Distinguishing between mechanisms of cell aggregation using pair-correlation functions

Many cell types form clumps or aggregates when cultured in vitro through a variety of mechanisms including rapid cell proliferation, chemotaxis, or direct cell-to-cell contact. In this paper we develop an agent-based model to explore the formation of aggregates in cultures where cells are initially distributed uniformly, at random, on a two-dimensional substrate. Our model includes unbiased random cell motion, together with two mechanisms which can produce cell aggregates: (i) rapid cell proliferation, and (ii) a biased cell motility mechanism where cells can sense other cells within a finite range, and will tend to move towards areas with higher numbers of cells. We then introduce a pair-correlation function which allows us to quantify aspects of the spatial patterns produced by our agent-based model. In particular, these pair-correlation functions are able to detect differences between domains populated uniformly at random (i.e. at the exclusion complete spatial randomness (ECSR) state) and those where the proliferation and biased motion rules have been employed - even when such differences are not obvious to the naked eye. The pair-correlation function can also detect the emergence of a characteristic inter-aggregate distance which occurs when the biased motion mechanism is dominant, and is not observed when cell proliferation is the main mechanism of aggregate formation. This suggests that applying the pair-correlation function to experimental images of cell aggregates may provide information about the mechanism associated with observed aggregates. As a proof of concept, we perform such analysis for images of cancer cell aggregates, which are known to be associated with rapid proliferation. The results of our analysis are consistent with the predictions of the proliferation-based simulations, which supports the potential usefulness of pair correlation functions for providing insight into the mechanisms of aggregate formation.

A Reliable Basis for Approximate Association Rules

For most of the work done in developing association rule mining, the primary focus has been on the efficiency of the approach and to a lesser extent the quality of the derived rules has been emphasized. Often for a dataset, a huge number of rules can be derived, but many of them can be redundant to other rules and thus are useless in practice. The extremely large number of rules makes it difficult for the end users to comprehend and therefore effectively use the discovered rules and thus significantly reduces the effectiveness of rule mining algorithms. If the extracted knowledge can’t be effectively used in solving real world problems, the effort of extracting the knowledge is worth little. This is a serious problem but not yet solved satisfactorily. In this paper, we propose a concise representation called Reliable Approximate basis for representing non-redundant approximate association rules. We prove that the redundancy elimination based on the proposed basis does not reduce the belief to the extracted rules. We also prove that all approximate association rules can be deduced from the Reliable Approximate basis. Therefore the basis is a lossless representation of approximate association rules.

Ticagrelor, a platelet aggregation inhibitor for the potential prevention and treatment of arterial thrombosis and acute coronary syndromes

Ticagrelor is an orally active ADP P2Y12 receptor antagonist in development by AstraZeneca plc for the reduction of recurrent ischemic events in patients with acute coronary syndromes (ACS). Prior to the development of ticagrelor, thienopyridine compounds, such as clopidogrel, were the focus of research into therapies for ACS. Although the thienopyridines are effective platelet aggregation inhibitors, they are prodrugs and, consequently, exert a slow onset of action. In addition, the variability in inter-individual metabolism of thienopyridine prodrugs has been associated with reduced efficacy in some patients. Ticagrelor is not a prodrug and exhibits a more rapid onset of action than the thienopyridine prodrugs. In clinical trials conducted to date, ticagrelor was a potent inhibitor of ADP-induced platelet aggregation and demonstrated effects that were comparable to clopidogrel. In a phase II, short-term trial, the bleeding profile of participants treated with ticagrelor was similar to that obtained with clopidogrel; however, an increased incidence of dyspnea was observed - an effect that has not been reported with the thienopyridines. Considering the occurrence of dyspnea, and the apparent non-superiority of ticagrelor to clopidogrel, it is difficult to justify a clear benefit to the continued development of ticagrelor. Outcomes from an ongoing phase III trial comparing ticagrelor with clopidogrel in 18,000 patients with ACS are likely to impact on the future development of ticagrelor.

Interestingness Measures for Multi-Level Association Rules

Association rule mining is one technique that is widely used when querying databases, especially those that are transactional, in order to obtain useful associations or correlations among sets of items. Much work has been done focusing on efficiency, effectiveness and redundancy. There has also been a focusing on the quality of rules from single level datasets with many interestingness measures proposed. However, with multi-level datasets now being common there is a lack of interestingness measures developed for multi-level and cross-level rules. Single level measures do not take into account the hierarchy found in a multi-level dataset. This leaves the Support-Confidence approach,which does not consider the hierarchy anyway and has other drawbacks, as one of the few measures available. In this paper we propose two approaches which measure multi-level association rules to help evaluate their interestingness. These measures of diversity and peculiarity can be used to help identify those rules from multi-level datasets that are potentially useful.

Concise representations for association rules in multi-level datasets

Association rule mining has made many advances in the area of knowledge discovery. However, the quality of the discovered association rules is a big concern and has drawn more and more attention recently. One problem with the quality of the discovered association rules is the huge size of the extracted rule set. Often for a dataset, a huge number of rules can be extracted, but many of them can be redundant to other rules and thus useless in practice. Mining non-redundant rules is a promising approach to solve this problem. In this paper, we firstly propose a definition for redundancy; then we propose a concise representation called Reliable basis for representing non-redundant association rules for both exact rules and approximate rules. An important contribution of this paper is that we propose to use the certainty factor as the criteria to measure the strength of the discovered association rules. With the criteria, we can determine the boundary between redundancy and non-redundancy to ensure eliminating as many redundant rules as possible without reducing the inference capacity of and the belief to the remaining extracted non-redundant rules. We prove that the redundancy elimination based on the proposed Reliable basis does not reduce the belief to the extracted rules. We also prove that all association rules can be deduced from the Reliable basis. Therefore the Reliable basis is a lossless representation of association rules. Experimental results show that the proposed Reliable basis can significantly reduce the number of extracted rules.

Investigating the use of association rules in improving recommender systems

Recommender systems are widely used online to help users find other products, items etc that they may be interested in based on what is known about that user in their profile. Often however user profiles may be short on information and thus when there is not sufficient knowledge on a user it is difficult for a recommender system to make quality recommendations. This problem is often referred to as the cold-start problem. Here we investigate whether association rules can be used as a source of information to expand a user profile and thus avoid this problem, leading to improved recommendations to users. Our pilot study shows that indeed it is possible to use association rules to improve the performance of a recommender system. This we believe can lead to further work in utilising appropriate association rules to lessen the impact of the cold-start problem.

Generating rules with predicates, terms and variables from the pruned neural networks

Artificial neural networks (ANN) have demonstrated good predictive performance in a wide range of applications. They are, however, not considered sufficient for knowledge representation because of their inability to represent the reasoning process succinctly. This paper proposes a novel methodology Gyan that represents the knowledge of a trained network in the form of restricted first-order predicate rules. The empirical results demonstrate that an equivalent symbolic interpretation in the form of rules with predicates, terms and variables can be derived describing the overall behaviour of the trained ANN with improved comprehensibility while maintaining the accuracy and fidelity of the propositional rules.