Data-driven methods towards learning the highly nonlinear inverse kinematics of tendon-driven surgical manipulators.

BACKGROUND: Accurate motion control of flexible surgical manipulators is crucial in tissue manipulation tasks. The tendon-driven serpentine manipulator (TSM) is one of the most widely adopted flexible mechanisms in minimally invasive surgery because of its enhanced maneuverability in torturous environments. TSM, however, exhibits high nonlinearities and conventional analytical kinematics model is insufficient to achieve high accuracy. METHODS: To account for the system nonlinearities, we applied a data driven approach to encode the system inverse kinematics. Three regression methods: extreme learning machine (ELM), Gaussian mixture regression (GMR) and K-nearest neighbors regression (KNNR) were implemented to learn a nonlinear mapping from the robot 3D position states to the control inputs. RESULTS: The performance of the three algorithms was evaluated both in simulation and physical trajectory tracking experiments. KNNR performed the best in the tracking experiments, with the lowest RMSE of 2.1275 mm. CONCLUSIONS: The proposed inverse kinematics learning methods provide an alternative and efficient way to accurately model the tendon driven flexible manipulator.

Participatory ergonomics for psychological factors evaluation in work system design.

It is a well recognized understanding that workers whose voice needs to be heard should be actively encouraged as full participants and involved in the early design stages of new ergonomic work system which encompass the development and implementation of new tools, workplaces, technologies or organizations. This paper presents a novel participatory strategy to evaluate three key psychological factors which are respectively mental fatigue, spiritual stress, and emotional satisfaction in work system design based on a modified version of Participatory Ergonomics (PE). In specific, it integrates a PE technique with a formulation view by combining the parallel development of PE strategies, frameworks and functions throughout the coverage of the entire work system design process, so as to bridge the gap between qualitative and quantitative analysis of psychological factors which can cause adverse or advantageous effects on worker's physiological and behavioral performance.

Structural insights into the design of small molecule inhibitors that selectively antagonize Mcl-1.

The screening of a small focused library of rhodanine derivatives as inhibitors of Bcl-2 proteins led to the discovery of two structurally related compounds with different binding profiles against the Bcl-XL and the Mcl-1 proteins. Subsequent NMR studies with mutant proteins and in silico docking studies provide a possible rationale for the observed specificity.

Structure-activity relationship studies of phenanthridine-based Bcl-XL inhibitors.

Despite their structural similarities, the natural products chelerythrine ( 5) and sanguinarine ( 6) target different binding sites on the pro-survival Bcl-X L protein. This paper details the synthesis of phenanthridine-based analogues of the natural products that were used to probe this difference in binding profiles. The inhibitory constants for these compounds were then measured in a fluorescence polarization assay against Bcl-X L and the tagged Bak-BH3 peptide. The results led to structure-activity relationship studies, which identified the structural motifs required for binding-site specificity as well as inhibitory activity. We also identified synthetic analogues of the natural products that display similar binding modes but with more potent IC 50 values.

Increased lipid peroxidation in sera of ALS patients: a potential biomarker of disease burden.

BACKGROUND: Markers of oxidative stress and immune activation are significantly elevated in postmortem ALS CNS tissue, although the relevance to pathogenesis is unclear. OBJECTIVE: To determine the degree and distribution of oxidative stress and immune activation in living ALS patients and whether these levels correlate with the rate of progression or extent of disease. METHOD: Serum and CSF samples from sporadic ALS (sALS) patients were assayed for 4-hydroxy-2,3-nonenal (HNE), a lipid peroxidation product, and monocyte chemoattractant protein-1alpha (MCP-1alpha), a beta-chemokine, by high-performance liquid chromatography and ELISA and compared with levels measured in disease and normal control subjects by one-way analysis of variance. SALS serum levels were analyzed in relation to rate of progression, stage of disease, and drug therapy. RESULTS: HNE levels were significantly elevated in the sera and spinal fluid of sALS patients compared with control populations and positively correlated with extent of disease but not rate of progression. MCP-1alpha levels were also elevated in the sera of sALS patients, with the exception of the neurodegenerative disease control subjects, but decreased with advancing disease. CSF MCP-1alpha levels were not different between the sampled populations. There was no correlation between serum HNE and MCP-1alpha levels in sALS patients and extent of disease. However, an inverse relationship between HNE and MCP-1alpha was demonstrable in vitro. Low levels of HNE stimulated release of MCP-1alpha from cultured human macrophages, whereas high levels inhibited release of MCP-1alpha. CONCLUSIONS: These data confirm the presence of increased oxidative stress and immune activation in ALS patients. HNE is also suggested as a possible biomarker of disease.

Presence of 4-hydroxynonenal in cerebrospinal fluid of patients with sporadic amyotrophic lateral sclerosis.

A marker of lipid peroxidation 4-hydroxynonenal (HNE) was elevated in the cerebrospinal fluid (CSF) of a patient with sporadic amyotrophic lateral sclerosis (sALS) compared with that of most patients with other neurological diseases. Such elevations of HNE were sufficient to kill cyclic adenosine monophosphate (cAMP)-differentiated motor neuron hybrid cells in vitro, and anti-oxidants prevented this HNE-dependent cell death. These data suggest that oxidative stress and lipid peroxidation are associated with and may promote motor neuron degeneration in sALS.

Spinal cord injury hypercalcemia: therapeutic profile.

During the course of hospitalization for comprehensive rehabilitation, a 14-year-old boy with C4 spinal cord injury and hypercalcemia was treated with 5 different treatment regimens which were instituted to reduce the hypercalcemia and associated complications. These regimens included low calcium diet, steroids, oral phosphates, intravenous saline, diuretics, hyperalimentation, calcitonin and spironolactone in various combinations, and mobilization. Careful metabolic monitoring carried out throughout hospitalization permitted the evaluation in retrospect of the impact of each treatment regimen, and, to a lesser extent, the impact of their individual components. Among all the therapeutic modalities, the most effective variables in reducing hypercalcemia in this patient were mobilization in the form of wheelchair sitting for long-term effects, and saline, furosemide, and calcitonin for short-term effects.