Biology subjects

Huynh, T.

Publications and source records attributed to Huynh, T..

16 recordsLinked to original sources

bioRxiv2026

LNA043 and ANGPTL3 Interactions with Integrin α5β1 and Fibronectin Drive Distinct Stromal and Immune Responses

Osteoarthritis (OA) is characterized by cartilage breakdown, extracellular matrix remodeling, and synovial inflammation. Dysregulated integrin 5{beta}1 signaling and fibronectin fragmentation are key drivers of OA progression. We found that in ihMSC, LNA043, Full length ANGPTL3 (FL-ANGPTL3, and C-terminal fibronogen-tlike domain of ANGPTL3 (C-ANGPTL3) interacted with both integrin 5{beta}1 and fibronectin, consistent with a multivalent binding mode supported by AlphaFold based structural predictions. FL-ANGPTL3 supported ihMSC adhesion and induced human monocyte migration, with both effects being dependent on integrin {beta}1. C-ANGPTL3 alone was sufficient to mediate these effects, although with reduced efficacy compared to the full-length protein. In contrast, LNA043 did not support ihMSC adhesion but retained integrin {beta}1-dependent monocyte migratory activity, defining a more selective functional profile and indicating that further truncation modulates downstream responses without abolishing integrin engagement. To further explore the biology of ANGPTL3 and the mechanism of action of LNA043 we employed a targeted RASL Seq profiling. We found that both FL- and C-ANGPTL3, but not LNA043, induced broad transcriptional reprogramming and counter regulated fibronectin fragment-driven inflammatory signaling in monocytes. We uncovered a role for ANGPTL3 in fibronectin-integrin 5{beta}1 signaling and showed that LNA043 preserves this interaction while uncoupling it from strong immune responses.

cell biology↗

bioRxiv2025

THE IMPACT OF ARTIFICIAL INTELLIGENCE ON UNIVERSITY STUDENTS PERCEPTIONS OF ENVIRONMENTAL CHALLENGES AND SUSTAINABLE SOLUTIONS

In the context of Vietnams higher education strongly transforming towards digitalization and sustainability, this study aims to analyze the impact of artificial intelligence (AI) on students awareness and intention to act for the environment. Based on the Extended Planned Behavior (TPB) model, the research model integrates two input factors: environmental awareness (EA) and the level of interaction with AI in environmental learning (AEEL), affecting three mediating factors: attitude (AT), subjective norm (SN) and perceived behavioral control (PBC), thereby predicting students green action intention (GAI). Data collected from 521 students at private university in Vietnam were processed using EFA, CFA and SEM. The results showed that both EA and AEEL had positive effects on AT, SN and PBC (p < 0.001). Among them, AEEL had the strongest influence on SN ({beta} = 0.281) and PBC ({beta} = 0.252). PBC had the strongest influence on GAI ({beta} = 0.312), followed by AT ({beta} = 0.274) and SN ({beta} = 0.267). Bootstrapping mediation analysis confirmed that the mediating variables (AT, SN, PBC) played an important role in linking EA and AEEL with GAI. In addition, cluster analysis showed that female students and senior students had significantly higher levels of AI engagement and action intention. These results suggest that AI not only serves as a learning support tool but also as a catalyst for sustainable behavior in higher education.

scientific communication and education↗

bioRxiv2024

CLCC1 promotes membrane fusion during herpesvirus nuclear egress.

ABSTRACT/SUMMARYHerpesvirales are an ancient viral order that infects species from mollusks to humans for life. During infection, these viruses translocate their large capsids from the nucleus to the cytoplasm independently from the canonical route through the nuclear pore. Instead, capsids dock at the inner nuclear membrane and bud into the perinuclear space. These perinuclear enveloped virions fuse with the outer nuclear membrane releasing the capsids into the cytoplasm for maturation into infectious virions. The budding stage is mediated by virally encoded proteins. But the mediator of the subsequent fusion stage is unknown. Here, using a whole-genome CRISPR screen with herpes simplex virus 1, we identified CLCC1 as an essential host factor for the fusion stage of nuclear egress. Loss of CLCC1 results in a defect in nuclear egress, accumulation of capsid-containing perinuclear vesicles, and a drop in viral titers. In uninfected cells, loss of CLCC1 causes a defect in nuclear pore complex insertion. Viral homologs of CLCC1 are present in herpesviruses that infect mollusks and fish. Our findings uncover an ancient cellular membrane fusion mechanism important for the fundamental cellular process of nuclear envelope morphogenesis that herpesviruses hijack for capsid transport.

microbiology↗

bioRxiv2024

Loss of the lysosomal protein CLN3 modifies the lipid content of the nuclear envelope leading to DNA damage and activation of YAP1 pro-apoptotic signaling

Batten disease is characterized by early-onset blindness, juvenile dementia and death during the second decade of life. The most common genetic causes are mutations in the CLN3 gene encoding a lysosomal protein. There are currently no therapies targeting the progression of the disease, mostly due to the lack of knowledge about the disease mechanisms. To gain insight into the impact of CLN3 loss on cellular signaling and organelle function, we generated CLN3 knock-out cells in a human cell line (CLN3-KO), and performed RNA sequencing to obtain the cellular transcriptome. Following a multi-dimensional transcriptome analysis, we identified the transcriptional regulator YAP1 as a major driver of the transcriptional changes observed in CLN3-KO cells. We further observed that YAP1 pro-apoptotic signaling is hyperactive as a consequence of CLN3 functional loss in retinal pigment epithelia cells, and in the hippocampus and thalamus of CLN3ex{Delta}7/8 mice, an established model of Batten disease. Loss of CLN3 activates YAP1 by a cascade of events that starts with the inability of releasing glycerophosphodiesthers from CLN3-KO lysosomes, which leads to perturbations in the lipid content of the nuclear envelope and nuclear dysmorphism. This results in increased number of DNA lesions, activating the kinase c-Abl, which phosphorylates YAP1, stimulating its pro-apoptotic signaling. Altogether, our results highlight a novel organelle crosstalk paradigm in which lysosomal metabolites regulate nuclear envelope content, nuclear shape and DNA homeostasis. This novel molecular mechanism underlying the loss of CLN3 in mammalian cells and tissues may open new c-Abl-centric therapeutic strategies to target Batten disease.

cell biology↗

bioRxiv2024

Efficient CRISPR genome editing and integrative genomic analyses reveal the mosaicism of Cas-induced mutations and pleiotropic effects of scarlet gene in an emerging model system

Despite the revolutionary impacts of CRISPR-Cas gene editing systems, the effective and widespread use of CRISPR technologies in emerging model organisms still faces significant challenges. These include the inefficiency in generating heritable mutations at the organismal level, limited knowledge about the genomic consequences of gene editing, and an inadequate understanding of the inheritance patterns of CRISPR-Cas-induced mutations. This study addresses these issues by 1) developing an efficient microinjection delivery method for CRISPR editing in the microcrustacean Daphnia pulex; 2) assessing the editing efficiency of Cas9 and Cas12a nucleases, examining mutation inheritance patterns, and analyzing the local and global mutation spectrum in the scarlet mutants; and 3) investigating the transcriptomes of scarlet mutants to understand the pleiotropic effects of scarlet underlying their swimming behavior changes. Our reengineered CRISPR microinjection method results in efficient biallelic editing with both nucleases. While indels are dominant in Cas-induced mutations, a few on-site large deletions (>1kb) are observed, most likely caused by microhomology-mediated end joining repair. Knock-in of a stop codon cassette to the scarlet locus was successful, despite complex induced mutations surrounding the target site. Moreover, extensive germline mosaicism exists in some mutants, which unexpectedly produce different phenotypes/genotypes in their asexual progenies. Lastly, our transcriptomic analyses unveil significant gene expression changes associated with scarlet knock-out and altered swimming behavior in mutants, including several genes (e.g., NMDA1, ABAT, CNTNAP2) involved in human neurodegenerative diseases. This study expands our understanding of the dynamics of gene editing in the tractable model organism Daphnia and highlights its promising potential as a neurological disease model.

genomics↗

bioRxiv2023

The Identification of IL-4 as a Regulator of Chimeric Antigen Receptor T Cell Exhaustion

Durable response to chimeric antigen receptor T (CART) cell therapy remains limited in part due to CART cell exhaustion. We investigated the regulation of CART cell exhaustion with three independent approaches including: a genome-wide CRISPR knockout screen using a validated in vitro model for exhaustion, RNA and ATAC sequencing on baseline and chronically stimulated CART cells, and RNA and ATAC sequencing on pre-infusion CART cell products from responders and non-responders in the ZUMA-1 clinical trial. Each of these approaches identified IL-4 as a key regulator of CART cell dysfunction. Further, when CART cells were treated with IL-4, they developed signs of exhaustion, but when CART cells were treated with an IL-4 monoclonal antibody, they showed improved antitumor efficacy and reduced signs of exhaustion in preclinical models. Therefore, our study identified both a novel role for IL-4 on CART cells and the improvement of CART cell therapy through IL-4 neutralization. Statement of SignificanceIdentifying regulators of CART cell exhaustion will not only enhance the fields understanding of therapeutic failure, but it will also provide avenues to enhance CART cell efficacy. This study reveals both a novel role for IL-4 in exhaustion and a strategy to improve CART cell activity through IL-4 neutralization.

immunology↗

bioRxiv2022

A Remarkable Adaptive Paradigm Of Heart Performance And Protection Emerges In Response To The Constitutive Challenge Of Marked Cardiac-Specific Overexpression Of Adenylyl Cyclase Type 8

Adult mice with cardiac-specific overexpression of adenylyl cyclase (AC) type VIII (TGAC8) adapt to an incessantly increased cAMP-induced cardiac workload ([~]30% increases in heart rate, ejection fraction and cardiac output) for up to a year without signs of heart failure or excessive mortality. Here we show that despite markedly increased cardiac work, classical cardiac hypertrophy markers were absent in TGAC8, total left ventricular (LV) mass was not increased: a reduced LV cavity volume in TGAC8 was encased by thicker LV walls harboring an increased number of small cardiac myocytes and a network of small interstitial non-cardiac myocytes, manifesting increased proliferation markers and compared to WT. Protein synthesis, proteosome activity, autophagy, and Nrf-2, Hsp90, ACC2 protein levels were increased in TGAC8, but LV ATP and phosphocreatine levels in vivo did not differ by genotype. 2,323 transcripts and 2,184 proteins identified in unbiased omics analyses, spanning a wide array of biological processes and molecular functions in numerous cellular compartments differed in TGAC8 vs WT; and over 250 canonical signaling pathways characteristic of adaptive survival circuitry of cancers, including PI3K and growth factor signaling, cytokine and T cell receptor signaling, immune responses, ROS scavenging, proliferation, protection from apoptosis, and nutrient sensing, were activated in TGAC8; and compared to WT there was a shift from fatty acid oxidation to increased aerobic glycolysis in the context of increased utilization of the pentose phosphate shunt and nucleotide synthesis. Thus, the adaptive paradigm, that becomes activated in the LV of TGAC8 in response to severe chronic, intense AC/PKA/Ca2+ signaling embodies many hallmarks of cancer.

physiology↗

bioRxiv2021

in silico Assessment of Antibody Drug Resistance to Bamlanivimab of SARS-CoV-2 Variant B.1.617

The highly infectious SARS-CoV-2 variant B.1.617 with double mutations E484Q and L452R in the receptor binding domain (RBD) of SARS-CoV-2s spike protein is worrisome. Demonstrated in crystal structures, the residues 452 and 484 in RBD are not in direct contact with interfacial residues in the angiotensin converting enzyme 2 (ACE2). This suggests that albeit there are some possibly nonlocal effects, the E484Q and L452R mutations might not significantly affect RBDs binding with ACE2, which is an important step for viral entry into host cells. Thus, without the known molecular mechanism, these two successful mutations (from the point of view of SARS-CoV-2) can be hypothesized to evade human antibodies. Using in silico all-atom molecular dynamics (MD) simulation as well as deep learning (DL) approaches, here we show that these two mutations significantly reduce the binding affinity between RBD and the antibody LY-CoV555 (also named as Bamlanivimab) that was proven to be efficacious for neutralizing the wide-type SARS-CoV-2. With the revealed molecular mechanism on how L452R and E484K evade LY-CoV555, we expect that more specific therapeutic antibodies can be accordingly designed and/or a precision mixing of antibodies can be achieved in a cocktail treatment for patients infected with the variant B.1.617. O_FIG_DISPLAY_L [Figure 1] M_FIG_DISPLAY C_FIG_DISPLAY

biophysics↗

bioRxiv2021

Insights on SARS-CoV-2's Mutations for Evading Human Antibodies: Sacrifice and Survival

Recent mutations on the receptor binding domain (RBD) of the SARS-CoV-2s spike protein have been manifested as the major cause of the wide and rapid spread of the virus. Especially, the variant B.1.351 in South Africa with the hallmark of triple mutations (N501Y, K417N and E484K) is worrisome. Quickly after the outbreak of this new variant, several studies showed that both N501Y and E484K can enhance the binding between RBD and the human ACE2 receptor. However, the mutation K417N seems to be unfavorable because it removes one interfacial salt-bridge. So far, it is still not well understood why the K417N mutation is selected in the viral evolution. Here, we show that despite the loss in the binding affinity (1.48 kcal/mol) between RBD and ACE2 the K417N mutation abolishes a buried interfacial salt-bridge between RBD and the neutralizing antibody CB6 and thus substantially reduces their binding energy by 9.59 kcal/mol, facilitating the variants to efficiently elude CB6 (as well as many other antibodies). Thus, when proliferating from person to person the virus might have adapted to the human immune system through evasive mutations. Taking into account limited and relevant experimental works in the field, we show that our theoretical predictions are consistent with existing experimental findings. By harnessing the revealed molecular mechanism for variants, it becomes feasible to redesign therapeutic antibodies accordingly to make them more efficacious. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC="FIGDIR/small/430088v1_ufig1.gif" ALT="Figure 1"> View larger version (52K): org.highwire.dtl.DTLVardef@1ce030eorg.highwire.dtl.DTLVardef@2a9f85org.highwire.dtl.DTLVardef@4f1265org.highwire.dtl.DTLVardef@140c0be_HPS_FORMAT_FIGEXP M_FIG C_FIG

biophysics↗

bioRxiv2021

Molecular Mechanism of the N501Y Mutation for Enhanced Binding between SARS-CoV-2's Spike Protein and Human ACE2 Receptor

Coronavirus disease 2019 (COVID-19) has been an ongoing global pandemic for over a year. Recently, an emergent SARS-CoV-2 variant (B.1.1.7) with an unusually large number of mutations had become highly contagious and wide-spreading in United Kingdom. From genome analysis, the N501Y mutation within the receptor binding domain (RBD) of the SARS-CoV-2s spike protein might have enhanced the viral proteins binding with the human angiotensin converting enzyme 2 (hACE2). The latter is the prelude for the virus entry into host cells. So far, the molecular mechanism of this enhanced binding is still elusive, which prevents us from assessing its effects on existing therapeutic antibodies. Using all atom molecular dynamics simulations, we demonstrated that Y501 in mutated RBD can be well coordinated by Y41 and K353 in hACE2 through hydrophobic interactions, increasing the overall binding affinity between RBD and hACE2 by about 0.81 kcal/mol. We further explored how the N501Y mutation might affect the binding between a neutralizing antibody (CB6) and RBD. We expect that our work can help researchers design proper measures responding to this urgent virus mutation, such as adding a modified/new neutralizing antibody specifically targeting at this variant in the therapeutic antibody cocktail. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=121 SRC="FIGDIR/small/425316v1_ufig1.gif" ALT="Figure 1"> View larger version (40K): org.highwire.dtl.DTLVardef@1231e91org.highwire.dtl.DTLVardef@abf67dorg.highwire.dtl.DTLVardef@1c3a288org.highwire.dtl.DTLVardef@e3ab52_HPS_FORMAT_FIGEXP M_FIG C_FIG

molecular biology↗

bioRxiv2020

Genome-wide binding analysis of 195 DNA Binding Proteins reveals "reservoir" promoters and human specific SVA-repeat family regulation

A key aspect in defining cell state is the complex choreography of DNA binding events in a given cell type, which in turn establishes a cell-specific gene-expression program. In the past two decades since the sequencing of the human genome there has been a deluge of genome-wide experiments which have measured gene-expression and DNA binding events across numerous cell-types and tissues. Here we re-analyze ENCODE data in a highly reproducible manner by utilizing standardized analysis pipelines, containerization, and literate programming with Rmarkdown. Our approach validated many findings from previous independent studies, underscoring the importance of ENCODEs goals in providing these reproducible data resources. This approach also revealed several new findings: (i) 1,362 promoters, termed reservoirs, have up to 111 different DNA binding-proteins localized on one promoter yet do not have any expression of steady-state RNA (ii) The human specific SVA repeat element may have been co-opted for enhancer regulation. Collectively, this study performed by the students of a CU Boulder computational biology class (BCHM 5631 - Spring 2020) demonstrates the value of reproducible findings and how resources like ENCODE that prioritize data standards can foster new findings with existing data in a didactic environment.

genomics↗

bioRxiv2020

NMDA receptors control cortical axonal projections via EPHRIN-B/EPHB signaling

Callosal projections from primary somatosensory cortex (S1) are key for processing somatosensory inputs and integrating sensory-motor information. How the callosal innervation pattern in S1 is formed during early postnatal development is not clear. We found that the normal termination pattern of these callosal projections is disrupted in cortex specific NMDAR mutants. Rather than projecting selectively to the primary/secondary somatosensory cortex (S1/S2) border, axons were uniformly distributed throughout S1. In addition, the density of this projection increased over postnatal life until the mice died by P30. By combining genetic and antibody-mediated loss of function, we demonstrated that it is NR2B-containing NMDA receptors in target S1 that mediate this guidance phenotype, thus playing a central role in interhemispheric connectivity. Furthermore, we found that this function of NMDA receptors in callosal circuit formation is independent of ion channel function and instead depends on interactions with EPHRIN-B/EPHB. Thus, NMDAR cooperates with EPHRIN-B/EPHB in target S1 to control the formation callosal circuits by acting as an accessory axon guidance receptor modulating EPH-dependent repulsion.

neuroscience↗

bioRxiv2020

Vicarious trial-and-error is enhanced during deliberation in human virtual navigation in a translational neuroeconomic task

Foraging tasks can provide valuable insights into decision-making, as animals choose how to allocate limited resources (such as time). In the "Restaurant Row" task, rodents move between several sites to obtain food rewards available after a variable delay, while in a translational version (the "Web-Surf") lacking the navigation component, humans are offered short videos. Both tasks have provided novel insights into decision-making and have been applied to addiction vulnerability and the impact of drug exposure on decision-making. We tested new tasks (the "Movie Row" and "Candy Row") which use virtual navigation to determine if the behavioral correlates of human decision-making are more broadly similar to those of rodents, and explored the relationship of task performance to smoking and obesity. Humans navigated a virtual maze presented on standard computers to obtain rewards (either short videos or candy) available after a variable delay. Behavior on the tasks replicated previous results for the Restaurant Row and Web-Surf. In conditions promoting deliberation, decision latency was elevated along with measures of vicarious trial-and-error (VTE), supporting VTE as a shared behavioral index of deliberation across species. Smoking status was not well-related to performance, while high BMI (> 25) individuals showed reduced sensitivity to a sunk-costs measure and stronger sensitivity to offer value for offers below the preferred delay. These data support the Movie and Candy Row as translational tools to study decision-making during foraging in humans, providing convergent results with a rodent navigation task and demonstrating the potential to provide novel insights relevant to public health.

neuroscience↗

bioRxiv2019

Growth-dependent activation of protein kinases links cell cycle progression to cell growth

In all cells, progression through the cell cycle occurs only when sufficient growth has occurred. Thus, cells must translate growth into a proportional signal that can be used to measure and transmit information about growth. Previous genetic studies in budding yeast suggested that related kinases called Gin4 and Hsl1 could play roles in mechanisms that measure bud growth; however, interpretation of the data was complicated by the use of gene deletions that cause complex terminal phenotypes. Here, we used the first conditional alleles of Gin4 and Hsl1 to more precisely define their functions. We show that excessive bud growth during a prolonged mitotic delay is an immediate consequence of inactivating Gin4 and Hsl1. Thus, acute loss of Gin4 and Hsl1 causes cells to behave as though they cannot detect that bud growth has occurred. We further show that Gin4 and Hsl1 undergo gradual hyperphosphorylation during bud growth that is dependent upon growth and correlated with the extent of growth. Moreover, gradual hyperphosphorylation of Gin4 during bud growth requires binding to anionic phospholipids that are delivered to the growing bud. While alternative models are possible, the data suggest that signaling lipids delivered to the growing bud generate a growth-dependent signal that could be used to measure bud growth.

cell biology↗

bioRxiv2019

A human ex vivo dengue virus neutralization assay identifies priority antibodies and epitopes for vaccines and therapeutics.

BackgroundDengue is the most prevalent arboviral disease, for which neither effective vaccines nor antivirals are available. Clinical trials with Dengvaxia, the first licensed dengue vaccine, show the conventional in vitro plaque reduction neutralization test (PRNT) failed to discriminate between neutralizing and non-neutralizing antibodies. A number of human monoclonal antibodies (mAbs) were characterized by PRNT as being neutralizers of virus infectivity for mammalian cells.\n\nMethodolody/Principle findingsWe developed a neutralization assay and tested the capacity of 12 mAbs to neutralize the infectiousness of dengue patient viremic blood in mosquitoes. We identified minimum concentrations of a subset of mAbs required to achieve dengue virus neutralization, and modelled the impact of a therapeutic mAb candidate on viremia.\n\nFive of the 12 mAbs (14c10, 2D22, 1L12, 747(4)B7, 753(3)C10), all of which target quaternary epitopes, potently inhibited dengue virus infection of Ae. aegypti. The potency of several mAbs was compromised in the context of patients with secondary serological profiles, possibly reflecting competition between the exogenously-added mAbs and the patients own antibody responses at or near the target epitopes. The minimum concentrations that mAbs neutralized DENV ranged from 0.1 - 5 {micro}g/mL. An Fc-disabled variant of mAb (14c10-LALA) was as potent as its parent mAb. Within-host mathematical modelling suggests infusion of 14c10-LALA could bring about rapid acceleration of viremia resolution in a typical patient.\n\nConclusions/SignificanceThese data delivered a unique assessment of anti-viral potency of a panel of human mAbs. Results support the advancement of dengue virus neutralization assays, and the development of therapeutics against flaviviruses, to which dengue virus and Zika virus belong.\n\nAuthor summaryDengue is the most prevalent arboviral disease affecting humans. There are no therapeutics for the disease. Antibody-mediated immunity against dengue is also not well-understood, as shown by the failure of the conventional neutralization assay used to predict the efficacy of Dengvaxia, the first licensed vaccine for the disease. It is likely that the neutralization assay targets non-neutralizing antibodies, but there are no validation assays available. To this end, we developed a novel virus neutralization assay, employing Aedes aegypti mosquitoes and viremic blood from dengue patients, to examine the virus-neutralizing potency of 12 human-derived monoclonal antibodies (mAbs). While all of these mAbs neutralized dengue virus using the conventional assay, seven of them failed to block dengue virus infections of mosquitoes using our assay. The remaining five mAbs neutralized at least one serotype of dengue virus and the minimum neutralizing concentrations of range from 0.1 - 5 {micro}g/mL. Using the minimum neutralizing concentration of a therapeutic mAb candidate, we investigated the impact of the mAb on viremia using a mathematical model and found the mAb accelerated the reduction of viremia. The results support the advancement of dengue virus neutralization assays, and the development of therapeutics for dengue.

immunology↗

bioRxiv2018

Real-time fine aerosol exposures in taconite mining operations

Respiratory health effects such as mesothelioma, silicosis, and lung cancer have been shown to be associated with working in the taconite mining industry. Taconite workers may also have elevated risks from cardiovascular disease (CVD), although the relationship of CVD to dust exposures at these mines has not been well-studied. Motivated by evidence from environmental epidemiological studies and occupational cohorts that have implicated the effects of fine particulates with increased risk of cardiovascular diseases, we conducted an air monitoring campaign to characterize fine aerosol concentrations at 91 locations across six taconite mines using an array of direct-reading instruments to obtain measurements of mass concentrations (PM2.5 or particles with aerodynamic diameter less than 2.5 m, and respirable particulate matter or RPM), alveolar-deposited surface area concentrations (ADSA), particle number concentrations (PN), and particle size distributions. To analyze these data, we fit a Bayesian hierarchical model with an AR(1) correlation structure to estimate exposure while accounting for temporal correlation. The highest estimated geometric means (GMs) were observed in the pelletizing and concentrating departments (pelletizing maintenance, balling drum operator, and concentrator operator) for PM2.5 and RPM. ADSA and PN generally had highest GMs in the pelletizing department, which processed large amounts of powder-like particles into iron pellets. The within-location variability (GSD_WL) generally ranged from 1 to 3 for all exposure metrics, except for a few locations which indicated changes of activities that caused the exposures to change. Between-location variability (GSD_BL) estimates were generally higher than GSD_WL, indicating larger differences in exposure levels at different locations between mines than at individual locations over the course of several hours. Ranking between PM2.5 and RPM generally agree with each other, whereas ADSA and PN were more consistent with each other, with some overlap with PM2.5 and RPM. Differences in ranking these groups may have potential implication for occupational epidemiological studies that rely on exposure information to detect an exposure-response relationship for various job groups. Future epidemiological studies investigating fine aerosol exposures and health risks in occupational settings are encouraged to use multiple metrics to see how they influence health outcomes risk.

epidemiology↗