Peroxiredoxin 2 as a chemotherapy responsiveness biomarker candidate in osteosarcoma revealed by proteomics

Purpose : We aimed to identify novel chemotherapy responsiveness biomarkers for osteosarcoma (OS) by investigating the global protein expression profile of 12 biopsy samples from OS patients. Experimental design : Six patients were classified as good responders and six as poor responders, according to the Huvos grading system. The protein expression profiles obtained by 2‐D DIGE consisted of 2250 protein spots. Results : Among them, we identified 55 protein spots whose intensity was significantly different (Bonferroni adjusted p‐value<0.01) between the two patient groups. Mass spectrometric protein identification demonstrated that the 55 spots corresponded to 38 distinct gene products including peroxiredoxin 2 (PRDX 2). Use of a specific antibody against PRDX 2 confirmed the differential expression of PRDX 2 between good and poor responders, while PRDX 2 levels as measured by Western blotting correlated highly with their corresponding 2‐D DIGE values. The predictive value of PRDX 2 expression was further confirmed by examining an additional four OS cases using Western blotting. Conclusions and clinical relevance : These results establish PRDX 2 as a candidate for chemotherapy responsiveness marker in OS. Measuring PRDX 2 in biopsy samples before treatment may contribute to more effective management of OS.     

Anatomic site‐specific proteomic signatures of gastrointestinal stromal tumors

The gastrointestinal stromal tumor (GIST) is the most common mesenchymal malignancy of the gastrointestinal tract. Its clinical course ranges widely from a curable disorder to a highly malignant disease. Although its clinical and molecular characteristics depend on the anatomic site of origin, the molecular background of GIST arising in different anatomical site has not been studied yet. To investigate the proteomic background of GIST, we examined the proteomic features corresponding to the anatomic site of tumor origin. Comparison of the proteomic profile of gastric (23 cases) and small intestinal (9 cases) GIST by 2‐DE revealed 105 protein spots with significantly different intensity (p <0.01) between the two groups. Mass spectrometric study identified 68 distinct proteins for these 105 protein spots, including cancer‐associated ones such as prohibitin, pigment epithelium‐derived factor, and alpha‐actinin 4. The intensity of 37/105 (35.2%) protein spots was significantly concordant with the corresponding mRNA levels (p <0.01). Although both 2‐D DIGE and microarray experiments showed significant up‐regulation of vimentin expression in small intestinal GIST, Western blotting did not show a significant difference between the two groups. In conclusion, our study demonstrates the proteins specially expressed in GIST depending on their site of origin, as well as the unique advantage offered by use of proteomics to acquire such data. The identified proteins may provide clues to understanding the different characteristics of GIST depending on their site of origin.     

Considerations for powering a clinical proteomics study: Normal variability in the human plasma proteome

Proteomics is increasingly being applied to the human plasma proteome to identify biomarkers of disease for use in non‐invasive assays. 2‐D DIGE, simultaneously analysing thousands of protein spots quantitatively and maintaining protein isoform information, is one technique adopted. Sufficient numbers of samples must be analysed to achieve statistical power; however, few reported studies have analysed inherent variability in the plasma proteome by 2‐D DIGE to allow power calculations. This study analysed plasma from 60 healthy volunteers by 2‐D DIGE. Two samples were taken, 7 days apart, allowing estimation of sensitivity of detection of differences in spot intensity between two groups using either a longitudinal (paired) or non‐paired design. Parameters for differences were: two‐fold normalised volume change, α of 0.05 and power of 0.8. Using groups of 20 samples, alterations in 1742 spots could be detected with longitudinal sampling, and in 1206 between non‐paired groups. Interbatch gel variability was small relative to the detection parameters, indicating robustness and reproducibility of 2‐D DIGE for analysing large sample sets. In summary, 20 samples can allow detection of a large number of proteomic alterations by 2‐D DIGE in human plasma, the sensitivity of detecting differences was greatly improved by longitudinal sampling and the technology was robust across batches.     

Towards a comprehensive proteome of normal and malignant human colon tissue by 2-D-LC-ESI-MS and 2-DE proteomics and identification of S100A12 as potential cancer biomarker

The aim of this study was to characterize the proteome of normal and malignant colonic tissue. We previously studied the colon proteome using 2‐DE and MALDI‐MS and identified 734 proteins (Roeßler, M., Rollinger, W., Palme S., Hagmann, M.‐L., et al.., Clin. Cancer Res. 2005, 11, 6550–6557). Here we report the identification of additional colon proteins from the same set of tissue samples using a complementary nano‐flow 2‐D‐LC‐ESI‐MS. In total, 484 proteins were identified in colon. Of these, 252 had also been identified by the 2‐DE/MALDI‐MS approach, whereas 232 proteins were unique to the 2‐D‐LC‐ESI‐MS analysis. Comparing protein expression in neoplastic and normal colon tissue indicated elevated expression of several proteins in colorectal cancer, among them the well established tumor marker carcinoembryonic antigen, as well as calnexin, 40S ribosomal protein S15a, serpin H1, and S100A12. Overexpression of these proteins was confirmed by immunoblotting. Serum levels of S100A12 were determined by ELISA and were found to be strongly elevated in colorectal cancer patients compared to healthy individuals. We conclude, that 2‐D‐LC‐ESI‐MS is a powerful approach to identify and compare protein profiles of tissue samples, that it is complementary to 2‐DE/MALDI‐MS approaches and has the potential to identify novel biomarkers.     

Development of a 42‐in. 2‐D/3‐D switchable display using multi‐view technology for public‐information‐display applications

Abstract— A 42‐in. 2‐D/3‐D switchable display operating in a parallax‐barrier‐type system consisting of liquid‐crystal displays (LCDs) has been developed. The system displays 2‐D images in full resolution, without any degradation to the original 2‐D images, and 3‐D autostereoscopic images with resolutions higher than SVGA with wide viewing zones electrically controlled by the parallax‐barrier system. The system is intended for use in public‐information displays (PIDs), a booming field, and as displays for gaming, medical, and simulation applications.     

Depth‐ and viewing‐angle‐enhanced 3‐D/2‐D switchable display system with high contrast ratio using multiple display devices and a lens array

Abstract— An improved 3‐D/2‐D switchable display system with enhanced depth and viewing angle by adding two LCD panels to an integral imaging system has been realized. The proposed system uses the see‐through property of an LCD panel and displays multiple sets of elemental images on the LCD panels to integrate them on multiple locations simultaneously. As a result, the depth of the 3‐D image can be enhanced. For wide viewing angles, the time‐multiplexing method was adopted by displaying mask patterns on the front LCD panel. In addition, another technique to increase the contrast ratio of the proposed system has also been developed. Some experimental results will be provided.     

Advanced impulsive‐driving technique for Super‐PVA panel

Abstract— Super‐PVA (S‐PVA) technology developed by Samsung has demonstrated excellent viewing‐angle performance. However, S‐PVA panels can place extra demands on charging time due to the time‐multiplexed driving scheme required to separately address two subpixels. Specifically, a 2G‐1D pixel structure theoretically requires subpixel charging in one‐half of the time available for a conventional panel. In this paper, a new LCD driving scheme, super impulsive technology (SIT), is proposed to improve motion‐blur reduction by driving an S‐PVA LCD panel at 120 Hz. The proposed scheme allows a 120‐Hz 2G‐1D panel to be driven with an adequate charging‐time margin while providing an impulsive driving effect for motion‐blur reduction. Considering that the cost of a 2G‐1D S‐PVA panel is comparable to that of a conventional 60‐Hz panel, this method achieves good performance at a reasonable price. The detailed algorithm and implementation method are explored and the performance improvements are verified.     

360°‐viewable cylindrical integral imaging system using a 3‐D/2‐D switchable and flexible backlight

Abstract— A 360°‐viewable cylindrical three‐dimensional (3‐D) display system based on integral imaging has been implemented. The proposed system is composed of a cylindrically arranged electroluminescent (EL) pinhole film, an EL film backlight, a barrier structure, and a transmission‐type flexible display panel. The cylindrically arranged point‐light‐source array, which is generated by the EL pinhole film reconstructs 360°‐viewable virtual 3‐D images at the center of the cylinder. In addition, the proposed system provides 3‐D/2‐D convertibility using the switching of EL pinhole film from a point light source to a surface light source. In this paper, the principle of operation, analysis of the viewing parameters, and the experimental results are presented.     

On reachable set estimation of two‐dimensional systems described by the Roesser model with time‐varying delays

In this paper, the problem of reachable set estimation of two‐dimensional (2‐D) discrete‐time systems described by the Roesser model with interval time‐varying delays is considered for the first time. New 2‐D weighted summation inequalities, which provide a tighter lower bound than the commonly used Jensen summation inequality, are proposed. Based on the Lyapunov‐Krasovskii functional approach, and by using the 2‐D weighted summation inequalities presented in this paper, new delay‐dependent conditions are derived to ensure the existence of an ellipsoid that bounds the system states in the presence of bounded disturbances. The derived conditions are expressed in terms of linear matrix inequalities, which can be solved by various computational tools to determine a smallest possible ellipsoidal bound. Applications to exponential stability analysis of 2‐D systems with delays are also presented. The effectiveness of the obtained results are illustrated by numerical examples.     

Observer‐based tracking control for switched stochastic systems based on a hybrid 2‐D model

This paper is concerned with the observer‐based output tracking problem for a class of linear switched stochastic systems with time delay and disturbance by using repetitive control approach. More precisely, a two‐dimensional hybrid model is incorporated to obtain and optimize the repetitive controller. In particular, the repetitive controller is used to improve the tracking performance through its continuous learning actions. In addition, an equivalent‐input‐disturbance estimator is incorporated into the repetitive control design approach to reduce the effect of the external disturbances. The main aim of the control design is to track the periodic reference signal with the measured output of the system under consideration even in the presence of an unknown bounded disturbance. By constructing a suitable Lyapunov‐Krasovskii functional and using average dwell time approach and Jensen inequality, sufficient conditions are obtained in terms of linear matrix inequalities to guarantee the mean‐square exponential stability of the considered system. Eventually, a numerical example is provided to demonstrate the effectiveness of the developed method.     

基于混合式拓扑结构的P2P信息查找系统的研究和设计

对等网络所面临的两个最基本的问题是如何进行信息有效查找、定位以及如何进行网络的自我管理。本文介绍了一种基于混合式拓扑结构的分布式信息查找(DHH)体制。该体制可以实现信息的高效查找和节点的自我管理,同时达到可扩展性、有效性、可靠性、负载均衡和用户匿名性等指标。