Regulation of albumin endocytosis by PSD95/Dlg/ZO-1 (PDZ) scaffolds - Interaction of Na+-H+ exchange regulatory factor-2 with ClC-5

The constitutive reuptake of albumin from the glomerular filtrate by receptor-mediated endocytosis is a key function of the renal proximal tubules. Both the Cl- channel ClC-5 and the Na+-H+ exchanger isoform 3 are critical components of the macromolecular endocytic complex that is required for albumin uptake, and therefore the cell-surface levels of these proteins may limit albumin endocytosis. This study was undertaken to investigate the potential roles of the epithelial PDZ scaffolds, Na+-H+ exchange regulatory factors, NHERF1 and NHERF2, in albumin uptake by opossum kidney ( OK) cells. We found that ClC-5 co-immunoprecipitates with NHERF2 but not NHERF1 from OK cell lysate. Experiments using fusion proteins demonstrated that this was a direct interaction between an internal binding site in the C terminus of ClC-5 and the PDZ2 module of NHERF2. In OK cells, NHERF2 is restricted to the intravillar region while NHERF1 is located in the microvilli. Silencing NHERF2 reduced both cell-surface levels of ClC-5 and albumin uptake. Conversely, silencing NHERF1 increased cell-surface levels of ClC-5 and albumin uptake, presumably by increasing the mobility of NHE3 in the membrane and its availability to the albumin uptake complex. Surface biotinylation experiments revealed that both NHERF1 and NHERF2 were associated with the plasma membrane and that NHERF2 was recruited to the membrane in the presence of albumin. The importance of the interaction between NHERF2 and the cytoskeleton was demonstrated by a significant reduction in albumin uptake in cells overexpressing an ezrin binding-deficient mutant of NHERF2. Thus NHERF1 and NHERF2 differentially regulate albumin uptake by mechanisms that ultimately alter the cell-surface levels of ClC-5.

A golden age of human pigmentation genetics

The zebrafish golden mutation is characterized by the production of small and irregular-shaped melanin granules, resulting in a lightening of the pigmented lateral stripes of the animal. The recent positional cloning and localization of the golden gene, combined with genotype-phenotype correlations of alleles of its human orthologue (SLC24A5) in African-American and African-Caribbean populations, provide insights into the genetic and molecular basis of human skin colour. SLC24A5 promotes melanin deposition through maturation of the melanosome, highlighting the importance of ion-exchange in the function of this organelle.

Erosion-corrosion of mild steel in hot caustic. Part I: NaOH solution

A novel apparatus, high-pressure/high-temperature nickel flow loop, was constructed to study the effect of the flow on the rate of erosion-corrosion of mild steel in hot caustic. It has been successfully used to measure the corrosion rate of 1020 steel in 2.75 M NaOH solution at a temperature of 160 degrees C and velocities of 0.32 and 2.5 m/s. In situ electrochemical methods were used to measure the corrosion rate such as the potentiodynamic sweep, the polarization resistance method, and electrochemical impedance spectroscopy (EIS). Also used were the weight-loss method and scanning electron microscopy (SEM). Eight electrodes/coupons were used to monitor the metal loss rate, four were placed at the low velocity section, while the other four were placed in the high velocity section. The first three coupons in each section were placed within the disturbed flow region, while the fourth was placed in a fully developed flow region. The corrosion rate of the coupons in the high velocity section was generally higher than that of the coupons in the low velocity section. One coupon in the disturbed flow region had a significantly higher corrosion rate than the others. (c) 2005 Elsevier Ltd. All rights reserved.

Erosion-corrosion of mild steel in hot caustic. Part II: The effect of acid cleaning

Corrosion rates of 1020 steel in 2.75 M NaOH solution at a temperature of 160 degrees C and velocities of 0.32 and 2.5 m/s were studied. The focus was on the effect of the acid cleaning which was performed by using strong, inhibited sulphuric acid in between the exposures to caustic. In situ electrochemical methods were used to measure the corrosion rate such as the potentiodynamic sweep and the polarization resistance method. Also used were the weight-loss method and scanning electron microscopy (SEM). Eight electrodes/coupons were used to monitor the metal loss rate, four were placed at the low velocity section, while the other four were placed in the high velocity section of a high temperature flow. The first three coupons in each section were placed within the disturbed flow region, while the fourth was placed in a fully developed flow region. During the exposure of mild steel to the inhibited acid, following the first caustic period, the corrosion rate increased significantly to between 3 and 10mm/y with a few electrodes experiencing as high as 50 mm/y. The second caustic period following the acidic period typically started with very high corrosion rates (20-80 mm/y). The length of this corrosion period was typically 2-3 h with a few exceptions when the high corrosion period lasted 7-10 h. Following the very high corrosion rates experienced at the beginning of the second caustic period, the corrosion rates were reduced sharply (as the corrosion potential increased) to nearly the same levels as those observed during the passive part of the first caustic period. (c) 2005 Elsevier Ltd. All rights reserved.

Experimental and analytical study of the effect of contact angle on liquid convective heat transfer in microchannels

In this paper we examine the effect of contact angle (or surface wettability) on the convective heat transfer coefficient in microchannels. Slip flow, where the fluid velocity at the wall is non-zero, is most likely to occur in microchannels due to its dependence on shear rate or wall shear stress. We show analytically that for a constant pressure drop, the presence of slip increases the Nusselt number. In a microchannel heat exchanger we modified the surface wettability from a contact angle of 20 degrees-120 degrees using thin film coating technology. Apparent slip flow is implied from pressure and flow rate measurements with a departure from classical laminar friction coefficients above a critical shear rate of approximately 10,000 s(-1). The magnitude of this departure is dependant on the contact angle with higher contact angles surfaces exhibiting larger pressure drop decreases. Similarly, the non-dimensional heat flux is found to decrease relative to laminar non-slip theory, and this decrease is also a function of the contact angle. Depending on the contact angle and the wall shear rate, variations in the heat transfer rate exceeding 10% can be expected. Thus the contact angle is an important consideration in the design of micro, and even more so, nano heat exchangers. (c) 2006 Elsevier Ltd. All rights reserved.

Using computational fluid dynamics in combating erosion-corrosion

Computational fluid dynamics was used to search for the links between the observed pattern of attack seen in a bauxite refinery's heat exchanger headers and the hydrodynamics inside the header. Validation of the computational fluid dynamics results was done by comparing then with flow parameters measured in a 1:5 scale model of the first pass header in the laboratory. Computational fluid dynamics simulations were used to establish hydrodynamic similarity between the 1:5 scale and full scale models of the first pass header. It was found that the erosion-corrosion damage seen at the tubesheet of the first pass header was a consequence of increased levels of turbulence at the tubesheet caused by a rapidly turning flow. A prismatic flow corrections device introduced in the past helped in rectifying the problem at the tubesheet but exaggerated the erosion-corrosion problem at the first pass header shell. A number of alternative flow correction devices were tested using computational fluid dynamics. Axial ribbing in the first pass header and an inlet flow diffuser have shown the best performance and were recommended for implementation. Computational fluid dynamics simulations have revealed a smooth orderly low turbulence flow pattern in the second, third and fourth pass as well as the exit headers where no erosion-corrosion was seen in practice. This study has confirmed that near-wall turbulence intensity, which can be successfully predicted by using computational fluid dynamics, is a good hydrodynamic predictor of erosion-corrosion damage in complex geometries. (c) 2006 Published by Elsevier Ltd.

Double-heater-wire circuits and heat-and-moisture exchangers and the risk of ventilator-associated pneumonia

Objective: To compare the incidence of ventilator-associated pneumonia (VAP) in patients ventilated in intensive care by means of circuits humidified with a hygroscopic heat-and-moisture exchanger with a bacterial viral filter (HME) or hot-water humidification with a heater wire in both inspiratory and expiratory circuit limbs (DHW) or the inspiratory limb only (SHW). Design: A prospective, randomized trial. Setting: A metropolitan teaching hospital's general intensive care unit. Patients: Three hundred eighty-one patients requiring a minimum period of mechanical ventilation of 48 hrs. Interventions: Patients were randomized to humidification with use of an HME (n = 190), SHW (n = 94), or DHW (n = 97). Measurements and Main Results. Study end points were VAP diagnosed on the basis of Clinical Pulmonary Infection Score (CPIS) (1), HME resistance after 24 hrs of use, endotracheal tube resistance, and HME use per patient. VAP occurred with similar frequency in all groups (13%, HME; 14%, DHW; 10%, SHW; p = 0.61) and was predicted only by current smoking (adjusted odds ratio [AOR], 2.1; 95% confidence interval [CI], 1.1-3.9; p =.03) and ventilation days (AOR, 1.05; 95% Cl, 1.0-1.2; p =.001); VAP was less likely for patients with an admission diagnosis of pneumonia (AOR, 0.40; 95% Cl, 0.4-0.2; p =.04). HME resistance after 24 hrs of use measured at a gas flow of 50 L/min was 0.9 cm H2O (0.4-2.9). Endotracheal tube resistance was similar for all three groups (16-19 cm H2O min/L; p =.2), as were suction frequency, secretion thickness, and blood on suctioning (p =.32, p =.06, and p =.34, respectively). The HME use per patient per day was 1.13. Conclusions: Humidification technique does not influence either VAP incidence or secretion characteristics, but HMEs may have air-flow resistance higher than manufacturer specifications after 24 hrs of use.

Shell-side transfer in shell-and-tube heat exchangers

Local mass transfer coefficients were determined by using the electrochemical technique. A simple model of a heat exchanger with segmental nickel tube joined to p.v.c. rods replaced the exchanger tubes. Measurements were made for both no-Ieakage, semi-leakage and total leakage configurations. Baffle-spacings of 47.6 mm, 66.6 mm, 97 mm and 149.2 mm wer studied. Also studied were the overall exchanger pressure drops for each configuration. The comparison of the heat transfer data with this work showed good agreement at high flow rates for the no-leakage case, but the agreement became poor for lower flow rates and leakage configurations. This disagreement was explained by non-analogous driving forces existing in the two systems. The no-leakage data showed length-wise variation of transfer coefficients along the exchanger length. The end compartments showing transfer coefficients inferior by up to 26% compared to tbe internal compartments, depending on Reynolds number. With the introduction of leakage streams this variation however became smaller than the experimental accuracy. A model is outlined to show the characteristic behaviour of individual electrode segments within the compartment. This was able to discriminate between cross and window zones for the no- leakage case, but no such distinction could be made for the leakage case. A flow area was found which, when incorporated in the Reynolds number, enabled the correlation of baffle-cut and baffle-spacing parameters for the no-leakage case . This area is the free flow area determined at the baffle edge. Addition of the leakage area to this flow area resulted in correlation of all commercial leakage geometrical parameters. The procedures used to correlate the pressure drop data from a total of eighteen different configurations on a single curve are also outlined.

Modelling of transient heat transfer in annealing furnaces

This is a study of heat transfer in a lift-off furnace which is employed in the batch annealing of a stack of coils of steel strip. The objective of the project is to investigate the various factors which govern the furnace design and the heat transfer resistances, so as to reduce the time of the annealing cycle, and hence minimize the operating costs. The work involved mathematical modelling of patterns of gas flow and modes of heat transfer. These models are: Heat conduction and its conjectures in the steel coils;Convective heat transfer in the plates separating the coils in the stack and in other parts of the furnace; and Radiative and convective heat transfer in the furnace by using the long furnace model. An important part of the project is the development of numerical methods and computations to solve the transient models. A limited number of temperature measurements was available from experiments on a test coil in an industrial furnace. The mathematical model agreed well with these data. The model has been used to show the following characteristics of annealing furnaces, and to suggest further developments which would lead to significant savings: - The location of the limiting temperature in a coil is nearer to the hollow core than to the outer periphery. - Thermal expansion of the steel tends to open the coils, reduces their thermal conductivity in the radial direction, and hence prolongs the annealing cycle. Increasing the tension in the coils and/or heating from the core would overcome this heat transfer resistance. - The shape and dimensions of the convective channels in the plates have significant effect on heat convection in the stack. An optimal design of a channel is shown to be of a width-to-height ratio equal to 9. - Increasing the cooling rate, by using a fluidized bed instead of the normal shell and tube exchanger, would shorten the cooling time by about 15%, but increase the temperature differential in the stack. - For a specific charge weight, a stack of different-sized coils will have a shorter annealing cycle than one of equally-sized coils, provided that production constraints allow the stacking order to be optimal. - Recycle of hot flue gases to the firing zone of the furnace would produce a. decrease in the thermal efficiency up to 30% but decreases the heating time by about 26%.

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.

Modified hydrogel matrices in fibre optic sensors

Common problems encountered in clinical sensing are those of non-biocompatibility, and slow response time of the device. The latter, also applying to chemical sensors, is possibly due to a lack of understanding of polymer support or membrane properties and hence failure to optimise membranes chosen for specific sensor applications. Hydrogels can be described as polymers which swell in water. In addition to this, the presence of water in the polymer matrix offers some control of biocompatibility. They thus provide a medium through which rapid transport of a sensed species to an incorporated reagent could occur. This work considers the feasibility of such a system, leading to the design and construction of an optical sensor test bed. The development of suitable membrane systems and of suitable coating techniques in order to apply them to the fibre optics is described. Initial results obtained from hydrogel coatings implied that the refractive index change in the polymer matrix, due to a change in water content with pH is the major factor contributing to the sensor response. However the presence of the colourimetric reagent was also altering the output signal obtained. An analysis of factors contributing to the overall response, such as colour change and membrane composition were made on both the test bed, via optical response, and on whole membranes via measurement of water content change. The investigation of coatings with low equilibrium water contents, of less than 10% was carried out and in fact a clearer signal response from the test bed was noted. Again these membranes were suprisingly responding via refractive index change, with the reagent playing a primary role in obtaining a sensible or non-random response, although not in a colourimetric fashion. A photographic study of these coatings revealed some clues as to the physical nature of these coatings and hence partially explained this phenomenon. A study of the transport properties of the most successful membrane, on a coated wire electrode and also on the fibre optic test bed, in a series of test environments, indicated that the reagent was possibly acting as an ion exchanger and hence having a major influence on transport and therefore sensor characteristics.

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.

Studies of the shellside performance of shell-and-tube heat exchangers

Accurate prediction of shellside pressure drop in a baffled shell-and-tube heat exchanger is very difficult because of the complicated shellside geometry. Ideally, all the shellside fluid should be alternately deflected across the tube bundle as it traverses from inlet to outlet. In practice, up to 60% of the shellside fluid may bypass the tube bundle or leak through the baffles. This short-circuiting of the main flow reduces the efficiency of the exchanger. Of the various shellside methods, it is shown that only the multi-stream methods, which attempt to obtain the shellside flow distribution, predict the pressure drop with any degree of accuracy, the various predictions ranging from -30% to +70%, generally overpredicting. It is shown that the inaccuracies are mainly due to the manner in which baffle leakage is modelled. The present multi-stream methods do not allow for interactions of the various flowstreams, and yet it is shown that three main effects are identified, a) there is a strong interaction between the main cross flow and the baffle leakage streams, enhancing the crossflow pressure drop, b) there is a further short-circuit not considered previously i.e. leakage in the window, and c) the crossflow does not penetrate as far, on average, as previously supposed. Models are developed for each of these three effects, along with a new windowflow pressure drop model, and it is shown that the effect of baffle leakage in the window is the most significant. These models developed to allow for various interactions, lead to an improved multi-stream method, named the "STREAM-INTERACTION" method. The overall method is shown to be consistently more accurate than previous methods, with virtually all the available shellside data being predicted to within ±30% and over 60% being within ±20%. The method is, thus, strongly recommended for use as a design method.

Energy conservation in the steel industry

The last few years have witnessed an unprecedented increase in the price of energy available to industry in the United Kingdom and worldwide. The steel industry, as a major consumer of energy delivered in U.K. (8% of national total and nearly 25% of industrial total) and whose energy costs currently form some 28% of the total manufacturing cost, is very much aware of the need to conserve energy. Because of the complexities of steelmaking processes it is imperative that a full understanding of each process and its interlinking role in an integrated steelworks is understood. An analysis of energy distribution shows that as much as 70% of heat input is dissipated to the environment in a variety of forms. Of these, waste gases offer the best potential for energy conservation. The study identifies areas for and discusses novel methods of energy conservation in each process. Application of these schemes in BSC works is developed and their economic incentives highlighted. A major part of this thesis describes design, development and testing of a novel ceramic rotary regenerator for heat recovery from high temperature waste gases, where no such system is available. The regenerator is a compact, efficient heat exchanger. Application of such a system to a reheating furnace provides a fuel saving of up to 40%. A mathematical model developed is verified on the pilot plant. The results obtained confirm the success of the concept and material selection and outlines the work needed to develop an industrial unit. Last, but not least, the key position of an energy manager in an energy conservation programme is identified and a new Energy Management Model for the BSC is developed.

The effects of the changing energy situation on demand for industrial heat exchangers

The Project arose during a period in which the World was still coming to terms with the effects and implications of the so called 'energy crisis' of 1973/74. Serck Heat Transfer is a manufacturer of heat exchangers which transfer heat between fluids of various sorts. As such the company felt that past and possible future changes in the energy situation could have an impact upon the demand for its products. The thesis represents the first attempt to examine the impact of changes in the energy situation (a major economic variable) on the long term demand for heat exchangers. The scope of the work was limited to the United Kingdom, this being the largest single market for Serek's products. The thesis analyses industrial heat exchanger markets and identifies those trends which are related to both the changing energy situation and the usage of heat exchangers. These trends have been interpreted In terms of projected values of heat exchanger demand. The projections cover the period 197S to the year 2000. Also examined in the thesis is the future energy situation both internationally and nationally and it is found that in the long term there will be increasing pressure on consumers to conserve energy through rising real prices. The possibility of a connection between energy consumption and heat exchanger demand is investigated and no significant correlation found. This appears to be because there are a number of determinants of demand besides energy related factors and also there is a wide diversity of individual markets for heat exchangers. Conclusions are that in all markets, bar one, the changing energy situation should lead to a higher level of heat exchanger demand than would otherwise be the case had the energy situation not changed. It is also pointed out that it is misleading to look at changes in one influence on the demand for a product and ignore others.