27 resultados para RNA Dynamic Structure

em Aston University Research Archive


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This paper undertakes an empirical analysis of the economic effects of military spending on the South African economy. It estimates a neo-classical model common in the literature at the level of the macroeconomy and at the level of the manufacturing sector. An attempt is made to improve upon the model by allowing the data to determine the dynamic structure of the model through an ARDL procedure. No significant impact of military spending is found in aggregate, but there is a significant negative impact for the manufacturing sector. This suggests that the cuts in domestic military procurement that have occurred since 1989 could lead to improved economic performance in South Africa through their impact on the manufacturing sector.

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The amplification of demand variation up a supply chain widely termed ‘the Bullwhip Effect’ is disruptive, costly and something that supply chain management generally seeks to minimise. Originally attributed to poor system design; deficiencies in policies, organisation structure and delays in material and information flow all lead to sub-optimal reorder point calculation. It has since been attributed to exogenous random factors such as: uncertainties in demand, supply and distribution lead time but these causes are not exclusive as academic and operational studies since have shown that orders and/or inventories can exhibit significant variability even if customer demand and lead time are deterministic. This increase in the range of possible causes of dynamic behaviour indicates that our understanding of the phenomenon is far from complete. One possible, yet previously unexplored, factor that may influence dynamic behaviour in supply chains is the application and operation of supply chain performance measures. Organisations monitoring and responding to their adopted key performance metrics will make operational changes and this action may influence the level of dynamics within the supply chain, possibly degrading the performance of the very system they were intended to measure. In order to explore this a plausible abstraction of the operational responses to the Supply Chain Council’s SCOR® (Supply Chain Operations Reference) model was incorporated into a classic Beer Game distribution representation, using the dynamic discrete event simulation software Simul8. During the simulation the five SCOR Supply Chain Performance Attributes: Reliability, Responsiveness, Flexibility, Cost and Utilisation were continuously monitored and compared to established targets. Operational adjustments to the; reorder point, transportation modes and production capacity (where appropriate) for three independent supply chain roles were made and the degree of dynamic behaviour in the Supply Chain measured, using the ratio of the standard deviation of upstream demand relative to the standard deviation of the downstream demand. Factors employed to build the detailed model include: variable retail demand, order transmission, transportation delays, production delays, capacity constraints demand multipliers and demand averaging periods. Five dimensions of supply chain performance were monitored independently in three autonomous supply chain roles and operational settings adjusted accordingly. Uniqueness of this research stems from the application of the five SCOR performance attributes with modelled operational responses in a dynamic discrete event simulation model. This project makes its primary contribution to knowledge by measuring the impact, on supply chain dynamics, of applying a representative performance measurement system.

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A CSSL- type modular FORTRAN package, called ACES, has been developed to assist in the simulation of the dynamic behaviour of chemical plant. ACES can be harnessed, for instance, to simulate the transients in startups or after a throughput change. ACES has benefited from two existing simulators. The structure was adapted from ICL SLAM and most plant models originate in DYFLO. The latter employs sequential modularisation which is not always applicable to chemical engineering problems. A novel device of twice- round execution enables ACES to achieve general simultaneous modularisation. During the FIRST ROUND, STATE-VARIABLES are retrieved from the integrator and local calculations performed. During the SECOND ROUND, fresh derivatives are estimated and stored for simultaneous integration. ACES further includes a version of DIFSUB, a variable-step integrator capable of handling stiff differential systems. ACES is highly formalised . It does not use pseudo steady- state approximations and excludes inconsistent and arbitrary features of DYFLO. Built- in debug traps make ACES robust. ACES shows generality, flexibility, versatility and portability, and is very convenient to use. It undertakes substantial housekeeping behind the scenes and thus minimises the detailed involvement of the user. ACES provides a working set of defaults for simulation to proceed as far as possible. Built- in interfaces allow for reactions and user supplied algorithms to be incorporated . New plant models can be easily appended. Boundary- value problems and optimisation may be tackled using the RERUN feature. ACES is file oriented; a STATE can be saved in a readable form and reactivated later. Thus piecewise simulation is possible. ACES has been illustrated and verified to a large extent using some literature-based examples. Actual plant tests are desirable however to complete the verification of the library. Interaction and graphics are recommended for future work.

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The operator hairpin ahead of the replicase gene in RNA bacteriophage MS2 contains overlapping signals for binding the coat protein and ribosomes. Coat protein binding inhibits further translation of the gene and forms the first step in capsid formation. The hairpin sequence was partially randomized to assess the importance of this structure element for the bacteriophage and to monitor alternative solutions that would evolve on the passaging of mutant phages. The evolutionary reconstruction of the operator failed in the majority of mutants. Instead, a poor imitation developed containing only some of the recognition signals for the coat protein. Three mutants were of particular interest in that they contained double nonsense codons in the lysis reading frame that runs through the operator hairpin. The simultaneous reversion of two stop codons into sense codons has a very low probability of occurring. Therefore the phage solved the problem by deleting the nonsense signals and, in fact, the complete operator, except for the initiation codon of the replicase gene. Several revertants were isolated with activities ranging from 1% to 20% of wild type. The operator, long thought to be a critical regulator, now appears to be a dispensable element. In addition, the results indicate how RNA viruses can be forced to step back to an attenuated form.

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In coliphage MS2 RNA a long-distance interaction (LDI) between an internal segment of the upstream coat gene and the start region of the replicase gene prevents initiation of replicase synthesis in the absence of coat gene translation. Elongating ribosomes break up the repressor LDI and thus activate the hidden initiation site. Expression studies on partial MS2 cDNA clones identified base pairing between 1427-1433 and 1738-1744, the so-called Min Jou (MJ) interaction, as the molecular basis for the long-range coupling mechanism. Here, we examine the biological significance of this interaction for the control of replicase gene translation. The LDI was disrupted by mutations in the 3'-side and the evolutionary adaptation was monitored upon phage passaging. Two categories of pseudorevertants emerged. The first type had restored the MJ interaction but not necessarily the native sequence. The pseudorevertants of the second type acquired a compensatory substitution some 80 nt downstream of the MJ interaction that stabilizes an adjacent LDI. In one examined case we confirmed that the second site mutations had restored coat-replicase translational coupling. Our results show the importance of translational control for fitness of the phage. They also reveal that the structure that buries the replicase start extends to structure elements bordering the MJ interaction.

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The design and synthesis of safe and efficient nonviral vectors for gene delivery has attracted significant attention in recent years. Previous experiments have revealed that the charge density of a polycation (the carrier) plays a crucial role in complexation and the release of the gene from the complex in the cytosol. In this work, we adopt an atomistic molecular dynamics simulation approach to study the complexation of short strand duplex RNA with six cationic carrier systems of varying charge and surface topology. The simulations reveal detailed molecular-level pictures of the structures and dynamics of the RNA-polycation complexes. Estimates for the binding free energy indicate that electrostatic contributions are dominant followed by van der Waals interactions. The binding free energy between the 8(+)polymers and the RNA is found to be larger than that of the 4(+)polymers, in general agreement with previously published data. Because reliable binding free energies provide an effective index of the ability of the polycationic carrier to bind the nucleic acid and also carry implications for the process of gene release within the cytosol, these novel simulations have the potential to provide us with a much better understanding of key mechanistic aspects of gene-polycation complexation and thereby advance the rational design of nonviral gene delivery systems.

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We use molecular dynamics simulations to compare the conformational structure and dynamics of a 21-base pair RNA sequence initially constructed according to the canonical A-RNA and A'-RNA forms in the presence of counterions and explicit water. Our study aims to add a dynamical perspective to the solid-state structural information that has been derived from X-ray data for these two characteristic forms of RNA. Analysis of the three main structural descriptors commonly used to differentiate between the two forms of RNA namely major groove width, inclination and the number of base pairs in a helical twist over a 30 ns simulation period reveals a flexible structure in aqueous solution with fluctuations in the values of these structural parameters encompassing the range between the two crystal forms and more. This provides evidence to suggest that the identification of distinct A-RNA and A'-RNA structures, while relevant in the crystalline form, may not be generally relevant in the context of RNA in the aqueous phase. The apparent structural flexibility observed in our simulations is likely to bear ramifications for the interactions of RNA with biological molecules (e.g. proteins) and non-biological molecules (e.g. non-viral gene delivery vectors). © CSIRO 2009.

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Due to environmental changes and business trends such as globalisation, outsourcing and virtualisation, more and more companies get involved in business activities that are outside their direct control. This typically occurs by entering into collaborative relationships and joint ventures with specialised companies in order to fulfil the demands of customers quickly (DiMaggio, 2001). Organisational structures that results from such collaborative relationships and joint ventures are referred to in this paper as enterprises and the management of them known as enterprise management. The authors use the definition of the European Commission (2003) that defines an enterprise as “… an entity, regardless of its legal form … including partnerships or associations regularly engaged in economic activities.” Therefore in its most simple form an enterprise could be a single integrated company. However, findings from this research show that enterprises can also be made up of parts of different companies and the structure of the enterprise is contingent upon a variety of different factors. The success of the enterprise as a collaborative venture depends on the ability of companies to intermediate their internal core competencies into other participating companies’ value streams and simultaneously outsource their own peripheral activities to companies that can perform them quicker, cheaper, and more effectively (Lal et al., 1995). In other words, the peripheral activities of one member-company must be complemented by a core competence of another member-company within an overall enterprise.

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This paper explores the importance of collaboration between different types of organizations within an enterprise. To achieve successful collaboration requires both endogenous and exogenous factors of each organization to be considered and a shared meta-strategy supported by shared cross-organizational processes and technology. A rolling business plan would periodically review, assess and reposition each organization within this meta-strategy according to how well they have contributed. We show that recent technological advances have made organizational structures more agile, organizational infra-structure more connected and the sharing of real-time information an operational reality; we also discuss the challenges and risks.

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Understanding the molecular mechanism of gene condensation is a key component to rationalizing gene delivery phenomena, including functional properties such as the stability of the gene-vector complex and the intracellular release of the gene. In this work, we adopt an atomistic molecular dynamics simulation approach to study the complexation of short strand duplex RNA with four cationic carrier systems of varying charge and surface topology at different charge ratios. At lower charge ratios, polymers bind quite effectively to siRNA, while at high charge ratios, the complexes are saturated and there are free polymers that are unable to associate with RNA. We also observed reduced fluctuations in RNA structures when complexed with multiple polymers in solution as compared to both free siRNA in water and the single polymer complexes. These novel simulations provide a much better understanding of key mechanistic aspects of gene-polycation complexation and thereby advance progress toward rational design of nonviral gene delivery systems.

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Smart structure sensors based on embedded fibre Bragg grating (FBG) arrays in aluminium alloy matrix by ultrasonic consolidation (UC) technique have been proposed and demonstrated successfully. The temperature, loading and bending responses of the embedded FBG arrays have been systematically characterized. The embedded FBGs exhibit an average temperature sensitivity of ~36 pm °C-1, which is three times higher than that of normal FBGs, a bending sensitivity of 0.73 nm/m-1 and a loading responsivity of ~0.1 nm kg-1 within the dynamic range from 0 kg to 3 kg. These initial experimental results clearly demonstrate that the UC produced metal matrix structures can be embedded with FBG sensor arrays to become smart structures with capabilities to monitor the structure operation and health conditions in applications.

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Contrary to the long-received theory of FDI, interest rates or rates of return can motivate foreign direct investment (FDI) in concert with the benefits of direct ownership. Thus, access to investor capital and capital markets is a vital component of the multinational’s competitive market structure. Moreover, multinationals can use their superior financial capacity as a competitive advantage in exploiting FDI opportunities in dynamic markets. They can also mitigate higher levels of foreign business risks under dynamic conditions by shifting more financial risk to creditors in the host economy. Furthermore, the investor’s expectation of foreign business risk necessarily commands a risk premium for exposing their equity to foreign market risk. Multinationals can modify the profit maximization strategy of their foreign subsidiaries to maximize growth or profits to generate this risk premium. In this context, we investigate how foreign subsidiaries manage their capital funding, business risk, and profit strategies with a diverse sample of 8,000 matched parents and foreign subsidiary accounts from multiple industries in 38 countries.We find that interest rates, asset prices, and expectations in capital markets have a significant effect on the capital movements of foreign subsidiaries. We also find that foreign subsidiaries mitigate their exposure to foreign business risk by modifying their capital structure and debt maturity. Further, we show how the operating strategy of foreign subsidiaries affects their preference for growth or profit maximization. We further show that superior shareholder value, which is a vital link for access to capital for funding foreign expansion in open market economies, is achieved through maintaining stability in the rate of growth and good asset utilization.

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This thesis describes the design and implementation of a new dynamic simulator called DASP. It is a computer program package written in standard Fortran 77 for the dynamic analysis and simulation of chemical plants. Its main uses include the investigation of a plant's response to disturbances, the determination of the optimal ranges and sensitivities of controller settings and the simulation of the startup and shutdown of chemical plants. The design and structure of the program and a number of features incorporated into it combine to make DASP an effective tool for dynamic simulation. It is an equation-oriented dynamic simulator but the model equations describing the user's problem are generated from in-built model equation library. A combination of the structuring of the model subroutines, the concept of a unit module, and the use of the connection matrix of the problem given by the user have been exploited to achieve this objective. The Executive program has a structure similar to that of a CSSL-type simulator. DASP solves a system of differential equations coupled to nonlinear algebraic equations using an advanced mixed equation solver. The strategy used in formulating the model equations makes it possible to obtain the steady state solution of the problem using the same model equations. DASP can handle state and time events in an efficient way and this includes the modification of the flowsheet. DASP is highly portable and this has been demonstrated by running it on a number of computers with only trivial modifications. The program runs on a microcomputer with 640 kByte of memory. It is a semi-interactive program, with the bulk of all input data given in pre-prepared data files with communication with the user is via an interactive terminal. Using the features in-built in the package, the user can view or modify the values of any input data, variables and parameters in the model, and modify the structure of the flowsheet of the problem during a simulation session. The program has been demonstrated and verified using a number of example problems.

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Software development methodologies are becoming increasingly abstract, progressing from low level assembly and implementation languages such as C and Ada, to component based approaches that can be used to assemble applications using technologies such as JavaBeans and the .NET framework. Meanwhile, model driven approaches emphasise the role of higher level models and notations, and embody a process of automatically deriving lower level representations and concrete software implementations. The relationship between data and software is also evolving. Modern data formats are becoming increasingly standardised, open and empowered in order to support a growing need to share data in both academia and industry. Many contemporary data formats, most notably those based on XML, are self-describing, able to specify valid data structure and content, and can also describe data manipulations and transformations. Furthermore, while applications of the past have made extensive use of data, the runtime behaviour of future applications may be driven by data, as demonstrated by the field of dynamic data driven application systems. The combination of empowered data formats and high level software development methodologies forms the basis of modern game development technologies, which drive software capabilities and runtime behaviour using empowered data formats describing game content. While low level libraries provide optimised runtime execution, content data is used to drive a wide variety of interactive and immersive experiences. This thesis describes the Fluid project, which combines component based software development and game development technologies in order to define novel component technologies for the description of data driven component based applications. The thesis makes explicit contributions to the fields of component based software development and visualisation of spatiotemporal scenes, and also describes potential implications for game development technologies. The thesis also proposes a number of developments in dynamic data driven application systems in order to further empower the role of data in this field.

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Paper-based phenolic laminates are used extensively in the electrical industry. Many small components are fabricated from these materials by the process known as punching. Recently an investigation was carried out to study the effect of processing variables on the punching properties. It was concluded that further work would be justified and that this should include a critical examination of the resin properties in a more controlled and systematic manner. In this investigation an attempt has been made to assess certain features of the resin structure in terms of thermomechanical properties. The number of crosslinks in the system was controlled using resins based on phenol and para-cresol formulations. Intramolecular hydrogen bonding effects were examined using substituted resins and a synthetically derived phenol based on 1,3-di-(o-hydroxyphenyl) propane.. A resin system was developed using the Friedel Crafts reaction to examine inter-molecular hydrogen bonding at the resin-paper interface. The punching properties of certain selected resins were assessed on a qualitative basis. In addition flexural and dynamic mechanical properties were determined in a general study of the structure-property relationships of these materials. It has been shown that certain features of the resin structure significantly influenced mechanical properties. :F'urther, it was noted that there is a close relationship between punching properties, mechanical damping and flexural strain. This work includes a critical examination of the curing mechanism and views are postulated in an attempt to extend knowledge in this area of the work. Finally, it is argued that future work should be based on a synthetic approach and that dynamic mechanical testing would provide a powerful tool In developing a deeper understanding of the resin fine structure.