Growing evidence indicates that glia pathology and amino-acid neurotransmitter system abnormalities contribute to the pathophysiology and possibly the pathogenesis of major depressive disorder. This ...study investigates changes in glial function occurring in the rat prefrontal cortex (PFC) after chronic unpredictable stress (CUS), a rodent model of depression. Furthermore, we analyzed the effects of riluzole, a Food and Drug Administration-approved drug for the treatment of amyotrophic laterosclerosis, known to modulate glutamate release and facilate glutamate uptake, on CUS-induced glial dysfunction and depressive-like behaviors. We provide the first experimental evidence that chronic stress impairs cortical glial function. Animals exposed to CUS and showing behavioral deficits in sucrose preference and active avoidance exhibited significant decreases in 13C-acetate metabolism reflecting glial cell metabolism, and glial fibrillary associated protein (GFAP) mRNA expression in the PFC. The cellular, metabolic and behavioral alterations induced by CUS were reversed and/or blocked by chronic treatment with the glutamate-modulating drug riluzole. The beneficial effects of riluzole on CUS-induced anhedonia and helplessness demonstrate the antidepressant action of riluzole in rodents. Riluzole treatment also reversed CUS-induced reductions in glial metabolism and GFAP mRNA expression. Our results are consistent with recent open-label clinical trials showing the drug's effect in mood and anxiety disorders. This study provides further validation of hypothesis that glial dysfunction and disrupted amino-acid neurotransmission contribute to the pathophysiology of depression and that modulation of glutamate metabolism, uptake and/or release represent viable targets for antidepressant drug development.
Electromyography (EMG) signals are becoming increasingly important in many applications, including clinical/biomedical, prosthesis or rehabilitation devices, human machine interactions, and more. ...However, noisy EMG signals are the major hurdles to be overcome in order to achieve improved performance in the above applications. Detection, processing and classification analysis in electromyography (EMG) is very desirable because it allows a more standardized and precise evaluation of the neurophysiological, rehabitational and assistive technological findings. This paper reviews two prominent areas; first: the pre-processing method for eliminating possible artifacts via appropriate preparation at the time of recording EMG signals, and second: a brief explanation of the different methods for processing and classifying EMG signals. This study then compares the numerous methods of analyzing EMG signals, in terms of their performance. The crux of this paper is to review the most recent developments and research studies related to the issues mentioned above.
Information users and usability constitute the main building blocks of today's electronic information world. This important new text is the first to give a holistic overview of all of the necessary ...issues relating to information users and the usability of information services in the digital world, including user-centred design, and the characteristics and behaviour of information users. This book helps readers understand why information users and the usability of information services are important and equips them to play a proper role in designing user-centred information systems and services and to properly exploit information services for the maximum benefit of users. It covers all of the major issues, the current situation and what the various research studies from around the world show. It includes chapters, covering: information users; human information behaviour; usability of information systems and services; usability: internet and web information services; usability: digital libraries and information services; barriers to information access and usability; the digital divide and social inclusion; the digital divide and usability of digital information services: the global perspectives; and, current issues and trends. It is an essential reading for researchers and practitioners interested in the design and evaluation of digital information systems and services, as well as for students on library, information, and digital library courses.
Several drugs have recently been reported to induce rapid antidepressant effects in clinical trials and rodent models. Although the cellular mechanisms involved remain unclear, reports suggest that ...increased glutamate transmission contributes to these effects. Here, we demonstrate that the antidepressant-like efficacy of three unique drugs, with reported rapid onset antidepressant properties, is coupled with a rapid transient rise in glutamate cycling in the medial prefronal cortex (mPFC) of awake rats as measured by ex vivo
H-
C-nuclear magnetic resonance spectroscopy. Rats were acutely pretreated by intraperitoneal injection with a single dose of ketamine (1, 3, 10, 30 and 80 mg kg
), Ro 25-6981 (1, 3 and 10 mg kg
), scopolamine (5, 25 and 100 μg kg
) or vehicle (controls). At fixed times after drug injection, animals received an intravenous infusion of 1,6-
C
glucose for 8 min to enrich the amino-acid pools of the brain with
C, followed by rapid euthanasia. The mPFC was dissected, extracted with ethanol and metabolite
C enrichments were measured. We found a clear dose-dependent effect of ketamine and Ro 25-6981 on behavior and the percentage of
C enrichment of glutamate, glutamine and GABA (γ-aminobutyric acid). Further, we also found an effect of scopolamine on both cycling and behavior. These studies demonstrate that three pharmacologically distinct classes of drugs, clinically related through their reported rapid antidepressant actions, share the common ability to rapidly stimulate glutamate cycling at doses pertinent for their antidepressant-like efficacy. We conclude that increased cycling precedes the antidepressant action at behaviorally effective doses and suggest that the rapid change in cycling could be used to predict efficacy of novel agents or identify doses with antidepressant activity.
In the machining of Ti alloys, it is challenging to optimise the cutting tool life and process productivity. It is not a trivial task to find an efficient strategy to improve the tool life during ...machining of Ti alloys using surface engineered tooling. In the case of rough turning operation with strong built up edge formation we establish that it can be achieved through the application of self-lubricating TiB2 PVD coating. It has been shown that the application of a TiB2 coating results in tool life improvement by over 60% compared to the uncoated tool and over 70% compared to the TiAlN coated tool. Comprehensive characterization of the coated vs. uncoated cutting tool wear performance was performed using optical 3D imaging, SEM/EDX and XPS methods. Various micro-mechanical characteristics of the TiB2 coating were evaluated. It was determined that tool life improvement using the TiB2 coating is mostly related to the ability of the coating layer to provide self-lubrication effect and in this way, very efficiently dissipate frictional energy. The coating also exhibited less substrate exposure as it fails indicating better protection of the coated tool surface. This is of particular importance for machining of materials like Ti, which have strong sticking intensity. It has been demonstrated that the TiB2 coating combines beneficial micro-mechanical characteristics and self-lubricating properties due to the formation of B-O tribo-films on the tool surface under operation. These tribo-films serve as a liquid lubricant formed in-situ on the tool surface under the elevated temperature of cutting. The formation of liquid tribo-films is an effective way to address intensive adhesive interaction followed by built up edge formation at the tool/chip interface, which is typical for roughing operations during Ti machining.
•TiB2 coating improves tool life during rough turning of Ti alloy with intensive buildup edge formation•This is mostly related to self-lubrication effect and better surface protection•Comprehensive characterization of TiB2 coating was performed•Generation of B-Ox tribo-films which are liquid at high temperatures of cutting minimises adhesive interaction at the tool/chip interface
Animals readily execute learned behaviors in a consistent manner over long periods of time, and yet no equally stable neural correlate has been demonstrated. How does the cortex achieve this stable ...control? Using the sensorimotor system as a model of cortical processing, we investigated the hypothesis that the dynamics of neural latent activity, which captures the dominant co-variation patterns within the neural population, must be preserved across time. We recorded from populations of neurons in premotor, primary motor and somatosensory cortices as monkeys performed a reaching task, for up to 2 years. Intriguingly, despite a steady turnover in the recorded neurons, the low-dimensional latent dynamics remained stable. The stability allowed reliable decoding of behavioral features for the entire timespan, while fixed decoders based directly on the recorded neural activity degraded substantially. We posit that stable latent cortical dynamics within the manifold are the fundamental building blocks underlying consistent behavioral execution.
Previous ¹³C magnetic resonance spectroscopy experiments have shown that over a wide range of neuronal activity, approximately one molecule of glucose is oxidized for every molecule of glutamate ...released by neurons and recycled through astrocytic glutamine. The measured kinetics were shown to agree with the stoichiometry of a hypothetical astrocyte-to-neuron lactate shuttle model, which predicted negligible functional neuronal uptake of glucose. To test this model, we measured the uptake and phosphorylation of glucose in nerve terminals isolated from rats infused with the glucose analog, 2-fluoro-2-deoxy- d -glucose (FDG) in vivo. The concentrations of phosphorylated FDG (FDG ₆P), normalized with respect to known neuronal metabolites, were compared in nerve terminals, homogenate, and cortex of anesthetized rats with and without bicuculline-induced seizures. The increase in FDG ₆P in nerve terminals agreed well with the increase in cortical neuronal glucose oxidation measured previously under the same conditions in vivo , indicating that direct uptake and oxidation of glucose in nerve terminals is substantial under resting and activated conditions. These results suggest that neuronal glucose-derived pyruvate is the major oxidative fuel for activated neurons, not lactate-derived from astrocytes, contradicting predictions of the original astrocyte-to-neuron lactate shuttle model under the range of study conditions.
Graphene oxide (GO) is promising in scalable production and has useful properties that include semiconducting behavior, catalytic reactivity, and aqueous dispersibility. In this study, we ...investigated the photochemical fate of GO under environmentally relevant sunlight conditions. The results indicate that GO readily photoreacts under simulated sunlight with the potential involvement of electron–hole pair creation. GO was shown to photodisproportionate to CO2, reduced materials similar to reduced GO (rGO) that are fragmented compared to the starting material, and low molecular-weight (LMW) species. Kinetic studies show that the rate of the initially rapid photoreaction of GO is insensitive to the dissolved oxygen content. In contrast, at longer time points (>10 h), the presence of dissolved oxygen led to a greater production of CO2 than the same GO material under N2-saturated conditions. Regardless, the rGO species themselves persist after extended irradiation equivalent to 2 months in natural sunlight, even in the presence of dissolved oxygen. Overall, our findings indicate that GO phototransforms rapidly under sunlight exposure, resulting in chemically reduced and persistent photoproducts that are likely to exhibit transport and toxic properties unique from parent GO.
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