903 resultados para K most critical paths
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Context. According to the sequential accretion model (or core-nucleated accretion model), giant planet formation is based first on the formation of a solid core which, when massive enough, can gravitationally bind gas from the nebula to form the envelope. The most critical part of the model is the formation time of the core: to trigger the accretion of gas, the core has to grow up to several Earth masses before the gas component of the protoplanetary disc dissipates. Aims: We calculate planetary formation models including a detailed description of the dynamics of the planetesimal disc, taking into account both gas drag and excitation of forming planets. Methods: We computed the formation of planets, considering the oligarchic regime for the growth of the solid core. Embryos growing in the disc stir their neighbour planetesimals, exciting their relative velocities, which makes accretion more difficult. Here we introduce a more realistic treatment for the evolution of planetesimals' relative velocities, which directly impact on the formation timescale. For this, we computed the excitation state of planetesimals, as a result of stirring by forming planets, and gas-solid interactions. Results: We find that the formation of giant planets is favoured by the accretion of small planetesimals, as their random velocities are more easily damped by the gas drag of the nebula. Moreover, the capture radius of a protoplanet with a (tiny) envelope is also larger for small planetesimals. However, planets migrate as a result of disc-planet angular momentum exchange, with important consequences for their survival: due to the slow growth of a protoplanet in the oligarchic regime, rapid inward type I migration has important implications on intermediate-mass planets that have not yet started their runaway accretion phase of gas. Most of these planets are lost in the central star. Surviving planets have masses either below 10 M⊕ or above several Jupiter masses. Conclusions: To form giant planets before the dissipation of the disc, small planetesimals (~0.1 km) have to be the major contributors of the solid accretion process. However, the combination of oligarchic growth and fast inward migration leads to the absence of intermediate-mass planets. Other processes must therefore be at work to explain the population of extrasolar planets that are presently known.
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Introduction: Drought is one of the most significant factors that limit plant productivity. Oxidative stress is a secondary event in many unfavorable environmental conditions. Intracellular proteases have a role in the metabolism reorganisation and nutrient remobilization under stress. In order to under stand the relative significance of oxidative stress and proteolysis in the yield reduction under drought, four varieties of Triticum aestivum L. with different field drought resistance were examined. Methods: A two-year field experiment was conducted. Analyses were performed on the upper most leaf of control plants and plants under water deficitat the stages most critical for yield reduction under drought (from jointing till milk ripeness). Leaf water deficit and electrolyte leakage, malondyaldehyde level, activities and isoenzymes of superoxide dismutase, catalase and peroxidase, leaf protein content and proteolytic activity were studied. Yield components were analyzed. Results: A general trend of increasing the membrane in stability and accumulation of lipid hydroperoxides was observed with some differences among varieties, especially under drought. The anti-oxidative enzyme activities were progressively enhanced, as well as the azocaseinolytic activities. The leaf protein content decreased under drought at the last phase. Differences among varieties were observed in the parameters under study. They were compared to yield components` reduction under water deprivation.
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In the framework of ACTRIS (Aerosols, Clouds, and Trace Gases Research Infrastructure Network) summer 2012 measurement campaign (8 June–17 July 2012), EARLINET organized and performed a controlled exercise of feasibility to demonstrate its potential to perform operational, coordinated measurements and deliver products in near-real time. Eleven lidar stations participated in the exercise which started on 9 July 2012 at 06:00 UT and ended 72 h later on 12 July at 06:00 UT. For the first time, the single calculus chain (SCC) – the common calculus chain developed within EARLINET for the automatic evaluation of lidar data from raw signals up to the final products – was used. All stations sent in real-time measurements of a 1 h duration to the SCC server in a predefined netcdf file format. The pre-processing of the data was performed in real time by the SCC, while the optical processing was performed in near-real time after the exercise ended. 98 and 79 % of the files sent to SCC were successfully pre-processed and processed, respectively. Those percentages are quite large taking into account that no cloud screening was performed on the lidar data. The paper draws present and future SCC users' attention to the most critical parameters of the SCC product configuration and their possible optimal value but also to the limitations inherent to the raw data. The continuous use of SCC direct and derived products in heterogeneous conditions is used to demonstrate two potential applications of EARLINET infrastructure: the monitoring of a Saharan dust intrusion event and the evaluation of two dust transport models. The efforts made to define the measurements protocol and to configure properly the SCC pave the way for applying this protocol for specific applications such as the monitoring of special events, atmospheric modeling, climate research and calibration/validation activities of spaceborne observations.
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One of the most critical aspects of G Protein Coupled Receptors (GPCRs) regulation is their rapid and acute desensitization following agonist stimulation. Phosphorylation of these receptors by GPCR kinases (GRK) is a major mechanism of desensitization. Considerable evidence from studies of rhodopsin kinase and GRK2 suggests there is an allosteric docking site for the receptor distinct from the GRK catalytic site. While the agonist-activated GPCR appears crucial for GRK activation, the molecular details of this interaction remain unclear. Recent studies suggested an important role for the N- and C-termini and domains in the small lobe of the kinase domain in allosteric activation; however, neither the mechanism of action of that site nor the RH domain contributions have been elucidated. To search for the allosteric site, we first indentified evolutionarily conserved sites within the RH and kinase domains presumably deterministic of protein function employing evolutionary trace (ET) methodology and crystal structures of GRK6. Focusing on a conserved cluster centered on helices 3, 9, and 10 in the RH domain, key residues of GRK5 and 6 were targeted for mutagenesis and functional assays. We found that a number of double mutations within helices 3, 9, and 10 and the N-terminus markedly reduced (50–90%) the constitutive phosphorylation of the β-2 Adrenergic Receptor (β2AR) in intact cells and phosphorylation of light-activated rhodopsin (Rho*) in vitro as compared to wild type (WT) GRK5 or 6. Based on these results, we designed peptide mimetics of GRK5 helix 9 both computationally and through chemical modifications with the goal of both confirming the importance of helix 9 and developing a useful inhibitor to disrupt the GPCR-GRK interaction. Several peptides were found to block Rho* phosphorylation by GRK5 including the native helix 9 sequence, Peptide Builder designed-peptide preserving only the key ET residues, and chemically locked helices. Most peptidomimetics showed inhibition of GRK5 activity greater than 80 % with an IC50 of ∼ 30 µM. Alanine scanning of helix 9 has further revealed both essential and non-essential residues for inhibition. Importantly, substitution of Arg 169 by an alanine in the native helix 9-based peptide gave an almost complete inhibition at 30 µM with an IC50 of ∼ 10 µM. In summary we report a previously unrecognized crucial role for the RH domain of GRK5 and 6, and the subsequent identification of a lead peptide inhibitor of protein-protein interaction with potential for specific blockade of GPCR desensitization. ^
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The purpose of this study is to determine the critical wear levels of the contact wire of the catenary on metropolitan lines. The study has focussed on the zones of contact wire where localised wear is produced, normally associated with the appearance of electric arcs. To this end, a finite element model has been developed to study the dynamics of pantograph-catenary interaction. The model includes a zone of localised wear and a singularity in the contact wire in order to simulate the worst case scenario from the point of view of stresses. In order to consider the different stages in the wire wear process, different depths and widths of the localised wear zone were defined. The results of the dynamic simulations performed for each stage of wear let the area of the minimum resistant section of the contact wire be determined for which stresses are greater than the allowable stress. The maximum tensile stress reached in the contact wire shows a clear sensitivity to the size of the local wear zone, defined by its width and depth. In this way, if the wear measurements taken with an overhead line recording vehicle are analysed, it will be possible to calculate the potential breakage risk of the wire. A strong dependence of the tensile forces of the contact wire has also been observed. These results will allow priorities to be set for replacing the most critical sections of wire, thereby making maintenance much more efficient. The results obtained show that the wire replacement criteria currently borne in mind have turned out to be appropriate, although in some wear scenarios these criteria could be adjusted even more, and so prolong the life cycle of the contact wire.
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The nuclear spin polarization of 129Xe can be enhanced by several orders of magnitude by using optical pumping techniques. The increased sensitivity of xenon NMR has allowed imaging of lungs as well as other in vivo applications. The most critical parameter for efficient delivery of laser-polarized xenon to blood and tissues is the spin-lattice relaxation time (T1) of xenon in blood. In this work, the relaxation of laser-polarized xenon in human blood is measured in vitro as a function of blood oxygenation. Interactions with dissolved oxygen and with deoxyhemoglobin are found to contribute to the spin-lattice relaxation time of 129Xe in blood, the latter interaction having greater effect. Consequently, relaxation times of 129Xe in deoxygenated blood are shorter than in oxygenated blood. In samples with oxygenation equivalent to arterial and venous blood, the 129Xe T1s at 37°C and a magnetic field of 1.5 T were 6.4 s ± 0.5 s and 4.0 s ± 0.4 s, respectively. The 129Xe spin-lattice relaxation time in blood decreases at lower temperatures, but the ratio of T1 in oxygenated blood to that in deoxygenated blood is the same at 37°C and 25°C. A competing ligand has been used to show that xenon binding to albumin contributes to the 129Xe spin-lattice relaxation in blood plasma. This technique is promising for the study of xenon interactions with macromolecules.
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The BCL-2 family of proteins is composed of both pro- and antiapoptotic regulators, although its most critical biochemical functions remain uncertain. The structural similarity between the BCL-XL monomer and several ion-pore-forming bacterial toxins has prompted electrophysiologic studies. Both BAX and BCL-2 insert into KCl-loaded vesicles in a pH-dependent fashion and demonstrate macroscopic ion efflux. Release is maximum at ≈pH 4.0 for both proteins; however, BAX demonstrates a broader pH range of activity. Both purified proteins also insert into planar lipid bilayers at pH 4.0. Single-channel recordings revealed a minimal channel conductance for BAX of 22 pS that evolved to channel currents with at least three subconductance levels. The final, apparently stable BAX channel had a conductance of 0.731 nS at pH 4.0 that changed to 0.329 nS when shifted to pH 7.0 but remained mildly Cl− selective and predominantly open. When BAX-incorporated lipid vesicles were fused to planar lipid bilayers at pH 7.0, a Cl−-selective (PK/PCl = 0.3) 1.5-nS channel displaying mild inward rectification was noted. In contrast, BCL-2 formed mildly K+-selective (PK/PCl = 3.9) channels with a most prominent initial conductance of 80 pS that increased to 1.90 nS. Fusion of BCL-2-incorporated lipid vesicles into planar bilayers at pH 7.0 also revealed mild K+ selectivity (PK/PCl = 2.4) with a maximum conductance of 1.08 nS. BAX and BCL-2 each form channels in artificial membranes that have distinct characteristics including ion selectivity, conductance, voltage dependence, and rectification. Thus, one role of these molecules may include pore activity at selected membrane sites.
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Alzheimer's disease produces a devastating decline in mental function, with profound effects on learning and memory. Early consequences of the disease include the specific loss of cholinergic neurons in brain, diminished cholinergic signaling, and the accumulation of β-amyloid peptide in neuritic plaques. Of the nicotinic acetylcholine receptors at risk, the most critical may be those containing the α7 gene product (α7-nAChRs), because they are widespread, have a high relative permeability to calcium, and regulate numerous cellular events in the nervous system. With the use of whole-cell patch–clamp recording we show here that nanomolar concentrations of β-amyloid peptides specifically and reversibly block α7-nAChRs on rat hippocampal neurons in culture. The block is noncompetitive, voltage-independent, and use-independent and is mediated through the N-terminal extracellular domain of the receptor. It does not appear to require either calcium influx or G protein activation. β-Amyloid blockade is likely to be a common feature of α7-nAChRs because it applies to the receptors at both somato-dendritic and presynaptic locations on rat hippocampal neurons and extends to homologous receptors on chick ciliary ganglion neurons as well. Because α7-nAChRs in the central nervous system are thought to have numerous functions and recently have been implicated in learning and memory, impaired receptor function in this case may contribute to cognitive deficits associated with Alzheimer's disease.
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Older people’s travel behaviour is affected by negative or positive critical incidents in the public transport environment. With the objective of identifying such inci- dents during whole trips and examining how travel beha- viour had changed, we have conducted in-depth interviews with 30 participants aged 65–91 years in the County of Stockholm, Sweden. Out of 469 incidents identified, 77 were reported to have resulted in travel behaviour change, 67 of them in a negative way. Most critical incidents were encountered in the physical environment on-board vehicles and at stations/stops as well as in pricing/ticketing. The findings show that more personal assistance, better driving behaviour, and swift maintenance of elevators and escala- tors are key facilitators that would improve predictability in travelling and enhance vulnerable older travellers’ feeling of security. The results demonstrate the benefit of involving different groups of end users in future planning and design, such that transport systems would meet the various needs of its end users.
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Thesis (Ph.D.)--University of Washington, 2016-06
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A review of the extant literature concludes that market-driven intangibles and innovations are increasingly considered to be the most critical firm-specific resources, but also finds a lack of elaboration of which types of these resources are most important. In this paper, we incorporate these observations into a conceptual model and link it to highly developed institutional settings for the model evaluation. From the point of view of firm revenue management, we can anticipate that performance advantages created through deployment of intellectual and relational capital in marketing and innovation are more likely to be superior. In essence, they constitute the integration of organisational intangibles both in cognitive and behavioural level to create an idiosyncratic combination for each firm. Our research findings show feasible paths for sharpening the edge of market-driven intangibles and innovations. We discuss the key results for research and practice.
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Purpose – The purpose of this paper is to help managers to successfully plan, implement, and operate enterprise resource planning (ERP) projects using a risk management framework. Design/methodology/approach – This paper adopted a combined literature review and case study method. Using literature review, the paper first identified major issues of managing ERP projects and develops a risk management framework for managing those issues. The proposed risk management framework was then applied to a ERP implementation project of a UK-based energy services group and its effectiveness for managing ERP projects implementation had been demonstrated. Additionally, the risk factors as identified from the case application are compared with the risk factors from the previous researches so as to suggest mitigating measures. Findings – All the risk factors are categorized into planning, implementation and operations phases along with project processes, organizational transformation and information technology (IT) perspectives. Project implementation phase is the most vulnerable to failure. The case study results reveal that the effect of other projects on on-going ERP project, management of overall IT architecture and non-availability of resources for organizational transformation are most critical from likelihood and impact perspectives. Managing risk across various phases of project and equal emphasize to effective project management, organizational transformation and IT adoption are the key to success in ERP implementation. Practical implications – The risk factors, which were identified using literature review and the case study, have great significance as mitigating measures of those risks may result successful implementation of ERP projects in the industry. Additionally, proposed risk management framework could be customized to implement ERP projects elsewhere. Originality/value – ERP projects are risky as they are capital intensive, technically complex, and call for organizational transformation. There are both success and failure stories. However, both researchers and practitioners agree, that if it can be implemented and operated successfully and benefits should be achievable. Although there are many studies on ERP implementation, little has been discussed on managing risks of ERP projects. Therefore, this paper bridges the gap.
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Whole life costing (WLC) has become the best practice in construction procurement and it is likely to be a major issue in predicting whole life costs of a construction project accurately. However, different expectations from different organizations throughout a project's life and the lack of data, monitoring targets, and long-term interest for many key players are obstacles to be overcome if WLC is to be implemented. A questionnaire survey was undertaken to investigate a set of ten common factors and 188 individual factors. These were grouped into eight critical categories (project scope, time, cost, quality, contract/administration, human resource, risk, and health and safety) by project phase, as perceived by the clients, contractors and subcontractors in order to identify critical success factors for whole life performance assessment (WLPA). Using a relative importance index, the top ten critical factors for each category, from the perspective of project participants, were analyzed and ranked. Their agreement on those categories and factors were analyzed using Spearman's rank correlation. All participants identify “Type of Project” as the most common critical factor in the eight categories for WLPA. Using the relative index ranking technique and weighted average methods, it was found that the most critical individual factors in each category were: “clarity of contract” (scope); “fixed construction period” (time); “precise project budget estimate” (cost); “material quality” (quality); “mutual/trusting relationships” (contract/administration); “leadership/team management” (human resource); and “management of work safety on site” (health and safety). There was relatively a high agreement on these categories among all participants. Obviously, with 80 critical factors of WLPA, there is a stronger positive relationship between client and contactor rather than contractor and subcontractor, client and subcontractor. Putting these critical factors into a criteria matrix can facilitate an initial framework of WLPA in order to aid decision making in the public sector in South Korea for evaluation/selection process of a construction project at the bid stage.
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A series of bis-salicylidene based N2S2 copper macrocycles were prepared, structurally characterised and subjected to electrochemical analysis. The aim was to investigate the effects of length of polymethylene chains between either the imine donors or the sulfur donors on redox state and potential of the metal. The complexes structurally characterised had either distorted square planar or tetrahedral geometries depending on their oxidation state (Cu2+ or Cu+, respectively), and the N-(CH2)n-N bridge was found to be most critical moiety in determining the redox potential and oxidation state of the copper macrocycles, with relatively little change in these properties caused by lengthening the S-(CH2)n-S bridge from two to three carbons. In fact, a weakness was observed in the complexes at the sulfur donor, as further lengthening of the S-(CH2)n-S methylene bridge to four carbons caused fission of the carbon-sulfur bond to give dimeric rings and supramolecular assemblies. Cu+ complexes could be oxidised to Cu2+ by tert-butylhydroperoxide, with a corresponding change in the spectrophotometric properties, and likewise Cu2+ complexes could be reduced to Cu+ by treatment with ß-mercaptoethylamine. However, repeated redox cycles appeared to compromise the stability of the macrocycles, most probably by a competing oxidation of the ligand. Thus the copper N2S2 macrocycles show potential as redox sensors, but further development is required to improve their performance in a biochemical environment.
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Enterprise resource planning (ERP) projects are risky. But if they are implemented appropriately, they can provide competitive advantage to organisations. Therefore, ERP implementation has become one of the most critical aspects of today's information management research. The main purpose of this article is to describe a new ERP risk assessment framework (RAF) that can be used to increase the success of ERP implementation. In this article, through a case study based in a leading UK-based energy service provider, we demonstrate the new RAF, which has been shown to help identify and mitigate risks in ERP implementation. In contrast to other research, this RAF identifies risks hierarchically in external engagement, programme management, work stream and work package levels across technical, schedule, operational, business and organisational categories. This not only helped to develop responses to mitigate risks but also facilitates on-going risk control.