1.2-μm semiconductor disk laser frequency doubled with periodically poled lithium tantalate crystal

In this letter, we demonstrate an optically pumped semiconductor disk laser frequency doubled with a periodically poled lithium tantalate crystal. Crystals with various lengths were tested for intracavity frequency conversion. The semiconductor disk laser exploited GaInNAs-based active region with GaAsAlAs distributed Bragg mirror to produce emission at 1.2- μm wavelength. The frequency doubled power up to 760 mW at the wavelength of 610 nm was achieved with a 2-mm-long crystal. © 2010 IEEE.

73 nm wavelength tuning from a frequency-doubled quantum-dot laser in PPKTP waveguides

A compact all-room-temperature CW 73-nm tunable laser source in the visible spectral region (574nm-647nm) has been demonstrated by frequency-doubling of a broadly-tunable InAs/GaAs quantum dot external-cavity diode laser in periodically-poled potassium titanyl phosphate waveguides with a maximum output power in excess of 12mW and a maximum conversion efficiency exceeding 10%. Three waveguides with different cross-sectional areas (4×4μm2, 3×5μm2 and 2x6μm2) were investigated. Introduction - Development of compact broadly tunable laser sources in the visible spectral region is currently very attractive area of research with applications ranging from photomedicine and biophotonics to confocal fluorescence microscopy and laser projection displays. In this respect, semiconductor lasers with their small size, high efficiency, reliability and low cost are very promising for realization of such sources by frequency­doubling of the infrared light in nonlinear crystal waveguides. Furthermore, the wide tunability offered by quantum-dot (QD) external-cavity diode lasers (ECDL), due to the temperature insensibility and broad gain bandwidth [1,2], is very promising for the development of tunable visible laser sources [3,4]. In this work we show a compact green-to-red tunable all­room-temperature CW laser source using a frequency-doubled InAs/GaAs QD-ECDL in periodically-poled potassium titanyl phosphate (PPKTP) crystal waveguides. This laser source generates frequency-doubled light over the 574nm-647nm wavelength range utilizing the significant difference in the effective refractive indices of high-order and low-order modes in multimode waveguides [3]. Experimental results - Experimental setup used in this work was similar to that described in [3] and consisted of a QD gain chip in the quasi­Littrow configuration and a PPKTP waveguide. Coarse wavelength tuning of the QD-ECDL between 1140 nm and 1300 nm at 20°C was possible for pump current of 1.5 A. The laser output was coupled into the PPKTP waveguide using an AR-coated 40x aspheric lens (NA ~ 0.55). The PPKTP frequency-doubling crystal (not AR coated) used in our work was 18 mm in length and was periodically poled for SHG (with the poling period of ~ 11.574 11m). The crystal contained 3 different waveguides with cross-sectional areas of ~ 4x4 11m2, 3x5 11m2 and 2x6 11m2. Both the pump laser and the PPKTP crystal were operating at room temperature. The waveguides with cross-sectional areas of 4x411m2, 3x511m2 and 2x611m2 demonstrated the tunability in the wavelength ranges of 577nm - 647nm, 576nm -643nm and 574nm - 641nm, respectively, with a maximum output power of 12.04mW at 606 nm Conclusion - We demonstrated a compact all-room-temperature broadly­tunable laser source operating in the visible spectral region between 574nm and 647nm. This laser source is based on second harmonic generation in PPKTP waveguides with different cross-sectional areas using an InAs/GaAs QD-ECDL References [I] E.U. Rafailov, M.A. Cataluna, and W. Sibbett, Nat. Phot. 1,395 (2007). [2] K.A. Fedorova, M.A. Cataluna, I. Krestnikov, D. Livshits, and E.U. Rafailov, Opt. Express 18(18), 19438-19443 (2010). [3] K.A. Fedorova, G.S. Sokolovskii, P.R. Battle, D.A. Livshits, and E.U. Rafailov, Laser Phys. Lett. 9, 790-795 (2012). [4] K.A. Fedorova,G.S. Sokolovskii, D.T. Nikitichev, P.R. Battle, I.L. Krestnikov, D.A. Livshits, and E.U. Rafailov, Opt. Lett. 38(15), 2835-2837 (2013) © 2014 IEEE.

Binocular combination at threshold: temporal filtering and summation of signals in separate ON and OFF channels

How does the brain combine spatio-temporal signals from the two eyes? We quantified binocular summation as the improvement in 2AFC contrast sensitivity for flickering gratings seen by two eyes compared with one. Binocular gratings in-phase showed sensitivity up to 1.8 times higher, suggesting nearly linear summation of contrasts. The binocular advantage decreased to 1.4 at lower spatial and higher temporal frequencies (0.25 cycle deg-1, 30 Hz). Dichoptic, antiphase gratings showed only a small binocular advantage, by a factor of 1.1 to 1.2, but no evidence of cancellation. We present a signal-processing model to account for the contrast-sensitivity functions and the pattern of binocular summation. It has linear sustained and transient temporal filters, nonlinear transduction, and half-wave rectification that creates ON and OFF channels. Binocular summation occurs separately within ON and OFF channels, thus explaining the phase-specific binocular advantage. The model also accounts for earlier findings on detection of brief antiphase flashes and the surprising finding that dichoptic antiphase flicker is seen as frequency-doubled (Cavonius et al, 1992 Ophthalmic and Physiological Optics 12 153 - 156). [Supported by EPSRC project GR/S74515/01].

The effect of antifoams upon recombinant protein production in yeast

Foaming during fermentation reduces the efficiency of the process leading to increased costs and reduced productivity. Foaming can be overcome by the use of chemical antifoaming agents, however their influence upon the growth of organisms and protein yield is poorly understood. The objective of this work was to evaluate the effects of different antifoams on recombinant protein production. Antifoam A, Antifoam C, J673A, P2000 and SB2121 were tested at different concentrations for their effect on the growth characteristics of Pichia pastoris producing GFP, EPO and A2aR and the yield of protein in shake flasks over 48 h. All antifoams tested increased the total GFP in the shake flasks compared to controls, at higher concentrations than would normally be used for defoaming purposes. The highest yield was achieved by adding 1 % P2000 which nearly doubled the total yield followed by 1 % SB2121, 1 % J673A, 0.6 % Antifoam A and lastly 0.8 % Antifoam C. The antifoams had a detrimental effect upon the production of EPO and A2aR in shake flasks, suggesting that their effects may be protein specific. The mechanisms of action of the antifoams was investigated and suggested that although the volumetric mass oxygen transfer coefficient (kLa) was influenced by the agents, their effect upon the concentration of dissolved oxygen did not contribute to the changes in growth or recombinant protein yield. Findings in small scale also suggested that antifoams of different compositions such as silicone polymers and alcoxylated fatty acid esters may influence growth characteristics of host organisms and the ability of the cells to secrete recombinant protein, indirectly affecting the protein yield. Upon scale-up, the concentration effects of the antifoams upon GFP yield in bioreactors was reversed, with lower concentrations producing a higher yield. These data suggest that antifoam can affect cells in a multifactorial manner and highlights the importance of screening for optimum antifoam types and concentrations for each bioprocesses.

Optical fibre sensors and their interrogation

This thesis describes novel developments in the fabrication and understanding of type IA fibre Bragg gratings, the uses of said gratings as optical sensors and the interrogation of optical sensors using tilted fibre Bragg gratings. This thesis presents the most detailed study of type IA gratings performed to date and provides the basis of a dual grating optical sensor capable of independently measuring strain and temperature. Until this work it was not known how to reliably fabricate type IA gratings or how they would react to high ambient temperatures, nor was it known what effect external parameters such as fibre type, dopant levels, inscription laser intensity, or hydrogenation levels would have on the physical properties of the grating. This comprehensive study has yielded answers to all of these unknowns and produced several unexpected uses for type IA gratings, such as the use of the previously unreported strong loss band at 1400nm to locally heat fibres by optical absorption and thereby fabricate optically tuneable gratings which do not affect directly adjacent standard gratings. Blazed fibre Bragg gratings have been studied in detail and used to produce several high quality prototype sensor interrogation systems yielding stability an accuracy values unsurpassed by similar devices reported in literature. An accurate distribution map of light radiated by blazed gratings is shown for the first time and has been studied in respect of polarisation state showing that for certain easily achievable conditions a blazed grating spectrometer may be deemed to be polarisation insensitive. In a novel implementation of the system, it is shown that the dynamic wavelength range of a blazed grating spectrometer may be at least doubled by superimposing blazed gratings.

Biosynthesis and separation of dextran fructose mixtures in a chromatographic reactor

A literature review of work carried out on batch and continuous chromatographic biochemical reactor-separators has been made. The major part of this work has involved the development of a batch chromatographic reactor-separator for the production of dextran and fructose by the enzymatic action of the enzyme dextransucrase on sucrose. In this reactor, simultaneous reaction and separation occurs thus reducing downstream processing and isolation of products as compared to the existing industrial process. The chromatographic reactor consisted of a glass column packed with a stationary phase consisting of cross linked polysytrene resin in the calcium form. The mobile phase consisted of diluted dextransucrase in deionised water. Initial experiments were carried out on a reactor separtor which had an internal diameter of 0.97cm and length of 1.5m. To study the effect of scale up the reactor diameter was doubled to 1.94cm and length increased to 1.75m. The results have shown that the chromatographic reactor uses more enzyme than a conventional batch reactor for a given conversion of sucrose and that an increase in void volume results in higher conversions of sucrose. A comparison of the molecular weight distribution of dextran produced by the chromatographic reactor was made with that from a conventional batch reactor. The results have shown that the chromatographic reactor produces 30% more dextran of molecular weight greater than 150,000 daltons at 20% w/v sucrose concentration than conventional reactors. This is because some of the fructose molecules are prevented as acting as acceptors in the chromatographic reactor due to their removal from the reaction zone. In the conventional reactor this is not possible and therefore a greater proportion of low molecular weight dextran is produced which does not have much clinical use. A theoretical model was developed to describe the behaviour of the reactor separator and this model was simulated using a computer. The simulation predictions showed good agreement with experimental results at high eluent flowrates and low conversions.

Foreign direct investment and corruption

In the last few decades, the world has witnessed an enormous growth in the volume of foreign direct investment (FDI). The global stock of FDI reached US$ 7.5 trillion in 2003 and accounted for 11% of world Gross Domestic Product, up from 7% in 1990. The sales of multinational enterprises at around US$ 19 trillion were more than double the level of world exports. Substantial FDI inflows went into transition countries. Inflows into one of the region's largest recipient, the Russian Federation, almost doubled, enabling Russia to become one of the five top FDI destinations in 2005-2006. FDI inflows in Russia have increased almost threefold from 13.6% in 2003 to 35% in 2007. In 2003, these flows were twice greater than those into China; whilst in 2007 they were six times larger. Russia's FDI inflows were also about 2.5 times greater than those of Brazil. Efficient government institutions are argued by many economists to foster FDI and growth as a result. However, the magnitude of this effect has yet to be measured. This thesis takes a Political Economy approach to explore, empirically, the potential impact of malfunctioning governmental institutions, proxied by three indices of perceived corruption, on FDI stocks accumulation/distribution within Russia over the period of 2002-2004. Using a regional data-set it concentrates on three areas relating to FDI. Firstly, it considers the significance, the size and the sign of the impact of perceived corruption on accumulation of FDI stocks within Russia. Secondly, it quantifies the impact of perceived corruption on the volume of FDI stocks simultaneously estimating the impact of the investment in public capital such as telecommunications and transportation networks on FDI in the presence of corruption. In particular, it addresses the question whether more corrupt regions in Russia are also those that could have accumulated more of FDI stocks, and investigates whether those 'more corrupt' regions would have had lower level of public capital investment. Finally, it examines whether decentralisation increases or decreases corruption and whether a larger extent of decentralisation has a positive or negative impact on FDI (stocks). The results of three studies are as follows. Firstly, along with market potential, corruption is found to be one of the key factors in explaining FDI distribution within Russia between 2002 and 2004. Secondly, corruption on average is found to be related to FDI positively suggesting that it may act as speed money: to save their time foreign direct investors might be willing to bribe the regional authorities so to move in front of the bureaucratic lines. Thirdly, although when corruption is controlled for, the impact of the latter on unobservable FDI is found to be on average positive, no association between FDI and public investment is observed with the only exception of transportation infrastructure (i.e., railway). The results might suggest therefore that it is possible that not only regions with high levels of perceived corruption attract more FDI but also that expansions in public capital investments are not accompanied by an increase of the volume of FDI (stocks) in regions with high levels of corruption. This casts some doubt on the productivity of the investment in public capital in these regions as it might be that bureaucrats may prefer to use these infrastructural projects for rent extraction. Finally, we find decentralisation to have a significant and positive impact on both FDI stock accumulation and corruption, suggesting that local governments may spend more on public goods to make the area more attractive to foreign investors but at the same time they may be interested into extracting rents from foreign investors. These results support the idea that the regulation of FDI is associated with and facilitated by a larger public sector, which distorts competition and introduces opportunities for rent-seeking by particular economic and political factors.

The role of insulin and the insulin-like growth factors in the proliferation of the rat thymic lymphocyte

Concanavalin A, provoked a 35-fold increase in the rate of proliferation of rat thymocytes. Insulin (10-6M), and insulin-like growth factor I (10-10M) approximately doubled the rate of DNA synthesis. Both of these structurally related molecules acted through the type I insulin-like growth factor receptor. The sequential addition of Concanavalin A and insulin, promoted a much greater proliferative response than to either of the two agonists alone. Insulin also increased the uptake of glucose and amino acids by the cells. Glucose uptake was enhanced at insulin concentrations of 10-6M and 10-10M. Amino acid uptake was more strongly affected at the higher concentration. Insulin-like growth factor I (10-11M) also enhanced amino acid uptake. The effects of insulin on metabolism were mediated by both insulin and type I insulin-like growth factor receptors. These effects were greatly enhanced after a pre-treatment with Concanavalin A. Concanavalin A provided a primary mitogenic signal to the cells. Amongst the responses was an increased expression of insulin and/or type I insulin-like growth factor receptors. The consequent enhanced cellular sensitivity to these agonists, enabled them to facilitate the passage of the cells through the cell cycle by: i) providing a secondary mitogenic signal, and ii) promoting the uptake of raw materials and energy substrates. The initiation of DNA synthesis and passage through the cell cycle was thus punctuated by the sequential expression of various cell surface receptors. This regulated cellular sensitivity, enabling them to react in a precisely orchestrated fashion to hormones and other molecules in their environment. The intracellular mechanism of insulin action remains an enigma. Although the presence of extracellular calcium was essential for insulin stimulation of amino acid uptake and DNA synthesis, the cation did not subserve a direct mediator function. Insulin promoted an increase in intracellular pH, which was mediated by the Na+/H+ antiport. Other mechanisms were probably also involved in mediating the full cellular response to insulin.

Land use monitoring in the Nigerian savanna using aerial photographs

Aerial photography was used to determine the land use in a test area of the Nigerian savanna in 1950 and 1972. Changes in land use were determined and correlated with accessibility, appropriate low technology methods being used to make it easy to extend the investigation to other areas without incurring great expense. A test area of 750 sq km was chosen located in Kaduna State of Nigeria. The geography of the area is summarised together with the local knowledge which is essential for accurate photo interpretation. A land use classification was devised and tested for use with medium scale aerial photography of the savanna. The two sets of aerial photography at 1:25 000 scale were sampled using systematic dot grids. A dot density of 8 1/2 dots per sq km was calculated to give an acceptable estimate of land use. Problems of interpretation included gradation between categories, sample position uncertainty and personal bias. The results showed that in 22 years the amount of cultivated land in the test area had doubled while there had been a corresponding decrease in the amount of uncultivated land particularly woodland. The intensity of land use had generally increased. The distribution of land use changes was analysed and correlated with accessibility. Highly significant correlations were found for 1972 which had not existed in 1950. Changes in land use could also be correlated with accessibility. It was concluded that in the 22 year test period there had been intensification of land use, movement of human activity towards the main road, and a decrease in natural vegetation particularly close to the road. The classification of land use and the dot grid method of survey were shown to be applicable to a savanna test area.

Pain response and follow-up of patients undergoing panretinal laser photocoagulation with reduced exposure times

Purpose - We performed a study of laser panretinal photocoagulation in 20 patients with proliferative retinopathy. We compared short exposure, high-energy laser settings with conventional settings, using a 532?nm, frequency doubled, Neodymium–Yag laser and assessed the patients in terms of pain experienced and effectiveness of treatment. Methods - Twenty patients having panretinal photocoagulation for the first time underwent random allocation to treatment of the superior and inferior hemi-retina. Treatment A used ‘conventional’ parameters: exposure time 0.1?s, power sufficient to produce a visible grey-white burns, spot size 300?µm. The other hemi- retina was treated with treatment B using exposure 0.02?s, 300?µm and sufficient power to have similar endpoint. All patients were asked to evaluate severity of pain on a visual analogue scale. (0=no pain, 10=most severe pain). All patients were masked as to the type of treatment and the order of carrying out the treatment on each patient was randomised. Patients underwent fundus photography and were followed up for 6–45 months. Results - Seventeen patients had proliferative diabetic retinopathy, two had ischaemic central retinal vein occlusion and one had ocular ischaemic syndrome. The mean response to treatment A was 5.11, compared to 1.40 treatment B, on the visual analogue scale, which was statistically significant (P=0.001). All patients preferred treatment B. Further treatments, if required, were performed with treatment B parameters and long-term follow-up has shown no evidence of undertreatment. Conclusions - Shortening exposure time of retinal laser is significantly less painful but equally effective as conventional parameters.

Antiproliferative effects of carbon monoxide on pancreatic cancer

Background - Carbon monoxide, the gaseous product of heme oxygenase, is a signalling molecule with a broad spectrum of biological activities. The aim of this study was to investigate the effects of carbon monoxide on proliferation of human pancreatic cancer. Methods - In vitro studies were performed on human pancreatic cancer cells (CAPAN-2, BxPc3, and PaTu-8902) treated with a carbon monoxide-releasing molecule or its inactive counterpart, or exposed to carbon monoxide gas (500 ppm/24 h). For in vivo studies, pancreatic cancer cells (CAPAN-2/PaTu-8902) were xenotransplanted subcutaneously into athymic mice, subsequently treated with carbon monoxide-releasing molecule (35 mg/kg b.w. i.p./day), or exposed to safe doses of carbon monoxide (500 ppm 1 h/day; n = 6 in each group). Results - Both carbon monoxide-releasing molecule and carbon monoxide exposure significantly inhibited proliferation of human pancreatic cancer cells (p < 0.05). A substantial decrease in Akt phosphorylation was observed in carbon monoxide-releasing molecule compared with inactive carbon monoxide-releasing molecule treated cancer cells (by 30–50%, p < 0.05). Simultaneously, carbon monoxide-releasing molecule and carbon monoxide exposure inhibited tumour proliferation and microvascular density of xenotransplanted tumours (p < 0.01), and doubled the survival rates (p < 0.005). Exposure of mice to carbon monoxide led to an almost 3-fold increase in carbon monoxide content in tumour tissues (p = 0.006). Conclusion - These data suggest a new biological function for carbon monoxide in carcinogenesis, and point to the potential chemotherapeutic/chemoadjuvant use of carbon monoxide in pancreatic cancer.

The release of nitric oxide from S-nitrosothiols promotes angiogenesis

Free nitric oxide (NO) reacts with sulphydryl residues to form S-nitrosothiols, which act as NO reservoirs. We sought to determine whether thiol-preserving agents and antioxidants, such as dithiothreitol (DTT) and vitamin C, induce NO release from S-nitrosylated proteins in endothelial cell cultures to promote angiogenesis. NO release was measured directly in cell supernatants using a Sievers NO Analyser, and in vitro angiogenesis was assessed by quantifying capillary-like tube network formation of porcine aortic endothelial cells (PAEC) on growth factor-reduced Matrigel. Incubation of PAEC with DTT or vitamin C significantly increased NO release in a concentration-dependent manner. However, the nitric oxide synthase (NOS) inhibitors, L-NNA and L-NIO, had no effect on DTT- or vitamin C-induced NO release, and there was no concomitant increase in the phosphorylation of endothelial NOS at serine-1177 following DTT or vitamin C treatment. DTT and vitamin C increased capillary-like tube network formation by nine- and two-fold, respectively, and the addition of copper ions doubled the effect of vitamin C. Surprisingly, DTT maintained endothelial tube networks for up to one month under serum-free conditions, and selective inhibitors of guanylyl cyclase (ODQ) and PKG (KT-5823) blocked this, demonstrating the requirement of cyclic GMP and PKG in this process. Both DTT and vitamin C are capable of releasing sufficient NO from S-nitrosothiols to induce capillary morphogenesis. This study provides the first evidence that increased denitrosylation leads to increased bioavailability of NO, independent of NOS activity, to promote sustained angiogenesis.

Orange light generation from a PPKTP waveguide end pumped by a cw quantum-dot tunable laser diode

A compact all-room-temperature frequency-doubling scheme generating cw orange light with a periodically poled potassium titanyl phosphate waveguide and a quantum-dot external cavity diode laser is demonstrated. A frequency-doubled power of up to 4.3 mW at the wavelength of 612.9 nm with a conversion efficiency exceeding 10% is reported. Second harmonic wavelength tuning between 612.9 nm and 616.3 nm by changing the temperature of the crystal is also demonstrated. © Springer-Verlag 2010.

Efficient generation of orange light by frequency-doubling of a quantum-dot laser radiation in a PPKTP waveguide

Orange light with maximum conversion efficiency exceeding 10% and CW output power of 12.04 mW, 10.45 mW and 6.24 mW has been generated at 606, 608, and 611 nm, respectively, from a frequency-doubled InAs/GaAs quantum-dot external-cavity diode laser by use of a periodically-poled KTP waveguides with different cross-sectional areas. The wider waveguide with the cross-sectional area of 4×4 μm demonstrated better results in comparison with the narrower waveguides (3×5 μm and 2×6 μm) which corresponded to lower coupling efficiency. Additional tuning of second harmonic light (between 606 and 614 nm) with similar conversion efficiency was possible by changing the crystal temperature. © 2014 Copyright SPIE.

Antiproliferative effects of carbon monoxide on pancreatic cancer

Background: Carbon monoxide, the gaseous product of heme oxygenase, is a signalling molecule with a broad spectrum of biological activities. The aim of this study was to investigate the effects of carbon monoxide on proliferation of human pancreatic cancer. Methods: In vitro studies were performed on human pancreatic cancer cells (CAPAN-2, BxPc3, and PaTu-8902) treated with a carbon monoxide-releasing molecule or its inactive counterpart, or exposed to carbon monoxide gas (500. ppm/24. h). For in vivo studies, pancreatic cancer cells (CAPAN-2/PaTu-8902) were xenotransplanted subcutaneously into athymic mice, subsequently treated with carbon monoxide-releasing molecule (35. mg/kg b.w. i.p./day), or exposed to safe doses of carbon monoxide (500. ppm 1. h/day; n=. 6 in each group). Results: Both carbon monoxide-releasing molecule and carbon monoxide exposure significantly inhibited proliferation of human pancreatic cancer cells (p<0.05). A substantial decrease in Akt phosphorylation was observed in carbon monoxide-releasing molecule compared with inactive carbon monoxide-releasing molecule treated cancer cells (by 30-50%, p<. 0.05). Simultaneously, carbon monoxide-releasing molecule and carbon monoxide exposure inhibited tumour proliferation and microvascular density of xenotransplanted tumours (p<0.01), and doubled the survival rates (p<0.005). Exposure of mice to carbon monoxide led to an almost 3-fold increase in carbon monoxide content in tumour tissues (p=0.006). Conclusion: These data suggest a new biological function for carbon monoxide in carcinogenesis, and point to the potential chemotherapeutic/chemoadjuvant use of carbon monoxide in pancreatic cancer. © 2013 Editrice Gastroenterologica Italiana S.r.l.