Analysis of the energies of the triple base triplets

Sixty-four sets of three-dimensional models of DNA triplex base triplets (TBT) were built up based on codons by homologous modeling method and their energies were minimized. According to sequence of TBT and orientation of the third ODN strand third, the energies of monomers and water-K+-TBT ternary complexes of TBT were analyzed. The results showed: (i) The energies of the symmetric parallel monomers are generally lower than those of the symmetric anti-parallel monomers of TBT, but the energies of the symmetric parallel ternary complexes are higher than those of the symmetric anti-parallel ternary complexes of TBT. (ii) No matter TBTs are monomers or ternary complexes, the energies of asymmetric parallel TBTs are generally lower than those of the asymmetric anti-parallel ones. (iii) Although the energies of the parallel TBTs are correlated with those of the anti-parallel ones, the energy differences are significant between them. The results here suggest the sequences of TBTs and the orientations of the third ODN strands are two of the key factors that can influence the formation and stability of TBT. (C) 2002 Elsevier Science B.V. All rights reserved.

The comparative analysis of the energies of conjugated triple base triplets and their applications

We built 64 sets of 3D models of DNA triplex base triplets (TBT) and minimized their energies. The TBTs were divided into 32 pairs of conjugated ones on the basis of their sequence characteristic, and the energies of each pair of them were compared and analyzed, the results showed: (i) The duplex DNA of which any strand contains at least a couple of A or T, has a preference for selecting the oligodeoxyribonucleic acid (ODN) strand containing abundant T to form TBT. (ii) The duplex DNA of which any strand contains at least a couple of G or C has a preference for selecting ODN containing abundant G to form symmetric antiparallel TBT, but selecting ODN containing abundant C to form asymmetric parallel TBT. (iii) The duplex DNA of which any strand contains only one of A, T, G or C has a preference for selecting ODN containing abundant pyrimidines (T or C) to form antiparallel TBT. Additionally, two examples of TBTs applications, in designing ODN to form triplex with duplex were presented. The energy calculation result revealed that 15-TCG is the best ligand of the HIV PPT duplex. The comparative analysis of energies of the conjugated TBTs provides directive significance for designing ODN strand that is easy to form triplex in theory. (C) 2002 Elsevier Science B.V. All rights reserved.

Tentative study of the coding sequences without 3-base periodicity

Fourier spectra of 120 short coding sequences (<1 200 bp) show that not all coding sequences are characterized by 3-base periodicity. Statistical analysis suggests that whether a coding sequence has 3-base periodicity may be related to the composition and distribution of bases, the usage and the order of the amino acids of the encoded protein as well as the synonymous codon usage. Generally, the content of A+U is higher than that of G+C in non-period-3 sequences, inversely in period-3 sequences. In the three codon positions, the base distribution in the non-periodic-3 sequences is more uniform than in the periodic-3 sequences. The usage biases of the amino acids and the codons in non-period-3 sequences are weaker than that in period-3 sequences. All of these phenomena should be considered sufficiently in predicting the genes and exons of DNA sequences by Fourier analysis method.

PNA(T).DNA(AT) triplexes with Hoogsteen base pairing are more favorable

Peptide nucleic acids (PNAs) are nucleic acid analogs with the deoxyribose phosphate backbone replaced by pseudo-peptide polymers to which the nucleobases are linked. The achiral, uncharged and rather flexible properties of the peptide backbone permit peptide nucleic acids more potential than oligonucleotides in application to antisence and antigenic reagents. The process of PNA binding to DNA duplex and forming triplex is the first step of PNA interacting with PNA. But there are no PNA.2DNA triplex crystal data up to date and little has been reported on the structure features and the force of the PNA.2DNA triplex. In this work, PNA(T).DNA(AT) triplexes are successfully built and the structures and forces to stabilize the triplex after optimizations and molecule dynamics are systematically examined, which are expected to aid in the application of PNAs as anticense and antigene agents.

Measuring the kinetics of amyloid fibril elongation using quartz crystal microbalances.

Kinetic measurements of amyloid growth provide insight into the free energy landscape of this supramolecular process and are crucial in the search for potent inhibitors of the main disorders with which it is associated, including Alzheimer's and Parkinson's diseases and Type II diabetes. In recent years, a new class of surface-bound biosensor assays, e.g., those based on surface plasmon resonance (SPR) and the quartz crystal microbalance (QCM) have been established as extremely valuable tools for kinetic measurements of amyloid formation. Here we describe detailed protocols of how QCM techniques can be used to monitor the elongation of amyloid fibrils in real time and to study the influence of external factors on the kinetics of amyloid growth with unprecedented accuracy.

Measuring shaft friction during earthquakes

The failure of piled foundations has been observed in many earthquake events. The manner in which a pile is able to support its applied superstructure loading during an earthquake is not yet fully understood, particularly with respect to the shaft friction capacity. In this paper, new pile group is presented which has been instrumented to measure the shaft friction distribution along the length of a pile. In addition, this pile group is able to measure the pore pressures directly beneath the pile tips. The pile group was tested in dynamic centrifuge experiments and showed differing shaft friction behaviour in dense and loose soil layers as well as strong dilation beneath the pile tips at the start of earthquake loading. A reduction in shaft friction was observed after the earthquake due to soil down-drag. © 2010 Taylor & Francis Group, London.

I did that! Measuring users' experience of agency in their own actions

Cognitive neuroscience defines the sense of agency as the experience of controlling one's own actions and, through this control, affecting the external world. We believe that the sense of personal agency is a key factor in how people experience interactions with technology. This paper draws on theoretical perspectives in cognitive neuroscience and describes two implicit methods through which personal agency can be empirically investigated. We report two experiments applying these methods to HCI problems. One shows that a new input modality - skin-based interaction - can substantially increase users' sense of agency. The second demonstrates that variations in the parameters of assistance techniques such as predictive mouse acceleration can have a significant impact on users' sense of agency. The methods presented provide designers with new ways of evaluating and refining empowering interaction techniques and interfaces, in which users experience an instinctive sense of control and ownership over their actions. Copyright 2012 ACM.

Transducer and base compliance alter the in situ 6 dof force measured from muscle during an isometric contraction in a multi-joint limb.

Although musculoskeletal models are commonly used, validating the muscle actions predicted by such models is often difficult. In situ isometric measurements are a possible solution. The base of the skeleton is immobilized and the endpoint of the limb is rigidly attached to a 6-axis force transducer. Individual muscles are stimulated and the resulting forces and moments recorded. Such analyses generally assume idealized conditions. In this study we have developed an analysis taking into account the compliances due to imperfect fixation of the skeleton, imperfect attachment of the force transducer, and extra degrees of freedom (dof) in the joints that sometimes become necessary in fixed end contractions. We use simulations of the rat hindlimb to illustrate the consequences of such compliances. We show that when the limb is overconstrained, i.e., when there are fewer dof within the limb than are restrained by the skeletal fixation, the compliances of the skeletal fixation and of the transducer attachment can significantly affect measured forces and moments. When the limb dofs and restrained dofs are matched, however, the measured forces and moments are independent of these compliances. We also show that this framework can be used to model limb dofs, so that rather than simply omitting dofs in which a limb does not move (e.g., abduction at the knee), the limited motion of the limb in these dofs can be more realistically modeled as a very low compliance. Finally, we discuss the practical implications of these results to experimental measurements of muscle actions.

An example of the use of neural computing techniques in materials science - The modelling of fatigue thresholds in Ni-base superalloys

Two adaptive numerical modelling techniques have been applied to prediction of fatigue thresholds in Ni-base superalloys. A Bayesian neural network and a neurofuzzy network have been compared, both of which have the ability to automatically adjust the network's complexity to the current dataset. In both cases, despite inevitable data restrictions, threshold values have been modelled with some degree of success. However, it is argued in this paper that the neurofuzzy modelling approach offers real benefits over the use of a classical neural network as the mathematical complexity of the relationships can be restricted to allow for the paucity of data, and the linguistic fuzzy rules produced allow assessment of the model without extensive interrogation and examination using a hypothetical dataset. The additive neurofuzzy network structure means that redundant inputs can be excluded from the model and simple sub-networks produced which represent global output trends. Both of these aspects are important for final verification and validation of the information extracted from the numerical data. In some situations neurofuzzy networks may require less data to produce a stable solution, and may be easier to verify in the light of existing physical understanding because of the production of transparent linguistic rules. © 1999 Elsevier Science S.A.

Measuring design investment in firms: Conceptual foundations and exploratory UK survey

The importance of design to company and national performance has been widely discussed, with a number of studies investigating the value or impact of design on performance. However, none of these studies has measured design investment as an input against which performance can be compared. As yet, there is no established way in which design investment might be measured. Without such a method, we cannot develop a reliable picture, akin to that for R&D spending, on the impact of design spending on company performance. This paper presents a conceptual framework for the measurement of design investment and applies this framework in a survey of UK firms. The framework describes design as being part of the creation and commercialization of new products and services. The survey highlights some surprising patterns of design spend in the reported sample and demonstrates the viability of the underpinning framework. A revised framework is proposed that situates design investment in the context of R&D. The model has implications for policy makers trying to understand the role and scale of design in the private sector, for managers wishing to optimize their design investments and for academics seeking to measure the value of design. © 2013 Published by Elsevier B.V.

A six sensor method for measuring acoustic properties in ducts.

An accurate description of sound propagation in a duct is important to obtain the sound power radiating from a source in both near and far fields. A technique has been developed and applied to decompose higher-order modes of sound emitted into a duct. Traditional experiments and theory based on two-sensor methods are limited to the plane-wave contribution to the sound field at low frequency. Due to the increase in independent measurements required, a computational method has been developed to simulate sensitivities of real measurements (e.g., noise) and optimize the set-up. An experimental rig has been constructed to decompose the first two modes using six independent measurements from surface, flush-mounted microphones. Experiments were initially performed using a loudspeaker as the source for validation. Subsequently, the sound emitted by a mixed-flow fan has been investigated and compared to measurements made in accordance with the internationally standardized in-duct fan measurement method. This method utilizes large anechoic terminations and a procedure involving averaging over measurements in space and time to account for the contribution from higher-order modes. The new method does not require either of these added complications and gives detail about the underlying modal content of the emitted sound.

Measuring EGFR Separations on Cells with ∼10 nm Resolution via Fluorophore Localization Imaging with Photobleaching

Detecting receptor dimerisation and other forms of clustering on the cell surface depends on methods capable of determining protein-protein separations with high resolution in the ∼10-50 nm range. However, this distance range poses a significant challenge because it is too large for fluorescence resonance energy transfer and contains distances too small for all other techniques capable of high-resolution in cells. Here we have adapted the technique of fluorophore localisation imaging with photobleaching to measure inter-receptor separations in the cellular environment. Using the epidermal growth factor receptor, a key cancer target molecule, we demonstrate ∼10 nm resolution while continuously covering the range of ∼10-80 nm. By labelling the receptor on cells expressing low receptor numbers with a fluorescent antagonist we have found inter-receptor separations all the way up from 8 nm to 59 nm. Our data are consistent with epidermal growth factor receptors being able to form homo-polymers of at least 10 receptors in the absence of activating ligands. © 2013 Needham et al.