A Halogen Bonding Perspective on Iodothyronine Deiodinase Activity

Iodothyronine deiodinases (Dios) are involved in the regioselective removal of iodine from thyroid hormones (THs). Deiodination is essential to maintain TH homeostasis, and disruption can have detrimental effects. Halogen bonding (XB) to the selenium of the selenocysteine (Sec) residue in the Dio active site has been proposed to contribute to the mechanism for iodine removal. Polybrominated diphenyl ethers (PBDEs) and polychlorinated biphenyls (PCBs) are known disruptors of various pathways of the endocrine system. Experimental evidence shows PBDEs and their hydroxylated metabolites (OH-BDEs) can inhibit Dio, while data regarding PCB inhibition are limited. These xenobiotics could inhibit Dio activity by competitively binding to the active site Sec through XB to prevent deiodination. XB interactions calculated using density functional theory (DFT) of THs, PBDEs, and PCBs to a methyl selenolate (MeSe-) arrange XB strengths in the order THs \u3e PBDEs \u3e PCBs in agreement with known XB trends. THs have the lowest energy C–X*-type unoccupied orbitals and overlap with the Se lp donor leads to high donor-acceptor energies and the greatest activation of the C–X bond. The higher energy C–Br* and C–Cl* orbitals similarly result in weaker donor-acceptor complexes and less activation of the C–X bond. Comparison of the I...Se interactions for the TH group suggest that a threshold XB strength may be required for dehalogenation. Only highly brominated PBDEs have binding energies in the same range as THs, suggesting that these compounds may inhibit Dio and undergo debromination. While these small models provide insight on the I...Se XB interaction itself, interactions with other active site residues are governed by regioselective preferences observed in Dios

The Importance of Worker Reputation Information in Microtask-Based Crowd Work Systems

This paper presents the first systematic investigation of the potential performance gains for crowd work systems, deriving from available information at the requester about individual worker reputation. In particular, we first formalize the optimal task assignment problem when workers’ reputation estimates are available, as the maximization of a monotone (sub-modular) function subject to Matroid constraints. Then, being the optimal problem NP-hard, we propose a simple but efficient greedy heuristic task allocation algorithm. We also propose a simple “maximum a-posteriori” decision rule and a decision algorithm based on message passing. Finally, we test and compare different solutions, showing that system performance can greatly benefit from information about workers’ reputation. Our main findings are that: i) even largely inaccurate estimates of workers’ reputation can be effectively exploited in the task assignment to greatly improve system performance; ii) the performance of the maximum a-posteriori decision rule quickly degrades as worker reputation estimates become inaccurate; iii) when workers’ reputation estimates are significantly inaccurate, the best performance can be obtained by combining our proposed task assignment algorithm with the message-passing decision algorithm

The influence of pulsed redox conditions on soil phosphorus

The effects of eleven pulsed reduction-oxidation cycles (20 and 2 days respectively) on soil phosphorus (P) dynamics are compared for 12 soils having contrasting properties and overfertilised with respect to P. Incubation conditions simulated transient waterlogging of the soil profile and involved repeated sampling and analysis of both the solution and solid phase P forms. An initial increase in P concentration occurred upto and including the fourth full cycle was followed by a sharp decline in concentration for all but one soil. Accompanying changes in the main extractable forms of P, which appeared to be cumulative, could be summarised as a general decline in the organic P fraction and an overall increase in amorphous associated inorganic forms of P. The fact that up to 60% of the total soil P was demonstrated to change its sensitivity for a particular extractant suggests that these operationally defined P forms can experience substantial transformations. There was also a suggestion that certain changes in P forms may not be reversible. While the laboratory conditions represent an extreme situation changes in timing and frequency of intense precipitation events, as predicted in many climate change scenarios, may increase the risk of episodic soil waterlogging. The potential onset of reducing conditions even for periods of less than twenty days will influence soil P dynamics and short-term bioavailable P. Various mechanisms are involved but the robustness of sequential extraction procedures and general soil test methods (e.g. Olsen) for quantifying and reliably distinguishing specific soil P forms/associations are questioned

Confluence reduction for Markov automata

Markov automata are a novel formalism for specifying systems exhibiting nondeterminism, probabilistic choices and Markovian rates. Recently, the process algebra MAPA was introduced to efficiently model such systems. As always, the state space explosion threatens the analysability of the models generated by such specifications. We therefore introduce confluence reduction for Markov automata, a powerful reduction technique to keep these models small. We define the notion of confluence directly on Markov automata, and discuss how to syntactically detect confluence on the MAPA language as well. That way, Markov automata generated by MAPA specifications can be reduced on-the-fly while preserving divergence-sensitive branching bisimulation. Three case studies demonstrate the significance of our approach, with reductions in analysis time up to an order of magnitude

A LOTOS Extension for the Performance Analysis of Distributed Systems

Performance analysis and formal correctness verification of computer communication protocols and distributed systems have traditionally been considered as two separate fields. However, their integration can be achieved by using formal description techniques as paradigms for the development of performance models. This paper presents a novel extension of LOTOS, one of the two formal specification languages that were standardized by ISO. The extension is specifically conceived to integrate performance analysis and formal verification. The extended language syntax and semantics are formally defined, along with a mapping from extended specifications to performance models, The mapping preserves the specified observable behavior. Two simple examples, a stop-and-wait protocol and a time-sharing system, are used to concretely demonstrate the new approach and to validate i

Complexity aided design: The FuturICT technological innovation paradigm

"In the next century, planet earth will don an electronic skin. It will use the Internet as a scaffold to support and transmit its sensations. This skin is already being stitched together. It consists of millions of embedded electronic measuring devices: thermostats, pressure gauges, pollution detectors, cameras, microphones, glucose sensors, EKGs, electroencephalographs. These will probe and monitor cities and endangered species, the atmosphere, our ships, highways and fleets of trucks, our conversations, our bodies-even our dreams ....What will the earth's new skin permit us to feel? How will we use its surges of sensation? For several years-maybe for a decade-there will be no central nervous system to manage this vast signaling network. Certainly there will be no central intelligence...some qualities of self-awareness will emerge once the Net is sensually enhanced. Sensuality is only one force pushing the Net toward intelligence”. These statements are quoted by an interview by Cherry Murray, Dean of the Harvard School of Engineering and Applied Sciences and Professor of Physics. It is interesting to outline the timeliness and highly predicting power of these statements. In particular, we would like to point to the relevance of the question "What will the earth's new skin permit us to feel?” to the work we are going to discuss in this paper. There are many additional compelling questions, as for example: "How can the electronic earth's skin be made more resilient?”; "How can the earth's electronic skin be improved to better satisfy the need of our society?”;"What can the science of complex systems contribute to this endeavour?” Graphical abstrac

The emerging energy web

There is a general need of elaborating energy-effective solutions for managing our increasingly dense interconnected world. The problem should be tackled in multiple dimensions -technology, society, economics, law, regulations, and politics- at different temporal and spatial scales. Holistic approaches will enable technological solutions to be supported by socio-economic motivations, adequate incentive regulation to foster investment in green infrastructures coherently integrated with adequate energy provisioning schemes. In this article, an attempt is made to describe such multidisciplinary challenges with a coherent set of solutions to be identified to significantly impact the way our interconnected energy world is designed and operated. Graphical abstrac