Analysing the ability to retain sidechain hydrogen-bonds in mutant proteins

Motivation: Hydrogen bonds are one of the most important inter-atomic interactions in biology. Previous experimental, theoretical and bioinformatics analyses have shown that the hydrogen bonding potential of amino acids is generally satisfied and that buried unsatisfied hydrogen-bond-capable residues are destabilizing. When studying mutant proteins, or introducing mutations to residues involved in hydrogen bonding, one needs to know whether a hydrogen bond can be maintained. Our aim, therefore, was to develop a rapid method to evaluate whether a sidechain can form a hydrogen-bond. Results: A novel knowledge-based approach was developed in which the conformations accessible to the residues involved are taken into account. Residues involved in hydrogen bonds in a set of high resolution crystal structures were analyzed and this analysis is then applied to a given protein. The program was applied to assess mutations in the tumour-suppressor protein, p53. This raised the number of distinct mutations identified as disrupting sidechain-sidechain hydrogen bonding from 181 in our previous analysis to 202 in this analysis.

Modelling: promoting creativity whilst forging links between science education and design and technology education

Educational reforms in many countries currently call for the development of knowledge-based societies. In particular, emphasis is placed on the promotion of creativity, especially in the areas of science education and of design and technology education. In this paper, perceptions of the nature of creativity and of the conditions for its realization are discussed. The notion of modelling as a creative act is outlined and the scope for using modelling as a bridge between science education and design and technology education explored. A model for the creative act of modelling is proposed and its major aspects elaborated upon. Finally, strategies for forging links between the two subjects are outlined.

When does ignorance make us smart? Additional factors guiding heuristic inference

“Fast & frugal” heuristics represent an appealing way of implementing bounded rationality and decision-making under pressure. The recognition heuristic is the simplest and most fundamental of these heuristics. Simulation and experimental studies have shown that this ignorance-driven heuristic inference can prove superior to knowledge based inference (Borges, Goldstein, Ortman & Gigerenzer, 1999; Goldstein & Gigerenzer, 2002) and have shown how the heuristic could develop from ACT-R’s forgetting function (Schooler & Hertwig, 2005). Mathematical analyses also demonstrate that, under certain conditions, a “less-is-more effect” will always occur (Goldstein & Gigerenzer, 2002). The further analyses presented in this paper show, however, that these conditions may constitute a special case and that the less-is-more effect in decision-making is subject to the moderating influence of the number of options to be considered and the framing of the question.

Verifying and fixing password authentication protocol

Password Authentication Protocol (PAP) is widely used in the Wireless Fidelity Point-to-Point Protocol to authenticate an identity and password for a peer. This paper uses a new knowledge-based framework to verify the PAP protocol and a fixed version. Flaws are found in both the original and the fixed versions. A new enhanced protocol is provided and the security of it is proved The whole process is implemented in a mechanical reasoning platform, Isabelle. It only takes a few seconds to find flaws in the original and the fixed protocol and to verify that the enhanced version of the PAP protocol is secure.

A hybridised evolutionary algorithm for multi-criterion minimum spanning tree problems

A hybridised and Knowledge-based Evolutionary Algorithm (KEA) is applied to the multi-criterion minimum spanning tree problems. Hybridisation is used across its three phases. In the first phase a deterministic single objective optimization algorithm finds the extreme points of the Pareto front. In the second phase a K-best approach finds the first neighbours of the extreme points, which serve as an elitist parent population to an evolutionary algorithm in the third phase. A knowledge-based mutation operator is applied in each generation to reproduce individuals that are at least as good as the unique parent. The advantages of KEA over previous algorithms include its speed (making it applicable to large real-world problems), its scalability to more than two criteria, and its ability to find both the supported and unsupported optimal solutions.

Livestock infectious disease and climate change: a review of selected literature

It is indisputable that climate is an important factor in many livestock diseases. Nevertheless, our knowledge of the impact of climate change on livestock infectious diseases is much less certain.Therefore, the aim of the article is to conduct a systematic review of the literature on the topic utilizing available retrospective data and information. Across a corpus of 175 formal publications,limited empirical evidence was offered to underpin many of the main arguments. The literature reviewed was highly polarized and often inconsistent regarding what the future may hold. Historical explorations were rare. However, identifying past drivers to livestock disease may not fully capture the extent that new and unknown drivers will influence future change. As such, our current predictive capacity is low. We offer a number of recommendations to strengthen this capacity in the coming years. We conclude that our current approach to research on the topic is limiting and unlikely to yield sufficient, actionable evidence to inform future praxis. Therefore, we argue for the creation of a reflexive, knowledge-based system, underpinned by a collective intelligence framework to support the drawing of inferences across the literature.

Resource determinants of strategy and performance: the case of British exporters

This study adopts the RBV of the firm in order to identify critical advantage-generating resources and capabilities with strong positive export strategy and performance implications. The proposed export performance model is tested using a structural equation modeling approach on a sample of 356 British exporters. We examine the individual as well as the concurrent (simultaneous) direct and indirect effects of five resource bundles on export performance. We find that four resources/capabilities: managerial, knowledge, planning, and technology, have a significant positive direct effect on export performance, while relational and physical resources exhibited no unique positive effect. We also find that the firm’s export strategy mediates the resource-performance nexus in the case of managerial and knowledge-based resources. The theoretical and methodological grounding of this study contributes to the advancement of export related research by providing better specification of the nature of the effects – direct or indirect – of particular resource factors on export performance.

Mid-term evaluation of African Technology Policy Studies Network Phase VI Strategic Plan: for the period January 1, 2009 to December 31, 2010

The African Technology Policy Studies Network (ATPS) is a multidisciplinary network of researchers, private sector actors, policymakers and civil society. ATPS has the vision to become the leading international centre of excellence and reference in science, technology and innovation (STI) systems research, training and capacity building, communication and sensitization, knowledge brokerage, policy advocacy and outreach in Africa. It has a Regional Secretariat in Nairobi Kenya, and operates through national chapters in 29 countries (including 27 in Africa and two Chapters in the United Kingdom and USA for Africans in the Diaspora) with an expansion plan to cover the entire continent by 2015. The ATPS Phase VI Strategic Plan aims to improve the understanding and functioning of STI processes and systems to strengthen the learning capacity, social responses, and governance of STI for addressing Africa's development challenges, with a specific focus on the Millennium Development Goals (MDGs). A team of external evaluators carried out a midterm review to assess the effectiveness and efficiency of the implementation of the Strategic Plan for the period January 1, 2009 to December 31, 2010. The evaluation methodology involved multiple quantitative and qualitative methods to assess the qualitative and quantitative inputs (human resources, financial resources, time, etc.) into ATPS activities (both thematic and facilitative) and their tangible and intangible outputs, outcomes and impacts. Methods included a questionnaire survey of ATPS members and stakeholders, key informant interviews, and focus group discussions (FGDs) with members in six countries. Effectiveness of Programmes Under all six strategic goals, very good progress has been made towards planned outputs and outcomes. This is evidenced by key performance indicators (KPIs) generated from desk review, ratings from the survey respondents, and the themes that run through the FGDs. Institutional and Programme Cost Effectiveness Institutional Effectiveness: assessment of institutional effectiveness suggests that adequate management frameworks are in place and are being used effectively and transparently. Also technical and financial accounting mechanisms are being followed in accordance with grant agreements and with global good practice. This is evidenced by KPIs generated from desk review. Programme Cost Effectiveness: assessment of cost-effectiveness of execution of programmes shows that organisational structure is efficient, delivering high quality, relevant research at relatively low cost by international standards. The evidence includes KPIs from desk review: administrative costs to programme cost ratio has fallen steadily, to around 10%; average size of research grants is modest, without compromising quality. There is high level of pro bono input by ATPS members. ATPS Programmes Strategic Evaluation ATPS research and STI related activities are indeed unique and well aligned with STI issues and needs facing Africa and globally. The multi-disciplinary and trans-boundary nature of the research activities are creating a unique group of research scientists. The ATPS approach to research and STI issues is paving the way for the so called Third Generation University (3GU). Understanding this unique positioning, an increasing number of international multilateral agencies are seeking partnership with ATPS. ATPS is seeing an increasing level of funding commitments by Donor Partners. Recommendations for ATPS Continued Growth and Effectiveness On-going reform of ATPS administrative structure to continue The on-going reforms that have taken place within the Board, Regional Secretariat, and at the National Chapter coordination levels are welcomed. Such reform should continue until fully functional corporate governance policy and practices are fully established and implemented across the ATPS governance structures. This will further strengthen ATPS to achieve the vision of being the leading STI policy brokerage organization in Africa. Although training in corporate governance has been carried out for all sectors of ATPS leadership structure in recent time, there is some evidence that these systems have not yet been fully implemented effectively within all the governance structures of the organization, especially at the Board and National chapter levels. Future training should emphasize practical application with exercises relevant to ATPS leadership structure from the Board to the National Chapter levels. Training on Transformational Leadership - Leading a Change Though a subject of intense debate amongst economists and social scientists, it is generally agreed that cultural mindsets and attitudes could enhance and/or hinder organizational progress. ATPS’s vision demands transformational leadership skills amongst its leaders from the Board members to the National Chapter Coordinators. To lead such a change, ATPS leaders must understand and avoid personal and cultural mindsets and value systems that hinder change, while embracing those that enhance it. It requires deliberate assessment of cultural, behavioural patterns that could hinder progress and the willingness to be recast into cultural and personal habits that make for progress. Improvement of relationship amongst the Board, Secretariat, and National Chapters A large number of ATPS members and stakeholders feel they do not have effective communications and/or access to Board, National Chapter Coordinators and Regional Secretariat activities. Effort should be made to improve the implementation of ATPS communication strategy to improve on information flows amongst the ATPS management and the members. The results of the survey and the FGDs suggest that progress has been made during the past two years in this direction, but more could be done to ensure effective flow of pertinent information to members following ATPS communications channels. Strategies for Increased Funding for National Chapters There is a big gap between the fundraising skills of the Regional Secretariat and those of the National Coordinators. In some cases, funds successfully raised by the Secretariat and disbursed to national chapters were not followed up with timely progress and financial reports by some national chapters. Adequate training in relevant skills required for effective interactions with STI key policy players should be conducted regularly for National Chapter coordinators and ATPS members. The ongoing training in grant writing should continue and be made continent-wide if funding permits. Funding of National Chapters should be strategic such that capacity in a specific area of research is built which, with time, will not only lead to a strong research capacity in that area, but also strengthen academic programmes. For example, a strong climate change programme is emerging at University of Nigeria Nsukka (UNN), with strong collaborations with Universities from neighbouring States. Strategies to Increase National Government buy-in and support for STI Translating STI research outcomes into policies requires a great deal of emotional intelligence, skills which are often lacking in the first and second generation universities. In the epoch of the science-based or 2GUs, governments were content with universities carrying out scientific research and providing scientific education. Now they desire to see universities as incubators of new science- or technology-based commercial activities, whether by existing firms or start-ups. Hence, governments demand that universities take an active and leading role in the exploitation of their knowledge and they are willing to make funds available to support such activities. Thus, for universities to gain the attention of national leadership they must become centres of excellence and explicit instruments of economic development in the knowledge-based economy. The universities must do this while working collaboratively with government departments, parastatals, and institutions and dedicated research establishments. ATPS should anticipate these shifting changes and devise programmes to assist both government and universities to relate effectively. New administrative structures in member organizations to sustain and manage the emerging STI multidisciplinary teams Second Generation universities (2GUs) tend to focus on pure science and often do not regard the application of their know-how as their task. In contrast, Third Generation Universities (3GUs) objectively stimulate techno-starters – students or academics – to pursue the exploitation or commercialisation of the knowledge they generate. They view this as being equal in importance to the objectives of scientific research and education. Administratively, research in the 2GU era was mainly monodisciplinary and departments were structured along disciplines. The emerging interdisciplinary scientific teams with focus on specific research areas functionally work against the current mono-disciplinary faculty-based, administrative structure of 2GUs. For interdisciplinary teams, the current faculty system is an obstacle. There is a need for new organisational forms for university management that can create responsibilities for the task of know-how exploitation. ATPS must anticipate this and begin to strategize solutions for their member institutions to transition to 3Gus administrative structure, otherwise ATPS growth will plateau, and progress achieved so far may be stunted.

Jmax-pruning: a facility for the information theoretic pruning of modular classification rules

The Prism family of algorithms induces modular classification rules in contrast to the Top Down Induction of Decision Trees (TDIDT) approach which induces classification rules in the intermediate form of a tree structure. Both approaches achieve a comparable classification accuracy. However in some cases Prism outperforms TDIDT. For both approaches pre-pruning facilities have been developed in order to prevent the induced classifiers from overfitting on noisy datasets, by cutting rule terms or whole rules or by truncating decision trees according to certain metrics. There have been many pre-pruning mechanisms developed for the TDIDT approach, but for the Prism family the only existing pre-pruning facility is J-pruning. J-pruning not only works on Prism algorithms but also on TDIDT. Although it has been shown that J-pruning produces good results, this work points out that J-pruning does not use its full potential. The original J-pruning facility is examined and the use of a new pre-pruning facility, called Jmax-pruning, is proposed and evaluated empirically. A possible pre-pruning facility for TDIDT based on Jmax-pruning is also discussed.

Computationally efficient induction of classification rules with the PMCRI and J-PMCRI frameworks

In order to gain knowledge from large databases, scalable data mining technologies are needed. Data are captured on a large scale and thus databases are increasing at a fast pace. This leads to the utilisation of parallel computing technologies in order to cope with large amounts of data. In the area of classification rule induction, parallelisation of classification rules has focused on the divide and conquer approach, also known as the Top Down Induction of Decision Trees (TDIDT). An alternative approach to classification rule induction is separate and conquer which has only recently been in the focus of parallelisation. This work introduces and evaluates empirically a framework for the parallel induction of classification rules, generated by members of the Prism family of algorithms. All members of the Prism family of algorithms follow the separate and conquer approach.

Animal infectious disease and climate change: a selected review

It is indisputable that climate is an important factor in many livestock diseases. Nevertheless, our knowledge of the impact of climate change on livestock infectious diseases is much less certain. Therefore, the aim of the article is to conduct a systematic review of the literature on the topic utilizing available retrospective data and information. Across a corpus of 175 formal publications, limited empirical evidence was offered to underpin many of the main arguments. The literature reviewed was highly polarized and often inconsistent regarding what the future may hold. Historical explorations were rare. However, identifying past drivers to livestock disease may not fully capture the extent that new and unknown drivers will influence future change. As such, our current predictive capacity is low. We offer a number of recommendations to strengthen this capacity in the coming years. We conclude that our current approach to research on the topic is limiting and unlikely to yield sufficient, actionable evidence to inform future praxis. Therefore, we argue for the creation of a reflexive, knowledge-based system, underpinned by a collective intelligence framework to support the drawing of inferences across the literature.

Evaluation and revision of inferential comprehension in narrative texts: an eye movement study

We investigated the processes of how adult readers evaluate and revise their situation model during reading by monitoring their eye movements as they read narrative texts and subsequent critical sentences. In each narrative text, a short introduction primed a knowledge-based inference, followed by a target concept that was either expected (e.g., “oven”) or unexpected (e.g., “grill”) in relation to the inferred concept. Eye movements showed that readers detected a mismatch between the new unexpected information and their prior interpretation, confirming their ability to evaluate inferential information. Just below the narrative text, a critical sentence included a target word that was either congruent (e.g., “roasted”) or incongruent (e.g., “barbecued”) with the expected but not the unexpected concept. Readers spent less time reading the congruent than the incongruent target word, reflecting the facilitation of prior information. In addition, when the unexpected (but not expected) concept had been presented, participants with lower verbal (but not visuospatial) working memory span exhibited longer reading times and made more regressions (from the critical sentence to previous information) on encountering congruent information, indicating difficulty in inhibiting their initial incorrect interpretation and revising their situation model

Where were the monsoon regions and arid zones in Asia prior to the Tibetan Plateau uplift?

The impact of the Tibetan Plateau uplift on the Asian monsoons and inland arid climates is an important but also controversial question in studies of paleoenvironmental change during the Cenozoic. In order to achieve a good understanding of the background for the formation of the Asian monsoons and arid environments, it is necessary to know the characteristics of the distribution of monsoon regions and arid zones in Asia before the plateau uplift. In this study, we discuss in detail the patterns of distribution of the Asian monsoon and arid regions before the plateau uplift on the basis of modeling results without topography from a global coupled atmosphere–ocean general circulation model, compare our results with previous simulation studies and available biogeological data, and review the uncertainties in the current knowledge. Based on what we know at the moment, tropical monsoon climates existed south of 20°N in South and Southeast Asia before the plateau uplift, while the East Asian monsoon was entirely absent in the extratropics. These tropical monsoons mainly resulted from the seasonal shifts of the Inter-Tropical Convergence Zone. There may have been a quasi-monsoon region in central-southern Siberia. Most of the arid regions in the Asian continent were limited to the latitudes of 20–40°N, corresponding to the range of the subtropical high pressure year-around. In the meantime, the present-day arid regions located in the relatively high latitudes in Central Asia were most likely absent before the plateau uplift. The main results from the above modeling analyses are qualitatively consistent with the available biogeological data. These results highlight the importance of the uplift of the Tibetan Plateau in the Cenozoic evolution of the Asian climate pattern of dry–wet conditions. Future studies should be focused on effects of the changes in land–sea distribution and atmospheric CO2 concentrations before and after the plateau uplift, and also on cross-comparisons between numerical simulations and geological evidence, so that a comprehensive understanding of the evolution of the Cenozoic paleoenvironments in Asia can be achieved.

Identifying key knowledge needs for evidence-based conservation of wild insect pollinators: a collaborative cross-sectoral exercise

In response to evidence of insect pollinator declines, organisations in many sectors, including the food and farming industry, are investing in pollinator conservation. They are keen to ensure that their efforts use the best available science. We convened a group of 32 ‘conservation practitioners’ with an active interest in pollinators and 16 insect pollinator scientists. The conservation practitioners include representatives from UK industry (including retail), environmental non-government organisations and nature conservation agencies. We collaboratively developed a long list of 246 knowledge needs relating to conservation of wild insect pollinators in the UK. We refined and selected the most important knowledge needs, through a three-stage process of voting and scoring, including discussions of each need at a workshop. We present the top 35 knowledge needs as scored by conservation practitioners or scientists. We find general agreement in priorities identified by these two groups. The priority knowledge needs will structure ongoing work to make science accessible to practitioners, and help to guide future science policy and funding. Understanding the economic benefits of crop pollination, basic pollinator ecology and impacts of pesticides on wild pollinators emerge strongly as priorities, as well as a need to monitor floral resources in the landscape.