Distance-based decision tree algorithms for label ranking

The problem of Label Ranking is receiving increasing attention from several research communities. The algorithms that have developed/adapted to treat rankings as the target object follow two different approaches: distribution-based (e.g., using Mallows model) or correlation-based (e.g., using Spearman’s rank correlation coefficient). Decision trees have been adapted for label ranking following both approaches. In this paper we evaluate an existing correlation-based approach and propose a new one, Entropy-based Ranking trees. We then compare and discuss the results with a distribution-based approach. The results clearly indicate that both approaches are competitive

Discovering a taste for the unusual: exceptional models for preference mining

Exceptional preferences mining (EPM) is a crossover between two subfields of data mining: local pattern mining and preference learning. EPM can be seen as a local pattern mining task that finds subsets of observations where some preference relations between labels significantly deviate from the norm. It is a variant of subgroup discovery, with rankings of labels as the target concept. We employ several quality measures that highlight subgroups featuring exceptional preferences, where the focus of what constitutes exceptional' varies with the quality measure: two measures look for exceptional overall ranking behavior, one measure indicates whether a particular label stands out from the rest, and a fourth measure highlights subgroups with unusual pairwise label ranking behavior. We explore a few datasets and compare with existing techniques. The results confirm that the new task EPM can deliver interesting knowledge.This research has received funding from the ECSEL Joint Undertaking, the framework programme for research and innovation Horizon 2020 (2014-2020) under Grant Agreement Number 662189-MANTIS-2014-1

Exceptional Preferences Mining

Exceptional Preferences Mining (EPM) is a crossover between two subfields of datamining: local pattern mining and preference learning. EPM can be seen as a local pattern mining task that finds subsets of observations where the preference relations between subsets of the labels significantly deviate from the norm; a variant of Subgroup Discovery, with rankings as the (complex) target concept. We employ three quality measures that highlight subgroups featuring exceptional preferences, where the focus of what constitutes 'exceptional' varies with the quality measure: the first gauges exceptional overall ranking behavior, the second indicates whether a particular label stands out from the rest, and the third highlights subgroups featuring unusual pairwise label ranking behavior. As proof of concept, we explore five datasets. The results confirm that the new task EPM can deliver interesting knowledge. The results also illustrate how the visualization of the preferences in a Preference Matrix can aid in interpreting exceptional preference subgroups

Cytotoxic effects of dillapiole on MDA-MB-231 cells involve the induction of apoptosis through the mitochondrial pathway by inducing an oxidative stress while altering the cytoskeleton network

Breast cancer is the world's leading cause of death among women. This situation imposes an urgent development of more selective and less toxic agents. The use of natural molecular fingerprints as sources for new bioactive chemical entities has proven to be a quite promising and efficient method. Here, we have demonstrated for the first time that dillapiole has broad cytotoxic effects against a variety tumor cells. For instance, we found that it can act as a pro-oxidant compound through the induction of reactive oxygen species (ROS) release in MDA-MB-231 cells. We also demonstrated that dillapiole exhibits anti-proliferative properties, arresting cells at the G0/G1 phase and its antimigration effects can be associated with the disruption of actin filaments, which in turn can prevent tumor cell proliferation. Molecular modeling studies corroborated the biological findings and suggested that dillapiole may present a good pharmacokinetic profile, mainly because its hydrophobic character, which can facilitate its diffusion through tumor cell membranes. All these findings support the fact that dillapiole is a promising anticancer agent

BFD-22 a new potential inhibitor of BRAF inhibits the metastasis of B16F10 melanoma cells and simultaneously increased the tumor immunogenicity

Benzofuroxan is an interesting ring system, which has shown a wide spectrum of biological responses against tumor cell lines. We investigated, herein, the antitumor effects of benzofuroxan derivatives (BFDs) in vitro and in a melanoma mouse model. Cytotoxic effects of twenty-two BFDs were determined by MTT assay. Effects of BFD-22 in apoptosis and cell proliferation were evaluated using Annexin V-FITC/PI and CFSE staining. In addition, the effects in the cell cycle were assessed. Flow cytometry, western blot, and fluorescence microscopy analysis were employed to investigate the apoptosis-related proteins and the BRAF signaling. Cell motility was also exploited through cell invasion and migration assays. Molecular docking approach was performed in order to verify the BFD-22 binding mode into the ATP catalytic site of BRAF kinase. Moreover, the BFD-22 antitumor effects were evaluated in a melanoma murine model using B16F10. BFD-22 was identified as a potential hit against melanoma cells. BFD-22 induced apoptosis and inhibited cell proliferation of B16F10 cells. BFD-22 has suppressed, indeed, the migratory and invasive behavior of B16F10 cells. Cyclin D1 and CDK4 expression were reduced leading to cell cycle arrest at G0/G1 phase. Of note, phosphorylation of BRAF at Ser338 was strongly down-regulated by BFD-22 in B16F10 cells. The accommodation/orientation into the binding site of BRAF was similar of BAY43-9006 (co-crystallized inhibitor of BRAF, sorafenib). Importantly, BFD-22 presented in vivo antimetastatic effects and showed better therapeutic efficacy than sorafenib and taxol. BFD-22 can be considered as a new lead compound and, then, can be helpful for the designing of novel drug candidates to treat melanoma

Impairment of the Plasmodium falciparum Erythrocytic Cycle Induced by Angiotensin Peptides

Plasmodium falciparum causes the most serious complications of malaria and is a public health problem worldwide with over 2 million deaths each year. The erythrocyte invasion mechanisms by Plasmodium sp. have been well described, however the physiological aspects involving host components in this process are still poorly understood. Here, we provide evidence for the role of renin-angiotensin system (RAS) components in reducing erythrocyte invasion by P. falciparum. Angiotensin II (Ang II) reduced erythrocyte invasion in an enriched schizont culture of P. falciparum in a dose-dependent manner. Using mass spectroscopy, we showed that Ang II was metabolized by erythrocytes to Ang IV and Ang-(1–7). Parasite infection decreased Ang-(1–7) and completely abolished Ang IV formation. Similar to Ang II, Ang-(1–7) decreased the level of infection in an A779 (specific antagonist of Ang-(1–7) receptor, MAS)-sensitive manner. 10−7 M PD123319, an AT2 receptor antagonist, partially reversed the effects of Ang-(1–7) and Ang II. However, 10−6 M losartan, an antagonist of the AT1 receptor, had no effect. Gs protein is a crucial player in the Plasmodium falciparum blood cycle and angiotensin peptides can modulate protein kinase A (PKA) activity; 10−8 M Ang II or 10−8 M Ang-(1–7) inhibited this activity in erythrocytes by 60% and this effect was reversed by 10−7 M A779. 10−6 M dibutyryl-cAMP increased the level of infection and 10−7 M PKA inhibitor decreased the level of infection by 30%. These results indicate that the effect of Ang-(1–7) on P. falciparum blood stage involves a MAS-mediated PKA inhibition. Our results indicate a crucial role for Ang II conversion into Ang-(1–7) in controlling the erythrocytic cycle of the malaria parasite, adding new functions to peptides initially described to be involved in the regulation of vascular tonus