Selection with melphalan or paclitaxel (Taxol) yields variants with different patterns of multidrug resistance, integrin expression and in vitro invasiveness

A melphalan-resistant variant (Roswell Park Memorial Institute (RPMI)-2650M1) and a paclitaxel-resistant variant (RPMI-1650Tx) of the drug-sensitive human nasal carcinoma cell line, RPMI-2650. were established. The multidrug resistance (MDR) phenotype in the RPMI-2650Tx appeared to be P-glycoprotein (PgP)-mediated. Overexpression of multidrug resistant protein (MRP) family members was observed in the RPMI-2650M1 cells, which were also much more invasive in vitro than the parental cell line or the paclitaxel-resistant variant. Increased expression of alpha (2), alpha (5), alpha (6), beta (1) and beta (4) integrin subunits, decreased expression of alpha (4) integrin subunit, stronger adhesion to collagen type IV, laminin, fibronectin and matrigel, increased expression of MMP-2 and MMP-9 and significant motility compared with the parental cells were observed, along with a high invasiveness in the RPMI-7650M1 cells. Decreased expression of the alpha (2) integrin subunit, decreased attachment to collagen type IV, absence of cytokeratin 18 expression, no detectable expression of gelatin-degrading proteases and poor motility may be associated with the non-invasiveness of the RPMI-2650Tx variant. These results suggest that melphalan exposure can result in not only a MDR phenotype. but could also make cancer cells more invasive, whereas paclitaxel exposure resulted in MDR without increasing the in vitro invasiveness in the RPMI-2650 cells. (C) 2001 Elsevier Science Ltd. All rights reserved.

Integrated structure selection and parameter optimisation for eng-genes neural models

The eng-genes concept involves the use of fundamental known system functions as activation functions in a neural model to create a 'grey-box' neural network. One of the main issues in eng-genes modelling is to produce a parsimonious model given a model construction criterion. The challenges are that (1) the eng-genes model in most cases is a heterogenous network consisting of more than one type of nonlinear basis functions, and each basis function may have different set of parameters to be optimised; (2) the number of hidden nodes has to be chosen based on a model selection criterion. This is a mixed integer hard problem and this paper investigates the use of a forward selection algorithm to optimise both the network structure and the parameters of the system-derived activation functions. Results are included from case studies performed on a simulated continuously stirred tank reactor process, and using actual data from a pH neutralisation plant. The resulting eng-genes networks demonstrate superior simulation performance and transparency over a range of network sizes when compared to conventional neural models. (c) 2007 Elsevier B.V. All rights reserved.

Desulfurisation of oils using ionic liquids: selection of cationic and anionic components to enhance extraction efficiency

Extraction of dibenzothiophene from dodecane using ionic liquids as the extracting phase has been investigated for a range of ionic liquids with varying cation classes (imidazolium, pyridinium, and pyrrolidinium) and a range of anion types using liquid-liquid partition studies and QSPR (quantitative structure-activity relationship) analysis. The partition ratio of dibenzothiophene to the ionic liquids showed a clear variation with cation class (dimethylpyridinium > methylpyridinium > pyridinium approximate to imidazolium approximate to pyrrolidinium), with much less significant variation with anion type. Polyaromatic quinolinium-based ionic liquids showed even greater extraction potential, but were compromised by higher melting points. For example, 1-butyl-6-methylquinolinium bis{(trifluoromethyl)sulfonyl} amide (mp 47 degrees C) extracted 90% of the available dibenzothiophene from dodecane at 60 degrees C.

Selection of an analytical method for evaluating bovine serum albumin concentrations in pharmaceutical polymeric formulations

Bovine serum albumin (BSA) is a commonly used model protein in the development of pharmaceutical formulations. In order to assay its release from various dosage forms, either the bicinchoninic acid (BCA) assay or a more specific size-exclusion high performance liquid chromatography (SE-HPLC) method are commonly employed. However, these can give erroneous results in the presence of some commonly-used pharmaceutical excipients. We therefore investigated the ability of these methods to accurately determine BSA concentrations in pharmaceutical formulations that also contained various polymers and compared them with a new and compared with a new reverse-phase (RP)–HPLC technique. We found that the RP-HPLC technique was the most suitable method. It gave a linear response in the range of 0.5 -100 µg/ml with a correlation coefficient of 0.9999, a limit of detection of 0.11 µg/ml and quantification of 0.33 µg/ml. The performed ‘t’ test for the estimated and theoretical concentration indicated no significant difference between them providing the accuracy. Low % relative standard deviation values (0.8-1.39%) indicate the precision of the method. Furthermore, the method was used to quantify in vitro BSA release from polymeric freeze-dried formulations.

Deciding between accounts of the selection task: A reply to Oaksford (2002)

In this paper we report on our attempts to fit the optimal data selection (ODS) model (Oaksford Chater, 1994; Oaksford, Chater, & Larkin, 2000) to the selection task data reported in Feeney and Handley (2000) and Handley, Feeney, and Harper (2002). Although Oaksford (2002b) reports good fits to the data described in Feeney and Handley (2000), the model does not adequately capture the data described in Handley et al. (2002). Furthermore, across all six of the experiments modelled here, the ODS model does not predict participants' behaviour at the level of selection rates for individual cards. Finally, when people's probability estimates are used in the modelling exercise, the model adequately captures only I out of 18 conditions described in Handley et al. We discuss the implications of these results for models of the selection task and claim that they support deductive, rather than probabilistic, accounts of the task.

Alternative antecedents, probabilities, and the suppression of fallacies in Wason's selection task

Three experiments examined the influence of a second rule on the pattern of card selections on Wason's selection task. In Experiment 1 participants received a version of the task with a single test rule or one of two versions of the task with the same original test rule together with a second rule. The probability of q was manipulated in the two-rules conditions by varying the size of the antecedent set in the second rule. The results showed a significant suppression of q card and not-p card selections in the alternative-rule conditions, but no difference as a function of antecedent set size. In Experiment 2 the size of the antecendent set in the two-rules conditions was manipulated using the context of a computer printing double-sided cards. The results showed a significant reduction of q card selections in the two-rules conditions, but no effect of p set size. In Experiment 3 the scenario accompanying the rule was manipulated, and it specified a single alternative antecedent or a number of alternative antecedents. The q card selection rates were not affected by the scenario manipulation but again were suppressed by the presence of a second rule. Our results suggest that people make inferences about the unseen side of the cards when engaging with the task and that these inferences are systematically influenced by the presence of a second rule, but are not influenced by the probabilistic characteristics of this rule. These findings are discussed in the context of decision theoretic views of selection task performance (Oaksford Chater, 1994).

The suppression of q card selections: Evidence for deductive inference in Wason's Selection Task

The results of three experiments investigating the role of deductive inference in Wason's selection task are reported. In Experiment 1, participants received either a standard one-rule problem or a task containing a second rule, which specified an alternative antecedent. Both groups of participants were asked to select those cards that they considered were necessary to test whether the rule common to both problems was true or false. The results showed a significant suppression of q card selections in the two-rule condition. In addition there was weak evidence for both decreased p selection and increased not-q selection. In Experiment 2 we again manipulated number of rules and found suppression of q card selections only. Finally, in Experiment 3 we compared one- and two-rule conditions with a two-rule condition where the second rule specified two alternative antecedents in the form of a disjunction. The q card selections were suppressed in both of the two-rule conditions but there was no effect of whether the second rule contained one or two alternative antecedents. We argue that our results support the claim that people make inferences about the unseen side of the cards when engaging with the indicative selection task.

Evaluation of the Q-method as a method of public participation in the selection of sustainable development indicators

The complexity of sustainable development means that it is often difficult to evaluate and communicate the concept effectively. One standard method to reduce complexity and improve Communication, while maintaining scientific objectivity, is to use selected indicators. The aim of this paper is to describe and evaluate a process Of public participation in the selection of sustainable development indicators that utilised the Q-method for discourse analysis. The Q-method was Utilised to combine public opinion with technical expertise to create a list of technically robust indicators that would be relevant to the public, The method comprises statement collection, statement analysis, Q-sorts and Q-sort analysis. The results of the Q-method generated a list of statements for which a preliminary list of indicators was then developed by a team of experts from the fields of environmental science, sustainable development and Psychology. Subsequently members of the public evaluated the preliminary list of indicators, to select a final list of indicators that were both technically sound and incorporated the views of the public. The Utilisation of the Q-method in this process was evaluated using previously published criteria. The application of the Q-method in this context needs to be considered not only by the quality of the indicators developed, but also from the perspective of the benefit of the process to the participants. it was concluded that the Q-method provided an effective framework for public participation in the selection of indicators as it allowed the public to discuss Sustainable development in familiar language and in the context of their daily lives. By combining this information with expert input, a list of technically robust indicators that resonate with the public was developed. The results demonstrated that many citizens are not aware Of Sustainable development, and if it is to be successfully communicated to them, then indicators and policy need to be couched in terms familiar and relevant to citizen and communities. (C) 2009 Elsevier Ltd. All rights reserved.