Stacking classifiers for anti-spam filtering of e-mail

We evaluate empirically a scheme for combining classifiers, known as stacked generalization, in the context of anti-spam filtering, a novel cost-sensitive application of text categorization. Unsolicited commercial e-mail, or "spam", floods mailboxes, causing frustration, wasting bandwidth, and exposing minors to unsuitable content. Using a public corpus, we show that stacking can improve the efficiency of automatically induced anti-spam filters, and that such filters can be used in real-life applications

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

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

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

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

A synergistic antiproliferation effect of curcumin and docosahexaenoic acid in SK-BR-3 breast cancer cells: unique signaling not explained by the effects of either compound alone

<p>Abstract</p> <p>Background</p> <p>Breast cancer is a collection of diseases in which molecular phenotypes can act as both indicators and mediators of therapeutic strategy. Therefore, candidate therapeutics must be assessed in the context of multiple cell lines with known molecular phenotypes. Docosahexaenoic acid (DHA) and curcumin (CCM) are dietary compounds known to antagonize breast cancer cell proliferation. We report that these compounds in combination exert a variable antiproliferative effect across multiple breast cell lines, which is synergistic in SK-BR-3 cells and triggers cell signaling events not predicted by the activity of either compound alone.</p> <p>Methods</p> <p>Dose response curves for CCM and DHA were generated for five breast cell lines. Effects of the DHA+ CCM combination on cell proliferation were evaluated using varying concentrations, at a fixed ratio, of CCM and DHA based on their individual ED₅₀. Detection of synergy was performed using nonlinear regression of a sigmoid dose response model and Combination Index approaches. Cell molecular network responses were investigated through whole genome microarray analysis of transcript level changes. Gene expression results were validated by RT-PCR, and western blot analysis was performed for potential signaling mediators. Cellular curcumin uptake, with and without DHA, was analyzed via flow cytometry and HPLC.</p> <p>Results</p> <p>CCM+DHA had an antiproliferative effect in SK-BR-3, MDA-MB-231, MDA-MB-361, MCF7 and MCF10AT cells. The effect was synergistic for SK-BR-3 (ER^-PR^-Her2⁺) relative to the two compounds individually. A whole genome microarray approach was used to investigate changes in gene expression for the synergistic effects of CCM+DHA in SK-BR-3 cells lines. CCM+DHA triggered transcript-level responses, in disease-relevant functional categories, that were largely non-overlapping with changes caused by CCM or DHA individually. Genes involved in cell cycle arrest, apoptosis, inhibition of metastasis, and cell adhesion were upregulated, whereas genes involved in cancer development and progression, metastasis, and cell cycle progression were downregulated. Cellular pools of PPARγ and phospho-p53 were increased by CCM+DHA relative to either compound alone. DHA enhanced cellular uptake of CCM in SK-BR-3 cells without significantly enhancing CCM uptake in other cell lines.</p> <p>Conclusions</p> <p>The combination of DHA and CCM is potentially a dietary supplemental treatment for some breast cancers, likely dependent upon molecular phenotype. DHA enhancement of cellular curcumin uptake is one potential mechanism for observed synergy in SK-BR-3 cells; however, transcriptomic data show that the antiproliferation synergy accompanies many signaling events unique to the combined presence of the two compounds.</p