The selectivity and metabolism of sulfonamide herbicide safeners in crops

Ph. D. ThesisCrop protection is increasingly challenged by demanding regulations, limited discovery of new herbicide/pesticide modes of action and increasing pest and weed resistance. Safeners, a diverse group of agrochemicals, have been developed to diversify the application of existing herbicides by selectively enhancing tolerance in large-grained cereal crops. While their exact mode of action remains to be determined, safener treatment results in the induction of xenobiotic detoxifying enzymes and associated transport proteins collectively termed the xenome. Key inducible xenome enzymes include glutathione S-transferases (GSTs) and cytochromes P450s (CYPs). This study’s aim was to investigate the molecular mechanism and selectivity of the recently developed sulfonamide safener cyprosulfamide [N-[4- (cyclopropylcarbamoyl)phenylsulfonyl]-2-methoxybenzamide] in maize (Zea Mays L.), wheat (Triticum Aestivum) and soybean (Glycine Max). The safening activity of cyprosulfamide (CSA) in protecting these crops from herbicide damage was assessed following exposure to herbicides thiencarbazone-methyl (TCM) and tembotrione (TBT) in greenhouse trials, where CSA protected maize, but not wheat and soybean from injury by both herbicides. This correlated with the relative degree of enhanced detoxification observed with herbicide TCM, where CSA enhanced its metabolism specifically in maize. To study the comparative activity with other sulfonamide safeners, the same plants were treated with metcamifen [2-methoxyN-{[4-(3-methylureido)phenyl]sulfonyl}benzamide]. In contrast to CSA, metcamifen was active in herbicide safening in maize and wheat, but not in soybean when tested in the greenhouse against the same herbicides, which was also associated with enhanced TCM metabolism in both maize and wheat with the safener. To examine the basis of the differential safening by CSA, its uptake, translocation and metabolism were studied in maize and wheat. The safener displayed increased mobility and translocation in wheat compared to maize but this did not correlate with activity. Metabolism studies showed more rapid metabolism in maize than in wheat, with the presence of a specific metabolite correlating with activity. Primary metabolites of CSA and metcamifen were identified and synthesised for activity testing in the greenhouse and in TCM metabolism studies. With the exception of one metcamifen metabolite, these primary biotransformation products were found to be inactive. Gene expression studies were designed in order to determine if CSA induced xenobiotic detoxifying enzymes prior to its metabolism. ZmGSTL1 a gene widely used as a marker for safening, was induced prior to the appearance of CSA metabolites in maize. To investigate the roles of CSA metabolism and safening in greater detail, Matrix Assisted Laser Desorption Ionisation (MALDI) Imaging Mass spectrometry was performed in maize, where CSA and TCM were applied on the same and on different leaves. The experiment showed that TCM metabolism was elevated when compounds were applied on the same leaf, indicating that the two compounds should be present in the same tissue for safening to be induced. The characterisation of the relationship between herbicide safeners and plant signalling mechanisms appears to be complex territory, but new insights provided by this study can help lead to the design of improved safeners, which will play an important role in the future of weed control

Tree-based Focused Web Crawling with Reinforcement Learning

A focused crawler aims at discovering as many web pages relevant to a target topic as possible, while avoiding irrelevant ones. Reinforcement Learning (RL) has been utilized to optimize focused crawling. In this paper, we propose TRES, an RL-empowered framework for focused crawling. We model the crawling environment as a Markov Decision Process, which the RL agent aims at solving by determining a good crawling strategy. Starting from a few human provided keywords and a small text corpus, that are expected to be relevant to the target topic, TRES follows a keyword set expansion procedure, which guides crawling, and trains a classifier that constitutes the reward function. To avoid a computationally infeasible brute force method for selecting a best action, we propose Tree-Frontier, a decision-tree-based algorithm that adaptively discretizes the large state and action spaces and finds only a few representative actions. Tree-Frontier allows the agent to be likely to select near-optimal actions by being greedy over selecting the best representative action. Experimentally, we show that TRES significantly outperforms state-of-the-art methods in terms of harvest rate (ratio of relevant pages crawled), while Tree-Frontier reduces by orders of magnitude the number of actions needed to be evaluated at each timestep

Existence and Complexity of Approximate Equilibria in Weighted Congestion Games

We study the existence of approximate pure Nash equilibria ($\alpha$-PNE) in weighted atomic congestion games with polynomial cost functions of maximum degree $d$. Previously it was known that $d$-approximate equilibria always exist, while nonexistence was established only for small constants, namely for $1.153$-PNE. We improve significantly upon this gap, proving that such games in general do not have $\tilde{\Theta}(\sqrt{d})$-approximate PNE, which provides the first super-constant lower bound. Furthermore, we provide a black-box gap-introducing method of combining such nonexistence results with a specific circuit gadget, in order to derive NP-completeness of the decision version of the problem. In particular, deploying this technique we are able to show that deciding whether a weighted congestion game has an $\tilde{O}(\sqrt{d})$-PNE is NP-complete. Previous hardness results were known only for the special case of exact equilibria and arbitrary cost functions. The circuit gadget is of independent interest and it allows us to also prove hardness for a variety of problems related to the complexity of PNE in congestion games. For example, we demonstrate that the question of existence of $\alpha$-PNE in which a certain set of players plays a specific strategy profile is NP-hard for any $\alpha < 3^{d/2}$, even for unweighted congestion games. Finally, we study the existence of approximate equilibria in weighted congestion games with general (nondecreasing) costs, as a function of the number of players $n$. We show that $n$-PNE always exist, matched by an almost tight nonexistence bound of $\tilde\Theta(n)$ which we can again transform into an NP-completeness proof for the decision problem

Decentralized provenance-aware publishing with nanopublications

Publication and archival of scientific results is still commonly considered the responsability of classical publishing companies. Classical forms of publishing, however, which center around printed narrative articles, no longer seem well-suited in the digital age. In particular, there exist currently no efficient, reliable, and agreed-upon methods for publishing scientific datasets, which have become increasingly important for science. In this article, we propose to design scientific data publishing as a web-based bottom-up process, without top-down control of central authorities such as publishing companies. Based on a novel combination of existing concepts and technologies, we present a server network to decentrally store and archive data in the form of nanopublications, an RDF-based format to represent scientific data. We show how this approach allows researchers to publish, retrieve, verify, and recombine datasets of nanopublications in a reliable and trustworthy manner, and we argue that this architecture could be used as a low-level data publication layer to serve the Semantic Web in general. Our evaluation of the current network shows that this system is efficient and reliable

The factor structure of the Strengths and Difficulties Questionnaire (SDQ) in Greek adolescents

<p>Abstract</p> <p>Background</p> <p>The Strengths and Difficulties Questionnaire (SDQ) is a practical, economic and user-friendly screening instrument of emotional and behavioural problems in children and adolescents. This study was aimed primarily at evaluating the factor structure of the Greek version of the SDQ.</p> <p>Methods</p> <p>A representative nationwide sample of 1,194 adolescents (11 to 17 years old) completed the questionnaire. Confirmatory factor analysis (CFA) was conducted to assess the factor structure of the SDQ.</p> <p>Results</p> <p>CFA supported the original five-factor structure. The modification of the model provided some improvements. Internal consistency was acceptable for total difficulties, emotional symptoms and prosocial behaviour scale, moderate for hyperactivity/inattention scale and inadequate for peer and conduct problems scale. Older adolescents (aged 15 to 17 years) reported more hyperactivity/inattention and conduct problems than younger ones (aged 11 to 14 years) and girls reported more emotional symptoms and less prosocial behaviour problems than boys. Adolescents of low socioeconomic status (SES) reported more difficulties than those of medium and high SES.</p> <p>Conclusion</p> <p>The Greek SDQ could be potentially considered as a community-wide screening instrument for adolescents' emotional and behavioural problems.</p