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Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing

Linnorm is a novel normalization and transformation method for the analysis of single cell RNA sequencing (scRNA-seq) data. Linnorm is developed to remove technical noises and simultaneously preserve biological variations in scRNA-seq data, such that existing statistical methods can be improved. Using real scRNA-seq data, we compared Linnorm with existing normalization methods, including NODES, SAMstrt, SCnorm, scran, DESeq and TMM. Linnorm shows advantages in speed, technical noise removal and preservation of cell heterogeneity, which can improve existing methods in the discovery of novel subtypes, pseudo-temporal ordering of cells, clustering analysis, etc. Linnorm also performs better than existing DEG analysis methods, including BASiCS, NODES, SAMstrt, Seurat and DESeq2, in false positive rate control and accuracy.

ContributorsYip, Shun H. (Author) / Wang, Panwen (Author) / Kocher, Jean-Pierre A. (Author) / Sham, Pak Chung (Author) / Wang, Junwen (Author) / College of Health Solutions (Contributor)
Created2017-09-18
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Description

Periodicities (repeating patterns) are observed in many human behaviors. Their strength may capture untapped patterns that incorporate sleep, sedentary, and active behaviors into a single metric indicative of better health. We present a framework to detect periodicities from longitudinal wrist-worn accelerometry data. GENEActiv accelerometer data were collected from 20 participants

Periodicities (repeating patterns) are observed in many human behaviors. Their strength may capture untapped patterns that incorporate sleep, sedentary, and active behaviors into a single metric indicative of better health. We present a framework to detect periodicities from longitudinal wrist-worn accelerometry data. GENEActiv accelerometer data were collected from 20 participants (17 men, 3 women, aged 35–65) continuously for 64.4±26.2 (range: 13.9 to 102.0) consecutive days. Cardiometabolic risk biomarkers and health-related quality of life metrics were assessed at baseline. Periodograms were constructed to determine patterns emergent from the accelerometer data. Periodicity strength was calculated using circular autocorrelations for time-lagged windows. The most notable periodicity was at 24 h, indicating a circadian rest-activity cycle; however, its strength varied significantly across participants. Periodicity strength was most consistently associated with LDL-cholesterol (r’s = 0.40–0.79, P’s < 0.05) and triglycerides (r’s = 0.68–0.86, P’s < 0.05) but also associated with hs-CRP and health-related quality of life, even after adjusting for demographics and self-rated physical activity and insomnia symptoms. Our framework demonstrates a new method for characterizing behavior patterns longitudinally which captures relationships between 24 h accelerometry data and health outcomes.

ContributorsBuman, Matthew (Author) / Hu, Feiyan (Author) / Newman, Eamonn (Author) / Smeaton, Alan F. (Author) / Epstein, Dana R. (Author) / College of Health Solutions (Contributor)
Created2016-01-04
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Description

Myoelectric artificial limbs can significantly advance the state of the art in prosthetics, since they can be used to control mechatronic devices through muscular activity in a way that mimics how the subjects used to activate their muscles before limb loss. However, surveys indicate that dissatisfaction with the functionality of

Myoelectric artificial limbs can significantly advance the state of the art in prosthetics, since they can be used to control mechatronic devices through muscular activity in a way that mimics how the subjects used to activate their muscles before limb loss. However, surveys indicate that dissatisfaction with the functionality of terminal devices underlies the widespread abandonment of prostheses. We believe that one key factor to improve acceptability of prosthetic devices is to attain human likeness of prosthesis movements, a goal which is being pursued by research on social and human–robot interactions. Therefore, to reduce early abandonment of terminal devices, we propose that controllers should be designed so as to ensure effective task accomplishment in a natural fashion. In this work, we have analyzed and compared the performance of three types of myoelectric controller algorithms based on surface electromyography to control an underactuated and multi-degrees of freedom prosthetic hand, the SoftHand Pro.

The goal of the present study was to identify the myoelectric algorithm that best mimics the native hand movements. As a preliminary step, we first quantified the repeatability of the SoftHand Pro finger movements and identified the electromyographic recording sites for able-bodied individuals with the highest signal-to-noise ratio from two pairs of muscles, i.e., flexor digitorum superficialis/extensor digitorum communis, and flexor carpi radialis/extensor carpi ulnaris. Able-bodied volunteers were then asked to execute reach-to-grasp movements, while electromyography signals were recorded from flexor digitorum superficialis/extensor digitorum communis as this was identified as the muscle pair characterized by high signal-to-noise ratio and intuitive control. Subsequently, we tested three myoelectric controllers that mapped electromyography signals to position of the SoftHand Pro. We found that a differential electromyography-to-position mapping ensured the highest coherence with hand movements. Our results represent a first step toward a more effective and intuitive control of myoelectric hand prostheses.

ContributorsFani, Simone (Author) / Bianchi, Matteo (Author) / Jain, Sonal (Author) / Simoes Pimenta Neto, Jose (Author) / Boege, Scott (Author) / Grioli, Giorgio (Author) / Bicchi, Antonio (Author) / Santello, Marco (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-10-17
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Description

Background: Falls are a major public health concern in older adults. Recent fall prevention guidelines recommend the use of multifactorial fall prevention programs (FPPs) that include exercise for community-dwelling older adults; however, the availability of sustainable, community-based FPPs is limited.

Methods: We conducted a 24-week quasi-experimental study to evaluate the efficacy

Background: Falls are a major public health concern in older adults. Recent fall prevention guidelines recommend the use of multifactorial fall prevention programs (FPPs) that include exercise for community-dwelling older adults; however, the availability of sustainable, community-based FPPs is limited.

Methods: We conducted a 24-week quasi-experimental study to evaluate the efficacy of a community-based, multifactorial FPP [Stay in Balance (SIB)] on dynamic and functional balance and muscular strength. The SIB program was delivered by allied health students and included a health education program focused on fall risk factors and a progressive exercise program emphasizing lower-extremity strength and balance. All participants initially received the 12-week SIB program, and participants were non-randomly assigned at baseline to either continue the SIB exercise program at home or as a center-based program for an additional 12 weeks. Adults aged 60 and older (n = 69) who were at-risk of falling (fall history or 2+ fall risk factors) were recruited to participate. Mixed effects repeated measures using Statistical Application Software Proc Mixed were used to examine group, time, and group-by-time effects on dynamic balance (8-Foot Up and Go), functional balance (Berg Balance Scale), and muscular strength (30 s chair stands and 30 s arm curls). Non-normally distributed outcome variables were log-transformed.

Results: After adjusting for age, gender, and body mass index, 8-Foot Up and Go scores, improved significantly over time [F(2,173) = 8.92, p = 0.0; T0 − T2 diff = 1.2 (1.0)]. Berg Balance Scores [F(2,173) = 29.0, p < 0.0001; T0 − T2 diff = 4.96 (0.72)], chair stands [F(2,171) = 10.17, p < 0.0001; T0 − T2 diff = 3.1 (0.7)], and arm curls [F(2,171) = 12.7, p < 0.02; T0 − T2 diff = 2.7 (0.6)] also all improved significantly over time. There were no significant group-by-time effects observed for any of the outcomes.

Conclusion: The SIB program improved dynamic and functional balance and muscular strength in older adults at-risk for falling. Our findings indicate continuing home-based strength and balance exercises at home after completion of a center-based FPP program may be an effective and feasible way to maintain improvements in balance and strength parameters.

ContributorsDer Ananian, Cheryl (Author) / Mitros, Melanie (Author) / Buman, Matthew (Author) / College of Health Solutions (Contributor)
Created2017-02-27
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Description

Introduction: Options currently available to individuals with upper limb loss range from prosthetic hands that can perform many movements, but require more cognitive effort to control, to simpler terminal devices with limited functional abilities. We attempted to address this issue by designing a myoelectric control system to modulate prosthetic hand

Introduction: Options currently available to individuals with upper limb loss range from prosthetic hands that can perform many movements, but require more cognitive effort to control, to simpler terminal devices with limited functional abilities. We attempted to address this issue by designing a myoelectric control system to modulate prosthetic hand posture and digit force distribution.

Methods: We recorded surface electromyographic (EMG) signals from five forearm muscles in eight able-bodied subjects while they modulated hand posture and the flexion force distribution of individual fingers. We used a support vector machine (SVM) and a random forest regression (RFR) to map EMG signal features to hand posture and individual digit forces, respectively. After training, subjects performed grasping tasks and hand gestures while a computer program computed and displayed online feedback of all digit forces, in which digits were flexed, and the magnitude of contact forces. We also used a commercially available prosthetic hand, the i-Limb (Touch Bionics), to provide a practical demonstration of the proposed approach’s ability to control hand posture and finger forces.

Results: Subjects could control hand pose and force distribution across the fingers during online testing. Decoding success rates ranged from 60% (index finger pointing) to 83–99% for 2-digit grasp and resting state, respectively. Subjects could also modulate finger force distribution.

Discussion: This work provides a proof of concept for the application of SVM and RFR for online control of hand posture and finger force distribution, respectively. Our approach has potential applications for enabling in-hand manipulation with a prosthetic hand.

ContributorsGailey, Alycia (Author) / Artemiadis, Panagiotis (Author) / Santello, Marco (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2017-02-01
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Description

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6Clow and Ly6Chi) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E2 is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene

Two distinct monocyte (Mo)/macrophage (Mp) subsets (Ly6Clow and Ly6Chi) orchestrate cardiac recovery process following myocardial infarction (MI). Prostaglandin (PG) E2 is involved in the Mo/Mp-mediated inflammatory response, however, the role of its receptors in Mos/Mps in cardiac healing remains to be determined. Here we show that pharmacological inhibition or gene ablation of the Ep3 receptor in mice suppresses accumulation of Ly6Clow Mos/Mps in infarcted hearts. Ep3 deletion in Mos/Mps markedly attenuates healing after MI by reducing neovascularization in peri-infarct zones. Ep3 deficiency diminishes CX3C chemokine receptor 1 (CX3CR1) expression and vascular endothelial growth factor (VEGF) secretion in Mos/Mps by suppressing TGFβ1 signaling and subsequently inhibits Ly6Clow Mos/Mps migration and angiogenesis. Targeted overexpression of Ep3 receptors in Mos/Mps improves wound healing by enhancing angiogenesis. Thus, the PGE2/Ep3 axis promotes cardiac healing after MI by activating reparative Ly6Clow Mos/Mps, indicating that Ep3 receptor activation may be a promising therapeutic target for acute MI.

ContributorsTang, Juan (Author) / Shen, Yujun (Author) / Chen, Guilin (Author) / Wan, Qiangyou (Author) / Wang, Kai (Author) / Zhang, Jian (Author) / Qin, Jing (Author) / Liu, Guizhu (Author) / Zuo, Shengkai (Author) / Tao, Bo (Author) / Yu, Yu (Author) / Wang, Junwen (Author) / Lazarus, Michael (Author) / Yu, Ying (Author) / College of Health Solutions (Contributor)
Created2017-03-03
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Description

The concept of postural synergies of the human hand has been shown to potentially reduce complexity in the neuromuscular control of grasping. By merging this concept with soft robotics approaches, a multi degrees of freedom soft-synergy prosthetic hand [SoftHand-Pro (SHP)] was created. The mechanical innovation of the SHP enables adaptive

The concept of postural synergies of the human hand has been shown to potentially reduce complexity in the neuromuscular control of grasping. By merging this concept with soft robotics approaches, a multi degrees of freedom soft-synergy prosthetic hand [SoftHand-Pro (SHP)] was created. The mechanical innovation of the SHP enables adaptive and robust functional grasps with simple and intuitive myoelectric control from only two surface electromyogram (sEMG) channels. However, the current myoelectric controller has very limited capability for fine control of grasp forces. We addressed this challenge by designing a hybrid-gain myoelectric controller that switches control gains based on the sensorimotor state of the SHP. This controller was tested against a conventional single-gain (SG) controller, as well as against native hand in able-bodied subjects. We used the following tasks to evaluate the performance of grasp force control: (1) pick and place objects with different size, weight, and fragility levels using power or precision grasp and (2) squeezing objects with different stiffness. Sensory feedback of the grasp forces was provided to the user through a non-invasive, mechanotactile haptic feedback device mounted on the upper arm. We demonstrated that the novel hybrid controller enabled superior task completion speed and fine force control over SG controller in object pick-and-place tasks. We also found that the performance of the hybrid controller qualitatively agrees with the performance of native human hands.

ContributorsFu, Qiushi (Author) / Santello, Marco (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2018-01-10
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Description

Modeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple TFs, is still challenging. In this study, we introduced an integrative method, LogicTRN, to decode TF–TF interactions that form TF

Modeling of transcriptional regulatory networks (TRNs) has been increasingly used to dissect the nature of gene regulation. Inference of regulatory relationships among transcription factors (TFs) and genes, especially among multiple TFs, is still challenging. In this study, we introduced an integrative method, LogicTRN, to decode TF–TF interactions that form TF logics in regulating target genes. By combining cis-regulatory logics and transcriptional kinetics into one single model framework, LogicTRN can naturally integrate dynamic gene expression data and TF-DNA-binding signals in order to identify the TF logics and to reconstruct the underlying TRNs. We evaluated the newly developed methodology using simulation, comparison and application studies, and the results not only show their consistence with existing knowledge, but also demonstrate its ability to accurately reconstruct TRNs in biological complex systems.

ContributorsYan, Bin (Author) / Guan, Daogang (Author) / Wang, Chao (Author) / Wang, Junwen (Author) / He, Bing (Author) / Qin, Jing (Author) / Boheler, Kenneth R. (Author) / Lu, Aiping (Author) / Zhang, Ge (Author) / Zhu, Hailong (Author) / College of Health Solutions (Contributor)
Created2017-10-19
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Description

Biological and robotic grasp and manipulation are undeniably similar at the level of mechanical task performance. However, their underlying fundamental biological vs. engineering mechanisms are, by definition, dramatically different and can even be antithetical. Even our approach to each is diametrically opposite: inductive science for the study of biological systems

Biological and robotic grasp and manipulation are undeniably similar at the level of mechanical task performance. However, their underlying fundamental biological vs. engineering mechanisms are, by definition, dramatically different and can even be antithetical. Even our approach to each is diametrically opposite: inductive science for the study of biological systems vs. engineering synthesis for the design and construction of robotic systems. The past 20 years have seen several conceptual advances in both fields and the quest to unify them. Chief among them is the reluctant recognition that their underlying fundamental mechanisms may actually share limited common ground, while exhibiting many fundamental differences. This recognition is particularly liberating because it allows us to resolve and move beyond multiple paradoxes and contradictions that arose from the initial reasonable assumption of a large common ground. Here, we begin by introducing the perspective of neuromechanics, which emphasizes that real-world behavior emerges from the intimate interactions among the physical structure of the system, the mechanical requirements of a task, the feasible neural control actions to produce it, and the ability of the neuromuscular system to adapt through interactions with the environment. This allows us to articulate a succinct overview of a few salient conceptual paradoxes and contradictions regarding under-determined vs. over-determined mechanics, under- vs. over-actuated control, prescribed vs. emergent function, learning vs. implementation vs. adaptation, prescriptive vs. descriptive synergies, and optimal vs. habitual performance. We conclude by presenting open questions and suggesting directions for future research. We hope this frank and open-minded assessment of the state-of-the-art will encourage and guide these communities to continue to interact and make progress in these important areas at the interface of neuromechanics, neuroscience, rehabilitation and robotics.

Created2017-10-09
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Description

Human physical interactions can be intrapersonal, e.g., manipulating an object bimanually, or interpersonal, e.g., transporting an object with another person. In both cases, one or two agents are required to coordinate their limbs to attain the task goal. We investigated the physical coordination of two hands during an object-balancing task

Human physical interactions can be intrapersonal, e.g., manipulating an object bimanually, or interpersonal, e.g., transporting an object with another person. In both cases, one or two agents are required to coordinate their limbs to attain the task goal. We investigated the physical coordination of two hands during an object-balancing task performed either bimanually by one agent or jointly by two agents. The task consisted of a series of static (holding) and dynamic (moving) phases, initiated by auditory cues. We found that task performance of dyads was not affected by different pairings of dominant and non-dominant hands. However, the spatial configuration of the two agents (side-by-side vs. face-to-face) appears to play an important role, such that dyads performed better side-by-side than face-to-face. Furthermore, we demonstrated that only individuals with worse solo performance can benefit from interpersonal coordination through physical couplings, whereas the better individuals do not. The present work extends ongoing investigations on human-human physical interactions by providing new insights about factors that influence dyadic performance. Our findings could potentially impact several areas, including robotic-assisted therapies, sensorimotor learning and human performance augmentation.

ContributorsMojtahedi, Keivan (Author) / Fu, Qiushi (Author) / Santello, Marco (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2017-11-07