204 research outputs found

    Planning For Claims: An Ethnography of Industry Culture

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    Claims by contractors for additional payments have been identified by commentators as a major source of difficulty in the industry. Ethnographic research with industry members reveals some key features of planning practices that underlie such events. Claims are sometimes planned at tender stage and sometimes during the course of a project. One practice at tender stage is a pricing technique that minimizes the tender price while maximizing the out-turn cost of a contract by exploiting mistakes in the bill of quantities. Another is the programming of work to maximize its vulnerability to delay. More reactive techniques may be employed during the course of the project, often to make up for an unanticipated increase in costs. These and other similar practices may be reported as features of an integrated culture, defined in such a way as to encompass activity and reject Cartesian dualism. The unique adequacy requirements of methods are suitable criteria for the evaluation of such reports. The claims culture arises from economic conditions in the industry, which include low entry barriers and competitive tendering. However, removal of these conditions alone cannot guarantee that the practices will cease

    Bounding clique-width via perfect graphs

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    We continue the study into the clique-width of graph classes defined by two forbidden induced graphs. We present three new classes of bounded clique-width and one of unbounded clique-width. The four new graph classes have in common that one of their two forbidden induced subgraphs is the diamond. To prove boundedness of clique-width for the first three cases we develop a technique based on bounding clique covering number in combination with reduction to subclasses of perfect graphs. We extend our proof of unboundedness for the fourth case to show that Graph Isomorphism is Graph Isomorphism-complete on the same graph class

    Postural control anomalies in children with Tourette syndrome

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    The goal of the present study was to determine whether postural control is affected in Gilles-de-la-Tourette syndrome (TS). Center of pressure (COP) displacements were recorded in children with TS and unaffected siblings (7-16 yrs) in three conditions using a force platform: 1) Eyes-Open, 2) Eyes-Closed, 3) One-Leg standing with eyes open. The COP range and velocity were higher in children with TS than in unaffected siblings in all conditions. These differences could not be attributed to age, present tic severity, comorbidities (hyperactivity and compulsions) or medication. The data suggest that sub-clinical postural control anomalies are present in TS

    Hamiltonicity below Dirac's condition

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    Dirac's theorem (1952) is a classical result of graph theory, stating that an nn-vertex graph (n3n \geq 3) is Hamiltonian if every vertex has degree at least n/2n/2. Both the value n/2n/2 and the requirement for every vertex to have high degree are necessary for the theorem to hold. In this work we give efficient algorithms for determining Hamiltonicity when either of the two conditions are relaxed. More precisely, we show that the Hamiltonian cycle problem can be solved in time cknO(1)c^k \cdot n^{O(1)}, for some fixed constant cc, if at least nkn-k vertices have degree at least n/2n/2, or if all vertices have degree at least n/2kn/2-k. The running time is, in both cases, asymptotically optimal, under the exponential-time hypothesis (ETH). The results extend the range of tractability of the Hamiltonian cycle problem, showing that it is fixed-parameter tractable when parameterized below a natural bound. In addition, for the first parameterization we show that a kernel with O(k)O(k) vertices can be found in polynomial time

    Muscle weakness and lack of reflex gain adaptation predominate during post-stroke posture control of the wrist

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    Instead of hyper-reflexia as sole paradigm, post-stroke movement disorders are currently considered the result of a complex interplay between neuronal and muscular properties, modified by level of activity. We used a closed loop system identification technique to quantify individual contributors to wrist joint stiffness during an active posture task. Continuous random torque perturbations applied to the wrist joint by a haptic manipulator had to be resisted maximally. Reflex provoking conditions were applied i.e. additional viscous loads and reduced perturbation signal bandwidth. Linear system identification and neuromuscular modeling were used to separate joint stiffness into the intrinsic resistance of the muscles including co-contraction and the reflex mediated contribution. Compared to an age and sex matched control group, patients showed an overall 50% drop in intrinsic elasticity while their reflexive contribution did not respond to provoking conditions. Patients showed an increased mechanical stability compared to control subjects. Post stroke, we found active posture tasking to be dominated by: 1) muscle weakness and 2) lack of reflex adaptation. This adds to existing doubts on reflex blocking therapy as the sole paradigm to improve active task performance and draws attention to muscle strength and power recovery and the role of the inability to modulate reflexes in post stroke movement disorders.Mechanical, Maritime and Materials Engineerin

    Phase I Study of Safety and Immunogenicity of an Escherichia coli-Derived Recombinant Protective Antigen (rPA) Vaccine to Prevent Anthrax in Adults

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    The fatal disease caused by Bacillus anthracis is preventable with a prophylactic vaccine. The currently available anthrax vaccine requires a lengthy immunization schedule, and simpler and more immunogenic options for protection against anthrax are a priority for development. In this report we describe a phase I clinical trial testing the safety and immunogenicity of an anthrax vaccine using recombinant Escherichia coli-derived, B. anthracis protective antigen (rPA).A total of 73 healthy adults ages 18-40 were enrolled and 67 received 2 injections separated by 4 weeks of either buffered saline placebo, or rPA formulated with or without 704 µg/ml Alhydrogel® adjuvant in increasing doses (5, 25, 50, 100 µg) of rPA. Participants were followed for one year and safety and immunologic data were assessed. Tenderness and warmth were the most common post-injection site reactions. No serious adverse events related to the vaccine were observed. The most robust humoral immune responses were observed in subjects receiving 50 µg of rPA formulated with Alhydrogel® with a geometric mean concentration of anti-rPA IgG antibodies of 283 µg/ml and a toxin neutralizing geometric 50% reciprocal geometric mean titer of 1061. The highest lymphoproliferative peak cellular response (median Lymphocyte Stimulation Index of 29) was observed in the group receiving 25 µg Alhydrogel®-formulated rPA.The vaccine was safe, well tolerated and stimulated a robust humoral and cellular response after two doses.ClinicalTrials.gov NCT00057525

    Construction of 3D models of the CYP11B family as a tool to predict ligand binding characteristics

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    Aldosterone is synthesised by aldosterone synthase (CYP11B2). CYP11B2 has a highly homologous isoform, steroid 11β-hydroxylase (CYP11B1), which is responsible for the biosynthesis of aldosterone precursors and glucocorticoids. To investigate aldosterone biosynthesis and facilitate the search for selective CYP11B2 inhibitors, we constructed three-dimensional models for CYP11B1 and CYP11B2 for both human and rat. The models were constructed based on the crystal structure of Pseudomonas Putida CYP101 and Oryctolagus Cuniculus CYP2C5. Small steric active site differences between the isoforms were found to be the most important determinants for the regioselective steroid synthesis. A possible explanation for these steric differences for the selective synthesis of aldosterone by CYP11B2 is presented. The activities of the known CYP11B inhibitors metyrapone, R-etomidate, R-fadrazole and S-fadrazole were determined using assays of V79MZ cells that express human CYP11B1 and CYP11B2, respectively. By investigating the inhibitors in the human CYP11B models using molecular docking and molecular dynamics simulations we were able to predict a similar trend in potency for the inhibitors as found in the in vitro assays. Importantly, based on the docking and dynamics simulations it is possible to understand the enantioselectivity of the human enzymes for the inhibitor fadrazole, the R-enantiomer being selective for CYP11B2 and the S-enantiomer being selective for CYP11B1

    Male-Specific Transfer and Fine Scale Spatial Differences of Newly Identified Cuticular Hydrocarbons and Triacylglycerides in a Drosophila Species Pair

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    We analyzed epicuticular hydrocarbon variation in geographically isolated populations of D. mojavensis cultured on different rearing substrates and a sibling species, D. arizonae, with ultraviolet laser desorption/ionization mass spectrometry (UV-LDI MS). Different body parts, i.e. legs, proboscis, and abdomens, of both species showed qualitatively similar hydrocarbon profiles consisting mainly of long-chain monoenes, dienes, trienes, and tetraenes. However, D. arizonae had higher amounts of most hydrocarbons than D. mojavensis and females of both species exhibited greater hydrocarbon amounts than males. Hydrocarbon profiles of D. mojavensis populations were significantly influenced by sex and rearing substrates, and differed between body parts. Lab food–reared flies had lower amounts of most hydrocarbons than flies reared on fermenting cactus substrates. We discovered 48 male- and species-specific hydrocarbons ranging in size from C22 to C50 in the male anogenital region of both species, most not described before. These included several oxygen-containing hydrocarbons in addition to high intensity signals corresponding to putative triacylglycerides, amounts of which were influenced by larval rearing substrates. Some of these compounds were transferred to female cuticles in high amounts during copulation. This is the first study showing that triacylglycerides may be a separate class of courtship-related signaling molecules in drosophilids. This study also extends the kind and number of epicuticular hydrocarbons in these species and emphasizes the role of larval ecology in influencing amounts of these compounds, many of which mediate courtship success within and between species

    To Fear is to Gain? The Role of Fear Recognition in Risky Decision Making in TBI Patients and Healthy Controls

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    Fear is an important emotional reaction that guides decision making in situations of ambiguity or uncertainty. Both recognition of facial expressions of fear and decision making ability can be impaired after traumatic brain injury (TBI), in particular when the frontal lobe is damaged. So far, it has not been investigated how recognition of fear influences risk behavior in healthy subjects and TBI patients. The ability to recognize fear is thought to be related to the ability to experience fear and to use it as a warning signal to guide decision making. We hypothesized that a better ability to recognize fear would be related to a better regulation of risk behavior, with healthy controls outperforming TBI patients. To investigate this, 59 healthy subjects and 49 TBI patients were assessed with a test for emotion recognition (Facial Expression of Emotion: Stimuli and Tests) and a gambling task (Iowa Gambling Task (IGT)). The results showed that, regardless of post traumatic amnesia duration or the presence of frontal lesions, patients were more impaired than healthy controls on both fear recognition and decision making. In both groups, a significant relationship was found between better fear recognition, the development of an advantageous strategy across the IGT and less risk behavior in the last blocks of the IGT. Educational level moderated this relationship in the final block of the IGT. This study has important clinical implications, indicating that impaired decision making and risk behavior after TBI can be preceded by deficits in the processing of fear
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