Molecular architecture of the human sinus node: insights into the function of the cardiac pacemaker.

BACKGROUND: Although we know much about the molecular makeup of the sinus node (SN) in small mammals, little is known about it in humans. The aims of the present study were to investigate the expression of ion channels in the human SN and to use the data to predict electrical activity. METHODS AND RESULTS: Quantitative polymerase chain reaction, in situ hybridization, and immunofluorescence were used to analyze 6 human tissue samples. Messenger RNA (mRNA) for 120 ion channels (and some related proteins) was measured in the SN, a novel paranodal area, and the right atrium (RA). The results showed, for example, that in the SN compared with the RA, there was a lower expression of Na(v)1.5, K(v)4.3, K(v)1.5, ERG, K(ir)2.1, K(ir)6.2, RyR2, SERCA2a, Cx40, and Cx43 mRNAs but a higher expression of Ca(v)1.3, Ca(v)3.1, HCN1, and HCN4 mRNAs. The expression pattern of many ion channels in the paranodal area was intermediate between that of the SN and RA; however, compared with the SN and RA, the paranodal area showed greater expression of K(v)4.2, K(ir)6.1, TASK1, SK2, and MiRP2. Expression of ion channel proteins was in agreement with expression of the corresponding mRNAs. The levels of mRNA in the SN, as a percentage of those in the RA, were used to estimate conductances of key ionic currents as a percentage of those in a mathematical model of human atrial action potential. The resulting SN model successfully produced pacemaking. CONCLUSIONS: Ion channels show a complex and heterogeneous pattern of expression in the SN, paranodal area, and RA in humans, and the expression pattern is appropriate to explain pacemaking.

Mining patterns and factors contributing to crash severity on road curves

Road curves are an important feature of road infrastructure and many serious crashes occur on road curves. In Queensland, the number of fatalities is twice as many on curves as that on straight roads. Therefore, there is a need to reduce drivers’ exposure to crash risk on road curves. Road crashes in Australia and in the Organisation for Economic Co-operation and Development(OECD) have plateaued in the last five years (2004 to 2008) and the road safety community is desperately seeking innovative interventions to reduce the number of crashes. However, designing an innovative and effective intervention may prove to be difficult as it relies on providing theoretical foundation, coherence, understanding, and structure to both the design and validation of the efficiency of the new intervention. Researchers from multiple disciplines have developed various models to determine the contributing factors for crashes on road curves with a view towards reducing the crash rate. However, most of the existing methods are based on statistical analysis of contributing factors described in government crash reports. In order to further explore the contributing factors related to crashes on road curves, this thesis designs a novel method to analyse and validate these contributing factors. The use of crash claim reports from an insurance company is proposed for analysis using data mining techniques. To the best of our knowledge, this is the first attempt to use data mining techniques to analyse crashes on road curves. Text mining technique is employed as the reports consist of thousands of textual descriptions and hence, text mining is able to identify the contributing factors. Besides identifying the contributing factors, limited studies to date have investigated the relationships between these factors, especially for crashes on road curves. Thus, this study proposed the use of the rough set analysis technique to determine these relationships. The results from this analysis are used to assess the effect of these contributing factors on crash severity. The findings obtained through the use of data mining techniques presented in this thesis, have been found to be consistent with existing identified contributing factors. Furthermore, this thesis has identified new contributing factors towards crashes and the relationships between them. A significant pattern related with crash severity is the time of the day where severe road crashes occur more frequently in the evening or night time. Tree collision is another common pattern where crashes that occur in the morning and involves hitting a tree are likely to have a higher crash severity. Another factor that influences crash severity is the age of the driver. Most age groups face a high crash severity except for drivers between 60 and 100 years old, who have the lowest crash severity. The significant relationship identified between contributing factors consists of the time of the crash, the manufactured year of the vehicle, the age of the driver and hitting a tree. Having identified new contributing factors and relationships, a validation process is carried out using a traffic simulator in order to determine their accuracy. The validation process indicates that the results are accurate. This demonstrates that data mining techniques are a powerful tool in road safety research, and can be usefully applied within the Intelligent Transport System (ITS) domain. The research presented in this thesis provides an insight into the complexity of crashes on road curves. The findings of this research have important implications for both practitioners and academics. For road safety practitioners, the results from this research illustrate practical benefits for the design of interventions for road curves that will potentially help in decreasing related injuries and fatalities. For academics, this research opens up a new research methodology to assess crash severity, related to road crashes on curves.

Generic one round group key exchange in the standard model

Minimizing complexity of group key exchange (GKE) protocols is an important milestone towards their practical deployment. An interesting approach to achieve this goal is to simplify the design of GKE protocols by using generic building blocks. In this paper we investigate the possibility of founding GKE protocols based on a primitive called multi key encapsulation mechanism (mKEM) and describe advantages and limitations of this approach. In particular, we show how to design a one-round GKE protocol which satisfies the classical requirement of authenticated key exchange (AKE) security, yet without forward secrecy. As a result, we obtain the first one-round GKE protocol secure in the standard model. We also conduct our analysis using recent formal models that take into account both outsider and insider attacks as well as the notion of key compromise impersonation resilience (KCIR). In contrast to previous models we show how to model both outsider and insider KCIR within the definition of mutual authentication. Our analysis additionally implies that the insider security compiler by Katz and Shin from ACM CCS 2005 can be used to achieve more than what is shown in the original work, namely both outsider and insider KCIR.

The impact of red light cameras on safety in Arizona

Red light cameras (RLCs) have been used in a number of US cities to yield a demonstrable reduction in red light violations; however, evaluating their impact on safety (crashes) has been relatively more difficult. Accurately estimating the safety impacts of RLCs is challenging for several reasons. First, many safety related factors are uncontrolled and/or confounded during the periods of observation. Second, “spillover” effects caused by drivers reacting to non-RLC equipped intersections and approaches can make the selection of comparison sites difficult. Third, sites selected for RLC installation may not be selected randomly, and as a result may suffer from the regression to the mean bias. Finally, crash severity and resulting costs need to be considered in order to fully understand the safety impacts of RLCs. Recognizing these challenges, a study was conducted to estimate the safety impacts of RLCs on traffic crashes at signalized intersections in the cities of Phoenix and Scottsdale, Arizona. Twenty-four RLC equipped intersections in both cities are examined in detail and conclusions are drawn. Four different evaluation methodologies were employed to cope with the technical challenges described in this paper and to assess the sensitivity of results based on analytical assumptions. The evaluation results indicated that both Phoenix and Scottsdale are operating cost-effective installations of RLCs: however, the variability in RLC effectiveness within jurisdictions is larger in Phoenix. Consistent with findings in other regions, angle and left-turn crashes are reduced in general, while rear-end crashes tend to increase as a result of RLCs.

Effects of transportation accessibility on residential property values: Application of spatial hedonic price model in Seoul, South Korea, metropolitan area

A number of studies have focused on estimating the effects of accessibility on housing values by using the hedonic price model. In the majority of studies, estimation results have revealed that housing values increase as accessibility improves, although the magnitude of estimates has varied across studies. Adequately estimating the relationship between transportation accessibility and housing values is challenging for at least two reasons. First, the monocentric city assumption applied in location theory is no longer valid for many large or growing cities. Second, rather than being randomly distributed in space, housing values are clustered in space—often exhibiting spatial dependence. Recognizing these challenges, a study was undertaken to develop a spatial lag hedonic price model in the Seoul, South Korea, metropolitan region, which includes a measure of local accessibility as well as systemwide accessibility, in addition to other model covariates. Although the accessibility measures can be improved, the modeling results suggest that the spatial interactions of apartment sales prices occur across and within traffic analysis zones, and the sales prices for apartment communities are devalued as accessibility deteriorates. Consistent with findings in other cities, this study revealed that the distance to the central business district is still a significant determinant of sales price.

Evaluation of the Scottsdale Loop 101 automated speed enforcement demonstration program

Speeding is recognized as a major contributing factor in traffic crashes. In order to reduce speed-related crashes, the city of Scottsdale, Arizona implemented the first fixed-camera photo speed enforcement program (SEP) on a limited access freeway in the US. The 9-month demonstration program spanning from January 2006 to October 2006 was implemented on a 6.5 mile urban freeway segment of Arizona State Route 101 running through Scottsdale. This paper presents the results of a comprehensive analysis of the impact of the SEP on speeding behavior, crashes, and the economic impact of crashes. The impact on speeding behavior was estimated using generalized least square estimation, in which the observed speeds and the speeding frequencies during the program period were compared to those during other periods. The impact of the SEP on crashes was estimated using 3 evaluation methods: a before-and-after (BA) analysis using a comparison group, a BA analysis with traffic flow correction, and an empirical Bayes BA analysis with time-variant safety. The analysis results reveal that speeding detection frequencies (speeds> or =76 mph) increased by a factor of 10.5 after the SEP was (temporarily) terminated. Average speeds in the enforcement zone were reduced by about 9 mph when the SEP was implemented, after accounting for the influence of traffic flow. All crash types were reduced except rear-end crashes, although the estimated magnitude of impact varies across estimation methods (and their corresponding assumptions). When considering Arizona-specific crash related injury costs, the SEP is estimated to yield about $17 million in annual safety benefits.

Empirical Bayes method in the study of traffic safety via heterogeneous negative multinomial model

In the study of traffic safety, expected crash frequencies across sites are generally estimated via the negative binomial model, assuming time invariant safety. Since the time invariant safety assumption may be invalid, Hauer (1997) proposed a modified empirical Bayes (EB) method. Despite the modification, no attempts have been made to examine the generalisable form of the marginal distribution resulting from the modified EB framework. Because the hyper-parameters needed to apply the modified EB method are not readily available, an assessment is lacking on how accurately the modified EB method estimates safety in the presence of the time variant safety and regression-to-the-mean (RTM) effects. This study derives the closed form marginal distribution, and reveals that the marginal distribution in the modified EB method is equivalent to the negative multinomial (NM) distribution, which is essentially the same as the likelihood function used in the random effects Poisson model. As a result, this study shows that the gamma posterior distribution from the multivariate Poisson-gamma mixture can be estimated using the NM model or the random effects Poisson model. This study also shows that the estimation errors from the modified EB method are systematically smaller than those from the comparison group method by simultaneously accounting for the RTM and time variant safety effects. Hence, the modified EB method via the NM model is a generalisable method for estimating safety in the presence of the time variant safety and the RTM effects.

How automated speed enforcement may reduce travel time variability and result in travel time savings : the case study of the loop 101 speed enforcement program in Scottsdale, Arizona

The city of Scottsdale Arizona implemented the first fixed photo Speed Enforcement camera demonstration Program (SEP) on a US freeway in 2006. A comprehensive before-and-after analysis of the impact of the SEP on safety revealed significant reductions in crash frequency and severity, which indicates that the SEP is a promising countermeasure for improving safety. However, there is often a trade off between safety and mobility when safety investments are considered. As a result, identifying safety countermeasures that both improve safety and reduce Travel Time Variability (TTV) is a desirable goal for traffic safety engineers. This paper reports on the analysis of the mobility impacts of the SEP by simulating the traffic network with and without the SEP, calibrated to real world conditions. The simulation results show that the SEP decreased the TTV: the risk of unreliable travel was at least 23% higher in the ‘without SEP’ scenario than in the ‘with SEP’ scenario. In addition, the total Travel Time Savings (TTS) from the SEP was estimated to be at least ‘569 vehicle-hours/year.’ Consequently, the SEP is an efficient countermeasure not only for reducing crashes but also for improving mobility through TTS and reduced TTV.

Fast content-based file type identification

Digital forensic examiners often need to identify the type of a file or file fragment based only on the content of the file. Content-based file type identification schemes typically use a byte frequency distribution with statistical machine learning to classify file types. Most algorithms analyze the entire file content to obtain the byte frequency distribution, a technique that is inefficient and time consuming. This paper proposes two techniques for reducing the classification time. The first technique selects a subset of features based on the frequency of occurrence. The second speeds classification by sampling several blocks from the file. Experimental results demonstrate that up to a fifteen-fold reduction in file size analysis time can be achieved with limited impact on accuracy.

Melanoma mouse model implicates metabotropic glutamate signaling in melanocytic neoplasia

To gain insight into melanoma pathogenesis, we characterized an insertional mouse mutant, TG3, that is predisposed to develop multiple melanomas. Physical mapping identified multiple tandem insertions of the transgene into intron 3 of Grm1 (encoding metabotropic glutamate receptor 1) with concomitant deletion of 70 kb of intronic sequence. To assess whether this insertional mutagenesis event results in alteration of transcriptional regulation, we analyzed Grm1 and two flanking genes for aberrant expression in melanomas from TG3 mice. We observed aberrant expression of only Grm1. Although we did not detect its expression in normal mouse melanocytes, Grm1 was ectopically expressed in the melanomas from TG3 mice. To confirm the involvement of Grm1 in melanocytic neoplasia, we created an additional transgenic line with Grm1 expression driven by the dopachrome tautomerase promoter. Similar to the original TG3, the Tg(Grm1)EPv line was susceptible to melanoma. In contrast to human melanoma, these transgenic mice had a generalized hyperproliferation of melanocytes with limited transformation to fully malignant metastasis. We detected expression of GRM1 in a number of human melanoma biopsies and cell lines but not in benign nevi and melanocytes. This study provides compelling evidence for the importance of metabotropic glutamate signaling in melanocytic neoplasia.