783 research outputs found
Gene therapy approaches to disease of the cornea and anterior chamber
No full textThe field of ocular gene therapy has become one of the most developed areas within the wider gene therapy field, however most work to date has focused upon the retina with the cornea, by comparison, having seen relatively little application of gene therapy. This thesis describes a program of work to further develop viral gene therapy approaches to the three cellular layers of the cornea, with particular emphasis upon the application of novel vector technologies and overcoming the various challenges presented by each layer. Gene therapy of the corneal endothelium has to date largely aimed to increase or maintain endothelial cell density to improve the quality of donor corneas for engraftment. Such a strategy however carries an inherent risk of oncogenesis and this study has therefore aimed to improve the safety profile of endothelial gene delivery methods. The transduction profile of various AAV serotypes within the corneal stroma was also investigated, and the most promising results applied in an augmentation gene therapy approach to prevent corneal neovascularisation. The selected methodology is shown to mediate high level transgene expression and, when delivering the antiangiogenic factor sFlt1, was highly effective in preventing haem (but not lymph) angiogenesis in a murine model of induced corneal neovascularisation. If long term gene delivery to the corneal epithelium is to be achieved it must be targeted to the limbal epithelial stem cells (LESCs) responsible for the continuous regeneration of the layer. This study has convincingly demonstrated gene delivery to these cells in vivo for the first time, with the methodology developed leading to a lasting transgene expression throughout the LESC daughter cell lineages that comprise the epithelium. In addition to potential application in the treatment of congenital epithelial dystrophies this technique may also provide new insights into LESC biology and the cellular dynamics of epithelial renewal
Number of texts per author vs. accuracy of MDA classifier.
No full text<p>This graph investigates accuracy versus the size of the training dataset for the MDA case, with a fixed set of 100 function words, for the benchmark English corpus of known texts given in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0054998#pone-0054998-t001" target="_blank">Table 1</a>. The upper curve shows the LOO-CV accuracy of MDA, as a function of the number of author texts, by deliberately limiting the size of the training dataset. The lower curve shows the MDA accuracy that is obtained by inputting the hold-out texts to the classifier at each step.</p
Towards an MDA Oriented Methodology
No full textThe author describes the need to introduce a methodology named MDA or Model Driven Architecture based on the concept of Open Distributed Application Construction (ODAC) to be used as a guide in the development of complex distributed applications. The reasons offered for the need of MDA are: 1. The emerging and proliferation of middleware technology. 2. The interoperability of the different middleware. 3. High cost of migration. 4. Problems of portability from one platform to another. And the advantages of MDA are: 1. An architecture based on the MDA approach will always be ready to deal with tomorrow’s “next big thing” 2. MDA will allow easier integration of applications and facilities across middle ware boundaries. 3. Allows cross-platform interoperability. Finally, the principles of the MDA will also be conveyed
Altered immunolocalization of FGF23 in murine femora metastasized with human breast carcinoma MDA-MB-231 cells
No full textIntroduction After the onset of bone metastasis, tumor cells appear to modify surrounding microenvironments for their benefit, and particularly, the levels of circulating fibroblast growth factor (FGF) 23 in patients with tumors have been highlighted. Materials and methods We have attempted to verify if human breast carcinoma MDA-MB-231 cells metastasized in the long bone of nu/nu mice would synthesize FGF23. Serum concentrations of calcium, phosphate (Pi) and FGF23 were measured in control nu/nu mice, bone-metastasized mice, and mice with mammary gland injected with MDA-MB-231 cells mimicking primary mammary tumors. Results and conclusions MDA-MB-231 cells revealed intense FGF23 reactivity in metastasized lesions, whereas MDA-MB-231 cells cultured in vitro or when injected into the mammary glands (without bone metastasis) showed weak FGF23 immunoreactivity. Although the bone-metastasized MDA-MB-231 cells abundantly synthesized FGF23, osteocytes adjacent to the FGF23-immunopositive tumors, unlike intact osteocytes, showed no FGF23. Despite significantly elevated serum FGF23 levels in bone-metastasized mice, there was no significant decrease in the serum Pi concentration when compared with the intact mice and mice with a mass of MDA-MB-231 cells in mammary glands. The metastasized femora showed increased expression and FGFR1 immunoreactivity in fibroblastic stromal cells, whereas femora of control mice showed no obvious FGFR1 immunoreactivity. Taken together, it seems likely that MDA-MB-231 cells synthesize FGF23 when metastasized to a bone, and thus affect FGFR1-positive stromal cells in the metastasized tumor nest in a paracrine manner
Harvesting software systems for MDA-based reengineering
No full textIn this paper we report on a feasibility study in reengineering legacy systems towards a model-driven architecture (MDA). Steps in our approach consist of (1) parsing the source code of the legacy system according to a grammar; (2) mapping the abstract syntax trees thus obtained to a grammar model that is defined in the Meta-Object Facility (MOF); (3) using model to model (M2M) transformations to turn the grammar model into a generic meta-model, called Generic-AST, in which information about software systems can be stored in a language-independent way; (4) mapping the GenericAST models, again using M2M transformations, to UML models that can be either used for code generation or for documentation purposes. The steps have been implemented in a prototype model harvesting tool that is based on Arc-Styler, the MDA environment provided by Interactive Objects. Our paper presents this approach, and reports on our experiences in applying the method to a 178 KLOC production system from the insurance domain written in PL/SQL.Software TechnologyElectrical Engineering, Mathematics and Computer Scienc
Exploring the novels of Zakes Mda
No full textLecture series presented by Associate Professor Gail Fincham, Department of English, University of Cape Town. This lecture series, focusing on the novels of famous South African author Zakes Mda, will be of interest to students of African literature and lovers of literature more generally
Malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) levels in canine serum: establishing reference intervals and influencing factors
No full textAuthor contributions:
Perez-Montero B.: Investigation, conceptualization, performing analytical methodology, data curation and writing original draft. Fermin-Rodriguez ML.: Conceptualization, supervision and reviewing original draft. Portero-Fuentes M.: Sample collection, reviewing original draft. Sarquis J.: IFAT methodology application, reviewing original draft. Caceres S.: Serum cortisol quantification, reviewing original drats. Illera del Portal J.C.: Serum cortisol quantification, providing resources. De Juan L.: Project administration, providing resources and reviewing original draft. Miro G.: Project administration, supervision and reviewing original draft. Cruz-Lopez F.: Supervision, data curation, validation of results, writing, reviewing and editing original draftBackground: Mounting evidence suggests that malondialdehyde (MDA) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) are valuable biomarkers of lipid and nucleic acid oxidation in numerous canine diseases. However, their application in clinical settings is limited due to the absence of reference intervals (RI) and the analytical inconsistencies. Therefore, this study aimed to characterize serum MDA and 8-OHdG concentrations in dogs, to establish assay-specific RI, and to identify biological, haematological and biochemical factors influencing these markers.
Methods: A total of 190 clinically healthy dogs were recruited, including pet dogs, working dogs and shelter dogs. Serum MDA concentration was measured by the Thiobarbituric Acid Reactive Substances (TBARS) assay, while 8-OHdG levels were determined by using a competitive ELISA. RI were established by non-parametric methods. Potential associations between oxidative stress (OS) biomarkers and multiple biological, haematological and biochemical factors were assessed using multivariate regression models.
Results: RI for serum MDA (1.85-14.51 µM) and 8-OHdG (0.06-0.75 ng/mL) were established in the reference population (144 and 143 dogs, respectively). The multivariate regression model for MDA revealed a positive association with total cholesterol concentration, and a negative association with monocyte count. 8-OHdG level was positively associated with urea concentration. Notably, both models also revealed a significant association between MDA and 8-OHdG. Biological factors, including the age and size of the animals, did not exert a significant influence on the results.
Conclusions: This is the first study to establish serum RI for MDA and 8-OHdG in a large and diverse canine population. Additionally, the multivariate regression models identified relevant haematological and biochemical, but not biological factors that should be considered when interpreting the results. These findings could significantly enhance the application of MDA and 8-OHdG as biomarkers in clinical settings, and promote further exploration of their value in canine diseasesDepto. de Medicina y Cirugía AnimalDepto. de FisiologíaDepto. de Sanidad AnimalFac. de VeterinariaCentro de Vigilancia Sanitaria Veterinaria (VISAVET)TRUEpu
Model Transformation with ATL into MDA from CIM to PIM Structured through MVC
No full textAbstractModels transformation is the most important key in Model Driven Architecture (MDA). The first transformation in MDA is Computing Independent Model (CIM) to Platform Independent Model (PIM) transformation, the second is PIM to Platform Specific Model (PSM) transformation. This latter transformation deals the two less abstract levels, PIM and PSM, for that most researchers focused on this kind of transformation. Nevertheless, the top level of abstraction, CIM, and its transformation to PIM is rarely discussed in research topics. Our goal in this paper is to represent an approach that allows mastering transformation from CIM to PIM in accordance with MDA. Our method based on creating a good CIM level, using construction rules, to facilitate the transformation to PIM level. Next, our transformation rules, implemented with Atlas Transformation Language (ATL), ensure a semi-automatic transformation from CIM to PIM. Our approach conforms to MDA, because it allows considering the business dimension in the CIM level, and it allows modelling this latter level by using Business Process Model and Notation (BPMN), this latter is the OMG standard for modelling the business process. However, we founded on UML to model PIM level, because UML is advocated by MDA in PIM. Our proposal results a set of classes, organized according to the Model View Controller (MVC)
Semantic model-driven development of web service architectures.
No full textBuilding service-based architectures has become a major area of interest since the advent of Web services. Modelling these architectures is a central activity. Model-driven development is a recent approach to developing software systems based on the idea of making models the central artefacts for design representation, analysis, and code generation.
We propose an ontology-based engineering methodology for semantic model-driven composition and transformation of Web service architectures. Ontology technology as a logic-based knowledge representation and reasoning framework can provide answers to the needs of sharable and reusable semantic models and descriptions needed for service engineering. Based on modelling, composition and code generation techniques for service architectures, our approach provides a methodological framework for ontology-based semantic service architecture
Good Practices for Software Configuration Management with MDA Metodology
No full textSoftware Configuration Management (SCM) forms part of the software development process. Its principal goal is to coordinate this development and minimize all possible errors. In order to meet its goal various activities are carried out, of which can be identified: items identification, change control, version control, audit and status reporting. Inside enterprise applications the software development can be guided from system model as methodology. The name of this methodology is Model Driven Architecture (MDA). The use of this methodology has the objectives of increasing development´s velocity through the automatic generation code as well as keeping updated all the documents belonging to the system in relation to the existing code. The ways to carry out the mentioned activities in the SCM process differ between projects that use MDA methodology and other projects that do not use MDA methodology. Some aspects must be taken into account during the implementation of each activity described in the SCM process. Following this, the author mentions some ideas to take into account in each aspect of the process to ensure giving a guide on how to proceed in front of these kinds of project that use MDA methodology
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