2,931 research outputs found

    Target value design: using collaboration and a lean approach to reduce construction cost

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    Target Costing is an effective management technique that has been used in manufacturing for decades to achieve cost predictability during new products development. Adoption of this technique promises benefits for the construction industry as it struggles to raise the number of successful outcomes and certainty of project delivery in terms of cost, quality and time. Target Value Design is a management approach that takes the best features of Target Costing and adapts them to the peculiarities of construction. In this paper the concept of Target Value Design is introduced based on the results of action research carried out on 12 construction projects in the USA. It has been shown that systemic application of Target Value Design leads to significant improvement of project performance – the final cost of projects was on average 15% less than market cost. The construction industry already has approaches that have similarities with elements of the Target Value Design process or uses the same terminology, e.g. Partnering and Target Cost Contracts, Cost planning, etc. Following an exploration of the similarities and differences Target Value Design is positioned as a form of Target Costing for construction that offers a more reliable route to successful projects outcomes

    Supercharging: An Investigation into the Effects of External Amino Acid Residue Charge on the Solubility and Internal Electric Character of Bound Ligands in a Heme-Binding de novo-Designed Protein

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    De novo protein design offers many interesting prospects both as a means to better understand natural protein dynamics and as a potential resource in biomedical and industrial applications. In this work I describe the modification of a simple, well-characterized heme-binding protein by altering side chain residue identities on the hydrophilic surface of the protein to produce variants with a range of net external charges. These charge modifications had a significant impact on nearly every measurable character of the protein. This work establishes the hard limits of supercharging within our experimental protein scaffold system, demonstrating that excessive positive charge increased the likelihood of amyloid plaque aggregation and excessive negative charge resulted in loss of the alpha-helix character essential to the protein’s heme-binding function. More moderately charged proteins demonstrated that solubility was significantly enhanced in net negatively charged proteins. We were also able to demonstrate a direct relationship between the change in charge of exterior residues and a change in the midpoint potential of the bound heme cofactor. This demonstrated the capacity to “tune” the electric character of bound cofactors without directly modifying the ligand binding site. We further demonstrate the relationship between the high differential between unbound and bound cofactor midpoint potentials and reduced binding affinity. This work supports the notion that covalently bound heme in natural proteins are attached in this manner in order to 4 prevent the heme from dissociating from the protein while still allowing for midpoint potentials greater than 300 mV different from free heme counterparts

    Antibacterial Properties of Nonwoven Wound Dressings Coated with Manuka Honey or Methylglyoxal

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    Manuka honey (MH) is used as an antibacterial agent in bioactive wound dressings via direct impregnation onto a suitable substrate. MH provides unique antibacterial activity when compared with conventional honeys, owing partly to one of its constituents, methylglyoxal (MGO). Aiming to investigate an antibiotic-free antimicrobial strategy, we studied the antibacterial activity of both MH and MGO (at equivalent MGO concentrations) when applied as a physical coating to a nonwoven fabric wound dressing. When physically coated on to a cellulosic hydroentangled nonwoven fabric, it was found that concentrations of 0.0054 mg cm−2 of MGO in the form of MH and MGO were sufficient to achieve a 100 colony forming unit % bacteria reduction against gram-positive Staphylococcus aureus and gram-negative Klebsiella pneumoniae, based on BS EN ISO 20743:2007. A 3- to 20-fold increase in MGO concentration (0.0170–0.1 mg cm−2) was required to facilitate a good antibacterial effect (based on BS EN ISO 20645:2004) in terms of zone of inhibition and lack of growth under the sample. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was also assessed for MGO in liquid form against three prevalent wound and healthcare-associated pathogens, i.e., Staphylococcus aureus, gram-negative Pseudomonas aeruginosa and gram-positive Enterococcus faecalis. Other than the case of MGO-containing fabrics, solutions with much higher MGO concentrations (128 mg L−1–1024 mg L−1) were required to provide either a bacteriostatic or bactericidal effect. The results presented in this study therefore demonstrate the relevance of an MGO-based coating as an environmentally friendly strategy for the design of functional dressings with antibiotic-free antimicrobial chemistries

    A survey of low-velocity collisional features in Saturn's F ring

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    Small (~50km scale), irregular features seen in Cassini images to be emanating from Saturn's F ring have been termed mini-jets by Attree et al. (2012). One particular mini-jet was tracked over half an orbital period, revealing its evolution with time and suggesting a collision with a local moonlet as its origin. In addition to these data we present here a much more detailed analysis of the full catalogue of over 800 F ring mini-jets, examining their distribution, morphology and lifetimes in order to place constraints on the underlying moonlet population. We find mini-jets randomly located in longitude around the ring, with little correlation to the moon Prometheus, and randomly distributed in time, over the full Cassini tour to date. They have a tendency to cluster together, forming complicated `multiple' structures, and have typical lifetimes of ~1d. Repeated observations of some features show significant evolution, including the creation of new mini-jets, implying repeated collisions by the same object. This suggests a population of <~1km radius objects with some internal strength and orbits spread over 100km in semi-major axis relative to the F ring but with the majority within 20km. These objects likely formed in the ring under, and were subsequently scattered onto differing orbits by, the perturbing action of Prometheus. This reinforces the idea of the F ring as a region with a complex balance between collisions, disruption and accretion.Comment: 21 pages, 12 figures. Accepted for publication in Icarus. Supplementary information available at http://www.maths.qmul.ac.uk/~attree/mini-jets

    Understanding the behavior of Prometheus and Pandora

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    We revisit the dynamics of Prometheus and Pandora, two small moons flanking Saturn's F ring. Departures of their orbits from freely precessing ellipses result from mutual interactions via their 121:118 mean motion resonance. Motions are chaotic because the resonance is split into four overlapping components. Orbital longitudes were observed to drift away from Voyager predictions, and a sudden jump in mean motions took place close to the time at which the orbits' apses were antialigned in 2000. Numerical integrations reproduce both the longitude drifts and the jumps. The latter have been attributed to the greater strength of interactions near apse antialignment (every 6.2 years), and it has been assumed that this drift-jump behavior will continue indefinitely. We re-examine the dynamics by analogy with that of a nearly adiabatic, parametric pendulum. In terms of this analogy, the current value of the action of the satellite system is close to its maximum in the chaotic zone. Consequently, at present, the two separatrix crossings per precessional cycle occur close to apse antialignment. In this state libration only occurs when the potential's amplitude is nearly maximal, and the 'jumps' in mean motion arise during the short intervals of libration that separate long stretches of circulation. Because chaotic systems explore the entire region of phase space available to them, we expect that at other times the system would be found in states of medium or low action. In a low action state it would spend most of the time in libration, and separatrix crossings would occur near apse alignment. We predict that transitions between these different states can happen in as little as a decade. Therefore, it is incorrect to assume that sudden changes in the orbits only happen near apse antialignment.Comment: 22 pages, 13 figs, Icarus accepte

    Dynamic lactate indices as predictors of outcome in critically ill patients

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    INTRODUCTION: Dynamic changes in lactate concentrations in the critically ill may predict patient outcome more accurately than static indices. We aimed to compare the predictive value of dynamic indices of lactatemia in the first 24 hours of intensive care unit (ICU) admission with the value of more commonly used static indices. METHODS: This was a retrospective observational study of a prospectively obtained intensive care database of 5,041 consecutive critically ill patients from four Australian university hospitals. We assessed the relationship between dynamic lactate values collected in the first 24 hours of ICU admission and both ICU and hospital mortality. RESULTS: We obtained 36,673 lactate measurements in 5,041 patients in the first 24 hours of ICU admission. Both the time weighted average lactate (LACTW₂₄) and the change in lactate (LACΔ₂₄) over the first 24 hours were independently predictive of hospital mortality with both relationships appearing to be linear in nature. For every one unit increase in LACTW₂₄ and LACΔ₂₄ the risk of hospital death increased by 37% (OR 1.37, 1.29 to 1.45; P < 0.0001) and by 15% (OR 1.15, 1.10 to 1.20; P < 0.0001) respectively. Such dynamic indices, when combined with Acute Physiology and Chronic Health Evaluation II (APACHE II) scores, improved overall outcome prediction (P < 0.0001) achieving almost 90% accuracy. When all lactate measures in the first 24 hours were considered, the combination of LACTW₂₄ and LACΔ₂₄ significantly outperformed (P < 0.0001) static indices of lactate concentration, such as admission lactate, maximum lactate and minimum lactate. CONCLUSIONS: In the first 24 hours following ICU admission, dynamic indices of hyperlactatemia have significant independent predictive value, improve the performance of illness severity score-based outcome predictions and are superior to simple static indices of lactate concentration

    Saturn’s F ring is intermittently shepherded by Prometheus

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    One of the stranger planetary rings is Saturn’s narrow, clumpy F ring, lying just outside the main rings, in a region disturbed by chaotic orbital dynamics. We show that the F ring has a stable “true core” that dominates its mass and is confined into discontinuous short arcs of particles larger than a few millimeters in radius. The more obvious micron-size particles seen in images, outlining and obscuring the true core, contribute only a small fraction of its mass. We found that these arcs of large particles orbit Saturn in a specific corotational resonance with the nearby 100-kilometer diameter ringmoon Prometheus, which stabilizes the F ring material and allows it to persist within the disturbed region for decades or longer. Toward the end of the observing period, a small chaotic glitch in the orbit of Prometheus temporarily disrupted the confinement, but the arcs seem to be able to adapt.</jats:p
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