ASU Scholarship Showcase

Five immunocompetent C57BL/6-cBrd/cBrd/Cr (albino C57BL/6) mice were injected with GL261-luc2 cells, a cell line sharing characteristics of human glioblastoma multiforme (GBM). The mice were imaged using magnetic resonance (MR) at five separate time points to characterize growth and development of the tumor. After 25 days, the final tumor volumes of the mice varied from 12 mm³ to 62 mm³, even though mice were inoculated from the same tumor cell line under carefully controlled conditions. We generated hypotheses to explore large variances in final tumor size and tested them with our simple reaction-diffusion model in both a 3-dimensional (3D) finite difference method and a 2-dimensional (2D) level set method. The parameters obtained from a best-fit procedure, designed to yield simulated tumors as close as possible to the observed ones, vary by an order of magnitude between the three mice analyzed in detail. These differences may reflect morphological and biological variability in tumor growth, as well as errors in the mathematical model, perhaps from an oversimplification of the tumor dynamics or nonidentifiability of parameters. Our results generate parameters that match other experimental in vitro and in vivo measurements. Additionally, we calculate wave speed, which matches with other rat and human measurements.

Background:
Data assimilation refers to methods for updating the state vector (initial condition) of a complex spatiotemporal model (such as a numerical weather model) by combining new observations with one or more prior forecasts. We consider the potential feasibility of this approach for making short-term (60-day) forecasts of the growth and spread of a malignant brain cancer (glioblastoma multiforme) in individual patient cases, where the observations are synthetic magnetic resonance images of a hypothetical tumor.

Results:
We apply a modern state estimation algorithm (the Local Ensemble Transform Kalman Filter), previously developed for numerical weather prediction, to two different mathematical models of glioblastoma, taking into account likely errors in model parameters and measurement uncertainties in magnetic resonance imaging. The filter can accurately shadow the growth of a representative synthetic tumor for 360 days (six 60-day forecast/update cycles) in the presence of a moderate degree of systematic model error and measurement noise.

Conclusions:
The mathematical methodology described here may prove useful for other modeling efforts in biology and oncology. An accurate forecast system for glioblastoma may prove useful in clinical settings for treatment planning and patient counseling.

Plasmodium vivax is the most prevalent malarial species in South America and exerts a substantial burden on the populations it affects. The control and eventual elimination of P. vivax are global health priorities. Genomic research contributes to this objective by improving our understanding of the biology of P. vivax and through the development of new genetic markers that can be used to monitor efforts to reduce malaria transmission. Here we analyze whole-genome data from eight field samples from a region in Cordóba, Colombia where malaria is endemic. We find considerable genetic diversity within this population, a result that contrasts with earlier studies suggesting that P. vivax had limited diversity in the Americas. We also identify a selective sweep around a substitution known to confer resistance to sulphadoxine-pyrimethamine (SP). This is the first observation of a selective sweep for SP resistance in this species. These results indicate that P. vivax has been exposed to SP pressure even when the drug is not in use as a first line treatment for patients afflicted by this parasite. We identify multiple non-synonymous substitutions in three other genes known to be involved with drug resistance in Plasmodium species. Finally, we found extensive microsatellite polymorphisms. Using this information we developed 18 polymorphic and easy to score microsatellite loci that can be used in epidemiological investigations in South America.

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.

Introduction: Fluorescence-guided surgery is one of the rapidly emerging methods of surgical “theranostics.” In this review, we summarize current fluorescence techniques used in neurosurgical practice for brain tumor patients as well as future applications of recent laboratory and translational studies.

Methods: Review of the literature.

Results: A wide spectrum of fluorophores that have been tested for brain surgery is reviewed. Beginning with a fluorescein sodium application in 1948 by Moore, fluorescence-guided brain tumor surgery is either routinely applied in some centers or is under active study in clinical trials. Besides the trinity of commonly used drugs (fluorescein sodium, 5-aminolevulinic acid, and indocyanine green), less studied fluorescent stains, such as tetracyclines, cancer-selective alkylphosphocholine analogs, cresyl violet, acridine orange, and acriflavine, can be used for rapid tumor detection and pathological tissue examination. Other emerging agents, such as activity-based probes and targeted molecular probes that can provide biomolecular specificity for surgical visualization and treatment, are reviewed. Furthermore, we review available engineering and optical solutions for fluorescent surgical visualization. Instruments for fluorescent-guided surgery are divided into wide-field imaging systems and hand-held probes. Recent advancements in quantitative fluorescence-guided surgery are discussed.

Conclusion: We are standing on the threshold of the era of marker-assisted tumor management. Innovations in the fields of surgical optics, computer image analysis, and molecular bioengineering are advancing fluorescence-guided tumor resection paradigms, leading to cell-level approaches to visualization and resection of brain tumors.

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.

Inbreeding in hermaphroditic plants can occur through two different mechanisms: biparental inbreeding, when a plant mates with a related individual, or self-fertilization, when a plant mates with itself. To avoid inbreeding, many hermaphroditic plants have evolved self-incompatibility (SI) systems which prevent or limit self-fertilization. One particular SI system—homomorphic SI—can also reduce biparental inbreeding. Homomorphic SI is found in many angiosperm species, and it is often assumed that the additional benefit of reduced biparental inbreeding may be a factor in the success of this SI system. To test this assumption, we developed a spatially-explicit, individual-based simulation of plant populations that displayed three different types of homomorphic SI. We measured the total level of inbreeding avoidance by comparing each population to a self-compatible population (NSI), and we measured biparental inbreeding avoidance by comparing to a population of self-incompatible plants that were free to mate with any other individual (PSI).

Because biparental inbreeding is more common when offspring dispersal is limited, we examined the levels of biparental inbreeding over a range of dispersal distances. We also tested whether the introduction of inbreeding depression affected the level of biparental inbreeding avoidance. We found that there was a statistically significant decrease in autozygosity in each of the homomorphic SI populations compared to the PSI population and, as expected, this was more pronounced when seed and pollen dispersal was limited. However, levels of homozygosity and inbreeding depression were not reduced. At low dispersal, homomorphic SI populations also suffered reduced female fecundity and had smaller census population sizes. Overall, our simulations showed that the homomorphic SI systems had little impact on the amount of biparental inbreeding in the population especially when compared to the overall reduction in inbreeding compared to the NSI population. With further study, this observation may have important consequences for research into the origin and evolution of homomorphic self-incompatibility systems.

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.

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.

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.