202 resultados para COMPLEX SUBUNIT-1


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Traditionally, the aquisition of skills and sport movement has been characterised by numerous repetitions of presumed model movement pattern to be acquired by learners. This approach has been questioned by research identifying the presence of individualised movement patterns and the low probability of occurrence of two identical movements within and between individuals. In contrast, the differential learning approach claims advantage for incurring variability in the learning process by adding stochastic perturbations during practice. These ideas are exemplified by data from a high jump experiment which compared the effectiveness of classical and a differential training approach with pre-post test design. Results showed clear advantages for the group with additional stochastic perturbation during the aquisition phase in comparison to classically trained athletes. Analogies to similar phenomenological effects in the neurobiological literature are discussed.

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Neurodegenerative disorders are heterogenous in nature and include a range of ataxias with oculomotor apraxia, which are characterised by a wide variety of neurological and ophthalmological features. This family includes recessive and dominant disorders. A subfamily of autosomal recessive cerebellar ataxias are characterised by defects in the cellular response to DNA damage. These include the well characterised disorders Ataxia-Telangiectasia (A-T) and Ataxia-Telangiectasia Like Disorder (A-TLD) as well as the recently identified diseases Spinocerebellar ataxia with axonal neuropathy Type 1 (SCAN1), Ataxia with Oculomotor Apraxia Type 2 (AOA2), as well as the subject of this thesis, Ataxia with Oculomotor Apraxia Type 1 (AOA1). AOA1 is caused by mutations in the APTX gene, which is located at chromosomal locus 9p13. This gene codes for the 342 amino acid protein Aprataxin. Mutations in APTX cause destabilization of Aprataxin, thus AOA1 is a result of Aprataxin deficiency. Aprataxin has three functional domains, an N-terminal Forkhead Associated (FHA) phosphoprotein interaction domain, a central Histidine Triad (HIT) nucleotide hydrolase domain and a C-terminal C2H2 zinc finger. Aprataxins FHA domain has homology to FHA domain of the DNA repair protein 5’ polynucleotide kinase 3’ phosphatase (PNKP). PNKP interacts with a range of DNA repair proteins via its FHA domain and plays a critical role in processing damaged DNA termini. The presence of this domain with a nucleotide hydrolase domain and a DNA binding motif implicated that Aprataxin may be involved in DNA repair and that AOA1 may be caused by a DNA repair deficit. This was substantiated by the interaction of Aprataxin with proteins involved in the repair of both single and double strand DNA breaks (XRay Cross-Complementing 1, XRCC4 and Poly-ADP Ribose Polymerase-1) and the hypersensitivity of AOA1 patient cell lines to single and double strand break inducing agents. At the commencement of this study little was known about the in vitro and in vivo properties of Aprataxin. Initially this study focused on generation of recombinant Aprataxin proteins to facilitate examination of the in vitro properties of Aprataxin. Using recombinant Aprataxin proteins I found that Aprataxin binds to double stranded DNA. Consistent with a role for Aprataxin as a DNA repair enzyme, this binding is not sequence specific. I also report that the HIT domain of Aprataxin hydrolyses adenosine derivatives and interestingly found that this activity is competitively inhibited by DNA. This provided initial evidence that DNA binds to the HIT domain of Aprataxin. The interaction of DNA with the nucleotide hydrolase domain of Aprataxin provided initial evidence that Aprataxin may be a DNA-processing factor. Following these studies, Aprataxin was found to hydrolyse 5’adenylated DNA, which can be generated by unscheduled ligation at DNA breaks with non-standard termini. I found that cell extracts from AOA1 patients do not have DNA-adenylate hydrolase activity indicating that Aprataxin is the only DNA-adenylate hydrolase in mammalian cells. I further characterised this activity by examining the contribution of the zinc finger and FHA domains to DNA-adenylate hydrolysis by the HIT domain. I found that deletion of the zinc finger ablated the activity of the HIT domain against adenylated DNA, indicating that the zinc finger may be required for the formation of a stable enzyme-substrate complex. Deletion of the FHA domain stimulated DNA-adenylate hydrolysis, which indicated that the activity of the HIT domain may be regulated by the FHA domain. Given that the FHA domain is involved in protein-protein interactions I propose that the activity of Aprataxins HIT domain may be regulated by proteins which interact with its FHA domain. We examined this possibility by measuring the DNA-adenylate hydrolase activity of extracts from cells deficient for the Aprataxin-interacting DNA repair proteins XRCC1 and PARP-1. XRCC1 deficiency did not affect Aprataxin activity but I found that Aprataxin is destabilized in the absence of PARP-1, resulting in a deficiency of DNA-adenylate hydrolase activity in PARP-1 knockout cells. This implies a critical role for PARP-1 in the stabilization of Aprataxin. Conversely I found that PARP-1 is destabilized in the absence of Aprataxin. PARP-1 is a central player in a number of DNA repair mechanisms and this implies that not only do AOA1 cells lack Aprataxin, they may also have defects in PARP-1 dependant cellular functions. Based on this I identified a defect in a PARP-1 dependant DNA repair mechanism in AOA1 cells. Additionally, I identified elevated levels of oxidized DNA in AOA1 cells, which is indicative of a defect in Base Excision Repair (BER). I attribute this to the reduced level of the BER protein Apurinic Endonuclease 1 (APE1) I identified in Aprataxin deficient cells. This study has identified and characterised multiple DNA repair defects in AOA1 cells, indicating that Aprataxin deficiency has far-reaching cellular consequences. Consistent with the literature, I show that Aprataxin is a nuclear protein with nucleoplasmic and nucleolar distribution. Previous studies have shown that Aprataxin interacts with the nucleolar rRNA processing factor nucleolin and that AOA1 cells appear to have a mild defect in rRNA synthesis. Given the nucleolar localization of Aprataxin I examined the protein-protein interactions of Aprataxin and found that Aprataxin interacts with a number of rRNA transcription and processing factors. Based on this and the nucleolar localization of Aprataxin I proposed that Aprataxin may have an alternative role in the nucleolus. I therefore examined the transcriptional activity of Aprataxin deficient cells using nucleotide analogue incorporation. I found that AOA1 cells do not display a defect in basal levels of RNA synthesis, however they display defective transcriptional responses to DNA damage. In summary, this thesis demonstrates that Aprataxin is a DNA repair enzyme responsible for the repair of adenylated DNA termini and that it is required for stabilization of at least two other DNA repair proteins. Thus not only do AOA1 cells have no Aprataxin protein or activity, they have additional deficiencies in PolyADP Ribose Polymerase-1 and Apurinic Endonuclease 1 dependant DNA repair mechanisms. I additionally demonstrate DNA-damage inducible transcriptional defects in AOA1 cells, indicating that Aprataxin deficiency confers a broad range of cellular defects and highlighting the complexity of the cellular response to DNA damage and the multiple defects which result from Aprataxin deficiency. My detailed characterization of the cellular consequences of Aprataxin deficiency provides an important contribution to our understanding of interlinking DNA repair processes.

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In the study of complex neurobiological movement systems, measurement indeterminacy has typically been overcome by imposing artificial modelling constraints to reduce the number of unknowns (e.g., reducing all muscle, bone and ligament forces crossing a joint to a single vector). However, this approach prevents human movement scientists from investigating more fully the role, functionality and ubiquity of coordinative structures or functional motor synergies. Advancements in measurement methods and analysis techniques are required if the contribution of individual component parts or degrees of freedom of these task-specific structural units is to be established, thereby effectively solving the indeterminacy problem by reducing the number of unknowns. A further benefit of establishing more of the unknowns is that human movement scientists will be able to gain greater insight into ubiquitous processes of physical self-organising that underpin the formation of coordinative structures and the confluence of organismic, environmental and task constraints that determine the exact morphology of these special-purpose devices.

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When complex projects go wrong they can go horribly wrong with severe financial consequences. We are undertaking research to develop leading performance indicators for complex projects, metrics to provide early warning of potential difficulties. The assessment of success of complex projects can be made by a range of stakeholders over different time scales, against different levels of project results: the project’s outputs at the end of the project; the project’s outcomes in the months following project completion; and the project’s impact in the years following completion. We aim to identify leading performance indicators, which may include both success criteria and success factors, and which can be measured by the project team during project delivery to forecast success as assessed by key stakeholders in the days, months and years following the project. The hope is the leading performance indicators will act as alarm bells to show if a project is diverting from plan so early corrective action can be taken. It may be that different combinations of the leading performance indicators will be appropriate depending on the nature of project complexity. In this paper we develop a new model of project success, whereby success is assessed by different stakeholders over different time frames against different levels of project results. We then relate this to measurements that can be taken during project delivery. A methodology is described to evaluate the early parts of this model. Its implications and limitations are described. This paper describes work in progress.

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The molecular and metal profile fingerprints were obtained from a complex substance, Atractylis chinensis DC—a traditional Chinese medicine (TCM), with the use of the high performance liquid chromatography (HPLC) and inductively coupled plasma atomic emission spectroscopy (ICP-AES) techniques. This substance was used in this work as an example of a complex biological material, which has found application as a TCM. Such TCM samples are traditionally processed by the Bran, Cut, Fried and Swill methods, and were collected from five provinces in China. The data matrices obtained from the two types of analysis produced two principal component biplots, which showed that the HPLC fingerprint data were discriminated on the basis of the methods for processing the raw TCM, while the metal analysis grouped according to the geographical origin. When the two data matrices were combined into a one two-way matrix, the resulting biplot showed a clear separation on the basis of the HPLC fingerprints. Importantly, within each different grouping the objects separated according to their geographical origin, and they ranked approximately in the same order in each group. This result suggested that by using such an approach, it is possible to derive improved characterisation of the complex TCM materials on the basis of the two kinds of analytical data. In addition, two supervised pattern recognition methods, K-nearest neighbors (KNNs) method, and linear discriminant analysis (LDA), were successfully applied to the individual data matrices—thus, supporting the PCA approach.

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In this study, biometric and structural engineering tool have been used to examine a possible relationship within Chuaria–Tawuia complex and micro-FTIR (Fourier Transform Infrared Spectroscopy) analyses to understand the biological affinity of Chuaria circularis Walcott, collected from the Mesoproterozoic Suket Shales of the Vindhyan Supergroup and the Neoproterozoic Halkal Shales of the Bhima Group of peninsular India. Biometric analyses of well preserved carbonized specimens show wide variation in morphology and uni-modal distribution. We believe and demonstrate to a reasonable extent that C. circularis most likely was a part of Tawuia-like cylindrical body of algal origin. Specimens with notch/cleft and overlapping preservation, mostly recorded in the size range of 3–5 mm, are of special interest. Five different models proposed earlier on the life cycle of C. circularis are discussed. A new model, termed as ‘Hybrid model’ based on present multidisciplinary study assessing cylindrical and spherical shapes suggesting variable cell wall strength and algal affinity is proposed. This model discusses and demonstrates varied geometrical morphologies assumed by Chuaria and Tawuia, and also shows the inter-relationship of Chuaria–Tawuia complex. Structural engineering tool (thin walled pressure vessel theory) was applied to investigate the implications of possible geometrical shapes (sphere and cylinder), membrane (cell wall) stresses and ambient pressure environment on morphologically similar C. circularis and Tawuia. The results suggest that membrane stresses developed on the structures similar to Chuaria–Tawuia complex were directly proportional to radius and inversely proportional to the thickness in both cases. In case of hollow cylindrical structure, the membrane stresses in circumferential direction (hoop stress) are twice of the longitudinal direction indicating that rupture or fragmentation in the body of Tawuia would have occurred due to hoop stress. It appears that notches and discontinuities seen in some of the specimens of Chuaria may be related to rupture suggesting their possible location in 3D Chuaria. The micro-FTIR spectra of C. circularis are characterized by both aliphatic and aromatic absorption bands. The aliphaticity is indicated by prominent alkyl group bands between 2800–3000 and 1300–1500 cm−1. The prominent absorption signals at 700–900 cm−1 (peaking at 875 and 860 cm−1) are due to aromatic CH out of plane deformation. A narrow, strong band is centred at 1540 cm−1 which could be COOH band. The presence of strong aliphatic bands in FTIR spectra suggests that the biogeopolymer of C. circularis is of aliphatic nature. The wall chemistry indicates the presence of ‘algaenan’—a biopolymer of algae.

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Purpose: The component modules in the standard BEAMnrc distribution may appear to be insufficient to model micro-multileaf collimators that have tri-faceted leaf ends and complex leaf profiles. This note indicates, however, that accurate Monte Carlo simulations of radiotherapy beams defined by a complex collimation device can be completed using BEAMnrc's standard VARMLC component module.---------- Methods: That this simple collimator model can produce spatially and dosimetrically accurate micro-collimated fields is illustrated using comparisons with ion chamber and film measurements of the dose deposited by square and irregular fields incident on planar, homogeneous water phantoms.---------- Results: Monte Carlo dose calculations for on- and off-axis fields are shown to produce good agreement with experimental values, even upon close examination of the penumbrae.--------- Conclusions: The use of a VARMLC model of the micro-multileaf collimator, along with a commissioned model of the associated linear accelerator, is therefore recommended as an alternative to the development or use of in-house or third-party component modules for simulating stereotactic radiotherapy and radiosurgery treatments. Simulation parameters for the VARMLC model are provided which should allow other researchers to adapt and use this model to study clinical stereotactic radiotherapy treatments.

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Ecological problems are typically multi faceted and need to be addressed from a scientific and a management perspective. There is a wealth of modelling and simulation software available, each designed to address a particular aspect of the issue of concern. Choosing the appropriate tool, making sense of the disparate outputs, and taking decisions when little or no empirical data is available, are everyday challenges facing the ecologist and environmental manager. Bayesian Networks provide a statistical modelling framework that enables analysis and integration of information in its own right as well as integration of a variety of models addressing different aspects of a common overall problem. There has been increased interest in the use of BNs to model environmental systems and issues of concern. However, the development of more sophisticated BNs, utilising dynamic and object oriented (OO) features, is still at the frontier of ecological research. Such features are particularly appealing in an ecological context, since the underlying facts are often spatial and temporal in nature. This thesis focuses on an integrated BN approach which facilitates OO modelling. Our research devises a new heuristic method, the Iterative Bayesian Network Development Cycle (IBNDC), for the development of BN models within a multi-field and multi-expert context. Expert elicitation is a popular method used to quantify BNs when data is sparse, but expert knowledge is abundant. The resulting BNs need to be substantiated and validated taking this uncertainty into account. Our research demonstrates the application of the IBNDC approach to support these aspects of BN modelling. The complex nature of environmental issues makes them ideal case studies for the proposed integrated approach to modelling. Moreover, they lend themselves to a series of integrated sub-networks describing different scientific components, combining scientific and management perspectives, or pooling similar contributions developed in different locations by different research groups. In southern Africa the two largest free-ranging cheetah (Acinonyx jubatus) populations are in Namibia and Botswana, where the majority of cheetahs are located outside protected areas. Consequently, cheetah conservation in these two countries is focussed primarily on the free-ranging populations as well as the mitigation of conflict between humans and cheetahs. In contrast, in neighbouring South Africa, the majority of cheetahs are found in fenced reserves. Nonetheless, conflict between humans and cheetahs remains an issue here. Conservation effort in South Africa is also focussed on managing the geographically isolated cheetah populations as one large meta-population. Relocation is one option among a suite of tools used to resolve human-cheetah conflict in southern Africa. Successfully relocating captured problem cheetahs, and maintaining a viable free-ranging cheetah population, are two environmental issues in cheetah conservation forming the first case study in this thesis. The second case study involves the initiation of blooms of Lyngbya majuscula, a blue-green algae, in Deception Bay, Australia. L. majuscula is a toxic algal bloom which has severe health, ecological and economic impacts on the community located in the vicinity of this algal bloom. Deception Bay is an important tourist destination with its proximity to Brisbane, Australia’s third largest city. Lyngbya is one of several algae considered to be a Harmful Algal Bloom (HAB). This group of algae includes other widespread blooms such as red tides. The occurrence of Lyngbya blooms is not a local phenomenon, but blooms of this toxic weed occur in coastal waters worldwide. With the increase in frequency and extent of these HAB blooms, it is important to gain a better understanding of the underlying factors contributing to the initiation and sustenance of these blooms. This knowledge will contribute to better management practices and the identification of those management actions which could prevent or diminish the severity of these blooms.

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This paper argues a model of complex system design for sustainable architecture within a framework of entropy evolution. The spectrum of sustainable architecture consists of the efficient use of energy and material resource in life-cycle of buildings, the active involvement of the occupants in micro-climate control within buildings, and the natural environmental context. The interactions of the parameters compose a complex system of sustainable architectural design, of which the conventional linear and fragmented design technologies are insufficient to indicate holistic and ongoing environmental performance. The complexity theory of dissipative structure states a microscopic formulation of open system evolution, which provides a system design framework for the evolution of building environmental performance towards an optimization of sustainability in architecture.

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This paper examines the role of intuition in the way that people operate unfamiliar devices. Intuition is a type of cognitive processing that is often non-conscious and utilises stored experiential knowledge. Intuitive interaction involves the use of knowledge gained from other products and/or experiences. Two initial experimental studies revealed that prior exposure to products employing similar features helped participants to complete set tasks more quickly and intuitively, and that familiar features were intuitively used more often than unfamiliar ones. A third experiment confirmed that performance is affected by a person's level of familiarity with similar technologies, and also revealed that appearance (shape, size and labelling of features) seems to be the variable that most affects time spent on a task and intuitive uses during that time. Age also seems to have an effect. These results and their implications are discussed.

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Background: The quality of stormwater runoff from ports is significant as it can be an important source of pollution to the marine environment. This is also a significant issue for the Port of Brisbane as it is located in an area of high environmental values. Therefore, it is imperative to develop an in-depth understanding of stormwater runoff quality to ensure that appropriate strategies are in place for quality improvement. ---------------- The Port currently has a network of stormwater sample collection points where event based samples together with grab samples are tested for a range of water quality parameters. Whilst this information provides a ‘snapshot’ of the pollutants being washed from the catchment/s, it does not allow for a quantifiable assessment of total contaminant loads being discharged to the waters of Moreton Bay. It also does not represent pollutant build-up and wash-off from the different land uses across a broader range of rainfall events which might be expected. As such, it is difficult to relate stormwater quality to different pollutant sources within the Port environment. ----------------- Consequently, this would make the source tracking of pollutants to receiving waters extremely difficult and in turn the ability to implement appropriate mitigation measures. Also, without this detailed understanding, the efficacy of the various stormwater quality mitigation measures implemented cannot be determined with certainty. --------------- Current knowledge on port stormwater runoff quality Currently, little knowledge exists with regards to the pollutant generation capacity specific to port land uses as these do not necessarily compare well with conventional urban industrial or commercial land use due to the specific nature of port activities such as inter-modal operations and cargo management. Furthermore, traffic characteristics in a port area are different to a conventional urban area. Consequently, as data inputs based on an industrial and commercial land uses for modelling purposes is questionable. ------------------ A comprehensive review of published research failed to locate any investigations undertaken with regards to pollutant build-up and wash-off for port specific land uses. Furthermore, there is very limited information made available by various ports worldwide about the pollution generation potential of their facilities. Published work in this area has essentially focussed on the water quality or environmental values in the receiving waters such as the downstream bay or estuary. ----------------- The Project: The research project is an outcome of the collaborative Partnership between the Port of Brisbane Corporation (POBC) and Queensland University of Technology (QUT). A key feature of this Partnership is the undertaking of ‘cutting edge’ research to strengthen the environmental custodianship of the Port area. This project aims to develop a port specific stormwater quality model to allow informed decision making in relation to stormwater quality improvement in the context of the increased growth of the Port. --------------- Stage 1 of the research project focussed on the assessment of pollutant build-up and wash-off using rainfall simulation from the current Port of Brisbane facilities with the longer-term objective of contributing to the development of ecological risk mitigation strategies for future expansion scenarios. Investigation of complex processes such as pollutant wash-off using naturally occurring rainfall events has inherent difficulties. These can be overcome using simulated rainfall for the investigations. ----------------- The deliverables for Stage 1 included the following: * Pollutant build-up and wash-off profiles for six primary land uses within the Port of Brisbane to be used for water quality model development. * Recommendations with regards to future stormwater quality monitoring and pollution mitigation measures. The outcomes are expected to deliver the following benefits to the Port of Brisbane: * The availability of Port specific pollutant build-up and wash-off data will enable the implementation of customised stormwater pollution mitigation strategies. * The water quality data collected would form the baseline data for a Port specific water quality model for mitigation and predictive purposes. * To be at the cutting-edge in terms of water quality management and environmental best practice in the context of port infrastructure. ---------------- Conclusions: The important conclusions from the study are: * It confirmed that the Port environment is unique in terms of pollutant characteristics and is not comparable to typical urban land uses. * For most pollutant types, the Port land uses exhibited lower pollutant concentrations when compared to typical urban land uses. * The pollutant characteristics varied across the different land uses and were not consistent in terms of the land use. Hence, the implementation of stereotypical structural water quality improvement devices could be of limited value. * The <150m particle size range was predominant in suspended solids for pollutant build-up as well as wash-off. Therefore, if suspended solids are targeted as the surrogate parameter for water quality improvement, this specific particle size range needs to be removed. ------------------- Recommendations: Based on the study results the following preliminary recommendations are made: * Due to the appreciable variation in pollutant characteristics for different port land uses, any water quality monitoring stations should preferably be located such that source areas can be easily identified. * The study results having identified significant pollutants for the different land uses should enable the development of a more customised water quality monitoring and testing regime targeting the critical pollutants. * A ‘one size fits all’ approach may not be appropriate for the different port land uses due to the varying pollutant characteristics. As such, pollution mitigation will need to be specifically tailored to suit the specific land use. * Any structural measures implemented for pollution mitigation to be effective should have the capability to remove suspended solids of size <150m. * Based on the results presented and the particularly the fact that the Port land uses cannot be compared to conventional urban land uses in relation to pollutant generation, consideration should be given to the development of a port specific water quality model.

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Presentation about research projects that build understanding of urban design and interactions and plan for future opportunities. What do we need to model?

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With the increasing complexity of modern day threats and the growing sophistication of interlinked and interdependent operating environments, Business Continuity Management (BCM) has emerged as a new discipline, offering a strategic approach to safeguarding organisational functions. Of significant interest is the application of BCM frameworks and strategies within critical infrastructure, and in particular the aviation industry. Given the increased focus on security and safety for critical infrastructures, research into the adoption of BCM principles within an airport environment provides valuable management outcomes and research into a previously neglected area of inquisition. This research has used a single case study methodology to identify possible impediments to BCM adoption and implementation by the Brisbane Airport Corporation (BAC). It has identified a number of misalignments between the required breadth of focus for a BCM program, identified differing views on specific roles and responsibilities required during a major disruptive event and illustrated the complexities of the Brisbane Airport which impede the understanding and implementation of effective Business Continuity Management Strategies.