Insulin-like growth factor-i : vitronectin complex-induced changes in gene expression effect breast cell survival and migration

Recent studies have demonstrated that IGF-I associates with VN through IGF-binding proteins (IGFBP) which in turn modulate IGF-stimulated biological functions such as cell proliferation, attachment and migration. Since IGFs play important roles in transformation and progression of breast tumours, we aimed to describe the effects of IGF-I:IGFBP:VN complexes on breast cell function and to dissect mechanisms underlying these responses. In this study we demonstrate that substrate-bound IGF-I:IGFBP:VN complexes are potent stimulators of MCF-7 breast cell survival, which is mediated by a transient activation of ERK/MAPK and sustained activation of PI3-K/AKT pathways. Furthermore, use of pharmacological inhibitors of the MAPK and PI3-K pathways confirms that both pathways are involved in IGF-I:IGFBP:VN complex-mediated increased cell survival. Microarray analysis of cells stimulated to migrate in response to IGF-I:IGFBP:VN complexes identified differential expression of genes with previously reported roles in migration, invasion and survival (Ephrin-B2, Sharp-2, Tissue-factor, Stratifin, PAI-1, IRS-1). These changes were not detected when the IGF-I analogue (\[L24]\[A31]-IGF-I), which fails to bind to the IGF-I receptor, was substituted; confirming the IGF-I-dependent differential expression of genes associated with enhanced cell migration. Taken together, these studies have established that IGF-I:IGFBP:VN complexes enhance breast cell migration and survival, processes central to facilitating metastasis. This study highlights the interdependence of ECM and growth factor interactions in biological functions critical for metastasis and identifies potential novel therapeutic targets directed at preventing breast cancer progression.

Bayes Factor based speaker segmentation for speaker diarization

This paper proposes the use of the Bayes Factor as a distance metric for speaker segmentation within a speaker diarization system. The proposed approach uses a pair of constant sized, sliding windows to compute the value of the Bayes Factor between the adjacent windows over the entire audio. Results obtained on the 2002 Rich Transcription Evaluation dataset show an improved segmentation performance compared to previous approaches reported in literature using the Generalized Likelihood Ratio. When applied in a speaker diarization system, this approach results in a 5.1% relative improvement in the overall Diarization Error Rate compared to the baseline.

Amine-sssisted route to fabricate LiNbO3 particles with a tunable shape

An ethylenediamine-assisted route has been designed for one-step synthesis of lithium niobate particles with a novel rodlike structure in an aqueous solution system. The morphological evolution for these lithium niobate rods was monitored via SEM: The raw materials form large lozenges first. These lozenges are a metastable intermediate of this reaction, and they subsequently crack into small rods after sufficiently long time. These small rods recrystallize and finally grow into individual lithium niobate rods. Interestingly, shape-controlled fabrication of lithium niobate powders was achieved through using different amine ligands. For instance, the ethylenediamine or ethanolamine ligan can induce the formation of rods, while n-butylamine prefers to construct hollow spheres. These as-obtained lithium niobate rods and hollow spheres may exhibit enhanced performance in an optical application field due to their distinctive structures. This effective ligand-tuned-morphology route can provide a new strategy to facilely achieve the shape-controlled synthesis of other niobates.

Luxury fashion: The role of innovation as a key contributing factor in the development of luxury fashion goods and sustainable fashion design

Luxury is a quality that is difficult to define as the historical concept of luxury appears to be both dynamic and culturally specific. The everyday definition explains a ‘luxury’ in relation to a necessity: a luxury (product or service) is defined as something that consumers want rather than need. However, the growth of global markets has seen a boom in what are now referred to as ‘luxury brands’. This branding of products as luxury has resulted in a change in the way consumers understand luxury goods and services. In their attempts to characterize a luxury brand, Fionda & Moore in their article “The anatomy of a Luxury Brand” summarize a range of critical conditions that are in addition to product branding “... including product and design attributes of quality, craftsmanship and innovative, creative and unique products” (Fionda & Moore, 2009). For the purposes of discussing fashion design however, quality and craftsmanship are inseparable while creativity and innovation exist under different conditions. The terms ‘creative’ and ‘innovative’ are often used inter-changeably and are connected with most descriptions of the design process, defining ‘design’ and ‘fashion’ in many cases. Christian Marxt and Fredrik Hacklin identify this condition in their paper “Design, product development, innovation: all the same in the end?”(Marxt & Hacklin, 2005) and suggest that design communities should be aware that the distinction between these terms, whilst once quite definitive, is becoming narrow to a point where they will mean the same thing. In relation to theory building in the discipline this could pose significant problems. Brett Richards (2003) identifies innovation as different from creativity in that innovation aims to transform and implement rather than simply explore and invent. Considering this distinction, in particular relation to luxury branding, may affect the way in which design can contribute to a change in the way luxury fashion goods might be perceived in a polarised fashion market, namely suggesting that ‘luxury’ is what consumers need rather than the ‘pile it high, sell it cheap’ fashion that the current market dynamic would indicate they want. This paper attempts to explore the role of innovation as a key contributing factor in luxury concepts, in particular the relationship between innovation and creativity, the conditions which enable innovation, the role of craftsmanship in innovation and design innovation in relation to luxury fashion products. An argument is presented that technological innovation can be demonstrated as a common factor in the development of luxury fashion product and that the connection between designer and maker will play an important role in the development of luxury fashion goods for a sustainable fashion industry.

Identifying rural disadvantage using a multiday travel diary

This paper identifies transport disadvantage using a 7 day activity-travel diary data from two rural case study areas. A composite participation index (PI) measure was developed for this study based on six indices measuring elements of travel and activity participation. Using the index the paper then goes on to compare these results, with the results obtained from other more traditional indicators used to identify transport disadvantage. These indicators are related to the size of activity space such as unique network distance travelled, number of unique locations visited, activity space area, activity duration, and fullness (shape) of activity spaces. The weaknesses of these indicator based measures are that: firstly, they do not take into account the relativity of the measure between different areas i.e. travel distance in terms of the wider context of available activities within an area; and secondly, these indicators are multi-dimensional and each represents a different qualitative aspect of travel and activity participation. As a result, six individual indices were developed to overcome these problems. These include: participation count index, participation length index, participation area index, participation duration index, participation type index, and participation frequency index. These are then aggregated to assess the relative performance in terms of these different indices and identify the nature of transport disadvantage. GIS was used to visualise individual travel patterns and to derive scores for both the indicator based measures and the index based measures. Factor analysis was conducted to derive weights of the individual indices to form the composite index measure. From this analysis, two intermediate indices were also derived using the underlying factors of the data related to these indices. Using the scores of all these measures, multiple regression analyses were conducted to identify patterns of transport disadvantage.

Plantar fasciitis : are pain and fascial thickness associated with arch shape and loading?

Background and Purpose Although plantar fascial thickening is a sonographic criterion for the diagnosis of plantar fasciitis, the effect of local loading and structural factors on fascial morphology are unknown. The purposes of this study were to compare sonographic measures of fascial thickness and radiographic measures of arch shape and regional loading of the foot during gait in individuals with and without unilateral plantar fasciitis and to investigate potential relationships between these loading and structural factors and the morphology of the plantar fascia in individuals with and without heel pain. Subjects The participants were 10 subjects with unilateral plantar fasciitis and 10 matched asymptomatic controls. Methods Heel pain on weight bearing was measured by a visual analog scale. Fascial thickness and static arch angle were determined from bilateral sagittal sonograms and weight-bearing lateral foot roentgenograms. Regional plantar loading was estimated from a pressure plate. Results On average, the plantar fascia of the symptomatic limb was thicker than the plantar fascia of the asymptomatic limb (6.1±1.4 mm versus 4.2±0.5 mm), which, in turn, was thicker than the fascia of the matched control limbs (3.4±0.5 mm and 3.5±0.6 mm). Pain was correlated with fascial thickness, arch angle, and midfoot loading in the symptomatic foot. Fascial thickness, in turn, was positively correlated with arch angle in symptomatic and asymptomatic feet and with peak regional loading of the midfoot in the symptomatic limb. Discussion and Conclusion The findings indicate that fascial thickness and pain in plantar fasciitis are associated with the regional loading and static shape of the arch.

Myocyte enhancer factor 2C : an osteoblast transcription factor identified by DMSO enhanced mineralization

Rapid mineralization of cultured osteoblasts could be a useful characteristic in stem-cell mediated therapies for fracture and other orthopaedic problems. Dimethyl sulfoxide (DMSO) is a small amphipathic solvent molecule capable of simulating cell differentiation. We report that, in primary human osteoblasts, DMSO dose-dependently enhanced the expression of osteoblast differentiation markers alkaline phosphatase (ALP) activity and extracellular matrix mineralization. Furthermore, similar DMSO mediated mineralization enhancement was observed in primary osteoblast-like cells differentiated from mouse mesenchymal cells derived from fat, a promising source of starter cells for cell-based therapy. Using a convenient mouse pre-osteoblast model cell line MC3T3-E1 we further investigated this phenomenon showing that numerous osteoblast-expressed genes were elevated in response to DMSO treatment and correlated with enhanced mineralization. Myocyte enhancer factor 2c (Mef2c) was identified as the transcription factor most induced by DMSO, among numerous DMSO-induced genes, suggesting a role for Mef2c in osteoblast gene regulation. Immunohistochemistry confirmed expression of Mef2c in osteoblast-like cells in mouse mandible, cortical and trabecular bone. shRNAi-mediated Mef2c gene silencing resulted in defective osteoblast differentiation, decreased ALP activity and matrix mineralization and knockdown of osteoblast specific gene expression, including osteocalcin and bone sialoprotein. Flow on knockdown of bone specific transcription factors, Runx2 and osterix by shRNAi knockdown of Mef2c suggests that Mef2c lies upstream of these two important factors in the cascade of gene expression in osteoblasts.