Mathematical modelling and control of agitated extraction columns

Liquid-liquid extraction has long been known as a unit operation that plays an important role in industry. This process is well known for its complexity and sensitivity to operation conditions. This thesis presents an attempt to explore the dynamics and control of this process using a systematic approach and state of the art control system design techniques. The process was studied first experimentally under carefully selected. operation conditions, which resembles the ranges employed practically under stable and efficient conditions. Data were collected at steady state conditions using adequate sampling techniques for the dispersed and continuous phases as well as during the transients of the column with the aid of a computer-based online data logging system and online concentration analysis. A stagewise single stage backflow model was improved to mimic the dynamic operation of the column. The developed model accounts for the variation in hydrodynamics, mass transfer, and physical properties throughout the length of the column. End effects were treated by addition of stages at the column entrances. Two parameters were incorporated in the model namely; mass transfer weight factor to correct for the assumption of no mass transfer in the. settling zones at each stage and the backmixing coefficients to handle the axial dispersion phenomena encountered in the course of column operation. The parameters were estimated by minimizing the differences between the experimental and the model predicted concentration profiles at steady state conditions using non-linear optimisation technique. The estimated values were then correlated as functions of operating parameters and were incorporated in·the model equations. The model equations comprise a stiff differential~algebraic system. This system was solved using the GEAR ODE solver. The calculated concentration profiles were compared to those experimentally measured. A very good agreement of the two profiles was achieved within a percent relative error of ±2.S%. The developed rigorous dynamic model of the extraction column was used to derive linear time-invariant reduced-order models that relate the input variables (agitator speed, solvent feed flowrate and concentration, feed concentration and flowrate) to the output variables (raffinate concentration and extract concentration) using the asymptotic method of system identification. The reduced-order models were shown to be accurate in capturing the dynamic behaviour of the process with a maximum modelling prediction error of I %. The simplicity and accuracy of the derived reduced-order models allow for control system design and analysis of such complicated processes. The extraction column is a typical multivariable process with agitator speed and solvent feed flowrate considered as manipulative variables; raffinate concentration and extract concentration as controlled variables and the feeds concentration and feed flowrate as disturbance variables. The control system design of the extraction process was tackled as multi-loop decentralised SISO (Single Input Single Output) as well as centralised MIMO (Multi-Input Multi-Output) system using both conventional and model-based control techniques such as IMC (Internal Model Control) and MPC (Model Predictive Control). Control performance of each control scheme was. studied in terms of stability, speed of response, sensitivity to modelling errors (robustness), setpoint tracking capabilities and load rejection. For decentralised control, multiple loops were assigned to pair.each manipulated variable with each controlled variable according to the interaction analysis and other pairing criteria such as relative gain array (RGA), singular value analysis (SVD). Loops namely Rotor speed-Raffinate concentration and Solvent flowrate Extract concentration showed weak interaction. Multivariable MPC has shown more effective performance compared to other conventional techniques since it accounts for loops interaction, time delays, and input-output variables constraints.

Combined bioreaction and separation in a simulated counter-current chromatographic bioreactor-separator system

The objective of this work has been to investigate the principle of combined bioreaction and separation in a simulated counter-current chromatographic bioreactor-separator system (SCCR-S). The SCCR-S system consisted of twelve 5.4cm i.d x 75cm long columns packed with calcium charged cross-linked polystyrene resin. Three bioreactions, namely the saccharification of modified starch to maltose and dextrin using the enzyme maltogenase, the hydrolysis of lactose to galactose and glucose in the presence of the enzyme lactase and the biosynthesis of dextran from sucrose using the enzyme dextransucrase. Combined bioreaction and separation has been successfully carried out in the SCCR-S system for the saccharification of modified starch to maltose and dextrin. The effects of the operating parameters (switch time, eluent flowrate, feed concentration and enzyme activity) on the performance of the SCCR-S system were investigated. By using an eluent of dilute enzyme solution, starch conversions of up to 60% were achieved using lower amounts of enzyme than the theoretical amount required by a conventional bioreactor to produce the same amount of maltose over the same time period. Comparing the SCCR-S system to a continuous annular chromatograph (CRAC) for the saccharification of modified starch showed that the SCCR-S system required only 34.6-47.3% of the amount of enzyme required by the CRAC. The SCCR-S system was operated in the batch and continuous modes as a bioreactor-separator for the hydrolysis of lactose to galactose and glucose. By operating the system in the continuous mode, the operating parameters were further investigated. During these experiments the eluent was deionised water and the enzyme was introduced into the system through the same port as the feed. The galactose produced was retarded and moved with the stationary phase to be purge as the galactose rich product (GalRP) while the glucose moved with the mobile phase and was collected as the glucose rich product (GRP). By operating at up to 30%w/v lactose feed concentrations, complete conversions were achieved using only 48% of the theoretical amount of enzyme required by a conventional bioreactor to hydrolyse the same amount of glucose over the same time period. The main operating parameters affecting the performance of the SCCR-S system operating in the batch mode were investigated and the results compared to those of the continuous operation of the SCCR-S system. . During the biosynthesis of dextran in the SCCR-S system, a method of on-line regeneration of the resin was required to operate the system continuously. Complete conversion was achieved at sucrose feed concentrations of 5%w/v with fructose rich. products (FRP) of up to 100% obtained. The dextran rich products were contaninated by small amounts of glucose and levan formed during the bioreaction. Mathematical modelling and computer simulation of the SCCR-S. system operating in the continuous mode for the hydrolysis of lactose has been carried out. .

Differential localization of GABAA receptor subunits in relation to rat striatopallidal and pallidopallidal synapses

As a central integrator of basal ganglia function, the external segment of the globus pallidus (GP) plays a critical role in the control of voluntary movement. The GP is composed of a network of inhibitory GABA-containing projection neurons which receive GABAergic input from axons of the striatum (Str) and local collaterals of GP neurons. Here, using electrophysiological techniques and immunofluorescent labeling we have investigated the differential cellular distribution of a1, a2 and a3 GABAA receptor subunits in relation to striatopallidal (Str-GP) and pallidopallidal (GP-GP) synapses. Electrophysiological investigations showed that zolpidem (100 nm; selective for the a1 subunit) increased the amplitude and the decay time of both Str-GP and GP-GP IPSCs, indicating the presence of the a1 subunits at both synapses. However, the application of drugs selective for the a2, a3 and a5 subunits (zolpidem at 400 nm, L-838,417 and TP003) revealed differential effects on amplitude and decay time of IPSCs, suggesting the nonuniform distribution of non-a1 subunits. Immunofluorescence revealed widespread distribution of the a1 subunit at both soma and dendrites, while double- and triple-immunofluorescent labeling for parvalbumin, enkephalin, gephyrin and the ?2 subunit indicated strong immunoreactivity for GABAAa3 subunits in perisomatic synapses, a region mainly targeted by local axon collaterals. In contrast, immunoreactivity for synaptic GABAAa2 subunits was observed in dendritic compartments where striatal synapses are preferentially located. Due to the kinetic properties which each GABAAa subunit confers, this distribution is likely to contribute differentially to both physiological and pathological patterns of activity.

The development of a multi-function computer-assisted instruction system using a hierarchical database structure as the lesson compendium.

Computer-Based Learning systems of one sort or another have been in existence for almost 20 years, but they have yet to achieve real credibility within Commerce, Industry or Education. A variety of reasons could be postulated for this, typically: - cost - complexity - inefficiency - inflexibility - tedium Obviously different systems deserve different levels and types of criticism, but it still remains true that Computer-Based Learning (CBL) is falling significantly short of its potential. Experience of a small, but highly successful CBL system within a large, geographically distributed industry (the National Coal Board) prompted an investigation into currently available packages, the original intention being to purchase the most suitable software and run it on existing computer hardware, alongside existing software systems. It became apparent that none of the available CBL packages were suitable, and a decision was taken to develop an in-house Computer-Assisted Instruction system according to the following criteria: - cheap to run; - easy to author course material; - easy to use; - requires no computing knowledge to use (as either an author or student) ; - efficient in the use of computer resources; - has a comprehensive range of facilities at all levels. This thesis describes the initial investigation, resultant observations and the design, development and implementation of the SCHOOL system. One of the principal characteristics c£ SCHOOL is that it uses a hierarchical database structure for the storage of course material - thereby providing inherently a great deal of the power, flexibility and efficiency originally required. Trials using the SCHOOL system on IBM 303X series equipment are also detailed, along with proposed and current development work on what is essentially an operational CBL system within a large-scale Industrial environment.

Interaction of peptides, peptidomimetics and other drug candidates with the DI/tripeptide transport system in intestinal epithelial cells, using the in vitro caco-2 cell culture system

An uptake system was developed using Caco-2 cell monolayers and the dipeptide, glycyl-[3H]L-proline, as a probe compound. Glycyl-[3H]L-proline uptake was via the di-/tripeptide transport system (DTS) and, exhibited concentration-, pH- and temperature-dependency. Dipeptides inhibited uptake of the probe, and the design of the system allowed competitors to be ranked against one another with respect to affinity for the transporter. The structural features required to ensure or increase interaction with the DTS were defined by studying the effect of a series of glycyl-L-proline and angiotensin-converting enzyme (ACE)-inhibitor (SQ-29852) analogues on the uptake of the probe. The SQ-29852 structure was divided into six domains (A-F) and competitors were grouped into series depending on structural variations within specific regions. Domain A was found to prefer a hydrophobic function, such as a phenyl group, and was intolerant to positive charges and H+ -acceptors and donors. SQ-29852 analogues were more tolerant of substitutions in the C domain, compared to glycyl-L-proline analogues, suggesting that interactions along the length of the SQ-29852 molecule may override the effects of substitutions in the C domain. SQ-29852 analogues showed a preference for a positive function, such as an amine group in this region, but dipeptide structures favoured an uncharged substitution. Lipophilic substituents in domain D increased affinity of SQ-29852 analogues with the DTS. A similar effect was observed for ACE-NEP inhibitor analogues. Domain E, corresponding to the carboxyl group was found to be tolerant of esterification for SQ-29852 analogues but not for dipeptides. Structural features which may increase interaction for one series of compounds, may not have the same effect for another series, indicating that the presence of multiple recognition sites on a molecule may override the deleterious effect of anyone change. Modifying current, poorly absorbed peptidomimetic structures to fit the proposed hypothetical model may improve oral bioavailability by increasing affinity for the DTS. The stereochemical preference of the transporter was explored using four series of compounds (SQ-29852, lysylproline, alanylproline and alanylalanine enantiomers). The L, L stereochemistry was the preferred conformation for all four series, agreeing with previous studies. However, D, D enantiomers were shown in some cases to be substrates for the DTS, although exhibiting a lower affinity than their L, L counterparts. All the ACE-inhibitors and β-lactam antibiotics investigated, produced a degree of inhibition of the probe, and thus show some affinity for the DTS. This contrasts with previous reports that found several ACE inhibitors to be absorbed via a passive process, thus suggesting that compounds are capable of binding to the transporter site and inhibiting the probe without being translocated into the cell. This was also shown to be the case for oligodeoxynucleotide conjugated to a lipophilic group (vitamin E), and highlights the possibility that other orally administered drug candidates may exert non-specific effects on the DTS and possibly have a nutritional impact. Molecular modelling of selected ACE-NEP inhibitors revealed that the three carbonyl functions can be oriented in a similar direction, and this conformation was found to exist in a local energy-minimised state, indicating that the carbonyls may possibly be involved in hydrogen-bond formation with the binding site of the DTS.

The measurement and significance of ATP pools in activated sludge treating coke oven liquors

Coke oven liquor is a toxic wastewater produced in large quantities by the Iron and Steel, and Coking Industries, and gives rise to major effluent treatment problems in those industries. Conscious of the potentially serious environmental impact of the discharge of such wastes, pollution control agencies in many countries have made progressively more stringent quality requirements for the discharge of the treated waste. The most common means of treating the waste is the activated sludge process. Problems with achieving consistently satisfactory treatment by this process have been experienced in the past. The need to improve the quality of the discharge of the treated waste prompted attempts by TOMLINS to model the process using Adenosine Triphosophnte (ATP) as a measure of biomass, but these were unsuccessful. This thesis describes work that was carried out to determine the significance of ATP in the activated sludge treatment of the waste. The use of ATP measurements in wastewater treatment were reviewed. Investigations were conducted into the ATP behaviour of the batch activated sludge treatment of two major components of the waste, phenol, and thiocyanate, and the continuous activated sludge treatment of the liquor itself, using laboratory scale apparatus. On the basis of these results equations were formulated to describe the significance of ATP as a measured activity and biomass in the treatment system. These were used as the basis for proposals to use ATP as a control parameter in the activated sludge treatment of coke oven liquor, and wastewaters in general. These had relevance both to the treatment of the waste in the reactor and to the settlement of the sludge produced in the secondary settlement stage of the treatment process.

Use of amino acids as counterions improves the solubility of the BCS II model drug, indomethacin

The number of new chemical entities (NCE) is increasing every day after the introduction of combinatorial chemistry and high throughput screening to the drug discovery cycle. One third of these new compounds have aqueous solubility less than 20µg/mL [1]. Therefore, a great deal of interest has been forwarded to the salt formation technique to overcome solubility limitations. This study aims to improve the drug solubility of a Biopharmaceutical Classification System class II (BCS II) model drug (Indomethacin; IND) using basic amino acids (L-arginine, L-lysine and L-histidine) as counterions. Three new salts were prepared using freeze drying method and characterised by FT-IR spectroscopy, proton nuclear magnetic resonance ((1)HNMR), Differential Scanning Calorimetry (DSC) and Thermogravimetric analysis (TGA). The effect of pH on IND solubility was also investigated using pH-solubility profile. Both arginine and lysine formed novel salts with IND, while histidine failed to dissociate the free acid and in turn no salt was formed. Arginine and lysine increased IND solubility by 10,000 and 2296 fold, respectively. An increase in dissolution rate was also observed for the novel salts. Since these new salts have improved IND solubility to that similar to BCS class I drugs, IND salts could be considered for possible waivers of bioequivalence.

A process framework for selecting supply system architecture in manufacturing supply chains and networks

The process framework comprises three phases, as follows: scope the supply chain/network; identify the options for supply system architecture and select supply system architecture. It facilitates a structured approach that analyses the supply chain/network contextual characteristics, in order to ensure alignment with the appropriate supply system architecture. The process framework was derived from comprehensive literature review and archival case study analysis. The review led to the classification of supply system architectures according to their orientation, whether integrated; partially integrated; co-ordinated or independent. The classification was combined with the characteristics that influence the selection of supply system architecture to encapsulate the conceptual framework. It builds upon existing frameworks and methodologies by focusing on structured procedure; supporting project management; facilitating participation and clarifying point of entry. The process framework was initially tested in three case study applications from the food, automobile and hand tool industries. A variety of industrial settings was chosen to illustrate transferability. The case study applications indicate that the process framework is a valid approach to the problem; however, further testing is required. In particular, the use of group support system technologies to support the process and the steps involving the participation of software vendors need further testing. However, the process framework can be followed due to the clarity of its presentation. It considers the issue of timing by including alternative decision-making techniques, dependent on the constraints. It is useful for ensuring a sound business case is developed, with supporting documentation and analysis that identifies the strategic and functional requirements of supply system architecture.

Enhancing student learning experience through a novel electronic coursework assessment and feedback management system

Recent National Student Surveys revealed that many U.K. university students are dissatisfied with the timeliness and usefulness of the feedback received from their tutors. Ensuring timeliness in marking often results in a reduction in the quality of feedback. In Computer Science where learning relies on practising and learning from mistakes, feedback that pin-points errors and explains means of improvement is important to achieve a good student learning experience. Though suitable use of Information and Communication Technology should alleviate this problem, existing Virtual Learning Environments and e-Assessment applications such as Blackboard/WebCT, BOSS, MarkTool and GradeMark are inadequate to support a coursework assessment process that promotes timeliness and usefulness of feedback while maintaining consistency in marking involving multiple tutors. We have developed a novel Internet application, called eCAF, for facilitating an efficient and transparent coursework assessment and feedback process. The eCAF system supports detailed marking scheme editing and enables tutors to use such schemes to pin-point errors in students' work so as to provide helpful feedback efficiently. Tutors can also highlight areas in a submitted work and associate helpful feedback that clearly links to the identified mistakes and the respective marking criteria. In light of the results obtained from a recent trial of eCAF, we discuss how the key features of eCAF may facilitate an effective and efficient coursework assessment and feedback process.

National system of innovation and technological learning:an integrated framework for understanding technological capability development in the Russian forestry sector

One of the issues in the innovation system literature is examination of technological learning strategies of laggard nations. Two distinct bodies of literature have contributed to our insight into forces driving learning and innovation, National Systems of Innovation (NSI) and technological learning literature. Although both literatures yield insights on catch-up strategies of 'latecomer' nations, the explanatory powers of each literature by itself is limited. In this paper, a possible way of linking the macro- and the micro-level approaches by incorporating enterprises as active learning entities into the learning and innovation system is proposed. The proposed model has been used to develop research hypotheses and indicate research directions and is relevant for investigating the learning strategies of firms in less technologically intensive industries outside East Asia.

Controlling system uncertainty in sport and work

An applied psychological framework for coping with performance uncertainty in sport and work systems is presented. The theme of personal control serves to integrate ideas prevalent in industrial and organisational psychology, the stress literature and labour process theory. These commonly focus on the promotion of tacit knowledge and learned resourcefulness in individual performers. Finally, data from an empirical evaluation of a development training programme to facilitate self-regulation skills in professional athletes are briefly highlighted.