990 resultados para Biochemical engineering


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Historically, asset management focused primarily on the reliability and maintainability of assets; organisations have since then accepted the notion that a much larger array of processes govern the life and use of an asset. With this, asset management’s new paradigm seeks a holistic, multi-disciplinary approach to the management of physical assets. A growing number of organisations now seek to develop integrated asset management frameworks and bodies of knowledge. This research seeks to complement existing outputs of the mentioned organisations through the development of an asset management ontology. Ontologies define a common vocabulary for both researchers and practitioners who need to share information in a chosen domain. A by-product of ontology development is the realisation of a process architecture, of which there is also no evidence in published literature. To develop the ontology and subsequent asset management process architecture, a standard knowledge-engineering methodology is followed. This involves text analysis, definition and classification of terms and visualisation through an appropriate tool (in this case, the Protégé application was used). The result of this research is the first attempt at developing an asset management ontology and process architecture.

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"This book investigates the origins and implications of the securitization crisis, described by the chief executive of ANZ as a "financial services bloodbath". Based on extensive interviews it offers an integrated series of case studies drawn from the United States, the United Kingdom and Australia. A central purpose is to not only chart what went wrong with the investment houses and why the regulatory systems failed, but also provide policy guidance. The book therefore combines the empirical with the normative. In so doing, it provides a route map to navigate one of the most significant financial and regulatory failures in modern times."

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In this paper we discuss our current efforts to develop and implement an exploratory, discovery mode assessment item into the total learning and assessment profile for a target group of about 100 second level engineering mathematics students. The assessment item under development is composed of 2 parts, namely, a set of "pre-lab" homework problems (which focus on relevant prior mathematical knowledge, concepts and skills), and complementary computing laboratory exercises which are undertaken within a fixed (1 hour) time frame. In particular, the computing exercises exploit the algebraic manipulation and visualisation capabilities of the symbolic algebra package MAPLE, with the aim of promoting understanding of certain mathematical concepts and skills via visual and intuitive reasoning, rather than a formal or rigorous approach. The assessment task we are developing is aimed at providing students with a significant learning experience, in addition to providing feedback on their individual knowledge and skills. To this end, a noteworthy feature of the scheme is that marks awarded for the laboratory work are primarily based on the extent to which reflective, critical thinking is demonstrated, rather than the amount of CBE-style tasks completed by the student within the allowed time. With regard to student learning outcomes, a novel and potentially critical feature of our scheme is that the assessment task is designed to be intimately linked to the overall course content, in that it aims to introduce important concepts and skills (via individual student exploration) which will be revisited somewhat later in the pedagogically more restrictive formal lecture component of the course (typically a large group plenary format). Furthermore, the time delay involved, or "incubation period", is also a deliberate design feature: it is intended to allow students the opportunity to undergo potentially important internal re-adjustments in their understanding, before being exposed to lectures on related course content which are invariably delivered in a more condensed, formal and mathematically rigorous manner. In our presentation, we will discuss in more detail our motivation and rationale for trailing such a scheme for the targeted student group. Some of the advantages and disadvantages of our approach (as we perceived them at the initial stages) will also be enumerated. In a companion paper, the theoretical framework for our approach will be more fully elaborated, and measures of student learning outcomes (as obtained from eg. student provided feedback) will be discussed.

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In this study, poly (e-caprolactone) [PCL] and its collagen composite blend (PCL=Col) were fabricated to scaffolds using electrospinning method. Incorporated collagen was present on the surface of the fibers, and it modulated the attachment and proliferation of pig bone marrow mesenchymal cells (pBMMCs). Osteogenic differentiation markers were more pronounced when these cells were cultured on PCL=Col fibrous meshes, as determined by immunohistochemistry for collagen type I, osteopontin, and osteocalcin. Matrix mineralization was observed only on osteogenically induced PCL=Col constructs. Long bone analogs were created by wrapping osteogenic cell sheets around the PCL=Col meshes to form hollow cylindrical cell-scaffold constructs. Culturing these constructs under dynamic conditions enhanced bone-like tissue formation and mechanical strength.We conclude that electrospun PCL=Col mesh is a promising material for bone engineering applications. Its combination with osteogenic cell sheets offers a novel and promising strategy for engineering of tubular bone analogs.

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Insufficient availability of osteogenic cells limits bone regeneration through cell-based therapies. This study investigated the potential of amniotic fluid–derived stem (AFS) cells to synthesize mineralized extracellular matrix within porous medical-grade poly-e-caprolactone (mPCL) scaffolds. The AFS cells were initially differentiated in two-dimensional (2D) culture to determine appropriate osteogenic culture conditions and verify physiologic mineral production by the AFS cells. The AFS cells were then cultured on 3D mPCL scaffolds (6-mm diameter9-mm height) and analyzed for their ability to differentiate to osteoblastic cells in this environment. The amount and distribution of mineralized matrix production was quantified throughout the mPCL scaffold using nondestructive micro computed tomography (microCT) analysis and confirmed through biochemical assays. Sterile microCT scanning provided longitudinal analysis of long-term cultured mPCL constructs to determine the rate and distribution of mineral matrix within the scaffolds. The AFS cells deposited mineralized matrix throughout the mPCL scaffolds and remained viable after 15 weeks of 3D culture. The effect of predifferentiation of the AFS cells on the subsequent bone formation in vivo was determined in a rat subcutaneous model. Cells that were pre-differentiated for 28 days in vitro produced seven times more mineralized matrix when implanted subcutaneously in vivo. This study demonstrated the potential of AFS cells to produce 3D mineralized bioengineered constructs in vitro and in vivo and suggests that AFS cells may be an effective cell source for functional repair of large bone defects

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Technology platforms originally developed for tissue engineering applications produce valuable models that mimic three-dimensional (3D) tissue organization and function to enhance the understanding of cell/tissue function under normal and pathological situations. These models show that when replicating physiological and pathological conditions as closely as possible investigators are allowed to probe the basic mechanisms of morphogenesis, differentiation and cancer. Significant efforts investigating angiogenetic processes and factors in tumorigenesis are currently undertaken to establish ways of targeting angiogenesis in tumours. Anti-angiogenic agents have been accepted for clinical application as attractive targeted therapeutics for the treatment of cancer. Combining the areas of tumour angiogenesis, combination therapies and drug delivery systems is therefore closely related to the understanding of the basic principles that are applied in tissue engineering models. Studies with 3D model systems have repeatedly identified complex interacting roles of matrix stiffness and composition, integrins, growth factor receptors and signalling in development and cancer. These insights suggest that plasticity, regulation and suppression of these processes can provide strategies and therapeutic targets for future cancer therapies. The historical perspective of the fields of tissue engineering and controlled release of therapeutics, including inhibitors of angiogenesis in tumours is becoming clearly evident as a major future advance in merging these fields. New delivery systems are expected to greatly enhance the ability to deliver drugs locally and in therapeutic concentrations to relevant sites in living organisms. Investigating the phenomena of angiogenesis and anti-angiogenesis in 3D in vivo models such as the Arterio-Venous (AV) loop mode in a separated and isolated chamber within a living organism adds another significant horizon to this perspective and opens new modalities for translational research in this field.

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Currently, well-established clinical therapeutic approaches for bone reconstruction are restricted to the transplantation of autografts and allografts, and the implantation of metal devices or ceramic-based implants to assist bone regeneration. Bone grafts possess osteoconductive and osteoinductive properties, however they are limited in access and availability and associated with donor site morbidity, haemorrhage, risk of infection, insufficient transplant integration, graft devitalisation, and subsequent resorption resulting in decreased mechanical stability. As a result, recent research focuses on the development of alternative therapeutic concepts. The field of tissue engineering has emerged as an important approach to bone regeneration. However, bench to bedside translations are still infrequent as the process towards approval by regulatory bodies is protracted and costly, requiring both comprehensive in vitro and in vivo studies. The subsequent gap between research and clinical translation, hence commercialization, is referred to as the ‘Valley of Death’ and describes a large number of projects and/or ventures that are ceased due to a lack of funding during the transition from product/technology development to regulatory approval and subsequently commercialization. One of the greatest difficulties in bridging the Valley of Death is to develop good manufacturing processes (GMP) and scalable designs and to apply these in pre-clinical studies. In this article, we describe part of the rationale and road map of how our multidisciplinary research team has approached the first steps to translate orthopaedic bone engineering from bench to bedside byestablishing a pre-clinical ovine critical-sized tibial segmental bone defect model and discuss our preliminary data relating to this decisive step.

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Many nations are experiencing a decline in the number of graduating engineers, an overall poor preparedness for engineering studies in tertiary institutions, and a lack of diversity in the field. Given the increasing importance of mathematics, science, engineering, and technology in our world, it is imperative that we foster an interest and drive to participate in engineering from an early age. This discuission paper argues for the intergration of engineering education within the elementary and middle school mathematics curricula. In doing so, we offer a definition of engineering education and address its core goals; consider some perceptions of engineering and engineering education held by teachers and students; and offer one approach to promoting engineering education within the elementary and middle school mathematics curriculum, namely through mathematical modeling.

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This paper argues for a future-oriented, inclusion of Engineering Model Eliciting Activities (EngMEAs) in elementary mathematics curricula. In EngMEAs students work with meaningful engineering problems that capitalise on and extend their existing mathematics and science learning, to develop, revise and document powerful models, while working in groups. The models developed by six groups of 12-year students in solving the Natural Gas activity are presented. Results showed that student models adequately solved the problem, although student models did not take into account all the data provided. Student solutions varied to the extent students employed the engineering context in their models and to their understanding of the mathematical concepts involved in the problem. Finally, recommendations for implementing EngMEAs and for further research are discussed.

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Engineering education for elementary school students is a new and increasingly important domain of research by mathematics, science, technology, and engineering educators. Recent research has raised questions about the context of engineering problems that are meaningful, engaging, and inspiring for young students. In the present study an environmental engineering activity was implemented in two classes of 11-year-old students in Cyprus. The problem required students to use the data to develop a procedure for selecting among alternative countries from which to buy water. Students created a range of models that adequately solved the problem although not all models took into account all of the data provided. The models varied in the number of problem factors taken into consideration and also in the different approaches adopted in dealing with the problem factors. At least two groups of students integrated into their models the environmental aspect of the problem (energy consumption, water pollution) and further refined their models. Results provide evidence that engineering model-eliciting activities can be successfully integrated in the elementary mathematics curriculum. These activities provide rich opportunities for students to deal with engineering contexts and to apply their learning in mathematics and science to solving real-world engineering problems.

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This paper first describes a new three-year, longitudinal project that is implementing engineering education in three middle schools in Australia (grade levels 7-9). This important domain is untapped in Australia. Hence, as a starting point, we conducted a context analysis to help situate engineering education in a school system. We report on this analysis with respect to findings from one of two literature-based surveys that gathered middle-school student responses in mathematics (n=172) and science (n=166) towards understanding their dispositions for engineering education. ANOVA indicated gender differences for 3 out of 23 items in both mathematics and science. In addition, the majority of students agreed or strongly agreed with 17 of the 23 survey items, however, there were some differences between mathematics and science. We conclude the paper with some recommendations for establishing engineering education in schools, including the development of partnerships among engineering and education faculties, school systems, and industry to develop contemporary engineering resources to support school-level mathematics, science, and technology.

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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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Many nations are experiencing a decline in the number of graduating engineers, an overall poor preparedness for engineering studies in tertiary institutions, and a lack of diversity in the field. Given the increasing importance of mathematics, science, engineering, and technology in our world, it is imperative that we foster an interest and drive to participate in engineering from an early age. This discussion paper argues for the integration of engineering education within the elementary and middle school mathematics curricula. In doing so, we offer a definition of engineering education and address its core goals; consider some perceptions of engineering and engineering education held by teachers and students; and offer one approach to promoting engineering education within the elementary and middle school mathematics curriculum, namely through mathematical modeling.

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Engineering is pivotal to any country's development. Yet there are insufficient engineers to take up available positions in many countries, including Australia (Engineers Australia, 2008). Engineering education is limited in Australia at the primary, middle and high school levels. One of the starting points for addressing this shortfall lies in preservice teacher education. This study explores second-year preservice teachers' potential to teach engineering in middle school, following their engagement with engineering concepts in their science curriculum unit and their teaching of engineering activities to Year 7 students. Using a literature-based pretest-posttest survey, items were categorised into four constructs (ie. personal professional attributes, student motivation, pedagogical knowledge and fused curricula). Results indicated that the preservice teachers' responses had not changed for instilling positive attitudes (88%) and accepting advice from colleagues (94%). However, there was statistical significance with 9 of the 25 survey items (p<0.05) after the preservice teachers' involvement in engineering activities. Fusing engineering education with other subjects, such as mathematics and science, is an essential first step in promoting preservice teachers' potential to implement engineering education in the middle school.

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Articular cartilage damage is a persistent and increasing problem with the aging population, and treatments to achieve biological repair or restoration remain a challenge. Cartilage tissue engineering approaches have been investigated for over 20 years, but have yet to achieve the consistency and effectiveness for widespread clinical use. One of the potential reasons for this is that the engineered tissues do not have or establish the normal zonal organization of cells and extracellular matrix that appears critical for normal tissue function. A number of approaches are being taken currently to engineer tissue that more closely mimics the organization of native articular cartilage. This review focuses on the zonal organization of native articular cartilage, strategies being used to develop such organization, the reorganization that occurs after culture or implantation, and future prospects for the tissue engineering of articular cartilage with biomimetic zones.