Search

We introduce the first complete nonparametric model for the astrophysical distribution of the binary black hole (BBH) population. Constructed from basis splines, we use these models to conduct the most comprehensive data-driven investigation of the BBH population to date, simultaneously fitting nonparametric models for the BBH mass ratio, spin magnitude and misalignment, and redshift distributions. With GWTC-3, we report the same features previously recovered with similarly flexible models of the mass distribution, most notably the peaks in merger rates at primary masses of ∼10 M _⊙ and ∼35 M _⊙ . Our model reports a suppressed merger rate at low primary masses and a mass-ratio distribution consistent with a power law. We infer a distribution for primary spin misalignments that peaks away from alignment, supporting conclusions of recent work. We find broad agreement with the previous inferences of the spin magnitude distribution: the majority of BBH spins are small ( a < 0.5), the distribution peaks at a ∼ 0.2, and there is mild support for a nonspinning subpopulation, which may be resolved with larger catalogs. With a modulated power law describing the BBH merger rate’s evolution in redshift, we see hints of the rate evolution either flattening or decreasing at z ∼ 0.2–0.5, but the full distribution remains entirely consistent with a monotonically increasing power law. We conclude with a discussion of the astrophysical context of our new findings and how nonparametric methods in gravitational-wave population inference are uniquely poised to complement to the parametric approach as we enter the data-rich era of gravitational-wave astronomy.

Several features in the mass spectrum of merging binary black holes (BBHs) have been identified using data from the Third Gravitational Wave Transient Catalog (GWTC-3). These features are of particular interest as they may encode the uncertain mechanism of BBH formation. We assess if the features are statistically significant or the result of Poisson noise due to the finite number of observed events. We simulate catalogs of BBHs whose underlying distribution does not have the features of interest, apply the analysis previously performed on GWTC-3, and determine how often such features are spuriously found. We find that one of the features found in GWTC-3, the peak at ∼35 M _☉ , cannot be explained by Poisson noise alone: peaks as significant occur in 1.7% of catalogs generated from a featureless population. This peak is therefore likely to be of astrophysical origin. The data is suggestive of an additional significant peak at ∼10 M _☉ , though the exact location of this feature is not resolvable with current observations. Additional structure beyond a power law, such as the purported dip at ∼14 M _☉ , can be explained by Poisson noise. We also provide a publicly available package, GWMockCat , that creates simulated catalogs of BBH events with correlated measurement uncertainty and selection effects according to user-specified underlying distributions and detector sensitivities.

Measurement of the semantic and syntactic similarity of human utterances is essential in allowing machines to understand dialogue with users. However, human language is complex, and the semantic meaning of an utterance is usually dependent upon the context at a given time and learnt experience of the meaning of the words that are used. This is particularly challenging when automatically understanding the meaning of social media, such as tweets, which can contain non-standard language. Short Text Semantic Similarity measures can be adapted to measure the degree of similarity of a pair of tweets. This work presents a new Semantic and Syntactic Similarity Measure (TSSSM) for political tweets. The approach uses word embeddings to determine semantic similarity and extracts syntactic features to overcome the limitations of current measures which may miss identical sequences of words. A large dataset of tweets focusing on the political domain were collected, pre-processed and used to train the word embedding model, with various experiments performed to determine the optimal model and parameters. A selection of tweet pairs were evaluated by humans for semantic equivalence and correlated against the measure. The new measure can be used in a variety of applications, including for identifying and analyzing political narratives. Experiments on three diverse human-labelled test datasets demonstrate that the measure outperforms an existing measure, performs well on tweets from the political domain and may also generalize outside the political domain.

Advanced LIGO and Advanced Virgo are monitoring the sky and collecting gravitational-wave strain data with sufficient sensitivity to detect signals routinely. In this paper we describe the data recorded by these instruments during their first and second observing runs. The main data products are gravitational-wave strain time series sampled at 16384 Hz. The datasets that include this strain measurement can be freely accessed through the Gravitational Wave Open Science Center at http://gw-openscience.org, together with data-quality information essential for the analysis of LIGO and Virgo data, documentation, tutorials, and supporting software.

In order to deal with an increasingly complex world, we need ever more sophisticated computational models that can help us make decisions wisely and understand the potential consequences of choices. But creating a model requires far more than just raw data and technical skills: it requires a close collaboration between model commissioners, developers, users and reviewers. Good modelling requires its users and commissioners to understand more about the whole process, including the different kinds of purpose a model can have and the different technical bases. This paper offers a guide to the process of commissioning, developing and deploying models across a wide range of domains from public policy to science and engineering. It provides two checklists to help potential modellers, commissioners and users ensure they have considered the most significant factors that will determine success. We conclude there is a need to reinforce modelling as a discipline, so that misconstruction is less likely; to increase understanding of modelling in all domains, so that the misuse of models is reduced; and to bring commissioners closer to modelling, so that the results are more useful.

Modellers of complex biological or social systems are often faced with an invidious choice: to use simple models with few mechanisms that can be fully analysed, or to construct complicated models that include all the features which are thought relevant. The former ensures rigour, the latter relevance. We discuss a method that combines these two approaches, beginning with a complex model and then modelling the complicated model with simpler models. The resulting "chain" of models ensures some rigour and relevance. We illustrate this process on a complex model of voting intentions, constructing a reduced model which agrees well with the predictions of the full model. Experiments with variations of the simpler model yield additional insights which are hidden by the complexity of the full model. This approach facilitated collaboration between social scientists and physicists-the complex model was specified based on the social science literature, and the simpler model constrained to agree (in core aspects) with the complicated model.

Pretreatment of lignocellulosic biomass is a prerequisite to overcome recalcitrance and allow enzyme accessibility to cellulose and maximize product recovery for improved economics of second-generation lignocellulosic bio-refineries. Recently, the three US-DOE funded Bioenergy Research Centers (Joint Bioenergy Institute (JBEI), Great Lakes Bioenergy Research Center (GLBRC), and BioEnergy Science Center (BESC)) compared ionic liquid (IL), dilute sulfuric acid (DA), and ammonia fiber expansion (AFEXTM) pretreatments and published comparative data on mass balance, total sugar yields, substrate accessibility, and microbial fermentation (Biotechnology for Biofuels 7: 71; 72 (2014)). In this study, corn stover solids from IL, DA, and AFEX pretreatments were compared to gain comprehensive, in-depth understanding of induced morphological and chemical changes incorporated to corn stover, and how they overcome the biomass recalcitrance. These studies reveal that biomass recalcitrance is overcome by combination of structural and chemical changes to carbohydrates and lignin after pretreatment. Thermal analysis indicates that AFEX and IL pretreated corn stover showed a lower thermal stability while DA pretreated corn stover showed the opposite. The surface roughness variations measured by SANS were correlated to the removal and redistribution of biomass components and was consistent with compositional analysis, AFM and confocal fluorescence imaging results. With AFM and confocal fluorescent microscopy, lignin was found to be re-deposited on cellulose surface with average cellulose fiber width significantly decreased for DA pretreated corn stover (one third of IL and AFEX). HSQC NMR spectra revealed a ~17.9% reduction of β-aryl ether units after AFEX, ~59.8% reduction after DA and >98% reduction after IL. Both NMR and SEC showed similar patterns of lignin depolymerization with highest degree of depolymerization observed for IL followed with DA and AFEX.

Patients with high risk salivary gland malignancies are at increased risk of local failure. We present our institutional experience with dose escalation using hypofractionated Stereotactic Body Radiotherapy (SBRT) in a subset of this rare disease. Over the course of 9 years, 10 patients presenting with skull base invasion, gross disease with one or more adverse features, or those treated with adjuvant radiation with three or more pathologic features were treated with intensity modulated radiation therapy followed by hypofractionated SBRT boost. Patients presented with variable tumor histologies, and in all but one, the tumors were classified as poorly differentiated high grade. Four patients had gross disease, 3 had gross residual disease, 3 had skull base invasion, and 2 patients had rapidly recurrent disease (≤ 6 months) that had been previously treated with surgical resection. The median Stereotactic Radiosurgery boost dose was 17.5 Gy (range 10-30 Gy) given in a median of 5 fractions (range 3-6 fractions) for a total median cumulative dose of 81.2 Gy (range 73.2-95.6 Gy). The majority of the patients received platinum based concurrent chemotherapy with their radiation. At a median follow-up of 32 months (range 12-120) for all patients and 43 months for surviving patients (range 12-120), actuarial 3-year locoregional control, distant control, progression free survival, and overall survival were 88%, 81%, 68%, and 79%, respectively. Only one patient failed locally and two failed distantly. Serious late toxicity included graft ulceration in 1 patient and osteoradionecrosis in another patient, both of which underwent surgical reconstruction. Six patients developed fibrosis. In a subset of patients with salivary gland malignancies with skull base invasion, gross disease, or those treated adjuvantly with three or more adverse pathologic features, hypofractionated SBRT boost to Intensity Modulated Radiotherapy yields good local control rates and acceptable toxicit

Background: Inverted papilloma (IP) of the nasal cavity is a benign tumor that 0.5-4% of all nasal tumors and have been known to rarely undergo malignant transformation to squamous carcinoma an even more rarely adenocarcinoma. Synchronous association with low grade esthesioneuroblastoma (ENB) has been reported in only one case report where a small sized lesion was treated with surgery alone. Here we report the first case of invasion of IP by high grade ENB with nodal metastasis that was treated with combined modality therapy.Case Presentation: A case of a 64 year-old African American gentleman presented to the otolaryngology with a three-month history of recurrent epistaxis. Imaging revealed a large right nasal cavity mass extending into the right sphenoid sinus but without intracranial extension. Surgical pathology revealed high grade ENB invading IP. An orbitofrontal craniotomy approach was used to achieve complete resection of the mass but with positive margins. Postoperative PET/CT showed nodal metastasis. The patient was then treated with adjuvant chemoradiation and remains without evidence of disease at 42 months post-treatment. We discuss the disease presentation, histopathologic features, and disease management with literature support.Conclusion: In this very rare disease presentation where two extremely rare malignancies collide, we show that aggressive management with trimodality therapy of surgery, adjuvant radiation with stereotactic radiosurgical boost, and adjuvant chemotherapy gives excellent results. Given the natural history of the disease, however, long follow up is needed to declare complete freedom from the disease.

Neutrophils are armed with both oxidant-dependent and –independent pathways for killing pathogens. Activation of the phagocyte NADPH oxidase constitutes an emergency response to infectious threat and results in the generation of antimicrobial reactive oxidants. In addition, NADPH oxidase activation in neutrophils is linked to activation of granular proteases and generation of neutrophil extracellular traps (NETs). NETosis involves the release of nuclear and granular components that can target extracellular pathogens. NETosis is activated during microbial threat and in certain conditions mimicking sepsis, and can result in both augmented host defense and inflammatory injury. In contrast, apoptosis, the physiological form of neutrophil death, not only leads to non-inflammatory cell death but also contributes to alleviate inflammation. Although there are significant gaps in knowledge regarding the specific contribution of NETs to host defense, we speculate that the coordinated activation of NADPH oxidase and NETosis maximizes microbial killing. Work in engineered mice and limited patient experience point to varying susceptibility of bacterial and fungal pathogens to NADPH oxidase versus NET constituents. Since reactive oxidants and NET constituents can injure host tissue, it is important that these pathways be tightly regulated. Recent work supports a role for NETosis in both acute lung injury and in autoimmunity. Knowledge gained about mechanisms that modulate NETosis may lead to novel therapeutic approaches to limit inflammation-associated injury.

Background: To review a single-institution experience with the management of parotid malignancies treated by fractionated stereotactic body radiosurgery (SBRT) Findings: Between 2003 and 2011, 13 patients diagnosed with parotid malignancies were treated with adjuvant or definitive SBRT to a median dose of 33 Gy (range 25–40 Gy). There were 11 male and 2 female patients with a median age of 80. Ten (10) patients declined conventional radiation treatment and 3 patients had received prior unrelated radiation therapy to neighboring structures with unavailable radiation records. Six (6) patients were treated with definitive intent while 7 patients were treated adjuvantly for adverse surgical or pathologic features. Five (5) patients had clinical or pathologic evidence of lymph node disease. Conclusions: At a median follow-up of 14 months only 1 patient failed locally, and 4 failed distantly. The actuarial 2-year overall survival, progression free survival, and local-regional control rates were 46%, 84%, and 47%, respectively. Statistical analysis revealed surgery as a positive predictor of overall survival while presence of gross disease was a negatively correlated factor (p

Acute respiratory distress syndrome (ARDS) is a complication of pulmonary disease that produces life-threatening hypoxaemia. Despite ventilation and hyperoxic therapies, undetected hypoxia can manifest in capillary beds leading to multi-organ failure. Ox66™ is an ingestible, solid-state form of oxygen designed to supplement oxygen deficits. Twenty-four anaesthetized rats underwent a two-hit model of respiratory distress (ARDS), where a single dose (5 mg/kg) of lipopolysaccharide (LPS) was given intratracheally, and then the respiratory tidal volume was reduced by 40%. After 60 min, animals were randomized to receive Ox66™, or normal saline (NS; vehicle control) via gavage or supplemental inspired oxygen (40% FiO 2 ). A second gavage was administered at 120 min. Cardiovascular function and blood oximetry/chemistry were measured alongside the peripheral spinotrapezius muscle's interstitial oxygenation (P ISF O 2 ). ARDS reduced mean arterial pressure (MAP) and P ISF O 2 compared to baseline (BL) for all treatment groups. Treatment with Ox66 or NS did not improve MAP, but 40% FiO 2 caused a rapid return to BL. P ISF O 2 improved after treatment with Ox66 ™ and 40% FiO 2 and remained elevated for both groups against NS until study conclusion. Both oxygen treatments also suppressed the inflammatory response to LPS, suggesting that Ox66 ™ can deliver therapeutically-impactful levels of oxygen in situations of pulmonary dysfunction.

Novel actinobacteriophage Soos was isolated and purified from Southern Indiana soil using host Gordonia rubripertincta NRRL B-16540. Sequencing revealed a 57,509 bp circularly permuted genome encoding 87 predicted protein-coding genes. Soos is only the third phage in cluster CP, along with phages Clawz and Sting., Competing Interests: The authors declare no conflict of interest.

Introduction: Interest in nuclear power as a cleaner and alternative energy source is increasing in many countries. Despite the relative safety of nuclear power, large-scale disasters such as the Fukushima Daiichi (Japan) and Chernobyl (Ukraine) meltdowns are a reminder that emergency preparedness and safety should be a priority. In an emergency situation, there is a need to balance the tension between a rapid response, preventing harm, protecting communities, and safeguarding workers and responders. The first line of defense for workers and responders is personal protective equipment (PPE), but the needs vary by situation and location. Better understanding this is vital to inform PPE needs for workers and responders during nuclear and radiological power plant accidents and emergencies., Study Objective: The aim of this study was to identify and describe the PPE used by different categories of workers and responders during nuclear and radiological power plant accidents and emergencies., Methods: A systematic literature review format following the PRISMA 2020 guidelines was utilized. Databases SCOPUS, PubMed, EMBASE, INSPEC, and Web of Science were used to retrieve articles that examined the PPE recommended or utilized by responders to nuclear radiological disasters at nuclear power plants (NPPs)., Results: The search terms yielded 6,682 publications. After removal of duplicates, 5,587 sources continued through the systematic review process. This yielded 23 total articles for review, and five articles were added manually for a total of 28 articles reviewed in this study. Plant workers, decontamination or decommissioning workers, paramedics, Emergency Medical Services (EMS), emergency medical technicians, military, and support staff were the categories of responders identified for this type of disaster. Literature revealed that protective suits were the most common item of PPE required or recommended, followed by respirators and gloves (among others). However, adherence issues, human errors, and physiological factors frequently emerged as hinderances to the efficacy of these equipment in preventing contamination or efficiency of these responders., Conclusion: If worn correctly and consistently, PPE will reduce exposure to ionizing radiation during a nuclear and radiological accident or disaster. For the best results, standardization of equipment recommendations, clear guidelines, and adequate training in its use is paramount. As fields related to nuclear power and nuclear medicine expand, responder safety should be at the forefront of emergency preparedness and response planning.

Short-chain per- and polyfluoroalkyl substances (PFAS) are highly stable and widely used environmental contaminants that pose potential health risks to humans. Aggregating reliable mechanistic information for safety assessments necessitates physiologically relevant high-throughput screening approaches. Here, we demonstrated the utility of a liver-on-a-chip model to investigate the effects of five short-chain PFAS at low (1 nM) and high (1 μM) concentrations on toxicologically-relevant gene expression profiles using the QuantiGene® Plex Assay. We found that the short-chain PFAS tested in this study modulated the expression of ABCG2, a gene encoding for the breast cancer resistance protein (BCRP), with marked and significant upregulation (up to 4-fold) observed for all but one of the short-chain PFAS tested. PFBS and HFPO-DA repressed SLCO1B3 expression, a gene that encodes for an essential liver-specific organic anion transporter. High concentrations of PFBS, PFHxA, and PFHxS upregulated the expression of genes encCYP1A1,CYP2B6 and CYP2C19 with the same treatments resulting in the repression of the expression of the gene encoding CYP1A2. This dysregulation could have consequences for the clearance of endogenous compounds and xenobiotics. However, we acknowledge that increased expression of genes encoding for transporters and biotransformation enzymes may or may not indicate changes to their protein expression or activity. Overall, our study provides important insights into the effects of short-chain PFAS on liver function and their potential implications for human health. The use of the liver-on-a-chip model in combination with the QuantiGene® Plex Assay may be a valuable tool for future high-throughput screening and gene expression profiling in toxicology studies., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

A growing public health concern, chronic Diesel Exhaust Particle (DEP) exposure is a heavy risk factor for the development of neurodegenerative diseases like Alzheimer's (AD). Considered the brain's first line of defense, the Blood-Brain Barrier (BBB) and perivascular microglia work in tandem to protect the brain from circulating neurotoxic molecules like DEP. Importantly, there is a strong association between AD and BBB dysfunction, particularly in the Aβ transporter and multidrug resistant pump, P-glycoprotein (P-gp). However, the response of this efflux transporter is not well understood in the context of environmental exposures, such as to DEP. Moreover, microglia are seldom included in in vitro BBB models, despite their significance in neurovascular health and disease. Therefore, the goal of this study was to evaluate the effect of acute (24 hr.) DEP exposure (2000 μg/ml) on P-gp expression and function, paracellular permeability, and inflammation profiles of the human in vitro BBB model (hCMEC/D3) with and without microglia (hMC3). Our results suggested that DEP exposure can decrease both the expression and function of P-gp in the BBB, and corroborated that DEP exposure impairs BBB integrity (i.e. increased permeability), a response that was significantly worsened by the influence of microglia in co-culture. Interestingly, DEP exposure seemed to produce atypical inflammation profiles and an unexpected general downregulation in inflammatory markers in both the monoculture and co-culture, which differentially expressed IL-1β and GM-CSF. Interestingly, the microglia in co-culture did not appear to influence the response of the BBB, save in the permeability assay, where it worsened the BBB's response. Overall, our study is important because it is the first (to our knowledge) to investigate the effect of acute DEP exposure on P-gp in the in vitro human BBB, while also investigating the influence of microglia on the BBB's responses to this environmental chemical., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Human exposures to perfluoroalkyl and polyfluoroalkyl substances (PFAS) have been linked to several diseases associated with adverse health outcomes. Animal studies have been conducted, though these may not be sufficient due to the inherent differences in metabolic processes between humans and rodents. Acquiring relevant data on the health effects of short-chain PFAS can be achieved through methods supported by in vitro human cell-based models. Specifically, cytotoxicity assays are the crucial first step to providing meaningful information used for determining safety and providing baseline information for further testing. To this end, we exposed human cell lines representative of six different tissue types, including colon (CaCo-2), liver (HepaRG), kidney (HEK293), brain (HMC-3), lung (MRC-5), and muscle (RMS-13) to five short-chain PFAS and two legacy PFAS. The exposure of the individual PFAS was assessed using a range of concentrations starting from a low concentration (10 -11 M) to a high concentration of (10 -4 M). Our results indicated that CaCo-2 and HEK293 cells were the least sensitive to PFAS exposure, while HMC-3, HepaRG, MRC-5, and RMS-13 demonstrated significant decreases in viability in a relatively narrow range (EC 50 ranging from 1 to 70 µM). The most sensitive cell line was the neural HMC-3 for all short- and long-chain PFAS (with EC 50 ranging from 1.34 to 2.73 µM). Our data suggest that PFAS do not exert toxicity on all cell types equally, and the cytotoxicity estimates we obtained varied from previously reported values. Overall, this study is novel because it uses human cell lines that have not been widely used to understand human health outcomes associated with PFAS exposure., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Introduction: Pulmonary dysfunction (PD) and its associated hypoxia present a complication to the care of many service members and can arise intrinsically via comorbidities or extrinsically by infection or combat-related trauma (burn, smoke inhalation, and traumatic acute lung injury). Current supportive treatments (e.g., ventilation and supplemental oxygen) relieve hypoxia but carry a significant risk of further lung injury that drives mortality. Ox66 is a novel, solid-state oxygenating compound capable of delivering oxygen via intravenous infusion., Materials and Methods: Male Sprague Dawley rats (N = 21; 250-300 g) were surgically prepared for cardiovascular monitoring, fluid infusion, mechanical ventilation, and intravital and phosphorescence quenching microscopy (interstitial oxygen tension; PISFO2) of the spinotrapezius muscle. Baselines (BL) were collected under anesthesia and spontaneous respiration. PD was simulated via hypoventilation (50% tidal volume reduction) and was maintained for 3 hours. Groups were randomized to receive Ox66, normal saline (NS; vehicle control), or Sham (no treatment) and were treated immediately following PD onset. Arterial blood samples (65 µL) and intravital images were taken hourly to assess blood gases and chemistry and changes in arteriolar diameter, respectively. Significance was taken at P < .05., Results: PD reduced PISFO2 for all groups; however, by 75 minutes, both NS and Sham were significantly lower than Ox66 and remained so until the end of PD. Serum lactate levels were lowest in the Ox66 group-even decreasing relative to BL-but only significant versus Sham. Furthermore, all Ox66 animals survived the full PD challenge, while one NS and two Sham animals died. No significant vasoconstrictive or vasodilative effect was noted within or between experimental groups., Conclusion: Treatment with intravenous Ox66 improved interstitial oxygenation in the spinotrapezius muscle-a recognized bellwether for systemic capillary function-suggesting an improvement in oxygen delivery. Ox66 offers a novel approach to supplemental oxygenation that bypasses lung injury and dysfunction., (© The Association of Military Surgeons of the United States 2022. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Acute respiratory distress syndrome (ARDS) features pulmonary dysfunction capable of causing life-threatening hypoxaemia. Ventilation and hyperoxic therapies force oxygen through dysfunctional alveoli but risk exacerbating damage. Ox66™ is an ingestible, solid-state oxygen product designed for oxygen supplementation. Eighteen anaesthetized, ventilated rats were subjected to a 40% reduction in tidal volume to produce a hypoventilatory simulation of the hypoxia in ARDS (HV-ARDS). After 60 min, animals were randomized to receive either normal saline (Saline; volume control) or Ox66 ™ gavage. Cardiovascular function and blood oximetry/chemistry were measured alongside interstitial oxygenation (P ISF O 2 ) of the peripheral spinotrapezius muscle. HV-ARDS reduced mean arterial pressure by ∼20% and P ISF O 2 by ∼35% for both groups. Ox66 ™ gavage treatment at 60 min improved P ISF O 2 over Saline ( p  < .0001), restoring baseline values, however, the effect was temporary. A second bolus at 120 min repeated the OX66 ™ P ISF O 2 response, which remained elevated over Saline ( p  < .01) until study end and was supported by systemic parameters of lactate, P a O 2 , SO 2 , and base deficit. Saline remained hypotensive, whereas Ox66 ™ became normotensive. Vasoconstriction was observed in the Saline, but not Ox66 ™ group. Supplemental oxygenation through Ox66 ™ gavage increased peripheral tissue oxygenation, warranting further study for disorders featuring dysfunction of pulmonary perfusion like ARDS.

Exposure to combustion-derived particulate matter (PM) such as diesel exhaust particles (DEP) is a public health concern because people in urban areas are continuously exposed, and once inhaled, fine and ultrafine DEP may reach the brain. The blood-brain barrier (BBB) endothelial cells (EC) and the perivascular microglia protect the brain from circulating pathogens and neurotoxic molecules like DEP. While the BBB-microglial interaction is critical for maintaining homeostasis, no study has previously evaluated the endothelial-microglial interaction nor comprehensively characterized these cells' inflammatory marker profiles under ultrafine DEP exposures in vitro. Therefore, the goal of this study was to investigate the in vitro rat EC-microglial co-culture under acute (24 h.) exposure to ultrafine DEP (0.002-20 μg/mL), by evaluating key mechanisms associated with PM toxicity: lactate dehydrogenase (LDH) leakage, reactive oxygen species (ROS) generation, cell metabolic activity (CMA) changes, and production of 27 inflammatory markers. These parameters were also evaluated in rat microglial and endothelial monocultures to determine whether the EC-microglial co-culture responded differently than the cerebrovasculature and microglia alone. While results indicated that ultrafine DEP exposure caused concentration-dependent increases in LDH leakage and ROS production in all groups, as expected, exposure also caused mixed responses in CMA and atypical cytokine/chemokine profiles in all groups, which was not expected. The inflammation assay results further suggested that the microglia were not classically activated under this exposure scenario, despite previous in vitro studies showing microglial activation (priming) at similar concentrations of ultrafine DEP. Additionally, compared to the cerebrovasculature alone, the EC-microglia interaction in the co-culture did not appear to cause changes in any parameter save in pro-inflammatory marker production, where the interaction appeared to cause an overall downregulation in cytokine/chemokine levels after ultrafine DEP exposure. Finally, to our knowledge, this is the first study to evaluate the influence of microglia on the BBB's ultrafine DEP-induced cytotoxic and inflammatory responses, which are heavily implicated in the pathogenesis of PM-related cerebrovascular dysfunction and neurodegeneration., (Copyright © 2021. Published by Elsevier B.V.)

Human exposure to environmental nanoparticles (NPs) may result in systemic distribution and accumulation of NPs. Depending on exposure conditions and their physiochemical properties, NPs could cross biological barriers and reach vital organs. This method describes an analytical technique that quantifies the nanoparticles' translocation through a sample human airway barrier. Silver nanoparticles (AgNPs) were used as the example nanoparticles due to their common use in nanotechnology. The analytical method introduced in this study allows mass measurements of both cellular uptake and translocation of AgNPs through the modeled barrier. Additionally, cytotoxicity was evaluated using a convenient assay to investigate adverse effects from AgNPs treatment. The assay measures cellular injury from each layer in the barrier independently. The assay does not engage cells physically for chemical reaction, therefore it is non-destructive to the model, and the model can be used for other purposes subsequently. To conclude, this study provides researchers with measurable tools for evaluating the translocation, cellular trafficking, uptake and toxic effects of metallic nanoparticles in the in vitro barrier format.• Quantitative evaluation of nanoparticles translocation through human airway barrier • Non-invasive and quantifiable toxicity evaluation for co-culture models ., Competing Interests: The authors declare no conflicts of interest., (© 2020 The Author(s).)