Integrin αvβ3 upregulates integrin-linked kinase expression in human ovarian cancer cells via enhancement of ILK gene transcription

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.

The role of extreme sports in lifestyle enhancement and wellness

Alternative sports are fast becoming the physical activity of choice. Participation rates are even outstripping more traditional activities such as golf. At their most extreme there is no second chance, the most likely outcome of a mismanaged error or accident is death. At this level participants enjoy activities such as B.A.S.E. (Buildings, Antennae, Space, Earth) jumping, big wave surfing, waterfall kayaking, extreme skiing, rope-free climbing and extreme mountaineering. Probably the most common explanation for participation in extreme sports is the notion that participation is just a matter of some people‟s need to take unnecessary risks. This study reports on findings that indicate a more positive experience. A phenomenological method was used via unstructured interviews with 15 extreme sports participants (ages 30 – 72 years) and other firsthand accounts. Extreme sport participants directly related their experience to personal transformations that spill over to life in general. Athletes report feelings of deep psychological wellbeing and meaningfulness. The extreme sport experience enables a participant to break through personal barriers and develop an understanding of their own resourcefulness and emotional, cognitive, physical and spiritual capabilities. Furthermore such a breakthrough also seems to trigger a change in personal philosophy or view on life. The extreme sport experience transforms a participant though not in terms of working towards an external (social or cultural) perception of identity or towards some constructed perception of an ideal self, but by touching something within.

Robust speech recognition using speech enhancement

Automatic Speech Recognition (ASR) has matured into a technology which is becoming more common in our everyday lives, and is emerging as a necessity to minimise driver distraction when operating in-car systems such as navigation and infotainment. In “noise-free” environments, word recognition performance of these systems has been shown to approach 100%, however this performance degrades rapidly as the level of background noise is increased. Speech enhancement is a popular method for making ASR systems more ro- bust. Single-channel spectral subtraction was originally designed to improve hu- man speech intelligibility and many attempts have been made to optimise this algorithm in terms of signal-based metrics such as maximised Signal-to-Noise Ratio (SNR) or minimised speech distortion. Such metrics are used to assess en- hancement performance for intelligibility not speech recognition, therefore mak- ing them sub-optimal ASR applications. This research investigates two methods for closely coupling subtractive-type enhancement algorithms with ASR: (a) a computationally-efficient Mel-filterbank noise subtraction technique based on likelihood-maximisation (LIMA), and (b) in- troducing phase spectrum information to enable spectral subtraction in the com- plex frequency domain. Likelihood-maximisation uses gradient-descent to optimise parameters of the enhancement algorithm to best fit the acoustic speech model given a word se- quence known a priori. Whilst this technique is shown to improve the ASR word accuracy performance, it is also identified to be particularly sensitive to non-noise mismatches between the training and testing data. Phase information has long been ignored in spectral subtraction as it is deemed to have little effect on human intelligibility. In this work it is shown that phase information is important in obtaining highly accurate estimates of clean speech magnitudes which are typically used in ASR feature extraction. Phase Estimation via Delay Projection is proposed based on the stationarity of sinusoidal signals, and demonstrates the potential to produce improvements in ASR word accuracy in a wide range of SNR. Throughout the dissertation, consideration is given to practical implemen- tation in vehicular environments which resulted in two novel contributions – a LIMA framework which takes advantage of the grounding procedure common to speech dialogue systems, and a resource-saving formulation of frequency-domain spectral subtraction for realisation in field-programmable gate array hardware. The techniques proposed in this dissertation were evaluated using the Aus- tralian English In-Car Speech Corpus which was collected as part of this work. This database is the first of its kind within Australia and captures real in-car speech of 50 native Australian speakers in seven driving conditions common to Australian environments.

Improving governance : practical methods and an analytic framework for the enhancement of democracy

Seven endemic governance problems are shown to be currently present in governments around the globe and at any level of government as well (for example municipal, federal). These problems have their roots traced back through more than two thousand years of political, specifically ‘democratic’, history. The evidence shows that accountability, transparency, corruption, representation, campaigning methods, constitutionalism and long-term goals were problematic for the ancient Athenians as well as modern international democratisation efforts encompassing every major global region. Why then, given the extended time period humans have had to deal with these problems, are they still present? At least part of the answer to this question is that philosophers, academics and NGOs as well as MNOs have only approached these endemic problems in a piecemeal manner with a skewed perspective on democracy. Their works have also been subject to the ebbs and flows of human history which essentially started and stopped periods of thinking. In order to approach the investigation of endemic problems in relation to democracy (as the overall quest of this thesis was to generate prescriptive results for the improvement of democratic government), it was necessary to delineate what exactly is being written about when using the term ‘democracy’. It is common knowledge that democracy has no one specific definition or practice, even though scholars and philosophers have been attempting to create a definition for generations. What is currently evident, is that scholars are not approaching democracy in an overly simplified manner (that is, it is government for the people, by the people) but, rather, are seeking the commonalities that democracies share, in other words, those items which are common to all things democratic. Following that specific line of investigation, the major practiced and theoretical versions of democracy were thematically analysed. After that, their themes were collapsed into larger categories, at which point the larger categories were comparatively analysed with the practiced and theoretical versions of democracy. Four democratic ‘particles’ (selecting officials, law, equality and communication) were seen to be present in all practiced and theoretical democratic styles. The democratic particles fused with a unique investigative perspective and in-depth political study created a solid conceptualisation of democracy. As such, it is argued that democracy is an ever-present element of any state government, ‘democratic’ or not, and the particles are the bodies which comprise the democratic element. Frequency- and proximity-based analyses showed that democratic particles are related to endemic problems in international democratisation discourse. The linkages between democratic particles and endemic problems were also evident during the thematic analysis as well historical review. This ultimately led to the viewpoint that if endemic problems are mitigated the act may improve democratic particles which might strengthen the element of democracy in the governing apparatus of any state. Such may actively minimise or wholly displace inefficient forms of government, leading to a government specifically tailored to the population it orders. Once the theoretical and empirical goals were attained, this thesis provided some prescriptive measures which government, civil society, academics, professionals and/or active citizens can use to mitigate endemic problems (in any country and at any level of government) so as to improve the human condition via better democratic government.

Sustainable fashion textiles design : value adding through technological enhancement

A key concern in the field of contemporary fashion/textiles design is the emergence of ‘fast fashion’: best explained as "buy it Friday, wear it Saturday and throw it away on Sunday" (O'Loughlin, 2007). In this contemporary retail atmosphere of “pile it high: sell it cheap” and “quick to market”, even designer goods have achieved a throwaway status. This modern culture of consumerism is the antithesis of sustainability and is proving a dilemma surrounding sustainable practice for designers and producers in the disciplines (de Blas, 2010). Design researchers including those in textiles/fashion have begun to explore what is a key question in the 21st century in order to create a vision and reason for their disciplines: Can products be designed to have added value to the consumer and hence contribute to a more sustainable industry? Fashion Textiles Design has much to answer for in contributing to the problems of unsustainable practices on a global scale in design, production and waste. However, designers within this field also have great potential to contribute to practical ‘real world’ solutions. ----- ----- This paper provides an overview of some of the design and technological developments from the fashion/textiles industry, endorsing a model where designers and technicians use their transferrable skills for wellbeing rather than desire. Smart materials in the form of responsive and adaptive fibres and fabrics combined with electro active devices, and ICT are increasingly shaping many aspects of society particularly in the leisure industry and interactive consumer products are ever more visible in healthcare. Combinations of biocompatible delivery devices with bio sensing elements can create analyse, sense and actuate early warning and monitoring systems which can be linked to data logging and patient records via intelligent networks. Patient sympathetic, ‘smart’ fashion/textiles applications based on interdisciplinary expertise utilising textiles design and technology is emerging. An analysis of a series of case studies demonstrates the potential of fashion textiles design practitioners to exploit the concept of value adding through technological garment and textiles applications and enhancement for health and wellbeing and in doing so contribute to a more sustainable future fashion/textiles design industry.

Integrin αvβ3 mediates upregulation of epidermal growth-factor receptor expression and activity in human ovarian cancer cells

Upon overexpression of integrin αvβ3 and its engagement by vitronectin, we previously showed enhanced adhesion, proliferation, and motility of human ovarian cancer cells. By studying differential expression of genes possibly related to these tumor biological events, we identified the epidermal growth-factor receptor (EGF-R) to be under control of αvβ3 expression levels. Thus in the present study we characterized αvβ3-dependent changes of EGF-R and found significant upregulation of its expression and activity which was reflected by prominent changes of EGF-R promoter activity. Upon disruption of DNA-binding motifs for the transcription factors p53, ETF, the repressor ETR, p50, and c-rel, respectively, we sought to identify DNA elements contributing to αvβ3-mediated EGF-R promoter induction. Both, the p53- and ETF-mutant, while exhibiting considerably lower EGF-R promoter activity than the wild type promoter, retained inducibility by αvβ3. Mutation of the repressor motif ETR, as expected, enhanced EGF-R promoter activity with a further moderate increase upon αvβ3 elevation. The p50-mutant displayed EGF-R promoter activity almost comparable to that of the wild type promoter with no impairment of induction by αvβ3. However, the activity of an EGF-R promoter mutant displaying a disrupted c-rel-binding motif did not only prominently decline, but, moreover, was not longer responsive to enhanced αvβ3, involving this DNA element in αvβ3-dependent EGF-R upregulation. Moreover, αvβ3 did not only increase the EGF-R but, moreover, also led to obvious co-clustering on the cancer cell surface. By studying αvβ3/EGF-R-effects on the focal adhesion kinase (FAK) and the mitogen activated protein kinases (MAPK) p44/42 (erk−1/erk−2), having important functions in synergistic crosstalk between integrins and growth-factor receptors, we found for both significant enhancement of expression and activity upon αvβ3/VN interaction and cell stimulation by EGF. Upregulation of the EGF-R by integrin αvβ3, both receptor molecules with a well-defined role as targets for cancer treatment, might represent an additional mechanism to adapt synergistic receptor signaling and crosstalk in response to an altered tumor cell microenvironment during ovarian cancer progression.

Bluetooth and Wi-Fi MAC address based crowd data collection and monitoring : benefits, challenges and enhancement

This paper firstly presents the benefits and critical challenges on the use of Bluetooth and Wi-Fi for crowd data collection and monitoring. The major challenges include antenna characteristics, environment’s complexity and scanning features. Wi-Fi and Bluetooth are compared in this paper in terms of architecture, discovery time, popularity of use and signal strength. Type of antennas used and the environment’s complexity such as trees for outdoor and partitions for indoor spaces highly affect the scanning range. The aforementioned challenges are empirically evaluated by “real” experiments using Bluetooth and Wi-Fi Scanners. The issues related to the antenna characteristics are also highlighted by experimenting with different antenna types. Novel scanning approaches including Overlapped Zones and Single Point Multi-Range detection methods will be then presented and verified by real-world tests. These novel techniques will be applied for location identification of the MAC IDs captured that can extract more information about people movement dynamics.

Promotion of Homologous Recombination and Genomic Stability by RAD51AP1 via RAD51 Recombinase Enhancement

Homologous recombination (HR) repairs chromosome damage and is indispensable for tumor suppression in humans. RAD51 mediates the DNA strand-pairing step in HR. RAD51 associated protein 1 (RAD51AP1) is a RAD51-interacting protein whose function has remained elusive. Knockdown of RAD51AP1 in human cells by RNA interference engenders sensitivity to different types of genotoxic stress, and RAD51AP1 is epistatic to the HR protein XRCC3. Moreover, RAD51AP1-depleted cells are impaired for the recombinational repair of a DNA double-strand break and exhibit chromatid breaks both spontaneously and upon DNA-damaging treatment. Purified RAD51AP1 binds both dsDNA and a D loop structure and, only when able to interact with RAD51, greatly stimulates the RAD51-mediated D loop reaction. Biochemical and cytological results show that RAD51AP1 functions at a step subsequent to the assembly of the RAD51-ssDNA nucleoprotein filament. Our findings provide evidence that RAD51AP1 helps maintain genomic integrity via RAD51 recombinase enhancement.

Enhancement of the chemoprotective enzymes glucuronosyl transferase and glutathione transferase in specific organs of the rat by the coffee components kahweol and cafestol

The coffee components kahweol and cafestol (K/C) have been reported to protect the colon and other organs of the rat against the formation of DNA adducts by 2-amino-1-methyl-6-phenylimidazo[4,5-b] pyridine (PhIP) and aflatoxin B1. PhIP is a cooked-food mutagen to which significant human exposure and a role in colon cancer etiology are attributed, and, interestingly, such cancers appear to develop at a lower rate in consumers of coffees with high amounts of K/C. Earlier studies in rodent liver have shown that a key role in the chemopreventive effect of K/C is likely to be due to the potential of these compounds to induce the detoxification of xenobiotics by glutathione transferase (GST) and to enhance the synthesis of the corresponding co-factor glutathione. However, mutagens like PhIP may also be detoxified by UDP-glucuronosyl transferase (UDPGT) for which data are lacking regarding a potential effect of K/C. Therefore, in the present study, we investigated the effect of K/C on UDPGT and, concomitantly, we studied overall GST and the pattern of individual GST classes, particularly GST-θ, which was not included in earlier experiments. In addition, we analyzed the organ-dependence of these potentially chemopreventive effects. K/C was fed to male F344 rats at 0.122% in the chow for 10 days. Enzyme activities in liver, kidney, lung, colon, salivary gland, pancreas, testis, heart and spleen were quantified using five characteristic substrates and the hepatic protein pattern of GST classes α, μ, and π was studied with affnity chromatography/HPLC. Our study showed that K/C is not only capable of increasing overall GST and GST classes α, μ, and π but also of enhancing UDGPT and GST-θ. All investigated K/C effects were strongest in liver and kidney, and some response was seen in lung and colon but none in the other organs. In summary, our results show that K/C treatment leads to a wide spectrum of increases in phase II detoxification enzymes. Notably, these effects occurred preferentially in the well perfused organs liver and kidney, which may thus not only contribute to local protection but also to anti-carcinogenesis in distant, less stimulated organs such as the colon.

Nanostructured silver-gold bimetallic SERS substrates for selective identification of bacteria in human blood

Surface-enhanced Raman spectroscopy (SERS) is a potentially important tool in the rapid and accurate detection of pathogenic bacteria in biological fluids. However, for diagnostic application of this technique, it is necessary to develop a highly sensitive, stable, biocompatible and reproducible SERS-active substrate. In this work, we have developed a silver–gold bimetallic SERS surface by a simple potentiostatic electrodeposition of a thin gold layer on an electrochemically roughened nanoscopic silver substrate. The resultant substrate was very stable under atmospheric conditions and exhibited the strong Raman enhancement with the high reproducibility of the recorded SERS spectra of bacteria (E. coli, S. enterica, S. epidermidis, and B. megaterium). The coating of the antibiotic over the SERS substrate selectively captured bacteria from blood samples and also increased the Raman signal in contrast to the bare surface. Finally, we have utilized the antibiotic-coated hybrid surface to selectively identify different pathogenic bacteria, namely E. coli, S. enterica and S. epidermidis from blood samples.

More human than you: Attributing humanness to self and others

People typically evaluate their in-groups more favorably than out-groups and themselves more favorably than others. Research on infrahumanization also suggests a preferential attribution of the “human essence” to in-groups, independent of in-group favoritism. The authors propose a corresponding phenomenon in interpersonal comparisons: People attribute greater humanness to themselves than to others, independent of self-enhancement. Study 1 and a pilot study demonstrated 2 distinct understandings of humanness—traits representing human nature and those that are uniquely human—and showed that only the former traits are understood as inhering essences. In Study 2, participants rated themselves higher than their peers on human nature traits but not on uniquely human traits, independent of selfenhancement. Study 3 replicated this “self-humanization” effect and indicated that it is partially mediated by attribution of greater depth to self versus others. Study 4 replicated the effect experimentally. Thus, people perceive themselves to be more essentially human than others.

Treatment of silk fibroin with poly(ethylene glycol) for the enhancement of corneal epithelial cell growth

A silk protein, fibroin, was isolated from the cocoons of the domesticated silkworm (Bombyx mori) and cast into membranes to serve as freestanding templates for tissue-engineered corneal cell constructs to be used in ocular surface reconstruction. In this study, we sought to enhance the attachment and proliferation of corneal epithelial cells by increasing the permeability of the fibroin membranes and the topographic roughness of their surface. By mixing the fibroin solution with poly(ethylene glycol) (PEG) of molecular weight 300 Da, membranes were produced with increased permeability and with topographic patterns generated on their surface. In order to enhance their mechanical stability, some PEG-treated membranes were also crosslinked with genipin. The resulting membranes were thoroughly characterized and compared to the non-treated membranes. The PEG-treated membranes were similar in tensile strength to the non-treated ones, but their elastic modulus was higher and elongation lower, indicating enhanced rigidity. The crosslinking with genipin did not induce a significant improvement in mechanical properties. In cultures of a human-derived corneal epithelial cell line (HCE-T), the PEG treatment of the substratum did not improve the attachment of cells and it enhanced only slightly the cell proliferation in the longer term. Likewise, primary cultures of human limbal epithelial cells grew equally well on both non-treated and PEG-treated membranes, and the stratification of cultures was consistently improved in the presence of an underlying culture of irradiated 3T3 feeder cells, irrespectively of PEG-treatment. Nevertheless, the cultures grown on the PEG-treated membranes in the presence of feeder cells did display a higher nuclear-to-cytoplasmic ratio suggesting a more proliferative phenotype. We concluded that while the treatment with PEG had a significant effect on some structural properties of the B. mori silk fibroin (BMSF) membranes, there were minimal gains in the performance of these materials as a substratum for corneal epithelial cell growth. The reduced mechanical stability of freestanding PEG-treated membranes makes them a less viable choice than the non-treated membranes.

Selectivity of human retinotopic visual cortex to S-cone-opponent, L/M-cone-opponent and achromatic stimulation

Our aim was to make a quantitative comparison of the response of the different visual cortical areas to selective stimulation of the two different cone-opponent pathways [long- and medium-wavelength (L/M)- and short-wavelength (S)-cone-opponent] and the achromatic pathway under equivalent conditions. The appropriate stimulus-contrast metric for the comparison of colour and achromatic sensitivity is unknown, however, and so a secondary aim was to investigate whether equivalent fMRI responses of each cortical area are predicted by stimulus contrast matched in multiples of detection threshold that approximately equates for visibility, or direct (cone) contrast matches in which psychophysical sensitivity is uncorrected. We found that the fMRI response across the two colour and achromatic pathways is not well predicted by threshold-scaled stimuli (perceptual visibility) but is better predicted by cone contrast, particularly for area V1. Our results show that the early visual areas (V1, V2, V3, VP and hV4) all have robust responses to colour. No area showed an overall colour preference, however, until anterior to V4 where we found a ventral occipital region that has a significant preference for chromatic stimuli, indicating a functional distinction from earlier areas. We found that all of these areas have a surprisingly strong response to S-cone stimuli, at least as great as the L/M response, suggesting a relative enhancement of the S-cone cortical signal. We also identified two areas (V3A and hMT+) with a significant preference for achromatic over chromatic stimuli, indicating a functional grouping into a dorsal pathway with a strong magnocellular input.