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At least 703 records · Page 39
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

The HUNTER Dynamic Human Reliability Analysis Tool: Development of a Module for Performance Shaping Factors

Human Unimodel for Nuclear Technology to Enhance Reliability (HUNTER) is a framework to support dynamic human reliability analysis (HRA) in communication with a variety of methods and tools. In this paper, how we have developed one of the HUNTER modules, the individual module for evaluating performance shaping factors (PSFs), is introduced. The PSF refers to any factor that influences human performance such as workload or complexity. It has been used for highlighting human errors and adjusting the error probabilities in the existing HRA. We consider the eight PSFs suggested in the Standardized Plant Analysis Risk-HRA (SPAR-H) method, which is the representative HRA method widely used in the nuclear field. To support our dynamic modeling using the eight SPAR-H PSFs, we reviewed human performance literature and developed data-based mathematical models to rate and quantify PSFs in the context of dynamic HRA. We also design the individual module composed of the two functions: 1) the PSF qualification function that automatically or manually evaluates a PSF level, and 2) the PSF quantification function that dynamically or statically determines the PSF multiplier values and integrate them to adjust human error probabilities (HEPs). How each function works with the SPAR-H PSFs and how the PSFs adjust the HEPs are investigated through literature and discussed in this paper.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2022

The HUNTER Dynamic Human Reliability Analysis Tool: Development of a Module for Performance Shaping Factors

The Human Unimodel for Nuclear Technology to Enhance Reliability (HUNTER) is a framework to support dynamic human reliability analysis (HRA) in communication with a variety of methods and tools. This paper explores how we developed one of the HUNTER modules: namely, the Individual module for evaluating performance shaping factors (PSFs). A PSF is any factor that influences human performance (e.g., workload or complexity). In the existing HRA, they are used to highlight human errors and adjust error probabilities. We consider the eight PSFs suggested in the Standardized Plant Analysis Risk-HRA (SPAR-H) method, a representative HRA method widely used in the nuclear field. To support our dynamic modeling using the eight SPAR-H PSFs, we reviewed the human performance literature and developed data-based mathematical models to rate and quantify PSFs in the context of dynamic HRA. We also designed the Individual module to consist of two functions: (1) the PSF qualification function for automatically or manually evaluating PSF levels, and (2) the PSF quantification function for dynamically or statically determining PSF multiplier values and integrating them to adjust human error probabilities (HEPs). How each function works in regard to the SPAR-H PSFs, and how the PSFs serve to adjust the HEPs, were investigated via literature review and are discussed in this paper.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2023

An Investigation of Time Distributions for Task Primitives to Support the HUNTER Dynamic Human Reliability Analysis

As an effort to support data collection for dynamic human reliability analysis (HRA), this study investigates time distributions for task primitives defined in the Goals, Operators, Methods, and Selection rules (GOMS)–Human Reliability Analysis (HRA) method. GOMS-HRA was developed to provide cognition-based time and human error probability information for dynamic HRA calculation in the Human Unimodel for Nuclear Technology to Enhance Reliability (HUNTER) framework. HUNTER is a framework to support the dynamic modelling of human error in conjunction with other modelling tools. In this paper, we investigate time distributions using experimental data collected from the Simplified Human Error Experimental Program (SHEEP) study, which suggests an HRA data collection framework to complement full-scope simulator research as well as collect input data for dynamic HRA using simplified simulators such as the Rancor Microworld Simulator. In this study, time required for GOMS-HRA task primitives to satisfy thirteen statistical distributions is investigated. Then, the time distributions from student operators and professional operators are compared and discussed. As a result, this study identified several time distributions on five GOMS-HRA task primitives at a statistically significant level. According to analyses to date, a greater number of significant time distributions was found in abnormal or emergency operating procedures rather than standard operating procedures. In the future, it is expected that the result of this study can provide objective reference on elapsed time data for task primitives as well as help to realistically simulate scenarios within dynamic HRA.

99 GENERAL AND MISCELLANEOUS↗
DOE OSTI2023

Human-Building Collaboration: Toward lighting enabled collaborative system design

The profession of lighting design is evolving as contemporary lighting systems increasingly rely on cutting-edge computational technologies, sensors, and IOT systems. This trend requires designers to incorporate ideas of automation, dynamic controls, and user-system interaction into their design logic. However, real-time lighting simulations are constrained by inherent limitations arising from the reductive assumptions inevitably introduced in simulated lighting environments. This raises the question of how can designers account for the discrepancies between simulated and real lighting environments, and how can collaboration between humans and autonomous lighting systems bridge this gap. To address this question, we propose a protocol for designing collaborative interactions between humans and systems. Furthermore, this protocol builds on the Human-Lighting System Interaction Framework and demonstrates how human and system intelligence can be combined to fine-tune lighting qualities in a given space. Our paper shows how interactive lighting systems can customize lighting based on user preferences in real-time and how global lighting configurations can be adjusted over time. Specifically, we demonstrate: a) Human-system collaboration assumptions and goals, as well as how the protocol can be integrated into digitally programmable lighting systems. b) Implementations of collaboration that reveal how system autonomy, performance, and user experience are improved over short and long-term timeframes. c) How lighting design can be enhanced beyond simulation-driven design optimization capacities. The associated affordances and limitations are discussed with respect to existing lighting simulation design frameworks.

autonomous systems↗
DOE OSTI2016

Frequent Nek1 overexpression in human gliomas

Never in mitosis A (NIMA)-related kinase 1 (Nek1) regulates cell cycle progression to mitosis. Its expression and potential functions in human gliomas have not been studied. Here, our immunohistochemistry (IHC) assay and Western blot assay results showed that Nek1 expression was significantly upregulated in fresh and paraffin-embedded human glioma tissues. Its level in normal brain tissues was low. Nek1 overexpression in human gliomas was correlated with the proliferation marker (Ki-67), tumor grade, Karnofsky performance scale (KPS) and more importantly, patients’ poor survival. Further studies showed that Nek1 expression level was also increased in multiple human glioma cell lines (U251-MG, U87-MG, U118, H4 and U373). Significantly, siRNA-mediated knockdown of Nek1 inhibited glioma cell (U87-MG/U251-MG) growth. Nek1 siRNA also sensitized U87-MG/U251-MG cells to temozolomide (TMZ), causing a profound apoptosis induction and growth inhibition. The current study indicates Nek1 might be a novel and valuable oncotarget of glioma, it is important for glioma cell growth and TMZ-resistance. - Highlights: • Nek1 is upregulated in multiple human glioma tissues and cell lines. • Nek1 overexpression correlates with glioma grades and patients’ KPS score. • Nek1 overexpression correlates with patients’ poor overall survival. • siRNA knockdown of Nek1 inhibits glioma cell growth. • siRNA knockdown of Nek1 sensitizes human glioma cells to temozolomide.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Dual inhibition of BRD4 and PI3K by SF2523 suppresses human prostate cancer cell growth in vitro and in vivo

Highlights: • SF2523 inhibits human prostate cancer cell survival and proliferation. • SF2523 induces apoptosis activation in human prostate cancer cells. • SF2523 inhibits BRD4-regulated proteins and AKT-S6K1 activation in prostate cancer cells. • SF2523 administration inhibits prostate cancer xenograft growth in SCID mice. Bromodomain-containing protein 4 (BRD4) and phosphatidylinositol 3-kinase (PI3K) are both key oncogenic proteins in human prostate cancer. In the current study, we examined the anti-prostate cancer cell activity by SF2523, a BRD4 and PI3K dual inhibitor. We showed that SF2523 potently inhibited survival and proliferation of the primary human prostate cancer cells. SF2523 induced profound apoptosis activation in prostate cancer cells. The dual inhibitor was yet non-cytotoxic to the prostate epithelial cells. At the molecular level, SF2523 downregulated BRD4-regulated genes (cyclin D1, c-Myc and androgen receptor) and almost blocked AKT-S6K1 activation in prostate cancer cells. In vivo, SF2523 intraperitoneal administration at the well-tolerated dose inhibited human prostate cancer xenograft growth in severe combined immunodeficient (SCID) mice. BRD4-regulated genes (cyclin D1, c-Myc and androgen receptor) and AKT-S6K1 activation were inhibited in SF2523-treated tumors. Together, dual inhibition of BRD4 and PI3K by SF2523 suppresses human prostate cancer cell growth in vitro and in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

AZD5153, a novel BRD4 inhibitor, suppresses human thyroid carcinoma cell growth in vitro and in vivo

Highlights: • AZD5153 inhibits thyroid carcinoma cell survival, proliferation and cell cycle progression. • AZD5153 induces apoptosis activation in human thyroid carcinoma cells. • BRD4 is over-expressed in human thyroid carcinoma cells. • AZD5153 downregulates c-Myc, Bcl-2 and cyclin D1 in human thyroid carcinoma cells. • AZD5153 oral administration inhibits TPC-1 xenograft growth in SCID mice. The development of novel anti-papillary thyroid carcinoma agents is urgent. AZD5153 is a novel and specific Bromodomain-containing protein 4 (BRD4) inhibitor. Here, we show that AZD5153 dose-dependently inhibited survival, proliferation and cell cycle progression in TPC-1 cells and primary human thyroid carcinoma cells. Yet, it was non-cytotoxic to the primary thyroid epithelial cells. AZD5153 induced caspase-3/-9 and apoptosis activation in TPC-1 cells and primary cancer cells. Its cytotoxicity in TPC-1 cells was significantly attenuated with co-treatment of the caspase inhibitors. BRD4 expression was elevated in TPC-1 and primary human thyroid carcinoma cells, but was low in the thyroid epithelial cells. BRD4-regulated proteins, including c-Myc, Bcl-2 and cyclin D1, were significantly downregulated following AZD5153 treatment in TPC-1 and primary cancer cells. In vivo, oral administration of AZD5153 at well-tolerated doses significantly inhibited TPC-1 xenograft growth in severe combined immunodeficient (SCID) mice. BRD4-dependent proteins, Myc, Bcl-2 and cyclin D1, were also downregulated in AZD5153-treated tumor tissues. Collectively, the results suggest that targeting BRD4 by AZD5153 inhibits human thyroid carcinoma cell growth in vitro and in vivo.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

The ionic liquid 1-octyl-3-methylimidazolium (M8OI) is an activator of the human estrogen receptor alpha

Highlights: • M8OI activates the human ERα and induces TFF1 in MCF7 cells. • M8OI is a super-activator of the mouse ERβ variant 2 receptor. • M8OI does not activate the human ERβ. Recent environmental sampling around a landfill site in the UK demonstrated that unidentified xenoestrogens were present at higher levels than control sites; that these xenoestrogens were capable of super-activating (resisting ligand-dependent antagonism) the murine variant 2 ERβ and that the ionic liquid 1-octyl-3-methylimidazolium chloride (M8OI) was present in some samples. To determine whether M8OI was a contributor to the xenoestrogen pool in the soils, activation of human estrogen receptors by M8OI was examined. M8OI activated the human ERα in MCF7 cells in a dose-response manner. These effects were inhibited by the ER antagonist ICI182780; occurred in the absence of any metabolism of M8OI and were confirmed on examination of ER-dependent induction of trefoil factor 1 mRNA in MCF7 cells. M8OI also super-activated the murine variant 2 ERβ in a murine hepatopancreatobiliary cell line. The human ERβ was not activated by M8OI when expressed in HEK293 cells. These data demonstrate that M8OI is a xenoestrogen capable of activating the human ERα and super-activating the murine variant 2 ERβ.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2020

Non-invasive (non-contact) measurements of human thermal physiology signals and thermal comfort/discomfort poses -A review

Heating, ventilation and air-conditioning (HVAC) systems have been adopted to create comfortable, healthy and safe indoor environments. In the control loop, the technical feature of the human demand-oriented supply can help operate HVAC effectively. Among many technical options, real time monitoring based on feedback signals from end users has been frequently reported as a critical technology to confirm optimizing building performance. Recent studies have incorporated human thermal physiology signals and thermal comfort/discomfort status as real-time feedback signals. A series of human subject experiments used to be conducted by primarily adopting subjective questionnaire surveys in a lab-setting study, which is limited in the application for reality. With the help of advanced technologies, physiological signals have been detected, measured and processed by using multiple technical formats, such as wearable sensors. Nevertheless, they mostly require physical contacts with the skin surface in spite of the small physical dimension and compatibility with other wearable accessories, such as goggles, and intelligent bracelets. Most recently, a low cost small infrared camera has been adopted for monitoring human facial images, which could detect the facial skin temperature and blood perfusion in a contactless way. Also, according to latest pilot studies, a conventional digital camera can generate infrared images with the help of new methods, such as the Euler video magnification technology. Human thermal comfort/discomfort poses can also be detected by video methods without contacting human bodies and be analyzed by the skeleton keypoints model. Here, new sensing technologies were summarized, their cons and pros were discussed, and extended applications for the demand-oriented ventilation were also reviewed as potential development and applications.

32 ENERGY CONSERVATION, CONSUMPTION, AND UTILIZATI↗
DOE OSTI2018

Ambient ultrafine particles activate human monocytes: Effect of dose, differentiation state and age of donors

Highlights: • UFP causes TNF-α secretion independently of ROS formation. • Differentiated THP-1 cells are more responsive to UFP exposure. • Age of donor does not contribute to the proinflammatory effect of UFP. Exposure to ambient particulate matter (PM) has been linked to adverse pulmonary and cardiovascular health effects. Activation of both inflammatory and oxidative stress pathways has been observed and may be a probable cause of these outcomes. We tested the hypothesis that in human monocytes, PM-induced oxidative and inflammatory responses are interrelated. A human monocytic cell line (THP-1) was used to determine if dose and differentiation state plays a role in the cellular response after a 24hr exposure to particles. Primary human monocytes derived from eight female, non-smoker donors (aged: 21, 24, 27, 28, 48, 49, 54 & 60yo) were used to determine if the age of donors modulates the response. Cells were treated with aqueous suspensions of ambient ultrafine particles (UFP, defined as smaller than 0.2 µm in size) or a media control for 24hr. After exposure, reactive oxygen species (ROS) formation was increased irrespective of dose or differentiation state of THP-1 cells. In the primary human monocytes, ROS formation was not significantly changed. The release of the proinflammatory cytokine, tumor necrosis factor alpha (TNF-α), was dose-dependent and greatest in differentiated compared to undifferentiated THP-1 cells exposed to UFP. In the Primary human monocytes, TNF-α secretion was increased irrespective of the age of the donor. Our results suggest that after a 24hr exposure to particles, general reactive oxygen species formation was nonspecific and uncorrelated to cytokine secretion which was consistently enhanced. Cytokines play an important role in orchestrating many immune responses and thus the ability of ambient particles to enhance robust secretion of a proinflammatory cytokine from primary human monocytes, and how this may influence the response to pathogens and alter disease states, needs to be further evaluated.

54 ENVIRONMENTAL SCIENCES↗
DOE OSTI2016

Inhibition of human anthracycline reductases by emodin — A possible remedy for anthracycline resistance

The clinical application of anthracyclines, like daunorubicin and doxorubicin, is limited by two factors: dose-related cardiotoxicity and drug resistance. Both have been linked to reductive metabolism of the parent drug to their metabolites daunorubicinol and doxorubicinol, respectively. These metabolites show significantly less anti-neoplastic properties as their parent drugs and accumulate in cardiac tissue leading to chronic cardiotoxicity. Therefore, we aimed to identify novel and potent natural inhibitors for anthracycline reductases, which enhance the anticancer effect of anthracyclines by preventing the development of anthracycline resistance. Human enzymes responsible for the reductive metabolism of daunorubicin were tested for their sensitivity towards anthrachinones, in particular emodin and anthraflavic acid. Intense inhibition kinetic data for the most effective daunorubicin reductases, including IC{sub 50}- and K{sub i}-values, the mode of inhibition, as well as molecular docking, were compiled. Subsequently, a cytotoxicity profile and the ability of emodin to reverse daunorubicin resistance were determined using multiresistant A549 lung cancer and HepG2 liver cancer cells. Emodin potently inhibited the four main human daunorubicin reductases in vitro. Further, we could demonstrate that emodin is able to synergistically sensitize human cancer cells towards daunorubicin at clinically relevant concentrations. Therefore, emodin may yield the potential to enhance the therapeutic effectiveness of anthracyclines by preventing anthracycline resistance via inhibition of the anthracycline reductases. In symphony with its known pharmacological properties, emodin might be a compound of particular interest in the management of anthracycline chemotherapy efficacy and their adverse effects. - Highlights: • Natural and synthetic compounds were identified as inhibitors for human daunorubicin reductases. • Emodin is a potent inhibitor for human daunorubicin reductases. • Emodin synergistically sensitizes multiresistant human cancer cells towards daunorubicin.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Hexavalent chromium induces chromosome instability in human urothelial cells

Numerous metals are well-known human bladder carcinogens. Despite the significant occupational and public health concern of metals and bladder cancer, the carcinogenic mechanisms remain largely unknown. Chromium, in particular, is a metal of concern as incidences of bladder cancer have been found elevated in chromate workers, and there is an increasing concern for patients with metal hip implants. However, the impact of hexavalent chromium (Cr(VI)) on bladder cells has not been studied. We compared chromate toxicity in two bladder cell lines; primary human urothelial cells and hTERT-immortalized human urothelial cells. Cr(VI) induced a concentration- and time-dependent increase in chromosome damage in both cell lines, with the hTERT-immortalized cells exhibiting more chromosome damage than the primary cells. Chronic exposure to Cr(VI) also induced a concentration-dependent increase in aneuploid metaphases in both cell lines which was not observed after a 24 h exposure. Aneuploidy induction was higher in the hTERT-immortalized cells. When we correct for uptake, Cr(VI) induces a similar amount of chromosome damage and aneuploidy suggesting that the differences in Cr(VI) sensitivity between the two cells lines were due to differences in uptake. The increase in chromosome instability after chronic chromate treatment suggests this may be a mechanism for chromate-induced bladder cancer, specifically, and may be a mechanism for metal-induced bladder cancer, in general. - Highlights: • Hexavalent chromium is genotoxic to human urothelial cells. • Hexavalent chromium induces aneuploidy in human urothelial cells. • hTERT-immortalized human urothelial cells model the effects seen in primary urothelial cells. • Hexavalent chromium has a strong likelihood of being carcinogenic for bladder tissue.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2016

Reduction of hexavalent chromium by fasted and fed human gastric fluid. II. Ex vivo gastric reduction modeling

To extend previous models of hexavalent chromium [Cr(VI)] reduction by gastric fluid (GF), ex vivo experiments were conducted to address data gaps and limitations identified with respect to (1) GF dilution in the model; (2) reduction of Cr(VI) in fed human GF samples; (3) the number of Cr(VI) reduction pools present in human GF under fed, fasted, and proton pump inhibitor (PPI)-use conditions; and (4) an appropriate form for the pH-dependence of Cr(VI) reduction rate constants. Rates and capacities of Cr(VI) reduction were characterized in gastric contents from fed and fasted volunteers, and from fasted pre-operative patients treated with PPIs. Reduction capacities were first estimated over a 4-h reduction period. Once reduction capacity was established, a dual-spike approach was used in speciated isotope dilution mass spectrometry analyses to characterize the concentration-dependence of the 2nd order reduction rate constants. These data, when combined with previously collected data, were well described by a three-pool model (pool 1 = fast reaction with low capacity; pool 2 = slow reaction with higher capacity; pool 3 = very slow reaction with higher capacity) using pH-dependent rate constants characterized by a piecewise, log-linear relationship. These data indicate that human gastric samples, like those collected from rats and mice, contain multiple pools of reducing agents, and low concentrations of Cr(VI) (< 0.7 mg/L) are reduced more rapidly than high concentrations. The data and revised modeling results herein provide improved characterization of Cr(VI) gastric reduction kinetics, critical for Cr(VI) pharmacokinetic modeling and human health risk assessment. - Highlights: • SIDMS allows for measurement of Cr(VI) reduction rate in gastric fluid ex vivo • Human gastric fluid has three reducing pools • Cr(VI) in drinking water at < 0.7 mg/L is rapidly reduced in human gastric fluid • Reduction rate is concentration- and pH-dependent • A refined PK model is used to characterize inter-individual variability in Cr(VI) gastric reduction capacity.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Comparative analysis of TCDD-induced AhR-mediated gene expression in human, mouse and rat primary B cells

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is a persistent environmental pollutant that activates the aryl hydrocarbon receptor (AhR) resulting in altered gene expression. In vivo, in vitro, and ex vivo studies have demonstrated that B cells are directly impaired by TCDD, and are a sensitive target as evidenced by suppression of antibody responses. The window of sensitivity to TCDD-induced suppression of IgM secretion among mouse, rat and human B cells is similar. Specifically, TCDD must be present within the initial 12 h post B cell stimulation, indicating that TCDD disrupts early signaling network(s) necessary for B lymphocyte activation and differentiation. Therefore, we hypothesized that TCDD treatment across three different species (mouse, rat and human) triggers a conserved, B cell-specific mechanism that is involved in TCDD-induced immunosuppression. RNA sequencing (RNA-Seq) was used to identify B cell-specific orthologous genes that are differentially expressed in response to TCDD in primary mouse, rat and human B cells. Time course studies identified TCDD-elicited differential expression of 515 human, 2371 mouse and 712 rat orthologous genes over the 24-h period. 28 orthologs were differentially expressed in response to TCDD in all three species. Overrepresented pathways enriched in all three species included cytokine-cytokine receptor interaction, ECM-receptor interaction, focal adhesion, regulation of actin cytoskeleton and pathways in cancer. Differentially expressed genes functionally associated with cell-cell signaling in humans, immune response in mice, and oxidation reduction in rats. Overall, these results suggest that despite the conservation of the AhR and its signaling mechanism, TCDD elicits species-specific gene expression changes. - Highlights: • Kovalova TAAP Highlights Nov. 2016 • RNA-Seq identified TCDD-induced gene expression in PWM-activated primary B cells. • TCDD elicited differential expression of 515 human, 2371 mouse and 712 rat orthologs. • 28 orthologs were differentially expressed in response to TCDD in all three species. • TCDD elicits mostly species-specific gene expression changes in activated B cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2017

Nickel-induced HIF-1α promotes growth arrest and senescence in normal human cells but lacks toxic effects in transformed cells

Nickel is a human carcinogen that acts as a hypoxia mimic by activating the transcription factor HIF-1α and hypoxia-like transcriptomic responses. Hypoxia and elevated HIF-1α are typically associated with drug resistance in cancer cells, which is caused by increased drug efflux and other mechanisms. Here we examined the role of HIF-1α in uptake of soluble Ni(II) and Ni(II)-induced cell fate outcomes using si/shRNA knockdowns and gene deletion models. We found that HIF-1α had no effect on accumulation of Ni(II) in two transformed (H460, A549) and two normal human cell lines (IMR90, WI38). The loss of HIF-1α also produced no significant impact on p53-dependent and p53-independent apoptotic responses or clonogenic survival of Ni(II)-treated transformed cells. In normal human cells, HIF-1α enhanced the ability of Ni(II) to inhibit cell proliferation and cause a permanent growth arrest (senescence). Consistent with its growth-suppressive effects, HIF-1α was important for upregulation of the cell cycle inhibitors p21 (CDKN1A) and p27 (CDKN1B). Irrespective of HIF-1α status, Ni(II) strongly increased levels of MYC protein but did not change protein expression of the cell cycle-promoting phosphatase CDC25A or the CDK inhibitor p16. Our findings indicate that HIF-1α limits propagation of Ni(II)-damaged normal cells, suggesting that it may act in a tumor suppressor-like manner during early stages of Ni(II) carcinogenesis. - Highlights: • HIF-1α enhances growth arrest and senescence by Ni(II) in normal human cells. • HIF-1α is important for upregulation of the cell cycle inhibitors p21 and p27 in Ni(II)-treated normal cells. • Apoptotic responses and clonogenic toxicity by Ni(II) in transformed human cells are HIF-1α independent. • HIF-1α does not affect Ni(II) accumulation in normal or transformed human cells.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2018

Comparative environmental and human health evaluations of thermolysis and solvolysis recycling technologies of carbon fiber reinforced polymer waste

Highlights: • Performed life cycle impact assessment (LCIA) of pyrolysis for CFRP waste recycling. • Performed LCIA of solvolysis using supercritical water (SCW) for CFRP recycling. • Performed comparative LCIA of pyrolysis vs SCW-based solvolysis for CFRP recycling. • Closed current knowledge gap about sustainability of SCW-based solvolysis. • Compared LCIA of pyrolyzer’s heating using natural gas in lieu of electricity. - Abstract: This quantitative research aims to compare environmental and human health impacts associated with two recycling technologies of CFRP waste. The ‘baseline’ recycling technology is the conventional thermolysis process via pyrolysis and the ‘alternative’ recycling technology is an emerging chemical treatment via solvolysis using supercritical water (SCW) to digest the thermoset matrix. Two Gate-to-Gate recycling models are developed using GaBi LCA platform. The selected functional unit (FU) is 1 kg CFRP waste and the geographical boundary of this comparative LCIA is defined to be within the U.S. The results of this comparative assessment brought to light new insights about the environmental and human health impacts of CFRP waste recycling via solvolysis using SCW and, therefore, helped close a gap in the current state of knowledge about sustainability of SCW-based solvolysis as compared to pyrolysis. Two research questions are posed to identify whether solvolysis recycling offers more environmental and human health gains relative to the conventional pyrolysis recycling. These research questions lay the basis for formulating two null hypotheses (H{sub 0,1} and H{sub 0,2}) and their associated research hypotheses (H{sub 1,1} and H{sub 1,2}). LCIA results interpretation included ‘base case’ scenarios, ‘sensitivity studies,’ and ‘scenarios analysis.’ The results revealed that: (a) recycling via solvolysis using SCW exhibits no gains in environmental and human health impacts relative to those impacts associated with recycling via pyrolysis and (b) use of natural gas in lieu of electricity for pyrolyzer’s heating reduces the environmental and human health impacts by 37% (lowest) and up to 95.7% (highest). It is recommended that on-going experimental efforts that focus only on identifying the best solvent for solvolysis-based recycling should also consider quantification of the energy intensity as well as environmental and human health impacts of the proposed solvents.

29 ENERGY PLANNING, POLICY, AND ECONOMY↗
DOE OSTI2017

Hypoxia regulates microRNA expression in the human carotid body

The carotid body (CB) is the key sensing organ for physiological oxygen levels in the body. Under conditions of low oxygen (hypoxia), the CB plays crucial roles in signaling to the cardiorespiratory center in the medulla oblongata for the restoration of oxygen homeostasis. How hypoxia regulates gene expression in the human CB remains poorly understood. While limited information on transcriptional regulation in animal CBs is available, the identity and impact of important post-transcriptional regulators such as non-coding RNAs, and in particular miRNAs are not known. Here we show using ex vivo experiments that indeed a number of miRNAs are differentially regulated in surgically removed human CB slices when acute hypoxic conditions were applied. Analysis of the hypoxia-regulated miRNAs shows that they target biological pathways with upregulation of functions related to cell proliferation and immune response and downregulation of cell differentiation and cell death functions. Comparative analysis of the human CB miRNAome with the global miRNA expression patterns of a large number of different human tissues showed that the CB miRNAome had a unique profile which reflects its highly specialized functional status. Nevertheless, the human CB miRNAome is most closely related to the miRNA expression pattern of brain tissues indicating that they may have the most similar developmental origins. - Highlights: • Hypoxia triggers differential expression of many miRNAs in the human carotid body. • This can lead to the upregulation of proliferation and immune response functions. • CB expression profile in the carotid body resembles the miRNA expression pattern in the brain. • miRNAs are involved in the regulation of carotid body functions including oxygen sensing.

60 APPLIED LIFE SCIENCES↗
DOE OSTI2021

A human cell type similar to murine central nervous system perivascular fibroblasts

Highlights: • Human diploid cell lines were established from tumor and non-tumor brain tissue. • Human cells share a common transcriptomic profile with murine perivascular fibroblasts. • Human cells resemble commercially available cell of presumed pericyte origin. The brain vasculature has several specific features, one of them being the blood-brain barrier (BBB), which supports and protects the brain by allowing for the passage of oxygen and nutrients, while at the same time preventing passage of pathogens and toxins. The BBB also prevents efficient delivery of drugs to the brain, e.g. for treatment of brain tumors. In the murine brain, perivascular fibroblasts were recently identified as a novel potential constituent of the BBB. Here we present the existence of human cells that could be the equivalent to the murine brain perivascular fibroblasts. Using RNA sequencing, we show a similar transcriptomic profile of cultured human brain cells and murine perivascular fibroblasts. These data open up a window for new hypotheses on cell types involved in human CNS diseases.

60 APPLIED LIFE SCIENCES↗