Model development and dynamic load-sharing analysis of longitudinal-connected air suspensions

The objective of this research was to investigate the effect of suspension parameters on dynamic load-sharing of longitudinal-connected air suspensions of a tri-axle semi-trailer. A novel nonlinear model of a multi-axle semi-trailer with longitudinal-connected air suspension was formulated based on fluid mechanics and thermodynamics and was validated through test results. The effects of suspension parameters on dynamic load-sharing and road-friendliness of the semi-trailer were analyzed. Simulation results indicate that the road-friendliness metric DLC (Dynamic Load Coefficient), is generally in accordance with the load-sharing metric - DLSC (Dynamic Load Sharing Coefficient). When the static height or static pressure increases, the DLSC optimization ratio declines monotonically. The effect of employing larger air lines and connectors on the DLSC optimization ratio gives varying results as road roughness increases and as driving speed increases. The results also indicate that if the air line diameter is always assumed to be larger than the connector diameter, the influence of air line diameter on load-sharing is more significant than that of the connector.

A non-linear dynamic analysis of heavy haul track line sleepers under wheel flat

Significant wheel-rail dynamic forces occur because of imperfections in the wheels and/or rail. One of the key responses to the transmission of these forces down through the track is impact force on the sleepers. Dynamic analysis of nonlinear systems is very complicated and does not lend itself easily to a classical solution of multiple equations. Trying to deduce the behaviour of track components from experimental data is very difficult because such data is hard to obtain and applies to only the particular conditions of the track being tested. The finite element method can be the best solution to this dilemma. This paper describes a finite element model using the software package ANSYS for various sized flat defects in the tread of a wheel rolling at a typical speed on heavy haul track. The paper explores the dynamic response of a prestressed concrete sleeper to these defects.

Rule-based transit signal priority control method using a real-time transit travel time prediction model

An advanced rule-based Transit Signal Priority (TSP) control method is presented in this paper. An on-line transit travel time prediction model is the key component of the proposed method, which enables the selection of the most appropriate TSP plans for the prevailing traffic and transit condition. The new method also adopts a priority plan re-development feature that enables modifying or even switching the already implemented priority plan to accommodate changes in the traffic conditions. The proposed method utilizes conventional green extension and red truncation strategies and also two new strategies including green truncation and queue clearance. The new method is evaluated against a typical active TSP strategy and also the base case scenario assuming no TSP control in microsimulation. The evaluation results indicate that the proposed method can produce significant benefits in reducing the bus delay time and improving the service regularity with negligible adverse impacts on the non-transit street traffic.

Designing a new robust on-line secondary path modeling technique for feedforward active noise control systems

Several approaches have been introduced in the literature for active noise control (ANC) systems. Since the filtered-x least-mean-square (FxLMS) algorithm appears to be the best choice as a controller filter, researchers tend to improve performance of ANC systems by enhancing and modifying this algorithm. This paper proposes a new version of the FxLMS algorithm, as a first novelty. In many ANC applications, an on-line secondary path modeling method using white noise as a training signal is required to ensure convergence of the system. As a second novelty, this paper proposes a new approach for on-line secondary path modeling on the basis of a new variable-step-size (VSS) LMS algorithm in feed forward ANC systems. The proposed algorithm is designed so that the noise injection is stopped at the optimum point when the modeling accuracy is sufficient. In this approach, a sudden change in the secondary path during operation makes the algorithm reactivate injection of the white noise to re-adjust the secondary path estimate. Comparative simulation results shown in this paper indicate the effectiveness of the proposed approach in reducing both narrow-band and broad-band noise. In addition, the proposed ANC system is robust against sudden changes of the secondary path model.

A microscopic simulation model to estimate Bus Rapid Transit (BRT) station service capacity with mixed stopping and non-stopping bus operation

Bus Rapid Transit (BRT) station is the interface between passenger and service. The station is crucial to line operation as it is typically the only location where buses can pass each other. Congestion may occur here when buses maneuvering into and out of the platform lane interfere with bus flow, or when a queue of buses forms upstream of the platform lane blocking the passing lane. However, some systems include operation where express buses pass the critical station, resulting in a proportion of non stopping buses. It is important to understand the operation of the critical busway station under this type of operation, as it affects busway line capacity. This study uses micro simulation to treat the BRT station operation and to analyze the relationship between station Limit state bus capacity (B_ls), Total Bus Capacity (B_ttl). First, the simulation model is developed for Limit state scenario and then a mathematical model is defined, calibrated for a specified range of controlled scenarios of mean and coefficient of variation of dwell time. Thereafter, the proposed B_ls model is extended to consider non stopping buses and B_ttlmodel is defined. The proposed models provides better understanding to the BRT line capacity and is useful for transit authorities for designing better BRT operation.

Characterisation of enterovirus 71 replication kinetics in human colorectal cell line, HT29

Hand, Foot and Mouth Disease (HFMD), a contagious viral disease that commonly affects infants and children with blisters and flu like symptoms, is caused by a group of enteroviruses such as Enterovirus 71 (EV71) and coxsackievirus A16 (CA16). However some HFMD caused by EV71 may further develop into severe neurological complications such as encephalitis and meningitis. The route of transmission was postulated that the virus transmit from one person to another through direct contact of vesicular fluid or droplet from the infected or via faecal-oral route. To this end, this study utilised a human colorectal adenocarcinoma cell line (HT29) with epithelioid morphology as an in vitro model for the investigation of EV71 replication kinetics. Using qPCR, viral RNA was first detected in HT29 cells as early as 12 h post infection (hpi) while viral protein was first detected at 48 hpi. A significant change in HT29 cells’ morphology was also observed after 48 hpi. Furthermore HT29 cell viability also significantly decreased at 72 hpi. Together, data from this study demonstrated that co-culture of HT29 with EV71 is a useful in vitro model to study the pathogenesis of EV71

In vitro and in vivo MMP gene expression localisation by In Situ-RT-PCR in cell culture and paraffin embedded human breast cancer cell line xenografts

Background Members of the matrix metalloproteinase (MMP) family of proteases are required for the degradation of the basement membrane and extracellular matrix in both normal and pathological conditions. In vitro, MT1-MMP (MMP-14, membrane type-1-MMP) expression is higher in more invasive human breast cancer (HBC) cell lines, whilst in vivo its expression has been associated with the stroma surrounding breast tumours. MMP-1 (interstitial collagenase) has been associated with MDA-MB-231 invasion in vitro, while MMP-3 (stromelysin-1) has been localised around invasive cells of breast tumours in vivo. As MMPs are not stored intracellularly, the ability to localise their expression to their cells of origin is difficult. Methods We utilised the unique in situ-reverse transcription-polymerase chain reaction (IS-RT-PCR) methodology to localise the in vitro and in vivo gene expression of MT1-MMP, MMP-1 and MMP-3 in human breast cancer. In vitro, MMP induction was examined in the MDA-MB-231 and MCF-7 HBC cell lines following exposure to Concanavalin A (Con A). In vivo, we examined their expression in archival paraffin embedded xenografts derived from a range of HBC cell lines of varied invasive and metastatic potential. Mouse xenografts are heterogenous, containing neoplastic human parenchyma with mouse stroma and vasculature and provide a reproducible in vivo model system correlated to the human disease state. Results In vitro, exposure to Con A increased MT1-MMP gene expression in MDA-MB-231 cells and decreased MT1-MMP gene expression in MCF-7 cells. MMP-1 and MMP-3 gene expression remained unchanged in both cell lines. In vivo, stromal cells recruited into each xenograft demonstrated differences in localised levels of MMP gene expression. Specifically, MDA-MB-231, MDA-MB-435 and Hs578T HBC cell lines are able to influence MMP gene expression in the surrounding stroma. Conclusion We have demonstrated the applicability and sensitivity of IS-RT-PCR for the examination of MMP gene expression both in vitro and in vivo. Induction of MMP gene expression in both the epithelial tumour cells and surrounding stromal cells is associated with increased metastatic potential. Our data demonstrate the contribution of the stroma to epithelial MMP gene expression, and highlight the complexity of the role of MMPs in the stromal-epithelial interactions within breast carcinoma.

A microscopic simulation model to estimate bus rapid transit station bus capacity

The Bus Rapid Transit (BRT) station is the interface between passengers and services. The station is crucial to line operation as it is typically the only location where buses can pass each other. Congestion may occur here when buses maneuvering into and out of the platform lane interfere with bus flow, or when a queue of buses forms upstream of the platform lane blocking the passing lane. Further, some systems include operation where express buses do not observe the station, resulting in a proportion of non-stopping buses. It is important to understand the operation of the station under this type of operation and its effect on BRT line capacity. This study uses microscopic traffic simulation modeling to treat the BRT station operation and to analyze the relationship between station bus capacity and BRT line bus capacity. First, the simulation model is developed for the limit state scenario and then a statistical model is defined and calibrated for a specified range of controlled scenarios of dwell time characteristics. A field survey was conducted to verify the parameters such as dwell time, clearance time and coefficient of variation of dwell time to obtain relevant station bus capacity. The proposed model for BRT bus capacity provides a better understanding of BRT line capacity and is useful to transit authorities in BRT planning, design and operation.

Assessing land-use and transport integration via a spatial composite indexing model

Achieving sustainable urban development is identified as one ultimate goal of many contemporary planning endeavours and has become central to formulation of urban planning policies. Within this concept, land-use and transport integration is highlighted as one of the most important and attainable policy objectives. In many cities, integration is embraced as an integral part of local development plans, and a number of key integration principles are identified. However, the lack of available evaluation methods to measure extent of urban sustainability levels prevents successful implementation of these principles. This paper introduces a new indicator-based spatial composite indexing model developed to measure sustainability performance of urban settings by taking into account land-use and transport integration principles. Model indicators are chosen via a thorough selection process in line with key principles of land-use and transport integration. These indicators are grouped into categories and themes according to their topical relevance. These indicators are then aggregated to form a spatial composite index to portray an overview of the sustainability performance of the pilot study area used for model demonstration. The study results revealed that the model is a practical instrument for evaluating success of local integration policies and visualizing sustainability performance of built environments and useful in both identifying problematic areas as well as formulating policy interventions.

Meta-analysis of individual patient data from randomized trials of chemotherapy plus cetuximab as first-line treatment for advanced non-small cell lung cancer

OBJECTIVES: Four randomized phase II/III trials investigated the addition of cetuximab to platinum-based, first-line chemotherapy in patients with advanced non-small cell lung cancer (NSCLC). A meta-analysis was performed to examine the benefit/risk ratio for the addition of cetuximab to chemotherapy. MATERIALS AND METHODS: The meta-analysis included individual patient efficacy data from 2018 patients and individual patient safety data from 1970 patients comprising respectively the combined intention-to-treat and safety populations of the four trials. The effect of adding cetuximab to chemotherapy was measured by hazard ratios (HRs) obtained using a Cox proportional hazards model and odds ratios calculated by logistic regression. Survival rates at 1 year were calculated. All applied models were stratified by trial. Tests on heterogeneity of treatment effects across the trials and sensitivity analyses were performed for all endpoints. RESULTS: The meta-analysis demonstrated that the addition of cetuximab to chemotherapy significantly improved overall survival (HR 0.88, p=0.009, median 10.3 vs 9.4 months), progression-free survival (HR 0.90, p=0.045, median 4.7 vs 4.5 months) and response (odds ratio 1.46, p<0.001, overall response rate 32.2% vs 24.4%) compared with chemotherapy alone. The safety profile of chemotherapy plus cetuximab in the meta-analysis population was confirmed as manageable. Neither trials nor patient subgroups defined by key baseline characteristics showed significant heterogeneity for any endpoint. CONCLUSION: The addition of cetuximab to platinum-based, first-line chemotherapy for advanced NSCLC significantly improved outcome for all efficacy endpoints with an acceptable safety profile, indicating a favorable benefit/risk ratio.

Lattice-based completely non-malleable public-key encryption in the standard model

An encryption scheme is non-malleable if giving an encryption of a message to an adversary does not increase its chances of producing an encryption of a related message (under a given public key). Fischlin introduced a stronger notion, known as complete non-malleability, which requires attackers to have negligible advantage, even if they are allowed to transform the public key under which the related message is encrypted. Ventre and Visconti later proposed a comparison-based definition of this security notion, which is more in line with the well-studied definitions proposed by Bellare et al. The authors also provide additional feasibility results by proposing two constructions of completely non-malleable schemes, one in the common reference string model using non-interactive zero-knowledge proofs, and another using interactive encryption schemes. Therefore, the only previously known completely non-malleable (and non-interactive) scheme in the standard model, is quite inefficient as it relies on generic NIZK approach. They left the existence of efficient schemes in the common reference string model as an open problem. Recently, two efficient public-key encryption schemes have been proposed by Libert and Yung, and Barbosa and Farshim, both of them are based on pairing identity-based encryption. At ACISP 2011, Sepahi et al. proposed a method to achieve completely non-malleable encryption in the public-key setting using lattices but there is no security proof for the proposed scheme. In this paper we review the mentioned scheme and provide its security proof in the standard model. Our study shows that Sepahi’s scheme will remain secure even for post-quantum world since there are currently no known quantum algorithms for solving lattice problems that perform significantly better than the best known classical (i.e., non-quantum) algorithms.

Development of optical ray tracing model of a standard parabolic trough collector

Parabolic trough concentrator collector is the most matured, proven and widespread technology for the exploitation of the solar energy on a large scale for middle temperature applications. The assessment of the opportunities and the possibilities of the collector system are relied on its optical performance. A reliable Monte Carlo ray tracing model of a parabolic trough collector is developed by using Zemax software. The optical performance of an ideal collector depends on the solar spectral distribution and the sunshape, and the spectral selectivity of the associated components. Therefore, each step of the model, including the spectral distribution of the solar energy, trough reflectance, glazing anti-reflection coating and the absorber selective coating is explained and verified. Radiation flux distribution around the receiver, and the optical efficiency are two basic aspects of optical simulation are calculated using the model, and verified with widely accepted analytical profile and measured values respectively. Reasonably very good agreement is obtained. Further investigations are carried out to analyse the characteristics of radiation distribution around the receiver tube at different insolation, envelop conditions, and selective coating on the receiver; and the impact of scattered light from the receiver surface on the efficiency. However, the model has the capability to analyse the optical performance at variable sunshape, tracking error, collector imperfections including absorber misalignment with focal line and de-focal effect of the absorber, different rim angles, and geometric concentrations. The current optical model can play a significant role in understanding the optical aspects of a trough collector, and can be employed to extract useful information on the optical performance. In the long run, this optical model will pave the way for the construction of low cost standalone photovoltaic and thermal hybrid collector in Australia for small scale domestic hot water and electricity production.

Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction : a model for cross-modulation

Background A feature of epithelial to mesenchymal transition (EMT) relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC. Methods PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome. Results When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4). Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse correlation with lower expression values being predictive of increased risk. Conclusion ST in combination with EGF directed a greater EMT via actin depolymerisation and focal contact size reduction, resulting in a loosening of cell-ECM attachment along with Snail1-Zeb1/δEF1 induction. This appeared fundamentally different to the EGF-induced EMT, highlighting the multiple pathways which can regulate EMT. Our findings add support for a functional role for Snail1 in invasive breast cancer.

Upregulated MT1-MMP/TIMP-2 axis in the TSU-Pr1-B1/B2 model of metastatic progression in transitional cell carcinoma of the bladder

Muscle invasive transitional cell carcinoma (TCC) of the bladder is associated with a high frequency of metastasis, resulting in poor prognosis for patients presenting with this disease. Models that capture and demonstrate step-wise enhancement of elements of the human metastatic cascade on a similar genetic background are useful research tools. We have utilized the transitional cell carcinoma cell line TSU-Pr1 to develop an in vivo experimental model of bladder TCC metastasis. TSU-Pr1 cells were inoculated into the left cardiac ventricle of SCID mice and the development of bone metastases was monitored using high resolution X-ray. Tumor tissue from a single bone lesion was excised and cultured in vitro to generate the TSU-Pr1-B1 subline. This cycle was repeated with the TSU-Pr1-B1 cells to generate the successive subline TSU-Pr1-B2. DNA profiling and karyotype analysis confirmed the genetic relationship of these three cell lines. In vitro, the growth rate of these cell lines was not significantly different. However, following intracardiac inoculation TSU-Pr1, TSU-Pr1-B1 and TSU-Pr1-B2 exhibited increasing metastatic potential with a concomitant decrease in time to the onset of radiologically detectable metastatic bone lesions. Significant elevations in the levels of mRNA expression of the matrix metalloproteases (MMPs) membrane type 1-MMP (MT1-MMP), MT2-MMP and MMP-9, and their inhibitor, tissue inhibitor of metalloprotease-2 (TIMP-2), across the progressively metastatic cell lines, were detected by quantitative PCR. Given the role of MT1-MMP and TIMP-2 in MMP-2 activation, and the upregulation of MMP-9, these data suggest an important role for matrix remodeling, particularly basement membrane, in this progression. The TSU-Pr1-B1/B2 model holds promise for further identification of important molecules.

LCC15-MB : a vimentin-positive human breast cancer cell line from a femoral bone metastasis

The LCC15-MB cell line was established from a femoral bone metastasis that arose in a 29-year-old woman initially diagnosed with an infiltrating ductal mammary adenocarcinoma. The tumor had a relatively high (8%) S-phase fraction and 1/23 positive lymph nodes (LN). Both the primary tumor and LN metastasis were positive for estrogen receptor (ER) and progesterone receptor (PgR), but lacked erbB2 expression. Approximately one year later, the patient presented with a 0.8 cm comedo-type intraductal mammary adenocarcinoma in the left breast that was negative for ER and PgR, but positive for erbB2. Thirty-five months after the initial diagnosis she was treated for acute skeletal metastasis, and stabilized with a hip replacement. At this time, tumor cells were removed from surplus involved bone, inoculated into cell culture, and developed into the LCC15-MB cell line. The bone metastasis was a poorly differentiated adenocarcinoma lacking ER, PgR, and erbB2, characteristics shared by the LCC15-MB cells, although ER can be re-expressed by treatment of the LCC15-MB cells for 5 days with 75 μM 5-aza-2'-deoxycytidine. The LCC15-MB cell line is tumorigenic when implanted subcutaneously in NCr nu/nu mice and produces long-bone metastases after intracardiac injection. Although the bone metastasis from which the LCC15-MB cell line was derived lacked vimentin (VIM) expression, the original primary tumor and lymph node metastasis were strongly VIM positive, as are LCC15-MB cells in vitro and in nude mice. The karyotype and isozyme profiles of LCC15-MB cells are consistent with its origin from a human female, with most chromosome counts in the hypertriploid range. Thirty-two marker chromosomes are present. These cells provide an in vitro/in vivo model in which to study the inter-relationships between ER, VIM, and bone metastasis in human breast cancer.