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2. Glutathione conjugates of the mercapturic acid pathway and guanine adduct as biomarkers of exposure to CEES, a sulfur mustard analog

Author

Roser, Marie, Béal, David, Eldin, Camille, Gudimard, Leslie, Caffin, Fanny, Gros-Désormeaux, Fanny, Léonço, Daniel, Fenaille, François, Junot, Christophe, Piérard, Christophe, and Douki, Thierry

Subjects
Quantitative Biology - Biomolecules
Abstract

Sulfur mustard (SM), a chemical warfare agent, is a strong alkylating compound that readily reacts with numerous biomolecules. The goal of the present work was to define and validate new biomarkers of exposure to SM that could be easily accessible in urine or plasma. Because investigations using SM are prohibited by the Organization for the Prohibition of Chemical Weapons, we worked with 2-chloroethyl ethyl sulfide (CEES), a monofunctional analog of SM. We developed an ultra-high-pressure liquid chromatography - tandem mass spectrometry approach (UHPLC-MS/MS) to the conjugate of CEES to glutathione and two of its metabolites, the cysteine and the N-acetyl-cysteine conjugates. The N7-guanine adduct of CEES (N7Gua-CEES) was also targeted. After synthesizing the specific biomarkers, a solid phase extraction protocol and a UHPLC-MS/MS method with isotopic dilution were optimized. We were able to quantify N7Gua-CEES in the DNA of HaCaT keratinocytes and of explants of human skin exposed to CEES. N7Gua-CEES was also detected in the culture medium of these two models, together with the glutathione and the cysteine conjugates. In contrast, the N-acetyl-cysteine conjugate was not detected. The method was then applied to plasma from mice cutaneously exposed to CEES. All four markers could be detected. Our present results thus validate both the analytical technique and the biological relevance of new, easily quantifiable biomarkers of exposure to CEES. Because CEES behaves very similarly to SM, the results are promising for application to this toxic of interest., Comment: Analytical and Bioanalytical Chemistry, Springer Verlag, 2020

Published
2021
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3. Differential proteomics highlights macrophage-specific responses to amorphous silica nanoparticles

Author

Dalzon, Bastien, Aude-Garcia, Catherine, Collin-Faure, Véronique, Diemer, Hélène, Béal, David, Dussert, Fanny, Fenel, Daphna, Schoehn, Guy, Cianférani, Sarah, Carrière, Marie, and Rabilloud, Thierry

Subjects
Quantitative Biology - Genomics
Abstract

The technological and economic benefits of engineered nanomaterials may be offset by their adverse effects on living organisms. One of the highly produced nanomaterials under such scrutiny is amorphous silica nanoparticles, which are known to have an appreciable, although reversible, inflammatory potential. This is due to their selective toxicity toward macrophages, and it is thus important to study the cellular responses of this cell type to silica nanoparticles to better understand the direct or indirect adverse effects of nanosilica. We have here studied the responses of the RAW264.7 murine macrophage cells and of the control MPC11 plasma cells to subtoxic concentrations of nanosilica, using a combination of pro-teomic and targeted approaches. This allowed us to document alterations in the cellular cytoskeleton, in the phagocytic capacity of the cells as well as their ability to respond to bacterial stimuli. More surprisingly, silica nanoparticles also induce a greater sensitivity of macrophages to DNA alkylating agents, such as styrene oxide, even at doses which do not induce any appreciable cell death.

Published
2018
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4. Changes of physico-chemical properties of nano-biomaterials by digestion fluids affect the physiological properties of epithelial intestinal cells and barrier models

Author

Antonello, Giulia, Marucco, Arianna, Gazzano, Elena, Kainourgios, Panagiotis, Ravagli, Costanza, Gonzalez-Paredes, Ana, Sprio, Simone, Padín-González, Esperanza, Soliman, Mahmoud G., Beal, David, Barbero, Francesco, Gasco, Paolo, Baldi, Giovanni, Carriere, Marie, Monopoli, Marco P., Charitidis, Costas A., Bergamaschi, Enrico, Fenoglio, Ivana, and Riganti, Chiara

Published
2022
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7. A chemical, structural and biophysical exploration into the nanoscale properties of amyloid fibrils

Author

Beal, David, Xue, Wei-Feng, and Tuite, Mick

Subjects
500, Q Science
Abstract

Amyloid structures have been identified as a key pathological marker in a range of conditions such as Alzheimer’s and Parkinson’s disease. A combination of their disease relevance and potential nanomaterial applications has made understanding amyloid formation and the source of its toxicity of great interest. The fragmentation of amyloid fibrils into smaller particles is important for the kinetics of their formation and how they elicit toxicity. This thesis sheds light on how fibrils formed from different proteins fragment, and compares their resistance to mechanical stress, in order to decipher if fibril fragmentation mechanism is fibril dependent or a property shared by amyloid fibrils in general. To accomplish these goals, this thesis is divided into three sections. The first part of this thesis develops methods for recombinant production and purification of Sup35NMC, Sup35NM and α-synuclein proteins. In vitro polymerisation conditions for these proteins and the commercial proteins lysozyme, β-lactoglobulin and insulin B chain has enabled, via AFM imaging methods and MatLab tracing, the calculation of persistence length from far larger populations than has previously been observed. The second part investigates the resistance to mechanical stress of α-synuclein, β-lactoglobulin and lysozyme fibrils using a fragmentation assay, which enables the determination and comparison of the fibrils’ resistance to mechanical stress. This work has demonstrated that polymer rigidity (Lp) is inherently linked to the resistance of the tested amyloid fibrils to mechanical stress. The third part of the thesis successfully implements a chemical labelling strategy using ‘click’ chemistry to allow a modification of fibril functionality. This has been applied to fluorescence labelling strategies and 19F-labelling for novel methods of determining the population size of amyloid fibrils by 19F DOSY NMR.

Published
2016

14. Modification of bacterial microcompartments with target biomolecules via post-translational SpyTagging

Author

Beal, David M, primary, Liang, Mingzhi, additional, Brown, Ian, additional, Budge, James D, additional, Burrows, Emily R, additional, Howland, Kevin, additional, Lee, Phoebe, additional, Martin, Sarah, additional, Morrell, Andrew, additional, Nemoto-Smith, Emi, additional, Roobol, Joanne, additional, Stanley, Maria, additional, Smales, C Mark, additional, and Warren, Martin J, additional

Published
2023
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18. Pre-validation of a reporter gene assay for oxidative stress for the rapid screening of nanobiomaterials

Author

Martin, Sebastin, primary, de Haan, Laura, additional, Miro Estruch, Ignacio, additional, Eder, Kai Moritz, additional, Marzi, Anne, additional, Schnekenburger, Jürgen, additional, Blosi, Magda, additional, Costa, Anna, additional, Antonello, Giulia, additional, Bergamaschi, Enrico, additional, Riganti, Chiara, additional, Beal, David, additional, Carrière, Marie, additional, Taché, Olivier, additional, Hutchison, Gary, additional, Malone, Eva, additional, Young, Lesley, additional, Campagnolo, Luisa, additional, La Civita, Fabio, additional, Pietroiusti, Antonio, additional, Devineau, Stéphanie, additional, Baeza, Armelle, additional, Boland, Sonja, additional, Zong, Cai, additional, Ichihara, Gaku, additional, Fadeel, Bengt, additional, and Bouwmeester, Hans, additional

Published
2022
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19. Pre-validation of a reporter gene assay for oxidative stress for the rapid screening of nanobiomaterials

Author

Martin, Sebastin, de Haan, Laura, Miro Estruch, Ignacio, Eder, Kai Moritz, Marzi, Anne, Schnekenburger, Jürgen, Blosi, Magda, Costa, Anna, Antonello, Giulia, Bergamaschi, Enrico, Riganti, Chiara, Beal, David, Carrière, Marie, Taché, Olivier, Hutchison, Gary, Malone, Eva, Young, Lesley, Campagnolo, Luisa, La Civita, Fabio, Pietroiusti, Antonio, Devineau, Stéphanie, Baeza, Armelle, Boland, Sonja, Zong, Cai, Ichihara, Gaku, Fadeel, Bengt, Bouwmeester, Hans, Martin, Sebastin, de Haan, Laura, Miro Estruch, Ignacio, Eder, Kai Moritz, Marzi, Anne, Schnekenburger, Jürgen, Blosi, Magda, Costa, Anna, Antonello, Giulia, Bergamaschi, Enrico, Riganti, Chiara, Beal, David, Carrière, Marie, Taché, Olivier, Hutchison, Gary, Malone, Eva, Young, Lesley, Campagnolo, Luisa, La Civita, Fabio, Pietroiusti, Antonio, Devineau, Stéphanie, Baeza, Armelle, Boland, Sonja, Zong, Cai, Ichihara, Gaku, Fadeel, Bengt, and Bouwmeester, Hans

Abstract

Engineered nanomaterials have been found to induce oxidative stress. Cellular oxidative stress, in turn, can result in the induction of antioxidant and detoxification enzymes which are controlled by the nuclear erythroid 2-related factor 2 (NRF2) transcription factor. Here, we present the results of a pre-validation study which was conducted within the frame of BIORIMA (“biomaterial risk management”) an EU-funded research and innovation project. For this we used an NRF2 specific chemically activated luciferase expression reporter gene assay derived from the human U2OS osteosarcoma cell line to screen for the induction of the NRF2 mediated gene expression following exposure to biomedically relevant nanobiomaterials. Specifically, we investigated Fe3O4-PEG-PLGA nanomaterials while Ag and TiO2 “benchmark” nanomaterials from the Joint Research Center were used as reference materials. The viability of the cells was determined by using the Alamar blue assay. We performed an interlaboratory study involving seven different laboratories to assess the applicability of the NRF2 reporter gene assay for the screening of nanobiomaterials. The latter work was preceded by online tutorials to ensure that the procedures were harmonized across the different participating laboratories. Fe3O4-PEG-PLGA nanomaterials were found to induce very limited NRF2 mediated gene expression, whereas exposure to Ag nanomaterials induced NRF2 mediated gene expression. TiO2 nanomaterials did not induce NRF2 mediated gene expression. The variability in the results obtained by the participating laboratories was small with mean intra-laboratory standard deviation of 0.16 and mean inter laboratory standard deviation of 0.28 across all NRF2 reporter gene assay results. We conclude that the NRF2 reporter gene assay is a suitable assay for the screening of nanobiomaterial-induced oxidative stress responses.

Published
2022

20. Additional file 1 of Changes of physico-chemical properties of nano-biomaterials by digestion fluids affect the physiological properties of epithelial intestinal cells and barrier models

Author

Antonello, Giulia, Marucco, Arianna, Gazzano, Elena, Kainourgios, Panagiotis, Ravagli, Costanza, Gonzalez-Paredes, Ana, Sprio, Simone, Padín-González, Esperanza, Soliman, Mahmoud G., Beal, David, Barbero, Francesco, Gasco, Paolo, Baldi, Giovanni, Carriere, Marie, Monopoli, Marco P., Charitidis, Costas A., Bergamaschi, Enrico, Fenoglio, Ivana, and Riganti, Chiara

Abstract

Additional file 1. Figure S1. Optical appearance of the colloidal suspensions before A) and after B) treatment with the SHDS. Figure S2. Size distribution of the samples directly incubated in SIF or after complete SHDS-treatment of A) LSNPs; B) CNPs, C) FNPs; D) HNPs. Figure S3. HNPs dissolution. Figure S4. Degradation of LSNPs by lipase. Table S1. Mean dH and PDI of NMs in DMEM+10% FBS (100 mg/ml), 24 h incubation. Figure S5. Aspect of the suspension of the (*) untreated and (**) SHDS-treated A) LSNPs, B) CNPs, C) FNPs and D) HNPs in cell medium. Figure S6. SDS-PAGE analysis showing the hard corona of (*) SHDS-treated and (**) untreated A) LSNPs, B) CNPs, C) FNPs and D) HNPs in cell medium and obtained by centrifugation, and E) ctrl without NBMs. Figure S7. LFQ intensity for different proteases inhibitor for FNPs untreated and SHDS-treated. Figure S8. Cells viability of A) Caco-2 cells and B) HCoEpiC cells after 24 h of incubation with SHDS fluids. Figure S9. Genotoxicity of HCT116 cells after 24 h of incubation with untreated and SHDS-treated NMs. Table S2. Tran-Epithelial Electrical Resistance (TEER) values of Caco-2 barrier model after 24 h of incubation. Figure S10. Scheme of representative SDHS treatment.

Published
2022
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27. A method to generate propulsor side forces

Author

Huyer, Stephen A., Dropkin, Amanda, Dick, James, and Beal, David

Subjects
Motor vehicles -- Mechanical properties, Motor vehicles -- Equipment and supplies, Force and energy -- Research, Engineering and manufacturing industries, Science and technology
Abstract

A computational study was performed to investigate a method to generate vehicle maneuvering forces from a propulsor alone. A ducted, preswirl propulsor was configured with an upstream stator row and downstream rotor. During normal operation, the upstream stator blades are all situated at the same pitch angle and preswirl the flow into the propulsor while generating a roll moment to counter the moment produced by the rotor. By varying the pitch angles of the stator blade about the circumference, it is possible to both generate a mean stator side force and subsequently vary the axial velocity and swirl that is ingested into the propulsor. The rotor then generates a side force in response to the inflow. Both potential flow and fully viscous 3D Reynolds averaged Navier-Stokes (RANS) computations were used to predict the stator forces, velocity field, and rotor response. Potential flow methods were used for initial examination of a wide variety of stator configurations. The most promising were then modeled using RANS. The RANS inflow was then computed and used as velocity boundary conditions during rotor blade design using potential flow methods. Blade parameters including blade number, rake, skew, and a combination of the two were varied to characterize their effects. RANS was used to then validate the final propulsor design. Computations demonstrated that total side force coefficients on the order of 0.1 and moment coefficients about the stator leading edge of 0.066 could be generated by the propulsor alone. This translates to an additional 50% control authority at 3 kn for current Navy 21' unmanned undersea vehicles. [DOI: 10.1115/1.4000745] Keywords: maneuvering, propulsor, hydrodynamics, experimental fluid dynamics, computational fluid dynamics

Published
2010

28. The Effect of Crossflow on Flapping Fins

Author

Beal, David N., Legris, Joseph D., Kellogg, Audrey B., Perkins, Matthew D., and Wilkinson, William S.

Abstract

Flapping fins can enable greater maneuverability in undersea vehicles. Most work to this point has only considered inflow perpendicular to the flapping stroke plane. However, this would not be true during maneuvers or while station keeping in a current. In this article, a simple model is presented which utilizes zero-crossflow data to predict the effect of crossflow on the forces produced by a flapping fin. This model compares well to experimental data taken over an array of crossflow and bias angles. The crossflow model may be useful for flapping fin vehicle simulations, feedforward models in vehicle controllers, and the development of a flapping fin controller that can compensate for inflow angle disturbances.

Published
2023
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29. Unsteady vortex flows produced by trailing edge articulation

Author

Huyer, Stephen A., Beal, David, Macumber, Daniel, and Annaswamy, Anuradha

Subjects
Vortex-motion -- Evaluation, Hydraulic measurements -- Evaluation, Submersibles -- Design and construction, Submersibles -- Mechanical properties, Reynolds number -- Measurement, Engineering and manufacturing industries, Science and technology
Abstract

The unsteady vortex flows produced by biologically inspired tail articulation are investigated. The application is to provide active means of reducing tonal noise due to upstream wake interaction with downstream propellers on underwater vehicles. By reducing the wake velocity defect, the periodic unsteady propeller blade pressure fluctuations that are the source of the noise should be reduced. Accordingly, experiments to measure the flows produced by an upstream stator fitted with a movable trailing edge were carried out in a water tunnel for Reynolds numbers in the range 75,000

Published
2008

33. Toxicity and chemical transformation of silver nanoparticles in A549 lung cells: dose-rate-dependent genotoxic impact

Author

Bobyk, Laure, primary, Tarantini, Adeline, additional, Beal, David, additional, Veronesi, Giulia, additional, Kieffer, Isabelle, additional, Motellier, Sylvie, additional, Valsami-Jones, Eugenia, additional, Lynch, Iseult, additional, Jouneau, Pierre-Henri, additional, Pernet-Gallay, Karin, additional, Aude-Garcia, Catherine, additional, Sauvaigo, Sylvie, additional, Douki, Thierry, additional, Rabilloud, Thierry, additional, and Carriere, Marie, additional

Published
2021
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35. Xeroderma Pigmentosum C (XPC) Mutations in Primary Fibroblasts Impair Base Excision Repair Pathway and Increase Oxidative DNA Damage

Author

Fayyad, Nour, primary, Kobaisi, Farah, additional, Beal, David, additional, Mahfouf, Walid, additional, Ged, Cécile, additional, Morice-Picard, Fanny, additional, Fayyad-Kazan, Mohammad, additional, Fayyad-Kazan, Hussein, additional, Badran, Bassam, additional, Rezvani, Hamid R., additional, and Rachidi, Walid, additional

Published
2020
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38. Impairment of Base Excision Repair in Dermal Fibroblasts Isolated From Nevoid Basal Cell Carcinoma Patients

Author

Charazac, Aurélie, primary, Fayyad, Nour, additional, Beal, David, additional, Bourgoin-Voillard, Sandrine, additional, Seve, Michel, additional, Sauvaigo, Sylvie, additional, Lamartine, Jérôme, additional, Soularue, Pascal, additional, Moratille, Sandra, additional, Martin, Michèle T., additional, Ravanat, Jean-Luc, additional, Douki, Thierry, additional, and Rachidi, Walid, additional

Published
2020
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41. Chasing interior ducts: in order for ducts within conditioned spaces to be effective, builders need to establish an effective air barrier around them. (New Construction)

Author

McIlvaine, Janet and Beal, David

Subjects
Energy conservation -- Measurement -- United States, Air conditioning -- Energy use -- Measurement, Business, Construction and materials industries, Home and garden, Energy use, Measurement
Abstract

Energy efficiency experts agree that minimizing duct leakage is one of the most important energy conservation measures they can take. It provides rapid payback from energy savings and mitigates the [...]

Published
2002

42. Allergy relief in humid climates: dust mites are a problem in new homes in humid climates. What keeps them away? (IAQ)

Author

Chandra, Subrato and Beal, David

Subjects
Mites -- Control -- Health aspects, House construction -- Health aspects, Allergens -- Prevention -- Control -- Health aspects, Business, Construction and materials industries, Home and garden
Abstract

The increasing incidence of allergy and asthma, particularly among children, is a worldwide concern. About 20% of the general population suffer from allergies, and about 5% suffer from asthma. Among [...]

Published
2002

47. Observations of the Spectral Distribution of Solar Irradiance at the Ground During SUCCESS

Author

Pilewskie, Peter, Goetz, Alexander F. H, Beal, David A, Bergstrom, Robert W, and Mariani, Peter

Subjects
Solar Physics
Abstract

During SUCCESS two independent and independently calibrated spectrometers were deployed at a surface site to determine the spectrally resolved downwelling solar irradiance. Preliminary evidence shows that for cloud-free conditions there is general agreement between measurements and model derived irradiance, at least to within instrumental and model uncertainties of 5%, with greatest disagreement Occurring in the 400 nm - 700 nm band. Cirrus effects are most prominent in the near-infrared bands beyond 1500 nm while the influence of very thin (subvisual) cirrus is evident in the scattered flux at the surface. Further remote sensing applications and the assessment of cloud absorption is contingent upon measurements of the surface spectral albedo.

Published
1998
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48. Affordable Energy-Efficient New Housing Solutions

Author

Chandra, Subrato, primary, Widder, Sarah H., additional, Bartlett, Rosemarie, additional, McIlvaine, Janet, additional, Chasar, David, additional, Beal, David, additional, Sutherland, Karen, additional, Abbott, , K., additional, Fonorow, Ken, additional, Eklund, Ken, additional, Lubliner, Michael, additional, Salzberg, Emily, additional, Peeks, B., additional, Hewes, T., additional, and Kosar, D., additional

Published
2012
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49. Pilot Residential Deep Energy Retrofits and the PNNL Lab Homes

Author

Widder, Sarah H., primary, Chandra, Subrato, additional, Parker, Graham B., additional, Sande, Susan, additional, Blanchard, Jeremy, additional, Stroer, Dennis, additional, McIlvaine, Janet, additional, Chasar, David, additional, Beal, David, additional, and Sutherland, Karen, additional

Published
2012
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50. Affordability in individuals' healthcare decision making: A concept analysis.

Author

Beal, David and Foli, Karen J.

Subjects
*DECISION making, *HEALTH services administration, *HEALTH policy, *POLICY sciences, *PURCHASING, *COST analysis, *PATIENTS' attitudes, *HEALTH & social status, *ECONOMICS, PATIENT Protection & Affordable Care Act
Abstract

This concept analysis aims to define affordability within the context of healthcare decision making. Affordability is a complex concept that influences an individual's healthcare decision making. In the year's post‐Affordable Care Act, the United States has seen an increase in insured individuals, but also an increase in underinsured healthcare consumers. Evidence for the concept attributes was found by searching the Cumulative Index of Nursing and Allied Health Literature, EconLit, Family & Society Studies Worldwide, Humanities Full Text, and PsychINFO databases. Literature was synthesized using the Walker and Avant approach. A new definition was derived with four defining attributes, as well as antecedents and consequences. Three cases are forwarded: the model, borderline, and contrary. In healthcare decision making, affordability is a subjective measure that individuals use in determining the ability to engage in a healthcare service or a durable good transaction. Affordability varies based on circumstances. The context of healthcare decision making of individuals stands in contrast to the decision‐making in health systems and to decisions unrelated to one's health. Affordability is a determinant of an individual's ability to engage in a transaction. As such, nurses and policymakers should attempt to understand affordability from the patient's perspective. [ABSTRACT FROM AUTHOR]

Published
2021
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