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Background: Carpal tunnel syndrome (CTS) is a compression neuropathy of the median nerve that results in sensorimotor deficits in the hand. Until recently, the effects of CTS on hand function have been studied using mostly two-digit grip tasks. The purpose of this study was to investigate the coordination of multi-digit forces

Background: Carpal tunnel syndrome (CTS) is a compression neuropathy of the median nerve that results in sensorimotor deficits in the hand. Until recently, the effects of CTS on hand function have been studied using mostly two-digit grip tasks. The purpose of this study was to investigate the coordination of multi-digit forces as a function of object center of mass (CM) during whole-hand grasping.

Methods: Fourteen CTS patients and age- and gender-matched controls were instructed to grasp, lift, hold, and release a grip device with five digits for seven consecutive lifts while maintaining its vertical orientation. The object CM was changed by adding a mass at different locations at the base of the object. We measured forces and torques exerted by each digit and object kinematics and analyzed modulation of these variables to object CM at object lift onset and during object hold. Our task requires a modulation of digit forces at and after object lift onset to generate a compensatory moment to counteract the external moment caused by the added mass and to minimize object tilt.

Results: We found that CTS patients learned to generate a compensatory moment and minimized object roll to the same extent as controls. However, controls fully exploited the available degrees of freedom (DoF) in coordinating their multi-digit forces to generate a compensatory moment, i.e., digit normal forces, tangential forces, and the net center of pressure on the finger side of the device at object lift onset and during object hold. In contrast, patients modulated only one of these DoFs (the net center of pressure) to object CM by modulating individual normal forces at object lift onset. During object hold, however, CTS patients were able to modulate digit tangential force distribution to object CM.

Conclusions: Our findings suggest that, although CTS did not affect patients’ ability to perform our manipulation task, it interfered with the modulation of specific grasp control variables. This phenomenon might be indicative of a lower degree of flexibility of the sensorimotor system in CTS to adapt to grasp task conditions.

ContributorsZhang, Wei (Author) / Johnston, Jamie A. (Author) / Ross, Mark A. (Author) / Coakley, Brandon J. (Author) / Gleason, Elizabeth A. (Author) / Dueck, Amylou C. (Author) / Santello, Marco (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2012-11-21
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Description

Studies on anticipatory planning of object manipulation showed initial task failure (i.e., object roll) when visual object shape cues are incongruent with other visual cues, such as weight distribution/density (e.g., symmetrically shaped object with an asymmetrical density). This suggests that shape cues override density cues. However, these studies typically only

Studies on anticipatory planning of object manipulation showed initial task failure (i.e., object roll) when visual object shape cues are incongruent with other visual cues, such as weight distribution/density (e.g., symmetrically shaped object with an asymmetrical density). This suggests that shape cues override density cues. However, these studies typically only measured forces, with digit placement constrained. Recent evidence suggests that when digit placement is unconstrained, subjects modulate digit forces and placement. Thus, unconstrained digit placement might be modulated on initial trials (since it is an explicit process), but not forces (since it is an implicit process). We tested whether shape and density cues would differentially influence anticipatory planning of digit placement and forces during initial trials of a two-digit object manipulation task. Furthermore, we tested whether shape cues would override density cues when cues are incongruent. Subjects grasped and lifted an object with the aim of preventing roll. In Experiment 1, the object was symmetrically shaped, but with asymmetrical density (incongruent cues). In Experiment 2, the object was asymmetrical in shape and density (congruent cues). In Experiment 3, the object was asymmetrically shaped, but with symmetrical density (incongruent cues). Results showed differential modulation of digit placement and forces (modulation of load force but not placement), but only when shape and density cues were congruent. When shape and density cues were incongruent, we found collinear digit placement and symmetrical force sharing. This suggests that congruent and incongruent shape and density cues differentially influence anticipatory planning of digit forces and placement. Furthermore, shape cues do not always override density cues. A continuum of visual cues, such as those alluding to shape and density, need to be integrated.

ContributorsLee-Miller, Trevor (Author) / Marneweck, Michelle (Author) / Santello, Marco (Author) / Gordon, Andrew M. (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-04-21
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Description

In this study, we present a novel methodology to infer indel parameters from multiple sequence alignments (MSAs) based on simulations. Our algorithm searches for the set of evolutionary parameters describing indel dynamics which best fits a given input MSA. In each step of the search, we use parametric bootstraps and

In this study, we present a novel methodology to infer indel parameters from multiple sequence alignments (MSAs) based on simulations. Our algorithm searches for the set of evolutionary parameters describing indel dynamics which best fits a given input MSA. In each step of the search, we use parametric bootstraps and the Mahalanobis distance to estimate how well a proposed set of parameters fits input data. Using simulations, we demonstrate that our methodology can accurately infer the indel parameters for a large variety of plausible settings. Moreover, using our methodology, we show that indel parameters substantially vary between three genomic data sets: Mammals, bacteria, and retroviruses. Finally, we demonstrate how our methodology can be used to simulate MSAs based on indel parameters inferred from real data sets.

ContributorsLevy Karin, Eli (Author) / Rabin, Avigayel (Author) / Ashkenazy, Haim (Author) / Shkedy, Dafna (Author) / Avram, Oren (Author) / Cartwright, Reed (Author) / Pupko, Tal (Author) / Biodesign Institute (Contributor)
Created2015-11-03
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Description

Mathematical models of infectious diseases are a valuable tool in understanding the mechanisms and patterns of disease transmission. It is, however, a difficult subject to teach, requiring both mathematical expertise and extensive subject-matter knowledge of a variety of disease systems. In this article, we explore several uses of zombie epidemics

Mathematical models of infectious diseases are a valuable tool in understanding the mechanisms and patterns of disease transmission. It is, however, a difficult subject to teach, requiring both mathematical expertise and extensive subject-matter knowledge of a variety of disease systems. In this article, we explore several uses of zombie epidemics to make mathematical modeling and infectious disease epidemiology more accessible to public health professionals, students, and the general public. We further introduce a web-based simulation, White Zed (http://cartwrig.ht/apps/whitezed/), that can be deployed in classrooms to allow students to explore models before implementing them. In our experience, zombie epidemics are familiar, approachable, flexible, and an ideal way to introduce basic concepts of infectious disease epidemiology.

ContributorsLofgren, Eric T. (Author) / Collins, Kristy M. (Author) / Smith, Tara C. (Author) / Cartwright, Reed (Author) / College of Liberal Arts and Sciences (Contributor)
Created2016-03
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Description

Mutation is the ultimate source of all genetic variation and is, therefore, central to evolutionary change. Previous work on Paramecium tetraurelia found an unusually low germline base-substitution mutation rate in this ciliate. Here, we tested the generality of this result among ciliates using Tetrahymena thermophila. We sequenced the genomes of

Mutation is the ultimate source of all genetic variation and is, therefore, central to evolutionary change. Previous work on Paramecium tetraurelia found an unusually low germline base-substitution mutation rate in this ciliate. Here, we tested the generality of this result among ciliates using Tetrahymena thermophila. We sequenced the genomes of 10 lines of T. thermophila that had each undergone approximately 1,000 generations of mutation accumulation (MA). We applied an existing mutation-calling pipeline and developed a new probabilistic mutation detection approach that directly models the design of an MA experiment and accommodates the noise introduced by mismapped reads. Our probabilistic mutation-calling method provides a straightforward way of estimating the number of sites at which a mutation could have been called if one was present, providing the denominator for our mutation rate calculations. From these methods, we find that T. thermophila has a germline base-substitution mutation rate of 7.61 × 10 -12 per-site, per cell division, which is consistent with the low base-substitution mutation rate in P. tetraurelia. Over the course of the evolution experiment, genomic exclusion lines derived from the MA lines experienced a fitness decline that cannot be accounted for by germline base-substitution mutations alone, suggesting that other genetic or epigenetic factors must be involved. Because selection can only operate to reduce mutation rates based upon the "visible" mutational load, asexual reproduction with a transcriptionally silent germline may allow ciliates to evolve extremely low germline mutation rates.

ContributorsLong, Hongan (Author) / Winter, David (Author) / Chang, Allan Y.-C. (Author) / Sung, Way (Author) / Wu, Steven (Author) / Balboa, Mariel (Author) / Azevedo, Ricardo B. R. (Author) / Cartwright, Reed (Author) / Lynch, Michael (Author) / Zufall, Rebecca A. (Author) / Biodesign Institute (Contributor)
Created2016-09-15
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Description

Humans are able to intuitively exploit the shape of an object and environmental constraints to achieve stable grasps and perform dexterous manipulations. In doing that, a vast range of kinematic strategies can be observed. However, in this work we formulate the hypothesis that such ability can be described in terms

Humans are able to intuitively exploit the shape of an object and environmental constraints to achieve stable grasps and perform dexterous manipulations. In doing that, a vast range of kinematic strategies can be observed. However, in this work we formulate the hypothesis that such ability can be described in terms of a synergistic behavior in the generation of hand postures, i.e., using a reduced set of commonly used kinematic patterns. This is in analogy with previous studies showing the presence of such behavior in different tasks, such as grasping. We investigated this hypothesis in experiments performed by six subjects, who were asked to grasp objects from a flat surface. We quantitatively characterized hand posture behavior from a kinematic perspective, i.e., the hand joint angles, in both pre-shaping and during the interaction with the environment. To determine the role of tactile feedback, we repeated the same experiments but with subjects wearing a rigid shell on the fingertips to reduce cutaneous afferent inputs. Results show the persistence of at least two postural synergies in all the considered experimental conditions and phases. Tactile impairment does not alter significantly the first two synergies, and contact with the environment generates a change only for higher order Principal Components. A good match also arises between the first synergy found in our analysis and the first synergy of grasping as quantified by previous work. The present study is motivated by the interest of learning from the human example, extracting lessons that can be applied in robot design and control. Thus, we conclude with a discussion on implications for robotics of our findings.

ContributorsDella Santina, Cosimo (Author) / Bianchi, Matteo (Author) / Averta, Giuseppe (Author) / Ciotti, Simone (Author) / Arapi, Visar (Author) / Fani, Simone (Author) / Battaglia, Edoardo (Author) / Giuseppe Catalano, Manuel (Author) / Santello, Marco (Author) / Bicchi, Antonio (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2017-08-29
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Description

Theoretical perspectives on anticipatory planning of object manipulation have traditionally been informed by studies that have investigated kinematics (hand shaping and digit position) and kinetics (forces) in isolation. This poses limitations on our understanding of the integration of such domains, which have recently been shown to be strongly interdependent. Specifically,

Theoretical perspectives on anticipatory planning of object manipulation have traditionally been informed by studies that have investigated kinematics (hand shaping and digit position) and kinetics (forces) in isolation. This poses limitations on our understanding of the integration of such domains, which have recently been shown to be strongly interdependent. Specifically, recent studies revealed strong covariation of digit position and load force during the loading phase of two-digit grasping. Here, we determined whether such digit force-position covariation is a general feature of grasping. We investigated the coordination of digit position and forces during five-digit whole-hand manipulation of an object with a variable mass distribution. Subjects were instructed to prevent object roll during the lift. As found in precision grasping, there was strong trial-to-trial covariation of digit position and force. This suggests that the natural variation of digit position that is compensated for by trial-to-trial variation in digit forces is a fundamental feature of grasp control, and not only specific to precision grasp. However, a main difference with precision grasping was that modulation of digit position to the object’s mass distribution was driven predominantly by the thumb, with little to no modulation of finger position. Modulation of thumb position rather than fingers is likely due to its greater range of motion and therefore adaptability to object properties. Our results underscore the flexibility of the central nervous system in implementing a range of solutions along the digit force-to-position continuum for dexterous manipulation.

ContributorsMarneweck, Michelle (Author) / Lee-Miller, Trevor (Author) / Santello, Marco (Author) / Gordon, Andrew M. (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-09-15
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Description

Of particular interest to the neuroscience and robotics communities is the understanding of how two humans could physically collaborate to perform motor tasks such as holding a tool or moving it across locations. When two humans physically interact with each other, sensory consequences and motor outcomes are not entirely predictable

Of particular interest to the neuroscience and robotics communities is the understanding of how two humans could physically collaborate to perform motor tasks such as holding a tool or moving it across locations. When two humans physically interact with each other, sensory consequences and motor outcomes are not entirely predictable as they also depend on the other agent’s actions. The sensory mechanisms involved in physical interactions are not well understood. The present study was designed (1) to quantify human–human physical interactions where one agent (“follower”) has to infer the intended or imagined—but not executed—direction of motion of another agent (“leader”) and (2) to reveal the underlying strategies used by the dyad. This study also aimed at verifying the extent to which visual feedback (VF) is necessary for communicating intended movement direction. We found that the control of leader on the relationship between force and motion was a critical factor in conveying his/her intended movement direction to the follower regardless of VF of the grasped handle or the arms. Interestingly, the dyad’s ability to communicate and infer movement direction with significant accuracy improved (>83%) after a relatively short amount of practice. These results indicate that the relationship between force and motion (interpreting as arm impedance modulation) may represent an important means for communicating intended movement direction between biological agents, as indicated by the modulation of this relationship to intended direction. Ongoing work is investigating the application of the present findings to optimize communication of high-level movement goals during physical interactions between biological and non-biological agents.

ContributorsMojtahedi, Keivan (Author) / Whitsell, Bryan (Author) / Artemiadis, Panagiotis (Author) / Santello, Marco (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2017-04-13
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Description

The most common evolutionary events at the molecular level are single-base substitutions, as well as insertions and deletions (indels) of short DNA segments. A large body of research has been devoted to develop probabilistic substitution models and to infer their parameters using likelihood and Bayesian approaches. In contrast, relatively little

The most common evolutionary events at the molecular level are single-base substitutions, as well as insertions and deletions (indels) of short DNA segments. A large body of research has been devoted to develop probabilistic substitution models and to infer their parameters using likelihood and Bayesian approaches. In contrast, relatively little has been done to model indel dynamics, probably due to the difficulty in writing explicit likelihood functions. Here, we contribute to the effort of modeling indel dynamics by presenting SpartaABC, an approximate Bayesian computation (ABC) approach to infer indel parameters from sequence data (either aligned or unaligned). SpartaABC circumvents the need to use an explicit likelihood function by extracting summary statistics from simulated sequences. First, summary statistics are extracted from the input sequence data. Second, SpartaABC samples indel parameters from a prior distribution and uses them to simulate sequences. Third, it computes summary statistics from the simulated sets of sequences. By computing a distance between the summary statistics extracted from the input and each simulation, SpartaABC can provide an approximation to the posterior distribution of indel parameters as well as point estimates. We study the performance of our methodology and show that it provides accurate estimates of indel parameters in simulations. We next demonstrate the utility of SpartaABC by studying the impact of alignment errors on the inference of positive selection. A C ++ program implementing SpartaABC is freely available in http://spartaabc.tau.ac.il.

ContributorsLevy Karin, Eli (Author) / Shkedy, Dafna (Author) / Ashkenazy, Haim (Author) / Cartwright, Reed (Author) / Pupko, Tal (Author) / Biodesign Institute (Contributor)
Created2017-05-01
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Description

The human hand has so many degrees of freedom that it may seem impossible to control. A potential solution to this problem is “synergy control” which combines dimensionality reduction with great flexibility. With applicability to a wide range of tasks, this has become a very popular concept. In this review,

The human hand has so many degrees of freedom that it may seem impossible to control. A potential solution to this problem is “synergy control” which combines dimensionality reduction with great flexibility. With applicability to a wide range of tasks, this has become a very popular concept. In this review, we describe the evolution of the modern concept using studies of kinematic and force synergies in human hand control, neurophysiology of cortical and spinal neurons, and electromyographic (EMG) activity of hand muscles. We go beyond the often purely descriptive usage of synergy by reviewing the organization of the underlying neuronal circuitry in order to propose mechanistic explanations for various observed synergy phenomena. Finally, we propose a theoretical framework to reconcile important and still debated concepts such as the definitions of “fixed” vs. “flexible” synergies and mechanisms underlying the combination of synergies for hand control.

ContributorsSantello, Marco (Author) / Baud-Bovy, Gabriel (Author) / Jorntell, Henrik (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2013-04-08