Modelling of Unsteady Gas-Dynamic Flow in a Pipe and at its Exit Using CFD

Traditionally the simulation of the thermodynamic aspects of the internal combustion engine has been undertaken using one-dimensional gas-dynamic models to represent the intake and exhaust systems. CFD analysis of engines has been restricted to modelling of in-cylinder flow structures. With the increasing accessibility of CFD software it is now worth considering its use for complete gas-dynamic engine simulation. This paper appraises the accuracy of various CFD models in comparison to a 1D gas-dynamic simulation. All of the models are compared to experimental data acquired on an apparatus that generates a single gas-dynamic pressure wave. The progress of the wave along a constant area pipe and its subsequent reflection from the open pipe end are recorded with a number of high speed pressure transducers. It was found that there was little to choose between the accuracy of the 1D model and the best CFD model. The CFD model did not require experimentally derived loss coefficients to accurately represent the open pipe end; however, it took several hundred times longer to complete its analysis. The best congruency between the CFD models and the experimental data was achieved using the RNG k-e turbulence model. The open end of the pipe was most effectively represented by surrounding it with a relatively small volume of cells connected to the rest of the environment using a pressure boundary.

Critical Role for STAT4 Activation by Type 1 Interferons in the Interferon-Y Response to Viral Infection

Interferons (IFNs) are essential for host defense. Although the antiviral effects of the type 1 IFNs IFN- and IFN- (IFN-/) have been established, their immunoregulatory functions, especially their ability to regulate IFN- production, are poorly understood. Here we show that IFN-/ activate STAT4 directly (STAT, signal transducers and activators of transcription) and that this is required for IFN- production during viral infections of mice, in concert with T cell receptor-derived signals. In contrast, STAT1 appears to negatively regulate IFN-/ induction of IFN-. Thus, type 1 IFNs, in addition to interleukin-12, provide pathways for innate regulation of adaptive immunity, and their immunoregulatory functions are controlled by modulating the activity of individual STATs.

Multivariate Statistical Analysis Applied to an IL6 Signal Transduction Model in Hepatocytes

This paper introduces the application of linear multivariate statistical techniques, including partial least squares (PLS), canonical correlation analysis (CCA) and reduced rank regression (RRR), into the area of Systems Biology. This new approach aims to extract the important proteins embedded in complex signal transduction pathway models.The analysis is performed on a model of intracellular signalling along the janus-associated kinases/signal transducers and transcription factors (JAK/STAT) and mitogen activated protein kinases (MAPK) signal transduction pathways in interleukin-6 (IL6) stimulated hepatocytes, which produce signal transducer and activator of transcription factor 3 (STAT3).A region of redundancy within the MAPK pathway that does not affect the STAT3 transcription was identified using CCA. This is the core finding of this analysis and cannot be obtained by inspecting the model by eye. In addition, RRR was found to isolate terms that do not significantly contribute to changes in protein concentrations, while the application of PLS does not provide such a detailed picture by virtue of its construction.This analysis has a similar objective to conventional model reduction techniques with the advantage of maintaining the meaning of the states prior to and after the reduction process. A significant model reduction is performed, with a marginal loss in accuracy, offering a more concise model while maintaining the main influencing factors on the STAT3 transcription.The findings offer a deeper understanding of the reaction terms involved, confirm the relevance of several proteins to the production of Acute Phase Proteins and complement existing findings regarding cross-talk between the two signalling pathways.

A Simple Triaxial System for Evaluating the Performance of Unsaturated Soils Under Repeated Loading

Unsaturated soils constitute a large proportion of the foundation materials supporting infrastructure throughout the world and they are subject to various loading conditions. This paper describes the development of a simple system for testing unsaturated soils under repeated loading. The equipment was comprised of a modified triaxial cell with hydraulic loading system, hall-effect transducers for on-sample strain measurements, and thermocouple psychrometer for suction measurements. A number of undrained monotonic and repeated loading triaxial tests were performed on compacted samples of kaolin clay in order to attest the newly developed system. The results yielded some useful information on the resilient modulus and permanent deformation of a soil when subjected to repeated loading. There is some difference between the failure deviator stress of samples subjected to repeated and monotonic loading, though repeated loading continued to result in a significant permanent deformation. This paper is aimed at demonstrating the key features of the equipment using preliminary data generated as part of the on-going research.

Erythropoietin-Induced Activation of the JAK2/STAT5, PI3K/Akt, and Ras/ERK Pathways Promotes Malignant Cell Behavior in a Modified Breast Cancer Cell Line

Abstract Erythropoietin (Epo), the major regulator of erythropoiesis, and its cognate receptor (EpoR) are also expressed in nonerythroid tissues, including tumors. Clinical studies have highlighted the potential adverse effects of erythropoiesis-stimulating agents when used to treat cancer-related anemia. We assessed the ability of EpoR to enhance tumor growth and invasiveness following Epo stimulation. A benign noninvasive rat mammary cell line, Rama 37, was used as a model system. Cell signaling and malignant cell behavior were compared between parental Rama 37 cells, which express few or no endogenous EpoRs, and a modified cell line stably transfected with human EpoR (Rama 37-28). The incubation of Rama 37-28 cells with pharmacologic levels of Epo led to the rapid and sustained increases in phosphorylation of signal transducers and activators of transcription 5, Akt, and extracellular signal-regulated kinase. The activation of these signaling pathways significantly increased invasion, migration, adhesion, and colony formation. The Epo-induced invasion capacity of Rama 37-28 cells was reduced by the small interfering RNA-mediated knockdown of EpoR mRNA levels and by inhibitors of the phosphoinositide 3-kinase/Akt and Ras/extracellular signal-regulated kinase signaling pathways with adhesion also reduced by Janus-activated kinase 2/signal transducers and activators of transcription 5 inhibition. These data show that Epo induces phenotypic changes in the behavior of breast cancer cell lines and establishes links between individual cell signaling pathways and the potential for cancer spread.

Development of a recombinant Fab-fragment based electrochemical immunosensor for deoxynivalenol detection in food samples

A reliable and cost-effective electrochemical method for the detection of deoxynivalenol (DON) in cereals and cereal-based food samples based on the use of a novel anti-DON Fab fragment is presented. The analytical system employed, Enzyme-Linked-Immunomagnetic-Electrochemical (ELIME) assay, is based on the use of immunomagnetic beads (IMBs) coupled with eight magnetized screen-printed electrodes (8-mScPEs) as electrochemical transducers.

Molecular dynamics studies of the STAT3 homodimer:DNA complex: relationships between STAT3 mutations and protein-DNA recognition.

Signal Transducers and Activators of Transcription (STAT) proteins are a group of latent cytoplasmic transcription factors involved in cytokine signaling. STAT3 is a member of the STAT family and is expressed at elevated levels in a large number of diverse human cancers and is now a validated target for anticancer drug discovery.. Understanding the dynamics of the STAT3 dimer interface, accounting for both protein-DNA and protein-protein interactions, with respect to the dynamics of the latent unphosphorylated STAT3 monomer, is important for designing potential small-molecule inhibitors of the activated dimer. Molecular dynamics (MD) simulations have been used to study the activated STAT3 homodimer:DNA complex and the latent unphosphorylated STAT3 monomer in an explicit water environment. Analysis of the data obtained from MD simulations over a 50 ns time frame has suggested how the transcription factor interacts with DNA, the nature of the conformational changes, and ways in which function may be affected. Examination of the dimer interface, focusing on the protein-DNA interactions, including involvement of water molecules, has revealed the key residues contributing to the recognition events involved in STAT3 protein-DNA interactions. This has shown that the majority of mutations in the DNA-binding domain are found at the protein-DNA interface. These mutations have been mapped in detail and related to specific protein-DNA contacts. Their structural stability is described, together with an analysis of the model as a starting-point for the discovery of novel small-molecule STAT3 inhibitors.

Performance of Unsaturated Compacted Clay Under Repeated Loading Effects of Confining Pressure, Initial Compaction Effort and Water Content

While a significant number of geotechnical structures are subjected to static loading, many, such as avement subgrade, also are subjected to cyclic or dynamic loading. While the performance of saturated soils under repeated, cyclic or dynamic loading conditions is still a topic of research, similar interests are growing when the soilcondition is unsaturated. This paper examines the performance of unsaturated soils under repeated loading. As part of the research, a triaxial system was developed which incorporates small strain measurements using Hall-effect transducers, in addition to suction measurements taken using a psychrometer. Tests were conducted on samples of kaolin under constant water mass conditions. The results address the effects of compaction effort and water content at the time of compaction on the overall performance of unsaturated soils, under different amplitudes of loading and different confining pressures. The results show that suction in the sample reduced with increasing number of loading cycles of the same magnitude. The resilient modulus initially increased with increasing water content up to approximately optimum water content, and substantially reduced with further increase in water content. Key Words: suction, resilient modulus, subgrade, repeated loading, small strain measurements, compaction.

Suppressors of cytokine signalling (SOCS): putative modulators of cytokine bioactivity in health and disease

Cytokines are important modulators of homeostatic processes such as development, haematopoiesis and host defence, A recently identified family of proteins, the supressors of cytokine signalling (SOCS) act as negative regulators of the key cytokine-activated signalling pathway, the Janus kinase/signal transducers and activators of transcription (JAK/STAT) cascade, In the current review, the discovery, structural features, regulation of expression, mechanisms of JAK/STAT inhibition and putative role in health and disease of the SOCS family are discussed.

Effects of confining pressure and water content on performance of unsaturated compacted clay under repeated loading

This paper examines the performance of unsaturated soils under repeated loading. As part of the research, a triaxial system was developed that incorporates small-strain measurements using Hall effect transducers, in addition to suction measurements taken using a psychrometer. Tests were conducted on samples of kaolin under constant water mass conditions. The results address the effects of compaction effort and water content at the time of compaction on the overall performance of unsaturated soils, under different amplitudes of loading and different confining pressures. The results show that suction in the sample reduced with increasing number of loading cycles of the same magnitude. The resilient modulus initially increased with increasing water content up to approximately optimum water content, and then reduced substantially with further increase in water content.

Analysis of IL6 Signal Transduction Model using Reduced Rank Regression

This work presents the application of reduced rank regression to the field of systems biology. A computational approach is used to investigate the mechanisms of the janus-associated kinases/signal transducers and transcription factors (JAK/STAT) and mitogen activated protein kinases (MAPK) signal transduction pathways in hepatic cells stimulated by interleukin-6. The results obtained identify the contribution of individual reactions to the dynamics of the model. These findings are compared to previously available results from sensitivity analysis of the model which focused on the parameters involved and their effect. This application of reduced rank regression allows for an understanding of the individual reaction terms involved in the modelled signal transduction pathways and has the benefit of being computationally inexpensive. The obtained results complement existing findings and also confirm the importance of several protein complexes in the MAPK pathway which hints at benefits that can be achieved by further refining the model.

PIAS1 is increased in human prostate cancer and enhances proliferation through inhibition of p21

Prostate cancer development and progression are associated with alterations in expression and function of elements of cytokine networks, some of which can activate multiple signaling pathways. Protein inhibitor of activated signal transducers and activators of transcription (PIAS)1, a regulator of cytokine signaling, may be implicated in the modulation of cellular events during carcinogenesis. This study was designed to investigate the functional significance of PIAS1 in models of human prostate cancer. We demonstrate for the first time that PIAS1 protein expression is significantly higher in malignant areas of clinical prostate cancer specimens than in normal tissues, thus suggesting a growth-promoting role for PIAS1. Expression of PIAS1 was observed in the majority of tested prostate cancer cell lines. In addition, we investigated the mechanism by which PIAS1 might promote prostate cancer and found that down-regulation of PIAS1 leads to decreased proliferation and colony formation ability of prostate cancer cell lines. This decrease correlates with cell cycle arrest in the G0/G1 phase, which is mediated by increased expression of p21(CIP1/WAF1). Furthermore, PIAS1 overexpression positively influences cell cycle progression and thereby stimulates proliferation, which can be mechanistically explained by a decrease in the levels of cellular p21. Taken together, our data reveal an important new role for PIAS1 in the regulation of cell proliferation in prostate cancer.

Feedback Networks and Self-Oscillating Objects

A system of self-designed microphones, speakers and transducers creating performable feedback networks and self-oscillating objects. Performance SARC Sonic Lab, Belfast, 18 March 2015

TRP channel expression in human gingival fibroblasts

Background: The transient receptor potential (TRP) super family of ion channels is believed to play a critical role in sensory physiology, acting as transducers for thermal, mechanical and chemical stimuli. Our understanding of the role of TRP channel expression in gingival fibroblasts is currently limited. The role of non-neuronal TRP channel expression is an area of much research interest particularly since TRP channel activation has recently been hypothesised to be associated with inflammation. Objectives: The present study was designed to determine the expression of TRPV1, TRPV2, TRPV3 and TRPV4 on human gingival fibroblasts. Methods: Human gingival fibroblasts were derived by explant culture from surgical tissue following ethical approval. Cells were maintained in Dulbecco's modified Eagle's medium (DMEM), containing 10% fetal calf serum (FCS) in 5% CO2. Cell lysates of gingival fibroblasts were electrophoresed and blotted on to nitrocellulose before probing with specific anti-TRP antibodies. Immunoreactive bands were detected using anti-species antibodies and chemiluminescent detection. Results: Gingival fibroblasts were shown to express proteins corresponding to the TRPV1, TRPV2, TRPV3 and TRPV4 channels as determined by western blotting. Conclusion: This study reports for the first time the expression of TRPV1, TRPV2, TRPV3 and TRPV4 by gingival fibroblasts. Knowledge of the expression of TRP channels by human gingival fibroblasts will guide future research on the roles of TRP channels in sensing the external environment in the oral cavity.

'Heat-sensing' TRP channel expression in human odontoblasts

Background: Thermal changes in the oral cavity are a common trigger of dental pain. Several members of the transient receptor potential (TRP) super family of ion channels are believed to play a critical role in sensory physiology, where they act as transducers for thermal, mechanical and chemical stimuli. Objectives: The present study was designed to determine the expression and functionality of the TRPV1 channel in human odontoblasts. Methods: Cultured human odontoblasts were derived from dental pulp cells induced with 2 mM beta-glycerophosphate. Molecular and protein expression of TRPV1 was confirmed by PCR, western blotting and immunohistochemistry. Functional expression of the ‘heat-sensing' TRPV1 channel was investigated using a Ca2+ microfluorimetry assay in the presence of agonists/antagonists or with appropriate adjustment of the recording chamber temperature. Results: The odontoblastic phenotype of the cells was confirmed by the expression of the odontoblast markers dentin sialophosphoprotein (DSPP) and nestin. Expression of TRPV1 in human odontoblastic cells was confirmed by PCR, western blotting and immunohistochemistry. Odontoblasts were shown to respond to pharmacological agonists and to increasing temperature by an increase in intracellular Ca2+. Both the pharmacological and temperature responses could be blocked by specific antagonists. These results indicate that odontoblasts may sense heat via TRPV1. Conclusion: This study reports that TRPV1 is expressed by human odontoblasts and is activated by specific pharmacological agonists and by heat.
This work was supported by Research Grants from the Royal College of Surgeons of Edinburgh and the British Endodontic Society