Nutrient-Driven O-GlcNAcylation at Promoters Impacts Genome-Wide RNA Pol II Distribution

Nutrient-driven O-GlcNAcylation has been linked to epigenetic regulation of gene expression in metazoans. In C. elegans, O-GlcNAc marks the promoters of over 800 developmental, metabolic, and stress-related genes; these O-GlcNAc marked genes show a strong 5′, promoter-proximal bias in the distribution of RNA Polymerase II (Pol II). In response to starvation or feeding, the steady state distribution of O-GlcNAc at promoters remain nearly constant presumably due to dynamic cycling mediated by the transferase OGT-1 and the O-GlcNAcase OGA-1. However, in viable mutants lacking either of these enzymes of O-GlcNAc metabolism, the nutrient-responsive GlcNAcylation of promoters is dramatically altered. Blocked O-GlcNAc cycling leads to a striking nutrient-dependent accumulation of O-GlcNAc on RNA Pol II. O-GlcNAc cycling mutants also show an exaggerated, nutrient-responsive redistribution of promoter-proximal RNA Pol II isoforms and extensive transcriptional deregulation. Our findings suggest a complex interplay between the O-GlcNAc modification at promoters, the kinase-dependent “CTD-code,” and co-factors regulating RNA Pol II dynamics. Nutrient-responsive O-GlcNAc cycling may buffer the transcriptional apparatus from dramatic swings in nutrient availability by modulating promoter activity to meet metabolic and developmental needs

Transformative Effects of ChatGPT on Modern Education: Emerging Era of AI Chatbots

ChatGPT, an AI-based chatbot, was released to provide coherent and useful replies based on analysis of large volumes of data. In this article, leading scientists, researchers and engineers discuss the transformative effects of ChatGPT on modern education. This research seeks to improve our knowledge of ChatGPT capabilities and its use in the education sector, identifying potential concerns and challenges. Our preliminary evaluation concludes that ChatGPT performed differently in each subject area including finance, coding and maths. While ChatGPT has the ability to help educators by creating instructional content, offering suggestions and acting as an online educator to learners by answering questions and promoting group work, there are clear drawbacks in its use, such as the possibility of producing inaccurate or false data and circumventing duplicate content (plagiarism) detectors where originality is essential. The often reported hallucinations within Generative AI in general, and also relevant for ChatGPT, can render its use of limited benefit where accuracy is essential. What ChatGPT lacks is a stochastic measure to help provide sincere and sensitive communication with its users. Academic regulations and evaluation practices used in educational institutions need to be updated, should ChatGPT be used as a tool in education. To address the transformative effects of ChatGPT on the learning environment, educating teachers and students alike about its capabilities and limitations will be crucial.Comment: Preprint submitted to IoTCPS Elsevier (2023

Modern computing: vision and challenges

Over the past six decades, the computing systems field has experienced significant transformations, profoundly impacting society with transformational developments, such as the Internet and the commodification of computing. Underpinned by technological advancements, computer systems, far from being static, have been continuously evolving and adapting to cover multifaceted societal niches. This has led to new paradigms such as cloud, fog, edge computing, and the Internet of Things (IoT), which offer fresh economic and creative opportunities. Nevertheless, this rapid change poses complex research challenges, especially in maximizing potential and enhancing functionality. As such, to maintain an economical level of performance that meets ever-tighter requirements, one must understand the drivers of new model emergence and expansion, and how contemporary challenges differ from past ones. To that end, this article investigates and assesses the factors influencing the evolution of computing systems, covering established systems and architectures as well as newer developments, such as serverless computing, quantum computing, and on-device AI on edge devices. Trends emerge when one traces technological trajectory, which includes the rapid obsolescence of frameworks due to business and technical constraints, a move towards specialized systems and models, and varying approaches to centralized and decentralized control. This comprehensive review of modern computing systems looks ahead to the future of research in the field, highlighting key challenges and emerging trends, and underscoring their importance in cost-effectively driving technological progress

Transformative effects of ChatGPT on modern education: emerging era of AI chatbots

ChatGPT, an AI-based chatbot, was released to provide coherent and useful replies based on analysis of large volumes of data. In this article, leading scientists, researchers and engineers discuss the transformative effects of ChatGPT on modern education. This research seeks to improve our knowledge of ChatGPT capabilities and its use in the education sector, identifying potential concerns and challenges. Our preliminary evaluation concludes that ChatGPT performed differently in each subject area including finance, coding and maths. While ChatGPT has the ability to help educators by creating instructional content, offering suggestions and acting as an online educator to learners by answering questions, transforming education through smartphones and IoT gadgets, and promoting group work, there are clear drawbacks in its use, such as the possibility of producing inaccurate or false data and circumventing duplicate content (plagiarism) detectors where originality is essential. The often reported “hallucinations” within GenerativeAI in general, and also relevant for ChatGPT, can render its use of limited benefit where accuracy is essential. What ChatGPT lacks is a stochastic measure to help provide sincere and sensitive communication with its users. Academic regulations and evaluation practices used in educational institutions need to be updated, should ChatGPT be used as a tool in education. To address the transformative effects of ChatGPT on the learning environment, educating teachers and students alike about its capabilities and limitations will be crucial

HLA-DQA1*05 carriage associated with development of anti-drug antibodies to infliximab and adalimumab in patients with Crohn's Disease

Anti-tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce the formation of anti-drug antibodies. The ability to identify patients at increased risk for development of anti-drug antibodies would facilitate selection of therapy and use of preventative strategies.This article is freely available via Open Access. Click on Publisher URL to access the full-text

Measurement of dielectric properties of medium loss samples at X-band frequencies

This work describes and evaluates a technique for determining dielectric properties, and presents results of dielectric measurement of some substances. Dielectric properties of some known dielectric materials are first measured and verified with our technique and then applied to conducting polymer materials. A non-destructive method based on the shift in resonance frequency and quality factor measurement of a resonant cavity placing a small-sized sample is used. Dielectric constant and loss factor measurement is performed with the aid of Spectrum Analyzer in the frequency range from 8GHZ to 12GHz. 3-D EM simulation studies using HFSS 11 software of the cavity with loading is compared with the measurement. The results indicated that using the resonant cavity with the technique is suitable for dielectric parameter measurement for small shaped medium loss samples having thickness in the range 4-6mm at X-Band frequencies

A potential role for nuclear factor of activated T-cells in receptor tyrosine kinase and G-protein-coupled receptor agonist-induced cell proliferation.

We have studied the role of nuclear factor of activated T-cells (NFAT) transcription factors in the induction of vascular smooth muscle cell (VSMC) growth by platelet-derived growth factor-BB (PDGF-BB) and thrombin, the receptor tyrosine kinase (RTK) and G-protein-coupled receptor (GPCR) agonists, respectively. NFATc1 but not NFATc2 or NFATc3 was translocated from the cytoplasm to the nucleus upon treatment of VSMCs with PDGF-BB or thrombin. Translocation of NFATc1 was followed by an increase in NFAT-DNA binding activity and NFAT-dependent reporter gene expression. Cyclosporin A (CsA), a potent and specific inhibitor of calcineurin, a calcium/calmodulin-dependent serine phosphatase involved in the dephosphorylation and activation of NFATs, blocked NFAT-DNA binding activity and NFAT-dependent reporter gene expression induced by PDGF-BB and thrombin. CsA also completely inhibited PDGF-BB- and thrombin-induced VSMC growth, as measured by DNA synthesis and cell number. In addition, forced expression of the NFAT-competing peptide VIVIT for calcineurin binding significantly attenuated the DNA synthesis induced by PDGF-BB and thrombin in VSMCs. Together, these findings for the first time demonstrate a role for NFATs in RTK and GPCR agonist-induced growth in VSMCs