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.

A holistic method to assess building energy efficiency combining D-S theory and the evidential reasoning approach

The assessment of building energy efficiency is one of the most effective measures for reducing building energy consumption. This paper proposes a holistic method (HMEEB) for assessing and certifying building energy efficiency based on the D-S (Dempster-Shafer) theory of evidence and the Evidential Reasoning (ER) approach. HMEEB has three main features: (i) it provides both a method to assess and certify building energy efficiency, and exists as an analytical tool to identify improvement opportunities; (ii) it combines a wealth of information on building energy efficiency assessment, including identification of indicators and a weighting mechanism; and (iii) it provides a method to identify and deal with inherent uncertainties within the assessment procedure. This paper demonstrates the robustness, flexibility and effectiveness of the proposed method, using two examples to assess the energy efficiency of two residential buildings, both located in the ‘Hot Summer and Cold Winter’ zone in China. The proposed certification method provides detailed recommendations for policymakers in the context of carbon emission reduction targets and promoting energy efficiency in the built environment. The method is transferable to other countries and regions, using an indicator weighting system to modify local climatic, economic and social factors.

Information and Communications for Engineers

Information and its communication is one of the most important areas in the modern world, and its developments are advancing at an ever increasing pace. To be able to assess and evaluate the importance of these developments, an understanding of the basic principles behind them is essential for the student of engineering. This book presents these principles in a coherent and understandable manner while at the same time ensuring that the arguments are based on sound scientific theory.

On the quantum mechanical scattering statistics of many particles

The probability of a quantum particle being detected in a given solid angle is determined by the S-matrix. The explanation of this fact in time-dependent scattering theory is often linked to the quantum flux, since the quantum flux integrated against a (detector-) surface and over a time interval can be viewed as the probability that the particle crosses this surface within the given time interval. Regarding many particle scattering, however, this argument is no longer valid, as each particle arrives at the detector at its own random time. While various treatments of this problem can be envisaged, here we present a straightforward Bohmian analysis of many particle potential scattering from which the S-matrix probability emerges in the limit of large distances.

Markov models of aging: theory and practice

We review and structure some of the mathematical and statistical models that have been developed over the past half century to grapple with theoretical and experimental questions about the stochastic development of aging over the life course. We suggest that the mathematical models are in large part addressing the problem of partitioning the randomness in aging: How does aging vary between individuals, and within an individual over the lifecourse? How much of the variation is inherently related to some qualities of the individual, and how much is entirely random? How much of the randomness is cumulative, and how much is merely short-term flutter? We propose that recent lines of statistical inquiry in survival analysis could usefully grapple with these questions, all the more so if they were more explicitly linked to the relevant mathematical and biological models of aging. To this end, we describe points of contact among the various lines of mathematical and statistical research. We suggest some directions for future work, including the exploration of information-theoretic measures for evaluating components of stochastic models as the basis for analyzing experiments and anchoring theoretical discussions of aging.

Time-resolved gas-phase kinetic, quantum chemical, and RRKM studies of reactions of silylene with alcohols

Time-resolved kinetic studies of silylene, SiH2, generated by laser flash photolysis of 1-silacyclopent-3-ene and phenylsilane, have been carried out to obtain rate constants for its bimolecular reactions with methanol, ethanol, 1-propanol, 1-butanol and 2-methyl-1-butanol. The reactions were studied in the gas phase over the pressure range 1-100 Torr in SF6 bath gas, at room temperature. In the study with methanol several buffer gases were used. All five reactions showed pressure dependences characteristic of third body assisted association reactions. The rate constant pressure dependences were modelled using RRKM theory, based on Eo values of the association complexes obtained by ab initio calculation (G3 level). Transition state models were adjusted to fit experimental fall-off curves and extrapolated to obtain k∞ values in the range 1.9 to 4.5 × 10-10 cm3 molecule-1 s-1. These numbers, corresponding to the true bimolecular rate constants, indicate efficiencies of between 16 and 67% of the collision rates for these reactions. In the reaction of SiH2 + MeOH there is a small kinetic component to the rate which is second order in MeOH (at low total pressures). This suggests an additional catalysed reaction pathway, which is supported by the ab initio calculations. These calculations have been used to define specific MeOH-for-H2O substitution effects on this catalytic pathway. Where possible our experimental and theoretical results are compared with those of previous studies.

The reaction between silylene and ammonia: some gas-phase kinetic and quantum chemical studies

Time-resolved kinetic studies of the reaction of silylene, SiH2, generated by 193 nm laser flash photolysis of silacyclopent-3-ene, have been carried out in the presence of ammonia, NH3. Second order kinetics were observed. The reaction was studied in the gas phase at 10 Torr total pressure in SF6 bath gas at each of the three temperatures, 299, 340 and 400 K. The second order rate constants (laser pulse energy of 60 mJ/pulse) fitted the Arrhenius equation: log(k/cm3 molecule-1 s-1) = (-10.37 ± 0.17) + (0.36 ± 1.12 kJ mol-1)/RTln10 Experiments at other pressures showed that these rate constants were unaffected by pressure in the range 10-100 Torr, but showed small decreases in value at 3 and 1 Torr. There was also a weak intensity dependence, with rate constants decreasing at laser pulse energies of 30 mJ/pulse. Ab initio calculations at the G3 level of theory, show that SiH2 + NH3 should form an initial adduct (donor-acceptor complex), but that energy barriers are too great for further reaction of the adduct. This implies that SiH2 + NH3 should be a pressure dependent association reaction. The experimental data are inconsistent with this and we conclude that SiH2 decays are better explained by reaction of SiH2 with the amino radical, NH2, formed by photodissociation of NH3 at 193 nm. The mechanism of this previously unstudied reaction is discussed.

Characterizing intuition in information systems research

The study of intuition is an emerging area of research in psychology, social sciences, and business studies. It is increasingly of interest to the study of management, for example in decision-making as a counterpoint to structured approaches. Recently work has been undertaken to conceptualize a construct for the intuitive nature of technology. However to-date there is no common under-standing of the term intuition in information systems (IS) research. This paper extends the study of intuition in IS research by using exploratory research to cate-gorize the use of the word “intuition” and related terms in papers published in two prominent IS journals over a ten year period. The entire text of MIS Quarterly and Information Systems Research was reviewed for the years 1999 through 2008 using searchable PDF versions of these publications. As far as could be deter-mined, this is the first application of this approach in the analysis of the text of IS academic journals. The use of the word “intuition” and related terms was catego-rized using coding consistent with Grounded Theory. The focus of this research was on the first two stages of Grounded Theory analysis - the development of codes and constructs. Saturation of coding was not reached: an extended review of these publications would be required to enable theory development. Over 400 incidents of the use of “intuition”, and related terms were found in the articles reviewed. The most prominent use of the term of “intuition” was coded as “Intui-tion as Authority” in which intuition was used to validate a research objective or finding; representing approximately 37 per cent of codes assigned. The second most common coding occurred in research articles with mathematical analysis, representing about 19 per cent of the codes assigned, for example where a ma-thematical formulation or result was “intuitive”. The possibly most impactful use of the term “intuition” was “Intuition as Outcome”, representing approximately 7 per cent of all coding, which characterized research results as adding to the intui-tive understanding of a research topic or phenomena. This research contributes to a greater theoretical understanding of intuition enabling insight into the use of intuition, and the eventual development of a theory on the use of intuition in academic IS research publications. It also provides potential benefits to practi-tioners by providing insight into and validation of the use of intuition in IS man-agement. Research directions include the creation of reflective and/or formative constructs for intuition in information systems research.

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.

Evaluation frameworks for information systems integration: from a semiotic lens

Information systems integration aims at the interaction, information exchange and interoperability between information systems, devices and units. Research efforts have contributed in evaluation of information systems integration on the development of evaluation frameworks. To improve the usability and measurability of evaluation, a review of existing evaluation frameworks including their evolution and classifications of different interoperability levels is conducted. The theory of organisational semiotics is used for a comparative analysis of the frameworks and future work.

Institutional pressures on financial services firms: the role of information systems in regulatory compliance

The financial crisis of 2008 led to new international regulatory controls for the governance, risk and compliance of financial services firms. Information systems play a critical role here as political, functional and social pressures may lead to the deinstitutionalization of existing structures, processes and practices. This research examines how an investment management system is introduced by a leading IT vendor across eight client sites in the post-crisis era. Using institutional theory, it examines changes in working practices occurring at the environmental and organizational levels and the ways in which technological interventions are used to apply disciplinary effects in order to prevent inappropriate behaviors. The results extend the constructs of deinstitutionalization and identify empirical predictors for the deinstitutionalization of compliance and trading practices within financial organizations.

Service oriented approach to facility management using extended building information modelling

Facility management (FM), from a service oriented approach, addresses the functions and requirements of different services such as energy management, space planning and security service. Different service requires different information to meet the needs arising from the service. Object-based Building Information Modelling (BIM) is limited to support FM services; though this technology is able to generate 3D models that semantically represent facility’s information dynamically over the lifecycle of a building. This paper presents a semiotics-inspired framework to extend BIM from a service-oriented perspective. The extended BIM, which specifies FM services and required information, will be able to express building service information in the right format for the right purposes. The service oriented approach concerns pragmatic aspect of building’s information beyond semantic level. The pragmatics defines and provides context for utilisation of building’s information. Semiotics theory adopted in this paper is to address pragmatic issues of utilisation of BIM for FM services.

Drawing from development: towards unifying theory and development of ICT4D

Within the literature, many authors have argued that the rapid growth of the field of Information and Communication Technologies for Development (ICT4D) has resulted in an emphasis on the applications rather than on theory. However, it is clear that it is not theories, rather the integration of theory and practice, that is often lacking. To address this gap, the authors begin by exploring some of the popular theoretical approaches to ICT4D with a view to identifying those theories relevant to shared impacts: development, delivery and communication. To unify practice and theory, we offer a framework to directly assess the impact of ICT4D on development.

Applying robust control theory to solve problems in bio-medical sciences: study of an apoptotic model

Biological models of an apoptotic process are studied using models describing a system of differential equations derived from reaction kinetics information. The mathematical model is re-formulated in a state-space robust control theory framework where parametric and dynamic uncertainty can be modelled to account for variations naturally occurring in biological processes. We propose to handle the nonlinearities using neural networks.