Open Access Publications

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Open access publications by faculty, postdocs, and graduate students in the Department of Biomedical Engineering.

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The Role of Sleep in Memory Consolidation and Reading in Dyslexia
(Journal of Cognitive Neuroscience, 2025-03-01) Solbi, Ali; Earle, F. Sayako
Dyslexia is a neurodevelopmental disorder characterized by reading difficulty, which has long been attributed to a phonological processing deficit. However, recent research suggests that general difficulties with learning and memory, but also in memory consolidation, may underlie disordered reading. This review article provides an overview of the relationship between learning and memory, memory consolidation during sleep, and reading and explores the emerging literature on consolidation during sleep in individuals with dyslexia. We consider evidence that sleep appears to be less effective for memory consolidation in children with dyslexia and how this may be related to their deficits in reading. This discussion highlights the need for further research to determine the extent to which atypical sleep patterns may contribute to learning deficits associated with disordered reading.
Osteocyte Dendrites: How Do They Grow, Mature, and Degenerate in Mineralized Bone?
(Cytoskeleton, 2024-12-09) Guerra, Rosa M.; Fowler, Velia M.; Wang, Liyun
Osteocytes, the most abundant bone cells, form an extensive cellular network via interconnecting dendrites. Like neurons in the brain, the long-lived osteocytes perceive mechanical and biological inputs and signal to other effector cells, leading to the homeostasis and turnover of bone tissues. Despite the appreciation of osteocytes' vital roles in bone biology, the initiation, growth, maintenance, and eventual degradation of osteocyte dendrites are poorly understood due to their full encasement by mineralized matrix. With the advancement of imaging modalities and genetic models, the architectural organization and molecular composition of the osteocyte dendrites, as well as their morphological changes with aging and diseases, have begun to be revealed. However, several long-standing mysteries remain unsolved, including (1) how the dendrites are initiated and elongated when a surface osteoblast becomes embedded as an osteocyte; (2) how the dendrites maintain a relatively stable morphology during their decades-long life span; (3) what biological processes control the dendrite morphology, connectivity, and stability; and (4) if these processes are influenced by age, sex, hormones, and mechanical loading. Our review of long, thin actin filament (F-actin)-containing processes extending from other cells leads to a working model that serves as a starting point to investigate the formation and maintenance of osteocyte dendrites and their degradation with aging and diseases.
Mechanical Properties of the Cortex in Older Adults and Relationships With Personality Traits
(Human Brain Mapping, 2025-02-06) Twohy, Kyra E.; Kramer, Mary K.; Diano, Alexa M.; Bailey, Olivia M.; Delgorio, Peyton L.; McIlvain, Grace; McGarry, Matthew D. J.; Martens, Christopher R.; Schwarb, Hillary; Hiscox, Lucy V.; Johnson, Curtis L.
Aging and neurodegeneration impact structural brain integrity and can result in changes to behavior and cognition. Personality, a relatively stable trait in adults as compared to behavior, in part relies on normative individual differences in cellular organization of the cerebral cortex, but links between brain structure and personality expression have been mixed. One key finding is that personality has been shown to be a risk factor in the development of Alzheimer's disease, highlighting a structure–trait relationship. Magnetic resonance elastography (MRE) has been used to noninvasively study age-related changes in tissue mechanical properties because of its high sensitivity to both the microstructural health and the structure–function relationship of the tissue. Recent advancements in MRE methodology have allowed for reliable property recovery of cortical subregions, which had previously presented challenges due to the complex geometry and overall thin structure. This study aimed to quantify age-related changes in cortical mechanical properties and the relationship of these properties to measures of personality in an older adult population (N = 57; age 60–85 years) for the first time. Mechanical properties including shear stiffness and damping ratio were calculated for 30 bilateral regions of the cortex across all four lobes, and the NEO Personality Inventory (NEO-PI) was used to measure neuroticism and conscientiousness in all participants. Shear stiffness and damping ratio were found to vary widely across regions of the cortex, upward of 1 kPa in stiffness and by 0.3 in damping ratio. Shear stiffness changed regionally with age, with some regions experiencing accelerated degradation compared to neighboring regions. Greater neuroticism (i.e., the tendency to experience negative emotions and vulnerability to stress) was associated with high damping ratio, indicative of poorer tissue integrity, in the rostral middle frontal cortex and the precentral gyrus. This study provides evidence of structure–trait correlates between physical mechanical properties and measures of personality in older adults and adds to the supporting literature that neurotic traits may impact brain health in cognitively normal aging.
MRI-based whole-brain elastography and volumetric measurements to predict brain age
(Biology Methods and Protocols, 2024-11-20) Claros-Olivares, Claudio Cesar; Clements, Rebecca G.; McIlvain, Grace; Johnson, Curtis L.; Brockmeier, Austin J.
Brain age, as a correlate of an individual’s chronological age obtained from structural and functional neuroimaging data, enables assessing developmental or neurodegenerative pathology relative to the overall population. Accurately inferring brain age from brain magnetic resonance imaging (MRI) data requires imaging methods sensitive to tissue health and sophisticated statistical models to identify the underlying age-related brain changes. Magnetic resonance elastography (MRE) is a specialized MRI technique which has emerged as a reliable, non-invasive method to measure the brain’s mechanical properties, such as the viscoelastic shear stiffness and damping ratio. These mechanical properties have been shown to change across the life span, reflect neurodegenerative diseases, and are associated with individual differences in cognitive function. Here, we aim to develop a machine learning framework to accurately predict a healthy individual’s chronological age from maps of brain mechanical properties. This framework can later be applied to understand neurostructural deviations from normal in individuals with neurodevelopmental or neurodegenerative conditions. Using 3D convolutional networks as deep learning models and more traditional statistical models, we relate chronological age as a function of multiple modalities of whole-brain measurements: stiffness, damping ratio, and volume. Evaluations on held-out subjects show that combining stiffness and volume in a multimodal approach achieves the most accurate predictions. Interpretation of the different models highlights important regions that are distinct between the modalities. The results demonstrate the complementary value of MRE measurements in brain age models, which, in future studies, could improve model sensitivity to brain integrity differences in individuals with neuropathology.
Actin Polymerization Status Regulates Tenocyte Homeostasis Through Myocardin-Related Transcription Factor-A
(Cytoskeleton, 2024-11-27) West, Valerie C.; Owen, Kaelyn E.; Inguito, Kameron L.; Ebron, Karl Matthew M.; Reiner, Tori N.; Mirack, Chloe E.; Le, Christian H.; Marqueti, Rita de Cassia; Snipes, Steven; Mousavizadeh, Rouhollah; King, Rylee E.; Elliott, Dawn M.; Parreno, Justin
The actin cytoskeleton is a potent regulator of tenocyte homeostasis. However, the mechanisms by which actin regulates tendon homeostasis are not entirely known. This study examined the regulation of tenocyte molecule expression by actin polymerization via the globular (G-) actin-binding transcription factor, myocardin-related transcription factor-a (MRTF). We determined that decreasing the proportion of G-actin in tenocytes by treatment with TGFβ1 increases nuclear MRTF. These alterations in actin polymerization and MRTF localization coincided with favorable alterations to tenocyte gene expression. In contrast, latrunculin A increases the proportion of G-actin in tenocytes and reduces nuclear MRTF, causing cells to acquire a tendinosis-like phenotype. To parse out the effects of F-actin depolymerization from regulation by MRTF, we treated tenocytes with cytochalasin D. Exposure of cells to cytochalasin D increases the proportion of G-actin in tenocytes. However, as compared to latrunculin A, cytochalasin D has a differential effect on MRTF localization by increasing nuclear MRTF. This led to an opposing effect on the regulation of a subset of genes. The differential regulation of genes by latrunculin A and cytochalasin D suggests that actin signals through MRTF to regulate a specific subset of genes. By targeting the deactivation of MRTF through the inhibitor CCG1423, we verify that MRTF regulates Type I Collagen, Tenascin C, Scleraxis, and α-smooth muscle actin in tenocytes. Actin polymerization status is a potent regulator of tenocyte homeostasis through the modulation of several downstream pathways, including MRTF. Understanding the regulation of tenocyte homeostasis by actin may lead to new therapeutic interventions against tendinopathies, such as tendinosis.
Muscular, temporal, and spatial responses to shoulder exosuit assistance during functional tasks
(Journal of Neurophysiology, 2024-11-01) Burch, Kaleb; Higginson, Jill
Shoulder exosuits are a promising new technology that could enable individuals with neuromuscular impairments to independently perform activities of daily living, however, scarce evidence exists to evaluate their ability to support such activities. Consequently, it is not understood how humans adapt motion in response to assistance from a shoulder exosuit. In this study, we developed a cable-driven shoulder exosuit and evaluated its effect on reaching and drinking tasks within a cohort of 18 healthy subjects to quantify changes to muscle activity and kinematics as well as trial-to-trial learning in duration and actuator switch timing. The exosuit successfully reduced mean muscle activity in the middle (reaching: 23.4 ± 26.3%, drinking: 20.0 ± 25.1%) and posterior (reaching: 12.8 ± 10.3%, drinking: 4.0 ± 7.2%) deltoid across both functional tasks. Likewise, the exosuit reduced integrated muscle activity in the middle deltoid (reaching: 22.2 ± 22.7%, drinking: 14.9 ± 27.0%). Exosuit assistance also altered kinematics such that individuals allowed their arms to follow forces applied by the exosuit. In terms of learning, subjects reduced movement duration by 15.6 ± 11.9% as they practiced using the exosuit. Reducing movement duration allowed subjects to reduce integrated muscle activity in the anterior (15.2 ± 10.3%), middle (14.7 ± 9.7%), and posterior (14.8 ± 9.7%) deltoids. Similarly, subjects activated the actuator switch earlier over the course of many assisted trials. The muscle activity reductions during both reaching and drinking demonstrate the promise of shoulder exosuits to enable independent function among individuals with neuromuscular impairments. The kinematic response to assistance and learning features observed in movement duration provide insight into human-exosuit interaction principles that could inform future exosuit development. NEW & NOTEWORTHY Shoulder exosuits assist arm function, but it is not understood how assistance affects motion. We evaluated spatiotemporal movement features and muscle activity during assisted and unassisted arm motions. Introducing the exosuit caused individuals to let their arms follow assistive forces. Furthermore, individuals learned to use the exosuit with practice by moving more quickly to reduce cumulative effort and by activating assistance earlier. These results demonstrate that individuals adapt exosuit-assisted motion to reduce effort.
Transforming CO2 into advanced 3D printed carbon nanocomposites
(Nature Communications, 2024-12-04) Crandall, Bradie S.; Naughton, Matthew; Park, Soyeon; Yu, Jia; Zhang, Chunyan; Mahtabian, Shima; Wang, Kaiying; Liang, Xinhua; Fu, Kelvin; Jiao, Feng
The conversion of CO2 emissions into valuable 3D printed carbon-based materials offers a transformative strategy for climate mitigation and resource utilization. Here, we 3D print carbon nanocomposites from CO2 using an integrated system that electrochemically converts CO2 into CO, followed by a thermocatalytic process that synthesizes carbon nanotubes (CNTs) which are then 3D printed into high-density carbon nanocomposites. A 200 cm2 electrolyzer stack is integrated with a thermochemical reactor for more than 45 h of operation, cumulatively synthesizing 37 grams of CNTs from CO2. A techno-economic analysis indicates a 90% cost reduction in CNT production on an industrial scale compared to current benchmarks, underscoring the commercial viability of the system. A 3D printing process is developed that achieves a high nanocomposite CNT concentration (38 wt%) while enhancing composite structural attributes via CNT alignment. With the rapidly rising demand for carbon nanocomposites, this CO2-to-nanocomposite process can make a substantial impact on global carbon emission reduction efforts.
Design and Evaluation of 3D-Printed Lattice Structures as High Flow Rate Aerosol Filters
(ACS Applied Engineering Materials, 2024-12-11) Yu, Yinkui; Zhang, Ning; Hoffman, Dominic; Rastogi, Dewansh; Woodward, Ian R.; Fromen, Catherine A.
Aerosol contamination presents significant challenges across various industries, ranging from healthcare to manufacturing. Over the past few years, open foam filters have gained prominence for their ability to efficiently capture particles while allowing reasonable airflow. In this work, we present the use of 3D-printed idealized open foam-like lattice structures as aerosol filtration media, leveraging advances in additive manufacturing to generate these highly tunable and modular filters. Using parametric design approaches, we fabricated lattice filters with four different unit cell geometries (Cubic, Kelvin, Octahedron, and Weaire–Phelan) via Digital Light Synthesis 3D printing and characterized these structures with X-ray microcomputed tomography. We compared the aerosol filtration performance of the different lattice unit cell geometries using 1 μm polystyrene latex (PSL) aerosol particles, finding the filtration performance to be positively correlated with the single-unit-cell specific surface area. We then expanded our evaluation of deposition efficiency in Kelvin cell lattice structures of varied porosities, again finding a correlation between the specific surface area and deposition performance. Experimental analysis confirmed that deposition primarily occurs through impaction and electrostatic mechanisms within the parameter space. Overall, our findings demonstrate that unit-cell-based lattices can achieve a wide range of aerosol filtration efficiencies (∼10–100%) across various operating conditions (1–4 m/s superficial velocity), offering a highly tunable in-line filtration medium capable of maintaining high efficiency even at elevated airflow rates. This work not only provides essential guidelines for designing and manufacturing 3D-printed lattices as customizable aerosol filters but also highlights the current limitations and challenges in producing these structures.
Zonal patterning of extracellular matrix and stromal cell populations along a perfusable cellular microchannel
(Lab on a Chip, 2024-10-21) Chernokal, Brea; Ferrick, Bryan J.; Gleghorn, Jason P.
The spatial organization of biophysical and biochemical cues in the extracellular matrix (ECM) in concert with reciprocal cell–cell signaling is vital to tissue patterning during development. However, elucidating the role an individual microenvironmental factor plays using existing in vivo models is difficult due to their inherent complexity. In this work, we have developed a microphysiological system to spatially pattern the biochemical, biophysical, and stromal cell composition of the ECM along an epithelialized 3D microchannel. This technique is adaptable to multiple hydrogel compositions and scalable to the number of zones patterned. We confirmed that the methodology to create distinct zones resulted in a continuous, annealed hydrogel with regional interfaces that did not hinder the transport of soluble molecules. Further, the interface between hydrogel regions did not disrupt microchannel structure, epithelial lumen formation, or media perfusion through an acellular or cellularized microchannel. Finally, we demonstrated spatially patterned tubulogenic sprouting of a continuous epithelial tube into the surrounding hydrogel confined to local regions with stromal cell populations, illustrating spatial control of cell–cell interactions and signaling gradients. This easy-to-use system has wide utility for modeling three-dimensional epithelial and endothelial tissue interactions with heterogeneous hydrogel compositions and/or stromal cell populations to investigate their mechanistic roles during development, homeostasis, or disease.
Global and local identifiability analysis of a nonlinear biphasic constitutive model in confined compression
(Journal of the Royal Society Interface, 2024-11-13) Peloquin, John M.; Elliott, Dawn M.
Application of biomechanical models relies on model parameters estimated from experimental data. Parameter non-identifiability, when the same model output can be produced by many sets of parameter values, introduces severe errors yet has received relatively little attention in biomechanics and is subtle enough to remain unnoticed in the absence of deliberate verification. The present work develops a global identifiability analysis method in which cluster analysis and singular value decomposition are applied to vectors of parameter–output variable correlation coefficients. This method provides a visual representation of which specific experimental design elements are beneficial or harmful in terms of parameter identifiability, supporting the correction of deficiencies in the test protocol prior to testing physical specimens. The method was applied to a representative nonlinear biphasic model for cartilaginous tissue, demonstrating that confined compression data does not provide identifiability for the biphasic model parameters. This result was confirmed by two independent analyses: local analysis of the Hessian of a sum-of-squares error cost function and observation of the behaviour of two optimization algorithms. Therefore, confined compression data are insufficient for the calibration of general-purpose biphasic models. Identifiability analysis by these or other methods is strongly recommended when planning future experiments.
Conjugation of Antibodies and siRNA Duplexes to Polymer Nanoparticles via Maleimide–Thiol Chemistry
(ACS Omega, 2024-11-18) Hoover, Elise C.; Chowdhury, Chitran Roy; Ruggiero, Olivia M.; Day, Emily S.
Polymeric nanoparticles (NPs) have shown great promise as highly modifiable platforms that can be applied across many different disease states. They are advantageous because they can encapsulate a range of hydrophobic and hydrophilic cargoes while having customizable surface properties. Depending on the desired biointerfacing capabilities, the surface of polymeric NPs can be modified with moieties, such as antibodies, peptides, nucleic acids, and more. The work presented here is intended to provide mechanistic insight into how different parameters influence the loading of antibodies, small interfering ribonucleic acids (siRNAs), or both on the surface of poly(lactic-co-glycolic acid) (PLGA) NPs via maleimide–thiol chemistry. Some of the conjugation parameters investigated include the buffer concentration, maleimide to protein ratio, and the addition of an excipient such as Tween-20. Through variation in the concentration of FZD7 antibodies added to the reaction mixture, we established tunable conjugation and found the upper limit of their loading density under the conditions tested. We also confirmed antibody conjugation through two different mechanisms: via a thiol-modified antibody or a thiol-modified poly(ethylene glycol) (PEG) linker. Conjugation of thiolated siRNA duplexes targeting β-catenin was also investigated through variations in both Tween-20 concentration and CaCl2 buffer concentration. Finally, the coconjugation of both antibodies and siRNA duplexes was explored. Overall, this work outlines a basis for tunable biomolecule loading on polymer NPs using maleimide–thiol chemistry and reveals the incredible versatility of polymer NP platforms.
Sequestration of gene products by decoys enhances precision in the timing of intracellular events
(Scientific Reports, 2024-11-08) Biswas, Kuheli; Dey, Supravat; Singh, Abhyudai
Expressed gene products often interact ubiquitously with binding sites at nucleic acids and macromolecular complexes, known as decoys. The binding of transcription factors (TFs) to decoys can be crucial in controlling the stochastic dynamics of gene expression. Here, we explore the impact of decoys on the timing of intracellular events, as captured by the time taken for the levels of a given TF to reach a critical threshold level, known as the first passage time (FPT). Although nonlinearity introduced by binding makes exact mathematical analysis challenging, employing suitable approximations and reformulating FPT in terms of an alternative variable, we analytically assess the impact of decoys. The stability of the decoy-bound TFs against degradation impacts FPT statistics crucially. Decoys reduce noise in FPT, and stable decoy-bound TFs offer greater timing precision with less expression cost than their unstable counterparts. Interestingly, when both bound and free TFs decay at the same rate, decoy binding does not directly alter FPT noise. We verify these results by performing exact stochastic simulations. These results have important implications for the precise temporal scheduling of events involved in the functioning of biomolecular clocks, development processes, cell-cycle control, and cell-size homeostasis.
We Will, We Will Shock You: Adaptive Versus Conventional Functional Electrical Stimulation in Individuals Post-Stroke
(Journal of Biomechanical Engineering, 2024-09-30) Donlin, Margo C.; Higginson, Jill S.
Functional electrical stimulation (FES) is often used in poststroke gait rehabilitation to address decreased walking speed, foot drop, and decreased forward propulsion. However, not all individuals experience clinically meaningful improvements in gait function with stimulation. Previous research has developed adaptive functional electrical stimulation (AFES) systems that adjust stimulation timing and amplitude at every stride to deliver optimal stimulation. The purpose of this work was to determine the effects of a novel AFES system on functional gait outcomes and compare them to the effects of the existing FES system. Twenty-four individuals with chronic poststroke hemiparesis completed 64-min walking trials on an adaptive and fixed-speed treadmill with no stimulation, stimulation from the existing FES system, and stimulation from the AFES system. There was no significant effect of stimulation condition on walking speed, peak dorsiflexion angle, or peak propulsive force. Walking speed was significantly faster and peak propulsive force was significantly larger on the adaptive treadmill (ATM) than the fixed-speed treadmill (both p < 0.0001). Dorsiflexor stimulation timing was similar between stimulation conditions, but plantarflexor stimulation timing was significantly improved with the AFES system compared to the FES system (p = 0.0059). Variability between and within subjects was substantial, and some subjects experienced clinically meaningful improvements in walking speed, peak dorsiflexion angle, and peak propulsive force. However, not all subjects experienced benefits, suggesting that further research to characterize which subjects exhibit the best instantaneous response to FES is needed to optimize poststroke gait rehabilitation using FES.
Self-assembled thin films as alternative surface textures in assistive aids with users who are blind
(Journal of Materials Chemistry B, 2024-09-05) Swain, Zachary; Derkaloustian, Maryanne; Hepler, Kayla A.; Nolin, Abigail; Damani, Vidhika S.; Bhattacharyya, Pushpita; Shrestha, Tulaja; Medina, Jared; Kayser, Laure V.; Dhong, Charles B.
Current tactile graphics primarily render tactile information for blind users through physical features, such as raised bumps or lines. However, the variety of distinctive physical features that can be created is effectively saturated, and alternatives to these physical features are not currently available for static tactile aids. Here, we explored the use of chemical modification through self-assembled thin films to generate distinctive textures in tactile aids. We used two silane precursors, n-butylaminopropyltrimethoxysilane and n-pentyltrichlorosilane, to coat playing card surfaces and investigated their efficacy as a tactile coating. We verified the surface coating process and examined their durability to repeated use by traditional materials characterization and custom mesoscale friction testing. Finally, we asked participants who were both congenitally blind and braille-literate to sort the cards based on touch. We found that participants were able to identify the correct coated card with 82% accuracy, which was significantly above chance, and two participants achieved 100% accuracy. This success with study participants demonstrates that surface coatings and surface modifications might augment or complement physical textures in next-generation tactile aids.
Roles and interplay of reinforcement-based and error-based processes during reaching and gait in neurotypical adults and individuals with Parkinson’s disease
(PLoS Computational Biology, 2024-10-14) Roth, Adam M.; Buggeln, John H.; Hoh, Joanna E.; Wood, Jonathan M.; Sullivan, Seth R.; Ngo, Truc T.; Calalo, Jan A.; Lokesh, Rakshith; Morton, Susanne M.; Grill, Stephen; Jeka, John J.; Carter, Michael J.; Cashaback, Joshua G. A.
From a game of darts to neurorehabilitation, the ability to explore and fine tune our movements is critical for success. Past work has shown that exploratory motor behaviour in response to reinforcement (reward) feedback is closely linked with the basal ganglia, while movement corrections in response to error feedback is commonly attributed to the cerebellum. While our past work has shown these processes are dissociable during adaptation, it is unknown how they uniquely impact exploratory behaviour. Moreover, converging neuroanatomical evidence shows direct and indirect connections between the basal ganglia and cerebellum, suggesting that there is an interaction between reinforcement-based and error-based neural processes. Here we examine the unique roles and interaction between reinforcement-based and error-based processes on sensorimotor exploration in a neurotypical population. We also recruited individuals with Parkinson’s disease to gain mechanistic insight into the role of the basal ganglia and associated reinforcement pathways in sensorimotor exploration. Across three reaching experiments, participants were given either reinforcement feedback, error feedback, or simultaneously both reinforcement & error feedback during a sensorimotor task that encouraged exploration. Our reaching results, a re-analysis of a previous gait experiment, and our model suggests that in isolation, reinforcement-based and error-based processes respectively boost and suppress exploration. When acting in concert, we found that reinforcement-based and error-based processes interact by mutually opposing one another. Finally, we found that those with Parkinson’s disease had decreased exploration when receiving reinforcement feedback, supporting the notion that compromised reinforcement-based processes reduces the ability to explore new motor actions. Understanding the unique and interacting roles of reinforcement-based and error-based processes may help to inform neurorehabilitation paradigms where it is important to discover new and successful motor actions. Author summary Reinforcement-based and error-based processes play a pivotal role in regulating our movements. Converging neuroanatomical evidence show interconnected reinforcement-based and error-based neural circuits. Yet is unclear how reinforcement-based and error-based processes interact to influence sensorimotor behavior. In our past work we showed that reinforcement-based and error-based processes are dissociable. Building on this work, here we show that these process can also interact to influence trial-by-trial sensorimotor behaviour.
A Moments-Based Analytical Approach for Cell Size Homeostasis
(IEEE Control Systems Letters, 2024-06-07) Nieto, César; Vargas-Garcia, Cesar Augusto; Singh, Abhyudai
This contribution explores mechanisms that regulate the dynamics of single-cell size, maintaining equilibrium around a target set point. Using the formalism of Stochastic Hybrid Systems (SHS), we consider continuous exponential growth in cell size (as determined by volume/mass/surface area). This continuous-time evolution is interspersed by cell division events that occur randomly as per a given size-dependent rate, and upon division, only one of the two daughter cells is tracked. We show that a size-independent division rate does not provide cell size homeostasis, in the sense that the variance in cell size increases unboundedly over time. Next, we consider a division rate proportional to cell size that yields the adder size control observed in several bacteria – a constant size is added on average between birth and division regardless of the newborn size. For this scenario, we obtain exact formulas for the steady-state moments (mean, variance, and skewness) of cell size. Expanding the SHS model, we explore a biologically relevant scenario where the time between successive division events is further divided into multiple discrete stages with size-dependent stage transitions. Exact moment computations demonstrate that increasing the number of stages reduces cell size variability (noise). We also find formulas considering uneven size partitioning between daughters during division, and where the division rate follows a power law of the cell size leading to deviations from adder size control. This letter provides a method for estimating model parameters from observed cell size distributions and enhances our understanding of mechanisms underlying cell size regulation.
Comparing single- and multi-post labeling delays for the measurements of resting cerebral and hippocampal blood flow for cerebrovascular testing in midlife adults
(Frontiers in Physiology, 2024-10-01) Decker, Kevin P.; Sanjana, Faria; Rizzi, Nick; Kramer, Mary K.; Cerjanic, Alexander M.; Johnson, Curtis L.; Martens, Christopher R.
Objectives: To assess the reliability and validity of measuring resting cerebral blood flow (CBF) and hippocampal CBF using a single-post-labeling delay (PLD) and a multi-PLD pseudo-continuous arterial spin labeling (pCASL) protocol for cerebrovascular reactivity (CVR) testing. Methods: 25 healthy, midlife adults (57 ± 4 years old) were imaged in a Siemens Prisma 3T magnetic resonance imaging (MRI) scanner. Resting CBF and hippocampal CBF were assessed using two pCASL protocols, our modified single-PLD protocol (pCASL-MOD) to accommodate the needs for CVR testing and the multi-PLD Human Connectome Project (HCP) Lifespan protocol to serve as the reference control (pCASL-HCP). During pCASL-MOD, CVR was calculated as the change in CBF from rest to hypercapnia (+9 mmHg increase in end-tidal partial pressure of carbon dioxide [PETCO2]) and then normalized for PETCO2. The reliability and validity in resting gray matter (GM) CBF, white matter (WM) CBF, and hippocampal CBF between pCASL-MOD and pCASL-HCP protocols were examined using correlation analyses, paired t-tests, and Bland Altman plots. Results: The pCASL-MOD and pCASL-HCP protocols were significantly correlated for resting GM CBF [r = 0.72; F (1, 23) = 25.24, p < 0.0001], WM CBF [r = 0.57; F (1, 23) = 10.83, p = 0.003], and hippocampal CBF [r = 0.77; F (1, 23) = 32.65, p < 0.0001]. However, pCASL-MOD underestimated resting GM CBF (pCASL-MOD: 53.7 ± 11.1 v. pCASL-HCP: 69.1 ± 13.1 mL/100 g/min; p < 0.0001), WM CBF (pCASL-MOD: 32.4 ± 4.8 v. pCASL-HCP: 35.5 ± 6.9 mL/100 g/min; p = 0.01), and hippocampal CBF (pCASL-MOD: 50.5 ± 9.0 v. pCASL-HCP: 68.1 ± 12.5 mL/100 g/min; p < 0.0001). PETCO2 increased by 8.0 ± 0.7 mmHg to induce CVR (GM CBF: 4.8% ± 2.6%; WM CBF 2.9% ± 2.5%; and hippocampal CBF: 3.4% ± 3.8%). Conclusion: Our single-PLD pCASL-MOD protocol reliably measured CBF and hippocampal CBF at rest given the significant correlation with the multi-PLD pCASL-HCP protocol. Despite the lower magnitude relative to pCASL-HCP, we recommend using our pCASL-MOD protocol for CVR testing in which an exact estimate of CBF is not required such as the assessment of relative change in CBF to hypercapnia.
Kinetics and Retention of Polystyrenesulfonate for Proteoglycan Replacement in Cartilage
(Biomacromolecules, 2024-08-14) Sundar, Shalini; Koopman, Allison; Manzoni, Thomas J.; Xie, Weiran; Bhatti, Qurat-Ul-Ain; Lo, Chun-Yuan; Damani, Vidhika S.; Yang, Ai Nin; Pochan, Darrin; Parreno, Justin; Engiles, Julie B.; Kayser, Laure V.; Dhong, Charles
Tissue hydration provides articular cartilage with dynamic viscoelastic properties. Early stage osteoarthritis (OA) is marked by loss of proteoglycans and glycosaminoglycans (GAG), lowering fixed charge density, and impairing tissue osmotic function. The most common GAG replacement, chondroitin sulfate (CS), has failed to show effectiveness. Here, we investigated a synthetic polyelectrolyte, poly(styrenesulfonate) (PSS), both as a model compound to investigate polyelectrolyte transport in cartilage, and as a potential candidate to restore bulk fixed charge density in cartilage with GAG loss. Through bovine explants and histology, we determined zonal-based effective diffusion coefficients for three different molecular weights of PSS. Compared to CS, PSS was retained longer in GAG-depleted cartilage in static and compression-based desorption experiments. We explained enhanced solute performance of PSS by its more compact morphology and higher charge density by small-angle X-ray scattering. This study may improve design of GAG mimetic molecules for repairing osmotic function in OA cartilage.
Neural network segmentation of disc volume from magnetic resonance images and the effect of degeneration and spinal level
(JOR Spine, 2024-09-04) Markhali, Milad I.; Peloquin, John M.; Meadows, Kyle D.; Newman, Harrah R.; Elliott, Dawn M.
Background Magnetic resonance imaging (MRI) noninvasively quantifies disc structure but requires segmentation that is both time intensive and susceptible to human error. Recent advances in neural networks can improve on manual segmentation. The aim of this study was to establish a method for automatic slice-wise segmentation of 3D disc volumes from subjects with a wide range of age and degrees of disc degeneration. A U-Net convolutional neural network was trained to segment 3D T1-weighted spine MRI. Methods Lumbar spine MRIs were acquired from 43 subjects (23–83 years old) and manually segmented. A U-Net architecture was trained using the TensorFlow framework. Two rounds of model tuning were performed. The performance of the model was measured using a validation set that did not cross over from the training set. The model version with the best Dice similarity coefficient (DSC) was selected in each tuning round. After model development was complete and a final U-Net model was selected, performance of this model was compared between disc levels and degeneration grades. Results Performance of the final model was equivalent to manual segmentation, with a mean DSC = 0.935 ± 0.014 for degeneration grades I–IV. Neither the manual segmentation nor the U-Net model performed as well for grade V disc segmentation. Compared with the baseline model at the beginning of round 1, the best model had fewer filters/parameters (75%), was trained using only slices with at least one disc-labeled pixel, applied contrast stretching to its input images, and used a greater dropout rate. Conclusion This study successfully trained a U-Net model for automatic slice-wise segmentation of 3D disc volumes from populations with a wide range of ages and disc degeneration. The final trained model is available to support scientific use.
Imidazolium-Based Sulfonating Agent to Control the Degree of Sulfonation of Aromatic Polymers and Enable Plastics-to-Electronics Upgrading
(JACS Au, 2024-07-03) Lo, Chun-Yuan; Koutsoukos, Kelsey P.; Nguyen, Dan My; Wu, Yuhang; Angel Trujillo, David Alejandro; Miller, Tabitha; Shrestha, Tulaja; Mackey, Ethan; Damani, Vidhika S.; Kanbur, Uddhav; Opila, Robert; Martin, David C.; Kaphan, David; Kayser, Laure V.
The accumulation of plastic waste in the environment is a growing environmental, economic, and societal challenge. Plastic upgrading, the conversion of low-value polymers to high-value materials, could address this challenge. Among upgrading strategies, the sulfonation of aromatic polymers is a powerful approach to access high-value materials for a range of applications, such as ion-exchange resins and membranes, electronic materials, and pharmaceuticals. While many sulfonation methods have been reported, achieving high degrees of sulfonation while minimizing side reactions that lead to defects in the polymer chains remains challenging. Additionally, sulfonating agents are most often used in large excess, which prevents precise control over the degree of sulfonation of aromatic polymers and their functionality. Herein, we address these challenges using 1,3-disulfonic acid imidazolium chloride ([Dsim]Cl), a sulfonic acid-based ionic liquid, to sulfonate aromatic polymers and upgrade plastic waste to electronic materials. We show that stoichiometric [Dsim]Cl can effectively sulfonate model polystyrene up to 92% in high yields, with minimal defects and high regioselectivity for the para position. Owing to its high reactivity, the use of substoichiometric [Dsim]Cl uniquely allows for precise control over the degree of sulfonation of polystyrene. This approach is also applicable to a wide range of aromatic polymers, including waste plastic. To prove the utility of our approach, samples of poly(styrene sulfonate) (PSS), obtained from either partially sulfonated polystyrene or expanded polystyrene waste, are used as scaffolds for poly(3,4-ethylenedioxythiophene) (PEDOT) to form the ubiquitous conductive material PEDOT:PSS. PEDOT:PSS from plastic waste is subsequently integrated into organic electrochemical transistors (OECTs) or as a hole transport layer (HTL) in a hybrid solar cell and shows the same performance as commercial PEDOT:PSS. This imidazolium-mediated approach to precisely sulfonating aromatic polymers provides a pathway toward upgrading postconsumer plastic waste to high-value electronic materials.

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