Localization of nervonic acid beta-oxidation in human and rodent peroxisomes: impaired oxidation in Zellweger syndrome and X-linked adrenoleukodystrophy

Studies with purified subcellular organelles from rat liver indicate that nervonic acid (C24:1) is beta-oxidized preferentially in peroxisomes. Lack of effect by etomoxir, inhibitor of mitochondrial beta-oxidation, on beta-oxidation of lignoceric acid (C24:0), a peroxisomal function, and that of nervonic acid (24:1) compared to the inhibition of palmitic acid (16:0) oxidation, a mitochondrial function, supports the conclusion that nervonic acid is oxidized in peroxisomes. Moreover, the oxidation of nervonic and lignoceric acids was deficient in fibroblasts from patients with defects in peroxisomal beta-oxidation [Zellweger syndrome (ZS) and X-linked adrenoleukodystrophy (X-ALD)]. Similar to lignoceric acid, the activation and beta-oxidation of nervonic acid was deficient in peroxisomes isolated from X-ALD fibroblasts. Transfection of X-ALD fibroblasts with human cDNA encoding for ALDP (X-ALD gene product) restored the oxidation of both nervonic and lignoceric acids, demonstrating that the same molecular defect may be responsible for the abnormality in the oxidation of nervonic as well as lignoceric acid. Moreover, immunoprecipitation of activities for acyl-CoA ligase for both lignoceric acid and nervonic acid indicate that saturated and monoenoic very long chain (VLC) fatty acids may be activated by the same enzyme. These results clearly demonstrate that similar to saturated VLC fatty acids (e.g., lignoceric acid), VLC monounsaturated fatty acids (e.g., nervonic acid) are oxidized preferentially in peroxisomes and that this activity is impaired in X-ALD. In view of the fact that the oxidation of unsaturated VLC fatty acids is defective in X-ALD patients, the efficacy of dietary monoene therapy, "Lorenzo's oil," in X-ALD needs to be evaluated.     

Transient liquid phase diffusion bonding and associated recrystallization phenomenon when joining ODS ferritic superalloys

Oxide dispersion strengthened (ODS) ferritic superalloys attribute their excellent intermediate and high temperature creep resistant properties to the distribution of an inert oxide, Y₂O₃ within highly directional and elongated grains. Careful selection of joining techniques is, therefore, of utmost importance so that the parent metal microstructure is not disrupted and is continuous across the bond line. Transient liquid phase (TLP) bonding is a suitable technique which has been used to join the ferritic superalloys MA957, MA956 and PM2000 using an amorphous foil based on an Fe-B-Si composition. To further minimize disruption to the parent alloy microstructure at the bond line, thin sputter coats based on the Fe-B-Si composition have also been used successfully for TLP bonding. Results have shown a boron-induced secondary recrystallized zone at the bond line in MA957 which acts as a barrier to further grain growth across the bond line on subsequent zone annealing. Differential scanning calorimetry shows that this recrystallization is triggered at 200 °C below the usual recrystallization temperature during heat treatment and occurs only when the metal filler melts and there is a free flux of boron into the base metal. Texture measurements show that the boron-induced recrystallization is of the same nature as the recrystallization produced by heat treatment but possesses a stronger directional 110 fibre texture. In contrast, grain growth across the bond line could be achieved in TLP bonds produced in MA956. However, a similar heat treatment for PM2000 produced simultaneous but independent secondary recrystallization both at the joint and in the bulk alloy. This difference in behaviour between these two similar alloys is attributed to differences in their thermomechanical processing.     

Microfluidic continuous magnetophoretic protein separation using nanoparticle aggregates

We demonstrate a microfluidic continuous-flow protein separation process in which silica-coated superparamagnetic nanoparticles interact preferentially with hemoglobin in a mixture with bovine serum albumin, and the resulting hemoglobin-nanoparticle aggregates are recovered online using magnetophoresis. We present detailed modeling and analysis of this process yielding quantitative estimates of the recovery of both proteins, validated by experiments. While several previous studies utilize an average particle size in modeling magnetophoretic particle trajectories or process design, in this study we emphasize the importance of accounting for particle size distributions in calculating particle recovery, and therefore in estimating separation efficiency. We combine experimentally measured size distributions of protein-nanoparticle aggregates with simulations of particle trajectories and provide a simple analytical method to calculate the efficiency of separation at various flow speeds, which fully accounts for heterogeneity in particle sizes. Our method can potentially be used for affinity based biomolecular separations at both analytical and preparative scales by exploiting well-established techniques to functionalize nanoparticle surfaces with selective ligands. Further, the modeling methodology presented here may be applied to provide better estimates of particle recovery in a broad range of magnetophoretic separation processes involving heterogeneity in particle sizes.     

Determining malicious executable distinguishing attributes and low-complexity detection

Detection of rapidly evolving malware requires classification techniques that can effectively and efficiently detect zero-day attacks. Such detection is based on a robust model of benign behavior and deviations from that model are used to detect malicious behavior. In this paper we propose a low-complexity host-based technique that uses deviations in static file attributes to detect malicious executables. We first develop simple statistical models of static file attributes derived from the empirical data of thousands of benign executables. Deviations among the attribute models of benign and malware executables are then quantified using information-theoretic (Kullback-Leibler-based) divergence measures. This quantification reveals distinguishing attributes that are considerably divergent between benign and malware executables and therefore can be used for detection. We use the benign models of divergent attributes in cross-correlation and log-likelihood frameworks to classify malicious executables. Our results, using over 4,000 malicious file samples, indicate that the proposed detector provides reasonably high detection accuracy, while having significantly lower complexity than existing detectors.     

Attention,polychronicity, and expertise in prospective memory performance: Programmers' vulnerability to habit intrusion error in multitasking

The paper examines prospective memory (ProM) in programmer multitasking and reports administration of a naturalistic atypical action. The study emphasizes on how attention, time orientation, and expertise affect ProM performance in multitasking among a group of computer science and engineering students (N=108). The results suggest that attention play a crucial role in multitasking and ProM performance with respect to whether or not a word display requires more attention to be devoted in monitoring and identifying it for an appropriate action. Polychrons exhibit lesser degree of ProM performance failure than monochrons whereas expertise does not have an effect. Finally, results show that out of overall ProM performance failure, habit intrusion errors comprise of 16.22% occurring 1.75 times in every 10 valid click responses of ProM task. Moreover, experts demonstrate a superior performance over novices in programming.     

Spatial sensitivity analysis of multi-criteria weights in GIS-based land suitability evaluation

With growing interest in extending GIS to support multi-criteria decision-making (MCDM) methods, enhancing GIS-based MCDM with sensitivity analysis (SA) procedures is crucial to understand the model behavior and its limitations. This paper presents a novel approach of examining multi-criteria weight sensitivity of a GIS-based MCDM model. It explores the dependency of model output on the weights of input parameters, identifying criteria that are especially sensitive to weight changes and to show the impacts of changing criteria weights on the model outcomes in spatial dimension. A methodology was developed to perform simulations where the weights associated with all criteria used for suitability modelling were varied one-at-a-time (OAT) to investigate their relative impacts on the final evaluation results. A tool which incorporates the OAT method with the Analytical Hierarchy Process (AHP) within the ArcGIS environment was implemented. It permits a range of user defined simulations to be performed to quantitatively evaluate model dynamic changes, measures the stability of results with respect to the variation of different parameter weights, and displays spatial change dynamics. A case study of irrigated cropland suitability assessment addressing the application of the new GIS-based AHP-SA tool is described. It demonstrates that the tool is spatial, simple and flexible.     

MTPSO algorithm for solving planar graph coloring problem

In this paper, we proposed a modified turbulent particle swarm optimization (named MTPSO) model for solving planar graph coloring problem based on particle swarm optimization. The proposed model is consisting of the walking one strategy, assessment strategy and turbulent strategy. The proposed MTPSO model can solve the planar graph coloring problem using four-colors more efficiently and accurately. Compared to the results shown in Cui et al. (2008), not only the experimental results of the proposed model can get smaller average iterations but can get higher correction coloring rate when the number of nodes is greater than 30.     

Effects of combined wrist deviation and forearm rotation on discomfort score

The aim of the study was to examine the pattern of the change in discomfort for combined wrist deviation and forearm rotation as joint angles increased away from neutral in a repetitive task. There were five levels of wrist deviation (neutral, 35% and 55% of the range of motion (ROM) in radial and ulnar deviation) and five levels of forearm rotation (neutral, 30% and 60% of the ROM in pronation and supination). Twenty-five participants performed a repetitive flexion task with a force of 10 N +/- 1 N at a frequency of 15 exertions per min, with replication after 1 week for six of the participants. A visual analogue scale was used for recording the discomfort scores. Repeated measures analysis of covariance with the Greenhouse-Geisser correction, where necessary, was used on transformed values of the discomfort scores. Grip test endurance time at 50% of maximum voluntary contraction was included as a covariate. Wrist deviation (p = 0.007) and forearm rotation (p = 0.001) were found to have significant effects. Interactions of the main factors were not significant and nor was the covariate. Quadratic regression equations were derived and were used to generate iso-discomfort contours, which show a useful area of low discomfort around the central neutral zone of wrist postures, but with steep increases in discomfort at the extreme combinations of wrist ulnar/radial deviation with forearm pronation/supination. Discomfort equations and contours, showing wrist and forearm postures, which are either acceptable or potentially injurious, are useful for the design of industrial tools, machine controls and workspaces. Reference to these can help to reduce the risk of musculoskeletal injury associated with the tasks or tools by avoiding poor postures with unacceptable deviations from neutral posture.     

A comprehensive solution for application‐level adaptation

Driven by the emergence of mobile and pervasive computing there is a growing demand for context‐aware software systems that can dynamically adapt to their run‐time environment. We present the results of project MADAM that has delivered a comprehensive solution for the development and operation of context‐aware, self‐adaptive applications. The main contributions of MADAM are (a) a sophisticated middleware that supports the dynamic adaptation of component‐based applications, and (b) an innovative model‐driven development methodology that is based on abstract adaptation models and corresponding model‐to‐code transformations. MADAM has demonstrated the viability of a general, integrated approach to application‐level adaptation. We discuss our experiences with two real‐world case studies that were built using the MADAM approach. Copyright © 2008 John Wiley & Sons, Ltd.     

Experimental analysis and numerical modelling of the forming process of polypropylene replicas of micro-cavities using hot embossing

Numerical modelling of the deformation of a polymer using the finite elements method in axisymetrical mode was performed using the LsDyna^® software to describe the filling of micro-cavities during the forming process of the material using the hot embossing. These simulations firstly allow verifying whether the chosen forming process conditions promote or not an optimized filling of the superficial cavities in order to achieve precise replicas which best reproduce the superficial topography of the mould. The simulations were carried out to evaluate the filling of the cavities taking into account the mechanical behaviour of the selected polymer into the model. Moreover, these models were developed to verify the effect of the distribution of the mould cavities on their filling. The influence of the mobility of non deformable rigid plates on the filling of the cavities represents an auxiliary variable. In the approach presented, the compression plates are assumed to be parallel and non deformable, whereas the polymer disk follows a rubbery behaviour around a temperature equal to 140°C. Globally the modelling results are satisfactory for they are rather close to the experimental observations conducted. In summary, the effect of the normal stress as also the distribution of micro-cavities at the mould surface seem to prevail in the case of the forming process by hot embossing.