Predicting proteinase specificities from free energy calculations

The role of the primary binding residue (P1) in complexes between three different subtilases (subtilisin Carlsberg, thermitase and proteinase K) and their canonical protein inhibitor eglin c have been studied by free energy calculations. Based on the crystal structures of eglin c in complex with subtilisin Carlsberg and thermitase, and a homology model of the eglin c-proteinase K complex, a total of 57 mutants have been constructed and docked into their host proteins. The binding free energy was then calculated using molecular dynamics (MD) simulations combined with the linear interaction energy (LIE) method for all complexes differing only in the nature of the amino acid at the P1 position. LIE calculations for 19 different complexes for each subtilase were thus carried out excluding proline. The effects of substitutions at the P1 position on the binding free energies are found to be very large, and positively charged residues (Arg, Lys and His) are particularly deleterious for all three enzymes. The charged variants of the acidic side chains are found to bind more favorably as compared to their protonated states in all three subtilases. Furthermore, hydrophobic amino acids are accommodated most favorably at the S1-site in all three enzymes. Comparison of the three series of binding free energies shows only minor differences in the 19 computed relative binding free energies among these subtilases. This is further reflected in the correlation coefficient between the 23 relative binding free energies obtained, including the possible protonation states of ionizable side chains, but excluding the P1 Pro, for subtilisin Carlsberg versus thermitase (0.95), subtilisin versus proteinase K (0.94) and thermitase versus proteinase K (0.96).     

Will musculoskeletal and visual stress change when Visual Display Unit (VDU) operators move from small offices to an ergonomically optimized office landscape?

This study investigated the effect of moving from small offices to a landscape environment for 19 Visual Display Unit (VDU) operators at Alcatel Denmark AS. The operators reported significantly improved lighting condition and glare situation. Further, visual discomfort was also significantly reduced on a Visual Analogue Scale (VAS). There was no significant correlation between lighting condition and visual discomfort neither in the small offices nor in the office landscape. However, visual discomfort correlated significantly with glare in small offices i.e. more glare is related to more visual discomfort. This correlation disappeared after the lighting system in the office landscape had been improved. There was also a significant correlation between glare and itching of the eyes as well as blurred vision in the small offices, i.e. more glare more visual symptoms. Experience of pain was found to reduce the subjective assessment of work capacity during VDU tasks. There was a significant correlation between visual discomfort and reduced work capacity in small offices and in the office landscape. When moving from the small offices to the office landscape, there was a significant reduction in headache as well as back pain. No significant changes in pain intensity in the neck, shoulder, forearm, and wrist/hand were observed.The pain levels in different body areas were significantly correlated with subjective assessment of reduced work capacity in small offices and in the office landscape.By careful design and construction of an office landscape with regard to lighting and visual conditions, transfer from small offices may be acceptable from a visual-ergonomic point of view.     

The impact of personality traits and professional experience on police officers’ shooting performance under pressure

We explored the impact of professional experience and personality on police officers’ shooting performance under pressure. We recruited: (1) regular officers, (2) officers wanting to join a specialised arrest unit (AU) (expected to possess more stress-resistant traits; pre-AU) and (3) officers from this unit (expected to also possess more professional experience; AU) (all male). In Phase 1, we determined personality traits and experience. In Phase 2, state anxiety, shot accuracy, decision-making (shoot/don’t shoot), movement speed and gaze behaviour were measured while officers performed a shooting test under low and high pressure. Results indicate minimal differences in personality among groups and superior performance of AU officers. Regression analyses showed that state anxiety and shooting performance under high pressure were first predicted by AU experience and second by certain personality traits. Results suggest that although personality traits attenuate the impact of high pressure, it is relevant experience that secures effective performance under pressure.

Practitioner Summary: To obtain information for police selection and training purposes, we let officers who differed in personality and experience execute a shooting test under low and high pressure. Outcomes indicate that experience affected anxiety and performance most strongly, while personality traits of thrill- and adventure-seeking and self-control also had an effect.     

Evalvid-RA: trace driven simulation of rate adaptive MPEG-4 VBR video

Due to the increasing deployment of conversational real-time applications like VoIP and videoconferencing, the Internet is today facing new challenges. Low end-to-end delay is a vital QoS requirement for these applications, and the best effort Internet architecture does not support this natively. The delay and packet loss statistics are directly coupled to the aggregated traffic characteristics when link utilization is close to saturation. In order to investigate the behavior and quality of such applications under heavy network load, it is therefore necessary to create genuine traffic patterns. Trace files of real compressed video and audio are text files containing the number of bytes per video and audio frame. These can serve as material to construct mathematical traffic models. They can also serve as traffic generators in network simulators since they determine the packet sizes and their time schedule. However, to inspect perceived quality, the compressed binary content is needed to ensure decoding of received media. The EvalVid streaming video tool-set enables this using a sophisticated reassembly engine. Nevertheless, there has been a lack of research solutions for rate adaptive media content. The Internet community fears a congestion collapse if the usage of non-adaptive media content continues to grow. This paper presents a solution named Evalvid-RA for the simulation of true rate adaptive video. The solution generates real rate adaptive MPEG-4 streaming traffic, using the quantizer scale for adjusting the sending rate. A feedback based VBR rate controller is used at simulation time, supporting TFRC and a proprietary congestion control system named P-AQM. Example ns-2 simulations of TFRC and P-AQM demonstrate Evalvid-RA’s capabilities in performing close-to-true rate adaptive codec operation with low complexity to enable the simulation of large networks with many adaptive media sources on a single computer.     

Bayesian estimation of Dirichlet mixture model with variational inference

In statistical modeling, parameter estimation is an essential and challengeable task. Estimation of the parameters in the Dirichlet mixture model (DMM) is analytically intractable, due to the integral expressions of the gamma function and its corresponding derivatives. We introduce a Bayesian estimation strategy to estimate the posterior distribution of the parameters in DMM. By assuming the gamma distribution as the prior to each parameter, we approximate both the prior and the posterior distribution of the parameters with a product of several mutually independent gamma distributions. The extended factorized approximation method is applied to introduce a single lower-bound to the variational objective function and an analytically tractable estimation solution is derived. Moreover, there is only one function that is maximized during iterations and, therefore, the convergence of the proposed algorithm is theoretically guaranteed. With synthesized data, the proposed method shows the advantages over the EM-based method and the previously proposed Bayesian estimation method. With two important multimedia signal processing applications, the good performance of the proposed Bayesian estimation method is demonstrated.     

Adaptive memory search for multidemand multidimensional knapsack problems

We describe a simple adaptive memory search method for the 0/1 Multidemand Multidimensional Knapsack Problem (0/1 MDMKP). The search balances the level of infeasibility against the quality of the solution, and uses a simple dynamic tabu search mechanism. A weighting scheme to balance out the differences in the tightness of the constraints is also implemented. Computational results on a portfolio of test problems taken from the literature are reported, showing very favorable results, both in terms of solution quality and the ability of the search to find feasible solutions.     

Topology-controlled volume rendering

Topology provides a foundation for the development of mathematically sound tools for processing and exploration of scalar fields. Existing topology-based methods can be used to identify interesting features in volumetric data sets, to find seed sets for accelerated isosurface extraction, or to treat individual connected components as distinct entities for isosurfacing or interval volume rendering. We describe a framework for direct volume rendering based on segmenting a volume into regions of equivalent contour topology and applying separate transfer functions to each region. Each region corresponds to a branch of a hierarchical contour tree decomposition, and a separate transfer function can be defined for it. The novel contributions of our work are: 1) a volume rendering framework and interface where a unique transfer function can be assigned to each subvolume corresponding to a branch of the contour tree, 2) a runtime method for adjusting data values to reflect contour tree simplifications, 3) an efficient way of mapping a spatial location into the contour tree to determine the applicable transfer function, and 4) an algorithm for hardware-accelerated direct volume rendering that visualizes the contour tree-based segmentation at interactive frame rates using graphics processing units (GPUs) that support loops and conditional branches in fragment programs     

Using hash tables to manage the time-storage complexity in a point location problem: Application to explicit model predictive control

The online computational burden of linear model predictive control (MPC) can be moved offline by using multi-parametric programming, so-called explicit MPC. The solution to the explicit MPC problem is a piecewise affine (PWA) state feedback function defined over a polyhedral subdivision of the set of feasible states. The online evaluation of such a control law needs to determine the polyhedral region in which the current state lies. This procedure is called point location; its computational complexity is challenging, and determines the minimum possible sampling time of the system. A new flexible algorithm is proposed which enables the designer to trade off between time and storage complexities. Utilizing the concept of hash tables and the associated hash functions, the proposed method solves an aggregated point location problem that overcomes prohibitive complexity growth with the number of polyhedral regions, while the storage–processing trade-off can be optimized via scaling parameters. The flexibility and power of this approach is supported by several numerical examples.