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  1. Abstract Human induced pluripotent stem cell-derived (iPSC) neural cultures offer clinically relevant models of human diseases, including Amyotrophic Lateral Sclerosis, Alzheimer’s, and Autism Spectrum Disorder. In situ characterization of the spatial-temporal evolution of cell state in 3D culture and subsequent 2D dissociated culture models based on protein expression levels and localizations is essential to understanding neural cell differentiation, disease state phenotypes, and sample-to-sample variability. Here, we apply PR obe-based I maging for S equential M ultiplexing (PRISM) to facilitate multiplexed imaging with facile, rapid exchange of imaging probes to analyze iPSC-derived cortical and motor neuron cultures that are relevant tomore »psychiatric and neurodegenerative disease models, using over ten protein targets. Our approach permits analysis of cell differentiation, cell composition, and functional marker expression in complex stem-cell derived neural cultures. Furthermore, our approach is amenable to automation, offering in principle the ability to scale-up to dozens of protein targets and samples.« less
    Free, publicly-accessible full text available December 1, 2022
  2. The prevalence of disease-driven mass mortality events is increasing, but our understanding of spatial variation in their magnitude, timing and triggers are often poorly resolved. Here, we use a novel range-wide dataset comprised 48 810 surveys to quantify how sea star wasting disease affected Pycnopodia helianthoides , the sunflower sea star, across its range from Baja California, Mexico to the Aleutian Islands, USA. We found that the outbreak occurred more rapidly, killed a greater percentage of the population and left fewer survivors in the southern half of the species's range. Pycnopodia now appears to be functionally extinct (greater than 99.2%more »declines) from Baja California, Mexico to Cape Flattery, Washington, USA and exhibited severe declines (greater than 87.8%) from the Salish Sea to the Gulf of Alaska. The importance of temperature in predicting Pycnopodia distribution rose more than fourfold after the outbreak, suggesting latitudinal variation in outbreak severity may stem from an interaction between disease severity and warmer waters. We found no evidence of population recovery in the years since the outbreak. Natural recovery in the southern half of the range is unlikely over the short term. Thus, assisted recovery will probably be required to restore the functional role of this predator on ecologically relevant time scales.« less
    Free, publicly-accessible full text available August 25, 2022
  3. Background Hypertension drives myocardial remodeling, leading to changes in structure, composition and mechanical behavior, including residual stress, which are linked to heart disease progression in a gender-specific manner. Emerging therapies are also targeting constituent-specific pathological features. All previous studies, however, have characterized remodeling in the intact tissue, rather than isolated tissue constituents, and did not include sex as a biological variable. Objective In this study we first identified the contribution of collagen fiber network and myocytes to the myocardial residual stress/strain in Dahl-Salt sensitive rats fed with high fat diet. Then, we quantified the effect of hypertension on the remodelingmore »of the left ventricle (LV), as well as the existence of sex-specific remodeling features. Methods We performed mechanical tests (opening angle, ring-test) and histological analysis on isolated constituents and intact tissue of the LV. Based on the measurements from the tests, we performed a stress analysis to evaluate the residual stress distribution. Statistical analysis was performed to identify the effects of constituent isolation, elevated blood pressure, and sex of the animal on the experimental measurements and modeling results. Results Hypertension leads to reduced residual stress/strain in the intact tissue, isolated collagen fibers, and isolated myocytes in male and female rats. Collagen remains the largest contributor to myocardial residual stress in both normotensive and hypertensive animals. We identified sex-differences in both hypertensive and normotensive animals. Conclusions We observed both constituent- and sex-specific remodeling features in the LV of an animal model of hypertension.« less
  4. We report on one of the highest sensitivity surveys for molecular lines in the frequency range 6.0 to 7.4 GHz conducted to date. The observations were done with the 305m Arecibo Telescope toward a sample of twelve intermediate/high-mass star forming regions. We searched for a large number of transitions of different molecules, including CH3OH and OH. The low RMS noise of our data (~5 mJy for most sources and transitions) allowed detection of spectral features that have not been seen in previous lower sensitivity observations of the sources, such as detection of excited OH and 6.7 GHz CH3OH absorption. Amore »review of 6.7 GHz CH3OH detections indicates an association between absorption and radio continuum sources in high-mass star forming regions, although selection biases in targeted projects and low sensitivity of blind surveys imply incompleteness. Absorption of excited OH transitions was also detected toward three sources. In particular, we confirm a broad 6.035 GHz OH absorption feature in G34.26+0.15 characterized by an asymmetric blue-shifted wing indicative of expansion, perhaps a large scale outflow in this HII region.« less
  5. Free, publicly-accessible full text available April 1, 2023
  6. Abstract The accurate simulation of additional interactions at the ATLAS experiment for the analysis of proton–proton collisions delivered by the Large Hadron Collider presents a significant challenge to the computing resources. During the LHC Run 2 (2015–2018), there were up to 70 inelastic interactions per bunch crossing, which need to be accounted for in Monte Carlo (MC) production. In this document, a new method to account for these additional interactions in the simulation chain is described. Instead of sampling the inelastic interactions and adding their energy deposits to a hard-scatter interaction one-by-one, the inelastic interactions are presampled, independent of the hardmore »scatter, and stored as combined events. Consequently, for each hard-scatter interaction, only one such presampled event needs to be added as part of the simulation chain. For the Run 2 simulation chain, with an average of 35 interactions per bunch crossing, this new method provides a substantial reduction in MC production CPU needs of around 20%, while reproducing the properties of the reconstructed quantities relevant for physics analyses with good accuracy.« less
    Free, publicly-accessible full text available December 1, 2023
  7. Abstract The ATLAS experiment at the Large Hadron Collider has a broad physics programme ranging from precision measurements to direct searches for new particles and new interactions, requiring ever larger and ever more accurate datasets of simulated Monte Carlo events. Detector simulation with Geant4 is accurate but requires significant CPU resources. Over the past decade, ATLAS has developed and utilized tools that replace the most CPU-intensive component of the simulation—the calorimeter shower simulation—with faster simulation methods. Here, AtlFast3, the next generation of high-accuracy fast simulation in ATLAS, is introduced. AtlFast3 combines parameterized approaches with machine-learning techniques and is deployed tomore »meet current and future computing challenges, and simulation needs of the ATLAS experiment. With highly accurate performance and significantly improved modelling of substructure within jets, AtlFast3 can simulate large numbers of events for a wide range of physics processes.« less
    Free, publicly-accessible full text available December 1, 2023
  8. We report measurements of the parity-conserving beam-normal single-spin elastic scattering asymmetries Bn on 12C and 27Al, obtained with an electron beam polarized transverse to its momentum direction. These measurements add an additional kinematic point to a series of previous measurements of Bn on 12C and provide a first measurement on 27Al. The experiment utilized the Qweak apparatus at Jefferson Lab with a beam energy of 1.158 GeV. The average laboratory scattering angle for both targets was 7.7∘, and the average Q2 for both targets was 0.024 37 GeV2 (Q=0.1561 GeV). The asymmetries are Bn=−10.68±0.90(stat)±0.57(syst) ppm for 12C and Bn=−12.16±0.58(stat)±0.62(syst) ppmmore »for 27Al. The results are consistent with theoretical predictions, and are compared to existing data. When scaled by Z/A, the Q dependence of all the far-forward angle (θ<10∘) data from 1H to 27Al can be described by the same slope out to Q≈0.35 GeV. Larger-angle data from other experiments in the same Q range are consistent with a slope about twice as steep.« less