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4,181 results on '"Ehinger A"'

1. First Measurement of Near- and Sub-Threshold $J/\psi$ Photoproduction off Nuclei

Author

Pybus, J. R., Ehinger, L., Kolar, T., Devkota, B., Sharp, P., Yu, B., Dalton, M. M., Dutta, D., Gao, H., Hen, O., Piasetzky, E., Santiesteban, S. N., Schmidt, A., Somov, A., Szumila-Vance, H., Adhikari, S., Asaturyan, A., Austregesilo, A., Gayoso, C. Ayerbe, Barlow, J., Berdnikov, V. V., Bhatt, H. D., Bhetuwal, Deepak, Black, T., Briscoe, W. J., Chung, G., Cole, P. L., Deur, A., Dotel, R., Egiyan, H., Eugenio, P., Fanelli, C., Gan, L., Gasparian, A., Guo, J., Hernandez, K., Higinbotham, D. W., Hurck, P., Jaegle, I., Jones, R. T., Kakoyan, V., Karki, A., Li, H., Li, W. B., Linera, G. R., Lyubovitskij, V., Marukyan, H., McCaughan, M. D., McCracken, M., Mizutani, K., Nguyen, D., Oresic, S., Ostrovidov, A. I., Papandreou, Z., Paudel, C., Peters, K., Ritman, J., Schick, A., Schwiening, J., Smith, A., Somov, S., Strakovsky, I., Suresh, K., Tarasov, V. V., Taylor, S., Xiao, T., Zhang, Z., and Zhou, X.

Subjects
Nuclear Experiment
Abstract

We report on the first measurement of $J/\psi$ photoproduction from nuclei in the photon energy range of $7$ to $10.8$ GeV, extending above and below the photoproduction threshold in the free proton of $\sim8.2$ GeV. The experiment used a tagged photon beam incident on deuterium, helium, and carbon, and the GlueX detector at Jefferson Lab to measure the semi-inclusive $A(\gamma,e^+e^-p)$ reaction with a dilepton invariant mass $M(e^+e^-)\sim m_{J/\psi}=3.1$ GeV. The incoherent $J/\psi$ photoproduction cross sections in the measured nuclei are extracted as a function of the incident photon energy, momentum transfer, and proton reconstructed missing light-cone momentum fraction. Comparisons with theoretical predictions assuming a dipole form factor allow extracting a gluonic radius for bound protons of $\sqrt{\langle r^2\rangle}=0.85\pm0.14$ fm. The data also suggest an excess of the measured cross section for sub-threshold production and for interactions with high missing light-cone momentum fraction protons. The measured enhancement can be explained by modified gluon structure for high-virtuality bound-protons.

Published
2024

2. KALE: An Artwork Image Captioning System Augmented with Heterogeneous Graph

Author

Jiang, Yanbei, Ehinger, Krista A., and Lau, Jey Han

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Artificial Intelligence
Abstract

Exploring the narratives conveyed by fine-art paintings is a challenge in image captioning, where the goal is to generate descriptions that not only precisely represent the visual content but also offer a in-depth interpretation of the artwork's meaning. The task is particularly complex for artwork images due to their diverse interpretations and varied aesthetic principles across different artistic schools and styles. In response to this, we present KALE Knowledge-Augmented vision-Language model for artwork Elaborations), a novel approach that enhances existing vision-language models by integrating artwork metadata as additional knowledge. KALE incorporates the metadata in two ways: firstly as direct textual input, and secondly through a multimodal heterogeneous knowledge graph. To optimize the learning of graph representations, we introduce a new cross-modal alignment loss that maximizes the similarity between the image and its corresponding metadata. Experimental results demonstrate that KALE achieves strong performance (when evaluated with CIDEr, in particular) over existing state-of-the-art work across several artwork datasets. Source code of the project is available at https://github.com/Yanbei-Jiang/Artwork-Interpretation., Comment: Accepted at IJCAI 2024

Published
2024

3. Sequential Amodal Segmentation via Cumulative Occlusion Learning

Author

Ao, Jiayang, Ke, Qiuhong, and Ehinger, Krista A.

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

To fully understand the 3D context of a single image, a visual system must be able to segment both the visible and occluded regions of objects, while discerning their occlusion order. Ideally, the system should be able to handle any object and not be restricted to segmenting a limited set of object classes, especially in robotic applications. Addressing this need, we introduce a diffusion model with cumulative occlusion learning designed for sequential amodal segmentation of objects with uncertain categories. This model iteratively refines the prediction using the cumulative mask strategy during diffusion, effectively capturing the uncertainty of invisible regions and adeptly reproducing the complex distribution of shapes and occlusion orders of occluded objects. It is akin to the human capability for amodal perception, i.e., to decipher the spatial ordering among objects and accurately predict complete contours for occluded objects in densely layered visual scenes. Experimental results across three amodal datasets show that our method outperforms established baselines.

Published
2024

4. Mitigating Challenges of the Space Environment for Onboard Artificial Intelligence: Design Overview of the Imaging Payload on SpIRIT

Author

del Castillo, Miguel Ortiz, Morgan, Jonathan, McRobbie, Jack, Therakam, Clint, Joukhadar, Zaher, Mearns, Robert, Barraclough, Simon, Sinnott, Richard, Woods, Andrew, Bayliss, Chris, Ehinger, Kris, Rubinstein, Ben, Bailey, James, Chapman, Airlie, and Trenti, Michele

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

Artificial intelligence (AI) and autonomous edge computing in space are emerging areas of interest to augment capabilities of nanosatellites, where modern sensors generate orders of magnitude more data than can typically be transmitted to mission control. Here, we present the hardware and software design of an onboard AI subsystem hosted on SpIRIT. The system is optimised for on-board computer vision experiments based on visible light and long wave infrared cameras. This paper highlights the key design choices made to maximise the robustness of the system in harsh space conditions, and their motivation relative to key mission requirements, such as limited compute resources, resilience to cosmic radiation, extreme temperature variations, distribution shifts, and very low transmission bandwidths. The payload, called Loris, consists of six visible light cameras, three infrared cameras, a camera control board and a Graphics Processing Unit (GPU) system-on-module. Loris enables the execution of AI models with on-orbit fine-tuning as well as a next-generation image compression algorithm, including progressive coding. This innovative approach not only enhances the data processing capabilities of nanosatellites but also lays the groundwork for broader applications to remote sensing from space., Comment: AI4Space 2024, 3rd Workshop on AI for Space, CVPR 2024

Published
2024

7. Perceiving Longer Sequences With Bi-Directional Cross-Attention Transformers

Author

Hiller, Markus, Ehinger, Krista A., and Drummond, Tom

Subjects
Computer Science - Computer Vision and Pattern Recognition
Abstract

We present a novel bi-directional Transformer architecture (BiXT) which scales linearly with input size in terms of computational cost and memory consumption, but does not suffer the drop in performance or limitation to only one input modality seen with other efficient Transformer-based approaches. BiXT is inspired by the Perceiver architectures but replaces iterative attention with an efficient bi-directional cross-attention module in which input tokens and latent variables attend to each other simultaneously, leveraging a naturally emerging attention-symmetry between the two. This approach unlocks a key bottleneck experienced by Perceiver-like architectures and enables the processing and interpretation of both semantics ('what') and location ('where') to develop alongside each other over multiple layers -- allowing its direct application to dense and instance-based tasks alike. By combining efficiency with the generality and performance of a full Transformer architecture, BiXT can process longer sequences like point clouds, text or images at higher feature resolutions and achieves competitive performance across a range of tasks like point cloud part segmentation, semantic image segmentation, image classification, hierarchical sequence modeling and document retrieval. Our experiments demonstrate that BiXT models outperform larger competitors by leveraging longer sequences more efficiently on vision tasks like classification and segmentation, and perform on par with full Transformer variants on sequence modeling and document retrieval -- but require $28\%$ fewer FLOPs and are up to $8.4\times$ faster., Comment: Accepted at NeurIPS 2024; Code and models will be available at https://github.com/mrkshllr/BiXT

Published
2024

8. Improving Denoising Diffusion Models via Simultaneous Estimation of Image and Noise

Author

Zhang, Zhenkai, Ehinger, Krista A., and Drummond, Tom

Subjects
Computer Science - Machine Learning, Computer Science - Artificial Intelligence, Computer Science - Computer Vision and Pattern Recognition
Abstract

This paper introduces two key contributions aimed at improving the speed and quality of images generated through inverse diffusion processes. The first contribution involves reparameterizing the diffusion process in terms of the angle on a quarter-circular arc between the image and noise, specifically setting the conventional $\displaystyle \sqrt{\bar{\alpha}}=\cos(\eta)$. This reparameterization eliminates two singularities and allows for the expression of diffusion evolution as a well-behaved ordinary differential equation (ODE). In turn, this allows higher order ODE solvers such as Runge-Kutta methods to be used effectively. The second contribution is to directly estimate both the image ($\mathbf{x}_0$) and noise ($\mathbf{\epsilon}$) using our network, which enables more stable calculations of the update step in the inverse diffusion steps, as accurate estimation of both the image and noise are crucial at different stages of the process. Together with these changes, our model achieves faster generation, with the ability to converge on high-quality images more quickly, and higher quality of the generated images, as measured by metrics such as Frechet Inception Distance (FID), spatial Frechet Inception Distance (sFID), precision, and recall.

Published
2023

10. Strong interaction physics at the luminosity frontier with 22 GeV electrons at Jefferson Lab

Author

Accardi, A., Achenbach, P., Adhikari, D., Afanasev, A., Akondi, C. S., Akopov, N., Albaladejo, M., Albataineh, H., Albrecht, M., Almeida-Zamora, B., Amaryan, M., Androić, D., Armstrong, W., Armstrong, D. S., Arratia, M., Arrington, J., Asaturyan, A., Austregesilo, A., Avakian, H., Averett, T., Gayoso, C. Ayerbe, Bacchetta, A., Balantekin, A. B., Baltzell, N., Barion, L., Barry, P. C., Bashir, A., Battaglieri, M., Bellini, V., Belov, I., Benhar, O., Benkel, B., Benmokhtar, F., Bentz, W., Bertone, V., Bhatt, H., Bianconi, A., Bibrzycki, L., Bijker, R., Binosi, D., Biswas, D., Boër, M., Boeglin, W., Bogacz, S. A., Boglione, M., Bondí, M., Boos, E. E., Bosted, P., Bozzi, G., Brash, E. J., Briceño, R. A., Brindza, P. D., Briscoe, W. J., Brodsky, S. J., Brooks, W. K., Burkert, V. D., Camsonne, A., Cao, T., Cardman, L. S., Carman, D. S., Carpinelli, M., Cates, G. D., Caylor, J., Celentano, A., Celiberto, F. G., Cerutti, M., Chang, L., Chatagnon, P., Chen, C., Chen, J.-P., Chetry, T., Christopher, A., Christy, E., Chudakov, E., Cisbani, E., Cloët, I. C., Cobos-Martinez, J. J., Cohen, E. O., Colangelo, P., Cole, P. L., Constantinou, M., Contalbrigo, M., Costantini, G., Cosyn, W., Cotton, C., Courtoy, A., Dusa, S. Covrig, Crede, V., Cui, Z.-F., D’Angelo, A., Döring, M., Dalton, M. M., Danilkin, I., Davydov, M., Day, D., De Fazio, F., De Napoli, M., De Vita, R., Dean, D. J., Defurne, M., de Paula, W., de Téramond, G. F., Deur, A., Devkota, B., Dhital, S., Di Nezza, P., Diefenthaler, M., Diehl, S., Dilks, C., Ding, M., Djalali, C., Dobbs, S., Dupré, R., Dutta, D., Edwards, R. G., Egiyan, H., Ehinger, L., Eichmann, G., Elaasar, M., Elouadrhiri, L., Alaoui, A. El, Fassi, L. El, Emmert, A., Engelhardt, M., Ent, R., Ernst, D. J., Eugenio, P., Evans, G., Fanelli, C., Fegan, S., Fernández-Ramírez, C., Fernandez, L. A., Fernando, I. P., Filippi, A., Fischer, C. S., Fogler, C., Fomin, N., Frankfurt, L., Frederico, T., Freese, A., Fu, Y., Gamberg, L., Gan, L., Gao, F., Garcia-Tecocoatzi, H., Gaskell, D., Gasparian, A., Gates, K., Gavalian, G., Ghoshal, P. K., Giachino, A., Giacosa, F., Giannuzzi, F., Gilfoyle, G.-P., Girod, F.-X., Glazier, D. I., Gleason, C., Godfrey, S., Goity, J. L., Golubenko, A. A., Gonzàlez-Solís, S., Gothe, R. W., Gotra, Y., Griffioen, K., Grocholski, O., Grube, B., Guèye, P., Guo, F.-K., Guo, Y., Guo, L., Hague, T. J., Hammoud, N., Hansen, J.-O., Hattawy, M., Hauenstein, F., Hayward, T., Heddle, D., Heinrich, N., Hen, O., Higinbotham, D. W., Higuera-Angulo, I. M., Hiller Blin, A. N., Hobart, A., Hobbs, T., Holmberg, D. E., Horn, T., Hoyer, P., Huber, G. M., Hurck, P., Hutauruk, P. T. P., Ilieva, Y., Illari, I., Ireland, D. G., Isupov, E. L., Italiano, A., Jaegle, I., Jarvis, N. S., Jenkins, D. J., Jeschonnek, S., Ji, C.-R., Jo, H. S., Jones, M., Jones, R. T., Jones, D. C., Joo, K., Junaid, M., Kageya, T., Kalantarians, N., Karki, A., Karyan, G., Katramatou, A. T., Kay, S. J. D., Kazimi, R., Keith, C. D., Keppel, C., Kerbizi, A., Khachatryan, V., Khanal, A., Khandaker, M., Kim, A., Kinney, E. R., Kohl, M., Kotzinian, A., Kriesten, B. T., Kubarovsky, V., Kubis, B., Kuhn, S. E., Kumar, V., Kutz, T., Leali, M., Lebed, R. F., Lenisa, P., Leskovec, L., Li, S., Li, X., Liao, J., Lin, H.-W., Liu, L., Liuti, S., Liyanage, N., Lu, Y., MacGregor, I. J. D., Mack, D. J., Maiani, L., Mamo, K. A., Mandaglio, G., Mariani, C., Markowitz, P., Marukyan, H., Mascagna, V., Mathieu, V., Maxwell, J., Mazouz, M., McCaughan, M., McKeown, R. D., McKinnon, B., Meekins, D., Melnitchouk, W., Metz, A., Meyer, C. A., Meziani, Z.-E., Mezrag, C., Michaels, R., Miller, G. A., Mineeva, T., Miramontes, A. S., Mirazita, M., Mizutani, K., Mkrtchyan, A., Mkrtchyan, H., Moffit, B., Mohanmurthy, P., Mokeev, V. I., Monaghan, P., Montaña, G., Montgomery, R., Moretti, A., Chàvez, J. M. Morgado, Mosel, U., Movsisyan, A., Musico, P., Nadeeshani, S. A., Nadolsky, P. M., Nakamura, S. X., Nazeer, J., Nefediev, A. V., Neupane, K., Nguyen, D., Niccolai, S., Niculescu, I., Niculescu, G., Nocera, E. R., Nycz, M., Olness, F. I., Ortega, P. G., Osipenko, M., Pace, E., Pandey, B., Pandey, P., Papandreou, Z., Papavassiliou, J., Pappalardo, L. L., Paredes-Torres, G., Paremuzyan, R., Park, S., Parsamyan, B., Paschke, K. D., Pasquini, B., Passemar, E., Pasyuk, E., Patel, T., Paudel, C., Paul, S. J., Peng, J.-C., Pentchev, L., Perrino, R., Perry, R. J., Peters, K., Petratos, G. G., Phelps, W., Piasetzky, E., Pilloni, A., Pire, B., Pitonyak, D., Pitt, M. L., Polosa, A. D., Pospelov, M., Postuma, A. C., Poudel, J., Preet, L., Prelovsek, S., Price, J. W., Prokudin, A., Puckett, A. J. R., Pybus, J. R., Qin, S.-X., Qiu, J.-W., Radici, M., Rashidi, H., Rathnayake, A. D., Raue, B. A., Reed, T., Reimer, P. E., Reinhold, J., Richard, J.-M., Rinaldi, M., Ringer, F., Ripani, M., Ritman, J., West, J. Rittenhouse, Rivero-Acosta, A., Roberts, C. D., Rodas, A., Rodini, S., Rodríguez-Quintero, J., Rogers, T. C., Rojo, J., Rossi, P., Rossi, G. C., Salmè, G., Santiesteban, S. N., Santopinto, E., Sargsian, M., Sato, N., Schadmand, S., Schmidt, A., Schmidt, S. M., Schnell, G., Schumacher, R. A., Schweitzer, P., Scimemi, I., Scott, K. C., Seay, D. A., Segovia, J., Semenov-Tian-Shansky, K., Seryi, A., Sharda, A. S., Shepherd, M. R., Shirokov, E. V., Shrestha, S., Shrestha, U., Shvedunov, V. I., Signori, A., Slifer, K. J., Smith, W. A., Somov, A., Souder, P., Sparveris, N., Spizzo, F., Spreafico, M., Stepanyan, S., Stevens, J. R., Strakovsky, I. I., Strauch, S., Strikman, M., Su, S., Sumner, B. C. L., Sun, E., Suresh, M., Sutera, C., Swanson, E. S., Szczepaniak, A. P., Sznajder, P., Szumila-Vance, H., Szymanowski, L., Tadepalli, A.-S., Tadevosyan, V., Tamang, B., Tarasov, V. V., Thiel, A., Tong, X.-B., Tyson, R., Ungaro, M., Urciuoli, G. M., Usman, A., Valcarce, A., Vallarino, S., Vaquera-Araujo, C. A., Venturelli, L., Vera, F., Vladimirov, A., Vossen, A., Wagner, J., Wei, X., Weinstein, L. B., Weiss, C., Williams, R., Winney, D., Wojtsekhowski, B., Wood, M. H., Xiao, T., Xu, S.-S., Ye, Z., Yero, C., Yuan, C.-P., Yurov, M., Zachariou, N., Zhang, Z., Zhao, Y., Zhao, Z. W., Zheng, X., Zhou, X., Ziegler, V., and Zihlmann, B.

Published
2024
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11. Tumour immune characterisation of primary triple-negative breast cancer using automated image quantification of immunohistochemistry-stained immune cells

Author

Suze Roostee, Daniel Ehinger, Mats Jönsson, Bengt Phung, Göran Jönsson, Gottfrid Sjödahl, Johan Staaf, and Mattias Aine

Subjects
Medicine, Science
Abstract

Abstract The tumour immune microenvironment (TIME) in breast cancer is acknowledged with an increasing role in treatment response and prognosis. With a growing number of immune markers analysed, digital image analysis may facilitate broader TIME understanding, even in single-plex IHC data. To facilitate analyses of the latter an open-source image analysis pipeline, Tissue microarray MArker Quantification (TMArQ), was developed and applied to single-plex stainings for p53, CD3, CD4, CD8, CD20, CD68, FOXP3, and PD-L1 (SP142 antibody) in a 218-patient triple negative breast cancer (TNBC) cohort with complementary pathology scorings, clinicopathological, whole genome sequencing, and RNA-sequencing data. TMArQ’s cell counts for analysed immune markers were on par with results from alternative methods and consistent with both estimates from human pathology review, different quantifications and classifications derived from RNA-sequencing as well as known prognostic patterns of immune response in TNBC. The digital cell counts demonstrated how immune markers are coexpressed in the TIME when considering TNBC molecular subtypes and DNA repair deficiency, and how combination of immune status with DNA repair deficiency status can improve the prognostic stratification in chemotherapy treated patients. These results underscore the value and potential of integrating TIME and specific tumour intrinsic alterations/phenotypes for the molecular understanding of TNBC.

Published
2024
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12. Novelty and Lifted Helpful Actions in Generalized Planning

Author

Lei, Chao, Lipovetzky, Nir, and Ehinger, Krista A.

Subjects
Computer Science - Artificial Intelligence
Abstract

It has been shown recently that successful techniques in classical planning, such as goal-oriented heuristics and landmarks, can improve the ability to compute planning programs for generalized planning (GP) problems. In this work, we introduce the notion of action novelty rank, which computes novelty with respect to a planning program, and propose novelty-based generalized planning solvers, which prune a newly generated planning program if its most frequent action repetition is greater than a given bound $v$, implemented by novelty-based best-first search BFS($v$) and its progressive variant PGP($v$). Besides, we introduce lifted helpful actions in GP derived from action schemes, and propose new evaluation functions and structural program restrictions to scale up the search. Our experiments show that the new algorithms BFS($v$) and PGP($v$) outperform the state-of-the-art in GP over the standard generalized planning benchmarks. Practical findings on the above-mentioned methods in generalized planning are briefly discussed., Comment: Accepted at SoCS 2023 (extended version)

Published
2023

13. Strong Interaction Physics at the Luminosity Frontier with 22 GeV Electrons at Jefferson Lab

Author

Accardi, A., Achenbach, P., Adhikari, D., Afanasev, A., Akondi, C. S., Akopov, N., Albaladejo, M., Albataineh, H., Albrecht, M., Almeida-Zamora, B., Amaryan, M., Androić, D., Armstrong, W., Armstrong, D. S., Arratia, M., Arrington, J., Asaturyan, A., Austregesilo, A., Avagyan, H., Averett, T., Gayoso, C. Ayerbe, Bacchetta, A., Balantekin, A. B., Baltzell, N., Barion, L., Barry, P. C., Bashir, A., Battaglieri, M., Bellini, V., Belov, I., Benhar, O., Benkel, B., Benmokhtar, F, Bentz, W., Bertone, V., Bhatt, H., Bianconi, A., Bibrzycki, L., Bijker, R., Binosi, D., Biswas, D., Boër, M., Boeglin, W., Bogacz, S. A., Boglione, M., Bondí, M., Boos, E. E., Bosted, P., Bozzi, G., Brash, E. J., Briceño, R. A., Brindza, P. D., Briscoe, W. J., Brodsky, S. J, Brooks, W. K., Burkert, V. D., Camsonne, A., Cao, T., Cardman, L. S., Carman, D. S., Carpinelli, M, Cates, G. D., Caylor, J., Celentano, A., Celiberto, F. G., Cerutti, M., Chang, Lei, Chatagnon, P., Chen, C., Chen, J-P, Chetry, T., Christopher, A., Christy, E., Chudakov, E., Cisbani, E., Cloët, I. C., Cobos-Martinez, J. J., Cohen, E. O., Colangelo, P., Cole, P. L., Constantinou, M., Contalbrigo, M., Costantini, G., Cosyn, W., Cotton, C., Courtoy, A., Dusa, S. Covrig, Crede, V., Cui, Z. -F., D'Angelo, A., Döring, M., Dalton, M. M., Danilkin, I., Davydov, M., Day, D., De Fazio, F., De Napoli, M., De Vita, R., Dean, D. J., Defurne, M., Deur, A., Devkota, B., Dhital, S., Di Nezza, P., Diefenthaler, M., Diehl, S., Dilks, C., Ding, M., Djalali, C., Dobbs, S., Dupré, R., Dutta, D., Edwards, R. G., Egiyan, H., Ehinger, L., Eichmann, G., Elaasar, M., Elouadrhiri, L., Alaoui, A. El, Fassi, L. El, Emmert, A., Engelhardt, M., Ent, R., Ernst, D. J, Eugenio, P., Evans, G., Fanelli, C., Fegan, S., Fernández-Ramírez, C., Fernandez, L. A., Fernando, I. P., Filippi, A., Fischer, C. S., Fogler, C., Fomin, N., Frankfurt, L., Frederico, T., Freese, A., Fu, Y., Gamberg, L., Gan, L., Gao, F., Garcia-Tecocoatzi, H., Gaskell, D., Gasparian, A., Gates, K, Gavalian, G., Ghoshal, P. K., Giachino, A., Giacosa, F., Giannuzzi, F., Gilfoyle, G. -P., Girod, F-X, Glazier, D. I., Gleason, C., Godfrey, S., Goity, J. L., Golubenko, A. A., Gonzàlez-Solís, S., Gothe, R. W., Gotra, Y., Griffioen, K., Grocholski, O., Grube, B., Guèye, P., Guo, F. -K., Guo, Y., Guo, L., Hague, T. J., Hammoud, N., Hansen, J. -O., Hattawy, M., Hauenstein, F., Hayward, T., Heddle, D., Heinrich, N., Hen, O., Higinbotham, D. W., Higuera-Angulo, I. M., Blin, A. N. Hiller, Hobart, A., Hobbs, T., Holmberg, D. E, Horn, T., Hoyer, P., Huber, G. M., Hurck, P., Hutauruk, P. T. P., Ilieva, Y., Illari, I., Ireland, D. G, Isupov, E. L., Italiano, A., Jaegle, I., Jarvis, N. S., Jenkins, DJ, Jeschonnek, S., Ji, C-R., Jo, H. S., Jones, M., Jones, R. T., Jones, D. C., Joo, K., Junaid, M., Kageya, T., Kalantarians, N., Karki, A., Karyan, G., Katramatou, A. T., Kay, S. J. D, Kazimi, R., Keith, C. D., Keppel, C., Kerbizi, A., Khachatryan, V., Khanal, A., Khandaker, M., Kim, A., Kinney, E. R., Kohl, M., Kotzinian, A., Kriesten, B. T., Kubarovsky, V., Kubis, B., Kuhn, S. E., Kumar, V., Kutz, T., Leali, M., Lebed, R. F., Lenisa, P., Leskovec, L., Li, S., Li, X., Liao, J., Lin, H. -W., Liu, L., Liuti, S., Liyanage, N., Lu, Y., MacGregor, I. J. D., Mack, D. J., Maiani, L, Mamo, K. A., Mandaglio, G., Mariani, C., Markowitz, P., Marukyan, H., Mascagna, V., Mathieu, V., Maxwell, J., Mazouz, M., McCaughan, M., McKeown, R. D., McKinnon, B., Meekins, D., Melnitchouk, W., Metz, A., Meyer, C. A., Meziani, Z. -E., Mezrag, C., Michaels, R., Miller, G. A., Mineeva, T., Miramontes, A. S., Mirazita, M., Mizutani, K., Mkrtchyan, H., Mkrtchyan, A., Moffit, B., Mohanmurthy, P., Mokeev, V. I., Monaghan, P., Montaña, G., Montgomery, R., Moretti, A., Chàvez, J. M. Morgado, Mosel, U., Movsisyan, A., Musico, P., Nadeeshani, S. A, Nadolsky, P. M., Nakamura, S. X., Nazeer, J., Nefediev, A. V., Neupane, K., Nguyen, D., Niccolai, S., Niculescu, I., Niculescu, G., Nocera, E. R., Nycz, M., Olness, F. I., Ortega, P. G., Osipenko, M., Pace, E., Pandey, B, Pandey, P., Papandreou, Z., Papavassiliou, J., Pappalardo, L. L., Paredes-Torres, G., Paremuzyan, R., Park, S., Parsamyan, B., Paschke, K. D., Pasquini, B., Passemar, E., Pasyuk, E., Patel, T., Paudel, C., Paul, S. J., Peng, J-C., Pentchev, L., Perrino, R., Perry, R. J., Peters, K., Petratos, G. G., Phelps, W., Piasetzky, E., Pilloni, A., Pire, B., Pitonyak, D., Pitt, M. L., Polosa, A. D., Pospelov, M., Postuma, A. C., Poudel, J., Preet, L., Prelovsek, S., Price, J. W., Prokudin, A., Puckett, A. J. R., Pybus, J. R., Qin, S. -X., Qiu, J. -W., Radici, M., Rashidi, H., Rathnayake, A. D, Raue, B. A., Reed, T., Reimer, P. E., Reinhold, J., Richard, J. -M., Rinaldi, M., Ringer, F., Ripani, M., Ritman, J., West, J. Rittenhouse, Rivero-Acosta, A., Roberts, C. D., Rodas, A., Rodini, S., Rodríguez-Quintero, J., Rogers, T. C., Rojo, J., Rossi, P., Rossi, G. C., Salmè, G., Santiesteban, S. N., Santopinto, E., Sargsian, M., Sato, N., Schadmand, S., Schmidt, A., Schmidt, S. M, Schnell, G., Schumacher, R. A., Schweitzer, P., Scimemi, I., Scott, K. C, Seay, D. A, Segovia, J., Semenov-Tian-Shansky, K., Seryi, A., Sharda, A. S, Shepherd, M. R., Shirokov, E. V., Shrestha, S., Shrestha, U., Shvedunov, V. I., Signori, A., Slifer, K. J., Smith, W. A., Somov, A., Souder, P., Sparveris, N., Spizzo, F., Spreafico, M., Stepanyan, S., Stevens, J. R., Strakovsky, I. I., Strauch, S., Strikman, M., Su, S., Sumner, B. C. L., Sun, E., Suresh, M., Sutera, C., Swanson, E. S., Szczepaniak, A. P, Sznajder, P., Szumila-Vance, H., Szymanowski, L., Tadepalli, A. -S., Tadevosyan, V., Tamang, B., Tarasov, V. V., Thiel, A., Tong, X. -B., Tyson, R., Ungaro, M., Urciuoli, G. M., Usman, A., Valcarce, A., Vallarino, S., Vaquera-Araujo, C. A., Venturelli, L., Vera, F., Vladimirov, A., Vossen, A., Wagner, J., Wei, X., Weinstein, L. B., Weiss, C., Williams, R., Winney, D., Wojtsekhowski, B., Wood, M. H., Xiao, T., Xu, S. -S., Ye, Z., Yero, C., Yuan, C. -P., Yurov, M., Zachariou, N., Zhang, Z., Zhao, Z. W., Zhao, Y., Zheng, X., Zhou, X., Ziegler, V., Zihlmann, B., de Paula, W, and de Téramond, G. F.

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

This document presents the initial scientific case for upgrading the Continuous Electron Beam Accelerator Facility (CEBAF) at Jefferson Lab (JLab) to 22 GeV. It is the result of a community effort, incorporating insights from a series of workshops conducted between March 2022 and April 2023. With a track record of over 25 years in delivering the world's most intense and precise multi-GeV electron beams, CEBAF's potential for a higher energy upgrade presents a unique opportunity for an innovative nuclear physics program, which seamlessly integrates a rich historical background with a promising future. The proposed physics program encompass a diverse range of investigations centered around the nonperturbative dynamics inherent in hadron structure and the exploration of strongly interacting systems. It builds upon the exceptional capabilities of CEBAF in high-luminosity operations, the availability of existing or planned Hall equipment, and recent advancements in accelerator technology. The proposed program cover various scientific topics, including Hadron Spectroscopy, Partonic Structure and Spin, Hadronization and Transverse Momentum, Spatial Structure, Mechanical Properties, Form Factors and Emergent Hadron Mass, Hadron-Quark Transition, and Nuclear Dynamics at Extreme Conditions, as well as QCD Confinement and Fundamental Symmetries. Each topic highlights the key measurements achievable at a 22 GeV CEBAF accelerator. Furthermore, this document outlines the significant physics outcomes and unique aspects of these programs that distinguish them from other existing or planned facilities. In summary, this document provides an exciting rationale for the energy upgrade of CEBAF to 22 GeV, outlining the transformative scientific potential that lies within reach, and the remarkable opportunities it offers for advancing our understanding of hadron physics and related fundamental phenomena., Comment: Updates to the list of authors; Preprint number changed from theory to experiment; Updates to sections 4 and 6, including additional figures

Published
2023

15. Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest

Author

Piel, Sarah, McManus, Meagan J., Heye, Kristina N., Beaulieu, Forrest, Fazelinia, Hossein, Janowska, Joanna I., MacTurk, Bryce, Starr, Jonathan, Gaudio, Hunter, Patel, Nisha, Hefti, Marco M., Smalley, Martin E., Hook, Jordan N., Kohli, Neha V., Bruton, James, Hallowell, Thomas, Delso, Nile, Roberts, Anna, Lin, Yuxi, Ehinger, Johannes K., Karlsson, Michael, Berg, Robert A., Morgan, Ryan W., and Kilbaugh, Todd J.

Published
2024
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18. Amodal Intra-class Instance Segmentation: Synthetic Datasets and Benchmark

Author

Ao, Jiayang, Ke, Qiuhong, and Ehinger, Krista A.

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

Images of realistic scenes often contain intra-class objects that are heavily occluded from each other, making the amodal perception task that requires parsing the occluded parts of the objects challenging. Although important for downstream tasks such as robotic grasping systems, the lack of large-scale amodal datasets with detailed annotations makes it difficult to model intra-class occlusions explicitly. This paper introduces two new amodal datasets for image amodal completion tasks, which contain a total of over 267K images of intra-class occlusion scenarios, annotated with multiple masks, amodal bounding boxes, dual order relations and full appearance for instances and background. We also present a point-supervised scheme with layer priors for amodal instance segmentation specifically designed for intra-class occlusion scenarios. Experiments show that our weakly supervised approach outperforms the SOTA fully supervised methods, while our layer priors design exhibits remarkable performance improvements in the case of intra-class occlusion in both synthetic and real images., Comment: Accepted at WACV 2024. Datasets are available at https://github.com/saraao/amodal-dataset

Published
2023

19. Effect of dimethyl fumarate on mitochondrial metabolism in a pediatric porcine model of asphyxia-induced in-hospital cardiac arrest

Author

Sarah Piel, Meagan J. McManus, Kristina N. Heye, Forrest Beaulieu, Hossein Fazelinia, Joanna I. Janowska, Bryce MacTurk, Jonathan Starr, Hunter Gaudio, Nisha Patel, Marco M. Hefti, Martin E. Smalley, Jordan N. Hook, Neha V. Kohli, James Bruton, Thomas Hallowell, Nile Delso, Anna Roberts, Yuxi Lin, Johannes K. Ehinger, Michael Karlsson, Robert A. Berg, Ryan W. Morgan, and Todd J. Kilbaugh

Subjects
Cardiac arrest, Asphyxia, Dimethyl fumarate, Heart, Brain, Metabolism, Medicine, Science
Abstract

Abstract Neurological and cardiac injuries are significant contributors to morbidity and mortality following pediatric in-hospital cardiac arrest (IHCA). Preservation of mitochondrial function may be critical for reducing these injuries. Dimethyl fumarate (DMF) has shown potential to enhance mitochondrial content and reduce oxidative damage. To investigate the efficacy of DMF in mitigating mitochondrial injury in a pediatric porcine model of IHCA, toddler-aged piglets were subjected to asphyxia-induced CA, followed by ventricular fibrillation, high-quality cardiopulmonary resuscitation, and random assignment to receive either DMF (30 mg/kg) or placebo for four days. Sham animals underwent similar anesthesia protocols without CA. After four days, tissues were analyzed for mitochondrial markers. In the brain, untreated CA animals exhibited a reduced expression of proteins of the oxidative phosphorylation system (CI, CIV, CV) and decreased mitochondrial respiration (p

Published
2024
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26. Identification of Novel BDNF-Specific Corticostriatal Circuitries

Author

Ehinger, Yann, Soneja, Drishti, Phamluong, Khanhky, Salvi, Alexandra, and Ron, Dorit

Subjects
Biological Psychology, Biomedical and Clinical Sciences, Psychology, Basic Behavioral and Social Science, Neurosciences, Behavioral and Social Science, Brain Disorders, 1.1 Normal biological development and functioning, Underpinning research, Neurological, Mice, Animals, Brain-Derived Neurotrophic Factor, Cerebral Cortex, Prefrontal Cortex, Corpus Striatum, Neurons, Neural Pathways, BDNF, circuitry, corticostriatal, dorsal striatum, mapping, PFC
Abstract

Brain-derived neurotrophic factor (BDNF) is released from axon terminals originating in the cerebral cortex onto striatal neurons. Here, we characterized BDNF neurons in the corticostriatal circuitry. First, we used BDNF-Cre and Ribotag transgenic mouse lines to label BDNF-positive neurons in the cortex and detected BDNF expression in all the subregions of the prefrontal cortex (PFC). Next, we used a retrograde viral tracing strategy, in combination with BDNF-Cre knock-in mice, to map the cortical outputs of BDNF neurons in the dorsomedial and dorsolateral striatum (DMS and DLS, respectively). We found that BDNF-expressing neurons located in the medial prefrontal cortex (mPFC) project mainly to the DMS, and those located in the primary and secondary motor cortices (M1 and M2, respectively) and agranular insular cortex (AI) project mainly to the DLS. In contrast, BDNF-expressing orbitofrontal cortical (OFC) neurons differentially target the dorsal striatum (DS) depending on their mediolateral and rostrocaudal location. Specifically, the DMS is mainly innervated by the medial and ventral part of the orbitofrontal cortex (MO and VO, respectively), whereas the DLS receives projections specifically from the lateral part of the OFC (LO). Together, our study uncovers previously unknown BDNF corticostriatal circuitries. These findings could have important implications for the role of BDNF signaling in corticostriatal pathways.

Published
2023

28. Image Amodal Completion: A Survey

Author

Ao, Jiayang, Ke, Qiuhong, and Ehinger, Krista A.

Subjects
Computer Science - Computer Vision and Pattern Recognition, Computer Science - Machine Learning
Abstract

Existing computer vision systems can compete with humans in understanding the visible parts of objects, but still fall far short of humans when it comes to depicting the invisible parts of partially occluded objects. Image amodal completion aims to equip computers with human-like amodal completion functions to understand an intact object despite it being partially occluded. The main purpose of this survey is to provide an intuitive understanding of the research hotspots, key technologies and future trends in the field of image amodal completion. Firstly, we present a comprehensive review of the latest literature in this emerging field, exploring three key tasks in image amodal completion, including amodal shape completion, amodal appearance completion, and order perception. Then we examine popular datasets related to image amodal completion along with their common data collection methods and evaluation metrics. Finally, we discuss real-world applications and future research directions for image amodal completion, facilitating the reader's understanding of the challenges of existing technologies and upcoming research trends., Comment: Accepted at Computer Vision and Image Understanding. See https://doi.org/10.1016/j.cviu.2023.103661 for the final version

Published
2022
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29. The BDNF Val68Met polymorphism causes a sex specific alcohol preference over social interaction and also acute tolerance to the anxiolytic effects of alcohol, a phenotype driven by malfunction of BDNF in the ventral hippocampus of male mice.

Author

Moffat, Jeffrey J, Sakhai, Samuel A, Hoisington, Zachary W, Ehinger, Yann, and Ron, Dorit

Subjects
Hippocampus, Animals, Humans, Mice, Alcoholism, Ethanol, Brain-Derived Neurotrophic Factor, Methionine, Anti-Anxiety Agents, Phenotype, Polymorphism, Single Nucleotide, Female, Male, Social Interaction, Alcohol, BDNF, BDNF Val/Met polymorphism, Ventral hippocampus, Genetics, Brain Disorders, Neurosciences, Behavioral and Social Science, Basic Behavioral and Social Science, Substance Misuse, Mental Health, Alcoholism, Alcohol Use and Health, Aetiology, 2.1 Biological and endogenous factors, 2.3 Psychological, social and economic factors, Mental health, Good Health and Well Being, BDNF Val/Met polymorphism, Medical and Health Sciences, Psychology and Cognitive Sciences, Psychiatry
Abstract

BackgroundThe brain-derived neurotrophic factor (BDNF) Valine 66 to Methionine human polymorphism results in impaired activity-dependent BDNF release and has been linked to psychiatric disorders including depression and anxiety. We previously showed that male knock-in mice carrying the mouse Methionine homolog (Met68BDNF) exhibit excessive and compulsive alcohol drinking behaviors as compared to the wild-type Val68BDNF mice.ObjectiveHere, we set out to determine the potential mechanism for the heightened and compulsive alcohol drinking phenotypes detected in Met68BDNF mice.ResultsWe found that male, but not female Met68BDNF mice exhibit social anxiety-like behaviors. We further show that male Met68BDNF mice exhibit a preference for alcohol over social interaction. In contrast, alcohol place preference without an alternative social reward, is similar in male Met68BDNF and Val68BDNF mice. Since the Met68BDNF mice show social anxiety phenotypes, we tested whether alcohol reliefs anxiety similarly in Met68BDNF and Val68BDNF mice and found that male, but not female Met68BDNF mice are insensitive to the acute anxiolytic action of alcohol. Finally, we show that this acute tolerance to alcohol-dependent anxiolysis can be restored by overexpressing wild-type Val68BDNF in the ventral hippocampus (vHC) of Met68BDNF mice.ConclusionsTogether, our results suggest that excessive alcohol drinking in the Met68BDNF may be attributed, in part, to heighted social anxiety and a lack of alcohol-dependent anxiolysis, a phenotype that is associated with malfunction of BDNF signaling in the vHC of male Met68BDNF mice.

Published
2023

30. State‐of‐the‐art therapies for Rett syndrome

Author

Panayotis, Nicolas, Ehinger, Yann, Felix, Marie Solenne, and Roux, Jean‐Christophe

Subjects
Medical Biotechnology, Biomedical and Clinical Sciences, Rare Diseases, Neurosciences, Brain Disorders, Neurodegenerative, Genetics, Mental Health, Pediatric, Gene Therapy, Rett Syndrome, Development of treatments and therapeutic interventions, 5.2 Cellular and gene therapies, Congenital, Mice, Animals, Humans, Art Therapy, Methyl-CpG-Binding Protein 2, Brain, Mutation, Neurons, Medical and Health Sciences, Pediatrics, Biomedical and clinical sciences, Health sciences, Psychology
Abstract

Rett syndrome (RTT) is an X-linked neurogenetic disorder caused by mutations of the MECP2 (methyl-CpG-binding protein 2) gene. Over two decades of work established MeCP2 as a protein with pivotal roles in the regulation of the epigenome, neuronal physiology, synaptic maintenance, and behaviour. Given the genetic aetiology of RTT and the proof of concept of its reversal in a mouse model, considerable efforts have been made to design therapeutic approaches to re-express MeCP2. By being at the forefront of the development of innovative gene therapies, research on RTT is of paramount importance for the treatment of monogenic neurological diseases. Here we discuss the recent advances and challenges of promising genetic strategies for the treatment of RTT including gene replacement therapies, gene/RNA editing strategies, and reactivation of the silenced X chromosome. WHAT THIS PAPER ADDS: Recent advances shed light on the promises of gene replacement therapy with new vectors designed to control the levels of MeCP2 expression. New developments in DNA/RNA editing approaches or reactivation of the silenced X chromosome open the possibility to re-express the native MeCP2 locus at endogenous levels. Current strategies still face limitations in transduction efficiency and future work is needed to improve brain delivery.

Published
2023

31. Comparison of two multiplexed portable cold-atom vacuum standards

Author

Ehinger, Lucas H., Acharya, Bishnu P., Barker, Daniel S., Fedchak, James A., Scherschligt, Julia, Tiesinga, Eite, and Eckel, Stephen

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

We compare the vacuum measured by two portable cold-atom vacuum standards (pCAVS) based on ultracold $^7$Li atoms. The pCAVS are quantum-based standards that use a priori scattering calculations to convert a measured loss rate of cold atoms from a conservative trap into a background gas pressure. Our pCAVS devices share the same laser system and measure the vacuum concurrently. The two pCAVS together detected a leak with a rate on the order of $10^{-6}$ Pa L/s. After fixing the leak, the pCAVS measured a pressure of about 40 nPa with 2.6 % uncertainty. The two pCAVS agree within their uncertainties, even when swapping some of their component parts. Operation of the pCAVS was found to cause some additional outgassing, on the order of $10^{-8}$ Pa L/s, which can be mitigated in the future by better thermal management., Comment: 7 pages, 3 figures, 1 table

Published
2022
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32. Digital PCR quantification of ultrahigh ERBB2 copy number identifies poor breast cancer survival after trastuzumab

Author

Pei Meng, Hina Dalal, Yilun Chen, Christian Brueffer, Sergii Gladchuk, Miguel Alcaide, Anna Ehinger, and Lao H. Saal

Subjects
Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract HER2/ERBB2 evaluation is necessary for treatment decision-making in breast cancer (BC), however current methods have limitations and considerable variability exists. DNA copy number (CN) evaluation by droplet digital PCR (ddPCR) has complementary advantages for HER2/ERBB2 diagnostics. In this study, we developed a single-reaction multiplex ddPCR assay for determination of ERBB2 CN in reference to two control regions, CEP17 and a copy-number-stable region of chr. 2p13.1, validated CN estimations to clinical in situ hybridization (ISH) HER2 status, and investigated the association of ERBB2 CN with clinical outcomes. 909 primary BC tissues were evaluated and the area under the curve for concordance to HER2 status was 0.93 and 0.96 for ERBB2 CN using either CEP17 or 2p13.1 as reference, respectively. The accuracy of ddPCR ERBB2 CN was 93.7% and 94.1% in the training and validation groups, respectively. Positive and negative predictive value for the classic HER2 amplification and non-amplification groups was 97.2% and 94.8%, respectively. An identified biological “ultrahigh” ERBB2 ddPCR CN group had significantly worse survival within patients treated with adjuvant trastuzumab for both recurrence-free survival (hazard ratio, HR: 3.3; 95% CI 1.1–9.6; p = 0.031, multivariable Cox regression) and overall survival (HR: 3.6; 95% CI 1.1–12.6; p = 0.041). For validation using RNA-seq data as a surrogate, in a population-based SCAN-B cohort (NCT02306096) of 682 consecutive patients receiving adjuvant trastuzumab, the ultrahigh-ERBB2 mRNA group had significantly worse survival. Multiplex ddPCR is useful for ERBB2 CN estimation and ultrahigh ERBB2 may be a predictive factor for decreased long-term survival after trastuzumab treatment.

Published
2024
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40. OneFlowTraX: a user-friendly software for super-resolution analysis of single-molecule dynamics and nanoscale organization

Author

Leander Rohr, Alexandra Ehinger, Luiselotte Rausch, Nina Glöckner Burmeister, Alfred J. Meixner, Julien Gronnier, Klaus Harter, Birgit Kemmerling, and Sven zur Oven-Krockhaus

Subjects
super-resolution microscopy, localization, single-particle tracking PALM, photoconvertible/-activatable fluorophores, cluster analysis, plasma membrane, Plant culture, SB1-1110
Abstract

Super-resolution microscopy (SRM) approaches revolutionize cell biology by providing insights into the nanoscale organization and dynamics of macromolecular assemblies and single molecules in living cells. A major hurdle limiting SRM democratization is post-acquisition data analysis which is often complex and time-consuming. Here, we present OneFlowTraX, a user-friendly and open-source software dedicated to the analysis of single-molecule localization microscopy (SMLM) approaches such as single-particle tracking photoactivated localization microscopy (sptPALM). Through an intuitive graphical user interface, OneFlowTraX provides an automated all-in-one solution for single-molecule localization, tracking, as well as mobility and clustering analyses. OneFlowTraX allows the extraction of diffusion and clustering parameters of millions of molecules in a few minutes. Finally, OneFlowTraX greatly simplifies data management following the FAIR (Findable, Accessible, Interoperable, Reusable) principles. We provide a detailed step-by-step manual and guidelines to assess the quality of single-molecule analyses. Applying different fluorophores including mEos3.2, PA-GFP, and PATagRFP, we exemplarily used OneFlowTraX to analyze the dynamics of plant plasma membrane-localized proteins including an aquaporin, the brassinosteroid receptor Brassinosteroid Insensitive 1 (BRI1) and the Receptor-Like Protein 44 (RLP44).

Published
2024
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41. Correlation of mitochondrial respiration in platelets, peripheral blood mononuclear cells and muscle fibers

Author

Emil Westerlund, Sigurður E. Marelsson, Michael Karlsson, Fredrik Sjövall, Imen Chamkha, Eleonor Åsander Frostner, Johan Lundgren, Vineta Fellman, Erik A. Eklund, Katarina Steding-Ehrenborg, Niklas Darin, Gesine Paul, Magnus J. Hansson, Johannes K. Ehinger, and Eskil Elmér

Subjects
Mitochondria, Biomarkers, Platelets, PMBCs, Muscle, Correlation, Science (General), Q1-390, Social sciences (General), H1-99
Abstract

There is a growing interest for the possibility of using peripheral blood cells (including platelets) as markers for mitochondrial function in less accessible tissues. Only a few studies have examined the correlation between respiration in blood and muscle tissue, with small sample sizes and conflicting results.This study investigated the correlation of mitochondrial respiration within and across tissues. Additional analyses were performed to elucidate which blood cell type would be most useful for assessing systemic mitochondrial function.There was a significant but weak within tissue correlation between platelets and peripheral blood mononuclear cells (PBMCs). Neither PBMCs nor platelet respiration correlated significantly with muscle respiration.Muscle fibers from a group of athletes had higher mass-specific respiration, due to higher mitochondrial content than non-athlete controls, but this finding was not replicated in either of the blood cell types. In a group of patients with primary mitochondrial diseases, there were significant differences in blood cell respiration compared to healthy controls, particularly in platelets. Platelet respiration generally correlated better with the citrate synthase activity of each sample, in comparison to PBMCs.In conclusion, this study does not support the theory that blood cells can be used as accurate biomarkers to detect minor alterations in muscle respiration. However, in some instances, pronounced mitochondrial abnormalities might be reflected across tissues and detectable in blood cells, with more promising findings for platelets than PBMCs.

Published
2024
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42. Pions in Proton Structure and Everywhere Else

Author

Alberg, Mary, Ehinger, Lucas, and Miller, Gerald A.

Subjects
Nuclear Theory, High Energy Physics - Phenomenology
Abstract

The pion cloud is important in nuclear physics and in a variety of low-energy hadronic phenomena. We argue that it is natural to expect it to also be important in lepton-proton deep inelastic scattering and Drell-Yan studies of proton structure. We compute the necessary consequences of the pion cloud in connection with the recent SeaQuest data. The effects are detailed by using the exact kinematics of the experiment. Good agreement with the measurements is obtained. Thus the universality of pionic effects is understood., Comment: 8 pages, 5 figures. Expanded discussion, added references. This version accepted for publication. arXiv admin note: text overlap with arXiv:1712.05814

Published
2021
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43. Comparison of SP142 and 22C3 PD-L1 assays in a population-based cohort of triple-negative breast cancer patients in the context of their clinically established scoring algorithms

Author

Gudbjörg Sigurjonsdottir, Tommaso De Marchi, Anna Ehinger, Johan Hartman, Ana Bosch, Johan Staaf, Fredrika Killander, and Emma Niméus

Subjects
Triple-negative breast cancer, PD-L1, Immunohistochemistry, SP142, 22C3, Concordance, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Immunohistochemical (IHC) PD-L1 expression is commonly employed as predictive biomarker for checkpoint inhibitors in triple-negative breast cancer (TNBC). However, IHC evaluation methods are non-uniform and further studies are needed to optimize clinical utility. Methods We compared the concordance, prognostic value and gene expression between PD-L1 IHC expression by SP142 immune cell (IC) score and 22C3 combined positive score (CPS; companion IHC diagnostic assays for atezolizumab and pembrolizumab, respectively) in a population-based cohort of 232 early-stage TNBC patients. Results The expression rates of PD-L1 for SP142 IC ≥ 1%, 22C3 CPS ≥ 10, 22C3 CPS ≥ 1 and 22C3 IC ≥ 1% were 50.9%, 27.2%, 53.9% and 41.8%, respectively. The analytical concordance (kappa values) between SP142 IC+ and these three different 22C3 scorings were 73.7% (0.48, weak agreement), 81.5% (0.63) and 86.6% (0.73), respectively. The SP142 assay was better at identifying 22C3 positive tumors than the 22C3 assay was at detecting SP142 positive tumors. PD-L1 (CD274) gene expression (mRNA) showed a strong positive association with all two-categorical IHC scorings of the PD-L1 expression, irrespective of antibody and cut-off (Spearman Rho ranged from 0.59 to 0.62; all p-values

Published
2023
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44. Slack K+ channels limit kainic acid-induced seizure severity in mice by modulating neuronal excitability and firing

Author

David Skrabak, Helmut Bischof, Thomas Pham, Peter Ruth, Rebekka Ehinger, Lucas Matt, and Robert Lukowski

Subjects
Biology (General), QH301-705.5
Abstract

Abstract Mutations of the Na+-activated K+ channel Slack (KCNT1) are associated with terrible epilepsy syndromes that already begin in infancy. Here we report increased severity of acute kainic acid-induced seizures in adult and juvenile Slack knockout mice (Slack−/−) in vivo. Fittingly, we find exacerbation of cell death following kainic acid exposure in organotypic hippocampal slices as well as dissociated hippocampal cultures from Slack−/− in vitro. Furthermore, in cultured Slack−/− neurons, kainic acid-triggered Ca2+ influx and K+ efflux as well as depolarization-induced tetrodotoxin-sensitive inward currents are higher compared to the respective controls. This apparent changes in ion homeostasis could possibly explain altered action potential kinetics of Slack−/− neurons: steeper rise slope, decreased threshold, and duration of afterhyperpolarization, which ultimately lead to higher action potential frequencies during kainic acid application or injection of depolarizing currents. Based on our data, we propose Slack as crucial gatekeeper of neuronal excitability to acutely limit seizure severity.

Published
2023
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45. NMOSD IgG Impact Retinal Cells in Murine Retinal Explants

Author

Hannah Nora Wolf, Veronika Ehinger, Larissa Guempelein, Pratiti Banerjee, Tania Kuempfel, Joachim Havla, and Diana Pauly

Subjects
NMOSD, autoantibodies, retina, chemokine, complement, local, Biology (General), QH301-705.5
Abstract

Neuromyelitis optica spectrum disorders (NMOSD) are chronic inflammatory diseases of the central nervous system, characterized by autoantibodies against aquaporin-4. The symptoms primarily involve severe optic neuritis and longitudinally extensive transverse myelitis. Although the disease progression is typically relapse-dependent, recent studies revealed retinal neuroaxonal degeneration unrelated to relapse activity, potentially due to anti-aquaporin-4-positive antibodies interacting with retinal glial cells such as Müller cells. In this exploratory study, we analysed the response of mouse retinal explants to NMOSD immunoglobulins (IgG). Mouse retinal explants were treated with purified IgG from patient or control sera for one and three days. We characterized tissue response patterns through morphological changes, chemokine secretion, and complement expression. Mouse retinal explants exhibited a basic proinflammatory response ex vivo, modified by IgG addition. NMOSD IgG, unlike control IgG, increased gliosis and decreased chemokine release (CCL2, CCL3, CCL4, and CXCL-10). Complement component expression by retinal cells remained unaltered by either IgG fraction. We conclude that human NMOSD IgG can possibly bind in the mouse retina, altering the local cellular environment. This intraretinal stress may contribute to retinal degeneration independent of relapse activity in NMOSD, suggesting a primary retinopathy.

Published
2023
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49. Author Correction: Combined protein and transcript single-cell RNA sequencing in human peripheral blood mononuclear cells

Author

Vallejo, Jenifer, Saigusa, Ryosuke, Gulati, Rishab, Suthahar, Sujit Silas Armstrong, Suryawanshi, Vasantika, Alimadadi, Ahmad, Durant, Christopher P, Ghosheh, Yanal, Roy, Payel, Ehinger, Erik, Pattarabanjird, Tanyaporn, Hanna, David B, Landay, Alan L, Tracy, Russell P, Lazar, Jason M, Mack, Wendy J, Weber, Kathleen M, Adimora, Adaora A, Hodis, Howard N, Tien, Phyllis C, Ofotokun, Igho, Heath, Sonya L, Shemesh, Avishai, McNamara, Coleen A, Lanier, Lewis L, Hedrick, Catherine C, Kaplan, Robert C, and Ley, Klaus

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Developmental Biology, Biological sciences
Abstract

The original article [1] contained significant errors in Fig 1A which necessitated correction; the figure has since been updated to the corrected version.

Published
2022

50. Combined protein and transcript single-cell RNA sequencing in human peripheral blood mononuclear cells

Author

Vallejo, Jenifer, Saigusa, Ryosuke, Gulati, Rishab, Armstrong Suthahar, Sujit Silas, Suryawanshi, Vasantika, Alimadadi, Ahmad, Durant, Christopher P, Ghosheh, Yanal, Roy, Payel, Ehinger, Erik, Pattarabanjird, Tanyaporn, Hanna, David B, Landay, Alan L, Tracy, Russell P, Lazar, Jason M, Mack, Wendy J, Weber, Kathleen M, Adimora, Adaora A, Hodis, Howard N, Tien, Phyllis C, Ofotokun, Igho, Heath, Sonya L, Shemesh, Avishai, McNamara, Coleen A, Lanier, Lewis L, Hedrick, Catherine C, Kaplan, Robert C, and Ley, Klaus

Subjects
Biological Sciences, Bioinformatics and Computational Biology, HIV/AIDS, Genetics, Clinical Research, Human Genome, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Female, Flow Cytometry, Gene Expression Profiling, HIV Infections, Humans, Leukocytes, Mononuclear, Sequence Analysis, RNA, Single-Cell Analysis, Transcriptome, CVD, HIV, scRNA-seq, Transcriptomes, Antibodies, Human, Developmental Biology, Biological sciences
Abstract

BackgroundCryopreserved peripheral blood mononuclear cells (PBMCs) are frequently collected and provide disease- and treatment-relevant data in clinical studies. Here, we developed combined protein (40 antibodies) and transcript single-cell (sc)RNA sequencing (scRNA-seq) in PBMCs.ResultsAmong 31 participants in the Women's Interagency HIV Study (WIHS), we sequenced 41,611 cells. Using Boolean gating followed by Seurat UMAPs (tool for visualizing high-dimensional data) and Louvain clustering, we identified 50 subsets among CD4+ T, CD8+ T, B, NK cells, and monocytes. This resolution was superior to flow cytometry, mass cytometry, or scRNA-seq without antibodies. Combined protein and transcript scRNA-seq allowed for the assessment of disease-related changes in transcriptomes and cell type proportions. As a proof-of-concept, we showed such differences between healthy and matched individuals living with HIV with and without cardiovascular disease.ConclusionsIn conclusion, combined protein and transcript scRNA sequencing is a suitable and powerful method for clinical investigations using PBMCs.

Published
2022

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