An approach for identifying the limit states of resilience of a water supply system

This paper presents an approach for identifying the limit states of resilience in a water supply system when influenced by different types of pressure (disturbing) forces. Understanding of systemic resilience facilitates identification of the trigger points for early managerial action to avoid further loss of ability to provide satisfactory service availability when the ability to supply water is under pressure. The approach proposed here is to illustrate the usefulness of a surrogate measure of resilience depicted in a three dimensional space encompassing independent pressure factors. That enables visualisation of the transition of the system-state (resilience) between high to low resilience regions and acts as an early warning trigger for decision-making. The necessity of a surrogate measure arises as a means of linking resilience to the identified pressures as resilience cannot be measured directly. The basis for identifying the resilience surrogate and exploring the interconnected relationships within the complete system, is derived from a meta-system model consisting of three nested sub-systems representing the water catchment and reservoir; treatment plant; and the distribution system and end-users. This approach can be used as a framework for assessing levels of resilience in different infrastructure systems by identifying a surrogate measure and its relationship to relevant pressures acting on the system.

In-cylinder pressure and inter-cycle variability analysis for a compression ignition engine : Bayesian approaches

This thesis introduced Bayesian statistics as an analysis technique to isolate resonant frequency information in in-cylinder pressure signals taken from internal combustion engines. Applications of these techniques are relevant to engine design (performance and noise), energy conservation (fuel consumption) and alternative fuel evaluation. The use of Bayesian statistics, over traditional techniques, allowed for a more in-depth investigation into previously difficult to isolate engine parameters on a cycle-by-cycle basis. Specifically, these techniques facilitated the determination of the start of pre-mixed and diffusion combustion and for the in-cylinder temperature profile to be resolved on individual consecutive engine cycles. Dr Bodisco further showed the utility of the Bayesian analysis techniques by applying them to in-cylinder pressure signals taken from a compression ignition engine run with fumigated ethanol.

The influence of fatty acid methyl ester profiles on inter-cycle variability in a heavy duty compression ignition engine

With the advent of alternative fuels, such as biodiesels and related blends, it is important to develop an understanding of their effects on inter-cycle variability which, in turn, influences engine performance as well as its emission. Using four methanol trans-esterified biomass fuels of differing carbon chain length and degree of unsaturation, this paper provides insight into the effect that alternative fuels have on inter-cycle variability. The experiments were conducted with a heavy-duty Cummins, turbo-charged, common-rail compression ignition engine. Combustion performance is reported in terms of the following key in-cylinder parameters: indicated mean effective pressure (IMEP), net heat release rate (NHRR), standard deviation of variability (StDev), coefficient of variation (CoV), peak pressure, peak pressure timing and maximum rate of pressure rise. A link is also established between the cyclic variability and oxygen ratio, which is a good indicator of stoichiometry. The results show that the fatty acid structures did not have a significant effect on injection timing, injection duration, injection pressure, StDev of IMEP, or the timing of peak motoring and combustion pressures. However, a significant effect was noted on the premixed and diffusion combustion proportions, combustion peak pressure and maximum rate of pressure rise. Additionally, the boost pressure, IMEP and combustion peak pressure were found to be directly correlated to the oxygen ratio. The emission of particles positively correlates with oxygen content in the fuel as well as in the air-fuel mixture resulting in a higher total number of particles per unit of mass.

Bandwidth considerations for multilevel converters

Multilevel converters can achieve an overall effective switch frequency multiplication and consequent ripple reduction through the cancellation of the lowest order switch frequency terms. This paper investigates the harmonic content and the frequency response of these multimodulator converters. It is shown that the transfer function of uniformly sampled modulators is a bessel function associated with the inherent sampling process. Naturally sampled modulators have a flat transfer function, but multiple switchings per switch cycle will occur unless the input is slew-rate limited. Lower sideband harmonics of the effective carrier frequency and, in uniform converters, harmonics of the input signal also limit the useful bandwidth. Observations about the effect of the number of converters, their type (naturally or uniformly sampled), and the ratio of modulating frequency and switch frequency are made

Making sense of purpose, direction and innovation : an embedded design led innovation case study in the Australian mining industry

The mining equipment technology services sector is driven by a reactive and user-centered design approach, with a technological focus on incremental new product development. As Australia moves out of its sustained mining boom, companies need to rethink their strategic position, to become agile to stay relevant in an enigmatic market. This paper reports on the first five months on an embedded case study within an Australian, family-owned mining manufacturer. The first author is currently engaged in a longitudinal design led innovation project, as a catalyst to guide the company’s journey to design integration. The results find that design led innovation could act as a channel for highlighting and exploring company disconnections with the marketplace and offer a customer-centric catalyst for internal change. Data collected for this study is from 12 analysed semistructured interviews, a focus group and a reflective journal, over a five-month period. This paper explores limitations to design integration, and highlights opportunities to explore and leverage entrepreneurial characteristics to stay agile, broaden innovation and future-proof through the next commodity cycle in the mining industry.

Ultimate flexural limit states analysis of prestressed concrete sleeper

Railway is one of the most important, reliable and widely used means of transportation, carrying freight, passengers, minerals, grains, etc. Thus, research on railway tracks is extremely important for the development of railway engineering and technologies. The safe operation of a railway track is based on the railway track structure that includes rails, fasteners, pads, sleepers, ballast, subballast and formation. Sleepers are very important components of the entire structure and may be made of timber, concrete, steel or synthetic materials. Concrete sleepers were first installed around the middle of last century and currently are installed in great numbers around the world. Consequently, the design of concrete sleepers has a direct impact on the safe operation of railways. The "permissible stress" method is currently most commonly used to design sleepers. However, the permissible stress principle does not consider the ultimate strength of materials, probabilities of actual loads, and the risks associated with failure, all of which could lead to the conclusion of cost-ineffectiveness and over design of current prestressed concrete sleepers. Recently the limit states design method, which appeared in the last century and has been already applied in the design of buildings, bridges, etc, is proposed as a better method for the design of prestressed concrete sleepers. The limit states design has significant advantages compared to the permissible stress design, such as the utilisation of the full strength of the member, and a rational analysis of the probabilities related to sleeper strength and applied loads. This research aims to apply the ultimate limit states design to the prestressed concrete sleeper, namely to obtain the load factors of both static and dynamic loads for the ultimate limit states design equations. However, the sleepers in rail tracks require different safety levels for different types of tracks, which mean the different types of tracks have different load factors of limit states design equations. Therefore, the core tasks of this research are to find the load factors of the static component and dynamic component of loads on track and the strength reduction factor of the sleeper bending strength for the ultimate limit states design equations for four main types of tracks, i.e., heavy haul, freight, medium speed passenger and high speed passenger tracks. To find those factors, the multiple samples of static loads, dynamic loads and their distributions are needed. In the four types of tracks, the heavy haul track has the measured data from Braeside Line (A heavy haul line in Central Queensland), and the distributions of both static and dynamic loads can be found from these data. The other three types of tracks have no measured data from sites and the experimental data are hardly available. In order to generate the data samples and obtain their distributions, the computer based simulations were employed and assumed the wheel-track impacts as induced by different sizes of wheel flats. A valid simulation package named DTrack was firstly employed to generate the dynamic loads for the freight and medium speed passenger tracks. However, DTrack is only valid for the tracks which carry low or medium speed vehicles. Therefore, a 3-D finite element (FE) model was then established for the wheel-track impact analysis of the high speed track. This FE model has been validated by comparing its simulation results with the DTrack simulation results, and with the results from traditional theoretical calculations based on the case of heavy haul track. Furthermore, the dynamic load data of the high speed track were obtained from the FE model and the distributions of both static and dynamic loads were extracted accordingly. All derived distributions of loads were fitted by appropriate functions. Through extrapolating those distributions, the important parameters of distributions for the static load induced sleeper bending moment and the extreme wheel-rail impact force induced sleeper dynamic bending moments and finally, the load factors, were obtained. Eventually, the load factors were obtained by the limit states design calibration based on reliability analyses with the derived distributions. After that, a sensitivity analysis was performed and the reliability of the achieved limit states design equations was confirmed. It has been found that the limit states design can be effectively applied to railway concrete sleepers. This research significantly contributes to railway engineering and the track safety area. It helps to decrease the failure and risks of track structure and accidents; better determines the load range for existing sleepers in track; better rates the strength of concrete sleepers to support bigger impact and loads on railway track; increases the reliability of the concrete sleepers and hugely saves investments on railway industries. Based on this research, many other bodies of research can be promoted in the future. Firstly, it has been found that the 3-D FE model is suitable for the study of track loadings and track structure vibrations. Secondly, the equations for serviceability and damageability limit states can be developed based on the concepts of limit states design equations of concrete sleepers obtained in this research, which are for the ultimate limit states.

Environmental sustainability of urban road transport : an integrated analysis for life cycle emission impact

Despite of significant contributions of urban road transport to global economy and society, it is one of the largest sources of local and global emission impact. In order to address the environmental concerns of urban road transport it is imperative to achieve a holistic understanding of contributory factors causing emissions which requires a complete look onto its whole life cycle. Previous studies were mainly based on segmental views which mostly studied environmental impacts of individual transport modes and very few considered impacts other than operational phase. This study develops an integrated life cycle inventory model for urban road transport emissions from a holistic modal perspective. Singapore case was used to demonstrate the model. Results show that total life cycle greenhouse gas emission from Singapore’s road transport sector is 7.8 million tons per year. The total amount of criteria air pollutants are also estimated in this study.

First-cycle rash and survival in patients with advanced non-small-cell lung cancer receiving cetuximab in combination with first-line chemotherapy : a subgroup analysis of data from the FLEX phase 3 study

Background: The randomised phase 3 First-Line Erbitux in Lung Cancer (FLEX) study showed that the addition of cetuximab to cisplatin and vinorelbine significantly improved overall survival compared with chemotherapy alone in the first-line treatment of advanced non-small-cell lung cancer (NSCLC). The main cetuximab-related side-effect was acne-like rash. Here, we assessed the association of this acne-like rash with clinical benefit. Methods: We did a subgroup analysis of patients in the FLEX study, which enrolled patients with advanced NSCLC whose tumours expressed epidermal growth factor receptor. Our landmark analysis assessed if the development of acne-like rash in the first 21 days of treatment (first-cycle rash) was associated with clinical outcome, on the basis of patients in the intention-to-treat population alive on day 21. The FLEX study is registered with ClinicalTrials.gov, number NCT00148798. Findings: 518 patients in the chemotherapy plus cetuximab group-290 of whom had first-cycle rash-and 540 patients in the chemotherapy alone group were alive on day 21. Patients in the chemotherapy plus cetuximab group with first-cycle rash had significantly prolonged overall survival compared with patients in the same treatment group without first-cycle rash (median 15·0 months [95% CI 12·8-16·4] vs 8·8 months [7·6-11·1]; hazard ratio [HR] 0·631 [0·515-0·774]; p<0·0001). Corresponding significant associations were also noted for progression-free survival (median 5·4 months [5·2-5·7] vs 4·3 months [4·1-5·3]; HR 0·741 [0·607-0·905]; p=0·0031) and response (rate 44·8% [39·0-50·8] vs 32·0% [26·0-38·5]; odds ratio 1·703 [1·186-2·448]; p=0·0039). Overall survival for patients without first-cycle rash was similar to that of patients that received chemotherapy alone (median 8·8 months [7·6-11·1] vs 10·3 months [9·6-11·3]; HR 1·085 [0·910-1·293]; p=0·36). The significant overall survival benefit for patients with first-cycle rash versus without was seen in all histology subgroups: adenocarcinoma (median 16·9 months, [14·1-20·6] vs 9·3 months [7·7-13·2]; HR 0·614 [0·453-0·832]; p=0·0015), squamous-cell carcinoma (median 13·2 months [10·6-16·0] vs 8·1 months [6·7-12·6]; HR 0·659 [0·472-0·921]; p=0·014), and carcinomas of other histology (median 12·6 months [9·2-16·4] vs 6·9 months [5·2-11·0]; HR 0·616 [0·392-0·966]; p=0·033). Interpretation: First-cycle rash was associated with a better outcome in patients with advanced NSCLC who received cisplatin and vinorelbine plus cetuximab as a first-line treatment. First-cycle rash might be a surrogate clinical marker that could be used to tailor cetuximab treatment for advanced NSCLC to those patients who would be most likely to derive a significant benefit. Funding: Merck KGaA. © 2011 Elsevier Ltd.

Reversibility of liver failure secondary to metastatic breast cancer by vinorelbine and cisplatin chemotherapy

Purpose: The development of liver metastases from breast cancer is associated with a very poor prognosis, estimated at 4 months median survival. Since treatment with many chemotherapeutic agents is relatively contraindicated, we assessed the safety, tolerability and potential efficacy of combination chemotherapy with vinorelbine and cisplatin (ViP). Method: Pilot study in 11 patients with histologically confirmed breast carcinoma, radiological evidence of liver metastases and serum bilirubin greater than 1.5 times the upper limit of normal. Patients received up to six cycles of cisplatin (75 mg/m 2) every 21 days and vinorelbine (20 mg/m 2) on days 1 and 8 of every 21-day cycle. Measurement of liver lesions was performed on CT scan every 8 weeks into treatment. Results: The most frequently reported adverse event was myelosuppression. Other adverse effects included nausea, vomiting and mild neurotoxicity. Two patients died after one treatment with ViP, one of whom suffered an intracerebral haemorrhage that was possibly treatment-related. Improvement in liver function tests was observed in 10 patients, and mean time to normalization of bilirubin levels was 36 days. Partial responses were documented radiologically in 7 out of 11 patients treated. Median overall survival from trial entry was 6.5 months (range 11-364 days), with one patient alive 13 months from trial entry. Conclusion: Normalization of liver function is possible with ViP treatment of metastatic breast cancer, offering the potential to prolong survival. Phase II clinical trials of this regimen in this patient group should include measurement of quality of life in order to assess risk versus benefit.

Biomechanical characteristics of peripheral diabetic neuropathy : a systematic review and meta-analysis of findings from the gait cycle, muscle activity and dynamic barefoot plantar pressure

Background: Diabetic peripheral neuropathy is an important cause of foot ulceration and limb loss. This systematic review and meta-analysis investigated the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and dynamic plantar pressures. Methods: Electronic databases were searched systematically for articles reporting the effect of diabetic peripheral neuropathy on gait, dynamic electromyography and plantar pressures. Searches were restricted to articles published between January 2000 and April 2012. Outcome measures assessed included spatiotemporal parameters, lower limb kinematics, kinetics, muscle activation and plantar pressure. Meta-analyses were carried out on all outcome measures reported by ≥3 studies. Findings: Sixteen studies were included consisting of 382 neuropathy participants, 216 diabetes controls without neuropathy and 207 healthy controls. Meta-analysis was performed on 11 gait variables. A high level of heterogeneity was noted between studies. Meta-analysis results suggested a longer stance time and moderately higher plantar pressures in diabetic peripheral neuropathy patients at the rearfoot, midfoot and forefoot compared to controls. Systematic review of studies suggested potential differences in the biomechanical characteristics (kinematics, kinetics, EMG) of diabetic neuropathy patients. However these findings were inconsistent and limited by small sample sizes.; Interpretation: Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies. Interpretation: Current evidence suggests that patients with diabetic peripheral neuropathy have elevated plantar pressures and occupy a longer duration of time in the stance-phase during gait. Firm conclusions are hampered by the heterogeneity and small sample sizes of available studies.

Mouse estrous cycle regulation of vaginal versus uterine cytokines, chemokines, α-/β-defensins and TLRs

This study investigates the cyclic changes in innate immunity in the female reproductive tract (FRT) of mice during the estrous cycle. By examining uterine and vaginal tissues and secretions we show that innate immunity varies with the stage of the estrous cycle and site in the FRT. Secretions from the uterine lumen contained cytokines and chemokines that were significantly higher at proestrus and estrus relative to that measured at diestrus. In contrast, analysis of vaginal secretions indicated that only IL-1β and CXCL1/mouse KC changed during the cycle, with highest levels measured at diestrus and estrus. In contrast, vaginal α-defensin 2 and β-defensins 1-4 mRNA levels peaked at proestrus and estrus and are expressed 1-4 logs greater than that seen in the uterus. These studies further indicate that TLR5 and TLR12 in the uterus, and TLR1, TLR2, TLR5 and TLR13 in the vagina varies with stage of the estrous cycle, with some peaking at proestrus/estrus and others at diestrus. Overall, these studies indicate that innate immune parameters in the uterus and vagina are separate and discrete, and regulated precisely during the estrous cycle.

Targeting amino acid transport in metastatic castration-resistant prostate cancer : effects on cell cycle, cell growth, and tumor development

Background L-type amino acid transporters (LATs) uptake neutral amino acids including L-leucine into cells, stimulating mammalian target of rapamycin complex 1 signaling and protein synthesis. LAT1 and LAT3 are overexpressed at different stages of prostate cancer, and they are responsible for increasing nutrients and stimulating cell growth. Methods We examined LAT3 protein expression in human prostate cancer tissue microarrays. LAT function was inhibited using a leucine analog (BCH) in androgen-dependent and -independent environments, with gene expression analyzed by microarray. A PC-3 xenograft mouse model was used to study the effects of inhibiting LAT1 and LAT3 expression. Results were analyzed with the Mann-Whitney U or Fisher exact tests. All statistical tests were two-sided. Results LAT3 protein was expressed at all stages of prostate cancer, with a statistically significant decrease in expression after 4–7 months of neoadjuvant hormone therapy (4–7 month mean = 1.571; 95% confidence interval = 1.155 to 1.987 vs 0 month = 2.098; 95% confidence interval = 1.962 to 2.235; P = .0187). Inhibition of LAT function led to activating transcription factor 4–mediated upregulation of amino acid transporters including ASCT1, ASCT2, and 4F2hc, all of which were also regulated via the androgen receptor. LAT inhibition suppressed M-phase cell cycle genes regulated by E2F family transcription factors including critical castration-resistant prostate cancer regulatory genes UBE2C, CDC20, and CDK1. In silico analysis of BCH-downregulated genes showed that 90.9% are statistically significantly upregulated in metastatic castration-resistant prostate cancer. Finally, LAT1 or LAT3 knockdown in xenografts inhibited tumor growth, cell cycle progression, and spontaneous metastasis in vivo. Conclusion Inhibition of LAT transporters may provide a novel therapeutic target in metastatic castration-resistant prostate cancer, via suppression of mammalian target of rapamycin complex 1 activity and M-phase cell cycle genes.

Transcutaneous immunization with combined cholera toxin and CpG adjuvant protects against Chlamydia muridarum genital tract infection

Chlamydia trachomatis is a pathogen of the genital tract and ocular epithelium. Infection is established by the binding of the metabolically inert elementary body (EB) to epithelial cells. These are taken up by endocytosis into a membrane-bound vesicle termed an inclusion. The inclusion avoids fusion with host lysosomes, and the EBs differentiate into the metabolically active reticulate body (RB), which replicates by binary fission within the protected environment of the inclusion. During the extracellular EB stage of the C. trachomatis life cycle, antibody present in genital tract or ocular secretions can inhibit infection both in vivo and in tissue culture. The RB, residing within the intracellular inclusion, is not accessible to antibody, and resolution of infection at this stage requires a cell-mediated immune response mediated by gamma interferon-secreting Th1 cells. Thus, an ideal vaccine to protect against C. trachomatis genital tract infection should induce both antibody (immunoglobulin A [IgA] and IgG) responses in mucosal secretions to prevent infection by chlamydial EB and a strong Th1 response to limit ascending infection to the uterus and fallopian tubes. In the present study we show that transcutaneous immunization with major outer membrane protein (MOMP) in combination with both cholera toxin and CpG oligodeoxynucleotides elicits MOMP-specific IgG and IgA in vaginal and uterine lavage fluid, MOMP-specific IgG in serum, and gamma interferon-secreting T cells in reproductive tract-draining caudal and lumbar lymph nodes. This immunization protocol resulted in enhanced clearance of C. muridarum (C. trachomatis, mouse pneumonitis strain) following intravaginal challenge of BALB/c mice.

Robert Waddington's cycle of abuse stretches beyond 50 years

THE Church of England banished serial pedophile priest Robert Waddington to Australia, where he abused children across a decade, after suspicions were raised about him molesting choirboys in his London parish. In an alleged church cover-up spanning almost 60 years, Waddington was suddenly and unexpectedly sent to a small school in regional Queensland in 1956 amid claims he was molesting the son of an English politician. Last month the Church of England ordered an independent inquiry into the handling of allegations against Waddington, after a joint investigation by The Australian and The Times of London. But it can now be revealed that Waddington - who died in 2007, facing allegations he abused students in Australia in the 1960s and English choirboys in the 80s and 90s - was molesting children as soon as he joined the church in 1953. The latest allegations have been made by Ray Munn, 70, who was recruited by Waddington, then a curate at St John's church in Bethnal Green, East London, to sing in the choir in 1953. He was almost immediately groomed by the Cambridge University-educated clergyman, who took him on holidays in the English countryside, before he began molesting the then 11-year-old.