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  1. Abstract Recent advances in brain clearing and imaging have made it possible to image entire mammalian brains at sub-micron resolution. These images offer the potential to assemble brain-wide atlases of neuron morphology, but manual neuron reconstruction remains a bottleneck. Several automatic reconstruction algorithms exist, but most focus on single neuron images. In this paper, we present a probabilistic reconstruction method, ViterBrain, which combines a hidden Markov state process that encodes neuron geometry with a random field appearance model of neuron fluorescence. ViterBrain utilizes dynamic programming to compute the global maximizer of what we call the most probable neuron path. We applied our algorithm to imperfect image segmentations, and showed that it can follow axons in the presence of noise or nearby neurons. We also provide an interactive framework where users can trace neurons by fixing start and endpoints. ViterBrain is available in our open-source Python package .
    Free, publicly-accessible full text available December 1, 2023
  2. Neuromorphology is crucial to identifying neuronal subtypes and understanding learning. It is also implicated in neurological disease. However, standard morphological analysis focuses on macroscopic features such as branching frequency and connectivity between regions, and often neglects the internal geometry of neurons. In this work, we treat neuron trace points as a sampling of differentiable curves and fit them with a set of branching B-splines. We designed our representation with the Frenet-Serret formulas from differential geometry in mind. The Frenet-Serret formulas completely characterize smooth curves, and involve two parameters, curvature and torsion. Our representation makes it possible to compute these parameters from neuron traces in closed form. These parameters are defined continuously along the curve, in contrast to other parameters like tortuosity which depend on start and end points. We applied our method to a dataset of cortical projection neurons traced in two mouse brains, and found that the parameters are distributed differently between primary, collateral, and terminal axon branches, thus quantifying geometric differences between different components of an axonal arbor. The results agreed in both brains, further validating our representation. The code used in this work can be readily applied to neuron traces in SWC format and is available inmore »our open-source Python package brainlit : .« less
  3. Abstract Background Human mesenchymal stem cells (hMSCs) are intensely researched for applications in cell therapeutics due to their unique properties, however, intrinsic therapeutic properties of hMSCs could be enhanced by genetic modification. Viral transduction is efficient, but suffers from safety issues. Conversely, nonviral gene delivery, while safer compared to viral, suffers from inefficiency and cytotoxicity, especially in hMSCs. To address the shortcomings of nonviral gene delivery to hMSCs, our lab has previously demonstrated that pharmacological ‘priming’ of hMSCs with the glucocorticoid dexamethasone can significantly increase transfection in hMSCs by modulating transfection-induced cytotoxicity. This work seeks to establish a library of transfection priming compounds for hMSCs by screening 707 FDA-approved drugs, belonging to diverse drug classes, from the NIH Clinical Collection at four concentrations for their ability to modulate nonviral gene delivery to adipose-derived hMSCs from two human donors. Results Microscope images of cells transfected with a fluorescent transgene were analyzed in order to identify compounds that significantly affected hMSC transfection without significant toxicity. Compound classes that increased transfection across both donors included glucocorticoids, antibiotics, and antihypertensives. Notably, clobetasol propionate, a glucocorticoid, increased transgene production 18-fold over unprimed transfection. Furthermore, compound classes that decreased transfection across both donors included flavonoids, antibiotics,more »and antihypertensives, with the flavonoid epigallocatechin gallate decreasing transgene production − 41-fold compared to unprimed transfection. Conclusions Our screen of the NCC is the first high-throughput and drug-repurposing approach to identify nonviral gene delivery priming compounds in two donors of hMSCs. Priming compounds and classes identified in this screen suggest that modulation of proliferation, mitochondrial function, and apoptosis is vital for enhancing nonviral gene delivery to hMSCs.« less
  4. Precise measurement of physiological signals is critical for the effective monitoring of human vital signs. Recent developments in computer vision have demonstrated that signals such as pulse rate and respiration rate can be extracted from digital video of humans, increasing the possibility of contact-less monitoring. This paper presents a novel approach to obtaining physiological signals and classifying stress states from thermal video. The proposed network–”StressNet”–features a hybrid emission representation model that models the direct emission and absorption of heat by the skin and underlying blood vessels. This results in an information-rich feature representation of the face, which is used by spatio-temporal network for reconstructing the ISTI ( Initial Systolic Time Interval : a measure of change in cardiac sympathetic activity that is considered to be a quantitative index of stress in humans). The reconstructed ISTI signal is fed into a stress-detection model to detect and classify the individual’s stress state (i.e. stress or no stress). A detailed evaluation demonstrates that StressNet achieves estimated the ISTI signal with 95% accuracy and detect stress with average precision of 0.842.
  5. Partial migration is a common phenomenon wherein populations include migratory and resident individuals. Whether an individual migrates or not has important ecological and management implications, particularly within protected populations. Within partially migratory populations of Oncorhynchus mykiss, migration is highly correlated with a specific genomic region, but it is unclear how well this region predicts migration at the individual level. Here, we relate sex and life history genotype, determined using >400 single nucleotide polymorphisms (SNPs) on the migratory-linked genomic region, to life history expression of marked juvenile O. mykiss from two tributaries to the South Fork Eel River, northern California. Most resident fish were resident genotypes (57% resident, 37% heterozygous, 6% migratory genotype) and male (78%). Most migratory fish were female (62%), but were a mixture of genotypes (30% resident, 45% heterozygous, 25% migratory genotype). Sex was more strongly correlated with life history expression than genotype, but the best-supported model included both. Resident genotypes regularly migrated, highlighting the importance of conserving the full suite of life history and genetic diversity in partially migratory populations.
  6. The objective of this investigation was to utilize the first-principles molecular dynamics computational approach to investigate the lithiation characteristics of empty silicon clathrates (Si 46 ) for applications as potential anode materials in lithium-ion batteries. The energy of formation, volume expansion, and theoretical capacity were computed for empty silicon clathrates as a function of Li. The theoretical results were compared against experimental data of long-term cyclic tests performed on half-cells using electrodes fabricated from Si 46 prepared using a Hofmann-type elimination–oxidation reaction. The comparison revealed that the theoretically predicted capacity (of 791.6 mAh/g) agreed with experimental data (809 mAh/g) that occurred after insertion of 48 Li atoms. The calculations showed that overlithiation beyond 66 Li atoms can cause large volume expansion with a volume strain as high as 120%, which may correlate to experimental observations of decreasing capacities from the maximum at 1030 mAh/g to 553 mA h/g during long-term cycling tests. The finding suggests that overlithiation beyond 66 Li atoms may have caused damage to the cage structure and led to lower reversible capacities.