492 resultados para TIME-LIKE GEODESICS


Relevância:

20.00% 20.00%

Publicador:

Resumo:

The interpretation of evidence dominates contemporary television crime shows. Inanimate objects and disparate facts are made to speak; technology and expert opinion wring out their stories. In examining these dead pieces of evidence, the investigators search for patterns, discovering living perpetrators and fugitives. Psychology comes in where the evidence is interpreted; the investigators try to think through perpetrators' minds and presumably perverse rationales. Objects are examined. Banal things become precious, put into bags, marked, date- and time-stamped, and stepped around carefully. After a crime, the objects involved are different. After a crime show, our gaze is different; everything is potentially incriminating, perverse. Bags without people don't make sense. Under this gaze, objects acquire a psychology. When we look at a crime scene, the evidence violates us. The work of Melbourne artist Cate Consandine is about objects and how they occupy the space that they occupy. In her practice as a sculptor and throughout her studies at the Victorian College of the Arts, the Sydney College of the Arts, and now Monash, her work has cultivated violent ambiguity. Consandine's work extends across a range of different media, particularly vidoe, objects and spaces. Like a crime show, it activates a particular type of inquisition from the viewer.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Drivers' ability to react to unpredictable events deteriorates when exposed to highly predictable and uneventful driving tasks. Particularly, highway design reduces the driving task mainly to a lane-keeping one. It contributes to hypovigilance and road crashes as drivers are often not aware that their driving behaviour is impaired. Monotony increases fatigue, however, the fatigue community has mainly focused on endogenous factors leading to fatigue such as sleep deprivation. This paper focuses on the exogenous factor monotony which contributes to hypovigilance. Objective measurements of the effects of monotonous driving conditions on the driver and the vehicle's dynamics is systematically reviewed with the aim of justifying the relevance of the need for a mathematical framework that could predict hypovigilance in real-time. Although electroencephalography (EEG) is one of the most reliable measures of vigilance, it is obtrusive. This suggests to predict from observable variables the time when the driver is hypovigilant. Outlined is a vision for future research in the modelling of driver vigilance decrement due to monotonous driving conditions. A mathematical model for predicting drivers’ hypovigilance using information like lane positioning, steering wheel movements and eye blinks is provided. Such a modelling of driver vigilance should enable the future development of an in-vehicle device that detects driver hypovigilance in advance, thus offering the potential to enhance road safety and prevent road crashes.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Synthetic polymers have attracted much attention in tissue engineering due to their ability to modulate biomechanical properties. This study investigated the feasibility of processing poly(varepsilon-caprolactone) (PCL) homopolymer, PCL-poly(ethylene glycol) (PEG) diblock, and PCL-PEG-PCL triblock copolymers into three-dimensional porous scaffolds. Properties of the various polymers were investigated by dynamic thermal analysis. The scaffolds were manufactured using the desktop robot-based rapid prototyping technique. Gross morphology and internal three-dimensional structure of scaffolds were identified by scanning electron microscopy and micro-computed tomography, which showed excellent fusion at the filament junctions, high uniformity, and complete interconnectivity of pore networks. The influences of process parameters on scaffolds' morphological and mechanical characteristics were studied. Data confirmed that the process parameters directly influenced the pore size, porosity, and, consequently, the mechanical properties of the scaffolds. The in vitro cell culture study was performed to investigate the influence of polymer nature and scaffold architecture on the adhesion of the cells onto the scaffolds using rabbit smooth muscle cells. Light, scanning electron, and confocal laser microscopy showed cell adhesion, proliferation, and extracellular matrix formation on the surface as well as inside the structure of both scaffold groups. The completely interconnected and highly regular honeycomb-like pore morphology supported bridging of the pores via cell-to-cell contact as well as production of extracellular matrix at later time points. The results indicated that the incorporation of hydrophilic PEG into hydrophobic PCL enhanced the overall hydrophilicity and cell culture performance of PCL-PEG copolymer. However, the scaffold architecture did not significantly influence the cell culture performance in this study.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The theme of this conference comes from the epitaph on the Lewis Carroll’s gravesite. “Is All our Life then But A Dream?” This seems fitting for a time when so much change in the terrain of English makes us feel as if we are somnambulating through a surrealist landscape. Like Lewis Carroll’s Alice, (Carroll, 2003) we might find ourselves at strange tea parties with bureaucratic mad hatters, and just when we think we have a grasp of applying new theory in our teaching, we fall down another rabbit hole, to swim in confusion as some queen calls out, ‘off with their heads!’. The shifting ground in English inevitably moves in response to waves of theory influencing classroom practice. Each new paradigm has claimed to liberate language learners from the flaws of the previous model. Each linguist or literary theorist who shaped the new paradigm no doubt dreamt of a new population emerging from school as more powerfully literate citizens than the previous generation.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Height is a complex physical trait that displays strong heritability. Adult height is related to length of the long bones, which is determined by growth at the epiphyseal growth plate. Longitudinal bone growth occurs via the process of endochondral ossification, where bone forms over the differentiating cartilage template at the growth plate. Estrogen plays a major role in regulating longitudinal bone growth and is responsible for inducing the pubertal growth spurt and fusion of the epiphyseal growth plate. However, the mechanism by which estrogen promotes epiphyseal fusion is poorly understood. It has been hypothesised that estrogen functions to regulate growth plate fusion by stimulating chondrocyte apoptosis, angiogenesis and bone cell invasion in the growth plate. Another theory has suggested that estrogen exposure exhausts the proliferative capacity of growth plate chondrocytes, which accelerates the process of chondrocyte senescence, leading to growth plate fusion. The overall objective of this study was to gain a greater understanding of the molecular mechanisms behind estrogen-mediated growth and height attainment by examining gene regulation in chondrocytes and the role of some of these genes in normal height inheritance. With the heritability of height so well established, the initial hypothesis was that genetic variation in candidate genes associated with longitudinal bone growth would be involved in normal adult height variation. The height-related genes FGFR3, CBFA1, ER and CBFA1 were screened for novel polymorphisms using denaturing HPLC and RFLP analysis. In total, 24 polymorphisms were identified. Two SNPs in ER (rs3757323 C>T and rs1801132 G>C) were strongly associated with adult male height and displayed an 8 cm and 9 cm height difference between homozygous genotypes, respectively. The TC haplotype of these SNPs was associated with a 6 cm decrease in height and remarkably, no homozygous carriers of the TC haplotype were identified in tall subjects. No significant associations with height were found for polymorphisms in the FGFR3, CBFA1 or VDR genes. In the epiphyseal growth plate, chondrocyte proliferation, matrix synthesis and chondrocyte hypertrophy are all major contributors to long bone growth. As estrogen plays such a significant role in both growth and final height attainment, another hypothesis of this study was that estrogen exerted its effects in the growth plate by influencing chondrocyte proliferation and mediating the expression of chondrocyte marker genes. The examination of genes regulated by estrogen in chondrocyte-like cells aimed to identify potential regulators of growth plate fusion, which may further elucidate mechanisms involved in the cessation of linear growth. While estrogen did not dramatically alter the proliferation of the SW1353 cell line, gene expression experiments identified several estrogen regulated genes. Sixteen chondrocyte marker genes were examined in response to estrogen concentrations ranging from 10-12 M to 10-8 M over varying time points. Of the genes analysed, IHH, FGFR3, collagen II and collagen X were not readily detectable and PTHrP, GHR, ER, BMP6, SOX9 and TGF1 mRNAs showed no significant response to estrogen treatments. However, the expression of MMP13, CBFA1, BCL-2 and BAX genes were significantly decreased. Interestingly, the majority of estrogen regulated genes in SW1353 cells are expressed in the hypertrophic zone of the growth plate. Estrogen is also known to regulate systemic GH secretion and local GH action. At the molecular level, estrogen functions to inhibit GH action by negatively regulating GH signalling. GH treated SW1353 cells displayed increases in MMP9 mRNA expression (4.4-fold) and MMP13 mRNA expression (64-fold) in SW1353 cells. Increases were also detected in their respective proteins. Treatment with AG490, an established JAK2 inhibitor, blocked the GH mediated stimulation of both MMP9 and MMP13 mRNA expression. The application of estrogen and GH to SW1353 cells attenuated GH-stimulated MMP13 levels, but did not affect MMP9 levels. Investigation of GH signalling revealed that SW1353 cells have high levels of activated JAK2 and exposure to GH, estrogen, AG490 and other signalling inhibitors did not affect JAK2 phosphorylation. Interestingly, AG490 treatment dramatically decreased ERK2 signalling, although GH did stimulate ERK2 phosphorylation above control levels. AG490 also decreased CBFA1 expression, a transcription factor known to activate MMP9 and MMP13. Finally, GH and estrogen treatment increased expression of SOCS3 mRNA, suggesting that SOCS3 may regulate JAK/STAT signalling in SW1353 cells. The modulation of GH-mediated MMP expression by estrogen in SW1353 cells represents a potentially novel mechanism by which estrogen may regulate longitudinal bone growth. However, further investigation is required in order to elucidate the precise mechanisms behind estrogen and GH regulation of MMP13 expression in SW1353 cells. This study has provided additional evidence that estrogen and the ER gene are major factors in the regulation of growth and the determination of adult height. Newly identified polymorphisms in the ER gene not only contribute to our understanding of the genetic basis of human height, but may also be useful in association studies examining other complex traits. This study also identified several estrogen regulated genes and indicated that estrogen modifies the expression of genes which are primarily expressed in the hypertrophic region of the epiphyseal growth plate. Furthermore, synergistic studies incorporating GH and estrogen have revealed the ability of estrogen to attenuate the effects of GH on MMP13 expression, revealing potential pathways by which estrogen may modulate growth plate fusion, longitudinal bone growth and even arthritis.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

In this third Quantum Interaction (QI) meeting it is time to examine our failures. One of the weakest elements of QI as a field, arises in its continuing lack of models displaying proper evolutionary dynamics. This paper presents an overview of the modern generalised approach to the derivation of time evolution equations in physics, showing how the notion of symmetry is essential to the extraction of operators in quantum theory. The form that symmetry might take in non-physical models is explored, with a number of viable avenues identified.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Following an early claim by Nelson & McEvoy suggesting that word associations can display `spooky action at a distance behaviour', a serious investigation of the potentially quantum nature of such associations is currently underway. In this paper quantum theory is proposed as a framework suitable for modelling the mental lexicon, specifically the results obtained from both intralist and extralist word association experiments. Some initial models exploring this hypothesis are discussed, and they appear to be capable of substantial agreement with pre-existing experimental data. The paper concludes with a discussion of some experiments that will be performed in order to test these models.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

For a number of years now it has been evident that the major issue facing science educators in the more developed countries of the world is the quantitative decline in enrolments in the senior secondary sciences, particularly the physical sciences, and in the number of higher achieving students applying for places in universities to undertake further studies in science. The deep malaise in school science to which these quantitative measures point has been elucidated by more qualitative studies of the students’ experience of studying science in secondary school in several of these countries (Sweden, Lindahl (2003); England, Simon and Osborne (2002); and Australia, Lyons (2005)). Remarkably concordant descriptions of these experiences can be summarized as: School science is: • transmission of knowledge from the teacher or the textbook to the students. • about content that is irrelevant and boring to our lives. • difficult to learn in comparison with other subjects Incidentally, the Australian study only involved consistently high achieving students; but even so, most of them found science more difficult than other more interesting subjects, and concluded that further science studies should be avoided unless they were needed for some career purpose. Other more representative confirmations of negative evaluations of the science curricula across Australia (and in particular states) are now available in Australia, from the large scale reviews of Goodrum, Hackling and Rennie (2001) and from the TIMSS (2002). The former reported that well under half of secondary students find the science at school relevant to my future, useful ion everyday life, deals with things I am concerned with and helps me make decisions about my health.. TIMSS found that 62 and 65 % of females and males in Year 4 agree with I like learning science, but by Year 8 only 26 and 33 % still agree. Students in Japan have been doubly notably because of (a) their high performance in international measures of science achievement like TIMSS and PISA and (b) their very low response to items in these studies which relate to interest in science. Ogura (2003) reported an intra-national study of students across Years 6-9 (upper primary through Junior High); interest in a range of their subjects (including science) that make up that country’s national curriculum. There was a steady decline in interest in all these subjects which might have indicated an adolescent reaction against schooling generally. However, this study went on to ask the students a further question that is very meaningful in the Japanese context, If you discount the importance of this subject for university entrance, is it worth studying? Science and mathematics remained in decline while all the other subjects were seen more positively. It is thus ironic, at a time when some innovations in curriculum and other research-based findings are suggesting ways that these failures of school science might be corrected, to find school science under a new demands that come from quite outside science education, and which certainly do not have the correction of this malaise as a priority. The positive curricular and research findings can be characterized as moves from within science education, whereas the new demands are moves that come from without science education. In this paper I set out these two rather contrary challenges to the teaching of science as it is currently practised, and go on to suggest a way forward that could fruitfully combine the two.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

President’s Report Hello fellow AITPM members, Welcome to the first edition of the AITPM National Newsletter for 2009! I trust we all had a relaxing break and managed to lose track of all things transport for just a little while. I know I had trouble doing so when hunting for a car space at the shopping centre, and experiencing new projects such as the Tugun Bypass – the new gateway between New South Wales and Queensland. Byron Bay is now as close as Noosa for those high profile beach goers of Brisbane. There was also my experience of the reduced posted speed of 90km/h on the Bruce Highway around the troublesome Gympie stretch, when returning from a short Fraser Coast holiday. I expect that this relatively inexpensive safety improvement will pay substantial dividends in terms of crash reduction. The Newsletter took its annual leave last month and is refreshed and ready for a new year to keep us all informed of the latest in traffic and transport engineering, planning and management. I would like to take this opportunity to acknowledge the ongoing significant contributions of many volunteers in the Newsletter’s production. Mr Andrew Hulse, AITPM’s Immediate Past National President, serves as the Editorial Coordinator on behalf of the Institute. Each Branch Committee also includes a Newsletter Coordinator and committee members frequently contribute as well. And the ongoing contributions of readers enable us to offer the Newsletter as a vehicle for dialogue and debate around our sector. If you would like to contribute please email AITPM’s administration officer Josephine Mitton at aitpm@aitpm.com or through your local Branch Committee. I would also like to welcome back on deck our Editor, Mr David Brown of Driven Media, who creates a fantastic package for us each month. Lastly, members would have received the Call for Papers for the AITPM 2009 National Conference, Traffic Beyond Tomorrow, to be held at the Adelaide Convention Centre between 5 – 7 August. Abstracts will be accepted up to 20 February 2009. We look forward to seeing everyone at this, our flagship event for the year. To all a good year ahead, Jon Bunker Post Script: We all will have seen through the media the enormous scale and nature of the two natural disasters Australia is experiencing at present. AITPM’s thoughts are with all of those members, family and friends who may be experiencing hardship as a result of the Victorian bushfires and North Queensland floods. AITPM is a not for profit organisation however the National Executive has taken the decision to donate in measure to the Red Cross Victorian Bushfire Disaster Relief fund and the Queensland Premier’s Disaster Relief fund as a gesture to support our fellow Australians in their time of need. Details about these funds can be found via the Victorian and Queensland Governments’ websites.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

President’s Report Hello fellow AITPM members, First I would like on behalf of all AITPM members to send our condolences to all who have been affected by February’s tragic bushfires in regional Victoria, and deliver our best wishes to all of those involved in the rebuilding efforts. Over time I expect that the Victorian Government’s Royal Commission will analyse the circumstances and put forward a range of measures which will improve fire safety in vulnerable areas. As transport professionals it will be important for us to consider the findings and look to undertaking any recommendations that relate to the work we do. Not only in Victoria, but nationwide. In particular, the importance of logistics was highlighted following the fire events. Donors across Australia were this time requested to donate money rather than goods, presumably due in part to problems associated with the transport system coping with additional uncoordinated freight load, whilst being needed to support emergency management vehicle and managed freight movements. Notwithstanding, it was wonderful to see otherwise difficult to obtain goods, such as animal feed, being donated from far afield and transported in kind by trucking operators. As stated in last month’s Newsletter, AITPM made a direct cash donation to the Red Cross Bushfire Appeal immediately following the events, and a further donation to the Queensland Premier’s Disaster Relief Fund to support recovery after the North Queensland floods, which claimed seven lives. Again, we will need to monitor how the rebuilding effort unfolds particularly in regional Victoria and centres including Ingham in North Queensland, but I would urge all AITPM members who are in a position to support the restoration of the affected communities to play a part, particularly over time once the initial shock subsides and the steady job of rebuilding is underway. Onto lighter matters, AITPM’s flagship event, the 2009 AITPM National Conference, Traffic Beyond Tomorrow, being held in Adelaide from 5 to 7 August, is fast approaching. www.aitpm.com has all of the details about how to register, sponsor a booth, and so forth. We are looking forward to catching up with our conference “regulars” and meeting with new folks to AITPM, and Australian traffic and transport planning and management. Adelaide is one of my favourite places to visit and I’m looking forward to riding the light rail line extension through town and checking out progress on the road system development. Best regards all, Jon Bunker

Relevância:

20.00% 20.00%

Publicador:

Resumo:

President’s Report Hello fellow AITPM members, A few weeks ago we saw another example of all levels of Government pulling together in real time to try to deal with a major transport incident, this time it was container loads of ammonium nitrate falling off the Pacific Adventurer during Cyclone Hamish and the associated major oil spill due to piercing of its hull off Moreton Bay in southern Queensland. The oil spill was extensive, affecting beaches and estuaries from Moreton Island north to the Sunshine Coast; a coastal stretch of at least 60km. We saw the Queensland Government, Brisbane, Moreton Bay and Sunshine Coast Regional Council crews deployed quickly once the gravity of the situation was realised to clean up toxic oil on beaches and prevent extensive upstream contamination. Environmental agencies public and private were quick to respond to help affected wildlife. The Navy’s HMAS Yarra and another minesweeper were deployed to search for the containers in the coastal area in an effort to have them salvaged before all ammonium nitrate could leach into and harm marine habitat, which would have a substantial impact not only on that environment but also the fishing industry. all of this during the final fortnight before a State election.) While this could be branded as a maritime problem, the road transport and logistics system was crucial to the cleanup. The private vehicular ferries were enlisted to transport plant and equipment from Brisbane to Moreton Island. The plant themselves, such as graders, were drawn from road building and maintenance inventory. Hundreds of Councils’ staff were released from other activities to undertake the cleanup. While it will take some time for us to know the long term impacts of this incident, it seems difficult to fault “grassroots” government crews and their private counterparts, such as Island tourism staff, in the initial cleanup effort. From a traffic planning and management perspective, we should also remember that this sort of incident has happened on road and rail corridors in the past, albeit on lesser scales. It underlines that we do need to continue to protect communities, commercial interests, and the environment through rigorous heavy vehicle management, planning and management of dangerous goods routesincluding rail corridors through urban areas), and carefully considered incident and disaster recovery plans and protocols. I’d like to close in reminding everyone again that AITPM’s flagship event, the 2009 AITPM National Conference, Traffic Beyond Tomorrow, is being held in Adelaide from 5 to 7 August. SA Branch President Paul Morris informs me that we have had over 50 paper submissions to date, from which a very balanced and informative programme of sessions has been prepared. www.aitpm.com has all of the details about how to register, sponsor a booth, session, etc. Best regards all, Jon Bunker

Relevância:

20.00% 20.00%

Publicador:

Resumo:

Sex hormone-binding globulin (SHBG) is a homodimeric plasma glycoprotein that is the major sex steroid carrier-protein in the bloodstream and functions also as a key regulator of steroid bioavailability within target tissues, such as the prostate. Additionally, SHBG binds to prostatic cell membranes via the putative and unidentified SHBG receptor (RSHBG), activating a signal transduction pathway implicated in stimulating both proliferation and expression of prostate specific antigen (PSA) in prostate cell lines in vitro. A yeast-two hybrid assay suggested an interaction between SHBG and kallikrein-related protease (KLK) 4, which is a serine protease implicated in the progression of prostate cancer. The potential interaction between these two proteins was investigated in this PhD thesis to determine whether SHBG is a proteolytic substrate of KLK4 and other members of the KLK family including KLK3/PSA, KLK7 and KLK14. Furthermore, the effects from SHBG proteolytic degradation on SHBG-regulated steroid bioavailability and the activation of the putative RSHBG signal transduction pathway were examined in the LNCaP prostate cancer cell line. SHBG was found to be a proteolytic substrate of the trypsin-like KLK4 and KLK14 in vitro, yielding several proteolysis fragments. Both chymotrypsin-like PSA and KLK7 displayed insignificant proteolytic activity against SHBG. The kinetic parameters of SHBG proteolysis by KLK4 and KLK14 demonstrate a strong enzyme-substrate binding capacity, possessing a Km of 1.2 ± 0.7 µM and 2.1 ± 0.6 µM respectively. The catalytic efficiencies (kcat/Km) of KLK4 and KLK14 proteolysis of SHBG were 1.6 x 104 M-1s-1 and 3.8 x 104 M-1s-1 respectively, which were comparable to parameters previously reported for peptide substrates. N-terminal sequencing of the fragments revealed cleavage near the junction of the N- and C-terminal laminin globulin-like (G-like) domains of SHBG, resulting in the division of the two globulins and ultimately the full degradation of these fragments by KLK4 and KLK14 over time. Proteolytic fragments that may retain steroid binding were rapidly degraded by both proteases, while fragments containing residues beyond the steroid binding pocket were less degraded over the same period of time. Degradation of SHBG was inhibited by the divalent metal cations calcium and zinc for KLK4, and calcium, zinc and magnesium for KLK14. The human secreted serine protease inhibitors (serpins), α1-antitrypsin and α2-antiplasmin, inhibited KLK4 and KLK14 proteolysis of SHBG; α1-antichymotrypsin inhibited KLK4 but not KLK14 activity. The inhibition by these serpins was comparable and in some cases more effective than general trypsin protease inhibitors such as aprotinin and phenylmethanesulfonyl fluoride (PMSF). The binding of 5α-dihydrotestosterone (DHT) to SHBG modulated interactions with KLK4 and KLK14. Steroid-free SHBG was more readily digested by both enzymes than DHT-bound SHBG. Moreover, a binding interaction exists between SHBG and pro-KLK4 and pro-KLK14, with DHT strengthening the binding to pro-KLK4 only. The inhibition of androgen uptake by cultured prostate cancer cells, mediated by SHBG steroid-binding, was examined to assess whether SHBG proteolysis by KLK4 and KLK14 modulated this process. Proteolytic digestion eliminated the ability of SHBG to inhibit the uptake of DHT from conditioned media into LNCaP cells. Therefore, the proteolysis of SHBG by KLK4 and KLK14 increased steroid bioavailability in vitro, leading to an increased uptake of androgens by prostate cancer cells. Interestingly, different transcriptional responses of PSA and KLK2, which are androgen-regulated genes, to DHT-bounsd SHBG treatment were observed between low and high passage number LNCaP cells (lpLNCaP and hpLNCaP respectively). HpLNCaP cells treated with DHT-bound SHBG demonstrated a significant synergistic upregulation of PSA and KLK2 above DHT or SHBG treatment alone, which is similar to previously reported downstream responses from RSHBG-mediated signaling activation. As this result was not seen in lpLNCaP cells, only hpLNCaP cells were further investigated to examine the modulation of potential RSHBG activity by KLK4 and KLK14 proteolysis of SHBG. Contrary to reported results, no increase in intracellular cAMP was observed in hpLNCaP cells when treated with SHBG in the presence and absence of either DHT or estradiol. As a result, the modulation of RSHBG-mediated signaling activation could not be determined. Finally, the identification of the RSHBG from both breast (MCF-7) and prostate cancer (LNCaP) cell lines was attempted. Fluorescently labeled peptides corresponding to the putative receptor binding domain (RBD) of SHBG were shown to be internalized by MCF-7 cells. Crosslinking of the RBD peptide to the cell surfaces of both MCF-7 and LNCaP cells, demonstrated the interaction of the peptide with several targets. These targets were then captured using RBD peptides synthesized onto a hydrophilic scaffold and analysed by mass spectrometry. The samples captured by the RBD peptide returned statistically significantly matches for cytokeratin 8, 18 and 19 as well as microtubule-actin crosslinking factor 1, which may indicate a novel interaction between SHBG and these proteins, but ultimately failed to detect a membrane receptor potentially responsible for the putative RSHBG-mediated signaling. This PhD project has reported the proteolytic processing of SHBG by two members of the kallikrein family, KLK4 and KLK14. The effect of SHBG proteolysis by KLK4 and KLK14 on RSHBG-mediated signaling activation was unable to be determined as the reported signal transduction pathway was not activated after treatment with SHBG, in combination with either DHT or estradiol. However, the digestion of SHBG by these two proteases positively regulated androgen bioavailability to prostate cancer cells in vitro. The increased uptake of androgens is deleterious in prostate cancer due to the promotion of proliferation, metastasis, invasion and the inhibition of apoptosis. The increased bioavailability of androgens, from SHBG proteolysis by KLK4 and KLK14, may therefore promote both carcinogenesis and progression of prostate cancer. Finally, this information may contribute to the development of therapeutic treatment strategies for prostate cancer by inhibiting the proteolysis of SHBG, by KLK4 and KLK14, to prevent the increased uptake of androgens by hormone-dependent cancerous tissues.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

The range of political information sources available to modern Australians is greater and more varied today than at any point in the nation’s history, incorporating print, broadcast, Internet, mainstream and non-mainstream media. In such a competitive media environment, the factors which influence the selection of some information sources above others are of interest to political agents, media institutions and communications researchers alike. A key factor in information source selection is credibility. At the same time that the range of political information sources is increasing rapidly, due to the development of new information and communication technologies, audience research suggests that trust in mainstream media organisations in many countries is declining. So if people distrust the mainstream media, but have a vast array of alternative political information sources available to them, what do their personal media consumption patterns look like? How can we analyse such media consumption patterns in a meaningful way? In this paper I will briefly map the development of media credibility research in the US and Australia, leading to a discussion of one of the most recent media credibility constructs to be shown to influence political information consumption, media scepticism. Looking at the consequences of media scepticism, I will then consider the associated media consumption construct, media diet, and evaluate its usefulness in an Australian, as opposed to US, context. Finally, I will suggest alternative conceptualisations of media diets which may be more suited to Australian political communications research.

Relevância:

20.00% 20.00%

Publicador:

Resumo:

In this paper, we use time series analysis to evaluate predictive scenarios using search engine transactional logs. Our goal is to develop models for the analysis of searchers’ behaviors over time and investigate if time series analysis is a valid method for predicting relationships between searcher actions. Time series analysis is a method often used to understand the underlying characteristics of temporal data in order to make forecasts. In this study, we used a Web search engine transactional log and time series analysis to investigate users’ actions. We conducted our analysis in two phases. In the initial phase, we employed a basic analysis and found that 10% of searchers clicked on sponsored links. However, from 22:00 to 24:00, searchers almost exclusively clicked on the organic links, with almost no clicks on sponsored links. In the second and more extensive phase, we used a one-step prediction time series analysis method along with a transfer function method. The period rarely affects navigational and transactional queries, while rates for transactional queries vary during different periods. Our results show that the average length of a searcher session is approximately 2.9 interactions and that this average is consistent across time periods. Most importantly, our findings shows that searchers who submit the shortest queries (i.e., in number of terms) click on highest ranked results. We discuss implications, including predictive value, and future research.