluating the length of pregnancy term and post-partum sterility in the data used here. PMID:12268733

  14. Time-resolved digital holographic microscopy of laser-induced forward transfer process

    PubMed Central

    Ma, H.; Venugopalan, V.

    2014-01-01

    We develop a method for time-resolved digital holographic microscopy to obtain time-resolved 3-D deformation measurements of laser induced forward transfer (LIFT) processes. We demonstrate nanometer axial resolution and nanosecond temporal resolution of our method which is suitable for measuring dynamic morphological changes in LIFT target materials. Such measurements provide insight into the early dynamics of the LIFT process and a means to examine the effect of laser and material parameters on LIFT process dynamics. PMID:24748724

  15. Time-resolved digital holographic microscopy of laser-induced forward transfer process.

    PubMed

    Ma, H; Venugopalan, V

    2014-03-01

    We develop a method for time-resolved digital holographic microscopy to obtain time-resolved 3-D deformation measurements of laser induced forward transfer (LIFT) processes. We demonstrate nanometer axial resolution and nanosecond temporal resolution of our method which is suitable for measuring dynamic morphological changes in LIFT target materials. Such measurements provide insight into the early dynamics of the LIFT process and a means to examine the effect of laser and material parameters on LIFT process dynamics. PMID:24748724

  16. Pressure overload-induced hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes.

    PubMed

    Yan, Xinhua; Schuldt, Adam J T; Price, Robert L; Amende, Ivo; Liu, Fen-Fen; Okoshi, Katashi; Ho, Kalon K L; Pope, Adèle J; Borg, Thomas K; Lorell, Beverly H; Morgan, James P

    2008-03-01

    The role of the angiotensin II type 2 (AT2) receptor in cardiac hypertrophy remains controversial. We studied the effects of AT2 receptors on chronic pressure overload-induced cardiac hypertrophy in transgenic mice selectively overexpressing AT2 receptors in ventricular myocytes. Left ventricular (LV) hypertrophy was induced by ascending aorta banding (AS). Transgenic mice overexpressing AT2 (AT2TG-AS) and nontransgenic mice (NTG-AS) were studied after 70 days of aortic banding. Nonbanded NTG mice were used as controls. LV function was determined by catheterization via LV puncture and cardiac magnetic resonance imaging. LV myocyte diameter and interstitial collagen were determined by confocal microscopy. Atrial natriuretic polypeptide (ANP) and brain natriuretic peptide (BNP) were analyzed by Northern blot. Sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA)2, inducible nitric oxide synthase (iNOS), endothelial NOS, ERK1/2, p70S6K, Src-homology 2 domain-containing protein tyrosine phosphatase-1, and protein serine/threonine phosphatase 2A were analyzed by Western blot. LV myocyte diameter and collagen were significantly reduced in AT2TG-AS compared with NTG-AS mice. LV anterior and posterior wall thickness were not different between AT2TG-AS and NTG-AS mice. LV systolic and diastolic dimensions were significantly higher in AT2TG-AS than in NTG-AS mice. LV systolic pressure and end-diastolic pressure were lower in AT2TG-AS than in NTG-AS mice. ANP, BNP, and SERCA2 were not different between AT2TG-AS and NTG-AS mice. Phospholamban (PLB) and the PLB-to-SERCA2 ratio were significantly higher in AT2TG-AS than in NTG-AS mice. iNOS was higher in AT2TG-AS than in NTG-AS mice but not significantly different. Our results indicate that AT2 receptor overexpression modified the pathological hypertrophic response to aortic banding in transgenic mice. PMID:18178728

  17. Real-time cell analysis for monitoring cholera toxin-induced human intestinal epithelial cell response.

    PubMed

    Ye, Julian; Luo, Yun; Fang, Weijia; Pan, Junhang; Zhang, Zheng; Zhang, Yanjun; Chen, Zhiping; Jin, Dazhi

    2015-04-01

    The pathogenic mechanism of Vibrio cholerae manifests as diarrhea and causes life-threatening dehydration. Here, we observe the human intestinal epithelial cells (HIEC) response to Cholera toxin (CT) by a real-time cell analysis (RTCA) platform, and disclose the difference from CT-induced cytotoxicity and others in HIEC. An HIEC cell of 1.0 × 10(5) cells/mL was characterized as the suitable concentration for each well. For experimentation, the assay requires an inoculation of CT dissolved in Dulbecco's phosphate-buffered saline with 0.1 % gelatin for a period of 18-25 h. The dimensionless impedance cell index curve presented characteristic dose- and time-dependent drop responses at the first stage, and the CT-induced cytotoxicity was the most remarkable following exposure for 18-25 h (P = 0.0002). Following the obvious cytotoxic reaction, the CI curve gradually increased over time until the original CI value, indicating that self-recovery occurred. The CT-induced CI curve for HIEC was different from that induced by other toxins, including diphtheria and Clostridium difficile toxin. Collectively, these results suggest that the CT-induced cytotoxicity in HIEC was absolutely different from that induced by C. difficile and other toxins because of the different pathogeneses that were correlated with the specific CI curve generated by the RTCA system. In summary, our data show that the assay described here is a convenient and rapid high-throughput tool for real-time monitoring of host cellular responses to CT on the basis of the characteristic CI curve. PMID:25510171

  18. Feeding-induced time course of changes in protein synthesis in neonatal pig skeletal muscle

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Feeding increases protein synthesis by promoting translation initiation, and in the neonate, this increase is greatest in skeletal muscle. This study aimed to identify the feeding-induced time course of the changes in protein synthesis and translation factor activation in muscle. Piglets (n=36; 5-7 ...

  19. LATE-TIME RADIO EMISSION FROM X-RAY-SELECTED TIDAL DISRUPTION EVENTS

    SciTech Connect

    Bower, Geoffrey C.; Cenko, S. Bradley; Silverman, Jeffrey M.; Bloom, Joshua S.; Metzger, Brian D.

    2013-02-15

    We present new observations with the Karl G. Jansky Very Large Array of seven X-ray-selected tidal disruption events (TDEs). The radio observations were carried out between 9 and 22 years after the initial X-ray discovery, and thus probe the late-time formation of relativistic jets and jet interactions with the interstellar medium in these systems. We detect a compact radio source in the nucleus of the galaxy IC 3599 and a compact radio source that is a possible counterpart to RX J1420.4+5334. We find no radio counterparts for five other sources with flux density upper limits between 51 and 200 {mu}Jy (3{sigma}). If the detections truly represent late radio emission associated with a TDE, then our results suggest that a fraction, {approx}> 10%, of X-ray-detected TDEs are accompanied by relativistic jets. We explore several models for producing late radio emission, including interaction of the jet with gas in the circumnuclear environment (blast wave model), and emission from the core of the jet itself. Upper limits on the radio flux density from archival observations suggest that the jet formation may have been delayed for years after the TDE, possibly triggered by the accretion rate dropping below a critical threshold of {approx}10{sup -2}-10{sup -3} M-dot {sub Edd}. The non-detections are also consistent with this scenario; deeper radio observations can determine whether relativistic jets are present in these systems. The emission from RX J1420.4+5334 is also consistent with the predictions of the blast wave model; however, the radio emission from IC 3599 is substantially underluminous, and its spectral slope is too flat, relative to the blast wave model expectations. Future radio monitoring of IC 3599 and RX J1420.4+5334 will help to better constrain the nature of the jets in these systems.

  20. Detection of selected intestinal helminths and protozoa at Hospital Universiti Sains Malaysia using multiplex real-time PCR.

    PubMed

    Basuni, M; Mohamed, Z; Ahmad, M; Zakaria, N Z; Noordin, R

    2012-09-01

    Intestinal parasites are the causative agents of a number of important human infections in developing countries. The objective of this study was to determine the prevalence of selected helminths and protozoan infections among patients admitted with gastrointestinal disorders at Hospital Universiti Sains Malaysia, Kelantan, Malaysia using multiplex real-time PCR. In addition microscopic examination was also performed following direct smear, zinc sulphate concentration and Kato-Katz thick smear techniques; and the presence of protozoan parasites was confirmed using trichrome and acid-fast stains. Of the 225 faecal samples analysed, 26.2% were positive for intestinal parasites by the multiplex real-time PCR, while 5.3% were positive by microscopy. As compared to microscopy, the multiplex real-time PCR detected 5.8 and 4.5 times more positives for the selected helminth and protozoan infections respectively. Among the selected helminths detected in this study, hookworm was the most prevalent by real-time PCR, while Ascaris lumbricoides was detected the most by microscopy. Meanwhile, among the selected protozoa detected in this study, Entamoeba histolytica was the most prevalent by real-time PCR, however microscopy detected equal number of cases with E. histolytica and Giardia lamblia. This study showed that real-time PCR can be used to obtain a more accurate prevalence data on intestinal helminths and protozoa. PMID:23018507

  1. A novel manganese complex selectively induces malignant glioma cell death by targeting mitochondria

    PubMed Central

    Geng, Ji; Li, Jing; Huang, Tao; Zhao, Kaidi; Chen, Qiuyun; Guo, Wenjie; Gao, Jing

    2016-01-01

    Despite advances in treatment, malignant glioma commonly exhibits recurrence, subsequently leading to a poor prognosis. As manganese (Mn) compounds can be transported by the transferrin-transferrin receptor system, the present study synthesized and examined the potential use of Adpa-Mn as a novel antitumor agent. Adpa-Mn time and dose-dependently inhibited U251 and C6 cell proliferation; however, it had little effect on normal astrocytes. Apoptosis was significantly elevated following treatment with Adpa-Mn, as detected by chromatin condensation, Annexin V/propidium iodide staining, cytochrome c release from mitochondria to the cytoplasm, and the activation of caspases-9, -7 and -3 and poly (ADP-ribose) polymerase. In addition, Adpa-Mn enhanced fluorescence intensity of monodansylcadaverine and elevated the expression levels of the autophagy-related protein microtubule-associated protein 1 light chain 3. Pretreatment with the autophagy inhibitors 3-methyladenine and chloroquine enhanced Adpa-Mn-induced cell inhibition, thus indicating that autophagy has an essential role in this process. Furthermore, evidence of mitochondrial dysfunction was detected in the Adpa-Mn-treated group, including disrupted membrane potential, elevated levels of reactive oxygen species (ROS) and depleted adenosine triphosphate. Conversely, treatment with the mitochondrial permeability transition inhibitor cyclosporin A reversed Adpa-Mn-induced ROS production, mitochondrial damage and cell apoptosis, thus suggesting that Adpa-Mn may target the mitochondria. Taken together, these data suggested that Adpa-Mn may be considered for use as a novel anti-glioma therapeutic option. PMID:27432745

  2. Conformational selection and induced fit for RNA polymerase and RNA/DNA hybrid backtracked recognition

    PubMed Central

    Wu, Jian; Ye, Wei; Yang, Jingxu; Chen, Hai-Feng

    2015-01-01

    RNA polymerase catalyzes transcription with a high fidelity. If DNA/RNA mismatch or DNA damage occurs downstream, a backtracked RNA polymerase can proofread this situation. However, the backtracked mechanism is still poorly understood. Here we have performed multiple explicit-solvent molecular dynamics (MD) simulations on bound and apo DNA/RNA hybrid to study backtracked recognition. MD simulations at room temperature suggest that specific electrostatic interactions play key roles in the backtracked recognition between the polymerase and DNA/RNA hybrid. Kinetics analysis at high temperature shows that bound and apo DNA/RNA hybrid unfold via a two-state process. Both kinetics and free energy landscape analyses indicate that bound DNA/RNA hybrid folds in the order of DNA/RNA contracting, the tertiary folding and polymerase binding. The predicted Φ-values suggest that C7, G9, dC12, dC15, and dT16 are key bases for the backtracked recognition of DNA/RNA hybrid. The average RMSD values between the bound structures and the corresponding apo ones and Kolmogorov-Smirnov (KS) P-test analyses indicate that the recognition between DNA/RNA hybrid and polymerase might follow an induced fit mechanism for DNA/RNA hybrid and conformation selection for polymerase. Furthermore, this method could be used to relative studies of specific recognition between nucleic acid and protein. PMID:26594643

  3. Neisseria lactamica selectively induces mitogenic proliferation of the naive B cell pool via cell surface Ig.

    PubMed

    Vaughan, Andrew T; Brackenbury, Louise S; Massari, Paola; Davenport, Victoria; Gorringe, Andrew; Heyderman, Robert S; Williams, Neil A

    2010-09-15

    Neisseria lactamica is a commensal bacteria that colonizes the human upper respiratory tract mucosa during early childhood. In contrast to the closely related opportunistic pathogen Neisseria meningitidis, there is an absence of adaptive cell-mediated immunity to N. lactamica during the peak age of carriage. Instead, outer membrane vesicles derived from N. lactamica mediate a B cell-dependent proliferative response in mucosal mononuclear cells that is associated with the production of polyclonal IgM. We demonstrate in this study that this is a mitogenic human B cell response that occurs independently of T cell help and any other accessory cell population. The ability to drive B cell proliferation is a highly conserved property and is present in N. lactamica strains derived from diverse clonal complexes. CFSE staining of purified human tonsillar B cells demonstrated that naive IgD(+) and CD27(-) B cells are selectively induced to proliferate by outer membrane vesicles, including the innate CD5(+) subset. Neither purified lipooligosaccharide nor PorB from N. lactamica is likely to be responsible for this activity. Prior treatment of B cells with pronase to remove cell-surface Ig or treatment with BCR-specific Abs abrogated the proliferative response to N. lactamica outer membrane vesicles, suggesting that this mitogenic response is dependent upon the BCR. PMID:20709949

  4. Hypoxia-induced gene expression results from selective mRNA partitioning to the endoplasmic reticulum

    PubMed Central

    Staudacher, Jonas J.; Naarmann-de Vries, Isabel S.; Ujvari, Stefanie J.; Klinger, Bertram; Kasim, Mumtaz; Benko, Edgar; Ostareck-Lederer, Antje; Ostareck, Dirk H.; Bondke Persson, Anja; Lorenzen, Stephan; Meier, Jochen C.; Blüthgen, Nils; Persson, Pontus B.; Henrion-Caude, Alexandra; Mrowka, Ralf; Fähling, Michael

    2015-01-01

    Protein synthesis is a primary energy-consuming process in the cell. Therefore, under hypoxic conditions, rapid inhibition of global mRNA translation represents a major protective strategy to maintain energy metabolism. How some mRNAs, especially those that encode crucial survival factors, continue to be efficiently translated in hypoxia is not completely understood. By comparing specific transcript levels in ribonucleoprotein complexes, cytoplasmic polysomes and endoplasmic reticulum (ER)-bound ribosomes, we show that the synthesis of proteins encoded by hypoxia marker genes is favoured at the ER in hypoxia. Gene expression profiling revealed that transcripts particularly increased by the HIF-1 transcription factor network show hypoxia-induced enrichment at the ER. We found that mRNAs favourably translated at the ER have higher conservation scores for both the 5′- and 3′-untranslated regions (UTRs) and contain less upstream initiation codons (uAUGs), indicating the significance of these sequence elements for sustained mRNA translation under hypoxic conditions. Furthermore, we found enrichment of specific cis-elements in mRNA 5′- as well as 3′-UTRs that mediate transcript localization to the ER in hypoxia. We conclude that transcriptome partitioning between the cytoplasm and the ER permits selective mRNA translation under conditions of energy shortage. PMID:25753659

  5. Spatially-Selective Membrane Permeabilization Induced by Cell-Solution Electrode Atmospheric Pressure Plasma Irradiation

    NASA Astrophysics Data System (ADS)

    Sasaki, Shota; Hokari, Yutaro; Kanzaki, Makoto; Kaneko, Toshiro

    2015-09-01

    Gene transfection, which is the process of deliberately introducing nucleic acids into cells, is expected to play an important role in medical treatment because the process is necessary for gene therapy and creation of induced pluripotent stem (iPS) cells. However, the conventional transfection methods have some problems, so we focus attention on promising transfection methods by atmospheric pressure plasma (APP). We have previously reported that the cell membrane permeability, which is closely related with gene transfection, is improved using a cell-solution electrode for generating He-APP. He-APP is irradiated to the solution containing the adherent cells and delivery materials such as fluorescent dyes (YOYO-1) and plasmid DNA (GFP). In case of YOYO-1 delivery, more than 80% of cells can be transferred only in the plasma-irradiated area and the spatially-selective membrane permeabilization is realized by the plasma irradiation. In addition, it is confirmed that plasmid DNA is transfected and the GFP genes are expressed using same APP irradiation system with no obvious cellular damage.

  6. Resveratrol Attenuates Exercise-Induced Adaptive Responses in Rats Selectively Bred for Low Running Performance

    PubMed Central

    Hart, Nikolett; Sarga, Linda; Csende, Zsolt; Koch, Lauren G.; Britton, Steven L.; Davies, Kelvin J.A.; Radak, Zsolt

    2014-01-01

    Low capacity runner (LCR) rats have been developed by divergent artificial selection for treadmill endurance capacity to explore an aerobic biology-disease connection. The beneficial effects of resveratrol supplementation have been demonstrated in endurance running. In this study it was examined whether 12 weeks of treadmill exercise training and/or resveratrol can retrieve the low running performance of the LCR and impact mitochondrial biogenesis and quality control. Resveratrol regressed running performance in trained LCR (p<0.05). Surprisingly, exercise and resveratrol treatments significantly decreased pAMPK/AMPK, SIRT1, SIRT4, forkhead transcription factor 1 (FOXO1) and mitochondrial transcription factor A (TFAM) levels in these animals (p<0.05). Mitochondrial fusion protein, HSP78 and polynucleotide phosphorylase were significantly induced in LCR-trained, LCR-resveratrol treated, LCR-trained and resveratol treated groups compared to LCR-controls. The data indicate that the AMPK-SIRT1-NAMPT-FOXO1 axis could be important to the limited aerobic endurance capacity of low running capacity rats. Resveratrol supplementation was not beneficial in terms of aerobic endurance performance, mitochondrial biogenesis, or quality control. PMID:24659933

  7. Platelet-activating factor induces selective pulmonary arterial hyperreactivity in isolated perfused rabbit lungs.

    PubMed

    Ohar, J A; Waller, K S; Dahms, T E

    1993-07-01

    The role of vasoreactivity in PAF-induced pulmonary hypertension (PHT) was assessed in isolated, perfused rabbit lungs. We evaluated the steady-state pulmonary vascular response to five vasoconstrictors: PGF2 alpha, norepinephrine, angiotensin II, PAF, and KCl. Pulmonary arterial pressure and pulmonary vascular resistance (PVR) were significantly greater in lungs of rabbits treated with PAF for 28 days than in control rabbits in response to PGF2 alpha and norepinephrine. When resistance was partitioned by the vascular occlusion method, at baseline the vascular resistance was equally distributed between arterial and venous segments in both experimental groups. Arterial resistance accounted for approximately 76% of PVR during norepinephrine injection and 60% of PVR during PGF2 alpha injection in PAF-treated lungs. Whereas arterial resistance accounted for approximately 63% of PVR during norepinephrine injection and 52% of PVR during PGF2 alpha injection in control lungs, there was no significant difference in the response to angiotensin II, acute PAF, and KCl in lungs from chronic PAF-treated rabbits compared with responses in control rabbit lungs, though the pressor response to acute PAF tended to be blunted in PAF-treated lungs. Chronic PAF treatment results in enhanced pulmonary arterial reactivity to selected autacoids in isolated perfused lungs. PMID:8317792

  8. Shock-induced deformation of nanocrystalline Al: Characterization with orientation mapping and selected area electron diffraction

    NASA Astrophysics Data System (ADS)

    Wang, L.; E, J. C.; Cai, Y.; Zhao, F.; Fan, D.; Luo, S. N.

    2015-02-01

    We investigate shock-induced deformation of columnar nanocrystalline Al with large-scale molecular dynamics simulations and implement orientation mapping (OM) and selected area electron diffraction (SAED) for microstructural analysis. Deformation mechanisms include stacking fault formation, pronounced twinning, dislocation slip, grain boundary (GB) sliding and migration, and lattice or partial grain rotation. GBs and GB triple junctions serve as the nucleation sites for crystal plasticity including twinning and dislocations, due to GB weakening, and stress concentrations. Grains with different orientations exhibit different densities of twins or stacking faults nucleated from GBs. GB migration occurs as a result of differential deformation between two grains across the GB. High strain rates, appropriate grain orientation and GBs contribute to deformation twinning. Upon shock compression, intra-grain dislocation and twinning nucleated from GBs lead to partial grain rotation and the formation of subgrains, while whole grain rotation is not observed. During tension, stress gradients associated with the tensile pulse give rise to intra-grain plasticity and then partial grain rotation. The simulated OM and SAED are useful to describe lattice/grain rotation, the formation of subgrains, GB migration and other microstructures.

  9. External magnetic field-induced selective biodistribution of magnetoliposomes in mice

    NASA Astrophysics Data System (ADS)

    García-Jimeno, Sonia; Escribano, Elvira; Queralt, Josep; Estelrich, Joan

    2012-08-01

    This study looked at the effect of an external magnet on the biodistribution of magnetoliposomes intravenously administrated in mice (8 mg iron/kg) with and without induced acute inflammation. Our results showed that due to enhanced vascular permeability, magnetoliposomes accumulated at the site of inflammation in the absence of an external magnetic field, but the amount of iron present increased under the effect of a magnet located at the inflammation zone. This increase was dependent on the time (20 or 60 min) of exposure of the external magnetic field. It was also observed that the presence of the magnet was associated with lower amounts of iron in the liver, spleen, and plasma than was found in mice in which a magnet had not been applied. The results of this study confirm that it is possible to target drugs encapsulated in magnetic particles by means of an external magnet.

  10. External magnetic field-induced selective biodistribution of magnetoliposomes in mice

    PubMed Central

    2012-01-01

    This study looked at the effect of an external magnet on the biodistribution of magnetoliposomes intravenously administrated in mice (8 mg iron/kg) with and without induced acute inflammation. Our results showed that due to enhanced vascular permeability, magnetoliposomes accumulated at the site of inflammation in the absence of an external magnetic field, but the amount of iron present increased under the effect of a magnet located at the inflammation zone. This increase was dependent on the time (20 or 60 min) of exposure of the external magnetic field. It was also observed that the presence of the magnet was associated with lower amounts of iron in the liver, spleen, and plasma than was found in mice in which a magnet had not been applied. The results of this study confirm that it is possible to target drugs encapsulated in magnetic particles by means of an external magnet. PMID:22883385

  11. A novel cdk2-selective inhibitor, SU9516, induces apoptosis in colon carcinoma cells.

    PubMed

    Lane, M E; Yu, B; Rice, A; Lipson, K E; Liang, C; Sun, L; Tang, C; McMahon, G; Pestell, R G; Wadler, S

    2001-08-15

    Recent studies have indicated that the development of cyclin-dependent kinase (cdk)2 inhibitors that deregulate E2F are a plausible pharmacological strategy for novel antineoplastic agents. We show here that 3-[1-(3H-Imidazol-4-yl)-meth-(Z)-ylidene]-5-methoxy-1,3-dihydro-indol-2-one (SU9516), a novel 3-substituted indolinone compound, binds to and selectively inhibits the activity of cdk2. This inhibition results in a time-dependent decrease (4-64%) in the phosphorylation of the retinoblastoma protein pRb, an increase in caspase-3 activation (5-84%), and alterations in cell cycle resulting in either a G(0)-G(1) or a G(2)-M block. We also report here cell line differences in the cdk-dependent phosphorylation of pRb. These findings demonstrate that SU9516 is a selective cdk2 inhibitor and support the theory that compounds that inhibit cdk2 are viable resources in the development of new antineoplastic agents. PMID:11507069

  12. Minimizing Surgically Induced Astigmatism at the Time of Cataract Surgery Using a Square Posterior Limbal Incision

    PubMed Central

    Ernest, Paul; Hill, Warren; Potvin, Richard

    2011-01-01

    Purpose. To compare the surgically induced astigmatism from clear corneal and square posterior limbal incisions at the time of cataract surgery. Methods. Surgically induced astigmatism was calculated for a set of eyes after cataract surgery using a temporal 2.2 mm square posterior limbal incision. Results were compared to similar available data from surgeons using clear corneal incisions of similar size. Results. Preoperative corneal astigmatism averaged 1.0 D and was not significantly different between the incision types. Surgically induced astigmatism with the 2.2 mm posterior limbal incision averaged 0.25 ± 0.14 D, significantly lower in magnitude than the aggregate surgically induced astigmatism produced by the 2.2 mm clear corneal incision (0.68 ± 0.49 D). Conclusion. The 2.2 mm square posterior limbal incision induced significantly less, and significantly less variable, surgically induced astigmatism relative to a similar-sized clear corneal incision. This is likely to improve refractive outcomes, particularly important with regard to premium intraocular lenses. PMID:22132310

  13. Intense Habitat-Specific Fisheries-Induced Selection at the Molecular Pan I Locus Predicts Imminent Collapse of a Major Cod Fishery

    PubMed Central

    Árnason, Einar; Hernandez, Ubaldo Benitez; Kristinsson, Kristján

    2009-01-01

    Predation is a powerful agent in the ecology and evolution of predator and prey. Prey may select multiple habitats whereby different genotypes prefer different habitats. If the predator is also habitat-specific the prey may evolve different habitat occupancy. Drastic changes can occur in the relation of the predator to the evolved prey. Fisheries exert powerful predation and can be a potent evolutionary force. Fisheries-induced selection can lead to phenotypic changes that influence the collapse and recovery of the fishery. However, heritability of the phenotypic traits involved and selection intensities are low suggesting that fisheries-induced evolution occurs at moderate rates at decadal time scales. The Pantophysin I (Pan I) locus in Atlantic cod (Gadus morhua), representing an ancient balanced polymorphism predating the split of cod and its sister species, is under an unusual mix of balancing and directional selection including current selective sweeps. Here we show that Pan I alleles are highly correlated with depth with a gradient of 0.44% allele frequency change per meter. AA fish are shallow-water and BB deep-water adapted in accordance with behavioral studies using data storage tags showing habitat selection by Pan I genotype. AB fish are somewhat intermediate although closer to AA. Furthermore, using a sampling design covering space and time we detect intense habitat-specific fisheries-induced selection against the shallow-water adapted fish with an average 8% allele frequency change per year within year class. Genotypic fitness estimates (0.08, 0.27, 1.00 of AA, AB, and BB respectively) predict rapid disappearance of shallow-water adapted fish. Ecological and evolutionary time scales, therefore, are congruent. We hypothesize a potential collapse of the fishery. We find that probabilistic maturation reaction norms for Atlantic cod at Iceland show declining length and age at maturing comparable to changes that preceded the collapse of northern cod at

  14. Fission dynamics within time-dependent Hartree-Fock. II. Boost-induced fission

    NASA Astrophysics Data System (ADS)

    Goddard, Philip; Stevenson, Paul; Rios, Arnau

    2016-01-01

    Background: Nuclear fission is a complex large-amplitude collective decay mode in heavy nuclei. Microscopic density functional studies of fission have previously concentrated on adiabatic approaches based on constrained static calculations ignoring dynamical excitations of the fissioning nucleus and the daughter products. Purpose: We explore the ability of dynamic mean-field methods to describe induced fission processes, using quadrupole boosts in the nuclide 240Pu as an example. Methods: Following upon the work presented in Goddard et al. [Phys. Rev. C 92, 054610 (2015)], 10.1103/PhysRevC.92.054610, quadrupole-constrained Hartree-Fock calculations are used to create a potential energy surface. An isomeric state and a state beyond the second barrier peak are excited by means of instantaneous as well as temporally extended gauge boosts with quadrupole shapes. The subsequent deexcitation is studied in a time-dependent Hartree-Fock simulation, with emphasis on fissioned final states. The corresponding fission fragment mass numbers are studied. Results: In general, the energy deposited by the quadrupole boost is quickly absorbed by the nucleus. In instantaneous boosts, this leads to fast shape rearrangements and violent dynamics that can ultimately lead to fission. This is a qualitatively different process than the deformation-induced fission. Boosts induced within a finite time window excite the system in a relatively gentler way and do induce fission but with a smaller energy deposition. Conclusions: The fission products obtained using boost-induced fission in time-dependent Hartree-Fock are more asymmetric than the fragments obtained in deformation-induced fission or the corresponding adiabatic approaches.

  15. Effect of nicotinic acid on the sleep time and tolerance induced by ethanol in the rat

    SciTech Connect

    Basilio, C.; Toro, A.; Yojay, L.

    1986-05-01

    The intraperitoneal (i.p.) administration (50 mg/kg) of nicotinic acid (NA), markedly decreased the sleep time of rats pretreated (10 min before), post-treated (10 min after) or simultaneously treated with ethanol (4 g/Kg i.p.). A similar effect was observed on the sleep time induced by pentobarbital (37 mg/Kg i.p.). Blood alcohol levels (BAL) were the same or slightly higher in the animals pretreated with NA than in the control animals pre-injected with saline. Nicotinamide and NAD had no effect. A total of three doses of ethanol, each one administered weekly or biweekly, induced tolerance, which persisted for approximately six weeks. After this period, a hypersensitivity to ethanol appeared to develop. This phenomenon was not observed when NA was pre-injected 10 min before each dose of ethanol. The sleep time of the latter animals did not change neither during the treatment period nor after six weeks without any treatment. BAL were slightly higher in NA treated than in control animals. The authors concluded that the effect of NA on the sleep time and tolerance induced by ethanol is not due to an increased rate of its metabolism and/or elimination but to a long-lasting effect that decreases the sensitivity of the nervous cells to ethanol. The mechanisms involved in the shortening of the sleep time as well as those responsible for the loss of the capacity to develop tolerance are under current investigation.

  16. Time-synchronized continuous wave laser-induced fluorescence on an oscillatory xenon discharge

    SciTech Connect

    MacDonald, N. A.; Cappelli, M. A.; Hargus, W. A. Jr.

    2012-11-15

    A novel approach to time-synchronizing laser-induced fluorescence measurements to an oscillating current in a 60 Hz xenon discharge lamp using a continuous wave laser is presented. A sample-hold circuit is implemented to separate out signals at different phases along a current cycle, and is followed by a lock-in amplifier to pull out the resulting time-synchronized fluorescence trace from the large background signal. The time evolution of lower state population is derived from the changes in intensity of the fluorescence excitation line shape resulting from laser-induced fluorescence measurements of the 6s{sup Prime }[1/2]{sub 1}{sup 0}-6p{sup Prime }[3/2]{sub 2} xenon atomic transition at {lambda}= 834.68 nm. Results show that the lower state population oscillates at twice the frequency of the discharge current, 120 Hz.

  17. Microbeam Studies of Diffusion Time Resolved Ion Beam Induced Charge Collection from Stripe-Like Junctions

    SciTech Connect

    GUO,B.N.; BOUANANI,M.E.; RENFROW,S.N.; WALSH,DAVID S.; DOYLE,BARNEY L.; ATON,T.J.; SMITH,E.B.; BAUMANN,R.C.; DUGGAN,J.L.; MCDANIEL,F.D.

    2000-06-14

    To design more radiation tolerant Integrated Circuits (ICs), it is essential to create and test accurate models of ionizing radiation induced charge collection dynamics within microcircuits. A new technique, Diffusion Time Resolved Ion Beam Induced Charge Collection (DTRIBICC), is proposed to measure the average arrival time of the diffused charge at the junction. Specially designed stripe-like junctions were experimentally studied using a 12 MeV carbon microbeam with a spot size of 1 {micro}m. The relative arrival time of ion-generated charge is measured along with the charge collection using a multiple parameter data acquisition system. The results show the importance of the diffused charge collection by junctions, which is especially significant in accounting for Multiple Bit Upset (MBUs) in digital devices.

  18. Time-synchronized continuous wave laser-induced fluorescence on an oscillatory xenon discharge.

    PubMed

    MacDonald, N A; Cappelli, M A; Hargus, W A

    2012-11-01

    A novel approach to time-synchronizing laser-induced fluorescence measurements to an oscillating current in a 60 Hz xenon discharge lamp using a continuous wave laser is presented. A sample-hold circuit is implemented to separate out signals at different phases along a current cycle, and is followed by a lock-in amplifier to pull out the resulting time-synchronized fluorescence trace from the large background signal. The time evolution of lower state population is derived from the changes in intensity of the fluorescence excitation line shape resulting from laser-induced fluorescence measurements of the 6s(')[1/2](1)(0)-6p(')[3/2](2) xenon atomic transition at λ = 834.68 nm. Results show that the lower state population oscillates at twice the frequency of the discharge current, 120 Hz. PMID:23206061

  19. Time to Talk: 6 Things to Know When Selecting a Complementary Health Practitioner

    MedlinePlus

    ... U V W X Y Z 6 Things To Know When Selecting a Complementary Health Practitioner Share: ... you’re looking for a complementary health practitioner to help treat a medical problem, it is important ...

  20. Time-dependent Navier-Stokes computations for flow-induced vibrations of vanes

    NASA Astrophysics Data System (ADS)

    Liu, B. L.; O'Farrel, J. M.; Holt, J. B.; Dougherty, N. S.

    Flows over two curved vane configurations were computed using a time-accurate compressible Navier-Stokes flow model. One configuration showed the presence of strong flow-induced vibrations at Strouhal numbers near 0.19 and 0.38 for bending and torsional excitation. In the other configuration, a simple modification reduced both types of response. Laminar flows were analyzed for the effects of flow-induced vibrations, and flow fields were solved for a rigid vane and a vane undergoing forced vibrations at prescribed amplitude and frequency simulating vibration response to a coupled vortex-shedding/elastic motion feedback cycle.

  1. Riding the lexical speedway: a critical review on the time course of lexical selection in speech production.

    PubMed

    Strijkers, Kristof; Costa, Albert

    2011-01-01

    Speech requires time. How much time often depends on the amount of labor the brain has to perform in order to retrieve the linguistic information related to the ideas we want to express. Although most psycholinguistic research in the field of language production has focused on the net result of time required to utter words in various experimental conditions, over the last years more and more researchers pursued the objective to flesh out the time course of particular stages implicated in language production. Here we critically review these studies, with particular interest for the time course of lexical selection. First, we evaluate the data underlying the estimates of an influential temporal meta-analysis on language production (Indefrey and Levelt, 2004). We conclude that those data alone are not sufficient to provide a reliable time frame of lexical selection. Next, we discuss recent neurophysiological evidence which we argue to offer more explicit insights into the time course of lexical selection. Based on this evidence we suggest that, despite the absence of a clear time frame of how long lexical selection takes, there is sufficient direct evidence to conclude that the brain initiates lexical access within 200 ms after stimulus presentation, hereby confirming Indefrey and Levelt's estimate. In a final section, we briefly review the proposed mechanisms which could lead to this rapid onset of lexical access, namely automatic spreading activation versus specific concept selection, and discuss novel data which support the notion of spreading activation, but indicate that the speed with which this principle takes effect is driven by a top-down signal in function of the intention to engage in a speech act. PMID:22144973

  2. Natural soil microbes alter flowering phenology and the intensity of selection on flowering time in a wild Arabidopsis relative

    PubMed Central

    Wagner, Maggie R.; Lundberg, Derek S.; Coleman-Derr, Devin; Tringe, Susannah G.; Dangl, Jeffery L.; Mitchell-Olds, Thomas

    2014-01-01

    Plant phenology is known to depend on many different environmental variables, but soil microbial communities have rarely been acknowledged as possible drivers of flowering time. Here we tested separately the effects of four naturally occurring soil microbiomes and their constituent soil chemistries on flowering phenology and reproductive fitness of Boechera stricta, a wild relative of Arabidopsis. Flowering time was sensitive to both microbes and the abiotic properties of different soils; varying soil microbiota also altered patterns of selection on flowering time. Thus, soil microbes potentially contribute to phenotypic plasticity of flowering time and to differential selection observed between habitats. We also describe a method to dissect the microbiome into single axes of variation that can help identify candidate organisms whose abundance in soil correlates with flowering time. This approach is broadly applicable to search for microbial community members that alter biological characteristics of interest. PMID:24698177

  3. Role of estrogen receptor β selective agonist in ameliorating portal hypertension in rats with CCl4-induced liver cirrhosis

    PubMed Central

    Zhang, Cheng-Gang; Zhang, Bin; Deng, Wen-Sheng; Duan, Ming; Chen, Wei; Wu, Zhi-Yong

    2016-01-01

    AIM: To investigate the role of diarylpropionitrile (DPN), a selective agonist of estrogen receptor β (ERβ), in liver cirrhosis with portal hypertension (PHT) and isolated hepatic stellate cells (HSCs). METHODS: Female Sprague-Dawley rats were ovariectomized (OVX), and liver cirrhosis with PHT was induced by CCl4 injection. DPN and PHTPP, the selective ERβ agonist and antagonist, were used as drug interventions. Liver fibrosis was assessed by hematoxylin and eosin (HE) and Masson’s trichrome staining and by analyzing smooth muscle actin expression. Hemodynamic parameters were determined in vivo using colored microspheres technique. Protein expression and phosphorylation were determined by immunohistochemical staining and Western blot analysis. Messenger RNA levels were analyzed by quantitative real-time polymerase chain reaction (qRT-PCR). Collagen gel contraction assay was performed using gel lattices containing HSCs treated with DPN, PHTPP, or Y-27632 prior to ET-1 addition. RESULTS: Treatment with DPN in vivo greatly lowered portal pressure and improved hemodynamic parameters without affecting mean arterial pressure, which was associated with the attenuation of liver fibrosis and intrahepatic vascular resistance (IHVR). In CCl4-treated rat livers, DPN significantly decreased the expression of RhoA and ROCK II, and even suppressed ROCK II activity. Moreover, DPN remarkedly increased the levels of endothelial nitric oxide synthase (eNOS) and phosphorylated eNOS, and promoted the activities of protein kinase G (PKG), which is an NO effector in the liver. Furthermore, DPN reduced the contractility of activated HSCs in the 3-dimensional stress-relaxed collagen lattices, and decreased the ROCK II activity in activated HSCs. Finally, in vivo/in vitro experiments demonstrated that MLC activity was inhibited by DPN. CONCLUSION: For OVX rats with liver cirrhosis, DPN suppressed liver RhoA/ROCK signal, facilitated NO/PKG pathways, and decreased IHVR, giving rise to

  4. Site selectivity in the reaction of Si(111)-(7 times 7) with Si sub 2 H sub 6

    SciTech Connect

    Avouris, Ph.; Bozso, F. )

    1990-03-22

    We find that the reaction of disilane with the Si(111)-(7{times}7) surface shows strong site selectivity. The reaction involves the fission of the Si-Si bond of Si{sub 2}H{sub 6} even at low temperatures and occurs preferentially at rest-atom sites of the 7{times}7 surface. The reaction of the products of the thermal dissociation of the surface-bound SiH{sub x} groups with surface dangling-bond sites is also site selective. We propose mechanisms to explain the above observations.

  5. DBD as a post-discharge bipolar ions source and selective ion-induced nucleation versus ions polarity

    NASA Astrophysics Data System (ADS)

    Bourgeois, E.; Jidenko, N.; Alonso, M.; Borra, J. P.

    2009-10-01

    Ions densities and mobilities in post-dielectric barrier discharge (post-DBD) are presented here. To extract ions from DBD and perform post-discharge measurements the best functioning conditions are low overpressure, high frequency (>=25 kHz, to avoid electrocollection) and low flow rate (1 lpm, to reduce dilution). Besides, ions densities in post-discharge increase with electrode temperature and, at low flow rates, with the number of discharge filaments by time and surface unit (controlled by voltage at fixed frequency). In both cases, the reinforcement of dielectric material surface polarization reduces the local electrocollection of ions inside DBD or increases the production of ions by subcritical avalanches outside filaments. Concerning mobility measurements, it is shown that for low saturation, vapours emitted from post-DBD polymer tubes only affect positive ions mobility due to selective ion-induced nucleation on positive ions. When metal post-DBD tubes are used, positive ions keep the same range of electric mobility at any temperature while there is a drop in negative ions mobility around 100 °C, probably related to a chemical transition between O3 and NOx.

  6. Extreme Hypoxic Conditions Induce Selective Molecular Responses and Metabolic Reset in Detached Apple Fruit.

    PubMed

    Cukrov, Dubravka; Zermiani, Monica; Brizzolara, Stefano; Cestaro, Alessandro; Licausi, Francesco; Luchinat, Claudio; Santucci, Claudio; Tenori, Leonardo; Van Veen, Hans; Zuccolo, Andrea; Ruperti, Benedetto; Tonutti, Pietro

    2016-01-01

    The ripening physiology of detached fruit is altered by low oxygen conditions with profound effects on quality parameters. To study hypoxia-related processes and regulatory mechanisms, apple (Malus domestica, cv Granny Smith) fruit, harvested at commercial ripening, were kept at 1°C under normoxic (control) and hypoxic (0.4 and 0.8 kPa oxygen) conditions for up to 60 days. NMR analyses of cortex tissue identified eight metabolites showing significantly different accumulations between samples, with ethanol and alanine displaying the most pronounced difference between hypoxic and normoxic treatments. A rapid up-regulation of alcohol dehydrogenase and pyruvate-related metabolism (lactate dehydrogenase, pyruvate decarboxylase, alanine aminotransferase) gene expression was detected under both hypoxic conditions with a more pronounced effect induced by the lowest (0.4 kPa) oxygen concentration. Both hypoxic conditions negatively affected ACC synthase and ACC oxidase transcript accumulation. Analysis of RNA-seq data of samples collected after 24 days of hypoxic treatment identified more than 1000 genes differentially expressed when comparing 0.4 vs. 0.8 kPa oxygen concentration samples. Genes involved in cell-wall, minor and major CHO, amino acid and secondary metabolisms, fermentation and glycolysis as well as genes involved in transport, defense responses, and oxidation-reduction appeared to be selectively affected by treatments. The lowest oxygen concentration induced a higher expression of transcription factors belonging to AUX/IAA, WRKY, HB, Zinc-finger families, while MADS box family genes were more expressed when apples were kept under 0.8 kPa oxygen. Out of the eight group VII ERF members present in apple genome, two genes showed a rapid up-regulation under hypoxia, and western blot analysis showed that apple MdRAP2.12 proteins were differentially accumulated in normoxic and hypoxic samples, with the highest level reached under 0.4 kPa oxygen. These data suggest

  7. Extreme Hypoxic Conditions Induce Selective Molecular Responses and Metabolic Reset in Detached Apple Fruit

    PubMed Central

    Cukrov, Dubravka; Zermiani, Monica; Brizzolara, Stefano; Cestaro, Alessandro; Licausi, Francesco; Luchinat, Claudio; Santucci, Claudio; Tenori, Leonardo; Van Veen, Hans; Zuccolo, Andrea; Ruperti, Benedetto; Tonutti, Pietro

    2016-01-01

    The ripening physiology of detached fruit is altered by low oxygen conditions with profound effects on quality parameters. To study hypoxia-related processes and regulatory mechanisms, apple (Malus domestica, cv Granny Smith) fruit, harvested at commercial ripening, were kept at 1°C under normoxic (control) and hypoxic (0.4 and 0.8 kPa oxygen) conditions for up to 60 days. NMR analyses of cortex tissue identified eight metabolites showing significantly different accumulations between samples, with ethanol and alanine displaying the most pronounced difference between hypoxic and normoxic treatments. A rapid up-regulation of alcohol dehydrogenase and pyruvate-related metabolism (lactate dehydrogenase, pyruvate decarboxylase, alanine aminotransferase) gene expression was detected under both hypoxic conditions with a more pronounced effect induced by the lowest (0.4 kPa) oxygen concentration. Both hypoxic conditions negatively affected ACC synthase and ACC oxidase transcript accumulation. Analysis of RNA-seq data of samples collected after 24 days of hypoxic treatment identified more than 1000 genes differentially expressed when comparing 0.4 vs. 0.8 kPa oxygen concentration samples. Genes involved in cell-wall, minor and major CHO, amino acid and secondary metabolisms, fermentation and glycolysis as well as genes involved in transport, defense responses, and oxidation-reduction appeared to be selectively affected by treatments. The lowest oxygen concentration induced a higher expression of transcription factors belonging to AUX/IAA, WRKY, HB, Zinc-finger families, while MADS box family genes were more expressed when apples were kept under 0.8 kPa oxygen. Out of the eight group VII ERF members present in apple genome, two genes showed a rapid up-regulation under hypoxia, and western blot analysis showed that apple MdRAP2.12 proteins were differentially accumulated in normoxic and hypoxic samples, with the highest level reached under 0.4 kPa oxygen. These data suggest

  8. Control and target gene selection for studies on UV-induced genotoxicity in whales

    PubMed Central

    2013-01-01

    Background Despite international success in reducing ozone-depleting emissions, ultraviolet radiation (UV) is not expected to decrease for several decades. Thus, it is pressing to implement tools that allow investigating the capacity of wildlife to respond to excessive UV, particularly species like cetaceans that lack anatomical or physiological protection. One approach is to examine epidermal expression of key genes involved in genotoxic stress response pathways. However, quantitation of mRNA transcripts requires previous standardization, with accurate selection of control and target genes. The latter is particularly important when working with environmental stressors such as UV that can activate numerous genes. Results Using 20 epidermal biopsies from blue, fin and sperm whale, we found that the genes encoding the ribosomal proteins L4 and S18 (RPL4 and RPS18) were the most suitable to use as controls, followed by the genes encoding phosphoglycerate kinase 1 (PGK1) and succinate dehydrogenase complex subunit A (SDHA). A careful analysis of the transcription pathways known to be activated by UV-exposure in humans and mice led us to select as target genes those encoding for i) heat shock protein 70 (HSP70) an indicator of general cell stress, ii) tumour suppressor protein P53 (P53), a transcription factor activated by UV and other cell stressors, and iii) KIN17 (KIN), a cell cycle protein known to be up-regulated following UV exposure. These genes were successfully amplified in the three species and quantitation of their mRNA transcripts was standardised using RPL4 and RPS18. Using a larger sample set of 60 whale skin biopsies, we found that the target gene with highest expression was HSP70 and that its levels of transcription were correlated with those of KIN and P53. Expression of HSP70 and P53 were both related to microscopic sunburn lesions recorded in the whales’ skin. Conclusion This article presents groundwork data essential for future qPCR-based studies

  9. Noise-induced standing waves in oscillatory systems with time-delayed feedback

    NASA Astrophysics Data System (ADS)

    Stich, Michael; Chattopadhyay, Amit K.

    2016-05-01

    In oscillatory reaction-diffusion systems, time-delay feedback can lead to the instability of uniform oscillations with respect to formation of standing waves. Here, we investigate how the presence of additive, Gaussian white noise can induce the appearance of standing waves. Combining analytical solutions of the model with spatiotemporal simulations, we find that noise can promote standing waves in regimes where the deterministic uniform oscillatory modes are stabilized. As the deterministic phase boundary is approached, the spatiotemporal correlations become stronger, such that even small noise can induce standing waves in this parameter regime. With larger noise strengths, standing waves could be induced at finite distances from the (deterministic) phase boundary. The overall dynamics is defined through the interplay of noisy forcing with the inherent reaction-diffusion dynamics.

  10. Highly efficient and selective pressure-assisted photon-induced polymerization of styrene

    NASA Astrophysics Data System (ADS)

    Guan, Jiwen; Song, Yang

    2016-06-01

    The polymerization process of condensed styrene to produce polystyrene as an industrially important polymeric material was investigated using a novel approach by combining external compression with ultraviolet radiation. The reaction evolution was monitored as a function of time and the reaction products were characterized by in situ Fourier transform infrared spectroscopy. By optimizing the loading pressures, we observed highly efficient and selective production of polystyrene of different tacticities. Specifically, at relatively low loading pressures, infrared spectra suggest that styrene monomers transform to amorphous atactic polystyrene (APS) with minor crystalline isotactic polystyrene. In contrast, APS was found to be the sole product when polymerization occurs at relatively higher loading pressures. The time-dependent reaction profiles allow the examination of the polymerization kinetics by analyzing the rate constant and activation volume as a function of pressure. As a result, an optimized pressure condition, which allows a barrierless reaction to proceed, was identified and attributed to the very desirable reaction yield and kinetics. Finally, the photoinitiated reaction mechanism and the growth geometry of the polymer chains were investigated from the energy diagram of styrene and by the topology analysis of the crystal styrene. This study shows strong promise to produce functional polymeric materials in a highly efficient and controlled manner.

  11. Highly efficient and selective pressure-assisted photon-induced polymerization of styrene.

    PubMed

    Guan, Jiwen; Song, Yang

    2016-06-01

    The polymerization process of condensed styrene to produce polystyrene as an industrially important polymeric material was investigated using a novel approach by combining external compression with ultraviolet radiation. The reaction evolution was monitored as a function of time and the reaction products were characterized by in situ Fourier transform infrared spectroscopy. By optimizing the loading pressures, we observed highly efficient and selective production of polystyrene of different tacticities. Specifically, at relatively low loading pressures, infrared spectra suggest that styrene monomers transform to amorphous atactic polystyrene (APS) with minor crystalline isotactic polystyrene. In contrast, APS was found to be the sole product when polymerization occurs at relatively higher loading pressures. The time-dependent reaction profiles allow the examination of the polymerization kinetics by analyzing the rate constant and activation volume as a function of pressure. As a result, an optimized pressure condition, which allows a barrierless reaction to proceed, was identified and attributed to the very desirable reaction yield and kinetics. Finally, the photoinitiated reaction mechanism and the growth geometry of the polymer chains were investigated from the energy diagram of styrene and by the topology analysis of the crystal styrene. This study shows strong promise to produce functional polymeric materials in a highly efficient and controlled manner. PMID:27276967

  12. Selected Demographic and Attitude Variables in Relation to Women's Motivation for Full-Time Employment, Part-Time Employment, Full-Time Homemaking and Volunteer Work.

    ERIC Educational Resources Information Center

    Gittman, Elizabeth

    The motivations of 275 women who were employed full-time, employed part-time, homemakers full-time or vounteeer workers were studied. Analysis of variance was used to test for differences between motivational groups within employment status categories on the demographic variables of personal income, age, educational level and number of children…

  13. Chronic heart failure selectively induces regional heterogeneity of insulin-responsive glucose transporters

    PubMed Central

    Ware, Bruce; Bevier, Marie; Nishijima, Yoshinori; Rogers, Suzanne; Carnes, Cynthia A.

    2011-01-01

    Glucose uptake across the sarcolemma is regulated by a family of membrane proteins called glucose transporters (GLUTs), which includes GLUT4 (the major cardiac isoform) and GLUT12 (a novel, second insulin-sensitive isoform). Potential regional patterns in glucose transport across the cardiac chambers have not been examined; thus, we hypothesized that insulin-responsive GLUT4 and -12 protein and gene expression would be chamber specific in healthy subjects and during chronic heart failure (HF). Using a canine model of tachypacing-induced, progressive, chronic HF, total GLUT protein and messenger RNA in both ventricles and atria (free wall and appendage) were investigated by immunoblotting and real-time PCR. In controls, GLUT4, but not GLUT12, protein content was significantly higher in the atria compared with the ventricles, with the highest content in the right atrium (RA; P < 0.001). GLUT4 and GLUT12 mRNA levels were similar across the cardiac chambers. During chronic HF, GLUT4 and GLUT12 protein content was highest in the left ventricle (LV; by 2.5- and 4.2-fold, respectively, P < 0.01), with a concomitant increase in GLUT4 and GLUT12 mRNA (P < 0.001). GLUT4, but not GLUT12, protein content was decreased in RA during chronic HF (P = 0.001). In conclusion, GLUT4 protein was differentially expressed across the chambers in the healthy heart, and this regional pattern was reversed during HF. Our data suggest that LV was the primary site dependent on both GLUT4 and GLUT12 during chronic HF. In addition, the paradoxical decrease in GLUT4 content in RA may induce perturbations in atrial energy production during chronic HF. PMID:21849635

  14. A novel manganese complex selectively induces malignant glioma cell death by targeting mitochondria.

    PubMed

    Geng, Ji; Li, Jing; Huang, Tao; Zhao, Kaidi; Chen, Qiuyun; Guo, Wenjie; Gao, Jing

    2016-09-01

    Despite advances in treatment, malignant glioma commonly exhibits recurrence, subsequently leading to a poor prognosis. As manganese (Mn) compounds can be transported by the transferrin‑transferrin receptor system, the present study synthesized and examined the potential use of Adpa‑Mn as a novel antitumor agent. Adpa‑Mn time and dose‑dependently inhibited U251 and C6 cell proliferation; however, it had little effect on normal astrocytes. Apoptosis was significantly elevated following treatment with Adpa‑Mn, as detected by chromatin condensation, Annexin V/propidium iodide staining, cytochrome c release from mitochondria to the cytoplasm, and the activation of caspases‑9, ‑7 and ‑3 and poly (ADP‑ribose) polymerase. In addition, Adpa‑Mn enhanced fluorescence intensity of monodansylcadaverine and elevated the expression levels of the autophagy‑related protein microtubule‑associated protein 1 light chain 3. Pretreatment with the autophagy inhibitors 3‑methyladenine and chloroquine enhanced Adpa‑Mn‑induced cell inhibition, thus indicating that autophagy has an essential role in this process. Furthermore, evidence of mitochondrial dysfunction was detected in the Adpa‑Mn‑treated group, including disrupted membrane potential, elevated levels of reactive oxygen species (ROS) and depleted adenosine triphosphate. Conversely, treatment with the mitochondrial permeability transition inhibitor cyclosporin A reversed Adpa‑Mn‑induced ROS production, mitochondrial damage and cell apoptosis, thus suggesting that Adpa‑Mn may target the mitochondria. Taken together, these data suggested that Adpa‑Mn may be considered for use as a novel anti‑glioma therapeutic option. PMID:27432745

  15. Effects of Morphine on Temporal Discrimination and Color Matching: General Disruption of Stimulus Control or Selective Effects on Timing?

    ERIC Educational Resources Information Center

    Ward, Ryan D.; Odum, Amy L.

    2005-01-01

    Discrepant effects of drugs on behavior maintained by temporal-discrimination procedures make conclusive statements about the neuropharmacological bases of timing difficult. The current experiment examined the possible contribution of a general, drug-induced disruption of stimulus control. Four pigeons responded on a three-component multiple…

  16. The selective D2 dopamine receptor antagonist eticlopride counteracts the ejaculatio praecox induced by the selective D2 dopamine agonist SND 919 in the rat.

    PubMed

    Ferrari, F; Giuliani, D

    1994-01-01

    The selective D2 antagonist eticlopride, at a dose (0.01 mg/kg, s.c.) that fails to modify the normal behavior of rats, significantly reversed all the behavioral effects exerted by the selective D2 agonist SND 919 (0.1 mg/kg, i.p.), namely, the stimulation of stretching-yawning, penile erection and sedation and the inhibition of grooming. In the copulatory test, eticlopride at the same dose did not affect animal sexual behavior but potently counteracted the reduction in mount and intromission frequency and latency to ejaculation induced by SND 919 at 0.1 mg/kg, a behavioral pattern which might possibly be proposed as an animal model for human ejaculatio praecox. PMID:7916439

  17. Initiation time of near-infrared laser-induced slip on the surface of silicon wafers

    SciTech Connect

    Choi, Sungho; Jhang, Kyung-Young

    2014-06-23

    We have determined the initiation time of laser-induced slip on a silicon wafer surface subjected to a near-infrared continuous-wave laser by numerical simulations and experiments. First, numerical analysis was performed based on the heat transfer and thermoelasticity model to calculate the resolved shear stress and the temperature-dependent yield stress. Slip initiation time was predicted by finding the time at which the resolved shear stress reached the yield stress. Experimentally, the slip initiation time was measured by using a laser scattering technique that collects scattered light from the silicon wafer surface and detects strong scattering when the surface slip is initiated. The surface morphology of the silicon wafer surface after laser irradiation was also observed using an optical microscope to confirm the occurrence of slip. The measured slip initiation times agreed well with the numerical predictions.

  18. Initiation time of near-infrared laser-induced slip on the surface of silicon wafers

    NASA Astrophysics Data System (ADS)

    Choi, Sungho; Jhang, Kyung-Young

    2014-06-01

    We have determined the initiation time of laser-induced slip on a silicon wafer surface subjected to a near-infrared continuous-wave laser by numerical simulations and experiments. First, numerical analysis was performed based on the heat transfer and thermoelasticity model to calculate the resolved shear stress and the temperature-dependent yield stress. Slip initiation time was predicted by finding the time at which the resolved shear stress reached the yield stress. Experimentally, the slip initiation time was measured by using a laser scattering technique that collects scattered light from the silicon wafer surface and detects strong scattering when the surface slip is initiated. The surface morphology of the silicon wafer surface after laser irradiation was also observed using an optical microscope to confirm the occurrence of slip. The measured slip initiation times agreed well with the numerical predictions.

  19. Direct Observation of the Surface Segregation of Cu in Pd by Time-Resolved Positron-Annihilation-Induced Auger Electron Spectroscopy

    SciTech Connect

    Mayer, J.; Hugenschmidt, C.; Schreckenbach, K.

    2010-11-12

    Density functional theory calculations predict the surface segregation of Cu in the second atomic layer of Pd which has not been unambiguously confirmed by experiment so far. We report measurements on Pd surfaces covered with three and six monolayers of Cu using element selective positron-annihilation-induced Auger electron spectroscopy (PAES) which is sensitive to the topmost atomic layer. Moreover, time-resolved PAES, which was applied for the first time, enables the investigation of the dynamics of surface atoms and hence the observation of the segregation process. The time constant for segregation was experimentally determined to {tau}=1.38(0.21) h, and the final segregated configuration was found to be consistent with calculations. Time-dependent PAES is demonstrated to be a novel element selective technique applicable for the investigation of, e.g., heterogeneous catalysis, corrosion, or surface alloying.

  20. Diversity and time delays induce resonance in a modular neuronal network

    NASA Astrophysics Data System (ADS)

    Jia, Y. B.; Yang, X. L.; Kurths, J.

    2014-12-01

    This paper focuses on the resonance dynamics of a modular neuronal network consisting of several small-world subnetworks. The considered network is composed of delay-coupled FitzHugh-Nagumo (FHN) neurons, whose characteristic parameters present diversity in the form of quenched noise. Our numerical results indicate that when such a network is subjected to an external subthreshold periodic signal, its collective response is optimized for an intermediate level of diversity, namely, a resonant behavior can be induced by an appropriate level of diversity. How the probabilities of intramodule and intermodule connections, as well as the number of subnetworks influence the diversity-induced resonance are also discussed. Further, conclusive evidences demonstrate the nontrivial role of time-delayed coupling on the diversity-induced resonance properties. Especially, multiple resonance is obviously detected when time delays are located at integer multiples of the oscillation period of the signal. Moreover, the phenomenon of fine-tuned delays in inducing multiple resonance remains when diversity is within an intermediate range. Our findings have implications that neural systems may profit from their generic diversity and delayed coupling to optimize the response to external stimulus.

  1. Real-Time, Selective Detection of Copper(II) Using Ionophore-Grafted Carbon-Fiber Microelectrodes.

    PubMed

    Yang, Yuanyuan; Ibrahim, Ahmad A; Hashemi, Parastoo; Stockdill, Jennifer L

    2016-07-19

    Rapid, selective detection of metals in complex samples remains an elusive goal that could provide critical analytical information for biological and environmental sciences and industrial waste management. Fast-scan cyclic voltammetry (FSCV) using carbon-fiber microelectrodes (CFMs) is an emerging technique for metal analysis with broad potential applicability because of its rapid response to changes in analyte concentration and minimal disturbance to the analysis medium. In this communication, we report the first effective application of covalently modified CFMs to achieve highly selective, subsecond Cu(II) measurements using FSCV. A two-part strategy is employed for maximum selectivity: Cu(II) binding is augmented by a covalently grafted ionophore, while binding of other metals is prevented by chemical blocking of nonselective surface adsorption sites. The resulting electrodes selectively detect Cu(II) in a complex medium comprising several interfering metals. Overall, this strategy represents a transformative innovation in real-time electrochemical detection of metal analytes. PMID:27079730

  2. Delay selection by spike-timing-dependent plasticity in recurrent networks of spiking neurons receiving oscillatory inputs.

    PubMed

    Kerr, Robert R; Burkitt, Anthony N; Thomas, Doreen A; Gilson, Matthieu; Grayden, David B

    2013-01-01

    Learning rules, such as spike-timing-dependent plasticity (STDP), change the structure of networks of neurons based on the firing activity. A network level understanding of these mechanisms can help infer how the brain learns patterns and processes information. Previous studies have shown that STDP selectively potentiates feed-forward connections that have specific axonal delays, and that this underlies behavioral functions such as sound localization in the auditory brainstem of the barn owl. In this study, we investigate how STDP leads to the selective potentiation of recurrent connections with different axonal and dendritic delays during oscillatory activity. We develop analytical models of learning with additive STDP in recurrent networks driven by oscillatory inputs, and support the results using simulations with leaky integrate-and-fire neurons. Our results show selective potentiation of connections with specific axonal delays, which depended on the input frequency. In addition, we demonstrate how this can lead to a network becoming selective in the amplitude of its oscillatory response to this frequency. We extend this model of axonal delay selection within a single recurrent network in two ways. First, we show the selective potentiation of connections with a range of both axonal and dendritic delays. Second, we show axonal delay selection between multiple groups receiving out-of-phase, oscillatory inputs. We discuss the application of these models to the formation and activation of neuronal ensembles or cell assemblies in the cortex, and also to missing fundamental pitch perception in the auditory brainstem. PMID:23408878

  3. Effects of selection and training on unit-level performance over time: a latent growth modeling approach.

    PubMed

    Van Iddekinge, Chad H; Ferris, Gerald R; Perrewé, Pamela L; Blass, Fred R; Heetderks, Thomas D; Perryman, Alexa A

    2009-07-01

    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 change in unit performance. Latent growth modeling analyses revealed significant variation in both the use and the change in use of selection and training across units. Change in selection and training was related to change in 2 proximal unit outcomes: customer service performance and retention. Change in service performance, in turn, was related to change in the more distal outcome of unit financial performance (i.e., profits). Selection and training also affected financial performance, both directly and indirectly (e.g., through service performance). Finally, results of a cross-lagged panel analysis suggested the existence of a reciprocal causal relationship between the utilization of the human resources practices and unit performance. However, there was some evidence to suggest that selection and training may be associated with different causal sequences, such that use of the training procedure appeared to lead to unit performance, whereas unit performance appeared to lead to use of the selection procedure. PMID:19594228

  4. Visible-Light-Induced Alkoxyl Radical Generation Enables Selective C(sp(3))-C(sp(3)) Bond Cleavage and Functionalizations.

    PubMed

    Jia, Kunfang; Zhang, Fuyuan; Huang, Hanchu; Chen, Yiyun

    2016-02-10

    The alkoxyl radical is an important reactive intermediate in mechanistic studies and organic synthesis; however, its current generation from alcohol oxidation heavily relies on transition metal activation under strong oxidative conditions. Here we report the first visible-light-induced alcohol oxidation to generate alkoxyl radicals by cyclic iodine(III) reagent catalysis under mild reaction conditions. The β-fragmentation of alkoxyl radicals enables selective C(sp(3))-C(sp(3)) bond cleavage and alkynylation/alkenylation reactions with various strained cycloalkanols, and for the first time with linear alcohols. PMID:26829105

  5. Feasibility of time-lapse AVO and AVOA analysis to monitor compaction-induced seismic anisotropy

    NASA Astrophysics Data System (ADS)

    He, Y.-X.; Angus, D. A.; Yuan, S. Y.; Xu, Y. G.

    2015-11-01

    Hydrocarbon reservoir production generally results in observable time-lapse physical property changes, such as velocity increases within a compacting reservoir. However, the physical property changes that lead to velocity changes can be difficult to isolate uniquely. Thus, integrated hydro-mechanical simulation, stress-sensitive rock physics models and time-lapse seismic modelling workflows can be employed to study the influence of velocity changes and induced seismic anisotropy due to reservoir compaction. We study the influence of reservoir compaction and compartmentalization on time-lapse seismic signatures for reflection amplitude variation with offset (AVO) and azimuth (AVOA). Specifically, the time-lapse AVO and AVOA responses are predicted for two models: a laterally homogeneous four-layer dipping model and a laterally heterogeneous graben structure reservoir model. Seismic reflection coefficients for different offsets and azimuths are calculated for compressional (P-P) and converted shear (P-S) waves using an anisotropic ray tracer as well as using approximate equations for AVO and AVOA. The simulations help assess the feasibility of using time-lapse AVO and AVOA signatures to monitor reservoir compartmentalization as well as evaluate induced stress anisotropy due to changes in the effective stress field. The results of this study indicate that time-lapse AVO and AVOA analysis can be applied as a potential means for qualitatively and semi-quantitatively linking azimuthal anisotropy changes caused by reservoir production to pressure/stress changes.

  6. Evaluating the time and temperature dependent biaxial strength of Gore-Select ® series 57 proton exchange membrane using a pressure loaded blister test

    NASA Astrophysics Data System (ADS)

    Grohs, Jacob R.; Li, Yongqiang; Dillard, David A.; Case, Scott W.; Ellis, Michael W.; Lai, Yeh-Hung; Gittleman, Craig S.

    Temperature and humidity fluctuations in operating fuel cells impose significant biaxial stresses in the constrained proton exchange membranes (PEMs) of a fuel cell stack. The strength of the PEM, and its ability to withstand cyclic environment-induced stresses, plays an important role in membrane integrity and consequently, fuel cell durability. In this study, a pressure loaded blister test is used to characterize the biaxial strength of Gore-Select ® series 57 over a range of times and temperatures. Hencky's classical solution for a pressurized circular membrane is used to estimate biaxial strength values from burst pressure measurements. A hereditary integral is employed to construct the linear viscoelastic analog to Hencky's linear elastic exact solution. Biaxial strength master curves are constructed using traditional time-temperature superposition principle techniques and the associated temperature shift factors show good agreement with shift factors obtained from constitutive (stress relaxation) and fracture (knife slit) tests of the material.

  7. Adaptation-Induced Compression of Event Time Occurs Only for Translational Motion

    PubMed Central

    Fornaciai, Michele; Arrighi, Roberto; Burr, David C.

    2016-01-01

    Adaptation to fast motion reduces the perceived duration of stimuli displayed at the same location as the adapting stimuli. Here we show that the adaptation-induced compression of time is specific for translational motion. Adaptation to complex motion, either circular or radial, did not affect perceived duration of subsequently viewed stimuli. Adaptation with multiple patches of translating motion caused compression of duration only when the motion of all patches was in the same direction. These results show that adaptation-induced compression of event-time occurs only for uni-directional translational motion, ruling out the possibility that the neural mechanisms of the adaptation occur at early levels of visual processing. PMID:27003445

  8. A practical MGA-ARIMA model for forecasting real-time dynamic rain-induced attenuation

    NASA Astrophysics Data System (ADS)

    Gong, Shuhong; Gao, Yifeng; Shi, Houbao; Zhao, Ge

    2013-05-01

    novel and practical modified genetic algorithm (MGA)-autoregressive integrated moving average (ARIMA) model for forecasting real-time dynamic rain-induced attenuation has been established by combining genetic algorithm ideas with the ARIMA model. It is proved that due to the introduction of MGA into the ARIMA(1,1,7) model, the MGA-ARIMA model has the potential to be conveniently applied in every country or area by creating a parameter database used by the ARIMA(1,1,7) model. The parameter database is given in this paper based on attenuation data measured in Xi'an, China. The methods to create the parameter databases in other countries or areas are offered, too. Based on the experimental results, the MGA-ARIMA model has been proved practical for forecasting dynamic rain-induced attenuation in real time. The novel model given in this paper is significant for developing adaptive fade mitigation technologies at millimeter wave bands.

  9. The effect of time variable stress shadows on rates of induced seismicity (Invited)

    NASA Astrophysics Data System (ADS)

    Dahm, T.; Becker, D.; Hainzl, S.; Fischer, T.

    2013-12-01

    Stress shadows, i.e. regions where stress is temporarily decreased and not increased, are difficult to identify for natural seismicity, since the overall rate of seismicity is typically small. Fluid injection experiments or mining operations often generate very high rates of induced seismicity, so that stress shadow effects are easily recognized. Well known examples comprise the backfront of seismicity observed during the shut-in phase of hydrofracture experiments, or the Kaiser effect in mining environments if the stress loading is periodic. We present examples of stress shadow effects on induced seismicity. We study the theoretical variation of seismicity rates from time dependent stressing models by means of rate and state frictional models. The controlling parameter are discussed at different reservoir and mining areas, and we discuss the predictability of seismicity rates and decay times. DB has been supported by the German research Foundation under Be4602/1-1.

  10. Bilberry extract (Antho 50) selectively induces redox-sensitive caspase 3-related apoptosis in chronic lymphocytic leukemia cells by targeting the Bcl-2/Bad pathway

    PubMed Central

    Alhosin, Mahmoud; León-González, Antonio J.; Dandache, Israa; Lelay, Agnès; Rashid, Sherzad K.; Kevers, Claire; Pincemail, Joël; Fornecker, Luc-Matthieu; Mauvieux, Laurent; Herbrecht, Raoul; Schini-Kerth, Valérie B.

    2015-01-01

    Defect in apoptosis has been implicated as a major cause of resistance to chemotherapy observed in B cell chronic lymphocytic leukaemia (B CLL). This study evaluated the pro-apoptotic effect of an anthocyanin-rich dietary bilberry extract (Antho 50) on B CLL cells from 30 patients and on peripheral blood mononuclear cells (PBMCs) from healthy subjects, and determined the underlying mechanism. Antho 50 induced concentration- and time-dependent pro-apoptotic effects in B CLL cells but little or no effect in PBMCs. Among the main phenolic compounds of the bilberry extract, delphinidin-3-O-glucoside and delphinidin-3-O-rutinoside induced a pro-apoptotic effect. Antho 50-induced apoptosis is associated with activation of caspase 3, down-regulation of UHRF1, a rapid dephosphorylation of Akt and Bad, and down-regulation of Bcl-2. Antho 50 significantly induced PEG-catalase-sensitive formation of reactive oxygen species in B CLL cells. PEG-catalase prevented the Antho 50-induced induction of apoptosis and related signaling. The present findings indicate that Antho 50 exhibits strong pro-apoptotic activity through redox-sensitive caspase 3 activation-related mechanism in B CLL cells involving dysregulation of the Bad/Bcl-2 pathway. This activity of Antho 50 involves the glucoside and rutinoside derivatives of delphinidin. They further suggest that Antho 50 has chemotherapeutic potential by targeting selectively B CLL cells. PMID:25757575

  11. Selective Influence of Circadian Modulation and Task Characteristics on Motor Imagery Time

    ERIC Educational Resources Information Center

    Debarnot, Ursula; Sahraoui, Djafar; Champely, Stephane; Collet, Christian; Guillot, Aymeric

    2012-01-01

    In this study, we examined the effect of circadian modulation on motor imagery (MI) time while also considering the effects of task complexity and duration. The ability to imagine in real time was influenced by circadian modulation in a simple walking condition, with longer MI times in the morning and evening sessions. By contrast, there was no…

  12. Time of travel of solutes in selected reaches of Ohio streams, 1973 and 1975

    USGS Publications Warehouse

    Westfall, Arthur O.

    1977-01-01

    The basic field data for time-of-travel measurements on six streams in Ohio are presented. In gereral, additional data on stream cross sections, tributary inflows, and chemical analyses for mainstream and tributary flows are given. Insufficient data were obtained to establish time-distance or time-discharge relationships.

  13. Stimulus Similarity and Encoding Time Influence Incidental Recognition Memory in Adult Monkeys with Selective Hippocampal Lesions

    ERIC Educational Resources Information Center

    Zeamer, Alyson; Meunier, Martine; Bachevalier, Jocelyne

    2011-01-01

    Recognition memory impairment after selective hippocampal lesions in monkeys is more profound when measured with visual paired-comparison (VPC) than with delayed nonmatching-to-sample (DNMS). To clarify this issue, we assessed the impact of stimuli similarity and encoding duration on the VPC performance in monkeys with hippocampal lesions and…

  14. The good, the bad, and the timely: how temporal order and moral judgment influence causal selection

    PubMed Central

    Reuter, Kevin; Kirfel, Lara; van Riel, Raphael; Barlassina, Luca

    2014-01-01

    Causal selection is the cognitive process through which one or more elements in a complex causal structure are singled out as actual causes of a certain effect. In this paper, we report on an experiment in which we investigated the role of moral and temporal factors in causal selection. Our results are as follows. First, when presented with a temporal chain in which two human agents perform the same action one after the other, subjects tend to judge the later agent to be the actual cause. Second, the impact of temporal location on causal selection is almost canceled out if the later agent did not violate a norm while the former did. We argue that this is due to the impact that judgments of norm violation have on causal selection—even if the violated norm has nothing to do with the obtaining effect. Third, moral judgments about the effect influence causal selection even in the case in which agents could not have foreseen the effect and did not intend to bring it about. We discuss our findings in connection to recent theories of the role of moral judgment in causal reasoning, on the one hand, and to probabilistic models of temporal location, on the other. PMID:25477851

  15. Full-Time Faculty Recruitment and Selection Strategies Practiced by Learning-Centered Community Colleges.

    ERIC Educational Resources Information Center

    Fowler-Hill, Sandra A.

    This report presents the results of a study of faculty recruitment and selection strategies used by self-reported learning-centered community colleges during the 1998-1999 academic year. The study examined six key principles of a learning college: (1) creates substantive change in learners; (2) engages students as partners in learning; (3) offers…

  16. Visual Marking: The Influence of Temporary Changes on Time-Based Visual Selection

    ERIC Educational Resources Information Center

    Watson, Derrick G.; Compton, Suzannah; Bailey, Hannah

    2011-01-01

    The preview benefit describes the finding that participants can prioritize the selection of new stimuli by the top-down inhibition of previously presented (previewed) items already in the field (Watson & Humphreys, 1997). Previous work has shown that if the old items undergo a permanent shape change when the new are added, then the old items…

  17. Caterpillars selected for large body size and short development time are more susceptible to oxygen-related stress

    PubMed Central

    Harrison, Jon F; Cease, Arianne J; VandenBrooks, John M; Albert, Todd; Davidowitz, Goggy

    2013-01-01

    Recent studies suggest that higher growth rates may be associated with reduced capacities for stress tolerance and increased accumulated damage due to reactive oxygen species. We tested the response of Manduca sexta (Sphingidae) lines selected for large or small body size and short development time to hypoxia (10 kPa) and hyperoxia (25, 33, and 40 kPa); both hypoxia and hyperoxia reduce reproduction and oxygen levels over 33 kPa have been shown to increase oxidative damage in insects. Under normoxic (21 kPa) conditions, individuals from the large-selected (big-fast) line were larger and had faster growth rates, slightly longer developmental times, and reduced survival rates compared to individuals from a line selected for small size (small-fast) or an unselected control line. Individuals from the big-fast line exhibited greater negative responses to hyperoxia with greater reductions in juvenile and adult mass, growth rate, and survival than the other two lines. Hypoxia generally negatively affected survival and growth/size, but the lines responded similarly. These results are mostly consistent with the hypothesis that simultaneous acquisition of large body sizes and short development times leads to reduced capacities for coping with stressful conditions including oxidative damage. This result is of particular importance in that natural selection tends to decrease development time and increase body size. PMID:23762517

  18. Acquisition of Some Selected Prepositions of Time by English Major Undergraduates at Balqa Applied University in Jordan

    ERIC Educational Resources Information Center

    Al-Qudah, Ayat Khalid

    2013-01-01

    This study aimed to identify the acquisition of some selected prepositions of time by English major undergraduates at Balqa Applied University in Jordan and to reveal any significant differences among their acquisition attributed to the academic level (1st, 2nd, 3rd and 4th year levels) and to studying "English Basic Grammar" course. A…

  19. Caterpillars selected for large body size and short development time are more susceptible to oxygen-related stress.

    PubMed

    Harrison, Jon F; Cease, Arianne J; Vandenbrooks, John M; Albert, Todd; Davidowitz, Goggy

    2013-05-01

    Recent studies suggest that higher growth rates may be associated with reduced capacities for stress tolerance and increased accumulated damage due to reactive oxygen species. We tested the response of Manduca sexta (Sphingidae) lines selected for large or small body size and short development time to hypoxia (10 kPa) and hyperoxia (25, 33, and 40 kPa); both hypoxia and hyperoxia reduce reproduction and oxygen levels over 33 kPa have been shown to increase oxidative damage in insects. Under normoxic (21 kPa) conditions, individuals from the large-selected (big-fast) line were larger and had faster growth rates, slightly longer developmental times, and reduced survival rates compared to individuals from a line selected for small size (small-fast) or an unselected control line. Individuals from the big-fast line exhibited greater negative responses to hyperoxia with greater reductions in juvenile and adult mass, growth rate, and survival than the other two lines. Hypoxia generally negatively affected survival and growth/size, but the lines responded similarly. These results are mostly consistent with the hypothesis that simultaneous acquisition of large body sizes and short development times leads to reduced capacities for coping with stressful conditions including oxidative damage. This result is of particular importance in that natural selection tends to decrease development time and increase body size. PMID:23762517

  20. Neutron-induced fission measurements at the time-of-flight facility nELBE

    DOE PAGESBeta

    Kögler, T.; Beyer, R.; Junghans, A. R.; Massarczyk, R.; Schwengner, R.; Wagner, A.

    2015-05-18

    Neutron-induced fission of ²⁴²Pu is studied at the photoneutron source nELBE. The relative fast neutron fission cross section was determined using actinide fission chambers in a time-of-flight experiment. A good agreement of present nuclear data with evalua- tions has been achieved in the range of 100 keV to 10 MeV.

  1. Effects of Selective iNOS Inhibitor on Spatial Memory in Recovered and Non-Recovered Ketamine Induced Anesthesia

    PubMed Central

    Tabrizian, Kaveh; Najafi, Sheyda; Belaran, Maryam; Hosseini-Sharifabad, Ali; Azami, Kian; Soodi, Maliheh; Kazemi, Ali; Kebriaeezadeh, Abbas; Sharifzadeh, Mohammad

    2011-01-01

    Nitric oxide (NO) is thought to be involved in spatial learning and memory in several brain areas such as hippocampus. This study examined the effects of post-training intrahippocampal microinjections of 1400W as a selective iNOS inhibitor on spatial memory, in anesthetized and non-anesthetized situations in rats. In the present work, 4-day training trials of animals were conducted. Spatial memory was tested 48 hours after the drug infusions. For microinjection of 1400W into CA1 region of the hippocampus in conscious animals, guide cannula was implanted into the CA1 area and 1400W was infused after recovery from surgical anesthesia. In anesthetized animals, 1400W was microinjected directly into CA1 region by Hamilton syringe during anesthesia. After completion of training, 1400W (10, 50 and 100 μM/side) were microinjected bilaterally (1 μL/side) and testing trials were performed 48 h after drug infusions in both groups of cannulated and non-cannulated rats. Significant reduction was observed in escape latency and traveled distance in animals that received 1400W (100 μM/side, *p < 0.05) via cannula after recovery in comparison with control group. Also, microinjection of 1400W (100 μM/side) in post recovery phase caused a significant (***p < 0.001) reduction in time and distance of finding the hidden platform in comparison with anesthetized situation. These findings suggest that 1400W has a significant improvement on spatial memory and memory enhancement induced by iNOS inhibitor can be affected by anesthesia in a period of time. PMID:24250424

  2. An in vitro selection for small molecule induced switching RNA molecules.

    PubMed

    Martini, Laura; Ellington, Andrew D; Mansy, Sheref S

    2016-08-15

    The selection of RNA and DNA aptamers now has a long history. However, the ability to directly select for conformational changes upon ligand binding has remained elusive. These difficulties have stymied attempts at making small molecule responsive strand displacement circuitry as well as synthetic riboswitches. Herein we present a detailed strand displacement based selection protocol to directly select for RNA molecules with switching activity. The library was based on a previously selected thiamine pyrophosphate riboswitch. The fully in vitro methodology gave sequences that showed strong strand displacement activity in the presence of thiamine pyrophosphate. Further, the selected sequences possessed riboswitch activity similar to that of natural riboswitches. The presented methodology should aid in the design of more complex, environmentally responsive strand displacement circuitry and in the selection of riboswitches responsive to toxic ligands. PMID:26899430

  3. Inducing changes in the bond length of diatomic molecules by time-symmetric chirped pulses

    SciTech Connect

    Chang, Bo Y.; Shin, Seokmin; Sola, Ignacio R.

    2010-12-15

    We show numerically that it is possible to change the structure of a simple molecule, that is, a diatomic molecule, where the bond length is modified at a precise timing with symmetrically chirped laser pulses. In the adiabatic regime, the process is fully time reversible, making it possible to design slow vibrations with large bond elongations. The scheme relies on the preparation of a separable state of both nuclear and electronic degrees of freedom with predominant amplitude on the dissociative (antibonding) electronic wave function. Shorter laser pulses can be used to dynamically induce larger bond elongations, preparing a highly excited vibrational wave packet in the ground potential as the laser is switched off.

  4. Selective inhibition of unfolded protein response induces apoptosis in pancreatic cancer cells

    PubMed Central

    Sun, Qiao-Yang; Torres-Fernandez, Lucia A; Tan, Siew Zhuan; Xiao, Jinfen; Lim, Su Lin; Garg, Manoj; Lee, Kian Leong; Kitajima, Shojiro; Takao, Sumiko; Leong, Wei Zhong; Sun, Haibo; Tokatly, Itay; Poellinger, Lorenz; Gery, Sigal; Koeffler, Phillip H

    2014-01-01

    Endoplasmic reticulum stress from unfolded proteins is associated with the proliferation of pancreatic tumor cells, making the many regulatory molecules of this pathway appealing targets for therapy. The objective of our study was to assess potential therapeutic efficacy of inhibitors of unfolded protein response (UPR) in pancreatic cancers focusing on IRE1α inhibitors. IRE1α-mediated XBP-1 mRNA splicing encodes a transcription factor that enhances transcription of chaperone proteins in order to reverse UPR. Proliferation assays using a panel of 14 pancreatic cancer cell lines showed a dose- and time-dependent growth inhibition by IRE1α-specific inhibitors (STF-083010, 2-Hydroxy-1-naphthaldehyde, 3-Ethoxy-5,6-dibromosalicylaldehyde, toyocamycin). Growth inhibition was also noted using a clonogenic growth assay in soft agar, as well as a xenograft in vivo model of pancreatic cancer. Cell cycle analysis showed that these IRE1α inhibitors caused growth arrest at either the G1 or G2/M phases (SU8686, MiaPaCa2) and induced apoptosis (Panc0327, Panc0403). Western blot analysis showed cleavage of caspase 3 and PARP, and prominent induction of the apoptotic molecule BIM. In addition, synergistic effects were found between either STF-083010, 2-Hydroxy-1-naphthaldehyde, 3-Ethoxy-5,6-dibromosalicylaldehyde, or toyocamycin and either gemcitabine or bortezomib. Our data suggest that use of an IRE1α inhibitor is a novel therapeutic approach for treatment of pancreatic cancers. PMID:24952679

  5. Selective inhibition of unfolded protein response induces apoptosis in pancreatic cancer cells.

    PubMed

    Chien, Wenwen; Ding, Ling-Wen; Sun, Qiao-Yang; Torres-Fernandez, Lucia A; Tan, Siew Zhuan; Xiao, Jinfen; Lim, Su Lin; Garg, Manoj; Lee, Kian Leong; Kitajima, Shojiro; Takao, Sumiko; Leong, Wei Zhong; Sun, Haibo; Tokatly, Itay; Poellinger, Lorenz; Gery, Sigal; Koeffler, Phillip H

    2014-07-15

    Endoplasmic reticulum stress from unfolded proteins is associated with the proliferation of pancreatic tumor cells, making the many regulatory molecules of this pathway appealing targets for therapy. The objective of our study was to assess potential therapeutic efficacy of inhibitors of unfolded protein response (UPR) in pancreatic cancers focusing on IRE1α inhibitors. IRE1α-mediated XBP-1 mRNA splicing encodes a transcription factor that enhances transcription of chaperone proteins in order to reverse UPR. Proliferation assays using a panel of 14 pancreatic cancer cell lines showed a dose- and time-dependent growth inhibition by IRE1α-specific inhibitors (STF-083010, 2-Hydroxy-1-naphthaldehyde, 3-Ethoxy-5,6-dibromosalicylaldehyde, toyocamycin). Growth inhibition was also noted using a clonogenic growth assay in soft agar, as well as a xenograft in vivo model of pancreatic cancer. Cell cycle analysis showed that these IRE1α inhibitors caused growth arrest at either the G1 or G2/M phases (SU8686, MiaPaCa2) and induced apoptosis (Panc0327, Panc0403). Western blot analysis showed cleavage of caspase 3 and PARP, and prominent induction of the apoptotic molecule BIM. In addition, synergistic effects were found between either STF-083010, 2-Hydroxy-1-naphthaldehyde, 3-Ethoxy-5,6-dibromosalicylaldehyde, or toyocamycin and either gemcitabine or bortezomib. Our data suggest that use of an IRE1α inhibitor is a novel therapeutic approach for treatment of pancreatic cancers. PMID:24952679

  6. Minimally oxidized LDL inhibits macrophage selective cholesteryl ester uptake and native LDL-induced foam cell formation[S

    PubMed Central

    Meyer, Jason M.; Ji, Ailing; Cai, Lei; van der Westhuyzen, Deneys R.

    2014-01-01

    Scavenger receptor-mediated uptake of oxidized LDL (oxLDL) is thought to be the major mechanism of foam cell generation in atherosclerotic lesions. Recent data has indicated that native LDL is also capable of contributing to foam cell formation via low-affinity receptor-independent LDL particle pinocytosis and selective cholesteryl ester (CE) uptake. In the current investigation, Cu2+-induced LDL oxidation was found to inhibit macrophage selective CE uptake. Impairment of selective CE uptake was significant with LDL oxidized for as little as 30 min and correlated with oxidative fragmentation of apoB. In contrast, LDL aggregation, LDL CE oxidation, and the enhancement of scavenger receptor-mediated LDL particle uptake required at least 3 h of oxidation. Selective CE uptake did not require expression of the LDL receptor (LDL-R) and was inhibited similarly by LDL oxidation in LDL-R−/− versus WT macrophages. Inhibition of selective uptake was also observed when cells were pretreated or cotreated with minimally oxidized LDL, indicating a direct inhibitory effect of this oxLDL on macrophages. Consistent with the effect on LDL CE uptake, minimal LDL oxidation almost completely prevented LDL-induced foam cell formation. These data demonstrate a novel inhibitory effect of mildly oxidized LDL that may reduce foam cell formation in atherosclerosis. PMID:24891335

  7. An Integral Method for Determining Induced Voltage in Time-Varying Wire Inductors

    SciTech Connect

    Fasenfest, B; White, D; Rockway, J

    2005-05-27

    This report documents the creation of software tools to model time-varying wire inductors. The class of inductors studied consists of arbitrary wire shapes in nonmagnetic material. When the wire structures are deformed, the inductance changes, and a voltage is induced. This voltage is of interest, for instance when the inductor is used to measure or sense a shockwave. An integral technique, which only requires integrating over the wire segments, is used to find the inductance at each time step, with backwards-difference approximations being used on successive time steps to determine the voltage. This method allows for arbitrary time-varying wire structures. It was tested for several canonical problems and used to model a double helix solenoid compressed by a shockwave.

  8. Epidermal Growth Factor Receptor-Targeted Photosensitizer Selectively Inhibits EGFR Signaling and Induces Targeted Phototoxicity In Ovarian Cancer Cells

    PubMed Central

    Abu-Yousif, Adnan O.; Moor, Anne C. E.; Zheng, Xiang; Savellano, Mark D.; Yu, Weiping; Selbo, Pål K.; Hasan, Tayyaba

    2012-01-01

    Targeted photosensitizer delivery to EGFR expressing cells was achieved in the present study using a high purity, targeted photoimmunoconjugate (PIC). When the PDT agent, benzoporphyin monoacid ring A (BPD) was coupled to an EGFR-targeting antibody (cetuximab), we observed altered cellular localization and selective phototoxicity of EGFR-positive cells, but no phototoxicity of EGFR-negative cells. Cetuximab in the PIC formulation blocked EGF-induced activation of the EGFR and downstream signaling pathways. Our results suggest that photoimmunotargeting is a useful dual strategy for the selective destruction of cancer cells and also exerts the receptor-blocking biological function of the antibody. PMID:22266098

  9. A quantitative method for evaluating numerical simulation accuracy of time-transient Lamb wave propagation with its applications to selecting appropriate element size and time step.

    PubMed

    Wan, Xiang; Xu, Guanghua; Zhang, Qing; Tse, Peter W; Tan, Haihui

    2016-01-01

    Lamb wave technique has been widely used in non-destructive evaluation (NDE) and structural health monitoring (SHM). However, due to the multi-mode characteristics and dispersive nature, Lamb wave propagation behavior is much more complex than that of bulk waves. Numerous numerical simulations on Lamb wave propagation have been conducted to study its physical principles. However, few quantitative studies on evaluating the accuracy of these numerical simulations were reported. In this paper, a method based on cross correlation analysis for quantitatively evaluating the simulation accuracy of time-transient Lamb waves propagation is proposed. Two kinds of error, affecting the position and shape accuracies are firstly identified. Consequently, two quantitative indices, i.e., the GVE (group velocity error) and MACCC (maximum absolute value of cross correlation coefficient) derived from cross correlation analysis between a simulated signal and a reference waveform, are proposed to assess the position and shape errors of the simulated signal. In this way, the simulation accuracy on the position and shape is quantitatively evaluated. In order to apply this proposed method to select appropriate element size and time step, a specialized 2D-FEM program combined with the proposed method is developed. Then, the proper element size considering different element types and time step considering different time integration schemes are selected. These results proved that the proposed method is feasible and effective, and can be used as an efficient tool for quantitatively evaluating and verifying the simulation accuracy of time-transient Lamb wave propagation. PMID:26315506

  10. Energetics of discrete selectivity bands and mutation-induced transitions in the calcium-sodium ion channels family.

    PubMed

    Kaufman, I; Luchinsky, D G; Tindjong, R; McClintock, P V E; Eisenberg, R S

    2013-11-01

    We use Brownian dynamics (BD) simulations to study the ionic conduction and valence selectivity of a generic electrostatic model of a biological ion channel as functions of the fixed charge Q(f) at its selectivity filter. We are thus able to reconcile the discrete calcium conduction bands recently revealed in our BD simulations, M0 (Q(f)=1e), M1 (3e), M2 (5e), with a set of sodium conduction bands L0 (0.5e), L1 (1.5e), thereby obtaining a completed pattern of conduction and selectivity bands vs Q(f) for the sodium-calcium channels family. An increase of Q(f) leads to an increase of calcium selectivity: L0 (sodium-selective, nonblocking channel) → M0 (nonselective channel) → L1 (sodium-selective channel with divalent block) → M1 (calcium-selective channel exhibiting the anomalous mole fraction effect). We create a consistent identification scheme where the L0 band is putatively identified with the eukaryotic sodium channel The scheme created is able to account for the experimentally observed mutation-induced transformations between nonselective channels, sodium-selective channels, and calcium-selective channels, which we interpret as transitions between different rows of the identification table. By considering the potential energy changes during permeation, we show explicitly that the multi-ion conduction bands of calcium and sodium channels arise as the result of resonant barrierless conduction. The pattern of periodic conduction bands is explained on the basis of sequential neutralization taking account of self-energy, as Q(f)(z,i)=ze(1/2+i), where i is the order of the band and z is the valence of the ion. Our results confirm the crucial influence of electrostatic interactions on conduction and on the Ca(2+)/Na(+) valence selectivity of calcium and sodium ion channels. The model and results could be also applicable to biomimetic nanopores with charged walls. PMID:24329301

  11. Energetics of discrete selectivity bands and mutation-induced transitions in the calcium-sodium ion channels family

    NASA Astrophysics Data System (ADS)

    Kaufman, I.; Luchinsky, D. G.; Tindjong, R.; McClintock, P. V. E.; Eisenberg, R. S.

    2013-11-01

    We use Brownian dynamics (BD) simulations to study the ionic conduction and valence selectivity of a generic electrostatic model of a biological ion channel as functions of the fixed charge Qf at its selectivity filter. We are thus able to reconcile the discrete calcium conduction bands recently revealed in our BD simulations, M0 (Qf=1e), M1 (3e), M2 (5e), with a set of sodium conduction bands L0 (0.5e), L1 (1.5e), thereby obtaining a completed pattern of conduction and selectivity bands vs Qf for the sodium-calcium channels family. An increase of Qf leads to an increase of calcium selectivity: L0 (sodium-selective, nonblocking channel) → M0 (nonselective channel) → L1 (sodium-selective channel with divalent block) → M1 (calcium-selective channel exhibiting the anomalous mole fraction effect). We create a consistent identification scheme where the L0 band is putatively identified with the eukaryotic sodium channel The scheme created is able to account for the experimentally observed mutation-induced transformations between nonselective channels, sodium-selective channels, and calcium-selective channels, which we interpret as transitions between different rows of the identification table. By considering the potential energy changes during permeation, we show explicitly that the multi-ion conduction bands of calcium and sodium channels arise as the result of resonant barrierless conduction. The pattern of periodic conduction bands is explained on the basis of sequential neutralization taking account of self-energy, as Qf(z,i)=ze(1/2+i), where i is the order of the band and z is the valence of the ion. Our results confirm the crucial influence of electrostatic interactions on conduction and on the Ca2+/Na+ valence selectivity of calcium and sodium ion channels. The model and results could be also applicable to biomimetic nanopores with charged walls.

  12. Precise time technology for selected Air Force systems: Present status and future requirements

    NASA Technical Reports Server (NTRS)

    Yannoni, N. F.

    1981-01-01

    Precise time and time interval (PTTI) technology is becoming increasingly significant to Air Force operations as digital techniques find expanded utility in military missions. Timing has a key role in the function as well as in navigation. A survey of the PTTI needs of several Air Force systems is presented. Current technology supporting these needs was reviewed and new requirements are emphasized for systems as they transfer from initial development to final operational deployment.

  13. Learning Rates and States from Biophysical Time Series: A Bayesian Approach to Model Selection and Single-Molecule FRET Data

    PubMed Central

    Bronson, Jonathan E.; Fei, Jingyi; Hofman, Jake M.; Gonzalez, Ruben L.; Wiggins, Chris H.

    2009-01-01

    Abstract Time series data provided by single-molecule Förster resonance energy transfer (smFRET) experiments offer the opportunity to infer not only model parameters describing molecular complexes, e.g., rate constants, but also information about the model itself, e.g., the number of conformational states. Resolving whether such states exist or how many of them exist requires a careful approach to the problem of model selection, here meaning discrimination among models with differing numbers of states. The most straightforward approach to model selection generalizes the common idea of maximum likelihood—selecting the most likely parameter values—to maximum evidence: selecting the most likely model. In either case, such an inference presents a tremendous computational challenge, which we here address by exploiting an approximation technique termed variational Bayesian expectation maximization. We demonstrate how this technique can be applied to temporal data such as smFRET time series; show superior statistical consistency relative to the maximum likelihood approach; compare its performance on smFRET data generated from experiments on the ribosome; and illustrate how model selection in such probabilistic or generative modeling can facilitate analysis of closely related temporal data currently prevalent in biophysics. Source code used in this analysis, including a graphical user interface, is available open source via http://vbFRET.sourceforge.net. PMID:20006957

  14. Giant spin splitting, strong valley selective circular dichroism and valley-spin coupling induced in silicene

    NASA Astrophysics Data System (ADS)

    Qu, Jinfeng; Peng, Xiangyang; Xiao, Di; Zhong, Jianxin

    2016-08-01

    Silicene is a potential candidate for valleytronics. However, in comparison with the transition metal dichalcogenides (TMDs), silicene has a tiny energy gap and zero spin splitting at its Dirac valleys, being unfavorable for valleytronic applications. Based on first principles calculations, we find that by proximity with Bi(111) bilayer, the Dirac valleys of silicene acquire a sizable energy gap and giant spin splittings, which are even larger than the splittings of Mo S2 . Our calculations show that the silicene over Bi layer exhibits a strong valley-contrasting circular dichroism, enabling selective optical pumping of valley carriers. Due to the time reversal symmetry and the breaking of inversion symmetry, the Berry curvatures and the spin splittings are opposite at the K and K' valleys of silicene, and hence the valley and spin are locked and can be simultaneously polarized. In this way, silicene and likely other similar Dirac materials can be comparable to TMDs in valleytronics, which not only adds a new dimension to the properties of silicene but also expands the members of the valleytronic family.

  15. Choline-induced selective fluorescence quenching of acetylcholinesterase conjugated Au@BSA clusters.

    PubMed

    Mathew, Meegle S; Baksi, Ananya; Pradeep, T; Joseph, Kuruvilla

    2016-07-15

    We have developed a highly selective sensitive fluorescent detection of acetylcholine (ACh) using bovine serum albumin (BSA) protected atomically precise clusters of gold. The gold quantum clusters (AuQC@BSA) synthesized using bovine serum albumin and conjugated with acetylcholinesterase (AChE), an enzyme specific for acetylcholine, resulting in AuQC@BSA-AChE. The enzyme, AChE hydrolyzes acetylcholine (ACh) to choline (Ch) which in turn interacts with AuQC@BSA-AChE and quenches its fluorescence, enabling sensing. We have carried out the real time monitoring of the hydrolysis of ACh using electrospray ionization mass spectrometry (ESI MS) to find out the mechanism of fluorescent quenching. The validity of present method for determination of concentration of acetylcholine in real system such as blood was demonstrated. Further, the sensor, AuQC@BSA-AChE can be easily coated on paper and an efficient and cheap sensor can be developed and detection limit for ACh is found to be 10nM. The fluorescent intensity of AuQC@BSA-AChE is sensitive towards acetylcholine in range of 10nM to 6.4µM. This suggests that AuQC@BSA-AChE has an excellent potential to be used for diagnosis of various neuropsychological and neuropsychiatric disorders. PMID:26921554

  16. Method and system for selecting data sampling phase for self timed interface logic

    DOEpatents

    Hoke, Joseph Michael; Ferraiolo, Frank D.; Lo, Tin-Chee; Yarolin, John Michael

    2005-01-04

    An exemplary embodiment of the present invention is a method for transmitting data among processors over a plurality of parallel data lines and a clock signal line. A receiver processor receives both data and a clock signal from a sender processor. At the receiver processor a bit of the data is phased aligned with the transmitted clock signal. The phase aligning includes selecting a data phase from a plurality of data phases in a delay chain and then adjusting the selected data phase to compensate for a round-off error. Additional embodiments include a system and storage medium for transmitting data among processors over a plurality of parallel data lines and a clock signal line.

  17. SU-E-I-60: The Correct Selection of Pitch and Rotation Time for Optimal CT Scanning : The Big Misconception

    SciTech Connect

    Ranallo, F; Szczykutowicz, T

    2014-06-01

    Purpose: To provide correct guidance in the proper selection of pitch and rotation time for optimal CT imaging with multi-slice scanners. Methods: There exists a widespread misconception concerning the role of pitch in patient dose with modern multi-slice scanners, particularly with the use of mA modulation techniques. We investigated the relationship of pitch and rotation time to image quality, dose, and scan duration, with CT scanners from different manufacturers in a way that clarifies this misconception. This source of this misconception may concern the role of pitch in single slice CT scanners. Results: We found that the image noise and dose are generally independent of the selected effective mAs (mA*time/ pitch) with manual mA technique settings and are generally independent of the selected pitch and /or rotation time with automatic mA modulation techniques. However we did find that on certain scanners the use of a pitch just above 0.5 provided images of equal image noise at a lower dose compared to the use of a pitch just below 1.0. Conclusion: The misconception that the use of a lower pitch over-irradiates patients by wasting dose is clearly false. The use of a lower pitch provides images of equal or better image quality at the same patient dose, whether using manual mA or automatic mA modulation techniques. By decreasing the pitch and the rotation times by equal amounts, both helical and patient motion artifacts can be reduced without affecting the exam time. The use of lower helical pitch also allows better scanning of larger patients by allowing a greater scan effective mAs, if the exam time can be extended. The one caution with the use of low pitch is not related to patient dose, but to the length of the scan time if the rotation time is not set short enough. Partial Research funding from GE HealthCare.

  18. Nickel Ions Selectively Inhibit Lipopolysaccharide-Induced Interleukin-6 Production by Decreasing Its mRNA Stability

    PubMed Central

    Asakawa, Sanki; Kishimoto, Yu; Takano, Takayuki; Okita, Kiyuki; Takakuwa, Shiho; Sato, Taiki; Hiratsuka, Masahiro; Takeuchi, Osamu; Hirasawa, Noriyasu

    2015-01-01

    Nickel (Ni) ions easily elute from many alloys and elicit inflammation and allergies. Previous studies have shown that infections due to the implantation of medical devices cause inflammation and enhance the elution of Ni ions (Ni2+). However, cross-talk between infection- and Ni2+-induced signaling pathways has not yet been elucidated in detail. In the present study, we investigated the effects of Ni2+ on the lipopolysaccharide (LPS)-induced production of cytokines in a LPS-induced air pouch-type inflammation model in BALB/c mice and the murine macrophage cell line RAW264. We demonstrated that Ni2+ inhibited the LPS-induced production of interleukin (IL)-6, but not that of tumor necrosis factor (TNF)-α both in vivo and in vitro. This inhibitory effect was also observed with cobalt ion (Co2+), but not with chloride ion (Cl-), zinc ion (Zn2+), or palladium ion (Pd2+), and was highly selective to the production of IL-6. Ni2+ did not inhibit the activation of ERK1/2, p38 MAPK, or JNK. Although Ni2+ decreased IL-6 mRNA levels, it failed to inhibit the LPS-induced activation of the IL-6 promoter. An experiment using actinomycin D, a transcription inhibitor, revealed that Ni2+ decreased the stability of IL-6 mRNA. Moreover, Ni2+ inhibited the LPS-induced expression of Arid5a, but not regnase-1. These results demonstrated that Ni2+ may have selectively inhibited the LPS-induced production of IL-6 by decreasing the Arid5a-dependent stabilization of IL-6 mRNA. PMID:25742007

  19. Nickel ions selectively inhibit lipopolysaccharide-induced interleukin-6 production by decreasing its mRNA stability.

    PubMed

    Asakawa, Sanki; Kishimoto, Yu; Takano, Takayuki; Okita, Kiyuki; Takakuwa, Shiho; Sato, Taiki; Hiratsuka, Masahiro; Takeuchi, Osamu; Hirasawa, Noriyasu

    2015-01-01

    Nickel (Ni) ions easily elute from many alloys and elicit inflammation and allergies. Previous studies have shown that infections due to the implantation of medical devices cause inflammation and enhance the elution of Ni ions (Ni²⁺). However, cross-talk between infection- and Ni²⁺-induced signaling pathways has not yet been elucidated in detail. In the present study, we investigated the effects of Ni2+ on the lipopolysaccharide (LPS)-induced production of cytokines in a LPS-induced air pouch-type inflammation model in BALB/c mice and the murine macrophage cell line RAW264. We demonstrated that Ni²⁺ inhibited the LPS-induced production of interleukin (IL)-6, but not that of tumor necrosis factor (TNF)-α both in vivo and in vitro. This inhibitory effect was also observed with cobalt ion (Co²⁺), but not with chloride ion (Cl⁻), zinc ion (Zn²⁺), or palladium ion (Pd²⁺), and was highly selective to the production of IL-6. Ni²⁺ did not inhibit the activation of ERK1/2, p38 MAPK, or JNK. Although Ni²⁺ decreased IL-6 mRNA levels, it failed to inhibit the LPS-induced activation of the IL-6 promoter. An experiment using actinomycin D, a transcription inhibitor, revealed that Ni²⁺ decreased the stability of IL-6 mRNA. Moreover, Ni²⁺ inhibited the LPS-induced expression of Arid5a, but not regnase-1. These results demonstrated that Ni²⁺ may have selectively inhibited the LPS-induced production of IL-6 by decreasing the Arid5a-dependent stabilization of IL-6 mRNA. PMID:25742007

  20. Selection and design of the secondary electron channel of the time-of-flight mass spectrometer

    NASA Astrophysics Data System (ADS)

    Fishkova, T. Ya.; Basalaev, A. A.; Kuz'michev, V. V.

    2016-03-01

    Computer simulation is carried out for selecting a compact electron-optical system of the channel for detecting secondary electrons formed during the interaction of xenon atoms or ions with energy of 1-30 keV with Xe atoms. The solid angle of passage of secondary electron beams in a wide range of their initial energies is calculated. The energy spectrum of secondary electrons with various energies is determined by constructing their deceleration curve.

  1. [Selection of suitable polypropylene tubes for DNA testing using real-time PCR].

    PubMed

    Shimizu, Eri; Futo, Satoshi; Masubuchi, Tomoko; Minegishi, Yasutaka; Kasahara, Masaki; Akiyama, Hiroshi; Teshima, Reiko; Hino, Akihiro; Mano, Jyunichi; Furui, Satoshi; Kitta, Kazumi

    2010-01-01

    Polypropylene microtubes (tubes) are generally used for bio-material tests in addition to PCR tests such as genetically modified organism (GMO) testings. However, the choice of suitable tubes is quite important, because it might influence the results: DNA binding and/or elution of chemical substances sometimes occurs. In this study, we established methods to select tubes with the most suitable characteristics for DNA testing. PMID:20208409

  2. Water availability as an agent of selection in introduced populations of Arabidopsis thaliana: impacts on flowering time evolution

    PubMed Central

    Stock, Amanda J.; McGoey, Brechann V.

    2015-01-01

    Flowering is one of the most influential events in the life history of a plant and one of the main determinants of reproductive investment and lifetime fitness. It is also a highly complex trait controlled by dozens of genes. Understanding the selective pressures influencing time to flowering, and being able to reliably predict how it will evolve in novel environments, are unsolved challenges for plant evolutionary geneticists. Using the model plant species, Arabidopsis thaliana, we examined the impact of simulated high and low winter precipitation levels on the flowering time of naturalized lines from across the eastern portion of the introduced North American range, and the fitness consequences of early versus late flowering. Flowering time order was significantly correlated across two environments—in a previous common garden experiment and in environmental chambers set to mimic mid-range photoperiod and temperature conditions. Plants in low water flowered earlier, had fewer basal branches and produced fewer fruits. Selection in both treatments favored earlier flowering and more basal branches. Our analyses revealed an interaction between flowering time and water treatment for fitness, where flowering later was more deleterious for fitness in the low water treatment. Our results are consistent with the hypothesis that differences in winter precipitation levels are one of the selective agents underlying a flowering time cline in introduced A. thaliana populations. PMID:25909038

  3. Real-time 2D spatially selective MRI experiments: Comparative analysis of optimal control design methods

    NASA Astrophysics Data System (ADS)

    Maximov, Ivan I.; Vinding, Mads S.; Tse, Desmond H. Y.; Nielsen, Niels Chr.; Shah, N. Jon

    2015-05-01

    There is an increasing need for development of advanced radio-frequency (RF) pulse techniques in modern magnetic resonance imaging (MRI) systems driven by recent advancements in ultra-high magnetic field systems, new parallel transmit/receive coil designs, and accessible powerful computational facilities. 2D spatially selective RF pulses are an example of advanced pulses that have many applications of clinical relevance, e.g., reduced field of view imaging, and MR spectroscopy. The 2D spatially selective RF pulses are mostly generated and optimised with numerical methods that can handle vast controls and multiple constraints. With this study we aim at demonstrating that numerical, optimal control (OC) algorithms are efficient for the design of 2D spatially selective MRI experiments, when robustness towards e.g. field inhomogeneity is in focus. We have chosen three popular OC algorithms; two which are gradient-based, concurrent methods using first- and second-order derivatives, respectively; and a third that belongs to the sequential, monotonically convergent family. We used two experimental models: a water phantom, and an in vivo human head. Taking into consideration the challenging experimental setup, our analysis suggests the use of the sequential, monotonic approach and the second-order gradient-based approach as computational speed, experimental robustness, and image quality is key. All algorithms used in this work were implemented in the MATLAB environment and are freely available to the MRI community.

  4. Real-time 2D spatially selective MRI experiments: Comparative analysis of optimal control design methods.

    PubMed

    Maximov, Ivan I; Vinding, Mads S; Tse, Desmond H Y; Nielsen, Niels Chr; Shah, N Jon

    2015-05-01

    There is an increasing need for development of advanced radio-frequency (RF) pulse techniques in modern magnetic resonance imaging (MRI) systems driven by recent advancements in ultra-high magnetic field systems, new parallel transmit/receive coil designs, and accessible powerful computational facilities. 2D spatially selective RF pulses are an example of advanced pulses that have many applications of clinical relevance, e.g., reduced field of view imaging, and MR spectroscopy. The 2D spatially selective RF pulses are mostly generated and optimised with numerical methods that can handle vast controls and multiple constraints. With this study we aim at demonstrating that numerical, optimal control (OC) algorithms are efficient for the design of 2D spatially selective MRI experiments, when robustness towards e.g. field inhomogeneity is in focus. We have chosen three popular OC algorithms; two which are gradient-based, concurrent methods using first- and second-order derivatives, respectively; and a third that belongs to the sequential, monotonically convergent family. We used two experimental models: a water phantom, and an in vivo human head. Taking into consideration the challenging experimental setup, our analysis suggests the use of the sequential, monotonic approach and the second-order gradient-based approach as computational speed, experimental robustness, and image quality is key. All algorithms used in this work were implemented in the MATLAB environment and are freely available to the MRI community. PMID:25863895

  5. Time-dependent changes of autophagy and apoptosis in lipopolysaccharide-induced rat acute lung injury

    PubMed Central

    Lin, Li; Zhang, Lijun; Yu, Liangzhu; Han, Lu; Ji, Wanli; Shen, Hui; Hu, Zhenwu

    2016-01-01

    Objective(s): Abnormal lung cell death including autophagy and apoptosis is the central feature in acute lung injury (ALI). To identify the cellular mechanisms and the chronology by which different types of lung cell death are activated during lipopolysaccharide (LPS)-induced ALI, we decided to evaluate autophagy (by LC3-II and autophagosome) and apoptosis (by caspase-3) at different time points after LPS treatment in a rat model of LPS-induced ALI. Materials and Methods: Sprague-Dawley rats were randomly divided into two groups: control group and LPS group. ALI was induced by LPS intraperitoneal injection (3 mg/kg). The lung tissues were collected to measure lung injury score by histopathological evaluation, the protein expression of LC3-II and caspase-3 by Western blot, and microstructural changes by electron microscopy analysis. Results: During ALI, lung cell death exhibited modifications in the death process at different stages of ALI. At early stages (1 hr and 2 hr) of ALI, the mode of lung cell death started with autophagy in LPS group and reached a peak at 2 hr. As ALI process progressed, apoptosis was gradually increased in the lung tissues and reached its maximal level at later stages (6 hr), while autophagy was time-dependently decreased. Conclusion: These findings suggest that activated autophagy and apoptosis might play distinct roles at different stages of LPS-induced ALI. This information may enhance the understanding of lung pathophysiology at the cellular level during ALI and pulmonary infection, and thus help optimize the timing of innovating therapeutic approaches in future experiments with this model. PMID:27482344

  6. Excess selenium increases Ca sup ++ -induced clotting times in chicks and rats

    SciTech Connect

    Herz, W.C.; Combs, G.F. Jr. )

    1991-03-11

    Calcium (Ca{sup ++})-induced clotting times (i.e., prothrombin times, PT times) in young White Leghorn chickens and male weanling Sprague Dawley rats were shown to be elevated in animals fed diets for 20-30 days containing excess Se. Clotting times of chicks were prolonged from those of controls in animals fed either deficient or excess Se, although all dietary treatment groups showed comparable concentrations of total plasma protein. Rats showed significantly prolonged PT times when fed Se at either 5 ppm or 10 ppm. The plasma activities of certain enzymes of hepatic origin (alanine aminotransferase, aspartate aminotransferase, {gamma}-glutamyl transpeptidase) in rats fed excess Se were comparable to those of controls, despite the increase in the PT times. Body weights and liver weights were significantly depressed in those animals only at the 10 ppm Se level. These results demonstrate increased PT times in both chicks and rats. In each species, this effect is independent of feed intake and body weight, and is apparent at levels of Se intake that do not affect other indicators of hepatic damage. Therefore, prolonged PT time may be an early indicator of sub-acute selenosis.

  7. Pursuing Benefit or Avoiding Detriment: Term-Time Job Selection of Sports Major Undergraduates

    ERIC Educational Resources Information Center

    Wu, Huan-Hung; Chen, Shan-Hua

    2013-01-01

    Higher education expansion accompanied with the tuition rising has resulted in the increasing number of term-time employed students in many countries. Taiwan is no exception to this trend. Thus, there were a few studies to explore the impact of term-time employment on undergraduates. However, very few researchers focus on how undergraduates make…

  8. Released Time for Faculty: Practices and Procedures in Selected Community Colleges.

    ERIC Educational Resources Information Center

    Munson, Ann

    A survey concerning released time for faculty was conducted of all the community colleges in Maryland, Mount Vernon College in Washington, D. C., and Northern Virginia Community College. Practices concerning the following types of released time were investigated: department or division chairman; curriculum development; curriculum coordinator;…

  9. Quantification of a Selective Expansion of T Cell Receptor Vβ by Superantigen Using Real-Time PCR.

    PubMed

    Park, Joo Youn; Seo, Keun Seok

    2016-01-01

    Selective expansion of T cells bearing specific T cell receptor Vβ segments is a hallmark of superantigens. Analyzing Vβ specificity of superantigens is important for characterizing newly discovered superantigens and understanding differential T cell responses to each toxin. Here, we describe a real-time PCR method using SYBR green I and primers specific to Cβ and Vβ genes for an absolute quantification. The established method was applied to quantify a selective expansion of T cell receptor Vβ expansion by superantigens and generated accurate, reproducible, and comparable results. PMID:26676047

  10. Modified constraint-induced movement therapy for clients with chronic stroke: interrupted time series (ITS) design

    PubMed Central

    Park, JuHyung; Lee, NaYun; Cho, YongHo; Yang, YeongAe

    2015-01-01

    [Purpose] The purpose of this study was to investigate the impact that modified constraint-induced movement therapy has on upper extremity function and the daily life of chronic stroke patients. [Subjects and Methods] Modified constraint-induced movement therapy was conduct for 2 stroke patients with hemiplegia. It was performed 5 days a week for 2 weeks, and the participants performed their daily living activities wearing mittens for 6 hours a day, including the 2 hours of the therapy program. The assessment was conducted 5 times in 3 weeks before and after intervention. The upper extremity function was measured using the box and block test and a dynamometer, and performance daily of living activities was assessed using the modified Barthel index. The results were analyzed using a scatterplot and linear regression. [Results] All the upper extremity functions of the participants all improved after the modified constraint-induced movement therapy. Performance of daily living activities by participant 1 showed no change, but the results of participant 2 had improved after the intervention. [Conclusion] Through the results of this research, it was identified that modified constraint-induced movement therapy is effective at improving the upper extremity functions and the performance of daily living activities of chronic stroke patients. PMID:25931770

  11. Modeling and inversion of stress-induced multicomponent seismic time shifts

    NASA Astrophysics Data System (ADS)

    Smith, Steven Shawn

    Subsurface pressure and temperature variations can alter rock properties both near and relatively far from the disturbance, causing detectable changes in seismic traveltimes. In this thesis, I first use traveltime variations to study velocity changes around a heated prototype nuclear waste storage tunnel. Then I model and invert compaction-induced multicomponent time shifts from depressurizing petroleum reservoirs. Heaters inside the tunnel replicate the thermal output of decaying radioactive waste, heating the tunnel over two years and maintaining a constant temperature for another two years. Time-lapse velocity models were constructed using temperature-dependent velocity data for granite and thermal profiles from boreholes in the tunnel wall. Matching check-shot and modeled waveforms indicate that the tunnel temperature can be monitored using seismic data. Further, the smooth, unperturbed velocity field lacks spatial perturbations, suggesting that no fluid or steam was present around the tunnel near the receiver array during the experiment. However, the combination of changing velocities and non-elastic, stress-induced acoustic emissions near the tunnel crown suggest that damage to the rock may occur. To study time shifts around a compacting reservoir, I employ geomechanical modeling of the compaction-induced stress/strain fields. Strain-dependent stiffness perturbations are obtained from the nonlinear theory of elasticity. Then full-waveform multicomponent seismic data are generated by finite-differences and used to estimate the time shifts of P-, S-, and PS-waves. P-wave time shifts are strongly influenced by compaction-induced velocity anisotropy around the reservoir. S-wave anisotropy is almost negligible, but S-wave shifts are 2-3 times larger than those of P-waves. PS-wave time-shift behavior significantly varies with the reflection point. Spatial time-shift distributions are exploited to study the sensitivity of each wave type to reservoir pressure ( Delta

  12. Time-of-day effects in implicit racial in-group preferences are likely selection effects, not circadian rhythms

    PubMed Central

    2016-01-01

    Time-of-day effects in human psychological functioning have been known of since the 1800s. However, outside of research specifically focused on the quantification of circadian rhythms, their study has largely been neglected. Moves toward online data collection now mean that psychological investigations take place around the clock, which affords researchers the ability to easily study time-of-day effects. Recent analyses have shown, for instance, that implicit attitudes have time-of-day effects. The plausibility that these effects indicate circadian rhythms rather than selection effects is considered in the current study. There was little evidence that the time-of-day effects in implicit attitudes shifted appropriately with factors known to influence the time of circadian rhythms. Moreover, even variables that cannot logically show circadian rhythms demonstrated stronger time-of-day effects than did implicit attitudes. Taken together, these results suggest that time-of-day effects in implicit attitudes are more likely to represent processes of selection rather than circadian rhythms, but do not rule out the latter possibility. PMID:27114886

  13. Time-of-day effects in implicit racial in-group preferences are likely selection effects, not circadian rhythms.

    PubMed

    Schofield, Timothy P

    2016-01-01

    Time-of-day effects in human psychological functioning have been known of since the 1800s. However, outside of research specifically focused on the quantification of circadian rhythms, their study has largely been neglected. Moves toward online data collection now mean that psychological investigations take place around the clock, which affords researchers the ability to easily study time-of-day effects. Recent analyses have shown, for instance, that implicit attitudes have time-of-day effects. The plausibility that these effects indicate circadian rhythms rather than selection effects is considered in the current study. There was little evidence that the time-of-day effects in implicit attitudes shifted appropriately with factors known to influence the time of circadian rhythms. Moreover, even variables that cannot logically show circadian rhythms demonstrated stronger time-of-day effects than did implicit attitudes. Taken together, these results suggest that time-of-day effects in implicit attitudes are more likely to represent processes of selection rather than circadian rhythms, but do not rule out the latter possibility. PMID:27114886

  14. Time-Resolved Emission Spectroscopic Study of Laser-Induced Steel Plasmas

    NASA Astrophysics Data System (ADS)

    L. Shah, M.; K. Pulhani, A.; M. Suri, B.; P. Gupta, G.

    2013-06-01

    Laser-induced steel plasma is generated by focusing a Q-switched Nd:YAG visible laser (532 nm wavelength) with an irradiance of ~ 1 × 109 W/cm2 on a steel sample in air at atmospheric pressure. An Echelle spectrograph coupled with a gateable intensified charge-coupled detector is used to record the plasma emissions. Using time-resolved spectroscopic measurements of the plasma emissions, the temperature and electron number density of the steel plasma are determined for many times of the detector delay. The validity of the assumption by the spectroscopic methods that the laser-induced plasma (LIP) is optically thin and is also in local thermodynamic equilibrium (LTE) has been evaluated for many delay times. From the temporal evolution of the intensity ratio of two Fe I lines and matching it with its theoretical value, the delay times where the plasma is optically thin and is also in LTE are found to be 800 ns, 900 ns and 1000 ns.

  15. Relaxation Time Distribution (RTD) of Spectral Induced Polarization (SIP) data from environmental studies

    NASA Astrophysics Data System (ADS)

    Ntarlagiannis, D.; Ustra, A.; Slater, L. D.; Zhang, C.; Mendonça, C. A.

    2015-12-01

    In this work we present an alternative formulation of the Debye Decomposition (DD) of complex conductivity spectra, with a new set of parameters that are directly related to the continuous Debye relaxation model. The procedure determines the relaxation time distribution (RTD) and two frequency-independent parameters that modulate the induced polarization spectra. The distribution of relaxation times quantifies the contribution of each distinct relaxation process, which can in turn be associated with specific polarization processes and characterized in terms of electrochemical and interfacial parameters as derived from mechanistic models. Synthetic tests show that the procedure can successfully fit spectral induced polarization (SIP) data and accurately recover the RTD. The procedure was applied to different data sets, focusing on environmental applications. We focus on data of sand-clay mixtures artificially contaminated with toluene, and crude oil-contaminated sands experiencing biodegradation. The results identify characteristic relaxation times that can be associated with distinct polarization processes resulting from either the contaminant itself or transformations associated with biodegradation. The inversion results provide information regarding the relative strength and dominant relaxation time of these polarization processes.

  16. Mucosal and systemic immune responses induced by a single time vaccination strategy in mice.

    PubMed

    González Aznar, Elizabeth; Romeu, Belkis; Lastre, Miriam; Zayas, Caridad; Cuello, Maribel; Cabrera, Osmir; Valdez, Yolanda; Fariñas, Mildrey; Pérez, Oliver

    2015-08-01

    Vaccination is considered by the World Health Organization as the most cost-effective strategy for controlling infectious diseases. In spite of great successes with vaccines, many infectious diseases are still leading killers, because of the inadequate coverage of many vaccines. Several factors have been responsible: number of doses, high vaccine reactogenicity, vaccine costs, vaccination policy, among others. Contradictorily, few vaccines are of single dose and even less of mucosal administration. However, more common infections occur via mucosa, where secretory immunoglobulin A plays an essential role. As an alternative, we proposed a novel protocol of vaccination called Single Time Vaccination Strategy (SinTimVaS) by immunizing 2 priming doses at the same time: one by mucosal route and the other by parenteral route. Here, the mucosal and systemic responses induced by Finlay adjuvants (AF Proteoliposome 1 and AF Cochleate 1) implementing SinTimVaS in BALB/c mice were evaluated. One intranasal dose of AF Cochleate 1 and an intramuscular dose of AF Proteoliposome 1 adsorbed onto aluminum hydroxide, with bovine serum albumin or tetanus toxoid as model antigens, administrated at the same time, induced potent specific mucosal and systemic immune responses. Also, we demonstrated that SinTimVaS using other mucosal routes like oral and sublingual, in combination with the subcutaneous route elicits immune responses. SinTimVaS, as a new immunization strategy, could increase vaccination coverage and reduce time-cost vaccines campaigns, adding the benefits of immune response in mucosa. PMID:26140382

  17. Reduction of primary freeze-drying time by electric field induced ice nucleus formation

    NASA Astrophysics Data System (ADS)

    Petersen, Ansgar; Rau, Guenter; Glasmacher, Birgit

    2006-08-01

    The potential of a high electric field was utilized to induce ice nucleus formation in aqueous solutions. Using this technique it was possible to reduce the primary drying time during lyophilization. Samples of 10% (w/v) hydroxyethylstarch (HES) solution were frozen at a constant rate of -1 K/min, while nucleation was initiated at temperatures of -1.5, -4.5 and -8.5°C. In contrast, spontaneous nucleation was observed in a range between -11.5 and -17.1°C. Electrically induced nucleus formation has proved to be a reliable method to start crystallization at a desired temperature. Continuous measurement of the weight allowed to determine the drying rate and to detect at which time primary drying was completed. The drying time and the drying rate were found to be strongly dependent on the nucleation temperature during freezing. A relation between the nucleation temperature, the structure of the frozen samples and the drying times could be established.

  18. Ex-plant retinal laser induced threshold studies in the millisecond time regime

    NASA Astrophysics Data System (ADS)

    Schulmeister, Karl; Husinsky, Johannes; Seiser, Bernhard; Edthofer, Florian; Tuschl, Helga; Lund, David J.

    2006-02-01

    Excised bovine retinas were used as model for threshold determination of laser induced thermal damage in the pulse regime of 1 ms to 655 ms for a range of laser spot size diameters. The thresholds as determined by fluorescence viability staining compare very well with the prediction of thermal damage models. Both models compare well with published and new Rhesus monkey threshold data. A distinctive dependence of the threshold on laser spot size diameter for different pulse duration was found which indicates that current (ICNIRP, ANSI and IEC) laser exposure limits for large spots can be increased in this pulse duration regime. A time dependent α max is proposed which only for the case of long exposure durations has the current value of 100 mrad, but decreases to smaller angles for short exposure durations, effectively increasing the permissible exposure level. An explanation based on intra-retinal scattering is offered for the unexpected spot size dependence for spot diameters less than about 80 µm. The time dependence and nature of damage is discussed for pulse durations shorter than 1 ms where bubble induced damage seems to lead to a threshold a factor of 10 lower than the thermally induced threshold, resulting in the need to lower the MPE values for this condition. Possible changes of the MPE values are offered and discussed.

  19. Differentiating induced and natural seismicity using space-time-magnitude statistics applied to the Coso Geothermal field

    USGS Publications Warehouse

    Schoenball, Martin; Davatzes, Nicholas C.; Glen, Jonathan M.

    2015-01-01

    A remarkable characteristic of earthquakes is their clustering in time and space, displaying their self-similarity. It remains to be tested if natural and induced earthquakes share the same behavior. We study natural and induced earthquakes comparatively in the same tectonic setting at the Coso Geothermal Field. Covering the preproduction and coproduction periods from 1981 to 2013, we analyze interevent times, spatial dimension, and frequency-size distributions for natural and induced earthquakes. Individually, these distributions are statistically indistinguishable. Determining the distribution of nearest neighbor distances in a combined space-time-magnitude metric, lets us identify clear differences between both kinds of seismicity. Compared to natural earthquakes, induced earthquakes feature a larger population of background seismicity and nearest neighbors at large magnitude rescaled times and small magnitude rescaled distances. Local stress perturbations induced by field operations appear to be strong enough to drive local faults through several seismic cycles and reactivate them after time periods on the order of a year.

  20. AP Selection Algorithm for Real-Time Communications through Mixed WLAN Environments

    NASA Astrophysics Data System (ADS)

    Morioka, Yasufumi; Higashino, Takeshi; Tsukamoto, Katsutoshi; Komaki, Shozo

    Recent rapid development of high-speed wireless access technologies has created mixed WLAN (Wireless LAN) environments where QoS capable APs coexist with legacy APs. To provide QoS guarantee in this mixed WLAN environment, this paper proposes a new AP selection algorithm. The proposed algorithm assigns an STA (Station) to an AP in the overall WLAN service area. Simulation results show improvement in the VoIP performance in terms of an eMOS (estimated Mean Opinion Score) value and the FTP throughput compared to conventional algorithms.

  1. Magnetic state selection in atomic frequency and time standards. [hydrogen masers

    NASA Technical Reports Server (NTRS)

    Peters, H. E.

    1982-01-01

    Atomic standards such as those based upon cesium and hydrogen rely upon magnetic state selection to obtain population inversion in the hyperfine transition levels. Use of new design approaches and improved magnetic materials has made it possible to fabricate improved state selectors of small size, and thus the efficiency of utilization of beam flux is greatly improved and the size and weight of the standard is reduced. The sensitivity to magnetic perturbations is also decreased, so that the accuracy and stability of the standard is improved. Several new state selector designs are illustrated and the application to standards utilizing different atomic species is analyzed.

  2. JOINT STRUCTURE SELECTION AND ESTIMATION IN THE TIME-VARYING COEFFICIENT COX MODEL

    PubMed Central

    Xiao, Wei; Lu, Wenbin; Zhang, Hao Helen

    2016-01-01

    Time-varying coefficient Cox model has been widely studied and popularly used in survival data analysis due to its flexibility for modeling covariate effects. It is of great practical interest to accurately identify the structure of covariate effects in a time-varying coefficient Cox model, i.e. covariates with null effect, constant effect and truly time-varying effect, and estimate the corresponding regression coefficients. Combining the ideas of local polynomial smoothing and group nonnegative garrote, we develop a new penalization approach to achieve such goals. Our method is able to identify the underlying true model structure with probability tending to one and simultaneously estimate the time-varying coefficients consistently. The asymptotic normalities of the resulting estimators are also established. We demonstrate the performance of our method using simulations and an application to the primary biliary cirrhosis data. PMID:27540275

  3. Effects of Type and Strength of Force Feedback on Movement Time in a Target Selection Task

    NASA Technical Reports Server (NTRS)

    Rorie, Robert Conrad; Vu, Kim-Phuong L.; Marayong, Panadda; Robles, Jose; Strybel, Thomas Z.; Battiste, Vernol

    2013-01-01

    Future cockpits will likely include new onboard technologies, such as cockpit displays of traffic information, to help support future flight deck roles and responsibilities. These new technologies may benefit from multimodal feedback to aid pilot information processing. The current study investigated the effects of multiple levels of force feedback on operator performance in an aviation task. Participants were presented with two different types of force feedback (gravitational and spring force feedback) for a discrete targeting task, with multiple levels of gain examined for each force feedback type. Approach time and time in target were recorded. Results suggested that the two highest levels of gravitational force significantly reduced approach times relative to the lowest level of gravitational force. Spring force level only affected time in target. Implications of these findings for the design of future cockpit displays will be discussed.

  4. Time of flight spectrometer for background-free positron annihilation induced Auger electron spectroscopy.

    PubMed

    Mukherjee, S; Shastry, K; Anto, C V; Joglekar, P V; Nadesalingam, M P; Xie, S; Jiang, N; Weiss, A H

    2016-03-01

    We describe a novel spectrometer designed for positron annihilation induced Auger electron spectroscopy employing a time-of-flight spectrometer. The spectrometer's new configuration enables us to implant monoenergetic positrons with kinetic energies as low as 1.5 eV on the sample while simultaneously allowing for the detection of electrons emitted from the sample surface at kinetic energies ranging from ∼500 eV to 0 eV. The spectrometer's unique characteristics made it possible to perform (a) first experiments demonstrating the direct transition of a positron from an unbound scattering state to a bound surface state and (b) the first experiments demonstrating that Auger electron spectra can be obtained down to 0 eV without the beam induced secondary electron background obscuring the low energy part of the spectra. Data are presented which show alternative means of estimating positron surface state binding energy and background-free Auger spectra. PMID:27036826

  5. Time of flight spectrometer for background-free positron annihilation induced Auger electron spectroscopy

    NASA Astrophysics Data System (ADS)

    Mukherjee, S.; Shastry, K.; Anto, C. V.; Joglekar, P. V.; Nadesalingam, M. P.; Xie, S.; Jiang, N.; Weiss, A. H.

    2016-03-01

    We describe a novel spectrometer designed for positron annihilation induced Auger electron spectroscopy employing a time-of-flight spectrometer. The spectrometer's new configuration enables us to implant monoenergetic positrons with kinetic energies as low as 1.5 eV on the sample while simultaneously allowing for the detection of electrons emitted from the sample surface at kinetic energies ranging from ˜500 eV to 0 eV. The spectrometer's unique characteristics made it possible to perform (a) first experiments demonstrating the direct transition of a positron from an unbound scattering state to a bound surface state and (b) the first experiments demonstrating that Auger electron spectra can be obtained down to 0 eV without the beam induced secondary electron background obscuring the low energy part of the spectra. Data are presented which show alternative means of estimating positron surface state binding energy and background-free Auger spectra.

  6. Evaluation of stress-induced cortisol response for use in a Morone selective breeding program

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Harry K. Dupree Stuttgart National Aquaculture Research Center (HKDSNARC) has initiated a selective breeding program aimed at improving production traits for sunshine bass, Morone chrysops X M. saxatilis, via multi-trait selection in the two parental species, white bass, Morone chrysops (Rafinesque)...

  7. Time-Resolved AMR measurements of current induced magnetization reversal in ferromagnetic nanowires

    NASA Astrophysics Data System (ADS)

    Guittienne, Ph.; Wegrowe, J.-E.; Kelly, D.; Ansermet, J.-Ph.

    2001-03-01

    Time-resolved detection of the magnetization switching in static magnetic fields was achieved by pulsing current densities of about 107 A/cm2 in single isolated Nickel nanowires (80nm in diameter, 6000 nm in length, electrodeposited in porous membranes), using a Weathstone bridge of a 1GHz bandwidth. This irreversible transition is found to occur in a time of about 10 ns. The time of switching within the pulse, tsw, is measured as a function of applied field and current. The temperature rise due to Joule heating is deduced from the change in resistance. The entire set of data tsw(H,T) are fitted with a simple activation law, with the energy barrier height as the unique fitting parameter. The results show a strong departure from pure thermal activation indicating a current-induced magnetization reversal.

  8. Phenology and Phenotypic Natural Selection on the Flowering Time of a Deceit-pollinated Tropical Orchid, Myrmecophila christinae

    PubMed Central

    PARRA-TABLA, VÍCTOR; VARGAS, CARLOS F.

    2004-01-01

    • Background and aims. Flowering phenology is described and the effect of flowering time on pollination success is evaluated in the deceit-pollinated tropical orchid, Myrmecophila christinae. It was expected that, due to this species' deceit pollination strategy and low observed pollinator visit rate, there would be a higher probability of natural selection events favouring individuals flowering away from the population flowering peak. • Methods. The study covers two consecutive years and four populations of M. christinae located along the north coast of the Yucatán Peninsula. For phenological and pollination success data, a total of 110 individuals were monitored weekly in 1998, and 83 individuals in 1999, during all the flowering and fruiting season. • Key results. The results showed significant differences in the probability of donating and receiving pollen throughout the flowering season. The probability of receiving or donating pollen increased the further an individual flowering was from the flowering peak. Regression analysis showed directional and disruptive phenotypic natural selection gradients, suggesting the presence of selection events unfavourable to flowering during flowering peak, for both male success (pollen removal) and female success (fruit production). However, the intensity and significance of the natural selection events varied between populations from year to year. The variation between seasons and populations was apparently due to variations in the density of reproductive individuals in each population and each season. • Conclusions. As in other deceit-pollinated orchids, natural selection in M. christinae favours individuals flowering early or late in relation to population peak flowering. However, results also suggested a fluctuating regime of selective events act on flowering time of M. christinae. PMID:15205176

  9. Time-of-day effect on a food-induced conditioned place preference task in monkeys.

    PubMed

    Monclaro, Antonielle V; Sampaio, Ana Cristhina; Ribeiro, Natália B; Barros, Marilia

    2014-02-01

    Time can be an important contextual cue for cognitive performance, with implications for reward-associated learned behaviors such as (drug and food) addiction. So, we analyzed: (1) if marmoset monkeys develop a place preference that is conditioned to previous pairings with a highly-palatable food reward; (2) if the response is strongest when training and testing times match - time stamp effect; and (3) if there is an optimal time of the day (morning vs. afternoon) when this preference occurs - time-of-day effect. Subjects were first habituated to a two-compartment conditioned-place-preference (CPP) box. Then, during six training sessions held either in the morning or afternoon, a mixture of jellybeans and live mealworms was made available in a specific compartment. Marmosets were subsequently tested for preferring the food-paired context at the circadian time that either matched or was different from that of training. Compared to baseline levels, only subjects trained and tested in the afternoon made significantly longer and more frequent visits to the food-paired context and with a shorter latency to first entry. Thus, highly-palatable food rewards induced a CPP response. This behavior was exhibited only when training and testing times overlapped and during a restricted circadian timeframe (afternoon), consistent with a time-stamp and time-of-day effect, respectively. In this case, time may have been an internal circadian contextual cue. Whether due to circadian-mediated oscillations in memory and/or reward processes, such findings may be applied to addiction and other learned behaviors. PMID:24280121

  10. Time dependent appearance of selected apoptotic markers and usefulness of their detection in vitro.

    PubMed

    Rudolf, Emil; Cervinka, Miroslav

    2002-01-01

    Many experiments have demonstrated that some cell lines are resistant to chemically induced apoptosis in vitro, and that apoptosis itself is far from being a homogenous phenomenon. Here we show that 10 microg/ml etoposide elicited only minor changes in Bowes human melanoma cells (temporary decrease in cell viability and proliferation, transient phospatidylserine externalization and caspase-3 activation), which weren't clearly capable to start apoptotic pathway in the entire treated population. On the other hand, potassium chromate at concentration of 150 microg/ml executed cell death bearing some features of apoptosis (cell blebbing, caspase-3 activation and cytoskeletal changes) but lacking or showing weakly others (DNA fragmentation and phospatidylserine externalization). Our results suggest that in detecting apoptosis several fault-proof detection systems are to be used to avoid misleading results and conclusions in each experimental setting. PMID:12587780

  11. Experience-induced malleability in neural encoding of pitch, timbre, and timing.

    PubMed

    Kraus, Nina; Skoe, Erika; Parbery-Clark, Alexandra; Ashley, Richard

    2009-07-01

    Speech and music are highly complex signals that have many shared acoustic features. Pitch, Timbre, and Timing can be used as overarching perceptual categories for describing these shared properties. The acoustic cues contributing to these percepts also have distinct subcortical representations which can be selectively enhanced or degraded in different populations. Musically trained subjects are found to have enhanced subcortical representations of pitch, timbre, and timing. The effects of musical experience on subcortical auditory processing are pervasive and extend beyond music to the domains of language and emotion. The sensory malleability of the neural encoding of pitch, timbre, and timing can be affected by lifelong experience and short-term training. This conceptual framework and supporting data can be applied to consider sensory learning of speech and music through a hearing aid or cochlear implant. PMID:19673837

  12. On the selection and evaluation of visual display symbology Factors influencing search and identification times

    NASA Technical Reports Server (NTRS)

    Remington, Roger; Williams, Douglas

    1986-01-01

    Three single-target visual search tasks were used to evaluate a set of cathode-ray tube (CRT) symbols for a helicopter situation display. The search tasks were representative of the information extraction required in practice, and reaction time was used to measure the efficiency with which symbols could be located and identified. Familiar numeric symbols were responded to more quickly than graphic symbols. The addition of modifier symbols, such as a nearby flashing dot or surrounding square, had a greater disruptive effect on the graphic symbols than did the numeric characters. The results suggest that a symbol set is, in some respects, like a list that must be learned. Factors that affect the time to identify items in a memory task, such as familiarity and visual discriminability, also affect the time to identify symbols. This analogy has broad implications for the design of symbol sets. An attempt was made to model information access with this class of display.

  13. Time of travel and dispersion in a selected reach of Roberts Creek, Clayton County, Iowa

    USGS Publications Warehouse

    Kolpin, D.W.; Kalkhoff, S.J.

    1992-01-01

    Time of travel was determined by dye tracing, using rhodamine WT as the tracer. One dyeinjection site and three sampling sites were used to measure time of travel. Two dye-tracing tests were conducted at discharges having flow-duration values of 48 and 80 percent. The discharges at the time of the two dye-tracing tests approximated medium- and low-flow conditions. The average stream velocity in the study area was 0.23 foot per second during medium-flow conditions, March 20 to 22,1990, and 0.07 foot per second during low-flow conditions, April 30 to May 12, 1990. The injected dye dispersed in a plume that lasted about 18 hours during medium flow and about 64 hours during low flow at the downstream site.

  14. Model-based planning and real-time predictive control for laser-induced thermal therapy

    PubMed Central

    Feng, Yusheng; Fuentes, David

    2014-01-01

    In this article, the major idea and mathematical aspects of model-based planning and real-time predictive control for laser-induced thermal therapy (LITT) are presented. In particular, a computational framework and its major components developed by authors in recent years are reviewed. The framework provides the backbone for not only treatment planning but also real-time surgical monitoring and control with a focus on MR thermometry enabled predictive control and applications to image-guided LITT, or MRgLITT. Although this computational framework is designed for LITT in treating prostate cancer, it is further applicable to other thermal therapies in focal lesions induced by radio-frequency (RF), microwave and high-intensity-focused ultrasound (HIFU). Moreover, the model-based dynamic closed-loop predictive control algorithms in the framework, facilitated by the coupling of mathematical modelling and computer simulation with real-time imaging feedback, has great potential to enable a novel methodology in thermal medicine. Such technology could dramatically increase treatment efficacy and reduce morbidity. PMID:22098360

  15. Calculation of surface diffusivity and residence time by molecular dynamics with application to nanoscale selective-area growth

    NASA Astrophysics Data System (ADS)

    Almeida, S.; Ochoa, E.; Chavez, J. J.; Zhou, X. W.; Zubia, D.

    2015-08-01

    The surface diffusivity and residence time were calculated by molecular dynamics simulations in order to solve the surface diffusion equations for selective-area growth. The calculations for CdTe/CdS material system were performed in substrates with Cd termination and S termination. The surface diffusivity and residence time were obtained at different temperatures (600 K, 800 K, 1000 K, 1200 K, and 1400 K). The thermal activation energies were extracted from Arrhenius equation for each substrate termination. Thereafter, values obtained by molecular dynamics were used in a surface diffusion model to calculate the surface concentration profile of adatoms. Alternating the surface termination has the potential to achieve nanoscale selective-area growth without the need of a dielectric film as a mask.

  16. Numerical analysis of curved frequency selective surface by finite-difference time-domain

    NASA Astrophysics Data System (ADS)

    Chen, Xin-yi; Wang, Jian-bo; Chen, Gui-bo; Sun, Guan-cheng; Lu, Jun

    2011-08-01

    Frequency selective surface is a monolayer or multilayer 2D periodic structure which is composed of multiple resonance units scattering by a two-dimensional periodic array on dielectric layer. FSS can't absorb radio frequency energy, but can filter the frequency which is therefore applied in microwave technique or stealth technology. The relative research on curved FSS is relatively scarce since the curved FSS structure can be obtained only when FSS is attached on the materials surfaces of curved structures in engineering application. However, curved FSS is widely applied in practical engineering; therefore, the research on curved FSS structure has important significance. In this paper, a curved FSS structure model of Y-pore unit is established and numerical simulated by means of FDTD. The influence of curvature on FSS transmission characteristics is studied according to the analysis on the changing of radar cross section (RCS). The results show: the center frequency point of the plane band pass FSS structure drifts after the curve surface deformation of the structure; the center frequency point of the curved band pass FSS structure drifts with the changing of the curvature radius, i. e. with the decreasing of curvature radius, the frequency point drifts towards high points and the transmittance decreases. The design of FSS radome demands of accurate and stable center resonance frequency; therefore, the actual situation of curved surface should be considered in practical engineering application when band pass FSS is made into frequency selection filtering radome. The curvature radius should be long enough to avoid center frequency drifting and transmittance deceasing.

  17. Nuclear receptor-induced transcription is driven by spatially and timely restricted waves of ROS

    PubMed Central

    Perillo, Bruno; Di Santi, Annalisa; Cernera, Gustavo; Ombra, Maria Neve; Castoria, Gabriella; Migliaccio, Antimo

    2014-01-01

    Gene expression is governed by chromatin mainly through posttranslational modifications at the N-terminal tails of nucleosomal histone proteins. According to the histone code theory, peculiar sets of such modifications (marks) give rise to reproducible final effects on transcription and, very recently, a further level of complexity has been highlighted in binary switches between specific marks at adjacent residues. In particular, disappearance of dimethyl-lysine 9 in histone H3 is faced by phosphorylation of the following serine during activation of gene expression. Demethylation of lysine 9 by the lysine-specific demethylase 1 (LSD1) is a pre-requisite for addition of the phosphoryl mark to serine 10 and an essential step in the transcriptional control by estrogens. It generates a local burst of oxygen reactive species (ROS) that induce oxidation of nearby nucleotides and recruitment of repair enzymes with a consequent formation of single or double stranded nicks on DNA that modify chromatin flexibility in order to allow correct assembly of the transcriptional machinery.   We describe here the molecular mechanism by which members of the family of nuclear receptors prevent the potential damage to DNA during transcription of target genes elicited by the use of ROS to shape chromatin. The mechanism is based on the presence of phosphorylated serine 10 in histone H3 to prevent unbalanced DNA oxidation waves. We also discuss the opportunities raised by the use of voluntary derangement of this servo system to induce selective death in hormone-responsive transformed cells. PMID:25482200

  18. Selective inhibition of calcium entry induced by benzylisoquinolines in rat smooth muscle.

    PubMed

    Anselmi, E; Fayos, G; Blasco, R; Candenas, L; Cortes, D; D'Ocon, P

    1992-04-01

    The mechanism of relaxant activity of six benzylisoquinolines was examined in order to determine the minimal structural requirements that enable these compounds to have either a non-specific action like papaverine or an inhibitory activity on calcium entry via potential-operated channels. All the alkaloids tested totally or partially relaxed KCl-depolarized rat uterus and inhibited oxytocin-induced rhythmic contractions. Only glaucine and laudanosine inhibited K(+)-induced uterine contractions more than oxytocin-induced uterine contractions. In Ca(+)-free medium, sustained contractions induced by oxytocin or vanadate were relaxed by the alkaloids tested except for glaucine and laudanosine indicating no inhibitory effect on intracellular calcium release. Those alkaloids containing an unsaturated heterocyclic ring (papaverine, papaverinol, papaveraldine, N-methylpapaverine and dehydropapaverine) exhibited a more specific activity than those with a tetrahydroisoquinoline ring. PMID:1355547

  19. Respiratory-Induced Prostate Motion Using Wavelet Decomposition of the Real-Time Electromagnetic Tracking Signal

    SciTech Connect

    Lin, Yuting; Liu, Tian; Yang, Xiaofeng; Wang, Yuenan; Khan, Mohammad K.

    2013-10-01

    Purpose: The objective of this work is to characterize and quantify the impact of respiratory-induced prostate motion. Methods and Materials: Real-time intrafraction motion is observed with the Calypso 4-dimensional nonradioactive electromagnetic tracking system (Calypso Medical Technologies, Inc. Seattle, Washington). We report the results from a total of 1024 fractions from 31 prostate cancer patients. Wavelet transform was used to decompose the signal to extract and isolate the respiratory-induced prostate motion from the total prostate displacement. Results: Our results show that the average respiratory motion larger than 0.5 mm can be observed in 68% of the fractions. Fewer than 1% of the patients showed average respiratory motion of less than 0.2 mm, whereas 99% of the patients showed average respiratory-induced motion ranging between 0.2 and 2 mm. The maximum respiratory range of motion of 3 mm or greater was seen in only 25% of the fractions. In addition, about 2% patients showed anxiety, indicated by a breathing frequency above 24 times per minute. Conclusions: Prostate motion is influenced by respiration in most fractions. Real-time intrafraction data are sensitive enough to measure the impact of respiration by use of wavelet decomposition methods. Although the average respiratory amplitude observed in this study is small, this technique provides a tool that can be useful if one moves to smaller treatment margins (≤5 mm). This also opens ups the possibility of being able to develop patient specific margins, knowing that prostate motion is not unpredictable.

  20. Modeling Time Dependent Earthquake Magnitude Distributions Associated with Injection-Induced Seismicity

    NASA Astrophysics Data System (ADS)

    Maurer, J.; Segall, P.

    2015-12-01

    Understanding and predicting earthquake magnitudes from injection-induced seismicity is critically important for estimating hazard due to injection operations. A particular problem has been that the largest event often occurs post shut-in. A rigorous analysis would require modeling all stages of earthquake nucleation, propagation, and arrest, and not just initiation. We present a simple conceptual model for predicting the distribution of earthquake magnitudes during and following injection, building on the analysis of Segall & Lu (2015). The analysis requires several assumptions: (1) the distribution of source dimensions follows a Gutenberg-Richter distribution; (2) in environments where the background ratio of shear to effective normal stress is low, the size of induced events is limited by the volume perturbed by injection (e.g., Shapiro et al., 2013; McGarr, 2014), and (3) the perturbed volume can be approximated by diffusion in a homogeneous medium. Evidence for the second assumption comes from numerical studies that indicate the background ratio of shear to normal stress controls how far an earthquake rupture, once initiated, can grow (Dunham et al., 2011; Schmitt et al., submitted). We derive analytical expressions that give the rate of events of a given magnitude as the product of three terms: the time-dependent rate of nucleations, the probability of nucleating on a source of given size (from the Gutenberg-Richter distribution), and a time-dependent geometrical factor. We verify our results using simulations and demonstrate characteristics observed in real induced sequences, such as time-dependent b-values and the occurrence of the largest event post injection. We compare results to Segall & Lu (2015) as well as example datasets. Future work includes using 2D numerical simulations to test our results and assumptions; in particular, investigating how background shear stress and fault roughness control rupture extent.

  1. Time Management Abilities of School Principals According to Gender: A Case Study in Selected Gauteng Schools

    ERIC Educational Resources Information Center

    Botha, R. J.

    2013-01-01

    According to the literature on school effectiveness and school improvement and the role of the school principal in this regard, the lack of time management skills and abilities among school principals can be regarded as one of the main factors that lead to principal inefficiency and ineffectiveness in the school context. But, how do male and…

  2. Lay-Offs and Short-Time Working in Selected OECD Countries.

    ERIC Educational Resources Information Center

    Grais, Bernard; And Others

    This report, which includes the conclusions of the Organisation for Economic Cooperation and Development (OECD) Working Party on Employment and Unemployment Statistics, analyzes arrangements for compensating workers in the OECD countries who are temporarily laid-off or subject to short-time work. In introductory sections to part 1, the concepts of…

  3. Time-Resolved Fluorescence in Lipid Bilayers: Selected Applications and Advantages over Steady State

    PubMed Central

    Amaro, Mariana; Šachl, Radek; Jurkiewicz, Piotr; Coutinho, Ana; Prieto, Manuel; Hof, Martin

    2014-01-01

    Fluorescence methods are versatile tools for obtaining dynamic and topological information about biomembranes because the molecular interactions taking place in lipid membranes frequently occur on the same timescale as fluorescence emission. The fluorescence intensity decay, in particular, is a powerful reporter of the molecular environment of a fluorophore. The fluorescence lifetime can be sensitive to the local polarity, hydration, viscosity, and/or presence of fluorescence quenchers/energy acceptors within several nanometers of the vicinity of a fluorophore. Illustrative examples of how time-resolved fluorescence measurements can provide more valuable and detailed information about a system than the time-integrated (steady-state) approach will be presented in this review: 1), determination of membrane polarity and mobility using time-dependent spectral shifts; 2), identification of submicroscopic domains by fluorescence lifetime imaging microscopy; 3), elucidation of membrane leakage mechanisms from dye self-quenching assays; and 4), evaluation of nanodomain sizes by time-resolved Förster resonance energy transfer measurements. PMID:25517142

  4. Adaptive and phase selective spike timing dependent plasticity in synaptically coupled neuronal oscillators.

    PubMed

    Kazantsev, Victor; Tyukin, Ivan

    2012-01-01

    We consider and analyze the influence of spike-timing dependent plasticity (STDP) on homeostatic states in synaptically coupled neuronal oscillators. In contrast to conventional models of STDP in which spike-timing affects weights of synaptic connections, we consider a model of STDP in which the time lags between pre- and/or post-synaptic spikes change internal state of pre- and/or post-synaptic neurons respectively. The analysis reveals that STDP processes of this type, modeled by a single ordinary differential equation, may ensure efficient, yet coarse, phase-locking of spikes in the system to a given reference phase. Precision of the phase locking, i.e. the amplitude of relative phase deviations from the reference, depends on the values of natural frequencies of oscillators and, additionally, on parameters of the STDP law. These deviations can be optimized by appropriate tuning of gains (i.e. sensitivity to spike-timing mismatches) of the STDP mechanism. However, as we demonstrate, such deviations can not be made arbitrarily small neither by mere tuning of STDP gains nor by adjusting synaptic weights. Thus if accurate phase-locking in the system is required then an additional tuning mechanism is generally needed. We found that adding a very simple adaptation dynamics in the form of slow fluctuations of the base line in the STDP mechanism enables accurate phase tuning in the system with arbitrary high precision. Adaptation operating at a slow time scale may be associated with extracellular matter such as matrix and glia. Thus the findings may suggest a possible role of the latter in regulating synaptic transmission in neuronal circuits. PMID:22412830

  5. Measurement of circulation time in the retinal vasculature using selective angiography.

    PubMed

    Khoobehi, B; Schuele, K M; Ali, O M; Peyman, G A

    1990-08-01

    Retinal circulation times (RCT) and mean circulation time (MCT) in the retinal vasculature have been used to determine the effect of ocular disease on retinal circulation. Both RCT and MCT are usually determined by measuring dye dilution curves during a traditional fluorescein angiogram. The authors present a variation of the dye dilution technique. The primary difference is that a fluorescent dye (carboxyfluorescein or calcein) was encapsulated in liposomes at a very high concentration. The dye was then released at a specific site in a retinal artery by the application of a laser pulse delivered through the pupil of the eye. The heat pulse produced by the laser lysed the liposomes in the targeted vessel, causing a stream of dye to be released. The time it took the dye front to pass through the artery and return through the vein (RCT) was then measured. To clarify the situation, two times were actually measured, the shortest path the dye traveled from the exposure site to a corresponding site on the vein (short RCT) and the longest path through the periphery to venous filling (long RCT). The measurements were made in both cynomolgus monkeys and squirrel monkeys. The local dye release achieved with this method was found to produce a more distinct dye front than traditional angiography while also eliminating the problem of recirculation. Choroidal background fluorescence, a factor that often obscures the dye front in traditional angiography, was minimal. Furthermore, it was possible to make individual measurements on each of the four arteries and to repeat the measurements several times. PMID:2402418

  6. Adaptive and Phase Selective Spike Timing Dependent Plasticity in Synaptically Coupled Neuronal Oscillators

    PubMed Central

    Kazantsev, Victor; Tyukin, Ivan

    2012-01-01

    We consider and analyze the influence of spike-timing dependent plasticity (STDP) on homeostatic states in synaptically coupled neuronal oscillators. In contrast to conventional models of STDP in which spike-timing affects weights of synaptic connections, we consider a model of STDP in which the time lags between pre- and/or post-synaptic spikes change internal state of pre- and/or post-synaptic neurons respectively. The analysis reveals that STDP processes of this type, modeled by a single ordinary differential equation, may ensure efficient, yet coarse, phase-locking of spikes in the system to a given reference phase. Precision of the phase locking, i.e. the amplitude of relative phase deviations from the reference, depends on the values of natural frequencies of oscillators and, additionally, on parameters of the STDP law. These deviations can be optimized by appropriate tuning of gains (i.e. sensitivity to spike-timing mismatches) of the STDP mechanism. However, as we demonstrate, such deviations can not be made arbitrarily small neither by mere tuning of STDP gains nor by adjusting synaptic weights. Thus if accurate phase-locking in the system is required then an additional tuning mechanism is generally needed. We found that adding a very simple adaptation dynamics in the form of slow fluctuations of the base line in the STDP mechanism enables accurate phase tuning in the system with arbitrary high precision. Adaptation operating at a slow time scale may be associated with extracellular matter such as matrix and glia. Thus the findings may suggest a possible role of the latter in regulating synaptic transmission in neuronal circuits. PMID:22412830

  7. Selected time-lapse movies of the east rift zone eruption of KĪlauea Volcano, 2004–2008

    USGS Publications Warehouse

    Orr, Tim R.

    2011-01-01

    Since 2004, the U.S. Geological Survey's Hawaiian Volcano Observatory has used mass-market digital time-lapse cameras and network-enabled Webcams for visual monitoring and research. The 26 time-lapse movies in this report were selected from the vast collection of images acquired by these camera systems during 2004–2008. Chosen for their content and broad aesthetic appeal, these image sequences document a variety of flow-field and vent processes from Kīlauea's east rift zone eruption, which began in 1983 and is still (as of 2011) ongoing.

  8. Modeling Injection Induced Seismicity with Poro-Elasticity and Time-Dependent Earthquake Nucleation

    NASA Astrophysics Data System (ADS)

    Lu, S.; Segall, P.

    2014-12-01

    The standard approach to modeling injection-induced seismicity (IIS) considers Coulomb failure stress changes accounting only for pore-pressure changes, which are solved by the diffusion equation. However, this "diffusion" triggering mechanism is not comprehensive. Lab experiments indicate earthquake nucleation also depends on stress history. Here we add two effects in modeling IIS: 1) poro-elastic coupling between solid stresses and pore-pressure, and 2) time dependent earthquake nucleation under applied stresses. In this model, we compute stress and pore-pressure changes due to a point source injecting in a homogeneous, poro-elastic full space (Rudnicki, 1986). The Coulomb stress history is used to compute seismicity rate changes based on the time-dependent nucleation model of Dieterich (1994). Our new model reveals: 1) poro-elastic coupling breaks the radial symmetry in seismicity, 2) nucleation introduces a characteristic nucleation time ta, which affects the temporal evolution of seismicity rates, and 3) for some fault geometries, the seismicity rate may increase following shut in. For constant injection flux, the log of seismicity rate scales with the change in Coulomb stress at short time, consistent with diffusion profiles. At longer time, the model predicts seismicity rates decaying with time, consistent with some observations. The contour shape and decay time are characterized by ta. For finite injection with box-car flux history, seismicity rates plummet near the injector, but may continue for some time at greater distance. Depending on fault orientations, seismicity rates may increase after shut-in due to coupling effects. It has been observed in some cases that the maximum magnitude of induced quakes occurs after shut-in. This may be understood by the fact that the volume of perturbed crust increases with injection time, which influences probability of triggering an event of a given magnitude. Whether coupling effects are important in post shut

  9. Revisiting the time domain induced polarization technique, from linearization to inversion

    NASA Astrophysics Data System (ADS)

    Kang, S.; Oldenburg, D.

    2015-12-01

    The induced polarization (IP) technique has been successful in mineral exploration, particularly for finding disseminated sulphide or porphyry deposits, but also in helping solve geotechnical and environmental problems. Electrical induced polarization (EIP) surveys use grounded electrodes and take measurements of the electric field while the current is both "on" and "off". Currently, 2D and 3D inversions of EIP data are generally carried out by first finding a background conductivity from the asymptotic "on-time" measurements. The DC resistivity problem is then linearized about that conductivity to obtain a linear relationship between the off-time data and the "pseudo-chargeability". The distribution of pseudo-chargeability in the earth is then interpreted within the context of the initial geoscience problem pursued. Despite its success, the current EIP implementation does have challenges. A fundamental assumption, that there is no electromagnetic induction (EM) effect, breaks down when the background is conductive. This is especially problematic in regions having conductive overburden. EM induction complicates, and sometimes overwhelms, the IP signal. To ameliorate this effect, we estimate the inductive signal, subtract it from the "off-time" data and invert the resultant IP data using the linearized formulation. We carefully examine the conditions under which this works. We also investigate the potential alterations to the linearized sensitivity function that are needed to allow a linearized inversion to be carried out. Inversions of EIP data recover a "chargeability" but this is not a uniquely defined quantity. There are multiple definitions of this property because there are a diverse number of ways in which an IP datum is defined. In time domain IP surveys, the data might be mV/V or a time-integrated voltage with units of ms. In reality however, data from an EIP survey have many time channels and each one can be inverted separately to produce a chargeability

  10. Selective inhibition by chloramphenicol of pregnenolone-16. cap alpha. -carbonitrile-inducible rat liver cytochrome P-450 isozymes

    SciTech Connect

    Graves, P.E.; Kaminsky, L.S.; Halpert, J.

    1986-03-01

    Pregnenolone-16 ..cap alpha..-carbonitrile (PCN) has been shown to induce, in male rats, cytochrome P-450 isozymes responsible for the formation of R-10-hydroxywarfarin and R-dehydrowarfarin. Antibodies to the major PCN-inducible isozyme (PB/PCN-E) inhibit both activities in microsomal preparations. Recently the authors have shown that PCN treatment of female rats also induces the formation of both R-warfarin metabolites. However, in both sexes chloramphenicol (CAP) treatment selectively inhibits only the rate of formation of the R-dehydrowarfarin. A decrease in microsomal P-450 content occurs after in vivo administration of CAP to PCN-treated rats of both sexes. This is in contrast to the lack of effect of CAP on P-450 levels in phenobarbital-treated rats. Covalent binding of /sup 14/C-CAP to microsomal protein in vitro was increased 3 to 4-fold following PCN treatment. Chromatographic evidences suggests the presence of at least two PCN-induced isozymes of similar molecular weights in both male and female rat liver microsomes. These data are consistent with the multiplicity of PCN-inducible P-450 in rat liver.

  11. Bacillus Calmette-Guérin vaccine induces a selective serotonin reuptake inhibitor (SSRI)-resistant depression like phenotype in mice.

    PubMed

    Vijaya Kumar, K; Rudra, Anjuman; Sreedhara, M V; Siva Subramani, T; Prasad, Durga Shiva; Das, Manish Lal; Murugesan, Senthil; Yadav, Rajbharan; Trivedi, Ravi Kumar; Louis, Justin V; Li, Yu-Wen; Bristow, Linda J; Naidu, Pattipati S; Vikramadithyan, Reeba Kannimel

    2014-11-01

    Preclinical studies have shown that administration of Bacillus Calmette-Guérin (BCG) vaccine induces depression-like behaviors in mice; however, the effect of antidepressant drug treatment has not been reported earlier. In the present study, we induced depression-like behavior by administering BCG vaccine to BALB/c mice. BCG treatment produced robust serum sickness as shown by a decrease in body weight, reduced spontaneous locomotor activity and reduced voluntary wheel running activity. BCG treatment also elevated plasma IL6 and IFNγ levels and produced a marked activation of lung IDO activity. At a time point when serum sickness-related behaviors had fully recovered (i.e., day 14) BCG-treated mice showed a significant increase in immobility in the forced swim test (FST) and tail suspension test (TST) indicative of a pro-depressant phenotype. We observed significant increase in [(3)H]PK11195 binding in cortex and hippocampus regions of BGC-treated mice in comparison to saline-treated mice indicating prominent neuroinflammation. Pharmacological evaluation of FST behavior in BCG-treated mice demonstrated selective resistance to the selective serotonin reuptake inhibitors (SSRIs) fluoxetine and escitalopram. In contrast the tricyclic antidepressant imipramine, the dual serotonin/norepinephrine reuptake inhibitor (SNRI) duloxetine, and the dual dopamine/norepinephrine reuptake inhibitor (DNRI) nomifensine retained antidepressant efficacy in these mice. The lack of efficacy with acute treatment with SSRIs could not be explained either by differences in drug exposure or serotonin transporter (SERT) occupancy. Our results demonstrate that BCG-vaccine induced depression like behavior is selectively resistant to SSRIs and could potentially be employed to evaluate novel therapeutic agents being developed to treat SSRI-resistance in humans. PMID:25016199

  12. Mechanism study of femtosecond laser induced selective metallization (FLISM) on glass surfaces

    NASA Astrophysics Data System (ADS)

    Xu, Jian; Liao, Yang; Zeng, Huidan; Cheng, Ya; Xu, Zhizhan; Sugioka, Koji; Midorikawa, Katsumi

    2008-07-01

    We investigate the mechanism of selective metallization on glass surfaces with the assistance of femtosecond laser irradiation followed by electroless plating. Irradiation of femtosecond laser makes it possible to selectively deposit copper microstructures in the irradiated area on glass surfaces coated with silver nitrate films. The energy-dispersive X-ray (EDX) analyses reveal that silver atoms are produced on the surface of grooves formed by laser ablation, which serve as catalysis seeds for subsequent electroless copper plating.

  13. QUASI-STELLAR OBJECT SELECTION ALGORITHM USING TIME VARIABILITY AND MACHINE LEARNING: SELECTION OF 1620 QUASI-STELLAR OBJECT CANDIDATES FROM MACHO LARGE MAGELLANIC CLOUD DATABASE

    SciTech Connect

    Kim, Dae-Won; Protopapas, Pavlos; Alcock, Charles; Trichas, Markos; Byun, Yong-Ik; Khardon, Roni

    2011-07-10

    We present a new quasi-stellar object (QSO) selection algorithm using a Support Vector Machine, a supervised classification method, on a set of extracted time series features including period, amplitude, color, and autocorrelation value. We train a model that separates QSOs from variable stars, non-variable stars, and microlensing events using 58 known QSOs, 1629 variable stars, and 4288 non-variables in the MAssive Compact Halo Object (MACHO) database as a training set. To estimate the efficiency and the accuracy of the model, we perform a cross-validation test using the training set. The test shows that the model correctly identifies {approx}80% of known QSOs with a 25% false-positive rate. The majority of the false positives are Be stars. We applied the trained model to the MACHO Large Magellanic Cloud (LMC) data set, which consists of 40 million light curves, and found 1620 QSO candidates. During the selection none of the 33,242 known MACHO variables were misclassified as QSO candidates. In order to estimate the true false-positive rate, we crossmatched the candidates with astronomical catalogs including the Spitzer Surveying the Agents of a Galaxy's Evolution LMC catalog and a few X-ray catalogs. The results further suggest that the majority of the candidates, more than 70%, are QSOs.

  14. Self-Induced Switchings between Multiple Space-Time Patterns on Complex Networks of Excitable Units

    NASA Astrophysics Data System (ADS)

    Ansmann, Gerrit; Lehnertz, Klaus; Feudel, Ulrike

    2016-01-01

    We report on self-induced switchings between multiple distinct space-time patterns in the dynamics of a spatially extended excitable system. These switchings between low-amplitude oscillations, nonlinear waves, and extreme events strongly resemble a random process, although the system is deterministic. We show that a chaotic saddle—which contains all the patterns as well as channel-like structures that mediate the transitions between them—is the backbone of such a pattern-switching dynamics. Our analyses indicate that essential ingredients for the observed phenomena are that the system behaves like an inhomogeneous oscillatory medium that is capable of self-generating spatially localized excitations and that is dominated by short-range connections but also features long-range connections. With our findings, we present an alternative to the well-known ways to obtain self-induced pattern switching, namely, noise-induced attractor hopping, heteroclinic orbits, and adaptation to an external signal. This alternative way can be expected to improve our understanding of pattern switchings in spatially extended natural dynamical systems like the brain and the heart.

  15. Inflammatory mediators in a short-time mouse model of doxorubicin-induced cardiotoxicity.

    PubMed

    Pecoraro, Michela; Del Pizzo, Mariagiovanna; Marzocco, Stefania; Sorrentino, Rosalinda; Ciccarelli, Michele; Iaccarino, Guido; Pinto, Aldo; Popolo, Ada

    2016-02-15

    Doxorubicin (DOXO) is commonly used to treat a wide range of malignant tumors, but its clinical use is limited by acute and chronic cardiotoxicity. The precise mechanism underlying DOXO-induced cardiotoxicity is still not completely elucidated, but cardiac inflammation seems to be involved. Effects of DOXO on proinflammatory cytokines, inflammatory cell infiltration, and necrosis have been proven only when a functional impairment has already occurred, so this study aimed to investigate the acute effect of DOXO administration in mouse heart. The results of our study demonstrated alterations in cardiac function parameters assessed by ultrasound within 24h after a single injection of DOXO, with a cumulative effect along the increase of the dose and the number of DOXO administrations. At the same time, DOXO causes a significant production of proinflammatory cytokines (such as TNF-α and IL-6) with a concomitant reduction of IL-10, a well-known antiinflammatory cytokine. Furthermore, overexpression of inducible nitric oxide synthase (iNOS) in heart tissue and increased levels of serum nitrite in DOXO-treated mice were detected. Notably, DOXO administration significantly increased nitrotyrosine expression in mouse heart. Our data support the hypothesis that these early events, could be responsible for the later onset of more severe deleterious remodeling leading to DOXO induced cardiomyopathy. PMID:26780402

  16. Time course of "escape" from calcitonin-induced inhibition of motility and resorption of disaggregated osteoclasts.

    PubMed

    Kanehisa, J

    1989-01-01

    The reversible calcitonin (CT)-induced inhibition of osteoclastic activity has been studied to clarify the mechanisms responsible for the so-called "escape phenomenon." Osteoclasts disaggregated from neonatal rabbits were cultured on glass coverslips or thin bovine bone slices. Resorption activity was evaluated by using time-lapse recording and scanning electron microscopy. Addition of CT to the cultures caused most osteoclasts on glass surfaces to be immotile and contracted. From 1.5 h onward, in cultures with CT, osteoclasts started to escape from CT-induced quiescence independently of other cells. CT also prevented osteoclasts on bone slices from excavating bone while concomitant cell immobility occurred. Inhibited osteoclasts were able to regain apparent bone-resorbing potency only after resumption of cytoplasmic immobility. The resumption of bone resorption could begin as early as 9.7 h after CT addition. The observations indicate that CT-induced inhibition of osteoclastic bone resorption is associated with inhibition of cytoplasmic motility and that the "escape" phenomenon reflects resumption of activity of osteoclasts that were previously inhibited by CT action rather than the resportive activity of newly formed osteoclasts. PMID:2765310

  17. Inducible, Dose-Adjustable and Time-Restricted Reconstitution of Stat1 Deficiency In Vivo

    PubMed Central

    Leitner, Nicole R.; Lassnig, Caroline; Rom, Rita; Heider, Susanne; Bago-Horvath, Zsuzsanna; Eferl, Robert; Müller, Simone; Kolbe, Thomas; Kenner, Lukas; Rülicke, Thomas; Strobl, Birgit; Müller, Mathias

    2014-01-01

    Signal transducer and activator of transcription (STAT) 1 is a key player in interferon (IFN) signaling, essential in mediating host defense against viruses and other pathogens. STAT1 levels are tightly regulated and loss- or gain-of-function mutations in mice and men lead to severe diseases. We have generated a doxycycline (dox) -inducible, FLAG-tagged Stat1 expression system in mice lacking endogenous STAT1 (i.e. Stat1ind mice). We show that STAT1 expression depends on the time and dose of dox treatment in primary cells and a variety of organs isolated from Stat1ind mice. In bone marrow-derived macrophages, a fraction of the amount of STAT1 present in WT cells is sufficient for full expression of IFN-induced genes. Dox-induced STAT1 established protection against virus infections in primary cells and mice. The availability of the Stat1ind mouse model will enable an examination of the consequences of variable amounts of STAT1. The model will also permit the study of STAT1 dose-dependent and reversible functions as well as of STAT1's contributions to the development, progression and resolution of disease. PMID:24489749

  18. Selective pharmacological blockade of the 5-HT7 receptor attenuates light and 8-OH-DPAT induced phase shifts of mouse circadian wheel running activity

    PubMed Central

    Shelton, Jonathan; Yun, Sujin; Losee Olson, Susan; Turek, Fred; Bonaventure, Pascal; Dvorak, Curt; Lovenberg, Timothy; Dugovic, Christine

    2015-01-01

    Recent reports have illustrated a reciprocal relationship between circadian rhythm disruption and mood disorders. The 5-HT7 receptor may provide a crucial link between the two sides of this equation since the receptor plays a critical role in sleep, depression, and circadian rhythm regulation. To further define the role of the 5-HT7 receptor as a potential pharmacotherapy to correct circadian rhythm disruptions, the current study utilized the selective 5-HT7 antagonist JNJ-18038683 (10 mg/kg) in three different circadian paradigms. While JNJ-18038683 was ineffective at phase shifting the onset of wheel running activity in mice when administered at different circadian time (CT) points across the circadian cycle, pretreatment with JNJ-18038683 blocked non-photic phase advance (CT6) induced by the 5-HT1A/7 receptor agonist 8-OH-DPAT (3 mg/kg). Since light induced phase shifts in mammals are partially mediated via the modulation of the serotonergic system, we determined if JNJ-18038683 altered phase shifts induced by a light pulse at times known to phase delay (CT15) or advance (CT22) wheel running activity in free running mice. Light exposure resulted in a robust shift in the onset of activity in vehicle treated animals at both times tested. Administration of JNJ-18038683 significantly attenuated the light induced phase delay and completely blocked the phase advance. The current study demonstrates that pharmacological blockade of the 5-HT7 receptor by JNJ-18038683 blunts both non-photic and photic phase shifts of circadian wheel running activity in mice. These findings highlight the importance of the 5-HT7 receptor in modulating circadian rhythms. Due to the opposite modulating effects of light resetting between diurnal and nocturnal species, pharmacotherapy targeting the 5-HT7 receptor in conjunction with bright light therapy may prove therapeutically beneficial by correcting the desynchronization of internal rhythms observed in depressed individuals. PMID:25642174

  19. Alive SMC(2) : Bayesian model selection for low-count time series models with intractable likelihoods.

    PubMed

    Drovandi, Christopher C; McCutchan, Roy A

    2016-06-01

    In this article we present a new method for performing Bayesian parameter inference and model choice for low- count time series models with intractable likelihoods. The method involves incorporating an alive particle filter within a sequential Monte Carlo (SMC) algorithm to create a novel exact-approximate algorithm, which we refer to as alive SMC2. The advantages of this approach over competing methods are that it is naturally adaptive, it does not involve between-model proposals required in reversible jump Markov chain Monte Carlo, and does not rely on potentially rough approximations. The algorithm is demonstrated on Markov process and integer autoregressive moving average models applied to real biological datasets of hospital-acquired pathogen incidence, animal health time series, and the cumulative number of prion disease cases in mule deer. PMID:26584211

  20. Variation of solar-selective properties of black chrome with plating time

    NASA Technical Reports Server (NTRS)

    Mcdonald, G. E.; Curtis, H. B.

    1975-01-01

    The spectral reflectance properties of a commercially prepared black chrome over dull nickel, both plated on steel, for various plating times of the black chrome were measured. The plating current was 180 amperes per square foot. Values of absorptance integrated over the solar spectrum, and of infrared emittance integrated over black-body radiation at 250 F were obtained. It is shown that plating between one and two minutes produces the optimum combination of highest heat absorbed and lowest heat lost by radiation.

  1. Testosterone attenuates and the selective estrogen receptor modulator, raloxifene, potentiates amphetamine-induced locomotion in male rats.

    PubMed

    Purves-Tyson, Tertia D; Boerrigter, Danny; Allen, Katherine; Zavitsanou, Katerina; Karl, Tim; Djunaidi, Vanezha; Double, Kay L; Desai, Reena; Handelsman, David J; Weickert, Cynthia Shannon

    2015-04-01

    Although sex steroids are known to modulate brain dopamine, it is still unclear how testosterone modifies locomotor behaviour controlled, at least in part, by striatal dopamine in adolescent males. Our previous work suggests that increasing testosterone during adolescence may bias midbrain neurons to synthesise more dopamine. We hypothesised that baseline and amphetamine-induced locomotion would differ in adult males depending on testosterone exposure during adolescence. We hypothesised that concomitant stimulation of estrogen receptor signaling, through a selective estrogen receptor modulator (SERM), raloxifene, can counter testosterone effects on locomotion. Male Sprague-Dawley rats at postnatal day 45 were gonadectomised (G) or sham-operated (S) prior to the typical adolescent testosterone increase. Gonadectomised rats were either given testosterone replacement (T) or blank implants (B) for six weeks and sham-operated (i.e. intact or endogenous testosterone group) were given blank implants. Subgroups of sham-operated, gonadectomised and gonadectomised/testosterone-replaced rats were treated with raloxifene (R, 5mg/kg) or vehicle (V), daily for the final four weeks. There were six groups (SBV, GBV, GTV, SBR, GBR, GTR). Saline and amphetamine-induced (1.25mg/kg) locomotion in the open field was measured at PND85. Gonadectomy increased amphetamine-induced locomotion compared to rats with endogenous or with exogenous testosterone. Raloxifene increased amphetamine-induced locomotion in rats with either endogenous or exogenous testosterone. Amphetamine-induced locomotion was negatively correlated with testosterone and this relationship was abolished by raloxifene. Lack of testosterone during adolescence potentiates and testosterone exposure during adolescence attenuates amphetamine-induced locomotion. Treatment with raloxifene appears to potentiate amphetamine-induced locomotion and to have an opposite effect to that of testosterone in male rats. PMID:25747465

  2. Liquid chromatography quadrupole time-of-flight mass spectrometry selective determination of ochratoxin A in wine.

    PubMed

    Rodríguez-Cabo, T; Rodríguez, I; Ramil, M; Cela, R

    2016-05-15

    The performance of liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) for ochratoxin A (OTA) determination in wine is evaluated for the first time. Sample preparation was optimized to obtain quantitative recoveries at the same time that the efficiency of electrospray ionization (ESI) remained unaltered between sample extracts and calibration standards. Under final conditions, samples (20 mL) were concentrated using a reversed-phase solid-phase extraction (SPE) cartridge, followed by OTA elution with 1 mL of ethyl acetate. The absolute recoveries of the method, established against calibration standards, were 91-121% and 90-113% (without and with internal standard correction, respectively), for wines fortified at 3 concentration levels. The attained LOQ (0.05 ng mL(-1)) remained below the maximum permitted OTA concentration (2 ng mL(-1)) in dry wines. The method was applied to different samples, with OTA being found in some dessert wines at concentrations below 1 ng mL(-1). The ethyl ester of OTA (OTC) could be identified in the same wine samples from its accurate full product ion spectra. PMID:26775988

  3. It's payback time: Preschoolers selectively request resources from someone they had benefitted.

    PubMed

    Paulus, Markus

    2016-08-01

    Expectations that others will reciprocate to the benefits they received from us play a crucial role for the establishment of stable reciprocal exchange within social relationships. In the current study, 3- to 5-year-old preschool children allocated in a first phase more resources to one recipient than to another recipient. Subsequently, they had the possibility to ask one of them for valuable resources. The results of Experiment 1 show that preschool children expect others to reciprocate and strategically ask the ones they benefitted more to share with them. Experiment 2 demonstrates that there was no selective resource request when the recipients were absent during children's resource allocations. Experiment 3 showed that children focused on the absolute amount of resources given to the recipients, but did not monitor their own relative generosity in judging to whom of the recipients they had been nicer. This study provides first evidence that preschool children possess reciprocity expectations and point thus to the strategic nature of early social behavior. (PsycINFO Database Record PMID:27359157

  4. Renoprotective Effects of a Highly Selective A3 Adenosine Receptor Antagonist in a Mouse Model of Adriamycin-induced Nephropathy.

    PubMed

    Min, Hye Sook; Cha, Jin Joo; Kim, Kitae; Kim, Jung Eun; Ghee, Jung Yeon; Kim, Hyunwook; Lee, Ji Eun; Han, Jee Young; Jeong, Lak Shin; Cha, Dae Ryong; Kang, Young Sun

    2016-09-01

    The concentration of adenosine in the normal kidney increases markedly during renal hypoxia, ischemia, and inflammation. A recent study reported that an A3 adenosine receptor (A3AR) antagonist attenuated the progression of renal fibrosis. The adriamycin (ADX)-induced nephropathy model induces podocyte injury, which results in severe proteinuria and progressive glomerulosclerosis. In this study, we investigated the preventive effect of a highly selective A3AR antagonist (LJ1888) in ADX-induced nephropathy. Three groups of six-week-old Balb/c mice were treated with ADX (11 mg/kg) for four weeks and LJ1888 (10 mg/kg) for two weeks as following: 1) control; 2) ADX; and 3) ADX + LJ1888. ADX treatment decreased body weight without a change in water and food intake, but this was ameliorated by LJ1888 treatment. Interestingly, LJ1888 lowered plasma creatinine level, proteinuria, and albuminuria, which had increased during ADX treatment. Furthermore, LJ1888 inhibited urinary nephrin excretion as a podocyte injury marker, and urine 8-isoprostane and kidney lipid peroxide concentration, which are markers of oxidative stress, increased after injection of ADX. ADX also induced the activation of proinflammatory and profibrotic molecules such as TGF-β1, MCP-1, PAI-1, type IV collagen, NF-κB, NOX4, TLR4, TNFα, IL-1β, and IFN-γ, but they were remarkably suppressed after LJ1888 treatment. In conclusion, our results suggest that LJ1888 has a renoprotective effect in ADX-induced nephropathy, which might be associated with podocyte injury through oxidative stress. Therefore, LJ1888, a selective A3AR antagonist, could be considered as a potential therapeutic agent in renal glomerular diseases which include podocyte injury and proteinuria. PMID:27510383

  5. Modeling of Time-correlated Detection of Fast Neutrons Emitted in Induced SNM Fission

    NASA Astrophysics Data System (ADS)

    Guckes, Amber; Barzilov, Alexander; Richardson, Norman

    Neutron multiplicity methods are widely used in the assay of fissile materials. Fission reactions release multiple neutrons simultaneously. Time-correlated detection of neutrons provides a coincidence signature that is unique to fission,which enables distinguishing it from other events. In general, fission neutrons are fast. Thermal neutron sensors require the moderation of neutrons prior to a detection event; therefore, the neutron's energy and the event's timing information may be distorted, resulting in the wide time windows in the correlation analysis. Fastneutron sensing using scintillators allows shortening the time correlation window. In this study, four EJ-299-33A plastic scintillator detectors with neutron/photon pulse shape discrimination properties were modeled usingthe MCNP6 code. This sensor array was studied for time-correlated detection of fast neutrons emitted inthe induced fission of 239Pu and (α,n) neutron sources. This paper presents the results of computational modeling of arrays of these plastic scintillator sensors as well as3He detectors equipped with a moderator.

  6. Time-Resolved Study of Nanoparticle Induced Apoptosis Using Microfabricated Single Cell Arrays

    PubMed Central

    Röttgermann, Peter J. F.; Dawson, Kenneth A.; Rädler, Joachim O.

    2016-01-01

    Cell fate decisions like apoptosis are heterogeneously implemented within a cell population and, consequently, the population response is recognized as sum of many individual dynamic events. Here, we report on the use of micro-patterned single-cell arrays for real-time tracking of nanoparticle-induced (NP) cell death in sets of thousands of cells in parallel. Annexin (pSIVA) and propidium iodide (PI), two fluorescent indicators of apoptosis, are simultaneously monitored after exposure to functionalized polystyrene (PS−NH2) nanobeads as a model system. We find that the distribution of Annexin onset times shifts to later times and broadens as a function of decreasing NP dose. We discuss the mean time-to-death as a function of dose, and show how the EC50 value depends both on dose and time of measurement. In addition, the correlations between the early and late apoptotic markers indicate a systematic shift from apoptotic towards necrotic cell death during the course of the experiment. Thus, our work demonstrates the potential of array-based single cell cytometry for kinetic analysis of signaling cascades in a high-throughput format. PMID:27600074

  7. Influence of injection timing on severity of cadmium-induced testicular toxicity in mice.

    PubMed

    Ohtani, Katsumi; Yanagiba, Yukie; Ashimori, Atsushige; Takeuchi, Asuka; Takada, Naoko; Togawa, Masako; Hasegawa, Tatsuya; Ikeda, Masayuki; Miura, Nobuhiko

    2013-02-01

    Cadmium (Cd) is one of the endocrine disrupter and is a well-known testicular toxicant. Recently, we reported that Cd-induced mortality was markedly different by injection timing. In this report, we investigated whether severity of testicular toxicity was affected by injection timing of Cd. C57BL/6J mice (male, 7 w) were received single intraperitoneal injection of CdCl(2) (4.5 mg/kg) at zeitgeber time 6 (ZT6) or ZT18; these injection timings showed highest (ZT6) or lowest (ZT18) mortality in our previous study (Miura, 2012). After one week of the injection, several parameters for testicular toxicity such as epididymal sperm motility and numbers of sperm head both in cauda epididymidis and testis were measured. At ZT6 injection group, all parameters examined were significantly reduced compared to the control group. However, very interestingly, no significant changes were observed at ZT18 injection group. We obtained similar results by another experiment in which mice were received single subcutaneous injection of CdCl(2) (4 or 6 mg/kg) followed by measuring the parameters ten days after the injection. This diurnal variation was not contradictory to the result of the lethal toxicity which we showed earlier. Therefore, our results indicate that the testicular toxicity of Cd is also influenced by the injection timing. PMID:23358149

  8. Time-Resolved Study of Nanoparticle Induced Apoptosis Using Microfabricated Single Cell Arrays.

    PubMed

    Röttgermann, Peter J F; Dawson, Kenneth A; Rädler, Joachim O

    2016-01-01

    Cell fate decisions like apoptosis are heterogeneously implemented within a cell population and, consequently, the population response is recognized as sum of many individual dynamic events. Here, we report on the use of micro-patterned single-cell arrays for real-time tracking of nanoparticle-induced (NP) cell death in sets of thousands of cells in parallel. Annexin (pSIVA) and propidium iodide (PI), two fluorescent indicators of apoptosis, are simultaneously monitored after exposure to functionalized polystyrene (PS - NH 2) nanobeads as a model system. We find that the distribution of Annexin onset times shifts to later times and broadens as a function of decreasing NP dose. We discuss the mean time-to-death as a function of dose, and show how the EC 50 value depends both on dose and time of measurement. In addition, the correlations between the early and late apoptotic markers indicate a systematic shift from apoptotic towards necrotic cell death during the course of the experiment. Thus, our work demonstrates the potential of array-based single cell cytometry for kinetic analysis of signaling cascades in a high-throughput format. PMID:27600074

  9. Time causal operational estimation of electric fields induced in the Earth's lithosphere during magnetic storms

    NASA Astrophysics Data System (ADS)

    Love, Jeffrey J.; Swidinsky, Andrei

    2014-04-01

    In support of projects for monitoring geomagnetic hazards for electric power grids, we develop a simple mathematical formalism, consistent with the time causality of deterministic physics, for estimating electric fields that are induced in the Earth's lithosphere during magnetic storms. For an idealized model of the lithosphere, an infinite half-space having uniform electrical conductivity properties described by a galvanic tensor, we work in the Laplace-transformed frequency domain to obtain a transfer function which, when convolved with measured magnetic field time series, gives an estimated electric field time series. Using data collected at the Kakioka, Japan observatory, we optimize lithospheric conductivity parameters by minimizing the discrepancy between model-estimated electric field variation and that actually measured. With our simple model, we can estimate 87% of the variance in storm time Kakioka electric field data; a more complicated model of lithospheric conductivity would be required to estimate the remaining 13% of the variance. We discuss how our estimation formalism might be implemented for geographically coordinated real-time monitoring of geoelectric fields.

  10. Effect of Powder Reuse Times on Additive Manufacturing of Ti-6Al-4V by Selective Electron Beam Melting

    NASA Astrophysics Data System (ADS)

    Tang, H. P.; Qian, M.; Liu, N.; Zhang, X. Z.; Yang, G. Y.; Wang, J.

    2015-03-01

    An advantage of the powder-bed-based metal additive manufacturing (AM) processes is that the powder can be reused. The powder reuse or recycling times directly affect the affordability of the additively manufactured parts, especially for the AM of titanium parts. This study examines the influence of powder reuse times on the characteristics of Ti-6Al-4V powder, including powder composition, particle size distribution (PSD), apparent density, tap density, flowability, and particle morphology. In addition, tensile samples were manufactured and evaluated with respect to powder reuse times and sample locations in the powder bed. The following findings were made from reusing the same batch of powder 21 times for AM by selective electron beam melting: (i) the oxygen (O) content increased progressively with increasing reuse times but both the Al content and the V content remained generally stable (a small decrease only); (ii) the powder became less spherical with increasing reuse times and some particles showed noticeable distortion and rough surfaces after being reused 16 times; (iii) the PSD became narrower and few satellite particles were observed after 11 times of reuse; (iv) reused powder showed improved flowability; and (v) reused powder showed no measurable undesired influence on the AM process and the samples exhibited highly consistent tensile properties, irrespective of their locations in the powder bed. The implications of these findings were discussed.

  11. SELECTIVE VULNERABILITY OF EMBRYONIC CELL POPULATIONS TO ETHANOL-INDUCED APOPTOSIS: IMPLICATIONS FOR ALCOHOL RELATED BIRTH DEFECTS AND NEURODEVELOPMENTAL DISORDER

    EPA Science Inventory

    The locations of cell death and resulting malformations in embryos following teratogen exposure vary depending on the teratogen used, the genotype of the conceptus, and the developmental stage of the embryo at time of exposure. To date, ethanol-induced cell death has been charac...

  12. Time evolution studies of laser induced chemical changes in InAs nanowire using Raman spectroscopy

    SciTech Connect

    Pal, Suparna; Aggarwal, R.; Kumari Gupta, Vandna; Ingale, Alka

    2014-07-07

    We report the study of time evolution of chemical changes on the surface of an InAs nanowire (NW) on laser irradiation in different power density regime, using Raman spectroscopy for a time span of 8–16 min. Mixture of metastable oxides like InAsO{sub 4,} As{sub 2}O{sub 3} are formed upon oxidation, which are reflected as sharp Raman peaks at ∼240–254 and 180–200 cm{sup −1}. Evidence of removal of arsenic layer by layer is also observed at higher power density. Position controlled laser induced chemical modification on a nanometer scale, without changing the core of the NW, can be useful for NW based device fabrication.

  13. Time resolved simulation of lightning by LIP. [laser-induced plasma

    NASA Technical Reports Server (NTRS)

    Jebens, D. S.; Lakkaraju, H. S.; Mckay, C. P.; Borucki, W. J.

    1992-01-01

    Results of time-resolved spectra of lightning simulation in air by laser-induced plasma (LIP) are reported. The measured electron temperatures varied from 17,000 +/-1000 K at 600 ns to 12,000 +/-1000 K at 4 microsec after the ignition of the plasma. Electron densities in the plasma varied from (7.0 +/-1.4) x 10 exp 17/cu cm to (9.0 +/-1.8) x 10 exp 16/cu cm for the above times. A comparison of state variables for LIP and natural lightning is presented. Immediately following the ignition, both natural lightning and LIP are found to reach temperatures in excess of 16,000 K and relax to ambient pressure with different rates. They are expected to approach the 2000-4000-K temperature range, which is important to chemical synthesis, in an asymptotically similar fashion.

  14. Reinforcing and timing properties of water in the schedule-induced drinking situation.

    PubMed

    Ruiz, Jorge A; López-Tolsa, Gabriela E; Pellón, Ricardo

    2016-06-01

    A series of recent studies from our laboratory have added to the preceding literature on the potential role of water (in addition to food) as a positive reinforcer in the schedule-induced drinking situation, thus suggesting that adjunctive behaviors might have motivational properties that make their engagement a preferable alternative. It has also been suggested that adjunctive behaviors serve as a behavioral clock that helps organisms to estimate time, making their engagement motivational, so that they enable more accurate time adjustment under temporal schedules. Here, we review some of these experiments on conditioned reinforcement and concurrent chains, as well as on temporal learning. Data presented in this article suggest that adjunctive behaviors may be a part of the behavior patterns maintained by reinforcement, thus serving towards a better performance in temporal tasks. PMID:27036231

  15. Spontaneous rearrangement of aminoalkylisothioureas into mercaptoalkylguanidines, a novel class of nitric oxide synthase inhibitors with selectivity towards the inducible isoform.

    PubMed Central

    Southan, G. J.; Zingarelli, B.; O'Connor, M.; Salzman, A. L.; Szabó, C.

    1996-01-01

    NOS. 6. In contrast to their potent effects on iNOS, some AATUs and MAGs were 20-100 times weaker than NG-methyl-L-arginine and NG-nitro-L-arginine as inhibitors of ecNOS as assessed by their effects on the conversion of L-arginine to L-citrulline in homogenates of bovine endothelial cells and by their pressor effects in anaesthetized rats. Thus mercaptoalkylguanidines represent a new class of NOS inhibitors with preference towards iNOS. 7. AETU and mercaptoethylguanidine (MEG), when given as infusions, gave slight decreases in MAP in control rats. However, infusions of AETU or MEG to endotoxin-treated rats caused an increase in MAP and restored 80% of the endotoxin-induced fall in MAP. 8. High doses of MEG (30-60 mg kg-1) caused a decrease in MAP of normal rats. This depressor effect may be a consequence of the in vivo oxidation of MEG to the disulphide, guanidinoethyldisulphide (GED), which caused pronounced, transient hypotensive responses in anaesthetized rats and caused endothelium-independent vasodilator responses in precontracted rat aortic rings in vitro. 9. In some cases, slight differences were observed in the activities of AATUs and the corresponding MAGs. These may be explained by the formation of other species from AATUs in physiological media. For example, AETU can give rise to small amounts of the potent ecNOS inhibitor, 2-aminothiazoline, in addition to MEG. This may account for the differences in the in vitro and in vivo effects of AETU and MEG. 10. In conclusion, the in vitro and in vivo effects of AETU and related aminoalkylisothioureas can be explained in terms of their intramolecular rearrangement to generate mercaptoalkylguanidines, a novel class of selective inhibitors of iNOS. PMID:8646406

  16. Spontaneous rearrangement of aminoalkylisothioureas into mercaptoalkylguanidines, a novel class of nitric oxide synthase inhibitors with selectivity towards the inducible isoform.

    PubMed

    Southan, G J; Zingarelli, B; O'Connor, M; Salzman, A L; Szabó, C

    1996-02-01

    NOS. 6. In contrast to their potent effects on iNOS, some AATUs and MAGs were 20-100 times weaker than NG-methyl-L-arginine and NG-nitro-L-arginine as inhibitors of ecNOS as assessed by their effects on the conversion of L-arginine to L-citrulline in homogenates of bovine endothelial cells and by their pressor effects in anaesthetized rats. Thus mercaptoalkylguanidines represent a new class of NOS inhibitors with preference towards iNOS. 7. AETU and mercaptoethylguanidine (MEG), when given as infusions, gave slight decreases in MAP in control rats. However, infusions of AETU or MEG to endotoxin-treated rats caused an increase in MAP and restored 80% of the endotoxin-induced fall in MAP. 8. High doses of MEG (30-60 mg kg-1) caused a decrease in MAP of normal rats. This depressor effect may be a consequence of the in vivo oxidation of MEG to the disulphide, guanidinoethyldisulphide (GED), which caused pronounced, transient hypotensive responses in anaesthetized rats and caused endothelium-independent vasodilator responses in precontracted rat aortic rings in vitro. 9. In some cases, slight differences were observed in the activities of AATUs and the corresponding MAGs. These may be explained by the formation of other species from AATUs in physiological media. For example, AETU can give rise to small amounts of the potent ecNOS inhibitor, 2-aminothiazoline, in addition to MEG. This may account for the differences in the in vitro and in vivo effects of AETU and MEG. 10. In conclusion, the in vitro and in vivo effects of AETU and related aminoalkylisothioureas can be explained in terms of their intramolecular rearrangement to generate mercaptoalkylguanidines, a novel class of selective inhibitors of iNOS. PMID:8646406

  17. Selective activation of cholinergic basal forebrain neurons induces immediate sleep-wake transitions.

    PubMed

    Han, Yong; Shi, Yu-feng; Xi, Wang; Zhou, Rui; Tan, Zhi-bing; Wang, Hao; Li, Xiao-ming; Chen, Zhong; Feng, Guoping; Luo, Minmin; Huang, Zhi-li; Duan, Shumin; Yu, Yan-qin

    2014-03-17

    The basal forebrain (BF) plays a crucial role in cortical activation [1, 2]. However, the exact role of cholinergic BF (ch-BF) neurons in the sleep-wake cycle remains unclear [3, 4]. We demonstrated that photostimulation of ch-BF neurons genetically targeted with channelrhodopsin 2 (ChR2) was sufficient to induce an immediate transition to waking or rapid eye movement (REM) sleep from slow-wave sleep (SWS). Light stimulation was most likely to induce behavioral arousal during SWS, but not during REM sleep, a result in contrast to the previously reported photostimulation of noradrenergic or hypocretin neurons that induces wake transitions from both SWS and REM sleep. Furthermore, the ratio of light-induced transitions from SWS to wakefulness or to REM sleep did not significantly differ from that of natural transitions, suggesting that activation of ch-BF neurons facilitates the transition from SWS but does not change the direction of the transition. Excitation of ch-BF neurons during wakefulness or REM sleep sustained the cortical activation. Stimulation of these neurons for 1 hr induced a delayed increase in the duration of wakefulness in the subsequent inactive period. Our results suggest that activation of ch-BF neurons alone is sufficient to suppress SWS and promote wakefulness and REM sleep. PMID:24613308

  18. Time course study of microglial and behavioral alterations induced by 6-hydroxydopamine in rats.

    PubMed

    Silva, Thiago Pereira da; Poli, Anicleto; Hara, Daniela Balz; Takahashi, Reinaldo Naoto

    2016-05-27

    Understanding the mechanisms responsible for nonmotor manifestations of Parkinson's disease (PD) is crucial in the search for new therapeutic approaches. The aim of the present study was to evaluate the time course of behavioral, neurochemical, and microglial responses after a retrograde partial lesion of the nigrostriatal pathway induced by bilateral injection of 6-hydroxydopamine (6-OHDA). The results showed that 6-OHDA was able to produce both anhedonic and anxiety behaviors; however, an increase of microglial density in some brain areas (substantia nigra, hippocampus and striatum) and deficits in locomotor activity was observed only one week after the lesion. Striatal levels of dopamine (DA) and dihydroxyphenylacetic acid (DOPAC) were reduced by approximately 60% at all times tested. Conversely, increased levels of serotonin (5-HT) and its metabolite were also noted in the striatum only at the first week. These data extend our previous findings and suggest that the retrograde and partial damage of dopaminergic neurons in the substantia nigra can induce effects resembling premotor symptoms of PD, two and three weeks after injury. PMID:27113204

  19. Alteration patterns of trabecular bone microarchitectural characteristics induced by osteoarthritis over time

    PubMed Central

    Lee, Joo Hyung; Chun, Keyoung Jin; Kim, Han Sung; Kim, Sang Ho; Han, Paul; Jun, Yongtae; Lim, Dohyung

    2012-01-01

    Information regarding the alteration of trabecular bone microarchitecture, which is one of the important criteria to estimate bone condition, induced by osteoarthritis (OA) is sparse. The current study therefore aimed to identify and quantify patterns of alterations in trabecular bone microarchitectural characteristics at tibial epiphysis induced by OA using in vivo microcomputed tomography. Fourteen 8-week-old female Sprague Dawley rats were randomly divided into control (n = 7) and OA (n = 7) groups. Rats in the OA group were administered monoiodoacetate into the knee-joint cavity. The tibial joints were scanned by in vivo microcomputed tomography at 0, 4, and 8 weeks after administration. Two-way analysis of variance with Tukey’s honestly significant difference post hoc test was carried out for statistical analyses. The results showed that patterns of alterations in the trabecular bone microarchitectural characteristics in the OA group were not different from those in the control group from 0 to 4 weeks (P > 0.05), but differed from 4 to 8 weeks (P < 0.05). In particular, both trabecular bone thickness and trabecular bone separation distributions over time (4–8 weeks) differed significantly (P < 0.05). These findings suggest that the patterns of bone microarchitecture changes brought about by OA should be periodically considered in the diagnosis and management of arthritic symptoms over time. Improved understanding of the alteration pattern on trabecular bone microarchitecture may assist in developing more targeted treatment interventions for OA. PMID:22956865

  20. Tolazoline decreases survival time during microwave-induced lethal heat stress in anesthetized rats

    SciTech Connect

    Jauchem, J.R.; Chang, K.S.; Frei, M.R.

    1996-03-01

    Effects of {alpha}-adrenergic antagonists have been studied during environmental heating but not during microwave-induced heating. Tolazoline may exert some of its effects via {alpha}-adrenergic blockade. In the present study, ketamine-anesthetized Sprague-Dawley rats were exposed to 2450-MHz microwaves at an average power density of 60 mW/cm{sup 2} (whole-body specific absorption rate of approximately 14 W/kg) until lethal temperatures were attained. The effects of tolazoline (10 mg/kg body weight) on physiological responses (including changes in body temperature, heart rate, blood pressure, and respiratory rate) were examined. Survival time was significantly shorter in the tolazoline group than in saline-treated animals. In general, heart rate and blood pressure responses were similar to those that occur during environmental heat stress. Heart rate, however, was significantly elevated in animals that received tolazoline, both before and during terminal microwave exposure. It is possible that changes associated with the elevated heart rate (e.g., less cardiac filling) in tolazoline-treated animals resulted in greater susceptibility to microwave-induced heating and the lower survival time. 47 refs., 3 figs., 2 tabs.