60 resultados para type three secretion system

em Queensland University of Technology - ePrints Archive


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The three-component reaction-diffusion system introduced in [C. P. Schenk et al., Phys. Rev. Lett., 78 (1997), pp. 3781–3784] has become a paradigm model in pattern formation. It exhibits a rich variety of dynamics of fronts, pulses, and spots. The front and pulse interactions range in type from weak, in which the localized structures interact only through their exponentially small tails, to strong interactions, in which they annihilate or collide and in which all components are far from equilibrium in the domains between the localized structures. Intermediate to these two extremes sits the semistrong interaction regime, in which the activator component of the front is near equilibrium in the intervals between adjacent fronts but both inhibitor components are far from equilibrium there, and hence their concentration profiles drive the front evolution. In this paper, we focus on dynamically evolving N-front solutions in the semistrong regime. The primary result is use of a renormalization group method to rigorously derive the system of N coupled ODEs that governs the positions of the fronts. The operators associated with the linearization about the N-front solutions have N small eigenvalues, and the N-front solutions may be decomposed into a component in the space spanned by the associated eigenfunctions and a component projected onto the complement of this space. This decomposition is carried out iteratively at a sequence of times. The former projections yield the ODEs for the front positions, while the latter projections are associated with remainders that we show stay small in a suitable norm during each iteration of the renormalization group method. Our results also help extend the application of the renormalization group method from the weak interaction regime for which it was initially developed to the semistrong interaction regime. The second set of results that we present is a detailed analysis of this system of ODEs, providing a classification of the possible front interactions in the cases of $N=1,2,3,4$, as well as how front solutions interact with the stationary pulse solutions studied earlier in [A. Doelman, P. van Heijster, and T. J. Kaper, J. Dynam. Differential Equations, 21 (2009), pp. 73–115; P. van Heijster, A. Doelman, and T. J. Kaper, Phys. D, 237 (2008), pp. 3335–3368]. Moreover, we present some results on the general case of N-front interactions.

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In this article, we analyze the three-component reaction-diffusion system originally developed by Schenk et al. (PRL 78:3781–3784, 1997). The system consists of bistable activator-inhibitor equations with an additional inhibitor that diffuses more rapidly than the standard inhibitor (or recovery variable). It has been used by several authors as a prototype three-component system that generates rich pulse dynamics and interactions, and this richness is the main motivation for the analysis we present. We demonstrate the existence of stationary one-pulse and two-pulse solutions, and travelling one-pulse solutions, on the real line, and we determine the parameter regimes in which they exist. Also, for one-pulse solutions, we analyze various bifurcations, including the saddle-node bifurcation in which they are created, as well as the bifurcation from a stationary to a travelling pulse, which we show can be either subcritical or supercritical. For two-pulse solutions, we show that the third component is essential, since the reduced bistable two-component system does not support them. We also analyze the saddle-node bifurcation in which two-pulse solutions are created. The analytical method used to construct all of these pulse solutions is geometric singular perturbation theory, which allows us to show that these solutions lie in the transverse intersections of invariant manifolds in the phase space of the associated six-dimensional travelling wave system. Finally, as we illustrate with numerical simulations, these solutions form the backbone of the rich pulse dynamics this system exhibits, including pulse replication, pulse annihilation, breathing pulses, and pulse scattering, among others.

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In this article, we analyze the stability and the associated bifurcations of several types of pulse solutions in a singularly perturbed three-component reaction-diffusion equation that has its origin as a model for gas discharge dynamics. Due to the richness and complexity of the dynamics generated by this model, it has in recent years become a paradigm model for the study of pulse interactions. A mathematical analysis of pulse interactions is based on detailed information on the existence and stability of isolated pulse solutions. The existence of these isolated pulse solutions is established in previous work. Here, the pulse solutions are studied by an Evans function associated to the linearized stability problem. Evans functions for stability problems in singularly perturbed reaction-diffusion models can be decomposed into a fast and a slow component, and their zeroes can be determined explicitly by the NLEP method. In the context of the present model, we have extended the NLEP method so that it can be applied to multi-pulse and multi-front solutions of singularly perturbed reaction-diffusion equations with more than one slow component. The brunt of this article is devoted to the analysis of the stability characteristics and the bifurcations of the pulse solutions. Our methods enable us to obtain explicit, analytical information on the various types of bifurcations, such as saddle-node bifurcations, Hopf bifurcations in which breathing pulse solutions are created, and bifurcations into travelling pulse solutions, which can be both subcritical and supercritical.

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Growing evidence suggests that a novel member of the Chlamydiales order, Waddlia chondrophila, is a potential agent of miscarriage in humans and abortion in ruminants. Due to the lack of genetic tools to manipulate chlamydia, genomic analysis is proving to be the most incisive tool in stimulating investigations into the biology of these obligate intracellular bacteria. 454/Roche and Solexa/Illumina technologies were thus used to sequence and assemble de novo the full genome of the first representative of the Waddliaceae family, W. chondrophila. The bacteria possesses a 2′116′312bp chromosome and a 15′593 bp low-copy number plasmid that might integrate into the bacterial chromosome. The Waddlia genome displays numerous repeated sequences indicating different genome dynamics from classical chlamydia which almost completely lack repetitive elements. Moreover, W. chondrophila exhibits many virulence factors also present in classical chlamydia, including a functional type III secretion system, but also a large complement of specific factors for resistance to host or environmental stresses. Large families of outer membrane proteins were identified indicating that these highly immunogenic proteins are not Chlamydiaceae specific and might have been present in their last common ancestor. Enhanced metabolic capability for the synthesis of nucleotides, amino acids, lipids and other co-factors suggests that the common ancestor of the modern Chlamydiales may have been less dependent on their eukaryotic host. The fine-detailed analysis of biosynthetic pathways brings us closer to possibly developing a synthetic medium to grow W. chondrophila, a critical step in the development of genetic tools. As a whole, the availability of the W. chondrophila genome opens new possibilities in Chlamydiales research, providing new insights into the evolution of members of the order Chlamydiales and the biology of the Waddliaceae.

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Upon infection, Legionella pneumophila uses the Dot/Icm type IV secretion system to translocate effector proteins from the Legionella-containing vacuole (LCV) into the host cell cytoplasm. The effectors target a wide array of host cellular processes that aid LCV biogenesis, including the manipulation of membrane trafficking. In this study, we used a hidden Markov model screen to identify two novel, non-eukaryotic soluble NSF attachment protein receptor (SNARE) homologs: the bacterial Legionella SNARE effector A (LseA) and viral SNARE homolog A proteins. We characterized LseA as a Dot/Icm effector of L. pneumophila, which has close homology to the Qc-SNARE subfamily. The lseA gene was present in multiple sequenced L. pneumophila strains including Corby and was well distributed among L. pneumophila clinical and environmental isolates. Employing a variety of biochemical, cell biological and microbiological techniques, we found that farnesylated LseA localized to membranes associated with the Golgi complex in mammalian cells and LseA interacted with a subset of Qa-, Qb- and R-SNAREs in host cells. Our results suggested that LseA acts as a SNARE protein and has the potential to regulate or mediate membrane fusion events in Golgi-associated pathways.

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A robust and reliable grid power interface system for wind turbines using a permanent-magnet synchronous generator (PMSG) is proposed in this paper, where an integration of a generator-side three-switch buck-type rectifier and a grid-side Z-source inverter is employed as a bridge between the generator and the grid. The modulation strategy for the proposed topology is developed from space-vector modulation and Z-source network operation principles. Two PMSG control methods, namely, unity-power-factor control and rotor-flux-orientation control (Id = 0), are studied to establish an optimized control scheme for the generator-side three-switch buck-type rectifier. The system control scheme decouples active- and reactive-power control through voltage-oriented control and optimizes PMSG control for the grid- and generator-side converters independently. Maximum power point tracking is implemented by adjusting the shoot-through duty cycles of the Z-source network. The design considerations of the passive components are also provided. The performances and practicalities of the designed architecture have been verified by simulations and experiments.

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Chlamydia trachomatis infections of the male and female reproductive tracts are the world's leading sexually transmitted bacterial disease, and can lead to damaging pathology, scarring and infertility. The resolution of chlamydial infection requires the development of adaptive immune responses to infection, and includes cell-mediated and humoral immunity. Whilst cluster of differentiation (CD)4+ T cells are known to be essential in clearance of infection [1], they are also associated with immune cell infiltration, autoimmunity and infertility in the testes [2-3]. Conversely, antibodies are less associated with inflammation, are readily transported into the reproductive tracts, and can offer lumenal neutralization of chlamydiae prior to infection. Antibodies, or immunoglobulins (Ig), play a supportive role in the resolution of chlamydial infections, and this thesis sought to define the function of IgA and IgG, against a variety of chlamydial antigens expressed during the intracellular and extracellular stages of the chlamydial developmental cycle. Transport of IgA and IgG into the mucosal lumen is facilitated by receptor-mediated transcytosis yet the expression profile (under normal conditions and during urogenital chlamydial infection) of the polymeric immunoglobulin receptor (pIgR) and the neonatal Fc receptor (FcRn) remains unknown. The expression profile of pIgR and FcRn in the murine male reproductive tract was found to be polarized to the lower and upper reproductive tract tissues respectively. This demonstrates that the two receptors have a tissue tropism, which must be considered when targeting pathogens that colonize different sites. In contrast, the expression of pIgR and FcRn in the female mouse was found to be distributed in both the upper and lower reproductive tracts. When urogenitally infected with Chlamydia muridarum, both male and female reproductive tracts up-regulated expression of pIgR and down-regulated expression of FcRn. Unsurprisingly, the up-regulation of pIgR increased the concentration of IgA in the lumen. However, down-regulation of FcRn, prevented IgG uptake and led to an increase or pooling of IgG in lumenal secretions. As previous studies have identified the importance of pIgR-mediated delivery of IgA, as well as the potential of IgA to bind and neutralize intracellular pathogens, IgA against a variety of chlamydial antigens was investigated. The protection afforded by IgA against the extracellular antigen major outer membrane protein (MOMP), was found to be dependent on pIgR expression in vitro and in vivo. It was also found that in the absence of pIgR, no protection was afforded to mice previously immunized with MOMP. The protection afforded from polyclonal IgA against the intracellular chlamydial antigens; inclusion membrane protein A (IncA), inclusion membrane proteins (IncMem) and secreted chlamydial protease-like activity factor (CPAF) were produced and investigated in vitro. Antigen-specific intracellular IgA was found to bind to the respective antigen within the infected cell, but did not significantly reduce inclusion formation (p > 0.05). This suggests that whilst IgA specific for the selected antigens was transported by pIgR to the chlamydial inclusion, it was unable to prevent growth. Similarly, immunization of male mice with intracellular chlamydial antigens (IncA or IncMem), followed by depletion CD4+ T cells, and subsequent urogenital C. muridarum challenge, provided minimal pIgR-mediated protection. Wild type male mice immunized with IncA showed a 57 % reduction (p < 0.05), and mice deficient in pIgR showed a 35 % reduction (p < 0.05) in reproductive tract chlamydial burden compared to control antigen, and in the absence of CD4+ T cells. This suggests that pIgR and secretory IgA (SIgA) were playing a protective role (21 % pIgR-mediated) in unison with another antigen-specific immune mechanism (36 %). Interestingly, IgA generated during a primary respiratory C. muridarum infection did not provide a significant amount of protection to secondary urogenital C. muridarum challenge. Together, these data suggest that IgA specific for an extracellular antigen (MOMP) can play a strong protective role in chlamydial infections, and that IgA targeting intracellular antigens is also effective but dependent on pIgR expression in tissues. However, whilst not investigated here, IgA targeting and blocking other intracellular chlamydial antigens, that are more essential for replication or type III secretion, may be more efficacious in subunit vaccines. Recently, studies have demonstrated that IgG can neutralize influenza virus by trafficking IgG-bound virus to lysosomes [4]. We sought to determine if this process could also traffic chlamydial antigens for degradation by lysosomes, despite Chlamydia spp. actively inhibiting fusion with the host endocytic pathway. As observed in pIgR-mediated delivery of anti-IncA IgA, FcRn similarly transported IgG specific for IncA which bound the inclusion membrane. Interestingly, FcRn-mediated delivery of anti-IncA IgG significantly decreased inclusion formation by 36 % (p < 0.01), and induced aberrant inclusion morphology. This suggests that unlike IgA, IgG can facilitate additional host cellular responses which affect the intracellular niche of chlamydial growth. Fluorescence microscopy revealed that IgG also bound the inclusion, but unlike influenza studies, did not induce the recruitment of lysosomes. Notably, anti-IncA IgG recruited sequestosomes to the inclusion membrane, markers of the ubiquitin/proteasome pathway and major histocompatibility complex (MHC) class I loading. To determine if the protection against C. muridarum infection afforded by IncA IgG in vitro translated in vivo, wild type mice and mice deficient in functional FcRn and MHC-I, were immunized, depleted of CD4+, and urogenitally infected with C. muridarum. Unlike in pIgR-deficient mice, the protection afforded from IncA immunization was completely abrogated in mice lacking functional FcRn and MHC-I/CD8+. Thus, both anti-IncA IgA and IgG can bind the inclusion in a pIgR and FcRn-mediated manner, respectively. However, only IgG mediates a higher reduction in chlamydial infection in vitro and in vivo suggesting more than steric blocking of IncA had occurred. Unlike anti-MOMP IgA, which reduced chlamydial infection of epithelial cells and male mouse tissues, IgG was found to enhance infectivity in vitro, and in vivo. Opsonization of EBs with MOMP-IgG enhanced inclusion formation of epithelial cells in a MOMP-IgG dose-dependent and FcRn-dependent manner. When MOMP-IgG opsonized EBs were inoculated into the vagina of female mice, a small but non-significant (p > 0.05) enhancement of cervicovaginal C. muridarum shedding was observed three days post infection in mice with functional FcRn. Interestingly, infection with opsonized EBs reduced the intensity of the peak of infection (day six) but protracted the duration of infection by 60 % in wild type mice only. Infection with EBs opsonized in IgG also significantly increased (p < 0.05) hydrosalpinx formation in the oviducts and induced lymphocyte infiltration uterine horns. As MOMP is an immunodominant antigen, and is widely used in vaccines, the ability of IgG specific to extracellular chlamydial antigens to enhance infection and induce pathology needs to be considered. Together, these data suggest that immunoglobulins play a dichotomous role in chlamydial infections, and are dependent on antigen specificity, FcRn and pIgR expression. FcRn was found to be highly expressed in upper male reproductive tract, whilst pIgR was dominantly expressed in the lower reproductive tract. Conversely, female mice expressed FcRn and pIgR in both the lower and upper reproductive tracts. In response to a normal chlamydial infection, pIgR is up-regulated increasing secretory IgA release, but FcRn is down-regulated preventing IgG uptake. Similarly to other studies [5-6], we demonstrate that IgA and IgG generated during primary chlamydial infections plays a minor role in recall immunity, and that antigen-specific subunit vaccines can offer more protection. We also show that both IgA and IgG can be used to target intracellular chlamydial antigens, but that IgG is more effective. Finally, IgA against the extracellular antigen MOMP can afford protection, whist IgG plays a deleterious role by increasing infectivity and inducing damaging immunopathology. Further investigations with additional antigens or combination subunit vaccines will enhance our understanding the protection afforded by antibodies against intracellular and extracellular pathogenic antigens, and help improve the development of an efficacious chlamydial vaccine.

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This PhD project has expanded the knowledge in the area of profluorescent nitroxides with regard to the synthesis and characterisations of novel profluorescent nitroxide probes as well as physical characterisation of the probe molecules in various polymer/physical environments. The synthesis of the first example of an azaphenalene-based fused aromatic nitroxide TMAO, [1,1,3,3-tetramethyl-2,3-dihydro-2-azaphenalen-2-yloxyl, was described. This novel nitroxide possesses some of the structural rigidity of the isoindoline class of nitroxides, as well as some properties akin to TEMPO nitroxides. Additionally, the integral aromatic ring imparts fluorescence that is switched on by radical scavenging reactions of the nitroxide, which makes it a sensitive probe for polymer degradation. In addition to the parent TMAO, 5 other azaphenalene derivatives were successfully synthesised. This new class of nitroxide was expected to have interesting redox properties when the structure was investigated by high-level ab initio molecular orbitals theory. This was expected to have implications with biological relevance as the calculated redox potentials for the azaphenalene ring class would make them potent antioxidant compounds. The redox potentials of 25 cyclic nitroxides from four different structural classes (pyrroline, piperidine, isoindoline and azaphenalene) were determined by cyclic voltammetry in acetonitrile. It was shown that potentials related to the one electron processes of the nitroxide were influenced by the type of ring system, ring substituents or groups surrounding the moiety. Favourable comparisons were found between theoretical and experimental potentials for pyrroline, piperidine and isoindoline ring classes. Substitution of these ring classes, were correctly calculated to have a small yet predictable effect on the potentials. The redox potentials of the azaphenalene ring class were underestimated by the calculations in all cases by at least a factor of two. This is believed to be due to another process influencing the redox potentials of the azaphenalene ring class which is not taken into account by the theoretical model. It was also possible to demonstrate the use of both azaphenalene and isoindoline nitroxides as additives for monitoring radical mediated damage that occurs in polypropylene as well as in more commercially relevant polyester resins. Polymer sample doped with nitroxide were exposed to both thermo-and photo-oxidative conditions with all nitroxides showing a protective effect. It was found that isoindoline nitroxides were able to indicate radical formation in polypropylene aged at elevated temperatures via fluorescence build-up. The azaphenalene nitroxide TMAO showed no such build-up of fluorescence. This was believed to be due to the more labile bond between the nitroxide and macromolecule and the protection may occur through a classical Denisov cycle, as is expected for commercially available HAS units. Finally, A new profluorescent dinitroxide, BTMIOA (9,10-bis(1,1,3,3- tetramethylisoindolin-2-yloxyl-5-yl)anthracene), was synthesised and shown to be a powerful probe for detecting changes during the initial stages of thermo-oxidative degradation of polypropylene. This probe, which contains a 9,10-diphenylanthracene core linked to two nitroxides, possesses strongly suppressed fluorescence due to quenching by the two nitroxide groups. This molecule also showed the greatest protective effect on thermo-oxidativly aged polypropylene. Most importantly, BTMIOA was found to be a valuable tool for imaging and mapping free-radical generation in polypropylene using fluorescence microscopy.

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The redox potentials of 25 cyclic nitroxides from four different structural classes (pyrrolidine, piperidine, isoindoline, and azaphenalene) were determined experimentally by cyclic voltammetry in acetonitrile, and also via high-level ab initio molecular orbital calculations. It is shown that the potentials are influenced by the type of ring system, ring substituents and/or groups surrounding the radical moiety. For the pyrrolidine, piperidine, and isoindolines there is excellent agreement (mean absolute deviation of 0.05 V) between the calculated and experimental oxidation potentials; for the azaphenalenes, however, there is an extraordinary discrepancy (mean absolute deviation of 0.60 V), implying that their one-electron oxidation might involve additional processes not considered in the theoretical calculations. This recently developed azaphenalene class of nitroxide represents a new variant of a nitroxide ring fused to an aromatic system and details of the synthesis of five derivatives involving differing aryl substitution are also presented.

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This paper raises the question of whether comparative national models of communications research can be developed, along the lines of Hallin and Mancini’s (2004) analysis of comparative media policy, or the work of Perraton and Clift (2004) on comparative national capitalisms. Taking consideration of communications research in Australia and New Zealand as its starting point, the paper will consider what are relevant variables in shaping an “intellectual milieu” for communications research in these countries, as compared to those of Europe, North America and Asia. Some possibly relevant variables include: • Type of media system (e.g. how significant is public service media?); • Political culture (e.g. are there significant left-of-centre political parties?); • Dominant intellectual traditions; • Level and types of research funding; • Overall structure of higher education system, and where communications sits within it. In considering whether such an exercise can or should be undertaken, we can also evaluate, as Hallin and Mancini do, the significance of potentially homogenizing forces. These would include globalization, new media technologies, and the rise of a global “audit culture”. The paper will raise these issues as questions that emerge as we consider, as Curran and Park (2000) and Thussu (2009) have proposed, what a “de-Westernized” media and communications research paradigm may look like.

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In this paper, the performance of voltage-source converter-based shunt and series compensators used for load voltage control in electrical power distribution systems has been analyzed and compared, when a nonlinear load is connected across the load bus. The comparison has been made based on the closed-loop frequency resopnse characteristics of the compensated distribution system. A distribution static compensator (DSTATCOM) as a shunt device and a dynamic voltage restorer (DVR) as a series device are considered in the voltage-control mode for the comparison. The power-quality problems which these compensator address include voltage sags/swells, load voltage harmonic distortions, and unbalancing. The effect of various system parameters on the control performance of the compensator can be studied using the proposed analysis. In particular, the performance of the two compensators are compared with the strong ac supply (stiff source) and weak ac-supply (non-still source) distribution system. The experimental verification of the analytical results derived has been obtained using a laboratory model of the single-phase DSTATCOM and DVR. A generalized converter topology using a cascaded multilevel inverter has been proposed for the medium-voltage distribution system. Simulation studies have been performed in the PSCAD/EMTDC software to verify the results in the three-phase system.

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With the emergence of multi-core processors into the mainstream, parallel programming is no longer the specialized domain it once was. There is a growing need for systems to allow programmers to more easily reason about data dependencies and inherent parallelism in general purpose programs. Many of these programs are written in popular imperative programming languages like Java and C]. In this thesis I present a system for reasoning about side-effects of evaluation in an abstract and composable manner that is suitable for use by both programmers and automated tools such as compilers. The goal of developing such a system is to both facilitate the automatic exploitation of the inherent parallelism present in imperative programs and to allow programmers to reason about dependencies which may be limiting the parallelism available for exploitation in their applications. Previous work on languages and type systems for parallel computing has tended to focus on providing the programmer with tools to facilitate the manual parallelization of programs; programmers must decide when and where it is safe to employ parallelism without the assistance of the compiler or other automated tools. None of the existing systems combine abstraction and composition with parallelization and correctness checking to produce a framework which helps both programmers and automated tools to reason about inherent parallelism. In this work I present a system for abstractly reasoning about side-effects and data dependencies in modern, imperative, object-oriented languages using a type and effect system based on ideas from Ownership Types. I have developed sufficient conditions for the safe, automated detection and exploitation of a number task, data and loop parallelism patterns in terms of ownership relationships. To validate my work, I have applied my ideas to the C] version 3.0 language to produce a language extension called Zal. I have implemented a compiler for the Zal language as an extension of the GPC] research compiler as a proof of concept of my system. I have used it to parallelize a number of real-world applications to demonstrate the feasibility of my proposed approach. In addition to this empirical validation, I present an argument for the correctness of the type system and language semantics I have proposed as well as sketches of proofs for the correctness of the sufficient conditions for parallelization proposed.

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This research is one of several ongoing studies conducted within the IT Professional Services (ITPS) research programme at Queensland University of Technology (QUT). In 2003, ITPS introduced the IS-Impact model, a measurement model for measuring information systems success from the viewpoint of multiple stakeholders. The model, along with its instrument, is robust, simple, yet generalisable, and yields results that are comparable across time, stakeholders, different systems and system contexts. The IS-Impact model is defined as “a measure at a point in time, of the stream of net benefits from the Information System (IS), to date and anticipated, as perceived by all key-user-groups”. The model represents four dimensions, which are ‘Individual Impact’, ‘Organizational Impact’, ‘Information Quality’ and ‘System Quality’. The two Impact dimensions measure the up-to-date impact of the evaluated system, while the remaining two Quality dimensions act as proxies for probable future impacts (Gable, Sedera & Chan, 2008). To fulfil the goal of ITPS, “to develop the most widely employed model” this research re-validates and extends the IS-Impact model in a new context. This method/context-extension research aims to test the generalisability of the model by addressing known limitations of the model. One of the limitations of the model relates to the extent of external validity of the model. In order to gain wide acceptance, a model should be consistent and work well in different contexts. The IS-Impact model, however, was only validated in the Australian context, and packaged software was chosen as the IS understudy. Thus, this study is concerned with whether the model can be applied in another different context. Aiming for a robust and standardised measurement model that can be used across different contexts, this research re-validates and extends the IS-Impact model and its instrument to public sector organisations in Malaysia. The overarching research question (managerial question) of this research is “How can public sector organisations in Malaysia measure the impact of information systems systematically and effectively?” With two main objectives, the managerial question is broken down into two specific research questions. The first research question addresses the applicability (relevance) of the dimensions and measures of the IS-Impact model in the Malaysian context. Moreover, this research question addresses the completeness of the model in the new context. Initially, this research assumes that the dimensions and measures of the IS-Impact model are sufficient for the new context. However, some IS researchers suggest that the selection of measures needs to be done purposely for different contextual settings (DeLone & McLean, 1992, Rai, Lang & Welker, 2002). Thus, the first research question is as follows, “Is the IS-Impact model complete for measuring the impact of IS in Malaysian public sector organisations?” [RQ1]. The IS-Impact model is a multidimensional model that consists of four dimensions or constructs. Each dimension is represented by formative measures or indicators. Formative measures are known as composite variables because these measures make up or form the construct, or, in this case, the dimension in the IS-Impact model. These formative measures define different aspects of the dimension, thus, a measurement model of this kind needs to be tested not just on the structural relationship between the constructs but also the validity of each measure. In a previous study, the IS-Impact model was validated using formative validation techniques, as proposed in the literature (i.e., Diamantopoulos and Winklhofer, 2001, Diamantopoulos and Siguaw, 2006, Petter, Straub and Rai, 2007). However, there is potential for improving the validation testing of the model by adding more criterion or dependent variables. This includes identifying a consequence of the IS-Impact construct for the purpose of validation. Moreover, a different approach is employed in this research, whereby the validity of the model is tested using the Partial Least Squares (PLS) method, a component-based structural equation modelling (SEM) technique. Thus, the second research question addresses the construct validation of the IS-Impact model; “Is the IS-Impact model valid as a multidimensional formative construct?” [RQ2]. This study employs two rounds of surveys, each having a different and specific aim. The first is qualitative and exploratory, aiming to investigate the applicability and sufficiency of the IS-Impact dimensions and measures in the new context. This survey was conducted in a state government in Malaysia. A total of 77 valid responses were received, yielding 278 impact statements. The results from the qualitative analysis demonstrate the applicability of most of the IS-Impact measures. The analysis also shows a significant new measure having emerged from the context. This new measure was added as one of the System Quality measures. The second survey is a quantitative survey that aims to operationalise the measures identified from the qualitative analysis and rigorously validate the model. This survey was conducted in four state governments (including the state government that was involved in the first survey). A total of 254 valid responses were used in the data analysis. Data was analysed using structural equation modelling techniques, following the guidelines for formative construct validation, to test the validity and reliability of the constructs in the model. This study is the first research that extends the complete IS-Impact model in a new context that is different in terms of nationality, language and the type of information system (IS). The main contribution of this research is to present a comprehensive, up-to-date IS-Impact model, which has been validated in the new context. The study has accomplished its purpose of testing the generalisability of the IS-Impact model and continuing the IS evaluation research by extending it in the Malaysian context. A further contribution is a validated Malaysian language IS-Impact measurement instrument. It is hoped that the validated Malaysian IS-Impact instrument will encourage related IS research in Malaysia, and that the demonstrated model validity and generalisability will encourage a cumulative tradition of research previously not possible. The study entailed several methodological improvements on prior work, including: (1) new criterion measures for the overall IS-Impact construct employed in ‘identification through measurement relations’; (2) a stronger, multi-item ‘Satisfaction’ construct, employed in ‘identification through structural relations’; (3) an alternative version of the main survey instrument in which items are randomized (rather than blocked) for comparison with the main survey data, in attention to possible common method variance (no significant differences between these two survey instruments were observed); (4) demonstrates a validation process of formative indexes of a multidimensional, second-order construct (existing examples mostly involved unidimensional constructs); (5) testing the presence of suppressor effects that influence the significance of some measures and dimensions in the model; and (6) demonstrates the effect of an imbalanced number of measures within a construct to the contribution power of each dimension in a multidimensional model.

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This paper presents an organisational learning system implemented across a three year period within a multi campus tertiary library. It proposes a three stage system, framed within a reflective evidence based practice process to foster professional engagement and lifelong learning of staff.