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691 results on '"A. Slowikowski"'

1. Immune responses in checkpoint myocarditis across heart, blood and tumour

Author

Blum, Steven M., Zlotoff, Daniel A., Smith, Neal P., Kernin, Isabela J., Ramesh, Swetha, Zubiri, Leyre, Caplin, Joshua, Samanta, Nandini, Martin, Sidney, Wang, Mike, Tirard, Alice, Song, Yuhui, Xu, Katherine H., Barth, Jaimie, Sen, Pritha, Slowikowski, Kamil, Tantivit, Jessica, Manakongtreecheep, Kasidet, Arnold, Benjamin Y., Nasrallah, Mazen, Pinto, Christopher J., McLoughlin, Daniel, Jackson, Monica, Chan, PuiYee, Lawless, Aleigha, Michaud, William A., Sharova, Tatyana, Nieman, Linda T., Gainor, Justin F., Wu, Catherine J., Juric, Dejan, Mino-Kenudson, Mari, Oliveira, Giacomo, Sullivan, Ryan J., Boland, Genevieve M., Stone, James R., Thomas, Molly F., Neilan, Tomas G., Reynolds, Kerry L., and Villani, Alexandra-Chloé

Published
2024
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2. Single-cell transcriptomic analyses reveal distinct immune cell contributions to epithelial barrier dysfunction in checkpoint inhibitor colitis.

Author

Thomas, Molly, Slowikowski, Kamil, Manakongtreecheep, Kasidet, Sen, Pritha, Samanta, Nandini, Tantivit, Jessica, Nasrallah, Mazen, Zubiri, Leyre, Smith, Neal, Tirard, Alice, Ramesh, Swetha, Arnold, Benjamin, Nieman, Linda, Chen, Jonathan, Eisenhaure, Thomas, Pelka, Karin, Song, Yuhui, Xu, Katherine, Jorgji, Vjola, Pinto, Christopher, Sharova, Tatyana, Glasser, Rachel, Chan, PuiYee, Sullivan, Ryan, Khalili, Hamed, Juric, Dejan, Boland, Genevieve, Dougan, Michael, Hacohen, Nir, Li, Bo, Reynolds, Kerry, and Villani, Alexandra-Chloé

Subjects
Humans, Immune Checkpoint Inhibitors, Colitis, Single-Cell Analysis, Intestinal Mucosa, Female, Male, Gene Expression Profiling, CD8-Positive T-Lymphocytes, Middle Aged, Programmed Cell Death 1 Receptor, Aged, Transcriptome, CTLA-4 Antigen, T-Lymphocytes, Regulatory, Colon, Epithelial Cells
Abstract

Immune checkpoint inhibitor (ICI) therapy has revolutionized oncology, but treatments are limited by immune-related adverse events, including checkpoint inhibitor colitis (irColitis). Little is understood about the pathogenic mechanisms driving irColitis, which does not readily occur in model organisms, such as mice. To define molecular drivers of irColitis, we used single-cell multi-omics to profile approximately 300,000 cells from the colon mucosa and blood of 13 patients with cancer who developed irColitis (nine on anti-PD-1 or anti-CTLA-4 monotherapy and four on dual ICI therapy; most patients had skin or lung cancer), eight controls on ICI therapy and eight healthy controls. Patients with irColitis showed expanded mucosal Tregs, ITGAEHi CD8 tissue-resident memory T cells expressing CXCL13 and Th17 gene programs and recirculating ITGB2Hi CD8 T cells. Cytotoxic GNLYHi CD4 T cells, recirculating ITGB2Hi CD8 T cells and endothelial cells expressing hypoxia gene programs were further expanded in colitis associated with anti-PD-1/CTLA-4 therapy compared to anti-PD-1 therapy. Luminal epithelial cells in patients with irColitis expressed PCSK9, PD-L1 and interferon-induced signatures associated with apoptosis, increased cell turnover and malabsorption. Together, these data suggest roles for circulating T cells and epithelial-immune crosstalk critical to PD-1/CTLA-4-dependent tolerance and barrier function and identify potential therapeutic targets for irColitis.

Published
2024

3. Optical vortices by an adaptive spiral phase plate

Author

Jankowski, T., Bennis, N ., Morawiak, P., Zografopoulos, D. C., Pakuła, A., Filipiak, M., Słowikowski, M., López-Higuera, J. M, and Algorri, J. F.

Subjects
Physics - Optics
Abstract

An Adaptive Spiral Phase Plate (ASPP) based on liquid crystal (LC) and the transmission electrode technique is theoretically and experimentally demonstrated. This ASPP design enables the generation of high-quality optical vortices with topological charges ranging from $\pm1$ to $\pm4$ using a single device (but using a higher birefringence LC and thickness this number can be multiplied by four). The continuous reconfigurability of the optical phase shift, achieved through a simple control mechanism involving only two low voltages, sets this device apart as the most accurate approximation to an ideal ASPP proposed to date. This device offers remarkable advantages, such as complete reconfigurability, allowing adjustment of operating wavelengths and topological charges. The fabrication process mirrors that of a standard LCD cell, ensuring a cost-effective and reliable solution. Its versatile applications, including fiber optics communications and atom manipulation, promise reduced fabrication costs for existing devices and the generation of diverse Orbital Angular Momentum (OAM) modes. In summary, the proposed ASPP stands as a pivotal advancement, providing superior light efficiency, simplicity, and the capability for on-the-fly reconfiguration in a variety of optical applications., Comment: 9 pages, 7 figures

Published
2023

5. Deconstruction of rheumatoid arthritis synovium defines inflammatory subtypes.

Author

Zhang, Fan, Jonsson, Anna, Nathan, Aparna, Millard, Nghia, Curtis, Michelle, Xiao, Qian, Gutierrez-Arcelus, Maria, Apruzzese, William, Watts, Gerald, Weisenfeld, Dana, Nayar, Saba, Rangel-Moreno, Javier, Meednu, Nida, Marks, Kathryne, Mantel, Ian, Kang, Joyce, Rumker, Laurie, Mears, Joseph, Slowikowski, Kamil, Weinand, Kathryn, Orange, Dana, Geraldino-Pardilla, Laura, Deane, Kevin, Tabechian, Darren, Ceponis, Arnoldas, Firestein, Gary, Maybury, Mark, Sahbudin, Ilfita, Ben-Artzi, Ami, Mandelin, Arthur, Nerviani, Alessandra, Lewis, Myles, Rivellese, Felice, Pitzalis, Costantino, Hughes, Laura, Horowitz, Diane, DiCarlo, Edward, Gravallese, Ellen, Boyce, Brendan, Moreland, Larry, Goodman, Susan, Perlman, Harris, Holers, V, Liao, Katherine, Filer, Andrew, Bykerk, Vivian, Wei, Kevin, Rao, Deepak, Donlin, Laura, Anolik, Jennifer, Brenner, Michael, and Raychaudhuri, Soumya

Subjects
Humans, Arthritis, Rheumatoid, Cytokines, Inflammation, Synovial Membrane, T-Lymphocytes, B-Lymphocytes, Genetic Predisposition to Disease, Phenotype, Single-Cell Gene Expression Analysis
Abstract

Rheumatoid arthritis is a prototypical autoimmune disease that causes joint inflammation and destruction1. There is currently no cure for rheumatoid arthritis, and the effectiveness of treatments varies across patients, suggesting an undefined pathogenic diversity1,2. Here, to deconstruct the cell states and pathways that characterize this pathogenic heterogeneity, we profiled the full spectrum of cells in inflamed synovium from patients with rheumatoid arthritis. We used multi-modal single-cell RNA-sequencing and surface protein data coupled with histology of synovial tissue from 79 donors to build single-cell atlas of rheumatoid arthritis synovial tissue that includes more than 314,000 cells. We stratified tissues into six groups, referred to as cell-type abundance phenotypes (CTAPs), each characterized by selectively enriched cell states. These CTAPs demonstrate the diversity of synovial inflammation in rheumatoid arthritis, ranging from samples enriched for T and B cells to those largely lacking lymphocytes. Disease-relevant cell states, cytokines, risk genes, histology and serology metrics are associated with particular CTAPs. CTAPs are dynamic and can predict treatment response, highlighting the clinical utility of classifying rheumatoid arthritis synovial phenotypes. This comprehensive atlas and molecular, tissue-based stratification of rheumatoid arthritis synovial tissue reveal new insights into rheumatoid arthritis pathology and heterogeneity that could inform novel targeted treatments.

Published
2023

6. Electrical Tuning of Terahertz Plasmonic Crystal Phases

Author

Sai, P., Korotyeyev, V. V., Dub, M., Słowikowski, M., Filipiak, M., But, D. B., Ivonyak, Yu., Sakowicz, M., Lyaschuk, Yu. M., Kukhtaruk, S. M., Cywiński, G., and Knap, W.

Subjects
Condensed Matter - Other Condensed Matter, Physics - Applied Physics
Abstract

We present an extensive study of resonant two-dimensional (2D) plasmon excitations in grating-gated quantum well heterostructures, which enable an electrical control of periodic charge carrier density profile. Our study combines theoretical and experimental investigations of nanometer-scale AlGaN/GaN grating-gate structures and reveals that all terahertz (THz) plasmonic resonances in these structures can be explained only within the framework of the plasmonic crystal model. We identify two different plasmonic crystal phases. The first is the delocalized phase, where THz radiation interacts with the entire grating-gate structure that is realized at a weakly modulated 2D electron gas (2DEG) regime. In the second, the localized phase, THz radiation interacts only with the ungated portions of the structure. This phase is achieved by fully depleting the gated regions, resulting in strong modulation. By gate-controlling of the modulation degree, we observe a continuous transition between these phases. We also discovered that unexpectedly the resonant plasma frequencies of ungated parts (in the localized phase) still depend on the gate voltage. We attribute this phenomenon to the specific depletion of the conductive profile in the ungated region of the 2DEG, the so-called edge gating effect. Although we study a specific case of plasmons in AlGaN/GaN grating-gate structures, our results have a general character and are applicable to any other semiconductor-based plasmonic crystal structures. Our work represents the first demonstration of an electrically tunable transition between different phases of THz plasmonic crystals, which is a crucial step towards a deeper understanding of THz plasma physics and the development of all-electrically tunable devices for THz optoelectronics., Comment: 16 pages, 14 figures

Published
2023
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7. SARS-CoV-2 infection elucidates features of pregnancy-specific immunity

Author

Dong Sun Oh, Eunha Kim, Rachelly Normand, Guangqing Lu, Lydia L. Shook, Amanda Lyall, Olyvia Jasset, Stepan Demidkin, Emily Gilbert, Joon Kim, Babatunde Akinwunmi, Jessica Tantivit, Alice Tirard, Benjamin Y. Arnold, Kamil Slowikowski, Marcia B. Goldberg, Michael R. Filbin, Nir Hacohen, Long H. Nguyen, Andrew T. Chan, Xu G. Yu, Jonathan Z. Li, Lael Yonker, Alessio Fasano, Roy H. Perlis, Ofer Pasternak, Kathryn J. Gray, Gloria B. Choi, David A. Drew, Pritha Sen, Alexandra-Chloé Villani, Andrea G. Edlow, and Jun R. Huh

Subjects
CP: Immunology, Biology (General), QH301-705.5
Abstract

Summary: Pregnancy is a risk factor for increased severity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and other respiratory infections, but the mechanisms underlying this risk are poorly understood. To gain insight into the role of pregnancy in modulating immune responses at baseline and upon SARS-CoV-2 infection, we collected peripheral blood mononuclear cells and plasma from 226 women, including 152 pregnant individuals and 74 non-pregnant women. We find that SARS-CoV-2 infection is associated with altered T cell responses in pregnant women, including a clonal expansion of CD4-expressing CD8+ T cells, diminished interferon responses, and profound suppression of monocyte function. We also identify shifts in cytokine and chemokine levels in the sera of pregnant individuals, including a robust increase of interleukin-27, known to drive T cell exhaustion. Our findings reveal nuanced pregnancy-associated immune responses, which may contribute to the increased susceptibility of pregnant individuals to viral respiratory infection.

Published
2024
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11. Single-cell meta-analysis of SARS-CoV-2 entry genes across tissues and demographics.

Author

Muus, Christoph, Luecken, Malte, Eraslan, Gökcen, Sikkema, Lisa, Waghray, Avinash, Heimberg, Graham, Kobayashi, Yoshihiko, Vaishnav, Eeshit, Subramanian, Ayshwarya, Smillie, Christopher, Jagadeesh, Karthik, Duong, Elizabeth, Fiskin, Evgenij, Torlai Triglia, Elena, Ansari, Meshal, Cai, Peiwen, Lin, Brian, Buchanan, Justin, Chen, Sijia, Shu, Jian, Haber, Adam, Chung, Hattie, Montoro, Daniel, Adams, Taylor, Aliee, Hananeh, Allon, Samuel, Andrusivova, Zaneta, Angelidis, Ilias, Ashenberg, Orr, Bassler, Kevin, Bécavin, Christophe, Benhar, Inbal, Bergenstråhle, Joseph, Bergenstråhle, Ludvig, Bolt, Liam, Braun, Emelie, Bui, Linh, Callori, Steven, Chaffin, Mark, Chichelnitskiy, Evgeny, Chiou, Joshua, Conlon, Thomas, Cuoco, Michael, Cuomo, Anna, Deprez, Marie, Duclos, Grant, Fine, Denise, Fischer, David, Ghazanfar, Shila, Gillich, Astrid, Giotti, Bruno, Gould, Joshua, Guo, Minzhe, Gutierrez, Austin, Habermann, Arun, Harvey, Tyler, He, Peng, Hou, Xiaomeng, Hu, Lijuan, Hu, Yan, Jaiswal, Alok, Ji, Lu, Jiang, Peiyong, Kapellos, Theodoros, Kuo, Christin, Larsson, Ludvig, Leney-Greene, Michael, Lim, Kyungtae, Litviňuková, Monika, Ludwig, Leif, Lukassen, Soeren, Luo, Wendy, Maatz, Henrike, Madissoon, Elo, Mamanova, Lira, Manakongtreecheep, Kasidet, Leroy, Sylvie, Mayr, Christoph, Mbano, Ian, McAdams, Alexi, Nabhan, Ahmad, Nyquist, Sarah, Penland, Lolita, Poirion, Olivier, Poli, Sergio, Qi, CanCan, Queen, Rachel, Reichart, Daniel, Rosas, Ivan, Schupp, Jonas, Shea, Conor, Shi, Xingyi, Sinha, Rahul, Sit, Rene, Slowikowski, Kamil, Slyper, Michal, Smith, Neal, Sountoulidis, Alex, Strunz, Maximilian, and Sullivan, Travis

Subjects
Adult, Aged, Aged, 80 and over, Alveolar Epithelial Cells, Angiotensin-Converting Enzyme 2, COVID-19, Cathepsin L, Datasets as Topic, Demography, Female, Gene Expression Profiling, Host-Pathogen Interactions, Humans, Lung, Male, Middle Aged, Organ Specificity, Respiratory System, SARS-CoV-2, Sequence Analysis, RNA, Serine Endopeptidases, Single-Cell Analysis, Virus Internalization
Abstract

Angiotensin-converting enzyme 2 (ACE2) and accessory proteases (TMPRSS2 and CTSL) are needed for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) cellular entry, and their expression may shed light on viral tropism and impact across the body. We assessed the cell-type-specific expression of ACE2, TMPRSS2 and CTSL across 107 single-cell RNA-sequencing studies from different tissues. ACE2, TMPRSS2 and CTSL are coexpressed in specific subsets of respiratory epithelial cells in the nasal passages, airways and alveoli, and in cells from other organs associated with coronavirus disease 2019 (COVID-19) transmission or pathology. We performed a meta-analysis of 31 lung single-cell RNA-sequencing studies with 1,320,896 cells from 377 nasal, airway and lung parenchyma samples from 228 individuals. This revealed cell-type-specific associations of age, sex and smoking with expression levels of ACE2, TMPRSS2 and CTSL. Expression of entry factors increased with age and in males, including in airway secretory cells and alveolar type 2 cells. Expression programs shared by ACE2+TMPRSS2+ cells in nasal, lung and gut tissues included genes that may mediate viral entry, key immune functions and epithelial-macrophage cross-talk, such as genes involved in the interleukin-6, interleukin-1, tumor necrosis factor and complement pathways. Cell-type-specific expression patterns may contribute to the pathogenesis of COVID-19, and our work highlights putative molecular pathways for therapeutic intervention.

Published
2021

12. Numerical and Experimental Demonstration of a Silicon Nitride-Based Ring Resonator Structure for Refractive Index Sensing

Author

Muhammad A. Butt, Łukasz Kozłowski, Michał Golas, Mateusz Slowikowski, Maciej Filipiak, Marcin Juchniewicz, Aleksandra Bieniek-Kaczorek, Michał Dudek, and Ryszard Piramidowicz

Subjects
silicon nitride, ring resonator, refractive index sensor, integrated photonics, finite element method, reactive ion etching, Technology, Engineering (General). Civil engineering (General), TA1-2040, Biology (General), QH301-705.5, Physics, QC1-999, Chemistry, QD1-999
Abstract

In optical communication and sensing, silicon nitride (SiN) photonics plays a crucial role. By adeptly guiding and manipulating light on a silicon-based platform, it facilitates the creation of compact and highly efficient photonic devices. This, in turn, propels advancements in high-speed communication systems and enhances the sensitivity of optical sensors. This study presents a comprehensive exploration wherein we both numerically and experimentally display the efficacy of a SiN-based ring resonator designed for refractive index sensing applications. The device’s sensitivity, numerically estimated at approximately 110 nm/RIU, closely aligns with the experimental value of around 112.5 nm/RIU. The RR sensor’s Q factor and limit of detection (LOD) are 1.7154 × 104 and 7.99 × 10−4 RIU, respectively. These congruent results underscore the reliability of the two-dimensional finite element method (2D-FEM) as a valuable tool for accurately predicting and assessing the device’s performance before fabrication.

Published
2024
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13. Author Correction: Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways

Author

Der, Evan, Suryawanshi, Hemant, Morozov, Pavel, Kustagi, Manjunath, Goilav, Beatrice, Ranabothu, Saritha, Izmirly, Peter, Clancy, Robert, Belmont, H Michael, Koenigsberg, Mordecai, Mokrzycki, Michele, Rominieki, Helen, Graham, Jay A, Rocca, Juan P, Bornkamp, Nicole, Jordan, Nicole, Schulte, Emma, Wu, Ming, Pullman, James, Slowikowski, Kamil, Raychaudhuri, Soumya, Guthridge, Joel, James, Judith, Buyon, Jill, Tuschl, Thomas, and Putterman, Chaim

Subjects
Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Immunology
Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Published
2019

14. Defining inflammatory cell states in rheumatoid arthritis joint synovial tissues by integrating single-cell transcriptomics and mass cytometry

Author

Zhang, Fan, Wei, Kevin, Slowikowski, Kamil, Fonseka, Chamith Y, Rao, Deepak A, Kelly, Stephen, Goodman, Susan M, Tabechian, Darren, Hughes, Laura B, Salomon-Escoto, Karen, Watts, Gerald FM, Jonsson, A Helena, Rangel-Moreno, Javier, Meednu, Nida, Rozo, Cristina, Apruzzese, William, Eisenhaure, Thomas M, Lieb, David J, Boyle, David L, Mandelin, Arthur M, Boyce, Brendan F, DiCarlo, Edward, Gravallese, Ellen M, Gregersen, Peter K, Moreland, Larry, Firestein, Gary S, Hacohen, Nir, Nusbaum, Chad, Lederer, James A, Perlman, Harris, Pitzalis, Costantino, Filer, Andrew, Holers, V Michael, Bykerk, Vivian P, Donlin, Laura T, Anolik, Jennifer H, Brenner, Michael B, and Raychaudhuri, Soumya

Subjects
Clinical Research, Autoimmune Disease, Arthritis, Human Genome, Rheumatoid Arthritis, Genetics, Aetiology, 2.1 Biological and endogenous factors, Inflammatory and immune system, Good Health and Well Being, Arthritis, Rheumatoid, Autoimmunity, Biomarkers, Computational Biology, Cross-Sectional Studies, Cytokines, Fibroblasts, Flow Cytometry, Gene Expression, Gene Expression Profiling, High-Throughput Nucleotide Sequencing, Histocompatibility Antigens Class II, Humans, Leukocytes, Monocytes, Signal Transduction, Single-Cell Analysis, Synovial Membrane, T-Lymphocyte Subsets, Transcriptome, Workflow, Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Immunology
Abstract

To define the cell populations that drive joint inflammation in rheumatoid arthritis (RA), we applied single-cell RNA sequencing (scRNA-seq), mass cytometry, bulk RNA sequencing (RNA-seq) and flow cytometry to T cells, B cells, monocytes, and fibroblasts from 51 samples of synovial tissue from patients with RA or osteoarthritis (OA). Utilizing an integrated strategy based on canonical correlation analysis of 5,265 scRNA-seq profiles, we identified 18 unique cell populations. Combining mass cytometry and transcriptomics revealed cell states expanded in RA synovia: THY1(CD90)+HLA-DRAhi sublining fibroblasts, IL1B+ pro-inflammatory monocytes, ITGAX+TBX21+ autoimmune-associated B cells and PDCD1+ peripheral helper T (TPH) cells and follicular helper T (TFH) cells. We defined distinct subsets of CD8+ T cells characterized by GZMK+, GZMB+, and GNLY+ phenotypes. We mapped inflammatory mediators to their source cell populations; for example, we attributed IL6 expression to THY1+HLA-DRAhi fibroblasts and IL1B production to pro-inflammatory monocytes. These populations are potentially key mediators of RA pathogenesis.

Published
2019

15. Tubular cell and keratinocyte single-cell transcriptomics applied to lupus nephritis reveal type I IFN and fibrosis relevant pathways.

Author

Der, Evan, Suryawanshi, Hemant, Morozov, Pavel, Kustagi, Manjunath, Goilav, Beatrice, Ranabothu, Saritha, Izmirly, Peter, Clancy, Robert, Belmont, H Michael, Koenigsberg, Mordecai, Mokrzycki, Michele, Rominieki, Helen, Graham, Jay A, Rocca, Juan P, Bornkamp, Nicole, Jordan, Nicole, Schulte, Emma, Wu, Ming, Pullman, James, Slowikowski, Kamil, Raychaudhuri, Soumya, Guthridge, Joel, James, Judith, Buyon, Jill, Tuschl, Thomas, Putterman, Chaim, and Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium

Subjects
Accelerating Medicines Partnership Rheumatoid Arthritis and Systemic Lupus Erythematosus (AMP RA/SLE) Consortium, Kidney Tubules, Keratinocytes, Skin, Humans, Lupus Nephritis, Fibrosis, Interferon Type I, Extracellular Matrix Proteins, Biopsy, Gene Expression Profiling, Computational Biology, Signal Transduction, Protein Binding, Cell Lineage, Single-Cell Analysis, Transcriptome, Immunology
Abstract

The molecular and cellular processes that lead to renal damage and to the heterogeneity of lupus nephritis (LN) are not well understood. We applied single-cell RNA sequencing (scRNA-seq) to renal biopsies from patients with LN and evaluated skin biopsies as a potential source of diagnostic and prognostic markers of renal disease. Type I interferon (IFN)-response signatures in tubular cells and keratinocytes distinguished patients with LN from healthy control subjects. Moreover, a high IFN-response signature and fibrotic signature in tubular cells were each associated with failure to respond to treatment. Analysis of tubular cells from patients with proliferative, membranous and mixed LN indicated pathways relevant to inflammation and fibrosis, which offer insight into their histologic differences. In summary, we applied scRNA-seq to LN to deconstruct its heterogeneity and identify novel targets for personalized approaches to therapy.

Published
2019

16. The immune cell landscape in kidneys of patients with lupus nephritis

Author

Arazi, Arnon, Rao, Deepak A, Berthier, Celine C, Davidson, Anne, Liu, Yanyan, Hoover, Paul J, Chicoine, Adam, Eisenhaure, Thomas M, Jonsson, A Helena, Li, Shuqiang, Lieb, David J, Zhang, Fan, Slowikowski, Kamil, Browne, Edward P, Noma, Akiko, Sutherby, Danielle, Steelman, Scott, Smilek, Dawn E, Tosta, Patti, Apruzzese, William, Massarotti, Elena, Dall’Era, Maria, Park, Meyeon, Kamen, Diane L, Furie, Richard A, Payan-Schober, Fernanda, Pendergraft, William F, McInnis, Elizabeth A, Buyon, Jill P, Petri, Michelle A, Putterman, Chaim, Kalunian, Kenneth C, Woodle, E Steve, Lederer, James A, Hildeman, David A, Nusbaum, Chad, Raychaudhuri, Soumya, Kretzler, Matthias, Anolik, Jennifer H, Brenner, Michael B, Wofsy, David, Hacohen, Nir, and Diamond, Betty

Subjects
Biomedical and Clinical Sciences, Immunology, Kidney Disease, Genetics, Autoimmune Disease, Clinical Research, Lupus, 2.1 Biological and endogenous factors, 1.1 Normal biological development and functioning, 4.1 Discovery and preclinical testing of markers and technologies, Inflammatory and immune system, Renal and urogenital, Biomarkers, Biopsy, Cluster Analysis, Computational Biology, Epithelial Cells, Flow Cytometry, Gene Expression Profiling, Gene Expression Regulation, Humans, Immunophenotyping, Interferons, Kidney, Leukocytes, Lupus Nephritis, Lymphocytes, Molecular Sequence Annotation, Myeloid Cells, Single-Cell Analysis, Transcriptome, Accelerating Medicines Partnership in SLE network, Biochemistry and cell biology
Abstract

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.

Published
2019

17. Impact of diabetes on the management and outcomes in atrial fibrillation: an analysis from the ESC-EHRA EORP-AF Long-Term General Registry

Author

Boriani, G., Lip, G.Y.H., Tavazzi, L., Maggioni, A.P., Dan, G.-A., Potpara, T., Nabauer, M., Marin, F., Kalarus, Z., Goda, A., Mairesse, G., Shalganov, T., Antoniades, L., Taborsky, M., Riahi, S., Muda, P., García Bolao, I., Piot, O., Etsadashvili, K., Simantirakis, E., Haim, M., Azhari, A., Najafian, J., Santini, M., Mirrakhimov, E., Kulzida, K.A., Erglis, A., Poposka, L., Burg, M., Crijns, H., Erküner, Ö., Atar, D., Lenarczyk, R., Martins Oliveira, M., Shah, D., Serdechnaya, E., Diker, E., Lane, D., Zëra, E., Ekmekçiu, U., Paparisto, V., Tase, M., Gjergo, H., Dragoti, J., Ciutea, M., Ahadi, N., el Husseini, Z., Raepers, M., Leroy, J., Haushan, P., Jourdan, A., Lepiece, C., Desteghe, L., Vijgen, J., Koopman, P., Van Genechten, G., Heidbuchel, H., Boussy, T., De Coninck, M., Van Eeckhoutte, H., Bouckaert, N., Friart, A., Boreux, J., Arend, C., Evrard, P., Stefan, L., Hoffer, E., Herzet, J., Massoz, M., Celentano, C., Sprynger, M., Pierard, L., Melon, P., Van Hauwaert, B., Kuppens, C., Faes, D., Van Lier, D., Van Dorpe, A., Gerardy, A., Deceuninck, O., Xhaet, O., Dormal, F., Ballant, E., Blommaert, D., Yakova, D., Hristov, M., Yncheva, T., Stancheva, N., Tisheva, S., Tokmakova, M., Nikolov, F., Gencheva, D., Kunev, B., Stoyanov, M., Marchov, D., Gelev, V., Traykov, V., Kisheva, A., Tsvyatkov, H., Shtereva, R., Bakalska-Georgieva, S., Slavcheva, S., Yotov, Y., Kubíčková, M., Marni Joensen, A., Gammelmark, A., Hvilsted Rasmussen, L., Dinesen, P., Krogh Venø, S., Sorensen, B., Korsgaard, A., Andersen, K., Fragtrup Hellum, C., Svenningsen, A., Nyvad, O., Wiggers, P., May, O., Aarup, A., Graversen, B., Jensen, L., Andersen, M., Svejgaard, M., Vester, S., Hansen, S., Lynggaard, V., Ciudad, M., Vettus, R., Maestre, A., Castaño, S., Cheggour, S., Poulard, J., Mouquet, V., Leparrée, S., Bouet, J., Taieb, J., Doucy, A., Duquenne, H., Furber, A., Dupuis, J., Rautureau, J., Font, M., Damiano, P., Lacrimini, M., Abalea, J., Boismal, S., Menez, T., Mansourati, J., Range, G., Gorka, H., Laure, C., Vassalière, C., Elbaz, N., Lellouche, N., Djouadi, K., Roubille, F., Dietz, D., Davy, J., Granier, M., Winum, P., Leperchois-Jacquey, C., Kassim, H., Marijon, E., Le Heuzey, J., Fedida, J., Maupain, C., Himbert, C., Gandjbakhch, E., Hidden-Lucet, F., Duthoit, G., Badenco, N., Chastre, T., Waintraub, X., Oudihat, M., Lacoste, J., Stephan, C., Bader, H., Delarche, N., Giry, L., Arnaud, D., Lopez, C., Boury, F., Brunello, I., Lefèvre, M., Mingam, R., Haissaguerre, M., Le Bidan, M., Pavin, D., Le Moal, V., Leclercq, C., Beitar, T., Martel, I., Schmid, A., Sadki, N., Romeyer-Bouchard, C., Da Costa, A., Arnault, I., Boyer, M., Piat, C., Lozance, N., Nastevska, S., Doneva, A., Fortomaroska Milevska, B., Sheshoski, B., Petroska, K., Taneska, N., Bakrecheski, N., Lazarovska, K., Jovevska, S., Ristovski, V., Antovski, A., Lazarova, E., Kotlar, I., Taleski, J., Kedev, S., Zlatanovik, N., Jordanova, S., Bajraktarova Proseva, T., Doncovska, S., Maisuradze, D., Esakia, A., Sagirashvili, E., Lartsuliani, K., Natelashvili, N., Gumberidze, N., Gvenetadze, R., Gotonelia, N., Kuridze, N., Papiashvili, G., Menabde, I., Glöggler, S., Napp, A., Lebherz, C., Romero, H., Schmitz, K., Berger, M., Zink, M., Köster, S., Sachse, J., Vonderhagen, E., Soiron, G., Mischke, K., Reith, R., Schneider, M., Rieker, W., Boscher, D., Taschareck, A., Beer, A., Oster, D., Ritter, O., Adamczewski, J., Walter, S., Frommhold, A., Luckner, E., Richter, J., Schellner, M., Landgraf, S., Bartholome, S., Naumann, R., Schoeler, J., Westermeier, D., William, F., Wilhelm, K., Maerkl, M., Oekinghaus, R., Denart, M., Kriete, M., Tebbe, U., Scheibner, T., Gruber, M., Gerlach, A., Beckendorf, C., Anneken, L., Arnold, M., Lengerer, S., Bal, Z., Uecker, C., Förtsch, H., Fechner, S., Mages, V., Martens, E., Methe, H., Schmidt, T., Schaeffer, B., Hoffmann, B., Moser, J., Heitmann, K., Willems, S., Klaus, C., Lange, I., Durak, M., Esen, E., Mibach, F., Mibach, H., Utech, A., Gabelmann, M., Stumm, R., Ländle, V., Gartner, C., Goerg, C., Kaul, N., Messer, S., Burkhardt, D., Sander, C., Orthen, R., Kaes, S., Baumer, A., Dodos, F., Barth, A., Schaeffer, G., Gaertner, J., Winkler, J., Fahrig, A., Aring, J., Wenzel, I., Steiner, S., Kliesch, A., Kratz, E., Winter, K., Schneider, P., Haag, A., Mutscher, I., Bosch, R., Taggeselle, J., Meixner, S., Schnabel, A., Shamalla, A., Hötz, H., Korinth, A., Rheinert, C., Mehltretter, G., Schön, B., Schön, N., Starflinger, A., Englmann, E., Baytok, G., Laschinger, T., Ritscher, G., Gerth, A., Dechering, D., Eckardt, L., Kuhlmann, M., Proskynitopoulos, N., Brunn, J., Foth, K., Axthelm, C., Hohensee, H., Eberhard, K., Turbanisch, S., Hassler, N., Koestler, A., Stenzel, G., Kschiwan, D., Schwefer, M., Neiner, S., Hettwer, S., Haeussler-Schuchardt, M., Degenhardt, R., Sennhenn, S., Brendel, M., Stoehr, A., Widjaja, W., Loehndorf, S., Logemann, A., Hoskamp, J., Grundt, J., Block, M., Ulrych, R., Reithmeier, A., Panagopoulos, V., Martignani, C., Bernucci, D., Fantecchi, E., Diemberger, I., Ziacchi, M., Biffi, M., Cimaglia, P., Frisoni, J., Giannini, I., Boni, S., Fumagalli, S., Pupo, S., Di Chiara, A., Mirone, P., Pesce, F., Zoccali, C., Malavasi, V.L., Mussagaliyeva, A., Ahyt, B., Salihova, Z., Koshum-Bayeva, K., Kerimkulova, A., Bairamukova, A., Lurina, B., Zuzans, R., Jegere, S., Mintale, I., Kupics, K., Jubele, K., Kalejs, O., Vanhear, K., Cachia, M., Abela, E., Warwicker, S., Tabone, T., Xuereb, R., Asanovic, D., Drakalovic, D., Vukmirovic, M., Pavlovic, N., Music, L., Bulatovic, N., Boskovic, A., Uiterwaal, H., Bijsterveld, N., De Groot, J., Neefs, J., van den Berg, N., Piersma, F., Wilde, A., Hagens, V., Van Es, J., Van Opstal, J., Van Rennes, B., Verheij, H., Breukers, W., Tjeerdsma, G., Nijmeijer, R., Wegink, D., Binnema, R., Said, S., Philippens, S., van Doorn, W., Szili-Torok, T., Bhagwandien, R., Janse, P., Muskens, A., van Eck, M., Gevers, R., van der Ven, N., Duygun, A., Rahel, B., Meeder, J., Vold, A., Holst Hansen, C., Engset, I., Dyduch-Fejklowicz, B., Koba, E., Cichocka, M., Sokal, A., Kubicius, A., Pruchniewicz, E., Kowalik-Sztylc, A., Czapla, W., Mróz, I., Kozlowski, M., Pawlowski, T., Tendera, M., Winiarska-Filipek, A., Fidyk, A., Slowikowski, A., Haberka, M., Lachor-Broda, M., Biedron, M., Gasior, Z., Kołodziej, M., Janion, M., Gorczyca-Michta, I., Wozakowska-Kaplon, B., Stasiak, M., Jakubowski, P., Ciurus, T., Drozdz, J., Simiera, M., Zajac, P., Wcislo, T., Zycinski, P., Kasprzak, J., Olejnik, A., Harc-Dyl, E., Miarka, J., Pasieka, M., Ziemińska-Łuć, M., Bujak, W., Śliwiński, A., Grech, A., Morka, J., Petrykowska, K., Prasał, M., Hordyński, G., Feusette, P., Lipski, P., Wester, A., Streb, W., Romanek, J., Woźniak, P., Chlebuś, M., Szafarz, P., Stanik, W., Zakrzewski, M., Kaźmierczak, J., Przybylska, A., Skorek, E., Błaszczyk, H., Stępień, M., Szabowski, S., Krysiak, W., Szymańska, M., Karasiński, J., Blicharz, J., Skura, M., Hałas, K., Michalczyk, L., Orski, Z., Krzyżanowski, K., Skrobowski, A., Zieliński, L., Tomaszewska-Kiecana, M., Dłużniewski, M., Kiliszek, M., Peller, M., Budnik, M., Balsam, P., Opolski, G., Tymińska, A., Ozierański, K., Wancerz, A., Borowiec, A., Majos, E., Dabrowski, R., Szwed, H., Musialik-Lydka, A., Leopold-Jadczyk, A., Jedrzejczyk-Patej, E., Koziel, M., Mazurek, M., Krzemien-Wolska, K., Starosta, P., Nowalany-Kozielska, E., Orzechowska, A., Szpot, M., Staszel, M., Almeida, S., Pereira, H., Brandão Alves, L., Miranda, R., Ribeiro, L., Costa, F., Morgado, F., Carmo, P., Galvao Santos, P., Bernardo, R., Adragão, P., Ferreira da Silva, G., Peres, M., Alves, M., Leal, M., Cordeiro, A., Magalhães, P., Fontes, P., Leão, S., Delgado, A., Costa, A., Marmelo, B., Rodrigues, B., Moreira, D., Santos, J., Santos, L., Terchet, A., Darabantiu, D., Mercea, S., Turcin Halka, V., Pop Moldovan, A., Gabor, A., Doka, B., Catanescu, G., Rus, H., Oboroceanu, L., Bobescu, E., Popescu, R., Dan, A., Buzea, A., Daha, I., Dan, G., Neuhoff, I., Baluta, M., Ploesteanu, R., Dumitrache, N., Vintila, M., Daraban, A., Japie, C., Badila, E., Tewelde, H., Hostiuc, M., Frunza, S., Tintea, E., Bartos, D., Ciobanu, A., Popescu, I., Toma, N., Gherghinescu, C., Cretu, D., Patrascu, N., Stoicescu, C., Udroiu, C., Bicescu, G., Vintila, V., Vinereanu, D., Cinteza, M., Rimbas, R., Grecu, M., Cozma, A., Boros, F., Ille, M., Tica, O., Tor, R., Corina, A., Jeewooth, A., Maria, B., Georgiana, C., Natalia, C., Alin, D., Dinu-Andrei, D., Livia, M., Daniela, R., Larisa, R., Umaar, S., Tamara, T., Ioachim Popescu, M., Nistor, D., Sus, I., Coborosanu, O., Alina-Ramona, N., Dan, R., Petrescu, L., Ionescu, G., Vacarescu, C., Goanta, E., Mangea, M., Ionac, A., Mornos, C., Cozma, D., Pescariu, S., Solodovnicova, E., Soldatova, I., Shutova, J., Tjuleneva, L., Zubova, T., Uskov, V., Obukhov, D., Rusanova, G., Isakova, N., Odinsova, S., Arhipova, T., Kazakevich, E., Zavyalova, O., Novikova, T., Riabaia, I., Zhigalov, S., Drozdova, E., Luchkina, I., Monogarova, Y., 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Turk, U.O., Ari, H., Polat, N., Toprak, N., Sucu, M., Akin Serdar, O., Taha Alper, A., Kepez, A., Yuksel, Y., Uzunselvi, A., Yuksel, S., Sahin, M., Kayapinar, O., Ozcan, T., Kaya, H., Yilmaz, M.B., Kutlu, M., Demir, M., Gibbs, C., Kaminskiene, S., Bryce, M., Skinner, A., Belcher, G., Hunt, J., Stancombe, L., Holbrook, B., Peters, C., Tettersell, S., Shantsila, A., Senoo, K., Proietti, M., Russell, K., Domingos, P., Hussain, S., Partridge, J., Haynes, R., Bahadur, S., Brown, R., McMahon, S., McDonald, J., Balachandran, K., Singh, R., Garg, S., Desai, H., Davies, K., Goddard, W., Galasko, G., Rahman, I., Chua, Y., Payne, O., Preston, S., Brennan, O., Pedley, L., Whiteside, C., Dickinson, C., Brown, J., Jones, K., Benham, L., Brady, R., Buchanan, L., Ashton, A., Crowther, H., Fairlamb, H., Thornthwaite, S., Relph, C., McSkeane, A., Poultney, U., Kelsall, N., Rice, P., Wilson, T., Wrigley, M., Kaba, R., Patel, T., Young, E., Law, J., Runnett, C., Thomas, H., McKie, H., Fuller, J., Pick, S., Sharp, A., Hunt, A., Thorpe, K., Hardman, C., Cusack, E., Adams, L., Hough, M., Keenan, S., Bowring, A., Watts, J., Zaman, J., Goffin, K., Nutt, H., Beerachee, Y., Featherstone, J., Mills, C., Pearson, J., Stephenson, L., Grant, S., Wilson, A., Hawksworth, C., Alam, I., Robinson, M., Ryan, S., Egdell, R., Gibson, E., Holland, M., Leonard, D., Mishra, B., Ahmad, S., Randall, H., Hill, J., Reid, L., George, M., McKinley, S., Brockway, L., Milligan, W., Sobolewska, J., Muir, J., Tuckis, L., Winstanley, L., Jacob, P., Kaye, S., Morby, L., Jan, A., Sewell, T., Boos, C., Wadams, B., Cope, C., Jefferey, P., Andrews, N., Getty, A., Suttling, A., Turner, C., Hudson, K., Austin, R., Howe, S., Iqbal, R., Gandhi, N., Brophy, K., Mirza, P., Willard, E., Collins, S., Ndlovu, N., Subkovas, E., Karthikeyan, V., Waggett, L., Wood, A., Bolger, A., Stockport, J., Evans, L., Harman, E., Starling, J., Williams, L., Saul, V., Sinha, M., Bell, L., Tudgay, S., Kemp, S., Frost, L., Ingram, T., Loughlin, A., Adams, C., Adams, M., Hurford, F., Owen, C., Miller, C., Donaldson, D., Tivenan, H., Button, H., Nasser, A., Jhagra, O., Stidolph, B., Brown, C., Livingstone, C., Duffy, M., Madgwick, P., Roberts, P., Greenwood, E., Fletcher, L., Beveridge, M., Earles, S., McKenzie, D., Beacock, D., Dayer, M., Seddon, M., Greenwell, D., Luxton, F., Venn, F., Mills, H., Rewbury, J., James, K., Roberts, K., Tonks, L., Felmeden, D., Taggu, W., Summerhayes, A., Hughes, D., Sutton, J., Felmeden, L., Khan, M., Walker, E., Norris, L., O'Donohoe, L., Mozid, A., Dymond, H., Lloyd-Jones, H., Saunders, G., Simmons, D., Coles, D., Cotterill, D., Beech, S., Kidd, S., Wrigley, B., Petkar, S., Smallwood, A., Jones, R., Radford, E., Milgate, S., Metherell, S., Cottam, V., Buckley, C., Broadley, A., Wood, D., Allison, J., Rennie, K., Balian, L., Howard, L., Pippard, L., Board, S., Pitt-Kerby, T., Ding, Wern Yew, Kotalczyk, Agnieszka, Boriani, Giuseppe, Marin, Francisco, Blomström-Lundqvist, Carina, Potpara, Tatjana S., Fauchier, Laurent, and Lip, Gregory.Y.H.

Published
2022
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18. The cannabinoid receptors system in horses: Tissue distribution and cellular identification in skin

Author

Piotr Kupczyk, Marta Rykala, Pawel Serek, Aleksandra Pawlak, Bartosz Slowikowski, Marcin Holysz, Grzegorz Chodaczek, Jan P. Madej, Piotr Ziolkowski, and Artur Niedzwiedz

Subjects
cannabinoid receptors, dermis, epidermis, fibroblasts, keratinocytes, PGP 9.5, Veterinary medicine, SF600-1100
Abstract

Abstract Background The endocannabinoid system (ECS) is composed of cannabinoid receptors type 1 (CBR1) and type 2 (CBR2), cannabinoid‐based ligands (endogenous chemically synthesized phytocannabinoids), and endogenous enzymes controlling their concentrations. Cannabinoid receptors (CBRs) have been identified in invertebrates and in almost all vertebrate species in the central and peripheral nervous system as well as in immune cells, where they control neuroimmune homeostasis. In humans, rodents, dogs, and cats, CBRs expression has been confirmed in the skin, and their expression and tissue distribution become disordered in pathological conditions. Cannabinoid receptors may be a possible therapeutic target in skin diseases. Objectives To characterize the distribution and cellular expression of CBRs in the skin of horses under normal conditions. Animals Fifteen healthy horses. Methods Using full‐thickness skin punch biopsy samples, skin‐derived primary epidermal keratinocytes and dermal‐derived cells, we performed analysis of Cnr1 and Cnr2 genes using real‐time PCR and CBR1 and CBR2 protein expression by confocal microscopy and Western blotting. Results Normal equine skin, including equine epidermal keratinocytes and dermal fibroblast‐like cells, all exhibited constant gene and protein expression of CBRs. Conclusions and Clinical Importance Our results represent a starting point for developing and translating new veterinary medicine‐based pharmacotherapies using ECS as a possible target.

Published
2022
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19. Cardiac troponins and adverse outcomes in European patients with atrial fibrillation: A report from the ESC-EHRA EORP atrial fibrillation general long-term registry

Author

Boriani, G., Lip, G.Y.H., Tavazzi, L., Maggioni, A.P., Dan, G-A., Potpara, T., Nabauer, M., Marin, F., Kalarus, Z., Fauchier, L., Goda, A., Mairesse, G., Shalganov, T., Antoniades, L., Taborsky, M., Riahi, S., Muda, P., García Bolao, I., Piot, O., Etsadashvili, K., Haim, M., Azhari, A., Najafian, J., Santini, M., Mirrakhimov, E., Kulzida, K., Erglis, A., Poposka, L., Burg, M.R., Crijns, H., Erküner, Ö., Atar, D., Lenarczyk, R., Martins Oliveira, M., Shah, D., Serdechnaya, E., Diker, E., Zëra, E., Ekmekçiu, U., Paparisto, V., Tase, M., Gjergo, H., Dragoti, J., Ciutea, M., Ahadi, N., el Husseini, Z., Raepers, M., Leroy, J., Haushan, P., Jourdan, A., Lepiece, C., Desteghe, L., Vijgen, J., Koopman, P., Van Genechten, G., Heidbuchel, H., Boussy, T., De Coninck, M., Van Eeckhoutte, H., Bouckaert, N., Friart, A., Boreux, J., Arend, C., Evrard, P., Stefan, L., Hoffer, E., Herzet, J., Massoz, M., Celentano, C., Sprynger, M., Pierard, L., Melon, P., Van Hauwaert, B., Kuppens, C., Faes, D., Van Lier, D., Van Dorpe, A., Gerardy, A., Deceuninck, O., Xhaet, O., Dormal, F., Ballant, E., Blommaert, D., Yakova, D., Hristov, M., Yncheva, T., Stancheva, N., Tisheva, S., Tokmakova, M., Nikolov, F., Gencheva, D., Kunev, B., Stoyanov, M., Marchov, D., Gelev, V., Traykov, V., Kisheva, A., Tsvyatkov, H., Shtereva, R., Bakalska-Georgieva, S., Slavcheva, S., Yotov, Y., Kubíčková, M., Marni Joensen, A., Gammelmark, A., Hvilsted Rasmussen, L., Dinesen, P., Krogh Venø, S., Sorensen, B., Korsgaard, A., Andersen, K., Fragtrup Hellum, C., Svenningsen, A., Nyvad, O., Wiggers, P., May, O., Aarup, A., Graversen, B., Jensen, L., Andersen, M., Svejgaard, M., Vester, S., Hansen, S., Lynggaard, V., Ciudad, M., Vettus, R., Maestre, A., Castaño, S., Cheggour, S., Poulard, J., Mouquet, V., Leparrée, S., Bouet, J., Taieb, J., Doucy, A., Duquenne, H., Furber, A., Dupuis, J., Rautureau, J., Font, M., Damiano, P., Lacrimini, M., Abalea, J., Boismal, S., Menez, T., Mansourati, J., Range, G., Gorka, H., Laure, C., Vassalière, C., Elbaz, N., Lellouche, N., Djouadi, K., Roubille, F., Dietz, D., Davy, J., Granier, M., Winum, P., Leperchois-Jacquey, C., Kassim, H., Marijon, E., Le Heuzey, J., Fedida, J., Maupain, C., Himbert, C., Gandjbakhch, E., Hidden-Lucet, F., Duthoit, G., Badenco, N., Chastre, T., Waintraub, X., Oudihat, M., Lacoste, J., Stephan, C., Bader, H., Delarche, N., Giry, L., Arnaud, D., Lopez, C., Boury, F., Brunello, I., Lefèvre, M., Mingam, R., Haissaguerre, M., Le Bidan, M., Pavin, D., Le Moal, V., Leclercq, C., Beitar, T., Martel, I., Schmid, A., Sadki, N., Romeyer-Bouchard, C., Da Costa, A., Arnault, I., Boyer, M., Piat, C., Lozance, N., Nastevska, S., Doneva, A., Fortomaroska Milevska, B., Sheshoski, B., Petroska, K., Taneska, N., Bakrecheski, N., Lazarovska, K., Jovevska, S., Ristovski, V., Antovski, A., Lazarova, E., Kotlar, I., Taleski, J., Kedev, S., Zlatanovik, N., Jordanova, S., Bajraktarova Proseva, T., Doncovska, S., Maisuradze, D., Esakia, A., Sagirashvili, E., Lartsuliani, K., Natelashvili, N., Gumberidze, N., Gvenetadze, R., Gotonelia, N., Kuridze, N., Papiashvili, G., Menabde, I., Glöggler, S., Napp, A., Lebherz, C., Romero, H., Schmitz, K., Berger, M., Zink, M., Köster, S., Sachse, J., Vonderhagen, E., Soiron, G., Mischke, K., Reith, R., Schneider, M., Rieker, W., Boscher, D., Taschareck, A., Beer, A., Oster, D., Ritter, O., Adamczewski, J., Walter, S., Frommhold, A., Luckner, E., Richter, J., Schellner, M., Landgraf, S., Bartholome, S., Naumann, R., Schoeler, J., Westermeier, D., William, F., Wilhelm, K., Maerkl, M., Oekinghaus, R., Denart, M., Kriete, M., Tebbe, U., Scheibner, T., Gruber, M., Gerlach, A., Beckendorf, C., Anneken, L., Arnold, M., Lengerer, S., Bal, Z., Uecker, C., Förtsch, H., Fechner, S., Mages, V., Martens, E., Methe, H., Schmidt, T., Schaeffer, B., Hoffmann, B., Moser, J., Heitmann, K., Willems, S., Klaus, C., Lange, I., Durak, M., Esen, E., Mibach, F., Mibach, H., Utech, A., Gabelmann, M., Stumm, R., Ländle, V., Gartner, C., Goerg, C., Kaul, N., Messer, S., Burkhardt, D., Sander, C., Orthen, R., Kaes, S., Baumer, A., Dodos, F., Barth, A., Schaeffer, G., Gaertner, J., Winkler, J., Fahrig, A., Aring, J., Wenzel, I., Steiner, S., Kliesch, A., Kratz, E., Winter, K., Schneider, P., Haag, A., Mutscher, I., Bosch, R., Taggeselle, J., Meixner, S., Schnabel, A., Shamalla, A., Hötz, H., Korinth, A., Rheinert, C., Mehltretter, G., Schön, B., Schön, N., Starflinger, A., Englmann, E., Baytok, G., Laschinger, T., Ritscher, G., Gerth, A., Dechering, D., Eckardt, L., Kuhlmann, M., Proskynitopoulos, N., Brunn, J., Foth, K., Axthelm, C., Hohensee, H., Eberhard, K., Turbanisch, S., Hassler, N., Koestler, A., Stenzel, G., Kschiwan, D., Schwefer, M., Neiner, S., Hettwer, S., Haeussler-Schuchardt, M., Degenhardt, R., Sennhenn, S., Brendel, M., Stoehr, A., Widjaja, W., Loehndorf, S., Logemann, A., Hoskamp, J., Grundt, J., Block, M., Ulrych, R., Reithmeier, A., Panagopoulos, V., Martignani, C., Bernucci, D., Fantecchi, E., Diemberger, I., Ziacchi, M., Biffi, M., Cimaglia, P., Frisoni, J., Giannini, I., Boni, S., Fumagalli, S., Pupo, S., Di Chiara, A., Mirone, P., Pesce, F., Zoccali, C., Malavasi, V.L., Mussagaliyeva, A., Ahyt, B., Salihova, Z., Koshum-Bayeva, K., Kerimkulova, A., Bairamukova, A., Lurina, B., Zuzans, R., Jegere, S., Mintale, I., Kupics, K., Jubele, K., Kalejs, O., Vanhear, K., Burg, M., Cachia, M., Abela, E., Warwicker, S., Tabone, T., Xuereb, R., Asanovic, D., Drakalovic, D., Vukmirovic, M., Pavlovic, N., Music, L., Bulatovic, N., Boskovic, A., Uiterwaal, H., Bijsterveld, N., De Groot, J., Neefs, J., van den Berg, N., Piersma, F., Wilde, A., Hagens, V., Van Es, J., Van Opstal, J., Van Rennes, B., Verheij, H., Breukers, W., Tjeerdsma, G., Nijmeijer, R., Wegink, D., Binnema, R., Said, S., Philippens, S., van Doorn, W., Szili-Torok, T., Bhagwandien, R., Janse, P., Muskens, A., van Eck, M., Gevers, R., van der Ven, N., Duygun, A., Rahel, B., Meeder, J., Vold, A., Holst Hansen, C., Engset, I., Dyduch-Fejklowicz, B., Koba, E., Cichocka, M., Sokal, A., Kubicius, A., Pruchniewicz, E., Kowalik-Sztylc, A., Czapla, W., Mróz, I., Kozlowski, M., Pawlowski, T., Tendera, M., Winiarska-Filipek, A., Fidyk, A., Slowikowski, A., Haberka, M., Lachor-Broda, M., Biedron, M., Gasior, Z., Kołodziej, M., Janion, M., Gorczyca-Michta, I., Wozakowska-Kaplon, B., Stasiak, M., Jakubowski, P., Ciurus, T., Drozdz, J., Simiera, M., Zajac, P., Wcislo, T., Zycinski, P., Kasprzak, J., Olejnik, A., Harc-Dyl, E., Miarka, J., Pasieka, M., Ziemińska-Łuć, M., Bujak, W., Śliwiński, A., Grech, A., Morka, J., Petrykowska, K., Prasał, M., Hordyński, G., Feusette, P., Lipski, P., Wester, A., Streb, W., Romanek, J., Woźniak, P., Chlebuś, M., Szafarz, P., Stanik, W., Zakrzewski, M., Kaźmierczak, J., Przybylska, A., Skorek, E., Błaszczyk, H., Stępień, M., Szabowski, S., Krysiak, W., Szymańska, M., Karasiński, J., Blicharz, J., Skura, M., Hałas, K., Michalczyk, L., Orski, Z., Krzyżanowski, K., Skrobowski, A., Zieliński, L., Tomaszewska-Kiecana, M., Dłużniewski, M., Kiliszek, M., Peller, M., Budnik, M., Balsam, P., Opolski, G., Tymińska, A., Ozierański, K., Wancerz, A., Borowiec, A., Majos, E., Dabrowski, R., Szwed, H., Musialik-Lydka, A., Leopold-Jadczyk, A., Jedrzejczyk-Patej, E., Koziel, M., Mazurek, M., Krzemien-Wolska, K., Starosta, P., Nowalany-Kozielska, E., Orzechowska, A., Szpot, M., Staszel, M., Almeida, S., Pereira, H., Brandão Alves, L., Miranda, R., Ribeiro, L., Costa, F., Morgado, F., Carmo, P., Galvao Santos, P., Bernardo, R., Adragão, P., Ferreira da Silva, G., Peres, M., Alves, M., Leal, M., Cordeiro, A., Magalhães, P., Fontes, P., Leão, S., Delgado, A., Costa, A., Marmelo, B., Rodrigues, B., Moreira, D., Santos, J., Santos, L., Terchet, A., Darabantiu, D., Mercea, S., Turcin Halka, V., Pop Moldovan, A., Gabor, A., Doka, B., Catanescu, G., Rus, H., Oboroceanu, L., Bobescu, E., Popescu, R., Dan, A., Buzea, A., Daha, I., Dan, G., Neuhoff, I., Baluta, M., Ploesteanu, R., Dumitrache, N., Vintila, M., Daraban, A., Japie, C., Badila, E., Tewelde, H., Hostiuc, M., Frunza, S., Tintea, E., Bartos, D., Ciobanu, A., Popescu, I., Toma, N., Gherghinescu, C., Cretu, D., Patrascu, N., Stoicescu, C., Udroiu, C., Bicescu, G., Vintila, V., Vinereanu, D., Cinteza, M., Rimbas, R., Grecu, M., Cozma, A., Boros, F., Ille, M., Tica, O., Tor, R., Corina, A., Jeewooth, A., Maria, B., Georgiana, C., Natalia, C., Alin, D., Dinu-Andrei, D., Livia, M., Daniela, R., Larisa, R., Umaar, S., Tamara, T., Ioachim Popescu, M., Nistor, D., Sus, I., Coborosanu, O., Alina-Ramona, N., Dan, R., Petrescu, L., Ionescu, G., Vacarescu, C., Goanta, E., Mangea, M., Ionac, A., Mornos, C., Cozma, D., Pescariu, S., Solodovnicova, E., Soldatova, I., Shutova, J., Tjuleneva, L., Zubova, T., Uskov, V., Obukhov, D., Rusanova, G., Isakova, N., Odinsova, S., Arhipova, T., Kazakevich, E., Zavyalova, O., Novikova, T., Riabaia, I., Zhigalov, S., Drozdova, E., Luchkina, I., Monogarova, Y., Hegya, D., Rodionova, L., Nevzorova, V., Lusanova, O., Arandjelovic, A., Toncev, D., Vukmirovic, L., Radisavljevic, M., Milanov, M., Sekularac, N., Zdravkovic, M., Hinic, S., Dimkovic, S., Acimovic, T., Saric, J., Radovanovic, S., Kocijancic, A., Obrenovic-Kircanski, B., Kalimanovska Ostric, D., Simic, D., Jovanovic, I., Petrovic, I., Polovina, M., Vukicevic, M., Tomasevic, M., Mujovic, N., Radivojevic, N., Petrovic, O., Aleksandric, S., Kovacevic, V., Mijatovic, Z., Ivanovic, B., Tesic, M., Ristic, A., Vujisic-Tesic, B., Nedeljkovic, M., Karadzic, A., Uscumlic, A., Prodanovic, M., Zlatar, M., Asanin, M., Bisenic, B., Vasic, V., Popovic, Z., Djikic, D., Sipic, M., Peric, V., Dejanovic, B., Milosevic, N., Backovic, S., Stevanovic, A., Andric, A., Pencic, B., Pavlovic-Kleut, M., Celic, V., Pavlovic, M., Petrovic, M., Vuleta, M., Petrovic, N., Simovic, S., Savovic, Z., Milanov, S., Davidovic, G., Iric-Cupic, V., Djordjevic, D., Damjanovic, M., Zdravkovic, S., Topic, V., Stanojevic, D., Randjelovic, M., Jankovic-Tomasevic, R., Atanaskovic, V., Antic, S., Simonovic, D., Stojanovic, M., Stojanovic, S., Mitic, V., Ilic, V., Petrovic, D., Deljanin Ilic, M., Ilic, S., Stoickov, V., Markovic, S., Mijatovic, A., Tanasic, D., Radakovic, G., Peranovic, J., Panic-Jelic, N., Vujadinovic, O., Pajic, P., Bekic, S., Kovacevic, S., García Fernandez, A., Perez Cabeza, A., Anguita, M., Tercedor Sanchez, L., Mau, E., Loayssa, J., Ayarra, M., Carpintero, M., Roldán Rabadan, I., Gil Ortega, M., Tello Montoliu, A., Orenes Piñero, E., Manzano Fernández, S., Marín, F., Romero Aniorte, A., Veliz Martínez, A., Quintana Giner, M., Ballesteros, G., Palacio, M., Alcalde, O., García-Bolao, I., Bertomeu Gonzalez, V., Otero-Raviña, F., García Seara, J., Gonzalez Juanatey, J., Dayal, N., Maziarski, P., Gentil-Baron, P., Koç, M., Onrat, E., Dural, I.E., Yilmaz, K., Özin, B., Tan Kurklu, S., Atmaca, Y., Canpolat, U., Tokgozoglu, L., Dolu, A.K., Demirtas, B., Sahin, D., Ozcan Celebi, O., Gagirci, G., Turk, U.O., Ari, H., Polat, N., Toprak, N., Sucu, M., Akin Serdar, O., Taha Alper, A., Kepez, A., Yuksel, Y., Uzunselvi, A., Yuksel, S., Sahin, M., Kayapinar, O., Ozcan, T., Kaya, H., Yilmaz, M.B., Kutlu, M., Demir, M., Gibbs, C., Kaminskiene, S., Bryce, M., Skinner, A., Belcher, G., Hunt, J., Stancombe, L., Holbrook, B., Peters, C., Tettersell, S., Shantsila, A., Lane, D., Senoo, K., Proietti, M., Russell, K., Domingos, P., Hussain, S., Partridge, J., Haynes, R., Bahadur, S., Brown, R., McMahon, S., McDonald, J., Balachandran, K., Singh, R., Garg, S., Desai, H., Davies, K., Goddard, W., Galasko, G., Rahman, I., Chua, Y., Payne, O., Preston, S., Brennan, O., Pedley, L., Whiteside, C., Dickinson, C., Brown, J., Jones, K., Benham, L., Brady, R., Buchanan, L., Ashton, A., Crowther, H., Fairlamb, H., Thornthwaite, S., Relph, C., McSkeane, A., Poultney, U., Kelsall, N., Rice, P., Wilson, T., Wrigley, M., Kaba, R., Patel, T., Young, E., Law, J., Runnett, C., Thomas, H., McKie, H., Fuller, J., Pick, S., Sharp, A., Hunt, A., Thorpe, K., Hardman, C., Cusack, E., Adams, L., Hough, M., Keenan, S., Bowring, A., Watts, J., Zaman, J., Goffin, K., Nutt, H., Beerachee, Y., Featherstone, J., Mills, C., Pearson, J., Stephenson, L., Grant, S., Wilson, A., Hawksworth, C., Alam, I., Robinson, M., Ryan, S., Egdell, R., Gibson, E., Holland, M., Leonard, D., Mishra, B., Ahmad, S., Randall, H., Hill, J., Reid, L., George, M., McKinley, S., Brockway, L., Milligan, W., Sobolewska, J., Muir, J., Tuckis, L., Winstanley, L., Jacob, P., Kaye, S., Morby, L., Jan, A., Sewell, T., Boos, C., Wadams, B., Cope, C., Jefferey, P., Andrews, N., Getty, A., Suttling, A., Turner, C., Hudson, K., Austin, R., Howe, S., Iqbal, R., Gandhi, N., Brophy, K., Mirza, P., Willard, E., Collins, S., Ndlovu, N., Subkovas, E., Karthikeyan, V., Waggett, L., Wood, A., Bolger, A., Stockport, J., Evans, L., Harman, E., Starling, J., Williams, L., Saul, V., Sinha, M., Bell, L., Tudgay, S., Kemp, S., Frost, L., Ingram, T., Loughlin, A., Adams, C., Adams, M., Hurford, F., Owen, C., Miller, C., Donaldson, D., Tivenan, H., Button, H., Nasser, A., Jhagra, O., Stidolph, B., Brown, C., Livingstone, C., Duffy, M., Madgwick, P., Roberts, P., Greenwood, E., Fletcher, L., Beveridge, M., Earles, S., McKenzie, D., Beacock, D., Dayer, M., Seddon, M., Greenwell, D., Luxton, F., Venn, F., Mills, H., Rewbury, J., James, K., Roberts, K., Tonks, L., Felmeden, D., Taggu, W., Summerhayes, A., Hughes, D., Sutton, J., Felmeden, L., Khan, M., Walker, E., Norris, L., O'Donohoe, L., Mozid, A., Dymond, H., Lloyd-Jones, H., Saunders, G., Simmons, D., Coles, D., Cotterill, D., Beech, S., Kidd, S., Wrigley, B., Petkar, S., Smallwood, A., Jones, R., Radford, E., Milgate, S., Metherell, S., Cottam, V., Buckley, C., Broadley, A., Wood, D., Allison, J., Rennie, K., Balian, L., Howard, L., Pippard, L., Board, S., Pitt-Kerby, T., Vitolo, Marco, Malavasi, Vincenzo L., Proietti, Marco, Diemberger, Igor, Fauchier, Laurent, Marin, Francisco, Nabauer, Michael, Potpara, Tatjana S., Dan, Gheorghe-Andrei, Kalarus, Zbigniew, Tavazzi, Luigi, Maggioni, Aldo Pietro, Lane, Deirdre A., Lip, Gregory Y.H., and Boriani, Giuseppe

Published
2022
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20. Methods for high-dimensional analysis of cells dissociated from cryopreserved synovial tissue

Author

Donlin, Laura T, Rao, Deepak A, Wei, Kevin, Slowikowski, Kamil, McGeachy, Mandy J, Turner, Jason D, Meednu, Nida, Mizoguchi, Fumitaka, Gutierrez-Arcelus, Maria, Lieb, David J, Keegan, Joshua, Muskat, Kaylin, Hillman, Joshua, Rozo, Cristina, Ricker, Edd, Eisenhaure, Thomas M, Li, Shuqiang, Browne, Edward P, Chicoine, Adam, Sutherby, Danielle, Noma, Akiko, Accelerating Medicines Partnership RA/SLE Network, Nusbaum, Chad, Kelly, Stephen, Pernis, Alessandra B, Ivashkiv, Lionel B, Goodman, Susan M, Robinson, William H, Utz, Paul J, Lederer, James A, Gravallese, Ellen M, Boyce, Brendan F, Hacohen, Nir, Pitzalis, Costantino, Gregersen, Peter K, Firestein, Gary S, Raychaudhuri, Soumya, Moreland, Larry W, Holers, V Michael, Bykerk, Vivian P, Filer, Andrew, Boyle, David L, Brenner, Michael B, and Anolik, Jennifer H

Subjects
Accelerating Medicines Partnership RA/SLE Network, Synovial Membrane, Humans, Arthritis, Rheumatoid, Cryopreservation, Flow Cytometry, High-Throughput Screening Assays, Accelerating Medicines Partnership, Arthroplasty, CyTOF, Mass cytometry, RNA sequencing, Rheumatoid arthritis, Synovial biopsy, Synovial tissue, Arthritis, Autoimmune Disease, Biotechnology, Human Genome, Clinical Research, Genetics, Bioengineering, 2.1 Biological and endogenous factors, Inflammatory and immune system, Arthritis & Rheumatology, Clinical Sciences, Immunology, Public Health and Health Services
Abstract

BackgroundDetailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership RA/SLE Network aims to deconstruct autoimmune pathology by examining cells within target tissues through multiple high-dimensional assays. Robust standardized protocols need to be developed before cellular phenotypes at a single cell level can be effectively compared across patient samples.MethodsMultiple clinical sites collected cryopreserved synovial tissue fragments from arthroplasty and synovial biopsy in a 10% DMSO solution. Mechanical and enzymatic dissociation parameters were optimized for viable cell extraction and surface protein preservation for cell sorting and mass cytometry, as well as for reproducibility in RNA sequencing (RNA-seq). Cryopreserved synovial samples were collectively analyzed at a central processing site by a custom-designed and validated 35-marker mass cytometry panel. In parallel, each sample was flow sorted into fibroblast, T-cell, B-cell, and macrophage suspensions for bulk population RNA-seq and plate-based single-cell CEL-Seq2 RNA-seq.ResultsUpon dissociation, cryopreserved synovial tissue fragments yielded a high frequency of viable cells, comparable to samples undergoing immediate processing. Optimization of synovial tissue dissociation across six clinical collection sites with ~ 30 arthroplasty and ~ 20 biopsy samples yielded a consensus digestion protocol using 100 μg/ml of Liberase™ TL enzyme preparation. This protocol yielded immune and stromal cell lineages with preserved surface markers and minimized variability across replicate RNA-seq transcriptomes. Mass cytometry analysis of cells from cryopreserved synovium distinguished diverse fibroblast phenotypes, distinct populations of memory B cells and antibody-secreting cells, and multiple CD4+ and CD8+ T-cell activation states. Bulk RNA-seq of sorted cell populations demonstrated robust separation of synovial lymphocytes, fibroblasts, and macrophages. Single-cell RNA-seq produced transcriptomes of over 1000 genes/cell, including transcripts encoding characteristic lineage markers identified.ConclusionsWe have established a robust protocol to acquire viable cells from cryopreserved synovial tissue with intact transcriptomes and cell surface phenotypes. A centralized pipeline to generate multiple high-dimensional analyses of synovial tissue samples collected across a collaborative network was developed. Integrated analysis of such datasets from large patient cohorts may help define molecular heterogeneity within RA pathology and identify new therapeutic targets and biomarkers.

Published
2018

24. Refining the role of de novo protein-truncating variants in neurodevelopmental disorders by using population reference samples

Author

Kosmicki, Jack A, Samocha, Kaitlin E, Howrigan, Daniel P, Sanders, Stephan J, Slowikowski, Kamil, Lek, Monkol, Karczewski, Konrad J, Cutler, David J, Devlin, Bernie, Roeder, Kathryn, Buxbaum, Joseph D, Neale, Benjamin M, MacArthur, Daniel G, Wall, Dennis P, Robinson, Elise B, and Daly, Mark J

Subjects
Biological Sciences, Genetics, 2.1 Biological and endogenous factors, Autism Spectrum Disorder, Exome, Genetic Predisposition to Disease, Genetic Variation, Humans, Intellectual Disability, Neurodevelopmental Disorders, Phenotype, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Recent research has uncovered an important role for de novo variation in neurodevelopmental disorders. Using aggregated data from 9,246 families with autism spectrum disorder, intellectual disability, or developmental delay, we found that ∼1/3 of de novo variants are independently present as standing variation in the Exome Aggregation Consortium's cohort of 60,706 adults, and these de novo variants do not contribute to neurodevelopmental risk. We further used a loss-of-function (LoF)-intolerance metric, pLI, to identify a subset of LoF-intolerant genes containing the observed signal of associated de novo protein-truncating variants (PTVs) in neurodevelopmental disorders. LoF-intolerant genes also carry a modest excess of inherited PTVs, although the strongest de novo-affected genes contribute little to this excess, thus suggesting that the excess of inherited risk resides in lower-penetrant genes. These findings illustrate the importance of population-based reference cohorts for the interpretation of candidate pathogenic variants, even for analyses of complex diseases and de novo variation.

Published
2017

25. Deep Learning Architectures

Author

Hosseini, Mohammad-Parsa, Lu, Senbao, Kamaraj, Kavin, Slowikowski, Alexander, Venkatesh, Haygreev C., Kacprzyk, Janusz, Series Editor, Pedrycz, Witold, editor, and Chen, Shyi-Ming, editor

Published
2020
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27. Single-cell transcriptomics in cancer: computational challenges and opportunities

Author

Jean Fan, Kamil Slowikowski, and Fan Zhang

Subjects
Medicine, Biochemistry, QD415-436
Abstract

Cancer: analyzing the RNA of single cells By analyzing gene expression patterns in individual tumor cells, researchers can gain patient-specific insights that might inform more effective cancer treatment. Tumors are highly dynamic and heterogeneous collections of cells. Single-cell transcriptomics techniques can offer a valuable window into that complexity but only if the appropriate computational tools are used to analyze the data. Jean Fan of Harvard University, Cambridge, USA, and colleagues have reviewed some of these computational strategies and how they can be employed in cancer research. Single-cell analysis algorithms, for example, can reveal characteristics that distinguish healthy cells from cancerous cells, or indicate how the cells within the tumor may be communicating with each other to promote malignant growth. These are still new technologies, however, and the authors highlight the limitations of the conclusions that can currently be drawn from such analyses.

Published
2020
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28. A positively selected FBN1 missense variant reduces height in Peruvian individuals

Author

Asgari, Samira, Luo, Yang, Akbari, Ali, Belbin, Gillian M., Li, Xinyi, Harris, Daniel N., Selig, Martin, Bartell, Eric, Calderon, Roger, Slowikowski, Kamil, Contreras, Carmen, Yataco, Rosa, Galea, Jerome T., Jimenez, Judith, Coit, Julia M., Farroñay, Chandel, Nazarian, Rosalynn M., O’Connor, Timothy D., Dietz, Harry C., Hirschhorn, Joel N., Guio, Heinner, Lecca, Leonid, Kenny, Eimear E., Freeman, Esther E., Murray, Megan B., and Raychaudhuri, Soumya

Published
2020
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30. Luminosity Measurement Method for the LHC: Event Selection and Absolute Luminosity Determination

Author

Krasny, M. W., Chwastowski, J., Cyz, A., and Słowikowski, K.

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

Absolute normalisation of the LHC measurements with O(1%) precision and their relative normalisation, for the data collected at variable centre-of-mass energies, or for variable beam particle species, with O(0.1%) precision is crucial for the LHC experimental programme but presently beyond the reach for the general purpose LHC detectors. This paper is the third in the series of papers presenting the measurement method capable to achieve such a goal., Comment: 31 pages, 15 figures

Published
2011

31. Luminosity measurement method for the LHC: The detector requirements studies

Author

Krasny, M. W., Chwastowski, J., Cyz, A., and Slowikowski, K.

Subjects
Physics - Instrumentation and Detectors, High Energy Physics - Experiment
Abstract

Absolute normalisation of the LHC measurements with a precision of O(1%) is desirable but beyond the reach of the present LHC detectors. This series of papers proposes and evaluates a measurement method capable to achieve such a precision target. In our earlier paper we have selected the phase-space region where the lepton pair production cross section in pp collisions at the LHC can be controlled with < 1 % precision and is large enough to reach a comparable statistical accuracy of the absolute luminosity measurement on the day-by-day basis. In the present one the performance requirements for a dedicated detector, indispensable to efficiently select events in the proposed phase-space region, are discussed., Comment: 26 pages, 13 figures

Published
2010

32. Common Genetic Variants Modulate Pathogen-Sensing Responses in Human Dendritic Cells

Author

Lee, Mark N, Ye, Chun, Villani, Alexandra-Chloé, Raj, Towfique, Li, Weibo, Eisenhaure, Thomas M, Imboywa, Selina H, Chipendo, Portia I, Ran, F Ann, Slowikowski, Kamil, Ward, Lucas D, Raddassi, Khadir, McCabe, Cristin, Lee, Michelle H, Frohlich, Irene Y, Hafler, David A, Kellis, Manolis, Raychaudhuri, Soumya, Zhang, Feng, Stranger, Barbara E, Benoist, Christophe O, De Jager, Philip L, Regev, Aviv, and Hacohen, Nir

Subjects
Infectious Diseases, Influenza, Genetics, Biodefense, Emerging Infectious Diseases, Vaccine Related, Prevention, Pneumonia & Influenza, Aetiology, 2.1 Biological and endogenous factors, Infection, Inflammatory and immune system, Adult, Autoimmune Diseases, Communicable Diseases, Dendritic Cells, Escherichia coli, Female, Gene-Environment Interaction, Genetic Loci, Genome-Wide Association Study, HEK293 Cells, Host-Pathogen Interactions, Humans, Influenza A virus, Interferon Regulatory Factor-7, Interferon-beta, Lipopolysaccharides, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, STAT Transcription Factors, Transcriptome, Young Adult, General Science & Technology
Abstract

Little is known about how human genetic variation affects the responses to environmental stimuli in the context of complex diseases. Experimental and computational approaches were applied to determine the effects of genetic variation on the induction of pathogen-responsive genes in human dendritic cells. We identified 121 common genetic variants associated in cis with variation in expression responses to Escherichia coli lipopolysaccharide, influenza, or interferon-β (IFN-β). We localized and validated causal variants to binding sites of pathogen-activated STAT (signal transducer and activator of transcription) and IRF (IFN-regulatory factor) transcription factors. We also identified a common variant in IRF7 that is associated in trans with type I IFN induction in response to influenza infection. Our results reveal common alleles that explain interindividual variation in pathogen sensing and provide functional annotation for genetic variants that alter susceptibility to inflammatory diseases.

Published
2014

33. Numerical and Experimental Demonstration of a Silicon Nitride-Based Ring Resonator Structure for Refractive Index Sensing.

Author

Butt, Muhammad A., Kozłowski, Łukasz, Golas, Michał, Slowikowski, Mateusz, Filipiak, Maciej, Juchniewicz, Marcin, Bieniek-Kaczorek, Aleksandra, Dudek, Michał, and Piramidowicz, Ryszard

Subjects
ELECTRON beam lithography, SILICON nitride, REFRACTIVE index, FINITE element method, QUALITY factor
Abstract

In optical communication and sensing, silicon nitride (SiN) photonics plays a crucial role. By adeptly guiding and manipulating light on a silicon-based platform, it facilitates the creation of compact and highly efficient photonic devices. This, in turn, propels advancements in high-speed communication systems and enhances the sensitivity of optical sensors. This study presents a comprehensive exploration wherein we both numerically and experimentally display the efficacy of a SiN-based ring resonator designed for refractive index sensing applications. The device's sensitivity, numerically estimated at approximately 110 nm/RIU, closely aligns with the experimental value of around 112.5 nm/RIU. The RR sensor's Q factor and limit of detection (LOD) are 1.7154 × 104 and 7.99 × 10−4 RIU, respectively. These congruent results underscore the reliability of the two-dimensional finite element method (2D-FEM) as a valuable tool for accurately predicting and assessing the device's performance before fabrication. [ABSTRACT FROM AUTHOR]

Published
2024
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34. Lymphocyte innateness defined by transcriptional states reflects a balance between proliferation and effector functions

Author

Maria Gutierrez-Arcelus, Nikola Teslovich, Alex R. Mola, Rafael B. Polidoro, Aparna Nathan, Hyun Kim, Susan Hannes, Kamil Slowikowski, Gerald F. M. Watts, Ilya Korsunsky, Michael B. Brenner, Soumya Raychaudhuri, and Patrick J. Brennan

Subjects
Science
Abstract

Innate T cells (ITC) contain many subsets and are poised to promptly respond to antigens and pathogens, but how this poised state is maintained is still unclear. Here the authors perform single-cell RNA-seq to align the various ITC subsets along an ‘innateness gradient’ that is associated with changes in proliferation and effector functions.

Published
2019
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35. Luminosity Measurement Method for LHC: The theoretical precision and the experimental challenges

Author

Krasny, M. W., Chwastowski, J., and Slowikowski, K.

Subjects
High Energy Physics - Experiment
Abstract

This is the first of the series of papers which present a precision method of the day-by-day monitoring of the absolute LHC luminosity. The method is based on the measurement of the rate of coplanar lepton pairs produced in peripheral collisions of the beams' particles. In the present paper we evaluate the modeling precision of the lepton pair production processes in proton-proton collisions, optimize the measurement region to achieve better than 1% accuracy of the predicted rates, and discuss the experimental challenges to filter out the luminosity monitoring lepton pairs at LHC., Comment: 20 pages, 16 figures

Published
2006
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36. Laurent Expansions for Vertex Operators

Author

Slowikowski, Wojtek

Subjects
Mathematical Physics, 81Q99
Abstract

A method is presented for using coherent vectors to calculate the explicit form of Schur polynomials which are the coefficients of Laurent expansion of a vertex operator.

Published
2004

37. Quantum theory of human communication

Author

Slowikowski, Wojtek and Nielsen, Erik B.

Subjects
Physics - General Physics, Physics - Physics and Society
Abstract

We use notions and techniques of Quantum Field Theory to formulate and investigate basic concepts and mechanisms of human communication. We start with attitudes which correspond to photons frequencies, then we introduce states-of-mind which correspond to wave functions. Finally, by way of the second quantization, we come to states-of-opinions which correspond to states of quantized radiation fields. In the present paper we shall only investigate superpositions of pairs of coherent states (e.g. the government and the opposition in a democratic country).

Published
2004

40. Toxoplasma myocarditis: An atypical case in an immunocompetent patient

Author

Katherine Mustafa, Jonathan Hillyard, Elizabeth Nowak, Jacek Slowikowski, Ijeoma Okogbue, and Dorothy Garner

Subjects
Toxoplasmosis, Myocarditis, Immunocompetent, Cardiac magnetic resonance imaging, Infectious and parasitic diseases, RC109-216
Abstract

Myocarditis occurs with a variety of infectious agents including viruses, bacteria, protozoa and parasites. We present a rare case of myocarditis secondary to Toxoplasma gondii in a 23-year-old immunocompetent male presenting with acute chest pain. Workup revealed evidence of biventricular myocarditis on cardiac magnetic resonance imaging, elevated Toxoplasma serologies with rising titers over time. The patient was treated with sulfadiazine and pyrimethamine for eighteen days with resolution of symptoms. This case highlights alternative diagnostic and treatment modalities for Toxoplasma myocarditis in immunocompetent hosts.

Published
2021
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41. Discovering in vivo cytokine-eQTL interactions from a lupus clinical trial

Author

Emma E. Davenport, Tiffany Amariuta, Maria Gutierrez-Arcelus, Kamil Slowikowski, Harm-Jan Westra, Yang Luo, Ciyue Shen, Deepak A. Rao, Ying Zhang, Stephen Pearson, David von Schack, Jean S. Beebe, Nan Bing, Sally John, Michael S. Vincent, Baohong Zhang, and Soumya Raychaudhuri

Subjects
eQTL, Interactions, Clinical trials, Cytokines, Biology (General), QH301-705.5, Genetics, QH426-470
Abstract

Abstract Background Cytokines are critical to human disease and are attractive therapeutic targets given their widespread influence on gene regulation and transcription. Defining the downstream regulatory mechanisms influenced by cytokines is central to defining drug and disease mechanisms. One promising strategy is to use interactions between expression quantitative trait loci (eQTLs) and cytokine levels to define target genes and mechanisms. Results In a clinical trial for anti-IL-6 in patients with systemic lupus erythematosus, we measure interferon (IFN) status, anti-IL-6 drug exposure, and whole blood genome-wide gene expression at three time points. We show that repeat transcriptomic measurements increases the number of cis eQTLs identified compared to using a single time point. We observe a statistically significant enrichment of in vivo eQTL interactions with IFN status and anti-IL-6 drug exposure and find many novel interactions that have not been previously described. Finally, we find transcription factor binding motifs interrupted by eQTL interaction SNPs, which point to key regulatory mediators of these environmental stimuli and therefore potential therapeutic targets for autoimmune diseases. In particular, genes with IFN interactions are enriched for ISRE binding site motifs, while those with anti-IL-6 interactions are enriched for IRF4 motifs. Conclusions This study highlights the potential to exploit clinical trial data to discover in vivo eQTL interactions with therapeutically relevant environmental variables.

Published
2018
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42. Methods for high-dimensional analysis of cells dissociated from cryopreserved synovial tissue

Author

Laura T. Donlin, Deepak A. Rao, Kevin Wei, Kamil Slowikowski, Mandy J. McGeachy, Jason D. Turner, Nida Meednu, Fumitaka Mizoguchi, Maria Gutierrez-Arcelus, David J. Lieb, Joshua Keegan, Kaylin Muskat, Joshua Hillman, Cristina Rozo, Edd Ricker, Thomas M. Eisenhaure, Shuqiang Li, Edward P. Browne, Adam Chicoine, Danielle Sutherby, Akiko Noma, Accelerating Medicines Partnership RA/SLE Network, Chad Nusbaum, Stephen Kelly, Alessandra B. Pernis, Lionel B. Ivashkiv, Susan M. Goodman, William H. Robinson, Paul J. Utz, James A. Lederer, Ellen M. Gravallese, Brendan F. Boyce, Nir Hacohen, Costantino Pitzalis, Peter K. Gregersen, Gary S. Firestein, Soumya Raychaudhuri, Larry W. Moreland, V. Michael Holers, Vivian P. Bykerk, Andrew Filer, David L. Boyle, Michael B. Brenner, and Jennifer H. Anolik

Subjects
Rheumatoid arthritis, Synovial tissue, Accelerating Medicines Partnership, RNA sequencing, CyTOF, Mass cytometry, Diseases of the musculoskeletal system, RC925-935
Abstract

Abstract Background Detailed molecular analyses of cells from rheumatoid arthritis (RA) synovium hold promise in identifying cellular phenotypes that drive tissue pathology and joint damage. The Accelerating Medicines Partnership RA/SLE Network aims to deconstruct autoimmune pathology by examining cells within target tissues through multiple high-dimensional assays. Robust standardized protocols need to be developed before cellular phenotypes at a single cell level can be effectively compared across patient samples. Methods Multiple clinical sites collected cryopreserved synovial tissue fragments from arthroplasty and synovial biopsy in a 10% DMSO solution. Mechanical and enzymatic dissociation parameters were optimized for viable cell extraction and surface protein preservation for cell sorting and mass cytometry, as well as for reproducibility in RNA sequencing (RNA-seq). Cryopreserved synovial samples were collectively analyzed at a central processing site by a custom-designed and validated 35-marker mass cytometry panel. In parallel, each sample was flow sorted into fibroblast, T-cell, B-cell, and macrophage suspensions for bulk population RNA-seq and plate-based single-cell CEL-Seq2 RNA-seq. Results Upon dissociation, cryopreserved synovial tissue fragments yielded a high frequency of viable cells, comparable to samples undergoing immediate processing. Optimization of synovial tissue dissociation across six clinical collection sites with ~ 30 arthroplasty and ~ 20 biopsy samples yielded a consensus digestion protocol using 100 μg/ml of Liberase™ TL enzyme preparation. This protocol yielded immune and stromal cell lineages with preserved surface markers and minimized variability across replicate RNA-seq transcriptomes. Mass cytometry analysis of cells from cryopreserved synovium distinguished diverse fibroblast phenotypes, distinct populations of memory B cells and antibody-secreting cells, and multiple CD4+ and CD8+ T-cell activation states. Bulk RNA-seq of sorted cell populations demonstrated robust separation of synovial lymphocytes, fibroblasts, and macrophages. Single-cell RNA-seq produced transcriptomes of over 1000 genes/cell, including transcripts encoding characteristic lineage markers identified. Conclusions We have established a robust protocol to acquire viable cells from cryopreserved synovial tissue with intact transcriptomes and cell surface phenotypes. A centralized pipeline to generate multiple high-dimensional analyses of synovial tissue samples collected across a collaborative network was developed. Integrated analysis of such datasets from large patient cohorts may help define molecular heterogeneity within RA pathology and identify new therapeutic targets and biomarkers.

Published
2018
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43. Functionally distinct disease-associated fibroblast subsets in rheumatoid arthritis

Author

Fumitaka Mizoguchi, Kamil Slowikowski, Kevin Wei, Jennifer L. Marshall, Deepak A. Rao, Sook Kyung Chang, Hung N. Nguyen, Erika H. Noss, Jason D. Turner, Brandon E. Earp, Philip E. Blazar, John Wright, Barry P. Simmons, Laura T. Donlin, George D. Kalliolias, Susan M. Goodman, Vivian P. Bykerk, Lionel B. Ivashkiv, James A. Lederer, Nir Hacohen, Peter A. Nigrovic, Andrew Filer, Christopher D. Buckley, Soumya Raychaudhuri, and Michael B. Brenner

Subjects
Science
Abstract

Synovial fibroblasts are thought to be central mediators of joint destruction in rheumatoid arthritis (RA). Here the authors use single-cell transcriptomics and flow cytometry to identify synovial fibroblast subsets that are expanded and display distinct tissue distribution and function in patients with RA.

Published
2018
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44. Selected Aspects of Implementation of 'EU Occupational Safety and Health (OSH) Strategic Framework 2014–2020' Connected with Automation & Robotics

Author

Słowikowski, Marcin, Zieliński, Jacek, Pilat, Zbigniew, Smater, Michał, Klimasara, Wojciech, Kacprzyk, Janusz, Series editor, Pal, Nikhil R., Advisory editor, Bello Perez, Rafael, Advisory editor, Corchado, Emilio S., Advisory editor, Hagras, Hani, Advisory editor, Kóczy, László T., Advisory editor, Kreinovich, Vladik, Advisory editor, Lin, Chin-Teng, Advisory editor, Lu, Jie, Advisory editor, Melin, Patricia, Advisory editor, Nedjah, Nadia, Advisory editor, Nguyen, Ngoc Thanh, Advisory editor, Wang, Jun, Advisory editor, Szewczyk, Roman, editor, and Kaliczyńska, Małgorzata, editor

Published
2017
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45. Immune Responses in Checkpoint Myocarditis Across Heart, Blood, and Tumor

Author

Blum, Steven M., primary, Zlotoff, Daniel A., additional, Smith, Neal P., additional, Kernin, Isabela J., additional, Ramesh, Swetha, additional, Zubiri, Leyre, additional, Caplin, Joshua, additional, Tirard, Alice, additional, Sen, Prith, additional, Song, Yuhui, additional, Barth, Jaimie L., additional, Slowikowski, Kamil, additional, Nasrallah, Mazen, additional, Tantivit, Jessica, additional, Manakongtreecheep, Kasidet, additional, Arnold, Benjamin Y., additional, McGuire, John, additional, Pinto, Christopher J., additional, McLoughlin, Daniel, additional, Jackson, Monica, additional, Chan, PuiYee, additional, Lawless, Aleigha, additional, Sharova, Tatyana, additional, Nieman, Linda T., additional, Gainor, Justin F., additional, Juric, Dejan, additional, Mino-Kenudsen, Mari, additional, Sullivan, Ryan J., additional, Boland, Genevieve M., additional, Stone, James R., additional, Thomas, Molly F., additional, Neilan, Tomas G., additional, Reynolds, Kerry L., additional, and Villani, Alexandra-Chloe, additional

Published
2023
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49. Deep Learning Architectures

Author

Hosseini, Mohammad-Parsa, primary, Lu, Senbao, additional, Kamaraj, Kavin, additional, Slowikowski, Alexander, additional, and Venkatesh, Haygreev C., additional

Published
2019
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50. Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types

Author

Finucane, Hilary K., Reshef, Yakir A., Anttila, Verneri, Slowikowski, Kamil, Gusev, Alexander, Byrnes, Andrea, Gazal, Steven, Loh, Po-Ru, Lareau, Caleb, Shoresh, Noam, Genovese, Giulio, Saunders, Arpiar, Macosko, Evan, Pollack, Samuela, Perry, John R. B., Buenrostro, Jason D., Bernstein, Bradley E., Raychaudhuri, Soumya, McCarroll, Steven, Neale, Benjamin M., and Price, Alkes L.

Published
2018
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