SeqDoC: rapid SNP and mutation detection by direct comparison of DNA sequence chromatograms

Background: This paper describes SeqDoC, a simple, web-based tool to carry out direct comparison of ABI sequence chromatograms. This allows the rapid identification of single nucleotide polymorphisms (SNPs) and point mutations without the need to install or learn more complicated analysis software. Results: SeqDoC produces a subtracted trace showing differences between a reference and test chromatogram, and is optimised to emphasise those characteristic of single base changes. It automatically aligns sequences, and produces straightforward graphical output. The use of direct comparison of the sequence chromatograms means that artefacts introduced by automatic base-calling software are avoided. Homozygous and heterozygous substitutions and insertion/deletion events are all readily identified. SeqDoC successfully highlights nucleotide changes missed by the Staden package 'tracediff' program. Conclusion: SeqDoC is ideal for small-scale SNP identification, for identification of changes in random mutagenesis screens, and for verification of PCR amplification fidelity. Differences are highlighted, not interpreted, allowing the investigator to make the ultimate decision on the nature of the change.

Molecular basis of intramolecular electron transfer in sulfite-oxidizing enzymes is revealed by high resolution structure of a heterodimeric complex of the catalytic molybdopterin subunit and a c-type cytochrome subunit

Sulfite-oxidizing molybdoenzymes convert the highly reactive and therefore toxic sulfite to sulfate and have been identified in insects, animals, plants, and bacteria. Although the well studied enzymes from higher animals serve to detoxify sulfite that arises from the catabolism of sulfur-containing amino acids, the bacterial enzymes have a central role in converting sulfite formed during dissimilatory oxidation of reduced sulfur compounds. Here we describe the structure of the Starkeya novella sulfite dehydrogenase, a heterodimeric complex of the catalytic molybdopterin subunit and a c-type cytochrome subunit, that reveals the molecular mechanism of intramolecular electron transfer in sulfite-oxidizing enzymes. The close approach of the two redox centers in the protein complex (Mo-Fe distance 16.6 angstrom) allows for rapid electron transfer via tunnelling or aided by the protein environment. The high resolution structure of the complex has allowed the identification of potential through-bond pathways for electron transfer including a direct link via Arg-55A and/or an aromatic-mediated pathway. A potential site of electron transfer to an external acceptor cytochrome c was also identified on the SorB subunit on the opposite side to the interaction with the catalytic SorA subunit.

Direct electrochemistry of human and rat NADPH cytochrome P450 reductase

The diflavo-protein NADPH cytochrome P450 reductase (CPR) is the key electron transfer partner for all drug metabolizing cytochrome P450 enzymes in humans. The protein delivers, consecutively, two electrons to the heme active site of the P450 in a carefully orchestrated process which ultimately leads to the generation of a high valent oxo-heme moiety. Despite its central role in P450 function, no direct electrochemical investigation of the purified protein has been reported. Here we report the first voltammetric study of purified human CPR where responses from both the FMN and FAD cofactors have been identified using both cyclic and square wave voltammetry. For human CPR redox responses at -2 and -278 mV (with a ratio of 1e(-):3e(-)) vs NHE were seen at pH 7.9 while the potentials for rat CPR at pH 8.0 were -20 and -254 mV. All redox responses exhibit a pH dependence of approximately -59 mV/pH unit consistent with proton coupled electron transfer reactions of equal stoichiometry. (c) 2006 Elsevier B.V. All rights reserved.

Validation of a generalized transfer function to noninvasively derive central blood pressure during exercise

Exercise brachial blood pressure ( BP) predicts mortality, but because of wave reflection, central ( ascending aortic) pressure differs from brachial pressure. Exercise central BP may be clinically important, and a noninvasive means to derive it would be useful. The purpose of this study was to test the validity of a noninvasive technique to derive exercise central BP. Ascending aortic pressure waveforms were recorded using a micromanometer-tipped 6F Millar catheter in 30 patients (56 +/- 9 years; 21 men) undergoing diagnostic coronary angiography. Simultaneous recordings of the derived central pressure waveform were acquired using servocontrolled radial tonometry at rest and during supine cycling. Pulse wave analysis of the direct and derived pressure signals was performed offline (SphygmoCor 7.01). From rest to exercise, mean arterial pressure and heart rate were increased by 20 +/- 10 mm Hg and 15 +/- 7 bpm, respectively, and central systolic BP ranged from 77 to 229 mm Hg. There was good agreement and high correlation between invasive and noninvasive techniques with a mean difference (+/- SD) for central systolic BP of -1.3 +/- 3.2 mm Hg at rest and -4.7 +/- 3.3 mm Hg at peak exercise ( for both r=0.995; P < 0.001). Conversely, systolic BP was significantly higher peripherally than centrally at rest (155 +/- 33 versus 138 +/- 32mm Hg; mean difference, -16.3 +/- 9.4mm Hg) and during exercise (180 +/- 34 versus 164 +/- 33 mm Hg; mean difference, -15.5 +/- 10.4 mm Hg; for both P < 0.001). True myocardial afterload is not reliably estimated by peripheral systolic BP. Radial tonometry and pulse wave analysis is an accurate technique for the noninvasive determination of central BP at rest and during exercise.

Models of psychological service provision under Australia's better outcomes in mental health care program

The Access to Allied Psychological Services component of Australia's Better Outcomes in Mental Health Care program enables eligible general practitioners to refer consumers to allied health professionals for affordable, evidence-based mental health care, via 108 projects conducted by Divisions of General Practice. The current study profiled the models of service delivery across these projects, and examined whether particular models were associated with differential levels of access to services. We found: 76% of projects were retaining their allied health professionals under contract, 28% via direct employment, and 7% some other way; Allied health professionals were providing services from GPs' rooms in 63% of projects, from their own rooms in 63%, from a third location in 42%; and The referral mechanism of choice was direct referral in 51% of projects, a voucher system in 27%, a brokerage system in 24%, and a register system in 25%. Many of these models were being used in combination. No model was predictive of differential levels of access, suggesting that the approach of adapting models to the local context is proving successful.

Implementation of Triple P-Positive Parenting Program in Hong Kong: Predictors of programme completion and clinical outcomes

This study examined the effectiveness of the Triple P-Positive Parenting Program in a government child health service delivery context with Chinese parents in Hong Kong. Specifically, the study sought to identify pre-intervention variables that might predict programme outcomes such as, level of clinical improvement and programme completion. Participants were 661 parents of pre-school and primary aged children participating in a group version of the Triple P-Positive Parenting Program. There were significant decreases in disruptive child behaviours, levels of parenting stress, general stress and anxiety and an increase in parenting sense of competence. Greater change in reports of child behaviour problems was related to lower levels of family income, new immigrant family status, and higher pre-intervention levels of parenting stress. The present study provides a profile of parents who are most likely to benefit from parent training programmes.

Foreign direct investment and local input linkages in Malaysia

This article examines variations in local input linkages in foreign transnational corporations in Malaysia. The extent to which transnational corporations foster such linkages, particularly in a developing host economy, has become an important issue for policy makers and others concerned with the long-term benefits associated with foreign direct investment. This article employs a unique data set, covering inward investors in the electrical and electronics industry, and analyzes in detail the determinants of variations in local input uses. The article develops a model of local input linkages, based on a transaction-cost framework using firm-specific factors, such as nationality of ownership, the age of the plant and its technology, and the extent to which firms employ locally recruited managers and engineers. In addition, the impacts of various policy measures on local input levels are discussed, and also the importance of the original motivation for investing in Malaysia. The article demonstrates that policy initiatives that target particular outcomes, such as stimulating exports or technology transfer, will result in a greater beneficial impact on the host country economy than more generic subsidies.

Foreign direct investment, access to finance, and innovation activity in Chinese enterprises

A recent, comprehensive database is used to investigate the link between inward foreign direct investment (FDI) and innovation activity in China. The results of the analysis suggest that private and collectively owned firms with foreign capital participation and those with good access to domestic bank loans innovate more than other firms do. Among enterprises not owned by the state, inward FDI at the sectoral level is positively associated with domestic innovative activity only among firms that engage in their own research and development or that have good access to domestic finance. At the sector level the effect of inward FDI into technology transfer is distinguished from the effect on domestic credit opportunities. FDI affecting credit is of little significance for state-owned enterprises and is independent of their access to finance. In contrast, better access to credit is an important channel through which FDI affects the innovation of domestic private and collectively owned enterprises.

Technology sourcing versus technology exploitation:An analysis of US foreign direct investment flows

The traditional paradigm of foreign direct investment (FDI) suggests that FDI is undertaken principally to exploit some firm-specific advantage in a foreign country which provides a locational advantage to the investor. However, recent theoretical work suggests a model of FDI in which the motivation is not to exploit existing technological advantages in a foreign country, but to access such technology and transfer it from the host economy to the investing multinational corporation via spillover effects. This paper tests the technology sourcing versus technology exploiting hypotheses for a panel of sectoral FDI flows between the United States and major OECD nations over a 15 year period. The research makes use of Patel and Vega's (Research Policy, 28, 145-55, 1999) taxonomy of sectors which are likely a priori to exhibit technology sourcing and exploiting behaviour respectively. While there is evidence that FDI flows into the United States are attracted to R and D intensive sectors, very little support is found for the technology sourcing hypothesis either for inward or outward FDI flows. The results suggest that, in aggregate, firm-specific 'ownership' effects remain powerful determinants of FDI flows.

Technology transfer to China:a study of strategy in 20 EU industrial companies

Foreign direct investment has been important in China's economic development since the early 1980s. In recent years, the volume of inward FDI into China, according to some estimates, has been second only to that into the USA. The Chinese government has emphasised the need for FDI to be coupled with the transfer of more advanced technologies to China. For foreign companies, technology transfer raises the risk of losing their technology based competitive advantage to potential competitor firms. This risk may be exacerbated by insufficient legal protection of intellectual property rights in China. After briefly reviewing the development of Chinese official policy on technology transfer, this paper considers the strategy adopted by EU companies regarding the transfer of technology; in particular in advanced technology sectors. The research on which the paper is based included an analysis of information gathered from 20 leading EU companies with investments in China and operating in high-technology sectors. Information was gathered from senior company managers based in both China and Europe during the second half of 1998. The main findings include a measure of reluctance on the part of EU companies to transfer their core technologies to China and to base R&D capability there. At the same time, the companies appear aware that this policy may be unsustainable in the longer-term in the face of Chinese official policy and a desire to expand their operations in China. While they attempt to protect their existing technological knowledge, most of them accept that there will be technology "leakage" and therefore the most effective strategy is to maintain their technological lead through R&D.

Flow and pressure drop on the shellside of cylindrical heat exchangers

This work presents pressure distributions and fluid flow patterns on the shellside of a cylindrical shell-and-tube heat exchanger. The apparatus used was constructed from glass enabling direct observation of the flow using a dye release technique and had ten traversable pressure instrumented tubes permitting detailed pressure distributions to be obtained. The `exchanger' had a large tube bundle (278 tubes) and main flow areas typical of practical designs. Six geometries were studied: three baffle spacings both with and without baffle leakage. Results are also presented of three-dimensional modelling of shellside flows using the Harwell Laboratory's FLOW3D code. Flow visualisation provided flow patterns in the central plane of the bundle and adjacent to the shell wall. Comparison of these high-lighted significant radial flow variations. In particular, separated regions, originating from the baffle tips, were observed. The size of these regions was small in the bundle central plane but large adjacent to the shell wall and extended into the bypass lane. This appeared to reduce the bypass flow area and hence the bypass flow fraction. The three-dimensional flow modelling results were presented as velocity vector and isobar maps. The vector maps illustrated regions of high and low velocity which could be prone to tube vibration and fouling. Separated regions were also in evidence. A non-uniform crossflow was discovered with, in general, higher velocities in the central plane of the bundle than near the shell wall._The form of the isobar maps calculated by FLOW3D was in good agreement with experimental results. In particular, larger pressure drops occurred across the inlet than outlet of a crossflow region and were higher near the upstream than downstream baffle face. The effect of baffle spacing and baffle leakage on crossflow and window pressure drop measurements was identified. Agreement between the current measurements, previously obtained data and commonly used design correlations/models was, in general, poor. This was explained in terms of the increased understanding of shellside flow. The bulk of previous data, which dervies from small-scale rigs with few tubes, have been shown to be unrepresentative of typical commerical units. The Heat Transfer and Fluid Flow Service design program TASC provided the best predictions of the current pressure drop results. However, a number of simple one-dimensional models in TASC are, individually, questionable. Some revised models have been proposed.

Heat transfer from molten materials to liquids

An apparatus was designed and constructed which enabled material to be melted and heated to a maximum temperature of 1000C and then flooded with a pre-heated liquid. A series of experiments to investigate the thermal interaction between molten metals (aluminium, lead and tin) and sub-cooled water were conducted. The cooling rates of the molten materials under conditions of flooding were measured with a high speed-thermocouple and recorded with a transient recorder. A simplified model for calculating heat fluxes and metal surface temperatures was developed and used. Experimental results yielded boiling heat transfer in the transition film and stable film regions of the classic boiling curve. Maximum and minimum heat fluxes were observed at nucleate boiling crisis and the Leidenfrost point respectively. Results indicate that heat transfer from molten metals to sub-cooled water is a function of temperature and coolant depth and not a direct function of the physical properties of the metals. Heat transfer in the unstable transition film boiling region suggests that boiling dynamics in this region where a stationary molten metal is under pool boiling conditions at atmospheric pressure would not initiate a fuel-coolant interaction. Low heat fluxes around the Leidenfrost point would provide efficient fuel-coolant decoupling by a stable vapour blanket to enable coarse mixing of the fuel and coolant to occur without appreciable loss of thermal energy from the fuel. The research was conducted by Gareph Boxley and was submitted for the degree of PhD at the University of Aston in Birmingham in 1980.

Mechanisms of chromium deposition and dissolution under direct and pulse reverse plating conditions

Baths containing sulphuric acid as catalyst and others with selected secondary catalysts (methane sulphonic acid - MSA, SeO2, a KBrO3/KIO3 mixture, indium, uranium and commercial high speed catalysts (HEEF-25 and HEEF-405)) were studied. The secondary catalysts influenced CCE, brightness and cracking. Chromium deposition mechanisms were studied in Part II using potentiostatic and potentiodynamic electroanalytical techniques under stationary and hydrodynamic conditions. Sulphuric acid as a primary catalyst and MSA, HEEF-25, HEEF-405 and sulphosalycilic acid as co-catalysts were explored for different rotation, speeds and scan rates. Maximum current was resolved into diffusion and kinetically limited components, and a contribution towards understanding the electrochemical mechanism is proposed. Reaction kinetics were further studied for H2SO4, MSA and methane disulphonic acid catalysed systems and their influence on reaction mechanisms elaborated. Charge transfer coefficient and electrochemical reaction rate orders for the first stage of the electrodeposition process were determined. A contribution was made toward understanding of H2SO4 and MSA influence on the evolution rate of hydrogen. Anodic dissolution of chromium in the chromic acid solution was studied with a number of techniques. An electrochemical dissolution mechanism is proposed, based on the results of rotating gold ring disc experiments and scanning electron microscopy. Finally, significant increases in chromium electrodeposition rates under non-stationary conditions (PRC mode) were studied and a deposition mechanisms is elaborated based on experimental data and theoretical considerations.

The multinational enterprise as a source of international knowledge flows:Direct evidence from Italy

This paper examines the determinants of technology transfer between parent firms and their international affiliates, and of knowledge spillovers from those affiliates to host-country firms. Using a unique data set of foreign multinational enterprise (MNE) affiliates based in Italy, we find that affiliate investment in R&D and investment in capital-embodied technology plays a significant role in determining the nature of intra-firm technology flows. However, the basis for any spillovers arising from MNE affiliates does not originate from codified knowledge associated with R&D, but rather from the productivity of the affiliate.

Technology transfer and sustainable industrial development for developing countries

This paper reports on a part of work for the UNIDO initiative on technology transfer for sustainable industrial development. The proposed technology transfer framework, adapted from the East Asian late industrialisers model, identifies two categories of countries requiring support for enhancing their technological capabilities: (a) very late industrialisers (“low income” developing countries), and (b) slow industrialisers (countries with sizeable manufacturing sectors but limited success in gaining international competitiveness) and three technology transfer routes: (a) through trade and aid to strengthen indigenous production for domestic markets (Route 1); (b) through FDI and contracting to develop export oriented firms (Route 2), and (c) through the supply chain of capital equipment and materials to develop local subcontracting capacity (Route 3). Very late industrialisers need support to start with Route 1 in selected sectors and upgrade through imported mature technologies. Appropriate product innovations are also possible. The slow industrialisers have more scope for increased technology transfer through Routes 2 and 3.