Using an in vitro human airway model to study the toxic effects of components of e-cigarettes

Cigarette smoke is a complex mixture of more than 4000 hazardous chemicals including the carcinogenic benzopyrenes. Nicotine, the most potent component of tobacco, is responsible for the addictive nature of cigarettes and is a major component of e-cigarette cartridges. Our study aims to investigate the toxicity of nicotine with special emphasis on the replacement of animals. Furthermore, we intend to study the effect of nicotine, cigarette smoke and e-cigarette vapours on human airways. In our current work, the BEAS 2B human bronchial epithelial cell line was used to analyse the effect of nicotine in isolation, on cell viability. Concentrations of nicotine from 1.1µM to 75µM were added to 5x105 cells per well in a 96 well plate and incubated for 24 hours. Cell titre blue results showed that all the nicotine treated cells were more metabolically active than the control wells (cells alone). These data indicate that, under these conditions, nicotine does not affect cell viability and in fact, suggests that there is a stimulatory effect of nicotine on metabolism. We are now furthering this finding by investigating the pro-inflammatory response of these cells to nicotine by measuring cytokine secretion via ELISA. Further work includes analysing nicotine exposure at different time points and on other epithelial cells lines like Calu-3.

Investigation of the coordinated functional activities of cytochrome P450 3A4 and P-glycoprotein in limiting the absorption of xenobiotics in Caco-2 cells

The coordination of the functional activities of intestinal CYP3A4 and P-gp in limiting the absorption of xenobiotics in Caco-2 cells was investigated. Growing Caco-2 cells were exposed to increasing concentrations of doxorubicin (1-2 μM) in plastic flasks to encourage a subpopulation of cells, that displayed an intrinsically higher multidrug resistance (mdr) phenotype than the parent cells, to survive and grow. Doxorubicin-exposed (hereinafter referred to as type I cells) and nonexposed Caco-2 cells (parent cells) on collagen-coated inserts were also treated with either 0 (control) or 0.25 μM 1α,25-dihydroxyvitamin D3 to promote cellular CYP3A4 expression. Increased P-gp protein expression, as detected by Western blotting, was noted in type I cells (213±54.35%) compared to that of parent cells (100±6.05%). Furthermore, they retained significantly less [3H]vincristine sulphate (p<0.05), a P-gp substrate, after efflux (272.89±11.86 fmol/mg protein) than the parent cells (381.39±61.82 fmol/mg protein). The expression of CYP3A4 in parental cells after 1α,25-dihydroxyvitamin D3 treatment was quantified to be 76.2±7.6 pmol/mg protein and comparable with that found in human jejunal enterocytes (70.0±20.0 pmol/mg protein). Type I cells, however, expressed a very low quantity of CYP3A4 both before and after the treatment that was beyond the minimum detection limit of Western blotting. Functionally, the rates of 1-hydroxylation of midazolam by CYP3A for both cell types ranged from 257.0±20.0 to 1057.0±46.0 pmol/min/mg protein. Type I cells, although having a higher P-gp expression and activity comparatively, metabolized midazolam less extensively than the parent cells. The results suggested that there were noncoordinated functional activities of intestinal CYP3A4 and P-gp in Caco-2 cells, although they both functioned independently to minimize intestinal epithelial absorption of xenobiotics. © 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association.

Automatic control of attenuation in a digital communication network

This thesis describes the investigation of an adaptive method of attenuation control for digital speech signals in an analogue-digital environment and its effects on the transmission performance of a national telecommunication network. The first part gives the design of a digital automatic gain control, able to operate upon a P.C.M. signal in its companded form and whose operation is based upon the counting of peaks of the digital speech signal above certain threshold levels. A study was ma.de of a digital automatic gain control (d.a.g.c.) in open-loop configuration and closed-loop configuration. The former was adopted as the means for carrying out the automatic control of attenuation. It was simulated and tested, both objectively and subjectively. The final part is the assessment of the effects on telephone connections of a d.a.g.c. that introduces gains of 6 dB or 12 dB. This work used a Telephone Connection Assessment Model developed at The University of Aston in Birmingham. The subjective tests showed that the d.a.g.c. gives advantage for listeners when the speech level is very low. The benefit is not great when speech is only a little quieter than preferred. The assessment showed that, when a standard British Telecom earphone is used, insertion of gain is desirable if speech voltage across the earphone terminals is below an upper limit of -38 dBV. People commented upon the presence of an adaptive-like effect during the tests. This could be the reason why they voted against the insertion of gain at level only little quieter than preferred, when they may otherwise have judged it to be desirable. A telephone connection with a d.a.g.c. in has a degree of difficulty less than half of that without it. The score Excellent plus Good is 10-30% greater.

CFD modelling of the fast pyrolysis of an in-flight cellulosic particle subjected to convective heat transfer

The pyrolysis of a freely moving cellulosic particle inside a 41.7mgs -1 source continuously fed fluid bed reactor subjected to convective heat transfer is modelled. The Lagrangian approach is adopted for the particle tracking inside the reactor, while the flow of the inert gas is treated with the standard Eulerian method for gases. The model incorporates the thermal degradation of cellulose to char with simultaneous evolution of gases and vapours from discrete cellulosic particles. The reaction kinetics is represented according to the Broido–Shafizadeh scheme. The convective heat transfer to the surface of the particle is solved by two means, namely the Ranz–Marshall correlation and the limit case of infinitely fast external heat transfer rates. The results from both approaches are compared and discussed. The effect of the different heat transfer rates on the discrete phase trajectory is also considered.

The toxic effects of anticholinesterases on muscle

It has been shown that acute administration of ecothiopate iodine in vivo caused an approximate 80% depression of acetylcholinesterase activity in the diaphragms of mice. Inhibition of acetylcholinesterase was accompanied by an influx of calcium at the junctional region of the diaphragm, which continued during subsequent progressive development of a severe myopathy located in the same region. Myopathy was accompanied by loss of creatine kinase from the muscle and was represented, at the light microscope level, by hypercontraction, Procion Yellow staining and loss of cross striations within the muscle fibres. It appeared to reach a point of maximum severity approximately 3-6 hours after ecothiopate administration and then, by means of some repair/regeneration process, regained an apparently normal morphology within 72 hours of the intoxication. At the ultrastructural level, ecothiopate-induced myopathy was recognised by loss of Z-lines, swelling and vacuolation of mitochondria and sarcoplasmic reticulum, dissarray of myofilaments, crystal formation, and sometimes, by the complete obliteration of sarcomeric structure. The development of myopathy in vitro was shown to be nerve-mediated and to require a functional acetylcholine receptor for its development It was successfully treated therapeutically in vivo by pyridine-2-aldoxime methiodide and prophylactically by pyridostigmine bromide. However, the use of a range of membrane-on channel blockers, and of leupeptin, an inhibitor of calcium-activated-neutral-protease, have been unsuccessful in the prevention of ecothiopate-induced myopathy.

The influence of memory in a threshold model for distributed task assignment

A nature inspired decentralised multi-agent algorithm is proposed to solve a problem of distributed task selection in which cities produce and store batches of different mail types. Agents must collect and process the mail batches, without a priori knowledge of the available mail at the cities or inter-agent communication. In order to process a different mail type than the previous one, agents must undergo a change-over during which it remains inactive. We propose a threshold based algorithm in order to maximise the overall efficiency (the average amount of mail collected). We show that memory, i.e. the possibility for agents to develop preferences for certain cities, not only leads to emergent cooperation between agents, but also to a significant increase in efficiency (above the theoretical upper limit for any memoryless algorithm), and we systematically investigate the influence of the various model parameters. Finally, we demonstrate the flexibility of the algorithm to changes in circumstances, and its excellent scalability.

Regeneration limit of classical Shannon capacity

Since Shannon derived the seminal formula for the capacity of the additive linear white Gaussian noise channel, it has commonly been interpreted as the ultimate limit of error-free information transmission rate. However, the capacity above the corresponding linear channel limit can be achieved when noise is suppressed using nonlinear elements; that is, the regenerative function not available in linear systems. Regeneration is a fundamental concept that extends from biology to optical communications. All-optical regeneration of coherent signal has attracted particular attention. Surprisingly, the quantitative impact of regeneration on the Shannon capacity has remained unstudied. Here we propose a new method of designing regenerative transmission systems with capacity that is higher than the corresponding linear channel, and illustrate it by proposing application of the Fourier transform for efficient regeneration of multilevel multidimensional signals. The regenerative Shannon limit -the upper bound of regeneration efficiency -is derived. © 2014 Macmillan Publishers Limited. All rights reserved.

Scavenging of halogen in recycling of halogen-based polymer materials

Pyrolytic recycling of materials for electronics and automotive is attractive because of the possibility of recovery of fuel and of precious metals from printed circuit. Due to the complexity of their composition an appropriate pre-treatment has to be performed in order to limit the evolution of dangerous halogen containing compounds which strongly impair the fuel quality. An advantageous pyrolysis approach implies the attempt of mineralisation of the organic bromine to the not volatile and harmless inorganic form using strong bases such as NaOH and KOH to reduce the amount of volatile and increasing the residue. The char stability is greatly variable depending on the substrate. Mg(OH)2 and Ca(OH)2 behave in a similar manner but to a lower extent. Carbonates and reducing agent such as LiAlH have been tested as well and their ability to scavenge bromine is discussed in terms of effectiveness and mechanism.

Analysis and improvement of performance in LCL filter-based PWM rectifier/inverter application using hybrid damping approach

A hybrid passive-active damping solution with improved system stability margin and enhanced dynamic performance is proposed for high power grid interactive converters. In grid connected active rectifier/inverter application, line side LCL filter improves the high frequency attenuation and makes the converter compatible with the stringent grid power quality regulations. Passive damping though offers a simple and reliable solution but it reduces overall converter efficiency. Active damping solutions do not increase the system losses but can guarantee the stable operation up to a certain speed of dynamic response which is limited by the maximum bandwidth of the current controller. This paper examines this limit and introduces a concept of hybrid passive-active damping solution with improved stability margin and high dynamic performance for line side LCL filter based active rectifier/inverter applications. A detailed design, analysis of the hybrid approach and trade-off between system losses and dynamic performance in grid connected applications are reported. Simulation and experimental results from a 10 kVA prototype demonstrate the effectiveness of the proposed solution. An analytical study on system stability and dynamic response with the variations of various controller and passive filter parameters is presented.

Kinetic studies of the photopolymerisation of acrylamide in aqueous solution:effects of bromoform as a Chain transfer agent

The effects of adding bromoform (CHBr3) as a potential chain transfer agent in the photopolymerisation of acrylamide (AM) in aqueous solution have been studied both in terms of influencing the rate of polymerisation and the molecular weight of the polyacrylamide (PAM) formed. Using 4,4′-azo-bis(4-cyanopentanoic acid) (ACPA) as photoinitiator, two different CHBr3 concentrations as chain transfer agent were compared: 0.5 and 2.0 mol % (relative to AM), the higher of which was determined by the limit of CHBr3 water solubility. The results showed that CHBr3 was an effective chain transfer agent that could regulate the molecular weight of the PAM formed without seriously affecting the polymerisation rate. It is concluded that chain transfer to CHBr3occurs by both Br and H atom transfer although Br transfer is the more favoured due to the weaker C-Br bond. Furthermore, Br transfer leads to Br-terminated chains in which the terminal C-Br bond can re-dissociate leading to re-initiation and re-propagation of the same chain, thereby maintaining the polymerisation rate. Continuing studies into how this mechanism can be exploited in order to synthesize water-soluble block copolymers of potential biomedical importance are currently in progress.

Investigating the prevalence of Salmonella in dogs within the Midlands region of the United Kingdom

Background - The intimate relationship between dogs and their owners has the potential to increase the risk of human exposure to bacterial pathogens. Over the past 40 years, there have been several reports on transmission of salmonellae from dogs to humans. This study therefore aimed to determine the prevalence of Salmonella in the faeces of dogs from the Midlands region of the United Kingdom to assess exposure risk and potential for zoonotic transmission. Results - A total of 436 apparently healthy dogs without diarrhoea from households (n = 126), rescue centres (n = 96), boarding kennels (n = 43), retired greyhound kennels (n = 39) and a pet nutrition facility (n = 132) were investigated for Salmonella shedding. Faecal samples were processed by an enrichment culture based method. The faeces from one dog (0.23 %; 95 % confidence limit 0.006 %, 1.27 %) was positive for Salmonella. The species was S. enterica subspecies arizonae. Conclusion - This study showed that the prevalence of Salmonella from faeces from apparently healthy dogs from a variety of housing conditions is low; however, Salmonella shedding was still identified.

Nonlinear limit of alternative method to 2 × 2 MIMO for LTE RoF system

Owing to the limited cell size of eNodeB (eNB), the relay node has emerged as an attractive solution for the long-term evolution (LTE) system. The nonlinear limit of the alternative method to multipleinput and multiple-output (MIMO) based on frequency division multiplexing (FDM) for orthogonal FDM (OFDM) is analysed over varying transmission spans. In this reported work, it is shown that the degradation pattern over the linear, intermixing and nonlinear propagation regions is consistent for the 2 and the 2.6 GHz bands. The proposed bands experienced a linear increase in the error vector magnitude (EVM) for both the linear and the nonlinear regions proportional to the increasing transmission spans. In addition, an optical launch power between -2 and 2 dBm achieved a significantly lower EVM than the LTE limit of 8% for the 10-60 km spans. © The Institution of Engineering and Technology 2014.

Measurement of H2S in vivo and in vitro by the monobromobimane method

The gasotransmitter hydrogen sulfide (H2S) is known as an important regulator in several physiological and pathological responses. Among the challenges facing the field is the accurate and reliable measurement of hydrogen sulfide bioavailability. We have reported an approach to discretely measure sulfide and sulfide pools using the monobromobimane (MBB) method coupled with reversed phase high-performance liquid chromatography (RP-HPLC). The method involves the derivatization of sulfide with excess MBB under precise reaction conditions at room temperature to form sulfide dibimane (SDB). The resultant fluorescent SDB is analyzed by RP-HPLC using fluorescence detection with the limit of detection for SDB (2 nM). Care must be taken to avoid conditions that may confound H2S measurement with this method. Overall, RP-HPLC with fluorescence detection of SDB is a useful and powerful tool to measure biological sulfide levels.