AI Researchers, Video Games Are Your Friends!

If you are an artificial intelligence researcher, you should look to video games as ideal testbeds for the work you do. If you are a video game developer, you should look to AI for the technology that makes completely new types of games possible. This chapter lays out the case for both of these propositions. It asks the question "what can video games do for AI", and discusses how in particular general video game playing is the ideal testbed for artificial general intelligence research. It then asks the question "what can AI do for video games", and lays out a vision for what video games might look like if we had significantly more advanced AI at our disposal. The chapter is based on my keynote at IJCCI 2015, and is written in an attempt to be accessible to a broad audience.Comment: in Studies in Computational Intelligence Studies in Computational Intelligence, Volume 669 2017. Springe

A 'large and valuable' Siwalik fossil collection in the archives of the Oxford University Museum of Natural History

This article describes results from a review of South Asian fossils in the Oxford University Museum of Natural History. These materials include two early 19th century collections of fossils from the Siwalik Hills in India. While this assemblage was summarised in 1837 by William Buckland as ‘large and valuable collections of fossil bones’, it has remained largely unstudied and unpublished in any detail since collection. Here, as a precursor to a comprehensive re-evaluation, we establish a chronological and geographical context of one collection event, provide details of its donor, and outline its history after arrival in Oxford. We then describe select taxa in the collection, including a well-preserved maxilla and toothrow of the large extinct giraffid, Sivatherium giganteum, as a basis to justify our current understanding of the biostratigraphic affinity of the assemblage. Conservatively, the collection is a ‘classic’ Upper Siwalik Plio-Pleistocene fauna, possibly the first to be transported to the UK. While further analyses will realise the scientific potential of the fossils, the narrative of their journey from India to Oxford remains incomplete. Further investigation of the hidden history of the collection is warranted

Can Machine Intelligence be Measured in the Same Way as Human intelligence?

In recent years the number of research projects on computer programs solving human intelligence problems in artificial intelligence (AI), artificial general intelligence, as well as in Cognitive Modelling, has significantly grown. One reason could be the interest of such problems as benchmarks for AI algorithms. Another, more fundamental, motivation behind this area of research might be the (implicit) assumption that a computer program that successfully can solve human intelligence problems has human-level intelligence and vice versa. This paper analyses this assumption

Herbert Alexander Simon: 15th June, 1916–9th February, 2001 A Life

We present a concise summary of the personal and professional life of Herbert Alexander Simon

2-Arylamino-6-ethynylpurines are cysteine-targeting irreversible inhibitors of Nek2 kinase

Renewed interest in covalent inhibitors of enzymes implicated in disease states has afforded several agents targeted at protein kinases of relevance to cancers. We now report the design, synthesis and biological evaluation of 6-ethynylpurines that act as covalent inhibitors of Nek2 by capturing a cysteine residue (Cys22) close to the catalytic domain of this protein kinase. Examination of the crystal structure of the non-covalent inhibitor 3-((6-cyclohexylmethoxy-7H-purin-2-yl)amino)benzamide in complex with Nek2 indicated that replacing the alkoxy with an ethynyl group places the terminus of the alkyne close to Cys22 and in a position compatible with the stereoelectronic requirements of a Michael addition. A series of 6-ethynylpurines was prepared and a structure activity relationship (SAR) established for inhibition of Nek2. 6-Ethynyl-N-phenyl-7H-purin-2-amine [IC50 0.15 μM (Nek2)] and 4-((6-ethynyl-7H-purin-2-yl)amino)benzenesulfonamide (IC50 0.14 μM) were selected for determination of the mode of inhibition of Nek2, which was shown to be time-dependent, not reversed by addition of ATP and negated by site directed mutagenesis of Cys22 to alanine. Replacement of the ethynyl group by ethyl or cyano abrogated activity. Variation of substituents on the N-phenyl moiety for 6-ethynylpurines gave further SAR data for Nek2 inhibition. The data showed little correlation of activity with the nature of the substituent, indicating that after sufficient initial competitive binding to Nek2 subsequent covalent modification of Cys22 occurs in all cases. A typical activity profile was that for 2-(3-((6-ethynyl-9H-purin-2-yl)amino)phenyl)acetamide [IC50 0.06 μM (Nek2); GI50 (SKBR3) 2.2 μM] which exhibited >5–10-fold selectivity for Nek2 over other kinases; it also showed > 50% growth inhibition at 10 μM concentration against selected breast and leukaemia cell lines. X-ray crystallographic analysis confirmed that binding of the compound to the Nek2 ATP-binding site resulted in covalent modification of Cys22. Further studies confirmed that 2-(3-((6-ethynyl-9H-purin-2-yl)amino)phenyl)acetamide has the attributes of a drug-like compound with good aqueous solubility, no inhibition of hERG at 25 μM and a good stability profile in human liver microsomes. It is concluded that 6-ethynylpurines are promising agents for cancer treatment by virtue of their selective inhibition of Nek2

Structure-guided design of purine-based probes for selective Nek2 inhibition

Nek2 (NIMA-related kinase 2) is a cell cycle-dependent serine/threonine protein kinase that regulates centrosome separation at the onset of mitosis. Overexpression of Nek2 is common in human cancers and suppression can restrict tumor cell growth and promote apoptosis. Nek2 inhibition with small molecules, therefore, offers the prospect of a new therapy for cancer. To achieve this goal, a better understanding of the requirements for selective-inhibition of Nek2 is required. 6-Alkoxypurines were identified as ATP-competitive inhibitors of Nek2 and CDK2. Comparison with CDK2-inhibitor structures indicated that judicious modification of the 6-alkoxy and 2-arylamino substituents could achieve discrimination between Nek2 and CDK2. In this study, a library of 6-cyclohexylmethoxy-2-arylaminopurines bearing carboxamide, sulfonamide and urea substituents on the 2-arylamino ring was synthesized. Few of these compounds were selective for Nek2 over CDK2, with the best result being obtained for 3-((6-(cyclohexylmethoxy)-9H-purin-2-yl)amino)-N,N-dimethylbenzamide (CDK2 IC50 = 7.0 μM; Nek2 IC50 = 0.62 μM) with >10-fold selectivity. Deletion of the 6-substituent abrogated activity against both Nek2 and CDK2. Nine compounds containing an (E)-dialkylaminovinyl substituent at C-6, all showed selectivity for Nek2, e.g. (E)-6-(2-(azepan-1-yl)vinyl)-N-phenyl-9H-purin-2-amine (CDK2 IC50 = 2.70 μM; Nek2 IC50 = 0.27 μM). Structural biology of selected compounds enabled a partial rationalization of the observed structure activity relationships and mechanism of Nek2 activation. This showed that carboxamide 11 is the first reported inhibitor of Nek2 in the DFG-in conformation

A Standardised Procedure for Evaluating Creative Systems: Computational Creativity Evaluation Based on What it is to be Creative

Computational creativity is a flourishing research area, with a variety of creative systems being produced and developed. Creativity evaluation has not kept pace with system development with an evident lack of systematic evaluation of the creativity of these systems in the literature. This is partially due to difficulties in defining what it means for a computer to be creative; indeed, there is no consensus on this for human creativity, let alone its computational equivalent. This paper proposes a Standardised Procedure for Evaluating Creative Systems (SPECS). SPECS is a three-step process: stating what it means for a particular computational system to be creative, deriving and performing tests based on these statements. To assist this process, the paper offers a collection of key components of creativity, identified empirically from discussions of human and computational creativity. Using this approach, the SPECS methodology is demonstrated through a comparative case study evaluating computational creativity systems that improvise music

Mechanisms of improved survival from intensive followup in colorectal cancer: a hypothesis

A meta-analysis of six randomised trials demonstrated that intensive followup in colorectal cancer was associated with an absolute reduction in all-cause 5-year mortality of 10% (95% confidence interval (CI): 4–16) – however, only two percent (95% CI: 0–5) was attributable to cure from salvage re-operations. We postulate that other factors, such as increased psychological well-being and/or altered lifestyle, and/or improved treatment of coincidental disease may contribute to the remaining lives saved, and form important future research questions

Exploring Action Dynamics as an Index of Paired-Associate Learning

Much evidence exists supporting a richer interaction between cognition and action than commonly assumed. Such findings demonstrate that short-timescale processes, such as motor execution, may relate in systematic ways to longer-timescale cognitive processes, such as learning. We further substantiate one direction of this interaction: the flow of cognition into action systems. Two experiments explored match-to-sample paired-associate learning, in which participants learned randomized pairs of unfamiliar symbols. During the experiments, their hand movements were continuously tracked using the Nintendo Wiimote. Across learning, participant arm movements are initiated and completed more quickly, exhibit lower fluctuation, and exert more perturbation on the Wiimote during the button press. A second experiment demonstrated that action dynamics index novel learning scenarios, and not simply acclimatization to the Wiimote interface. Results support a graded and systematic covariation between cognition and action, and recommend ways in which this theoretical perspective may contribute to applied learning contexts

A Preference for Contralateral Stimuli in Human Object- and Face-Selective Cortex

Visual input from the left and right visual fields is processed predominantly in the contralateral hemisphere. Here we investigated whether this preference for contralateral over ipsilateral stimuli is also found in high-level visual areas that are important for the recognition of objects and faces. Human subjects were scanned with functional magnetic resonance imaging (fMRI) while they viewed and attended faces, objects, scenes, and scrambled images in the left or right visual field. With our stimulation protocol, primary visual cortex responded only to contralateral stimuli. The contralateral preference was smaller in object- and face-selective regions, and it was smallest in the fusiform gyrus. Nevertheless, each region showed a significant preference for contralateral stimuli. These results indicate that sensitivity to stimulus position is present even in high-level ventral visual cortex