Engineering topics

Cao, Qian

Publications and source records attributed to Cao, Qian.

12 records

DOE OSTI2024

Applying queueing theory to evaluate wait-time-savings of triage algorithms

Abstract In the past decade, artificial intelligence (AI) algorithms have made promising impacts in many areas of healthcare. One application is AI-enabled prioritization software known as computer-aided triage and notification (CADt). This type of software as a medical device is intended to prioritize reviews of radiological images with time-sensitive findings, thus shortening the waiting time for patients with these findings. While many CADt devices have been deployed into clinical workflows and have been shown to improve patient treatment and clinical outcomes, quantitative methods to evaluate the wait-time-savings from their deployment are not yet available. In this paper, we apply queueing theory methods to evaluate the wait-time-savings of a CADt by calculating the average waiting time per patient image without and with a CADt device being deployed. We study two workflow models with one or multiple radiologists (servers) for a range of AI diagnostic performances, radiologist’s reading rates, and patient image (customer) arrival rates. To evaluate the time-saving performance of a CADt, we use the difference in the mean waiting time between the diseased patient images in the with-CADt scenario and that in the without-CADt scenario as our performance metric. As part of this effort, we have developed and also share a software tool to simulate the radiology workflow around medical image interpretation, to verify theoretical results, and to provide confidence intervals for the performance metric we defined. We show quantitatively that a CADt triage device is more effective in a busy, short-staffed reading setting, which is consistent with our clinical intuition and simulation results. Although this work is motivated by the need for evaluating CADt devices, the evaluation methodology presented in this paper can be applied to assess the time-saving performance of other types of algorithms that prioritize a subset of customers based on binary outputs.

Thompson, Yee Lam Elim (ORCID:0000000196537707)↗

DOE OSTI2024

Methodology for Good Machine Learning with Multi‐Omics Data

In 2020, Novartis Pharmaceuticals Corporation and the U.S. Food and Drug Administration (FDA) started a 4‐year scientific collaboration to approach complex new data modalities and advanced analytics. The scientific question was to find novel radio‐genomics‐based prognostic and predictive factors for HR+/HER− metastatic breast cancer under a Research Collaboration Agreement. This collaboration has been providing valuable insights to help successfully implement future scientific projects, particularly using artificial intelligence and machine learning. This tutorial aims to provide tangible guidelines for a multi‐omics project that includes multidisciplinary expert teams, spanning across different institutions. We cover key ideas, such as “maintaining effective communication” and “following good data science practices,” followed by the four steps of exploratory projects, namely (1) plan, (2) design, (3) develop, and (4) disseminate. We break each step into smaller concepts with strategies for implementation and provide illustrations from our collaboration to further give the readers actionable guidance.

Pharmacology & Pharmacy↗

DOE OSTI2021

Transcription factor FOXC1 positively regulates SFRP1 expression in androgenetic alopecia

Androgenetic alopecia (AGA) is the most common type of hair loss dysfunction. Secreted frizzled related protein 1 (SFRP1) is found to be associated with hair loss, but its role in AGA and the regulation mechanism of its transcription level is unclear. The aim of our study is to explore the expression of SFRP1 in AGA samples and its transcriptional mechanism. Male frontal and occipital scalp hair follicles from AGA patients were collected, and human dermal papilla cells (DPCs) were isolated and cultured. SFRP1 gene was cloned and constructed into recombinant plasmids to perform dual-luciferase reporter assay. Transcription factor binding sites were predicted through the Jaspar website and further confirmed by the chromatin immunoprecipitation (ChIP) assay. Expression of genes in DPCs was determined by immunofluorescence (IF) staining, quantitative real-time PCR (qRT-PCR) and western blotting. Our findings showed that SFRP1 was highly expressed in DPCs of AGA patients. The core promoter region of SFRP1 was from −100 to +50 bp and was found to be positively regulated by forkhead box C1 (FOXC1), a transcription factor related to hair growth, both at mRNA and protein level in DPCs. Our study suggests that FOXC1 plays an important role in regulating SFRP1 transcription, which may provide new insights into the development of therapeutic strategies for the treatment of AGA.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2021

Involvement of TFAP2A in the activation of GSDMD gene promoter in hyperoxia-induced ALI

Highlights: • Hyperoxia exposure increases GSDMD expression in rat lung tissue and A549 cells. • The core promoter region of GSDMD located in −98/-12 bp relative to TSS. • E2F4 and TFAP2A positively regulate the basal transcriptional activity of GSDMD by directly binding to its promoter. • TFAP2A directly drives the expression of GSDMD in hyperoxia-inducedA549 cells. • TFAP2A expression is increased in lung tissues of rats with hyperoxia-induced ALI and linearly correlated with GSDMD. Oxygen therapy is a common treatment in neonatal intensive care units, but long-term continuous hyperoxia ventilation may induce acute lung injury (ALI). Gasdermin D (GSDMD)-mediated pyroptosis participates in various diseases including ALI, but the role of GSDMD in hyperoxia-induced ALI is yet understood. Here, we showed a significant increase in GSDMD after exposure to high oxygen. To elucidate the molecular mechanisms involved in GSDMD regulation, we identified the core promoter of GSDMD, −98 ~ −12 bp relative to the transcriptional start site (TSS). The results of mutational analysis, overexpression or siRNA interference, EMSA and ChIP demonstrated that E2F4 and TFAP2A positively regulate the transcriptional activity of the GSDMD by binding to its promoter. However, only TFAP2A showed a regulatory effect on the expression of GSDMD. Moreover, TFAP2A was increased in the lung tissues of rats exposed to hyperoxia and showed a strong linear correlation with GSDMD. Our results indicated that TFAP2A positively regulates the GSDMD expression via binding to the promoter region of GSDMD.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2020

Floods due to Atmospheric Rivers along the U.S. West Coast: The Role of Antecedent Soil Moisture in a Warming Climate

Precipitation extremes are projected to become more frequent along the U.S. West Coast due to increased atmospheric river (AR) activity, but the frequency of less intense precipitation events may decrease. Antecedent soil moisture (ASM) conditions can have a large impact on flood responses, especially if prestorm precipitation decreases. Taken together with increased antecedent evaporative demand due to warming, this would result in reduced soil moisture at the onset of extreme precipitation events. In this work, we examine the impact of ASM on AR-related floods in a warming climate in three basins that form a transect along the U.S. Pacific Coast: the Chehalis River basin in Washington, the Russian River basin in Northern California, and the Santa Margarita River basin in Southern California. Additionally, we ran the Distributed Hydrology Soil Vegetation Model (DHSVM) over the three river basins using forcings downscaled from 10 global climate models (GCMs). We examined the dynamic role of ASM by comparing the changes in the largest 50, 100, and 150 extreme events in two periods, 1951–2000 and 2050–99. In the Chehalis basin, the projected fraction of AR-related extreme discharge events slightly decreases. In the Russian basin, this fraction increases, however, and more substantially so in the Santa Margarita basin. This is due to increases in AR-related extreme precipitation events, as well as the fact that the relationship of extreme precipitation to extreme discharge is strengthened by projected increases in year-to-year volatility of annual precipitation in California, which increases the likelihood of concurrent occurrence of large storms and wet ASM conditions.

54 ENVIRONMENTAL SCIENCES↗

DOE OSTI2019

Fiber-amplifier-pumped, 1-MHz, 1-µJ, 21-µm, femtosecond OPA with chirped-pulse DFG front-end

High-repetition-rate, high-power, few-cycle mid-infrared lasers with carrier-envelope phase (CEP) stabilization are ideal driving sources for studying strong-field nonlinear processes, such as strong-field driven electron emission, solid-state high-harmonic generation, and nonlinear microscopy. Here, we report on a 1-MHz, 1-μJ, femtosecond, 2.1-µm optical parametric amplifier (OPA), pumped by a Yb-doped fiber chirped-pulse amplifier (CPA) and seeded by a chirped-pulse difference-frequency generation (DFG) front-end providing positively chirped 2.1-μm signal pulses. The home-built multi-stage 1030-nm Yb-doped fiber CPA pump laser generates >55-μJ near-transform-limited (245-fs) pulses at 1 MHz repetition rate using a novel 4-pass all-fiber stretcher/front-end for careful dispersion/spectral management. The chirped-pulse DFG scheme is achieved by wave-mixing the 1030 nm pump pulse with a dispersive wave at 645–735 nm generated in a photonic crystal fiber, allowing passive CEP stability of the 2.1-µm pulses. The 2.1-μm pulse is amplified to 1 μJ in a two-stage dispersion-managed optical parametric amplifier (OPA) with a pump energy of ~21 μJ resulting in 95-fs pulses with nice beam profile without additional pulse compression. Multi-μJ, sub-30 fs pulses can be obtained at full pump energy and additional dispersion compensation. The fiber-amplifier-based mid-infrared OPA can be directly applied to high-harmonic generation in solids and optical-field-driven nanophotonic devices and is a compact front-end for a future high-power, high-repetition-rate, long wavelengths CEP-stabilized source for gas-phase high-order harmonic generation.

71 CLASSICAL AND QUANTUM MECHANICS, GENERAL PHYSIC↗

DOE OSTI2018

The LncRNA MALAT1 regulates CD80 transcription via the NF-κB signaling pathway in the A549 cell line

CD80 has been known to be a co-stimulatory factor expressed in antigen presenting cells (APCs) involved in T-cell activation. It can be expressed in non-bone marrow-derived cells induced by lipopolysaccharide (LPS) or other stimulators, and directly involved in the pathogenesis following T cell activation. However, the intricate transcription mechanisms that underlying the upregulation of CD80 expression levels in LPS-activated non-bone marrow-derived cells is still unknown. LncRNAs are confirmed to be involved in transcriptional regulation by influencing transcription factors. Therefore, we wanted to determine whether the lncRNA MALAT1, which has been found to be related to LPS-induced inflammation, could regulate the transcription of CD80. Our results showed that CD80 was upregulated in low-dose LPS-activated A549 cells in a NF-κB-dependent manner. The lncRNA MALAT1 can interfere with NF-κB activation and disrupt its binding efficiency with the CD80 promoter. Thus, the lncRNA MALAT1 can regulate CD80 transcription via the NF-κB signaling pathway in the LPS-activated A549 cell line.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

STING positively regulates human ORMDL3 expression through TBK1-IRF3-STAT6 complex mediation

Highlights: • STING and ORMDL3 genes expression was increased in patients with recurrent wheeze. • STING upregulates ORMDL3 expression and promoter activity in cells. • ORMDL3 is positively associated with the STING-TBK1-IRF3/STAT6 signaling pathway. • STING increases the ORMDL3 expression in asthma and recurrent wheeze by promoting both the expression and activity of the TBK1-IRF3-STAT6 complex. Orosomucoid 1-like protein 3 (ORMDL3) is an asthma candidate gene associated with virus-triggered recurrent wheeze. Stimulator of interferon gene (STING) controls TLR-independent cytosolic responses to viruses. However, the association of STING with ORMDL3 is unclear. Here, we have shown that ORMDL3 expression shows a linear correlation with STING in recurrent wheeze patients. In elucidating the molecular mechanisms of the ORMDL3-STING relationship, we found that STING promoted the transcriptional activity of ORMDL3, which was significantly associated with increased levels of interferon regulatory factor 3 (IRF3) and signal transducer and activator of transcription 6 (STAT6). Further study showed that via activation of TANK binding kinase 1 (TBK1), STING enhanced the phosphorylation and binding of IRF3 and STAT6, which upregulated ORMDL3 by binding to the promoter. Our results showed that STING positively regulated ORMDL3 through the TBK1-IRF3-STAT6 complex.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2018

Tunable, Ultrafast Fiber-Laser between 1.15 μm and 1.35 μm for Harmonic Generation Microscopy in Human Skin

We demonstrate a fiber-optic ultrafast tunable source for harmonic generation microscopy (HGM) in human skin. The source is based on a 31-MHz Er-fiber laser followed by self-phase modulation enabled spectral selection (SESS). The resulting pulses are tunable between 1.15 and 1.35 μm with up to >10-nJ pulse energy and ~100-fs pulse duration. Here we employ this source to drive a scanning microscope for HGM imaging of ex vivo human skin. A systematic investigation on imaging depth versus excitation wavelength reveals that excitation wavelengths in the 1.15-1.25 μm range exhibit low optical attenuation within the tissue and allows larger imaging depth for HGM in human skin. HGM driven by fiber-based SESS sources constitutes an enabling tool for noninvasive virtual skin biopsy in clinical applications.

60 APPLIED LIFE SCIENCES↗

DOE OSTI2016

A spatially distributed model for assessment of the effects of changing land use and climate on urban stream quality: Development of a Spatially Distributed Urban Water Quality Model

While the effects of land use change in urban areas have been widely examined, the combined effects of climate and land use change on the quality of urban and urbanizing streams have received much less attention. We describe a modeling framework that is applicable to the evaluation of potential changes in urban water quality and associated hydrologic changes in response to ongoing climate and landscape alteration. The grid-based spatially distributed model, DHSVM-WQ, is an outgrowth of the Distributed Hydrology-Soil-Vegetation Model (DHSVM) that incorporates modules for assessing hydrology and water quality in urbanized watersheds at a high spatial and temporal resolution. DHSVM-WQ simulates surface runoff quality and in-stream processes that control the transport of nonpoint-source (NPS) pollutants into urban streams. We configure DHSVM-WQ for three partially urbanized catchments in the Puget Sound region to evaluate the water quality responses to current conditions and projected changes in climate and/or land use over the next century. Here we focus on total suspended solids (TSS) and total phosphorus (TP) from nonpoint sources (runoff), as well as stream temperature. The projection of future land use is characterized by a combination of densification in existing urban or partially urban areas, and expansion of the urban footprint. The climate change scenarios consist of individual and concurrent changes in temperature and precipitation. Future precipitation is projected to increase in winter and decrease in summer, while future temperature is projected to increase throughout the year. Our results show that urbanization has a much greater effect than climate change on both the magnitude and seasonal variability of streamflow, TSS and TP loads largely due to substantially increased streamflow, and particularly winter flow peaks. Water temperature is more sensitive to climate warming scenarios than to urbanization and precipitation changes. Future urbanization and climate change together are predicted to significantly increase annual mean streamflow (up to 55%), water temperature (up to 1.9 ºC), TSS load (up to 182%), and TP load (up to 74%).

Sun, Ning↗

DOE OSTI2016

Climate and land cover effects on the temperature of Puget Sound streams: Assessment of Climate and Land Use Impacts on Stream Temperature

We apply an integrated hydrology-stream temperature modeling system, DHSVM-RBM, to examine the response of the temperature of the major streams draining to Puget Sound to land cover and climate change. We first show that the model construct is able to reconstruct observed historic streamflow and stream temperature variations at a range of time scales. We then explore the relative effect of projected future climate and land cover change, including riparian vegetation, on streamflow and stream temperature. Streamflow in summer is likely to decrease as the climate warms especially in snowmelt-dominated and transient river basins despite increased streamflow in their lower reaches associated with urbanization. Changes in streamflow also result from changes in land cover, and changes in stream shading result from changes in riparian vegetation, both of which influence stream temperature. However, we find that the effect of riparian vegetation changes on stream temperature is much greater than land cover change over the entire basin especially during summer low flow periods. Furthermore, while future projected precipitation change will have relatively modest effects on stream temperature, projected future air temperature increases will result in substantial increases in stream temperature especially in summer. These summer stream temperature increases will be associated both with increasing air temperature, and projected decreases in low flows. We find that restoration of riparian vegetation could mitigate much of the projected summer stream temperature increases. We also explore the contribution of riverine thermal loadings to the heat balance of Puget Sound, and find that the riverine contribution is greatest in winter, when streams account for up to 1/8 of total thermal inputs (averaged from December through February), with larger effects in some sub-basins. We project that the riverine impact on thermal inputs to Puget Sound will become greater with both urbanization and climate change in winter but become smaller in summer due to climate change.

Cao, Qian↗

DOE OSTI2014

Non-covalent interactions of nitrous oxide with aromatic compounds: Spectroscopic and computational evidence for the formation of 1:1 complexes

We present the first study of intermolecular interactions between nitrous oxide (N{sub 2}O) and three representative aromatic compounds (ACs): phenol, cresol, and toluene. The infrared spectroscopic experiments were performed in a Ne matrix and were supported by high-level quantum chemical calculations. Comparisons of the calculated and experimental vibrational spectra provide direct identification and characterization of the 1:1 N{sub 2}O-AC complexes. Our results show that N{sub 2}O is capable of forming non-covalently bonded complexes with ACs. Complex formation is dominated by dispersion forces, and the interaction energies are relatively low (about −3 kcal mol{sup −1}); however, the complexes are clearly detected by frequency shifts of the characteristic bands. These results suggest that N{sub 2}O can be bound to the amino-acid residues tyrosine or phenylalanine in the form of π complexes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗