970 resultados para Pro-oxidant agent
Resumo:
Passenger experience has become a major factor that influences the success of an airport. In this context, passenger flow simulation has been used in designing and managing airports. However, most passenger flow simulations failed to consider the group dynamics when developing passenger flow models. In this paper, an agent-based model is presented to simulate passenger behaviour at the airport check-in and evacuation process. The simulation results show that the passenger behaviour can have significant influences on the performance and utilisation of services in airport terminals. The model was created using AnyLogic software and its parameters were initialised using recent research data published in the literature.
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In this paper we implemented six different boarding strategies (Wilma, Steffen, Reverse Pyramid, Random, Blocks and By letter) in order to minimize boarding time and turnaround time for Boeing 777 and Airbus 380 aircrafts by using Agent-based modelling approach. In the simulation, we divided passengers into six different categories which are group size more than 5 people, passengers with child, gold members, first class passengers, business class passengers and economy class passengers. Results from the simulation demonstrates Reverse Pyramid method is the best boarding method for Boeing 777 and Steffen method is the best boarding method for Airbus 380.
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A tissue inhibitor of metalloproteinases-2 (TIMP-2)-independent mechanism for generating the first activational cleavage of pro-matrix metalloproteinase-2 (MMP-2) was identified in membrane type-1 MMP (MT1-MMP)-transfected MCF-7 cells and confirmed in TIMP-2-deficient fibroblasts. In contrast, the second MMP-2-activational step was found to be TIMP-2 dependent in both systems. MMP-2 hemopexin C-terminal domain was found to be critical for the first step processing, confirming a need for membrane tethering. We propose that the intermediate species of MMP-2 forms the well-established trimolecular complex (MT1-MMP/TIMP-2/MMP-2) for further TIMP-2-dependent autocatalytic cleavage to the fully active species. This alternate mechanism may supplement the traditional TIMP-2-mediated first step mechanism.
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This thesis investigates the influence of passenger group dynamics on passengers' behaviour in an international airport. A simulation model is built to analyse passengers' behaviour during airport departure processes and during an emergency event. Results from the model showed that passengers' group dynamics have significant influences on the performance and utilisation of airport services. The agent-based model also provides a convenient way to investigate the effectiveness of space design and service allocations, which may contribute to the enhancement of passenger airport experiences.
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To harness safe operation of Web-based systems in Web environments, we propose an SSPA (Server-based SHA-1 Page-digest Algorithm) to verify the integrity of Web contents before the server issues an HTTP response to a user request. In addition to standard security measures, our Java implementation of the SSPA, which is called the Dynamic Security Surveillance Agent (DSSA), provides further security in terms of content integrity to Web-based systems. Its function is to prevent the display of Web contents that have been altered through the malicious acts of attackers and intruders on client machines. This is to protect the reputation of organisations from cyber-attacks and to ensure the safe operation of Web systems by dynamically monitoring the integrity of a Web site's content on demand. We discuss our findings in terms of the applicability and practicality of the proposed system. We also discuss its time metrics, specifically in relation to its computational overhead at the Web server, as well as the overall latency from the clients' point of view, using different Internet access methods. The SSPA, our DSSA implementation, some experimental results and related work are all discussed
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CLE can be a life-changing event in a law student’s education. It can open their eyes to the day-to-day operation of justice and provide them with examples of possible career paths they may never have thought existed. Yet it can also provide long-term benefits for CLCs and academics. Recent CLE models have moved towards partnerships with external organisations and away from on-site legal clinics. Some examples have exhibited success with a multidisciplinary approach involving students from non-law disciplines to provide a holistic approach to a CLC’s needs. Such a multidisciplinary approach is of particular benefit in community lawyering clinics where students are engaged in social change lawyering. The QUT/EDO partnership presents a new model in the environmental clinic landscape in Australia. Initial feedback suggests that the clinic has assisted students in gaining insight into the access to justice issues arising from mining activities and to raise the level of understanding and awareness among community members of their legal rights to protect the environment. Looking at ways to increase partnerships between universities and CLCs is of vital importance in the future, given recent federal government CLC funding cuts. The legal clinic model has great potential to evolve and contribute in ensuring the continued operation of legal initiatives to protect the environment in the public interest.
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We implemented six different boarding strategies (Wilma, Steffen, Reverse Pyramid, Random, Blocks and By letter) in order to investigate boarding times for Boeing 777 and Airbus 380 aircraft. We also introduce three new boarding methods to find the optimum boarding strategy. Our models explicitly simulate the behaviour of groups of people travelling together and we explicitly simulate the timing to store their luggage as part of the boarding process. Results from the simulation demonstrates the Reverse Pyramid method is the best boarding method for Boeing 777, and the Steffen method is the best boarding method for Airbus 380. For the new suggested boarding methods, aisle first boarding method is the best boarding strategy for Boeing 777 and row arrangement method is the best boarding strategy for Airbus 380. Overall best boarding strategy is aisle first boarding method for Boeing 777 and Steffen method for Airbus 380.
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Chitinase 3-like 1 (CHI3L1 or YKL40) is a secreted glycoprotein highly expressed in tumours from patients with advanced stage cancers, including prostate cancer (PCa). The exact function of YKL40 is poorly understood, but it has been shown to play an important role in promoting tumour angiogenesis and metastasis. The therapeutic value and biological function of YKL40 are unknown in PCa. The objective of this study was to examine the expression and function of YKL40 in PCa. Gene expression analysis demonstrated that YKL40 was highly expressed in metastatic PCa cells when compared with less invasive and normal prostate epithelial cell lines. In addition, the expression was primarily limited to androgen receptor-positive cell lines. Evaluation of YKL40 tissue expression in PCa patients showed a progressive increase in patients with aggressive disease when compared with those with less aggressive cancers and normal controls. Treatment of LNCaP and C4-2B cells with androgens increased YKL40 expression, whereas treatment with an anti-androgen agent decreased the gene expression of YKL40 in androgen-sensitive LNCaP cells. Furthermore, knockdown of YKL40 significantly decreased invasion and migration of PCa cells, whereas overexpression rendered them more invasive and migratory, which was commensurate with an enhancement in the anchorage-independent growth of cells. To our knowledge, this study characterises the role of YKL40 for the first time in PCa. Together, these results suggest that YKL40 plays an important role in PCa progression and thus inhibition of YKL40 may be a potential therapeutic strategy for the treatment of PCa.
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Agent-based modeling and simulation (ABMS) may fit well with entrepreneurship research and practice because the core concepts and basic premises of entrepreneurship coincide with the characteristics of ABMS. However, it is difficult to find cases where ABMS is applied to entrepreneurship research. To apply ABMS to entrepreneurship and organization studies, designing a conceptual model is important; thus to effectively design a conceptual model, various mixed method approaches are being attempted. As a new mixed method approach to ABMS, this study proposes a bibliometric approach to designing agent based models, which establishes and analyzes a domain corpus. This study presents an example on the venture creation process using the bibliometric approach. This example shows us that the results of the multi-agent simulations on the venturing process based on the bibliometric approach are close to each nation’s surveyed data on the venturing activities. In conclusion, by the bibliometric approach proposed in this study, all the agents and the agents’ behaviors related to a phenomenon can be extracted effectively, and a conceptual model for ABMS can be designed with the agents and their behaviors. This study contributes to the entrepreneurship and organization studies by promoting the application of ABMS.
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The biological function of inhibin-a subunit (INHa) in prostate cancer (PCa) is currently unclear. A recent study associated elevated levels of INHa in PCa patients with a higher risk of recurrence. This prompted us to use clinical specimens and functional studies to investigate the pro-tumourigenic and pro-metastatic function of INHa. We conducted a cross-sectional study to determine a link between INHa expression and a number of clinicopathological parameters including Gleason score, surgical margin, extracapsular spread, lymph node status and vascular endothelial growth factor receptor-3 expression, which are well-established prognostic factors of PCa. In addition, using two human PCa cell lines (LNCaP and PC3) representing androgen-dependent and -independent PCa respectively, we investigated the biological function of elevated levels of INHa in advanced cancer. Elevated expression of INHa in primary PCa tissues showed a higher risk of PCa patients being positive for clinicopathological parameters outlined above. Overexpressing INHa in LNCaP and PC3 cells demonstrated two different and cell-type-specific responses. INHa-positive LNCaP demonstrated reduced tumour growth whereas INHa-positive PC3 cells demonstrated increased tumour growth and metastasis through the process of lymphangiogenesis. This study is the first to demonstrate a pro-tumourigenic and pro-metastatic function for INHa associated with androgen-independent stage of metastatic prostate disease. Our results also suggest that INHa expression in the primary prostate tumour can be used as a predictive factor for prognosis of PCa.
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BACKGROUND: The use of nonstandardized N-terminal pro-B-type natriuretic peptide (NT-proBNP) assays can contribute to the misdiagnosis of heart failure (HF). Moreover, there is yet to be established a common consensus regarding the circulating forms of NT-proBNP being used in current assays. We aimed to characterize and quantify the various forms of NT-proBNP in the circulation of HF patients. METHODS: Plasma samples were collected from HF patients (n = 20) at rest and stored at -80 degrees C. NT-proBNP was enriched from HF patient plasma by use of immunoprecipitation followed by mass spectrometric analysis. Customized homogeneous sandwich AlphaLISA (R) immunoassays were developed and validated to quantify 6 fragments of NT-proBNP. RESULTS: Mass spectrometry identified the presence of several N- and C-terminally processed forms of circulating NT-proBNP, with physiological proteolysis between Pro2-Leu3, Leu3-Gly4, Pro6-Gly7, and Pro75-Arg76. Consistent with this result, AlphaLISA immunoassays demonstrated that antibodies targeting the extreme N or C termini measured a low apparent concentration of circulating NT-proBNP. The apparent circulating NT-proBNP concentration was increased with antibodies targeting nonglycosylated and nonterminal epitopes (P < 0.05). CONCLUSIONS: In plasma collected from HF patients, immunoreactive NT-proBNP was present as multiple N- and C-terminally truncated fragments of the full length NT-proBNP molecule. Immunodetection of NT-proBNP was significantly improved with the use of antibodies that did not target these terminal regions. These findings support the development of a next generation NT-proBNP assay targeting nonterminal epitopes as well as avoiding the central glycosylated region of this molecule. (c) 2013 American Association for Clinical Chemistry
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Chronic kidney disease (CKD) in ageing is a burden on health systems worldwide. Rat models of age-related CKD linked with obesity and hypertension were used to investigate alterations in oxidant handling and energy metabolism to identify gene targets or markers for age-related CKD. Young adult (3 months) and old (21–24 months) spontaneously-hypertensive (SHR), normotensive Wistar-Kyoto (WKY) and Wistar rats (normotensive, obese in ageing) were compared for renal functional and physiological parameters, renal fibrosis and inflammation, oxidative stress (hemeoxygenase-1/HO-1), apoptosis and cell injury (including Bax:Bcl-2), phosphorylated and non-phosphorylated forms of oxidant and energy sensing proteins (p66Shc, AMPK), signal transduction proteins (ERK1/2, PKB), and transcription factors (NF-κB, FoxO1). All old rats were normoglycemic. Renal fibrosis, tubular epithelial apoptosis, interstitial macrophages and myofibroblasts (all p < 0.05), p66Shc/phospho-p66 (p < 0.05), Bax/Bcl-2 ratio (p < 0.05) and NF-κB expression (p < 0.01) were highest in old obese Wistars. Expression of phospho-FoxO/FoxO was elevated in old Wistars (p < 0.001) and WKYs (p < 0.01). SHRs had high levels in young and old rats. Expression of PKB, phospho-PKB, ERK1/2 and phospho-ERK1/2 were significantly elevated in all aged animals. These results suggest that obesity and hypertension have differing oxidant handling and signalling pathways that act in the pathogenesis of age-related CKD
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Aims: Caveolin-1 (cav1) is reported to have both cell survival and pro-apoptotic characteristics. This may be explained by its localisation or phosphorylation in injured cells. This study investigated the role of cav1 in kidney cells of different nephron origin and developmental state after oxidative stress. Methods: Renal MCDK distal tubular, HK2 proximal tubular epithelial cells and HEK293T renal embryonic cells were treated with 1mM hydrogen peroxide. Apoptosis, loss of cell adhesion, and cell survival were compared with expression of cav1 in its non-phosphorylated and phosphorylated (p-cav1) forms. Cav1 was transfected into the HEK293T cells, or caveolae were disrupted with filipin or nystatin in HK2 cells, to investigate functions of cav1 and p-cav1. Results: Oxidative stress induced more apoptosis in HK2s than MDCKs (p<0.05). HK2s had lower endogenous cav1 and p-cav1 than MDCKs (p<0.05). Both cell lines had increased p-cav1, but not cav1, with oxidative stress. This increase was greatest in MDCKs (p<0.01). Cav1 was located mainly in the plasma membrane of untreated cells and translocated to the cytoplasm with oxidative stress in both cell lines, more so in MDCKs. Disruption of caveolae caused cytoplasmic translocation of cav1 in HK2s, but did not alter high levels of oxidative stress-induced apoptosis. When HEK293Ts lacking endogenous cav1 were transfected with cav1, oxidant-induced apoptosis and loss of cell adhesion was decreased (p<0.01), and p-cav1 was induced by treatment. Conclusion: Cav1 expression and localisation in kidney cells is not anti-apoptotic, but increased expression of p-cav1 may promote cell survival after oxidative stress. © 2008 Royal College of Pathologists of Australasia.
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Inhibition of FASN has emerged as a promising therapeutic target in cancer, and numerous inhibitors have been investigated. However, severe pharmacological limitations have challenged their clinical testing. The synthetic FASN inhibitor triclosan, which was initially developed as a topical antibacterial agent, is merely affected by these pharmacological limitations. Yet, little is known about its mechanism in inhibiting the growth of cancer cells. Here we compared the cellular and molecular effects of triclosan in a panel of eight malignant and non-malignant prostate cell lines to the well-known FASN inhibitors C75 and orlistat, which target different partial catalytic activities of FASN. Triclosan displayed a superior cytotoxic profile with a several-fold lower IC50 than C75 or orlistat. Structure-function analysis revealed that alcohol functionality of the parent phenol is critical for inhibitory action. Rescue experiments confirmed that end product starvation was a major cause of cytotoxicity. Importantly, triclosan, C75 and orlistat induced distinct changes to morphology, cell cycle, lipid content and the expression of key enzymes of lipid metabolism, demonstrating that inhibition of different partial catalytic activities of FASN activates different metabolic pathways. These finding combined with its well-documented pharmacological safety profile make triclosan a promising drug candidate for the treatment of prostate cancer.
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As of now, there is little evidence on the questions of whether pro bono services are effective, whether lawyer charity is a cheaper way to provide them (because it does cost money to do pro bono), or whether it would in fact be more efficient and effective if firms and attorneys stopped giving their time and instead donated money to the organizations already specializing in these clients and causes. Pro bono may or may not be an efficient way of doing socially important work; at this point, we simply do not know