Expression of c-ets-1 mRNA is associated with an invasive, EMT-derived phenotype in breast carcinoma cell lines

We have previously observed in vitro that some stromal proteinases (MMP- 2, MT1-MMP) were expressed or activated by invasive carcinoma cell lines exhibiting mesenchymal features, presumably acquired through an epithelial to mesenchymal transition (EMT). To examine the potential contribution of c- ets-1 to this phenotype, we have compared here the expression of c-ets-1 with invasiveness in vitro and expression of vimentin, E-cadherin, uPA, MMP-1 and MMP-3 in a panel of human breast cancer cell lines. Our results clearly demonstrate an association between c-ets-1 expression and the invasive, EMT- derived phenotype, which is typified by the expression of vimentin and the lack of E-cadherin. While absent from the two non-invasive, vimentin-negative cell lines, c-ets-1 was abundantly expressed in all the four vimentin- positive lines. However, we could not find a clear quantitative or qualitative relationship between the expression of c-ets-1 and the three proteinases known to he regulated by c-ets-1, except that when they were expressed, it was only in the invasive c-ets-1-positive lines. UPA mRNAs were found in three of the four vimentin-positive lines, MMP-1 in two of the four, and MMP-3 could not be detected in any of the cell lines. Intriguingly, MDA- MB-435 cells, which exhibit the highest metastatic potential of these cell lines in nude mice, expressed vimentin and c-ets-1, but lacked expression of these three proteinases, at least under the culture conditions employed. Taken together, our results show that c-ets-1 expression is associated with an invasive, EMT-derived phenotype in breast cancer cells, although it is apparently not sufficient to ensure the expression of uPA, MMP-1 or MMP-3, in the vimentin-positive cells. Such proteases regulation is undoubtedly qualified by the cellular context. This study therefore advances our understanding of the molecular regulation of invasiveness in EMT-associated carcinoma progression, and suggests that c-ets-1 may contribute to the invasive phenotype in carcinoma cells.

Never too old : engaging retired people inventing the future with MaKey MaKey

Within HCI, aging is often viewed in terms of designing assistive technologies to improve the lives of older people, such as those who are suffering from frailty or memory loss. Our research adopts a very different approach, reframing the relationship in terms of wisdom, creativity and invention. We ran a series of workshops where groups of retirees, aged between early 60s and late 80s, used the MaKey MaKey inventor's toolkit. We asked them to think about inventing the future and suggest ideas for new technologies. Our findings showed that they not only rose to the challenge but also mastered the technology, collaborated intensely together while using it and freely and at length discussed their own, their family's and others' relationship with technology. We discuss the value of empowering people in this way and consider what else could be invented to enable more people to be involved in the design and use of creative technologies.

Beyond ethnography: Engagement and reciprocity as foundations for design research out here

This paper explores an emerging paradigm for HCI design research based primarily upon engagement, reciprocity and doing. Much HCI research begins with an investigatory and analytic ethnographic approach before translating to design. Design may come much later in the process and may never benefit the community that is researched. However in many settings it is difficult for researchers to access the privileged ethnographer position of observer and investigator. Moreover rapid ethnographic research often does not seem the best or most appropriate course of action. We draw upon a project working with a remote Australian Aboriginal community to illustrate an alternative approach in Indigenous research, where the notion of reciprocity is first and foremost. We argue that this can lead to sustainable designs, valid research and profound innovation. This paper received the ACM CHI Best Paper Award, which is awarded to the top 1% of papers submitted to the ACM CHI conference.

The effect of multiplayer dynamic difficulty adjustment on the player experience of video games

Multiplayer Dynamic Difficulty Adjustment (mDDA) is a method of reducing the difference in player performance and subsequent challenge in competitive multiplayer video games. As a balance of between player skill and challenge experienced is necessary for optimal player experience, this experimental study investigates the effects of mDDA and awareness of its presence on player performance and experience using subjective and biometric measures. Early analysis indicates that mDDA normalizes performance and challenge as expected, but awareness of its presence can reduce its effectiveness.

Autonomy in technology design

Issues of autonomy impact motivation, the user experience and even psychological wellbeing, yet many questions surrounding design for autonomy remain unanswered. This workshop will explore theory, issues and design strategies related to autonomy drawing on theoretical frameworks available in psychology and looking at autonomy from multiple levels. These include user autonomy within the context of software environments, technologies that increase autonomy in daily life, and how technologies might foster autonomy as a component of psychological development.

Invisible connections : investigating older people's emotions and social relations around objects

The advent of the Internet of Things creates an interest in how people might interrelate through and with networks of internet enabled objects. With an emphasis on fostering social connection and physical activity among older people, this preliminary study investigated objects that people over the age of 65 years viewed as significant to them. We conducted contextual interviews in people's homes about their significant objects in order to understand the role of the objects in their lives, the extent to which they fostered emotional and social connections and physical activity, and how they might be augmented through internet connection. Discussion of significant objects generated considerable emotion in the participants. We identified objects of comfort and routine, objects that exhibited status, those that fostered independence and connection, and those that symbolized relationships with loved ones. These findings lead us to consider implications for the design of interconnected objects.

High level of MT-MMP expression is associated with invasiveness of cervical cancer cells

MMP-2 (gelatinase A) has been associated with the invasive potential of many cancer cells both in vitro and in vivo. It is now becoming clear that the activation of this enzyme might be a key step in tumor invasion. This activation process has been shown to be a membrane-associated pathway inducible by various agents such as collagen type I, concanavalin A or TGF-β, but its physiological regulation is still largely unresolved. MT-MMP was recently discovered and described as a potential gelatinase-A activator. In the present study, we investigated the expression of MT-MMP (membrane-type metalloproteinase) in cervical cancer cells both in vitro and in vivo. Comparing several in vitro-transformed cervical cell lines, previously shown to display different invasive potentials, our results showed that the ability of cells to overexpress MT-MMP mRNA following ConA induction correlated with their ability to activate gelatinase A and with a highly invasive behavior. Moreover, using immunohistochemistry and in situ hybridization, we found a higher level of MT-MMP expression in invasive cervical carcinoma and lymphnode metastases compared to its expression in non-invasive CIN III lesions. Our in vivo observations also clearly demonstrated a cooperation between stromal and tumor cells for the production of MT-MMP. Taken together, our results clearly correlated high level MT-MMP expression with invasiveness, and thus suggested that MT-MMP might play a crucial role in cervical tumor invasion.

SCRAMSPACE : Radical-Farming Scramjet for access to space

Scramjet-based launch systems offer considerable promise for safe, reliable and economical access to space. A general Scramjets introduction is first provided, followed by the specifics of Australian Scramjet Research and the recent progress in inlet-injection radical-farming scramjets as part of the SCRAMSPACE program. Through both flight and ground tests, leveraging Australias world leadership in scramjet R&D, the SCRAMSPACE project is designed to answer key scientific and technological questions and build an industry-ready talent pool for a future Australian space industry. An extensive descriptions of all phases of the development of the SCRAMSPACE I scramjet-powered free-flight experiment are described in these lecture notes.

Unbalance identification in large steam turbo-generator unit using a model-based method

Fault identification in industrial machine is a topic of major importance under engineering point of view. In fact, the possibility to identify not only the type, but also the severity and the position of a fault occurred along a shaft-line allows quick maintenance and shorten the downtime. This is really important in the power generation industry where the units are often of several tenths of meters long and where the rotors are enclosed by heavy and pressure-sealed casings. In this paper, an industrial experimental case is presented related to the identification of the unbalance on a large size steam turbine of about 1.3 GW, belonging to a nuclear power plant. The case history is analyzed by considering the vibrations measured by the condition monitoring system of the unit. A model-based method in the frequency domain, developed by the authors, is introduced in detail and it is then used to identify the position of the fault and its severity along the shaft-line. The complete model of the unit (rotor – modeled by means of finite elements, bearings – modeled by linearized damping and stiffness coefficients and foundation – modeled by means of pedestals) is analyzed and discussed before being used for the fault identification. The assessment of the actual fault was done by inspection during a scheduled maintenance and excellent correspondence was found with the identified one by means of authors’ proposed method. Finally a complete discussion is presented about the effectiveness of the method, even in presence of a not fine tuned machine model and considering only few measuring planes for the machine vibration.

Supramolecular organization in fluorene/indenofluorene-oligothiophene alternating conjugated copolymers

A series of conjugated copolymers containing fluorene or indenofluorene units alternating with oligothiophene segments, with potential interest for use as the active layer in field-effect transistors, is investigated. Atomic force microscopy analysis of the morphology of thin deposits shows either the formation of fibrillar structures, which are the signature of long-range π stacking, or the presence of untextured aggregates, resulting from disordered assembly. These morphologies are interpreted in terms of the supramolecular organization of the conjugated chains. Molecular modeling simulations indicate that the commensurability between the lengths of the monomer units and the presence of alkyl side groups are the two key structural factors governing the chain organization into highly ordered assemblies. The most favorable structures are those combining fluorene (indenofluorene) units with unsubstituted bithiophene (terthiophene) segments.

Configuring retroreflective markings to enhance the night-time conspicuity of road workers

This study investigated whether the night-time conspicuity of road workers can be enhanced by positioning retroreflective strips on the moveable joints in patterns that convey varying degrees of biological motion. Participants were 24 visually normal adults (12 young M = 26.8 years; 12 older M = 72.9 years). Visual acuity, contrast sensitivity and glare sensitivity were recorded for each participant. Experimenters acting as road workers walked in place on a closed road circuit within simulated road work sites, facing either the oncoming driver or the roadway (presenting sideways to the driver) and wearing one of four clothing conditions: (i) standard road worker vest; (ii) standard vest plus thigh-mounted retroreflective strips; (iii) standard vest plus retroreflective strips on ankles and knees; (iv) standard vest plus retroreflective strips positioned on the extremities in a configuration that conveyed biological motion (“biomotion”). As they drove along the closed road participants were instructed to press a button to indicate when they first recognized that a road worker was present. The results demonstrated that regardless of the direction of walking, road workers wearing biomotion clothing were recognized at significantly (p < 0.05) longer distances (3×), relative to the standard vest alone. Response distances were significantly shorter for the older drivers. Contrast sensitivity was a better predictor of the ability to recognize road workers than was visual acuity or glare sensitivity. We conclude that adding retroreflective strips in the biomotion configuration can significantly improve road worker conspicuity regardless of the road worker's orientation and the age of the driver.

Differential effects of refractive blur on day and night-time driving performance

Purpose To investigate the effect of different levels of refractive blur on real-world driving performance measured under day and nighttime conditions. Methods Participants included 12 visually normal, young adults (mean age = 25.8 ± 5.2 years) who drove an instrumented research vehicle around a 4 km closed road circuit with three different levels of binocular spherical refractive blur (+0.50 diopter sphere [DS], +1.00 DS, +2.00 DS) compared with a baseline condition. The subjects wore optimal spherocylinder correction and the additional blur lenses were mounted in modified full-field goggles; the order of testing of the blur conditions was randomized. Driving performance was assessed in two different sessions under day and nighttime conditions and included measures of road signs recognized, hazard detection and avoidance, gap detection, lane-keeping, sign recognition distance, speed, and time to complete the course. Results Refractive blur and time of day had significant effects on driving performance (P < 0.05), where increasing blur and nighttime driving reduced performance on all driving tasks except gap judgment and lane keeping. There was also a significant interaction between blur and time of day (P < 0.05), such that the effects of blur were exacerbated under nighttime driving conditions; performance differences were evident even for +0.50 DS blur relative to baseline for some measures. Conclusions The effects of blur were greatest under nighttime conditions, even for levels of binocular refractive blur as low as +0.50 DS. These results emphasize the importance of accurate and up-to-date refractive correction of even low levels of refractive error when driving at night.