Matrix metalloproteinases during wound healing - a double edged sword

The extracellular matrix (ECM) provides a framework for cells and gives skin its tensile strength and elasticity. Loss of its integrity necessitates the clearing of damaged components and the deposition of firstly a provisional matrix and later remodelling of the ECM to support a functionally intact tissue. Matrix metalloproteinases (MMPs) are an important family of enzymes that function in the breakdown of the ECM and modulate the function of many biologically active molecules housed in the ECM. Through their enzymatic actions MMPs play a role in fundamental processes such as immune cell infiltration and ECM remodelling during wound repair. Their tight control is necessary for timely wound healing and excessive MMP activity participates in the development and persistence of chronic wounds, while reduced activity contributes to fibrosis. A number of inhibitors have been designed to target this activity and improve wound healing with limited success. Novel strategies are currently being investigated to improve wound healing by targeting MMP modulating molecules.

Short signature without random oracles and the SDH assumption in bilinear groups

We describe a short signature scheme that is strongly existentially unforgeable under an adaptive chosen message attack in the standard security model. Our construction works in groups equipped with an efficient bilinear map, or, more generally, an algorithm for the Decision Diffie-Hellman problem. The security of our scheme depends on a new intractability assumption we call Strong Diffie-Hellman (SDH), by analogy to the Strong RSA assumption with which it shares many properties. Signature generation in our system is fast and the resulting signatures are as short as DSA signatures for comparable security. We give a tight reduction proving that our scheme is secure in any group in which the SDH assumption holds, without relying on the random oracle model.

Improving megasite management performance through incentives : lessons learned from the Shanghai Expo construction

As the biggest expo site in history, construction of the Shanghai Expo site faced a lot of challenges, including involvement of lots of investors, megaconstruction scale, concurrent construction mode, involvement of more than 40,000 migrant workers, and extremely tight completion deadlines, among others. Consequently, these challenges imposed great obstacles on accomplishing the safety, quality, and environmental goals. Through a case study of the Shanghai Expo construction, this paper paper presents the design and implementation of multicriteria incentives in megaprojects to accomplish the safety, quality, and environmental goals. Both quantitative and qualitative findings were triangulated to demonstrate the outcome of the incentives. Six critical success factors (CSFs) for the incentives, rule design, process orientation, top management support, training and promotion, communication in process, and process learning and improvement are identified and validated through case study data and content analysis. It is believed that the findings of this paper can enhance understanding of multicriteria incentive schemes in general and provide insights in implementing these incentive schemes in future megaprojects, particularly in the People’s Republic of China (PRC).

Motion Control of Marine Craft

Marine craft (surface vessels, underwater vehicles, and offshore rigs) perform operations that require tight motion control. During the past three decades, there has been an increasing demand for higher accuracy and reliability of marinecraft motion control systems. Today, these control systems are an enabling factor for single and multicraft marine operations. This chapter provides an overview of the main characteristics and design aspects of motion control systems for marine craft. In particular, we discuss the architecture of the control system, the functionality of its main components, the characteristics of environmental disturbances, control objectives, and essential aspects of modeling and motion control design.

A diode for correction-less small field output factor measurements

Introduction Due to their high spatial resolution diodes are often used for small field relative output factor measurements. However, a field size specific correction factor [1] is required and corrects for diode detector over-response at small field sizes. A recent Monte Carlo based study has shown that it is possible to design a diode detector that produces measured relative output factors that are equivalent to those in water. This is accomplished by introducing an air gap at the upstream end of the diode [2]. The aim of this study was to physically construct this diode by placing an ‘air cap’ on the end of a commercially available diode (the PTW 60016 electron diode). The output factors subsequently measured with the new diode design were compared to current benchmark small field output factor measurements. Methods A water-tight ‘cap’ was constructed so that it could be placed over the upstream end of the diode. The cap was able to be offset from the end of the diode, thus creating an air gap. The air gap width was the same as the diode width (7 mm) and the thickness of the air gap could be varied. Output factor measurements were made using square field sizes of side length from 5 to 50 mm, using a 6 MV photon beam. The set of output factor measurements were repeated with the air gap thickness set to 0, 0.5, 1.0 and 1.5 mm. The optimal air gap thickness was found in a similar manner to that proposed by Charles et al. [2]. An IBA stereotactic field diode, corrected using Monte Carlo calculated kq,clin,kq,msr values [3] was used as the gold standard. Results The optimal air thickness required for the PTW 60016 electron diode was 1.0 mm. This was close to the Monte Carlo predicted value of 1.15 mm2. The sensitivity of the new diode design was independent of field size (kq,clin,kq,msr = 1.000 at all field sizes) to within 1 %. Discussion and conclusions The work of Charles et al. [2] has been proven experimentally. An existing commercial diode has been converted into a correction-less small field diode by the simple addition of an ‘air cap’. The method of applying a cap to create the new diode leads to the diode being dual purpose, as without the cap it is still an unmodified electron diode.

Induction of epithelial to mesenchymal transition in PMC42-LA human breast carcinoma cells by carcinoma-associated fibroblast secreted factors

Background Breast carcinoma is accompanied by changes in the acellular and cellular components of the microenvironment, the latter typified by a switch from fibroblasts to myofibroblasts. Methods: We utilised conditioned media cultures, Western blot analysis and immunocytochemistry to investigate the differential effects of normal mammary fibroblasts (NMFs) and mammary cancer-associated fibroblasts (CAFs) on the phenotype and behaviour of PMC42-LA breast cancer cells. NMFs were obtained from a mammary gland at reduction mammoplasty, and CAFs from a mammary carcinoma after resection. Results We found greater expression of myofibroblastic markers in CAFs than in NMFs. Medium from both CAFs and NMFs induced novel expression of α-smooth muscle actin and cytokeratin-14 in PMC42-LA organoids. However, although conditioned media from NMFs resulted in distribution of vimentin-positive cells to the periphery of PMC42-LA organoids, this was not seen with CAF-conditioned medium. Upregulation of vimentin was accompanied by a mis-localization of E-cadherin, suggesting a loss of adhesive function. This was confirmed by visualizing the change in active β-catenin, localized to the cell junctions in control cells/ cells in NMF-conditioned medium, to inactive β-catenin, localized to nuclei and cytoplasm in cells in CAF-conditioned medium. Conclusion We found no significant difference between the influences of NMFs and CAFs on PMC42-LA cell proliferation, viability, or apoptosis; significantly, we demonstrated a role for CAFs, but not for NMFs, in increasing the migratory ability of PMC42-LA cells. By concentrating NMF-conditioned media, we demonstrated the presence of factor(s) that induce epithelial-mesenchymal transition in NMF-conditioned media that are present at higher levels in CAF-conditioned media. Our in vitro results are consistent with observations in vivo showing that alterations in stroma influence the phenotype and behaviour of surrounding cells and provide evidence for a role for CAFs in stimulating cancer progression via an epithelial-mesenchymal transition. These findings have implications for our understanding of the roles of signalling between epithelial and stromal cells in the development and progression of mammary carcinoma.

Hepatocyte growth factor stimulates invasion across reconstituted basement membranes by a new human small intestinal cell line

Hepatocyte growth factor/scatter factor (HGF/SF) is a protein growth factor whose pleiotropic effects on epithelial cells include the stimulation of motility, mitosis and tubulogenesis. These responses are mediated by the cell surface tyrosine kinase receptor c-met. Because both the cytokine and receptor are found in the gastrointestinal tract, we have studied the effects of HGF/SF on transformed gut epithelial cells which express c-met. Here we describe the response of a new transformed human jejunal epithelioid cell line (HIE-7) to HGF/SF. Morphologically HIE-7 cells are immature. Their epithelial lineage was confirmed by reactivity with the epithelial specific antibodies AE1/AE3, Cam 5.2, Ber-EP4 and anti-EMA and is consistent with their expression of c-met mRNA and protein. In addition, electron microscopic analysis revealed the presence of primitive junctions and rudimentary microvilli, but features of polarization were absent. When grown on reconstituted basement membranes, HIE-7 cells formed closely associated multicellular cord-like structures adjacent to acellular spaces. However, the cells did not mature structurally, form lumen-like structures or express disaccharidase mRNA, even in the presence of recombinant HGF (rHGF). On the other hand, rHGF induced HIE-7 cells to scatter and stimulated their rapid migration in a modified wound assay. To determine whether the motogenic effect caused by rHGF is associated with HIE-7 cell invasiveness across reconstituted basement membranes, a Boyden chamber chemoinvasion assay was performed. rHGF stimulated a 10-fold increase in the number of HIE-7 cells that crossed the basement membrane barrier, while only stimulating a small increase in chemotaxis across a collagen IV matrix, suggesting that the cytokine activates matrix penetration by these cells. rHGF also stimulated the invasion of basement membranes by an undifferentiated rat intestinal cell line (IEC-6) and by two human colon cancer cell lines which are poorly differentiated (DLD-1 and SW 948). In contrast, two moderately well differentiated colon cancer cell lines (Caco-2 and HT-29) did not manifest an invasive response when exposed to rHGF. These results suggest that HGF/SF may play a significant role in the invasive behavior of anaplastic and poorly differentiated gut epithelial tumors.

Vimentin and epithelial-mesenchymal transition in human breast cancer : observations in vitro and in vivo

Breast cancer is a highly prevalent disease among women worldwide. While the expression of certain proteins within these tumours is used for prognosis and selection of therapies, there is a continuing need for additional markers to be identified. A considerable amount of current literature, based predominantly on cell culture systems, suggests that a major mechanism responsible for the progression of breast cancer is due to tumour cells losing their epithelial features and gaining mesenchymal properties. These events are proposed to be very similar to the epithelial-mesenchymal transition (EMT) process that has been well characterised in embryonic development. For the developmental and putative cancer EMT, the cell intermediate filament status changes from a keratin-rich network which connects to adherens junctions and hemidesmosomes, to a vimentin-rich network connecting to focal adhesions. This review summarises observations of vimentin expression in breast cancer model systems, and discusses the potential role of EMT in human breast cancer progression, and the prognostic usefulness of vimentin expression.

Expression of β1 integrin in laminin-adhesion-selected human colon cancer cell lines of varying tumorigenicity

Laminin has been shown to promote the malignant phenotype and the expression of certain laminin receptors has been correlated with the malignant character of the tumors. Here new cell lines were isolated from a human colon cancer cell line (LCC-C1) based on their adhesiveness to laminin. The laminin-adherent subclone formed large tumors in nude mice, whereas the laminin-nonadherent subclone failed to form sizable tumors. Only the laminin-adherent subclone adhered to laminin and invaded through Matrigel-coated filters. The adhesive and invasive ability of the cells was almost completely blocked by low concentrations (1.0 μg/ml) of anti-β1 integrin antibody. The amounts of total cellular β1 integrin protein were similar in the two subclones when compared by Western blot, and the mRNA levels also did not differ. The localization of β1 integrin laminin receptor varied in the two subclones; the laminin-adherent subclone showed a linear distribution along the cell-cell junctions, while the laminin-nonadherent subclone did not stain between the cells. Using laminin-Sepharose affinity chromatography, more β1 integrin was obtained from the laminin-adherent subclone. These findings suggest that alterations in the affinity of β1 integrin for laminin and in its membrane distribution might be involved in the increased tumorigenicity observed in colon cancer cells.

Epidermal growth factor-induced epithelio-mesenchymal transition in human breast carcinoma cells

PMC42-LA cells display an epithelial phenotype: the cells congregate into pavement epithelial sheets in which E-cadherin and β-catenin are localized at cell-cell borders. They abundantly express cytokeratins, although 5% to 10% of the cells also express the mesenchymal marker vimentin. Stimulation of PMC42-LA cells with epidermal growth factor (EGF) leads to epithelio-mesenchymal transition-like changes including up-regulation of vimentin and down-regulation of E-cadherin. Vimentin expression is seen in virtually all cells, and this increase is abrogated by treatment of cells with an EGF receptor antagonist. The expression of the mesenchyme-associated extracellular matrix molecules fibronectin and chondroitin sulfate proteoglycan also increase in the presence of EGF. PMC42-LA cells adhere rapidly to collagen I, collagen IV, and laminin-1 substrates and markedly more slowly to fibronectin and vitronectin. EGF increases the speed of cell adhesion to most of these extracellular matrix molecules without altering the order of adhesive preference. EGF also caused a time-dependent increase in the motility of PMC42-LA cells, commensurate with the degree of vimentin staining. The increase in motility was at least partly chemokinetic, because it was evident both with and without chemoattractive stimuli. Although E-cadherin staining at cell-cell junctions disappeared in response to EGF, β-catenin persisted at the cell periphery. Further analysis revealed that N-cadherin was present at the cell-cell junctions of untreated cells and that expression was increased after EGF treatment. N- and E-cadherin are not usually coexpressed in human carcinoma cell lines but can be coexpressed in embryonic tissues, and this may signify an epithelial cell population prone to epithelio-mesenchymal-like responses.

Построение автоматической навигационной системы малогабаритного беспилотного летательного аппарата многократного применения = Development of automatic navigation management system for small unmanned aerial vehicle

Современный этап развития комплексов автоматического управления и навигации малогабаритными БЛА многократного применения предъявляет высокие требования к автономности, точности и миниатюрности данных систем. Противоречивость требований диктует использование функционального и алгоритмического объединения нескольких разнотипных источников навигационной информации в едином вычислительном процессе на основе методов оптимальной фильтрации. Получили широкое развитие бесплатформенные инерциальные навигационные системы (БИНС) на основе комплексирования данных микромеханических датчиков инерциальной информации и датчиков параметров движения в воздушном потоке с данными спутниковых навигационных систем (СНС). Однако в современных условиях такой подход не в полной мере реализует требования к помехозащищённости, автономности и точности получаемой навигационной информации. Одновременно с этим достигли значительного прогресса навигационные системы, использующие принципы корреляционно экстремальной навигации по оптическим ориентирам и цифровым картам местности. Предлагается схема построения автономной автоматической навигационной системы (АНС) для БЛА многоразового применения на основе объединения алгоритмов БИНС, спутниковой навигационной системы и оптической навигационной системы. The modern stage of automatic control and guidance systems development for small unmanned aerial vehicles (UAV) is determined by advanced requirements for autonomy, accuracy and size of the systems. The contradictory of the requirements dictates novel functional and algorithmic tight coupling of several different onboard sensors into one computational process, which is based on methods of optimal filtering. Nowadays, data fusion of micro-electro mechanical sensors of inertial measurement units, barometric pressure sensors, and signals of global navigation satellite systems (GNSS) receivers is widely used in numerous strap down inertial navigation systems (INS). However, the systems do not fully comply with such requirements as jamming immunity, fault tolerance, autonomy, and accuracy of navigation. At the same time, the significant progress has been recently demonstrated by the navigation systems, which use the correlation extremal principle applied for optical data flow and digital maps. This article proposes a new architecture of automatic navigation management system (ANMS) for small UAV, which combines algorithms of strap down INS, satellite navigation and optical navigation system.

Исследования и испытания алгоритмов автоматической пилотажно-навигационной системы малогабаритного беспилотного летательного аппарата = Research and testing of automatic navigation management system’s algorithms for small unmanned aerial vehicle

В статье представлено развитие принципа построения автоматической пилотажно-навигационной системы (АПНС) для беспилотного летательного аппарата (БЛА). Принцип заключается в синтезе комплексных систем управления БПЛА не только на основе использования алгоритмов БИНС, но и алгоритмов, объединяющих в себе решение задач формирования и отработки сформированной траектории резервированной системой управления и навигации. Приведены результаты аналитического исследования и данные летных экспериментов разработанных алгоритмов АПНС БЛА, обеспечивающих дополнительное резервирование алгоритмов навигации и наделяющих БЛА новым функциональной способностью по выходу в заданную точку пространства с заданной скоростью в заданный момент времени с учетом атмосферных ветровых возмущений. Предложена и испытана методика идентификации параметров воздушной атмосферы: направления и скорости W ветра. Данные летных испытаний полученного решения задачи терминальной навигации демонстрируют устойчивую работу синтезированных алгоритмов управления в различных метеоусловиях. The article presents a progress in principle of development of automatic navigation management system (ANMS) for small unmanned aerial vehicle (UAV). The principle defines a development of integrated control systems for UAV based on tight coupling of strap down inertial navigation system algorithms and algorithms of redundant flight management system to form and control flight trajectory. The results of the research and flight testing of the developed ANMS UAV algorithms are presented. The system demonstrates advanced functional redundancy of UAV guidance. The system enables new UAV capability to perform autonomous multidimensional navigation along waypoints with controlled speed and time of arrival taking into account wind. The paper describes the technique for real-time identification of atmosphere parameters such as wind direction and wind speed. The flight test results demonstrate robustness of the algorithms in diverse meteorological conditions.

Crime, Justice and Social Democracy: Proceedings of the Second International Conference, 2013, volume 2

The refereed papers contained in this volume of conference proceedings were among those presented at the 2nd International Conference on Crime, Justice and Social Democracy, hosted by the Crime and Justice Research Centre, Faculty of Law, QUT, from 8 – 11 July 2013. The conference attracted an impressive list of speakers from Australasia, Europe, North America and Latin America. These seven papers can be viewed at the Crime and Justice Research Centre’s website at http://crimejusticeconference.com/publications/ as can Volume 1 representing another 26 selected papers from the conference. As with the papers contained in the first volume, this set of papers raises important questions about the links between crime, justice and social democracy, and continues the contribution that the Crime and Justice Research Centre makes towards engaging with these topics. We thank all those who submitted papers for review for this second volume of proceedings, as well as the peer reviewers for taking the time to review the papers, often within very tight timelines.

Beyond point forecasting : evaluation of alternative prediction intervals for tourist arrivals

This paper evaluates the performances of prediction intervals generated from alternative time series models, in the context of tourism forecasting. The forecasting methods considered include the autoregressive (AR) model, the AR model using the bias-corrected bootstrap, seasonal ARIMA models, innovations state space models for exponential smoothing, and Harvey’s structural time series models. We use thirteen monthly time series for the number of tourist arrivals to Hong Kong and Australia. The mean coverage rates and widths of the alternative prediction intervals are evaluated in an empirical setting. It is found that all models produce satisfactory prediction intervals, except for the autoregressive model. In particular, those based on the biascorrected bootstrap perform best in general, providing tight intervals with accurate coverage rates, especially when the forecast horizon is long.

Converse results to the Wiener attack on RSA

A well-known attack on RSA with low secret-exponent d was given by Wiener about 15 years ago. Wiener showed that using continued fractions, one can efficiently recover the secret-exponent d from the public key (N,e) as long as d < N 1/4. Interestingly, Wiener stated that his attack may sometimes also work when d is slightly larger than N 1/4. This raises the question of how much larger d can be: could the attack work with non-negligible probability for d=N 1/4 + ρ for some constant ρ > 0? We answer this question in the negative by proving a converse to Wiener’s result. Our result shows that, for any fixed ε > 0 and all sufficiently large modulus lengths, Wiener’s attack succeeds with negligible probability over a random choice of d < N δ (in an interval of size Ω(N δ )) as soon as δ > 1/4 + ε. Thus Wiener’s success bound dtight. We also obtain a converse result for a natural class of extensions of the Wiener attack, which are guaranteed to succeed even when δ > 1/4. The known attacks in this class (by Verheul and Van Tilborg and Dujella) run in exponential time, so it is natural to ask whether there exists an attack in this class with subexponential run-time. Our second converse result answers this question also in the negative.