Sustained gene expression in transplanted skin fibroblasts in rats

Retrovirus-mediated gene transfer into adult skin fibroblasts has provided measurable amounts of therapeutic proteins in animal models. However, the major problem emerging from these experiments was a limited time of vector encoded gene expression once transduced cells were engrafted We hypothesized that sustained transduced gene expression in quiescent fibroblasts in vivo might be obtained by using a fibronectin (Fn) promoter. Fibronectin plays a key role in cell adhesion, migration and wound healing and is up-regulated in quiescent fibroblasts. Retroviral vectors containing human adenosine deaminase (ADA) cDNA linked to rat fibronectin promoter (LNFnA) or viral LTR promoter (LASN) were compared for their ability to express ADA from transduced primary rat skin fibroblasts in vivo. Skin grafts formed from fibroblasts transduced with LNFnA showed strong human ADA enzyme activity from 1 week to 3 months. In contrast, skin grafts containing LASN-transduced fibroblasts tested positive for human ADA for weeks 1 and 2, were faintly positive at week 3 and showed no human ADA expression at 1, 2 and 3 months. Thus, a fibronectin promoter provided sustained transduced gene expression at high levels for at least 3 months in transplanted rat skin fibroblasts, perhaps permitting the targeting of this tissue for human gene therapy.

Surface characterization of 6H-SiC (0001) substrates in indentation and abrasive machining

Surface characterization of 6H-SiC (0001) substrates in indentation and abrasive machining was carried out to investigate microfracture, residual damage, and surface roughness associated with material removal and surface generation. Brittle versus plastic deformation was studied using Vickers indention and nano-indentation. To characterize the abrasive machining response, the 6H-SiC (0001) substrates were ground using diamond wheels with grit sizes of 25, 15 and 7 mum, and then polished with diamond suspensions of 3 and 0.05 mum. It is found that in indentation, there was a scale effect for brittle versus plastic deformation in 6H-SiC substrates. Also, in grinding, the scales of fracture and surface roughness of the substrates decreased with a decrease in diamond grit size. However, in polishing, a reduction in grit size of diamond suspensions gave no significant improvement in surface roughness. Furthermore, the results showed that fracture-free 6H-SiC (0001) surfaces were generated in polishing with the existence of the residual crystal defects, which were associated with the origin of defects in single crystal growth. (C) 2003 Elsevier Ltd. All rights reserved.

High speed versus conventional grinding in high removal rate machining of alumina and alumina-titania

High removal rate (up to 16.6 mm(3)/s per mm) grinding of alumina and alumina-titania was investigated with respect to material removal and basic grinding parameters using a resin-bond 160 mu m grit diamond wheel at the speeds of 40 and 160 m/s, respectively. The results show that the material removal for the single-phase polycrystalline alumina and the two-phase alumina-titania composite revealed identical mechanisms of microfracture and grain dislodgement under the grinding conditioned selected. There were no distinct differences in surface roughness and morphology for both materials ground at either conventional or high speed. An increase in material removal rate did not necessarily worsen the surface toughness for the two materials at both speeds. Also the grinding forces for the two ceramics demonstrated similar characteristics at any grinding speeds and specific removal rates. Both normal and tangential grinding forces and their force ratios at the high speed were lower than those at the conventional speed, regardless of removal rates. An increase in specific removal rate caused more rapid increases in normal and tangential forces obtained at the conventional grinding speed than those at the high speed. Furthermore, it is found that the high speed grinding at all the removal rates exerted a great amount of coolant-induced normal forces in grinding zone, which were 4-6 times higher than the pure normal grinding forces. (c) 2004 Elsevier Ltd. All rights reserved.

Cognitive fit between conceptual schemas and internal problem representations: The case of geospatio-temporal conceptual schema comprehension

Geospatio-temporal conceptual models provide a mechanism to explicitly represent geospatial and temporal aspects of applications. Such models, which focus on both what and when/where, need to be more expressive than conventional conceptual models (e.g., the ER model), which primarily focus on what is important for a given application. In this study, we view conceptual schema comprehension of geospatio-temporal data semantics in terms of matching the external problem representation (that is, the conceptual schema) to the problem-solving task (that is, syntactic and semantic comprehension tasks), an argument based on the theory of cognitive fit. Our theory suggests that an external problem representation that matches the problem solver's internal task representation will enhance performance, for example, in comprehending such schemas. To assess performance on geospatio-temporal schema comprehension tasks, we conducted a laboratory experiment using two semantically identical conceptual schemas, one of which mapped closely to the internal task representation while the other did not. As expected, we found that the geospatio-temporal conceptual schema that corresponded to the internal representation of the task enhanced the accuracy of schema comprehension; comprehension time was equivalent for both. Cognitive fit between the internal representation of the task and conceptual schemas with geospatio-temporal annotations was, therefore, manifested in accuracy of schema comprehension and not in time for problem solution. Our findings suggest that the annotated schemas facilitate understanding of data semantics represented on the schema.

Understanding conceptual schemas: exploring the role of application and IS domain knowledge

Although information systems (IS) problem solving involves knowledge of both the IS and application domains, little attention has been paid to the role of application domain knowledge. In this study, which is set in the context of conceptual modeling, we examine the effects of both IS and application domain knowledge on different types of schema understanding tasks: syntactic and semantic comprehension tasks and schema-based problem-solving tasks. Our thesis was that while IS domain knowledge is important in solving all such tasks, the role of application domain knowledge is contingent upon the type of understanding task under investigation. We use the theory of cognitive fit to establish theoretical differences in the role of application domain knowledge among the different types of schema understanding tasks. We hypothesize that application domain knowledge does not influence the solution of syntactic and semantic comprehension tasks for which cognitive fit exists, but does influence the solution of schema-based problem-solving tasks for which cognitive fit does not exist. To assess performance on different types of conceptual schema understanding tasks, we conducted a laboratory experiment in which participants with high- and low-IS domain knowledge responded to two equivalent conceptual schemas that represented high and low levels of application knowledge (familiar and unfamiliar application domains). As expected, we found that IS domain knowledge is important in the solution of all types of conceptual schema understanding tasks in both familiar and unfamiliar applications domains, and that the effect of application domain knowledge is contingent on task type. Our findings for the EER model were similar to those for the ER model. Given the differential effects of application domain knowledge on different types of tasks, this study highlights the importance of considering more than one application domain in designing future studies on conceptual modeling.