Biomechanical mechanism for transitions in phase and frequency of arm and leg swing during walking

As humans increase walking speed, there are concurrent transitions in the frequency ratio between arm and leg movements from 2:1 to 1:1 and in the phase relationship between the movements of the two arms from in-phase to out-of-phase. Superharmonic resonance of a pendulum with monofrequency excitation had been proposed as a potential model for this phenomenon. In this study, an alternative model of paired pendulums with multiple-frequency excitations is explored. It was predicted that the occurrence of the concurrent transitions was a function of (1) changes in the magnitude ratio of shoulder accelerations at step and stride frequencies that accompany changes in walking speed and (2) proximity of these frequencies to the natural resonance frequencies of the arms modeled as a pair of passive pendulums. Model predictions were compared with data collected from 14 healthy young subjects who were instructed to walk on a treadmill. Walking speeds were manipulated between 0.18 and 1.52 m/s in steps of 0.22 m/s. Kinematic data for the arms and shoulders were collected using a 3D motion analysis system, and simulations were conducted in which the movements of a double-pendulum system excited by the accelerations at the suspension point were analyzed to determine the extent to which the arms acted as passive pendulums. It was confirmed that the acceleration waveforms at the shoulder are composed primarily of stride and step frequency components. Between the shoulders, the stride frequency components were out-of-phase, while the step frequency components were in-phase. The amplitude ratio of the acceleration waveform components at the step and stride frequencies changed as a function of walking speed and were associated with the occurrence of the transitions. Simulation results using these summed components as excitatory inputs to the double-pendulum system were in agreement with actual transitions in 80% of the cases. The potential role of state-dependent active muscle contraction at shoulder joints on the occurrence of the transitions was discussed. Due to the tendency of arm movements to stay in the vicinity of their primary resonance frequency, these active muscle forces were hypothesized to function as escapements that created limit cycle oscillations at the shoulder’s resonant frequency.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/47437/1/422_2004_Article_503.pd

Effect of timing of hip extension assistance during loaded walking with a soft exosuit

Background: Recent advances in wearable robotic devices have demonstrated the ability to reduce the metabolic cost of walking by assisting the ankle joint. To achieve greater gains in the future it will be important to determine optimal actuation parameters and explore the effect of assisting other joints. The aim of the present work is to investigate how the timing of hip extension assistance affects the positive mechanical power delivered by an exosuit and its effect on biological joint power and metabolic cost during loaded walking. In this study, we evaluated 4 different hip assistive profiles with different actuation timings: early-start-early-peak (ESEP), early-start-late-peak (ESLP), late-start-early-peak (LSEP), late-start-late-peak (LSLP). Methods: Eight healthy participants walked on a treadmill at a constant speed of 1.5 m · s-1 while carrying a 23 kg backpack load. We tested five different conditions: four with the assistive profiles described above and one unpowered condition where no assistance was provided. We evaluated participants’ lower limb kinetics, kinematics, metabolic cost and muscle activation. Results: The variation of timing in the hip extension assistance resulted in a different amount of mechanical power delivered to the wearer across conditions; with the ESLP condition providing a significantly higher amount of positive mechanical power (0.219 ± 0.006 W · kg-1) with respect to the other powered conditions. Biological joint power was significantly reduced at the hip (ESEP and ESLP) and at the knee (ESEP, ESLP and LSEP) with respect to the unpowered condition. Further, all assistive profiles significantly reduced the metabolic cost of walking compared to the unpowered condition by 5.7 ± 1.5 %, 8.5 ± 0.9 %, 6.3 ± 1.4 % and 7.1 ± 1.9 % (mean ± SE for ESEP, ESLP, LSEP, LSLP, respectively). Conclusions: The highest positive mechanical power delivered by the soft exosuit was reported in the ESLP condition, which showed also a significant reduction in both biological hip and knee joint power. Further, the ESLP condition had the highest average metabolic reduction among the powered conditions. Future work on autonomous hip exoskeletons may incorporate these considerations when designing effective control strategies. Electronic supplementary material The online version of this article (doi:10.1186/s12984-016-0196-8) contains supplementary material, which is available to authorized users

Consistent phenological shifts in the making of a biodiversity hotspot: the Cape flora

Background The best documented survival responses of organisms to past climate change on short (glacial-interglacial) timescales are distributional shifts. Despite ample evidence on such timescales for local adaptations of populations at specific sites, the long-term impacts of such changes on evolutionary significant units in response to past climatic change have been little documented. Here we use phylogenies to reconstruct changes in distribution and flowering ecology of the Cape flora - South Africa's biodiversity hotspot - through a period of past (Neogene and Quaternary) changes in the seasonality of rainfall over a timescale of several million years. Results Forty-three distributional and phenological shifts consistent with past climatic change occur across the flora, and a comparable number of clades underwent adaptive changes in their flowering phenology (9 clades; half of the clades investigated) as underwent distributional shifts (12 clades; two thirds of the clades investigated). Of extant Cape angiosperm species, 14-41% have been contributed by lineages that show distributional shifts consistent with past climate change, yet a similar proportion (14-55%) arose from lineages that shifted flowering phenology. Conclusions Adaptive changes in ecology at the scale we uncover in the Cape and consistent with past climatic change have not been documented for other floras. Shifts in climate tolerance appear to have been more important in this flora than is currently appreciated, and lineages that underwent such shifts went on to contribute a high proportion of the flora's extant species diversity. That shifts in phenology, on an evolutionary timescale and on such a scale, have not yet been detected for other floras is likely a result of the method used; shifts in flowering phenology cannot be detected in the fossil record

Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas

This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin

Spatial Organization and Molecular Correlation of Tumor-Infiltrating Lymphocytes Using Deep Learning on Pathology Images

Beyond sample curation and basic pathologic characterization, the digitized H&E-stained images of TCGA samples remain underutilized. To highlight this resource, we present mappings of tumorinfiltrating lymphocytes (TILs) based on H&E images from 13 TCGA tumor types. These TIL maps are derived through computational staining using a convolutional neural network trained to classify patches of images. Affinity propagation revealed local spatial structure in TIL patterns and correlation with overall survival. TIL map structural patterns were grouped using standard histopathological parameters. These patterns are enriched in particular T cell subpopulations derived from molecular measures. TIL densities and spatial structure were differentially enriched among tumor types, immune subtypes, and tumor molecular subtypes, implying that spatial infiltrate state could reflect particular tumor cell aberration states. Obtaining spatial lymphocytic patterns linked to the rich genomic characterization of TCGA samples demonstrates one use for the TCGA image archives with insights into the tumor-immune microenvironment

Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context

Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts