947 resultados para Reduced model
Resumo:
Component-based development (CBD) has become an important emerging topic in the software engineering field. It promises long-sought-after benefits such as increased software reuse, reduced development time to market and, hence, reduced software production cost. Despite the huge potential, the lack of reasoning support and development environment of component modeling and verification may hinder its development. Methods and tools that can support component model analysis are highly appreciated by industry. Such a tool support should be fully automated as well as efficient. At the same time, the reasoning tool should scale up well as it may need to handle hundreds or even thousands of components that a modern software system may have. Furthermore, a distributed environment that can effectively manage and compose components is also desirable. In this paper, we present an approach to the modeling and verification of a newly proposed component model using Semantic Web languages and their reasoning tools. We use the Web Ontology Language and the Semantic Web Rule Language to precisely capture the inter-relationships and constraints among the entities in a component model. Semantic Web reasoning tools are deployed to perform automated analysis support of the component models. Moreover, we also proposed a service-oriented architecture (SOA)-based semantic web environment for CBD. The adoption of Semantic Web services and SOA make our component environment more reusable, scalable, dynamic and adaptive.
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Developmental neurotoxicity is a major issue in human health and may have lasting neurological implications. In this preliminary study we exposed differentiating Ntera2/clone D1 (NT2/D1) cell neurospheres to known human teratogens classed as non-embryotoxic (acrylamide), weakly embryotoxic (lithium, valproic acid) and strongly embryotoxic (hydroxyurea) as listed by European Centre for the Validation of Alternative Methods (ECVAM) and examined endpoints of cell viability and neuronal protein marker expression specific to the central nervous system, to identify developmental neurotoxins. Following induction of neuronal differentiation, valproic acid had the most significant effect on neurogenesis, in terms of reduced viability and decreased neuronal markers. Lithium had least effect on viability and did not significantly alter the expression of neuronal markers. Hydroxyurea significantly reduced cell viability but did not affect neuronal protein marker expression. Acrylamide reduced neurosphere viability but did not affect neuronal protein marker expression. Overall, this NT2/D1 -based neurosphere model of neurogenesis, may provide the basis for a model of developmental neurotoxicity in vitro.
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A paradox of memory research is that repeated checking results in a decrease in memory certainty, memory vividness and confidence [van den Hout, M. A., & Kindt, M. (2003a). Phenomenological validity of an OCD-memory model and the remember/know distinction. Behaviour Research and Therapy, 41, 369–378; van den Hout, M. A., & Kindt, M. (2003b). Repeated checking causes memory distrust. Behaviour Research and Therapy, 41, 301–316]. Although these findings have been mainly attributed to changes in episodic long-term memory, it has been suggested [Shimamura, A. P. (2000). Toward a cognitive neuroscience of metacognition. Consciousness and Cognition, 9, 313–323] that representations in working memory could already suffer from detrimental checking. In two experiments we set out to test this hypothesis by employing a delayed-match-to-sample working memory task. Letters had to be remembered in their correct locations, a task that was designed to engage the episodic short-term buffer of working memory [Baddeley, A. D. (2000). The episodic buffer: a new component in working memory? Trends in Cognitive Sciences, 4, 417–423]. Of most importance, we introduced an intermediate distractor question that was prone to induce frustrating and unnecessary checking on trials where no correct answer was possible. Reaction times and confidence ratings on the actual memory test of these trials confirmed the success of this manipulation. Most importantly, high checkers [cf. VOCI; Thordarson, D. S., Radomsky, A. S., Rachman, S., Shafran, R, Sawchuk, C. N., & Hakstian, A. R. (2004). The Vancouver obsessional compulsive inventory (VOCI). Behaviour Research and Therapy, 42(11), 1289–1314] were less accurate than low checkers when frustrating checking was induced, especially if the experimental context actually emphasized the irrelevance of the misleading question. The clinical relevance of this result was substantiated by means of an extreme groups comparison across the two studies. The findings are discussed in the context of detrimental checking and lack of distractor inhibition as a way of weakening fragile bindings within the episodic short-term buffer of Baddeley's (2000) model. Clinical implications, limitations and future research are considered.
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Background - Our previous studies showed that the direct injection of an adenovirus construct expressing urokinase-type plasminogen activator (uPA) into experimental venous thrombi significantly reduces thrombus weight. The systemic use of adenovirus vectors is limited by inherent hepatic tropism and inflammatory response. As macrophages are recruited into venous thrombi, it is reasonable to speculate that these cells could be used to target the adenovirus uPA (ad-uPA) gene construct to the thrombus. The aims of this study were to determine whether macrophages transduced with ad-uPA have increased fibrinolytic activity and whether systemic injection of transduced cells could be used to target uPA expression to the thrombus and reduce its size. Methods - The effect of up-regulating uPA was examined in an immortalized macrophage cell line (MM6) and macrophages differentiated from human blood monocyte-derived macrophages (HBMMs). Cells were infected with ad-uPA or blank control virus (ad-blank). Fibrinolytic mediator expression, cell viability, and cytokine expression were measured by activity assays and enzyme-linked immunosorbent assays. Monocyte migration was measured using a modified Boyden chamber assay. A model of venous thrombosis was developed and characterized in mice with severe combined immunodeficiency (SCID). This model was used to study whether systemically administered macrophages over-expressing uPA reduced thrombus size. Uptake of HBMMs into the thrombus induced in these mice was confirmed by a combination of PKH2-labeled cell tracking and colocalization with human leukocyte antigen (HLA) by immunohistology. Results - Compared with ad-blank, treated HBMMs transduction with ad-uPA increased uPA production by >1000-fold (P = .003), uPA activity by 150-fold (P = .0001), and soluble uPA receptor (uPAR) by almost twofold (P = .043). Expression of plasminogen activator inhibitor (PAI-1) and PAI-2 was decreased by about twofold (P = .011) and threefold (P = .005), respectively. Up-regulation of uPA had no effect on cell viability or inflammatory cytokine production compared with ad-blank or untreated cells. Ad-uPA transduction increased the migration rate of HBMMs (about 20%, P = .03) and MM6 cells (>twofold, P = .005) compared with ad-blank treated controls. Human macrophage recruitment into the mouse thrombus was confirmed by the colocalization of HLA with the PKH2-marked cells. Systemic injection of uPA-up-regulated HBMMs reduced thrombus weight by approximately 20% compared with ad-blank (P = .038) or sham-treated controls (P = .0028). Conclusion - Transduction of HBBM with ad-uPA increases their fibrinolytic activity. Systemic administration of uPA up-regulated HBBMs reduced thrombus size in an experimental model of venous thrombosis. Alternative methods of delivering fibrinolytic agents are worth exploring.
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Atrophy of skeletal muscle is due to a depression in protein synthesis and an increase in degradation. Studies in vitro have suggested that activation of the dsRNA-dependent protein kinase (PKR) may be responsible for these changes in protein synthesis and degradation. In order to evaluate whether this is also applicable to cancer cachexia the action of a PKR inhibitor on the development of cachexia has been studied in mice bearing the MAC16 tumour. Treatment of animals with the PKR inhibitor (5 mg kg-1) significantly reduced levels of phospho-PKR in muscle down to that found in non-tumour-bearing mice, and effectively attenuated the depression of body weight, with increased muscle mass, and also inhibited tumour growth. There was an increase in protein synthesis in skeletal muscle, which paralleled a decrease in eukaryotic initiation factor 2α phosphorylation. Protein degradation rates in skeletal muscle were also significantly decreased, as was proteasome activity levels and expression. Myosin levels were increased up to values found in non-tumour-bearing animals. Proteasome expression correlated with a decreased nuclear accumulation of nuclear factor-κB (NF-κB). The PKR inhibitor also significantly inhibited tumour growth, although this appeared to be a separate event from the effect on muscle wasting. These results suggest that inhibition of the autophosphorylation of PKR may represent an appropriate target for the attenuation of muscle atrophy in cancer cachexia. © 2007 Cancer Research UK.
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We modify a nonlinear σ model (NLσM) for the description of a granular disordered system in the presence of both the Coulomb repulsion and the Cooper pairing. We show that under certain controlled approximations the action of this model is reduced to the Ambegaokar-Eckern-Schön (AES) action, which is further reduced to the Bose-Hubbard (or “dirty-boson”) model with renormalized coupling constants. We obtain an effective action which is more general than the AES one but still simpler than the full NLσM action. This action can be applied in the region of parameters where the reduction to the AES or the Bose-Hubbard model is not justified. This action may lead to a different picture of the superconductor-insulator transition in two-dimensional systems.
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Purpose: To evaluate lenses produced by excimer laser ablation of poly(methyl methacrylate) (PMMA) plates. Setting: University research laboratory. Methods: Two Nidek EC-5000 scanning-slit excimer laser systems were used to ablate plane-parallel plates of PMMA. The ablated lenses were examined by focimetry, interferometry, and mechanical surface profiling. Results: The spherical optical powers of the lenses matched the expected values, but the cylindrical powers were generally lower than intended. Interferometry revealed marked irregularity in the surface of negative corrections, which often had a positive “island” at their center. Positive corrections were generally smoother. These findings were supported by the results of mechanical profiling. Contrast sensitivity measurements carried out when observing through ablated lenses whose power had been neutralized with a suitable spectacle lens of opposite sign confirmed that the surface irregularities of the ablated lenses markedly reduced contrast sensitivity over a range of spatial frequencies. Conclusion: Improvements in beam delivery systems seem desirable.
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A model of human leucopenia has been developed further in the female mouse. Following daily administration to female mice of 50 mg/kg of the aromatase inhibitor aminoglutethimide, significant falls in platelet and white cell counts occurred after 2 and 3 weeks. At week 4, drug dosage was stopped and the cell counts recovered at the end of that week, although on rechallenge at the beginning of week 5, both platelet and white cell counts fell rapidly. Administration to the mice of structural analogues of aminoglutethimide, such as WSP-3, glutethimide and 4-nitroglutethimide, showed no reductions in platelet and white cell counts. The haemotoxicity of aminoglutethimide over 21 days was unaffected by the presence of either the P-450 inhibitor SKF-525A or the hepatic P-450 inducer phenobarbitone. However, the co-administration of cimetidine abolished the haemotoxicity of aminoglutethimide in terms of platelet and white cell levels. In in vitro studies, both aminoglutethimide and WSP-3 were oxidised to cytotoxic species, although aminoglutethimide was significantly more cytotoxic than WSP-3. The NADPH-dependent covalent binding of 14C aminoglutethimide to mouse microsomes in vitro was significantly reduced by the presence of cimetidine. The activation of the compound to reactive species in vitro, the inhibitory effects of cimetidine in vivo and in vitro, as well as the rapid fall in the in vivo white cell count on rechallenge with aminoglutethimide suggest that this model illustrates a form of leucopenia which may be related to hapten formation and subsequent immune-mediated platelet and white cell lysis. © 2003 Elsevier B.V. All rights reserved.
Resumo:
Design verification in the digital domain, using model-based principles, is a key research objective to address the industrial requirement for reduced physical testing and prototyping. For complex assemblies, the verification of design and the associated production methods is currently fragmented, prolonged and sub-optimal, as it uses digital and physical verification stages that are deployed in a sequential manner using multiple systems. This paper describes a novel, hybrid design verification methodology that integrates model-based variability analysis with measurement data of assemblies, in order to reduce simulation uncertainty and allow early design verification from the perspective of satisfying key assembly criteria.
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In studies of complex heterogeneous networks, particularly of the Internet, significant attention was paid to analysing network failures caused by hardware faults or overload. There network reaction was modelled as rerouting of traffic away from failed or congested elements. Here we model network reaction to congestion on much shorter time scales when the input traffic rate through congested routes is reduced. As an example we consider the Internet where local mismatch between demand and capacity results in traffic losses. We describe the onset of congestion as a phase transition characterised by strong, albeit relatively short-lived, fluctuations of losses caused by noise in input traffic and exacerbated by the heterogeneous nature of the network manifested in a power-law load distribution. The fluctuations may result in the network strongly overreacting to the first signs of congestion by significantly reducing input traffic along the communication paths where congestion is utterly negligible. © 2013 IEEE.
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Human Resource (HR) systems and practices generally referred to as High Performance Work Practices (HPWPs), (Huselid, 1995) (sometimes termed High Commitment Work Practices or High Involvement Work Practices) have attracted much research attention in past decades. Although many conceptualizations of the construct have been proposed, there is general agreement that HPWPs encompass a bundle or set of HR practices including sophisticated staffing, intensive training and development, incentive-based compensation, performance management, initiatives aimed at increasing employee participation and involvement, job safety and security, and work design (e.g. Pfeffer, 1998). It is argued that these practices either directly and indirectly influence the extent to which employees’ knowledge, skills, abilities, and other characteristics are utilized in the organization. Research spanning nearly 20 years has provided considerable empirical evidence for relationships between HPWPs and various measures of performance including increased productivity, improved customer service, and reduced turnover (e.g. Guthrie, 2001; Belt & Giles, 2009). With the exception of a few papers (e.g., Laursen &Foss, 2003), this literature appears to lack focus on how HPWPs influence or foster more innovative-related attitudes and behaviours, extra role behaviors, and performance. This situation exists despite the vast evidence demonstrating the importance of innovation, proactivity, and creativity in its various forms to individual, group, and organizational performance outcomes. Several pertinent issues arise when considering HPWPs and their relationship to innovation and performance outcomes. At a broad level is the issue of which HPWPs are related to which innovation-related variables. Another issue not well identified in research relates to employees’ perceptions of HPWPs: does an employee actually perceive the HPWP –outcomes relationship? No matter how well HPWPs are designed, if they are not perceived and experienced by employees to be effective or worthwhile then their likely success in achieving positive outcomes is limited. At another level, research needs to consider the mechanisms through which HPWPs influence –innovation and performance. The research question here relates to what possible mediating variables are important to the success or failure of HPWPs in impacting innovative behaviours and attitudes and what are the potential process considerations? These questions call for theory refinement and the development of more comprehensive models of the HPWP-innovation/performance relationship that include intermediate linkages and boundary conditions (Ferris, Hochwarter, Buckley, Harrell-Cook, & Frink, 1999). While there are many calls for this type of research to be made a high priority, to date, researchers have made few inroads into answering these questions. This symposium brings together researchers from Australia, Europe, Asia and Africa to examine these various questions relating to the HPWP-innovation-performance relationship. Each paper discusses a HPWP and potential variables that can facilitate or hinder the effects of these practices on innovation- and performance- related outcomes. The first paper by Johnston and Becker explores the HPWPs in relation to work design in a disaster response organization that shifts quickly from business as usual to rapid response. The researchers examine how the enactment of the organizational response is devolved to groups and individuals. Moreover, they assess motivational characteristics that exist in dual work designs (normal operations and periods of disaster activation) and the implications for innovation. The second paper by Jørgensen reports the results of an investigation into training and development practices and innovative work behaviors (IWBs) in Danish organizations. Research on how to design and implement training and development initiatives to support IWBs and innovation in general is surprisingly scant and often vague. This research investigates the mechanisms by which training and development initiatives influence employee behaviors associated with innovation, and provides insights into how training and development can be used effectively by firms to attract and retain valuable human capital in knowledge-intensive firms. The next two papers in this symposium consider the role of employee perceptions of HPWPs and their relationships to innovation-related variables and performance. First, Bish and Newton examine perceptions of the characteristics and awareness of occupational health and safety (OHS) practices and their relationship to individual level adaptability and proactivity in an Australian public service organization. The authors explore the role of perceived supportive and visionary leadership and its impact on the OHS policy-adaptability/proactivity relationship. The study highlights the positive main effects of awareness and characteristics of OHS polices, and supportive and visionary leadership on individual adaptability and proactivity. It also highlights the important moderating effects of leadership in the OHS policy-adaptability/proactivity relationship. Okhawere and Davis present a conceptual model developed for a Nigerian study in the safety-critical oil and gas industry that takes a multi-level approach to the HPWP-safety relationship. Adopting a social exchange perspective, they propose that at the organizational level, organizational climate for safety mediates the relationship between enacted HPWS’s and organizational safety performance (prescribed and extra role performance). At the individual level, the experience of HPWP impacts on individual behaviors and attitudes in organizations, here operationalized as safety knowledge, skills and motivation, and these influence individual safety performance. However these latter relationships are moderated by organizational climate for safety. A positive organizational climate for safety strengthens the relationship between individual safety behaviors and attitudes and individual-level safety performance, therefore suggesting a cross-level boundary condition. The model includes both safety performance (behaviors) and organizational level safety outcomes, operationalized as accidents, injuries, and fatalities. The final paper of this symposium by Zhang and Liu explores leader development and relationship between transformational leadership and employee creativity and innovation in China. The authors further develop a model that incorporates the effects of extrinsic motivation (pay for performance: PFP) and employee collectivism in the leader-employee creativity relationship. The papers’ contributions include the incorporation of a PFP effect on creativity as moderator, rather than predictor in most studies; the exploration of the PFP effect from both fairness and strength perspectives; the advancement of knowledge on the impact of collectivism on the leader- employee creativity link. Last, this is the first study to examine three-way interactional effects among leader-member exchange (LMX), PFP and collectivism, thus, enriches our understanding of promoting employee creativity. In conclusion, this symposium draws upon the findings of four empirical studies and one conceptual study to provide an insight into understanding how different variables facilitate or potentially hinder the influence various HPWPs on innovation and performance. We will propose a number of questions for further consideration and discussion. The symposium will address the Conference Theme of ‘Capitalism in Question' by highlighting how HPWPs can promote financial health and performance of organizations while maintaining a high level of regard and respect for employees and organizational stakeholders. Furthermore, the focus on different countries and cultures explores the overall research question in relation to different modes or stages of development of capitalism.
Resumo:
Muscle invasive urinary bladder cancer is one of the most lethal cancers and its detection at the time of transurethral resection remains limited and diagnostic methods are urgently needed. We have developed a muscle invasive transitional cell carcinoma (TCC) model of the bladder using porcine bladder scaffold and the human bladder cancer cell line 5637. The progression of implanted cancer cells to muscle invasion can be monitored by measuring changes in the spectrum of endogenous fluorophores such as reduced nicotinamide dinucleotide (NADH) and flavins. We believe this could act as a useful tool for the study of fluorescence dynamics of developing muscle invasive bladder cancer in patients.
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This dissertation comprised two experiments, which addressed three main goals: (a) to test a new paradigm for measuring objectively the accuracy of alibis, (b) to explore the effectiveness of three retrieval cues (time only, location only, and time-and-location) in an alibi context, and (c) to explore the metacognitive strategies of innocent alibi providers who experience different financial incentives as well as different motivations for reporting (be informative vs. be convincing). ^ The novel paradigm appears promising: by surreptitiously controlling the whereabouts of future alibi providers during a critical time, objective accuracy measurements were in fact possible. Such accuracy measurements revealed that time-cued retrieval can be devastating to innocent alibi providers. Participants who attempted to recall their whereabouts via a time cue were significantly less accurate than participants who attempted recall via a location cue (Experiment 1). ^ Innocent alibi providers, when cued effectively, may not, however, report their memories differently from memory reporters in non-alibi contexts. When cued effectively, participants who experienced a goal of being convincing did not differ in accuracy from participants who experienced a goal of merely being informative (Experiment 2). Similarly, participants did not differ from one another in accuracy across different levels of financial incentive (Experiment 2). ^ Despite the indistinguishable accuracy rates of alibi providers and non-alibi memory reporters when retrieval was cued effectively, proffering mistaken alibis presents a real risk for innocent suspects. Future research needs to address methods by which that risk can be reduced. ^
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A brackish water ecotone of coastal bays and lakes, mangrove forests, salt marshes, tidal creeks, and upland hammocks separates Florida Bay, Biscayne Bay, and the Gulf of Mexico from the freshwater Everglades. The Everglades mangrove estuaries are characterized by salinity gradients that vary spatially with topography and vary seasonally and inter-annually with rainfall, tide, and freshwater flow from the Everglades. Because of their location at the lower end of the Everglades drainage basin, Everglades mangrove estuaries have been affected by upstream water management practices that have altered the freshwater heads and flows and that affect salinity gradients. Additionally, interannual variation in precipitation patterns, particularly those caused to El Nin˜o events, control freshwater inputs and salinity dynamics in these estuaries. Two major external drivers on this system are water management activities and global climate change. These drivers lead to two major ecosystem stressors: reduced freshwater flow volume and duration, and sea-level rise. Major ecological attributes include mangrove forest production, soil accretion, and resilience; coastal lake submerged aquatic vegetation; resident mangrove fish populations; wood stork (Mycteria americana) and roseate spoonbill (Platelea ajaja) nesting colonies; and estuarine crocodilian populations. Causal linkages between stressors and attributes include coastal transgression, hydroperiods, salinity gradients, and the ‘‘white zone’’ freshwater/estuarine interface. The functional estuary and its ecological attributes, as influenced by sea level and freshwater flow, must be viewed as spatially dynamic, with a possible near-term balancing of transgression but ultimately a long-term continuation of inland movement. Regardless of the spatio-temporal timing of this transgression, a salinity gradient supportive of ecologically functional Everglades mangrove estuaries will be required to maintain the integrity of the South Florida ecosystem.
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Software engineering researchers are challenged to provide increasingly more powerful levels of abstractions to address the rising complexity inherent in software solutions. One new development paradigm that places models as abstraction at the forefront of the development process is Model-Driven Software Development (MDSD). MDSD considers models as first class artifacts, extending the capability for engineers to use concepts from the problem domain of discourse to specify apropos solutions. A key component in MDSD is domain-specific modeling languages (DSMLs) which are languages with focused expressiveness, targeting a specific taxonomy of problems. The de facto approach used is to first transform DSML models to an intermediate artifact in a HLL e.g., Java or C++, then execute that resulting code.^ Our research group has developed a class of DSMLs, referred to as interpreted DSMLs (i-DSMLs), where models are directly interpreted by a specialized execution engine with semantics based on model changes at runtime. This execution engine uses a layered architecture and is referred to as a domain-specific virtual machine (DSVM). As the domain-specific model being executed descends the layers of the DSVM the semantic gap between the user-defined model and the services being provided by the underlying infrastructure is closed. The focus of this research is the synthesis engine, the layer in the DSVM which transforms i-DSML models into executable scripts for the next lower layer to process.^ The appeal of an i-DSML is constrained as it possesses unique semantics contained within the DSVM. Existing DSVMs for i-DSMLs exhibit tight coupling between the implicit model of execution and the semantics of the domain, making it difficult to develop DSVMs for new i-DSMLs without a significant investment in resources.^ At the onset of this research only one i-DSML had been created for the user- centric communication domain using the aforementioned approach. This i-DSML is the Communication Modeling Language (CML) and its DSVM is the Communication Virtual machine (CVM). A major problem with the CVM's synthesis engine is that the domain-specific knowledge (DSK) and the model of execution (MoE) are tightly interwoven consequently subsequent DSVMs would need to be developed from inception with no reuse of expertise.^ This dissertation investigates how to decouple the DSK from the MoE and subsequently producing a generic model of execution (GMoE) from the remaining application logic. This GMoE can be reused to instantiate synthesis engines for DSVMs in other domains. The generalized approach to developing the model synthesis component of i-DSML interpreters utilizes a reusable framework loosely coupled to DSK as swappable framework extensions.^ This approach involves first creating an i-DSML and its DSVM for a second do- main, demand-side smartgrid, or microgrid energy management, and designing the synthesis engine so that the DSK and MoE are easily decoupled. To validate the utility of the approach, the SEs are instantiated using the GMoE and DSKs of the two aforementioned domains and an empirical study to support our claim of reduced developmental effort is performed.^