A discrete gas-cavity model that considers the frictional effects of unsteady pipe flow

Abstract not availableAnton Bergant, Uroš Karadžić, John Vitovský, Igor Vušanović, Angus R. Simpso

The role of inflammation in HPV infection of the Oesophagus

BACKGROUND: Several human cancers are known to be associated with inflammation and/or viral infections. However, the influence of tumour-related inflammation on viral uptake is largely unknown. In this study we used oesophageal squamous cell carcinoma (OSCC) as a model system since this type of cancer is associated with chronic irritation, inflammation and viral infections. Although still debated, the most important viral infection seems to be with Human Papillomavirus (HPV). The present study focused on a possible correlation between inflammation, OSCC development and the influence of HPV infection. METHODS: A total of 114 OSCC biopsies and corresponding normal tissue were collected at Groote Schuur Hospital and Tygerberg Hospital, Cape Town (South Africa), that were subjected to RNA and DNA isolation. RNA samples were analysed by quantitative Light Cycler RT-PCR for the expression of selected genes involved in inflammation and infection, while conventional PCR was performed on the DNA samples to assess the presence of integrated viral DNA. Further, an in vitro infection assay using HPV pseudovirions was established to study the influence of inflammation on viral infectivity using selected cell lines. RESULTS: HPV DNA was found in about 9% of OSCC patients, comprising predominantly the oncogenic type HPV18. The inflammatory markers IL6 and IL8 as well as the potential HPV receptor ITGA6 were significantly elevated while IL12A was downregulated in the tumour tissues. However, none of these genes were expressed in a virus-dependent manner. When inflammation was mimicked with various inflammatory stimulants such as benzo-alpha-pyrene, lipopolysaccharide and peptidoglycan in oesophageal epithelial cell lines in vitro, HPV18 pseudovirion uptake was enhanced only in the benzo-alpha-pyrene treated cells. Interestingly, HPV pseudovirion infectivity was independent of the presence of the ITGA6 receptor on the surface of the tested cells. CONCLUSION: This study showed that although the carcinogen benzo-alpha-pyrene facilitated HPV pseudovirion uptake into cells in culture, HPV infectivity was independent of inflammation and seems to play only a minor role in oesophageal cancer

Closure to “Systematic Evaluation of One-Dimensional Unsteady Friction Models in Simple Pipelines”

J. P. Vítkovský, A. Bergant, A. R. Simpson and M. F. Lamber

A boundary layer growth model for one-dimensional turbulent unsteady pipe friction

Unsteady flow in pipe networks is efficiently modelled using a one-dimensional flow approximation. It is general practice in engineering to assume a quasi-steady state approximation of the friction for unsteady pipe flows. The result of this approximation is an under-estimation of the damping during fast transient events. To remedy this shortcoming, an unsteady friction model is often employed. Unsteady friction models for laminar flow can be theoretically determined and have been successfully used for many years. However, the same cannot be said for unsteady friction in turbulent flows. A number of empirical unsteady friction models have been formulated, but only perform well for certain unsteady transient event types. This paper presents a new unsteady friction model for turbulent flows based on the growth and destruction of the boundary layer during a transient event.MF Lambert, JP Vítkovský, AR Simpson & A Bergan

Recent Sediments of Makirina Cove (Northern Dalmatia, Croatia): Their Origin Viewed Through a Multidisciplinary Approach

Makirina Cove was formed by the Holocene sea-level rise which caused a marine ingression into the depression formed within Albian–Cenomanian dolomites at approximately 4.5 ka B.P. At present, Makirina Cove represents an restricted, stressed, shallow-marine (<2m) ecosystem characterized by varying seawater temperatures (0–35°C) as well as fluctuating salinities (up to 41‰) affected by seasonally enhanced evaporation, continuous freshwater supply through on-shore and submarine springs associated with the coastal karst area and surface run-off episodes. These environmental conditions have been conducive to high primary production of organic matter resulting in the formation of organic-rich deposits which contain up to 5 wt.% of organic carbon. Up to the present times, 3.5 m of sediments have been deposited indicating a relatively high sedimentation rate estimated at 0.75 m/1.0 ka in the northern central part of the Cove. The sediments are being deposited mostly as poorly sorted clayey–sandy silts. The distribution and concentration of most of the chemical elements is dependant on the mineralogical composition and granulometric features of the Makirina sediments, which show values more or less similar to those from the Central Adriatic. Accordingly, there is a positive correlation with Al and K concentrations increasing off-shore and with the depth being associated with increasing concentrations of clay minerals within the clay fraction. The same holds true for concentrations of some trace elements, especially Mo and Se which is consistent with the distribution pattern of sulphides. Selenium is preferentially enriched in authigenic pyrite and it is probably the major source of Se in the Makirina Cove sediments. The concentrations of Ca, Mg and Sr decrease off-shore and they are linked to the composition of the surrounding carbonate rocks. The saturation indices show that the water is supersaturated with respect to carbonates enabling the precipitation of authigenic amorphous or crystalline carbonate phases from the pore water in the upper segment of the sediment column. According to the oxygen isotopic (δ18O) composition, molluscs precipitated their carbonate shells mostly during warmer periods (May to November) at or near isotopic equilibrium with their ambient waters. The carbon isotopic δ13C composition of mollusc carbonate shells is environmentally affected due to oxidation and decomposition of organic matter as well as influxes of fresh water into the Cove, indicating their formation out of the predicted isotopic equilibrium with atmospheric CO2. Palynological and organic carbon isotopic (δ13C) composition shows that the sedimentary organic matter (SOM) is 70–90% lipid- and hydrogen-rich and on average 2/3 marine derived (mainly phytoplankton, bacteria and marine macrophytes) and 1/3 terrestrially derived (mainly woody tissue). The variations in composition of SOM have been noted as a function of the distance from the shore. The type and the preservation state of SOM and pyrite as well as the measurements of Eh, pH, total alkalinity, dissolved inorganic carbon (DIC) and the enrichment of redox-sensitive trace elements, indicate oxygen-depleted depositional conditions and that the sediment is highly reductive even in the uppermost segment at the sediment/water interface. According to the results obtained from the applied methods, the features of Makirina sediments strongly reflect the given depositional conditions within this restricted, stressed, shallow-marine environment where these organic-rich sediments originate, and may therefore serve as a calibration standard in further investigations

Numerical error in weighting function-based unsteady friction models for pipe transients

The accurate simulation of pressure transients in pipelines and pipe networks is becoming increasingly important in water engineering. Applications such as inverse transient analysis for condition assessment, leak detection, and pipe roughness calibration require accurate modeling of transients for longer simulation periods that, in many situations, requires improved modeling of unsteady frictional behavior. In addition, the numerical algorithm used for unsteady friction should be highly efficient, as inverse analysis requires the transient model to be run many times. A popular model of unsteady friction that is applicable to a short-duration transient event type is the weighting function-based type, as first derived by Zielke in 1968. Approximation of the weighting function with a sum of exponential terms allows for a considerable increase in computation speed using recursive algorithms. A neglected topic in the application of such models is evaluation of numerical error. This paper presents a discussion and quantification of the numerical errors that occur when using weighting function-based models for the simulation of unsteady friction in pipe transients. Comparisons of numerical error arising from approximations are made in the Fourier domain where exact solutions can be determined. Additionally, the relative importance of error in unsteady friction modeling and unsteady friction itself in the context of general simulation is discussed.John Vítkovský, Mark Stephens, Anton Bergant, Angus Simpson, and Martin Lamber

Recent Sediments of Makirina Cove (Northern Dalmatia, Croatia): Their Origin Viewed Through a Multidisciplinary Approach

Makirina Cove was formed by the Holocene sea-level rise which caused a marine ingression into the depression formed within Albian–Cenomanian dolomites at approximately 4.5 ka B.P. At present, Makirina Cove represents an restricted, stressed, shallow-marine (<2m) ecosystem characterized by varying seawater temperatures (0–35°C) as well as fluctuating salinities (up to 41‰) affected by seasonally enhanced evaporation, continuous freshwater supply through on-shore and submarine springs associated with the coastal karst area and surface run-off episodes. These environmental conditions have been conducive to high primary production of organic matter resulting in the formation of organic-rich deposits which contain up to 5 wt.% of organic carbon. Up to the present times, 3.5 m of sediments have been deposited indicating a relatively high sedimentation rate estimated at 0.75 m/1.0 ka in the northern central part of the Cove. The sediments are being deposited mostly as poorly sorted clayey–sandy silts. The distribution and concentration of most of the chemical elements is dependant on the mineralogical composition and granulometric features of the Makirina sediments, which show values more or less similar to those from the Central Adriatic. Accordingly, there is a positive correlation with Al and K concentrations increasing off-shore and with the depth being associated with increasing concentrations of clay minerals within the clay fraction. The same holds true for concentrations of some trace elements, especially Mo and Se which is consistent with the distribution pattern of sulphides. Selenium is preferentially enriched in authigenic pyrite and it is probably the major source of Se in the Makirina Cove sediments. The concentrations of Ca, Mg and Sr decrease off-shore and they are linked to the composition of the surrounding carbonate rocks. The saturation indices show that the water is supersaturated with respect to carbonates enabling the precipitation of authigenic amorphous or crystalline carbonate phases from the pore water in the upper segment of the sediment column. According to the oxygen isotopic (δ18O) composition, molluscs precipitated their carbonate shells mostly during warmer periods (May to November) at or near isotopic equilibrium with their ambient waters. The carbon isotopic δ13C composition of mollusc carbonate shells is environmentally affected due to oxidation and decomposition of organic matter as well as influxes of fresh water into the Cove, indicating their formation out of the predicted isotopic equilibrium with atmospheric CO2. Palynological and organic carbon isotopic (δ13C) composition shows that the sedimentary organic matter (SOM) is 70–90% lipid- and hydrogen-rich and on average 2/3 marine derived (mainly phytoplankton, bacteria and marine macrophytes) and 1/3 terrestrially derived (mainly woody tissue). The variations in composition of SOM have been noted as a function of the distance from the shore. The type and the preservation state of SOM and pyrite as well as the measurements of Eh, pH, total alkalinity, dissolved inorganic carbon (DIC) and the enrichment of redox-sensitive trace elements, indicate oxygen-depleted depositional conditions and that the sediment is highly reductive even in the uppermost segment at the sediment/water interface. According to the results obtained from the applied methods, the features of Makirina sediments strongly reflect the given depositional conditions within this restricted, stressed, shallow-marine environment where these organic-rich sediments originate, and may therefore serve as a calibration standard in further investigations

Developments in unsteady pipe flow friction modelling

This paper reviews a number of unsteady friction models for transient pipe flow. Two distinct unsteady friction models, the Zielke and the Brunone models, are investigated in detail. The Zielke model, originally developed for transient laminar flow, has been selected to verify its effectiveness for "low Reynolds number" transient turbulent flow. The Brunone model combines local inertia and wall friction unsteadiness. This model is verified using the Vardy's analytically deduced shear decay coefficient C* to predict the Brunone's friction coefficient k rather than use the traditional trial and error method for estimating k. The two unsteady friction models have been incorporated into the method of characteristics water hammer algorithm. Numerical results from the quasi-steady friction model and the Zielke and the Brunone unsteady friction models are compared with results of laboratory measurements for water hammer cases with laminar and low Reynolds number turbulent flows. Conclusions about the range of validity for the three friction models are drawn. In addition, the convergence and stability of these models are addressed.Anton Bergant, Angus Ross Simpson, John Vìtkovsk

Novel GC-rich DNA-binding compound produced by a genetically engineered mutant of the mithramycin producer Streptomyces argillaceus exhibits improved transcriptional repressor activity: implications for cancer therapy

The aureolic acid antibiotic mithramycin (MTM) binds selectively to GC-rich DNA sequences and blocks preferentially binding of proteins, like Sp1 transcription factors, to GC-rich elements in gene promoters. Genetic approaches can be applied to alter the MTM biosynthetic pathway in the producing microorganism and obtain new products with improved pharmacological properties. Here, we report on a new analog, MTM SDK, obtained by targeted gene inactivation of the ketoreductase MtmW catalyzing the last step in MTM biosynthesis. SDK exhibited greater activity as transcriptional inhibitor compared to MTM. SDK was a potent inhibitor of Sp1-dependent reporter activity and interfered minimally with reporters of other transcription factors, indicating that it retained a high degree of selectivity toward GC-rich DNA-binding transcription factors. RT–PCR and microarray analysis showed that SDK repressed transcription of multiple genes implicated in critical aspects of cancer development and progression, including cell cycle, apoptosis, migration, invasion and angiogenesis, consistent with the pleiotropic role of Sp1 family transcription factors. SDK inhibited proliferation and was a potent inducer of apoptosis in ovarian cancer cells while it had minimal effects on viability of normal cells. The new MTM derivative SDK could be an effective agent for treatment of cancer and other diseases with abnormal expression or activity of GC-rich DNA-binding transcription factors