The development of a model system and high throughput assay for the study of interactions between zinc finger proteins and DNA

It has been recognised for some time that a full code of amino acid-based recognition of DNA sequences would be useful. Several approaches, which utilise small DNA binding motifs called zinc fingers, are presently employed. None of the current approaches successfully combine a combinatorial approach to the elucidation of a code with a single stage high throughput screening assay. The work outlined here describes the development of a model system for the study of DNA protein interactions and the development of a high throughput assay for detection of such interactions. A zinc finger protein was designed which will bind with high affinity and specificity to a known DNA sequence. For future work it is possible to mutate the region of the zinc finger responsible for the specificity of binding, in order to observe the effect on the DNA / protein interactions. The zinc finger protein was initially synthesised as a His tagged product. It was not possible however to develop a high throughput assay using the His tagged zinc finger protein. The gene encoding the zinc finger protein was altered and the protein synthesised as a Glutathione S-Transferase (GST) fusion product. A successful assay was developed using the GST protein and Scintillation Proximity Assay technology (Amersham Pharmacia Biotech). The scintillation proximity assay is a dynamic assay that allows the DNA protein interactions to be studied in "real time". This assay not only provides a high throughput method of screening zinc finger proteins for potential ligands but also allows the effect of addition of reagents or competitor ligands to be monitored.

A comparison of two distributed large-volume measurement systems:the mobile spatial co-ordinate measuring system and the indoor global positioning system

Advances in the area of industrial metrology have generated new technologies that are capable of measuring components with complex geometry and large dimensions. However, no standard or best-practice guides are available for the majority of such systems. Therefore, these new systems require appropriate testing and verification in order for the users to understand their full potential prior to their deployment in a real manufacturing environment. This is a crucial stage, especially when more than one system can be used for a specific measurement task. In this paper, two relatively new large-volume measurement systems, the mobile spatial co-ordinate measuring system (MScMS) and the indoor global positioning system (iGPS), are reviewed. These two systems utilize different technologies: the MScMS is based on ultrasound and radiofrequency signal transmission and the iGPS uses laser technology. Both systems have components with small dimensions that are distributed around the measuring area to form a network of sensors allowing rapid dimensional measurements to be performed in relation to large-size objects, with typical dimensions of several decametres. The portability, reconfigurability, and ease of installation make these systems attractive for many industries that manufacture large-scale products. In this paper, the major technical aspects of the two systems are briefly described and compared. Initial results of the tests performed to establish the repeatability and reproducibility of these systems are also presented. © IMechE 2009.

Collaborative filtering and deep learning based recommendation system for cold start items

Recommender system is a specific type of intelligent systems, which exploits historical user ratings on items and/or auxiliary information to make recommendations on items to the users. It plays a critical role in a wide range of online shopping, e-commercial services and social networking applications. Collaborative filtering (CF) is the most popular approaches used for recommender systems, but it suffers from complete cold start (CCS) problem where no rating record are available and incomplete cold start (ICS) problem where only a small number of rating records are available for some new items or users in the system. In this paper, we propose two recommendation models to solve the CCS and ICS problems for new items, which are based on a framework of tightly coupled CF approach and deep learning neural network. A specific deep neural network SADE is used to extract the content features of the items. The state of the art CF model, timeSVD++, which models and utilizes temporal dynamics of user preferences and item features, is modified to take the content features into prediction of ratings for cold start items. Extensive experiments on a large Netflix rating dataset of movies are performed, which show that our proposed recommendation models largely outperform the baseline models for rating prediction of cold start items. The two proposed recommendation models are also evaluated and compared on ICS items, and a flexible scheme of model retraining and switching is proposed to deal with the transition of items from cold start to non-cold start status. The experiment results on Netflix movie recommendation show the tight coupling of CF approach and deep learning neural network is feasible and very effective for cold start item recommendation. The design is general and can be applied to many other recommender systems for online shopping and social networking applications. The solution of cold start item problem can largely improve user experience and trust of recommender systems, and effectively promote cold start items.

The DRAMA methodology for analysing strategy and its links with production system design

This paper describes a methodology: 'decision rules for analyzing manufacturing activities', which is designed to be a practical system of enquiry linking a strategic analysis to the design of production systems. The paper describes the development of the system, an industry specific design methodology, into DRAMA II which is a model that serves as an analytical tool for studying decision processes and implementation of production systems.

Ingroup and outgroup minorities:differential impact upon public and private responses

The experiment which is presented in this paper was designed to overcome some of the problems associated with previous research investigating the effects of social categorization and minority influence. Sixty-eight fourteen-year-old British Secondary School pupils indicated their attitudes towards a 'grant for pupils' before and after reading a text which advocated a minority position. The text was attributed as being the work of either pupils from their own school (ingroup minority) or from a school they discriminated against (outgroup minority). Responses were either made in ‘public’ (by telling subjects that other pupils would see their responses) or in ‘private’ (by subjects putting their responses into a ‘ballot box’). The results showed that on public responses ingroup minorities had more influence than outgroup minorities while there was no difference on private responses. Also, greater change occurred when responses were made in private than in public. These results are compatible with the intergroup analysis of minority influence.

Bifurcation study for a vertical channel with constant flux and large aspect ratio

Using suitable coupled Navier-Stokes Equations for an incompressible Newtonian fluid we investigate the linear and non-linear steady state solutions for both a homogeneously and a laterally heated fluid with finite Prandtl Number (Pr=7) in the vertical orientation of the channel. Both models are studied within the Large Aspect Ratio narrow-gap and under constant flux conditions with the channel closed. We use direct numerics to identify the linear stability criterion in parametric terms as a function of Grashof Number (Gr) and streamwise infinitesimal perturbation wavenumber (making use of the generalised Squire’s Theorem). We find higher harmonic solutions at lower wavenumbers with a resonance of 1:3exist, for both of the heating models considered. We proceed to identify 2D secondary steady state solutions, which bifurcate from the laminar state. Our studies show that 2D solutions are found not to exist in certain regions of the pure manifold, where we find that 1:3 resonant mode 2D solutions exist, for low wavenumber perturbations. For the homogeneously heated fluid, we notice a jump phenomenon existing between the pure and resonant mode secondary solutions for very specific wavenumbers .We attempt to verify whether mixed mode solutions are present for this model by considering the laterally heated model with the same geometry. We find mixed mode solutions for the laterally heated model showing that a bridge exists between the pure and 1:3 resonant mode 2D solutions, of which some are stationary and some travelling. Further, we show that for the homogeneously heated fluid that the 2D solutions bifurcate in hopf bifurcations and there exists a manifold where the 2D solutions are stable to Eckhaus criterion, within this manifold we proceed to identify 3D tertiary solutions and find that the stability for said 3D bifurcations is not phase locked to the 2D state. For the homogeneously heated model we identify a closed loop within the neutral stability curve for higher perturbation wavenumubers and analyse the nature of the multiple 2D bifurcations around this loop for identical wavenumber and find that a temperature inversion occurs within this loop. We conclude that for a homogeneously heated fluid it is possible to have abrup ttransitions between the pure and resonant 2D solutions, and that for the laterally heated model there exist a transient bifurcation via mixed mode solutions.

Fast x-ray spectroscopy study of ethene on clean and SO4 precovered Pt{111}

The adsorption and decomposition of ethylene over a Pt{111} single crystalsurface has been investigated by fast x-ray spectroscopy. At 100 K ethene displays precursor-mediated adsorption kinetics, adopting a single environment with a saturation C2H4 coverage of 0.25 ML and binding energy of 283.2 eV. Thermal decomposition proceeds above 240 K via dehydrogenation to ethylidyne with an activation barrier of 57±3 kJ mol−1 and preexponential factor ν=1×1010±0.5 s−1. Site-blocking by preadsorbed SO4 reduces the saturation ethene coverage but induces a new, less reactive π-bonded ethene species centered around 283.9 eV, which in turn decomposes to ethylidyne at 350 K.

A fast XPS study of propene decomposition over clean and sulphated Pt{111}

The thermal decomposition of propene over clean and sulphate precovered Pt{111} has been followed by Fast XPS. The saturation propene coverage over the clean surface is 0.21 mL at 90 K. Propene is stable up to 200 K, above which molecular desorption and dehydrogenation result in the formation of a stable propylidyne intermediate adlayer at 300 K. Propylidyne decomposes above 400 K eventually forming graphitic carbon above 800 K. Preadsorbed surface sulphate promotes room temperature propene combustion associated with the decomposition of a thermally unstable alkyl--sulphate complex. Propylidyne also forms as on clean Pt{111}, but is less reactive, its decomposition above 450 K triggering partial oxidation with residual surface oxygen to liberate gas phase CO.

Diabetic retinopathy and blockade of the renin–angiotensin system:new data from the DIRECT study programme

The pathogenesis and medical management of diabetic retinopathy is reviewed. The importance of good control of blood glucose and blood pressure remain key elements in the prevention and treatment of diabetic retinopathy, and a number of specific metabolic pathways have been identified that may be useful additional targets for therapeutic intervention. Trial data, however, aimed specifically to answer the questions of optimum medical management are limited, so the DIRECT study of renin-angiotensin blockade using oral candesartan 32 mg daily is a welcome addition to our knowledge. This arose from the promising improvement of retinopathy outcomes in the EUCLID study of lisinopril in type I diabetes. In DIRECT, 5 years of candesartan treatment in type I diabetes reduced the incidence of retinopathy by two or more steps (EDTRS) in severity by 18% (P = 0.0508) and, in a post hoc analysis, reduced the incidence of retinopathy by three-step progression by 35% (P = 0.034). In type I diabetes patients there was no effect on progression of established retinopathy. In contrast, in type II diabetes, 5 years of candesartan treatment resulted in 34% regression of retinopathy (P ≤0.009). Importantly, an overall significant change towards less-severe retinopathy was noted in both type I and II diabetes (P0.03). Although there is still no absolute proof that these effects were specific to RAS blockade, or just an effect of lower blood pressure, it is reasonable to conclude that candesartan has earned a place in the medical management of diabetic retinopathy, to prevent the problem in type I diabetes and to treat the early stages in type II diabetes. © 2010 Macmillan Publishers Limited All rights reserved.

A distributed and key-position fiber sensing system based on LPFG and WFBG assisted OTDR

An enhanced fiber sensing system used for distributed bending and key-position sensing is reported by integrating WFBGs, LPFG and OTDR, which also achieves strain and temperature sensitivities up to 0.047mv/με and 0.675mv/°C respectively. © 2014 OSA.

Extended reach of 116 Gb/s DP-QPSK transmission using random DFB fiber laser based Raman amplification and bidirectional second-order pumping

We propose a novel random DFB fiber laser based Raman amplification using bidirectional second-order pumping. This extends the reach of 116 Gb/s DP-QPSK WDM transmission up to 7915 km, compared with other Raman amplification techniques.

Transmission performance improvement using random DFB laser based Raman amplification and bidirectional second-order pumping

We demonstrate that a distributed Raman amplification scheme based on random distributed feedback (DFB) fiber laser enables bidirectional second-order Raman pumping without increasing relative intensity noise (RIN) of the signal. This extends the reach of 10 × 116 Gb/s DP-QPSK WDM transmission up to 7915 km, compared with conventional Raman amplification schemes. Moreover, this scheme gives the longest maximum transmission distance among all the Raman amplification schemes presented in this paper, whilst maintaining relatively uniform and symmetric signal power distribution, and is also adjustable in order to be highly compatible with different nonlinearity compensation techniques, including mid-link optical phase conjugation (OPC) and nonlinear Fourier transform (NFT).