Publications by authors named "Andrew Petersen"

Lithium metal is regarded as the "holy grail" of lithium-ion battery anodes due to its exceptionally high theoretical capacity (3800 mAh g) and lowest possible electrochemical potential (-3.04 V vs Li/Li); however, lithium suffers from the dendritic formation that leads to parasitic reactions and cell failure. In this work, we stabilize fast-charging lithium metal plating/stripping with dual-function alloying -nitrate additives (: Ag, Bi, Ga, In, and Zn).

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Central norepinephrine (NE) neurons, located mainly in the locus coeruleus (LC), are implicated in diverse psychiatric and neurodegenerative diseases and are an emerging target for drug discovery. To facilitate their study, we developed a method to generate 40-60% human LC-NE neurons from human pluripotent stem cells. The approach depends on our identification of ACTIVIN A in regulating LC-NE transcription factors in dorsal rhombomere 1 (r1) progenitors.

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Drug-induced nephrotoxicity is a leading cause of drug attrition, partly due to the limited relevance of pre-clinical models of the proximal tubule. Culturing proximal tubule epithelial cells (PTECs) under fluid flow to mimic physiological shear stress has been shown to improve select phenotypes, but existing flow systems are expensive and difficult to implement by non-experts in microfluidics. Here, we designed and fabricated an accessible and modular flow system for culturing PTECs under physiological shear stress, which induced native-like cuboidal morphology, downregulated pathways associated with hypoxia, stress, and injury, and upregulated xenobiotic metabolism pathways.

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The Middle East plays a central role in human history harbouring a vast diversity of ethnic, cultural and religious groups. However, much remains to be understood about past and present genomic diversity in this region. Here we present a multidisciplinary bioarchaeological analysis of two individuals dated to the late 7th and early 8th centuries, the Umayyad Era, from Tell Qarassa, an open-air site in modern-day Syria.

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Many acquired or inherited forms of heart disease as well as drugs are known to increase the susceptibility of patients to arrhythmias. To predict arrhythmogenic events and discover new therapeutic strategies to mitigate them, approaches to efficiently quantify the velocity of propagation in engineered cardiac tissues are important research tools. In this chapter, we describe how to collect videos of propagating calcium waves in engineered cardiac tissues with a high-speed camera mounted on an inverted fluorescence microscope.

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Modeling age-related neurodegenerative disorders with human stem cells are difficult due to the embryonic nature of stem cell-derived neurons. We developed a chemical cocktail to induce senescence of iPSC-derived neurons to address this challenge. We first screened small molecules that induce embryonic fibroblasts to exhibit features characteristic of aged fibroblasts.

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Gonadotropin-releasing hormone (GnRH) neurons in the hypothalamus play a key role in the regulation of reproductive function. In this study, we sought an efficient method for generating GnRH neurons from human embryonic and induced pluripotent stem cells (hESC and hiPSC, respectively). First, we found that exposure of primitive neuroepithelial cells, rather than neuroprogenitor cells, to fibroblast growth factor 8 (FGF8), was more effective in generating GnRH neurons.

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Bacillus anthracis, the causative agent of anthrax, continues to be a prominent biological warfare and bioterrorism threat. Vaccination is likely to remain the most effective and user-friendly public health measure to counter this threat in the foreseeable future. The commercially available AVA BioThrax vaccine has a number of shortcomings where improvement would lead to a more practical and effective vaccine for use in the case of an exposure event.

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Reprogramming of somatic cells into induced pluripotent stem cells (iPSCs) and their differentiation into neural lineages is a revolutionary experimental system for studying neurological disorders, including intellectual and developmental disabilities (IDDs). However, issues related to variability and reproducibility have hindered translating preclinical findings into drug discovery. Here, we identify areas for improvement by conducting a comprehensive review of 58 research articles that utilized iPSC-derived neural cells to investigate genetically defined IDDs.

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Controlled electrical stimulation is essential for evaluating the physiology of cardiac tissues engineered in heart-on-a-chip devices. However, existing stimulation techniques, such as external platinum electrodes or opaque microelectrode arrays patterned on glass substrates, have limited throughput, reproducibility, or compatibility with other desirable features of heart-on-a-chip systems, such as the use of tunable culture substrates, imaging accessibility, or enclosure in a microfluidic device. In this study, indium tin oxide (ITO), a conductive, semi-transparent, and biocompatible material, was deposited onto glass and polydimethylsiloxane (PDMS)-coated coverslips as parallel or point stimulation electrodes using laser-cut tape masks.

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Contraction of cardiac myocytes depends on energy generated by the mitochondria. During cardiac development and disease, the structure and function of the mitochondrial network in cardiac myocytes is known to remodel in concert with many other factors, including changes in nutrient availability, hemodynamic load, extracellular matrix (ECM) rigidity, cell shape, and maturation of other intracellular structures. However, the independent role of each of these factors on mitochondrial network architecture is poorly understood.

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Disruptions to cardiac tissue microstructure are common in diseased or injured myocardium and are known substrates for arrhythmias. However, we have a relatively coarse understanding of the relationships between myocardial tissue microstructure, propagation velocity and calcium cycling, due largely to the limitations of conventional experimental tools. To address this, we used microcontact printing to engineer strands of cardiac tissue with eight different widths, quantified several structural and functional parameters and established correlation coefficients.

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Myocardial infarction and heart failure are leading causes of death worldwide, in large part because adult human myocardium has extremely limited regeneration capacity. Zebrafish are a powerful model for identifying new strategies for human cardiac repair because their hearts regenerate after relatively severe injuries. Zebrafish are also relatively scalable and compatible with many genetic tools.

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Yersinia pestis, the causative agent of pneumonic plague, induces a highly lethal infection if left untreated. Currently, there is no FDA-approved vaccine against this pathogen; however, USAMRIID has developed a recombinant fusion protein, F1-V, that has been shown to induce protection against pneumonic plague. Many F1-V-based vaccine formulations require prime-boost immunization to achieve protective immunity, and there are limited reports of rapid induction of protective immunity (≤ 14 days post-immunization (DPI)).

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In ventricular myocardium, extracellular matrix (ECM) remodeling is a hallmark of physiological and pathological growth, coincident with metabolic rewiring of cardiac myocytes. However, the direct impact of the biochemical and mechanical properties of the ECM on the metabolic function of cardiac myocytes is mostly unknown. Furthermore, understanding the impact of distinct biomaterials on cardiac myocyte metabolism is critical for engineering physiologically-relevant models of healthy and diseased myocardium.

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Astrocytes display diverse morphologies in different regions of the central nervous system. Whether astrocyte diversity is attributable to developmental processes and bears functional consequences, especially in humans, is unknown. RNA-seq of human pluripotent stem cell-derived regional astrocytes revealed distinct transcript profiles, suggesting differential functional properties.

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Despite the development of massively parallel computing hardware including inexpensive graphics processing units (GPUs), it has remained infeasible to simulate the folding of atomistic proteins at room temperature using conventional molecular dynamics (MD) beyond the microsecond scale. Here, we report the folding of atomistic, implicitly solvated protein systems with folding times τ ranging from ∼10 μs to ∼100 ms using the weighted ensemble (WE) strategy in combination with GPU computing. Starting from an initial structure or set of structures, WE organizes an ensemble of GPU-accelerated MD trajectory segments via intermittent pruning and replication events to generate statistically unbiased estimates of rate constants for rare events such as folding; no biasing forces are used.

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Pigs harbor several different species of mycoplasmas, of which Mycoplasma hyopneumoniae presents the most significant economic impact on the swine industry. While ELISAs are the predominant diagnostic assay to measure antibody responses during infection with M. hyopneumoniae, the assay itself is only a rough estimate of the total antibody response.

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Seven human induced pluripotent stem cell (iPSC) lines were generated from fibroblasts from three neonatal individuals using non-integrative reprogramming. Most control iPSCs are derived from adults, so these iPSCs meet the need for control iPSCs from young individuals. Donors were from different ethnicities and these lines provide unique genetic profiles.

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CRISPR/Cas9 guided gene-editing is a potential therapeutic tool, however application to neurodegenerative disease models has been limited. Moreover, conventional mutation correction by gene-editing would only be relevant for the small fraction of neurodegenerative cases that are inherited. Here we introduce a CRISPR/Cas9-based strategy in cell and animal models to edit endogenous amyloid precursor protein (APP) at the extreme C-terminus and reciprocally manipulate the amyloid pathway, attenuating APP-β-cleavage and Aβ production, while up-regulating neuroprotective APP-α-cleavage.

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Introduction: In the myocardium, rapid propagation of action potentials and subsequent calcium waves is critical for synchronizing the contraction of cardiac myocytes and maximizing cardiac output. In many pathological settings, diverse remodeling of the tissue microenvironment is correlated with arrhythmias and decreased cardiac output, but the precise impact of tissue remodeling on propagation is not completely understood. Our objective was to delineate how multiple features within the cardiac tissue microenvironment modulate propagation velocity.

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Reporter lines generated in human pluripotent stem cells can be highly useful for the analysis of specific cell types and lineages in live cultures. We created the first human rod reporter line using CRISPR/Cas9 genome editing to replace one allele of the Neural Retina Leucine zipper (NRL) gene with an eGFP transgene in the WA09 human embryonic stem cell (hESC) line. After confirming successful targeting, three-dimensional optic vesicle structures were produced to examine reporter specificity and to track rod differentiation in culture.

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Alzheimer's disease (AD) is a common neurodegenerative disorder and the leading cause of cognitive impairment. Due to insufficient understanding of the disease mechanisms, there are no efficient therapies for AD. Most studies have focused on neuronal cells, but astrocytes have also been suggested to contribute to AD pathology.

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