4,742 research outputs found
Using Gaussian Processes to Optimise Concession in Complex Negotiations against Unknown Opponents
In multi-issue automated negotiation against unknown opponents, a key part of effective negotiation is the choice of concession strategy. In this paper, we develop a principled concession strategy, based on Gaussian processes predicting the opponent's future behaviour. We then use this to set the agent's concession rate dynamically during a single negotiation session. We analyse the performance of our strategy and show that it outperforms the state-of-the-art negotiating agents from the 2010 Automated Negotiating Agents Competition, in both a tournament setting and in self-play, across a variety of negotiation domains
Negotiating Concurrently with Unknown Opponents in Complex, Real-Time Domains
We propose a novel strategy to enable autonomous agents to negotiate concurrently with multiple, unknown opponents in real-time, over complex multi-issue domains. We formalise our strategy as an optimisation problem, in which decisions are based on probabilistic information about the opponents' strategies acquired during negotiation. In doing so, we develop the first principled approach that enables the coordination of multiple, concurrent negotiation threads for practical negotiation settings. Furthermore, we validate our strategy using the agents and domains developed for the International Automated Negotiating Agents Competition (ANAC), and we benchmark our strategy against the state-of-the-art. We find that our approach significantly outperforms existing approaches, and this difference improves even further as the number of available negotiation opponents and the complexity of the negotiation domain increases
Migrating Boundaries
The boundaries between land parcels usually are assumed to be static and unchanging. However, not all land borders are stable. An important land boundary that routinely ambulates is the border between what is publicly and privately owned along U.S. coastal shores. This coastal boundary recently has been the subject of renewed attention from the courts, scholars, and even the popular press in the wake of Hurricane Sandy. This Article offers an economic analysis of why the boundary generally ambulates, rather than remaining perpetually fixed as land borders usually are assumed to do. It also considers whether the legal border generally should continue to migrate in an era of sea level rise due to climate change
Migrating Boundaries
The boundaries between land parcels usually are assumed to be static and unchanging. However, not all land borders are stable. An important land boundary that routinely ambulates is the border between what is publicly and privately owned along U.S. coastal shores. This coastal boundary recently has been the subject of renewed attention from the courts, scholars, and even the popular press in the wake of Hurricane Sandy. This Article offers an economic analysis of why the boundary generally ambulates, rather than remaining perpetually fixed as land borders usually are assumed to do. It also considers whether the legal border generally should continue to migrate in an era of sea level rise due to climate change
Copper-catalysed C-H functionalisation gives access to 2-aminobenzimidazoles
This paper describes the development, optimisation and exemplification of a copper-catalysed C–H functionalisation to form pharmaceutically relevant 2-aminobenzimidazoles from aryl-guanidines. High throughput screening was used as a tool to identify a catalytically active copper source, DoE was used for reaction optimisation and a range of aryl-guanidines were prepared and exposed to the optimum conditions to afford a range of 2-aminobenzimidazoles in moderate to good yields. The methodology has been applied to the synthesis of Emedastine, a marketed anti-histamine pharmaceutical compound, with the key cyclisation step performed on a gram-scale
Multiple prebiotic metals mediate translation.
Today, Mg2+ is an essential cofactor with diverse structural and functional roles in life's oldest macromolecular machine, the translation system. We tested whether ancient Earth conditions (low O2, high Fe2+, and high Mn2+) can revert the ribosome to a functional ancestral state. First, SHAPE (selective 2'-hydroxyl acylation analyzed by primer extension) was used to compare the effect of Mg2+, Fe2+, and Mn2+ on the tertiary structure of rRNA. Then, we used in vitro translation reactions to test whether Fe2+ or Mn2+ could mediate protein production, and quantified ribosomal metal content. We found that (i) Mg2+, Fe2+, and Mn2+ had strikingly similar effects on rRNA folding; (ii) Fe2+ and Mn2+ can replace Mg2+ as the dominant divalent cation during translation of mRNA to functional protein; and (iii) Fe and Mn associate extensively with the ribosome. Given that the translation system originated and matured when Fe2+ and Mn2+ were abundant, these findings suggest that Fe2+ and Mn2+ played a role in early ribosomal evolution
Knockdown of the schizophrenia susceptibility gene TCF4 alters gene expression and proliferation of progenitor cells from the developing human neocortex
BACKGROUND:
Common variants in the TCF4 gene are among the most robustly supported genetic risk factors for schizophrenia. Rare TCF4 deletions and loss-of-function point mutations cause Pitt-Hopkins syndrome, a developmental disorder associated with severe intellectual disability.
METHODS:
To explore molecular and cellular mechanisms by which TCF4 perturbation could interfere with human cortical development, we experimentally reduced the endogenous expression of TCF4 in a neural progenitor cell line derived from the developing human cerebral cortex using RNA interference. Effects on genome-wide gene expression were assessed by microarray, followed by Gene Ontology and pathway analysis of differentially expressed genes. We tested for genetic association between the set of differentially expressed genes and schizophrenia using genome-wide association study data from the Psychiatric Genomics Consortium and competitive gene set analysis (MAGMA). Effects on cell proliferation were assessed using high content imaging.
RESULTS:
Genes that were differentially expressed following TCF4 knockdown were highly enriched for involvement in the cell cycle. There was a nonsignificant trend for genetic association between the differentially expressed gene set and schizophrenia. Consistent with the gene expression data, TCF4 knockdown was associated with reduced proliferation of cortical progenitor cells in vitro.
LIMITATIONS:
A detailed mechanistic explanation of how TCF4 knockdown alters human neural progenitor cell proliferation is not provided by this study.
CONCLUSION:
Our data indicate effects of TCF4 perturbation on human cortical progenitor cell proliferation, a process that could contribute to cognitive deficits in individuals with Pitt-Hopkins Syndrome and risk for schizophrenia
Challenges in the delivery of e-government through kiosks
Kiosks are increasingly being heralded as a technology through which governments, government departments and local authorities or municipalities can engage with citizens. In particular, they have attractions in their potential to bridge the digital divide. There is some evidence to suggest that the citizen uptake of kiosks and indeed other channels for e-government, such as web sites, is slow, although studies on the use of kiosks for health information provision offer some interesting perspectives on user behaviour with kiosk technology. This article argues that the delivery of e-government through kiosks presents a number of strategic challenges, which will need to be negotiated over the next few years in order that kiosk applications are successful in enhancing accessibility to and engagement with e-government. The article suggests that this involves consideration of: the applications to be delivered through a kiosk; one stop shop service and knowledge architectures; mechanisms for citizen identification; and, the integration of kiosks within the total interface between public bodies and their communities. The article concludes by outlining development and research agendas in each of these areas.</p
Utility of the new Movement Disorder Society clinical diagnostic criteria for Parkinson's disease applied retrospectively in a large cohort study of recent onset cases
Objective:
To examine the utility of the new Movement Disorder Society (MDS) diagnostic criteria in a large cohort of Parkinson's disease (PD) patients.
Methods:
Recently diagnosed (<3.5 years) PD cases fulfilling United Kingdom (UK) brain bank criteria in Tracking Parkinson's, a UK multicenter prospective natural history study were assessed by retrospective application of the MDS criteria.
Results:
In 2000 cases, 1835 (91.7%) met MDS criteria for PD, either clinically established (n = 1261, 63.1%) or clinically probable (n = 574, 28.7%), leaving 165 (8.3%) not fulfilling criteria. Clinically established cases were significantly more likely to have limb rest tremor (89.3%), a good l-dopa response (79.5%), and olfactory loss (71.1%), than clinically probable cases (60.6%, 44.4%, and 34.5% respectively), but differences between probable PD and ‘not PD’ cases were less evident. In cases not fulfilling criteria, the mean MDS UPDRS3 score (25.1, SD 13.2) was significantly higher than in probable PD (22.3, SD 12.7, p = 0.016) but not established PD (22.9, SD 12.0, p = 0.066). The l-dopa equivalent daily dose of 341 mg (SD 261) in non-PD cases was significantly higher than in probable PD (250 mg, SD 214, p < 0.001) and established PD (308 mg, SD 199, p = 0.025). After 30 months' follow-up, 89.5% of clinically established cases at baseline remained as PD (established/probable), and 86.9% of those categorized as clinically probable at baseline remained as PD (established/probable). Cases not fulfilling PD criteria had more severe parkinsonism, in particular relating to postural instability, gait problems, and cognitive impairment.
Conclusion:
Over 90% of cases clinically diagnosed as early PD fulfilled the MDS criteria for PD. Those not fulfilling criteria may have an atypical parkinsonian disorder or secondary parkinsonism that is not correctly identified by the UK Brain Bank criteria, but possibly by the new criteria
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