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Introduction Over the past decade, various protocols were established to ensure efficient differentiation of hiPSC into cardiomyocytes (CMs). A major limitation, however, remained the batch-to-batch variability of hiPSC-CM efficiency and cell number. Here, we suggest an approach in which concomitant GSK-3β inhibition and removal of cell-cell contact inhibition, resulted in a massive proliferative response of hiPSC-CMs1–3. This efficient method allows expansion and passaging of functional hiPSC-CMs, that routinely can be cryopreserved and subsequently used as a stable cell source for the downstream applications, such 3D in vitro models for the disease modelling of dilated cardiomyopathy (DCM). We focussed on the deletion of arginine 14 in the PLN gene (R14del), which is associated with severe heart failure in DCM patients, associated with arrhythmias, cardiac fibrosis and premature death. Methods Subsequent expansion of hiPSC-CM cultures is generally modest ( Results We observed that proliferating hiPSC-CMs, especially within the first 2 passages, can routinely be cryopreserved and subsequently further expanded or utilized in downstream applications. Moreover, using this strategy, it is possible to produce ultimately >1 billion CMs within 3–5 weeks starting with one differentiation batch of day 11 hiPSC-CMs, without the need for cell sorting or selection. Expanded hiPSC-CMs retain their capacity to mature and allows fibrin-based engineered heart tissues (EHTs) formation. Previously expanded CMs from PLNR14del patient-specific hiPSC were used to generate EHT and displayed a reduced force phenotype (0.137±0.012 mN) vs healthy control (0.229±0.030 mN) and isogenic control (0.224±0.008 mN) in previously expanded CMs. Conclusion We provpresent a novel strategy for the massive expansion of functional hiPSC-CMs with concomitant GSK-3β inhibition and low cell density culture that ultimately generates up to a 250-fold increase in hiPSC-CM numbers. Expansion healthy control hiPSC-CMs does not limit the subsequent maturation process, and moreover cells remain fully functional such as required for downstream tissue engineering approaches. Therefore, CM expansion forms a well-controlled platform for upscaling hiPSC-CM production for functional 3-dimensionale PLN cardiac disease models, large drug screenings and multiple translational/regenerative applications. Funding Acknowledgement Type of funding sources: Foundation. Main funding source(s): PLN Foundation

An organic/amorphous silicon(a-Si) hybrid tandem solar cell has been fabricated using poly(diketopyrrolopyrrole-terthiophene) (PDPP3T) as the active layer in organic solar cell. High external quantum efficiency (8.32%) and a fill factor (FF) of 0.76 are achieved under AM 1.5 illumination. The Voc of the tandem solar cells are almost equivalent to the sum of the sub-cells. The high performance of the device results from the complementary absorption spectra of two sub-cells. The SEM cross-sectional image of the device has been analysed and the distributions of the component elements can be clearly observed.

Transparent objects are prevalent across many environments of interest for dexterous robotic manipulation. Such transparent material leads to considerable uncertainty for robot perception and manipulation, and remains an open challenge for robotics. This problem is exacerbated when multiple transparent objects cluster into piles of clutter. In household environments, for example, it is common to encounter piles of glassware in kitchens, dining rooms, and reception areas, which are essentially invisible to modern robots. We present the GlassLoc algorithm for grasp pose detection of transparent objects in transparent clutter using plenoptic sensing. GlassLoc classifies graspable locations in space informed by a Depth Likelihood Volume (DLV) descriptor. We extend the DLV to infer the occupancy of transparent objects over a given space from multiple plenoptic viewpoints. We demonstrate and evaluate the GlassLoc algorithm on a Michigan Progress Fetch mounted with a first-generation Lytro. The effectiveness of our algorithm is evaluated through experiments for grasp detection and execution with a variety of transparent glassware in minor clutter., Accepted to the 2019 IEEE/RSJ International Conference on Intelligent Robots and Systems. Contact: Zheming Zhou, zhezhou@umich.edu

Robotic Learning from Demonstration (LfD) allows anyone, not just experts, to program a robot for an arbitrary task. Many LfD methods focus on low level primitive actions such as manipulator trajectories. Complex multistep task with many primitive actions must be learned from demonstration if LfD is to encompass the full range of task a user may desire. Existing methods represent the high level task in various forms including, finite state machines, decision trees, formal logic, among others. Behavior trees are proposed as an alternative representation of high level task. Behavior trees are an execution model for the control of a robot designed for real time execution, modularity, and, consequently, transparency. Real time execution allows the robot to reactively perform the task. Modularity allows the reuse of learned primitive actions and high level task in new situations, speeding up the process of learning in new scenarios. Transparency allows users to understand and interactively modify the learned model. Behavior trees are used to represent high level tasks by building on the relationship it has with decision trees. We demonstrate a human teaching our Fetch robot a household cleaning task.

Pluripotent stem cells offer an unparalleled opportunity to investigate cardiac physiology, pharmacology, toxicology and pathophysiology. In this paper we describe the use of both mouse (Nkx2-5(eGFP/w)) and human (NKX2-5(eGFP/w)) pluripotent stem cell reporter lines, differentiated toward cardiac lineage, for live single cell high acquisition rate calcium imaging. We also assess the potential of NKX2-5(eGFP/w) cardiac lineage cells for use toxicological screening as well as establish their sensitivity to a shift between low and high oxygen environments. Differentiated mouse Nkx2-5(eGFP/w) cells demonstrated a wide range of spontaneous oscillation rates that could be reduced by ryanodine (10μM), thapsigargin (1μM) and ZD7288 (10μM). In contrast human NKX2-5(eGFP/w) cell activity was only reduced by thapsigargin (1μM). Human cell survival was sensitive to the addition of trastuzumab and doxorubicin, while the switch from a low to a high oxygen environment affected oscillation frequency. We suggest that the human NKX2-5(eGFP/w) cells are less suitable for studies of compounds affecting cardiac pacemaker activity than mouse Nkx2-5(eGFP/w) cells, but are very suitable for cardiac toxicity studies.

To investigate the optimal anticoagulation methods and monitoring strategy for Chinese patients undergoing heart valve replacement, which is potentially quite different from western populations.In this multicenter prospective cohort study, the anticoagulation and monitoring strategy data was acquired from 25 773 in-hospital patients in 35 medical centers and 20 519 patients in outpatient clinic in 11 medical centers from January 1st, 2011 to December 31th, 2015.As for in-hospital patients, mean age of study population was (48.6±11.2) years old; main etiology of valve pathology was rheumatic (87.5%) origin among study cohort; 94.8% of study population received mechanical valve implantation; international normalized ratio (INR) monitoring (in all the study centers) and low-intensity anticoagulation strategy (31 hospitals chose target INR range of 1.5-2.5, and actual values of INR among 89.2% of 100 069 in-hospital monitoring samples were 1.5-2.5), with mean actual INR values of 1.84±0.53, and warfarin dosage of (2.82±0.93) mg/d were widely adopted among the study centers; strategies of in-hospital warfarin administration were similar in all the study centers; complication rates of low-intensity anticoagulation strategy were low in severe hemorrhage (0.02%), thrombosis (0.05%), and thromboembolism (0.05%) events, without anticoagulation-related death.As for 18 974 outpatient clinic patients, the follow-up rate was 92.47%, with a total of 30 012 patient-years (Pty). Anticoagulation-related morbidity and mortality rates were 0.67% and 0.15% Pty; major hemorrhage morbidity and mortality rates were 0.25% and 0.13% Pty; thromboembolism morbidity and mortality rates were 0.45% and 0.03% Pty.The mean dosage of warfarin daily dosage was (2.85±1.23) mg/d and INR value was 1.82±0.57.No significant regional difference in the intensity of anticoagulation therapy was noted during the study.INR can be used as a normalized indicator for intensity of anticoagulation therapy in China.The optimal anticoagulation intensity with INR range from 1.5 to 2.5 is safe and effective for Chinese patients with heart valve replacement, and there is no significant regional difference in the intensity of anticoagulation therapy.

The dynamic charging performances of a cool energy storage system with coil pipes were studied. The n-tetradecane was taken as phase change material and the aqueous ethylene glycol solution of 25% volumetric concentration was considered as a heat transfer fluid. A numerical model based on energy balance equations of the phase change material and the heat transfer fluid was developed to investigate the variations of temperatures of the phase change material and heat transfer fluid, solid fraction and cool storage rate with time during the charging process. The effects of the inlet temperatures and the flow rates of the heat transfer fluid on the outlet temperature of the heat transfer fluid, cool storage rate, and solid fraction were discussed. It is concluded that the higher flow rate of the heat transfer fluid or the lower inlet temperature of the heat transfer fluid result in the higher cool storage rate and less time for the charging process. It took about 5 h for the charging process with the...

The dynamic characteristics of a solar thermal storage system using a packed bed with spherical capsules during the discharging process are studied. According to the energy balance of a solar thermal storage system, the dynamic discharging processes model of a packed bed with spherical capsules is presented. Paraffin is taken as a phase change material and water is used as a heat transfer fluid. The temperatures of phase change material and heat transfer fluid, solid fraction, and heat released rate are investigated. The effects of inlet temperature of heat transfer fluid and flow rate of heat transfer fluid on the time for discharging and heat released rate are also discussed.

Objective: The purpose of this study was to evaluate the safety and efficacy of hydroxyurea (HU) in spinal muscular atrophy (SMA) in a randomized, double-blind, placebo-controlled trial. Methods: Twenty-eight patients with type 2 SMA and 29 patients with type 3 SMA were randomly assigned (2:1) to receive HU or matching placebo for 18 months. HU was initiated at 10 mg/kg/day with an 8-week titration to 20 mg/kg/day. Subjects were assessed at baseline (T0) and monthly for the first 2 months (T1–T2) and then every 2 months throughout treatment (T3–T10) and posttreatment periods (T11–T13). The primary outcome measures were the Gross Motor Function Measure (GMFM), Manual Muscle Test (MMT), and serum full-length survivor motor neuron (flSMN) mRNA. The secondary outcome measures were Modified Hammersmith Functional Motor Scale and forced vital capacity (FVC). Results: Fifty-five patients completed this trial, which lasted from March 2007 to June 2009. Except for neutropenia, we found no differences in adverse events between the 2 groups. Compared with the placebo group, the HU group had −1.88 for GMFM (p = 0.11), −0.55 for MMT (p = 0.49), and 2.17 for flSMN mRNA (p = 0.13). Similarly, we found no difference in mean improvement of the secondary endpoints. Both groups had a trend toward a decline in FVC with little change in strength and motor function. Conclusion: Under the current regimen and schedule, HU brought about no improvement in patients with type 2 and 3 SMA, and its main side effect was neutropenia. Classification of evidence: This trial provides Class I evidence that HU 20 mg/kg/day does not effectively treat SMA.

This paper presents a new method for CE-EC determination of Mercaptopurine (MP), one of the most important medicines for inflammatory bowel disease (IBD) and acute lymphoblastic leukemia (ALL) treatment, in a PMMA-based microfluidic chip. A simple and reliable process for preparing the template of gold nanoelectrode ensemble (GNEE) and fabricating the integrated microfluidic chip is reported in the present study. The use of GNEE electrodes for both electric current decoupling and signal sensing in the proposed CE-EC chip not only enhances the signal response but also decreases the background noise during detection. Results show that a good detection limit of 100 nM for detecting mercaptopurine is achieved with the proposed method. In addition, the measured results also shows a good linear response between the detected CE-EC signals and the concentration of MP within the range of 100 nM-10 mM (R2 = 0.989). The proposed microchip device provides a novel and fast detection method for mercaptopurine analysis.

This paper presents an experimental and numerical study of the impact of a particle stream onto a particle bed using a 2D slot model. The numerical simulation is performed by means of the discrete element method (DEM). The results show that the DEM simulation can reproduce the experimental results well under comparative conditions. The dynamics in the formation of a crater is then analyzed in terms of velocity field, force structure, bottom stress distribution and energy exchange based on the DEM results. It is shown that as a result of impact by the falling particles, the particles in the top central region of the particle bed have relatively large velocities and contact forces. The velocities and forces propagate into the bed, and reach the bottom of the base layer quickly. They then continue to propagate leftwards and rightwards to create a crater. During the impact process, most of the energy from the falling particles is dissipated due to the inelastic collision and frictional contacts between particles, and only a small amount of the energy contributes to the formation of the crater. The crater size is shown to be affected by the discharging rate, discharging height and materials properties, and be related to the ratio of the input energy from the falling stream to the inertial energy from the original packing.

Water shortage resulting from both natural conditions and human activities has been proved to be a bottleneck that chokes development in arid and semiarid regions. Systems analysis provides an effective way of clarifying conflicts between water supply and demand. In this study, an arid/semiarid region water management (ASRWM) model is developed for sound planning of a water resources system. The proposed model is founded on interval-fuzzy multiobjective programing (IFMOP) for effectively reflecting complexities of the study system and expediently facilitating solution of the model. Member-ship functions for modeling objectives and constraints are formulated to reflect uncertainties in different system components and their interrelationships. To evaluate the applicability of the proposed model, a case study for the Luopu County in northwestern China has been undertaken. The modeling outputs generated through scenario analyses are based on in-depth examination of several sensitive issues including farming, ...

Tenofovir disoproxil fumarate (TDF) has demonstrated long-term efficacy and a high barrier to resistance in multiple chronic hepatitis B (CHB) populations outside of China. This study aimed to evaluate the efficacy and safety of TDF compared with adefovir dipivoxil (ADV) in Chinese patients with CHB during 48 weeks of treatment (ClinicalTrial.gov number, NCT01300234). A Phase 3, multicentred, randomized, double-blind, controlled trial compared the efficacy and safety of TDF with ADV in Chinese patients with CHB. The primary endpoint was the proportion of patients with HBV DNA400 copies/mL in each treatment group at Week 48, using an unpooled Z-test for superiority. Secondary endpoints included viral suppression, serologic response, histological improvement, normalization of alanine aminotransferase (ALT) levels and the emergence of resistance mutations. A total of 509 patients, 202 hepatitis B e antigen (HBeAg)-positive and 307 HBeAg-negative, with HBV DNA ≥10(5) copies/mL received either TDF 300 mg od or ADV 10 mg od. At Week 48, TDF demonstrated superior viral suppression compared with ADV in both HBeAg-positive (76.7% vs 18.2%, P0.0001) and HBeAg-negative (96.8% vs 71.2%, P0.0001) patients. The majority of patients in both treatment arms achieved ALT normalization (85%). No resistance to TDF was observed. The frequency of adverse events was comparable between treatment arms (TDF 3.9% vs ADV 4.8%). In this double-blind, randomized, clinical trial, TDF demonstrated superiority over ADV with respect to viral suppression in Chinese patients with CHB at 48 weeks of treatment and without the development of resistance.

Photodissociation of propane at 157 nm excitation has been investigated using the photofragment translational spectroscopic (PTS) technique. Three dissociation channels have been experimentally observed: the atomic hydrogen (H) elimination, the molecular hydrogen (H2) elimination, and the methyl radical (CH3) elimination. Product translational energy distributions have been measured and relative branching ratios have also been estimated, which indicate that all these three processes are significant. The site effects on the H and H2 elimination have been quantified by investigating the photodissociation of the four propane isotopomers: CH3CD2CH3, CD3CH2CD3, CH2DCH2CH2D, and CD3CD2CD3. Experimental results indicate that the yield of the H elimination from the two terminal CH3 groups (terminal-H elimination) is larger than that from the internal CH2 group (internal-H elimination). H2 elimination from the internal carbon atom of propane (2,2-H2 elimination) is the dominant process while H2 elimination channel...

Site effects on the molecular hydrogen elimination from propane at 157 nm excitation have been studied using the photofragment translational spectroscopic technique. Experimental results indicate that H2 elimination from the internal carbon of propane (2,2-elimination) is predominant while eliminations from the terminal carbon (1,1- and 1,3-elimination) and the vicinal carbons (1,2-elimination) are minor. The translational energy distributions obtained for these processes also show that the dynamics of H2 eliminations from different sites are significantly different. Relative branching ratios of the atomic hydrogen (H) and the molecular hydrogen (H2) elimination processes were also determined.

In this study, a hybrid GIS-supported watershed modelling system is developed for integrated planning of water pollution control in the Lake Erhai basin, China. The system comprises a GIS-supported database, simulation/optimization models, and user interfaces developed through Arc/Info and Arc View. An inexactfuzzy multi-objective optimization model is developed for assessing a variety of system objectives and generating desired decision alternatives. It can effectively reflect uncertain, interactive and multi-objective features of the study system, and its solutions provide decision makers with a flexible decision space. The GIS technology is used for managing spatial and non-spatial data, linking models, and providing interfaces between the models and their users. The developed modelling system allows regional planners to obtain desired plans of human activities under a variety of objectives and constraints and to examine consequences and impacts resulting from alternative management practices.

Metallothioneins (MTs), containing over 33% cysteine content and lacking both aromatic amino acids and histidine, are metal binding proteins with low molecular weight (7-14 kDa). The metal ions are bound exclusively through thiolate coordination complexes which involve all 20 cysteine residues (Dunn et al. 1987). The MTs can be induced by and bind metals such as cadmium, copper, mercury, silver and zinc (Roesijadi 1992) and are capable of binding 6-7 atoms of cadmium or zinc per mole (Kagi and Schaffer 1988; Hamer 1985). The metals bound to MTs can be removed by exposure to low pH. MTs exist in vertebrates, aquatic invertebrates (Roesijadi 1992), certain bacteria (Olafson et al. 1988) and fusion yeast (Hamer et al. 1985). These proteins are found most abundant in liver, kidney, pancreas and intestine of animals, and the expression of these proteins showed a dose-response relation with the degrees of heavy metal pollution. Expression of MTs has also found to be induced by steroid hormones, interferons, certain chemicals, hepatotoxic solvent, and stresses (Kagi and Schaffer 1988). MTs have been implicated in the involvement of metabolism of copper and zinc (Cousins 1985), and in detoxification of pollutant metals, such as cadmium and mercury (Kagi and Kojima 1987). Moreover, MTs have been indicated to be an efficient scavenger for free OH(Dunn et al. 1987).

Background : A furazolidone-containing therapeutic regimen for Helicobacter pylori infection has attracted special interest in the face of a rising world-wide metronidazole resistant H. pylori, and the expense of currently used antimicrobial regimens. Aim : To evaluate the efficacy of furazolidone-containing regimens in eradicating H. pylori. Methods : One-hundred and forty H. pylori positive patients with endoscopically confirmed duodenal ulcer or functional dyspepsia received one of four different regimens to eradicate H. pylori. In the first trial, the patients were randomly assigned to receive a 1-week course of furazolidone 100 mg b.d. and clarithromycin 250 mg b.d., with either tripotassium dicitrato bismuthate (TDB) 240 mg b.d. (FCB group) or lansoprazole 30 mg daily (FCL group). In the second trial, the patients were randomly assigned to receive a 1-week course of clarithromycin 250 mg b.d. and omeprazole 20 mg daily, with either furazolidone 100 mg b.d. (FCO group) or metronidazole 400 mg b.d. (MCO group). Endoscopy was repeated 4 weeks following completion of therapy with re-assessment of H. pylori status on gastric biopsies by histology and culture. Results : Four patients (1 in FCB, 1 in FCO and 2 in MCO groups) dropped out because they refused a follow-up endoscopy. Eradication rates of H. pylori on an intention-to-treat basis in the FCB, FCL, FCO and MCO groups were 91% (32/35, 95% CI: 82–99%), 91% (32/35, CI: 82–99%), 86% (30/35, CI: 74–97%) and 74% (26/35, CI: 60–89%) (all P > 0.05), respectively. Mild side-effects occurred in 15% of the 140 patients. In MCO group, the eradication rate in the patients infected with metronidazole-sensitive isolates of H. pylori was 86%, but dropped to 67% in those with metronidazole-resistance strains (P = 0.198). Conclusion : One-week regimens containing furazolidone and clarithromycin in combination with TDB or a proton pump inhibitor fulfil the criteria for successful H. pylori therapy.

Photodissociation of 1,1-difluoroethylene (F2CCH2) at 157 nm has been investigated using photofragment translational spectroscopy. Five dissociation channels have been experimentally observed; molecular HF elimination, H atom elimination, molecular hydrogen (H2) elimination, F atom elimination, and double bond breaking. Molecular HF elimination and H atom elimination channels are found to be the two major dissociation pathways in photodissociation of F2CCH2 at 157 nm excitation. Molecular hydrogen (H2) elimination and double bond cleavage are also significant, while F atom elimination is a minor process. Product translational energy distributions for all dissociation channels have also been measured. All translational energy releases are peaked at energies away from zero, indicating that the dissociation of F2CCH2 at 157 nm excitation most likely occurs with exit barriers on the ground electronic potential surface through internal conversion from the initially excited electronic state. Branching ratios an...

A current-expansion technique is proposed to analyze the waveguide discontinuities of irregular shape. Roof-top and rectangular-pipe sub-domain functions are used in an electric-field integral-equation formulation to adequately expand the three-dimensional current densities of an irregularly-shaped conductor. It is therefore applicable to quite general discontinuity configurations. Numerical results for a variety of waveguide discontinuities including open-ends, bends, and T junctions have been demonstrated and verified by the available published data.

In this study, an inexact fuzzy multiobjective programming (IFMOP) method is developed and applied to a case study of water pollution control planning in the Lake Erhai Basin. The IFMOP improves upon the existing multiobjective programming methods with advantages in data availability, solution algorithm, computational requirement and result interpretation. The case study project was supported by the United Nations Environment Programme (UNEP). The results indicate that desired schemes for a number of system activities in different subareas/periods were obtained. Inheriting uncertain natures of the model inputs, the majority of solutions present as inexact values which provide decision-makers with a flexible decision space. Generally, the modeling results would provide scientific bases for the formulation of policies/strategies regarding regional socio-economic development and environmental protection.

Lamivudine (LAM) and adefovir (ADV) are widely used in most Asian countries, though monotherapy is associated with the occurrence of resistance.To evaluate the efficiency of LAM and ADV combined treatment of chronic hepatitis B patients with compensated cirrhosis.206 eligible Chinese patients were randomly assigned in a 1:1 ratio to receive either LAM or ADV for the first 24 weeks. According to virologic response at 24 weeks, the patients either continued to monotherapy or switched to combined therapy for 48 weeks. After 48 weeks, all patients received LAM and ADV combined therapy for 96 weeks.Serum HBV DNA levels significantly decreased in patients with ADV or LAM monotherapy and continuously reduced after the combined therapy. Serum ALT normalized rate were 88.24% and 81.37% at week 48, and 95.74% and 87.36% at week 96 in ADV and LAM group respectively, comparing to 60.78% and 56.73% in ADV and LAM groups at baseline. The accumulated virological breakthrough rate at week 48 and 96 was significantly higher in LAM group.Both combination strategies were resulted in the long term virological, biochemical improvement in Chinese chronic hepatitis B patients with compensated cirrhosis.

The characteristics of nine common drill failure modes have been analyzed. To facilitate detecting and diagnosing these failure modes, a multi-sensor approach is developed. Based on the dynamic characteristics of three different measurements including thrust, torque, and lateral vibration, necessary signatures are extracted for the nine failure modes. Experimental tests were conducted to confirm the characteristics of these nine drill failure modes.

An integrated lattice filter adaptive control system is developed for the control of time-varying CMM structural vibrations. An efficient algorithm is developed to provide a link between the adaptive lattice filter and the minimum variance control by directly utilizing the lattice filter parameters at time t − 1 for control. The approach avoids the conversion to system parameters and is therefore computationally efficient for applications of real time control. To fully utilize the benefit of the lattice filter, a heuristic criterion for on-line order determination is developed using the lattice filter parameters. With a linear computational cost, the developed algorithm will perform on-line system order determination, parameter tracking, and control calculation at each sampling instance. The simulation result shows that the approximation of output prediction is reasonable and the integrated lattice filter adaptive control can reduce the system settling time by 82 percent as compared with no control.

The integrated fast lattice filter adaptive control algorithm developed in Part 1 of this paper will be implemented for the control of the structural vibration of a coordinate measuring machine (CMM). The structural vibration of a CMM exhibits time-varying dynamic characteristics. For auxiliary control, the probe head acceleration was measured to compute the voltage input to the servo motor of the CMM. The developed algorithm uses directly the lattice filter parameters to track and control the CMM structural dynamics and is implemented on a Sheffield horizontal arm Coordinate Measuring Machine using a floating point Digital Signal Processor TMS320C30. Through experiments, significant reduction of the CMM settling time has been achieved by suppressing the structural vibration. In certain configurations, the reduction was 95 percent.

The calibration scheme of robot forward kinematics presented in this paper has a number of features. Firstly, robot kinematic errors are modeled in a recursive format and as such, the number of measurements that need to be taken for calibration can be determined by studying the rate of convergence of estimation error covariance. Secondly, a simplified adaptive filtering algorithm is used to deal with unknown measurement noise statistics and unknown robot motion repeatability characteristics in estimating the kinematic errors. Thirdly, a laser interferometry system is used to measure positions of a robot end-effector in world coordinates. The measurement system was implemented in experiments involving a three degree-of-freedom gantry robot. The adaptive filtering of the experimental data identified 0.5 to 1.5 percent errors in representative kinematic parameters of the given robot by taking into account measurement noise and robot repeatability.

This paper presents a systematic study of various monitoring methods suitable for automated monitoring of manufacturing processes. In general, monitoring is composed of two phases: learning and classification. In the learning phase, the key issue is to establish the relationship between monitoring indices (selected signature features) and the process conditions. Based on this relationship and the current sensor signals, the process condition is then estimated in the classification phase. The monitoring methods discussed in this paper include pattern recognition, fuzzy systems, decision trees, expert systems and neural networks. A brief review of signal processing techniques commonly used in monitoring, such as statistical analysis, spectral analysis, system modeling, bi-spectral analysis and time-frequency distribution, is also included.

In Part 2 of this paper, three applications of automated monitoring of manufacturing processes are presented to demonstrate the use of monitoring methods discussed in Part 1 of the paper. These applications are: (1) tool condition monitoring in turning, (2) machining condition monitoring in tapping, and (3) metallographic condition monitoring in arc welding. For each application, a background review, monitoring index selection and experimental setup are first presented. Then, monitoring methods discussed in Part 1 of the paper were applied and the test results are investigated. Discussions of the monitoring success rate, sensitivity, robustness, monitoring index selection, and decision under uncertainty are also included.

This paper is the first attempt to implement a knowledge-based diagnostic approach for the auto-body assembly process launch. This approach enables quick detection and localization of assembly process faults based on in-line dimensional measurements. The proposed approach includes an auto-body assembly knowledge representation and a diagnostic reasoning mechanism. The knowledge representation is comprised of the product, tooling, process, and measurement representations in the form of hierarchical groups. The diagnostic reasoning performs fault diagnostic in three steps. First, an initial statistical analysis of measurement data is performed. Next, the Candidate Component and Candidate Station with the hypothetical fault are searched. Finally, the fault symptom is identified and the root cause is suggested. Two case studies are presented to demonstrate the implementation of the proposed method.

The digitization of mathematically unknown free-form curves is frequently required. Current industrial practice relies on the experience of an operator to determine the direction of a CMM probe's approaching vector and the number of samples to represent a complex curve. An automatic procedure is proposed to generate recursively the approaching vector direction as well as the sampling rate. Several techniques including a linear prediction, a polynomial prediction, and a spline interpolation method have been presented and compared. Experimental results show that the spline interpolation method provides the best digitization accuracy and requires the least number of sampling points.

A process fault identification and classification scheme for an automobile door assembly process is presented based on multivariate in-line dimensional measurements and principal component factor analysis. First, the door assembly process and the dimensional measurement system are briefly introduced. Second, the technique of principal component factor analysis is presented for process fault identification. Process faults are summarized based on off-line identified case studies. Finally a machine classification scheme based on principal components and principal factors is presented and evaluated, using the pattern knowledge obtained off-line. This scheme is shown to be effective in classifying process faults using production data.

An algorithm for generating an optimum CMM inspection path is developed to improve the throughput of CMMs. In this algorithm, a modified 3-D ray tracing technique is applied to an octree database of a CMM configuration space to detect obstacles between any two target points. After an obstacle is detected, collision-free silhouette contour vertices of the object are generated, from a selection criterion, as potential points of a vertex path. As the ray advances, a sequential-decision-making technique is used to derive the suboptimum vertex path from possible collision-free vertex paths. After the suboptimum vertex path is generated, a selection strategy is employed to ensure a correct edge path sequence for deriving an optimum edge point path. A 3-D simulation shows that the proposed global algorithm eliminates the dynamically undesirable characteristics of octree based algorithms and saves searching time in congested work spaces by finding paths around colliding objects. Actual measurement of a test part indicates that the proposed method can reduce the inspection time to less than half as compared to the interactive graphic method.

A systematic approach is presented to obtain the best door gap quality through optimal door fitting in automobile body manufacturing. First, three indexes of gap quality are defined; they are: (1) door gap width deviation relative to design nominal; (2) door gap parallelism; and (3) car-to-car gap consistency. Then the door-fitting problem is formulated into a general constrained optimization problem. The effects of optimal door fitting on the three quality indexes are evaluated through computer simulation. These results provide a lower bound on the design of nominal door gap by considering process capability. Finally, a computer-aided fixture adjustment scheme is developed to orient a door in a body side opening to achieve the optimal fitting. The amount of adjustment, with the desired orientation obtained from optimization, is calculated based on parametrically modeled local surface features of the fixture and the door. The adequacy of door feature modeling is verified through a door-fitting experiment.

A preemptive diagnostic system has been developed to detect minor machine failures before machine breakdown for a computer controlled robotic drilling end-effector. By using the Dynamic Data System (DDS) approach, a set of discrete time series data taken from the continuous vibration signal of the machine is analyzed to detect machine failure and to distinguish failures due to the spindle, gears, air motors, and ball bearings of the machine drive system. Experiments validate that the proposed diagnostic method can identify spindle, air motors, gear, and bearing defects in the Robotic Drilling Unit.

Acoustic emission (AE) has been chosen as a means of monitoring cutting system changes from remote sensor locations. The determination of a processing strategy which can remove signal transmission path variability has been explored. This strategy, termed homomorphic processing, is developed and tested on both simulated and experimentally collected data. The recovery properties of this strategy are analyzed in terms of both AE source characterization and signal path transmission effects. These properties are found to be influenced by the choice of homomorphic lifter cutoff time. Guidelines are given for the selection of this parameter. Spectral representations of the recovered AE source show that signatures collected at remote sensor locations can be successfully used to identify process and structural changes in the cutting system.

Thyroid hormone, 3, 3', 5-triiodo-L-thyronine (T(3)), mediates cell growth, development and differentiation by binding to its nuclear receptors (TRs). The role of TRs in cancer is still undefined. Notably, hyperthyroxinemia has been reported to influence the rate of colon cancer in an experimental model of carcinogenesis in rats. Previous microarray analysis revealed that cathepsin H (CTSH) is upregulated by T(3) in HepG2-TR cells. We verified that mRNA and protein expression of CTSH are induced by T(3) in HepG2-TR cells and in thyroidectomized rats following administration of T(3). The possible thyroid hormone-responsive elements of the CTSH promoter localized to the nucleotides -2038 to -1966 and -1565 to -1501 regions. An in vitro functional assay showed that CTSH can increase metastasis. J7 cells overexpressing CTSH were inoculated into severe combined immune-deficient mice and these J7-CTSH mice displayed a greater metastatic potential than did J7-control mice. The clinicopathologic significance of CTSH expression in hepatocellular carcinoma (HCC) was also investigated. The CTSH overexpressing in HCC was associated with the presence of microvascular invasion (P=0.037). The microvascular invasion characteristic is closely related to our in vitro characterization of CTSH function. Our results show that T(3)-mediated upregulation of CTSH led to matrix metallopeptidase or extracellular signal-regulated kinase activation and increased cell migration. This study demonstrated that CTSH overexpression in a subset hepatoma may be TR dependent and suggests that this overexpression has an important role in hepatoma progression.

The prediction of catastrophic cutting tool fracture is explored through monitoring the acoustic emission (AE) from a cutting process. A prediction parameter is derived which combines the AE signal with a physical model of a cracked tool to form an estimate of the spatial energy release rate. Monitoring the energy release rate is found to be largely dependent on the detection of crack advancement. Experiments were performed with both new and artificially cracked inserts during interrupted cutting. Epoches denoting crack advancement were detected through high time homomorphic analysis of the acquired AE signals. AE bursts prior to and leading up to fracture were analyzed for crack advancement. The calculated energy release rate was found to exponentially increase as fracture was approached. Crack advancement could be feasibly detected approximately six cuts prior to fracture.

An error compensation system has been developed to enhance the time-variant volumetric accuracy of a 3-axis machining center by correcting the existing machine errors through sensing, metrology, and computer control techniques. A general methodology has been developed to synthesize both the geometric and thermal errors of machines into a time-variant volumetric error model. Instead of the well-known 21 geometric error components, 32 machine linkage errors are formulated as a 4D error field including the space domain and the time domain. Different types of models are proposed for different kinds of thermal error components. A compensation controller based on an IBM/PC has been linked with a CNC controller to compensate for machine errors in real time. This scheme has been implemented on a horizontal machining center and has been shown, using metrology instruments, to improve the machine accuracy by an order of magnitude. A cut workpiece inspected using a coordinate measuring machine (CMM) has also shown that dimension errors have been reduced from 92.4 μm to 18.9 μm in a dimension of 404 × 310 mm2 and the depth difference of milled surfaces has been reduced from 196 μm to 8 μm.