Switched electromechanical dynamics for transient phase control of brushed DC servomotor.

Robotic tasks often exceed the scope of steady-state or periodic behavior, which necessitates generally-applicable models of actuators intended to generate transient or aperiodic motion. However, existing electromechanical models of servomotors typically omit consideration of the switching power converter circuits required for directional, speed, or torque control. In this study, a multi-domain framework is established for switched electromechanical dynamics in servomotor systems for their analysis and control in general aperiodic tasks including transient phases. The switched electromechanical dynamics is derived from the individual models of the internal DC motor, gear train, and H-bridge circuit. The coupled models comprehensively integrate all possible distinct switching configurations of on-state, off-state, and dead time. A combination of cycle averaging with piecewise analytical solutions of the non-smooth dynamics is introduced to handle different temporal scales from high-frequency electrical to low-frequency mechanical variables. System parameters were estimated from experimental data using a dual-servomotor test platform. The model was validated for predictive accuracy against measured data in two distinct tasks-dynamic braking of a pendulum system and sinusoidal trajectory following. The model was also used to formulate the servomotor power consumption, which was implemented for optimal control demonstration and energy analysis. In particular, the servomotor power consumption model provided true optimality (minimization) when compared with the squared rotor torque and the positive rotor mechanical power that are commonly used as proxy models. While the focus of this work is on permanent-magnet, armature-controlled brushed DC servomotors, the approach is applicable to general electromechanical systems with switching-based control.

Tramadol use is associated with enhanced postoperative outcomes in breast cancer patients: a retrospective clinical study with in vitro confirmation.

BACKGROUND: There is growing interest in the effect of postoperative analgesics on oncological outcomes after cancer surgery. We investigated the impact of tramadol after breast cancer surgery on recurrence and mortality and explored the mechanism by which tramadol affects cultured breast cancer cells in vitro. METHODS: Electronic medical records of patients who underwent breast cancer surgery between November 2005 and December 2010 at Severance Hospital in Korea were reviewed. Cox regression analyses were used to identify factors related to postoperative recurrence and mortality. We performed the sensitivity test with propensity score matching to adjust for selection bias. In addition, we investigated the effects of tramadol on human breast adenocarcinoma (Michigan Cancer Foundation-7 [MCF-7]) cells via assessment of cell viability, clonogenic assay, and cell cycle analysis in vitro. RESULTS: Of 2588 breast cancer patients, 36.4% had received tramadol. Those who received tramadol had a 0.71-fold decreased risk of recurrence and a 0.56-fold decrease in mortality. The MCF-7 cell viability assays showed that tramadol had an anti-proliferative effect by cell cycle arrest, suppressing colony formation, and regulation of oestrogen and progesterone receptors. Tramadol induced apoptosis of MCF-7 cells via extracellular signal-regulated kinases by decreasing of 5-hydroxytryptamine (HT)2B receptor and transient receptor potential vanilloid-1 expression. CONCLUSIONS: After breast cancer surgery, patients who received tramadol had a decreased risk of postoperative recurrence and mortality. The anti-tumour effect of tramadol appears to involve inhibition of proliferation, induction of apoptosis, and effects on 5-HT2B receptor and TRPV-1.

1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG) reduces hepatic injury in concanavalin A-treated mice.

1-palmitoyl-2-linoleoyl-3-acetyl-rac-glycerol (PLAG), a chemically synthesized monoacetyldiaglyceride, is one of the constituents in Sika deer antlers and has been known traditionally as having immunomodulatory effects. However, the mechanism by which PLAG controls neutrophil migration, which evokes liver injury in the hepatitis animal model, remains largely unknown. This study was designed to evaluate the immunomodulatory effects of PLAG on cytokine secretion and neutrophil migration in vivo and in vitro. Concanavalin A (Con A) induced leukocyte infiltration in the liver and increased plasma cytokine levels. Pretreatment with PLAG reduced the levels of interleukin (IL)-4, IL-6, IL-10, and CXCL2, but maintained interferon (IFN)-γ levels and modulated neutrophil recruitment toward the liver. Furthermore, the mRNA and protein levels of IL-4 and CXCL2 in liver tissue were also decreased in the Con A-treated mice. Liver histology analyses showed that PLAG reduced Con A-induced hepatic necrosis, which was accompanied by leukocyte infiltration. The in vitro studies revealed that PLAG reduced IL-4 secretion in Con A stimulated T cell and blocked signal transducer and activator of transcription 6 (STAT6) Con A induced hepatocyte. PLAG attenuated IL-4 induced activation of atypical protein kinase C (PKC)/STAT6 in hepatocytes and inhibited neutrophil migration toward the liver tissue through suppression of IL-8/vascular cell adhesion molecule (VCAM) expression. These results suggest that PLAG could mitigate excess neutrophil migration into liver tissue and potentially have a therapeutic effect on immune-mediated liver injury.

Effect of belly board with bladder compression device on small bowel displacement from the radiotherapy field for rectal cancer.

BACKGROUND: The aim of this study was to investigate the effect of a belly board (BB) with the addition of a bladder compression device (BCD) for small bowel (SB) displacement from the radiotherapy field for rectal cancer. PATIENTS AND METHODS: Computed tomography (CT) scans of 38 rectal cancer patients positioned on a BB were analyzed and compared with CT scans from the same patients after the addition of a BCD. The BCD moves the inferior border of the BB from the pubic symphysis to the lumbosacral junction. The treated and irradiated volumes of the SB and bladder were compared. The irradiated volume ratio of SB to abdominopelvic cavity (APC) and that of bladder to APC were analyzed. RESULTS: With the BCD, the treated and irradiated volumes of SB decreased significantly (49.1 ± 48.0 vs. 60.9 ± 50.9 cc, p = 0.006 and 207.5 ± 140.8 vs. 482.8 ± 214.2 cc, p < 0.001, respectively). The irradiated volume ratio of bladder to APC with the BCD increased considerably compared to that without the BCD (25.2 ± 11.5 vs. 18.7 ± 10.5%, p < 0.001), and the ratio of irradiated volume of SB to APC decreased significantly with the BCD (18.8 ± 12.4 vs. 31.8 ± 12.1%, p < 0.001). CONCLUSION: This study showed that the addition of a BCD to the BB could effectively provide further displacement of SB from the rectal cancer radiotherapy field.

Quantifying dynamic characteristics of human walking for comprehensive gait cycle.

Normal human walking typically consists of phases during which the body is statically unbalanced while maintaining dynamic stability. Quantifying the dynamic characteristics of human walking can provide better understanding of gait principles. We introduce a novel quantitative index, the dynamic gait measure (DGM), for comprehensive gait cycle. The DGM quantifies the effects of inertia and the static balance instability in terms of zero-moment point and ground projection of center of mass and incorporates the time-varying foot support region (FSR) and the threshold between static and dynamic walking. Also, a framework of determining the DGM from experimental data is introduced, in which the gait cycle segmentation is further refined. A multisegmental foot model is integrated into a biped system to reconstruct the walking motion from experiments, which demonstrates the time-varying FSR for different subphases. The proof-of-concept results of the DGM from a gait experiment are demonstrated. The DGM results are analyzed along with other established features and indices of normal human walking. The DGM provides a measure of static balance instability of biped walking during each (sub)phase as well as the entire gait cycle. The DGM of normal human walking has the potential to provide some scientific insights in understanding biped walking principles, which can also be useful for their engineering and clinical applications.

The potential of accelerometers in the evaluation of stability of total knee arthroplasty.

An accelerometer attached to the anterior proximal tibia was investigated as an evaluation of knee stability of Total Knee Arthroplasty (TKA) patients while performing daily activities. Acceleration data of 38 TKA knees with a minimum follow up of 6months were compared with 34 control knees. The activities performed were: walking three steps forward and coming to a sudden stop; turning in the direction of non-tested knee; sit-to-stand; and stepping up and down from a 7 inch step. The acceleration results showed significant differences between TKA and controls while stepping down and while turning in the non-tested knee direction. The higher accelerations with the TKA group may have represented an objective measure of stability, even if this was not directly discernible to the patient.

Space suit glove design with advanced metacarpal phalangeal joints and robotic hand evaluation.

BACKGROUND: One area of space suits that is ripe for innovation is the glove. Existing models allow for some fine motor control, but the power grip--the act of grasping a bar--is cumbersome due to high torque requirements at the knuckle or metacarpal phalangeal joint (MCP). This area in particular is also a major source of complaints of pain and injury as reported by astronauts. METHOD: This paper explores a novel fabrication and patterning technique that allows for more freedom of movement and less pain at this crucial joint in the manned space suit glove. The improvements are evaluated through unmanned testing, manned testing while depressurized in a vacuum glove box, and pressurized testing with a robotic hand. RESULTS: MCP joint flex score improved from 6 to 6.75 (out of 10) in the final glove relative to the baseline glove, and torque required for flexion decreased an average of 17% across all fingers. Qualitative assessments during unpressurized and depressurized manned testing also indicated the final glove was more comfortable than the baseline glove. DISCUSSION: The quantitative results from both human subject questionnaires and robotic torque evaluation suggest that the final iteration of the glove design enables flexion at the MCP joint with less torque and more comfort than the baseline glove.

Proteomic analysis of the hepatic tissue of Long-Evans Cinnamon (LEC) rats according to the natural course of Wilson disease.

Copper-induced toxicity is important in the pathogenic process of Wilson's disease (WD). Using Long-Evans Cinnamon (LEC) rats, an animal model of WD, the study was undertaken to identify proteins involved in the process of WD and to investigate their functional roles in copper-induced hepatotoxicity. In early stages, expression levels of mitochondrial matrix proteins including agmatinase, isovaleryl coenzyme A dehydrogenase, and cytochrome b5 were downregulated. As mitochondrial injuries progressed, along with subsequent apoptotic processes, expressions of malate dehydrogenase 1, annexin A5, transferrin, S-adenosylhomocysteine hydrolase, and sulfite oxidase 1 were differentially regulated. Notably, the expression of malate dehydrogenase 1 was downregulated while the annexin A5 was overexpressed in an age-dependent manner, indicating that these proteins may be involved in the WD process. In addition, pronounced under-expression of S-adenosylhomocysteine hydrolase in elderly LEC rats, also involved in monoamine neurotransmitter metabolism, indicates that this protein might be related to the development of neurological manifestations in WD. The results of our study help to understand the pathogenic process of WD in hepatic tissues, identifying the important proteins associated with the disease process of WD, and to investigate the molecular pathogenic process underlying the development of neurological manifestations in WD.

Distinct clinical courses according to presenting phenotypes and their correlations to ATP7B mutations in a large Wilson's disease cohort.

INTRODUCTION AND AIMS: Wide phenotypic and genotypic heterogeneities in Wilson's disease (WD) have been reported, hampering the study of their correlations. The goal of this study was to identify the factors related to these diversities. METHODS: Clinical courses and molecular genetic characteristics were analysed in 237 unrelated Korean WD families. The average follow-up period was 8.2 ± 5.8 years. RESULTS: Presenting phenotypes were classified as H1 (12.2%), H2 (42.4%), N1 (21.6%), N2 (0.4%), NX (0.4%), presymptomatic (22.4%) and other (0.4%), modifying the guidelines by Ferenci and colleagues. Age at presentation was youngest and cirrhosis was rarest in the presymptomatic group. Decompensated cirrhosis was the highest in the H1 group. Favourable outcome was rarest in the N1 group. Forty-seven (11 novel) ATP7B mutations were identified in 85% of the 474 alleles. Multiplex ligation-dependent probe amplification assays in ATP7B and analyses of ATOX1 and COMMD1 genes identified no additional mutations. Yeast complementation assays demonstrated functional perturbation of the seven novel missense mutants. Five major mutations, p.Arg778Leu, p.Ala874Val, p.Asn1270Ser, p.Lys838SerfsX35 and p.Leu1083Phe, accounted for 63% of the alleles. H1 was more common, age at presentation was younger and N1+N2+NX tended to be less common in patients with nonsense, frame shifting or splicing mutations than in those with missense mutations alone. Patients with both mutations in the transduction (Td) or the ATP hinge domain showed presymptomatic or hepatic manifestations but no neurological manifestation. CONCLUSIONS: The presenting phenotype strongly affects the clinical outcome of WD, and is related to the ATP7B mutation type and location, providing an evidence for genotype-phenotype correlations in WD.

NDRG2 expression decreases with tumor stages and regulates TCF/beta-catenin signaling in human colon carcinoma.

NDRG (N-Myc downstream-regulated gene)-2 is a member of the NDRG family. Although it has been suggested that NDRG2 is involved in cellular differentiation and tumor suppression, its intracellular signal and regulatory mechanism are not well known. Here, we show the differential expression of NDRG2 in human colon carcinoma cell lines and tissues by reverse transcription-polymerase chain reaction and immunohistochemical analyses with monoclonal antibody against NDRG2. NDRG2 was strongly expressed in normal colonic mucosa and colonic adenomatous tissues (25 of 25) but not in all invasive cancer tissues [44 of 99 (44%)]. Most distinctive results indicated that the high expression level of NDRG2 has a positive correlation with tumor differentiation and inverse correlation with tumor invasion depth and Dukes' stage of colon adenocarcinoma. To investigate the roles of NDRG2 in tumorigenesis, we used in vitro cell culture system. SW620 colon cancer cell line with a low level of intrinsic NDRG2 protein was transfected with NDRG2-expressing plasmid. TOPflash luciferase reporter assay showed that the transcriptional activity of T-cell factor (TCF)/lymphoid enhancer factor (LEF) was reduced by NDRG2 introduction, but not by the introduction of mutant NDRG2 generated by deletion or site-directed mutagenesis. Intracellular beta-catenin levels were slightly reduced in the NDRG2-transfected SW620 cells and this regulation of beta-catenin stability and TCF/LEF activity were mediated through the modulation of glycogen synthase kinase-3beta activity by NDRG2 function. Our results suggest that NDRG2 might play a pivotal role as a potent tumor suppressor by the attenuation of TCF/beta-catenin signaling for the maintenance of healthy colon tissues.

Effects of erlotinib in EGFR mutated non-small cell lung cancers with resistance to gefitinib.

PURPOSE: Most lung cancers with activating epidermal growth factor receptor (EGFR) mutations respond to gefitinib; however, resistance to this tyrosine kinase inhibitor (TKI) invariably ensues. The T790M mutation occurs in 50% and MET amplification in 20% of TKI-resistant tumors. Other secondary mutations (D761Y and L747S) are rare. Our goal was to determine the effects of erlotinib 150 mg/d in EGFR mutated patients resistant to gefitinib 250 mg/d, because the EGFR TKI erlotinib is given at a higher biologically active dose than gefitinib. EXPERIMENTAL DESIGN: Retrospective review of 18 EGFR mutated (exon 19 deletions, L858R, and L861Q) patients that were given gefitinib and subsequently erlotinib. Seven patients had tumor resampling after TKI therapy and were analyzed for secondary EGFR mutations and MET amplification. RESULTS: Most patients (14 of 18) responded to gefitinib with median progression-free survival of 11 months (95% confidence interval, 4-16). After gefitinib resistance (de novo or acquired), 78% (14 of 18) of these patients displayed progressive disease while on erlotinib with progression-free survival of 2 months (95% confidence interval, 2-3). Six of 7 resampled patients acquired the T790M mutation, and 0 of 3 had MET amplification. Only 1 gefitinib-resistant patient with the acquired L858R-L747S EGFR, which in vitro is sensitive to achievable serum concentrations of erlotinib 150 mg/d, achieved a partial response to erlotinib. CONCLUSIONS: In EGFR mutated tumors resistant to gefitinib 250 mg/d, a switch to erlotinib 150 mg/d does not lead to responses in most patients. These findings are consistent with preclinical models, because the common mechanisms of TKI resistance (T790M and MET amplification) in vitro are not inhibited by clinically achievable doses of gefitinib or erlotinib. Alternative strategies to overcome TKI resistance must be evaluated.

Stability of Mina v2 for Robot-Assisted Balance and Locomotion.

The assessment of the risk of falling during robot-assisted locomotion is critical for gait control and operator safety, but has not yet been addressed through a systematic and quantitative approach. In this study, the balance stability of Mina v2, a recently developed powered lower-limb robotic exoskeleton, is evaluated using an algorithmic framework based on center of mass (COM)- and joint-space dynamics. The equivalent mechanical model of the combined human-exoskeleton system in the sagittal plane is established and used for balance stability analysis. The properties of the Linear Linkage Actuator, which is custom-designed for Mina v2, are analyzed to obtain mathematical models of torque-velocity limits, and are implemented as constraint functions in the optimization formulation. For given feet configurations of the robotic exoskeleton during flat ground walking, the algorithm evaluates the maximum allowable COM velocity perturbations along the fore-aft directions at each COM position of the system. The resulting velocity extrema form the contact-specific balance stability boundaries (BSBs) of the combined system in the COM state space, which represent the thresholds between balanced and unbalanced states for given contact configurations. The BSBs are obtained for the operation of Mina v2 without crutches, thus quantifying Mina v2's capability of maintaining balance through the support of the leg(s). Stability boundaries in single and double leg supports are used to analyze the robot's stability performance during flat ground walking experiments, and provide design and control implications for future development of crutch-less robotic exoskeletons.

Perioperative serum creatinine changes and ureteral injury.

PURPOSE: To illustrate a simple method that screens for ureteral injury in the acute postoperative period after urogynecologic surgeries. METHODS: Serum creatinine measurements in the preoperative (baseline) and postoperative periods of urogynecologic surgeries were determined and the correlation of the change to ureteral injury and/or obstruction analyzed. The sample size calculation showed 7 cases and 28 controls were sufficient to detect significant changes in creatinine. Each of the seven cases was matched for age and type of surgery with a control patient in a 1:4 ratio following standard protocol. RESULTS: Chart review of patients (273 cases) undergoing urogynecologic surgeries from October 2009 to June 2014 were undertaken. There were 7 cases of ureteral injury and 28 matching control cases. All cases had intraoperative cystoscopy confirming bilateral ureteral flow. In the ureteral injury group, blockage of ureter was confirmed by CT scan with IV contrast. There was a 59.8% increase in serum creatinine levels postoperative in the ureteral injury group versus a 3.8% decrease in controls. A difference of creatinine levels greater than or equal to 0.3 mg/dL over baseline was evident in ureteral injury cases. CONCLUSION: A small change in serum creatinine level over baseline after urogynecologic surgery alerted the possibility of ureteral injury or obstruction. A simple and inexpensive evaluation of perioperative creatinine levels can promptly diagnose ureteral damage in the acute postoperative period for gynecologic reconstructive surgeries.

Instantaneous Metabolic Cost of Walking: Joint-Space Dynamic Model with Subject-Specific Heat Rate.

A subject-specific model of instantaneous cost of transport (ICOT) is introduced from the joint-space formulation of metabolic energy expenditure using the laws of thermodynamics and the principles of multibody system dynamics. Work and heat are formulated in generalized coordinates as functions of joint kinematic and dynamic variables. Generalized heat rates mapped from muscle energetics are estimated from experimental walking metabolic data for the whole body, including upper-body and bilateral data synchronization. Identified subject-specific energetic parameters-mass, height, (estimated) maximum oxygen uptake, and (estimated) maximum joint torques-are incorporated into the heat rate, as opposed to the traditional in vitro and subject-invariant muscle parameters. The total model metabolic energy expenditure values are within 5.7 ± 4.6% error of the measured values with strong (R2 > 0.90) inter- and intra-subject correlations. The model reliably predicts the characteristic convexity and magnitudes (0.326-0.348) of the experimental total COT (0.311-0.358) across different subjects and speeds. The ICOT as a function of time provides insights into gait energetic causes and effects (e.g., normalized comparison and sensitivity with respect to walking speed) and phase-specific COT, which are unavailable from conventional metabolic measurements or muscle models. Using the joint-space variables from commonly measured or simulated data, the models enable real-time and phase-specific evaluations of transient or non-periodic general tasks that use a range of (aerobic) energy pathway similar to that of steady-state walking.

Computational evaluation of load carriage effects on gait balance stability.

Evaluating the effects of load carriage on gait balance stability is important in various applications. However, their quantification has not been rigorously addressed in the current literature, partially due to the lack of relevant computational indices. The novel Dynamic Gait Measure (DGM) characterizes gait balance stability by quantifying the relative effects of inertia in terms of zero-moment point, ground projection of center of mass, and time-varying foot support region. In this study, the DGM is formulated in terms of the gait parameters that explicitly reflect the gait strategy of a given walking pattern and is used for computational evaluation of the distinct balance stability of loaded walking. The observed gait adaptations caused by load carriage (decreased single support duration, inertia effects, and step length) result in decreased DGM values (p < 0.0001), which indicate that loaded walking motions are more statically stable compared with the unloaded normal walking. Comparison of the DGM with other common gait stability indices (the maximum Floquet multiplier and the margin of stability) validates the unique characterization capability of the DGM, which is consistently informative of the presence of the added load.

A joint-space numerical model of metabolic energy expenditure for human multibody dynamic system.

Metabolic energy expenditure (MEE) is a critical performance measure of human motion. In this study, a general joint-space numerical model of MEE is derived by integrating the laws of thermodynamics and principles of multibody system dynamics, which can evaluate MEE without the limitations inherent in experimental measurements (phase delays, steady state and task restrictions, and limited range of motion) or muscle-space models (complexities and indeterminacies from excessive DOFs, contacts and wrapping interactions, and reliance on in vitro parameters). Muscle energetic components are mapped to the joint space, in which the MEE model is formulated. A constrained multi-objective optimization algorithm is established to estimate the model parameters from experimental walking data also used for initial validation. The joint-space parameters estimated directly from active subjects provide reliable MEE estimates with a mean absolute error of 3.6 ± 3.6% relative to validation values, which can be used to evaluate MEE for complex non-periodic tasks that may not be experimentally verifiable. This model also enables real-time calculations of instantaneous MEE rate as a function of time for transient evaluations. Although experimental measurements may not be completely replaced by model evaluations, predicted quantities can be used as strong complements to increase reliability of the results and yield unique insights for various applications.

Acceleration-based joint stability parameters for total knee arthroplasty that correspond with patient-reported instability.

There is no universally accepted definition of human joint stability, particularly in nonperiodic general activities of daily living. Instability has proven to be a difficult parameter to define and quantify, since both spatial and temporal measures need to be considered to fully characterize joint stability. In this preliminary study, acceleration-based parameters were proposed to characterize the joint stability. Several time-statistical parameters of acceleration and jerk were defined as potential stability measures, since anomalous acceleration or jerk could be a symptom of poor control or stability. An inertial measurement unit attached at the level of the tibial tubercle of controls and patients following total knee arthroplasty was used to determine linear acceleration of the knee joint during several activities of daily living. The resulting accelerations and jerks were compared with patient-reported instability as determined through a standard questionnaire. Several parameters based on accelerations and jerks in the anterior/posterior direction during the step-up/step-down activity were significantly different between patients and controls and correlated with patient reports of instability in that activity. The range of the positive to negative peak acceleration and infinity norm of acceleration, in the anterior/posterior direction during the step-up/step-down activity, proved to be the best indicators of instability. As time derivatives of displacement, these acceleration-based parameters represent spatial and temporal information and are an important step forward in developing a definition and objective quantification of human joint stability that can complement the subjective patient report.

Determining the three-dimensional relation between the skeletal elements of the human shoulder complex.

In this paper, we present an inverse kinematics method to determining human shoulder joint motion coupling relationship based on experimental data in the literature. This work focuses on transferring Euler-angle-based coupling equations into a relationship based on the Denavit-Hartenberg (DH) method. We use analytical inverse kinematics to achieve the transferring. For a specific posture, we can choose points on clavicle, scapula, and humerus and represent the end-effector positions based on Euler angles or DH method. For both Euler and DH systems, the end-effectors have the same Cartesian positions. Solving these equations related to end-effector positions yields DH joint angles for that posture. The new joint motion coupling relationship is obtained by polynomial and cosine fitting of the DH joint angles for all different postures.