Before initiating a walking movement, the central nervous system forms a motor plan, a set of motor commands predicted to accomplish task-specific goals. To be effective, motor plans must be continually updated to consider an ever-changing external environment. Despite being an inherent part of walking, how the nervous system adapts...
Myoelectric pattern recognition-based upper limb prostheses measure electromyographic (EMG) signals from the residual limb and learn to identify muscle activity patterns that correspond to intended gestures. To train an accurate pattern recognition controller, it is essential that the training signals typify signals measured in real-world scenarios. When these conditions are...
Stairs and curbs often present as an exhausting environmental barrier for individuals with bilateral cerebral palsy (CP) due to their lower limb motor impairments. Indeed, performance in stair-climbing in this population has a higher correlation with disruption of mobility than walking. Community members affected by CP consider impaired mobility a...
Like many diseases, atherosclerotic cardiovascular disease is driven by the activity of inflammatory cells. Using molecular imaging to target and analyze populations of inflammatory cells is one promising strategy to non-invasively assess atherosclerosis progression. However, current molecular imaging contrast agents are not suited for such targeted imaging applications. Nanomaterial-based strategies...
Everyday tasks, such as putting on a jacket or reaching up to a shelf, often become more challenging for older adults. These tasks rely on the ability to generate three-dimensional torques about the shoulder and to adapt these torques across activities. Shoulder strength and muscle coordination impact shoulder torque production,...
The current view in neuroscience holds that the brain, together with its sensory and motor structures and the environment, form a closed-loop system – a sensorimotor loop – in which the brain receives information from the environment and converts it into a motor response while simultaneously making predictions about future...
Each neuron in the primary motor cortex (M1) is like a musician in an orchestra, contributing to a larger harmony under the constraint of a “neural manifold”—a geometric score describing the correlated signals produced by the neural musicians that drive movement. Despite the widespread recognition of the importance of M1...
Radiofrequency ablation is a minimally-invasive treatment method that aims to destroy undesired tissue by exposing it to alternating current in the 100 kHz to 800 kHz frequency range and heating it until it is destroyed via coagulative necrosis. Ablation treatment is gaining momentum especially in cancer research, where the undesired...
The dynamics of human joints are fundamental characteristic of the human motor system, and altered joint impedance can hinder mobility. Individuals with transtibial amputation typically experience slower and energetically costly gait, while individuals with chronic stroke experience persisting gait deficits arising from spasticity, hypertonia and paresis. Investigating joint impedance of...
A stroke occurs when blood flow in the brain is impaired and often causes damage to corticospinal tract projections that control the muscles of the upper-extremity. Due to this damage, 50-70% of stroke survivors experience long-term upper-extremity functional deficits(Faria-Fortini, Michaelsen, Cassiano, & Teixeira-Salmela, 2011). These deficits result from motor impairments...
Bioelectronic devices at the biotic/abiotic interface face a number of key challenges that include device degradation when exposed to biological fluid, their elicited immune response due to mechanical mismatch, and poor signal transduction. Organic electronic materials and their devices, such as organic electrochemical transistors (OECTs) address these shortcomings. They can...
4D Flow MRI is a phase-contrast magnetic resonance imaging method that enables direct measurement of velocities in three orthogonal directions throughout the heartbeat. This permits direct quantification of hemodynamic parameters, including flow, mean velocity, peak velocity, and pulsatility, for individual cerebral vessels. Despite ongoing research into neurovascular applications of 4D...
Wireless power strategies are critical to system level implementation of bio-integrated devices. To achieve mechanically robust, manufacturable systems, batteries are often integrated as an on-board power source to support sensing, wireless communication and signal conditioning. Unfortunately, most sources of battery power use hazardous and environmentally harmful materials, which frustrate incorporation...
The goal of the work reported here was to answer two important questions with regards to LTVV use for patients with ARDS: 1) How do we measure adoption? and 2) What are the drivers of provider adoption? To this end, I have demonstrated the influence of patient height, hypoxemia severity,...
Chromatin, a complex nuclear structure comprised of DNA, histones, RNA, and other nuclear proteins, is one of the most critical components within the cell because it houses the genetic information and its organization regulates important cellular functions, such as transcription, replication, and repair. Its structural organization is well understood at...
Vimentin intermediate filaments (VIFs) provide mechanical integrity to cells and serve as markers of tissue origin and cell differentiation. Several non-mechanical roles for vimentin have recently been reported, including regulation of key pathways that control cell growth, cell signaling, and cell motility. Here, I present the role of vimentin in...
Magnetic resonance imaging (MRI) is used widely and frequently in the clinical setting to image and diagnose patients. In addition to the anatomical scans that can be acquired using MRI, different kinds of physiological parameters, such as blood flow, can be obtained by utilizing pulse sequence, scan protocol and post-processing....
Ankle sprains are the most common musculoskeletal injury. After an ankle sprain, about 40% of individuals develop Chronic Ankle Instability (CAI), resulting in recurrent sprains, the ankle giving way, or feelings of instability. Most sprains occur due to excess inversion of the ankle. Frontal-plane ankle stiffness quantifies the ankle’s ability...
Proprioception, or the sense of one’s body in space, provides critical feedback that the brain usesto generate controlled movements. When proprioceptive feedback is lost, people find it difficult
to perform even basic motor tasks. Despite its importance, proprioceptive coding of single
neurons in the cuneate nucleus (CN), the most peripheral...
The last decade has witnessed a rapid transformation in our understanding of the structure of chromatin, the nuclear complex of DNA and its structural proteins. While, barring mutations, the DNA sequence in each cell of the human body is the same, it is the structure of the chromatin complex that...
Optical microscopy is one of the most ubiquitous tools for functional imaging of biological phenomena. While relatively non-destructive to living organisms, light microscopy’s spatial resolution is diffraction limited, restricting the minimum resolvable features. On the other hand, high resolution techniques such as electron microscopy or STORM, have several orders of...
Shoulder (glenohumeral joint) osteoarthritis causes pain, limits daily activities, and frequently requires joint replacement surgery. In shoulder osteoarthritis, the glenoid bone surface erodes in one of two ways: symmetrically (concentric deformity) or asymmetrically (eccentric deformity). Shoulder replacements in patients with eccentric deformities fail and require additional, revision surgery more often...
Cancer progression is a complex process, leading to metastatic spread of primary tumor cells that colonize distant vital organs and mortality if not stopped. Since clinical strategies to stem this progression are still being developed, it is of great importance to detect this end stage metastatic spread as early as...
Single-molecule localization microscopy (SMLM) has significantly stimulated the development of methods to quantitatively visualize and characterize biomolecules in vitro and in situ. SMLM is a class of super-resolution microscopy (SRM) techniques, which exploits the “on-off” switching of individual fluorescent molecules to estimate their location with nanometer precision and offers spatial...
End-stage renal disease, or kidney failure, can result from acute kidney injury or sustained kidney damage in the form of chronic kidney disease. As the prevalence of end-stage renal disease continues to rise, the gold-standard treatment—kidney transplantation—is increasingly restricted by the shortage of transplantable donor kidneys. Bioengineered kidney tissues may...
Microfluidic technologies enable multi-tissue culture and precise control of media exchange and therefore have significant potential to create more complex in vitro models of reproductive systems, including endocrine cycles. However, microfluidic technologies have largely been applied to gamete-level culture in reproductive biology, with very little progress in organ-level culture. Herein...
In environments ranging from natural ecosystems to living organisms, small molecule signals and nanoscale forces communicate important information regarding chemical contamination and pollution, pathogenesis, and physical stressors. As these stimuli are often well below detection limits for our own senses, we depend on biosensing technologies to monitorthem. Many biosensors operate...
Nanocarriers are nanometer-sized (1-1000 nm) structures capable of encapsulating cargo. This encapsulation can drastically alter the pharmacokinetic properties of the cargo, while also allowing for the rational design and engineering of the nanocarrier itself. Poly(ethylene glycol)-block-poly(propylene sulfide) is an amphiphilic diblock copolymer capable of self-assembling into diverse nanocarriers. The purpose...
Nanomaterials are broadly defined as materials that exhibit at least one dimension that is less than 1,000 nm. Encompassed within nanomaterials are a class of constructs known as nanocarriers, which are applied as delivery vehicles for both encapsulated and covalently bound payloads. Poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-b-PPS) is an amphiphilic block...
The shoulder is the most mobile joint in the human body, allowing for the execution of complex and athletic tasks. Unfortunately, such expansive mobility comes at a cost. The shoulder is prone to instability, or painful symptoms associated with increased humeral head translation, and dislocation. To prevent dislocations and maintain...
Nucleic acids such as DNA or RNA of various lengths and structures have a wide scope of functions as therapeutic entities compared to conventional drugs. For instance, native and modified forms of nucleic acids can be used for gene silencing, genome editing, gene replacement, immune system modulation, and theranostics. While...
A one-time, unilateral injury to the developing brain can interrupt the typical process of development and result in motor impairments that evolve over the course of the whole life-span. The timing of injury relative to neural development has implications for the continued refinement of the nervous system and the descending...
Bio-integrated electronics with advanced monitoring capabilities have garnered considerable interest as a means of expanding patient care beyond traditional hospital and clinic settings. These mechanically soft microsystems, many of which are bioresorbable and wireless, have the potential to replace bulky, rigid, and wired medical technologies by matching or exceeding their...
Cancer has long been the second-leading cause of death in the United States and represents the leading cause of death in midlife (age 40-60). While the prognosis for many cancers has vastly improved over the last thirty years, many cancers remain elusive due to the late-onset of symptoms, the specific...
Nanoparticles are nanometer scale (1-1000 nm) structures capable of encapsulating a diverse range of cargoes. Encapsulation of a cargo can drastically alter its pharmacokinetics, cytotoxicity, and biodistribution while allowing for informed and rational design of the nanoparticle itself. Poly(ethylene glycol)-block-poly(propylene sulfide) (PEG-b-PPS) is an amphiphilic diblock co-polymer able to self-assemble...
Found in 1-2% of the population, bicuspid aortic valve (BAV) is the most common congenital cardiovascular disease and is associated with increased risk of aortic valve dysfunction and aortic disease. Current treatment is focused on surgical intervention either after the development of symptomatic aortic stenosis/regurgitation or aortic diameter thresholds. However,...
We have a remarkable ability to perform complex, coordinated movements without much conscious effort. In addition to the computations required to generate commands for muscles, a key aspect of coordinated motor control is incorporating sensory feedback about the movement. One of the most important feedback routes is through proprioception, the...
Chromatin is the biological material that packages our genetic information. In humans, 2 meters of linear DNA is compacted into an approximately 6 μm nucleus. Our DNA is transcribed into RNA, which is then translated into proteins. Cellular phenotype, the composite of all cellular functions, is defined by the entire...
The physical structure of chromatin has recently emerged as a key contributor to genome regulation and cellular function. Chromatin packing dictates the conformation of the 2-meter-long DNA polymer within the ~10 μm cell nucleus. This conformation can influence gene function by regulating the accessibility of molecular regulators to DNA, altering...
Humans have a remarkable ability to create stable walking patterns that can resist and recover from perturbations. Unfortunately, this ability is substantially impaired after a stroke, limiting mobility and contributing to a high fall rate. To facilitate gait training during post-stroke rehabilitation, clinicians often incorporate body-weight support (BWS) systems that...
Atrial fibrillation (AF) is the most common cardiac arrhythmia, and associated with increased risk for ischemic stroke and mortality. While the risk of stroke has been shown to be reduced with the use of oral anticoagulants like Warfarin, these medications are predictably linked with an increased risk of bleeding, and...
Persons with spinal cord injuries can use state-of-the-art brain-computer interfaces to control robotic arms. Despite this high-tech solution, their movements are slow and imprecise, much like those made by individuals who have lost proprioception, the sense of body position and movement. Intracortical microstimulation (ICMS) used to reactivate neural circuits in...
Nucleic acids not only are the building blocks of life but also a class of attractive macromolecular therapeutics. However, the delivery of therapeutic oligonucleotides into cells has been a major challenge due to their large size and highly negatively charged backbone. Spherical nucleic acids (SNAs) are a class of emerging...
Fluorescence microscopy has become a widely used tool in many research areas. However, its spatial resolution, limited to 250 nm by the diffraction limit of light, has restricted direct observation of details of ultrastructural biology. In recent years, spectroscopic single-molecule localization microscopy (sSMLM), one of super-resolution imaging techniques, has been...
Over the past decade, wearables have become pervasive in our lives. Healthcare wearables like a smartwatch continuously monitor personal health status and provide personalized feedback to motivate progress towards medically recommended goals. While present set of on-body electronics empowers users to visualize health status outside of clinic spaces, its traditionally...
Nucleic acid therapeutics can be drug molecules with high programmability, minimal off-target effects, and the capability to address “undruggable” targets for diseases. In addition, each time a new drug is needed, one needs to only change the sequence as opposed to finding an entirely new structure. One nucleic acid type...
Atrial fibrillation (AF) is the most common arrhythmia in adults in the United States. Despite its prevalence, the etiology of AF and its adverse effects are not completely understood, which has made treatment of AF difficult. However, left atrial (LA) fibrosis is associated with worsening and propagating AF. Additionally, research...
We rely on the properties of our skeletal muscles to traverse our world, interact with objects, and complete everyday tasks. The macroscopic properties of muscles that endow us with these abilities arise from the material properties of muscle fibers and the surrounding extracellular matrix (ECM), as well as how they...
Nanocarriers, structures with at least one dimension on the nanoscale (1-1000 nm), have been engineered for delivery of various cargoes. The shape and flexibility of nanocarriers are important parameters that influence their biological performance. Self-assembling polymeric filamentous nanocarriers, known as filomicelles (FM), are of great interest to nanomedicine due to...
We perform many movements every day without much deliberation. However, moving can be seen as a form of decision-making since one of many possible movements must be selected and executed. The decision-making processes that underlie movements are influenced by various factors, including sensory perception, energetics, time, perceived rates of failure...