Syntaxin 11 binds Vti1b and regulates late endosome to lysosome fusion in macrophages

Syntaxin 11 (Stx11) is a SNARE protein enriched in cells of the immune system. Loss or mutation of Stx11 results in familial hemophagocytic lymphohistiocytosis type-4 (FHL-4), an autosomal recessive disorder of immune dysregulation characterized by high levels of inflammatory cytokines along with defects in T-cell and natural killer cell function. We show here Stx11 is located on endosomalmembranes including late endosomes and lysosomes in macrophages. While Stx11 did not form a typical trans-SNARE complex, it did bind to the Q-SNARE Vti1b and was able to regulate the availability of Vti1b to form the Q-SNARE complexes Stx6/Stx7/Vtib and Stx7/Stx8/Vti1b. The mutant form of Stx11 sequestered Vti1b from forming the Q-SNARE complex that mediates late endosome to lysosome fusion. Depletion of Stx11 in activated macrophages leads to an accumulation of enlarged late endocytic compartments, increased trafficking to the cell surface and inhibition of late endosome to lysosome fusion. These phenotypes arerescued by the expression of an siRNA-resistant Stx11 construct in Stx11-depleted cells. Our results suggest that by regulating the availability of Vti1b, Stx11 regulates trafficking steps between late endosomes, lysosomes and the cell surface in macrophages.

Reliability of clinical measurement for assessing spinal fusion: An experimental sheep study

Study Design. A sheep study designed to compare the accuracy of static radiographs, dynamic radiographs, and computed tomographic (CT) scans for the assessment of thoracolumbar facet joint fusion as determined by micro-CT scanning. Objective. To determine the accuracy and reliability of conventional imaging techniques in identifying the status of thoracolumbar (T13-L1) facet joint fusion in a sheep model. Summary of Background Data. Plain radiographs are commonly used to determine the integrity of surgical arthrodesis of the thoracolumbar spine. Many previous studies of fusion success have relied solely on postoperative assessment of plain radiographs, a technique lacking sensitivity for pseudarthrosis. CT may be a more reliable technique, but is less well characterized. Methods. Eleven adult sheep were randomized to either attempted arthrodesis using autogenous bone graft and internal fixation (n = 3) or intentional pseudarthrosis (IP) using oxidized cellulose and internal fixation (n = 8). After 6 months, facet joint fusion was assessed by independent observers, using (1) plain static radiography alone, (2) additional dynamic radiographs, and (3) additional reconstructed spiral CT imaging. These assessments were correlated with high-resolution micro-CT imaging to predict the utility of the conventional imaging techniques in the estimation of fusion success. Results. The capacity of plain radiography alone to correctly predict fusion or pseudarthrosis was 43% and was not improved using plain radiography and dynamic radiography with also a 43% accuracy. Adding assessment by reformatted CT imaging to the plain radiography techniques increased the capacity to predict fusion outcome to 86% correctly. The sensitivity, specificity, and accuracy of static radiography were 0.33, 0.55, and 0.43, respectively, those of dynamic radiography were 0.46, 0.40, and 0.43, respectively, and those of radiography plus CT were 0.88, 0.85, and 0.86, respectively. Conclusion. CT-based evaluation correlated most closely with high-resolution micro-CT imaging. Neither plain static nor dynamic radiographs were able to predict fusion outcome accurately. © 2012 Lippincott Williams & Wilkins.

Sequential Fusion Using Correlated Decisions for Controlled Verification Errors

Fusion techniques have received considerable attention for achieving lower error rates with biometrics. A fused classifier architecture based on sequential integration of multi-instance and multi-sample fusion schemes allows controlled trade-off between false alarms and false rejects. Expressions for each type of error for the fused system have previously been derived for the case of statistically independent classifier decisions. It is shown in this paper that the performance of this architecture can be improved by modelling the correlation between classifier decisions. Correlation modelling also enables better tuning of fusion model parameters, ‘N’, the number of classifiers and ‘M’, the number of attempts/samples, and facilitates the determination of error bounds for false rejects and false accepts for each specific user. Error trade-off performance of the architecture is evaluated using HMM based speaker verification on utterances of individual digits. Results show that performance is improved for the case of favourable correlated decisions. The architecture investigated here is directly applicable to speaker verification from spoken digit strings such as credit card numbers in telephone or voice over internet protocol based applications. It is also applicable to other biometric modalities such as finger prints and handwriting samples.

Use of Bayesian MUNE to show differing rate of loss of motor units in subgroups of ALS

Objectives To evaluate differences among patients with different clinical features of ALS, we used our Bayesian method of motor unit number estimation (MUNE). Methods We performed serial MUNE studies on 42 subjects who fulfilled the diagnostic criteria for ALS during the course of their illness. Subjects were classified into three subgroups according to whether they had typical ALS (with upper and lower motor neurone signs) or had predominantly upper motor neurone weakness with only minor LMN signs, or predominantly lower motor neurone weakness with only minor UMN signs. In all subjects we calculated the half life of MUs, defined as the expected time for the number of MUs to halve, in one or more of the abductor digiti minimi (ADM), abductor pollicis brevis (APB) and extensor digitorum brevis (EDB) muscles. Results The mean half life of MUs was less in subjects who had typical ALS with both upper and lower motor neurone signs than in those with predominantly upper motor neurone weakness or predominantly lower motor neurone weakness. In 18 subjects we analysed the estimated size of the MUs and demonstrated the appearance of large MUs in subjects with upper or lower motor neurone predominant weakness. We found that the appearance of large MUs was correlated with the half life of MUs. Conclusions Patients with different clinical features of ALS have different rates of loss and different sizes of MUs. Significance: These findings could indicate differences in disease pathogenesis.

Condition deterioration prediction of bridge elements using Dynamic Bayesian Networks (DBNs)

The ability of bridge deterioration models to predict future condition provides significant advantages in improving the effectiveness of maintenance decisions. This paper proposes a novel model using Dynamic Bayesian Networks (DBNs) for predicting the condition of bridge elements. The proposed model improves prediction results by being able to handle, deterioration dependencies among different bridge elements, the lack of full inspection histories, and joint considerations of both maintenance actions and environmental effects. With Bayesian updating capability, different types of data and information can be utilised as inputs. Expert knowledge can be used to deal with insufficient data as a starting point. The proposed model established a flexible basis for bridge systems deterioration modelling so that other models and Bayesian approaches can be further developed in one platform. A steel bridge main girder was chosen to validate the proposed model.

Sequential fusion of decisions from adaptive and random samples for controlled verification of errors

Fusion techniques have received considerable attention for achieving performance improvement with biometrics. While a multi-sample fusion architecture reduces false rejects, it also increases false accepts. This impact on performance also depends on the nature of subsequent attempts, i.e., random or adaptive. Expressions for error rates are presented and experimentally evaluated in this work by considering the multi-sample fusion architecture for text-dependent speaker verification using HMM based digit dependent speaker models. Analysis incorporating correlation modeling demonstrates that the use of adaptive samples improves overall fusion performance compared to randomly repeated samples. For a text dependent speaker verification system using digit strings, sequential decision fusion of seven instances with three random samples is shown to reduce the overall error of the verification system by 26% which can be further reduced by 6% for adaptive samples. This analysis novel in its treatment of random and adaptive multiple presentations within a sequential fused decision architecture, is also applicable to other biometric modalities such as finger prints and handwriting samples.

Sequential fusion of decisions with favorable dependence for controlled verification errors

Statistical dependence between classifier decisions is often shown to improve performance over statistically independent decisions. Though the solution for favourable dependence between two classifier decisions has been derived, the theoretical analysis for the general case of 'n' client and impostor decision fusion has not been presented before. This paper presents the expressions developed for favourable dependence of multi-instance and multi-sample fusion schemes that employ 'AND' and 'OR' rules. The expressions are experimentally evaluated by considering the proposed architecture for text-dependent speaker verification using HMM based digit dependent speaker models. The improvement in fusion performance is found to be higher when digit combinations with favourable client and impostor decisions are used for speaker verification. The total error rate of 20% for fusion of independent decisions is reduced to 2.1% for fusion of decisions that are favourable for both client and impostors. The expressions developed here are also applicable to other biometric modalities, such as finger prints and handwriting samples, for reliable identity verification.

Severity of driver injury and vehicle damage in traffic crashes at intersections: A Bayesian hierarchical analysis

Most crash severity studies ignored severity correlations between driver-vehicle units involved in the same crashes. Models without accounting for these within-crash correlations will result in biased estimates in the factor effects. This study developed a Bayesian hierarchical binomial logistic model to identify the significant factors affecting the severity level of driver injury and vehicle damage in traffic crashes at signalized intersections. Crash data in Singapore were employed to calibrate the model. Model fitness assessment and comparison using Intra-class Correlation Coefficient (ICC) and Deviance Information Criterion (DIC) ensured the suitability of introducing the crash-level random effects. Crashes occurring in peak time, in good street lighting condition, involving pedestrian injuries are associated with a lower severity, while those in night time, at T/Y type intersections, on right-most lane, and installed with red light camera have larger odds of being severe. Moreover, heavy vehicles have a better resistance on severe crash, while crashes involving two-wheel vehicles, young or aged drivers, and the involvement of offending party are more likely to result in severe injuries.

Applying Bayesian hierarchical models to examine motorcycle crashes at signalized intersections

Motorcycles are overrepresented in road traffic crashes and particularly vulnerable at signalized intersections. The objective of this study is to identify causal factors affecting the motorcycle crashes at both four-legged and T signalized intersections. Treating the data in time-series cross-section panels, this study explores different Hierarchical Poisson models and found that the model allowing autoregressive lag 1 dependent specification in the error term is the most suitable. Results show that the number of lanes at the four-legged signalized intersections significantly increases motorcycle crashes largely because of the higher exposure resulting from higher motorcycle accumulation at the stop line. Furthermore, the presence of a wide median and an uncontrolled left-turn lane at major roadways of four-legged intersections exacerbate this potential hazard. For T signalized intersections, the presence of exclusive right-turn lane at both major and minor roadways and an uncontrolled left-turn lane at major roadways of T intersections increases motorcycle crashes. Motorcycle crashes increase on high-speed roadways because they are more vulnerable and less likely to react in time during conflicts. The presence of red light cameras reduces motorcycle crashes significantly for both four-legged and T intersections. With the red-light camera, motorcycles are less exposed to conflicts because it is observed that they are more disciplined in queuing at the stop line and less likely to jump start at the start of green.

Bayesian hierarchical analysis on crash prediction models

Traditional crash prediction models, such as generalized linear regression models, are incapable of taking into account the multilevel data structure, which extensively exists in crash data. Disregarding the possible within-group correlations can lead to the production of models giving unreliable and biased estimates of unknowns. This study innovatively proposes a -level hierarchy, viz. (Geographic region level – Traffic site level – Traffic crash level – Driver-vehicle unit level – Vehicle-occupant level) Time level, to establish a general form of multilevel data structure in traffic safety analysis. To properly model the potential cross-group heterogeneity due to the multilevel data structure, a framework of Bayesian hierarchical models that explicitly specify multilevel structure and correctly yield parameter estimates is introduced and recommended. The proposed method is illustrated in an individual-severity analysis of intersection crashes using the Singapore crash records. This study proved the importance of accounting for the within-group correlations and demonstrated the flexibilities and effectiveness of the Bayesian hierarchical method in modeling multilevel structure of traffic crash data.

Hotspot Identification: A Full Bayesian Hierarchical Modeling Approach

This study proposes a full Bayes (FB) hierarchical modeling approach in traffic crash hotspot identification. The FB approach is able to account for all uncertainties associated with crash risk and various risk factors by estimating a posterior distribution of the site safety on which various ranking criteria could be based. Moreover, by use of hierarchical model specification, FB approach is able to flexibly take into account various heterogeneities of crash occurrence due to spatiotemporal effects on traffic safety. Using Singapore intersection crash data(1997-2006), an empirical evaluate was conducted to compare the proposed FB approach to the state-of-the-art approaches. Results show that the Bayesian hierarchical models with accommodation for site specific effect and serial correlation have better goodness-of-fit than non hierarchical models. Furthermore, all model-based approaches perform significantly better in safety ranking than the naive approach using raw crash count. The FB hierarchical models were found to significantly outperform the standard EB approach in correctly identifying hotspots.

Fusion of morphological images for airborne target detection

Several track-before-detection approaches for image based aircraft detection have recently been examined in an important automated aircraft collision detection application. A particularly popular approach is a two stage processing paradigm which involves: a morphological spatial filter stage (which aims to emphasize the visual characteristics of targets) followed by a temporal or track filter stage (which aims to emphasize the temporal characteristics of targets). In this paper, we proposed new spot detection techniques for this two stage processing paradigm that fuse together raw and morphological images or fuse together various different morphological images (we call these approaches morphological reinforcement). On the basis of flight test data, the proposed morphological reinforcement operations are shown to offer superior signal to-noise characteristics when compared to standard spatial filter options (such as the close-minus-open and adaptive contour morphological operations). However, system operation characterised curves, which examine detection verses false alarm characteristics after both processing stages, illustrate that system performance is very data dependent.

A proposed validation framework for expert elicited Bayesian Networks

The popularity of Bayesian Network modelling of complex domains using expert elicitation has raised questions of how one might validate such a model given that no objective dataset exists for the model. Past attempts at delineating a set of tests for establishing confidence in an entirely expert-elicited model have focused on single types of validity stemming from individual sources of uncertainty within the model. This paper seeks to extend the frameworks proposed by earlier researchers by drawing upon other disciplines where measuring latent variables is also an issue. We demonstrate that even in cases where no data exist at all there is a broad range of validity tests that can be used to establish confidence in the validity of a Bayesian Belief Network.