Prediction of cis/trans isomerization in proteins using PSI-BLAST profiles and secondary structure information

Background The majority of peptide bonds in proteins are found to occur in the trans conformation. However, for proline residues, a considerable fraction of Prolyl peptide bonds adopt the cis form. Proline cis/trans isomerization is known to play a critical role in protein folding, splicing, cell signaling and transmembrane active transport. Accurate prediction of proline cis/trans isomerization in proteins would have many important applications towards the understanding of protein structure and function. Results In this paper, we propose a new approach to predict the proline cis/trans isomerization in proteins using support vector machine (SVM). The preliminary results indicated that using Radial Basis Function (RBF) kernels could lead to better prediction performance than that of polynomial and linear kernel functions. We used single sequence information of different local window sizes, amino acid compositions of different local sequences, multiple sequence alignment obtained from PSI-BLAST and the secondary structure information predicted by PSIPRED. We explored these different sequence encoding schemes in order to investigate their effects on the prediction performance. The training and testing of this approach was performed on a newly enlarged dataset of 2424 non-homologous proteins determined by X-Ray diffraction method using 5-fold cross-validation. Selecting the window size 11 provided the best performance for determining the proline cis/trans isomerization based on the single amino acid sequence. It was found that using multiple sequence alignments in the form of PSI-BLAST profiles could significantly improve the prediction performance, the prediction accuracy increased from 62.8% with single sequence to 69.8% and Matthews Correlation Coefficient (MCC) improved from 0.26 with single local sequence to 0.40. Furthermore, if coupled with the predicted secondary structure information by PSIPRED, our method yielded a prediction accuracy of 71.5% and MCC of 0.43, 9% and 0.17 higher than the accuracy achieved based on the singe sequence information, respectively. Conclusion A new method has been developed to predict the proline cis/trans isomerization in proteins based on support vector machine, which used the single amino acid sequence with different local window sizes, the amino acid compositions of local sequence flanking centered proline residues, the position-specific scoring matrices (PSSMs) extracted by PSI-BLAST and the predicted secondary structures generated by PSIPRED. The successful application of SVM approach in this study reinforced that SVM is a powerful tool in predicting proline cis/trans isomerization in proteins and biological sequence analysis.

A comparison of alternative bankruptcy prediction models

Early models of bankruptcy prediction employed financial ratios drawn from pre-bankruptcy financial statements and performed well both in-sample and out-of-sample. Since then there has been an ongoing effort in the literature to develop models with even greater predictive performance. A significant innovation in the literature was the introduction into bankruptcy prediction models of capital market data such as excess stock returns and stock return volatility, along with the application of the Black–Scholes–Merton option-pricing model. In this note, we test five key bankruptcy models from the literature using an upto- date data set and find that they each contain unique information regarding the probability of bankruptcy but that their performance varies over time. We build a new model comprising key variables from each of the five models and add a new variable that proxies for the degree of diversification within the firm. The degree of diversification is shown to be negatively associated with the risk of bankruptcy. This more general model outperforms the existing models in a variety of in-sample and out-of-sample tests.

Action inquiry into the use of standardized evaluation tools for music therapy : a real life journey within a parent-child community program

Sing & Grow is an early intervention music therapy project that provides community group music therapy programs to families with young children who encounter risk factors that may impact on parenting and optimal child develop variety of evaluation tools were devised and used over the first 3 years of the project. Upon the subsequent funding and expansion of the project at the end of this period, it was necessary to find, test and devise more rigorous, valid and reliable measures to withstand the scrutiny of researchers, and to combat the concerns and criticisms associated with the previous methods of data collection. An action inquiry project was therefore undertaken with two groups of project participants to trial the use of the Parenting Stress Index and Depression, Anxiety and Stress Scales, both recommended by leading psychologists. Key findings that will be discussed include the friction between the deficit-focussed nature of many psychometric tools and the strengths-based approach taken in service delivery, the level of difficulty in terms of literacy and comprehension for vulnerable respondents, and the lack of one tool with the ability to comprehensively measure all aspects of a broad scoping program. Keywords: music therapy, evaluation, PSI, DASS, action inquiry.

Having a yarn about smoking : using action research to develop a 'no smoking' policy within an Aboriginal health organisation

Objectives: This article reports on a culturally appropriate process of development of a smoke-free workplace policy within the peak Aboriginal Controlled Community Health Organisation in Victoria, Australia. Smoking is acknowledged as being responsible for at least 20% of all deaths in Aboriginal communities in Australia, and many Aboriginal health workers smoke. Methods: The smoke-free workplace policy was developed using the iterative, discursive and experience-based methodology of Participatory Action Research, combined with the culturally embedded concept of ‘having a yarn’. Results: Staff members initially identified smoking as a topic to be avoided within workplace discussions. This was due, in part, to grief (everyone had suffered a smoking related bereavement). Further, there was anxiety that discussing smoking would result in culturally difficult conflict. The use of yarning opened up a safe space for discussion and debate,enabling development of a policy that was accepted across the organisation. Conclusions: Within Aboriginal organisations, it is not sufficient to focus on the outcomes of policy development. Rather, due attention must be paid to the process employed in development of policy, particularly when that policy is directly related to an emotionally and communally weighted topic such as smoking.

Exploring the parameter space of a rabbit ventricular action potential model to investigate the effect of variation on action potential and calcium transients

Computational models for cardiomyocyte action potentials (AP) often make use of a large parameter set. This parameter set can contain some elements that are fitted to experimental data independently of any other element, some elements that are derived concurrently with other elements to match experimental data, and some elements that are derived purely from phenomenological fitting to produce the desired AP output. Furthermore, models can make use of several different data sets, not always derived for the same conditions or even the same species. It is consequently uncertain whether the parameter set for a given model is physiologically accurate. Furthermore, it is only recently that the possibility of degeneracy in parameter values in producing a given simulation output has started to be addressed. In this study, we examine the effects of varying two parameters (the L-type calcium current (I(CaL)) and the delayed rectifier potassium current (I(Ks))) in a computational model of a rabbit ventricular cardiomyocyte AP on both the membrane potential (V(m)) and calcium (Ca(2+)) transient. It will subsequently be determined if there is degeneracy in this model to these parameter values, which will have important implications on the stability of these models to cell-to-cell parameter variation, and also whether the current methodology for generating parameter values is flawed. The accuracy of AP duration (APD) as an indicator of AP shape will also be assessed.

Parameter estimation for a phenomenological model of the cardiac action potential

The action potential (ap) of a cardiac cell is made up of a complex balance of ionic currents which flow across the cell membrane in response to electrical excitation of the cell. Biophysically detailed mathematical models of the ap have grown larger in terms of the variables and parameters required to model new findings in subcellular ionic mechanisms. The fitting of parameters to such models has seen a large degree of parameter and module re-use from earlier models. An alternative method for modelling electrically exciteable cardiac tissue is a phenomenological model, which reconstructs tissue level ap wave behaviour without subcellular details. A new parameter estimation technique to fit the morphology of the ap in a four variable phenomenological model is presented. An approximation of a nonlinear ordinary differential equation model is established that corresponds to the given phenomenological model of the cardiac ap. The parameter estimation problem is converted into a minimisation problem for the unknown parameters. A modified hybrid Nelder–Mead simplex search and particle swarm optimization is then used to solve the minimisation problem for the unknown parameters. The successful fitting of data generated from a well known biophysically detailed model is demonstrated. A successful fit to an experimental ap recording that contains both noise and experimental artefacts is also produced. The parameter estimation method’s ability to fit a complex morphology to a model with substantially more parameters than previously used is established.

Research in action for community informatics : A matter for conversation (editorial introduction)

This special issue of the Journal of Community Informatics brings together people from a diverse range of disciplines to discuss how academic researchers and community practitioners and activists can work together to explore the use of information and communication technologies, social media, augmented reality, and other forms of network technologies for research and action in pursuit of social responsibility. The aim is to connect people with ideas, ideas with research projects, and harness new media to further inquiry into socially just outcomes in our community. Some of the papers are based on presentations given at the "Research for Action: Networking University and Community for Social Responsibility" workshop chaired by Matthew Allen and Marcus Foth, at the Making Links 2010 conference in Perth, WA on 15 Nov 2010.