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...
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....
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...
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...
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...
One method of cancer treatment is to thermally ablate (destroy) tumor masses using heat caused by electric current, or Joule heating. This particular modality is called radiofrequency ablation (RFA), due to the use of electric currents in the 100 kHz to 800 kHz frequency range. Computationally, RFA is simulated as...
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...
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...
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...
Motor planning is fundamental to the performance of everyday reaching movements. The influence of planning is not limited to voluntary movements but extends to involuntary movements initiated in response to sensory stimuli, such as postural perturbations applied to the arm. Stroke alters voluntary reaching and the involuntary response to perturbations,...
The role of nuclei nanoenvironment in cellular function has been a challenging problem in biology due to the lack of chromatin 3-dimension (3D) structure imaging/capturing techniques and theory connecting physical structure of chromatin to transcription. Recent studies on optical properties measurement on biological sample techniques, nanoscale imaging techniques and chromatin...
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...
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...
Despite improvements to diagnostics and treatment methods, colorectal cancer remains the second leading cause of cancer death in the United States. Colonoscopies, the gold standard for colorectal cancer screening, can significantly increase the patient’s chance of survival through early detection. However, colonoscopy cost, surgical complications, and patient bowel preparations limit...
Neurons are sensitive to the mechanical properties of their environment and show better growth, survival and differentiation when they are cultured in soft environments with mechanical properties similar to those of the brain compared to other tissues. Within the central nervous system (CNS), there is also a range of mechanical...
Maneuvering your limbs requires both accurate commands for how to move, and accurate feedback of their true movements. Conventional prosthetic arms currently lack this sense of proprioceptive feedback, which can make daily tasks difficult without close visual monitoring. Although studies have successfully provided artificial proprioceptive feedback to improve control, this...
Label-free assays, and particularly those based on the combination of mass spectroscopy with surface chemistries, enable high-throughput experiments of a broad range of reactions. However, these methods can still require the incorporation of functional groups that allow immobilization of reactants and products to surfaces prior to analysis. In this thesis,...
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,...
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...
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...
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...
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...
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,...
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...
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...
Decisions in naturalistic environments usually feature delayed and uncertain outcomes that can only be reached after a sequence of actions are performed. For example, canonical stalking and pursuit strategies used by terrestrial predators often involve stages of concealment, pauses where the predator remains motionless, and high speed chase sequences. The...
In nature, materials with complex architectures are formed through hierarchical self-assembly. Therefore, the study and design of hierarchically assembling materials is important in producing materials that mimic biological structures and is a key challenge in biomaterials science and engineering. In articular cartilage, hierarchical assembly of extracellular matrix (ECM) components provides...
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...
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...
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...
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...
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...
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,...
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...
Transplantation is necessary and often the only viable treatment for many forms of end stage organ failure. While advances in immunosuppressive therapies have facilitated largely blocking acute rejection, 5-10 year post-transplant attrition rates have not significantly improved in the past 30 years. The predominant antigen facilitating the alloimmune response is...
Bio-inspired materials have a distinct advantage over other materials by virtue of their mimicry of nature’s own products, which have been subjected to the inimitable tests of time and evolutionary pressure. Here we have taken instruction from natural nanostructures that are ubiquitous across the animal kingdom, namely high-density lipoproteins (HDL)....
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...
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...
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...
Coordinated movement relies on the precise and controlled activation of populations of motor units, which convert the commands of the nervous system into muscle forces. Motor unit firing patterns are often nonlinear and generated through the response to a combination of ionotropic excitatory and inhibitory commands, as well as metabotropic...
Soft materials in nature are formed through programmed self-assembly of biomolecules to create complex architectures and optimized physical properties. It is therefore a key challenge in biomaterials science and engineering to understand the principles that govern the structure and properties of such materials, and the interactions between their different components....
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...
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...
Nanocarriers as structures with at least one dimension in the nanometer scale are capable of loading small molecule therapeutics that would otherwise have poor bioavailability, non- specific uptake, and off target effects. Polymeric nanocarriers can be modified to tune their chemical and biological behavior to better suit the intended application....
Nanocarriers are drug delivery vehicles that have at least one dimension at the nanoscale (10-9 m). Engineering the nanocarrier surface is a strategy for targeting drug delivery to specific cell types to enhance efficacy and minimize side effects. A useful analogy is to consider how the chassis of an automotive...
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...
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...
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...
