The role of Lean at the interface with between operations management and applied services within a large aerospace organisation: a boundary spanning perspective

Increased complexity in large design and manufacturing organisations requires improvements at the operations management (OM)–applied service (AS) interface areas to improve project effectiveness. The aim of this paper is explore the role of Lean in improving the longitudinal efficiency of the OM–AS interface within a large aerospace organisation using Lean principles and boundary spanning theory. The methodology was an exploratory longitudinal case approach including exploratory interviews (n = 21), focus groups (n = 2), facilitated action-research workshops (n = 2) and two trials or experiments using longitudinal data involving both OM and AS personnel working at the interface. The findings draw upon Lean principles and boundary spanning theory to guide and interpret the findings. It was found that misinterpretation, and forced implementation, of OM-based Lean terminology and practice in the OM–AS interface space led to delays and misplaced resources. Rather both OM and AS staff were challenged to develop a cross boundary understanding of Lean-based boundary (knowledge) objects in interpreting OM requests. The longitudinal findings from the experiments showed that the development of Lean Performance measurements and lean Value Stream constructs was more successful when these Lean constructs were treated as boundary (knowledge) objects requiring transformation over time to orchestrate improved effectiveness and in leading to consistent terminology and understanding between the OM–AS boundary spanning team.

GeneGrid: Architecture, Implementation and Application

The emergence of Grid computing technology has opened up an unprecedented opportunity for biologists to share and access data, resources and tools in an integrated environment leading to a greater chance of knowledge discovery. GeneGrid is a Grid computing framework that seamlessly integrates a myriad of heterogeneous resources spanning multiple administrative domains and locations. It provides scientists an integrated environment for the streamlined access of a number of bioinformatics programs and databases through a simple and intuitive interface. It acts as a virtual bioinformatics laboratory by allowing scientists to create, execute and manage workflows that represent bioinformatics experiments. A number of cooperating Grid services interact in an orchestrated manner to provide this functionality. This paper gives insight into the details of the architecture, components and implementation of GeneGrid.

Calibration of the Radiocarbon Time Scale for the Southern Hemisphere: AD 1850-950

We have conducted a series of radiocarbon measurements on decadal samples of dendrochronologically dated wood from both hemispheres, spanning 1000 years (McCormac et al. 1998; Hogg et al. this issue). Using the data presented in Hogg et al., we show that during the period AD 950-1850 the 14C offset between the hemispheres is not constant, but varies periodically (~130 yr periodicity) with amplitudes varying between 1 and 10‰ (i.e. 8-80 yr), with a consequent effect on the 14C calibration of material from the Southern Hemisphere. A large increase in the offset occurs between AD 1245 and 1355. In this paper, we present a Southern Hemisphere high-precision calibration data set (SHCal02) that comprises measurements from New Zealand, Chile, and South Africa. This data, and a new value of 41 ± 14 yr for correction of the IntCal98 data for the period outside the range given here, is proposed for use in calibrating Southern Hemisphere 14C dates.

A strategy for designing inhibitors of alpha-synuclein aggregation and toxicity as a novel treatment for Parkinson's disease and related disorders.

Convergent biochemical and genetic evidence suggests that the formation of alpha-synuclein (alpha-syn) protein deposits is an important and, probably, seminal step in the development of Parkinson's disease (PD), dementia with Lewy bodies (DLB) and multiple system atrophy (MSA). It has been reported that transgenic animals overexpressing human alpha-syn develop lesions similar to those found in the brain in PD, together with a progressive loss of dopaminergic cells and associated abnormalities of motor function. Inhibiting and/or reversing alpha-syn self-aggregation could, therefore, provide a novel approach to treating the underlying cause of these diseases. We synthesized a library of overlapping 7-mer peptides spanning the entire alpha-syn sequence, and identified amino acid residues 64-100 of alpha-syn as the binding region responsible for its self-association. Modified short peptides containing alpha-syn amino acid sequences from part of this binding region (residues 69-72), named alpha-syn inhibitors (ASI), were found to interact with full-length alpha-syn and block its assembly into both early oligomers and mature amyloid-like fibrils. We also developed a cell-permeable inhibitor of alpha-syn aggregation (ASID), using the polyarginine peptide delivery system. This ASID peptide was able to inhibit the DNA damage induced by Fe(II) in neuronal cells transfected with alpha-syn(A53T), a familial PD-associated mutation. ASI peptides without this delivery system did not reverse levels of Fe(II)-induced DNA damage. Furthermore, the ASID peptide increased (P

A novel diagnostic test detects a low frequency of the hemicentin Gln5345Arg variant among Northern Irish age related macular degeneration patients.

Purpose: Age related macular degeneration (AMD) is a common cause of severe vision loss. Identification of genes involved in AMD will facilitate early detection and ultimately help to identify pathways for treatment for this disorder. The A16,263G mutation in the HEMICENTIN-1 gene produces a non-conservative substitution of arginine for glutamine at codon 5345 which has been implicated in familial AMD. The aim of this study is to develop a rapid diagnostic assay for the detection of this mutation and to evaluate its frequency in a sample of AMD patients. Methods: A primer probe set was designed from exon 104 of the HEMICENTIN-1 gene to differentiate between mutant and wild type alleles. A region spanning the mutation was amplified by PCR using a LightCycler (Roche Diagnostic). The mutation was then detected by melt curve analysis of the hybrid formed between the PCR product and a specific fluorescent probe. The frequency of the mutation within the Northern Ireland population was evaluated by assaying 508 affected AMD patients, 25 possibly affected and 163 controls. Results: This assay clearly discriminates between the A16,263G mutant and wild type HEMICENTIN-1 alleles. The wild type sequence has a single base mismatch with the probe which decreases the stability of the hybrid, resulting in a lower TM (TM=51.27 °C) than that observed for the perfectly matched mutant allele (TM=59.9 °C). The mutant allele was detected in only one of the 696 subjects, an affected AMD patient. Conclusions: We describe a rapid assay for the genotyping of the Gln5345Arg mutation using real-time fluorescence PCR to facilitate rapid processing of samples through combined amplification and detection steps. These characteristics are suitable for a clinical setting where high throughput diagnostic procedures are required. The frequency of this mutation within the Northern Ireland population has been estimated at 0.2%, concurring with previous findings that this mutation is a rare variant associated with AMD. A rapid diagnostic assay will facilitate a reliable and convenient evaluation of the frequency of the Gln5345Arg mutation and its association with AMD within other populations.

The VLT-FLAMES survey of massive stars: Observations in the Galactic clusters NGC 3293, NGC 4755 and NGC 6611

We introduce a new survey of massive stars in the Galaxy and the Magellanic Clouds using the Fibre Large Array Multi- Element Spectrograph ( FLAMES) instrument at the Very Large Telescope ( VLT). Here we present observations of 269 Galactic stars with the FLAMES- Giraffe Spectrograph ( R similar or equal to 25 000), in fields centered on the open clusters NGC3293, NGC4755 and NGC6611. These data are supplemented by a further 50 targets observed with the Fibre- Fed Extended Range Optical Spectrograph ( FEROS, R = 48 000). Following a description of our scientific motivations and target selection criteria, the data reduction methods are described; of critical importance the FLAMES reduction pipeline is found to yield spectra that are in excellent agreement with less automated methods. Spectral classifications and radial velocity measurements are presented for each star, with particular attention paid to morphological peculiarities and evidence of binarity. These observations represent a significant increase in the known spectral content of NGC3293 and NGC4755, and will serve as standards against which our subsequent FLAMES observations in the Magellanic Clouds will be compared.

The WASP Project and the SuperWASP Cameras

The SuperWASP cameras are wide-field imaging systems at the Observatorio del Roque de los Muchachos on the island of La Palma in the Canary Islands, and at the Sutherland Station of the South African Astronomical Observatory. Each instrument has a field of view of some 482 deg2 with an angular scale of 13.7" pixel-1, and is capable of delivering photometry with accuracy better than 1% for objects having V~7.0-11.5. Lower quality data for objects brighter than V~15.0 are stored in the project archive. The systems, while designed to monitor fields with high cadence, are capable of surveying the entire visible sky every 40 minutes. Depending on the observational strategy, the data rate can be up to 100 Gbytes per night. We have produced a robust, largely automatic reduction pipeline and advanced archive, which are used to serve the data products to the consortium members. The main science aim of these systems is to search for bright transiting exoplanet systems suitable for spectroscopic follow-up observations. The first 6 month season of SuperWASP-North observations produced light curves of ~6.7 million objects with 12.9 billion data points.

Co-inheritance of two rare genodermatoses (Papillon Lefevre syndrome and Oculocutaneous Albinism Type 1) in two families

The co-occurrence of two rare recessive genetic conditions in apparently unrelated individuals or families is extremely rare. Two geographically distant and apparently unrelated families were identified in which individuals were simultaneously affected by two rare recessive mendelian syndromes, Papillon-Lefevre syndrome and type 1 oculocutaneous albinism. The families were tested for mutations in the causative genes, cathepsin C (CTSC) and tyrosinase (TYR), respectively, by direct sequencing. To assess the relationship of the two families, both families were tested for polymorphisms at eight microsatellite markers spanning both CTSC and TYR loci. Independent mutations (c.318-1G-->A and c.817G-->C/p.W272C) were identified in CTSC and TYR, respectively, that were shared by the affected individuals in both families. The two affected genes lie close together on chromosome bands 11q14.2-14.3, and studies with linked genetic markers suggested that the families shared a small chromosomal segment carrying both mutations that had been transmitted intact from a remote common ancestor. The co-occurrence of the two rare diseases in multiple families depends on their shared chromosomal location, but not on any shared pathogenic mechanism.

Status of SuperWASP I (La Palma)

SuperWASP is an ultra-wide field (over 300 sq. degrees) photometric survey project designed to monitor stars between 7 - 15 mag to high precision and with high cadence over long (greater than or equal to2 months) timescales. The primary science goal of this project is the detection of exoplanetary transits, as well as NEOs and optical transients. The resulting photometric catalogue will be made public via a web-based interface. The SuperWASP instrument consists of an array of cameras each with a 7.8degrees x 7.8degrees field of view, guided by a robotic fork mount and sited in a fibreglass enclosure at the Observatorio de Roque de los Muchachos (ORM), La Palma, Canary Islands. In this progress report, we describe the specifications of the instrument, its semi-automated operation and pipeline data reduction.

The WASP project in the era of robotic telescope networks

We present the current status of the WASP project, a pair of wide angle photometric telescopes, individually called SuperWASP. SuperWASP-I is located in La Palma, and SuperWASP-II at Sutherland in South Africa. SW-I began operations in April 2004. SW-II is expected to be operational in early 2006. Each SuperWASP instrument consists of up to 8 individual cameras using ultra-wide field lenses backed by high-quality passively cooled CCDs. Each camera covers 7.8 x 7.8 sq degrees of sky, for nearly 500 sq degrees of total sky coverage. One of the current aims of the WASP project is the search for extra-solar planet transits with a focus on brighter stars in the magnitude range similar to 8 to 13. Additionally, WASP will search for, optical transients, track Near-Earth Objects, and study many types of variable stars and extragalactic objects. The collaboration has developed a custom-built reduction pipeline that achieves better than I percent photometric precision. We discuss future goals, which include: nightly on-mountain reductions that could be used to automatically drive alerts via a small robotic telescope network, and possible roles of the WASP telescopes as providers in such a network. Additional technical details of the telescopes, data reduction, and consortium members and institutions can be found on the web site at: http://www.superwasp.org/. (c) 2006 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

CRYBB1 mutation associated with congenital cataract and microcornea

The molecular characterization of a UK family with an autosomal dominant congenital cataract associated with microcornea is reported. METHODS: Family history and clinical data were recorded. This phenotype was linked to a 7.6 cM region of chromosome 22q11.2-q12.2, spanning the beta-crystallin gene cluster (ZMax of 3.91 for marker D22S1114 at theta=0). Candidate genes were PCR amplified and screened for mutations on both strands using direct sequencing. RESULTS: Sequencing of the coding regions and flanking intronic sequences of CRYBB2 and CRYBB1 showed the presence of a novel, heterozygous X253R change in exon 6 of CRYBB1. SSCP analysis confirmed that this sequence change segregated with the disease phenotype in all available family members and was not found in 109 ethnically matched controls. CONCLUSIONS: X253R is predicted to elongate the COOH-terminal extension of the protein and would be expected to disrupt beta-crystallin interactions. This is the first documented involvement of CRYBB1 in ocular development beyond cataractogenesis.

Virtex FPGA Implementation of a Pipelined Adaptive LMS Predictor for Electronic Support Measures Receivers

High-speed field-programmable gate array (FPGA) implementations of an adaptive least mean square (LMS) filter with application in an electronic support measures (ESM) digital receiver, are presented. They employ "fine-grained" pipelining, i.e., pipelining within the processor and result in an increased output latency when used in the LMS recursive system. Therefore, the major challenge is to maintain a low latency output whilst increasing the pipeline stage in the filter for higher speeds. Using the delayed LMS (DLMS) algorithm, fine-grained pipelined FPGA implementations using both the direct form (DF) and the transposed form (TF) are considered and compared. It is shown that the direct form LMS filter utilizes the FPGA resources more efficiently thereby allowing a 120 MHz sampling rate.

Structure-activity studies on position 14 of human alpha-calcitonin gene-related peptide

A structure-activity study was performed to examine the role of position 14 of human alpha-calcitonin gene-related peptide (h-alpha-CGRP) in activating the CGRP receptor. Interestingly, position 14 of h-alpha-CGRP contains a glycyl residue and is part of an alpha-helix spanning residues 8-18. Analogues [Ala(14)]-h-alpha-CGRP, [Aib(14)]-h-alpha-CGRP, [Asp(14)]-h-alpha-CGRP, [Asn(14)]-h-alpha-CGRP, and [Pro(14)]-h-alpha-CGRP were synthesized by solid phase peptide methodology and purified by RP-HPLC. Secondary structure was measured by circular dichroism spectroscopy. Agonist activities were determined as the analogues' ability to stimulate amylase secretion from guinea pig pancreatic acini and to relax precontracted porcine coronary arteries. Analogues [Ala(1)4]-h-alpha-CGRP, [Aib(14)]-h-alpha-CGRP, [Asp(14)]-h-alpha-CGRP, and [Asn(14)]-h-alpha-CGRP, all containing residues with a high helical propensity in position 14, were potent full agonists compared to h-alpha-CGRP in both tissues. Interestingly, replacement of Gly(14) of h-alpha-CGRP with these residues did not substantially increase the helical content of these analogues. [Pro(14)]-h-alpha-CGRP, predictably, has significantly lower helical content and is a 20-fold less potent agonist on coronary artery, known to contain CGRP-1 receptor subtypes, and an antagonist on pancreatic acini, known to contain CGRP-2 receptor subtypes. In conclusion, the residue in position 14 plays a structural role in stabilizing the alpha-helix spanning residues 8-18. The alpha-helix is crucial for maintaining highly potent agonist effects of h-alpha-CGRP at CGRP receptors. The wide variety of functional groups that can be tolerated in position 14 with no substantial modification of agonist effects suggests the residue in this position is not in contact with the CGRP receptor. [Pro(14)]-h-alpha-CGRP may be a useful pharmacological tool to distinguish between CGRP-1 and CGRP-2 receptor subtypes.

Ion Association in [bmim][PF6]/Naphthalene Mixtures: An Experimental and Computational Study

Mixtures of room temperature ionic liquids (IL) with neutral organic molecules provide a valuable testing ground to investigate the interplay of the ionic and molecular-dipolar state in dense Coulomb systems at near ambient conditions. In the present study, the viscosity eta and the ionic conductivity a of 1-n-butyl-3-methylimidazolium hexafluorophosphate ([bmim][PF6])/naphthalene mixtures at T = 80 degrees C have been measured at 10 stoichiometries spanning the composition range from pure naphthalene to pure [bmim][PF6]. The viscosity grows nearly monotonically with increasing IL mole fraction (x), whereas the conductivity per ion displays a clear peak at x approximate to 15%. The origin of this maximum has been investigated using molecular dynamics simulations based on a classical force field. Snapshots of the simulated samples show that the conductivity maximum is due to the gradual transition in the IL component from an ionic state at high x to a dipolar fluid made of neutral ion pairs at low x. At concentrations x <0.20 the ion pairs condense into molecular-thin filaments bound by dipolar forces and extending in between nanometric droplets of IL. These results are confirmed and complemented by the computation of dynamic and transport properties in [bmim][PF6]/naphthalene mixtures at low IL concentration.