The interaction between master production scheduling and detailed capacity requirements planning : closing the loop in manufacturing resource planning (MRPII) systems

The widespread implementation of Manufacturing Resource Planning (MRPII) systems in this country and abroad and the reported dissatisfaction with their use formed the initial basis of this piece of research which concentrates on the fundamental theory and design of the Closed Loop MRPII system itself. The dissertation concentrates on two key aspects namely; how Master Production Scheduling is carried out in differing business environments and how well the `closing of the loop' operates by checking the capcity requirements of the different levels of plans within an organisation. The main hypothesis which is tested is that in U.K. manufacturing industry, resource checks are either not being carried out satisfactorily or they are not being fed back to the appropriate plan in a timely fashion. The research methodology employed involved initial detailed investigations into Master Scheduling and capacity planning in eight diverse manufacturing companies. This was followed by a nationwide survey of users in 349 companies, a survey of all the major suppliers of Production Management software in the U.K. and an analysis of the facilities offered by current software packages. The main conclusion which is drawn is that the hypothesis is proved in the majority of companies in that only just over 50% of companies are attempting Resource and Capacity Planning and only 20% are successfully feeding back CRP information to `close the loop'. Various causative factors are put forward and remedies are suggested.

Women’s Entrepreneurship: closing the gender gap in access to financial and other services and in social entrepreneurship

This study explores differences between men and women entrepreneurs and social entrepreneurs. It explores the barriers and discriminatory effects that hinder women’s entrepreneurship, including access to finance in the European Union. The study includes four case studies covering the situation in the Czech Republic, Italy, Sweden, and the United Kingdom.

The second intracellular loop of the calcitonin gene-related peptide receptor provides molecular determinants for signal transduction and cell surface expression

The calcitonin gene-related peptide (CGRP) receptor is a heterodimer of a family B G-protein-coupled receptor, calcitonin receptor-like receptor (CLR), and the accessory protein receptor activity modifying protein 1. It couples to Gs, but it is not known which intracellular loops mediate this. We have identified the boundaries of this loop based on the relative position and length of the juxtamembrane transmembrane regions 3 and 4. The loop has been analyzed by systematic mutagenesis of all residues to alanine, measuring cAMP accumulation, CGRP affinity, and receptor expression. Unlike rhodopsin, ICL2 of the CGRP receptor plays a part in the conformational switch after agonist interaction. His-216 and Lys-227 were essential for a functional CGRP-induced cAMP response. The effect of (H216A)CLR is due to a disruption to the cell surface transport or surface stability of the mutant receptor. In contrast, (K227A)CLR had wild-type expression and agonist affinity, suggesting a direct disruption to the downstream signal transduction mechanism of the CGRP receptor. Modeling suggests that the loop undergoes a significant shift in position during receptor activation, exposing a potential G-protein binding pocket. Lys-227 changes position to point into the pocket, potentially allowing it to interact with bound G-proteins. His-216 occupies a position similar to that of Tyr-136 in bovine rhodopsin, part of the DRY motif of the latter receptor. This is the first comprehensive analysis of an entire intracellular loop within the calcitonin family of G-protein-coupled receptor. These data help to define the structural and functional characteristics of the CGRP-receptor and of family B G-protein-coupled receptors in general. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

The use of loop mirrors and chirped fibre Bragg gratings in actively-modelocked fibre lasers

The development of an all-optical communications infrastructure requires appropriate optical switching devices and supporting hardware. This thesis presents several novel fibre lasers which are useful pulse sources for high speed optical data processing and communications. They share several attributes in common: flexibility, stability and low-jitter output. They all produce short (picosecond) and are suitable as sources for soliton systems. The lasers are all-fibre systems using erbium-doped fibre for gain, and are actively-modelocked using a dual-wavelength nonlinear optical loop mirror (NOLM) as a modulator. Control over the operating wavelength and intra-cavity dispersion is obtained using a chirped in-fibre Bragg grating.Systems operating both at 76MHz and gigahertz frequencies are presented, the latter using a semiconductor laser amplifier to enhance nonlinear action in the loop mirror. A novel dual-wavelength system in which two linear cavities share a common modulator is presented with results which show that the jitter between the two wavelengths is low enough for use in switching experiments with data rates of up to 130Gbit/s.

Functional split and crosslinking of the membrane domain of the β subunit of proton-translocating transhydrogenase from Escherichia coli

Proton pumping nicotinamide nucleotide transhydrogenase from Escherichia coli contains an α subunit with the NAD(H)-binding domain I and a β subunit with the NADP(H)-binding domain III. The membrane domain (domain II) harbors the proton channel and is made up of the hydrophobic parts of the α and β subunits. The interface in domain II between the α and the β subunits has previously been investigated by cross-linking loops connecting the four transmembrane helices in the α subunit and loops connecting the nine transmembrane helices in the β subunit. However, to investigate the organization of the nine transmembrane helices in the β subunit, a split was introduced by creating a stop codon in the loop connecting transmembrane helices 9 and 10 by a single mutagenesis step, utilizing an existing downstream start codon. The resulting enzyme was composed of the wild-type α subunit and the two new peptides β1 and β2. As compared to other split membrane proteins, the new transhydrogenase was remarkably active and catalyzed activities for the reduction of 3-acetylpyridine-NAD + by NADPH, the cyclic reduction of 3-acetylpyridine-NAD + by NADH (mediated by bound NADP(H)), and proton pumping, amounting to about 50-107% of the corresponding wild-type activities. These high activities suggest that the α subunit was normally folded, followed by a concerted folding of β1 + β2. Cross-linking of a βS105C-βS237C double cysteine mutant in the functional split cysteine-free background, followed by SDS-PAGE analysis, showed that helices 9, 13, and 14 were in close proximity. This is the first time that cross-linking between helices in the same β subunit has been demonstrated.

A quantitative study of the pathological changes in the cerebellum in 15 cases of variant Creutzfeldt–Jakob disease (vCJD)

Aims: To determine in the cerebellum in variant Creutzfeldt–Jakob disease (vCJD): (i) whether the pathology affected all laminae; (ii) the spatial topography of the pathology along the folia; (iii) spatial correlations between the pathological changes; and (iv) whether the pathology was similar to that of the common methionine/methionine Type 1 subtype of sporadic CJD. Methods: Sequential cerebellar sections of 15 cases of vCJD were stained with haematoxylin and eosin, or immunolabelled with monoclonal antibody 12F10 against prion protein (PrP) and studied using spatial pattern analysis. Results: Loss of Purkinje cells was evident compared with control cases. Densities of the vacuolation and the protease-resistant form of prion protein (PrPSc) (diffuse and florid plaques) were greater in the granule cell layer (GL) than the molecular layer (ML). In the ML, vacuoles and PrPSc plaques occurred in clusters regularly distributed along the folia with larger clusters of vacuoles and diffuse plaques in the GL. There was a negative spatial correlation between the vacuoles and the surviving Purkinje cells in the ML. There was a positive spatial correlation between the vacuoles and diffuse PrPSc plaques in the ML and GL. Conclusions: (i) all laminae were affected by the pathology, the GL more severely than the ML; (ii) the pathology was topographically distributed along the folia especially in the Purkinje cell layer and ML; (iii) pathological spread may occur in relation to the loop of anatomical connections involving the cerebellum, thalamus, cerebral cortex and pons; and (iv) there were pathological differences compared with methionine/methionine Type 1 sporadic CJD.

Nonlinear loop mirror-based all-optical signal processing in fiber-optic communications

All-optical data processing is expected to play a major role in future optical communications. The fiber nonlinear optical loop mirror (NOLM) is a valuable tool in optical signal processing applications. This paper presents an overview of our recent advances in developing NOLM-based all-optical processing techniques for application in fiber-optic communications. The use of in-line NOLMs as a general technique for all-optical passive 2R (reamplification, reshaping) regeneration of return-to-zero (RZ) on-off keyed signals in both high-speed, ultralong-distance transmission systems and terrestrial photonic networks is reviewed. In this context, a theoretical model enabling the description of the stable propagation of carrier pulses with periodic all-optical self-regeneration in fiber systems with in-line deployment of nonlinear optical devices is presented. A novel, simple pulse processing scheme using nonlinear broadening in normal dispersion fiber and loop mirror intensity filtering is described, and its employment is demonstrated as an optical decision element at a RZ receiver as well as an in-line device to realize a transmission technique of periodic all-optical RZ-nonreturn-to-zero-like format conversion. The important issue of phase-preserving regeneration of phase-encoded signals is also addressed by presenting a new design of NOLM based on distributed Raman amplification in the loop fiber. © 2008 Elsevier Inc. All rights reserved.

Picosecond soliton transmission using concatenated nonlinear optical loop mirror intensity filters

We investigate the use of nonlinear optical loop mirrors as saturable absorbers in picosecond soliton transmission systems. It is found that they allow short (1–5-ps) pulses to be propagated through chains of optical amplifiers spaced at intervals of typically 10 km. The loop mirror removes dispersive waves and stabilizes the peak amplitude of the soliton. An additional advantage is that the self-frequency shift of the soliton may be suppressed by bandwidth filtering without causing growth of dispersive waves at the center of the passband. The timing jitter and soliton interactions present in the scheme are also described.

Aminoglycoside-induced changes in the renal handling of cations in the Fischer 344 rat

Disturbances of cation homeostasis, particularly hypomagnesaemia, are a frequent consequence of treatment with aminoglycoside antibiotics. These disturbances are thought to result from renal wasting of cations and administration of gentamicin to rats has been shown to produce hypercalciuria and hypermagnesiuria. The aims of this study were to attempt to elucidate these responses in anaesthetised rats infused with gentamicin and to use this model to investigate the mechanisms of these effects. Fischer 344 rats were anaesthetised and surgically prepared for clearance experiments. Infusion of gentamicin in isotonic saline increased urinary output of calcium and magnesium while sodium and potassium output were unaffected. These elevations in calcium and magnesium excretion were explained by reduced tubular reabsorption of these cations. Both the hypercalciuric and hypermagnesiuric responses to gentamicin were extremely rapid and were sustained during drug infusion; when gentamicin infusion ceased both responses were rapidly reversible. Infusion of another aminoglycoside, tobramycin, produced very similar effects to gentamicin. The hypercalciuria and hypermagnesiuria caused by gentimicin infusion were unaffected by parathyroidectomy. The peak increases in calcium and magnesium output brought about by infusion of gentamicin with frusemide were not significantly different to the increases produced by frusemide alone. The site at which gentamicin interferes with calcium and magnesium reabsorption cannot be firmly deduced from these results. However, the known close association between calcium and sodium reabsorption in the proximal tubule implies that gentamicin is unlikely to change proximal calcium reabsorption without a similar change in proximal sodium reabsorption. The similarity between the hypercalciuric and hypermagnesiuric effects of frusemide alone and the effects of frusemide infused simultaneously with gentamicin suggests that gentamicin may act at the same site as the diuretic, the thick ascending limb of the loop of Henle.

The effects of nitrogen mustard on plasma membrane function

The antitumour bifunctional alkylating agent nitrogen mustard (HN2) inhibited the unidirectional influx of the potassium congener, 86 rubidium, into murine PC6A plasmacytoma cells and L1210 leukaemia cells. The proliferation of L1210 cells in vitro was characterised and shown to be sentitive to HN2. 86Rubidium influx into cells from rapidly-dividing cultures was more sensitive to inhibition by HN2 than that of cells from stationary cultures. Three components of unidirectional 86Rb+ & K+ influx into proliferating L1210 cells were identified pharmacologically: approximately 40% was active to the Na+ K+ ATPase inhibitor ouabain (10-3M), 40% was sensitive to the `loop' diuretics bumetanide (10-4M) and furosemide (10-3M) and the remainder was insensitive to both ouabain and furosemide. HN2 (10-5M) selectively inhibited the diuretic-sensitive component, which was entirely dependent upon extracellular Na+ and Cl- ions, and was presumed to represent Na+ K+ Cl- cotransport activity. The system did not mediate K+ /K+ exchange or unidirectional 86Rb+ efflux; accordingly, 86Rb+ efflux was insensitive to HN2. Inhibition of 86Rb & K+ influx by 10-5M HN2 was accompanied by approximately 35% of cell volume under isosmotic conditions; thus intracellular Na+ and K+ concentrations remained unchanged. These effects followed lethal damage to the cells but preceded actual cell death; other cellular functions were maintained including accumulation of cycloleucine, transmembrane potential, permeability to trypan blue, intracellular pH, total intracellular glutathione and calcium concentrations. No evidence was found that elevated cAMP levels or reduced ATP levels were involved in modulation of 86Rb+ & K+ influx. However, the Na+ - depedent transport of an amino acid was inhibited in a manner which appeared to be independent of 86Rb & K+ influx. An HN2-resistant L1210R cell line was also resistant to furosemide, and lacked a component of 86Rb+ & K+ influx which was sensitive to furosemide (10-3M). The results strongly suggest that the Na+ K+ Cl- costransporter of L1210 cells is a cellular target for HN2. This lesion is discussed with reference to the cytotoxic effects of the agent.

Bandpass switching based on a nonlinear optical loop mirror and an in-fibre grating reflector

Nonlinear optical loop mirror (NOLM) requires breaking the loop symmetry to enable the counter propagating pulses to acquire a differential π phase shift. This is achieved with either an asymmetric fused fibre coupler at the input or by the inclusion of an asymmetrically located gain or loss element within the loop. By introducing a frequency selective loss element, nonlinear switching may be confined to a narrow band of wavelengths or multiple wavelengths. This configuration may have applications in time-wavelength demultiplexing. We demonstrate this technique of bandpass switching in the soliton regime using a fibre-Bragg grating reflector as the wavelength dependent loss.