Leveraging New Plans in AgentSpeak(PL)

Many papers have been written on the anticancer properties of dietary flavonoids, and a range of potential mechanisms of action of flavonoids. However, most dietary flavonoids - notably polyphenolic flavonoids—have very poor ADME properties, and the levels necessary to stop growth of tumour cells cannot be sustained in a human body trough dietary intake alone. At present no flavonoid based drugs are clinically used in cancer therapy. Thus, whereas epidemiological and pre-clinical data seem to indicate a high potential for flavonoids, from the point of view of the pharmaceutical industry and drug developers, they are considered poor candidates. The flavones—which constitute a subgroup of the flavonoids—show some structural analogy with oestrogen and are known to interact with human oestrogen receptors, either as agonist or as antagonist. They are classed as phytoestrogens, and may play a role in cancer prevention through a mechanism of action possibly similar to that of the clinically used medication tamoxifen. Flavones are abundantly present in common fruits and vegetables, many of which have been associated with cancer prevention. Their phytoestrogen activity makes that they can assert their biological action at concentrations that are realistically achievable in the human systemic circulation

Source authoring for multilingual generation of personalised object descriptions

We present the source authoring facilities of a natural language generation system that produces personalised descriptions of objects in multiple natural languages starting from language-independent symbolic information in ontologies and databases as well as pieces of canned text. The system has been tested in applications ranging from museum exhibitions to presentations of computer equipment for sale. We discuss the architecture of the overall system, the resources that the authors manipulate, the functionality of the authoring facilities, the system's personalisation mechanisms, and how they relate to source authoring. A usability evaluation of the authoring facilities is also presented, followed by more recent work on reusing information extracted from existing databases and documents, and supporting the owl ontology specification language

Teaching functional patterns through robotic applications

We present our approach to teaching functional programming to First Year Computer Science stu- dents at Middlesex University through projects in robotics. A holistic approach is taken to the cur- riculum, emphasising the connections between different subject areas. A key part of the students’ learning is through practical projects that draw upon and integrate the taught material. To support these, we developed the Middlesex Robotic plaTfOrm (MIRTO), an open-source platform built using Raspberry Pi, Arduino, HUB-ee wheels and running Racket (a LISP dialect). In this paper we present the motivations for our choices and explain how a number of concepts of functional programming may be employed when programming robotic applications. We present some students’ work with robotics projects: we consider the use of robotics projects to have been a success, both for their value in reinforcing students’ understanding of programming concepts and for their value in motivating the students

Optimizing investments in cyber hygiene for protecting healthcare users

Cyber hygiene measures are often recommended for strengthening an organization’s security posture, especially for protecting against social engineering attacks that target the human element. However, the related recommendations are typically the same for all organizations and their employees, regardless of the nature and the level of risk for different groups of users. Building upon an existing cybersecurity investment model, this paper presents a tool for optimal selection of cyber hygiene safeguards, which we refer as the Optimal Safeguards Tool (OST). The model combines game theory and combinatorial optimization (0-1 Knapsack) taking into account the probability of each user group to being attacked, the value of assets accessible by each group, and the efficacy of each control for a particular group. The model considers indirect cost as the time employees could require for learning and trainning against an implemented control. Utilizing a game-theoretic framework to support the Knapsack optimization problem permits us to optimally select safeguards’ application levels minimizing the aggregated expected damage within a security investment budget. We evaluate OST in a healthcare domain use case. In particular, on the Critical Internet Security (CIS) Control group 17 for implementing security awareness and training programs for employees belonging to the ICT, clinical and administration personnel of a hospital. We compare the strategies implemented by OST against alternative common-sense defending approaches for three different types of attackers: Nash, Weighted and Opportunistic. Our results show that Nash defending strategies are consistently better than the competing strategies for all attacker types with a minor exception where the Nash defending strategy, for a specific game, performs at least as good as other common-sense approaches. Finally, we illustrate the alternative investment strategies on different Nash equilibria (called plans) and discuss the optimal choice using the framework of 0-1 Knapsack optimization

Tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1–mediated metabolism to the product 4′ hydroxy tangeretin

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Tangeretin is a polymethoxylated flavone with multifaceted anticancer activity. In the present study, the metabolism and further antiproliferative activity of tangeretin was evaluated in the CYP1 expressing human breast cancer cell lines MCF7 and MDA–MB–468 and the normal breast cell line MCF10A. Tangeretin was converted to 4ʹ OH tangeretin by recombinant CYP1 enzymes and in MCF7 and MDA–MB–468 cells. This metabolite was absent in MCF10A cells that did not express CYP1 enzymes. Tangeretin exhibited submicromolar IC50 (0.25±0.15 μM) in MDA–MB–468 cells, whereas it was less active in MCF7 cells (13.5±0.8 μM) and completely inactive in MCF10A cells (>100 μM). In MDA–MB–468 cells that were coincubated with the CYP1 inhibitor acacetin, an approximately 70–fold increase was noted in the IC50 (18±1.6 μM) of tangeretin. In the presence of the CYP1 inhibitor acacetin, the conversion of tangeretin to 4ʹ OH tangeretin was significantly reduced in MDA–MB–468 cells (2.55±0.19 μM vs. 6.33±0.12 μM). The mechanism of antiproliferative action involved cell cycle arrest at the G1 phase for MCF7 and MDA–MB–468 cells, whereas the cell cycle of MCF10A cells was unaffected by 10 μM of tangeretin treatment for 24 and/or 48 h. Tangeretin was further shown to induce CYP1 enzyme activity and CYP1A1/CYP1B1 protein expression in MCF7 and MDA–MB–468 cells. Taken collectively, the results suggest that tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1–mediated metabolism to the product 4ʹ hydroxy tangeretin

Nobiletin bioactivation in MDA-MB-468 breast cancer cells by cytochrome P450 CYP1 enzymes.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI linkNobiletin is a fully methoxylated flavone that has demonstrated anticancer activity via multiple modes of action. In the present study, the metabolism and further antiproliferative activity of nobiletin was evaluated in the CYP1 expressing human breast cancer cell line MDA–MB–468 and the normal breast cell line MCF10A. Nobiletin was metabolized in MDA–MB–468 cells to a single-demethylated derivative assigned NP1. This metabolite was absent in MCF10A cells that did not express CYP1 enzymes. Nobiletin exhibited submicromolar IC50 (0.1±0.04 μM) in MDA–MB–468 cells, whereas it was considerably less active in MCF10A cells (40 μM). In the presence of the CYP1 inhibitor acacetin, the conversion of nobiletin to NP1 was significantly reduced in MDA–MB–468 cells. Furthermore, a significant increase was noted in the population of the cells at the G1 phase, following treatment with nobiletin (10 μM) for 24 h compared with the control cells treated with DMSO (0.1%) alone (55.9±0.14 vs. 45.6±1.96), whereas the cell cycle of MCF10A cells was not significantly altered under the same treatment conditions. Taken collectively, the results suggest that nobiletin is selectively bioactivated in MDA–MB–468 breast cancer cells via metabolism by the CYP1 family of enzymes

Techniques for direct experimental evaluation of structure-transport relationships in disordered porous solids

Determining structure-transport relationships is critical to optimising the activity and selectivity performance of porous pellets acting as heterogeneous catalysts for diffusion-limited reactions. For amorphous porous systems determining the impact of particular aspects of the void space on mass transport often requires complex characterization and modelling steps to deconvolve the specific influence of the feature in question. These characterization and modelling steps often have limited accuracy and precision. It is the purpose of this work to present a case-study demonstrating the use of a more direct experimental evaluation of the impact of pore network features on mass transport. The case study evaluated the efficacy of the macropores of a bidisperse porous foam structure on improving mass transport over a purely mesoporous system. The method presented involved extending the novel integrated gas sorption and mercury porosimetry method to include uptake kinetics. Results for the new method were compared with those obtained by the alternative NMR cryodiffusometry technique, and found to lead to similar conclusions. It was found that the experimentally-determined degree of influence of the foam macropores was in line with expectations from a simple resistance model for a disconnected macropore network

MIRTO: an open-source robotic platform for education

This paper introduces the MIddlesex RoboTic platfOrm (MIRTO), an open-source platform that has been used for teaching First Year Computer Science students since the academic year 2013/2014, with the aim of providing a physical manifestation of Software Engineering concepts that are often delivered using only abstract or synthetic case studies. In this paper we provide a detailed description of the platform, whose hardware specifications and software libraries are all released open source; we describe a number of teaching usages of the platform, report students’ projects, and evaluate some of its aspects in terms of effectiveness, usability, and maintenance

MIRTO: an open-source robotic platform for education

This paper introduces the MIddlesex RoboTic platfOrm (MIRTO), an open-source platform that has been used for teaching First Year Computer Science students since the academic year 2013/2014, with the aim of providing a physical manifestation of Software Engineering concepts that are often delivered using only abstract or synthetic case studies. In this paper we provide a detailed description of the platform, whose hardware specifications and software libraries are all released open source; we describe a number of teaching usages of the platform, report students’ projects, and evaluate some of its aspects in terms of effectiveness, usability, and maintenance

Cytochrome P450 CYP1 metabolism of hydroxylated flavones and flavonols: Selective bioactivation of luteolin in breast cancer cells.

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Natural flavonoids with methoxy substitutions are metabolized by CYP1 enzymes to yield the corresponding demethylated products. The present study aimed to characterize the metabolism and further antiproliferative activity of the hydroxylated flavonoids apigenin, luteolin, scutellarein, kaempferol and quercetin in CYP1 recombinant enzymes and in the CYP1 expressing cell lines MCF7 and MDA–MB–468, respectively. Apigenin was converted to luteolin and scutellarein, whereas kaempferol was metabolized only to quercetin by recombinant CYP1 enzymes. Luteolin metabolism yielded 6 hydroxyluteolin only by recombinant CYP1B1, whereas CYP1A1 and CYP1A2 were not capable of metabolizing this compound. Molecular modeling demonstrated that CYP1B1 favored the A ring orientation of apigenin and luteolin to the heme group compared with CYP1A1. The IC50 of the compounds luteolin, scutellarein and 6 hydroxyluteolin was significantly lower in MDA–MB–468, MCF7 and MCF10A cells compared with that of apigenin. Similarly, the IC50 of quercetin in MDA–MB–468 cells was significantly lower compared with that of kaempferol. The most potent compound was luteolin in MDA–MB–468 cells (IC50= 2±0.3 μM). In the presence of the CYP1-inhibitors α-napthoflavone and/or acacetin, luteolin activation was lessened. Taken collectively, the data demonstrate that the metabolism of hydroxylated flavonoids by cytochrome P450 CYP1 enzymes, notably CYP1A1 and CYP1B1, can enhance their antiproliferative activity in breast cancer cells. In addition, this antiproliferative activity is attributed to the combined action of the parent compound and the corresponding CYP1 metabolites