Molecular modelling studies of binding of DACD derivatives into G-Quadruplex DNA: comparison of force field and quantum polarized ligand docking methods

The DNA G-qadruplexes are one of the targets being actively explored for anti-cancer therapy by inhibiting them through small molecules. This computational study was conducted to predict the binding strengths and orientations of a set of novel dimethyl-amino-ethyl-acridine (DACA) analogues that are designed and synthesized in our laboratory, but did not diffract in Synchrotron light.Thecrystal structure of DNA G-Quadruplex(TGGGGT)4(PDB: 1O0K) was used as target for their binding properties in our studies.We used both the force field (FF) and QM/MM derived atomic charge schemes simultaneously for comparing the predictions of drug binding modes and their energetics. This study evaluates the comparative performance of fixed point charge based Glide XP docking and the quantum polarized ligand docking schemes. These results will provide insights on the effects of including or ignoring the drug-receptor interfacial polarization events in molecular docking simulations, which in turn, will aid the rational selection of computational methods at different levels of theory in future drug design programs. Plenty of molecular modelling tools and methods currently exist for modelling drug-receptor or protein-protein, or DNA-protein interactionssat different levels of complexities.Yet, the capasity of such tools to describevarious physico-chemical propertiesmore accuratelyis the next step ahead in currentresearch.Especially, the usage of most accurate methods in quantum mechanics(QM) is severely restricted by theirtedious nature. Though the usage of massively parallel super computing environments resulted in a tremendous improvement in molecular mechanics (MM) calculations like molecular dynamics,they are still capable of dealing with only a couple of tens to hundreds of atoms for QM methods. One such efficient strategy that utilizes thepowers of both MM and QM are the QM/MM hybrid methods. Lately, attempts have been directed towards the goal of deploying several different QM methods for betterment of force field based simulations, but with practical restrictions in place. One of such methods utilizes the inclusion of charge polarization events at the drug-receptor interface, that is not explicitly present in the MM FF.

Grid warehousing of molecular dynamics protein unfolding data

With the increasing awareness of protein folding disorders, the explosion of genomic information, and the need for efficient ways to predict protein structure, protein folding and unfolding has become a central issue in molecular sciences research. Molecular dynamics computer simulations are increasingly employed to understand the folding and unfolding of proteins. Running protein unfolding simulations is computationally expensive and finding ways to enhance performance is a grid issue on its own. However, more and more groups run such simulations and generate a myriad of data, which raises new challenges in managing and analyzing these data. Because the vast range of proteins researchers want to study and simulate, the computational effort needed to generate data, the large data volumes involved, and the different types of analyses scientists need to perform, it is desirable to provide a public repository allowing researchers to pool and share protein unfolding data. This paper describes efforts to provide a grid-enabled data warehouse for protein unfolding data. We outline the challenge and present first results in the design and implementation of the data warehouse.

Teachers’ knowledge and experiences of Information Advice and Guidance: some implications for the current policy context in England

Good information and career guidance about what post-compulsory educational routes are available and where these routes lead is important in ensuring that young people make choices that are most appropriate to their needs and aspirations. Yet the Association of School and College Leaders (2011) express fears that future provision will be inadequate. This paper reports the findings from an on-line survey of 300 secondary school teachers, and follow up telephone interviews with 18 in the South East of England which explored teachers’ experiences of delivering post-compulsory educational and career guidance and their knowledge and confidence in doing so. Results suggest that teachers lack confidence in delivering information, advice and guidance outside their own area of specialism and experience. In particular, teachers knew little in relation to alternative local provision of post-16 education and lacked knowledge of more non-traditional, vocational routes. This paper will therefore raises important policy considerations with respect to supporting teachers’ knowledge, ability and confidence in delivering information in relation to future pathways and career guidance.

Information communication technologies and distance education in Sri Lanka: a case study of two universities

Sri Lanka's participation rates in higher education are low and have risen only slightly in the last few decades; the number of places for higher education in the state university system only caters for around 3% of the university entrant age cohort. The literature reveals that the highly competitive global knowledge economy increasingly favours workers with high levels of education who are also lifelong learners. This lack of access to higher education for a sizable proportion of the labour force is identified as a severe impediment to Sri Lanka‟s competitiveness in the global knowledge economy. The literature also suggests that Information and Communication Technologies are increasingly relied upon in many contexts in order to deliver flexible learning, to cater especially for the needs of lifelong learners in today‟s higher educational landscape. The government of Sri Lanka invested heavily in ICTs for distance education during the period 2003-2009 in a bid to increase access to higher education; but there has been little research into the impact of this. To address this lack, this study investigated the impact of ICTs on distance education in Sri Lanka with respect to increasing access to higher education. In order to achieve this aim, the research focused on Sri Lanka‟s effort from three perspectives: policy perspective, implementation perspective and user perspective. A multiple case study research using an ethnographic approach was conducted to observe Orange Valley University‟s and Yellow Fields University‟s (pseudonymous) implementation of distance education programmes using questionnaires, qualitative interviewing and document analysis. In total, data for the analysis was collected from 129 questionnaires, 33 individual interviews and 2 group interviews. The research revealed that ICTs have indeed increased opportunities for higher education; but mainly for people of affluent families from the Western Province. Issues identified were categorized under the themes: quality assurance, location, language, digital literacies and access to resources. Recommendations were offered to tackle the identified issues in accordance with the study findings. The study also revealed the strong presence of a multifaceted digital divide in the country. In conclusion, this research has shown that iii although ICT-enabled distance education has the potential to increase access to higher education the present implementation of the system in Sri Lanka has been less than successful.

Consumers' attitudes, trust and willingness to pay for food information

Market failure can be corrected using different regulatory approaches ranging from high to low intervention. Recently, classic regulations have been criticized as costly and economically irrational and thus policy makers are giving more consideration to soft regulatory techniques such as information remedies. However, despite the plethora of food information conveyed by different media there appears to be a lack of studies exploring how consumers evaluate this information and how trust towards publishers influence their choices for food information. In order to fill such a gap, this study investigates questions related to topics which are more relevant to consumers, who should disseminate trustful food information, and how communication should be conveyed and segmented. Primary data were collected both through qualitative (in depth interviews and focus groups) and quantitative research (web and mail surveys). Attitudes, willingness to pay for food information and trust towards public and private sources conveying information through a new food magazine were assessed using both multivariate statistical methods and econometric analysis. The study shows that consumer attitudes towards food information topics can be summarized along three cognitive-affective dimensions: the agro-food system, enjoyment and wellness. Information related to health risks caused by nutritional disorders and food safety issues caused by bacteria and chemical substances is the most important for about 90% of respondents. Food information related to regulations and traditions is also considered important for more than two thirds of respondents, while information about food production and processing techniques, life style and food fads are considered less important by the majority of respondents. Trust towards food information disseminated by public bodies is higher than that observed for private bodies. This behavior directly affects willingness to pay (WTP) for food information provided by public and private publishers when markets are shocked by a food safety incident. WTP for consumer association (€ 1.80) and the European Food Safety Authority (€ 1.30) are higher than WTP for the independent and food industry publishers which cluster around zero euro. Furthermore, trust towards the type of publisher also plays a key role in food information market segmentation together with socio-demographic and economic variables such as gender, age, presence of children and income. These findings invite policy makers to reflect on the possibility of using information remedies conveyed using trusted sources of information to specific segments of consumers as an interesting soft alternative to the classic way of regulating modern food markets.

Applications of micromorphology to understanding activity areas and site formation processes in experimental hut floors

Experimental buildings at Butser Ancient Farm and St. Fagans (UK) and Lejre (Denmark) were sampled to investigate micromorphology of known activity areas, to contribute to our understanding of the internal use of space in excavated buildings and formation processes of house floor deposits. The experimental buildings provided important information relating to activity residues and sediments over the 16 years that the buildings were in use. Specifically, these results contribute to our understanding of the routes and cycles for transportation of materials in occupation contexts, which can be used to inform archaeological studies. It has been possible to identify internal ‘hot spots’ within the buildings for the deposition of activity residues and for the formation of specific deposit types. Analysis also highlighted postdepositional alterations occurring in internal occupation deposits, which has provided a means of identifying roofed and unroofed spaces in the archaeological record.

Transaction costs, information technologies and the choice of marketplace among farmers in Northern Ghana

Using a transactions costs framework, we examine the impact of information and communication technologies (mobile phones and radios) use on market participation in developing country agricultural markets using a novel transaction-level data set of Ghanaian farmers. Our analysis of the choice of markets by farmers suggests that market information from a broader range of markets may not always induce farmers to sell in more distant markets; instead farmers may use broader market information to enhance their bargaining power in closer markets. Finally, we find weak evidence on the impact of using mobile phones in attracting farm gate buyers.

Information sources, ICTs and price information in rural agricultural markets

The spread and rapid uptake of mobile telephony in Sub-Saharan Africa has highlighted the potential role of Information Communication Technologies in improving market participation and welfare outcomes for farm producers in agricultural produce markets. This article explores the influence of different sources of information and transmission technologies on the quantum and reliability of market information flowing to farm producers, based on a survey of farm households in northern Ghana. Our results suggest that the principal role of radio broadcasts and mobile telephony is in providing a broader knowledge of markets by enhancing the quantum of market information flowing to farm producers. They do not, however, appear to have a significant impact on the quality/reliability of price information obtained by farmers for making marketing decisions. Information sources appear to be the chief determinant of the reliability of price information, with price information obtained from extension agents being the most credible. Our results provide some useful insights for the design and implementation of Market Information Systems aimed at encouraging market participation by rural farm producers in agricultural markets.

A radial basis function network classifier to maximise leave-one-out mutual information

tWe develop an orthogonal forward selection (OFS) approach to construct radial basis function (RBF)network classifiers for two-class problems. Our approach integrates several concepts in probabilisticmodelling, including cross validation, mutual information and Bayesian hyperparameter fitting. At eachstage of the OFS procedure, one model term is selected by maximising the leave-one-out mutual infor-mation (LOOMI) between the classifier’s predicted class labels and the true class labels. We derive theformula of LOOMI within the OFS framework so that the LOOMI can be evaluated efficiently for modelterm selection. Furthermore, a Bayesian procedure of hyperparameter fitting is also integrated into theeach stage of the OFS to infer the l2-norm based local regularisation parameter from the data. Since eachforward stage is effectively fitting of a one-variable model, this task is very fast. The classifier construc-tion procedure is automatically terminated without the need of using additional stopping criterion toyield very sparse RBF classifiers with excellent classification generalisation performance, which is par-ticular useful for the noisy data sets with highly overlapping class distribution. A number of benchmarkexamples are employed to demonstrate the effectiveness of our proposed approach.

Information customization and food choice

In this paper we employ a hypothetical discrete choice experiment (DCE) to examine how much consumers are willing to pay to use technology to customize their food shopping. We conjecture that customized information provision can aid in the composition of a healthier shop. Our results reveal that consumers are prepared to pay relatively more for individual specic information as opposed to generic nutritional information that is typically provided on food labels. In arriving at these results we have examined various model specications including those that make use of ex-post de-brieng questions on attribute nonattendance and attribute ranking information and those that consider the time taken to complete the survey. Our main results are robust to the various model specications we examine

Design of a unified data with business rules storage model for OLTP and OLAP systems

This paper reviews the literature concerning the practice of using Online Analytical Processing (OLAP) systems to recall information stored by Online Transactional Processing (OLTP) systems. Such a review provides a basis for discussion on the need for the information that are recalled through OLAP systems to maintain the contexts of transactions with the data captured by the respective OLTP system. The paper observes an industry trend involving the use of OLTP systems to process information into data, which are then stored in databases without the business rules that were used to process information and data stored in OLTP databases without associated business rules. This includes the necessitation of a practice, whereby, sets of business rules are used to extract, cleanse, transform and load data from disparate OLTP systems into OLAP databases to support the requirements for complex reporting and analytics. These sets of business rules are usually not the same as business rules used to capture data in particular OLTP systems. The paper argues that, differences between the business rules used to interpret these same data sets, risk gaps in semantics between information captured by OLTP systems and information recalled through OLAP systems. Literature concerning the modeling of business transaction information as facts with context as part of the modelling of information systems were reviewed to identify design trends that are contributing to the design quality of OLTP and OLAP systems. The paper then argues that; the quality of OLTP and OLAP systems design has a critical dependency on the capture of facts with associated context, encoding facts with contexts into data with business rules, storage and sourcing of data with business rules, decoding data with business rules into the facts with the context and recall of facts with associated contexts. The paper proposes UBIRQ, a design model to aid the co-design of data with business rules storage for OLTP and OLAP purposes. The proposed design model provides the opportunity for the implementation and use of multi-purpose databases, and business rules stores for OLTP and OLAP systems. Such implementations would enable the use of OLTP systems to record and store data with executions of business rules, which will allow for the use of OLTP and OLAP systems to query data with business rules used to capture the data. Thereby ensuring information recalled via OLAP systems preserves the contexts of transactions as per the data captured by the respective OLTP system.

Asymmetric information, credit market condition, and entrepreneurial finance

The issue of imperfect information plays a much more important role in financing “informationally opaque” small businesses than in financing large companies.1 This chapter examines the asymmetric information issue in entrepreneurial finance from two perspectives: the effects of relationship lending and the impacts of credit market concentration on entrepreneurial financial behavior. These two perspectives are strongly linked to each other via the asymmetric information issue in entrepreneurial finance. Existing literature has recognized the important role played by relationship lending in alleviating the problem of asymmetric information. However, mixed empirical results have been reported. For example, it has been found that the development of relationship lending can improve the availability of finance for small businesses borrowers (Petersen and Rajan, 1994) and reduce the costs of finance (Berger and Udell, 1995). Meanwhile, with monopoly power, banks may extract rents, in terms of charging higher-than-market interest rates, from small businesscustomers who have very concentrated banking relationships (Ongena and Smith, 2001). In addition, both favorable and unfavorable effects of credit market concentration on financing small businesses have been acknowledged. Small business borrowers may have to pay a higher-than-market price on loans (Degryse and Ongena, 2005) and are more likely to be financially constrained (Cetorelli, 2004) than in competitive markets. On the other hand, empirical studies have shown that market concentration create a strong motive for lenders to invest in private information from small business customers, and therefore a concentrated market is more efficient in terms of private information acquisition (Han et al., 2009b). The objective of this chapter is to investigate, by reviewing existing literature, the role played by relationship lending and the effects of market concentration on financing entrepreneurial businesses that are supposed to be informationally opaque. In the first section we review literature on the important role played by asymmetric information in entrepreneurial finance from two perspectives: asymmetric information and relationship lending, and the theoretical modeling of asymmetric information. Then we examine the relationship between capital market conditions and entrepreneurial finance and attempt to answer two questions: Why is the capital market condition important for entrepreneurial finance? and What are the effects of capital market conditions on entrepreneurial financial behavior in terms of discouraged borrowers, cash holding, and the availability and costs of finance?