113 resultados para OV-275


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We previously showed that integrin alphavbeta3 overexpression and engagement by its ligand vitronectin increased adhesion, motility, and proliferation of human ovarian cancer cells. In search of differentially regulated genes involved in these tumor biological events, we previously identified the integrin-linked kinase (ILK) to be under control of alphavbeta3. In the present investigation we demonstrated significantly upregulated ILK protein as a function of alphavbeta3 in two ovarian cancer cell lines, OV-MZ-6 and OVCAR-3, and proved co-localization at the surface of alphavbeta3-overexpressing cells adherent to vitronectin. Increase of ILK protein was reflected by enhanced ILK promoter activity, an effect, which we further characterized with regard to transcriptional response elements involved. Abrogation of NF-kappaB/c-rel or p53 binding augmented ILK promoter activity and preserved induction by alphavbeta3. The AP1-mutant exhibited decreased promoter activity but was also still inducible by alphavbeta3. Disruption of the two DNA consensus motifs for Ets proteins led to divergent observations: mutation of the Ets motif at promoter position -462 bp did not significantly alter promoter activity but still allowed response to alphavbeta3. In contrast, disruption of the second Ets motif at position -85 bp did not only lead to slightly diminished promoter activity but also, in that case, abrogated ILK promoter induction by alphavbeta3. Subsequent co-transfection studies with ets-1 in the presence of the second Ets motif led to additional induction of ILK promoter activity. Taken together, these data suggest that ets-1 binding to the second Ets DNA motif strongly contributes to alphavbeta3-mediated ILK upregulation. By increasing ILK as an important integrin-proximal kinase, alphavbeta3 may promote its intracellular signaling and tumor biological processes arising thereof in favor of ovarian cancer metastasis.

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An alternative learning approach for destructive testing of structural specimens in civil engineering is explored by using a remote laboratory experimentation method. The remote laboratory approach focuses on overcoming the constraints in the hands-on experimentation without compromising the understanding of the students on the concepts and mechanics of reinforced concrete structures. The goal of this study is to evaluate whether or not the remote laboratory experimentation approach can become a standard in civil engineering teaching. The teaching activity using remote-laboratory experimentation is presented here and the outcomes of this activity are outlined. The experience and feedback gathered from this study are used to improve the remote-laboratory experimentation approach in future years to other aspects of civil engineering where destructive testing is essential.

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Improved public awareness of the environment and available technologies will continue to highlight the importance of sustainable housing in the coming years. Despite this potential, the majority of new housing development in Australia is still “project homes” with few tangible sustainability measures. Stakeholders tend to have different perceptions and priorities on sustainability. To promote the uptake of sustainable housing products, a study of the critical issues affecting the implementation of sustainable housing is necessary. This research investigates multiple factors that may influence key stakeholders’ decision-making towards sustainable housing adoption. Drawing insights from combined questionnaire and interview studies, 12 critical factors and their interrelationships are identified based on professional views in the Australian housing industry. The mutual influences, or driving force and dependency, of these factors are further investigated via Interpretive Structural Modelling (ISM) to distinguish those requiring prominent and immediate attention. A hierarchical model is developed to help key stakeholders prioritise actions when implementing sustainable housing.

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A method is proposed to describe force or compound muscle action potential (CMAP) trace data collected in an electromyography study for motor unit number estimation (MUNE). Experimental data was collected using incre- mental stimulation at multiple durations. However, stimulus information, vital for alternate MUNE methods, is not comparable for multiple duration data and therefore previous methods of MUNE (Ridall et al., 2006, 2007) cannot be used with any reliability. Hypothesised ring combinations of motor units are mod- elled using a multiplicative factor and Bayesian P-spline formulation. The model describes the process for force and CMAP in a meaningful way.

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The Marine Systems Simulator (MSS) is an environment which provides the necessary resources for rapid implementation of mathematical models of marine systems with focus on control system design. The simulator targets models¡Xand provides examples ready to simulate¡Xof different floating structures and its systems performing various operations. The platform adopted for the development of MSS is Matlab/Simulink. This allows a modular simulator structure, and the possibility of distributed development. Openness and modularity of software components have been the prioritized design principles, which enables a systematic reuse of knowledge and results in efficient tools for research and education. This paper provides an overview of the structure of the MSS, its features, current accessability, and plans for future development.

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Background The behaviour of tumour cells depends on factors such as genetics and the tumour microenvironment. The latter plays a crucial role in normal mammary gland development and also in breast cancer initiation and progression. Breast cancer tissues tend to be highly desmoplastic and dense matrix as a pre-existing condition poses one of the highest risk factors for cancer development. However, matrix influence on tumour cell gene expression and behaviour such as cell migration is not fully elucidated. Results We generated high-density (HD) matrices that mimicked tumour collagen content of 20 mg/cm3 that were ~14-fold stiffer than low-density (LD) matrix of 1 mg/cm3. Live-cell imaging showed breast cancer cells utilizing cytoplasmic streaming and cell body contractility for migration within HD matrix. Cell migration was blocked in the presence of both the ROCK inhibitor, Y-27632, and the MMP inhibitor, GM6001, but not by the drugs individually. This suggests roles for ROCK1 and MMP in cell migration are complicated by compensatory mechanisms. ROCK1 expression and protein activity, were significantly upregulated in HD matrix but these were blocked by treatment with a histone deacetylase (HDAC) inhibitor, MS-275. In HD matrix, the inhibition of ROCK1 by MS-275 was indirect and relied upon protein synthesis and Notch1. Inhibition of Notch1 using pooled siRNA or DAPT abrogated the inhibition of ROCK1 by MS-275. Conclusion Increased matrix density elevates ROCK1 activity, which aids in cell migration via cell contractility. The upregulation of ROCK1 is epigenetically regulated in an indirect manner involving the repression of Notch1. This is demonstrated from inhibition of HDACs by MS-275, which caused an upregulation of Notch1 levels leading to blockade of ROCK1 expression.

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In the present study, we examined a panel of human breast cancer cell lines with regard to their expression of CD44 and ability to bind and degrade hyaluronan. The cell lines expressed varying amounts of different molecular weight forms of CD44 (85-200 kDa) and, in general, those that expressed the greatest amounts of CD44 were the most invasive as judged by in vitro assays. In addition, the ability to bind and degrade hyaluronan was restricted to the cell lines expressing high levels of CD44, and both these functions were blocked by an antibody to CD44 (Hermes-1). Moreover, the rate of [3H]hyaluronan degradation was highly correlated with the amount of CD44 (r = 0.951, P < 0.0001), as well as with the invasive potential of the cells. Scatchard analysis of the [3H]hyaluronan binding of these cells revealed the existence of significant differences in both their binding capacity and their dissociation constant. To determine the source of this deviation, the different molecular weight forms of CD44 were partially separated by gel filtration chromatography. In all cell lines, the 85 kDa form was able to bind hyaluronan, although with different affinities. In contrast, not all of the high molecular weight forms of CD44 had this ability. These results illustrate the diversity of CD44 molecules in invasive tumor cells, and suggest that one of their major functions is to degrade hyaluronan.

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Solving indeterminate algebraic equations in integers is a classic topic in the mathematics curricula across grades. At the undergraduate level, the study of solutions of non-linear equations of this kind can be motivated by the use of technology. This article shows how the unity of geometric contextualization and spreadsheet-based amplification of this topic can provide a discovery experience for prospective secondary teachers and information technology students. Such experience can be extended to include a transition from a computationally driven conjecturing to a formal proof based on a number of simple yet useful techniques.

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The main purpose of the current study was to provide empirical evidence to support or refute assumptions of phenotypic deficits in motivation for children with Down syndrome. Children with moderate intellectual disability associated with etiologies other than Down syndrome were recruited in an extension of a previous study that involved children with Down syndrome and typically developing children. The participants were 29 children with moderate intellectual disability and 33 children with Down syndrome who were matched on mental age to 33 typically developing children, aged 3 to 8 years. Mastery motivation was assessed on task measures of curiosity, preference for challenge, and persistence, as well as parental reports. There were no significant group differences on the mastery motivation tasks. Parental ratings of mastery motivation differed, with typically developing children generally being rated more highly than each of the disability groups. The view that motivational deficits are part of the Down syndrome behavioural phenotype was not supported.

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The primary aim of this paper was to investigate heterogeneity in language abilities of children with a confirmed diagnosis of an ASD (N = 20) and children with typical development (TD; N = 15). Group comparisons revealed no differences between ASD and TD participants on standard clinical assessments of language ability, reading ability or nonverbal intelligence. However, a hierarchical cluster analysis based on spoken nonword repetition and sentence repetition identified two clusters within the combined group of ASD and TD participants. The first cluster (N = 6) presented with significantly poorer performances than the second cluster (N = 29) on both of the clustering variables in addition to single word and nonword reading. The significant differences between the two clusters occur within a context of Cluster 1 having language impairment and a tendency towards more severe autistic symptomatology. Differences between the oral language abilities of the first and second clusters are considered in light of diagnosis, attention and verbal short term memory skills and reading impairment.

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The phylogenetic relationships of the beetle superfamily Tenebrionoidea are investigated using the most comprehensive genetic data set compiled to date. With ∼34,000 described species in approximately 1250 genera and 28 families, Tenebrionoidea represent one of the most diverse and species-rich superfamilies of beetles. The interfamilial relationships of the Tenebrionoidea are poorly known; previous morphological and molecular phylogenies recovered few well-supported and often conflicting relationships between families. Here we present a molecular phylogeny of Tenebrionoidea based on genes commonly used to resolve family and superfamily-level phylogenies of beetles (18S, 28S, 16S, 12S, tRNA Val and COI). The alignment spanned over 6.5 KB of DNA sequence and over 300 tenebrionoid genera from 24 of the 28 families were sampled. Maximum Likelihood and Bayesian analysis could not resolve deeper level divergences within the superfamily and very few relationships between families were supported. Increasing gene coverage in the alignment by removing taxa with missing data did not improve clade support but when rogue taxa were removed increased resolution was recovered. Investigation of signal strength suggested conflicting phylogenetic signal was present in the standard genes used for beetle phylogenetics, even when rogue taxa were removed. Our study of Tenebrionoidea highlights that even with relatively comprehensive taxon sampling within a lineage, this standard set of genes is unable to resolve relationships within this superfamily.

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Large scale solar plants are gaining recognition as potential energy sources for future. In this paper, the feasibility of using electric vehicles (EVs) to control a solar powered micro-grid is investigated in detail. The paper presents a PSCAD/EMTDC based model for the solar powered micro-grid with EVs. EVs are expected to have both the vehicle-to-grid (V2G) and grid-to-vehicle (G2V) capability, through which energy can either be injected into or extracted from the solar powered micro-grid to control its energy imbalance. Using the model, the behaviour of the micro-grid is investigated under a given load profile, and the results indicate that a minimum number of EVs are required to meet the energy imbalance and it is time dependent and influenced by various factors such as depth of charge, commuting profiles, reliability etc...

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In recent years there has been considerable discussion afforded to the challenges facing the future of information education in Australia. This paper reports a study that explored the characteristics and experiences of Australia’s information educators. The study was undertaken as part of a larger project, which was designed to establish a consolidated and holistic picture of the Australian information profession, and identify how its future education could be mediated in a cohesive and sustainable manner. Sixty-nine of Australia’s information educators completed an online questionnaire that gathered data on aspects such as age, gender, rank, qualifications, work activities, and job satisfaction. The key findings from this study confirm that a number of pressing issues are confronting information educators in Australia. For example, Australia’s information educators are considerably older than that the total Australian academic workforce; over half the information educators who participated in the study are looking to retire in the next ten years; and, Australia’s information educators spend more time on service activities then other disciplines within Australia’s education system and are place a stronger importance on teaching over research. Left unaddressed these issues will have significant implications for the future of information education as well as the broader information profession. Many of the key observations drawn from this study may also have relevance to other disciplines in the Australian educational context.

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Here we report that the Saccharomyces cerevisiae RBP29 (SGN1, YIR001C) gene encodes a 29-kDa cytoplasmic protein that binds to mRNA in vivo. Rbp29p can be co-immunoprecipitated with the poly(A) tail-binding protein Pab1p from crude yeast extracts in a dosageand RNA-dependent manner. In addition, recombinant Rbp29p binds preferentially to poly(A) with nanomolar binding affinity in vitro. Although RBP29 is not essential for cell viability, its deletion exacerbates the slow growth phenotype of yeast strains harboring mutations in the eIF4G genes TIF4631 and TIF4632. Furthermore, overexpression of RBP29 suppresses the temperaturesensitive growth phenotype of specific tif4631, tif4632, and pab1 alleles. These data suggest that Rbp29p is an mRNA-binding protein that plays a role in modulating the expression of cytoplasmic mRNA.

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Background Small RNA sequencing is commonly used to identify novel miRNAs and to determine their expression levels in plants. There are several miRNA identification tools for animals such as miRDeep, miRDeep2 and miRDeep*. miRDeep-P was developed to identify plant miRNA using miRDeep’s probabilistic model of miRNA biogenesis, but it depends on several third party tools and lacks a user-friendly interface. The objective of our miRPlant program is to predict novel plant miRNA, while providing a user-friendly interface with improved accuracy of prediction. Result We have developed a user-friendly plant miRNA prediction tool called miRPlant. We show using 16 plant miRNA datasets from four different plant species that miRPlant has at least a 10% improvement in accuracy compared to miRDeep-P, which is the most popular plant miRNA prediction tool. Furthermore, miRPlant uses a Graphical User Interface for data input and output, and identified miRNA are shown with all RNAseq reads in a hairpin diagram. Conclusions We have developed miRPlant which extends miRDeep* to various plant species by adopting suitable strategies to identify hairpin excision regions and hairpin structure filtering for plants. miRPlant does not require any third party tools such as mapping or RNA secondary structure prediction tools. miRPlant is also the first plant miRNA prediction tool that dynamically plots miRNA hairpin structure with small reads for identified novel miRNAs. This feature will enable biologists to visualize novel pre-miRNA structure and the location of small RNA reads relative to the hairpin. Moreover, miRPlant can be easily used by biologists with limited bioinformatics skills.