Talented suppliers? Strategic change and innovation in the UK aerospace industry

The 1990s marked the start of extensive re-structuring in the aerospace industry throughout the world. While the ensuing consolidation among prime contractors has been widely researched, the changes affecting the aerospace supply chain have received less attention. This study focuses on the re-structuring taking place within the supply chain of the UK aerospace industry. The findings point to extensive re-structuring. Unlike most earlier studies the lean supply model was found to be a powerful influence, with suppliers moving away from subcontractor status and instead taking on the mantle of ‘talented’ suppliers. While some of the implications of lean supply, in terms of the dynamics of innovation, were not apparent, there were modest signs of increased process innovation on the part of some suppliers

A Multi-wavelength View of the TeV Blazar Markarian 421: Correlated Variability, Flaring, and Spectral Evolution

We report results from a multi-wavelength monitoring campaign on Mrk 421 over the period of 2003-2004. The source was observed simultaneously at TeV and X-ray energies, with supporting observations frequently carried out at optical and radio wavelengths. The large amount of simultaneous data has allowed us to examine the variability of Mrk 421 in detail. The variabilities are generally correlated between the X-ray and gamma-ray bands, although the correlation appears to be fairly loose. The light curves show the presence of flares with varying amplitudes on a wide range of timescales both at X-ray and TeV energies. Of particular interest is the presence of TeV flares that have no coincident counterparts at longer wavelengths, because the phenomenon seems difficult to understand in the context of the proposed emission models for TeV blazars. We have also found that the TeV flux reached its peak days before the X-ray flux during a giant flare in 2004. Such a difference in the development of the flare presents a further challenge to the emission models. Mrk 421 varied much less at optical and radio wavelengths. Surprisingly, the normalized variability amplitude in optical seems to be comparable to that in radio, perhaps suggesting the presence of different populations of emitting electrons in the jet. The spectral energy distribution (SED) of Mrk 421 is seen to vary with flux, with the two characteristic peaks moving toward higher energies at higher fluxes. We have failed to fit the measured SEDs with a one-zone SSC model; introducing additional zones greatly improves the fits. We have derived constraints on the physical properties of the X-ray/gamma-ray flaring regions from the observed variability (and SED) of the source. The implications of the results are discussed. (Abridged)Comment: 32 pages, 12 figures, to appear in Ap

A Search for TeV Gamma-Ray Emission from High-Peaked Flat Spectrum Radio Quasars Using the Whipple Air-Cherenkov Telescope

Blazars have traditionally been separated into two broad categories based upon their optical emission characteristics; BL Lacs, with faint or no emission lines, and flat spectrum radio quasars (FSRQs) with prominent, broad emission lines. The spectral energy distribution of FSRQs has generally been thought of as being more akin to the low-peaked BL Lacs, which exhibit a peak in the infrared region of the spectrum, as opposed to high-peaked BL Lacs (HBLs), which exhibit a peak in UV/X-ray region of the spectrum. All blazars currently confirmed as sources of TeV emission are HBLs. Recent surveys have found several FSRQs exhibiting spectral properties similar to HBLs, particularly the synchrotron peak frequency. These objects are potential sources of TeV emission according to several models of blazar jet emission and blazar evolution. Measurements of TeV flux or upper limits could impact existing theories explaining the links between different blazar types and could have a significant impact on our understanding of the nature of objects that are capable of TeV emission. In particular, the presence (or absence) of TeV emission from FSRQs could confirm (or cast doubt upon) recent evolutionary models that expect intermediate objects in a transitionary state between FSRQ and BL Lac. The Whipple 10 meter imaging air-Cherenkov gamma-ray telescope is well suited for TeV gamma-ray observations. Using the Whipple telescope, we have taken data on a small selection of nearby(z<0.1 in most cases), high-peaked FSRQs. Although one of the objects, B2 0321+33, showed marginal evidence of flaring, no significant emission was detected. The implications of this paucity of emission and the derived upper limits are discussed.Comment: accepted for publication in Astrophysical Journa

Metabolic Network for the Biosynthesis of Intra- and Extracellular alpha-Glucans Required for Virulence of Mycobacterium tuberculosis

Mycobacterium tuberculosis synthesizes intra- and extracellular alpha-glucans that were believed to originate from separate pathways. The extracellular glucose polymer is the main constituent of the mycobacterial capsule that is thought to be involved in immune evasion and virulence. However, the role of the alpha-glucan capsule in pathogenesis has remained enigmatic due to an incomplete understanding of alpha-glucan biosynthetic pathways preventing the generation of capsule-deficient mutants. Three separate and potentially redundant pathways had been implicated in alpha-glucan biosynthesis in mycobacteria: the GlgC-GlgA, the Rv3032 and the TreS-Pep2-GlgE pathways. We now show that alpha-glucan in mycobacteria is exclusively assembled intracellularly utilizing the building block alpha-maltose-1-phosphate as the substrate for the maltosyltransferase GlgE, with subsequent branching of the polymer by the branching enzyme GlgB. Some alpha-glucan is exported to form the alpha-glucan capsule. There is an unexpected convergence of the TreS-Pep2 and GlgC-GlgA pathways that both generate alpha-maltose-1-phosphate. While the TreS-Pep2 route from trehalose was already known, we have now established that GlgA forms this phosphosugar from ADP-glucose and glucose 1-phosphate 1000-fold more efficiently than its hitherto described glycogen synthase activity. The two routes are connected by the common precursor ADPglucose, allowing compensatory flux from one route to the other. Having elucidated this unexpected configuration of the metabolic pathways underlying alpha-glucan biosynthesis in mycobacteria, an M. tuberculosis double mutant devoid of alpha-glucan could be constructed, showing a direct link between the GlgE pathway, alpha-glucan biosynthesis and virulence in a mouse infection model

Assembly of α-Glucan by GlgE and GlgB in Mycobacteria and Streptomycetes

Actinomycetes, such as mycobacteria and streptomycetes, synthesize α-glucan with α-1,4 linkages and α-1,6 branching to help evade immune responses and to store carbon. α-Glucan is thought to resemble glycogen except for having shorter constituent linear chains. However, the fine structure of α-glucan and how it can be defined by the maltosyl transferase GlgE and branching enzyme GlgB were not known. Using a combination of enzymolysis and mass spectrometry, we compared the properties of α-glucan isolated from actinomycetes with polymer synthesized in vitro by GlgE and GlgB. We now propose the following assembly mechanism. Polymer synthesis starts with GlgE and its donor substrate, α-maltose 1-phosphate, yielding a linear oligomer with a degree of polymerization (∼16) sufficient for GlgB to introduce a branch. Branching involves strictly intrachain transfer to generate a C chain (the only constituent chain to retain its reducing end), which now bears an A chain (a nonreducing end terminal branch that does not itself bear a branch). GlgE preferentially extends A chains allowing GlgB to act iteratively to generate new A chains emanating from B chains (nonterminal branches that themselves bear a branch). Although extension and branching occur primarily with A chains, the other chain types are sometimes extended and branched such that some B chains (and possibly C chains) bear more than one branch. This occurs less frequently in α-glucans than in classical glycogens. The very similar properties of cytosolic and capsular α-glucans from Mycobacterium tuberculosis imply GlgE and GlgB are sufficient to synthesize them both

The First VERITAS Telescope

The first atmospheric Cherenkov telescope of VERITAS (the Very Energetic Radiation Imaging Telescope Array System) has been in operation since February 2005. We present here a technical description of the instrument and a summary of its performance. The calibration methods are described, along with the results of Monte Carlo simulations of the telescope and comparisons between real and simulated data. The analysis of TeV $\gamma$-ray observations of the Crab Nebula, including the reconstructed energy spectrum, is shown to give results consistent with earlier measurements. The telescope is operating as expected and has met or exceeded all design specifications.Comment: Accepted by Astroparticle Physic

The crystal structure of the Thermus aquaticus DnaB helicase monomer

The ring-shaped hexameric DnaB helicase unwinds duplex DNA at the replication fork of eubacteria. We have solved the crystal structure of the full-length Thermus aquaticus DnaB monomer, or possibly dimer, at 2.9 Å resolution. DnaB is a highly flexible two domain protein. The C-terminal domain exhibits a RecA-like core fold and contains all the conserved sequence motifs that are characteristic of the DnaB helicase family. The N-terminal domain contains an additional helical hairpin that makes it larger than previously appreciated. Several DnaB mutations that modulate its interaction with primase are found in this hairpin. The similarity in the fold of the DnaB N-terminal domain with that of the C-terminal helicase-binding domain (HBD) of the DnaG primase also includes this hairpin. Comparison of hexameric homology models of DnaB with the structure of the papillomavirus E1 helicase suggests the two helicases may function through different mechanisms despite their sharing a common ancestor

Class-specific restrictions define primase interactions with DNA template and replicative helicase

Bacterial primase is stimulated by replicative helicase to produce RNA primers that are essential for DNA replication. To identify mechanisms regulating primase activity, we characterized primase initiation specificity and interactions with the replicative helicase for gram-positive Firmicutes (Staphylococcus, Bacillus and Geobacillus) and gram-negative Proteobacteria (Escherichia, Yersinia and Pseudomonas). Contributions of the primase zinc-binding domain, RNA polymerase domain and helicase-binding domain on de novo primer synthesis were determined using mutated, truncated, chimeric and wild-type primases. Key residues in the β4 strand of the primase zinc-binding domain defined class-associated trinucleotide recognition and substitution of these amino acids transferred specificity across classes. A change in template recognition provided functional evidence for interaction in trans between the zinc-binding domain and RNA polymerase domain of two separate primases. Helicase binding to the primase C-terminal helicase-binding domain modulated RNA primer length in a species-specific manner and productive interactions paralleled genetic relatedness. Results demonstrated that primase template specificity is conserved within a bacterial class, whereas the primase–helicase interaction has co-evolved within each species

Studying the association between musculoskeletal disorders, quality of life and mental health. A primary care pilot study in rural Crete, Greece

<p>Abstract</p> <p>Background</p> <p>The burden of musculoskeletal disorders (MSD) on the general health and well-being of the population has been documented in various studies. The objective of this study was to explore the association between MSD and the quality of life and mental health of patients and to discuss issues concerning care seeking patterns in rural Greece.</p> <p>Methods</p> <p>Patients registered at one rural Primary Care Centre (PCC) in Crete were invited to complete the Nordic Musculoskeletal Questionnaire (NMQ) for the analysis of musculoskeletal symptoms, together with validated instruments for measuring health related quality of life (SF-36) and mental distress (GHQ-28).</p> <p>Results</p> <p>The prevalence rate of MSD was found to be 71.2%, with low back and knee pain being the most common symptoms. Most conditions significantly impaired the quality of life, especially the physical dimensions of SF-36. Depression was strongly correlated to most MSD (<it>p </it>< 0.001). Multiple logistic analyses revealed that patients who consulted the PCC due to MSD were likely to have more mental distress or impaired physical functioning compared to those who did not.</p> <p>Conclusion</p> <p>Musculoskeletal disorders were common in patients attending the rural PCC of this study and were associated with a poor quality of life and mental distress that affected their consultation behaviour.</p

Prediction of uncomplicated pregnancies in obese women: A prospective multicentre study

BACKGROUND: All obese pregnant women are considered at equal high risk with respect to complications in pregnancy and birth, and are commonly managed through resource-intensive care pathways. However, the identification of maternal characteristics associated with normal pregnancy outcomes could assist in the management of these pregnancies. The present study aims to identify the factors associated with uncomplicated pregnancy and birth in obese women, and to assess their predictive performance. METHODS: Data form obese women (BMI ≥ 30 kg/m 2 ) with singleton pregnancies included in the UPBEAT trial were used in this analysis. Multivariable logistic regression was used to identify sociodemographic, clinical and biochemical factors at 15 +0 to 18 +6 weeks' gestation associated with uncomplicated pregnancy and birth, defined as delivery of a term live-born infant without antenatal or labour complications. Predictive performance was assessed using area under the receiver operating characteristic curve (AUROC). Internal validation and calibration were also performed. Women were divided into fifths of risk and pregnancy outcomes were compared between groups. Sensitivity, specificity, and positive and negative predictive values were calculated using the upper fifth as the positive screening group. RESULTS: Amongst 1409 participants (BMI 36.4, SD 4.8 kg/m 2 ), the prevalence of uncomplicated pregnancy and birth was 36% (505/1409). Multiparity and increased plasma adiponectin, maternal age, systolic blood pressure and HbA1c were independently associated with uncomplicated pregnancy and birth. These factors achieved an AUROC of 0.72 (0.68-0.76) and the model was well calibrated. Prevalence of gestational diabetes, preeclampsia and other hypertensive disorders, preterm birth, and postpartum haemorrhage decreased whereas spontaneous vaginal delivery increased across the fifths of increasing predicted risk of uncomplicated pregnancy and birth. Sensitivity, specificity, and positive and negative predictive values were 38%, 89%, 63% and 74%, respectively. A simpler model including clinical factors only (no biomarkers) achieved an AUROC of 0.68 (0.65-0.71), with sensitivity, specificity, and positive and negative predictive values of 31%, 86%, 56% and 69%, respectively. CONCLUSION: Clinical factors and biomarkers can be used to help stratify pregnancy and delivery risk amongst obese pregnant women. Further studies are needed to explore alternative pathways of care for obese women demonstrating different risk profiles for uncomplicated pregnancy and birth