483 results on '"Keller, Mark P."'
Search Results
2. Effects of Stray Magnetic Field on Transition-Edge Sensors in Gamma-Ray Microcalorimeters
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Keller, Mark W., Wessels, A. L., Becker, D. T., Bennett, D. A., Carpenter, M. H., Croce, M. P., Gard, J. D., Imrek, J., Mates, J. A. B., Morgan, K. M., Ortiz, N. J., Schmidt, D. R., Schreiber, K. A., Swetz, D. S., and Ullom, J. N.
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- 2024
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3. The chromatin landscape of healthy and injured cell types in the human kidney.
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Gisch, Debora, Brennan, Michelle, Lake, Blue, Basta, Jeannine, Keller, Mark, Melo Ferreira, Ricardo, Akilesh, Shreeram, Ghag, Reetika, Lu, Charles, Cheng, Ying-Hua, Collins, Kimberly, Parikh, Samir, Rovin, Brad, Robbins, Lynn, Stout, Lisa, Conklin, Kimberly, Diep, Dinh, Zhang, Bo, Knoten, Amanda, Barwinska, Daria, Asghari, Mahla, Sabo, Angela, Ferkowicz, Michael, Sutton, Timothy, Kelly, Katherine, De Boer, Ian, Rosas, Sylvia, Kiryluk, Krzysztof, Hodgin, Jeffrey, Alakwaa, Fadhl, Winfree, Seth, Jefferson, Nichole, Türkmen, Aydın, Gaut, Joseph, Gehlenborg, Nils, Phillips, Carrie, El-Achkar, Tarek, Dagher, Pierre, Hato, Takashi, Zhang, Kun, Himmelfarb, Jonathan, Kretzler, Matthias, Mollah, Shamim, Jain, Sanjay, Rauchman, Michael, and Eadon, Michael
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Humans ,Chromatin ,Kidney ,Kidney Tubules ,Proximal ,Health Status ,Cell Count - Abstract
There is a need to define regions of gene activation or repression that control human kidney cells in states of health, injury, and repair to understand the molecular pathogenesis of kidney disease and design therapeutic strategies. Comprehensive integration of gene expression with epigenetic features that define regulatory elements remains a significant challenge. We measure dual single nucleus RNA expression and chromatin accessibility, DNA methylation, and H3K27ac, H3K4me1, H3K4me3, and H3K27me3 histone modifications to decipher the chromatin landscape and gene regulation of the kidney in reference and adaptive injury states. We establish a spatially-anchored epigenomic atlas to define the kidneys active, silent, and regulatory accessible chromatin regions across the genome. Using this atlas, we note distinct control of adaptive injury in different epithelial cell types. A proximal tubule cell transcription factor network of ELF3, KLF6, and KLF10 regulates the transition between health and injury, while in thick ascending limb cells this transition is regulated by NR2F1. Further, combined perturbation of ELF3, KLF6, and KLF10 distinguishes two adaptive proximal tubular cell subtypes, one of which manifested a repair trajectory after knockout. This atlas will serve as a foundation to facilitate targeted cell-specific therapeutics by reprogramming gene regulatory networks.
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- 2024
4. Identification of genetic drivers of plasma lipoprotein size in the Diversity Outbred mouse population.
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Price, Tara, Emfinger, Christopher, Schueler, Kathryn, King, Sarah, Nicholson, Rebekah, Beck, Tim, Yandell, Brian, Summers, Scott, Holland, William, Krauss, Ronald, Keller, Mark, and Attie, Alan
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HDL ,LDL ,VLDL ,apolipoproteins ,ceramides ,genetic architecture ,genomics ,lipoproteins/metabolism ,Female ,Humans ,Mice ,Animals ,Collaborative Cross Mice ,Genome-Wide Association Study ,Lipoproteins ,Quantitative Trait Loci ,Phenotype ,Lipoproteins ,VLDL - Abstract
Despite great progress in understanding lipoprotein physiology, there is still much to be learned about the genetic drivers of lipoprotein abundance, composition, and function. We used ion mobility spectrometry to survey 16 plasma lipoprotein subfractions in 500 Diversity Outbred mice maintained on a Western-style diet. We identified 21 quantitative trait loci (QTL) affecting lipoprotein abundance. To refine the QTL and link them to disease risk in humans, we asked if the human homologs of genes located at each QTL were associated with lipid traits in human genome-wide association studies. Integration of mouse QTL with human genome-wide association studies yielded candidate gene drivers for 18 of the 21 QTL. This approach enabled us to nominate the gene encoding the neutral ceramidase, Asah2, as a novel candidate driver at a QTL on chromosome 19 for large HDL particles (HDL-2b). To experimentally validate Asah2, we surveyed lipoproteins in Asah2-/- mice. Compared to wild-type mice, female Asah2-/- mice showed an increase in several lipoproteins, including HDL. Our results provide insights into the genetic regulation of circulating lipoproteins, as well as mechanisms by which lipoprotein subfractions may affect cardiovascular disease risk in humans.
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- 2023
5. Missense variants in SORT1 are associated with LDL-C in an Amish population.
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Mitok, Kelly, Schueler, Kathryn, King, Sarah, Orr, Joseph, Ryan, Kathleen, Keller, Mark, Mitchell, Braxton, Shuldiner, Alan, Attie, Alan, and Krauss, Ronald
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LDL/metabolism ,SORT1 ,cholesterol/metabolism ,dyslipidemias ,genetic association ,genetic linkage ,lipoproteins/metabolism ,lipoproteins/receptors ,missense variant ,sortilin ,Humans ,Mice ,Animals ,Cholesterol ,LDL ,Genome-Wide Association Study ,Amish ,Mice ,Inbred C57BL ,Cholesterol ,Adaptor Proteins ,Vesicular Transport - Abstract
Common noncoding variants at the human 1p13.3 locus associated with SORT1 expression are among those most strongly associated with low-density lipoprotein cholesterol (LDL-C) in human genome-wide association studies. However, validation studies in mice and cell lines have produced variable results regarding the directionality of the effect of SORT1 on LDL-C. This, together with the fact that the 1p13.3 variants are associated with expression of several genes, has raised the question of whether SORT1 is the causal gene at this locus. Using whole exome sequencing in members of an Amish population, we identified coding variants in SORT1 that are associated with increased (rs141749679, K302E) and decreased (rs149456022, Q225H) LDL-C. Further, analysis of plasma lipoprotein particle subclasses by ion mobility in a subset of rs141749679 (K302E) carriers revealed higher levels of large LDL particles compared to noncarriers. In contrast to the effect of these variants in the Amish, the sortilin K302E mutation introduced into a C57BL/6J mouse via CRISPR/Cas9 resulted in decreased non-high-density lipoprotein cholesterol, and the sortilin Q225H mutation did not alter cholesterol levels in mice. This is indicative of different effects of these mutations on cholesterol metabolism in the two species. To our knowledge, this is the first evidence that naturally occurring coding variants in SORT1 are associated with LDL-C, thus supporting SORT1 as the gene responsible for the association of the 1p13.3 locus with LDL-C.
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- 2023
6. Correction: Flexible Superconducting Wiring for Integration with Low-Temperature Detector and Readout Fabrication
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O’Neil, Galen, Swetz, Daniel, Doriese, Randy, Schmidt, Dan, Vale, Leila, Weber, Joel, Singh, Robinjeet, Keller, Mark, Vissers, Michael, Morgan, Kelsey, Mates, John, Roy, Avirup, and Ullom, Joel
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- 2024
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7. Evidence of extreme domain wall speeds under ultrafast optical excitation
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Jangid, Rahul, Hagström, Nanna Zhou, Madhavi, Meera, Rockwell, Kyle, Shaw, Justin M., Brock, Jeffrey A., Pancaldi, Matteo, De Angelis, Dario, Capotondi, Flavio, Pedersoli, Emanuele, Nembach, Hans T., Keller, Mark W., Bonetti, Stefano, Fullerton, Eric E., Iacocca, Ezio, Kukreja, Roopali, and Silva, Thomas J.
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Condensed Matter - Mesoscale and Nanoscale Physics - Abstract
Time-resolved ultrafast EUV magnetic scattering was used to test a recent prediction of >10 km/s domain wall speeds by optically exciting a magnetic sample with a nanoscale labyrinthine domain pattern. Ultrafast distortion of the diffraction pattern was observed at markedly different timescales compared to the magnetization quenching. The diffraction pattern distortion shows a threshold-dependence with laser fluence, not seen for magnetization quenching, consistent with a picture of domain wall motion with pinning sites. Supported by simulations, we show that a speed of $\approx$ 66 km/s for highly curved domain walls can explain the experimental data. While our data agree with the prediction of extreme, non-equilibrium wall speeds locally, it differs from the details of the theory, suggesting that additional mechanisms are required to fully understand these effects., Comment: 5 pages, 4 figures; Supplemental Material: 9 pages, 9 figures
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- 2023
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8. Loss of ZNF148 enhances insulin secretion in human pancreatic β cells
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de Klerk, Eleonora, Xiao, Yini, Emfinger, Christopher H, Keller, Mark P, Berrios, David I, Loconte, Valentina, Ekman, Axel A, White, Kate L, Cardone, Rebecca L, Kibbey, Richard G, Attie, Alan D, and Hebrok, Matthias
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Biomedical and Clinical Sciences ,Health Sciences ,Clinical Research ,Biotechnology ,Stem Cell Research ,Diabetes ,Genetics ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Underpinning research ,Aetiology ,Metabolic and endocrine ,Generic health relevance ,Humans ,Insulin-Secreting Cells ,Insulin Secretion ,Glucose ,Insulin ,Exocytosis ,DNA-Binding Proteins ,Transcription Factors ,Embryonic stem cells ,Islet cells ,Metabolism ,Stem cells ,Biomedical and clinical sciences ,Health sciences - Abstract
Insulin secretion from pancreatic β cells is essential to the maintenance of glucose homeostasis. Defects in this process result in diabetes. Identifying genetic regulators that impair insulin secretion is crucial for the identification of novel therapeutic targets. Here, we show that reduction of ZNF148 in human islets, and its deletion in stem cell-derived β cells (SC-β cells), enhances insulin secretion. Transcriptomics of ZNF148-deficient SC-β cells identifies increased expression of annexin and S100 genes whose proteins form tetrameric complexes involved in regulation of insulin vesicle trafficking and exocytosis. ZNF148 in SC-β cells prevents translocation of annexin A2 from the nucleus to its functional place at the cell membrane via direct repression of S100A16 expression. These findings point to ZNF148 as a regulator of annexin-S100 complexes in human β cells and suggest that suppression of ZNF148 may provide a novel therapeutic strategy to enhance insulin secretion.
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- 2023
9. Genetic architecture of heart mitochondrial proteome influencing cardiac hypertrophy.
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Chella Krishnan, Karthickeyan, El Hachem, Elie-Julien, Keller, Mark P, Patel, Sanjeet G, Carroll, Luke, Vegas, Alexis Diaz, Gerdes Gyuricza, Isabela, Light, Christine, Cao, Yang, Pan, Calvin, Kaczor-Urbanowicz, Karolina Elżbieta, Shravah, Varun, Anum, Diana, Pellegrini, Matteo, Lee, Chi Fung, Seldin, Marcus M, Rosenthal, Nadia A, Churchill, Gary A, Attie, Alan D, Parker, Benjamin, James, David E, and Lusis, Aldons J
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Mitochondria ,Animals ,Mice ,Inbred Strains ,Mice ,Cardiomegaly ,Electron Transport Complex I ,Mitochondrial Proteins ,Proteome ,DNA ,Mitochondrial ,Heart Failure ,computational biology ,genetic ,association studies ,genetics ,genomics ,heart failure ,hypertrophy ,metabolic syndrome ,mitochondria ,mouse ,proteomics ,systems biology ,Human Genome ,Heart Disease ,Biotechnology ,Genetics ,Cardiovascular ,Underpinning research ,1.1 Normal biological development and functioning ,2.1 Biological and endogenous factors ,Aetiology ,Biochemistry and Cell Biology - Abstract
Mitochondria play an important role in both normal heart function and disease etiology. We report analysis of common genetic variations contributing to mitochondrial and heart functions using an integrative proteomics approach in a panel of inbred mouse strains called the Hybrid Mouse Diversity Panel (HMDP). We performed a whole heart proteome study in the HMDP (72 strains, n=2-3 mice) and retrieved 848 mitochondrial proteins (quantified in ≥50 strains). High-resolution association mapping on their relative abundance levels revealed three trans-acting genetic loci on chromosomes (chr) 7, 13 and 17 that regulate distinct classes of mitochondrial proteins as well as cardiac hypertrophy. DAVID enrichment analyses of genes regulated by each of the loci revealed that the chr13 locus was highly enriched for complex-I proteins (24 proteins, P=2.2E-61), the chr17 locus for mitochondrial ribonucleoprotein complex (17 proteins, P=3.1E-25) and the chr7 locus for ubiquinone biosynthesis (3 proteins, P=6.9E-05). Follow-up high resolution regional mapping identified NDUFS4, LRPPRC and COQ7 as the candidate genes for chr13, chr17 and chr7 loci, respectively, and both experimental and statistical analyses supported their causal roles. Furthermore, a large cohort of Diversity Outbred mice was used to corroborate Lrpprc gene as a driver of mitochondrial DNA (mtDNA)-encoded gene regulation, and to show that the chr17 locus is specific to heart. Variations in all three loci were associated with heart mass in at least one of two independent heart stress models, namely, isoproterenol-induced heart failure and diet-induced obesity. These findings suggest that common variations in certain mitochondrial proteins can act in trans to influence tissue-specific mitochondrial functions and contribute to heart hypertrophy, elucidating mechanisms that may underlie genetic susceptibility to heart failure in human populations.
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- 2023
10. Megahertz‐rate ultrafast X‐ray scattering and holographic imaging at the European XFEL
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Hagström, Nanna Zhou, Schneider, Michael, Kerber, Nico, Yaroslavtsev, Alexander, Parra, Erick Burgos, Beg, Marijan, Lang, Martin, Günther, Christian M, Seng, Boris, Kammerbauer, Fabian, Popescu, Horia, Pancaldi, Matteo, Neeraj, Kumar, Polley, Debanjan, Jangid, Rahul, Hrkac, Stjepan B, Patel, Sheena KK, Ovcharenko, Sergei, Turenne, Diego, Ksenzov, Dmitriy, Boeglin, Christine, Baidakova, Marina, von Korff Schmising, Clemens, Borchert, Martin, Vodungbo, Boris, Chen, Kai, Luo, Chen, Radu, Florin, Müller, Leonard, Flórez, Miriam Martínez, Philippi-Kobs, André, Riepp, Matthias, Roseker, Wojciech, Grübel, Gerhard, Carley, Robert, Schlappa, Justine, Van Kuiken, Benjamin E, Gort, Rafael, Mercadier, Laurent, Agarwal, Naman, Le Guyader, Loïc, Mercurio, Giuseppe, Teichmann, Martin, Delitz, Jan Torben, Reich, Alexander, Broers, Carsten, Hickin, David, Deiter, Carsten, Moore, James, Rompotis, Dimitrios, Wang, Jinxiong, Kane, Daniel, Venkatesan, Sandhya, Meier, Joachim, Pallas, Florent, Jezynski, Tomasz, Lederer, Maximilian, Boukhelef, Djelloul, Szuba, Janusz, Wrona, Krzysztof, Hauf, Steffen, Zhu, Jun, Bergemann, Martin, Kamil, Ebad, Kluyver, Thomas, Rosca, Robert, Spirzewski, Michał, Kuster, Markus, Turcato, Monica, Lomidze, David, Samartsev, Andrey, Engelke, Jan, Porro, Matteo, Maffessanti, Stefano, Hansen, Karsten, Erdinger, Florian, Fischer, Peter, Fiorini, Carlo, Castoldi, Andrea, Manghisoni, Massimo, Wunderer, Cornelia Beatrix, Fullerton, Eric E, Shpyrko, Oleg G, Gutt, Christian, Sanchez-Hanke, Cecilia, Dürr, Hermann A, Iacocca, Ezio, Nembach, Hans T, Keller, Mark W, Shaw, Justin M, Silva, Thomas J, Kukreja, Roopali, Fangohr, Hans, Eisebitt, Stefan, Kläui, Mathias, Jaouen, Nicolas, Scherz, Andreas, Bonetti, Stefano, and Jal, Emmanuelle
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X-Rays ,Lasers ,Radiography ,Holography ,holography ,magnetic X-ray scattering ,soft X-rays ,ultrafast X-ray imaging ,XFEL ,Condensed Matter Physics ,Optical Physics ,Physical Chemistry (incl. Structural) ,Biophysics - Abstract
The advent of X-ray free-electron lasers (XFELs) has revolutionized fundamental science, from atomic to condensed matter physics, from chemistry to biology, giving researchers access to X-rays with unprecedented brightness, coherence and pulse duration. All XFEL facilities built until recently provided X-ray pulses at a relatively low repetition rate, with limited data statistics. Here, results from the first megahertz-repetition-rate X-ray scattering experiments at the Spectroscopy and Coherent Scattering (SCS) instrument of the European XFEL are presented. The experimental capabilities that the SCS instrument offers, resulting from the operation at megahertz repetition rates and the availability of the novel DSSC 2D imaging detector, are illustrated. Time-resolved magnetic X-ray scattering and holographic imaging experiments in solid state samples were chosen as representative, providing an ideal test-bed for operation at megahertz rates. Our results are relevant and applicable to any other non-destructive XFEL experiments in the soft X-ray range.
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- 2022
11. OME-Zarr: a cloud-optimized bioimaging file format with international community support
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Moore, Josh, Basurto-Lozada, Daniela, Besson, Sébastien, Bogovic, John, Bragantini, Jordão, Brown, Eva M., Burel, Jean-Marie, Casas Moreno, Xavier, de Medeiros, Gustavo, Diel, Erin E., Gault, David, Ghosh, Satrajit S., Gold, Ilan, Halchenko, Yaroslav O., Hartley, Matthew, Horsfall, Dave, Keller, Mark S., Kittisopikul, Mark, Kovacs, Gabor, Küpcü Yoldaş, Aybüke, Kyoda, Koji, le Tournoulx de la Villegeorges, Albane, Li, Tong, Liberali, Prisca, Lindner, Dominik, Linkert, Melissa, Lüthi, Joel, Maitin-Shepard, Jeremy, Manz, Trevor, Marconato, Luca, McCormick, Matthew, Lange, Merlin, Mohamed, Khaled, Moore, William, Norlin, Nils, Ouyang, Wei, Özdemir, Bugra, Palla, Giovanni, Pape, Constantin, Pelkmans, Lucas, Pietzsch, Tobias, Preibisch, Stephan, Prete, Martin, Rzepka, Norman, Samee, Sameeul, Schaub, Nicholas, Sidky, Hythem, Solak, Ahmet Can, Stirling, David R., Striebel, Jonathan, Tischer, Christian, Toloudis, Daniel, Virshup, Isaac, Walczysko, Petr, Watson, Alan M., Weisbart, Erin, Wong, Frances, Yamauchi, Kevin A., Bayraktar, Omer, Cimini, Beth A., Gehlenborg, Nils, Haniffa, Muzlifah, Hotaling, Nathan, Onami, Shuichi, Royer, Loic A., Saalfeld, Stephan, Stegle, Oliver, Theis, Fabian J., and Swedlow, Jason R.
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- 2023
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12. Symmetry-dependent ultrafast manipulation of nanoscale magnetic domains
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Hagström, Nanna Zhou, Jangid, Rahul, Meera, Turenne, Diego, Brock, Jeffrey, Lamb, Erik S., Stoychev, Boyan, Schlappa, Justine, Gerasimova, Natalia, Van Kuiken, Benjamin, Gort, Rafael, Mercadier, Laurent, Guyader, Loïc Le, Samartsev, Andrey, Scherz, Andreas, Mercurio, Giuseppe, Dürr, Hermann A., Reid, Alexander H., Arora, Monika, Nembach, Hans T., Shaw, Justin M., Jal, Emmanuelle, Fullerton, Eric E., Keller, Mark W., Kukreja, Roopali, Bonetti, Stefano, Silva, Thomas J., and Iacocca, Ezio
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Condensed Matter - Mesoscale and Nanoscale Physics - Abstract
Symmetry is a powerful concept in physics, but its applicability to far-from-equilibrium states is still being understood. Recent attention has focused on how far-from-equilibrium states lead to spontaneous symmetry breaking. Conversely, ultrafast optical pumping can be used to drastically change the energy landscape and quench the magnetic order parameter in magnetic systems. Here, we find a distinct symmetry-dependent ultrafast behaviour by use of ultrafast x-ray scattering from magnetic patterns with varying degrees of isotropic and anisotropic symmetry. After pumping with an optical laser, the scattered intensity reveals a radial shift exclusive to the isotropic component and exhibits a faster recovery time from quenching for the anisotropic component. These features arise even when both symmetry components are concurrently measured, suggesting a correspondence between the excitation and the magnetic order symmetry. Our results underline the importance of symmetry as a critical variable to manipulate the magnetic order in the ultrafast regime.
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- 2021
13. PPTC7 maintains mitochondrial protein content by suppressing receptor-mediated mitophagy
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Niemi, Natalie M., Serrano, Lia R., Muehlbauer, Laura K., Balnis, Catherine E., Wei, Lianjie, Smith, Andrew J., Kozul, Keri-Lyn, Forny, Merima, Connor, Olivia M., Rashan, Edrees H., Shishkova, Evgenia, Schueler, Kathryn L., Keller, Mark P., Attie, Alan D., Friedman, Jonathan R., Pagan, Julia K., Coon, Joshua J., and Pagliarini, David J.
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- 2023
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14. Sample multiplexing-based targeted pathway proteomics with real-time analytics reveals the impact of genetic variation on protein expression
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Yu, Qing, Liu, Xinyue, Keller, Mark P., Navarrete-Perea, Jose, Zhang, Tian, Fu, Sipei, Vaites, Laura P., Shuken, Steven R., Schmid, Ernst, Keele, Gregory R., Li, Jiaming, Huttlin, Edward L., Rashan, Edrees H., Simcox, Judith, Churchill, Gary A., Schweppe, Devin K., Attie, Alan D., Paulo, Joao A., and Gygi, Steven P.
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- 2023
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15. β3-adrenergic receptor downregulation leads to adipocyte catecholamine resistance in obesity
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Valentine, Joseph M, Ahmadian, Maryam, Keinan, Omer, Abu-Odeh, Mohammad, Zhao, Peng, Zhou, Xin, Keller, Mark P, Gao, Hui, Yu, Ruth T, Liddle, Christopher, Downes, Michael, Zhang, Jin, Lusis, Aldons J, Attie, Alan D, Evans, Ronald M, Rydén, Mikael, and Saltiel, Alan R
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Biochemistry and Cell Biology ,Medical Physiology ,Biomedical and Clinical Sciences ,Biological Sciences ,Genetics ,Obesity ,Diabetes ,Nutrition ,2.1 Biological and endogenous factors ,Cancer ,Oral and gastrointestinal ,3T3-L1 Cells ,Adipocytes ,Animals ,Catecholamines ,Down-Regulation ,Drug Resistance ,Energy Metabolism ,Lipolysis ,Male ,Mice ,Receptors ,Adrenergic ,beta-3 ,Signal Transduction ,Adipose tissue ,Cell Biology ,G proteins ,Metabolism ,Medical and Health Sciences ,Immunology ,Biological sciences ,Biomedical and clinical sciences ,Health sciences - Abstract
The dysregulation of energy homeostasis in obesity involves multihormone resistance. Although leptin and insulin resistance have been well characterized, catecholamine resistance remains largely unexplored. Murine β3-adrenergic receptor expression in adipocytes is orders of magnitude higher compared with that of other isoforms. While resistant to classical desensitization pathways, its mRNA (Adrb3) and protein expression are dramatically downregulated after ligand exposure (homologous desensitization). β3-Adrenergic receptor downregulation also occurs after high-fat diet feeding, concurrent with catecholamine resistance and elevated inflammation. This downregulation is recapitulated in vitro by TNF-α treatment (heterologous desensitization). Both homologous and heterologous desensitization of Adrb3 were triggered by induction of the pseudokinase TRIB1 downstream of the EPAC/RAP2A/PI-PLC pathway. TRIB1 in turn degraded the primary transcriptional activator of Adrb3, CEBPα. EPAC/RAP inhibition enhanced catecholamine-stimulated lipolysis and energy expenditure in obese mice. Moreover, adipose tissue expression of genes in this pathway correlated with body weight extremes in a cohort of genetically diverse mice and with BMI in 2 independent cohorts of humans. These data implicate a signaling axis that may explain reduced hormone-stimulated lipolysis in obesity and resistance to therapeutic interventions with β3-adrenergic receptor agonists.
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- 2022
16. International comparisons of laboratory values from the 4CE collaborative to predict COVID-19 mortality
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Weber, Griffin M, Hong, Chuan, Xia, Zongqi, Palmer, Nathan P, Avillach, Paul, L’Yi, Sehi, Keller, Mark S, Murphy, Shawn N, Gutiérrez-Sacristán, Alba, Bonzel, Clara-Lea, Serret-Larmande, Arnaud, Neuraz, Antoine, Omenn, Gilbert S, Visweswaran, Shyam, Klann, Jeffrey G, South, Andrew M, Loh, Ne Hooi Will, Cannataro, Mario, Beaulieu-Jones, Brett K, Bellazzi, Riccardo, Agapito, Giuseppe, Alessiani, Mario, Aronow, Bruce J, Bell, Douglas S, Benoit, Vincent, Bourgeois, Florence T, Chiovato, Luca, Cho, Kelly, Dagliati, Arianna, DuVall, Scott L, Barrio, Noelia García, Hanauer, David A, Ho, Yuk-Lam, Holmes, John H, Issitt, Richard W, Liu, Molei, Luo, Yuan, Lynch, Kristine E, Maidlow, Sarah E, Malovini, Alberto, Mandl, Kenneth D, Mao, Chengsheng, Matheny, Michael E, Moore, Jason H, Morris, Jeffrey S, Morris, Michele, Mowery, Danielle L, Ngiam, Kee Yuan, Patel, Lav P, Pedrera-Jimenez, Miguel, Ramoni, Rachel B, Schriver, Emily R, Schubert, Petra, Balazote, Pablo Serrano, Spiridou, Anastasia, Tan, Amelia LM, Tan, Byorn WL, Tibollo, Valentina, Torti, Carlo, Trecarichi, Enrico M, Wang, Xuan, Kohane, Isaac S, Cai, Tianxi, and Brat, Gabriel A
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Health Services and Systems ,Health Sciences ,Basic Behavioral and Social Science ,Behavioral and Social Science ,Good Health and Well Being ,Consortium for Clinical Characterization of COVID-19 by EHR ,Health services and systems - Abstract
Given the growing number of prediction algorithms developed to predict COVID-19 mortality, we evaluated the transportability of a mortality prediction algorithm using a multi-national network of healthcare systems. We predicted COVID-19 mortality using baseline commonly measured laboratory values and standard demographic and clinical covariates across healthcare systems, countries, and continents. Specifically, we trained a Cox regression model with nine measured laboratory test values, standard demographics at admission, and comorbidity burden pre-admission. These models were compared at site, country, and continent level. Of the 39,969 hospitalized patients with COVID-19 (68.6% male), 5717 (14.3%) died. In the Cox model, age, albumin, AST, creatine, CRP, and white blood cell count are most predictive of mortality. The baseline covariates are more predictive of mortality during the early days of COVID-19 hospitalization. Models trained at healthcare systems with larger cohort size largely retain good transportability performance when porting to different sites. The combination of routine laboratory test values at admission along with basic demographic features can predict mortality in patients hospitalized with COVID-19. Importantly, this potentially deployable model differs from prior work by demonstrating not only consistent performance but also reliable transportability across healthcare systems in the US and Europe, highlighting the generalizability of this model and the overall approach.
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- 2022
17. Genetic mapping of microbial and host traits reveals production of immunomodulatory lipids by Akkermansia muciniphila in the murine gut
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Zhang, Qijun, Linke, Vanessa, Overmyer, Katherine A., Traeger, Lindsay L., Kasahara, Kazuyuki, Miller, Ian J., Manson, Daniel E., Polaske, Thomas J., Kerby, Robert L., Kemis, Julia H., Trujillo, Edna A., Reddy, Thiru R., Russell, Jason D., Schueler, Kathryn L., Stapleton, Donald S., Rabaglia, Mary E., Seldin, Marcus, Gatti, Daniel M., Keele, Gregory R., Pham, Duy T., Gerdt, Joseph P., Vivas, Eugenio I., Lusis, Aldons J., Keller, Mark P., Churchill, Gary A., Blackwell, Helen E., Broman, Karl W., Attie, Alan D., Coon, Joshua J., and Rey, Federico E.
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- 2023
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18. What the BTBR/J mouse has taught us about diabetes and diabetic complications
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Keller, Mark P., Hudkins, Kelly L., Shalev, Anath, Bhatnagar, Sushant, Kebede, Melkam A., Merrins, Matthew J., Davis, Dawn Belt, Alpers, Charles E., Kimple, Michelle E., and Attie, Alan D.
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- 2023
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19. Near-Unity Spin Hall Ratio in Ni$_x$Cu$_{1-x}$ Alloys
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Keller, Mark W., Gerace, Katy S., Arora, Monika, Delczeg-Czirjak, Erna Krisztina, Shaw, Justin M., and Silva, T. J.
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Condensed Matter - Mesoscale and Nanoscale Physics - Abstract
We report a large spin Hall effect in the 3$d$ transition metal alloy Ni$_x$Cu$_{1-x}$ for $x\in\left\{ 0.3,0.75\right\} $, detected via the ferromagnetic resonance of a Permalloy (Py = Ni$_{80}$Fe$_{20}$) film deposited in a bilayer with the alloy. A thickness series at $x$ = 0.6, for which the alloy is paramagnetic at room temperature, allows us to determine the spin Hall ratio $\theta_{\rm{SH}}\approx1$, spin diffusion length $\lambda_{\rm{s}}$, spin mixing conductance $G_{\uparrow\downarrow}$, and damping $\alpha_{\rm{SML}}$ due to spin memory loss . We compare our results with similar experiments on Py/Pt bilayers measured using the same method. Ab initio band structure calculations with disorder and spin-orbit coupling suggest an intrinsic spin Hall effect in Ni$_x$Cu$_{1-x}$ alloys, although the experiments here cannot distinguish between extrinsic and intrinsic mechanisms., Comment: New ab initio calculations of Ni-Cu alloy band structure added; new author; new fig in main text and new appendix describing calculations
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- 2019
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20. International electronic health record-derived COVID-19 clinical course profiles: the 4CE consortium
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Brat, Gabriel A, Weber, Griffin M, Gehlenborg, Nils, Avillach, Paul, Palmer, Nathan P, Chiovato, Luca, Cimino, James, Waitman, Lemuel R, Omenn, Gilbert S, Malovini, Alberto, Moore, Jason H, Beaulieu-Jones, Brett K, Tibollo, Valentina, Murphy, Shawn N, Yi, Sehi L’, Keller, Mark S, Bellazzi, Riccardo, Hanauer, David A, Serret-Larmande, Arnaud, Gutierrez-Sacristan, Alba, Holmes, John J, Bell, Douglas S, Mandl, Kenneth D, Follett, Robert W, Klann, Jeffrey G, Murad, Douglas A, Scudeller, Luigia, Bucalo, Mauro, Kirchoff, Katie, Craig, Jean, Obeid, Jihad, Jouhet, Vianney, Griffier, Romain, Cossin, Sebastien, Moal, Bertrand, Patel, Lav P, Bellasi, Antonio, Prokosch, Hans U, Kraska, Detlef, Sliz, Piotr, Tan, Amelia LM, Ngiam, Kee Yuan, Zambelli, Alberto, Mowery, Danielle L, Schiver, Emily, Devkota, Batsal, Bradford, Robert L, Daniar, Mohamad, Daniel, Christel, Benoit, Vincent, Bey, Romain, Paris, Nicolas, Serre, Patricia, Orlova, Nina, Dubiel, Julien, Hilka, Martin, Jannot, Anne Sophie, Breant, Stephane, Leblanc, Judith, Griffon, Nicolas, Burgun, Anita, Bernaux, Melodie, Sandrin, Arnaud, Salamanca, Elisa, Cormont, Sylvie, Ganslandt, Thomas, Gradinger, Tobias, Champ, Julien, Boeker, Martin, Martel, Patricia, Esteve, Loic, Gramfort, Alexandre, Grisel, Olivier, Leprovost, Damien, Moreau, Thomas, Varoquaux, Gael, Vie, Jill-Jênn, Wassermann, Demian, Mensch, Arthur, Caucheteux, Charlotte, Haverkamp, Christian, Lemaitre, Guillaume, Bosari, Silvano, Krantz, Ian D, South, Andrew, Cai, Tianxi, and Kohane, Isaac S
- Subjects
Health Services and Systems ,Health Sciences ,Good Health and Well Being ,Databases ,Outcomes research ,Viral infection ,Health services and systems - Abstract
We leveraged the largely untapped resource of electronic health record data to address critical clinical and epidemiological questions about Coronavirus Disease 2019 (COVID-19). To do this, we formed an international consortium (4CE) of 96 hospitals across five countries (www.covidclinical.net). Contributors utilized the Informatics for Integrating Biology and the Bedside (i2b2) or Observational Medical Outcomes Partnership (OMOP) platforms to map to a common data model. The group focused on temporal changes in key laboratory test values. Harmonized data were analyzed locally and converted to a shared aggregate form for rapid analysis and visualization of regional differences and global commonalities. Data covered 27,584 COVID-19 cases with 187,802 laboratory tests. Case counts and laboratory trajectories were concordant with existing literature. Laboratory tests at the time of diagnosis showed hospital-level differences equivalent to country-level variation across the consortium partners. Despite the limitations of decentralized data generation, we established a framework to capture the trajectory of COVID-19 disease in patients and their response to interventions.
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- 2020
21. FAM13A affects body fat distribution and adipocyte function.
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Fathzadeh, Mohsen, Li, Jiehan, Rao, Abhiram, Cook, Naomi, Chennamsetty, Indumathi, Seldin, Marcus, Zhou, Xiang, Sangwung, Panjamaporn, Gloudemans, Michael J, Keller, Mark, Attie, Allan, Yang, Jing, Wabitsch, Martin, Carcamo-Orive, Ivan, Tada, Yuko, Lusis, Aldons J, Shin, Myung Kyun, Molony, Cliona M, McLaughlin, Tracey, Reaven, Gerald, Montgomery, Stephen B, Reilly, Dermot, Quertermous, Thomas, Ingelsson, Erik, and Knowles, Joshua W
- Abstract
Genetic variation in the FAM13A (Family with Sequence Similarity 13 Member A) locus has been associated with several glycemic and metabolic traits in genome-wide association studies (GWAS). Here, we demonstrate that in humans, FAM13A alleles are associated with increased FAM13A expression in subcutaneous adipose tissue (SAT) and an insulin resistance-related phenotype (e.g. higher waist-to-hip ratio and fasting insulin levels, but lower body fat). In human adipocyte models, knockdown of FAM13A in preadipocytes accelerates adipocyte differentiation. In mice, Fam13a knockout (KO) have a lower visceral to subcutaneous fat (VAT/SAT) ratio after high-fat diet challenge, in comparison to their wild-type counterparts. Subcutaneous adipocytes in KO mice show a size distribution shift toward an increased number of smaller adipocytes, along with an improved adipogenic potential. Our results indicate that GWAS-associated variants within the FAM13A locus alter adipose FAM13A expression, which in turn, regulates adipocyte differentiation and contribute to changes in body fat distribution.
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- 2020
22. Revealing the nature of the ultrafast magnetic phase transition in Ni by correlating extreme ultraviolet magneto-optic and photoemission spectroscopies
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You, Wenjing, Tengdin, Phoebe, Chen, Cong, Shi, Xun, Zusin, Dmitriy, Zhang, Yingchao, Gentry, Christian, Blonsky, Adam, Keller, Mark, Oppeneer, Peter M., Kapteyn, Henry, Tao, Zhensheng, and Murnane, Margaret
- Subjects
Condensed Matter - Materials Science - Abstract
By correlating time- and angle-resolved photoemission and time-resolved transverse- magneto- optical Kerr effect measurements, both at extreme ultraviolet wavelengths, we uncover the universal nature of the ultrafast photoinduced magnetic phase transition in Ni. This allows us to explain the ultrafast magnetic response of Ni at all laser fluences - from a small reduction of the magnetization at low laser fluences, to complete quenching at high laser fluences. Both probe methods exhibit the same demagnetization and recovery timescales. We further show that the ultrafast demagnetization in Ni is indeed a magnetic phase transition that is launched within 20 fs, followed by demagnetization of the material within ~200 fs, and subsequent recovery of the magnetization on timescales ranging from 500 fs to >70 ps. We also provide evidence of two competing channels with two distinct timescales in the recovery process, that suggest the presence of coexisting phases in the material., Comment: 20 pages, 4 figures
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- 2017
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23. Systems genetics approach uncovers associations between host amylase locus, gut microbiome and metabolic traits in hyperlipidemic mice
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Zhang, Qijun, primary, Hutchison, Evan R., additional, Pan, Calvin, additional, Warren, Matthew F., additional, Keller, Mark P., additional, Attie, Alan D., additional, Lusis, Aldons J., additional, and Rey, Federico E., additional
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- 2024
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24. Proteomic pathways to metabolic disease and type 2 diabetes in the pancreatic islet
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Yau, Belinda, Naghiloo, Sheyda, Diaz-Vegas, Alexis, Carr, Austin V., Van Gerwen, Julian, Needham, Elise J., Jevon, Dillon, Chen, Sing-Young, Hoehn, Kyle L., Brandon, Amanda E., Macia, Laurence, Cooney, Gregory J., Shortreed, Michael R., Smith, Lloyd M., Keller, Mark P., Thorn, Peter, Larance, Mark, James, David E., Humphrey, Sean J., and Kebede, Melkam A.
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- 2021
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25. Reversal of hypertriglyceridemia in diabetic BTBR ob/ob mice does not prevent nephropathy
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Attie, Alan D., Schueler, Kathryn M., Keller, Mark P., Mitok, Kelly A., Simonett, Shane P., Hudkins, Kelly L., Mehrotra, Kunaal, Graham, Mark J., Lee, Richard G., and Alpers, Charles E.
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- 2021
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26. Author Correction: Genetic mapping of microbial and host traits reveals production of immunomodulatory lipids by Akkermansia muciniphila in the murine gut
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Zhang, Qijun, Linke, Vanessa, Overmyer, Katherine A., Traeger, Lindsay L., Kasahara, Kazuyuki, Miller, Ian J., Manson, Daniel E., Polaske, Thomas J., Kerby, Robert L., Kemis, Julia H., Trujillo, Edna A., Reddy, Thiru R., Russell, Jason D., Schueler, Kathryn L., Stapleton, Donald S., Rabaglia, Mary E., Seldin, Marcus, Gatti, Daniel M., Keele, Gregory R., Pham, Duy T., Gerdt, Joseph P., Vivas, Eugenio I., Lusis, Aldons J., Keller, Mark P., Churchill, Gary A., Blackwell, Helen E., Broman, Karl W., Attie, Alan D., Coon, Joshua J., and Rey, Federico E.
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- 2023
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27. Protein N-Glycans in Healthy and Sclerotic Glomeruli in Diabetic Kidney Disease
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Veličković, Dušan, Shapiro, John P., Parikh, Samir V., Rovin, Brad, Toto, Robert D., Vazquez, Miguel A., Poggio, Emilio D., O'Toole, John F., Sedor, John R., Alexandrov, Theodore, Jain, Sanjay, Bitzer, Markus, Hodgin, Jeffrey, Veličković, Marija, Sharma, Kumar, Anderton, Christopher R., Adeyi, Oyedele A., Alakwaa, Fadhl, Alexandrov, Theodore, Allen, Jamie L., Alpers, Charles E., Alvear, Alison Bunio, Ambekar, Akhil, Ancheta, Joed, Anderton, Christopher R., Angus, Sophia A., Anjani, Kavya, Appelbaum, Paul S., Ardayfio, Joseph, Arora, Tanima, Ascani, Heather K., Asghari, Mahla, El-Achkar, Tarek M., Athar, Humra, Atta, Mohamed G., Aulisio, Mark P., Aw, Stephanie J., Azeloglu, Evren U., Bagne, Cathy A., Balderes, Olivia, Balis, Ulysses G.J., Barasch, Jonathan, Barisoni, Laura, Barwinska, Daria, Basta, Jeannine, Bebiak, Jack, Beck, Laurence H., Berge, Jerica M., Berglund, Ashley C., Bernard, Lauren, Berry, Brooke, Beyda, David H., Bhanushali, Jini Ashok, Bitzer, Markus, Bjornstad, Petter, Blanc, Victoria M., Blank, Kristina N., Bledsoe, Sharon B., Bogen, Steve, Bomback, Andrew S., Bonevich, Nikole, Border, Samuel, Börner, Katy, Bowen, William S., Boys, Charlotte, Bracamonte, Erika R., Bream, Peter R., Brosius, Frank C., Brown, Keith D., Budiman, Tifanny, Bueckle, Andreas, Bui, J.T., James, T., Burg, Ashley R., Burgess, Adam, Bush, Lakeshia, Bush, William S., Cai, Qi, Calixte, Marie Florence, Cameron-Wheeler, Tashas, Campbell, Kirk N, Campbell, Taneisha, Campbell, Catherine, Campos, Baltazar, Canetta, Pietro A., Cantley, Lloyd G, Caramori, M. Luiza, Carmona-Powell, Eunice, Carson, Jonas M, Chan, Lili, Chen, Sarah W, Chen, Yijiang, Cheng, Ying-Hua, Bejarano, Maria Chilo, Choe, Kisurb, Cimino, James G., Coca, Steven G., Coleman, Alyson, Colley, Madeline E., Collie, Mary M., Colona, Mia R., Commander, Clayton W., Conlon, Kristine, Conser, Ninive, Cooperman, Leslie, Corona-Villalobos, Celia P., Crawford, Dana C., Creger, Nathan, Cuevas-Rios, Yarieli, D'Agati, Vivette ., Dagher, Pierre c., de Boer, Ian H., de Caestecker, M.P, de Cos, Marina, Gonçalves, Joana P., Dekker, Matthew, Demeke, Dawit, Dighe, Ashveena L, Ding, Yanli, Djambazova, Katerina V., Donohoe, Isabel, Dowd, Frederick, Drawz, P.E., Dufresne, Martin, Dull, Rachel, Dunn, Kenneth W., Duran, Daniel Damian, Eadon, Michael T, Eddy, Sean, Elder, Michele M, Fallegger, Robin, Farrow, Melissa A, Ferkowicz, Michael, Fine, Derek M., Flanagan, Siobhan M., Fogo, Agnes B., Fox, Monica L., Frey, Renee, Froment, Anne, Gaba, Ron C., Gadegbeku, Crystal A, Gaut, Joseph P., Gehlenborg, Nils, Geraghty, Molly C, Ghag, Reetika, Gilliam, Matthew, Ginley, Brandon, Gisch, Debora, Gordon, Ronald E., Gorman, Brittney L., Greka, Anna, Grewenow, Stephanie M., Gurung, Bhupendra Kumar, Guthrie, Leah, Hacohen, Nir, Haddad, Samuel, Hall, Daniel E., Hansen, Jens, Harindhanavudhi, Tasma, Hartman, John, Hayashi, Lynda, Haydak, Jonathan, He, John Cijiang, He, Yongqun, Hedayati, S. Susan, Henderson, Dori, Henderson, Joel M, Hendricks, Allen R, Henshaw, Asari, Herlitz, Leal, Hernandez, Jeanine, Herr, Bruce W., Himmelfarb, Jonathan, Hodgin, Jeffrey B., Hoofnagle, Andrew N, Horowitz, Carol R., Hsieh, E.W.Y., Huynh, Courtney, Iyengar, Ravi, Jain, Sanjay, Janowczyk, Andrew, Jeffers, Vivian, Jefferson, Nichole M., Jennette, J Charles, Johansen, Camille, Jolly, Stacey, Jones, Christopher J., Jones, Jennifer L., Jones, Kiasha, Joyeux, Cienn N., Ju, Wenjun, Judd, Audra M., Kakade, Vijayakumar R, Kakarla, Dhatri, Kaspari, Rachel R., Kaushal, Madhurima, Keefe, Nicole, Keller, Mark S., Kelley, Sara S., Kellum, John A., Kelly, K. J., Kelly, Tanika N., Kermani, Asra, Kiryluk, Krzysztof, Klett, Susan, Knight, Richard A., Knoten, Amanda, Koch, Gina, Koewler, Robert, Kretzler, Matthias, Kruse, Angela R.S., Küchenhoff, Leonie, Lake, Blue B., Lardenoije, Roy, Larson, Astrid, Larson, Brandon G, Lash, James P., Laszik, Zoltan G., Lecker, Stewart H., Lee, Simon C., Lee, Sora, Lefferts, Sean, Li, Xiang, Lienczewski, Chrysta C, Limonte, Christine P, Lucarelli, Nicholas, Lukowski, Jessica, Lutnick, Brendon, Ma, Shihong, Ma, Sisi, Madabhushi, Anant, Maikhor, Shana, Mao, Weiguang, Mariani, Laura H., Markovic, Marina, Marquez, Nicole, Marshall, Jamie L., McAdams, Meredith C, McClelland, Robyn L., McCown, Phillip J., McMahon, Gearoid Michael, McMurray, Amy, Mehl, Karla, Meliambro, Kristin, Ferreira, Ricardo Melo, Mendoza, Katherine, Menez, Steven, Menon, Rajasree, Meza, Natalie, Migas, Lukasz G., Miller, R. Tyler, Mimar, Sayat, Minor, Brittany C, Mody, Priya, Moeckel, Gilbert W., Moledina, D.G., Molina-Guzman, Jenny, Monroy-Trujillo, Jose M, Morales, Alexander, Moreno, Vanessa, Mottl, Amy K., Mukatash, Tariq, Munar, Dane, Murugan, Raghavan, Nachman, Patrick H., Nadkarni, Girish N, Naglah, Ahmed, Nair, Viji, Nam, Yunbi, Narasimhan, R., Nwanne, Gerald, O'Malley, Charles, O'Toole, John F., Toro, Fernanda Ochoa, Oliver, George (Holt), Onul, Ingrid F, Otto, Edgar A., Palevsky, Paul M., Palmer, Ellen, Pamreddy, Annapurna, Parikh, Chirag R., Parikh, Samir V, Park, Christopher, Park, Harold, Paša-Tolić, Ljiljana, Patel, Jiten, Patel, Marissa, Patlis, Boris S., Paul, Anindya S., Phuong, Jimmy, Pillai, Anil, Pinkeney, Roy, Plisiewicz, Alexa, Poggio, Emilio D, Pollack, Ari, Prasad, Pottumarthi V, Pyle, Laura, Quardokus, Ellen M., Quiroga, Arabela, Ragi, Nagarjunachary, Randhawa, Parmjeet, Randle, Teresa, Rao, Via, Rauchman, Michael, Rauwolf, Nicolas J, Reamy, Rebecca, Record, Elizabeth G., Redmond, Devona, Rennke, Helmut, Renteria, Amada, Rezaei, Kasra A, Rhodes, Rosamond, Ricardo, Ana C., Rice, Samuel, Rivera, Marcelino, Roberts, Glenda V., Rosas, R., Sylvia, E., Rose, Michael P., Rosen, Seymour, Rosenberg, Avi Z., Rosenberg, Michael S., Rosengart, Matthew R., Rovin, Brad H., Roy, Neil, Roy-Chaudhury, Prabir, Rubinsky, Melissa D., Sabo, Angela R., Saez-Rodriguez, Julio, Safadi, Sami, Samari, Imane H., Sanora, Ana Celina, Sarder, Pinaki, Sarkisova, Natalya, Sarwal, Minnie M, Saul, John, Saunders, Milda R., Schaub, Jennifer A., Schmidt, IM, Scott, Raymond, Scroggins, Aaron, Sealfon, Rachel S. G., Sedor, John R., Sendrey, Dianna, Setty, Suman, Shah, Sonya, Shariff, Saad Mohammed, Sharma, Kumar, Shaw, Melissa M., Sigdel, Tara K, Silva, Paolo S., Snyder, Jaime, Snyder, Michelle L., Spates-Harden, Kassandra, Sperati, C. John, Spraggins, Jeffrey M., Srivastava, Anand, Stashevsky, Jennifer, Steck, Becky, Stillman, Isaac E, Stutzke, Christy, Subramanian, Lalita, Sun, Jennifer K., Rajan, Sandhya Sundar, Sutton, Timothy A., Taliercio, Jonathan J, Tan, Roderick, Tanevski, Jovan, Thajudeen, Bijin, Thurman, Joshua M., Tokita, Joji, Torrealba, Jose R., Toto, Robert D, Tout, Haneen, Troyanskaya, Olga G, Tsosie, Rebecca, Turner, Jeffrey M, Tuttle, Katherine R., Ugwuowo, Ugochukwu, Upadhyay, Ashish, Valerius, M. Todd, Van de Plas, Raf, Varela, German, Vazquez, Miguel A., Velickovic, Dusan, Venkatachalam, Manjeri, Verdoes, Abraham, Verma, Ashish, Victoria-Castro, Angela M., Vijayan, Anitha, Villalobos, Alexander, Viloria, Noralinda B., Vinovskis, Carissa, Vita, Tina, Waikar, Sushrut S., Wang, Ashley R., Wang, Bangchen, Wang, Nancy, Wang, Ruikang, Wangperawong, Artit, Ward, Stephen C, Warfield, Curtis, Weins, Astrid, Wen, Natasha, Wen, Yumeng, Wilcox, Adam, Williams, James C., Williams, Kayleen, Williams, Mark E., Wilson, F. Perry, Winfree, Seth, Winters, James, Wofford, Stephanie, Wolf, Susan M., Wong, Aaron, Woodhead, Gregory, Wright, Devin M., Wright, Zach, Wright, Zoe, Wrobel, Julia, Xing, Fuyong, Xu, Alan, Yadati, Pranav, Ye, Hongping, Young, Bessie A., Yu, Guanghao, Mon-Wei Yu, Samuel, Zeinoun, Gabriel, Zeitler, Evan M., Zhang, Bo, Zhang, Guanshi, and Zhang, Yi
- Published
- 2024
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28. The dissection of expression quantitative trait locus hotspots
- Author
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Tian, Jianan, Keller, Mark P., Broman, Aimee Teo, Kendziorski, Christina, Yandell, Brian S., Attie, Alan D., and Broman, Karl W.
- Subjects
Statistics - Applications ,Quantitative Biology - Genomics - Abstract
Studies of the genetic loci that contribute to variation in gene expression frequently identify loci with broad effect on gene expression: expression quantitative trait locus (eQTL) hotspots. We describe a set of exploratory graphical methods as well as a formal likelihood-based test for assessing whether a given hotspot is due to one or multiple polymorphisms. We first look at the pattern of effects of the locus on the expression traits that map to the locus: the direction of the effects, as well as the degree of dominance. A second technique is to focus on the individuals that exhibit no recombination event in the region, apply dimensionality reduction (such as with linear discriminant analysis) and compare the phenotype distribution in the non-recombinants to that in the recombinant individuals: If the recombinant individuals display a different expression pattern than the non-recombinants, this indicates the presence of multiple causal polymorphisms. In the formal likelihood-based test, we compare a two-locus model, with each expression trait affected by one or the other locus, to a single-locus model. We apply our methods to a large mouse intercross with gene expression microarray data on six tissues., Comment: 40 pages, 6 figures, 3 supplemental figures, and a separate PDF file (FileS1.pdf) with an additional 35 pages of figures; made small changes to text on pages 26-31 in response to reviewers' comments; corrected a number of typographical errors and added acknowledgment of an additional grant
- Published
- 2015
29. Suppression of Spin Pumping Between Ni$_{80}$Fe$_{20}$ and Cu by a Graphene Interlayer
- Author
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Gannett, Will, Keller, Mark W., Nembach, Hans T., Silva, Thomas J., and Debay, Ann Chiaramonti
- Subjects
Condensed Matter - Mesoscale and Nanoscale Physics ,Condensed Matter - Materials Science - Abstract
We compare ferromagnetic resonance measurements of Permalloy Ni$_{80}$Fe$_{20}$ (Py) films sputtered onto Cu(111) films with and without a graphene (Gr) interlayer grown by chemical vapor deposition before Py deposition. A two-angle sputtering method ensured that neither Gr nor Py was degraded by the sample preparation process. We find the expected damping enhancement from spin pumping for the Py/Cu case and no detectable enhancement for the Py/Gr/Cu case. Since damping is sensitive to effects other than spin pumping, we used magnetometry to verify that differences in Py magnetostatic properties are not responsible for the difference in damping. We attribute the suppression of spin pumping in Py/Gr/Cu to the large contact resistance of the Gr/Cu interface.
- Published
- 2015
30. From methylene bridged diindole to carbonyl linked benzimidazoleindole: Development of potent and metabolically stable PCSK9 modulators
- Author
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Xie, Haibo, Yang, Ka, Winston-McPherson, Gabrielle N., Stapleton, Donnie S., Keller, Mark P., Attie, Alan D., Smith, Kerry A., and Tang, Weiping
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- 2020
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31. Heme biosynthesis regulates BCAA catabolism and thermogenesis in brown adipose tissue
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Duerre, Dylan J, primary, Hansen, Julia K, additional, John, Steven, additional, Jen, Annie, additional, Carrillo, Noah, additional, Bui, Hoang, additional, Bao, Yutong, additional, Fabregat, Matias, additional, Overmyer, Katherine, additional, Shishkova, Evgenia, additional, Keller, Mark P, additional, Anderson, Richard A, additional, Cryns, Vincent L, additional, Attie, Alan D., additional, Coon, Joshua, additional, Fan, Jing, additional, and Galmozzi, Andrea, additional
- Published
- 2023
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32. Genetic analysis of obesity-induced diabetic nephropathy in BTBR mice
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Keller, Mark P., primary, O’Connor, Chris, additional, Bitzer, Markus, additional, Schueler, Kathryn L., additional, Stapleton, Donald S., additional, Emfinger, Christopher H., additional, Broman, Aimee Teo, additional, Hodgin, Jeffrey B., additional, and Attie, Alan D., additional
- Published
- 2023
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33. Identification and correction of sample mix-ups in expression genetic data: A case study
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Broman, Karl W., Keller, Mark P., Broman, Aimee Teo, Kendziorski, Christina, Yandell, Brian S., Sen, Saunak, and Attie, Alan D.
- Subjects
Statistics - Applications - Abstract
In a mouse intercross with more than 500 animals and genome-wide gene expression data on six tissues, we identified a high proportion (18%) of sample mix-ups in the genotype data. Local expression quantitative trait loci (eQTL; genetic loci influencing gene expression) with extremely large effect were used to form a classifier to predict an individual's eQTL genotype based on expression data alone. By considering multiple eQTL and their related transcripts, we identified numerous individuals whose predicted eQTL genotypes (based on their expression data) did not match their observed genotypes, and then went on to identify other individuals whose genotypes did match the predicted eQTL genotypes. The concordance of predictions across six tissues indicated that the problem was due to mix-ups in the genotypes (though we further identified a small number of sample mix-ups in each of the six panels of gene expression microarrays). Consideration of the plate positions of the DNA samples indicated a number of off-by-one and off-by-two errors, likely the result of pipetting errors. Such sample mix-ups can be a problem in any genetic study, but eQTL data allow us to identify, and even correct, such problems. Our methods have been implemented in an R package, R/lineup., Comment: 63 pages, 9 figures, 20 supplemental figures, and 5 supplemental tables. In version 2: added two supplemental figures in response to reviewers' comments, and corrected a problem in Figure S13 (points at the boundary between genotype groups were inadvertently omitted, which gave the false impression of clear separation between the groups). In version 3: fixed a few typos
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- 2014
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34. Controlling the electronic structure of graphene using surface-adsorbate interactions
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Matyba, Piotr, Carr, Adra V., Chen, Cong, Miller, David L., Peng, Guowen, Mathias, Stefan, Mavrikakis, Manos, Dessau, Daniel S., Keller, Mark W., Kapteyn, Henry C., and Murnane, Margaret
- Subjects
Condensed Matter - Materials Science - Abstract
We show that strong coupling between graphene and the substrate is mitigated when 0.8 monolayer of Na is adsorbed and consolidated on top graphene-on-Ni(111). Specifically, the {\pi} state is partially restored near the K-point and the energy gap between the {\pi} and {\pi}* states reduced to 1.3 eV after adsorption, as measured by angle-resolved photoemission spectroscopy. We show that this change is not caused by intercalation of Na to underneath graphene but it is caused by an electronic coupling between Na on top and graphene. We show further that graphene can be decoupled to a much higher extent when Na is intercalated to underneath graphene. After intercalation, the energy gap between the {\pi} and {\pi}* states is reduced to 0 eV and these states are identical as in freestanding and n-doped graphene. We conclude thus that two mechanisms of decoupling exist: a strong decoupling through intercalation, which is the same as one found using noble metals, and a weak decoupling caused by electronic interaction with the adsorbate on top.
- Published
- 2014
35. Viv: multiscale visualization of high-resolution multiplexed bioimaging data on the web
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Manz, Trevor, Gold, Ilan, Patterson, Nathan Heath, McCallum, Chuck, Keller, Mark S., Herr, II, Bruce W., Börner, Katy, Spraggins, Jeffrey M., and Gehlenborg, Nils
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- 2022
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36. INFIMA leverages multi-omics model organism data to identify effector genes of human GWAS variants
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Dong, Chenyang, Simonett, Shane P., Shin, Sunyoung, Stapleton, Donnie S., Schueler, Kathryn L., Churchill, Gary A., Lu, Leina, Liu, Xiaoxiao, Jin, Fulai, Li, Yan, Attie, Alan D., Keller, Mark P., and Keleş, Sündüz
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- 2021
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37. A large-scale genome–lipid association map guides lipid identification
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Linke, Vanessa, Overmyer, Katherine A., Miller, Ian J., Brademan, Dain R., Hutchins, Paul D., Trujillo, Edna A., Reddy, Thiru R., Russell, Jason D., Cushing, Emily M., Schueler, Kathryn L., Stapleton, Donald S., Rabaglia, Mary E., Keller, Mark P., Gatti, Daniel M., Keele, Gregory R., Pham, Duy, Broman, Karl W., Churchill, Gary A., Attie, Alan D., and Coon, Joshua J.
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- 2020
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38. Giant Secondary Grain Growth in Cu Films on Sapphire
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Miller, David L., Keller, Mark W., Shaw, Justin M., Rice, Katherine P., Keller, Robert R., and Diederichsen, Kyle M.
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Condensed Matter - Materials Science - Abstract
Single crystal metal films on insulating substrates are attractive for microelectronics and other applications, but they are difficult to achieve on macroscopic length scales. The conventional approach to obtaining such films is epitaxial growth at high temperature using slow deposition in ultrahigh vacuum conditions. Here we describe a different approach: sputter deposition at modest temperatures followed by annealing to induce secondary grain growth. We show that polycrystalline as-deposited Cu on \alpha-Al2O3(0001) can be transformed into Cu(111) with centimeter-sized grains. Employing optical microscopy, x-ray diffraction, and electron backscatter diffraction to characterize the films before and after annealing, we find a particular as-deposited grain structure that promotes the growth of giant grains upon annealing. To demonstrate one potential application of such films, we grow graphene by chemical vapor deposition on wafers of annealed Cu and obtain epitaxial graphene grains of 0.2 mm diameter., Comment: 5 figures
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- 2013
39. Epitaxial (111) Films of Cu, Ni, and Cu$_xNi$_y$ on {\alpha}-Al$_2$O$_3$(0001) for Graphene Growth by Chemical Vapor Deposition
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Miller, David L., Keller, Mark W., Shaw, Justin M., Chiaramonti, Ann N., and Keller, Robert R.
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Condensed Matter - Materials Science - Abstract
Films of (111)-textured Cu, Ni, and Cu$_x$Ni$_y$ were evaluated as substrates for chemical vapor deposition of graphene. A metal thickness of 400 nm to 700 nm was sputtered onto a substrate of $\alpha-$Al$_2$O$_3$(0001) at temperatures of 250 C to 650 C. The films were then annealed at 1000 C in a tube furnace. X-ray and electron backscatter diffraction measurements showed all films have (111) texture but have grains with in-plane orientations differing by $60^{\circ}$. The in-plane epitaxial relationship for all films was $[110]_{metal}$||$[10\bar{1}0]_{{Al}_{2}{O}_{3}}$. Reactive sputtering of Al in O$_2$ before metal deposition resulted in a single in-plane orientation over 97 % of the Ni film but had no significant effect on the Cu grain structure. Transmission electron microscopy showed a clean Ni/Al$_2$O$_3$ interface, confirmed the epitaxial relationship, and showed that formation of the $60^{\circ}$ twin grains was associated with features on the Al$_2$O$_3$ surface. Increasing total pressure and Cu vapor pressure during annealing decreased the roughness of Cu and and Cu$_x$Ni$_y$ films. Graphene grown on the Ni(111) films was more uniform than that grown on polycrystalline Ni/SiO$_2$ films, but still showed thickness variations on a much smaller length scale than the distance between grains.
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- 2012
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40. Electron Counting Capacitance Standard with an improved five-junction R-pump
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Camarota, Benedetta, Scherer, Hansjoerg, Keller, Mark W, Lotkhov, Sergey V, Willenberg, Gerd-Dietmar, and Ahlers, Franz Josef
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Condensed Matter - Mesoscale and Nanoscale Physics ,Condensed Matter - Other Condensed Matter - Abstract
The Electron Counting Capacitance Standard currently pursued at PTB aims to close the Quantum Metrological Triangle with a final precision of a few parts in 10^7. This paper reports the considerable progress recently achieved with a new generation of single-electron tunnelling devices. A five-junction R-pump was operated with a relative charge transfer error of five electrons in 10^7, and was used to successfully perform single-electron charging of a cryogenic capacitor. The preliminary result for the single-electron charge quantum has an uncertainty of less than two parts in 10^6 and is consistent with the value of the elementary charge., Comment: 16 pages, 9 figures, 1 table
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- 2011
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41. Causal graphical models in systems genetics: A unified framework for joint inference of causal network and genetic architecture for correlated phenotypes
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Neto, Elias Chaibub, Keller, Mark P., Attie, Alan D., and Yandell, Brian S.
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Statistics - Applications - Abstract
Causal inference approaches in systems genetics exploit quantitative trait loci (QTL) genotypes to infer causal relationships among phenotypes. The genetic architecture of each phenotype may be complex, and poorly estimated genetic architectures may compromise the inference of causal relationships among phenotypes. Existing methods assume QTLs are known or inferred without regard to the phenotype network structure. In this paper we develop a QTL-driven phenotype network method (QTLnet) to jointly infer a causal phenotype network and associated genetic architecture for sets of correlated phenotypes. Randomization of alleles during meiosis and the unidirectional influence of genotype on phenotype allow the inference of QTLs causal to phenotypes. Causal relationships among phenotypes can be inferred using these QTL nodes, enabling us to distinguish among phenotype networks that would otherwise be distribution equivalent. We jointly model phenotypes and QTLs using homogeneous conditional Gaussian regression models, and we derive a graphical criterion for distribution equivalence. We validate the QTLnet approach in a simulation study. Finally, we illustrate with simulated data and a real example how QTLnet can be used to infer both direct and indirect effects of QTLs and phenotypes that co-map to a genomic region., Comment: Published in at http://dx.doi.org/10.1214/09-AOAS288 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org)
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- 2010
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42. Theory for a dissipative droplet soliton excited by a spin torque nanocontact
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Hoefer, M. A., Silva, T. J., and Keller, Mark W.
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Condensed Matter - Materials Science ,Condensed Matter - Mesoscale and Nanoscale Physics ,Condensed Matter - Other Condensed Matter ,Nonlinear Sciences - Pattern Formation and Solitons - Abstract
A novel type of solitary wave is predicted to form in spin torque oscillators when the free layer has a sufficiently large perpendicular anisotropy. In this structure, which is a dissipative version of the conservative droplet soliton originally studied in 1977 by Ivanov and Kosevich, spin torque counteracts the damping that would otherwise destroy the mode. Asymptotic methods are used to derive conditions on perpendicular anisotropy strength and applied current under which a dissipative droplet can be nucleated and sustained. Numerical methods are used to confirm the stability of the droplet against various perturbations that are likely in experiments, including tilting of the applied field, non-zero spin torque asymmetry, and non-trivial Oersted fields. Under certain conditions, the droplet experiences a drift instability in which it propagates away from the nanocontact and is then destroyed by damping., Comment: 15 pages, 12 figures
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- 2010
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43. Non-white frequency noise in spin torque oscillators and its effect on spectral linewidth
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Keller, Mark W., Pufall, M. R., Rippard, W. H., and Silva, T. J.
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Condensed Matter - Other Condensed Matter ,Condensed Matter - Materials Science - Abstract
We measure the power spectral density of frequency fluctuations in nanocontact spin torque oscillators over time scales up to 50 ms. We use a mixer to convert oscillator signals ranging from 10 GHz to 40 GHz into a band near 70 MHz before digitizing the time domain waveform. We analyze the waveform using both zero crossing time stamps and a sliding Fourier transform, discuss the different limitations and advantages of these two methods, and combine them to obtain a frequency noise spectrum spanning more than five decades of Fourier frequency $f$. For devices having a free layer consisting of either a single Ni$_{\text{}80}$Fe$_{\text{}20}$ layer or a Co/Ni multilayer we find a frequency noise spectrum that is white at large $f$ and varies as \emph{$1/f$} at small $f$. The crossover frequency ranges from $\approx\unit[10^{4}]{Hz}$ to $\approx\unit[10^{6}]{Hz}$ and the $1/f$ component is stronger in the multilayer devices. Through actual and simulated spectrum analyzer measurements, we show that $1/f$ frequency noise causes both broadening and a change in shape of the oscillator's spectral line as measurement time increases. Our results indicate that the long term stability of spin torque oscillators cannot be accurately predicted from models based on thermal (white) noise sources.
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- 2010
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44. Spin Transfer Dynamics in Spin Valves with Out-of-plane Magnetized CoNi Free Layers
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Rippard, William H., Deac, Alina M., Pufall, Matthew R., Shaw, Justin M., Keller, Mark W., Russek, Stephen E., Bauer, Gerrit E. W., and Serpico, Claudio
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Condensed Matter - Mesoscale and Nanoscale Physics ,Condensed Matter - Other Condensed Matter - Abstract
We have measured spin transfer-induced dynamics in magnetic nanocontact devices having a perpendicularly magnetized Co/Ni free layer and an in-plane magnetized CoFe fixed layer. The frequencies and powers of the excitations agree well with the predictions of the single-domain model and indicate that the excited dynamics correspond to precessional orbits with angles ranging from zero to 90 degrees as the applied current is increased at a fixed field. From measurements of the onset current as a function of applied field strength we estimate the magnitude of the spin torque asymmetry parameter lambda ~ 1.5. By combining these with spin torque ferromagnetic resonance measurements, we also estimate the spin wave radiation loss in these devices.
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- 2009
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45. Time domain measurement of phase noise in a spin torque oscillator
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Keller, Mark W., Kos, A. B., Silva, T. J., Rippard, W. H., and Pufall, M. R.
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Condensed Matter - Mesoscale and Nanoscale Physics - Abstract
We measure oscillator phase from the zero crossings of the voltage vs. time waveform of a spin torque nanocontact oscillating in a vortex mode. The power spectrum of the phase noise varies with Fourier frequency $f$ as $1/f^2$, consistent with frequency fluctuations driven by a thermal source. The linewidth implied by phase noise alone is about 70 % of that measured using a spectrum analyzer. A phase-locked loop reduces the phase noise for frequencies within its 3 MHz bandwidth., Comment: 6 pages, 5 figures, supplementary material. Submitted to {Appl. Phys. Lett.}
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- 2009
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46. Genetic Analysis of Obesity-Induced Diabetic Nephropathy in BTBR Mice.
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Keller, Mark P., O’Connor, Chris, Bitzer, Markus, Schueler, Kathryn L., Stapleton, Donald S., Emfinger, Christopher H., Broman, Aimee Teo, Hodgin, Jeffrey B., and Attie, Alan D.
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DIABETIC nephropathies , *LOCUS (Genetics) , *CHRONIC kidney failure , *SINGLE nucleotide polymorphisms , *MICE , *MISSENSE mutation - Abstract
Diabetic nephropathy (DN) is the leading cause of end-stage renal disease in the U.S. and has a significant impact on human suffering. Leptin-deficient BTBR (BTBRob/ob) mice develop hallmark features of obesity-induced DN, whereas leptin-deficient C57BL/6J (B6ob/ob) mice do not. To identify genetic loci that underlie this strain difference, we constructed an F2 intercross between BTBRob/ob and B6ob/ob mice. We isolated kidneys from 460 F2 mice and histologically scored them for percent mesangial matrix and glomerular volume (∼50 glomeruli per mouse), yielding ∼45,000 distinct measures in total. The same histological measurements were made in kidneys from B6 and BTBR mice, either lean or obese (Lepob/ob), at 4 and 10 weeks of age, allowing us to assess the contribution of strain, age, and obesity to glomerular pathology. All F2 mice were genotyped for ∼5,000 single nucleotide polymorphisms (SNPs), ∼2,000 of which were polymorphic between B6 and BTBR, enabling us to identify a quantitative trait locus (QTL) on chromosome 7, with a peak at ∼30 Mbp, for percent mesangial matrix, glomerular volume, and mesangial volume. The podocyte-specific gene nephrin (Nphs1) is physically located at the QTL and contains high-impact SNPs in BTBR, including several missense variants within the extracellular immunoglobulin-like domains. Article Highlights: Diabetes is the leading cause of end-stage renal disease. We previously discovered that the BTBR mouse strain carrying the ob mutation at the leptin gene is an excellent model of human diabetic nephropathy and has been widely adopted by basic scientists and the pharmaceutical industry. Genetic factors play a role in susceptibility to diabetic nephropathy. We carried out a linkage study in a sample of mice generated from an intercross between the BTBR and C57BL/6J strains carrying the ob mutation. We identified a single locus and provided evidence that the leading candidate gene at this locus is nephrin. [ABSTRACT FROM AUTHOR]
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- 2024
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47. Novel regulators of islet function identified from genetic variation in mouse islet Ca2+ oscillations
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Emfinger, Christopher H, primary, Clark, Lauren E, primary, Yandell, Brian, additional, Schueler, Kathryn L, additional, Simonett, Shane P, additional, Stapleton, Donnie S, additional, Mitok, Kelly A, additional, Merrins, Matthew J, additional, Keller, Mark P, additional, and Attie, Alan D, additional
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- 2023
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48. Author Response: Novel regulators of islet function identified from genetic variation in mouse islet Ca2+ oscillations
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Emfinger, Christopher H, primary, Clark, Lauren E, additional, Yandell, Brian, additional, Schueler, Kathryn L, additional, Simonett, Shane P, additional, Stapleton, Donnie S, additional, Mitok, Kelly A, additional, Merrins, Matthew J, additional, Keller, Mark P, additional, and Attie, Alan D, additional
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- 2023
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49. OR12-03 The Pancreatic Islet Alpha Cell Arginine Transporter SLC7A2 Regulates Arginine-induced Glucagon Secretion and Glycemia
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Stanley, Jade E, primary, Reuter, Austin, additional, Sellick, Katelyn, additional, Attie, Alan D, additional, Keller, Mark P, additional, and Dean, E Danielle, additional
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- 2023
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50. Pancreatic islet α cell function and proliferation requires the arginine transporter SLC7A2
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Spears, Erick, primary, Stanley, Jade E, additional, Shou, Matthew, additional, Dai, Chunhua, additional, Bradley, Amber, additional, Yin, Linlin, additional, Li, Xuan, additional, Sellick, Katelyn, additional, Poffenberger, Greg, additional, Coate, Katie C, additional, Shrestha, Shristi D, additional, Jenkins, Regina, additional, Sloop, Kyle, additional, Wilson, Keith T, additional, Attie, Alan D., additional, Keller, Mark P, additional, Chen, Wenbiao, additional, Powers, Alvin C, additional, and Dean, E. Danielle, additional
- Published
- 2023
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