Oxygen free radicals denature human IgG and increase its reactivity with rheumatoid factor antibody

Rheumatoid inflammation is characterised by the production of rheumatoid factor antibodies directed against denatured IgG. Oxygen free radicals have the potential to denature all manner of proteins and can be generated by activated phagocytic cells in the inflamed joint. By modifying routine ELISA and nephelometric procedures for measuring rheumatoid factor, (i.e. substituting free radical altered IgG for rabbit and heat aggregated IgG as antigens) we have observed that oxygen radicals, generated by (1) UV light and (2) PMA-activated neutrophils, give rise to monomeric and polymeric forms of IgG which have increased reactivity towards IgM and IgA polyclonal rheumatoid factor antibodies. We conclude that free radical alteration of IgG may be a stimulus to the formation of immune complexes with rheumatoid factor antibody, thereby promoting and amplifying tissue damage during rheumatoid inflammation.

Local shell-side coefficients in shell and tube exchanges the use of a mass transfer technique

A diffusion-controlled electrochemical mass transfer technique has been employed in making local measurements of shell-side coefficients in segmentally baffled shell and tube heat exchangers. Corresponding heat transfer data are predicted through the Chilton and Colburn heat and mass transfer analogy. Mass transfer coefficients were measured for baffle spacing lengths of individual tubes in an internal baffle compartment. Shell-side pressure measurements were also made. Baffle compartment average coefficients derived from individual tube coefficients are shown to be in good agreement with reported experimental bundle average heat transfer data for a heat exchanger model of similar geometry. Mass transfer coefficients of individual tubes compare favourably with those obtained previously by another mass transfer technique. Experimental data are reported for a variety of segmental baffle configurations over the shell-side Reynolds number range 100 to 42 000. Baffles with zero clearances were studied at three baffle cuts and two baffle spacings. Baffle geometry is shown to have a large effect on the distribution of tube coefficients within the baffle compartment. Fluid "jetting" is identified with some baffle configurations. No simple characteristic velocity is found to correlate zonal or baffle compartment average mass transfer data for the effect of both baffle cut and baffle spacing. Experiments with baffle clearances typical of commercial heat exchangers are also reported. The effect of leakage streams associated with these baffles is identified. Investigations were extended to double segmental baffles for which no data had previously been published. The similarity in the shell-side characteristics of this baffle arrangement and two parallel single segmental baffle arrangements is demonstrated. A general relationship between the shell-side mass transfer performance and pressure drop was indicated by the data for all the baffle configurations examined.

Statnote 15: the non-parametric correlation coefficients

If in a correlation test, one or both variables are small whole numbers, scores based on a limited scale, or percentages, a non-parametric correlation coefficient should be considered as an alternative to Pearson’s ‘r’. Kendall’s t and Spearman’s rs are similar tests but the former should be considered if the analysis is to be extended to include partial correlations. If the data contain many tied values, then gamma should be considered as a suitable test.

Hydrogels for dermal applications

This thesis is concerned with the development of hydrogels that adhere to skin and can be used for topical or trans dermal release of active compounds for therapeutic or cosmetic use. The suitability of a range of monomers and initiator systems for the production of skin adhesive hydro gels by photopolymerisation was explored and an approximate order of monomer reactivity in aqueous solution was determined. Most notably, the increased reactivity of N-vinyl pyrrolidone within an aqueous system, as compared to its low rate of polymerisation in organic solvents, was observed. The efficacy of a series of photoinitiator systems for the preparation of sheet hydrogels was investigated. Supplementary redox and thermal initiators were also examined. The most successful initiator system was found to be Irgacure 184, which is commonly used in commercial moving web production systems that employ photopolymerisation. The influence of ionic and non-ionic monomers, crosslinking systems, water and glycerol on the adhesive and dynamic mechanical behaviour of partially hydrated hydrogel systems was examined. The aim was to manipulate hydrogel behaviour to modify topical and transdermal delivery capability and investigated the possibility of using monomer combinations that would influence the release characteristics of gels by modifying their hydrophobic and ionic nature. The copolymerisation of neutral monomers (N-vinyl pyrrolidone, N,N-dimethyl acrylamide and N-acryloyl morpholine) with ionic monomers (2-acrylamido-2-methylpropane sulphonic acid; sodium salt, and the potassium salt of 3-sulphopropyl acrylate) formed the basis of the study. Release from fully and partially hydrated hydrogels was studied, using model compounds and a non-steroidal anti-inflammatory drug, Ibuprofen. Release followed a common 3-stage kinetic profile that includes an initial burst phase, a secondary phase of approximate first order release and a final stage of infinitesimally slow release such that the compound is effectively retained within the hydrogel. Use of partition coefficients, the pKa of the active and a knowledge of charge-based and polar interactions of polymer and drug were complementary in interpreting experimental results. In summary, drug ionisation, hydrogel composition and external release medium characteristics interact to influence release behaviour. The information generated provides the basis for the optimal design of hydrogels for specific dermal release applications and some understanding of the limitations of these systems for controlled release applications.

Transfer coefficients over inclined tube banks

The thesis presents experimental results for shell-side transfer coefficients and pressure drops across four different tube banks, using small-scale models, with yawed tubes, as found in many types of heat exchangers, boilers and nuclear reactors. The tube banks investigated have a staggered tube layout on a rotated square pitch, with a 1.25 pitch-to-diameter ratio. The angle of attack was varied between 45o and 90o. An extensive range of Reynolds number, i.e. 0.5. to 12,600, covering so-called laminar, transition and turbulent flows, was investigated. A diffusion-controlled electrochemical mass transfer technique has been employed to measure mass transfer coefficients. The heat transfer coefficients may be then readily obtained from the mass transfer values by applying the well-established Chilton-Colburn analogy. The results for the normal tube bank, which forms the base case for the study on inclined tube banks, show close agreement with previous work. The transfer coefficients and pressure drops of the inclined tube banks are compared with results from the ideal normal tube bank to examine the effect of inclination angle on heat transfer and pressure drop variations. The variation of the transfer coefficients row-by-row and the entrance and exit effects have also been investigated. An auxilary investigation has been carried out on the role of natural convection. A preliminary correlation of transfer coefficients and pressure drops against the variation in the yaw angle has been attempted. The results are discussed in the light of the few existing theoretical treatments and experimental data for these situations, and recommendations made for future work.

Non-Linear oil firm force coefficients for a journal bearing operating under aligned and misaligned conditions

It is well established that hydrodynamic journal bearings are responsible for self-excited vibrations and have the effect of lowering the critical speeds of rotor systems. The forces within the oil film wedge, generated by the vibrating journal, may be represented by displacement and velocity coefficient~ thus allowing the dynamical behaviour of the rotor to be analysed both for stability purposes and for anticipating the response to unbalance. However, information describing these coefficients is sparse, misleading, and very often not applicable to industrial type bearings. Results of a combined analytical and experimental investigation into the hydrodynamic oil film coefficients operating in the laminar region are therefore presented, the analysis being applied to a 120 degree partial journal bearing having a 5.0 in diameter journal and a LID ratio of 1.0. The theoretical analysis shows that for this type of popular bearing, the eight linearized coefficients do not accurately describe the behaviour of the vibrating journal based on the theory of small perturbations, due to them being masked by the presence of nonlinearity. A method is developed using the second order terms of Taylor expansion whereby design charts are provided which predict the twentyeight force coefficients for both aligned, and for varying amounts of journal misalignment. The resulting non-linear equations of motion are solved using a modified Newton-Raphson method whereby the whirl trajectories are obtained, thus providing a physical appreciation of the bearing characteristics under dynamically loaded conditions.

Drag coefficients with applications to satellite orbits

In the last twenty or so years the results of theory and experiment have produced much information on the characteristics of gas-surface interactions relevant to a satellite in hyperthermal free-molecular flow. This thesis contains reviews of the rarefied gas dynamics applicable to satellites and has attempted to compare existing models of gas-surface interaction with contemporary knowledge of such systems. It is shown that a more natural approach would be to characterise the gas-surface interaction using the normal and tangential momentum accommodation coefficients, igma' and igma respectively, specifically in the form igma = constant , igma' = igma'0 -igma'1sec i where i is the angle subtended between the incident flow and the surface normal and igma,igma'0 and igma'1 are constants. Adopting these relationships, the effects of atmospheric lift on inclination, i, and atmospheric drag on the semi-major axis, a, and eccentricity, e, have been investigated. Applications to ANS-1 (1974-70A) show that the observed perturbation in i can be ascribed primarily to non-zero igma'1 whilst perturbations in a and e produce constraint equations between the three parameters. The numerical results seem to imply that a good theoretical orbit is achieved despite a much lower drag coefficient than anticipated by earlier theories.

Abnormal retinal vascular reactivity in individuals with impaired glucose tolerance:a preliminary study

To investigate the relationship between vascular function parameters measured at the retinal and systemic level and known markers for cardiovascular risk in patients with impaired glucose tolerance (IGT). Sixty age- and gender- matched White-European adults (30 IGT and 30 normal glucose tolerance -NGT) were recruited for the study. Fasting plasma glucose, lipids and 24-hour blood pressure (BP) was measured in all subjects. Systemic vascular and endothelial function was assessed using carotid-artery intimal media thickness (cIMT) and flow mediated dilation (FMD). Retinal vascular reactivity was assessed by the Dynamic Retinal Vessel Analyser (DVA). Additionally, blood glutathione (GSH, GSSG and tGSH) and plasma von-Willebrand (vWF) factor levels were also measured. Individuals with IGT demonstrated higher BP values (p<0.001), fasting TG and TG:HDL ratios (p<0.001) than NGT subjects. Furthermore, Total:HDL-C ratios and Framingham scores were raised (p=0.010 and p<0.001 respectively). Blood glutathione levels (GSH, GSSG and tGSH) were lower (p<0.001, p=0.039 and p<0.001 respectively) while plasma vWF was increased (p=0.014) in IGT subjects compared to controls. IGT individuals also demonstrated higher IMT in right and left carotid arteries (p=0.017 and p=0.005, respectively) alongside larger brachial artery diameter (p=0.015), lower FMD% (p=0.026) and GTN induced dilation (GID) (p=0.012) than healthy controls. At the retinal arterial level, the IGT subjects showed higher baseline fluctuations (BDF) (p=0.026), longer reaction time (RT) (p=0.032) and reduced baseline-corrected flicker response (bFR) (p=0.045). In IGT subjects retinal BDF correlated with and Total:HDL (p= 0.003) and HDL-C (p= 0.004). Arterial RT also correlated with FMD (p=0.017) in IGT but not NGT subjects. In IGT individuals there is a relationship between macro- and microvascular function, as well as a direct correlation between the observed retinal microcirculatory changes and established plasma markers for CVD. Multifactorial preventive interventions to decrease vascular risk in these individuals should be considered.

Quantitative interpretation of diffusion-ordered NMR spectra:can we rationalize small molecule diffusion coefficients?

Appealingly simple: A new method is described that allows the diffusion coefficient of a small molecule to be estimated given only the molecular weight and the viscosity of the solvent used. This method makes possible the quantitative interpretation of the diffusion domain of diffusion-ordered NMR spectra (see picture). © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Tailoring the temperature and strain coefficients of Type I and Type IA dual grating sensors:the impact of hydrogenation conditions

We report experimental findings for tailoring the temperature and strain coefficients of Type I and Type IA fibre Bragg gratings by influencing the photosensitivity presensitization of the host optical fibre. It is shown that by controlling the level of hydrogen saturation, via hot and cold hydrogenation, it is possible to produce gratings with lower thermal coefficients. Furthermore, there is a larger difference between the Type I and Type IA thermal coefficients and a significant improvement in the matrix condition number, which impacts the ability to recover accurate temperature and strain data using the Type 1-1A dual grating sensor. © 2006 IOP Publishing Ltd.