Characterisation of tumoral markers correlated with ErbB2 (HER2/Neu) overexpression and metastasis in breast cancer

The receptor tyrosine kinase ErbB2 (HER2/neu) is overexpressed in ?30% of breast cancers and is associated with poor prognosis and an increased likelihood of metastasis. Clinical treatments such as trastuzumab are effective in less than 35% of women diagnosed as ErbB2‐positive, highlighting the necessity of searching for novel targets and alternative therapies. Herein, a proteomic screening strategy combining quantitative‐based gel electrophoresis and MS was used to compare the protein expression of 48 normal human breast and tumour tissues differing in ErbB2 expression and lymph node status. The aim was to identify proteins associated with the aggressive phenotype of ErbB2‐positive breast cancer which could be potential biomarkers of the disease as well as therapy targets. In total, 177 protein isoforms (107 gene products) differentially expressed between tissue groups were identified. Immunohistochemical staining of a tissue‐microarray was used for validation of selected protein candidates. We found that expression of HSP90α, laminin and GSTP1 significantly correlated with ErbB2 expression, while others such as AGR2, NM23H1 and Annexin 2 were overexpressed in greater than 40% of tumours. Finally, knocking‐down the expression by RNA interference of three candidates, AGR2, Transgelin2 and NM23H1 resulted in an enhanced invasive capacity of MDA‐MB435 cells. These data support the involvement of these targets in tumour progression and identify them as novel biomarkers of the disease.     

Is GRP78/BiP a potential salivary biomarker in patients with rheumatoid arthritis?

Purpose : In the last few years, serum and joint synovial fluid have been extensively analyzed for the proteomic research of rheumatoid arthritis (RA) biomarkers. Nonetheless, to date, there have been no studies investigating salivary biomarkers in this condition. Therefore, aim of this study is to investigate the presence of potential biomarkers of RA in human whole saliva. Experimental design : We combined 2‐DE and MS to analyze the whole saliva protein profile of 20 RA patients in comparison with 20 sex‐ and age‐matched healthy subjects. Results : Eight salivary proteins resulted differentially expressed, namely calgranulin A, calgranulin B, apolipoprotein A‐1, 6‐phosphogluconate dehydrogenase, peroxiredoxin 5, epidermal fatty acid‐binding protein, 78 kDa glucose‐regulated protein precursor (GRP78/BiP), and 14‐3‐3 proteins. It is particularly interesting that chaperone GRP78/BiP showed the greatest increase in RA patients. This finding was validated by Western Blot analysis and the over‐expression of GRP78/BiP appear to be distinctive of RA and drugs treatment independent. Conclusions and clinical relevance : This study provides a rationale for further studies aimed at evaluating any correlation between GRP78/BiP and different clinical/serological aspects of the disease in order to improve the diagnostic algorithms of RA.     

Ontology‐based model‐driven development of a destination management portal: Experience and lessons learned

We present a case study in model‐driven development of an e‐tourism portal that we chose to develop through generation from a domain model encoded as an ontology. We present (1) the requirements of e‐tourism portal, which dictated its high‐level design; (2) the principles behind our implementation strategy, including the use of a domain ontology as a starting model within the context of a model‐driven transformational approach; (3) the ontology development process and the code generation strategy used; and (4) the lessons learned. In particular, we compare our experiences to those reported in the model‐driven engineering (MDE) literature along 3 dimensions, ie, (1) the impact of MDE on the development process, (2) the choice of the modeling approach, and (3) the impact of code generation on design and code quality and testing. Overall, our experiences corroborated some of the theoretical claims and many of the practical experiences with MDE. Key findings include (1) model‐driven development makes maintenance, not development, more efficient; (2) it does require a higher skill level than traditional development; (3) clients and managers need to be educated into what incrementality means in a generative approach; (4) UML is neither necessary nor sufficient to handle the required representational flexibility; (5) it is difficult to build models that are good for both human consumption and code generation; and (6) it is difficult to generate code that is, simultaneously, efficient, pretty, and easy to maintain. We conclude by summarizing the findings of the paper.     

Min‐degree constrained minimum spanning tree problem: complexity,properties, and formulations

This paper addresses a new combinatorial problem, the Min‐Degree Constrained Minimum Spanning Tree (md‐MST), that can be stated as: given a weighted undirected graph with positive costs on the edges and a node‐degrees function , the md‐MST is to find a minimum cost spanning tree T of G, where each node i of T either has at least a degree of or is a leaf node. This problem is closely related to the well‐known Degree Constrained Minimum Spanning Tree (d‐MST) problem, where the degree constraint is an upper bound instead. The general NP‐hardness for the md‐MST is established and some properties related to the feasibility of the solutions for this problem are presented, in particular we prove some bounds on the number of internal and leaf nodes. Flow‐based formulations are proposed and computational experiments involving the associated Linear Programming (LP) relaxations are presented.     

The new route for realization of 1‐μm‐pixel‐pitch high‐resolution displays

A new pixel structure for the realization of a 1‐μm‐pixel‐pitch display was developed. This structure, named vertically stacked thin‐film transistor (VST), was based on the conventional back‐channel etched thin‐film transistor (TFT), but all the layers except the horizontal gate line were vertically stacked on the embedded data line, enabling the implementation of high‐resolution display panels. The VST device with a channel length of 1 μm showed a high field effect mobility of more than 50 cm²/Vs and low subthreshold slope of 78 mV per decade. It also shows a high uniform electrical characteristic over the entire 6‐in. wafer. The development of a new pixel architecture is expected to enable the implementation of 1‐μm‐pixel‐pitch high‐resolution displays such as spatial light modulators for digital holograms.     

Cover Picture: Proteomics – Clinical Applications 1/2008

In this issue of Proteomics you will find the following highlighted articles: Colon Cancer Complements to 2‐DE from 2‐D‐LC “When you have a good thing going, run with it” – Quote from paleolithic philosopher and hunting consultant. In this case, Thierolf et al. took a colon cancer sample set well‐characterized by 2‐DE‐MALDI PMF and ran it through a 2‐D‐LC‐ESI‐MS protocol. The samples of malignant and normal tissues from the same patient, analyzed by 2‐DE‐MALDI and mass fingerprinting (reported elsewhere) yielded 734 unique proteins. When the same tissue specimens were analyzed by 2‐D‐LC‐ESI‐MS, 484 proteins were identified, 232 of them new and 252 that had been ID’d in the earlier work. The two unique sets exhibited similar functional and ontological profiles, confirming the complementarity of the two methods. Using the data to select up‐regulated proteins for evaluation of potential for serving as biomarkers, they chose S100A12 as particularly interesting. An ELISA found that it was more sensitive but less discriminating than carcinoembryonic antigen. S100A12 is also an inflammation marker. Thierolf, M. et al., Proteomics Clin. Appl. 2008, 2, 11–22 Urinary bladder cancer: A proteomic approach Standing at number five on the US cancer frequency list, urinary bladder cancer costs almost $3 billion a year. No acceptable early detection tests have been developed – it seems no one will volunteer for a “routine” annual cystoscopy, so the 5‐year survival rate has stayed below 50% for many years. Several urinary biomarkers have been developed but fall short in their frequency of false positives or false negatives. Using 2‐DE/MALDI‐TOF MS and Ingenuity Systems’ Pathway Analysis software, Li et al. surveyed invasive urothelial carcinomas for up‐regulated proteins and settled on Choro­ideremia‐like protein (CHML) out of 21 candidates. Immunohistochemistry and Western blotting verified the specificity. The functional pathways found are part of the lipid metabolism, inflammation and molecular transport machinery and CHML is part of the Rab geranylgeranylation pathway. More work is needed to understand the diagnostic potential of CHML. Li, J. et al., Proteomics Clin. Appl. 2008, 2, 78–89. Angina: Looking for markers in all the right places Angina, the chest pain associated with heart attacks, has two forms: stable (SAP) and unstable (UAP). SAP is relieved by rest. UAP pain persists at rest and is often due to formation of a clot which can lead to major or fatal damage (ischemia, myocardial infarct). The ability to distinguish the two would be a boon to hospital emergency care facilities because admission and intensive care are not required for SAP. Brown et al. report here the use of anti‐leukocyte antibody arrays to analyze circulating cells by surface CD antigen type. Starting with 82 antibodies, they could readily distinguish healthy from SAP and UAP cases from 8 and 19 spot intensity differences, respectively. SAP and UAP could be separated with seven markers using spot intensity and cluster analysis, but not as cleanly, possibly because SAP has a tendency to convert to UAP. Brown, A. et al., Proteomics Clin. Appl. 2008, 2, 90–98.     

In this issue: Proteomics – Clinical Applications 1/2008

In this issue of Proteomics you will find the following highlighted articles: Colon Cancer Complements to 2‐DE from 2‐D‐LC “When you have a good thing going, run with it” – Quote from paleolithic philosopher and hunting consultant. In this case, Thierolf et al. took a colon cancer sample set well‐characterized by 2‐DE‐MALDI PMF and ran it through a 2‐D‐LC‐ESI‐MS protocol. The samples of malignant and normal tissues from the same patient, analyzed by 2‐DE‐MALDI and mass fingerprinting (reported elsewhere) yielded 734 unique proteins. When the same tissue specimens were analyzed by 2‐D‐LC‐ESI‐MS, 484 proteins were identified, 232 of them new and 252 that had been ID’d in the earlier work. The two unique sets exhibited similar functional and ontological profiles, confirming the complementarity of the two methods. Using the data to select up‐regulated proteins for evaluation of potential for serving as biomarkers, they chose S100A12 as particularly interesting. An ELISA found that it was more sensitive but less discriminating than carcinoembryonic antigen. S100A12 is also an inflammation marker. Thierolf, M. et al., Proteomics Clin. Appl. 2008, 2, 11–22 Urinary bladder cancer: A proteomic approach Standing at number five on the US cancer frequency list, urinary bladder cancer costs almost $3 billion a year. No acceptable early detection tests have been developed – it seems no one will volunteer for a “routine” annual cystoscopy, so the 5‐year survival rate has stayed below 50% for many years. Several urinary biomarkers have been developed but fall short in their frequency of false positives or false negatives. Using 2‐DE/MALDI‐TOF MS and Ingenuity Systems’ Pathway Analysis software, Li et al. surveyed invasive urothelial carcinomas for up‐regulated proteins and settled on Choro­ideremia‐like protein (CHML) out of 21 candidates. Immunohistochemistry and Western blotting verified the specificity. The functional pathways found are part of the lipid metabolism, inflammation and molecular transport machinery and CHML is part of the Rab geranylgeranylation pathway. More work is needed to understand the diagnostic potential of CHML. Li, J. et al., Proteomics Clin. Appl. 2008, 2, 78–89. Angina: Looking for markers in all the right places Angina, the chest pain associated with heart attacks, has two forms: stable (SAP) and unstable (UAP). SAP is relieved by rest. UAP pain persists at rest and is often due to formation of a clot which can lead to major or fatal damage (ischemia, myocardial infarct). The ability to distinguish the two would be a boon to hospital emergency care facilities because admission and intensive care are not required for SAP. Brown et al. report here the use of anti‐leukocyte antibody arrays to analyze circulating cells by surface CD antigen type. Starting with 82 antibodies, they could readily distinguish healthy from SAP and UAP cases from 8 and 19 spot intensity differences, respectively. SAP and UAP could be separated with seven markers using spot intensity and cluster analysis, but not as cleanly, possibly because SAP has a tendency to convert to UAP. Brown, A. et al., Proteomics Clin. Appl. 2008, 2, 90–98.     

Proteomic analysis of sera of asymptomatic,early‐stage patients with Wilson's disease

Wilson's disease (WD) is characterized by excessive accumulation of intracellular copper in liver and extrahepatic tissues, leading to significant oxidative stress and tissue damage. To date, several diagnostic biomarkers for WD such as serum ceruloplasmin, serum or urine copper levels and copper content in liver have been identified. However, these biomarkers may not be convincing for the diagnosis in some WD patients. To identify additional novel diagnostic biomarkers, we compared the serum protein profiles of asymptomatic childhood WD patients (n=20), without neurologic manifestation or liver cirrhosis, with normal controls (n=13). Fourteen spots, five up‐regulated and nine down‐regulated (>2‐fold), were differentially expressed in WD patients in comparison to normal control on 2‐DE. Among them, three spots were down‐regulated in both male and female WD. MS/MS analysis revealed that the three spots were complement component C3, complement factor B and alpha‐2 macroglobulin. By comparative proteome analysis, complement component C3, complement factor B and alpha‐2 macroglobulin, which are related to oxidative stress and inflammation, turned out to be good candidates for novel diagnostic biomarkers for early stages of WD.     

A novel gate driver circuit for depletion‐mode a‐IGZO TFTs

In this paper, a novel gate driver circuit, which can achieve high reliability for depletion mode in a‐InGaZnO thin‐film transistors (TFTs), was proposed. To prevent the leakage current paths for Q node effectively, the new driving method was proposed by adopting the negative gate‐to‐source voltage (V_GS) value for pull‐down units. The results showed all the V_OUT voltage waveforms were maintained at VGH voltage despite depletion‐mode operation. The proposed circuit could also obtain stable V_OUT voltage when the threshold voltage for all TFTs was changed from ?6.5 to +11.5 V. Therefore, the circuit can achieve high reliability regardless of threshold voltage value for a‐IGZO TFTs. In addition, the output characteristics and total power consumption were shown for the alternating current (AC)–driven and direct current (DC)–driven methods based on 120‐Hz full‐HD graphics (1920 × 1080) display panel. The results showed that the AC‐driven method could achieve improved V_OUT characteristics compared with DC‐driven method since the leakage current path for Q node can be completely eliminated. Although power consumption of the AC‐driven method can be slightly increased compared with the DC‐driven method for enhancement mode, consumption can be lower when the operation has depletion‐mode characteristics by preventing a leakage current path for pull‐down units. Consequently, the proposed gate driver circuit can overcome the problems caused by the characteristics of a‐IGZO TFTs.     

Some Remarks on the Role of Minimal Length of Positive Maps in Constructing Entanglement Witnesses

The main objective of this paper is to discuss correspondence between the concept of entanglement witnesses (self-adjoint operators on a composite Hilbert space that are, in general, not positive, but are positive on separable states) and positive maps which are not completely positive. The notion of minimal length of linear positive map is introduced and the role of this quantity in the constructing of entanglement witnesses is explained.Presented at the 36th Symposium on Mathematical Physics, ‘Open Systems & Quantum Information’, Toruń, Poland, June 9-12, 2004.Supported by the Grant PBZ-MIN-008/P03/2003.     

A decomposition approach for the kinematic synthesis of tendon‐driven manipulators

This article describes a decomposition methodology for the kinematic synthesis of tendon‐driven manipulators (TDMs). Based on the QR factorization, the complex transformation between vectors in the tendon‐space and the joint‐space of an n‐DOF TDM with n+1 tendons is decomposed as a two‐step transformation. An orientation matrix is used to characterize the vector transformation between the (n+1)‐dimensional tendon‐space and the n‐dimensional intermediate equivalent tendon‐space. An equivalent structure matrix is also introduced for the vector transformation between the n‐dimensional equivalent tendon‐space and n‐dimensional joint‐space. Design equations for synthesizing a TDM to possess kinematic isotropic transmission characteristics with proper tendon routing and pulley sizes are derived. ©1999 John Wiley & Sons, Inc.     

Active‐matrix organic light‐emitting displays employing two thin‐film‐transistor a‐Si:H pixels on flexible stainless‐steel foil

Abstract— An active‐matrix organic light‐emitting diode (AMOLED) display driven by hydrogenated amorphous‐silicon thin‐film transistors (a‐Si:H TFTs) on flexible, stainless‐steel foil was demonstrated. The 2‐TFT voltage‐programmed pixel circuits were fabricated using a standard a‐Si:H process at maximum temperature of 280°C in a bottom‐gate staggered source‐drain geometry. The 70‐ppi monochrome display consists of (48 × 4) × 48 subpixels of 92 ×369 μm each, with an aperture ratio of 48%. The a‐Si:H TFT pixel circuits drive top‐emitting green electrophosphorescent OLEDs to a peak luminance of 2000 cd/m².     

Identification of melanoma‐specific serological markers using proteomic analyses

The discovery of novel melanoma markers for not only early detection but also monitoring disease status is promising to improve the clinical outcome of patients. In the present study, we performed proteomic comparative analysis of plasma proteins between healthy volunteers and melanoma patients using NanoLC and MALDI‐TOF‐MS. As a result, we were successful in identifying nine proteins that were specifically expressed in melanoma plasma compared with healthy plasma, most of which had not previously been identified as plasma markers of melanoma. The mRNA expression levels of four proteins [pro‐platelet basic protein precursor (PPBP), serum amyloid A2 (SAA2), complement factor H‐related protein 1 precursor (FHR1), inter‐alpha‐trypsin inhibitor heavy chain H4 precursor (IAIH4)] were prominently up‐regulated in several melanoma cell lines compared with melanocytes. Moreover, two proteins (PPBP, SAA) were shown to be expressed in tumor specimens from melanoma patients. In the survival time analysis regarding melanoma patients, the semi‐quantified plasma PPBP levels were statistically negatively correlated with the survival time. Most interestingly, the significant survival benefit was seen in low PBPP level group (< index 20) versus high level (≥ index 20) group. The results suggest that PPBP might be a novel promising serological marker and a prognostic factor specific to melanomas.     

Proteomic Helicobacter pylori biomarkers discriminative of low-grade gastric MALT lymphoma and duodenal ulcer

To date no reliable diagnostic method exists to predict, among the very large and clinically heterogeneous group of Helicobacter pylori‐infected patients, the extremely small group at risk for developing low‐grade gastric MALT lymphoma (LG‐MALT). Search of proteomic biomarkers holds promise for the classification of the H. pylori strains with regard to this severe clinical outcome. In the present study 69 H. pylori strains isolated from patients with two different H. pylori‐associated diseases, duodenal ulcer (DU, n=29) and LG‐MALT (n=40) were used. Protein expression patterns of the strains were analyzed by using the high‐throughput methodology SELDI. Selected proteins were purified by means of chromatographic and electrophoretic methods in view of further sequencing by LC‐MS/MS. Univariate analysis (Mann–Whitney test) of the protein expression patterns generated nine significant biomarkers that can discriminate between H. pylori strains from patients with DU and LG‐MALT. These biomarkers are of low molecular weight, ranging from 6 to 26.6 kDa. Among them, two are overexpressed in LG‐MALT strains and seven – in DU strains. Two biomarker proteins, one overexpressed in LG‐MALT strains (13.2 kDa) and another one – overexpressed in DU strains (26.6 kDa), were purified to homogeneity and identified by using LC‐MS/MS as a 50S ribosomal protein L7/L12 and a urease subunit, respectively. These biomarkers can be included in novel protein arrays for the differential diagnosis of H. pylori‐associated clinical outcomes.     

Post-transplant proteinuria associated with everolimus: Definition of main features with proteomics

Little is known on both the composition and mechanism(s) of proteinuria associated with the use of mTOR inhibitors, in particular of Everolimus (E). We characterized urinary proteins utilizing an integrated proteomics approach (quantitative essays, 2‐DE, MALDI‐TOF, Western blot) in 48 renal transplant recipients who were alternatively treated with E (n = 31) or with enteric coated mycophenolic acid (EC‐MPA) (n = 17). Twelve E patients (39%) developed high (>3 g/day) or intermediate proteinuria (1–3 g) compared to four (23%) of the EC‐MPA group. Urinary proteins (p<0.001), β2 microglobulin (p<0.001) and α1microglobulin (p<0.025) were higher in E than in EC‐MPA, appeared more rapidly and were inversely correlated with the day of treatment. Proteomics showed a marked increase of all urinary components in E and EC‐MPA patients, major changes involving typical components of glomerular damage (albumin, α1‐Zn glycoprotein, α2HS glycoprotein, leucin‐richα2‐glycoprotein) and specific bio‐markers for E (clusters of α1‐antitrypsin fragments and monoclonal λ chains). Finally, inter‐α‐trypsin‐inhibitor heavy chain H4 precursor was decreased in E and EC‐MPA urine compared to normal urine. In conclusion, E induced massive and generalized proteinuria of mixed glomerular and tubular origin that was correlated with the start of treatment and reached a nephrotic range in few cases. Specific urinary markers reflect renal alterations related to the transplant or specific alterations associated with the drug.     

Broadband gap‐coupled half‐hexagonal microstrip antenna fed by microstrip‐line resonator

Half‐hexagonal microstrip antenna (H‐HMSA) is a compact version of HMSA, as it resonates at the same fundamental mode frequency. In this article, a compact configuration of a single layer, broadband gap‐coupled H‐HMSA has been proposed. Gap‐coupled H‐HMSA is fed indirectly by a λ/2 microstrip‐line resonator. Broad bandwidth (BW) is achieved with an effective use of resonance introduced by λ/2 resonator and gap‐coupled half‐hexagonal radiating patches. A peak gain of 7.07 dBi and measured BW (S₁₁ ≤ ?10 dB) of 11.5% at the center frequency of 5.2 GHz have been achieved, which occupies a small volume of 0.023 λ₀³ including the ground plane. The radiation patterns remain in the broadside direction throughout the return loss BW. Simulated results of the proposed antenna configuration are experimentally validated with good agreement.     

Influence of intermolecular interactions on the formation of spontaneous orientation polarization in organic semiconducting films

Spontaneous orientation polarization (SOP) has been frequently observed in the evaporated films of organic light‐emitting diode materials. Because SOP modifies the charge injection and the accumulation properties of the device, understanding and controlling SOP is crucial in optimizing the performance of the device. In this study, we investigated the dominant factors for SOP formation by focusing on intermolecular interactions. We examined the giant surface potential characteristics of coevaporated films incorporating 1,3,5‐tris(1‐phenyl‐1H‐benzimidazol‐2‐yl)benzene (TPBi) that is a typical polar molecule exhibiting SOP. In the coevaporated films of TPBi and nonpolar molecules such as 4,4′‐bis(N‐carbazolyl)‐1,1′‐biphenyl and 4,4′,4″‐tris (carbazol‐9‐yl)triphenylamine, the orientation degree of the permanent dipole moment (PDM) of TPBi is significantly enhanced with diluted TPBi density, though the enhancement is weak on the film with N,N′‐bis(1‐naphthyl)‐N,N′‐diphenyl‐1,1′‐biphenyl‐4,4′‐diamine. The results indicate that the PDM interaction between polar molecules results as a negative factor for SOP formation. Furthermore, we found that SOP formation is suppressed by the surface treatment of the self‐assembled monolayer on the gold substrate, indicating a positive effect of the van der Waals interaction between the molecule and the substrate surface.     

Reliable control design for composite‐driven scheme based on delay networked T‐S fuzzy system

This paper is focused on reliable controller design for a composite‐driven scheme of networked control systems via Takagi‐Sugeno fuzzy model with probabilistic actuator fault under time‐varying delay. The proposed scheme is distinguished from the other schemes as mentioned in this paper. Aims of this article are to solve the control problem by considering the H_∞, dissipative, and L₂?L_∞ constraints in a unified way. Firstly, to improve the efficient utilization of bandwidth, the adaptive composite‐driven scheme is introduced. In such a scenario, the channel transmission mechanism can be adjusted between adaptive event‐triggered generator scheme and time‐driven scheme. In this study, the threshold is dependent on a new adaptive law, which can be obtained online rather than a predefined constant. With a constant threshold, it is difficult to get the variation of the system. Secondly, a novel fuzzy Lyapunov‐Krasovskii functional is constructed to design the fuzzy controller, and delay‐dependent conditions for stability and performance analysis of the control system are obtained. Then, LMI‐based conditions for the existence of the desired fuzzy controller are presented. Finally, an inverted pendulum that is controlled through the channel is provided to illustrate the effectiveness of the proposed method.     

Identification of distinctive protein expression patterns in colorectal adenoma

Purpose: As a pre‐malignant precursor, adenoma provides an ideal tissue for proteome profiling to investigate early colorectal cancer development and provide possible targets for preventive interventions. The aim of this study was to identify patterns of differential protein expression that distinguish colorectal adenoma from normal tissue. Experimental design: Twenty paired samples of adenoma and normal mucosa were analysed by 2‐DE and MALDI‐TOF/TOF MS to detect proteins with ≥2‐fold differential expression. Results: Four proteins were up‐regulated in adenoma (Annexin A3, S100A11, S100P and eIF5A‐1) and three were down‐regulated (Galectin‐1, S100A9 and FABPL). S100P, galectin‐1, S100A9 and FABPL expression was localised by immunohistochemistry. Conclusions and clinical relevance: Distinctive patterns of in vivo protein expression in colorectal adenoma were identified for the first time. These proteins have important functions in cell differentiation, proliferation and metabolism, and may play a crucial role in early colorectal carcinogenesis. The ability to recognise premalignant lesions may have important applications in cancer prevention.     

A new family of hybrid 4‐DOF parallel mechanisms with two platforms and its application to a footpad device

This paper proposes a new family of 4‐degrees‐of‐freedom (DOF) parallel mechanisms with two platforms and its application to a footpad device that can simulate the spatial motions of the human foot. The new mechanism consists of front and rear platforms, and three limbs. Two limbs with 6‐DOF serial joints (P ‐S‐P‐P) are attached to each platform and are perpendicular to the base plate, while the middle limb is attached to the revolute joint that connects the front and rear platforms. The middle limb is driven by the 2‐DOF driving mechanism that is equivalent to active serial prismatic and revolute joints (P_e ‐R_e ), or prismatic and prismatic joints (P_e ‐P_e ) with two base‐fixed prismatic actuators. Since the middle limb perpendicular to the base plate has 3‐DOF serial joints (P_e ‐R_e ‐R or P_e ‐P_e ‐R), two new 4‐DOF parallel mechanisms with two platforms can generate pitch motion of each platform, and roll and heave motions (1T‐3R) or pitch motion of each platform and two translational motions (2T‐2R) at both platforms, according to the type of the 2‐DOF driving mechanism. Kinematic analyses of the 1T‐3R mechanism were performed, including inverse and forward kinematics and velocity analysis. Based on the 1T‐3R mechanism, a footpad device was designed to generate foot trajectories for natural walking. © 2005 Wiley Periodicals, Inc.