990 resultados para Pleckstrin Homology Domain
Resumo:
In this age of ever-increasing information technology (IT) driven environments, governments/or public sector organisations (PSOs) are expected to demonstrate the business value of the investment in IT and take advantage of the opportunities offered by technological advancements. Strategic alignment (SA) emerged as a mechanism to bridge the gap between business and IT missions, objectives, and plans in order to ensure value optimisation from investment in IT and enhance organisational performance. However, achieving and sustaining SA remains a challenge requiring even more agility nowadays to keep up with turbulent organisational environments. The shared domain knowledge (SDK) between the IT department and other diverse organisational groups is considered as one of the factors influencing the successful implementation of SA. However, SDK in PSOs has received relatively little empirical attention. This paper presents findings from a study which investigated the influence of SDK on SA within organisations in the Australian public sector. The developed research model examined the relationship of SDK between business and IT domains with SA using a survey of 56 public sector professionals and executives. A key research contribution is the empirical demonstration that increasing levels of SDK between IT and business groups leads to increased SA.
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A home embodies a sensorial space that is layered with personal memories and traces of history. The success of a home in providing a strong sense of place depends on various factors such as geographical location, climatic conditions, and occupants’ world-views and perceptions. This paper explores Muslims’ perceptions of privacy, modesty and hospitality within their homes through their lived experiences. This case study focuses on three Muslim families living in Australian designed homes within the same suburb of Brisbane, Australia. The study provides prefatory insight into the ways in which these families perform their daily activities and entertain their guests without jeopardizing their privacy needs. The study examines the significance of modesty in the design of Muslim homes as a means by which family members are able to achieve optimum privacy while simultaneously extending hospitality to guests inside and outside their homes. The findings of this study provide opportunities too, for expanding research into culturally adaptable housing systems to help meet the changing needs of Australian multicultural society.
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Iterative computational models have been used to investigate the regulation of bone fracture healing by local mechanical conditions. Although their predictions replicate some mechanical responses and histological features, they do not typically reproduce the predominantly radial hard callus growth pattern observed in larger mammals. We hypothesised that this discrepancy results from an artefact of the models’ initial geometry. Using axisymmetric finite element models, we demonstrated that pre-defining a field of soft tissue in which callus may develop introduces high deviatoric strains in the periosteal region adjacent to the fracture. These bone-inhibiting strains are not present when the initial soft tissue is confined to a thin periosteal layer. As observed in previous healing models, tissue differentiation algorithms regulated by deviatoric strain predicted hard callus forming remotely and growing towards the fracture. While dilatational strain regulation allowed early bone formation closer to the fracture, hard callus still formed initially over a broad area, rather than expanding over time. Modelling callus growth from a thin periosteal layer successfully predicted the initiation of hard callus growth close to the fracture site. However, these models were still susceptible to elevated deviatoric strains in the soft tissues at the edge of the hard callus. Our study highlights the importance of the initial soft tissue geometry used for finite element models of fracture healing. If this cannot be defined accurately, alternative mechanisms for the prediction of early callus development should be investigated.
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The ultimate goal of profiling is to identify the major behavioral and personality characteristics to narrow the suspect pool. Inferences about offender characteristics can be accomplished deductively, based on the analysis of discrete offender behaviors established within a particular case. They can also be accomplished inductively, involving prediction based on abstract offender averages from group data (these methods and the logic on which they are based is detailed extensively in Chapters 2 and 4). As discussed, these two approaches are by no means equal.
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Criminal profiling is an investigative tool used around the world to infer the personality and behavioural characteristics of an offender based on their crime. Case linkage, the process of determining discreet connections between crimes of the same offender, is a practice that falls under the general banner of criminal profiling and has been widely criticized. Two theories, behavioural consistency and the homology assumption, are examined and their impact on profiling in general and case linkage specifically is discussed...
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A FitzHugh-Nagumo monodomain model has been used to describe the propagation of the electrical potential in heterogeneous cardiac tissue. In this paper, we consider a two-dimensional fractional FitzHugh-Nagumo monodomain model on an irregular domain. The model consists of a coupled Riesz space fractional nonlinear reaction-diffusion model and an ordinary differential equation, describing the ionic fluxes as a function of the membrane potential. Secondly, we use a decoupling technique and focus on solving the Riesz space fractional nonlinear reaction-diffusion model. A novel spatially second-order accurate semi-implicit alternating direction method (SIADM) for this model on an approximate irregular domain is proposed. Thirdly, stability and convergence of the SIADM are proved. Finally, some numerical examples are given to support our theoretical analysis and these numerical techniques are employed to simulate a two-dimensional fractional Fitzhugh-Nagumo model on both an approximate circular and an approximate irregular domain.
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Experimental studies have found that when the state-of-the-art probabilistic linear discriminant analysis (PLDA) speaker verification systems are trained using out-domain data, it significantly affects speaker verification performance due to the mismatch between development data and evaluation data. To overcome this problem we propose a novel unsupervised inter dataset variability (IDV) compensation approach to compensate the dataset mismatch. IDV-compensated PLDA system achieves over 10% relative improvement in EER values over out-domain PLDA system by effectively compensating the mismatch between in-domain and out-domain data.
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This paper analyzes the limitations upon the amount of in- domain (NIST SREs) data required for training a probabilistic linear discriminant analysis (PLDA) speaker verification system based on out-domain (Switchboard) total variability subspaces. By limiting the number of speakers, the number of sessions per speaker and the length of active speech per session available in the target domain for PLDA training, we investigated the relative effect of these three parameters on PLDA speaker verification performance in the NIST 2008 and NIST 2010 speaker recognition evaluation datasets. Experimental results indicate that while these parameters depend highly on each other, to beat out-domain PLDA training, more than 10 seconds of active speech should be available for at least 4 sessions/speaker for a minimum of 800 speakers. If further data is available, considerable improvement can be made over solely out-domain PLDA training.
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In this paper we introduce a novel domain-invariant covariance normalization (DICN) technique to relocate both in-domain and out-domain i-vectors into a third dataset-invariant space, providing an improvement for out-domain PLDA speaker verification with a very small number of unlabelled in-domain adaptation i-vectors. By capturing the dataset variance from a global mean using both development out-domain i-vectors and limited unlabelled in-domain i-vectors, we could obtain domain- invariant representations of PLDA training data. The DICN- compensated out-domain PLDA system is shown to perform as well as in-domain PLDA training with as few as 500 unlabelled in-domain i-vectors for NIST-2010 SRE and 2000 unlabelled in-domain i-vectors for NIST-2008 SRE, and considerable relative improvement over both out-domain and in-domain PLDA development if more are available.
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Background There is increasing evidence supporting the concept of cancer stem cells (CSCs), which are responsible for the initiation, growth and metastasis of tumors. CSCs are thus considered the target for future cancer therapies. To achieve this goal, identifying potential therapeutic targets for CSCs is essential. Methods We used a natural product of vitamin E, gamma tocotrienol (gamma-T3), to treat mammospheres and spheres from colon and cervical cancers. Western blotting and real-time RT-PCR were employed to identify the gene and protein targets of gamma-T3 in mammospheres. Results We found that mammosphere growth was inhibited in a dose dependent manner, with total inhibition at high doses. Gamma-T3 also inhibited sphere growth in two other human epithelial cancers, colon and cervix. Our results suggested that both Src homology 2 domain-containing phosphatase 1 (SHP1) and 2 (SHP2) were affected by gamma-T3 which was accompanied by a decrease in K- and H-Ras gene expression and phosphorylated ERK protein levels in a dose dependent way. In contrast, expression of self-renewal genes TGF-beta and LIF, as well as ESR signal pathways were not affected by the treatment. These results suggest that gamma-T3 specifically targets SHP2 and the RAS/ERK signaling pathway. Conclusions SHP1 and SHP2 are potential therapeutic targets for breast CSCs and gamma-T3 is a promising natural drug for future breast cancer therapy.
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The stoned locus in Drosophila encodes two proteins StonedA (STNA) and StonedB (STNB), both of which have been suggested to act as adaptins in mediating synaptic vesicle recycling. A combination of immunological, genetic and biochemical studies have shown an interaction of STNA and STNB with the C2B domain of Synaptotagmin-I (SYT-1), an integral synaptic vesicle protein that mediates Ca2+-dependent exocytosis, as well as endocytosis. The C2B domain of SYT-1 contains an AP-2 binding site that controls the size of recycled vesicles, and a C-terminal tryptophan-containing motif that acts as an internalization signal. Investigation of SYT-1 mutations in Drosophila has shown that altering the Ca2+ binding region of the C2B domain, results in a reduction in the rate of vesicle recycling, implicating this region in SYT-I endocytosis. In this poster, we report the molecular dissection of the interactions between the STNA and STNB proteins and the C2B domain of SYT-1. Deletion of the AP-2 binding site decreased the binding of both STNA and STNB. However, C-terminal deletions of the C2B domain significantly increased STNB binding. In contrast, the same C-terminal deletions reduced the affinity of the C2B domain for STNA. The possible interactions of both STNB and STNA with the Ca2+ binding region of SYT-1 will be also investigated.
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In a victory for corporate control of cultural heritage, the Supreme Court of the United States has rejected a constitutional challenge to the Sonny Bono Copyright Term Extension Act 1998 (U.S.) by a majority of seven to two. This paper evaluates the litigation in terms of policy debate in a number of discourses — history, intellectual property law, constitutional law and freedom of speech, cultural heritage, economics and competition policy, and international trade. It argues that the extension of the copyright term will inhibit the dissemination of cultural works through the use of new technologies — such as Eric Eldred's Eldritch Press and Project Gutenberg. It concludes that there is a need to resist the attempts of copyright owners to establish the Sonny Bono Copyright Term Extension Act 1998 (U.S.) as an international model for other jurisdictions — such as Australia.