Hepatoma-derived growth factor (HDGF) is a nucleus-targeting mitogen for various types of cells. Besides, HDGF overexpression is associated with tumor progression and poor survival outcome in patients with hepatocellular carcinoma (HCC) and lung cancer. HDGF is capable of promoting the proliferation and migration in various types of cells. HDGF is composed of 240 amino acids and contains 2 putative bipartite nuclear localization signals (NLSs). By dividing HDGF into two deletion domains: PWWP (residues 1-100) and C140 (residues 101-240), we found that both PWWP and C140 domains are capable of promoting nuclear localization, However, only C140 domain promoted cell proliferation and migration as HDGF. Mutation in NLS domains abrogated the nuclear localization and growth-promoting function, but not the migratory potential of HDGF. Beside, Ser165 was predicted as putative cdc2 phosphorylation site. In vitro kinase assay indicated that Ser165 of HDGF is the phosphorylated site of cdc2 kinase. We also demonstrated that mutations in cdc2 phoshprylation site did not affect the nuclear localization, proliferation-stimulating activities of HDGF but enhance migration-stimulating abilities of HDGF. Recently, the HDGF domain containing residues 81 to 100 is shown to be responsible for binding to membrane receptor in NIH3T3 cells. Besides, Lys96 plays a pivotal role for receptor binding. By generation of HDGF Lys96A mutant protein, we found that mutation of Lys96 indeed caused a prominent reduction in cellular binding affinity of HDGF to NIH3T3 cells and affect cell migration. In summary, the NLSs are essential for the mitogenic effect of HDGF, but not required for migration. And the cdc2 phoshorylation site is important for NIH3T3 migration. The Lys96 of HDGF play an important role of membrane receptor binding and cell migration.

No description available.

Thesis (MEng) -- Stellenbosch University, 2014. / ENGLISH ABSTRACT: See PDF for abstract. / AFRIKKANSE OPSOMMING: Sien PDF vir die opsomming.

Bakgrund: Kolonisering och spridning av multiresistenta bakterier (MRB) är ett ökande problem både i samhället och i sjukvården idag. MRB smittar genom kontaktsmitta, genom direkt personkontakt eller kontakt av kontaminerade ytor. Frågor rörande patientsäkerhet påverkar alla inom hälso- och sjukvårdens organisationer, men huvudansvaret att utveckla ledningssystem för att ett systematiskt kvalitetsarbete ska kunna bedrivas, ligger på vårdorganisationen- och vårdgivaren. Kunskapsbrist om MRB hos vårdpersonal samt brist på tydliga riktlinjer i vården i det kliniska arbetet kan påverka attityder till och bemötande av patienter med MRB. Syfte: Att belysa vårdorganisationers ansvar, sjuksköterskans kunskaper om MRB samt hens attityder till och bemötande av patienter med MRB- smitta. Metod: Studien gjordes som en litteraturöversikt där tio vetenskapliga artiklar analyserades för att framställa resultatet. Resultat: I resultatet framkom att vårdorganisationen och ledarskapet var av stor vikt för sjuksköterskans förutsättningar att ge god och säker vård till patienter med MRB. Kunskaperna om MRB var oftast låga. Attityder och bemötande visade sig i de flesta fall också påverkas av kunskapsnivån. Dålig kunskap och brist på erfarenhet av patienter med MRB kunde även relateras till ökade rädslor hos sjuksköterskor att smittas av MRB. Diskussion: Resultatet diskuterades mot Travelbee´s teori om mellanmänskliga relationer och konsensusbegreppet vårdande. Vårdorganisationens ansvar och kunskaper hos sjuksköterskor om MRB tycks vara de faktorer som mest påverkade bemötandet gentemot och attityderna till patienter med MRB. / Background: Colonization and transmission of MDRB is an increasing problem today, both in society and in health care settings. MDRB is most commonly transmitted through cross-contamination through personal contact and contact with contaminated surfaces. Patient safety affects everybody within health care settings. Main responsibility lies with healthcare organizations and caregivers, to develop management systems for systematic quality improvement. Knowledge deficiency of MDRB among health care personnel and lack of clear guidelines in health care settings may influence the attitudes and behaviour towards patients with MDRB. Aim: To illustrate healthcare organizations responsibilities, nurses’ knowledge of MDRB and nurses’ attitudes and behaviour towards patients with MDRB. Method: The study was conducted as a literature review and ten scientific papers were analysed to generate the results. Results: The results showed that healthcare organizations and leadership were of great importance for the nurses’ ability to provide good and safe care for patients with MDRB. Knowledge about MDRB was also proved to be low. Deficient knowledge and lack of experience of caring for patients with MDRB among nurses might also influence their own fears of contracting MDRB. Discussions: The results were discussed against Travelbee’s Intrapersonal relationship- theory and the concept of caring. Healthcare organizations responsibility and nurses’ knowledge of MDRB seemed to be the eminent factors that influenced both behaviour and attitudes towards patients with MDRB.

<p>  </p> <p>There has been a growing interest within the aerospace industry for shifting towards a digital twin approach, for reliable assessment of individual components during the product lifecycle - across design, manufacturing, and in-service maintenance, repair & overhaul (MRO) stages. The transition towards digital twins relies on continuous updating of the product lifecycle datasets and interoperable exchange of data applicable to components, thereby permitting engineers to utilize current state information to make more-informed downstream decisions. In this thesis, we primarily develop a framework to store, track, update, and retrieve product lifecycle data applicable to a serialized component, its features, and individual locations. </p> <p>From a structural integrity standpoint, the fatigue performance of a component is inherently tied to the component geometry, its material state, and applied loading conditions. The manufacturing process controls the underlying material microstructure, which in turn governs the mechanical properties and ultimately the performance. The processing also controls the residual stress distributions within the component volume, which influences the durability and damage tolerance of the component. Hence, we have demonstrated multiple use cases for fatigue life assessment of critical aerospace components, by using the developed framework for efficiently tracking and retrieving (i) the current geometric state, (ii) the material microstructure state, and (iii) residual stress distributions.</p> <p>Model-based definitions (MBDs) present opportunities to capture both geometric and non-geometric data using 3D computer-aided design (CAD) models, with the overarching aim to disseminate product information across different stages of the lifecycle. MBDs can potentially eliminate error-prone information exchange associated with traditional paper-based drawings and improve the fidelity of component details, captured using 3D CAD models. However, current CAD capabilities limit associating the material information with the component’s shape definition. Furthermore, the material attributes of interest, viz., material microstructures and residual stress distributions, can vary across the component volume. To this end, in the first part of the thesis, we implement a CAD-based tool to store and retrieve metadata using point objects within a CAD model, thereby creating associations to spatial locations within the component. The tool is illustrated for storage and retrieval of bulk residual stresses developed during the manufacturing of a turbine disk component, acquired from process modeling and characterization. Further, variations in residual stress distribution owing to process model uncertainties have been captured as separate instances of the disk’s CAD models to represent part-to-part variability as an analogy to track individual serialized components for digital twins. The propagation of varying residual stresses from these CAD models within the damage tolerance analysis performed at critical locations in the disk has been demonstrated. The combination of geometric and non-geometric data inside the MBD, via storage of spatial and feature varying information, presents opportunities to create digital replica or digital twin(s) of actual component(s) with location-specific material state information.</p> <p>To fully realize a digital twin description of components, it is crucial to dynamically update information tied to a component as it evolves across the lifecycle, and subsequently track and retrieve current state information. Hence, in the second part of the thesis, we propose a dynamic data linking approach to include material information within the MBDs. As opposed to storing material datasets directly within the CAD model in the previous approach, we externally store and update the material datasets and create data linkages between material datasets and features within the CAD models. To this end, we develop a model-based feature information network (MFIN), a software agnostic framework for linking, updating, searching, and retrieving of relevant information across a product’s lifecycle. The use case of a damage tolerance analysis for a compressor bladed-disk (blisk) is demonstrated, wherein Ti-6Al-4V blade(s) are linear friction welded to the Ti-6Al-4V disk, comprising well-defined regions exhibiting grain refinement and high residuals stresses. By capturing the location-specific microstructural information and residual stress fields at the weld regions, this information was accessed within the MFIN and used for downstream damage tolerant analysis. The introduction of the MFIN framework facilitates access to dynamically evolving as well as location-specific data for use within physics-based models.</p> <p>In the third part of thesis, we extend the MFIN framework to enable a physics-based, microstructure sensitive and location-specific fatigue life analysis of a component. Traditionally, aerospace components are treated as monolithic structures during lifing, wherein microstructural information at individual locations are not necessarily considered. The resulting fatigue life estimates are conservative and associated with large uncertainty bounds, especially in components with gradient microstructures or distinct location-specific microstructures, thereby leading to under usage of the component’s capabilities. To improve precision in the fatigue estimates, a location-specific lifing framework is enabled via MFIN, for tracking and retrieval of microstructural information at distinct locations for subsequent use within a crystal plasticity-based fatigue life prediction model. A use case for lifing dual-microstructure heat treated LSHR turbine disk component is demonstrated at two locations, near the bore (fine grains) and near the rim (coarse grains) regions. We employ the framework to access (a) the grain size statistics and (b) the macroscopic strain fields to inform precise boundary conditions for the crystal plasticity finite-element analysis. The illustrated approach to conduct a location-specific predictive analysis of components presents opportunities for tailoring the manufacturing process and resulting microstructures to meet the component’s targeted requirements.</p> <p>For reliably conducting structural integrity analysis of a component, it is crucial to utilize their precise geometric description. The component geometries encounter variations from nominal design geometries, post manufacturing or after service. However, traditionally, stress analyses are based on nominal part geometries during assessment of these components. In the last part of the thesis, we expand the MFIN framework to dynamically capture deviations in the part geometry via physical measurements, to create a new instance of the CAD model and the associated structural analysis. This automated workflow enables engineers for improved decision-making by assessing (i) as-manufactured part geometries that fall outside of specification requirements during the materials review board or (ii) in-service damages in parts during the MRO stages of the lifecycle. We demonstrate a use case to assess the structural integrity of a turbofan blade that had experienced foreign object damage (FOD) during service. The as-designed geometry was updated based on coordinate measurements of the damaged blade surfaces, by applying a NURBS surface fit, and subsequently utilized for downstream finite-element stress analysis. The ramifications of the FOD on the local stresses within the part are illustrated, providing critical information to the engineers for their MRO decisions. The automated flow of information from geometric inspection within structural analysis, enabled by MFIN, presents opportunities for effectively assessing products by utilizing their current geometries and improving decision-making during the product lifecycle.</p>