379 research outputs found

    A Theoretical Study of One- and Two-Photon Activity of D-Luciferin

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    In the present work, we have theoretically studied the one and two-photon absorption (OPA and TPA) probabilities of the native D-luciferin molecule and attempted to find the origin of its larger TPA cross-sections in polar solvents than in non-polar ones. The calculations using state-of-the-art linear and quadratic response theory in the framework of time-dependent density functional theory using hybrid B3LYP functional and cc-pVDZ basis set suggests that two-photon transition probability of this molecule increases with increasing solvent polarity. In order to explicate our present findings, we employed the generalized few-state-model and inspected the role of different optical channels related to the TPA process. We have found that the two-photon transition probability is always guided by a destructive interference term, the magnitude of which decreases with increasing solvent polarity. Furthermore, we have evaluated OPA parameters of D-luciferin and noticed that the the excitation energy is in very good agreement with the available experimental results

    Neural cell adhesion molecule-mediated fyn activation promotes GABAergic synapse maturation in postnatal mouse cortex

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    GABAergic basket interneurons form perisomatic synapses, which are essential for regulating neural networks, and their alterations are linked to various cognitive dysfunction. Maturation of basket synapses in postnatal cortex is activity dependent. In particular, activity-dependent downregulation of polysialiac acid carried by the neural cell adhesion molecule (NCAM) regulates the timing of their maturation. Whether and how NCAM per se affects GABAergic synapse development is unknown. Using single-cell genetics to knock out NCAM in individual basket interneurons in mouse cortical slice cultures, at specific developmental time periods, we found that NCAM loss during perisomatic synapse formation impairs the process of basket cell axonal branching and bouton formation. However, loss of NCAM once the synapses are already formed did not show any effect. We further show that NCAM120 and NCAM140, but not the NCAM180 isoform, rescue the phenotype. Finally, we demonstrate that a dominant-negative form of Fyn kinase mimics, whereas a constitutively active form of Fyn kinase rescues, the effects of NCAM knockdown. Altogether, our data suggest that NCAM120/NCAM140-mediated Fyn activation promotes GABAergic synapse maturation in postnatal cortex

    Joining of carbon fibre reinforced polymer (CFRP) composites and aluminium alloys – A review

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    This paper investigates comprehensive knowledge regarding joining CFRP and aluminium alloys in available literature in terms of available methods, bonding processing and mechanism and properties. The methods employed comprise the use of adhesive, self-piercing rivet, bolt, clinching and welding to join only CFRP and aluminium alloys. The non-thermal joining methods received great attention though the welding process has high potential in joining these materials. Except adhesive bonding and welding, other joining methods require the penetration of metallic pins through joining parts and therefore, surface preparation is unimportant. No model is found to predict the properties of jointed structures, which makes it difficult to select one over another in applications. The choice of bonding methods depends primarily on the specific applications. The load-bearing mechanism of bolted joints is predominantly the friction that is the first stage resistance. Hybrid joints performance is enhanced by combining rivets, clinch or bolts with adhesives

    Strengthening Effect after Disintegration of Stainless Steel Using Pulsating Water Jet

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    The article deals with the measurement of micro-hardness of the track by the action of ultrasonic excitation of pulsating water jet. The cumulative effect of liquid matter in the form of droplets concentrated in waveform measurements was provided in horizontal and vertical direction to material core (AISI 304). The material was subjected to pressures of p = 40, 50 and 60 MPa with the actuator working at a frequency of 20,14 kHz and traverse speed v = 1,1 mm/s, v = 0,80 mm/s and v = 0,30 mm/s respectively. The micro hardness measurement was carried out after machining it by pulsating water jet. The values were recorded in the zone located transversally under the trace to the depth of 1,5 mm with 0,1 mm distance between successive points. It was found that the deformation of material was ascertained from the boundary to the outer environment created by pulsating water jet to the inner core of the material. The results indicate that the pressure was the most influential parameter, which was responsible for the deformation strengthening of the material

    A screen of chemical modifications identifies position-specific modification by UNA to most potently reduce siRNA off-target effects

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    Small interfering RNAs (siRNAs) are now established as the preferred tool to inhibit gene function in mammalian cells yet trigger unintended gene silencing due to their inherent miRNA-like behavior. Such off-target effects are primarily mediated by the sequence-specific interaction between the siRNA seed regions (position 2–8 of either siRNA strand counting from the 5′-end) and complementary sequences in the 3′UTR of (off-) targets. It was previously shown that chemical modification of siRNAs can reduce off-targeting but only very few modifications have been tested leaving more to be identified. Here we developed a luciferase reporter-based assay suitable to monitor siRNA off-targeting in a high throughput manner using stable cell lines. We investigated the impact of chemically modifying single nucleotide positions within the siRNA seed on siRNA function and off-targeting using 10 different types of chemical modifications, three different target sequences and three siRNA concentrations. We found several differently modified siRNAs to exercise reduced off-targeting yet incorporation of the strongly destabilizing unlocked nucleic acid (UNA) modification into position 7 of the siRNA most potently reduced off-targeting for all tested sequences. Notably, such position-specific destabilization of siRNA–target interactions did not significantly reduce siRNA potency and is therefore well suited for future siRNA designs especially for applications in vivo where siRNA concentrations, expectedly, will be low

    Characterization of Friction Surfaced Coatings of AISI 316 Tool over High-Speed-Steel Substrate

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    Nowadays friction surfacing (FS) has become a popular solid state surface coating technology suitable for a range of substrates. The technology has the ability to produce coatings with marginal dilution and good metallurgical bonding. The present study has aimed at producing a single-track and a three-track overlapping coatings on high-speed steel substrates using an AISI 316 consumable rod. Microhardness of coatings was examined by a Vickers micro hardness tester. Coatings of all the friction surfaced samples in as-deposited condition showed significant hardness. The infrared thermography showed that the peak temperature achieved by the AISI 316 coating was about 1020 ͦ C. The coatings, thus attained, were further analysed for their microstructural features and interfacial characteristics by using FE-SEM. The EDX analysis showed the presence of nickel, chromium and oxygen, which indicates the formation of oxide compounds. The formation of AISI 316 deposits on the HSS substrate and the effect of coating overlapping are discussed in this article

    A Dynamic Model of Interactions of Ca^(2+), Calmodulin, and Catalytic Subunits of Ca^(2+)/Calmodulin-Dependent Protein Kinase II

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    During the acquisition of memories, influx of Ca^(2+) into the postsynaptic spine through the pores of activated N-methyl-D-aspartate-type glutamate receptors triggers processes that change the strength of excitatory synapses. The pattern of Ca^(2+) influx during the first few seconds of activity is interpreted within the Ca^(2+)-dependent signaling network such that synaptic strength is eventually either potentiated or depressed. Many of the critical signaling enzymes that control synaptic plasticity, including Ca^(2+)/calmodulin-dependent protein kinase II (CaMKII), are regulated by calmodulin, a small protein that can bind up to 4 Ca^(2+) ions. As a first step toward clarifying how the Ca^(2+)-signaling network decides between potentiation or depression, we have created a kinetic model of the interactions of Ca^(2+), calmodulin, and CaMKII that represents our best understanding of the dynamics of these interactions under conditions that resemble those in a postsynaptic spine. We constrained parameters of the model from data in the literature, or from our own measurements, and then predicted time courses of activation and autophosphorylation of CaMKII under a variety of conditions. Simulations showed that species of calmodulin with fewer than four bound Ca^(2+) play a significant role in activation of CaMKII in the physiological regime, supporting the notion that processing ofCa^(2+) signals in a spine involves competition among target enzymes for binding to unsaturated species of CaM in an environment in which the concentration of Ca^(2+) is fluctuating rapidly. Indeed, we showed that dependence of activation on the frequency of Ca^(2+) transients arises from the kinetics of interaction of fluctuating Ca^(2+) with calmodulin/CaMKII complexes. We used parameter sensitivity analysis to identify which parameters will be most beneficial to measure more carefully to improve the accuracy of predictions. This model provides a quantitative base from which to build more complex dynamic models of postsynaptic signal transduction during learning

    Desynchronization of Neocortical Networks by Asynchronous Release of GABA at Autaptic and Synaptic Contacts from Fast-Spiking Interneurons

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    An activity-dependent long-lasting asynchronous release of GABA from identified fast-spiking inhibitory neurons in the neocortex can impair the reliability and temporal precision of activity in a cortical network
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