279 research outputs found

    Tracking public attitudes toward ChatGPT on Twitter using sentiment analysis and topic modeling

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    ChatGPT sets a new record with the fastest-growing user base, as a chatbot powered by a large language model (LLM). While it demonstrates state-of-the-art capabilities in a variety of language-generating tasks, it also raises widespread public concerns regarding its societal impact. In this paper, we utilize natural language processing approaches to investigate the public attitudes towards ChatGPT by applying sentiment analysis and topic modeling techniques to Twitter data. Our result shows that the overall sentiment is largely neutral to positive, which also holds true across different occupation groups. Among a wide range of topics mentioned in tweets, the most popular topics are Artificial Intelligence, Search Engines, Education, Writing, and Question Answering

    Voltage-Gated Sodium Channel Nav1.6 S-Palmitoylation Regulates Channel Functions and Neuronal Excitability

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    Indiana University-Purdue University Indianapolis (IUPUI)The voltage-gated sodium channels (VGSCs) are critical determinants of neuronal excitability. They set the threshold for action potential generation. The VGSC isoform Nav1.6 participates in various physiological processes and contributes to distinct pathological conditions, but how Nav1.6 function is differentially regulated in different cell types and subcellular locations is not clearly understood. Some VGSC isoforms are subject to S-palmitoylation and exhibit altered functional properties in different S-palmitoylation states. This dissertation investigates the role of S-palmitoylation in Nav1.6 regulation and explores the consequences of S-palmitoylation in modulating neuronal excitability in physiological and pathological conditions. The aims of this dissertation were to 1) provide biochemical and electrophysiological evidence of Nav1.6 regulation by S-palmitoylation and identify specific S-palmitoylation sites in Nav1.6 that are important for excitability modulation, 2) determine the biophysical consequences of epilepsy-associated mutations in Nav1.6 and employ computational models for excitability prediction and 3) test the modulating effects of S-palmitoylation on aberrant Nav1.6 activity incurred by epilepsy mutations. To address these aims, an acyl-biotin exchange assay was used for Spalmitoylation detection and whole-cell electrophysiology was used for channel characterization and excitability examination. The results demonstrate that 1) Nav1.6 is biochemically modified and functionally regulated by S-palmitoylation in an isoform- and site-specific manner and altered S-palmitoylation status of the channel results in substantial changes of neuronal excitability, 2) epilepsy associated Nav1.6 mutations affect different aspects of channel function, but may all converge to gain-of-function alterations with enhanced resurgent currents and increased neuronal excitability and 3) S-palmitoylation can target specific Nav1.6 properties and could possibly be used to rescue abnormal channel function in diseased conditions. Overall, this dissertation reveals S-palmitoylation as a new mechanism for Nav1.6 regulation. This knowledge is critical for understanding the potential role of S-palmitoylation in isoform-specific regulation for VGSCs and providing potential targets for the modulation of excitability disorders.2022-05-0

    Distinct functional alterations in SCN8A epilepsy mutant channels

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    SCN8A is a novel causal gene for early infantile epileptic encephalopathy. It is well accepted that gain-of-function mutations in SCN8A underlie the disorder, but the remarkable heterogeneity of its clinical presentation and poor treatment response demand for better understanding of the disease mechanisms. Here, we characterize a new epilepsy-related SCN8A mutation, R850Q, in human Nav1.6. We show that it is a gain-of-function mutation, with a hyperpolarizing shift in voltage dependence of activation, a 2-fold increase of persistent current and a slowed decay of resurgent current. We systematically compare its biophysics with three other SCN8A epilepsy mutations, T767I, R1617Q and R1872Q, in the human Nav1.6 channel. Although all of these mutations are gain-of-function, the mutations affect different aspects of channel properties. One commonality we discovered is an alteration of resurgent current kinetics, but the mechanisms by which resurgent currents are augmented is not yet clear for all of the mutations. Computational simulations predict increased excitability of neurons carrying these mutations with differential enhancement by open channel block

    Thermal simulation modeling of a hydrostatic machine feed platform

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    Hydrostatic guideways are widely applied into precision and ultra-precision machine tools. Meanwhile, the oil film heat transfer causes thermal disturbance to the machine accuracy. Therefore, it is necessary to study the mechanism of the oil film heat transfer and the heat-transfer-reducing method to improve the machine accuracy. This paper describes a comprehensive thermal finite element (FE) simulation modeling method for the hydrostatic machine feed platform to study methods of reducing machine thermal errors. First of all, the generating heat power of viscous hydraulic oil flowing between parallel planes is calculated based on the Bernoulli equation. This calculation is then employed for the simulation load calculations for the closed hydrostatic guideways, which is adopted by the hydrostatic machine feed platform. Especially, in these load calculations, the changing of oil film thickness (resulted from external loads) and the changing of oil dynamic viscosity (influenced by its temperature) are taken into account. Based on these loads, thermal FE simulation modeling of the hydrostatic machine feed platform is completed to predict and analyze its thermal characteristics. The reliability of this simulation modeling method is verified by experiments. The studies demonstrate that the hydrostatic machine thermal error degree is determined by the oil film heat transfer scale, and this scale is mainly influenced by the relative oil supply temperature to ambient temperature (quantitative comparison of oil supply temperature and ambient temperature). Furthermore, the reduction of the absolute value of this relative oil supply temperature can reduce the oil film heat transfer scale and improve the machine accuracy

    Model-free adaptive iterative learning control of melt pool width in wire arc additive manufacturing

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    © 2020, Springer-Verlag London Ltd., part of Springer Nature. Wire arc additive manufacturing (WAAM) is a Direct Energy Deposition (DED) technology, which utilize electrical arc as heat source to deposit metal material bead by bead to make up the final component. However, issues like the lack of assurance in accuracy, repeatability and stability hinder the further application in industry. Therefore, a Model Free Adaptive Iterative Learning Control (MFAILC) algorithm was developed to be applied in WAAM process in this study. The dynamic process of WAAM is modelled by adaptive neuro fuzzy inference system (ANFIS). Based on this ANFIS model, simulations are performed to demonstrate the effectiveness of MFAILC algorithm. Furthermore, experiments are conducted to investigate the tracking performance and robustness of the MFAILC controller. This work will help to improve the forming accuracy and automatic level of WAAM

    Regression-based approach for testing the association between multi-region haplotype configuration and complex trait

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    <p>Abstract</p> <p>Background</p> <p>It is quite common that the genetic architecture of complex traits involves many genes and their interactions. Therefore, dealing with multiple unlinked genomic regions simultaneously is desirable.</p> <p>Results</p> <p>In this paper we develop a regression-based approach to assess the interactions of haplotypes that belong to different unlinked regions, and we use score statistics to test the null hypothesis of non-genetic association. Additionally, multiple marker combinations at each unlinked region are considered. The multiple tests are settled via the <it>minP </it>approach. The <it>P </it>value of the "best" multi-region multi-marker configuration is corrected via Monte-Carlo simulations. Through simulation studies, we assess the performance of the proposed approach and demonstrate its validity and power in testing for haplotype interaction association.</p> <p>Conclusion</p> <p>Our simulations showed that, for binary trait without covariates, our proposed methods prove to be equal and even more powerful than htr and hapcc which are part of the FAMHAP program. Additionally, our model can be applied to a wider variety of traits and allow adjustment for other covariates. To test the validity, our methods are applied to analyze the association between four unlinked candidate genes and pig meat quality.</p

    S-Palmitoylation of the sodium channel Nav1.6 regulates its activity and neuronal excitability

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    S-Palmitoylation is a reversible post-translational lipid modification that dynamically regulates protein functions. Voltage-gated sodium channels are subjected to S-palmitoylation and exhibit altered functions in different S-palmitoylation states. Our aim was to investigate whether and how S-palmitoylation regulates Nav1.6 channel function and to identify S-palmitoylation sites that can potentially be pharmacologically targeted. Acyl-biotin exchange assay showed that Nav1.6 is modified by S-palmitoylation in the mouse brain and in a Nav1.6 stable HEK 293 cell line. Using whole-cell voltage clamp, we discovered that enhancing S-palmitoylation with palmitic acid increases Nav1.6 current, whereas blocking S-palmitoylation with 2-bromopalmitate reduces Nav1.6 current and shifts the steady-state inactivation in the hyperpolarizing direction. Three S-palmitoylation sites (Cys1169, Cys1170, and Cys1978) were identified. These sites differentially modulate distinct Nav1.6 properties. Interestingly, Cys1978 is exclusive to Nav1.6 among all Nav isoforms and is evolutionally conserved in Nav1.6 among most species. Cys1978S-palmitoylation regulates current amplitude uniquely in Nav1.6. Furthermore, we showed that eliminating S-palmitoylation at specific sites alters Nav1.6-mediated excitability in dorsal root ganglion neurons. Therefore, our study reveals S-palmitoylation as a potential isoform-specific mechanism to modulate Nav activity and neuronal excitability in physiological and diseased conditions

    Strong Electronic Interaction of Amorphous Fe2O3 Nanosheets with Single‐Atom Pt toward Enhanced Carbon Monoxide Oxidation

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    Platinum‐based catalysts are critical to several chemical processes, but their efficiency is not satisfying enough in some cases, because only the surface active‐site atoms participate in the reaction. Henceforth, catalysts with single‐atom dispersions are highly desirable to maximize their mass efficiency, but fabricating these structures using a controllable method is still challenging. Most previous studies have focused on crystalline materials. However, amorphous materials may have enhanced performance due to their distorted and isotropic nature with numerous defects. Here reported is the facile synthesis of an atomically dispersed catalyst that consists of single Pt atoms and amorphous Fe2O3 nanosheets. Rational control can regulate the morphology from single atom clusters to sub‐nanoparticles. Density functional theory calculations show the synergistic effect resulted from the strong binding and stabilization of single Pt atoms with the strong metal‐support interaction between the in situ locally anchored Pt atoms and Fe2O3 lead to a weak CO adsorption. Moreover, the distorted amorphous Fe2O3 with O vacancies is beneficial for the activation of O2, which further facilitates CO oxidation on nearby Pt sites or interface sites between Pt and Fe2O3, resulting in the extremely high performance for CO oxidation of the atomic catalyst.An atomically Pt dispersed catalyst on amorphous Fe2O3 nanosheets is developed. The size effect of Pt and phase effect of support are explored. The synergistic effect results from the strong metal‐support interactions between the single Pt atoms and the amorphous Fe2O3 structure supports lead to an enhanced CO oxidation performance.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/151833/1/adfm201904278-sup-0001-S1.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151833/2/adfm201904278.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/151833/3/adfm201904278_am.pd
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