Robust performance analysis on YAWL process models with advanced constructs

The importance of actively managing and analyzing business processes is acknowledged more than ever in organizations nowadays. Business processes form an essential part of an organization and their ap-plication areas are manifold. Most organizations keep records of various activities that have been carried out for auditing purposes, but they are rarely used for analysis purposes. This paper describes the design and implementation of a process analysis tool that replays, analyzes and visualizes a variety of performance metrics using a process definition and its execution logs. Performing performance analysis on existing and planned process models offers a great way for organizations to detect bottlenecks within their processes and allow them to make more effective process improvement decisions. Our technique is applied to processes modeled in the YAWL language. Execution logs of process instances are compared against the corresponding YAWL process model and replayed in a robust manner, taking into account any noise in the logs. Finally, performance characteristics, obtained from replaying the log in the model, are projected onto the model.

A fission yeast homolog of Int-6, the mammalian oncoprotein and eIF3 subunit, induces drug resistance when overexpressed

Through a screen to identify genes that induce multi-drug resistance when overexpressed, we have identified a fission yeast homolog of Int-6, a component of the human translation initiation factor eIF3. Disruption of the murine Int-6 gene by mouse mammary tumor virus (MMTV) has been implicated previously in tumorigenesis, although the underlying mechanism is not yet understood. Fission yeast Int6 was shown to interact with other presumptive components of eIF3 in vivo, and was present in size fractions consistent with its incorporation into a 43S translation preinitiation complex. Drug resistance induced by Int6 overexpression was dependent on the AP-1 transcription factor Pap1, and was associated with increased abundance of Pap1-responsive mRNAs, but not with Pap1 relocalization. Fission yeast cells lacking the int6 gene grew slowly. This growth retardation could be corrected by the expression of full length Int6 of fission yeast or human origin, or by a C-terminal fragment of the fission yeast protein that also conferred drug resistance, but not by truncated human Int-6 proteins corresponding to the predicted products of MMTV-disrupted murine alleles. Studies in fission yeast may therefore help to explain the ways in which Int-6 function can be perturbed during MMTV-induced mammary tumorigenesis.

Evaluation of coronary angiographic projections to balance the clinical yield with the radiation risk

Objective: Radiation safety principles dictate that imaging procedures should minimise the radiation risks involved, without compromising diagnostic performance. This study aims to define a core set of views that maximises clinical information yield for minimum radiation risk. Angiographers would supplement these views as clinically indicated. Methods: An algorithm was developed to combine published data detailing the quality of information derived for the major coronary artery segments through the use of a common set of views in angiography with data relating to the dose–area product and scatter radiation associated with these views. Results: The optimum view set for the left coronary system comprised four views: left anterior oblique (LAO) with cranial (Cr) tilt, shallow right anterior oblique (AP-RAO) with caudal (Ca) tilt, RAO with Ca tilt and AP-RAO with Cr tilt. For the right coronary system three views were identified: LAO with Cr tilt, RAO and AP-RAO with Cr tilt. An alternative left coronary view set including a left lateral achieved minimally superior efficiency (,5%), but with an ,8% higher radiation dose to the patient and 40% higher cardiologist dose. Conclusion: This algorithm identifies a core set of angiographic views that optimises the information yield and minimises radiation risk. This basic data set would be supplemented by additional clinically determined views selected by the angiographer for each case. The decision to use additional views for diagnostic angiography and interventions would be assisted by referencing a table of relative radiation doses for the views being considered.

Point-to-point speed enforcement

This report reviews the use of point-to-point speed enforcement internationally in order to provide principles for better practice for its use in Australia and New Zealand. Point-to-point enforcement is a relatively new technological approach to speed enforcement which involves measuring the average speed of vehicles passing a series of cameras, by using automatic number plate recognition (ANPR) and other technologies. The approach has been implemented or trialled in a number of countries including Australia, New Zealand, the United Kingdom, the Netherlands, Austria, Italy, Switzerland and France. The major research activities were undertaken for the preparation of this report included: (1) an extensive review of the international literature; (2) stakeholder consultation with international and domestic organisations. To date, there have been no formal evaluations of point-to- point speed enforcement in Australia or New Zealand.

A dual-polarized microstrip antenna array with port decoupling for MIMO systems

Utilization of multiport-antennas represents an appropriate way for the mitigation of multi-path fading in wireless communication systems. However, to obtain low correlation between the signals from different antenna ports and to prevent gain reduction by cross-talk, large antenna elements spacing is expected. Polarization diversity allows signal separation even with small antenna spacing. Although it is effective, polarization diversity alone does not suffice once the number of antennas exceeds the number of orthogonal polarizations. This paper presents an approach which combines a novel array concept with the use of dual polarization. The theory is verified by a compact dual polarized patch antenna array, which consists of four elements and a decoupling network.

In vitro and in vivo studies on protease-activated receptor-2

Protease-activated receptor-2 (PAR2) is a G protein coupled receptor (GPCR) that is activated by proteolytic cleavage of its amino terminal domain by trypsin-like serine proteases. Cleavage of this receptor exposes a neoepitope, termed the tethered ligand (TL), which binds intramolecularly within the receptor to stimulate signal transduction via coupled G proteins. PAR2-mediated signal transduction is also experimentally stimulated by hexapeptides (agonist peptides; APs) that are homologous to the TL sequence. Due to the irreversible nature of PAR2 proteolysis, downstream signal transduction is tightly regulated. Following activation, PAR2 is rapidly uncoupled from downstream signalling by the post-translational modifications phosphorylation and ubiquination which facilitate interactions with â- arrestin. This scaffolding protein couples PAR2 to the internalisation machinery initiating its desensitisation and trafficking through the early and late endosomes followed by receptor degradation. PAR2 is widely expressed in mammalian tissues with key roles for this receptor in cardiovascular, respiratory, nervous and musculoskeletal systems. This receptor has also been linked to pathological states with aberrant expression and signalling noted in several cancers. In prostate cancer, PAR2 signalling induces migration and proliferation of tumour derived cell lines, while elevated receptor expression has been noted in malignant tissues. Importantly, a role for this receptor has also been suggested in prostate cancer bone metastasis as coexpression of PAR2 and a proteolytic activator has been demonstrated by immunohistochemical analysis. Based on these data, the primary focus of this project has been on two aspects of PAR2 biology. The first is characterisation of cellular mechanisms that regulate PAR2 signalling and trafficking. The second aspect is the role of this receptor in prostate cancer bone metastasis. In addition, to permit these studies, it was first necessary to evaluate the specificity of the commercially available anti-PAR2 antibodies SAM11, C17, N19 and H99. The evaluation of the four commercially available antibodies was assessed using four techniques: immunoprecipitation; Western blot analysis; immunofluorescence; and flow cytometry. These approaches demonstrated that three of the antibodies efficiently detect ectopically expressed PAR2 by each of these techniques. A significant finding from this study was that N19 was the only antibody able to specifically detect N-glycosylated endogenous PAR2 by Western blot analysis. This analysis was performed on lysates from prostate cancer derived cell lines and tissue derived from wildtype and PAR2 knockout mice. Importantly, further evaluation demonstrated that this antibody also efficiently detects endogenous PAR2 at the cell surface by flow cytometry. The anti-PAR2 antibody N19 was used to explore the in vitro role of palmitoylation, the post-translational addition of palmitate, in PAR2 signalling, trafficking, cell surface expression and desensitization. Significantly, use of the palmitoylation inhibitor 2-bromopalmitate indicated that palmitate addition is important in trafficking of PAR2 endogenously expressed by prostate cancer cell lines. This was supported by palmitate labelling experiments using two approaches which showed that PAR2 stably expressed by CHO cells is palmitoylated and that palmitoylation occurs on cysteine 361. Another key finding from this study is that palmitoylation is required for optimal PAR2 signalling as Ca2+ flux assays indicated that in response to trypsin agonism, palmitoylation deficient PAR2 is ~9 fold less potent than wildtype receptor with a reduction of about 33% in the maximum signal induced via the mutant receptor. Confocal microscopy, flow cytometry and cell surface biotinylation analyses demonstrated that palmitoylation is required for efficient cell surface expression of PAR2. Importantly, this study also identified that palmitoylation of this receptor within the Golgi apparatus is required for efficient agonist-induced rab11amediated trafficking of PAR2 to the cell surface. Interestingly, palmitoylation is also required for receptor desensitization, as agonist-induced â-arrestin recruitment and receptor degradation were markedly reduced in CHO-PAR2-C361A cells compared with CHO-PAR2 cells. Collectively, these data provide new insights on the life cycle of PAR2 and demonstrate that palmitoylation is critical for efficient signalling, trafficking, cell surface localization and degradation of this receptor. This project also evaluated PAR2 residues involved in ligand docking. Although the extracellular loop (ECL)2 of PAR2 is known to be required for agonist-induced signal transduction, the binding pocket for receptor agonists remains to be determined. In silico homology modelling, based on a crystal structure for the prototypical GPCR rhodopsin, and ligand docking were performed to identify PAR2 transmembrane (TM) amino acids potentially involved in agonist binding. These methods identified 12 candidate residues that were mutated to examine the binding site of the PAR2 TL, revealed by trypsin cleavage, as well as of the soluble ligands 2f-LIGRLO-NH2 and GB110, which are both structurally based on the AP SLIGRLNH2. Ligand binding was evaluated from the impact of the mutated residues on PAR2-mediated calcium mobilisation. An important finding from these experiments was that mutation of residues Y156 and Y326 significantly reduced 2f-LIGRLO-NH2 and GB110 agonist activity. L307 was also important for GB110 activity. Intriguingly, mutation of PAR2 residues did not alter trypsin-induced signalling to the same extent as for the soluble agonists. The reason for this difference remains to be further examined by in silico and in vitro experimentation and, potentially, crystal structure studies. However, these findings identified the importance of TM domains in PAR2 ligand docking and will enhance the design of both PAR2 agonists and potentially agents to inhibit signalling (antagonists). The potential importance of PAR2 in prostate cancer bone metastasis was examined using a mouse model. In patients, prostate cancer bone metastases cause bone growth by disrupting bone homeostasis. In an attempt to mimic prostate cancer growth in bone, PAR2 responsive 22Rv1 prostate cancer cells, which form mixed osteoblastic and osteolytic lesions, were injected into the proximal aspect of mouse tibiae. A role for PAR2 was assessed by treating these mice with the recently developed PAR2 antagonist GB88. As controls, animals bearing intra-tibial tumours were also treated with vehicle (olive oil) or the prostate cancer chemotherapeutic docetaxel. The effect of these treatments on bone was examined radiographically and by micro-CT. Consistent with previous studies, 22Rv1 tumours caused osteoblastic periosteal spicule formation and concurrent osteolytic bone loss. Significantly, blockade of PAR2 signalling reduced the osteoblastic and osteolytic phenotype of 22Rv1 tumours in bone. No bone defects were detected in mice treated with docetaxel. These qualitative data will be followed in the future by quantitative micro-CT analysis as well as histology and histomorphometry analysis of already collected tissues. Nonetheless, these preliminary experiments highlight a potential role for PAR2 in prostate cancer growth in bone. In summary, in vitro studies have defined mechanisms regulating PAR2 activation, downstream signalling and trafficking and in vivo studies point to a potential role for this receptor in prostate cancer bone metastasis. The outcomes of this project are that a greater understanding of the biology of PAR2 may lead to the development of strategies to modulate the function of this receptor in disease.

Comparison and modification of car following models toward a more accurate microscopic simulation parameters reproduction

Traffic safety studies demand more than what current micro-simulation models can provide as they presume that all drivers of motor vehicles exhibit safe behaviours. Several car-following models are used in various micro-simulation models. This research compares the mainstream car following models’ capabilities of emulating precise driver behaviour parameters such as headways and Time to Collisions. The comparison firstly illustrates which model is more robust in the metric reproduction. Secondly, the study conducted a series of sensitivity tests to further explore the behaviour of each model. Based on the outcome of these two steps exploration of the models, a modified structure and parameters adjustment for each car-following model is proposed to simulate more realistic vehicle movements, particularly headways and Time to Collision, below a certain critical threshold. NGSIM vehicle trajectory data is used to evaluate the modified models performance to assess critical safety events within traffic flow. The simulation tests outcomes indicate that the proposed modified models produce better frequency of critical Time to Collision than the generic models, while the improvement on the headway is not significant. The outcome of this paper facilitates traffic safety assessment using microscopic simulation.

Evaluation of the cost-effectiveness of strategies claiming to reduce the risk of surgical site infections following primary total hip arthroplasty

Background Total hip arthroplasty (THA) is a commonly performed procedure and numbers are increasing with ageing populations. One of the most serious complications in THA are surgical site infections (SSIs), caused by pathogens entering the wound during the procedure. SSIs are associated with a substantial burden for health services, increased mortality and reduced functional outcomes in patients. Numerous approaches to preventing these infections exist but there is no gold standard in practice and the cost-effectiveness of alternate strategies is largely unknown. Objectives The aim of this project was to evaluate the cost-effectiveness of strategies claiming to reduce deep surgical site infections following total hip arthroplasty in Australia. The objectives were: 1. Identification of competing strategies or combinations of strategies that are clinically relevant to the control of SSI related to hip arthroplasty 2. Evidence synthesis and pooling of results to assess the volume and quality of evidence claiming to reduce the risk of SSI following total hip arthroplasty 3. Construction of an economic decision model incorporating cost and health outcomes for each of the identified strategies 4. Quantification of the effect of uncertainty in the model 5. Assessment of the value of perfect information among model parameters to inform future data collection Methods The literature relating to SSI in THA was reviewed, in particular to establish definitions of these concepts, understand mechanisms of aetiology and microbiology, risk factors, diagnosis and consequences as well as to give an overview of existing infection prevention measures. Published economic evaluations on this topic were also reviewed and limitations for Australian decision-makers identified. A Markov state-transition model was developed for the Australian context and subsequently validated by clinicians. The model was designed to capture key events related to deep SSI occurring within the first 12 months following primary THA. Relevant infection prevention measures were selected by reviewing clinical guideline recommendations combined with expert elicitation. Strategies selected for evaluation were the routine use of pre-operative antibiotic prophylaxis (AP) versus no use of antibiotic prophylaxis (No AP) or in combination with antibiotic-impregnated cement (AP & ABC) or laminar air operating rooms (AP & LOR). The best available evidence for clinical effect size and utility parameters was harvested from the medical literature using reproducible methods. Queensland hospital data were extracted to inform patients’ transitions between model health states and related costs captured in assigned treatment codes. Costs related to infection prevention were derived from reliable hospital records and expert opinion. Uncertainty of model input parameters was explored in probabilistic sensitivity analyses and scenario analyses and the value of perfect information was estimated. Results The cost-effectiveness analysis was performed from a health services perspective using a hypothetical cohort of 30,000 THA patients aged 65 years. The baseline rate of deep SSI was 0.96% within one year of a primary THA. The routine use of antibiotic prophylaxis (AP) was highly cost-effective and resulted in cost savings of over $1.6m whilst generating an extra 163 QALYs (without consideration of uncertainty). Deterministic and probabilistic analysis (considering uncertainty) identified antibiotic prophylaxis combined with antibiotic-impregnated cement (AP & ABC) to be the most cost-effective strategy. Using AP & ABC generated the highest net monetary benefit (NMB) and an incremental $3.1m NMB compared to only using antibiotic prophylaxis. There was a very low error probability that this strategy might not have the largest NMB (<5%). Not using antibiotic prophylaxis (No AP) or using both antibiotic prophylaxis combined with laminar air operating rooms (AP & LOR) resulted in worse health outcomes and higher costs. Sensitivity analyses showed that the model was sensitive to the initial cohort starting age and the additional costs of ABC but the best strategy did not change, even for extreme values. The cost-effectiveness improved for a higher proportion of cemented primary THAs and higher baseline rates of deep SSI. The value of perfect information indicated that no additional research is required to support the model conclusions. Conclusions Preventing deep SSI with antibiotic prophylaxis and antibiotic-impregnated cement has shown to improve health outcomes among hospitalised patients, save lives and enhance resource allocation. By implementing a more beneficial infection control strategy, scarce health care resources can be used more efficiently to the benefit of all members of society. The results of this project provide Australian policy makers with key information about how to efficiently manage risks of infection in THA.

Achilles tendinopathy has an aberrant strain response to eccentric exercise

Purpose: Eccentric exercise has become the treatment of choice for Achilles tendinopathy. However, little is known about the acute response of tendons to eccentric exercise or the mechanisms underlying its clinical benefit. This research evaluated the sonographic characteristics and acute anteroposterior (AP) strain response of control (healthy), asymptomatic, and symptomatic Achilles tendons to eccentric exercise. Methods: Eleven male adults with unilateral midportion Achilles tendinopathy and nine control male adults without tendinopathy participated in the research. Sagittal sonograms of the Achilles tendon were acquired immediately before and after completion of a common eccentric rehabilitation exercise protocol and again 24 h later. Tendon thickness, echogenicity, and AP strain were determined 40 mm proximal to the calcaneal insertion. Results: Compared with the control tendon, both the asymptomatic and symptomatic tendons were thicker (P < 0.05) and hypoechoic (P < 0.05) at baseline. All tendons decreased in thickness immediately after eccentric exercise (P < 0.05). The symptomatic tendon was characterized by a significantly lower AP strain response to eccentric exercise compared with both the asymptomatic and control tendons (P < 0.05). AP strains did not differ in the control and asymptomatic tendons. For all tendons, preexercise thickness was restored 24 h after exercise completion. Conclusions: These observations support the concept that Achilles tendinopathy is a bilateral or systemic process and structural changes associated with symptomatic tendinopathy alter fluid movement within the tendon matrix. Altered fluid movement may disrupt remodeling and homeostatic processes and represents a plausible mechanism underlying the progression of tendinopathy.

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 self-tuning feedforward active noise control system

This paper proposes a self-tuning feedforward active noise control (ANC) system with online secondary path modeling. The step-size parameters of the controller and modeling filters have crucial rule on the system performance. In literature, these parameters are adjusted by trial-and-error. In other words, they are manually initialized before system starting, which require performing extensive experiments to ensure the convergence of the system. Hence there is no guarantee that the system could perform well under different situations. In the proposed method, the appropriate values for the step-sizes are obtained automatically. Computer simulation results indicate the effectiveness of the proposed method.

An efficient online secondary path estimation for feedback active noise control systems

In practical cases for active noise control (ANC), the secondary path has usually a time varying behavior. For these cases, an online secondary path modeling method that uses a white noise as a training signal is required to ensure convergence of the system. The modeling accuracy and the convergence rate are increased when a white noise with a larger variance is used. However, the larger variance increases the residual noise, which decreases performance of the system and additionally causes instability problem to feedback structures. A sudden change in the secondary path leads to divergence of the online secondary path modeling filter. To overcome these problems, this paper proposes a new approach for online secondary path modeling in feedback ANC systems. The proposed algorithm uses the advantages of white noise with larger variance to model the secondary path, but the injection is stopped at the optimum point to increase performance of the algorithm and to prevent the instability effect of the white noise. In this approach, instead of continuous injection of the white noise, a sudden change in secondary path during the operation makes the algorithm to reactivate injection of the white noise to correct the secondary path estimation. In addition, the proposed method models the secondary path without the need of using off-line estimation of the secondary path. Considering the above features increases the convergence rate and modeling accuracy, which results in a high system performance. Computer simulation results shown in this paper indicate effectiveness of the proposed method.

A variable step-size FxLMS algorithm for feedforward active noise control systems based on a new online secondary path modelling technique

Several approaches have been introduced in literature for active noise control (ANC) systems. Since 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 FxLMS algorithm. In many ANC applications an online secondary path modelling method using a white noise as a training signal is required to ensure convergence of the system. This paper also proposes a new approach for online secondary path modelling in feedfoward ANC systems. The proposed algorithm stops injection of the white noise at the optimum point and reactivate the injection during the operation, if needed, to maintain performance of the system. Benefiting new version of FxLMS algorithm and not continually injection of white noise makes the system more desirable and improves the noise attenuation performance. Comparative simulation results indicate effectiveness of the proposed approach.

A new online secondary path modelling method for feedforward active noise control systems

An online secondary path modelling method using a white noise as a training signal is required in many applications of active noise control (ANC) to ensure convergence of the system. Not continually injection of white noise during system operation makes the system more desirable. The purposes of the proposed method are two folds: controlling white noise by preventing continually injection, and benefiting white noise with a larger variance. The modelling accuracy and the convergence rate increase when a white noise with larger variance is used, however larger the variance increases the residual noise, which decreases performance of the system. This paper proposes a new approach for online secondary path modelling in feedfoward ANC systems. The proposed algorithm uses the advantages of the white noise with larger variance to model the secondary path, but the injection is stopped at the optimum point to increase performance of the system. Comparative simulation results shown in this paper indicate effectiveness of the proposed approach in controlling active noise.

Benefiting white noise in developing feedforward active noise control systems

In many applications of active noise control (ANC), an online secondary path modelling method using a white noise as a training signal is required to ensure convergence of the system. The modelling accuracy and the convergence rate increase when a white noise with larger variance is used, however larger the variance increases the residual noise, which decreases performance of the system. The proposed algorithm uses the advantages of the white noise with larger variance to model the secondary path, but the injection is stopped at the optimum point to increase performance of the system. In this approach, instead of continuous injection of the white noise, a sudden change in secondary path during the operation makes the algorithm to reactivate injection of the white noise to adjust the secondary path estimation. Comparative simulation results shown in this paper indicate effectiveness of the proposed method.