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.

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.

Interaction of calcitonin-gene-related peptide with its receptors

The receptor for calcitonin-gene-related peptide (CGRP) is a heterodimer formed by calcitonin-receptor-like receptor (CRLR), a type II (family B) G-protein-coupled receptor, and receptor-activity-modifying protein 1 (RAMP1), a single-membrane-pass protein. It is likely that the first seven or so amino acids of CGRP (which form a disulphide-bonded loop) interact with the transmembrane domain of CRLR to cause receptor activation. The rest of the CGRP molecule falls into three domains. Residues 28-37 and 8-18 are normally required for high-affinity binding, while residues 19-27 form a hinge region. The 28-37 region is almost certainly in direct contact with the receptor; 8-18 may make additional receptor contacts or may stabilize an appropriate conformation of 28-37. It is likely that these regions of CGRP interact both with CRLR and with the extracellular domain of RAMP1.

Picosecond soliton transmission using concatenated nonlinear optical loop-mirror intensity filters

The issues involved in employing nonlinear optical loop mirrors (NOLMs) as intensity filters in picosecond soliton transmission were examined in detail. It was shown that inserting NOLMs into a periodically amplified transmission line allowed picosecond solitons to be transmitted under conditions considered infeasible until now. The loop mirrors gave dual function, removing low-power background dispersive waves through saturable absorption and applying a negative feedback mechanism to control the amplitude of the solitons. The stochastic characteristics of the pulses that were due to amplifier spontaneous-emission noise were investigated, and a number of new properties were determined. In addition, the mutual interaction between pulses was also significantly different from that observed for longer-duration solitons. The impact of Raman scattering in the computations was included and it was shown that soliton self-frequency shifts may be eliminated by appropriate bandwidth restrictions.

In silico modelling of the interaction of flavonoids with human P-glycoprotein nucleotide-binding domain

A three-dimensional model of human ABCB1 nucleotide-binding domain (NBD) was developed by homology modelling using the high-resolution human TAP1 transporter structure as template. Interactions between NBD and flavonoids were investigated using in silico docking studies. Ring-A of unmodified flavonoid was located within the NBD P-loop with the 5-hydroxyl group involved in hydrogen bonding with Lys1076. Ring-B was stabilised by hydrophobic stacking interactions with Tyr1044. The 3-hydroxyl group and carbonyl oxygen were extensively involved in hydrogen bonding interactions with amino acids within the NBD. Addition of prenyl, benzyl or geranyl moieties to ring-A (position-6) and hydrocarbon substituents (O-n-butyl to O-n-decyl) to ring-B (position-4) resulted in a size-dependent decrease in predicted docking energy which reflected the increased binding affinities reported in vitro.