Coherence and anticoherence resonance in high-concentration erbium-doped fiber laser

We report an experimental study of low-frequency (~10 kHz) self-pulsing of the output intensity in a high- concentration erbium-doped fiber laser. We suggest that the fast intensity fluctuations caused by multimode and polarization instabilities play the role of an external noise source, leading to low-frequency auto-oscillations through a coherence resonance scenario.

Upconversion assisted self-pulsing in a high-concentration erbium doped fiber laser

We report results on experimental and theoretical characterisation of self-pulsing in high concentration erbium doped fibre laser which is free from erbium clusters. Unlike previous models of self-pulsing accounting for pair-induced quenching (PIQ) on the clustered erbium ions, new model has been developed with accounting for statistical nature of the excitation migration and upconversion and resonance-like pumpto-signal intensity noise transfer. The obtained results are in a good agreement with the experimental data.

Concentration of the UK stock market

During 1999 and 2000 a large number of articles appeared in the financial press which argued that the concentration of the FTSE 100 had increased. Many of these reports suggested that stock market volatility in the UK had risen, because the concentration of its stock markets had increased. This study undertakes a comprehensive measurement of stock market concentration using the FTSE 100 index. We find that during 1999, 2000 and 2001 stock market concentration was noticeably higher than at any other time since the index was introduced. When we measure the volatility of the FTSE 100 index we do not find an association between concentration and its volatility. When we examine the variances and covariance’s of the FTSE 100 constituents we find that security volatility appears to be positively related to concentration changes but concentration and the size of security covariances appear to be negatively related. We simulate the variance of four versions of the FTSE 100 index; in each version of the index the weighting structure reflects either an equally weighted index, or one with levels of low, intermediate or high concentration. We find that moving from low to high concentration has very little impact on the volatility of the index. To complete the study we estimate the minimum variance portfolio for the FTSE 100, we then compare concentration levels of this index to those formed on the basis of market weighting. We find that realised FTSE index weightings are higher than for the minimum variance index.

αα'-trehalose 6,6'-dibehenate in non-phospholipid-based liposomes enables direct interaction with trehalose, offering stability during freeze-drying

Trehalose is a well known protector of biostructures like liposomes and proteins during freeze-drying, but still today there is a big debate regarding its mechanism of action. In previous experiments we have shown that trehalose is able to protect a non-phospholipid-based liposomal adjuvant (designated CAF01) composed of the cationic dimethyldioctadecylammonium (DDA) and trehalose 6,6-dibehenate (TDB) during freeze-drying [D. Christensen, C. Foged, I. Rosenkrands, H.M. Nielsen, P. Andersen, E.M. Agger, Trehalose preserves DDA/TDB liposomes and their adjuvant effect during freeze-drying, Biochim. Biophys. Acta, Biomembr. 1768 (2007) 2120-2129]. Furthermore it was seen that TDB is required for the stabilizing effect of trehalose. Herein, we show using the Langmuir-Blodgett technique that a high concentration of TDB present at the water-lipid interface results in a surface pressure around 67 mN/m as compared to that of pure DDA which is approximately 47 mN/m in the compressed state. This indicates that the attractive forces between the trehalose head group of TDB and water are greater than those between the quaternary ammonium head group of DDA and water. Furthermore, addition of trehalose to a DDA monolayer containing small amounts of TDB also increases the surface pressure, which is not observed in the absence of TDB. This suggests that even small amounts of trehalose groups on TDB present at the water-lipid interface associate free trehalose to the liposome surface, presumably by hydrogen bonding between the trehalose head groups of TDB and the free trehalose molecules. Hence, for CAF01 the TDB component not only stabilizes the cationic liposomes and enhances the immune response but also facilitates the cryo-/lyoprotection by trehalose through direct interaction with the head group of TDB. Furthermore the results indicate that direct interaction with liposome surfaces is necessary for trehalose to enable protection during freeze-drying.

Formulation and characterisation of lyophilised rapid disintegrating tablets using amino acids as matrix forming agents

Despite recent advances in the formulation of lyophilised rapid disintegrating tablets (RDTs), the inclusion of matrix supporting/disintegration enhancing agents has been limited to the use of saccharides and polyols. In this study, the feasibility of using amino acids as matrix forming agents in lyophilised RDTs was investigated. Twelve amino acids were chosen (alanine, arginine, threonine, glycine, cysteine, serine, histidine, lysine, valine, asparagine, glutamine and proline), and the suitability for freeze drying, mechanical properties and disintegration time after inclusion of the amino acids at varied concentration were studied. In addition, the porosity of the RDTs and wettability profile of the amino acids were investigated to understand the mechanisms of disintegration. The results suggest the suitability of these amino acids for the lyophilisation regime, as they displayed satisfactory safety margin between the glass transition and shelf temperature (-40 degrees C), except proline-based formulations. Moreover, the crystallisation behavior of alanine, glycine, cysteine and serine at high concentration increased the stability of the formulation. The characterisation of the RDTs suggests that high concentration of the amino acids is required to enhance the mechanical properties, whereas only optimum concentrations promote the disintegration. Moreover, wetting time of the amino acid and porosity of the tablet are the two factors that control the disintegration of RDTs.

Mass transfer characteristics of two-aqueous-phase liquid-liquid mixtures

Mass transfer rates were studied using the falling drop method. Cibacron Blue 3 GA dye was the transferring solute from the salt phase to the PEG phase. Measurements were undertaken for several concentrations of the dye and the phase-forming solutes and with a range of different drop sizes, e.g. 2.8, 3.0 and 3.7 mm. The dye was observed to be present in the salt phase as finely dispersed solids but a model confirmed that the mass transfer process could still be described by an equation based upon the Whitman two-film model. The overall mass transfer coefficient increased with increasing concentration of the dye. The apparent mass transfer coefficient ranged from 1 x 10-5 to 2 x 10 -4 m/s. Further experiments suggested that mass transfer was enhanced at high concentration by several mechanisms. The dye was found to change the equilibrium composition of the two phases, leading to transfer of salt between the drop and continuous phases. It also lowered the interfacial tension (i.e. from 1.43 x 10-4 N/m for 0.01% w/w dye concentration to 1.07 x 10-4 N/m for 0.2% w/w dye concentration) between the two phases, which could have caused interfacial instabilities (Marangoni effects). The largest drops were deformable, which resulted in a significant increase in the mass transfer rate. Drop size distribution and Sauter mean drop diameter were studied on-line in a 1 litre agitated vessel using a laser diffraction technique. The effects of phase concentration, dispersed phase hold-up and impeller speed were investigated for the salt-PEG system. An increase in agitation speed in the range 300 rpm to 1000 rpm caused a decrease in mean drop diameter, e.g. from 50 m to 15 m. A characteristic bimodal drop size distribution was established within a very short time. An increase in agitation rate caused a shift of the larger drop size peak to a smaller size.

On the transmission properties of synapses made between granule cells and cerebellar Purkinje cells

In the cerebellar cortex, forms of both long-term depression (LTD) and long-term potentiation (LTP) can be observed at parallel fibre (PF) - Purkinje cell (PC) synapses. A presynaptic variant of cerebellar LTP can be evoked in PCs by raised frequency stimulation (RFS) of parallel fibre at 4-16Hz for 15s. This form of LTP is dependent on protein kinase A (PKA) and nitric oxide (NO), and can spread to distant synapses. Application of an extracellular NO scavenger, cPTIO, was found to prevent the spread of LTP to distant PF synapses in rat cerebellar slices. G-substrate may be an important mediator of the NO-dependent pathway for LTD. 8-16Hz RFS of PFs without a high concentration of calcium chelator in the postsynaptic cell evokes LTD. In cerebellar slices from wild-type and transgenic, G-substrate knockout mice, 8Hz RFS was applied to PFs, with a low concentration of postsynaptic calcium chelator. In PCs from wild-type mice, LTD predominated, whereas in those from transgenic mice LTP predominated. The ascending axon (AA) segment of the granule cell axon forms synapses with PCs as well as the PF segment. PPF and fluctuation analysis of EPSCs in rat PCs confirmed that the release sites of AA synapses have a greater probability of transmitter release than PF synapses. Furthermore, AA release sites have greater mean quantal amplitude than PF synapses, which is not due to a different type of postsynaptic receptor. AA synapses were found to have limited capacity to undergo the presynaptic variant of LTP, and were potentiated less than PF synapses in the presence of the PKA activator, forskolin. AA synapses also did not undergo the postsynaptic form of LTP, nor LTD induced by conjunctive stimulation of climbing fibre and PF.

The behaviour of polymer quenchants

The internationally accepted Wolfson Heat Treatment Centre Engineering Group test was used to evaluate the cooling characteristics of the most popular commercial polymer quenchants: polyalkylene glycols, polyvinylpyrrolidones and polyacrylates. Prototype solutions containing poly(ethyloxazoline) were also examined. Each class of polymer was capable of providing a wide range of cooling rates depending on the product formulation, concentration, temperature, agitation, ageing and contamination. Cooling rates for synthetic quenchants were generally intermediate between those of water and oil. Control techniques, drag-out losses and response to quenching in terms of hardness and residual stress for a plain carbon steel, were also considered. A laboratory scale method for providing a controllable level of forced convection was developed. Test reproducibility was improved by positioning the preheated Wolfson probe 25mm above the geometric centre of a 25mm diameter orifice through which the quenchant was pumped at a velocity of 0.5m/s. On examination, all polymer quenchants were found to operate by the same fundamental mechanism associated with their viscosity and ability to form an insulating polymer-rich-film. The nature of this film, which formed at the vapour/liquid interface during boiling, was dependent on the polymer's solubility characteristics. High molecular weight polymers and high concentration solutions produced thicker, more stable insulating films. Agitation produced thinner more uniform films. Higher molecular weight polymers were more susceptible to degradation, and increased cooling rates, with usage. Polyvinylpyrrolidones can be cross-linked resulting in erratic performance, whilst the anionic character of polyacrylates can lead to control problems. Volatile contaminants tend to decrease the rate of cooling and salts to increase it. Drag-out increases upon raising the molecular weight of the polymer and its solution viscosity. Kinematic viscosity measurements are more effective than refractometer readings for concentration control, although a quench test is the most satisfactory process control method.

Primary production, financial constraints and economic instability:Zambia since independence.

A systematic analysis is presented of the economic consequences of the abnormally high concentration of Zambia's exports on a commodity whose price is exceptionally unstable. Zambian macro-economic variables in the post-independence years are extensively documented, showing acute instability and decline, particularly after the energy price revolution and the collapse of copper prices. The relevance of stabilization policies designed to correct short-term disequilibrium is questioned. It is, therefore, a pathological case study of externally induced economic instability, complementing other studies in this area which use cross-country analysis of a few selected variables. After a survey of theory and issues pertaining to development, finance and stabilization, the emergence of domestic and foreign financial constraints on the Zambian economy is described. The world copper industry is surveyed and an examination of commodity and world trade prices concludes that copper showed the highest degree of price instability. Specific aspects of Zambia's economy identified for detailed analysis include: its unprofitable mining industry, external payments disequilibrium, a constrained government budget, potentially inflationary monetary growth, and external indebtedness. International comparisons are used extensively, but major copper exporters are subjected to closer scrutiny. An appraisal of policy options concludes the study.

Ordered mixing of drugs with particulate excipients

A novel direct compression tableting excipient has been made by recrystallisation of lactose. The particles produced had high porosity, high specific surface area and high surface roughness. The resistance to segregation of ordered mixes formed between a model drug; potassium chloride and the excipients recrystallised lactose, spray crystallised maltose-dextrose (Emdexl and a direct compacting sugar (Dipac) was studied using a vibrational segregation model. The highly porous excipients, Emdex and recrystallised lactose formed ordered mixes which did not segregate even at high accelerations and low frequencies whereas the relatively smooth excipient, Dipac, displayed marked segregation in most vibration conditions. The vibrations were related to practical conditions measured in pharmaceutical process machinery. The time required to form an ordered mix was inversely related to the stability of the mix when subjected to vibration. An ultracentrifuge technique was developed to determine the interparticle adhesion forces holding drug and excipient particles together as ordered units. Excipient powders such as Emdex and recrystallised lactose, which formed non-segregating ordered mixes, had high interparticle adhesion forces. Other ordered mixes that segregated when subjected to different vibration conditions were found to have large quantities of weekly-bound drug particles; such mixes included those with Dipac as the carrier excipient as well as those containing a high concentration of drug. The electrostatic properties of different drug and excipient powders were studied using a Faraday well and an electrometer. Excipient powders such as Emdex and recrystallised lactose which formed stable ordered mixes also had a widely different surface charge in comparison with drug particles, whereas Dipac had a similar surface charge to the drug particles and formed unstable ordered mixes. A specially constructed triboelectric charging apparatus based on an air cyclone was developed to increase the affinity of drug particles for different excipient particles. Using triboelectrification to increase the interparticle adhesion forces, the segregation tendencies of unstable ordered mixes were greatly reduced. The stability of ordered mixes is shown to be related to both the surface physical characteristics and the surface electrical properties of the constituent carrier (excipientl particles.

Prodrugs of antiviral phosphonates

Phosphonoformate and phosphonoacetate are effective antiviral agents, however they are charged at physiological pH and as such penetration into cells and diffusion across the blood-brain bamer is limited. In an attempt to increase the lipophilicity and improve the transport properties of these molecules, prodrugs were synthesised and their stabilities and reconversion to the parent compound subsequently investigated by the techniques of 31P nuclear magnetic resonance spectroscopy and high performance liquid Chromatography. A series of 4-substituted dibenzyl (methoxycarbonyl)phosphonates were prepared and found to be hydrolytically unstable giving predominantly the diesters, benzyl (methoxycarbonyl)phosphonates. This instability arose from the electron-withdrawing effect of the carbonyl group promoting nucleophilic attack at phosphorus. It was possible to influence the mechanism and, to some extent, the rate of hydrolysis of the phosphonoformate triesters to the diesters by varying the electronic nature of the substituent in the 4-position of the aromatic ring. Strongly electron-withdrawing groups increased the sensitivity of phosphorus to nucleophilic attack, thus promoting P-O .bond cleavage and rapid hydrolysis. Conversely, weakly electron-withdrawing substituents encouraged C-O bond fission, presumably through resonance stabilisation of the benzyl carbonium ion. The loss of the protecting group on phosphorus was in competition with nucleophilic attack at the carbonyl group, resulting in P-C bond cleavage with dibenzyl phosphite formation. The high instability and P-C bond fission make triesters unsuitable prodrug forms of phosphonoformate. A range of chemically stable triesters of phosphonoacetate were synthesised and their bioactivation investigated. Di(benzoyloxymethyl) (methoxycarbonylmethyl)phosphonates degraded to the relevant benzoyloxymethyl (methoxycarbonylmethyl)phosphonate in the presence of esterase. The enzymatic activation was restricted to the removal of only one protecting group from phosphorus, most likely due to the close proximity of the benzoyloxy ester function to the anionic charge on the diester. However, in similar systems di(4-alkanoyloxybenzyl) (methoxycarbonylmethyl)phosphonates degraded in the presence of esterase with the loss of both protecting groups on phosphorus to give the monoester, (methoxycarbonylmethyl)phosphonate, via the intermediary of the unstable 4-hydroxy benzyl esters. The methoxycarbonyl function remained intact. The rate of enzymatic hydrolysis and subsequent removal of the protecting groups on phosphorus was dependent on the nature of the alkanoyl group and was most rapid for the 4-nbutanoyloxybenzyl and 4-iso-butanoyloxybenzyl esters of phosphonoacetate. This provides a strategy for the design of a prodrug with sufficient stability in plasma to reach the central nervous system in high concentration, wherein rapid metabolism to the active drug by brain-associated enzymes occurs.

Preparation, optimisation and characterisation of lyophilised rapid disintegrating tablets based on gelatin and saccharide

Despite recent success, rapidly disintegrating lyophilized tablets still face problems of low mechanical strength and higher disintegration times resulting in poor patient compliance. The aim of the current work was to carry out a systematic study to understand the factors controlling mechanical properties of these formulations. The work investigated the influence of two bloom strengths of gelatin: low (60 bloom) and high (225 bloom) at different stock solution concentrations (2, 5, 7.5, and 10 %w/w). This was followed by investigation of addition of five saccharides (xylitol, glucose, trehalose, maltotriose and mannitol) at varied concentration range (10-80 %w/w) to decipher their influence on disintegration time, mechanical and thermal properties of the formulation. The results indicated that the disintegration time of the tablets dramatically decreased by decreasing the concentration and bloom strength of gelatin in the stock solution. However the mechanical properties of the tablets were mainly influenced by the concentration of gelatin rather than the bloom strength. The addition of saccharides resulted in enhancement of tablet properties and was concentration dependent. All the saccharides improved the fractubility of the tablets significantly at high concentration (equal or higher than 40% w/w). However, only high concentration (equal or higher than 40% w/w) of trehalose, maltotriose and mannitol significantly enhanced the hardness. Additionally, mannitol crytallised during freeze drying and consequently produced elegant tablets, whilst the other saccarides exhibited lyoprotectant activity as they were able to retain amorphous status. Based on the above findings, an optimized formulation was also successfully developed and characterized to deliver 100 microg dose of Clonidine HCl.

Carbon nanotube-polycarbonate composites for ultrafast lasers

Carbon nanotube polycarbonate composites with controlled nanotube-bundle size are prepared by dispersion with conjugated polymers followed by blending with polycarbonate. The composite has uniform sub-micrometer nanotube bundles in high concentration, shows strong nonlinear optical absorption, and generates 193 fs pulses when used as passive mode-locker in a fiber laser.

Palmitate promotes monocyte atherogenicity via de novo ceramide synthesis

Elevated plasma free fatty acids (FAs) are associated with increased risk of cardiovascular disease. This study investigates the effects of the saturated FA palmitate and unsaturated FA oleate on monocyte phenotype and function. Incubation of human U937 and THP-1 monocytes with palmitate for 24h increased cell surface expression of integrin CD11b and scavenger receptor CD36 in a concentration-dependent manner with some decrease in mitochondrial reducing capacity at high concentration (300µM). Monocytes incubated with palmitate, but not oleate, showed increased uptake of oxidized LDL and increased adhesion to rat aortic endothelium, particularly at bifurcations. The palmitate-induced increase in CD11b and CD36 expression was associated with increased cellular C16 ceramide and sphingomyelin, loss of reduced glutathione, and increased reactive oxygen species (ROS). Increased monocyte surface CD11b and CD36 was inhibited by fumonisin B1, an inhibitor of de novo ceramide synthesis, but not by the superoxide dismutase mimetic MnTBap. In contrast, MnTBap prevented the mitochondrial ROS increase and metabolic inhibition due to 300µM palmitate. This study demonstrates that in viable monocytes, palmitate but not oleate increases expression of surface CD11b and CD36. Palmitate increases monocyte adhesion to the aortic wall and promotes uptake of oxidized LDL and this involves de novo ceramide synthesis.

Poor fluorinated graphene sheets carboxymethylcellulose polymer composite mode locker for erbium doped fiber laser

We report poor fluorinated graphene sheets produced by thermal exfoliation embedding in carboxymethylcellulose polymer composite (GCMC) as an efficient mode locker for erbium doped fiber laser. Two GCMC mode lockers with different concentration have been fabricated. The GCMC based mode locked fiber laser shows stable soliton output pulse shaping with repetition rate of 28.5MHz and output power of 5.5 mW was achieved with the high concentration GCMC, while a slightly higher output power of 6.9 mW was obtained using the low concentration GCMC mode locker.