14,934 research outputs found

    A virtual object-location task for children: Gender and videogame experience influence navigation; age impacts memory and completion time

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    The use of virtual reality-based tasks for studying memory has increased considerably. Most of the studies that have looked at child population factors that influence performance on such tasks have been focused on cognitive variables. However, little attention has been paid to the impact of non-cognitive skills. In the present paper, we tested 52 typically-developing children aged 5-12 years in a virtual object-location task. The task assessed their spatial short-term memory for the location of three objects in a virtual city. The virtual task environment was presented using a 3D application consisting of a 120" stereoscopic screen and a gamepad interface. Measures of learning and displacement indicators in the virtual environment, 3D perception, satisfaction, and usability were obtained. We assessed the children's videogame experience, their visuospatial span, their ability to build blocks, and emotional and behavioral outcomes. The results indicate that learning improved with age. Significant effects on the speed of navigation were found favoring boys and those more experienced with videogames. Visuospatial skills correlated mainly with ability to recall object positions, but the correlation was weak. Longer paths were related with higher scores of withdrawal behavior, attention problems, and a lower visuospatial span. Aggressiveness and experience with the device used for interaction were related with faster navigation. However, the correlations indicated only weak associations among these variables

    Dominant negative phenotype of Bacillus thuringiensis Cry1Ab, Cry11Aa and Cry4Ba mutants suggest hetero-oligomer formation among different Cry toxins.

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    Background - Bacillus thuringiensis Cry toxins are used worldwide in the control of different insect pests important in agriculture or in human health. The Cry proteins are pore-forming toxins that affect the midgut cell of target insects. It was shown that non-toxic Cry1Ab helix a-4 mutants had a dominant negative (DN) phenotype inhibiting the toxicity of wildtype Cry1Ab when used in equimolar or sub-stoichiometric ratios (1:1, 0.5:1, mutant:wt) indicating that oligomer formation is a key step in toxicity of Cry toxins. Methodology/Principal Findings - The DN Cry1Ab-D136N/T143D mutant that is able to block toxicity of Cry1Ab toxin, was used to analyze its capacity to block the activity against Manduca sexta larvae of other Cry1 toxins, such as Cry1Aa, Cry1Ac, Cry1Ca, Cry1Da, Cry1Ea and Cry1Fa. Cry1Ab-DN mutant inhibited toxicity of Cry1Aa, Cry1Ac and Cry1Fa. In addition, we isolated mutants in helix a-4 of Cry4Ba and Cry11Aa, and demonstrate that Cry4Ba-E159K and Cry11Aa-V142D are inactive and completely block the toxicity against Aedes aegypti of both wildtype toxins, when used at sub-stoichiometric ratios, confirming a DN phenotype. As controls we analyzed Cry1Ab-R99A or Cry11Aa-E97A mutants that are located in helix a-3 and are affected in toxin oligomerization. These mutants do not show a DN phenotype but were able to block toxicity when used in 10:1 or 100:1 ratios (mutant:wt) probably by competition of binding with toxin receptors. Conclusions/Significance - We show that DN phenotype can be observed among different Cry toxins suggesting that may interact in vivo forming hetero-oligomers. The DN phenotype cannot be observed in mutants affected in oligomerization, suggesting that this step is important to inhibit toxicity of other toxin

    Predicting Isoform-Selective Carbonic Anhydrase Inhibitors via Machine Learning and Rationalizing Structural Features Important for Selectivity

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    Carbonic anhydrases (CAs) catalyze the physiological hydration of carbon dioxide and are among the most intensely studied pharmaceutical target enzymes. A hallmark of CA inhibition is the complexation of the catalytic zinc cation in the active site. Human (h) CA isoforms belonging to different families are implicated in a wide range of diseases and of very high interest for therapeutic intervention. Given the conserved catalytic mechanisms and high similarity of many hCA isoforms, a major challenge for CA-based therapy is achieving inhibitor selectivity for hCA isoforms that are associated with specific pathologies over other widely distributed isoforms such as hCA I or hCA II that are of critical relevance for the integrity of many physiological processes. To address this challenge, we have attempted to predict compounds that are selective for isoform hCA IX, which is a tumor-associated protein and implicated in metastasis, over hCA II on the basis of a carefully curated data set of selective and nonselective inhibitors. Machine learning achieved surprisingly high accuracy in predicting hCA IX-selective inhibitors. The results were further investigated, and compound features determining successful predictions were identified. These features were then studied on the basis of X-ray structures of hCA isoform-inhibitor complexes and found to include substructures that explain compound selectivity. Our findings lend credence to selectivity predictions and indicate that the machine learning models derived herein have considerable potential to aid in the identification of new hCA IX-selective compounds

    Preparation of Dipteran Larvae for Scanning Electron Microscopy with Special Reference to Myiasigen Dipteran Species

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    Although controversy exists concerning the role of chemical fixatives in scanning electron microscopy (SEM) studies of Dipteran larvae, we have observed that filtered 10% formaldehyde solution gives excellent results as a preservative. After immersing in vivo in formaldehyde, the larvae material is preserved for prolonged periods (up to 8 months), before examination with SEM. As a fixative, formaldehyde preserves the structure of the larval cuticle and produces no visible artifacts. Moreover, postfixation is not necessary. Due to pecularities of the way of life of Wohlfahrtia magnifica (principally the accumulations of necrotic tissue, purulent particles, and other types of substances that often adhere to the numerous spines of larvae), this species must be cleaned before examination by SEM. Manual cleaning with alternating bidistilled water and 0.9% saline solution proved to be a rapid, easy and inexpensive method that gave good results. Both lyophilization drying and critical point drying were used before sputtering the material. While lyophilization drying proved to be the most effective method for instars II and III, critical point drying was the best technique for study of specimens belonging to instar I. The optimum time for drying and conditions for lyophilization and sputter-coating with gold were determined experimentally. Samples were mounted on SEM stubs with double-sided adhesive and silver conductive paint. The method proposed is easy and effective for the SEM study of larvae myiasis-producing diptera

    The effect of calcitriol, paricalcitol, and a calcimimetic on extraosseous calcifications in uremic rats

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    Vitamin D derivatives and calcimimetics are used to treat secondary hyperparathyroidism in patients with chronic renal failure. We investigated the effect of calcitriol, paricalcitol, and the calcimimetic AMG 641 on soft-tissue calcification in uremic rats with secondary hyperparathyroidism. Control and uremic rats were treated with vehicle, calcitriol, paricalcitol, AMG 641, or a combination of AMG 641 plus calcitriol or paricalcitol. Parathyroid hormone levels were reduced by all treatments but were better controlled by the combination of paricalcitol and AMG 641. The calcimimetic alone did not induce extraosseous calcification but co-administration of AMG 641 reduced soft-tissue calcification and aortic mineralization in both calcitriol- and paricalcitol-treated rats. Survival was significantly reduced in rats treated with calcitriol and this mortality was attenuated by co-treatment with AMG 641. Our study shows that extraskeletal calcification was present in animals treated with calcitriol and paricalcitol but not with AMG 641. When used in combination with paricalcitol, AMG 641 provided excellent control of secondary hyperparathyroidism and prevented mortality associated with the use of vitamin D derivatives without causing tissue calcification

    On the Reliability of Cross Correlation Function Lag Determinations in Active Galactic Nuclei

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    Many AGN exhibit a highly variable luminosity. Some AGN also show a pronounced time delay between variations seen in their optical continuum and in their emission lines. In effect, the emission lines are light echoes of the continuum. This light travel-time delay provides a characteristic radius of the region producing the emission lines. The cross correlation function (CCF) is the standard tool used to measure the time lag between the continuum and line variations. For the few well-sampled AGN, the lag ranges from 1-100 days, depending upon which line is used and the luminosity of the AGN. In the best sampled AGN, NGC 5548, the H_beta lag shows year-to-year changes, ranging from about 8.7 days to about 22.9 days over a span of 8 years. In this paper it is demonstrated that, in the context of AGN variability studies, the lag estimate using the CCF is biased too low and subject to a large variance. Thus the year-to-year changes of the measured lag in NGC 5548 do not necessarily imply changes in the AGN structure. The bias and large variance are consequences of finite duration sampling and the dominance of long timescale trends in the light curves, not due to noise or irregular sampling. Lag estimates can be substantially improved by removing low frequency power from the light curves prior to computing the CCF.Comment: To appear in the PASP, vol 111, 1999 Nov; 37 pages; 10 figure

    Science with an ngVLA: Resolving the Radio Complexity of EXor and FUor-type Systems with the ngVLA

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    Episodic accretion may be a common occurrence in the evolution of young pre-main sequence stars and has important implications for our understanding of star and planet formation. Many fundamental aspects of what drives the accretion physics, however, are still unknown. The ngVLA will be a key tool in understanding the nature of these events. The high spatial resolution, broad spectral coverage, and unprecedented sensitivity will allow for the detailed analysis of outburst systems. The proposed frequency range of the ngVLA allows for observations of the gas, dust, and non-thermal emission from the star and disk.Comment: 8 pages, 1 figure, To be published in the ASP Monograph Series, "Science with a Next-Generation VLA", ed. E. J. Murphy (ASP, San Francisco, CA

    Poly(styrene-co-vinylbenzylchloride-co-divinylbenzene) coated iron oxide: Synthesis and effects on size and morphology

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    Iron oxide nanoparticles were coated with a polymer synthesized from the monomers of styrene, divinylbenzene, and vinylbenzylchloride. The resultant polymer microspheres from synthesis without nanoparticle loading are primarily monodispersed with a diameter of 3.45 μm as measured by scanning electron microscopy. The addition of 1% nanoparticles by mass appears to decrease the size of the microspheres down to 2.04 μm as well as increase the polydispersity. This trend is also seen to continue as you add more nanoparticles to the system going from 3.45 μm with 0% nanoparticles down to below 1 μm for 5% nanoparticles. This indicates that the particles are not just incorporated into the polymer matrix but act as nucleation sites to begin the polymerization process. The polymerization process was found to have no effect on the nanoparticles themselves as the magnetic characterization showed only a mass dilution in saturation when corrected by thermal gravimetric analysis
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