Benchmarking pKa prediction

Background: pKa values are a measure of the protonation of ionizable groups in proteins. Ionizable groups are involved in intra-protein, protein-solvent and protein-ligand interactions as well as solubility, protein folding and catalytic activity. The pKa shift of a group from its intrinsic value is determined by the perturbation of the residue by the environment and can be calculated from three-dimensional structural data. Results: Here we use a large dataset of experimentally-determined pKas to analyse the performance of different prediction techniques. Our work provides a benchmark of available software implementations: MCCE, MEAD, PROPKA and UHBD. Combinatorial and regression analysis is also used in an attempt to find a consensus approach towards pKa prediction. The tendency of individual programs to over- or underpredict the pKa value is related to the underlying methodology of the individual programs. Conclusion: Overall, PROPKA is more accurate than the other three programs. Key to developing accurate predictive software will be a complete sampling of conformations accessible to protein structures

What can we say about seed fields for galactic dynamos?

We demonstrate that a quasi-uniform cosmological seed field is a much less suitable seed for a galactic dynamo than has often been believed. The age of the Universe is insufficient for a conventional galactic dynamo to generate a contemporary galactic magnetic field starting from such a seed, accepting conventional estimates for physical quantities. We discuss modifications to the scenario for the evolution of galactic magnetic fields implied by this result. We also consider briefly the implications of a dynamo number that is significantly larger than that given by conventional estimates

Towards a lightweight generic computational grid framework for biological research

Background: An increasing number of scientific research projects require access to large-scale computational resources. This is particularly true in the biological field, whether to facilitate the analysis of large high-throughput data sets, or to perform large numbers of complex simulations – a characteristic of the emerging field of systems biology. Results: In this paper we present a lightweight generic framework for combining disparate computational resources at multiple sites (ranging from local computers and clusters to established national Grid services). A detailed guide describing how to set up the framework is available from the following URL: http://igrid-ext.cryst.bbk.ac.uk/portal_guide/. Conclusion: This approach is particularly (but not exclusively) appropriate for large-scale biology projects with multiple collaborators working at different national or international sites. The framework is relatively easy to set up, hides the complexity of Grid middleware from the user, and provides access to resources through a single, uniform interface. It has been developed as part of the European ImmunoGrid project

Statistical deconvolution of enthalpic energetic contributions to MHC-peptide binding affinity

Background: MHC Class I molecules present antigenic peptides to cytotoxic T cells, which forms an integral part of the adaptive immune response. Peptides are bound within a groove formed by the MHC heavy chain. Previous approaches to MHC Class I-peptide binding prediction have largely concentrated on the peptide anchor residues located at the P2 and C-terminus positions. Results: A large dataset comprising MHC-peptide structural complexes was created by re-modelling pre-determined x-ray crystallographic structures. Static energetic analysis, following energy minimisation, was performed on the dataset in order to characterise interactions between bound peptides and the MHC Class I molecule, partitioning the interactions within the groove into van der Waals, electrostatic and total non-bonded energy contributions. Conclusion: The QSAR techniques of Genetic Function Approximation (GFA) and Genetic Partial Least Squares (G/PLS) algorithms were used to identify key interactions between the two molecules by comparing the calculated energy values with experimentally-determined BL50 data. Although the peptide termini binding interactions help ensure the stability of the MHC Class I-peptide complex, the central region of the peptide is also important in defining the specificity of the interaction. As thermodynamic studies indicate that peptide association and dissociation may be driven entropically, it may be necessary to incorporate entropic contributions into future calculations

Precongruences and Parametrized Coinduction for Logics for Behavioral Equivalence

We present a new proof system for equality of terms which present elements of the final coalgebra of a finitary set functor. This is most important when the functor is finitary, and we improve on logical systems which have already been proposed in several papers. Our contributions here are (1) a new logical rule which makes for proofs which are somewhat easier to find, and (2) a soundness/completeness theorem which works for all finitary functors, in particular removing a weak pullback preservation requirement that had been used previously. Our work is based on properties of precongruence relations and also on a new parametrized coinduction principle

GPCRTree: online hierarchical classification of GPCR function

Background: G protein-coupled receptors (GPCRs) play important physiological roles transducing extracellular signals into intracellular responses. Approximately 50% of all marketed drugs target a GPCR. There remains considerable interest in effectively predicting the function of a GPCR from its primary sequence. Findings: Using techniques drawn from data mining and proteochemometrics, an alignment-free approach to GPCR classification has been devised. It uses a simple representation of a protein's physical properties. GPCRTree, a publicly-available internet server, implements an algorithm that classifies GPCRs at the class, sub-family and sub-subfamily level. Conclusion: A selective top-down classifier was developed which assigns sequences within a GPCR hierarchy. Compared to other publicly available GPCR prediction servers, GPCRTree is considerably more accurate at every level of classification. The server has been available online since March 2008 at URL: http://igrid-ext.cryst.bbk.ac.uk/gpcrtree

Enhancing Intercultural Understanding for Pre-service Teachers Through Developing and Sustaining Education Abroad Experiences

This article discusses two education abroad programs that afford pre-service teachers with purposeful opportunities to enhance their intercultural competence through immersion in teaching internships in British schools. The programs, in London and Nottingham, provide pre-service teachers with direct experiences that engage them with diverse instructional perspectives and challenge their ideas underpinning U.S. norms for teaching and learning. The Nottingham program focuses on the discipline of history and about how the past is taught, while the London program has an urban education focus that serves participants across a variety of disciplines. Both programs are a 15 week semester abroad for teaching interns following their domestic student teaching semester. Focused on teacher leadership and intercultural learning, this value-added semester builds upon four prior semesters of school placements, requires a master-level research project, and directly engages interns in school-based activities. This paper highlights the two programs with specific attention paid to purposefully facilitating intercultural learning. Implications for both initiating and sustaining international experiences for pre-service teacher education are addressed.

BOSH:Bayesian Optimization by Sampling Hierarchically

Deployments of Bayesian Optimization (BO) for functions with stochastic evaluations, such as parameter tuning via cross validation and simulation optimization, typically optimize an average of a fixed set of noisy realizations of the objective function. However, disregarding the true objective function in this manner finds a high-precision optimum of the wrong function. To solve this problem, we propose Bayesian Optimization by Sampling Hierarchically (BOSH), a novel BO routine pairing a hierarchical Gaussian process with an information-theoretic framework to generate a growing pool of realizations as the optimization progresses. We demonstrate that BOSH provides more efficient and higher-precision optimization than standard BO across synthetic benchmarks, simulation optimization, reinforcement learning and hyper-parameter tuning tasks

Promoting Intercultural Competence in Professional Spaces: Education Abroad Experiences in England for Social Studies Pre-Service Teachers

This article presents a qualitative case study of U.S. social studies pre-service teachers (PSTs) interning in England. We explore how these experiences influence their teaching and their orientation towards culture and cultural difference, and how the structure of education abroad programs are designed to support growth in cultural competence and orientations towards teaching history. Participants are enrolled in a teacher education program that affords social studies PSTs an opportunity to study abroad in England post-student teaching. For this study the developmental model of intercultural sensitivity (DMIS) provided the conceptual frame to explore intercultural competence as it presents a continuum of ethnocentric to ethnorelative perspectives (Hammer & Bennett, 2003). Using this conceptual framework, data were collected from 32 social studies PSTs representing three annual cohorts who participated in the education abroad program from 2015-2017. Data from weekly student journals were captured and qualitatively analyzed. Participants wrote journal entries prior to departure, while abroad, and upon reentry to the United States in response to instructor generated prompts. Three broad themes emerged across the data: (1) living and interning in English society challenged facets of PSTs’ cultural identity and professional practices, (2) PSTs more critically examined their orientation towards social studies education as a discipline, and (3) PSTs expanded their awareness of broader educational issues and concerns. Implications offer insight to how education abroad programs impact pre-service social studies teachers’ pedagogical practices