Polymeric prodrugs of mitomycin C designed for tumour tropism and sustained activation

Prodrugs of mitomycin C (MMC) based on soluble poly-[N-(2-hydroxyethyl)-L-glutamine] (pHEG) polymers have been evaluated as tumour-targeted drugs. These materials are designed to exploit the enhanced permeability of tumour vasculature, combining a passive tumour tropism with decreased systemic liberation of free MMC. A tri- or tetrapeptide linkage (e.g. Gly-Phe-Ala-Leu) between pHEG and the aziridine nitrogen of MMC can combine good hydrolytic stability with rapid cleavage by lysosomal enzymes, releasing free MMC. The conjugates showed decreased systemic toxicity and could be administered to mice at a total MMC dose of 15 mg/kg i.v., compared with just 6 mg/kg for free MMC. Conjugates also showed better activity against animal models of established tumours, achieving up to 77% increased life span (ILS) against solid P388 leukaemia, compared with only 23% for free MMC, and up to 121% ILS against solid C26 colorectal carcinoma, compared with no activity for the free drug. Improving the therapeutic index of anticancer drugs by combining tumour tropism with decreased systemic toxicity is a versatile approach that should produce a new generation of improved anticancer agents.     

Thermal-lens and photo-acoustic methods for the determination of SiC thermal properties

In this paper we report the use of photothermal techniques such as Thermal lens (TL) spectrometry, Photoacoustic and heat capacity, ρc_p, to determine the thermo-optical parameters, such as thermal conductivity (K), thermal diffusivity (D), specific heat (c_p) and the optical path dependence with temperature (ds/dT), of an undoped polycrystalline 3C-SiC. To our knowledge, this is the first time that Thermal lens technique is used for wide band-gap systems. Results obtained for the polycrystalline sample with TL technique indicates that ds/dT is negative at room temperature. Moreover, the obtained values of thermal diffusivity and thermal conductivity are in good agreement with that found in the literature, indicating that the phototermal techniques can be used to obtain the referred parameters in circumstances where other techniques cannot be used, for example, in harsh environments.     

Learning user preferences of route choice behaviour for adaptive route guidance

As the use of navigation systems becomes more widespread, the demand for advanced functions of navigation systems also increases. In the light of user satisfaction, personalisation of route guidance by incorporating user preferences is one of the most desired features. A user model applied to personalised route guidance is presented. The user model adaptively updates route selection rules when it discovers the predicted choice differs from the actual choice of the driver. This study employs a decision tree learning algorithm, the C4.5 algorithm, which has advantages over other data mining methods in terms of its comprehensible model structure. Simulation experiments with a real-world network were conducted to analyse the applicability of the model to adaptive route guidance and the accuracy of its prediction     

An experiment for showing some kind of artificial understanding

In this paper we design an experiment which can be depicted as a simple scenario, a very limited 'world'. In this world, there are an actor that can pursue a project and an observer that is keeping its eyes on the actor. We try to show in the experiment that the observer can to some degree understand the actor based on its knowledge and some metaphors, i.e. understand what the actor is doing and why. As the conclusion of this experiment, we try to show some features of 'understanding'. These are (1) that 'understanding' has to be based on some preliminary knowledge; (2) that 'understanding' is a process of incremental learning; (3) that, as for symbolic systems, some metaphors are necessary for mapping real entities into concepts in mind.     

Metastasis induced by overexpression of p185neu-T after orthotopic injection into a prostatic epithelial cell line (NbE)

The effects of the composition of bacteriological growth media on the light output in a chemiluminometric assay of beta-galactosidase in Escherichia coli using 1,2-dioxetane substrates has been studied. In this assay a basic conflict exists between conditions that promote optimal bacterial growth and those conducive to maximal chemiluminescence. Common medium ingredients such as yeast or beef extract, protein hydrolysates and lactose suppress light emission and/or lead to high backgrounds. Quenching of light emission is probably partly due to light absorption by medium ingredients such as oxgall, and partly to interference with the reaction triggering the chemiluminescent process. Elevated backgrounds are caused by the presence of high concentrations of protein hydrolysates, which interact with the alkali in the accelerator solution. Only two purposely developed media, i.e. ILM and Colicult are shown to reconcile the requirements of growth support with that of optimal luminescent properties.