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1. Distribution of SiO2 nanoparticles in 3D liver microtissues

Author

Fleddermann J, Susewind J, Peuschel H, Koch M, Tavernaro I, and Kraegeloh A

Subjects
Silica nanoparticles, Human hepatocarcinoma cells, Spheroids, Penetration, Medicine (General), R5-920
Abstract

Jana Fleddermann,1 Julia Susewind,2 Henrike Peuschel,1 Marcus Koch,1 Isabella Tavernaro,1 Annette Kraegeloh1 1INM – Leibniz Institute for New Materials, Saarbrücken, Germany; 2Pharmacelsus GmbH, Saarbrücken, Germany Introduction: Nanoparticles (NPs) are used in numerous products in technical fields and biomedicine; their potential adverse effects have to be considered in order to achieve safe applications. Besides their distribution in tissues, organs, and cellular localization, their impact and penetration during the process of tissue formation occurring in vivo during liver regeneration are critical steps for establishment of safe nanomaterials.Materials and methods: In this study, 3D cell culture of human hepatocarcinoma cells (HepG2) was used to generate cellular spheroids, serving as in vitro liver microtissues. In order to determine their differential distribution and penetration depth in HepG2 spheroids, SiO2 NPs were applied either during or after spheroid formation. The NP penetration was comprehensively studied using confocal laser scanning microscopy and scanning electron microscopy.Results: Spheroids were exposed to 100 µg mL-1 SiO2 NPs either at the beginning of spheroid formation, or during or after formation of spheroids. Microscopy analyses revealed that NP penetration into the spheroid is limited. During and after spheroid formation, SiO2 NPs penetrated about 20 µm into the spheroids, corresponding to about three cell layers. In contrast, because of the addition of SiO2 NPs simultaneously to cell seeding, NP agglomerates were located also in the spheroid center. Application of SiO2 NPs during the process of spheroid formation had no impact on final spheroid size.Conclusion: Understanding the distribution of NPs in tissues is essential for biomedical applications. The obtained results indicate that NPs show only limited penetration into already formed tissue, which is probably caused by the alteration of the tissue structure and cell packing density during the process of spheroid formation. Keywords: silica nanoparticles, human hepatocarcinoma cells, spheroids, penetration

Published
2019

2. Detailed Report on the Measurement of the Positive Muon Anomalous Magnetic Moment to 0.20 ppm

Author

Aguillard, D. P., Albahri, T., Allspach, D., Anisenkov, A., Badgley, K., Baeßler, S., Bailey, I., Bailey, L., Baranov, V. A., Barlas-Yucel, E., Barrett, T., Barzi, E., Bedeschi, F., Berz, M., Bhattacharya, M., Binney, H. P., Bloom, P., Bono, J., Bottalico, E., Bowcock, T., Braun, S., Bressler, M., Cantatore, G., Carey, R. M., Casey, B. C. K., Cauz, D., Chakraborty, R., Chapelain, A., Chappa, S., Charity, S., Chen, C., Cheng, M., Chislett, R., Chu, Z., Chupp, T. E., Claessens, C., Convery, M. E., Corrodi, S., Cotrozzi, L., Crnkovic, J. D., Dabagov, S., Debevec, P. T., Di Falco, S., Di Sciascio, G., Donati, S., Drendel, B., Driutti, A., Duginov, V. N., Eads, M., Edmonds, A., Esquivel, J., Farooq, M., Fatemi, R., Ferrari, C., Fertl, M., Fienberg, A. T., Fioretti, A., Flay, D., Foster, S. B., Friedsam, H., Froemming, N. S., Gabbanini, C., Gaines, I., Galati, M. D., Ganguly, S., Garcia, A., George, J., Gibbons, L. K., Gioiosa, A., Giovanetti, K. L., Girotti, P., Gohn, W., Goodenough, L., Gorringe, T., Grange, J., Grant, S., Gray, F., Haciomeroglu, S., Halewood-Leagas, T., Hampai, D., Han, F., Hempstead, J., Hertzog, D. W., Hesketh, G., Hess, E., Hibbert, A., Hodge, Z., Hong, K. W., Hong, R., Hu, T., Hu, Y., Iacovacci, M., Incagli, M., Kammel, P., Kargiantoulakis, M., Karuza, M., Kaspar, J., Kawall, D., Kelton, L., Keshavarzi, A., Kessler, D. S., Khaw, K. S., Khechadoorian, Z., Khomutov, N. V., Kiburg, B., Kiburg, M., Kim, O., Kinnaird, N., Kraegeloh, E., Krylov, V. A., Kuchinskiy, N. A., Labe, K. R., LaBounty, J., Lancaster, M., Lee, S., Li, B., Li, D., Li, L., Logashenko, I., Campos, A. Lorente, Lu, Z., Lucà, A., Lukicov, G., Lusiani, A., Lyon, A. L., MacCoy, B., Madrak, R., Makino, K., Mastroianni, S., Miller, J. P., Miozzi, S., Mitra, B., Morgan, J. P., Morse, W. M., Mott, J., Nath, A., Ng, J. K., Nguyen, H., Oksuzian, Y., Omarov, Z., Osofsky, R., Park, S., Pauletta, G., Piacentino, G. M., Pilato, R. N., Pitts, K. T., Plaster, B., Počanić, D., Pohlman, N., Polly, C. C., Price, J., Quinn, B., Qureshi, M. U. H., Ramachandran, S., Ramberg, E., Reimann, R., Roberts, B. L., Rubin, D. L., Sakurai, M., Santi, L., Schlesier, C., Schreckenberger, A., Semertzidis, Y. K., Shemyakin, D., Sorbara, M., Stapleton, J., Still, D., Stöckinger, D., Stoughton, C., Stratakis, D., Swanson, H. E., Sweetmore, G., Sweigart, D. A., Syphers, M. J., Tarazona, D. A., Teubner, T., Tewsley-Booth, A. E., Tishchenko, V., Tran, N. H., Turner, W., Valetov, E., Vasilkova, D., Venanzoni, G., Volnykh, V. P., Walton, T., Weisskopf, A., Welty-Rieger, L., Winter, P., Wu, Y., Yu, B., Yucel, M., Zeng, Y., and Zhang, C.

Subjects
High Energy Physics - Experiment, High Energy Physics - Phenomenology, Nuclear Experiment
Abstract

We present details on a new measurement of the muon magnetic anomaly, $a_\mu = (g_\mu -2)/2$. The result is based on positive muon data taken at Fermilab's Muon Campus during the 2019 and 2020 accelerator runs. The measurement uses $3.1$ GeV$/c$ polarized muons stored in a $7.1$-m-radius storage ring with a $1.45$ T uniform magnetic field. The value of $ a_{\mu}$ is determined from the measured difference between the muon spin precession frequency and its cyclotron frequency. This difference is normalized to the strength of the magnetic field, measured using Nuclear Magnetic Resonance (NMR). The ratio is then corrected for small contributions from beam motion, beam dispersion, and transient magnetic fields. We measure $a_\mu = 116 592 057 (25) \times 10^{-11}$ (0.21 ppm). This is the world's most precise measurement of this quantity and represents a factor of $2.2$ improvement over our previous result based on the 2018 dataset. In combination, the two datasets yield $a_\mu(\text{FNAL}) = 116 592 055 (24) \times 10^{-11}$ (0.20 ppm). Combining this with the measurements from Brookhaven National Laboratory for both positive and negative muons, the new world average is $a_\mu$(exp) $ = 116 592 059 (22) \times 10^{-11}$ (0.19 ppm)., Comment: 48 pages, 29 figures; 4 pages of Supplement Material; version accepted for publication in Physical Review D

Published
2024

3. The role of the intestinal microvasculature in inflammatory bowel disease: studies with a modified Caco-2 model including endothelial cells resembling the intestinal barrier in vitro

Author

Kasper JY, Hermanns MI, Cavelius C, Kraegeloh A, Jung T, Danzebrink R, Unger RE, and Kirkpatrick CJ

Subjects
intestinal microvasculature, inflammatory bowel disease, intestinal barrier in vitro, Caco-2, ISO-HAS-1, inflammation, nano-sized contrast agents, Medicine (General), R5-920
Abstract

Jennifer Y Kasper,1 Maria Iris Hermanns,1 Christian Cavelius,2 Annette Kraegeloh,2 Thomas Jung,3 Rolf Danzebrink,3 Ronald E Unger,1 Charles James Kirkpatrick1 1Institute of Pathology, University Medical Center, Mainz, 2Leibniz Institute for New Materials, 3NanoGate AG, Goettelborn, Saarbrücken, Germany Abstract: The microvascular endothelium of the gut barrier plays a crucial role during inflammation in inflammatory bowel disease. We have modified a commonly used intestinal cell model based on the Caco-2 cells by adding microvascular endothelial cells (ISO-HAS-1). Transwell filters were used with intestinal barrier-forming Caco-2 cells on top and the ISO-HAS-1 on the bottom of the filter. The goal was to determine whether this coculture mimics the in vivo situation more closely, and whether the model is suitable to evaluate interactions of, for example, prospective nanosized drug vehicles or contrast agents with this coculture in a physiological and inflamed state as it would occur in inflammatory bowel disease. We monitored the inflammatory responsiveness of the cells (release of IL-8, soluble intercellular adhesion molecule 1, and soluble E-selectin) after exposure to inflammatory stimuli (lipopolysaccharide, TNF-α, INF-γ, IL1-β) and a nanoparticle (Ba/Gd: coprecipitated BaSO4 and Gd(OH)3), generally used as contrast agents. The barrier integrity of the coculture was evaluated via the determination of transepithelial electrical resistance and the apparent permeability coefficient (Papp) of NaFITC. The behavior of the coculture Caco-1/ISO-HAS-1 was compared to the respective monocultures Caco-2 and ISO-HAS-1. Based on transepithelial electrical resistance, the epithelial barrier integrity of the coculture remained stable during incubation with all stimuli, whereas the Papp decreased after exposure to the cytokine mixture (TNF-α, INF-γ, IL1-β, and Ba/Gd). Both the endothelial and epithelial monocultures showed a high inflammatory response in both the upper and lower transwell-compartments. However, in the coculture, inflammatory mediators were only detected on the epithelial side and not on the endothelial side. Thus in the coculture, based on the Papp, the epithelial barrier appears to prevent a potential inflammatory overreaction in the underlying endothelial cells. In summary, this coculture model exhibits in vivo-like features, which cannot be observed in conventional monocultures, making the former more suitable to study interactions with external stimuli. Keywords: intestinal microvasculature, inflammatory bowel disease, intestinal barrier in vitro, Caco-2, ISO-HAS-1, soluble E-selectin, sICAM-1, nanosized gadolinium contrast agent

Published
2016

4. Measurement of the Positive Muon Anomalous Magnetic Moment to 0.20 ppm

Author

Aguillard, D. P., Albahri, T., Allspach, D., Anisenkov, A., Badgley, K., Baeßler, S., Bailey, I., Bailey, L., Baranov, V. A., Barlas-Yucel, E., Barrett, T., Barzi, E., Bedeschi, F., Berz, M., Bhattacharya, M., Binney, H. P., Bloom, P., Bono, J., Bottalico, E., Bowcock, T., Braun, S., Bressler, M., Cantatore, G., Carey, R. M., Casey, B. C. K., Cauz, D., Chakraborty, R., Chapelain, A., Chappa, S., Charity, S., Chen, C., Cheng, M., Chislett, R., Chu, Z., Chupp, T. E., Claessens, C., Convery, M. E., Corrodi, S., Cotrozzi, L., Crnkovic, J. D., Dabagov, S., Debevec, P. T., Di Falco, S., Di Sciascio, G., Drendel, B., Driutti, A., Duginov, V. N., Eads, M., Edmonds, A., Esquivel, J., Farooq, M., Fatemi, R., Ferrari, C., Fertl, M., Fienberg, A. T., Fioretti, A., Flay, D., Foster, S. B., Friedsam, H., Froemming, N. S., Gabbanini, C., Gaines, I., Galati, M. D., Ganguly, S., Garcia, A., George, J., Gibbons, L. K., Gioiosa, A., Giovanetti, K. L., Girotti, P., Gohn, W., Goodenough, L., Gorringe, T., Grange, J., Grant, S., Gray, F., Haciomeroglu, S., Halewood-Leagas, T., Hampai, D., Han, F., Hempstead, J., Hertzog, D. W., Hesketh, G., Hess, E., Hibbert, A., Hodge, Z., Hong, K. W., Hong, R., Hu, T., Hu, Y., Iacovacci, M., Incagli, M., Kammel, P., Kargiantoulakis, M., Karuza, M., Kaspar, J., Kawall, D., Kelton, L., Keshavarzi, A., Kessler, D. S., Khaw, K. S., Khechadoorian, Z., Khomutov, N. V., Kiburg, B., Kiburg, M., Kim, O., Kinnaird, N., Kraegeloh, E., Krylov, V. A., Kuchinskiy, N. A., Labe, K. R., LaBounty, J., Lancaster, M., Lee, S., Li, B., Li, D., Li, L., Logashenko, I., Campos, A. Lorente, Lu, Z., Lucà, A., Lukicov, G., Lusiani, A., Lyon, A. L., MacCoy, B., Madrak, R., Makino, K., Mastroianni, S., Miller, J. P., Miozzi, S., Mitra, B., Morgan, J. P., Morse, W. M., Mott, J., Nath, A., Ng, J. K., Nguyen, H., Oksuzian, Y., Omarov, Z., Osofsky, R., Park, S., Pauletta, G., Piacentino, G. M., Pilato, R. N., Pitts, K. T., Plaster, B., Počanić, D., Pohlman, N., Polly, C. C., Price, J., Quinn, B., Qureshi, M. U. H., Ramachandran, S., Ramberg, E., Reimann, R., Roberts, B. L., Rubin, D. L., Santi, L., Schlesier, C., Schreckenberger, A., Semertzidis, Y. K., Shemyakin, D., Sorbara, M., Stapleton, J., Still, D., Stöckinger, D., Stoughton, C., Stratakis, D., Swanson, H. E., Sweetmore, G., Sweigart, D. A., Syphers, M. J., Tarazona, D. A., Teubner, T., Tewsley-Booth, A. E., Tishchenko, V., Tran, N. H., Turner, W., Valetov, E., Vasilkova, D., Venanzoni, G., Volnykh, V. P., Walton, T., Weisskopf, A., Welty-Rieger, L., Winter, P., Wu, Y., Yu, B., Yucel, M., Zeng, Y., and Zhang, C.

Subjects
High Energy Physics - Experiment
Abstract

We present a new measurement of the positive muon magnetic anomaly, $a_\mu \equiv (g_\mu - 2)/2$, from the Fermilab Muon $g\!-\!2$ Experiment using data collected in 2019 and 2020. We have analyzed more than 4 times the number of positrons from muon decay than in our previous result from 2018 data. The systematic error is reduced by more than a factor of 2 due to better running conditions, a more stable beam, and improved knowledge of the magnetic field weighted by the muon distribution, $\tilde{\omega}'^{}_p$, and of the anomalous precession frequency corrected for beam dynamics effects, $\omega_a$. From the ratio $\omega_a / \tilde{\omega}'^{}_p$, together with precisely determined external parameters, we determine $a_\mu = 116\,592\,057(25) \times 10^{-11}$ (0.21 ppm). Combining this result with our previous result from the 2018 data, we obtain $a_\mu\text{(FNAL)} = 116\,592\,055(24) \times 10^{-11}$ (0.20 ppm). The new experimental world average is $a_\mu (\text{Exp}) = 116\,592\,059(22)\times 10^{-11}$ (0.19 ppm), which represents a factor of 2 improvement in precision., Comment: 8 pages, 3 figures

Published
2023
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5. Estimating the modulatory effects of nanoparticles on neuronal circuits using computational upscaling

Author

Busse M, Stevens D, Kraegeloh A, Cavelius C, Vukelic M, Arzt E, and Strauss DJ

Subjects
Medicine (General), R5-920
Abstract

Michael Busse,1 David Stevens,3 Annette Kraegeloh,2 Christian Cavelius,2 Mathias Vukelic,1 Eduard Arzt,2 Daniel J Strauss1,2 1Systems Neuroscience and Neurotechnology Unit, Saarland University, Faculty of Medicine, Neurocenter, and Saarland University of Applied Sciences, Homburg/Saarbruecken, Germany; 2Leibniz Institute for New Materials, Saarbruecken, Germany; 3Department of Physiology, Saarland University, Faculty of Medicine, Homburg/Saarbruecken, Germany Background: Beside the promising application potential of nanotechnologies in engineering, the use of nanomaterials in medicine is growing. New therapies employing innovative nanocarrier systems to increase specificity and efficacy of drug delivery schemes are already in clinical trials. However the influence of the nanoparticles themselves is still unknown in medical applications, especially for complex interactions in neural systems. The aim of this study was to investigate in vitro effects of coated silver nanoparticles (cAgNP) on the excitability of single neuronal cells and to integrate those findings into an in silico model to predict possible effects on neuronal circuits. Methods: We first performed patch clamp measurements to investigate the effects of nanosized silver particles, surrounded by an organic coating, on excitability of single cells. We then determined which parameters were altered by exposure to those nanoparticles using the Hodgkin–Huxley model of the sodium current. As a third step, we integrated those findings into a well-defined neuronal circuit of thalamocortical interactions to predict possible changes in network signaling due to the applied cAgNP, in silico. Results: We observed rapid suppression of sodium currents after exposure to cAgNP in our in vitro recordings. In numerical simulations of sodium currents we identified the parameters likely affected by cAgNP. We then examined the effects of such changes on the activity of networks. In silico network modeling indicated effects of local cAgNP application on firing patterns in all neurons in the circuit. Conclusion: Our sodium current simulation shows that suppression of sodium currents by cAgNP results primarily by a reduction in the amplitude of the current. The network simulation shows that locally cAgNP-induced changes result in changes in network activity in the entire network, indicating that local application of cAgNP may influence the activity throughout the network. Keywords: coated silver nanoparticles, modeling, patch clamp recordings, neuronal circuit model, neuromodulatory effect, nanocarriers, nonviral vectors, Llinás model

Published
2013

8. Developmental delay can precede neurologic regression in early onset metachromatic leukodystrophy

Author

Adang, Laura Ann, Groeschel, Samuel, Grzyb, Chloe, D'Aiello, Russell, Gavazzi, Francesco, Sherbini, Omar, Bronner, Nowa, Patel, Akshilkumar, Vincent, Ariel, Sevagamoorthy, Anjana, Mutua, Sylvia, Muirhead, Kayla, Schmidt, Johanna, Pizzino, Amy, Yu, Emily, Jin, Danielle, Eichler, Florian, Fraser, Jamie L., Emrick, Lisa, Van Haren, Keith, Boulanger, Jean-Martin, Ruzhnikov, Maura, Sylvain, Michel, Nguyen, Cam-Tu Émilie, Potic, Ana, Keller, Stephanie, Fatemi, Ali, Uebergang, Eloise, Poe, Michele, Yazdani, Pouneh Amir, Bernat, John, Lindstrom, Kristen, Bonkowsky, Joshua L., Bernard, Genevieve, Stutterd, Chloe A., Orchard, Paul, Gupta, Ashish O., Ljungberg, Merete, Groenborg, Sabine, Zambon, Alberto, Locatelli, Sara, Fumagalli, Francesca, Elguen, Saskia, Kehrer, Christiane, Krägeloh-Mann, Ingeborg, Shults, Justine, Vanderver, Adeline, and Escolar, Maria L.

Published
2024
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10. Measurement of the anomalous precession frequency of the muon in the Fermilab Muon g-2 experiment

Author

Albahri, T., Anastasi, A., Anisenkov, A., Badgley, K., Baeßler, S., Bailey, I., Baranov, V. A., Barlas-Yucel, E., Barrett, T., Basti, A., Bedeschi, F., Berz, M., Bhattacharya, M., Binney, H. P., Bloom, P., Bono, J., Bottalico, E., Bowcock, T., Cantatore, G., Carey, R. M., Casey, B. C. K., Cauz, D., Chakraborty, R., Chang, S. P., Chapelain, A., Charity, S., Chislett, R., Choi, J., Chu, Z., Chupp, T. E., Corrodi, S., Cotrozzi, L., Crnkovic, J. D., Dabagov, S., Debevec, P. T., Di Falco, S., Di Meo, P., Di Sciascio, G., Di Stefano, R., Driutti, A., Duginov, V. N., Eads, M., Esquivel, J., Farooq, M., Fatemi, R., Ferrari, C., Fertl, M., Fienberg, A. T., Fioretti, A., Flay, D., Frlež, E., Froemming, N. S., Fry, J., Gabbanini, C., Galati, M. D., Ganguly, S., Garcia, A., George, J., Gibbons, L. K., Gioiosa, A., Giovanetti, K. L., Girotti, P., Gohn, W., Gorringe, T., Grange, J., Grant, S., Gray, F., Haciomeroglu, S., Halewood-Leagas, T., Hampai, D., Han, F., Hempstead, J., Herrod, A. T., Hertzog, D. W., Hesketh, G., Hibbert, A., Hodge, Z., Holzbauer, J. L., Hong, K. W., Hong, R., Iacovacci, M., Incagli, M., Kammel, P., Kargiantoulakis, M., Karuza, M., Kaspar, J., Kawall, D., Kelton, L., Keshavarzi, A., Kessler, D., Khaw, K. S., Khechadoorian, Z., Khomutov, N. V., Kiburg, B., Kiburg, M., Kim, O., Kim, Y. I., King, B., Kinnaird, N., Kraegeloh, E., Kuchibhotla, A., Kuchinskiy, N. A., Labe, K. R., LaBounty, J., Lancaster, M., Lee, M. J., Lee, S., Leo, S., Li, B., Li, D., Li, L., Logashenko, I., Campos, A. Lorente, Lucà, A., Lukicov, G., Lusiani, A., Lyon, A. L., MacCoy, B., Madrak, R., Makino, K., Marignetti, F., Mastroianni, S., Miller, J. P., Miozzi, S., Morse, W. M., Mott, J., Nath, A., Nguyen, H., Osofsky, R., Park, S., Pauletta, G., Piacentino, G. M., Pilato, R. N., Pitts, K. T., Plaster, B., Počanić, D., Pohlman, N., Polly, C. C., Price, J., Quinn, B., Raha, N., Ramachandran, S., Ramberg, E., Ritchie, J. L., Roberts, B. L., Rubin, D. L., Santi, L., Schlesier, C., Schreckenberger, A., Semertzidis, Y. K., Shemyakin, D., Smith, M. W., Sorbara, M., Stöckinger, D., Stapleton, J., Stoughton, C., Stratakis, D., Stuttard, T., Swanson, H. E., Sweetmore, G., Sweigart, D. A., Syphers, M. J., Tarazona, D. A., Teubner, T., Tewsley-Booth, A. E., Thomson, K., Tishchenko, V., Tran, N. H., Turner, W., Valetov, E., Vasilkova, D., Venanzoni, G., Walton, T., Weisskopf, A., Welty-Rieger, L., Winter, P., Wolski, A., and Wu, W.

Subjects
High Energy Physics - Experiment, Nuclear Experiment
Abstract

The Muon g-2 Experiment at Fermi National Accelerator Laboratory (FNAL) has measured the muon anomalous precession frequency $\omega_a$ to an uncertainty of 434 parts per billion (ppb), statistical, and 56 ppb, systematic, with data collected in four storage ring configurations during its first physics run in 2018. When combined with a precision measurement of the magnetic field of the experiment's muon storage ring, the precession frequency measurement determines a muon magnetic anomaly of $a_{\mu}({\rm FNAL}) = 116\,592\,040(54) \times 10^{-11}$ (0.46 ppm). This article describes the multiple techniques employed in the reconstruction, analysis and fitting of the data to measure the precession frequency. It also presents the averaging of the results from the eleven separate determinations of \omega_a, and the systematic uncertainties on the result., Comment: 29 pages, 19 figures. Published in Physical Review D

Published
2021
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11. Magnetic Field Measurement and Analysis for the Muon g-2 Experiment at Fermilab

Author

Albahri, T., Anastasi, A., Badgley, K., Baeßler, S., Bailey, I., Baranov, V. A., Barlas-Yucel, E., Barrett, T., Bedeschi, F., Berz, M., Bhattacharya, M., Binney, H. P., Bloom, P., Bono, J., Bottalico, E., Bowcock, T., Cantatore, G., Carey, R. M., Casey, B. C. K., Cauz, D., Chakraborty, R., Chang, S. P., Chapelain, A., Charity, S., Chislett, R., Choi, J., Chu, Z., Chupp, T. E., Conway, A., Corrodi, S., Cotrozzi, L., Crnkovic, J. D., Dabagov, S., Debevec, P. T., Di Falco, S., Di Meo, P., Di Sciascio, G., Di Stefano, R., Driutti, A., Duginov, V. N., Eads, M., Esquivel, J., Farooq, M., Fatemi, R., Ferrari, C., Fertl, M., Fienberg, A. T., Fioretti, A., Flay, D., Froemming, N. S., Gabbanini, C., Galati, M. D., Ganguly, S., Garcia, A., George, J., Gibbons, L. K., Gioiosa, A., Giovanetti, K. L., Girotti, P., Gohn, W., Gorringe, T., Grange, J., Grant, S., Gray, F., Haciomeroglu, S., Halewood-Leagas, T., Hampai, D., Han, F., Hempstead, J., Herrod, A. T., Hertzog, D. W., Hesketh, G., Hibbert, A., Hodge, Z., Holzbauer, J. L., Hong, K. W., Hong, R., Iacovacci, M., Incagli, M., Kammel, P., Kargiantoulakis, M., Karuza, M., Kaspar, J., Kawall, D., Kelton, L., Keshavarzi, A., Kessler, D., Khaw, K. S., Khechadoorian, Z., Khomutov, N. V., Kiburg, B., Kiburg, M., Kim, O., Kim, Y. I., King, B., Kinnaird, N., Kraegeloh, E., Kuchinskiy, N. A., Labe, K. R., LaBounty, J., Lancaster, M., Lee, M. J., Lee, S., Li, B., Li, D., Li, L., Logashenko, I., Campos, A. Lorente, Lucà, A., Lukicov, G., Lusiani, A., Lyon, A. L., MacCoy, B., Madrak, R., Makino, K., Marignetti, F., Mastroianni, S., Miller, J. P., Miozzi, S., Morse, W. M., Mott, J., Nath, A., Nguyen, H., Osofsky, R., Park, S., Pauletta, G., Piacentino, G. M., Pilato, R. N., Pitts, K. T., Plaster, B., Počanić, D., Pohlman, N., Polly, C. C., Price, J., Quinn, B., Raha, N., Ramachandran, S., Ramberg, E., Ritchie, J. L., Roberts, B. L., Rubin, D. L., Santi, L., Schlesier, C., Schreckenberger, A., Semertzidis, Y. K., Shemyakin, D., Smith, M. W., Sorbara, M., Stöckinger, D., Stapleton, J., Stoughton, C., Stratakis, D., Stuttard, T., Swanson, H. E., Sweetmore, G., Sweigart, D. A., Syphers, M. J., Tarazona, D. A., Teubner, T., Tewsley-Booth, A. E., Thomson, K., Tishchenko, V., Tran, N. H., Turner, W., Valetov, E., Vasilkova, D., Venanzoni, G., Walton, T., Weisskopf, A., Welty-Rieger, L., Winter, P., Wolski, A., and Wu, W.

Subjects
High Energy Physics - Experiment, Nuclear Experiment
Abstract

The Fermi National Accelerator Laboratory has measured the anomalous precession frequency $a^{}_\mu = (g^{}_\mu-2)/2$ of the muon to a combined precision of 0.46 parts per million with data collected during its first physics run in 2018. This paper documents the measurement of the magnetic field in the muon storage ring. The magnetic field is monitored by nuclear magnetic resonance systems and calibrated in terms of the equivalent proton spin precession frequency in a spherical water sample at 34.7$^\circ$C. The measured field is weighted by the muon distribution resulting in $\tilde{\omega}'^{}_p$, the denominator in the ratio $\omega^{}_a$/$\tilde{\omega}'^{}_p$ that together with known fundamental constants yields $a^{}_\mu$. The reported uncertainty on $\tilde{\omega}'^{}_p$ for the Run-1 data set is 114 ppb consisting of uncertainty contributions from frequency extraction, calibration, mapping, tracking, and averaging of 56 ppb, and contributions from fast transient fields of 99 ppb., Comment: Added one citation and corrected missing normalization in Eqs (35) and (36)

Published
2021
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12. Measurement of the Positive Muon Anomalous Magnetic Moment to 0.46 ppm

Author

Abi, B., Albahri, T., Al-Kilani, S., Allspach, D., Alonzi, L. P., Anastasi, A., Anisenkov, A., Azfar, F., Badgley, K., Baeßler, S., Bailey, I., Baranov, V. A., Barlas-Yucel, E., Barrett, T., Barzi, E., Basti, A., Bedeschi, F., Behnke, A., Berz, M., Bhattacharya, M., Binney, H. P., Bjorkquist, R., Bloom, P., Bono, J., Bottalico, E., Bowcock, T., Boyden, D., Cantatore, G., Carey, R. M., Carroll, J., Casey, B. C. K., Cauz, D., Ceravolo, S., Chakraborty, R., Chang, S. P., Chapelain, A., Chappa, S., Charity, S., Chislett, R., Choi, J., Chu, Z., Chupp, T. E., Convery, M. E., Conway, A., Corradi, G., Corrodi, S., Cotrozzi, L., Crnkovic, J. D., Dabagov, S., De Lurgio, P. M., Debevec, P. T., Di Falco, S., Di Meo, P., Di Sciascio, G., Di Stefano, R., Drendel, B., Driutti, A., Duginov, V. N., Eads, M., Eggert, N., Epps, A., Esquivel, J., Farooq, M., Fatemi, R., Ferrari, C., Fertl, M., Fiedler, A., Fienberg, A. T., Fioretti, A., Flay, D., Foster, S. B., Friedsam, H., Frlež, E., Froemming, N. S., Fry, J., Fu, C., Gabbanini, C., Galati, M. D., Ganguly, S., Garcia, A., Gastler, D. E., George, J., Gibbons, L. K., Gioiosa, A., Giovanetti, K. L., Girotti, P., Gohn, W., Gorringe, T., Grange, J., Grant, S., Gray, F., Haciomeroglu, S., Hahn, D., Halewood-Leagas, T., Hampai, D., Han, F., Hazen, E., Hempstead, J., Henry, S., Herrod, A. T., Hertzog, D. W., Hesketh, G., Hibbert, A., Hodge, Z., Holzbauer, J. L., Hong, K. W., Hong, R., Iacovacci, M., Incagli, M., Johnstone, C., Johnstone, J. A., Kammel, P., Kargiantoulakis, M., Karuza, M., Kaspar, J., Kawall, D., Kelton, L., Keshavarzi, A., Kessler, D., Khaw, K. S., Khechadoorian, Z., Khomutov, N. V., Kiburg, B., Kiburg, M., Kim, O., Kim, S. C., Kim, Y. I., King, B., Kinnaird, N., Korostelev, M., Kourbanis, I., Kraegeloh, E., Krylov, V. A., Kuchibhotla, A., Kuchinskiy, N. A., Labe, K. R., LaBounty, J., Lancaster, M., Lee, M. J., Lee, S., Leo, S., Li, B., Li, D., Li, L., Logashenko, I., Campos, A. Lorente, Lucà, A., Lukicov, G., Luo, G., Lusiani, A., Lyon, A. L., MacCoy, B., Madrak, R., Makino, K., Marignetti, F., Mastroianni, S., Maxfield, S., McEvoy, M., Merritt, W., Mikhailichenko, A. A., Miller, J. P., Miozzi, S., Morgan, J. P., Morse, W. M., Mott, J., Motuk, E., Nath, A., Newton, D., Nguyen, H., Oberling, M., Osofsky, R., Ostiguy, J. -F., Park, S., Pauletta, G., Piacentino, G. M., Pilato, R. N., Pitts, K. T., Plaster, B., Počanić, D., Pohlman, N., Polly, C. C., Popovic, M., Price, J., Quinn, B., Raha, N., Ramachandran, S., Ramberg, E., Rider, N. T., Ritchie, J. L., Roberts, B. L., Rubin, D. L., Santi, L., Sathyan, D., Schellman, H., Schlesier, C., Schreckenberger, A., Semertzidis, Y. K., Shatunov, Y. M., Shemyakin, D., Shenk, M., Sim, D., Smith, M. W., Smith, A., Soha, A. K., Sorbara, M., Stöckinger, D., Stapleton, J., Still, D., Stoughton, C., Stratakis, D., Strohman, C., Stuttard, T., Swanson, H. E., Sweetmore, G., Sweigart, D. A., Syphers, M. J., Tarazona, D. A., Teubner, T., Tewsley-Booth, A. E., Thomson, K., Tishchenko, V., Tran, N. H., Turner, W., Valetov, E., Vasilkova, D., Venanzoni, G., Volnykh, V. P., Walton, T., Warren, M., Weisskopf, A., Welty-Rieger, L., Whitley, M., Winter, P., Wolski, A., Wormald, M., Wu, W., and Yoshikawa, C.

Subjects
High Energy Physics - Experiment, Nuclear Experiment
Abstract

We present the first results of the Fermilab Muon g-2 Experiment for the positive muon magnetic anomaly $a_\mu \equiv (g_\mu-2)/2$. The anomaly is determined from the precision measurements of two angular frequencies. Intensity variation of high-energy positrons from muon decays directly encodes the difference frequency $\omega_a$ between the spin-precession and cyclotron frequencies for polarized muons in a magnetic storage ring. The storage ring magnetic field is measured using nuclear magnetic resonance probes calibrated in terms of the equivalent proton spin precession frequency ${\tilde{\omega}'^{}_p}$ in a spherical water sample at 34.7$^{\circ}$C. The ratio $\omega_a / {\tilde{\omega}'^{}_p}$, together with known fundamental constants, determines $a_\mu({\rm FNAL}) = 116\,592\,040(54)\times 10^{-11}$ (0.46\,ppm). The result is 3.3 standard deviations greater than the standard model prediction and is in excellent agreement with the previous Brookhaven National Laboratory (BNL) E821 measurement. After combination with previous measurements of both $\mu^+$ and $\mu^-$, the new experimental average of $a_\mu({\rm Exp}) = 116\,592\,061(41)\times 10^{-11}$ (0.35\,ppm) increases the tension between experiment and theory to 4.2 standard deviations, Comment: 10 pages; 4 figures

Published
2021
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13. Beam dynamics corrections to the Run-1 measurement of the muon anomalous magnetic moment at Fermilab

Author

Albahri, T., Anastasi, A., Badgley, K., Baeßler, S., Bailey, I., Baranov, V. A., Barlas-Yucel, E., Barrett, T., Bedeschi, F., Berz, M., Bhattacharya, M., Binney, H. P., Bloom, P., Bono, J., Bottalico, E., Bowcock, T., Cantatore, G., Carey, R. M., Casey, B. C. K., Cauz, D., Chakraborty, R., Chang, S. P., Chapelain, A., Charity, S., Chislett, R., Choi, J., Chu, Z., Chupp, T. E., Corrodi, S., Cotrozzi, L., Crnkovic, J. D., Dabagov, S., Debevec, P. T., Di Falco, S., Di Meo, P., Di Sciascio, G., Di Stefano, R., Driutti, A., Duginov, V. N., Eads, M., Esquivel, J., Farooq, M., Fatemi, R., Ferrari, C., Fertl, M., Fiedler, A., Fienberg, A. T., Fioretti, A., Flay, D., Frlež, E., Froemming, N. S., Fry, J., Gabbanini, C., Galati, M. D., Ganguly, S., Garcia, A., George, J., Gibbons, L. K., Gioiosa, A., Giovanetti, K. L., Girotti, P., Gohn, W., Gorringe, T., Grange, J., Grant, S., Gray, F., Haciomeroglu, S., Halewood-Leagas, T., Hampai, D., Han, F., Hempstead, J., Herrod, A. T., Hertzog, D. W., Hesketh, G., Hibbert, A., Hodge, Z., Holzbauer, J. L., Hong, K. W., Hong, R., Iacovacci, M., Incagli, M., Kammel, P., Kargiantoulakis, M., Karuza, M., Kaspar, J., Kawall, D., Kelton, L., Keshavarzi, A., Kessler, D., Khaw, K. S., Khechadoorian, Z., Khomutov, N. V., Kiburg, B., Kiburg, M., Kim, O., Kim, Y. I., King, B., Kinnaird, N., Korostelev, M., Kraegeloh, E., Kuchinskiy, N. A., Labe, K. R., LaBounty, J., Lancaster, M., Lee, M. J., Lee, S., Li, B., Li, D., Li, L., Logashenko, I., Campos, A. Lorente, Lucà, A., Lukicov, G., Lusiani, A., Lyon, A. L., MacCoy, B., Madrak, R., Makino, K., Marignetti, F., Mastroianni, S., Miller, J. P., Miozzi, S., Morse, W. M., Mott, J., Nath, A., Newton, D., Nguyen, H., Osofsky, R., Park, S., Pauletta, G., Piacentino, G. M., Pilato, R. N., Pitts, K. T., Plaster, B., Počanić, D., Pohlman, N., Polly, C. C., Price, J., Quinn, B., Raha, N., Ramachandran, S., Ramberg, E., Ritchie, J. L., Roberts, B. L., Rubin, D. L., Santi, L., Sathyan, D., Schlesier, C., Schreckenberger, A., Semertzidis, Y. K., Smith, M. W., Sorbara, M., Stöckinger, D., Stapleton, J., Stoughton, C., Stratakis, D., Stuttard, T., Swanson, H. E., Sweetmore, G., Sweigart, D. A., Syphers, M. J., Tarazona, D. A., Teubner, T., Tewsley-Booth, A. E., Thomson, K., Tishchenko, V., Tran, N. H., Turner, W., Valetov, E., Vasilkova, D., Venanzoni, G., Walton, T., Weisskopf, A., Welty-Rieger, L., Winter, P., Wolski, A., and Wu, W.

Subjects
Physics - Accelerator Physics, High Energy Physics - Experiment
Abstract

This paper presents the beam dynamics systematic corrections and their uncertainties for the Run-1 data set of the Fermilab Muon g-2 Experiment. Two corrections to the measured muon precession frequency $\omega_a^m$ are associated with well-known effects owing to the use of electrostatic quadrupole (ESQ) vertical focusing in the storage ring. An average vertically oriented motional magnetic field is felt by relativistic muons passing transversely through the radial electric field components created by the ESQ system. The correction depends on the stored momentum distribution and the tunes of the ring, which has relatively weak vertical focusing. Vertical betatron motions imply that the muons do not orbit the ring in a plane exactly orthogonal to the vertical magnetic field direction. A correction is necessary to account for an average pitch angle associated with their trajectories. A third small correction is necessary because muons that escape the ring during the storage time are slightly biased in initial spin phase compared to the parent distribution. Finally, because two high-voltage resistors in the ESQ network had longer than designed RC time constants, the vertical and horizontal centroids and envelopes of the stored muon beam drifted slightly, but coherently, during each storage ring fill. This led to the discovery of an important phase-acceptance relationship that requires a correction. The sum of the corrections to $\omega_a^m$ is 0.50 $\pm$ 0.09 ppm; the uncertainty is small compared to the 0.43 ppm statistical precision of $\omega_a^m$., Comment: 35 pages, 29 figures. Accepted by Phys. Rev. Accel. Beams

Published
2021
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16. Evaluation of the Transport and Binding of Dopamine-Loaded PLGA Nanoparticles for the Treatment of Parkinson’s Disease Using In Vitro Model Systems

Author

Karin Danz, Jana Fleddermann, Marcus Koch, Elena Fecioru, Lorenz Maahs, Nicole Kinsinger, Johannes Krämer, Annette Kraegeloh, and Sylvia Wagner

Subjects
nanoparticles, blood–brain barrier, transport study, in vitro models, Parkinson’s disease, Pharmacy and materia medica, RS1-441
Abstract

The treatment of Parkinson’s disease has been moving into the focus of pharmaceutical development. Yet, the necessity for reliable model systems in the development phase has made research challenging and in vivo models necessary. We have established reliable, reproducible in vitro model systems to evaluate the binding and transport of dopamine-loaded PLGA nanoparticles for the treatment of Parkinson’s disease and put the results in context with comparable in vivo results. The in vitro models have provided similar results concerning the usability of the investigated nanoparticles as the previously used in vivo models and thus provide a good alternative in line with the 3R principles in pharmaceutical research.

Published
2024
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17. Impact of mucus modulation by N-acetylcysteine on nanoparticle toxicity

Author

Enkeleda Meziu, Kristela Shehu, Marcus Koch, Marc Schneider, and Annette Kraegeloh

Subjects
Calu-3 cells, Polystyrene nanoparticles, Mucus penetration, Cytotoxicity, Air interface culture (AIC), Pharmacy and materia medica, RS1-441
Abstract

Human respiratory mucus is a biological hydrogel that forms a protective barrier for the underlying epithelium. Modulation of the mucus layer has been employed as a strategy to enhance transmucosal drug carrier transport. However, a drawback of this strategy is a potential reduction of the mucus barrier properties, in particular in situations with an increased exposure to particles. In this study, we investigated the impact of mucus modulation on its protective role. In vitro mucus was produced by Calu-3 cells, cultivated at the air-liquid interface for 21 days and used for further testing as formed on top of the cells. Analysis of confocal 3D imaging data revealed that after 21 days Calu-3 cells secrete a mucus layer with a thickness of 24 ± 6 μm. Mucus appeared to restrict penetration of 500 nm carboxyl-modified polystyrene particles to the upper 5–10 μm of the layer. Furthermore, a mucus modulation protocol using aerosolized N-acetylcysteine (NAC) was developed. This treatment enhanced the penetration of particles through the mucus down to deeper layers by means of the mucolytic action of NAC. These findings were supported by cytotoxicity data, indicating that intact mucus protects the underlying epithelium from particle-induced effects on membrane integrity. The impact of NAC treatment on the protective properties of mucus was probed by using 50 and 100 nm amine-modified and 50 nm carboxyl-modified polystyrene nanoparticles, respectively. Cytotoxicity was only induced by the amine-modified particles in combination with NAC treatment, implying a reduced protective function of modulated mucus. Overall, our data emphasize the importance of integrating an assessment of the protective function of mucus into the development of therapy approaches involving mucus modulation.

Published
2023
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18. New Limit on the Permanent Electric Dipole Moment of $^{129}$Xe using $^{3}$He Comagnetometry and SQUID Detection

Author

Sachdeva, N., Fan, I., Babcock, E., Burghoff, M., Chupp, T. E., Degenkolb, S., Fierlinger, P., Haude, S., Kraegeloh, E., Kilian, W., Knappe-Grüneberg, S., Kuchler, F., Liu, T., Marino, M., Meinel, J., Rolfs, K., Salhi, Z., Schnabel, A., Singh, J. T., Stuiber, S., Terrano, W. A., Trahms, L., and Voigt, J.

Subjects
Physics - Atomic Physics
Abstract

We report results of a new technique to measure the electric dipole moment of $^{129}$Xe with $^3$He comagnetometry. Both species are polarized using spin-exchange optical pumping, transferred to a measurement cell, and transported into a magnetically shielded room, where SQUID magnetometers detect free precession in applied electric and magnetic fields. The result from a one week measurement campaign in 2017 and a 2.5 week campaign in 2018, combined with detailed study of systematic effects, is $d_A(^{129}\mathrm{Xe}) = (1.4 \pm 6.6_\mathrm{stat} \pm 2.0_\mathrm{syst})\times10^{-28}~e\,\mathrm{cm}$. This corresponds to an upper limit of $|d_A(^{129}\mathrm{Xe})| < 1.4 \times 10^{-27} ~e\,\mathrm{cm}~(95\%~\mathrm{CL})$, a factor of five more sensitive than the limit set in 2001., Comment: To be published in Physical Review Letters. arXiv admin note: substantial text overlap with arXiv:1902.02864

Published
2019
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20. Effect of Thomas Rotation on the Lorentz Transformation of Electromagnetic fields

Author

Malhotra, Lakshya, Golub, Robert, Kraegeloh, Eva, Nouri, Nima, and Plaster, Bradley

Subjects
Physics - Classical Physics
Abstract

A relativistic particle undergoing successive boosts which are non collinear will experience a rotation of its coordinate axes with respect to the boosted frame. This rotation of coordinate axes is caused by a relativistic phenomenon called Thomas Rotation. We assess the importance of Thomas rotation in the calculation of physical quantities like electromagnetic fields in the relativistic regime. We calculate the electromagnetic field tensor for general three dimensional successive boosts in the particle's rest frame as well as the laboratory frame. We then compare the electromagnetic field tensors obtained by a direct boost $\vec{\beta} + \delta \vec{\beta}$ and successive boosts $\vec{\beta}$ and $\Delta \vec{\beta}$ and check their consistency with Thomas rotation. This framework might be important to situations such as the calculation of frequency shifts for relativistic spin-1/2 particles undergoing Larmor precession in electromagnetic fields with small field non-uniformities., Comment: 18 pages, 4 figures

Published
2019

21. A new measurement of the permanent electric dipole moment of $^{129}$Xe using $^{3}$He comagnetometry and SQUID detection

Author

Sachdeva, N., Fan, I., Babcock, E., Burghoff, M., Chupp, T. E., Degenkolb, S., Fierlinger, P., Kraegeloh, E., Kilian, W., Knappe-Grüneberg, S., Kuchler, F., Liu, T., Marino, M., Meinel, J., Salhi, Z., Schnabel, A., Singh, J. T., Stuiber, S., Terrano, W. A., Trahms, L., and Voigt, J.

Subjects
Physics - Atomic Physics, Physics - Instrumentation and Detectors
Abstract

We describe a new technique to measure the EDM of $^{129}$Xe with $^3$He comagnetometry. Both species are polarized using spin-exchange optical pumping, transferred to a measurement cell, and transported into a magnetically shielded room, where SQUID magnetometers detect free precession in applied electric and magnetic fields. The result of a one week run combined with a detailed study of systematic effects is $d_A(^{129}\mathrm{Xe}) = (0.26 \pm 2.33_\mathrm{stat} \pm 0.72_\mathrm{syst})\times10^{-27}~e\,\mathrm{cm}$. This corresponds to an upper limit of $|d_A(^{129}\mathrm{Xe})| < 4.81\times 10^{-27} ~e\,\mathrm{cm}~(95\%~\mathrm{CL})$, a factor of 1.4 more sensitive than the previous limit.

Published
2019

22. Loss-of-function mutations in UDP-Glucose 6-Dehydrogenase cause recessive developmental epileptic encephalopathy.

Author

Hengel, Holger, Bosso-Lefèvre, Célia, Grady, George, Szenker-Ravi, Emmanuelle, Li, Hankun, Pierce, Sarah, Lebigot, Élise, Tan, Thong-Teck, Eio, Michelle Y, Narayanan, Gunaseelan, Utami, Kagistia Hana, Yau, Monica, Handal, Nader, Deigendesch, Werner, Keimer, Reinhard, Marzouqa, Hiyam M, Gunay-Aygun, Meral, Muriello, Michael J, Verhelst, Helene, Weckhuysen, Sarah, Mahida, Sonal, Naidu, Sakkubai, Thomas, Terrence G, Lim, Jiin Ying, Tan, Ee Shien, Haye, Damien, Willemsen, Michèl AAP, Oegema, Renske, Mitchell, Wendy G, Pierson, Tyler Mark, Andrews, Marisa V, Willing, Marcia C, Rodan, Lance H, Barakat, Tahsin Stefan, van Slegtenhorst, Marjon, Gavrilova, Ralitza H, Martinelli, Diego, Gilboa, Tal, Tamim, Abdullah M, Hashem, Mais O, AlSayed, Moeenaldeen D, Abdulrahim, Maha M, Al-Owain, Mohammed, Awaji, Ali, Mahmoud, Adel AH, Faqeih, Eissa A, Asmari, Ali Al, Algain, Sulwan M, Jad, Lamyaa A, Aldhalaan, Hesham M, Helbig, Ingo, Koolen, David A, Riess, Angelika, Kraegeloh-Mann, Ingeborg, Bauer, Peter, Gulsuner, Suleyman, Stamberger, Hannah, Ng, Alvin Yu Jin, Tang, Sha, Tohari, Sumanty, Keren, Boris, Schultz-Rogers, Laura E, Klee, Eric W, Barresi, Sabina, Tartaglia, Marco, Mor-Shaked, Hagar, Maddirevula, Sateesh, Begtrup, Amber, Telegrafi, Aida, Pfundt, Rolph, Schüle, Rebecca, Ciruna, Brian, Bonnard, Carine, Pouladi, Mahmoud A, Stewart, James C, Claridge-Chang, Adam, Lefeber, Dirk J, Alkuraya, Fowzan S, Mathuru, Ajay S, Venkatesh, Byrappa, Barycki, Joseph J, Simpson, Melanie A, Jamuar, Saumya S, Schöls, Ludger, and Reversade, Bruno

Subjects
Organoids, Animals, Zebrafish, Humans, Epilepsy, Syndrome, Oxidoreductases, Pedigree, Kinetics, Genes, Recessive, Alleles, Adolescent, Child, Child, Preschool, Infant, Female, Male, Protein Domains, Loss of Function Mutation, Preschool, Genes, Recessive
Abstract

Developmental epileptic encephalopathies are devastating disorders characterized by intractable epileptic seizures and developmental delay. Here, we report an allelic series of germline recessive mutations in UGDH in 36 cases from 25 families presenting with epileptic encephalopathy with developmental delay and hypotonia. UGDH encodes an oxidoreductase that converts UDP-glucose to UDP-glucuronic acid, a key component of specific proteoglycans and glycolipids. Consistent with being loss-of-function alleles, we show using patients' primary fibroblasts and biochemical assays, that these mutations either impair UGDH stability, oligomerization, or enzymatic activity. In vitro, patient-derived cerebral organoids are smaller with a reduced number of proliferating neuronal progenitors while mutant ugdh zebrafish do not phenocopy the human disease. Our study defines UGDH as a key player for the production of extracellular matrix components that are essential for human brain development. Based on the incidence of variants observed, UGDH mutations are likely to be a frequent cause of recessive epileptic encephalopathy.

Published
2020

28. Zerebralparesen

Author

Krägeloh-Mann, Ingeborg, Hoffmann, Georg. F., Section editor, Hoffmann, Georg F., editor, Lentze, Michael J., editor, Spranger, Jürgen, editor, Zepp, Fred, editor, Berner, Reinhard, editor, Schaub, Jürgen, Founding Editor, and Schulte, Franz-Josef, Founding Editor

Published
2020
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31. Nervensystem

Author

Boltshauser, E., Kaindl, A. M., Ipsiroglu, O., Krägeloh-Mann, I., Rostásy, K., Schöning, M., Stöckler-Ipsiroglu, S., Krauß, J., Schweitzer, T., Speer, Christian P., editor, Gahr, Manfred, editor, and Dötsch, Jörg, editor

Published
2019
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39. High-dose intranasal application of titanium dioxide nanoparticles induces the systemic uptakes and allergic airway inflammation in asthmatic mice

Author

Shaza Abdulnasser Harfoush, Matthias Hannig, Duc Dung Le, Sebastian Heck, Maximilian Leitner, Albert Joachim Omlor, Isabella Tavernaro, Annette Kraegeloh, Ralf Kautenburger, Guido Kickelbick, Andreas Beilhack, Markus Bischoff, Juliane Nguyen, Martina Sester, Robert Bals, and Quoc Thai Dinh

Subjects
Asthma, Titanium dioxide nanoparticles, Ovalbumin, Airway inflammation, Hyperresponsiveness, systemic uptake, Diseases of the respiratory system, RC705-779
Abstract

Abstract Background Titanium dioxide nanoparticles (TiO2 NPs) have a wide range of applications in several industrial and biomedical domains. Based on the evidence, the workers exposed to inhaled nanosized TiO2 powder are more susceptible to the risks of developing respiratory diseases. Accordingly, this issue has increasingly attracted the researchers’ interest in understanding the consequences of TiO2 NPs exposure. Regarding this, the present study was conducted to analyze the local effects of TiO2 NPs on allergic airway inflammation and their uptake in a mouse model of ovalbumin (OVA)-induced allergic airway inflammation. Methods For the purpose of the study, female BALB/c mice with or without asthma were intranasally administered with TiO2 NPs. The mice were subjected to histological assessment, lung function testing, scanning electron microscopy (SEM), inductively coupled plasma mass spectrometry (ICP-MS), and NP uptake measurement. In addition, T helper (Th) 1/Th2 cytokines were evaluated in the lung homogenate using the enzyme-linked immunosorbent assay. Results According to the results, the mice receiving OVA alone or OVA plus TiO2 NPs showed eosinophilic infiltrates and mucus overproduction in the lung tissues, compared to the controls. Furthermore, a significant elevation was observed in the circulating Th2 cytokines, including interleukin (IL)-4, IL-5, and IL-13 after NP exposure. The TiO2 NPs were taken up by alveolar macrophages at different time points. As the results of the SEM and ICP-MS indicated, TiO2 NPs were present in most of the organs in both asthmatic and non-asthmatic mice. Conclusion Based on the findings of the current study, intranasally or inhalation exposure to high-dose nanosized TiO2 particles appears to exacerbate the allergic airway inflammation and lead to systemic uptake in extrapulmonary organs. These results indicate the very important need to investigate the upper limit of intranasally or inhalation exposure to nanosized TiO2 particles in occupational and environmental health policy.

Published
2020
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42. Safe innovation approach: Towards an agile system for dealing with innovations

Author

Soeteman-Hernandez, Lya G., Apostolova, Margarita D., Bekker, Cindy, Dekkers, Susan, Grafström, Roland C., Groenewold, Monique, Handzhiyski, Yordan, Herbeck-Engel, Petra, Hoehener, Karl, Karagkiozaki, Varvara, Kelly, Sean, Kraegeloh, Annette, Logothetidis, Stergios, Micheletti, Christian, Nymark, Penny, Oomen, Agnes, Oosterwijk, Thies, Rodríguez-LLopis, Isabel, Sabella, Stefania, Sanchez Jiménez, Araceli, Sips, Adriënne J.A.M., Suarez- Merino, Blanca, Tavernaro, Isabella, van Engelen, Jacqueline, Wijnhoven, Susan W.P., and Noorlander, Cornelle W.

Published
2019
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