Evaluation of solute-solvent interactions from solvent blue-shifts of n → π* transitions of C=O, C=S, NO2 and N=N groups: hydrogen bond energies of various donor-acceptor systems

Effects of non-polar, polar and proton-donating solvents on the n → π* transitions of C=O, C=S, NO2 and N=N groups have been investigated. The shifts of the absorption maxima in non-polar and polar solvents have been related to the electrostatic interactions between solute and solvent molecules, by employing the theory of McRAE. In solvents which can donate protons the solvent shifts are mainly determined by solute-solvent hydrogen bonding. Isobestic points have been found in the n → π* bonds of ethylenetrithio-carbonate in heptane-alcohol and heptane-chloroform solvent systems, indicating the existence of equilibria between the hydrogen bonded and the free species of the solute. Among the different proton-donating solvents studied water produces the largest blue-shifts. The blue-shifts in alcohols decrease in the order 2,2,2-trifluoroethanol, methanol, ethanol, isopropanol and t-butanol, the blue-shift in trifluoroethanol being nearly equal to that in water. This trend is exactly opposite to that for the self-association of alcohols. It is suggested that electron-withdrawing groups not merely decrease the extent of self-association of alcohols, but also increase the ability to donate hydrogen bonds. The approximate hydrogen-bond energies for several donor-acceptor systems have been estimated. In a series of aliphatio ketones and nitro compounds studied, the blue-shifts and consequently the hydrogen bond energies decrease with the decrease in the electron-withdrawing power of the alkyl groups. It is felt that electron-withdrawing groups render the chromophores better proton acceptors, and the alcohols better donors. A linear relationship between n → π* transition frequency and the infrared frequency of ethylenetrithiocarbonate has been found. It is concluded that stabilization of the electronic ground states of solute molecules by electrostatic and/or hydrogen-bond interactions determines the solvent shifts.

On the Benefits and Problems of the Object-Oriented Paradigm including a Finnish Study

Several researchers are of the opinion that there are many benefits in using the object-oriented paradigm in information systems development. If the object-oriented paradigm is used, the development of information systems may, for example, be faster and more efficient. On the other hand, there are also several problems with the paradigm. For example, it is often considered complex, it is often difficult to make use of the reuse concept and it is still immature in some areas. Although there are several interesting features in the object-oriented paradigm, there is still little comprehensive knowledge of the benefits and problems associated with it. The objective of the following study was to investigate and to gain more understanding of the benefits and problems of the object-oriented paradigm. A review of previous studies was made and twelve benefits and twelve problems were established. These benefits and problems were then analysed, studied and discussed. Further a survey and some case studies were made in order to get some knowledge on what benefits and problems with the object-oriented paradigm Finnish software companies had experienced. One hundred and four companies answered the survey that was sent to all Finnish software companies with five or more employees. The case studies were made with six large Finnish software companies. The major finding was that Finnish software companies were exceptionally positive towards the object-oriented information systems development and had experienced very few of the proposed problems. Finally two models for further research were developed. The first model presents connections between benefits and the second between problems.

Voluntary Control of Multisaccade Gaze Shifts During Movement Preparation and Execution

Ramakrishnan A, Chokhandre S, Murthy A. Voluntary control of multisaccade gaze shifts during movement preparation and execution. J Neurophysiol 103: 2400-2416, 2010. First published February 17, 2010; doi: 10.1152/jn.00843.2009. Although the nature of gaze control regulating single saccades is relatively well documented, how such control is implemented to regulate multisaccade gaze shifts is not known. We used highly eccentric targets to elicit multisaccade gaze shifts and tested the ability of subjects to control the saccade sequence by presenting a second target on random trials. Their response allowed us to test the nature of control at many levels: before, during, and between saccades. Although the saccade sequence could be inhibited before it began, we observed clear signs of truncation of the first saccade, which confirmed that it could be inhibited in midflight as well. Using a race model that explains the control of single saccades, we estimated that it took about 100 ms to inhibit a planned saccade but took about 150 ms to inhibit a saccade during its execution. Although the time taken to inhibit was different, the high subject-wise correlation suggests a unitary inhibitory control acting at different levels in the oculomotor system. We also frequently observed responses that consisted of hypometric initial saccades, followed by secondary saccades to the initial target. Given the estimates of the inhibitory process provided by the model that also took into account the variances of the processes as well, the secondary saccades (average latency similar to 215 ms) should have been inhibited. Failure to inhibit the secondary saccade suggests that the intersaccadic interval in a multisaccade response is a ballistic stage. Collectively, these data indicate that the oculomotor system can control a response until a very late stage in its execution. However, if the response consists of multiple movements then the preparation of the second movement becomes refractory to new visual input, either because it is part of a preprogrammed sequence or as a consequence of being a corrective response to a motor error.

Relation between effective atomic charge and chemical shifts in X-ray absorption spectra of transition-metal compounds

Chemical shifts of K absorption discontinuities, Delta E, of several manganese, iron and cobalt oxides with the metal in the formal oxidation states between +2 and +4, have been measured. These data, together with data in the literature on other compounds of these metals, can be fitted into the expression Delta E=aq+bq2, where q is the effective atomic charge on the metal. Theoretical considerations also support this functional relationship between Delta E and q.

29Si NMR chemical shifts in silicates

29Si chemical shifts in a wide variety of silicates in crystalline, glassy and gel states have been related to a parameter, P, which takes into account the electronegativity and the structural description of the silicate units as well as the ionic potential of the modifier cation. The relation, δ(ppm)=28.4 [1−exp(−P)]−110.5, besides having predictive value, satisfactorily accounts for all the available chemical-shifts data on silicates and shows the right kind of limiting behaviour, with δ approaching the Q0 value at large P.

Fuzzy Coherence: Making Sense of Continuity in Hypertext Narratives

Hypertexts are digital texts characterized by interactive hyperlinking and a fragmented textual organization. Increasingly prominent since the early 1990s, hypertexts have become a common text type both on the Internet and in a variety of other digital contexts. Although studied widely in disciplines like hypertext theory and media studies, formal linguistic approaches to hypertext continue to be relatively rare. This study examines coherence negotiation in hypertext with particularly reference to hypertext fiction. Coherence, or the quality of making sense, is a fundamental property of textness. Proceeding from the premise that coherence is a subjectively evaluated property rather than an objective quality arising directly from textual cues, the study focuses on the processes through which readers interact with hyperlinks and negotiate continuity between hypertextual fragments. The study begins with a typological discussion of textuality and an overview of the historical and technological precedents of modern hypertexts. Then, making use of text linguistic, discourse analytical, pragmatic, and narratological approaches to textual coherence, the study takes established models developed for analyzing and describing conventional texts, and examines their applicability to hypertext. Primary data derived from a collection of hyperfictions is used throughout to illustrate the mechanisms in practice. Hypertextual coherence negotiation is shown to require the ability to cognitively operate between local and global coherence by means of processing lexical cohesion, discourse topical continuities, inferences and implications, and shifting cognitive frames. The main conclusion of the study is that the style of reading required by hypertextuality fosters a new paradigm of coherence. Defined as fuzzy coherence, this new approach to textual sensemaking is predicated on an acceptance of the coherence challenges readers experience when the act of reading comes to involve repeated encounters with referentially imprecise hyperlinks and discourse topical shifts. A practical application of fuzzy coherence is shown to be in effect in the way coherence is actively manipulated in hypertext narratives.

Data rectification and detection of trend shifts in jet engine path measurements using median filters and fuzzy logic

Filtering methods are explored for removing noise from data while preserving sharp edges that many indicate a trend shift in gas turbine measurements. Linear filters are found to be have problems with removing noise while preserving features in the signal. The nonlinear hybrid median filter is found to accurately reproduce the root signal from noisy data. Simulated faulty data and fault-free gas path measurement data are passed through median filters and health residuals for the data set are created. The health residual is a scalar norm of the gas path measurement deltas and is used to partition the faulty engine from the healthy engine using fuzzy sets. The fuzzy detection system is developed and tested with noisy data and with filtered data. It is found from tests with simulated fault-free and faulty data that fuzzy trend shift detection based on filtered data is very accurate with no false alarms and negligible missed alarms.

Open source drug discovery- A new paradigm of collaborative research in tuberculosis drug development

It is being realized that the traditional closed-door and market driven approaches for drug discovery may not be the best suited model for the diseases of the developing world such as tuberculosis and malaria, because most patients suffering from these diseases have poor paying capacity. To ensure that new drugs are created for patients suffering from these diseases, it is necessary to formulate an alternate paradigm of drug discovery process. The current model constrained by limitations for collaboration and for sharing of resources with confidentiality hampers the opportunities for bringing expertise from diverse fields. These limitations hinder the possibilities of lowering the cost of drug discovery. The Open Source Drug Discovery project initiated by Council of Scientific and Industrial Research, India has adopted an open source model to power wide participation across geographical borders. Open Source Drug Discovery emphasizes integrative science through collaboration, open-sharing, taking up multi-faceted approaches and accruing benefits from advances on different fronts of new drug discovery. Because the open source model is based on community participation, it has the potential to self-sustain continuous development by generating a storehouse of alternatives towards continued pursuit for new drug discovery. Since the inventions are community generated, the new chemical entities developed by Open Source Drug Discovery will be taken up for clinical trial in a non-exclusive manner by participation of multiple companies with majority funding from Open Source Drug Discovery. This will ensure availability of drugs through a lower cost community driven drug discovery process for diseases afflicting people with poor paying capacity. Hopefully what LINUX the World Wide Web have done for the information technology, Open Source Drug Discovery will do for drug discovery. (C) 2011 Elsevier Ltd. All rights reserved.

Crowd Sourcing a New Paradigm for Interactome Driven Drug Target Identification in Mycobacterium tuberculosis

A decade since the availability of Mycobacterium tuberculosis (Mtb) genome sequence, no promising drug has seen the light of the day. This not only indicates the challenges in discovering new drugs but also suggests a gap in our current understanding of Mtb biology. We attempt to bridge this gap by carrying out extensive re-annotation and constructing a systems level protein interaction map of Mtb with an objective of finding novel drug target candidates. Towards this, we synergized crowd sourcing and social networking methods through an initiative `Connect to Decode' (C2D) to generate the first and largest manually curated interactome of Mtb termed `3interactome pathway' (IPW), encompassing a total of 1434 proteins connected through 2575 functional relationships. Interactions leading to gene regulation, signal transduction, metabolism, structural complex formation have been catalogued. In the process, we have functionally annotated 87% of the Mtb genome in context of gene products. We further combine IPW with STRING based network to report central proteins, which may be assessed as potential drug targets for development of drugs with least possible side effects. The fact that five of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lends credence to our unique approach.