Dynamic Modelling of a Two-link Flexible Manipulator System Incorporating Payload

This paper presents dynamic modelling of a twolink flexible manipulator based on closed-form equations of motion. The kinematic model is based on standard frame transformation matrices describing both rigid rotation and modal displacement, under small deflection assumption. The Lagrangian approach is used to derive the dynamic model of the structure. Links are modelled as Euler-Bernoulli beams with proper clamped-mass boundary conditions. A dynamic model of the system, incorporating structural damping, hub inertia and payload, is developed using finite assumed mode methods. Explicit equations of motions are detailed by assuming two modes of vibration for each link. Moreover, effects of payload on the response of the flexible manipulator are discussed. Extensive results that validate the theoretical derivation are presented in the time and frequency domains

CONTINUOUS MONITORING OF MOVEMENT IN PATIENTS WITH PARKINSON'S DISEASE USING INERTIAL SENSORS

Gait impairment is a hallmark of Parkinson's disease (PD). The assessment of gait and balance in the clinic may not adequately reflect mobility in daily life. It is often reported that patients with PD walk better when they are examined in an outpatient clinic or in a research laboratory than at home. Continuous monitoring of mobility during spontaneous daily activities may provide clinicians and patients with objective measures of the quality of their mobility. We show that continuous monitoring of spontaneous gait with wearable inertial sensors during daily activities is feasible for patients with PD. We tested 13 patients with PD and 8 healthy controls to evaluate the feasibility of using wearable inertial sensors at home for one week. The inertial system successfully detects walking bouts and provides sixteen objective measures that can characterize gait changes in patients with PD

Inertial and Time-of-Arrival Ranging Sensor Fusion

Wearable devices with embedded kinematic sensors including triaxial accelerometers, gyroscopes, and magnetometers are becoming widely used in applications for tracking human movement in domains that include sports, motion gaming, medicine, and wellness. The kinematic sensors can be used to estimate orientation, but can only estimate changes in position over short periods of time. We developed a prototype sensor that includes ultra wideband ranging sensors and kinematic sensors to determine the feasibility of fusing the two sensor technologies to estimate both orientation and position. We used a state space model and applied the unscented Kalman filter to fuse the sensor information. Our results demonstrate that it is possible to estimate orientation and position with less error than is possible with either sensor technology alone. In our experiment we obtained a position root mean square error of 5.2 cm and orientation error of 4.8° over a 15 min recording

A fatigue multi-site cracks model using coalescence, short and long crack growth laws, for anodized aluminum alloys

It has been shown that decrease of the fatigue life of aluminium alloys treated with anodization can be explained by the degradation of surface condition due to pickling. In order to predict fatigue life of anodized aluminium alloys, a multi-site crack growth model is developed by considering the pickling pits sites as initial flaws from which fatigue cracks develop. A map of the pickled surface is built from topography measurement with a contact profilometer. Then the pits are detected and their sizes are defined (depth, length and width). At the beginning of the calculation, a short crack growth law is used for crack having depths less than grain size. Then Paris long crack growth law is used. The coalescence of cracks is considered when their lengths increased by its crack tip plastic zone are large enough to interact with other neighbouring short cracks. The fatigue life is calculated for Kmax achieving 70 % KIC

Tumor suppressor p53 binds with high affinity to CTG-CAG trinucleotide repeats and induces topological alterations in mismatched duplexes

DNA binding is central to the ability of p53 to function as a tumor suppressor. In line with the remarkable functional versatility of p53, which can act on DNA as a transcription, repair, recombination, replication, and chromatin accessibility factor, the modes of p53 interaction with DNA are also versatile. One feature common to all modes of p53-DNA interaction is the extraordinary sensitivity of p53 to the topology of its target DNA. Whereas the strong impact of DNA topology has been demonstrated for p53 binding to sequence-specific sites or to DNA lesions, the possibility that DNA structure-dependent recognition may underlie p53 interaction with other types of DNA has not been addressed until now. We demonstrate for the first time that conformationally flexible CTG·CAG trinucleotide repeats comprise a novel class of p53-binding sites targeted by p53 in a DNA structure-dependent mode in vitro and in vivo. Our major finding is that p53 binds to CTG·CAG tracts by different modes depending on the conformation of DNA. Although p53 binds preferentially to hairpins formed by either CTG or CAG strands, it can also bind to linear forms of CTG·CAG tracts such as canonic B DNA or mismatched duplex. Intriguingly, by binding to a mismatched duplex p53 can induce further topological alterations in DNA, indicating that p53 may act as a DNA topology-modulating factor

Impaired glucose tolerance in adults with Duchenne and Becker muscular dystrophy

The aim of this study was to determine the response to an oral glucose tolerance test (OGTT) in adult males with Becker muscular dystrophy (BMD) and Duchenne muscular dystrophy (DMD), and to investigate whether body composition contributes to any variance in the glucose response. Twenty-eight adult males with dystrophinopathy (BMD, n = 13; DMD, n = 15) and 12 non-dystrophic controls, ingested 75 g oral anhydrous glucose solution. Fingertip capillary samples were assessed for glucose at 30-min intervals over 2-h post glucose ingestion. Fat free mass relative to body mass (FFM/BM) and body fat (BF%) was assessed using bioelectrical impedance. Vastus lateralis muscle anatomical cross sectional area (VL ACSA) was measured using B-mode ultrasonography. Blood glucose was higher in MD groups than control at 60, 90 and 120 min post ingestion of glucose. Compared to controls, FFM/BM and VL ACSA were lower in MD groups compared to controls (p < 0.001). Glucose tolerance values at 120 min were correlated with FFM/BM and BF% in the BMD group only. Our results suggest that glucose tolerance is impaired following OGTT in adult males with BMD and DMD. It is recommended that adults with BMD and DMD undertake routine glucose tolerance assessments to allow early detection of impaired glucose tolerance

Determinants of R-loop formation at convergent bidirectionally transcribed trinucleotide repeats

R-loops have been described at immunoglobulin class switch sequences, prokaryotic and mitochondrial replication origins, and disease-associated (CAG)n and (GAA)n trinucleotide repeats. The determinants of trinucleotide R-loop formation are unclear. Trinucleotide repeat expansions cause diseases including DM1 (CTG)n, SCA1 (CAG)n, FRAXA (CGG)n, FRAXE (CCG)n and FRDA (GAA)n. Bidirectional convergent transcription across these disease repeats can occur. We find R-loops formed when CTG or CGG and their complementary strands CAG or CCG were transcribed; GAA transcription, but not TTC, yielded R-loops. R-loop formation was sensitive to DNA supercoiling, repeat length, insensitive to repeat interruptions, and formed by extension of RNA:DNA hybrids in the RNA polymerase. R-loops arose by transcription in one direction followed by transcription in the opposite direction, and during simultaneous convergent bidirectional transcription of the same repeat forming double R-loop structures. Since each transcribed disease repeat formed R-loops suggests they may have biological functions

Habitual physical activity and cardiometabolic risk factors in adults with cerebral palsy

2014 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY license(http://creativecommons.org/licenses/by/3.0/).This article has been made available through the Brunel Open Access Publishing Fund.Adults with cerebral palsy (CP) are known to participate in reduced levels of total physical activity. There is no information available however, regarding levels of moderate-to-vigorous physical activity (MVPA) in this population. Reduced participation in MVPA is associated with several cardiometabolic risk factors. The purpose of this study was firstly to compare levels of sedentary, light, MVPA and total activity in adults with CP to adults without CP. Secondly, the objective was to investigate the association between physical activity components, sedentary behavior and cardiometabolic risk factors in adults with CP. Adults with CP (n = 41) age 18–62 yr (mean ± SD = 36.5 ± 12.5 yr), classified in Gross Motor Function Classification System level I (n = 13), II (n = 18) and III (n = 10) participated in this study. Physical activity was measured by accelerometry in adults with CP and in age- and sex-matched adults without CP over 7 days. Anthropometric indicators of obesity, blood pressure and several biomarkers of cardiometabolic disease were also measured in adults with CP. Adults with CP spent less time in light, moderate, vigorous and total activity, and more time in sedentary activity than adults without CP (p < 0.01 for all). Moderate physical activity was associated with waist-height ratio when adjusted for age and sex (β = −0.314, p < 0.05). When further adjustment was made for total activity, moderate activity was associated with waist-height ratio (β = −0.538, p < 0.05), waist circumference (β = −0.518, p < 0.05), systolic blood pressure (β = −0.592, p < 0.05) and diastolic blood pressure (β = −0.636, p < 0.05). Sedentary activity was not associated with any risk factor. The findings provide evidence that relatively young adults with CP participate in reduced levels of MVPA and spend increased time in sedentary behavior, potentially increasing their risk of developing cardiometabolic disease

Transplantation of Photoreceptor Precursors Isolated via a Cell Surface Biomarker Panel From Embryonic Stem Cell-Derived Self-Forming Retina.

Loss of photoreceptors due to retinal degeneration is a major cause of untreatable blindness. Cell replacement therapy, using pluripotent stem cell-derived photoreceptor cells, may be a feasible future treatment. Achieving safe and effective cell replacement is critically dependent on the stringent selection and purification of optimal cells for transplantation. Previously, we demonstrated effective transplantation of post-mitotic photoreceptor precursor cells labelled by fluorescent reporter genes. As genetically labelled cells are not desirable for therapy, here we developed a surface biomarker cell selection strategy for application to complex pluripotent stem cell differentiation cultures. We show that a five cell surface biomarker panel CD73(+)CD24(+)CD133(+)CD47(+)CD15(-) facilitates the isolation of photoreceptor precursors from three-dimensional self-forming retina differentiated from mouse embryonic stem cells. Importantly, stem cell-derived cells isolated using the biomarker panel successfully integrate and mature into new rod photoreceptors in the adult mouse retinae after subretinal transplantation. Conversely, unsorted or negatively selected cells do not give rise to newly integrated rods after transplantation. The biomarker panel also removes detrimental proliferating cells prior to transplantation. Notably, we demonstrate how expression of the biomarker panel is conserved in the human retina and propose that a similar selection strategy will facilitate isolation of human transplantation-competent cells for therapeutic application. Stem Cells 2015;33:2469-2482

Moving from evidence-based medicine to evidence-based health.

While evidence-based medicine (EBM) has advanced medical practice, the health care system has been inconsistent in translating EBM into improvements in health. Disparities in health and health care play out through patients' limited ability to incorporate the advances of EBM into their daily lives. Assisting patients to self-manage their chronic conditions and paying attention to unhealthy community factors could be added to EBM to create a broader paradigm of evidence-based health. A perspective of evidence-based health may encourage physicians to consider their role in upstream efforts to combat socially patterned chronic disease