479 research outputs found

    Integrated Intelligent training and job aiding for combustion turbine engines

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    This paper describes an ongoing program to augment such an expert system gas turbine startup advisor, known as the EPRI SA VANT System, by including an intelligent training package. It will give a brief background on the SA VANT development and an overview of its evolution into a full-blown Gas Turbine Information System (GTIS) for rapid access of on-line documentation, diagnostics, and training. In particular, the paper will address: (1) the conversion of the knowledge base used by the SA VANT startup advisor so that it can be used for both training and job aiding; and (2) the hypertext-oriented user manuals being incorporated into the system for rapidly accessing on-line documentation at the job site

    Obstacles to Success of Students with Autism Spectrum Disorder in General Education Settings

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    The purpose of this study was to survey teacher opinions of 14 potential obstacles to teaching in general education classes attended by students with autism spectrum disorder (ASD). The anonymous participant responses were received from 16 elementary school teachers, 60 middle school teachers, and 131 high school teachers. Participants completed a questionnaire in which they rated 14 items. Rating data were uploaded to STATA data analysis software. The Kruskal-Wallis (K-W) statistic was used to analyze and interpret the data. Results identified items that significantly discriminated among teachers of the three grade levels and show a difference in the perceptions of teachers at different grade levels for some obstacles. Teachers at the elementary school level generally perceived greater obstacles than teachers at the middle school level, who perceived greater obstacles than those at the high school level. The results can be considered by educators and service providers when identifying professional development topics and resources to assist educators and service providers in the provision of instruction to maximize the potential for academic and social success for students with ASD in general education settings

    Thermodynamic and Kinetic Analysis of Sensitivity Amplification in Biological Signal Transduction

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    Based on a thermodynamic analysis of the kinetic model for the protein phosphorylation-dephosphorylation cycle, we study the ATP (or GTP) energy utilization of this ubiquitous biological signal transduction process. It is shown that the free energy from hydrolysis inside cells, ΔG\Delta G (phosphorylation potential), controls the amplification and sensitivity of the switch-like cellular module; the response coefficient of the sensitivity amplification approaches the optimal 1 and the Hill coefficient increases with increasing ΔG\Delta G. We discover that zero-order ultrasensitivity is mathematically equivalent to allosteric cooperativity. Furthermore, we show that the high amplification in ultrasensitivity is mechanistically related to the proofreading kinetics for protein biosynthesis. Both utilize multiple kinetic cycles in time to gain temporal cooperativity, in contrast to allosteric cooperativity that utilizes multiple subunits in a protein.Comment: 19 pages, 7 figure

    Strategies to Promote Meaningful Student Engagement in Online Settings

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    Distance learning or online education has increased significantly over the past decade to coincide with easy access to technology and the availability of multifaceted learning management system software that can be used to develop asynchronous educational experiences (Ginder et al., 2018). The increased demand for online education, as well as unprecedented circumstances (Covid-19 Pandemic) that require quick changes to instructional delivery alternatives, have resulted in many traditional face-to-face programs transitioning into online and hybrid (e.g., part online and part face-to-face) programs across curriculum content areas to attract and retain full and part-time learners (DuPont et al., 2018). Effective online instruction must be engaging and meaningful/relevant. Course authors and instructors in higher education must incorporate strategies to maximize student engagement to develop high-quality learning experiences in online environments (Fallahi, 2019; Weidlich & Bastiaens, 2018). This article discusses the application of varied strategies and instructional practices to help instructors in post-secondary educational settings enhance the quality of teaching and social presence in the online learning environment. The strategies addressed are connected to the teachers’ ability to integrate multifaceted learning goals into instructional planning and delivery in order to create effective online learning environments that may improve outcomes for students across settings and content areas (Dixson, 2015; Henrie et al., 2015; Moore & Shemberger, 2019)

    Maladaptation and the paradox of robustness in evolution

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    Background. Organisms use a variety of mechanisms to protect themselves against perturbations. For example, repair mechanisms fix damage, feedback loops keep homeostatic systems at their setpoints, and biochemical filters distinguish signal from noise. Such buffering mechanisms are often discussed in terms of robustness, which may be measured by reduced sensitivity of performance to perturbations. Methodology/Principal Findings. I use a mathematical model to analyze the evolutionary dynamics of robustness in order to understand aspects of organismal design by natural selection. I focus on two characters: one character performs an adaptive task; the other character buffers the performance of the first character against perturbations. Increased perturbations favor enhanced buffering and robustness, which in turn decreases sensitivity and reduces the intensity of natural selection on the adaptive character. Reduced selective pressure on the adaptive character often leads to a less costly, lower performance trait. Conclusions/Significance. The paradox of robustness arises from evolutionary dynamics: enhanced robustness causes an evolutionary reduction in the adaptive performance of the target character, leading to a degree of maladaptation compared to what could be achieved by natural selection in the absence of robustness mechanisms. Over evolutionary time, buffering traits may become layered on top of each other, while the underlying adaptive traits become replaced by cheaper, lower performance components. The paradox of robustness has widespread implications for understanding organismal design

    Nathaniel Hawthorne's satire of Transcendentalism in "The Artist of the Beautiful"

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    The consensus among modern critics is that Nathaniel Hawthorne's story "The Artist of the Beautiful" is a type of parable that may be given various interpretations, all of which cast the artist as an admirable character opposed to forces that seek to destroy him. My thesis is that the artist is the object of Hawthorne's satire, and through him Hawthorne is retaliating against Emerson for articles in the Dial that can be read as deprecating Hawthorne. By nature sensitive and proud, Hawthorne adopted a defensive, ironical style while still a boy. Perhaps he derived the style from the speech and writings of his times, for it was popular among the masses as well as among the intellectuals. He retained and polished the style in his mature writings and sometimes used it as an outlet for resentment against those who offended him

    PCR-based generation of shRNA libraries from cDNAs

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    BACKGROUND: The use of small interfering RNAs (siRNAs) to silence target gene expression has greatly facilitated mammalian genetic analysis by generating loss-of-function mutants. In recent years, high-throughput, genome-wide screening of siRNA libraries has emerged as a viable approach. Two different methods have been used to generate short hairpin RNA (shRNA) libraries; one is to use chemically synthesized oligonucleotides, and the other is to convert complementary DNAs (cDNAs) into shRNA cassettes enzymatically. The high cost of chemical synthesis and the low efficiency of the enzymatic approach have hampered the widespread use of screening with shRNA libraries. RESULTS: We report here an improved method for constructing genome-wide shRNA libraries enzymatically. The method includes steps of cDNA fragmentation and endonuclease MmeI digestion to generate 19-bp fragments, capping the 19-bp cDNA fragments with a hairpin oligonucleotide, and amplification of the hairpin structures by PCR. The PCR step converts hairpins into double-stranded DNAs that contain head-to-head cDNA fragments that can be cloned into a vector downstream of a Pol III promoter. CONCLUSION: This method can readily be used to generate shRNA libraries from a small amount of mRNA and thus can be used to create cell- or tissue-specific libraries

    T-Cell activation: a queuing theory analysis at low agonist density

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    We analyze a simple linear triggering model of the T-cell receptor (TCR) within the framework of queuing theory, in which TCRs enter the queue upon full activation and exit by downregulation. We fit our model to four experimentally characterized threshold activation criteria and analyze their specificity and sensitivity: the initial calcium spike, cytotoxicity, immunological synapse formation, and cytokine secretion. Specificity characteristics improve as the time window for detection increases, saturating for time periods on the timescale of downregulation; thus, the calcium spike (30 s) has low specificity but a sensitivity to single-peptide MHC ligands, while the cytokine threshold (1 h) can distinguish ligands with a 30% variation in the complex lifetime. However, a robustness analysis shows that these properties are degraded when the queue parameters are subject to variation—for example, under stochasticity in the ligand number in the cell-cell interface and population variation in the cellular threshold. A time integration of the queue over a period of hours is shown to be able to control parameter noise efficiently for realistic parameter values when integrated over sufficiently long time periods (hours), the discrimination characteristics being determined by the TCR signal cascade kinetics (a kinetic proofreading scheme). Therefore, through a combination of thresholds and signal integration, a T cell can be responsive to low ligand density and specific to agonist quality. We suggest that multiple threshold mechanisms are employed to establish the conditions for efficient signal integration, i.e., coordinate the formation of a stable contact interface
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