159 research outputs found

    Metabolism Of Queuosine, A Modified Nucleoside, In Escherichia Coli And Caenorhabditis Elegans And Dual Function Of Bovine Mitochondrial Initiation Factor 2 As Initiation Factors 1 And 2 In Escherichia Coli

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    The studies reported in this thesis address firstly, the biology of a modified nucleoside, Queuosine (Q) and secondly, the properties of mitochondrial translation initiation factor 2. A summary of the relevant literature on both these topics is presented in Chapter 1. Section I of this ‘General Introduction’ summarizes the literature on biosynthesis and physiological importance of Queuosine. Section II is a brief review of the current understanding of translation initiation in Eubacteria. Information about the mitochondrial translation initiation apparatus also features as a subsection. The next chapter (Chapter 2), describes the ‘Materials and Methods’ used throughout the experimental work presented in the thesis. It is followed by three chapters containing experimental work as described below:- i) Biosynthesis of Queuosine (Q) in Escherichia coli Q is a hypermodification of guanosine found at the wobble position of tRNAs with GUN anticodons. Q is thought to be produced via a complex multistep pathway, the details of which are not known. It was found in our laboratory that a naturally occurring strain of E. coli B105 lacked Q modification in the tRNAs. As the known enzymes of Q biosynthesis were functional in this strain, it presented us with the opportunity to uncover novel component(s) of Q biosynthetic pathway. In the present work, a genetic screen was developed to map the defect in E. coli B105 to a previously uncharacterised gene, ybaX, predicted to code for a 231 amino acid long protein with a pI of 5.6. Further genetic analyses showed that YbaX functions at a step leading to production of preQ0, the first known intermediate in the generally accepted pathway that utilizes GTP as the starting molecule. The gene ybaX has been renamed as queC. Using a combination of bioinformatics based prediction and gene knockouts, we have also been able to place two more genes, queD and queE at the initial step in Q biosynthesis, suggesting that the initial reaction of Q biosynthesis might be more complex and mechanistically different than what has been proposed earlier. ii) Caenorhabditis elegans as a Model System to Study Queuosine Metabolism in Metazoa Animals are thought to obtain Q (or its analogs) as a micronutrient from dietary sources such as gut microflora, and the corresponding base is then inserted in the substrate tRNAs by tRNA guanine transglycosylase (TGT). In animal cells, changes in the abundance of Q have been shown to correlate with diverse phenomena including stress tolerance, cell proliferation and tumor growth but the precise function of Q in animal tRNAs remains unknown. A major obstacle in the study of Q metabolism in higher organisms has been the requirement of a chemically defined medium to cause Q depletion in animals. Having discovered that E. coli B105 has a block in the initial step of Q biosynthesis, we reasoned that this strain could be used as a Q- diet for organisms like C. elegans, which naturally feed on bacteria. An analysis of C. elegans tRNA revealed that as in the other higher animals, tRNAs in the worm C. elegans, are modified by Q and its sugar derivatives. When the worms were fed on Q deficient E. coli B105, Q modification was absent from the worm tRNAs suggesting that C. elegans lacks a de novo pathway of Q biosynthesis. The inherent advantages of C. elegans as a model organism, the speed and simplicity of conferring a Q deficient phenotype on it, make it an ideal system to investigate the function of Q modification in tRNA. By microinjecting tgt-1-gfp constructs into C. elegans, we could also demonstrate that a major form of TGT is localised to the nucleus, suggesting that insertion of Q into the tRNAs could be occurring in the nucleus. iii) Dual Function of Bovine Mitochondrial Initiation Factor 2 as Initiation Factors 1 and 2 in Escherichia coli Translation initiation factors 1 and 2 (IF1 and IF2) are known as ‘universal translation initiation factors’ due to the presence of their homologs in all living organisms. Homologs of these factors are also present in the chloroplast, however, a unique situation exists in the mitochondria where IF2 homolog (IF2mt) is known to occur but an IF1 like factor is not found. We have engineered a system of E. coli knockouts to allow the study of IF2mt in a prokaryotic milieu. We found that the bovine IF2mt complements an E. coli strain wherein the gene for IF2 is knocked out, providing the first proof of a mitochondrial translation initiation factor working in a eubacterial system. This conservation of function is especially interesting in light of the recent reports revealing significant differences between the mitochondrial and eubacterial ribosomes. Further, we found that the IF2mt can also support a double knockout of IF1 and IF2 genes in E. coli, suggesting that IF2mt possesses both IF1 and IF2 like activities in E. coli. This finding offers an explanation for the lack of an IF1 like factor in mitochondria. Molecular modeling of bovine IF2mt indicated that a conserved insertion found in all mitochondrial IF2s, may form a protruding α-helix that could stabilize IF2mt on ribosomes. This insertion could in principle function as IF1 and we have explored the role of this conserved insertion both in vivo and in vitro, by generating mutants of IF2mt and EcoIF2, to lose or gain the conserved insertion respectively

    Cyberbullying And Cyberstalking: Their Influence on The Social and Emotional Development of Teenagers in India

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    The advent of the internet and digital communication has revolutionized the way teenagers interact, learn, and express themselves. However, along with the benefits of technology, there come significant challenges, particularly in the form of cyberbullying and cyberstalking. These online threats have a profound influence on the social and emotional development of teenagers in India, affecting their well-being, relationships, and overall growth. This comprehensive article explores the prevalence, types, and consequences of cyberbullying and cyberstalking in the Indian context. Drawing from existing research, case studies, and interviews, it highlights the need for effective preventive measures and intervention strategies to protect adolescents\u27 mental health and development in the digital age. Sometimes, in today\u27s modern society, we lose touch with our roots because we\u27re too focused on showing off. We also don\u27t always know how someone will react, especially when they spend a lot of time online. In India, there aren\u27t any specific laws that directly address cyberbullying and cyberstalking, leaving victims without proper protection

    On the optimality of likelihood ratio test for prospect theory-based binary hypothesis testing

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    In this letter, the optimality of the likelihood ratio test (LRT) is investigated for binary hypothesis testing problems in the presence of a behavioral decision-maker. By utilizing prospect theory, a behavioral decision-maker is modeled to cognitively distort probabilities and costs based on some weight and value functions, respectively. It is proved that the LRT may or may not be an optimal decision rule for prospect theory-based binary hypothesis testing, and conditions are derived to specify different scenarios. In addition, it is shown that when the LRT is an optimal decision rule, it corresponds to a randomized decision rule in some cases; i.e., nonrandomized LRTs may not be optimal. This is unlike Bayesian binary hypothesis testing, in which the optimal decision rule can always be expressed in the form of a nonrandomized LRT. Finally, it is proved that the optimal decision rule for prospect theory-based binary hypothesis testing can always be represented by a decision rule that randomizes at most two LRTs. Two examples are presented to corroborate the theoretical results.Manuscript received August 13, 2018; revised October 5, 2018; accepted October 16, 2018. Date of publication October 22, 2018; date of current version November 5, 2018. The work of P. K. Varshney was supported by Air Force Office of Scientific Research under Grant FA9550-17-1-0313 under the DDDAS program. The associate editor coordinating the review of this manuscript and approving it for publication was Dr. Ashish Pandharipande. (Corresponding author: Sinan Gezici.) S. Gezici is with the Department of Electrical and Electronics Engineering, Bilkent University, Ankara 06800, Turkey (e-mail:,[email protected])

    State Estimation of Linear Systems With Sparse Inputs and Markov-Modulated Missing Outputs

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    In this paper, we consider the problem of estimating the states of a linear dynamical system whose inputs are jointly sparse and outputs at a few unknown time instants are missing. We model the missing data mechanism using a Markov chain with two states representing the missing and non-missing data. This mechanism with memory governed by the Markov chain models intermittent outages due to communication channels and occlusions corresponding to moving objects. We rely on the sparse Bayesian learning framework to derive an estimation algorithm that uses Kalman smoothing to handle temporal correlation and the Viterbi algorithm to handle missing data. Further, we demonstrate the utility of our algorithm by applying it to the frequency division duplexed multiple input multiple output downlink channel estimation problem.Green Open Access added to TU Delft Institutional Repository ‘You share, we take care!’ – Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Signal Processing System

    Problems in Task Scheduling in Multiprocessor System

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    This Contemporary computer systems are multiprocessor or multicomputer machines. Their efficiency depends on good methods of administering the executed works. Fast processing of a parallel application is possible only when its parts are appropriately ordered in time and space. This calls for efficient scheduling policies in parallel computer systems. In this work deterministic problems of scheduling are considered. The classical scheduling theory assumed that the application in any moment of time is executed by only one processor. This assumption has been weakened recently, especially in the context of parallel and distributed computer systems. This monograph is devoted to problems of deterministic scheduling applications or tasks according to the scheduling terminology requiring more than one processor simultaneously. We name such applications multiprocessor tasks. In this work the complexity of open multiprocessor task scheduling problems has been established. Algorithms for scheduling multiprocessor tasks on parallel and dedicated processors are proposed. For a special case of applications with regular structure which allow for dividing it into parts of arbitrary size processed independently in parallel, a method of finding optimal scattering of work in a distributed computer system is proposed. The applications with such regular characteristics are called divisible tasks. The concept of a divisible task enables creation of tractable computation models in a wide class of computer architectures such as chains, stars, meshes, hypercubes, multistage networks. Divisible task method gives rise to the evaluation of computer system performance. Examples of such performance evaluation are presented. This work summarizes earlier works of the author as well as contains new original results. Mukul Varshney | Jyotsna | Abhakiran Rajpoot | Shivani Garg "Problems in Task Scheduling in Multiprocessor System" Published in International Journal of Trend in Scientific Research and Development (ijtsrd), ISSN: 2456-6470, Volume-1 | Issue-4 , June 2017, URL: https://www.ijtsrd.com/papers/ijtsrd2198.pd

    Exciting journey of 10 years from genomes to fields and markets: Some success stories of genomics-assisted breeding in chickpea, pigeonpea and groundnut

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    AbstractLegume crops such as chickpea, pigeonpea and groundnut, mostly grown in marginal environments, are the major source of nutrition and protein to the human population in Asia and Sub-Saharan Africa. These crops, however, have a low productivity, mainly due to their exposure to several biotic and abiotic stresses in the marginal environments. Until 2005, these crops had limited genomics resources and molecular breeding was very challenging. During the last decade (2005–2015), ICRISAT led demand-driven innovations in genome science and translated the massive genome information in breeding. For instance, large-scale genomic resources including draft genome assemblies, comprehensive genetic and physical maps, thousands of SSR markers, millions of SNPs, several high-throughput as well as low cost marker genotyping platforms have been developed in these crops. After mapping several breeding related traits, several success stories of translational genomics have become available in these legumes. These include development of superior lines with enhanced drought tolerance in chickpea, enhanced and pyramided resistance to Fusarium wilt and Ascochyta blight in chickpea, enhanced resistance to leaf rust in groundnut, improved oil quality in groundnut and utilization of markers for assessing purity of hybrids/parental lines in pigeonpea. Some of these stories together with future prospects have been discussed

    Scalable and Decentralized Algorithms for Anomaly Detection via Learning-Based Controlled Sensing

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    We address the problem of sequentially selecting and observing processes from a given set to find the anomalies among them. The decision-maker observes a subset of the processes at any given time instant and obtains a noisy binary indicator of whether or not the corresponding process is anomalous. We develop an anomaly detection algorithm that chooses the processes to be observed at a given time instant, decides when to stop taking observations, and declares the decision on anomalous processes. The objective of the detection algorithm is to identify the anomalies with an accuracy exceeding the desired value while minimizing the delay in decision making. We devise a centralized algorithm where the processes are jointly selected by a common agent as well as a decentralized algorithm where the decision of whether to select a process is made independently for each process. Our algorithms rely on a Markov decision process defined using the marginal probability of each process being normal or anomalous, conditioned on the observations. We implement the detection algorithms using the deep actor-critic reinforcement learning framework. Unlike prior work on this topic that has exponential complexity in the number of processes, our algorithms have computational and memory requirements that are both polynomial in the number of processes. We demonstrate the efficacy of these algorithms using numerical experiments by comparing them with state-of-the-art methods.Green Open Access added to TU Delft Institutional Repository 'You share, we take care!' - Taverne project https://www.openaccess.nl/en/you-share-we-take-care Otherwise as indicated in the copyright section: the publisher is the copyright holder of this work and the author uses the Dutch legislation to make this work public.Signal Processing System
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