Condition monitoring and diagnosis of injector faults in a diesel engine using in-cylinder pressure and acoustic emission techniques

Failing injectors are one of the most common faults in diesel engines. The severity of these faults could have serious effects on diesel engine operations such as engine misfire, knocking, insufficient power output or even cause a complete engine breakdown. It is thus essential to prevent such faults from occurring by monitoring the condition of these injectors. In this paper, the authors present the results of an experimental investigation on identifying the signal characteristics of a simulated incipient injector fault in a diesel engine using both in-cylinder pressure and acoustic emission (AE) techniques. A time waveform event driven synchronous averaging technique was used to minimize or eliminate the effect of engine speed variation and amplitude fluctuation. It was found that AE is an effective method to detect the simulated injector fault in both time (crank angle) and frequency (order) domains. It was also shown that the time domain in-cylinder pressure signal is a poor indicator for condition monitoring and diagnosis of the simulated injector fault due to the small effect of the simulated fault on the engine combustion process. Nevertheless, good correlations between the simulated injector fault and the lower order components of the enveloped in-cylinder pressure spectrum were found at various engine loading conditions.

A descriptive approach for power system stability and security assessment

Power system dynamic analysis and security assessment are becoming more significant today due to increases in size and complexity from restructuring, emerging new uncertainties, integration of renewable energy sources, distributed generation, and micro grids. Precise modelling of all contributed elements/devices, understanding interactions in detail, and observing hidden dynamics using existing analysis tools/theorems are difficult, and even impossible. In this chapter, the power system is considered as a continuum and the propagated electomechanical waves initiated by faults and other random events are studied to provide a new scheme for stability investigation of a large dimensional system. For this purpose, the measured electrical indices (such as rotor angle and bus voltage) following a fault in different points among the network are used, and the behaviour of the propagated waves through the lines, nodes, and buses is analyzed. The impact of weak transmission links on a progressive electromechanical wave using energy function concept is addressed. It is also emphasized that determining severity of a disturbance/contingency accurately, without considering the related electromechanical waves, hidden dynamics, and their properties is not secure enough. Considering these phenomena takes heavy and time consuming calculation, which is not suitable for online stability assessment problems. However, using a continuum model for a power system reduces the burden of complex calculations

Rational design of serine protease inhibitors

Proteases regulate a spectrum of diverse physiological processes, and dysregulation of proteolytic activity drives a plethora of pathological conditions. Understanding protease function is essential to appreciating many aspects of normal physiology and progression of disease. Consequently, development of potent and specific inhibitors of proteolytic enzymes is vital to provide tools for the dissection of protease function in biological systems and for the treatment of diseases linked to aberrant proteolytic activity. The studies in this thesis describe the rational design of potent inhibitors of three proteases that are implicated in disease development. Additionally, key features of the interaction of proteases and their cognate inhibitors or substrates are analysed and a series of rational inhibitor design principles are expounded and tested. Rational design of protease inhibitors relies on a comprehensive understanding of protease structure and biochemistry. Analysis of known protease cleavage sites in proteins and peptides is a commonly used source of such information. However, model peptide substrate and protein sequences have widely differing levels of backbone constraint and hence can adopt highly divergent structures when binding to a protease’s active site. This may result in identical sequences in peptides and proteins having different conformations and diverse spatial distribution of amino acid functionalities. Regardless of this, protein and peptide cleavage sites are often regarded as being equivalent. One of the key findings in the following studies is a definitive demonstration of the lack of equivalence between these two classes of substrate and invalidation of the common practice of using the sequences of model peptide substrates to predict cleavage of proteins in vivo. Another important feature for protease substrate recognition is subsite cooperativity. This type of cooperativity is commonly referred to as protease or substrate binding subsite cooperativity and is distinct from allosteric cooperativity, where binding of a molecule distant from the protease active site affects the binding affinity of a substrate. Subsite cooperativity may be intramolecular where neighbouring residues in substrates are interacting, affecting the scissile bond’s susceptibility to protease cleavage. Subsite cooperativity can also be intermolecular where a particular residue’s contribution to binding affinity changes depending on the identity of neighbouring amino acids. Although numerous studies have identified subsite cooperativity effects, these findings are frequently ignored in investigations probing subsite selectivity by screening against diverse combinatorial libraries of peptides (positional scanning synthetic combinatorial library; PS-SCL). This strategy for determining cleavage specificity relies on the averaged rates of hydrolysis for an uncharacterised ensemble of peptide sequences, as opposed to the defined rate of hydrolysis of a known specific substrate. Further, since PS-SCL screens probe the preference of the various protease subsites independently, this method is inherently unable to detect subsite cooperativity. However, mean hydrolysis rates from PS-SCL screens are often interpreted as being comparable to those produced by single peptide cleavages. Before this study no large systematic evaluation had been made to determine the level of correlation between protease selectivity as predicted by screening against a library of combinatorial peptides and cleavage of individual peptides. This subject is specifically explored in the studies described here. In order to establish whether PS-SCL screens could accurately determine the substrate preferences of proteases, a systematic comparison of data from PS-SCLs with libraries containing individually synthesised peptides (sparse matrix library; SML) was carried out. These SML libraries were designed to include all possible sequence combinations of the residues that were suggested to be preferred by a protease using the PS-SCL method. SML screening against the three serine proteases kallikrein 4 (KLK4), kallikrein 14 (KLK14) and plasmin revealed highly preferred peptide substrates that could not have been deduced by PS-SCL screening alone. Comparing protease subsite preference profiles from screens of the two types of peptide libraries showed that the most preferred substrates were not detected by PS SCL screening as a consequence of intermolecular cooperativity being negated by the very nature of PS SCL screening. Sequences that are highly favoured as result of intermolecular cooperativity achieve optimal protease subsite occupancy, and thereby interact with very specific determinants of the protease. Identifying these substrate sequences is important since they may be used to produce potent and selective inhibitors of protolytic enzymes. This study found that highly favoured substrate sequences that relied on intermolecular cooperativity allowed for the production of potent inhibitors of KLK4, KLK14 and plasmin. Peptide aldehydes based on preferred plasmin sequences produced high affinity transition state analogue inhibitors for this protease. The most potent of these maintained specificity over plasma kallikrein (known to have a very similar substrate preference to plasmin). Furthermore, the efficiency of this inhibitor in blocking fibrinolysis in vitro was comparable to aprotinin, which previously saw clinical use to reduce perioperative bleeding. One substrate sequence particularly favoured by KLK4 was substituted into the 14 amino acid, circular sunflower trypsin inhibitor (SFTI). This resulted in a highly potent and selective inhibitor (SFTI-FCQR) which attenuated protease activated receptor signalling by KLK4 in vitro. Moreover, SFTI-FCQR and paclitaxel synergistically reduced growth of ovarian cancer cells in vitro, making this inhibitor a lead compound for further therapeutic development. Similar incorporation of a preferred KLK14 amino acid sequence into the SFTI scaffold produced a potent inhibitor for this protease. However, the conformationally constrained SFTI backbone enforced a different intramolecular cooperativity, which masked a KLK14 specific determinant. As a consequence, the level of selectivity achievable was lower than that found for the KLK4 inhibitor. Standard mechanism inhibitors such as SFTI rely on a stable acyl-enzyme intermediate for high affinity binding. This is achieved by a conformationally constrained canonical binding loop that allows for reformation of the scissile peptide bond after cleavage. Amino acid substitutions within the inhibitor to target a particular protease may compromise structural determinants that support the rigidity of the binding loop and thereby prevent the engineered inhibitor reaching its full potential. An in silico analysis was carried out to examine the potential for further improvements to the potency and selectivity of the SFTI-based KLK4 and KLK14 inhibitors. Molecular dynamics simulations suggested that the substitutions within SFTI required to target KLK4 and KLK14 had compromised the intramolecular hydrogen bond network of the inhibitor and caused a concomitant loss of binding loop stability. Furthermore in silico amino acid substitution revealed a consistent correlation between a higher frequency of formation and the number of internal hydrogen bonds of SFTI-variants and lower inhibition constants. These predictions allowed for the production of second generation inhibitors with enhanced binding affinity toward both targets and highlight the importance of considering intramolecular cooperativity effects when engineering proteins or circular peptides to target proteases. The findings from this study show that although PS-SCLs are a useful tool for high throughput screening of approximate protease preference, later refinement by SML screening is needed to reveal optimal subsite occupancy due to cooperativity in substrate recognition. This investigation has also demonstrated the importance of maintaining structural determinants of backbone constraint and conformation when engineering standard mechanism inhibitors for new targets. Combined these results show that backbone conformation and amino acid cooperativity have more prominent roles than previously appreciated in determining substrate/inhibitor specificity and binding affinity. The three key inhibitors designed during this investigation are now being developed as lead compounds for cancer chemotherapy, control of fibrinolysis and cosmeceutical applications. These compounds form the basis of a portfolio of intellectual property which will be further developed in the coming years.

The workplace context of sexual harassment in Australia : policing the gender borders

The paper draws on a three year Australian Research Council funded project entitled Sexual Harassment in Australia: Context Outcomes and Prevention. The research to date suggests there is some slippage between legal definitions and community understandings of what constitutes sexual harassment. Moreover, while sexual harassment is often seen by the community and within organisations as the fault of one aberrant individual, in certain workplace contexts sexual harassment is used to ‘police the gender borders’, that is to exclude women and men who do not conform to the dominant workplace gender norms. This type of sexual harassment is a collective form of behaviour often perpetrated by co-workers in male-dominated workplaces which is designed to humiliate ‘outsiders’ so they appear incompetent and will be forced to leave the organisation. While much previous research that has focused on this type of sexual harassment has taken place in military and policing settings, our emerging findings suggest that it is present in a far broader range of workplace contexts. Prevention of this form of sexual harassment is challenging and goes to the heart of organisational culture and work organisation.

Acoustic emission for diesel engine monitoring: A review and preliminary

Vibration analysis has been a prime tool in condition monitoring of rotating machines, however, its application to internal combustion engines remains a challenge because engine vibration signatures are highly non-stationary that are not suitable for popular spectrum-based analysis. Signal-to-noise ratio is a main concern in engine signature analysis due to severe background noise being generated by consecutive mechanical events, such as combustion, valve opening and closing, especially in multi-cylinder engines. Acoustic Emission (AE) has been found to give excellent signal-to-noise ratio allowing discrimination of fine detail of normal or abnormal events during a given cycle. AE has been used to detect faults, such as exhaust valve leakage, fuel injection behaviour, and aspects of the combustion process. This paper presents a review of AE application to diesel engine monitoring and preliminary investigation of AE signature measured on an 18-cylinder diesel engine. AE is compared with vibration acceleration for varying operating conditions: load and speed. Frequency characteristics of AE from those events are analysed in time-frequency domain via short time Fourier trasform. The result shows a great potential of AE analysis for detection of various defects in diesel engines.

Integrated approach for HP-LNG pump diagnosis and prognostics based on health state probability estimation

This paper presents an innovative prognostics model based on health state probability estimation embedded in the closed loop diagnostic and prognostic system. To employ an appropriate classifier for health state probability estimation in the proposed prognostic model, the comparative intelligent diagnostic tests were conducted using five different classifiers applied to the progressive fault levels of three faults in HP-LNG pump. Two sets of impeller-rubbing data were employed for the prediction of pump remnant life based on estimation of discrete health state probability using an outstanding capability of SVM and a feature selection technique. The results obtained were very encouraging and showed that the proposed prognosis system has the potential to be used as an estimation tool for machine remnant life prediction in real life industrial applications.

Reduced sampling efficiency causes degraded Vernier hyperacuity with normal aging: Vernier acuity in position noise

Vernier acuity, a form of visual hyperacuity, is amongst the most precise forms of spatial vision. Under optimal conditions Vernier thresholds are much finer than the inter-photoreceptor distance. Achievement of such high precision is based substantially on cortical computations, most likely in the primary visual cortex. Using stimuli with added positional noise, we show that Vernier processing is reduced with advancing age across a wide range of noise levels. Using an ideal observer model, we are able to characterize the mechanisms underlying age-related loss, and show that the reduction in Vernier acuity can be mainly attributed to the reduction in efficiency of sampling, with no significant change in the level of internal position noise, or spatial distortion, in the visual system.

Development of distributed fuzzy systems with a runtime-adaptable mobile components framework

A distributed fuzzy system is a real-time fuzzy system in which the input, output and computation may be located on different networked computing nodes. The ability for a distributed software application, such as a distributed fuzzy system, to adapt to changes in the computing network at runtime can provide real-time performance improvement and fault-tolerance. This paper introduces an Adaptable Mobile Component Framework (AMCF) that provides a distributed dataflow-based platform with a fine-grained level of runtime reconfigurability. The execution location of small fragments (possibly as little as few machine-code instructions) of an AMCF application can be moved between different computing nodes at runtime. A case study is included that demonstrates the applicability of the AMCF to a distributed fuzzy system scenario involving multiple physical agents (such as autonomous robots). Using the AMCF, fuzzy systems can now be developed such that they can be distributed automatically across multiple computing nodes and are adaptable to runtime changes in the networked computing environment. This provides the opportunity to improve the performance of fuzzy systems deployed in scenarios where the computing environment is resource-constrained and volatile, such as multiple autonomous robots, smart environments and sensor networks.

Diesel engine problems, acoustic emission signals and simulated misfire faults

This paper discusses commonly encountered diesel engine problems and the underlying combustion related faults. Also discussed are the methods used in previous studies to simulate diesel engine faults and the initial results of an experimental simulation of a common combustion related diesel engine fault, namely diesel engine misfire. This experimental fault simulation represents the first step towards a comprehensive investigation and analysis into the characteristics of acoustic emission signals arising from combustion related diesel engine faults. Data corresponding to different engine running conditions was captured using in-cylinder pressure, vibration and acoustic emission transducers along with both crank-angle encoder and top-dead centre signals. Using these signals, it was possible to characterise the diesel engine in-cylinder pressure profiles and the effect of different combustion conditions on both vibration and acoustic emission signals.

Quality of work life and turnover intention in primary healthcare organisations : a cross-sectional study of registered nurses in Saudi Arabia

Purpose: The purpose of this study was to improve the retention of primary healthcare (PHC) nurses through exploring and assessing their quality of work life (QWL) and turnover intention. Design and methods: A cross-sectional survey design was used in this study. Data were collected using a questionnaire comprising four sections (Brooks’ survey of Quality of Nursing Work Life [QNWL], Anticipated Turnover Intention, open-ended questions and demographic characteristics). A convenience sample was recruited from 143 PHC centres in Jazan, Saudi Arabia. A response rate of 87% (n = 508/585) was achieved. The SPSS v17 for Windows and NVivo 8 were used for analysis purposes. Procedures and tests used in this study to analyse the quantitative data were descriptive statistics, t-test, ANOVA, General Linear Model (GLM) univariate analysis, standard multiple regression, and hierarchical multiple regression. Qualitative data obtained from responses to the open-ended questions were analysed using the NVivo 8. Findings: Quantitative findings suggested that PHC nurses were dissatisfied with their work life. Respondents’ scores ranged between 45 and 218 (mean = 139.45), which is lower than the average total score on Brooks’ Survey (147). Major influencing factors were classified under four dimensions. First, work life/home life factors: unsuitable working hours, lack of facilities for nurses, inability to balance work with family needs and inadequacy of vacations’ policy. Second, work design factors: high workload, insufficient workforce numbers, lack of autonomy and undertaking many non-nursing tasks. Third, work context factors: management practices, lack of development opportunities, and inappropriate working environment in terms of the level of security, patient care supplies and unavailability of recreation room. Finally, work world factors: negative public image of nursing, and inadequate payment. More positively, nurses were notably satisfied with their co-workers. Conversely, 40.4% (n = 205) of the respondents indicated that they intended to leave their current employment. The relationships between QWL and demographic variables of gender, age, marital status, dependent children, dependent adults, nationality, ethnicity, nursing tenure, organisational tenure, positional tenure, and payment per month were significant (p < .05). The eta squared test for these demographics indicates a small to medium effect size of the variation in QWL scores. Using the GLM univariate analysis, education level was also significantly related to the QWL (p < .05). The relationships between turnover intention and demographic variables including gender, age, marital status, dependent children, education level, nursing tenure, organisational tenure, positional tenure, and payment per month were significant (p < .05). The eta squared test for these demographics indicates a small to moderate effect size of the variation in the turnover intention scores. Using the GLM univariate analysis, the dependent adults’ variable was also significantly related to turnover intention (p < .05). Turnover intention was significantly related to QWL. Using standard multiple regression, 26% of the variance in turnover intention was explained by the QWL F (4,491), 43.71, p < .001, with R² = .263. Further analysis using hierarchical multiple regression found that the total variance explained by the model as a whole (demographics and QWL) was 32.1%, F (17.433) = 12.04, p < .001. QWL explained an additional 19% of the variance in turnover intention, after controlling for demographic variables, R squared change =.19, F change (4, 433) = 30.190, p < .001. The work context variable makes the strongest unique contribution (-.387) to explain the turnover intention, followed by the work design dimension (-.112). The qualitative findings reaffirmed the quantitative findings in terms of QWL and turnover intention. However, the home life/work life and work world dimensions were of great important to both QWL and turnover intention. The qualitative findings revealed a number of new factors that were not included in the survey questionnaire. These included being away from family, lack of family support, social and cultural aspects, accommodation facilities, transportation, building and infrastructure of PHC, nature of work, job instability, privacy at work, patients and community, and distance between home and workplace. Conclusion: Creating and maintaining a healthy work life for PHC nurses is very important to improve their work satisfaction, reduce turnover, enhance productivity and improve nursing care outcomes. Improving these factors could lead to a higher QWL and increase retention rates and therefore reinforcing the stabilisation of the nursing workforce. Significance of the research: Many countries are examining strategies to attract and retain the health care workforce, particularly nurses. This study identified factors that influence the QWL of PHC nurses as well as their turnover intention. It also determined the significant relationship between QWL and turnover intention. In addition, the present study tested Brooks’ survey of QNWL on PHC nurses for the first time. The qualitative findings of this study revealed a number of new variables regarding QWL and turnover intention of PHC nurses. These variables could be used to improve current survey instruments or to develop new research surveys. The study findings could be also used to develop and appropriately implement plans to improve QWL. This may help to enhance the home and work environments of PHC nurses, improve individual and organisational performance, and increase nurses’ commitment. This study contributes to the existing body of research knowledge by presenting new data and findings from a different country and healthcare system. It is the first of its kind in Saudi Arabia, especially in the field of PHC. It has examined the relationship between QWL and turnover intention of PHC nurses for the first time using nursing instruments. The study also offers a fresh explanation (new framework) of the relationship between QWL and turnover intention among PHC nurses, which could be used or tested by researchers in other settings. Implications for further research: Review of the extant literature reveals little in-depth research on the PHC workforce, especially in terms of QWL and organisational turnover in developing countries. Further research is required to develop a QWL tool for PHC nurses, taking into consideration the findings of the current study along with the local culture. Moreover, the revised theoretical framework of the current study could be tested in further research in other regions, countries or healthcare systems in order to identify its ability to predict the level of PHC nurses’ QWL and their intention to leave. There is a need to conduct longitudinal research on PHC organisations to gain an in-depth understanding of the determents of and changes in QWL and turnover intention of PHC nurses at various points of time. An intervention study is required to improve QWL and retention among PHC nurses using the findings of the current study. This would help to assess the impact of such strategies on reducing turnover of PHC nurses. Focusing on the location of the current study, it would be valuable to conduct another study in five years’ time to examine the percentage of actual turnover among PHC nurses compared with the reported turnover intention in the current study. Further in-depth research would also be useful to assess the impact of the local culture on the perception of expatriate nurses towards their QWL and their turnover intention. A comparative study is required between PHC centres and hospitals as well as the public and private health sector agencies in terms of QWL and turnover intention of nursing personnel. Findings may differ from sector to sector according to variations in health systems, working environments and the case mix of patients.

Examining Exposure of Motorcycles at Signalized Intersections

Crash statistics in Singapore from 2001 to 2005 have shown that motorcycles are involved in about 54% of intersection crashes. The overall involvement of motorcycles in crashes as the not-at-fault party is about 43% but at intersections, the corresponding percentage is increased to 57%. Quasi-induced exposure estimates show that the motorcycle exposure rate at signalized intersections is 41.7% even though motorcycles account for only 19% of the vehicle population. This study seeks to examine in greater details, the problem of motorcycle exposure at signalized intersections. In particular, the exposure arising from potential crashes with red light running vehicles from the conflicting stream at four signalized intersections is investigated. The results show that motorcycles are more exposed because they tend to accumulate near the stop-line during the red phase to facilitate an earlier discharge during the initial period of the green which is the more vulnerable period. At sites where there are more weaving opportunities because the lanes are wider or where there are exclusive right-turn lanes, the accumulation is higher and hence an increased exposure is observed. The analysis also shows that the presence of heavy vehicles tends to decrease motorcycle exposure as their weaving opportunities become restricted as well as there is a greater reluctance for them to weave past or queue alongside the heavy vehicles and their effects intensify for narrower lane width.

Right-angle crash vulnerability of motorcycles at signalized intersections : mixed logit analysis

Motorcycles are particularly vulnerable in right-angle crashes at signalized intersections. The objective of this study is to explore how variations in roadway characteristics, environmental factors, traffic factors, maneuver types, human factors as well as driver demographics influence the right-angle crash vulnerability of motorcycles at intersections. The problem is modeled using a mixed logit model with a binary choice category formulation to differentiate how an at-fault vehicle collides with a not-at-fault motorcycle in comparison to other collision types. The mixed logit formulation allows randomness in the parameters and hence takes into account the underlying heterogeneities potentially inherent in driver behavior, and other unobserved variables. A likelihood ratio test reveals that the mixed logit model is indeed better than the standard logit model. Night time riding shows a positive association with the vulnerability of motorcyclists. Moreover, motorcyclists are particularly vulnerable on single lane roads, on the curb and median lanes of multi-lane roads, and on one-way and two-way road type relative to divided-highway. Drivers who deliberately run red light as well as those who are careless towards motorcyclists especially when making turns at intersections increase the vulnerability of motorcyclists. Drivers appear more restrained when there is a passenger onboard and this has decreased the crash potential with motorcyclists. The presence of red light cameras also significantly decreases right-angle crash vulnerabilities of motorcyclists. The findings of this study would be helpful in developing more targeted countermeasures for traffic enforcement, driver/rider training and/or education, safety awareness programs to reduce the vulnerability of motorcyclists.

Effectiveness of red light cameras on the right-angle crash involvement of motorcycles

Red light cameras (RLC) have been used to reduce right-angle collisions at signalized intersections. However, the effect of RLCs on motorcycle crashes has not been well investigated. The objective of this study is to evaluate the effectiveness of RLCs on motorcycle safety in Singapore. This is done by comparing their exposure, proneness of at-fault right-angle crashes as well as the resulting right-angle collisions at RLC with those at non-RLC sites. Estimating the crash vulnerability from not-at-fault crash involvements, the study shows that with a RLC, the relative crash vulnerability or crash-involved exposure of motorcycles at right-angle crashes is reduced. Furthermore, field investigation of motorcycle maneuvers reveal that at non-RLC arms, motorcyclists usually queue beyond the stop-line, facilitating an earlier discharge and hence become more exposed to the conflicting stream. However at arms with a RLC, motorcyclists are more restrained to avoid activating the RLC and hence become less exposed to conflicting traffic during the initial period of the green. The study also shows that in right-angle collisions, the proneness of at-fault crashes of motorcycles is lowest among all vehicle types. Hence motorcycles are more likely to be victims than the responsible parties in right-angle crashes. RLCs have also been found to be very effective in reducing at-fault crash involvements of other vehicle types which may implicate exposed motorcycles in the conflicting stream. Taking all these into account, the presence of RLCs should significantly reduce the vulnerability of motorcycles at signalized intersections.

Developing targeted countermeasures to improve motorcycle safety

The fatality and injury rate of motorcyclists per registered vehicle are higher than those of other motor vehicles by 13 and 7 times respectively. The crash involvement rate of motorcyclists as a victim party is 58% at intersections and as an offending party is 67% at expressways. Previous research efforts showed that the motorcycle safety programs are not very effective in improving motorcycle safety. This is perhaps due to inefficient design of safety program as specific causal factors may not be well explored. The objective of this study is to propose more sophisticated countermeasures and awareness programs for improving motorcycle safety after analyzing specific causal factors for motorcycle crashes at intersections and expressways. Methodologically this study applies the binary logistic model to explore the at-fault or not-at-fault crash involvement of motorcyclists at those locations. A number of explanatory variables representing roadway characteristics, environmental factors, motorcycle descriptions, and rider demographics have been evaluated. Results shows that the night time crash occurrence, presence of red light camera, lane position, rider age, licence class, and multivehicle collision significantly affect the fault of motorcyclists involved in crashes at intersections. On the other hand, the night time crash occurrence, lane position, speed limit, rider age, licence class, engine capacity, riding with pillion passenger, foreign registered motorcycles, and multivehicle collision has been found to be significant at expressways. Legislate to wear reflective clothes and using reflective markings on the motorcycles and helmets are suggested as an effective countermeasure for reducing their vulnerability. The red light cameras at intersections reduce the vulnerability of motorcycles and hence motorcycle flow and motorcycle crashes should be considered during installation of red light cameras. At signalized intersections, motorcyclists may be taught to follow correct movement and queuing rather than weaving through the traffic as it leads them to become victims of other motorists. The riding simulators in the training centers can be useful to demonstrate the proper movement and queuing at junctions. Riding with pillion passenger and excess speed at expressways are found to significantly influence the at at-fault crash involvement of the motorcyclists. Hence the motorcyclists should be advised to concentrate more on riding while riding with pillion passenger and encouraged to avoid excess speed at expressways. Very young and very older group of riders are found to be at-fault than middle aged groups. Hence this group of riders should be targeted for safety improvement. This can be done by arranging safety talks and programs in motorcycling clubs in colleges and universities as well as community riding clubs with high proportion of elderly riders. It is recommended that the driving centers may use the findings of this study to include in licensure program to make motorcyclists more aware of the different factors which expose the motorcyclists to crash risks so that more defensive riding may be needed.

Non-combinatorial library screening reveals subsite cooperativity and identifies new high-efficiency substrates for kallikrein-related peptidase 14

An array of substrates link the tryptic serine protease, kallikrein-related peptidase 14 (KLK14), to physiological functions including desquamation and activation of signaling molecules associated with inflammation and cancer. Recognition of protease cleavage sequences is driven by complementarity between exposed substrate motifs and the physicochemical signature of an enzyme's active site cleft. However, conventional substrate screening methods have generated conflicting subsite profiles for KLK14. This study utilizes a recently developed screening technique, the sparse matrix library, to identify five novel high-efficiency sequences for KLK14. The optimal sequence, YASR, was cleaved with higher efficiency (k(cat)/K(m)=3.81 ± 0.4 × 10(6) M(-1) s(-1)) than favored substrates from positional scanning and phage display by 2- and 10-fold, respectively. Binding site cooperativity was prominent among preferred sequences, which enabled optimal interaction at all subsites as indicated by predictive modeling of KLK14/substrate complexes. These simulations constitute the first molecular dynamics analysis of KLK14 and offer a structural rationale for the divergent subsite preferences evident between KLK14 and closely related KLKs, KLK4 and KLK5. Collectively, these findings highlight the importance of binding site cooperativity in protease substrate recognition, which has implications for discovery of optimal substrates and engineering highly effective protease inhibitors.