238 results on '"Israel, F."'
Search Results
2. Luminescent Analysis of Eu3+ and Tb3+ Flufenamate Complexes Doped in PMMA Polymer: Unexpected Terbium Green Emission under Sunlight Exposure
- Author
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Israel P. Assunção, Israel F. Costa, Paulo R. S. Santos, Ercules E. S. Teotonio, Maria Claudia F. C. Felinto, Ulrich Kynast, Wagner M. Faustino, Oscar Malta, and Hermi F. Brito
- Published
- 2022
3. Chemokine receptors in GtoPdb v.2023.1
- Author
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Albert Zlotnik, Osamu Yoshie, Mohib Uddin, Marcus Thelen, Alexander H. Sparre-Ulrich, Silvano Sozzani, Antal Rot, Mette M. Rosenkilde, Amanda E. I. Proudfoot, Christine A. Power, Joost J. Oppenheim, Hisayuki Nomiyama, Robert J. B. Nibbs, Philip M. Murphy, Georgios L. Moschovakis, Amy E. Monaghan, Kouji Matsushima, Alberto Mantovani, Andrew D. Luster, Massimo Locati, Richard Horuk, Rebecca Hills, Gerard J. Graham, Joshua M. Farber, Reinhold Förster, Christophe Combadiere, Israel F. Charo, Amanda M. Burkhardt, Adit Ben-Baruch, and Francoise Bachelerie
- Subjects
General Medicine ,General Chemistry - Abstract
Chemokine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Chemokine Receptors [438, 437, 32]) comprise a large subfamily of 7TM proteins that bind one or more chemokines, a large family of small cytokines typically possessing chemotactic activity for leukocytes. Additional hematopoietic and non-hematopoietic roles have been identified for many chemokines in the areas of embryonic development, immune cell proliferation, activation and death, viral infection, and as antibacterials, among others. Chemokine receptors can be divided by function into two main groups: G protein-coupled chemokine receptors, which mediate leukocyte trafficking, and "Atypical chemokine receptors", which may signal through non-G protein-coupled mechanisms and act as chemokine scavengers to downregulate inflammation or shape chemokine gradients [32].Chemokines in turn can be divided by structure into four subclasses by the number and arrangement of conserved cysteines. CC (also known as β-chemokines; n= 28), CXC (also known as α-chemokines; n= 17) and CX3C (n= 1) chemokines all have four conserved cysteines, with zero, one and three amino acids separating the first two cysteines respectively. C chemokines (n= 2) have only the second and fourth cysteines found in other chemokines. Chemokines can also be classified by function into homeostatic and inflammatory subgroups. Most chemokine receptors are able to bind multiple high-affinity chemokine ligands, but the ligands for a given receptor are almost always restricted to the same structural subclass. Most chemokines bind to more than one receptor subtype. Receptors for inflammatory chemokines are typically highly promiscuous with regard to ligand specificity, and may lack a selective endogenous ligand. G protein-coupled chemokine receptors are named acccording to the class of chemokines bound, whereas ACKR is the root acronym for atypical chemokine receptors [33]. There can be substantial cross-species differences in the sequences of both chemokines and chemokine receptors, and in the pharmacology and biology of chemokine receptors. Endogenous and microbial non-chemokine ligands have also been identified for chemokine receptors. Many chemokine receptors function as HIV co-receptors, but CCR5 is the only one demonstrated to play an essential role in HIV/AIDS pathogenesis. The tables include both standard chemokine receptor names [693] and aliases.
- Published
- 2023
4. Multi-agent system for steel manufacturing process
- Author
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Angel R. Ricardo, Israel F. Benítez, Guillermo González, and José R. Nuñez
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Intelligent control ,Artificial intelligence ,General Computer Science ,Agents ,Electrical and Electronic Engineering ,Decision support systems ,Integrated manufacturing - Abstract
This work was carried out in the company ACINOX Las Tunas, Cuba, to design an integrated automation architecture based on intelligent agents for control, monitoring, and decision-making in the production process that guarantees an improvement in planning and management of the process in the steelwork plant. The great differences of technologies and systems of each steel mill and the multiple restrictions, methods, and techniques, within a wide dynamic strongly concatenated, do not generalize automation systems feasibly. In our research, we use international research results and the experience of the plant technologists to create three levels of distributed intelligent architecture: business, production planning-control, and steel manufacturing. Each level manages to integrate and balance the particular and general interests for efficient decision-making combined between hierarchy and heterarchy in this steelwork plant, which will be reflected in a reduction of at least 99% of the time used for decision-making concerning the current system, which can lead to a decrease in refractory costs, energy consumption, and production cost. The effectiveness of the solution is demonstrated with scenario validation and expert evaluation.
- Published
- 2022
5. Luminescence properties of BaMO4:Eu3+ (M: Mo or W) phosphors derived from co-precipitation reaction
- Author
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Renan P. Moreira, Leonardo H.C. Francisco, Israel F. Costa, Helliomar P. Barbosa, Ercules E.S. Teotonio, Maria C.F.C. Felinto, Oscar L. Malta, and Hermi F. Brito
- Subjects
FÓSFORO ,Mechanics of Materials ,Mechanical Engineering ,Materials Chemistry ,Metals and Alloys - Published
- 2023
6. On the experimental determination of 4f-4f Intensity parameters from the emission spectra of europium (III) compounds
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Lucca Blois, Albano N. Carneiro Neto, Ricardo L. Longo, Israel F. Costa, Tiago B. Paolini, Hermi F. Brito, and Oscar L. Malta
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EURÓPIO ,Atomic and Molecular Physics, and Optics ,Electronic, Optical and Magnetic Materials - Published
- 2022
7. Central molecular zones in galaxies: multitransition survey of dense gas tracers HCN, HNC, and HCO+
- Author
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Israel, F. P.
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Space and Planetary Science ,Astrophysics of Galaxies (astro-ph.GA) ,FOS: Physical sciences ,Astronomy and Astrophysics ,Astrophysics - Astrophysics of Galaxies - Abstract
New HCN, HNC, and HCO+ measurements of 46 normal galaxies in transitions up to J=4-3 are included in a multitransition database covering HCN and HCO+ (130 galaxies) and HNC (94 galaxies). The near-linear luminosity relations are dominated by distance effects and do not reflect galaxy physical properties. Individual galaxies show significant dispersion in both their luminosity and line ratio. Line ratios do not correlate well with either luminosities or other line ratios. Only the normalized J-transition ladders of HCN and HCO+ and the J=1-0 12CO/13CO isotopologue ratio are positively correlated with CO and far infrared (FIR) luminosity. The HCN and HCO+ molecules have very similar intensities and trace the same gas. In galaxies dominated by an active nucleus, HCO+ intensities are depressed relative to HCN intensities. Only a small fraction of the CO emission is directly associated with gas emitting in HCN and HCO, yet a significant fraction of even that gas appears to be translucent molecular gas. In the observed galaxy centers, the HCN/CO line intensity ratio is not a proxy for the dense gas fraction. Likewise, the FIR/HCN and FIR/CO ratios are not proxies for the star formation efficiency. The observed molecular line emission is fully consistent with UV-photon heating boosted by significant mechanical heating. The molecular gas sampled by HCN and HCO+ has low kinetic temperatures T(kin)=10-50 K, low densities n(H)=10^4-10^5 cm^(-3), and low optical depths in the ground-state lines. Most of the gas sampled by CO has densities lower by one to two orders of magnitude. For a mechanical heating fraction of 0.5, a modest energy input of only G=300 Go is required. A proper understanding of star formation requires a more appropriate determination of the gas mass than provided by the intensities of individual HCN or CO transitions., Comment: 19 pages, 11 figures, 8 tables, accepted by Astronomy & Astrophysics
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- 2022
- Full Text
- View/download PDF
8. CCR2 inhibition reduces tumor myeloid cells and unmasks a checkpoint inhibitor effect to slow progression of resistant murine gliomas
- Author
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Thomas J. Schall, Joseph Flores-Toro, Rakesh K. Jain, Matthew R. Sarkisian, James Campbell, Jeffrey K. Harrison, Meenal Datta, Adithya Gopinath, Rajinder Singh, Israel F. Charo, Duane Mitchell, and Defang Luo
- Subjects
CD4-Positive T-Lymphocytes ,Myeloid ,Receptors, CCR2 ,medicine.medical_treatment ,Programmed Cell Death 1 Receptor ,Population ,CX3C Chemokine Receptor 1 ,CD8-Positive T-Lymphocytes ,B7-H1 Antigen ,Mice ,Lymphocytes, Tumor-Infiltrating ,Glioma ,Tumor Microenvironment ,medicine ,Animals ,Humans ,Myeloid Cells ,Gene Knock-In Techniques ,education ,Chemokine CCL2 ,Mice, Knockout ,education.field_of_study ,Tumor microenvironment ,Multidisciplinary ,business.industry ,Myeloid-Derived Suppressor Cells ,Immunotherapy ,Biological Sciences ,medicine.disease ,Survival Analysis ,Mice, Inbred C57BL ,Disease Models, Animal ,medicine.anatomical_structure ,Myeloid-derived Suppressor Cell ,Cancer research ,Bone marrow ,Glioblastoma ,business ,CD8 - Abstract
Immunotherapy directed at the PD-L1/PD-1 axis has produced treatment advances in various human cancers. Unfortunately, progress has not extended to glioblastoma (GBM), with phase III clinical trials assessing anti-PD-1 monotherapy failing to show efficacy in newly diagnosed and recurrent tumors. Myeloid-derived suppressor cells (MDSCs), a subset of immunosuppressive myeloid derived cells, are known to infiltrate the tumor microenvironment of GBM. Growing evidence suggests the CCL2–CCR2 axis is important for this process. This study evaluated the combination of PD-1 blockade and CCR2 inhibition in anti-PD-1–resistant gliomas. CCR2 deficiency unmasked an anti-PD-1 survival benefit in KR158 glioma-bearing mice. CD11b(+)/Ly6C(hi)/PD-L1(+) MDSCs within established gliomas decreased with a concomitant increase in overall CCR2(+) cells and MDSCs within bone marrow of CCR2-deficient mice. The CCR2 antagonist CCX872 increased median survival as a monotherapy in KR158 glioma-bearing animals and further increased median and overall survival when combined with anti-PD-1. Additionally, combination of CCX872 and anti-PD-1 prolonged median survival time in 005 GSC GBM-bearing mice. In both models, CCX872 decreased tumor associated MDSCs and increased these cells within the bone marrow. Examination of tumor-infiltrating lymphocytes revealed an elevated population, increased IFNγ expression, indicating enhanced cytolytic activity, as well as decreased expression of exhaustion markers in CD4(+) and CD8(+) T cells following combination treatment. These data establish that combining CCR2 and PD-1 blockade extends survival in clinically relevant murine glioma models and provides the basis on which to advance this combinatorial treatment toward early-phase human trials.
- Published
- 2019
9. Paisagem Experimental
- Author
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Lucia Maria Sá Antunes Costa and Israel F. Nunes
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General Medicine - Abstract
The links among public space, landscape, and contemporary art are the central theme of this paper. In shaping a landscape design essay for a public park on a silted waterfront in the city of Ilhéus - BA, Brazil, dynamic alter-natives are introduced for the renovation of the public space, based upon the diversification of common uses. The purpose is to build a connection between landscape and art through the re-signification of the natural and cultural processes of the specific site, which may promote a new collective sense of place. The work presents as its theoretical support studies that look at the landscape from its active aspect and discuss the extended field of contemporary art. The paper concludes stressing the importance of the active role of landscape architecture in urban places reconfiguration. Key-Words: Landscape architecture, Urban park, Contemporary Art
- Published
- 2019
10. Efficacy of Chemokine Receptor Inhibition in Treating IL-36α–Induced Psoriasiform Inflammation
- Author
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Ton Dang, Israel F. Charo, Dale Newland, Alice Kumamoto, Vicky Chhina, Thomas J. Schall, Mali Venkat Reddy, Mcmahon Jeffrey P, Karen Ebsworth, Rajinder Singh, Simon Yau, James Campbell, Yu Wang, Shirley Liu, Penglie Zhang, and Linda S. Ertl
- Subjects
Receptors, CCR6 ,T cell ,Immunology ,Anti-Inflammatory Agents ,Inflammation ,C-C chemokine receptor type 6 ,Receptors, Interleukin-8B ,Mice ,03 medical and health sciences ,Chemokine receptor ,0302 clinical medicine ,Immune system ,medicine ,Animals ,Psoriasis ,Immunology and Allergy ,CXC chemokine receptors ,Psoriasiform Dermatitis ,Skin ,Mice, Inbred BALB C ,business.industry ,Dendritic cell ,medicine.anatomical_structure ,medicine.symptom ,business ,Interleukin-1 ,030215 immunology - Abstract
Several types of psoriasiform dermatitis are associated with increased IL-36 cytokine activity in the skin. A rare, but severe, psoriasis-like disorder, generalized pustular psoriasis (GPP), is linked to loss-of-function mutations in the gene encoding IL-36RA, an important negative regulator of IL-36 signaling. To understand the effects of IL-36 dysregulation in a mouse model, we studied skin inflammation induced by intradermal injections of preactivated IL-36α. We found the immune cells infiltrating IL-36α–injected mouse skin to be of dramatically different composition than those infiltrating imiquimod-treated skin. The IL-36α–induced leukocyte population comprised nearly equal numbers of CD4+ αβ T cells, neutrophils, and inflammatory dendritic cells, whereas the imiquimod-induced population comprised γδ T cells and neutrophils. Ligands for chemokine receptors CCR6 and CXCR2 are increased in both GPP and IL-36α–treated skin, which led us to test an optimized small-molecule antagonist (CCX624) targeting CCR6 and CXCR2 in the IL-36α model. CCX624 significantly reduced the T cell, neutrophil, and inflammatory dendritic cell infiltrates and was more effective than saturating levels of an anti–IL-17RA mAb at reducing inflammatory symptoms. These findings put CCR6 and CXCR2 forward as novel targets for a mechanistically distinct therapeutic approach for inflammatory skin diseases involving dysregulated IL-36 signaling, such as GPP.
- Published
- 2019
11. Configurable sublinear circuits for quantum state preparation
- Author
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Israel F. Araujo, Daniel K. Park, Teresa B. Ludermir, Wilson R. Oliveira, Francesco Petruccione, and Adenilton J. da Silva
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FOS: Computer and information sciences ,Quantum Physics ,Computer Science - Emerging Technologies ,TheoryofComputation_GENERAL ,FOS: Physical sciences ,Statistical and Nonlinear Physics ,Theoretical Computer Science ,Electronic, Optical and Magnetic Materials ,Emerging Technologies (cs.ET) ,Modeling and Simulation ,ComputerSystemsOrganization_MISCELLANEOUS ,Signal Processing ,Electrical and Electronic Engineering ,Quantum Physics (quant-ph) - Abstract
The theory of quantum algorithms promises unprecedented benefits of harnessing the laws of quantum mechanics for solving certain computational problems. A persistent obstacle to using such algorithms for solving a wide range of real-world problems is the cost of loading classical data to a quantum state. Several quantum circuit-based methods have been proposed for encoding classical data as probability amplitudes of a quantum state. However, they require either quantum circuit depth or width to grow linearly with the data size, even though the other dimension of the quantum circuit grows logarithmically. In this paper, we present a configurable bidirectional procedure that addresses this problem by tailoring the resource trade-off between quantum circuit width and depth. In particular, we show a configuration that encodes an $N$-dimensional state by a quantum circuit with $O(\sqrt{N})$ width and depth and entangled information in ancillary qubits. We show a proof-of-principle on five quantum computers and compare the results.
- Published
- 2021
- Full Text
- View/download PDF
12. Inflation and factor shares
- Author
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Alcalá Agulló, Francisco, Sancho, Israel F., Universitat Autònoma de Barcelona. Unitat de Fonaments de l'Anàlisi Econòmica, and Institut d'Anàlisi Econòmica
- Subjects
Inflació (Finances) ,Divisió del treball - Abstract
We use results from the literature on the determinants of price-cost margins to derive an equation relating labor's share of national income to the inflation rate (as well as to the output gap, the unemployment rate and the capital stock per worker). The equation is tested with a panel of 15 OECD countries. We obtain a robust positive relationship between inflation and the labor share. Our results suggest that disinflation is not distributively neutral, provide empirical support for the distinct concern about price stability shown by trade unions and employers' organizations, and help explaining the negative impact of inflation on growth.
- Published
- 2021
13. List of Contributors
- Author
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Gregory Aaen, Israel F. Abroms, Ulrika Ådén, Gunnar Ahlsten, Robert B. Aird, Samiah A. Al-Zaidy, Fred Andermann, Banu Anlar, Alexis Arzimanoglou, Stephen Ashwal, Erika Augustine, Karen Ballaban-Gil, Nigel S. Bamford, Charles F. Barlow, Thomas Bast, David Bates, Robert J. Baumann, Enrico Bertini, Alidor Beya, Michael Blaw, John Bodensteiner, Daniel J. Bonthius, Amy E. Brin, Knut Brockmann, John Keith Brown, Stuart B. Brown, Audrey Christine Brumback, Michelle Bureau, James R. Burke, Annie Bye, Carol Camfield, Peter Camfield, Jaume Campistol Plana, Dee James Canale, Onasis Caneris, Roberto H. Caraballo, Alison Chantal Caviness, Hsiao-Tuan Chao, Catherine A. Chapman, Enrique Chaves-Carballo, Yoon-Jae Cho, Hans-Jürgen Christen, Harry T. Chugani, Giovanni Cioni, David Clark, Edward Robert Scheffer Cliff, Frederick B. Cochran, Bruce H. Cohen, Maynard M. Cohen, Kevin Collins, Athanasios Covanis, Macdonald Critchley, J. Helen Cross, Patricia K. Crumrine, Paolo Curatolo, Pamela A. Davies, Gabrielle deVeber, Darryl C. De Vivo, Linda S. de Vries, Liesbeth De Waele, William DeMyer, Anita Devlin, William B. Dobyns, W. Edwin Dodson, Kirsty Donald, Frank H. Duffy, David W. Dunn, Henry G. Dunn, Leon S. Dure, Paul Richard Dyken, Férechté Encha-Razavi, Gerald Erenberg, Melinda L. Estes, Philippe Evrard, Donna Ferriero, Peggy Ferry, Archie Fine, Edward J. Fine, John S. Fine, Richard S. Finkel, Alain Fischer, Christine Fischer, Lance Fogan, Glenn W. Fowler, Yitzchak Frank, Heather J. Fullerton, Tetsuo Furukawa, Ronald S. Gabriel, Aristea S. Galanopoulou, David Gardner-Medwin, Bhuwan Garg, Pierre Genton, Mark S. George, Thierry Gineste, Christopher C. Giza, Nathalie Goemans, Gerald S. Golden, Jeffrey Alan Golden, Gary W. Goldstein, Christopher Gomez, Manuel R. Gomez, Timothy Gomez, Howard P. Goodkin, Neil Gordon, Pierre Gressens, Helmut Groger, Renzo Guerrini, Christina A. Gurnett, Emanuela Gussoni, Richard Haas, Bengt Hagberg, Jerome S. Haller, Adam L. Hartman, Fred Haruda, Deborah Hirtz, Gwendolyn R. Hogan, Guy M. Hunt, Susan T. Iannaccone, Terrie Eleanor Inder, Victor Ionasescu, Katrien Jansen, Yuwu Jiang, Henry J. Kaminski, Shigehiko Kamoshita, Peter B. Kang, David M. Kaufman, Walter E. Kaufmann, Edward M. Kaye, Peter Kellaway, Rhona S. Kelley, Charles Kennedy, Young-Min Kim, Michael Kirby, Adam Kirton, Eliane Kobayashi, Eric H. Kossoff, Michail Koutroumanidis, Lauren Krupp, Bernadette M. Lange, Douglas J. Lanska, Mary Jo Lanska, Paul D. Larsen, Samuel J. Lassoff, John Laterra, Bernard Lemieux, Nicholas J. Lenn, William J. Logan, Elizabeth Lomax, Lawrence D. Longo, A. Lorris Betz, Bala V. Manyam, Warren A. Marks, E. Wayne Massey, Laszlo J. Mate, Ian McKinlay, William T. McLean, Ailsa McLellan, Mark F. Mehler, Johannes C. Melchior, David J. Michelson, Steven P. Miller, Suzanne L. Miller, J. Gordon Millichap, Robert A. Minns, Eli M. Mizrahi, Ann B. Moser, Solomon L. Moshé, Hiltrud Muhle, Francesco Muntoni, Sakkubai Naidu, Vinodh Narayanan, Nardo Nardocci, Jeffrey J. Neil, Ann Neumeyer, Michael J. Noetzel, Yoshiko Nomura, Douglas R. Nordli, Kathryn North, Yoko Ohtsuka, Finbar J.K. O’Callaghan, Roger J. Packer, Gregory M. Pastores, Marc C. Patterson, Phillip L. Pearl, Michel Philippart, Helena S. Pihko, Gordon Piller, Thomas F. Platz, Annapurna Poduri, Michael A. Pollack, Brenda E. Porter, Michèle Provis, Dietz Rating, Harold Reich, Bernd Remler, Jong M. Rho, Peter Richards, Edward P. Richardson, Sylvia O. Richardson, E. Steve Roach, Arthur L. Rose, Marvin P. Rozear, Lucien J. Rubinstein, Robert S. Rust, Arushi Gahlot Saini, Suzanne Saint-Anne Dargassies, Harvey B. Sarnat, Mohammad Sarwar, Richard Satran, Sanford Schneider, Waltraud Schrank, Rodney C. Scott, Syndi Seinfeld, Duygu Selcen, Nenad Sestan, Steven Shapiro, Elliott H. Sherr, Michael Shevell, Lloyd Shield, Richard L. Sidman, Faye S. Silverstein, Michael Sinnreich, O. Carter Snead, Regan Solomons, Emilio Soria-Duran, Carl E. Stafstrom, E. Steven Roach, Harold Stevens, Hans Michael Strassburg, David A. Stumpf, Thomas Sullivan, Herbert M. Swick, Charles N. Swisher, Takao Takahashi, Ingrid Tein, Laura Tochen, Eva E. Thomas, Alan Thompson, Svinder S. Toor, H. Richard Tyler, Peter Uldall, David K. Urion, Ahsan Moosa Naduvil Valappil, Ronald Van Toorn, Jennifer Vermilion, Doris Vidaver, Betty R. Vohr, Brigitte Vollmer, Joseph J. Volpe, Deborah P. Waber, Mark S. Wainwright, Lucius Waites, Christopher Walsh, Adolf Weindl, Mary Anne Whelan, Larry E. White, Vicky Holets Whittemore, Jo Wilmshurst, Elaine Wirrell, Nicole I. Wolf, Paul Youssef, John Zempel, Huda Y. Zoghbi, Sameer M. Zuberi, and Mary Zupanc
- Published
- 2021
14. Sir William Gowers
- Author
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Israel F. Abroms
- Published
- 2021
15. Chemokine receptors (version 2020.5) in the IUPHAR/BPS Guide to Pharmacology Database
- Author
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Joost J. Oppenheim, Robert J. B. Nibbs, Joshua M. Farber, Amanda E. I. Proudfoot, Kouji Matsushima, Alberto Mantovani, Andrew D. Luster, Hisayuki Nomiyama, Osamu Yoshie, Christophe Combadière, Israel F. Charo, Rebecca Hills, Marcus Thelen, Mette M. Rosenkilde, Françoise Bachelerie, Massimo Locati, Antal Rot, Richard Horuk, Amanda M. Burkhardt, Reinhold Förster, Christine A. Power, Mohib Uddin, Alexander Hovard Sparre-Ulrich, Amy E. Monaghan, Philip M. Murphy, Adit Ben-Baruch, Silvano Sozzani, Georgios Leandros Moschovakis, Albert Zlotnik, and Gerard J. Graham
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Chemokine ,Chemokine receptor ,Immune system ,biology ,Downregulation and upregulation ,medicine ,biology.protein ,Inflammation ,Chemotaxis ,medicine.symptom ,Pharmacology ,Ligand (biochemistry) ,Receptor - Abstract
Chemokine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Chemokine Receptors [431, 430, 32]) comprise a large subfamily of 7TM proteins that bind one or more chemokines, a large family of small cytokines typically possessing chemotactic activity for leukocytes. Additional hematopoietic and non-hematopoietic roles have been identified for many chemokines in the areas of embryonic development, immune cell proliferation, activation and death, viral infection, and as antibiotics, among others. Chemokine receptors can be divided by function into two main groups: G protein-coupled chemokine receptors, which mediate leukocyte trafficking, and "Atypical chemokine receptors", which may signal through non-G protein-coupled mechanisms and act as chemokine scavengers to downregulate inflammation or shape chemokine gradients [32].Chemokines in turn can be divided by structure into four subclasses by the number and arrangement of conserved cysteines. CC (also known as β-chemokines; n= 28), CXC (also known as α-chemokines; n= 17) and CX3C (n= 1) chemokines all have four conserved cysteines, with zero, one and three amino acids separating the first two cysteines respectively. C chemokines (n= 2) have only the second and fourth cysteines found in other chemokines. Chemokines can also be classified by function into homeostatic and inflammatory subgroups. Most chemokine receptors are able to bind multiple high-affinity chemokine ligands, but the ligands for a given receptor are almost always restricted to the same structural subclass. Most chemokines bind to more than one receptor subtype. Receptors for inflammatory chemokines are typically highly promiscuous with regard to ligand specificity, and may lack a selective endogenous ligand. G protein-coupled chemokine receptors are named acccording to the class of chemokines bound, whereas ACKR is the root acronym for atypical chemokine receptors [33]. There can be substantial cross-species differences in the sequences of both chemokines and chemokine receptors, and in the pharmacology and biology of chemokine receptors. Endogenous and microbial non-chemokine ligands have also been identified for chemokine receptors. Many chemokine receptors function as HIV co-receptors, but CCR5 is the only one demonstrated to play an essential role in HIV/AIDS pathogenesis. The tables include both standard chemokine receptor names [684] and aliases.
- Published
- 2020
16. Об экспериментальном определении параметров интенсивности 4f-4f-переходов по спектрам излучения соединений европия (III)
- Author
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Tiago Becerra Paolini, Albano N. Carneiro Neto, Israel F. Costa, Oscar L. Malta, Ricardo L. Longo, Lucca Blois, and Hermi F. Brito
- Subjects
Atomic and Molecular Physics, and Optics - Abstract
Eu3+ complexes and specially β-diketonate compounds are well known and studied in several areas due to their luminescence properties, such as sensors and lightning devices. A unique feature of the Eu3+ ion is the experimental determination of the 4f-4f intensity parameters Ωλ directly from the emission spectrum. The equations for determining Ωλ from the emission spectra are different for the detection of emitted power compared to modern equipment that detects photons per second. It is shown that the differences between Ωλ determined by misusing the equations are sizable for Ω4 (ca. 15.5%) for several Eu3+β-diketonate complexes and leads to differences of ca. 5% in the intrinsic quantum yields Q_Ln^Ln. Due to the unique features of trivalent lanthanide ions, such as the shielding of 4f-electrons, which lead to small covalency and crystal field effects, a linear correlation was observed between Ωλ obtained using the emitted power and photon counting equations. We stress that care should be exercised with the type of detection should be taken and provide the correction factors for the intensity parameters. In addition, we suggest that the integrated intensity (proportional to the areas of the emission band) and the centroid (or barycenter) of the transition for obtaining Ωλ should be determined in the properly Jacobian-transformed spectrum in wavenumbers (or energy). Due to the small widths of the emission bands of typical 4f-4f transitions, the areas and centroids of the bands do not depend on the transformation within the experimental uncertainties. These assessments are relevant because they validate previously determined Ωλ without the proper spectral transformation.
- Published
- 2022
17. P0973ALLOSTERIC C-C CHEMOKINE RECEPTOR TYPE 2 (CCR2) INHIBITION IMPROVES RENAL FUNCTION IN A MURINE MODEL OF DIABETIC NEPHROPATHY
- Author
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Zhenhua Miao, James Campbell, Rajinder Singh, Yu Wang, Yibin Zeng, Mcmahon Jeffrey P, Xiaoli Liu, Thomas J. Schall, Shichang Miao, Israel F. Charo, Bin Zhao, Linda S. Ertl, Christopher I. Li, Penglie Zhang, Ton Dang, and Dale Newland
- Subjects
Diabetic nephropathy ,Transplantation ,CCR2 ,Nephrology ,Murine model ,C-C Chemokine Receptor Type 2 ,business.industry ,medicine ,Cancer research ,Renal function ,medicine.disease ,business - Abstract
Background and Aims Diabetic nephropathy (DN) is a syndrome characterized by pathological levels of proteinuria, glomerular lesions and reduction in the glomerular filtration rate (GFR) in diabetic patients. Several lines of evidence support a role of CCR2 in the pathogenesis of DN. Recent studies have demonstrated that existing small molecule CCR2 antagonists can be placed in two classes, distinguished by their interaction with one of two distinct binding sites on CCR2: an extracellular site for which antagonists compete directly with native ligands (the orthosteric site), or an intracellular allosteric binding site. To better understand the functional differences between these antagonists we compared an example of each class in a murine model of DN. Our results revealed that the allosteric, but not the orthosteric CCR2 inhibitors ameliorated the proteinuria and improved glomerular histopathology in this model of DN. Method We used db/db mice to model DN. Several structurally distinct CCR2 inhibitors with that bind to either the allosteric (CCR2-RA-[R] and CCX872) or orthosteric (MK-0812 and CCX598) sites were compared. Pharmacokinetic (PK) properties and renal functional parameters were assessed, including trough drug levels and proteinuria (urinary albumin excretion rate UAER; urine albumin creatinine ratio UACR). Histopathology and electron microscopy (EM) were performed to assess any potential tissue-protective effects of the antagonists. Results Both the allosteric inhibitors (CCR2-RA-[R] and CCX872) and the orthosteric inhibitors (MK-0812 and CCX598) were potent CCR2 antagonists with desirable PK in mouse in so far as both classes effectively blocked CCR2-mediated monocyte migration into the peritoneal cavity in the thioglycollate-induced peritonitis model. At comparable drug coverage levels, CCR2-RA-[R] and CCX872 rapidly and significantly reduced UAER/UACR (CCX872: 70 % at day 7 vs vehicle, p Conclusion Allosteric antagonists of CCR2 provide significant and rapid renal protection in the db/db murine model of DN, as evidenced by improvements in renal function and histological parameters, while potent orthosteric CCR2 antagonists were not effective in the model. Our data suggest that targeting the effectiveness of CCR2 antagonists in DN are directly dependent on binding to the allosteric site of CCR2.
- Published
- 2020
18. P0336INHIBITION C-C CHEMOKINE RECEPTOR TYPE 2 (CCR2) ON ACTIVATED KIDNEY PARIETAL EPITHELIAL CELLS REVEALS A NEW THERAPEUTIC APPROACH FOR CHRONIC KIDNEY DISEASES
- Author
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Thomas J. Schall, Bin Zhao, James Campbell, Yu Wang, Zhenhua Miao, Israel F. Charo, Christopher I. Li, Linda S. Ertl, and Rajinder Singh
- Subjects
Transplantation ,CCR2 ,Kidney ,biology ,business.industry ,animal diseases ,hemic and immune systems ,Inflammation ,Kidney Glomerulus ,medicine.disease ,Beta Chemokine ,Diabetic nephropathy ,Immune system ,medicine.anatomical_structure ,Nephrology ,parasitic diseases ,medicine ,Cancer research ,biology.protein ,medicine.symptom ,Antibody ,business - Abstract
Background and Aims We have recently demonstrated that small molecule inhibitors of CCR2 rapidly reduced proteinuria and preserved renal structure in animal models of diabetic nephropathy (DN) and focal segmental glomerular sclerosis (FSGS). Similar beneficial effects of CCR2 inhibition were also observed in DN patients in a large diabetic nephropathy Phase 2 clinical trial. Despite its rapid and robust effects in these kidney diseases, the mechanism by which CCR2 inhibition affords such renal protection remains unclear. CCR2 is well-known to be expressed on cells of the immune system, where it mediates inflammation and immunological functions by controlling the trafficking of monocytes and T cells. However, immune cell expression of CCR2 may not adequately explain the rapid pharmacologic benefits of CCR2 inhibitors in DN and FSGS because these diseases do not exhibit appreciable kidney inflammation. To better understand the protective mechanism(s) of CCR2 inhibition in renal diseases, we have used a variety of in vivo nephropathy models to determine if CCR2 is expressed on kidney parenchymal cells. Our results suggest that a subset of CD45 negative, renal parietal epithelial cells express CCR2. Method To characterize CCR2 expression in the kidney we used CCR2 RFP heterozygous mice (CCR2RFP/+) in which one copy of CCR2 was replaced by red fluorescent protein (RFP), whose expression is under the control of the endogenous CCR2 promoter. This approach provided a highly sensitive method for CCR2 detection by both flow cytometry and immunofluorescence, and compensated for the lack of validated, commercially available anti-CCR2 antibodies. Enriched glomerular cells were obtained by a non-enzymatic disruption of kidneys, followed by centrifugation at low speed (80gs), and sieving through 300µm and 150µm meshes. The Adriamycin (ADR)-nephropathy model with CCR2 RFP heterozygous mice was used to determine CCR2 expression on renal cells. 5/6 nephrectomy models of FSGS, as well as the db/db diabetic nephropathy model were used to access the change of activated parietal epithelial cells and proteinuria, both in the presence and absence of a CCR2 inhibitor in the setting of kidney injury. Results We observed dramatic increases in the number of activated parietal epithelial cells (PECs, identified as CD133+CD24+CD44hi cells by flow cytometry) in all three renal disease models. In the ADR nephropathy model, we found that in 30-40% of activated PEC cells within an enriched population of glomerular cells expressed CCR2/RFP. CD44hi RFP+ increased much more dramatically than CD44hi RFP- cells in response to ADR, and this was highly correlated with proteinuria, suggesting that CCR2 plays an important role in PEC cell activation and kidney pathology in ADR induced kidney injury. Furthermore, we found that blocking CCR2 with the CCR2-specific antagonist CCX872 significantly reduced both proteinuria and the number of activated PECs in the 5/6 nephropathy and db/db diabetic nephropathy models. Conclusion This is the first report that CCR2 is present on a subset of activated renal PECs. This population is markedly upregulated during kidney injury in a variety of murine models of nephropathy. Changes in the abundance CCR2+ activated PECs in the glomerular enriched preparations in response to CCR2 inhibition suggests that CCR2 antagonism may represent a novel approach for the treatment of chronic kidney disease.
- Published
- 2020
19. Luminescence properties of the Ln–EDTA complexes covalently linked to the chitosan biopolymers containing β-diketonate as antenna ligands
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Israel F. Costa, José G.P. Espínola, Maria C. F. C. Felinto, Ercules E.S. Teotonio, Hermi F. Brito, Wagner M. Faustino, and Gilvan P. Pires
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Luminescence ,Photoluminescence ,Biophysics ,02 engineering and technology ,engineering.material ,Ligands ,Lanthanoid Series Elements ,01 natural sciences ,chemistry.chemical_compound ,Biopolymers ,Coordination Complexes ,Polymer chemistry ,Epichlorohydrin ,Edetic Acid ,Chitosan ,LUMINESCÊNCIA ,Ligand ,010401 analytical chemistry ,Antenna effect ,Ketones ,021001 nanoscience & nanotechnology ,0104 chemical sciences ,chemistry ,Chemistry (miscellaneous) ,Luminescent Measurements ,engineering ,Biopolymer ,0210 nano-technology ,Phosphorescence ,Hybrid material - Abstract
This paper reports on the preparation, characterization, and photoluminescence properties of novel hybrid materials, in which the EDTA-Ln-L complexes (where L: H2 O, acac, bzac, dbm, and tta ligands, and Ln: Eu, Gd, and Tb) were covalently linked to the precursor medium molecular weight chitosan surface (CS) matrices or on the chitosan surfaces previously crosslinked with epichlorohydrin (CSech). The emission spectra of these materials were characterized by intraconfigurational-4fN transitions centred on the Eu3+ and Tb3+ ions. Some broad bands from the polymeric matrix were also observed in the emission spectra, however the relative intensities of the intraconfigurational bands increased significantly for systems containing diketonate ligands when the antenna effect became more efficient. The values of the radiative rates (Arad ) were higher for crosslinked hybrid systems with epichlorohydrin, while nonradiative rates (Anrad ) presented the opposite behaviour. These data contributed to an increase in the values of emission quantum efficiency (η) for crosslinked materials. The effect of the modification process and antenna ligand on the values of intensities, intensity parameters Ω2 e Ω4 of the Eu3+ complexes were also investigated. The results showed that the crosslinked biopolymer surfaces have great potential for applications in molecular devices light converters.
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- 2020
20. A divide-and-conquer algorithm for quantum state preparation
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Adenilton J. da Silva, Israel F. Araujo, Daniel K. Park, and Francesco Petruccione
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Divide and conquer algorithms ,FOS: Computer and information sciences ,Computer Science - Machine Learning ,Speedup ,Quantum machine learning ,Quantum information ,Computer science ,Science ,FOS: Physical sciences ,02 engineering and technology ,Information technology ,01 natural sciences ,Article ,Computational science ,Machine Learning (cs.LG) ,Quantum circuit ,Quantum state ,0103 physical sciences ,0202 electrical engineering, electronic engineering, information engineering ,010306 general physics ,Quantum ,Quantum computer ,Quantum Physics ,Multidisciplinary ,Computer Science::Information Retrieval ,TheoryofComputation_GENERAL ,Qubit ,ComputerSystemsOrganization_MISCELLANEOUS ,Medicine ,020201 artificial intelligence & image processing ,Quantum Physics (quant-ph) ,Qubits - Abstract
Advantages in several fields of research and industry are expected with the rise of quantum computers. However, the computational cost to load classical data in quantum computers can impose restrictions on possible quantum speedups. Known algorithms to create arbitrary quantum states require quantum circuits with depth O(N) to load an N-dimensional vector. Here, we show that it is possible to load an N-dimensional vector with exponential time advantage using a quantum circuit with polylogarithmic depth and entangled information in ancillary qubits. Results show that we can efficiently load data in quantum devices using a divide-and-conquer strategy to exchange computational time for space. We demonstrate a proof of concept on a real quantum device and present two applications for quantum machine learning. We expect that this new loading strategy allows the quantum speedup of tasks that require to load a significant volume of information to quantum devices.
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- 2020
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21. Chemokine receptors (version 2019.5) in the IUPHAR/BPS Guide to Pharmacology Database
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Christophe Combadière, Rebecca Hills, Israel F. Charo, Christine A. Power, Gerard J. Graham, Silvano Sozzani, Joshua M. Farber, Robert J. B. Nibbs, Philip M. Murphy, Osamu Yoshie, Kouji Matsushima, Adit Ben-Baruch, Richard Horuk, Andrew D. Luster, Alberto Mantovani, Amanda E. I. Proudfoot, Massimo Locati, Albert Zlotnik, Hisayuki Nomiyama, Joost J. Oppenheim, Marcus Thelen, Mohib Uddin, Françoise Bachelerie, Reinhold Förster, Amy E. Monaghan, Antal Rot, Georgios Leandros Moschovakis, and Mette M. Rosenkilde
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Chemokine ,Chemokine receptor ,Immune system ,Downregulation and upregulation ,medicine ,biology.protein ,Inflammation ,Chemotaxis ,medicine.symptom ,Biology ,Pharmacology ,Receptor ,Ligand (biochemistry) - Abstract
Chemokine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Chemokine Receptors [426, 425, 32]) comprise a large subfamily of 7TM proteins that bind one or more chemokines, a large family of small cytokines typically possessing chemotactic activity for leukocytes. Additional hematopoietic and non-hematopoietic roles have been identified for many chemokines in the areas of embryonic development, immune cell proliferation, activation and death, viral infection, and as antibiotics, among others. Chemokine receptors can be divided by function into two main groups: G protein-coupled chemokine receptors, which mediate leukocyte trafficking, and "Atypical chemokine receptors", which may signal through non-G protein-coupled mechanisms and act as chemokine scavengers to downregulate inflammation or shape chemokine gradients [32].Chemokines in turn can be divided by structure into four subclasses by the number and arrangement of conserved cysteines. CC (also known as β-chemokines; n= 28), CXC (also known as α-chemokines; n= 17) and CX3C (n= 1) chemokines all have four conserved cysteines, with zero, one and three amino acids separating the first two cysteines respectively. C chemokines (n= 2) have only the second and fourth cysteines found in other chemokines. Chemokines can also be classified by function into homeostatic and inflammatory subgroups. Most chemokine receptors are able to bind multiple high-affinity chemokine ligands, but the ligands for a given receptor are almost always restricted to the same structural subclass. Most chemokines bind to more than one receptor subtype. Receptors for inflammatory chemokines are typically highly promiscuous with regard to ligand specificity, and may lack a selective endogenous ligand. G protein-coupled chemokine receptors are named acccording to the class of chemokines bound, whereas ACKR is the root acronym for atypical chemokine receptors [33]. There can be substantial cross-species differences in the sequences of both chemokines and chemokine receptors, and in the pharmacology and biology of chemokine receptors. Endogenous and microbial non-chemokine ligands have also been identified for chemokine receptors. Many chemokine receptors function as HIV co-receptors, but CCR5 is the only one demonstrated to play an essential role in HIV/AIDS pathogenesis. The tables include both standard chemokine receptor names [675] and aliases.
- Published
- 2019
22. CC chemokine receptor 2 promotes recruitment of myeloid cells associated with insulin resistance in nonalcoholic fatty liver disease
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Thomas J. Schall, Mcmahon Jeffrey P, Richard D. Parker, Chris Corbett, Penglie Zhang, Linda S. Ertl, David H. Adams, Matthew J. Walters, Christopher J. Weston, Dale Newland, Philip N. Newsome, Israel F. Charo, Trageen Baumart, Karen Ebsworth, Rajinder Singh, Zhenhua Miao, James Campbell, and Matthew J. Armstrong
- Subjects
Blood Glucose ,Male ,0301 basic medicine ,CCR2 ,Physiology ,Anti-Inflammatory Agents ,Lipopolysaccharide Receptors ,Adipose tissue ,Monocytes ,0302 clinical medicine ,Non-alcoholic Fatty Liver Disease ,Nonalcoholic fatty liver disease ,Medicine ,Chemokine CCL2 ,CD11b Antigen ,Chemotaxis ,Gastroenterology ,hemic and immune systems ,Middle Aged ,Liver ,Female ,030211 gastroenterology & hepatology ,medicine.symptom ,Mannose Receptor ,Signal Transduction ,Research Article ,Receptors, CCR2 ,CD11c ,Receptors, Cell Surface ,Inflammation ,03 medical and health sciences ,Insulin resistance ,Physiology (medical) ,Animals ,Humans ,Lectins, C-Type ,Glycated Hemoglobin ,Hepatology ,business.industry ,medicine.disease ,Obesity ,CD11c Antigen ,Mice, Inbred C57BL ,Disease Models, Animal ,Mannose-Binding Lectins ,030104 developmental biology ,Cancer research ,Insulin Resistance ,business ,CC chemokine receptors - Abstract
Nonalcoholic fatty liver disease (NAFLD) is a common disease, closely associated with obesity and insulin resistance. We investigated the presence of a subset of myeloid cells associated with metabolic disturbance in the liver of patients with NAFLD and a murine model of obesity-induced liver disease. Gene and protein expression in liver and serum was investigated with RT-PCR or ELISA and correlated to clinical disease. Liver-infiltrating immune cells were isolated from normal or diseased human liver for flow cytometric analysis. In animal experiments, mice were fed a high-fat diet (60% of calories from fat) for 16 wk, or high-fat diet with 30% fructose for 32 wk to induce steatohepatitis and fibrosis. A small molecule inhibitor of CC chemokine receptor 2 (CCR2), CCX872, was administered to some mice. A subset of CD11c+CD206+ immune cells was enriched in human liver tissue, and greater infiltration was observed in NAFLD. The presence of CD11c+CD206+ myeloid cells correlated with systemic insulin resistance. CD11c+CD206+ cells expressed high levels of CCR2, and liver CC chemokine ligand 2 (CCL2) expression was increased in nonalcoholic steatohepatitis and correlated with disease activity. In mice, CCR2 inhibition reduced infiltration of liver CD11b+CD11c+F4/80+ monocytes, which are functional homologs of human CD11c+CD206+ cells, and improved liver injury and glycemic control. A role for CCR2/CCL2 in human NAFLD has long been postulated. These data confirm a role for this chemokine/receptor axis, through mediating adipose and hepatic infiltration of myeloid cells. Inhibition of CCR2 improved hepatic inflammation and fibrosis in murine models of NAFLD. These data confirm the rationale for targeting CCR2 to treat NAFLD. NEW & NOTEWORTHY These data show for the first time that CD11c+CD206+ myeloid cells, previously associated with human adipose tissue inflammation, infiltrate into liver tissue in nonalcoholic fatty liver disease. These cells express CCR2. Inhibition of CCR2 in mice inhibits hepatic inflammation caused by a murine homolog of these myeloid cells and improves experimental liver disease.
- Published
- 2018
23. Abstract 1274: CCX559 is a potent orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity
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Ton Dang, Ashton Easterday, Rajinder Singh, Kathleen Sullivan, Christopher I. Li, Yu Wang, Yibin Zeng, Penglie Zhang, Scamp Ryan J, Christopher S. Lange, Pingchen Fan, Thomas J. Schall, Niky Zhao, Darren Mcmurtrie, Shirley Liu, Ju Yang, Linda S. Ertl, Ryan Ong, Lui Rebecca M, Vicky Chhina, Marta Vilalta, Israel F. Charo, and Alice Kumamoto
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Cancer Research ,biology ,Chemistry ,medicine.drug_class ,T cell ,T-cell receptor ,Monoclonal antibody ,Peripheral blood mononuclear cell ,Immune system ,medicine.anatomical_structure ,Oncology ,Cancer cell ,biology.protein ,medicine ,Cancer research ,Antibody ,PD-L1 inhibitor - Abstract
Introduction: Cancer cells can escape tumor-specific T cell responses via engagement of inhibitory immune checkpoints. PD-L1/PD-1 interaction is one of the major checkpoints that limit effector T cell function against cancer cells, and monoclonal antibodies that block this interaction have been approved as therapies in multiple tumor indications. As a next generation therapy, small molecule inhibitors of PD-L1 potentially have advantageous properties compared to approved monoclonal antibodies, such as better penetration into solid tumors, reduced immunogenicity, lack of Fc-mediated side effects, convenience of oral administration, and lower cost of goods. We therefore embarked on an effort to identify and develop an orally available small molecule capable of targeting PD-L1/PD-1 interactions. Methods: Inhibition of the PD-L1/PD-1 interaction was measured using a binding assay, followed by a cell culture system assessing PD-1 inhibition of T cell receptor (TCR) activation. Human T cell responses were assessed in vitro using the mixed lymphocyte reaction (MLR) assay, and a human peripheral blood mononuclear cell (PBMC)-mediated tumor cell killing assay. For in vivo studies CCX559 was dosed orally in a syngeneic tumor model and in a human tumor cell/PBMC co-implantation model in immune deficient mice. Results: Using structural information and focused medicinal chemistry, we identified CCX559 as a potent inhibitor of PD-L1 interaction with PD-1. CCX559 prevented PD-L1/PD-1 inhibition of TCR signaling in a cell-based reporter assay, increased IFNγ secretion in allogeneic MLR assays, and increased tumor cell killing by human PBMCs. We demonstrated that CCX559 potentially employs multiple mechanisms to inhibit PD-L1, which are distinct from those published for human anti-PD-L1 antibodies. In murine tumor models, orally administered CCX559 reduced tumor growth similarly to a clinically-approved anti-human PD-L1 antibody. Summary: CCX559 is a highly potent, small molecule PD-L1 inhibitor that can be orally administered. CCX559 enhanced primary human T cell activity in vitro and demonstrated anti-tumor efficacy in two murine tumor models. Based on its unique mechanism of PD-L1 inhibition, strong anti-tumor activity, desirable drug properties, and good safety profile, we plan to advance CCX559 into clinical development in the first half of 2021. Citation Format: Chris Li, Marta Vilalta, Linda S. Ertl, Yu Wang, Yibin Zeng, Pingchen Fan, Christopher Lange, Darren McMurtrie, Ju Yang, Rebecca Lui, Ryan Scamp, Vicky Chhina, Alice Kumamoto, Ryan Ong, Ton Dang, Ashton Easterday, Niky Zhao, Shirley Liu, Rajinder Singh, Israel Charo, Kathleen Sullivan, Thomas J. Schall, Penglie Zhang. CCX559 is a potent orally-administered small molecule PD-L1 inhibitor that induces anti-tumor immunity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 1274.
- Published
- 2021
24. The effect of variety and sowing date on the growth, development, yield and quality of common buckwheat (Fagopyrum esculentum Moench)
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Israel F. N. Domingos and Paul E. Bilsborrow
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0106 biological sciences ,biology ,Soil Science ,Sowing ,Growing season ,04 agricultural and veterinary sciences ,Plant Science ,biology.organism_classification ,01 natural sciences ,Crop ,Pseudocereal ,Agronomy ,Yield (wine) ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,Gluten free ,Quadrat ,Agronomy and Crop Science ,Fagopyrum ,010606 plant biology & botany - Abstract
The pseudocereal buckwheat (Fagopyrum species) has a wide range of agronomic and health benefits that make it a promising crop for sustainable agricultural production. Buckwheat is gluten free and has been shown to provide health benefits beyond basic nutrition. This study examined the effect of sowing date on growth, development, yield and nutritional quality of the varieties Bamby and Cebelica over 3 growing seasons (2016−18) in north-east England. The low grain yield of 0.77 t ha−1 (average across varieties, sowing date and season) was associated with a prolonged growing season (150–190 days) in the cool temperate climate of north-east England. The highest grain yield of 1.42 t ha−1 was achieved from the variety Bamby in 2017 although there was no significant effect of variety or sowing date on grain yield. The average quadrat grain yield of 1.63 t ha-1 (based on quadrat sampling) was much higher than the average combine yield and likely reflects significant seed losses at harvest attributable to the very small seed and asynchronous crop ripening/maturity. The average protein 15.2 %, Fe of 104.5–138.7 mg kg−1 and Zn (average of 31.3 mg kg−1) concentrations are generally higher than those reported for the major cereals. Late sowing resulted in a large 7.5-fold decline in total antioxidants with the highest concentration (5165.5 μg g-1) found in the variety Bamby sown in mid-April. Buckwheat has clear potential for production in the organic and low-input sectors in northern England if the significant seed losses at harvest can be avoided as there is increased market demand for gluten-free products helping promote human health.
- Published
- 2021
25. PROTOCOL: Agronomic biofortification strategies to increase grain zinc concentrations for improved nutritional quality of wheat, maize and rice: a systematic review
- Author
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Zed Rengel, Carlo Leifert, Ismail Cakmak, Paul E. Bilsborrow, Gavin B. Stewart, Israel F. N. Domingos, and Marcin Barański
- Subjects
0106 biological sciences ,Protocol (science) ,business.industry ,Biofortification ,General Social Sciences ,chemistry.chemical_element ,04 agricultural and veterinary sciences ,Nutritional quality ,Zinc ,Biology ,01 natural sciences ,Biotechnology ,lcsh:Social Sciences ,lcsh:H ,chemistry ,040103 agronomy & agriculture ,0401 agriculture, forestry, and fisheries ,business ,010606 plant biology & botany - Published
- 2017
26. Chemokine receptors (version 2019.4) in the IUPHAR/BPS Guide to Pharmacology Database
- Author
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Andrew D. Luster, Mette M. Rosenkilde, Christophe Combadière, Kouji Matsushima, Rebecca Hills, Alberto Mantovani, Albert Zlotnik, Amanda E. I. Proudfoot, Richard Horuk, Joshua M. Farber, Israel F. Charo, Silvano Sozzani, Françoise Bachelerie, Hisayuki Nomiyama, Reinhold Förster, Osamu Yoshie, Massimo Locati, Christine A. Power, Philip M. Murphy, Marcus Thelen, Antal Rot, Adit Ben-Baruch, Joost Oppenheim, Amy E. Monaghan, Georgios Leandros Moschovakis, Gerard J. Graham, and Robert J. B. Nibbs
- Subjects
Chemokine ,Chemokine receptor ,Immune system ,biology ,Downregulation and upregulation ,medicine ,biology.protein ,Inflammation ,Chemotaxis ,medicine.symptom ,Pharmacology ,Ligand (biochemistry) ,Receptor - Abstract
Chemokine receptors (nomenclature as agreed by the NC-IUPHAR Subcommittee on Chemokine Receptors [417, 416, 31]) comprise a large subfamily of 7TM proteins that bind one or more chemokines, a large family of small cytokines typically possessing chemotactic activity for leukocytes. Additional hematopoietic and non-hematopoietic roles have been identified for many chemokines in the areas of embryonic development, immune cell proliferation, activation and death, viral infection, and as antibiotics, among others. Chemokine receptors can be divided by function into two main groups: G protein-coupled chemokine receptors, which mediate leukocyte trafficking, and "Atypical chemokine receptors", which may signal through non-G protein-coupled mechanisms and act as chemokine scavengers to downregulate inflammation or shape chemokine gradients [31].Chemokines in turn can be divided by structure into four subclasses by the number and arrangement of conserved cysteines. CC (also known as β-chemokines; n= 28), CXC (also known as α-chemokines; n= 17) and CX3C (n= 1) chemokines all have four conserved cysteines, with zero, one and three amino acids separating the first two cysteines respectively. C chemokines (n= 2) have only the second and fourth cysteines found in other chemokines. Chemokines can also be classified by function into homeostatic and inflammatory subgroups. Most chemokine receptors are able to bind multiple high-affinity chemokine ligands, but the ligands for a given receptor are almost always restricted to the same structural subclass. Most chemokines bind to more than one receptor subtype. Receptors for inflammatory chemokines are typically highly promiscuous with regard to ligand specificity, and may lack a selective endogenous ligand. G protein-coupled chemokine receptors are named acccording to the class of chemokines bound, whereas ACKR is the root acronym for atypical chemokine receptors [32]. There can be substantial cross-species differences in the sequences of both chemokines and chemokine receptors, and in the pharmacology and biology of chemokine receptors. Endogenous and microbial non-chemokine ligands have also been identified for chemokine receptors. Many chemokine receptors function as HIV co-receptors, but CCR5 is the only one demonstrated to play an essential role in HIV/AIDS pathogenesis. The tables include both standard chemokine receptor names [657] and aliases.
- Published
- 2019
27. FP017Critical Equilibrium between CCL2 Secretion and Its Constitutive Re-Uptake by CCR2: An Elegant Mechanism for Regulating CCL2 Levels in the Blood
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Israel F. Charo, Penglie Zhang, Ton Dang, Thomas J. Schall, Niky Zhao, Rajinder Singh, Linda S. Ertl, James Campbell, Yu Wang, and Simon Yau
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Transplantation ,CCR2 ,Nephrology ,business.industry ,Medicine ,Secretion ,CCL2 ,business ,Mechanism (sociology) ,Cell biology - Published
- 2019
28. FP240CCR2 INHIBITION IMPROVES RENAL FUNCTION IN MURINE MODELS OF CHRONIC KIDNEY DISEASE
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Israel F. Charo, Penglie Zhang, Simon Yau, Xiaoli Liu, Ton Dang, Dale Newland, Bin Zhao, James Campbell, Xiaoping Zang, Yu Wang, Yibin Zeng, Rajinder Singh, Mcmahon Jeffrey P, Zhenhua Miao, Linda S. Ertl, Antoni Krasinski, Thomas J. Schall, and Shichang Miao
- Subjects
Transplantation ,medicine.medical_specialty ,Nephrology ,business.industry ,Urology ,Medicine ,Renal function ,business ,medicine.disease ,Kidney disease - Published
- 2019
29. CCR2 deficiency alters activation of microglia subsets in traumatic brain injury
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Gina Benedetto, Isabella Imhof, Brian T. Wipke, Mary C. Nakamura, Huy Tran, Luyi Li, Walter L. Eckalbar, Israel F. Charo, Chun Jimmie Ye, James Campbell, Michael Craft, Eréne C. Niemi, Christine L. Hsieh, Gabriela Schmajuk, Stefka Gyoneva, Kerri Somebang, Luke Jandreski, Iris Lo, Judy K. Shigenaga, T. Michael Gill, Brian A. Zabel, Joshua Rudolph, S. Scott Panter, and Edward D. Plowey
- Subjects
Traumatic ,Male ,CCR2 ,Myeloid ,Interferon Regulatory Factor-7 ,Medical Physiology ,microglia ,Inbred C57BL ,Monocytes ,neuroinflammation ,Mice ,Receptors ,Brain Injuries, Traumatic ,2.1 Biological and endogenous factors ,Antigens, Ly ,Aetiology ,Biology (General) ,innate immunity ,Mice, Knockout ,Microglia ,traumatic brain injury ,Brain ,medicine.anatomical_structure ,Interferon Type I ,medicine.symptom ,Physical Injury - Accidents and Adverse Effects ,Traumatic brain injury ,QH301-705.5 ,Receptors, CCR2 ,Knockout ,Down-Regulation ,Brain damage ,Traumatic Brain Injury (TBI) ,General Biochemistry, Genetics and Molecular Biology ,single-cell RNA sequencing ,Article ,medicine ,Genetics ,Animals ,Humans ,dendritic cells ,Antigens ,Maze Learning ,Neuroinflammation ,Traumatic Head and Spine Injury ,business.industry ,Animal ,Monocyte ,Macrophages ,Neurosciences ,Dendritic cell ,medicine.disease ,Brain Disorders ,Chemokine CXCL10 ,Mice, Inbred C57BL ,Disease Models, Animal ,Ly ,nervous system ,Brain Injuries ,Immunology ,Disease Models ,Biochemistry and Cell Biology ,business ,type I IFN - Abstract
SUMMARY In traumatic brain injury (TBI), a diversity of brain resident and peripherally derived myeloid cells have the potential to worsen damage and/or to assist in healing. We define the heterogeneity of microglia and macrophage phenotypes during TBI in wild-type (WT) mice and Ccr2−/− mice, which lack macrophage influx following TBI and are resistant to brain damage. We use unbiased single-cell RNA sequencing methods to uncover 25 microglia, monocyte/macrophage, and dendritic cell subsets in acute TBI and normal brains. We find alterations in transcriptional profiles of microglia subsets in Ccr2−/− TBI mice compared to WT TBI mice indicating that infiltrating monocytes/macrophages influence microglia activation to promote a type I IFN response. Preclinical pharmacological blockade of hCCR2 after injury reduces expression of IFN-responsive gene, Irf7, and improves outcomes. These data extend our understanding of myeloid cell diversity and crosstalk in brain trauma and identify therapeutic targets in myeloid subsets., Graphical Abstract, In brief By single-cell RNA sequencing of traumatically injured and normal brains from wild-type and Ccr2−/− mice, Somebang et al. define microglia, macrophage, and dendritic cell phenotypes in TBI. Targeting mouse and/or human CCR2 reduces specific TBI brain CNS myeloid compartments, dampens type I interferon responses, and improves cognition after TBI.
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- 2019
30. CCR2 Inhibition Reduces Tumor‐Associated Myeloid‐Derived Suppressor Cells and Unmasks an α‐PD‐1 Effect to Slow Tumor Progression in Checkpoint Inhibitor Resistant Gliomas
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James Campbell, Adithya Gopinath, Joseph Flores-Toro, Defang Luo, Rajinder Singh, Jeffrey L. Harrison, Duane Mitchell, Thomas J. Schall, and Israel F. Charo
- Subjects
CCR2 ,business.industry ,Immune checkpoint inhibitors ,medicine.disease ,Biochemistry ,nervous system diseases ,Tumor progression ,Genetics ,Cancer research ,Myeloid-derived Suppressor Cell ,Medicine ,business ,Molecular Biology ,Biotechnology ,Glioblastoma - Abstract
INTRODUCTION Immuno-therapy directed at the PD-1/PD-L1 axis has yielded significant treatment advances in various human cancers. However, these outcomes have not extended to glioblastoma (GBM), wit...
- Published
- 2019
31. CCL7 Is a Negative Regulator of Cutaneous Inflammation Following Leishmania major Infection
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Jean K. Lim, Kihong Lim, Deborah J. Fowell, Susana V. Bardina, Israel F. Charo, Jill Ford, Wuyuan Lu, and Angela Hughson
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lcsh:Immunologic diseases. Allergy ,0301 basic medicine ,CCR1 ,skin ,endocrine system ,CCR2 ,Chemokine ,Neutrophils ,Chemokine CXCL2 ,Immunology ,Gene Expression ,Leishmaniasis, Cutaneous ,Inflammation ,macrophage ,Biology ,CCL7 ,Statistics, Nonparametric ,Mice ,03 medical and health sciences ,0302 clinical medicine ,Immune system ,Cell Movement ,medicine ,Animals ,Immunology and Allergy ,Leishmania major ,Chemokine CCL7 ,Original Research ,Mice, Knockout ,Analysis of Variance ,Mice, Inbred BALB C ,Innate immune system ,chemokine ,Interleukin-17 ,biology.organism_classification ,3. Good health ,Mice, Inbred C57BL ,030104 developmental biology ,Neutrophil Infiltration ,parasite ,biology.protein ,medicine.symptom ,lcsh:RC581-607 ,030215 immunology - Abstract
The chemokine CCL7 (MCP3) is known to promote the recruitment of many innate immune cell types including monocytes and neutrophils to sites of bacterial and viral infection and eosinophils and basophils to sites of allergic inflammation. CCL7 upregulation has been associated with many inflammatory settings including infection, cardiovascular disease, and the tumor microenvironment. CCL7's pleotropic effects are due in part to its ability to bind numerous chemokine receptors, namely CCR1, CCR2, CCR3, CCR5, and CCR10. CCL7-blockade or CCL7-deficiency is often marked by decreased inflammation and poor pathogen control. In the context of Leishmania major infection, CCL7 is specifically upregulated in the skin one-2 weeks after infection but its role in L. major control is unclear. To determine CCL7's impact on the response to L. major we infected WT and CCL7−/− C57BL/6 mice. L. major infection of CCL7-deficient mice led to an unexpected increase in inflammation in the infected skin 2 weeks post-infection. A broad increase in immune cell subsets was observed but was dominated by enhanced neutrophilic infiltration. Increased neutrophil recruitment was associated with an enhanced IL-17 gene profile in the infected skin. CCL7 was shown to directly antagonize neutrophil migration in vitro and CCL7 add-back in vivo specifically reduced neutrophil influx into the infected skin revealing an unexpected role for CCL7 in limiting neutrophil recruitment during L. major infection. Enhanced neutrophilic infiltration in CCL7-deficient mice changed the balance of L. major infected host cells with an increase in the ratio of infected neutrophils over monocytes/macrophages. To determine the consequence of CCL7 deficiency on L. major control we analyzed parasite load cutaneously at the site of infection and viscerally in the draining LN and spleen. The CCL7−/− mice supported robust cutaneous parasite control similar to their WT C57BL/6 counterparts. In contrast, CCL7-deficiency led to greater parasite dissemination and poor parasite control in the spleen. Our studies reveal a novel role for CCL7 in negatively regulating cutaneous inflammation, specifically neutrophils, early during L. major infection. We propose that CCL7-mediated dampening of the early immune response in the skin may limit the ability of the parasite to disseminate without compromising cutaneous control.
- Published
- 2019
32. Tuning emitting color of electroluminescent devices containing Tris(2-acyl-1,3-indandionate)aluminum(III) complexes as emitting layers
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Hermi F. Brito, Rian E. Aderne, Maria C. F. C. Felinto, Marco Cremona, Ercules E.S. Teotonio, Wagner M. Faustino, Israel F. Costa, Harold C. Avila, and Jandeilson de Lima Moura
- Subjects
chemistry.chemical_classification ,LUMINESCÊNCIA ,Materials science ,Absorption spectroscopy ,General Chemistry ,Electroluminescence ,Acceptor ,Coordination complex ,chemistry ,OLED ,Physical chemistry ,Fourier transform infrared spectroscopy ,Thermal analysis ,Luminescence - Abstract
In this study, a novel type of tris(2-acyl-1,3-indandione)-aluminum(III) coordination compounds of the general formula [Al(acind)3]H2O, where 2-acyl-1,3-indandione (acind), 2-acetyl-1,3-indandione (aind), 2-benzoyl-1,3-indandione (bind), and 4-methyl-2-benzoyl-1,3-indandione (mbind), were synthesized and characterized by elemental analysis (CHN), Fourier transform infrared (FTIR) and nuclear magnetic resonance (1H NMR) spectroscopies, thermal analysis (TG/DTG and DTA), and optical absorption spectroscopy in the UV-Vis region. These compounds present remarkably high green luminescence in powder and in thin-film forms. However, when these compounds are applied in glass/ITO/β-NPB/spiro-2CBP/[Al(acind)3]/Al and glass/ITO/β-NPB/[Al(acind)3]/LiF/Al electroluminescent devices, where spiro-2CBP is 2,7-bis(carbazol-9-yl)-9,9-spirobifluorene and β-NPB is N,N’-bis(naphthalen-2-yl)-N,N’-bis(phenyl)-benzidine, the emission color tuned from green to red, reflecting a change from the direct charge recombination in the emitting layer of the [Al(acind)3] complexes to an exciplex-based emission in which [Al(acind)3] complexes and spiro 2-CBP acted as acceptor and donor, respectively. These results suggest that [Al(acind)3] complexes have potential applications as molecular light converter materials for fabricating new electroluminescent devices.
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- 2019
33. Experimental and theoretical investigations of the [Ln(β-dik)(NO3)2(phen)2]⋅H2O luminescent complexes
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Israel F. Costa, Iran F. da Silva, Paulo R.S. Santos, Oscar L. Malta, Albano N. Carneiro Neto, Ercules E.S. Teotonio, Renata Diniz, Dariston K. S. Pereira, Maria Helena Araujo, Hermi F. Brito, Renaldo T. Moura, and Wagner M. Faustino
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chemistry.chemical_classification ,Thermogravimetric analysis ,Quenching (fluorescence) ,Materials science ,Biophysics ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Biochemistry ,Atomic and Molecular Physics, and Optics ,0104 chemical sciences ,Coordination complex ,chemistry ,Elemental analysis ,Physical chemistry ,Experimental methods ,Fourier transform infrared spectroscopy ,0210 nano-technology ,Luminescence ,Monoclinic crystal system - Abstract
In this work, the coordination compounds presenting the formulas [Eu(acac)(NO3)2 (phen)2]⋅H2O (Eu1) and [Eu(bzac)(NO3)2(phen)2]⋅H2O (Eu2), acac: acetylacetonate, bzac: benzoylacetonate and, phen: 1,10-phenantroline, were successfully synthesized and some spectroscopic properties were investigated by theoretical and experimental methods. These compounds were characterized via elemental analysis, FTIR spectroscopy and thermogravimetric analysis (TGA). The X-ray diffraction data revealed that the compound Eu1 crystallizes in the monoclinic space group P2/n. Spectroscopic data showed that ligand-to-metal charge transfer states (LMCT) in the [Eu(β-dik)(NO3)2(phen)2]⋅H2O complexes (β-dik: acac or bzac) are redshift as compared with [Eu(β-dik)3(phen)] complexes. These data showed that LMCT states play the most important role on the luminescence quenching in the complexes Eu1 and Eu2, which only exhibit high luminescence intensities at low temperatures. Furthermore, the role of changes in the chemical environment on the intensity parameters Ωλ (λ = 2 and 4) have been investigated from the theoretical point of view for the complexes Eu1 to Eu2, and from these to tris β–dik complexes. Interestingly, the theoretical intensity parameters ratio Ω2/Ω4 calculated are in a good agreement with those experimental ones.
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- 2020
34. Luminescent hybrid materials functionalized with lanthanide ethylenodiaminotetraacetate complexes containing β-diketonate as antenna ligands
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Wagner M. Faustino, Franklin P. Aguiar, Jandeilson de Lima Moura, Hermi F. Brito, José G.P. Espínola, Ercules E.S. Teotonio, Maria C. F. C. Felinto, Israel F. Costa, and Tiago Becerra Paolini
- Subjects
Lanthanide ,Materials science ,Photoluminescence ,FOTOLUMINESCÊNCIA ,Silica gel ,Inorganic chemistry ,Biophysics ,Phosphor ,02 engineering and technology ,General Chemistry ,010402 general chemistry ,021001 nanoscience & nanotechnology ,Condensed Matter Physics ,01 natural sciences ,Biochemistry ,Atomic and Molecular Physics, and Optics ,0104 chemical sciences ,chemistry.chemical_compound ,chemistry ,Intramolecular force ,Polymer chemistry ,Molecule ,0210 nano-technology ,Hybrid material ,Luminescence - Abstract
Three organic–inorganic hybrid materials based on silica gel functionalized with (3-aminopropyl)trimethoxysilane (APTS), [3-(2-aminoetilamino)-propil]-trimetoxissilano (DAPTS) and 3-[2-(2-aminoetilamino)etilamino] propiltrimetoxysilane (TAPTS) and subsequently modified with EDTA derivative were prepared by nonhomogeneous route and were then characterized. The resulting materials named SilXN-EDTA (X=1 for APTS, 2 for DAPTS and 3 for TAPTS) were used to obtain new lanthanide Ln3+-β-diketonate (Ln3+=Eu3+, Gd3+ and Tb3+) complexes covalently linked to the functionalized silica gel surfaces (named SilXN-EDTALn-dik, dik=tta, dbm, bzac and acac). The photophysical properties of the new luminescent materials were investigated and compared with those with similar system presenting water molecules coordinated to the lanthanide ions, SilXN-EDTALn-H2O. The SilXN-EDTAEu-dik and SilXN-EDTATb-dik systems displayed characteristic red and green luminescence when excited by UV radiation. Furthermore, the quantitative results showed that the emission quantum efficiency (η), experimental intensity parameters Ω2 and Ω4, and Einstein's emission coefficient (A0J) of the SilXN-EDTAEu-dik materials were largely dependent on the ligands. Based on the luminescence data, the most efficient intramolecular energy transfer processes were found to the SilXN-EDTAEu-dik (dik: tta and dbm) and SilXN-EDTATb-acac materials, which exhibited more pure emission colors. These materials are promising red and green phosphors, respectively.
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- 2016
35. Abstract 5693: Anti-tumor effect of orally available small molecule PD-L1 inhibitors in a murine model of colon adenocarcinoma
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Thomas J. Schall, Ashton Easterday, Christopher S. Lange, Pingchen Fan, Shirley Liu, Rajinder Singh, Penglie Zhang, Ton Dang, Yu Wang, Linda S. Ertl, Marta Vilalta, Yibin Zeng, Israel F. Charo, Simon Yau, Shijie 'Chris' Li, Alice Kumamoto, Ju Yang, Darren Mcmurtrie, Ryan Ong, Lui Rebecca M, and Vicky Chhina
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Cancer Research ,Tumor microenvironment ,biology ,Chemistry ,medicine.medical_treatment ,Peripheral blood mononuclear cell ,Immune checkpoint ,Immune system ,Oncology ,Cancer immunotherapy ,In vivo ,PD-L1 ,biology.protein ,Cancer research ,medicine ,Antibody - Abstract
Introduction: Antibody-based therapies targeting the Programmed cell Death-1/ Programmed Death-Ligand 1 (PD-1/PD-L1) immune checkpoint axis have achieved great success in cancer immunotherapy in recent years. As a next generation therapy, small molecule inhibitors of PD-1/PD-L1 offer the potential for increased tumor penetration, shorter half-life (to better manage immune related adverse events), and lower cost. We therefore embarked on an effort to identify and develop orally available small molecules capable of targeting PD-L1. Methods: We designed and optimized a number of small molecule PD-L1 inhibitors which potently disrupted the interaction of PD-1 with PD-L1. Active compounds were first profiled by an ELISA assay measuring inhibition of the PD-1/PD-L1 interaction, followed by a functional cell-based reporter assay, mixed lymphocyte reaction (MLR) assay, and human peripheral blood mononuclear cell (PBMC)-mediated tumor cell killing assay. Targeted medicinal chemistry efforts were employed to improve potency and oral bioavailability, and candidate compounds were then evaluated in murine tumor models. Due to the specific reactivity of these compounds to human PD-L1 (but not murine PD-L1), a syngeneic tumor model with murine MC-38 colon tumor cells expressing human PD-L1 (MC38-hPD-L1 tumor model) was used. Results: The optimized PD-L1 inhibitors were highly potent in cell-based reporter assay, the MLR assay and PBMC-mediated tumor cell killing assays. These compounds also possess high oral bioavailability and desirable safety profiles. In the MC38-hPD-L1 tumor model, Lead compounds potently reduced tumor growth similarly to an anti-human PD-L1 antibody, which was used as a positive control for the experiments. The tumor microenvironment analysis by flow cytometry demonstrated that these compounds almost completely occupied human PD-L1 on the tumor cells in vivo, and thus could potently block the interaction of PD-1/PD-L1 and enhance the immune responses against tumor. Summary: We have identified and advanced unique small molecule inhibitors of human PD-L1 by rational design and optimization. Molecules resulting from these efforts exhibited marked inhibition of the PD-1/PD-L1 interaction and signaling in vitro, and potent anti-tumor effects in an animal model. Citation Format: Shijie "Chris" Li, Marta Vilalta, Linda S. Ertl, Yu Wang, Yibin Zeng, Pingchen Fan, Christopher Lange, Darren McMurtrie, Ju Yang, Rebecca Lui, Ryan Ong, Vicky Chhina, Alice Kumamoto, Simon Yau, Ton Dang, Ashton Easterday, Shirley Liu, Rajinder Singh, Israel Charo, Thomas J. Schall, Penglie Zhang. Anti-tumor effect of orally available small molecule PD-L1 inhibitors in a murine model of colon adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 5693.
- Published
- 2020
36. Antagonists of chemokine receptor CCR9 synergize with anti-TNFα immunotherapy to reduce inflammation in the MDR1a−/− mouse model of colitis
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James J Campbell, Linda S Ertl, Karen J Ebsworth, Jeffrey P McMahon, Penglie J Zhang, Vicky J Chhina, Israel F Charo, and Thomas J Schall
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Immunology ,Immunology and Allergy - Abstract
The development of anti-TNFα immunotherapies has led to great advances in quality of life for Crohn’s and colitis patients, and has allowed a reduction in steroid use for these diseases. However, a significant proportion of IBD patients is resistant to anti-TNFα agents, or becomes resistant over time. Preclinical research and clinical trials suggest that CCR9 antagonism can effectively reduce colon inflammation. CCR9 is expressed on a subset of T cells dedicated to intestinal trafficking. Antagonism of this receptor inhibits the accumulation of T cells within inflamed intestinal epithelium and lamina propria. Since anti-TNFα and CCR9 antagonists act through entirely different mechanisms, we asked whether these two approaches might synergize and expand the effectiveness and scope of each therapy. We used a piroxicam-accelerated version of the MDR1a−/− spontaneous colitis model in mice. We have found that combined dosing of piroxicam-fed MDR1a−/− mice with a CCR9 antagonist and an anti-TNFα MAb significantly reverses loss of body weight, diarrhea score and colon inflammation. The combined dosing was more effective than anti-TNFα or CCR9 antagonist alone, as measured by colon length/weight ratio, neutrophil accumulation in the colonic epithelium and reversal of the loss in body weight characteristic of this model. These data suggest that combining a CCR9 antagonist with existing anti-TNFα treatment regimens may extend the benefits of anti-TNFα immunotherapy to a larger class of patients suffering from IBD, and may prolong the effectiveness of anti-TNFα immunotherapy for those patients already undergoing such treatments.
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- 2020
37. Is planting trees the solution to reducing flood risks?
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Nik Nur Azwanida Binti Zakaria, Thilanka Kumari Ranathunga Ranathunga Mudiyanselage, Steven James Banks, Elisa Lopez-Capel, David Hodgson, Matthew Grainger, Beth Clark, Friederike C. Bolam, Jake Cowton, Enas Sufar, Gultakin Hasanaliyeva, Ian George Merrell, Hassan Ashraa Kalee, Jayne Carrick, Cosmos Adjei, Garima Gupta, David Duba Golicha, Carl Warren Charles Samuel, Mwanajuma Salim Othman, Israel F. N. Domingos, Idiegberanoise Oikeh, Ivone Maritza Campos Luna, Amelia Magistrali, Gavin B. Stewart, Mohd Shaiful Azman Bin Abdul Rahim, and Philip Alexander Watson
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Environmental Engineering ,020205 medical informatics ,Flood myth ,Tree planting ,0208 environmental biotechnology ,Geography, Planning and Development ,Bayesian network ,Forestry ,02 engineering and technology ,020801 environmental engineering ,0202 electrical engineering, electronic engineering, information engineering ,Environmental science ,Tree cover ,Safety, Risk, Reliability and Quality ,Water Science and Technology - Published
- 2018
38. IMMU-51. THE COMBINATION OF CCR2 ANTAGONIST AND PD-1 BLOCKADE PROLONGS SURVIVAL IN IMMUNE CHECKPOINT INHIBITOR RESISTANT GLIOMAS
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Adithya Gopinath, Thomas J. Schall, James Campbell, Rajinder Singh, Joseph Flores-Toro, Jeffrey L. Harrison, Defang Luo, and Israel F. Charo
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Cancer Research ,Tumor microenvironment ,business.industry ,Immune checkpoint inhibitors ,Cancer ,medicine.disease ,Abstracts ,Chemokine receptor ,medicine.anatomical_structure ,Oncology ,Glioma ,Macrophage-1 antigen ,Myeloid-derived Suppressor Cell ,Cancer research ,Medicine ,Neurology (clinical) ,Bone marrow ,business - Abstract
INTRODUCTION: Immuno-therapy directed at the PD-1/PD-L1 axis has produced significant treatment advances in various human cancers. Unfortunately, this progress has not extended to glioblastoma, with recent clinical trials failing to show efficacy of anti-PD-1 monotherapy in recurrent tumors. Commonly employed murine glioma models exhibit varied responsiveness to anti-PD-1 monotherapy, e.g. GL261 gliomas are sensitive while KR158 tumors are resistant. Previously, we reported that combining PD-1 blockade with either chemokine receptor CCR2 deficiency or a CCR2 antagonist improved survival over anti-PD-1 monotherapy in GL261 gliomas. This was associated with reduced numbers of MDSCs within tumors. The current study evaluated the combination of PD-1 blockade and a novel CCR2 antagonist in anti-PD-1 resistant gliomas. OBJECTIVE: Determine if combination anti-PD-1/CCR2 antagonist therapy is an effective treatment in anti-PD-1 insensitive gliomas. METHODS: Overall survival and immune cell characteristics were determined in KR158 and 005GSC gliomas established in either CCR2 deficient or wild type mice treated with CCR2 antagonist (CCX872) and/or PD-1 blockade. RESULTS: CCR2 deficiency unmasked an anti-PD-1 survival benefit in KR158 glioma-bearing mice. CCX872 increased median survival as a monotherapy in KR158 tumor-bearing animals, and significantly increased median and durable overall survival when combined with anti-PD-1. In 005GSC tumors, the combination of CCX872 and anti-PD-1 prolonged median survival time. Increases in overall CCR2(+) cells and CD11b(+)/Ly6C(hi) myeloid derived suppressor cells (MDSC, known to be CCR2(+)) were evident in the bone marrow of CCR2-deficient mice. Additionally, these mice exhibited decreased MDSCs within established gliomas. The data demonstrate CCX872/anti-PD-1 synergize to increase survival in clinically relevant glioma models via reduced MDSC infiltration, resulting in a tumor microenvironment favorable for anti-PD-1 efficacy. CONCLUSION: The combination of CCX872 and anti-PD-1 is effective in clinically relevant murine glioma models, providing a basis on which to progress this novel combinatorial treatment toward early phase human trials.
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- 2018
39. A dynamic spectrum of monocytes arising from the in situ reprogramming of CCR2+ monocytes at a site of sterile injury
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Zhutian Zeng, Björn Petri, Daniela Dal-Secco, Jing Wang, Elzbieta Kolaczkowska, Paul Kubes, Connie H.Y. Wong, Israel F. Charo, Richard M. Ransohoff, and Craig N. Jenne
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CCR2 ,Receptors, CCR2 ,medicine.medical_treatment ,Immunology ,CX3C Chemokine Receptor 1 ,Inflammation ,Biology ,Monocytes ,Proinflammatory cytokine ,Mice ,Cell Movement ,In vivo ,medicine ,Animals ,Immunology and Allergy ,Mice, Knockout ,Wound Healing ,Microscopy, Confocal ,digestive, oral, and skin physiology ,Brief Definitive Report ,Cellular Reprogramming ,Cytokine ,Liver ,Receptors, Chemokine ,medicine.symptom ,Wound healing ,Reprogramming ,Intravital microscopy - Abstract
In response to sterile liver injury, CCR2hiCX3CR1low inflammatory monocytes infiltrate the liver and form a ringlike structure around the injury site. The cells then transition into CCR2lowCX3CR1hi alternative monocytes that enter the injury site; this phenotypic transition was required for optimal repair., Monocytes are recruited from the blood to sites of inflammation, where they contribute to wound healing and tissue repair. There are at least two subsets of monocytes: classical or proinflammatory (CCR2hiCX3CR1low) and nonclassical, patrolling, or alternative (CCR2lowCX3CR1hi) monocytes. Using spinning-disk confocal intravital microscopy and mice with fluorescent reporters for each of these subsets, we were able to track the dynamic spectrum of monocytes that enter a site of sterile hepatic injury in vivo. We observed that the CCR2hiCX3CR1low monocytes were recruited early and persisted for at least 48 h, forming a ringlike structure around the injured area. These monocytes transitioned, in situ, from CCR2hiCx3CR1low to CX3CR1hiCCR2low within the ringlike structure and then entered the injury site. This phenotypic conversion was essential for optimal repair. These results demonstrate a local, cytokine driven reprogramming of classic, proinflammatory monocytes into nonclassical or alternative monocytes to facilitate proper wound-healing.
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- 2015
40. Modeling of reconfigurable distributed manufacturing control systems
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Maurício Fontoura Blos, Israel F. Benítez-Pina, Paulo Eigi Miyagi, Diolino Jose dos Santos Filho, and Robson Marinho da Silva
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Flexibility (engineering) ,Engineering ,business.industry ,Distributed computing ,Interoperability ,Control reconfiguration ,Reuse ,Petri net ,Control and Systems Engineering ,Control system ,Systems engineering ,Architecture ,business ,Distributed manufacturing - Abstract
This paper presents a method to design a reconfigurable distributed manufacturing control systems which integrates heterogeneous technologies of facilities that are geographically distributed. Due to the heterogeneity of the environment, the method explores concepts of different techniques and takes the best practices from each one. Mechanisms for reconfiguration are proposed using holonic and multi-agent systems techniques. The service-oriented architecture concept is applied to define the interfaces for communication. A combined top-down and bottom- up approach is described using Petri net models. An application example demonstrates the characteristics and advantages of the proposed method, such as autonomy, reactivity, reuse models, interoperability and reconfiguration flexibility.
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- 2015
41. CCR2 Deficiency Impairs Macrophage Infiltration and Improves Cognitive Function after Traumatic Brain Injury
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Sarah H. Wang, Myrna L. Cozen, Eric J. Huang, Mary C. Nakamura, Jialing Liu, Deborah Bingham, Christine L. Hsieh, Eréne C. Niemi, Israel F. Charo, Jiasheng Zhang, and Chih Cheng Lee
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Male ,CCR2 ,Myeloid ,animal diseases ,Hippocampus ,Open field ,Mice ,Receptors ,Macrophage ,chemotaxis ,Postural Balance ,Mice, Knockout ,CD11b Antigen ,traumatic brain injury ,Brain ,hemic and immune systems ,Motor coordination ,medicine.anatomical_structure ,Neurological ,Mental health ,medicine.symptom ,Psychology ,behavior studies ,Physical Injury - Accidents and Adverse Effects ,Receptors, CCR2 ,Traumatic brain injury ,Knockout ,Clinical Sciences ,Inflammation ,macrophage ,Traumatic Brain Injury (TBI) ,Motor Activity ,parasitic diseases ,medicine ,Animals ,Maze Learning ,Traumatic Head and Spine Injury ,Neurology & Neurosurgery ,flow cytometry ,Macrophages ,Neurosciences ,Original Articles ,brain injury ,medicine.disease ,Brain Disorders ,nervous system ,inflammation ,Brain Injuries ,Immunology ,Neurology (clinical) ,Cognition Disorders - Abstract
Traumatic brain injury (TBI) provokes inflammatory responses, including a dramatic rise in brain macrophages in the area of injury. The pathway(s) responsible for macrophage infiltration of the traumatically injured brain and the effects of macrophages on functional outcomes are not well understood. C-C-chemokine receptor 2 (CCR2) is known for directing monocytes to inflamed tissues. To assess the role of macrophages and CCR2 in TBI, we determined outcomes in CCR2-deficient (Ccr2(-/-)) mice in a controlled cortical impact model. We quantified brain myeloid cell numbers post-TBI by flow cytometry and found that Ccr2(-/-) mice had greatly reduced macrophage numbers (∼80-90% reduction) early post-TBI, compared with wild-type mice. Motor, locomotor, and cognitive outcomes were assessed. Lack of Ccr2 improved locomotor activity with less hyperactivity in open field testing, but did not affect anxiety levels or motor coordination on the rotarod three weeks after TBI. Importantly, Ccr2(-/-) mice demonstrated greater spatial learning and memory, compared with wild-type mice eight weeks after TBI. Although there was no difference in the volume of tissue loss, Ccr2(-/-) mice had significantly increased neuronal density in the CA1-CA3 regions of the hippocampus after TBI, compared with wild-type mice. These data demonstrate that Ccr2 directs the majority of macrophage homing to the brain early after TBI and indicates that Ccr2 may facilitate harmful responses. Lack of Ccr2 improves functional recovery and neuronal survival. These results suggest that therapeutic blockade of CCR2-dependent responses may improve outcomes following TBI.
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- 2014
42. IL-17-Secreting γδ T Cells Are Completely Dependent upon CCR6 for Homing to Inflamed Skin
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Ton Dang, Mcmahon Jeffrey P, Shirley Liu, Dale Newland, James Campbell, Yu Wang, Linda S. Ertl, Karen Ebsworth, Thomas J. Schall, Penglie Zhang, Rajinder Singh, Israel F. Charo, and Zhenhua Miao
- Subjects
0301 basic medicine ,Receptors, CCR6 ,T cell ,T-Lymphocytes ,Immunology ,Population ,chemical and pharmacologic phenomena ,Inflammation ,C-C chemokine receptor type 6 ,Biology ,03 medical and health sciences ,Mice ,0302 clinical medicine ,Antigen ,Cell Movement ,Psoriasis ,medicine ,Immunology and Allergy ,Animals ,education ,Skin ,Mice, Knockout ,education.field_of_study ,Mice, Inbred BALB C ,Interleukin-17 ,hemic and immune systems ,Receptors, Antigen, T-Cell, gamma-delta ,medicine.disease ,030104 developmental biology ,medicine.anatomical_structure ,Interleukin-23 Subunit p19 ,Interleukin 17 ,medicine.symptom ,030215 immunology ,Homing (hematopoietic) - Abstract
mAbs that neutralize IL-17 or its receptor have proven efficacious in treating moderate-to-severe psoriasis, confirming IL-17 as an important driver of this disease. In mice, a rare population of T cells, γδT17 cells, appears to be a dominant source of IL-17 in experimental psoriasis. These cells traffic between lymph nodes and the skin, and are identified by their coexpression of the TCR variable regions γ4 and δ4. These cells are homologous to the Vγ9Vδ2 T cell population identified in human psoriatic plaques. In this study we report that a potent and specific small molecule antagonist of the CCR6 chemokine receptor, CCX2553, was efficacious in reducing multiple aspects of psoriasis in two different murine models of the disease. Administration of CCX2553 ameliorated skin inflammation in both the IL-23–induced ear swelling model and the topical imiquimod model, and significantly reduced the number of γδT17 cells in inflamed skin. γδT17 cells were greatly reduced in imiquimod-treated skin of CCR6−/− mice, but adoptively transferred wild-type (CCR6+/+) γδT17 cells homed normally to the skin of imiquimod-treated CCR6−/− mice. Our data suggest that γδT17 cells are completely dependent on CCR6 for homing to psoriasiform skin. Thus, CCR6 may constitute a novel target for a mechanistically distinct therapeutic approach to treating psoriasis.
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- 2017
43. HIFI Spectroscopy of ${\rm H_2O}$ submm Lines in Nuclei of Actively Star Forming Galaxies
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Liu, L., Weiss, A., Perez-Beaupuits, J. P., Güsten, R., Liu, D., Gao, Y., Menten, K. M., van der Werf, P., Israel, F. P., Harris, A., Martin-Pintado, J., Requena-Torres, M. A., and Stutzki, J.
- Subjects
Astrophysics of Galaxies (astro-ph.GA) ,FOS: Physical sciences ,Astrophysics - Astrophysics of Galaxies - Abstract
We present a systematic survey of multiple velocity-resolved H$_2$O spectra using Herschel/HIFI towards nine nearby actively star forming galaxies. The ground-state and low-excitation lines (E$_{\rm up}\,\le 130\,{\rm K}$) show profiles with emission and absorption blended together, while absorption-free medium-excitation lines ($130\,{\rm K}\, \le\, E_{\rm up}\,\le\,350\,{\rm K}$) typically display line shapes similar to CO. We analyze the HIFI observation together with archival SPIRE/PACS H$_2$O data using a state-of-the-art 3D radiative transfer code which includes the interaction between continuum and line emission. The water excitation models are combined with information on the dust- and CO spectral line energy distribution to determine the physical structure of the interstellar medium (ISM). We identify two ISM components that are common to all galaxies: A warm ($T_{\rm dust}\,\sim\,40-70\,{\rm K}$), dense ($n({\rm H})\,\sim\,10^5-10^6\,{\rm cm^{-3}}$) phase which dominates the emission of medium-excitation H$_2$O lines. This gas phase also dominates the FIR emission and the CO intensities for $J_{\rm up} > 8$. In addition a cold ($T_{\rm dust}\,\sim\,20-30\,{\rm K}$), dense ($n({\rm H})\sim\,10^4- 10^5\,{\rm cm^{-3}}$) more extended phase is present. It outputs the emission in the low-excitation H$_2$O lines and typically also produces the prominent line absorption features. For the two ULIRGs in our sample (Arp 220 and Mrk 231) an even hotter and more compact (R$_s\,\le\,100$ pc) region is present which is possibly linked to AGN activity. We find that collisions dominate the water excitation in the cold gas and for lines with $E_{\rm up}\le300\,{\rm K}$ and $E_{\rm up}\le800\,{\rm K}$ in the warm and hot component, respectively. Higher energy levels are mainly excited by IR pumping., Accepted by ApJ, in press
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- 2017
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44. Differential roles of microglia and monocytes in the inflamed central nervous system
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Nobuhiko Ohno, Pauline M. Wu, Ryo Yamasaki, Lindsey Uehlein, Oleg Butovsky, Israel F. Charo, Weiwei Hu, Jessica Lin, Min Zhu, Jinyu Gu, LiPing Liu, Howard L. Weiner, Debra Dixon, Grahame J. Kidd, Nathan Sun, Jar Chi Lee, Anne C. Cotleur, Ron Cialic, Musab M. Zorlu, Anna Rietsch, Haiyan Lu, Richard M. Ransohoff, Sarah E. Taylor, Crina M. Floruta, Camille Doykan, and Nöroloji
- Subjects
Central Nervous System ,Pathology ,medicine.medical_specialty ,Encephalomyelitis ,Immunology ,Inflammation ,Research & Experimental Medicine ,Biology ,Article ,Monocytes ,CX3CR1 ,medicine ,Animals ,Humans ,Immunology and Allergy ,Macrophage ,Microglia ,Monocyte ,Multiple sclerosis ,Experimental autoimmune encephalomyelitis ,medicine.disease ,medicine.anatomical_structure ,nervous system ,medicine.symptom - Abstract
Phagocytic monocyte-derived macrophages associate with the nodes of Ranvier and initiate demyelination while microglia clear debris and display a suppressed metabolic gene signature in EAE., In the human disorder multiple sclerosis (MS) and in the model experimental autoimmune encephalomyelitis (EAE), macrophages predominate in demyelinated areas and their numbers correlate to tissue damage. Macrophages may be derived from infiltrating monocytes or resident microglia, yet are indistinguishable by light microscopy and surface phenotype. It is axiomatic that T cell–mediated macrophage activation is critical for inflammatory demyelination in EAE, yet the precise details by which tissue injury takes place remain poorly understood. In the present study, we addressed the cellular basis of autoimmune demyelination by discriminating microglial versus monocyte origins of effector macrophages. Using serial block-face scanning electron microscopy (SBF-SEM), we show that monocyte-derived macrophages associate with nodes of Ranvier and initiate demyelination, whereas microglia appear to clear debris. Gene expression profiles confirm that monocyte-derived macrophages are highly phagocytic and inflammatory, whereas those arising from microglia demonstrate an unexpected signature of globally suppressed cellular metabolism at disease onset. Distinguishing tissue-resident macrophages from infiltrating monocytes will point toward new strategies to treat disease and promote repair in diverse inflammatory pathologies in varied organs.
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- 2014
45. Measurement, Control and Evaluation of Low-Power Contactor Switches under Overload Current
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Joaquin H Rodriguez-Rodrigez, Ricardo Guevara-Gordillo, Rito Mijarez, Israel F Vazquez-Gutierrez, and Angel E Gomez-Sanchez
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Engineering ,Cyclic stress ,Control and Optimization ,business.industry ,Applied Mathematics ,Electrical engineering ,Load rating ,Current (fluid) ,business ,Instrumentation ,Voltage drop ,Power (physics) ,Contactor - Abstract
Load rating of contactor switches is an important issue for diverse industrial power applications requiring varied connections. This paper presents a simple procedure to evaluate the current-carrying capabilities of contactor switches under overload cyclic stress. An experimental setup is proposed to measure test current, contact voltage drop, and temperature at the contacts and cable connectors. Results are presented for ON–OFF controlled commutated current at 500% and 1000% overload of a contactor in the ON position. The attained results and the criteria for contactors selection in power applications are given.
- Published
- 2014
46. Targeting Chemokine Receptors CCR6 and CXCR2 in A Murine Model Of IL-36a-Induced Pustular Psoriasis
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James J Campbell, Karen Ebsworth, Linda Ertl, Jeffrey P McMahon, Yu Wang, Simon Yau, Venkat R Mali, Vicky Chhina, Alice Kumamoto, Shirley Liu, Ton Dang, Dale Newland, Israel F Charo, Penglie Zhang, Thomas J Schall, and Rajinder Singh
- Subjects
Immunology ,Immunology and Allergy - Abstract
Several types of psoriasiform dermatitis are associated with increased IL-36 cytokine activity in the skin. A rare but severe psoriasis-like disorder, generalized pustular psoriasis (GPP), is linked to loss-of-function mutations in the gene encoding IL-36RA, an important negative regulator of IL-36 signaling. To understand the effects of IL-36 dysregulation in a mouse model, we studied skin inflammation induced by intradermal injections of pre-activated IL-36α. This type of inflammation was characterized by markedly increased total skin thickness and epidermal thickness. The inflammation was accompanied by increased concentrations of CCR6 and CXCR2 ligand chemokines in the skin, and large accumulations of CD4 T cells, neutrophils, and inflammatory DC. The accumulated inflammatory subsets in IL-36α-treated skin all expressed either CCR6 or CXCR2 to some extent, prompting the hypothesis that increased CCR6 and CXCR2 ligand concentrations in IL-36α-treated skin might constitute a viable target for relieving inflammation in this model. We found that the orally bioavailable small molecule CCR6/CXCR2 antagonist CCX624 did indeed reverse inflammatory cell accumulation in skin, as well as decrease total skin thickness and epidermal thickness. CCX624 was effective in both prophylactic and therapeutic dosing regimens. CCX624 treatment was more effective than saturating doses of anti-TNFα or anti-IL17RA, which are used in the clinic for treating GPP as first or second line treatments (respectively). These findings put CCR6 and CXCR2 forward as novel targets for a mechanistically distinct therapeutic approach for inflammatory skin diseases involving dysregulated IL-36 signaling, such as GPP.
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- 2019
47. Coleoptera of forensic interest: A study of seasonal community composition and succession in Lisbon, Portugal
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Israel F. Silva, Pedro Martins da Silva, María Dolores García García, Catarina Prado e Castro, and Artur R. M. Serrano
- Subjects
food.ingredient ,Swine ,Silphidae ,Pathology and Forensic Medicine ,food ,Abundance (ecology) ,Histeridae ,Animals ,Saprinus ,Forensic Pathology ,Creophilus maxillosus ,Margarinotus brunneus ,Portugal ,biology ,Ecology ,Temperature ,Feeding Behavior ,biology.organism_classification ,Dermestidae ,Coleoptera ,Larva ,Postmortem Changes ,Seasons ,Species richness ,Entomology ,Law - Abstract
Some Coleoptera are recognised as being forensically important as post-mortem interval (PMI) indicators, especially in the later stages of cadaver decomposition. Because insect species and their timings of appearance in cadavers vary according to geographic location, it is important to know their succession patterns, as well as seasonality at a regional level. In this study, we aimed to contribute to broaden this knowledge by surveying beetle communities from the Lisbon area during the four seasons of the year, using piglet carcasses as animal models. Five stages were recognised during the decomposition process and they could be separated taking into account the occurrence and abundance of the specific groups of Coleoptera collected. Decay stages in general recorded higher abundance and richness of beetle species. A total of 82 species were identified, belonging to 28 families, in a total of 1968 adult Coleoptera collected. Autumn yielded the highest values of species abundance and richness, while the lowest values were recorded during winter. Staphylinidae was the most abundant family in all seasons, although in spring and summer Dermestidae was also quite dominant. In general, most species were related to the decay stages, particularly Margarinotus brunneus (Histeridae) and Creophilus maxillosus (Staphylinidae), and also Saprinus detersus (Histeridae) and Thanatophilus sinuatus (Silphidae), while only few were related to the dry stage, namely Oligota pusillima (Staphylinidae) and Dermestidae spp. larvae. On the other hand, Anotylus complanatus and Atheta pertyi (Staphylinidae) were apparently more associated with the fresh and bloated stages, respectively. The presence of some species was markedly seasonal, allowing a season characterisation based on the occurrence of certain taxa, which can be useful for forensic purposes.
- Published
- 2013
48. Regulation of Adaptive Immunity by the Fractalkine Receptor during Autoimmune Inflammation
- Author
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Makiko Mizutani, Paula A. Pino, Richard M. Ransohoff, Astrid E. Cardona, Jenny A. Garcia, Thomas G. Forsthuber, Israel F. Charo, and Sandra M. Cardona
- Subjects
Central Nervous System ,Chemokine ,Adoptive cell transfer ,T-Lymphocytes ,Autoimmunity ,Adaptive Immunity ,Neurodegenerative ,Inbred C57BL ,Lymphocyte Activation ,Mice ,Receptors ,CX3CR1 ,2.1 Biological and endogenous factors ,Immunology and Allergy ,Myeloid Cells ,Aetiology ,Encephalomyelitis ,Microglia ,Interleukin-17 ,Experimental autoimmune encephalomyelitis ,Acquired immune system ,medicine.anatomical_structure ,Neurological ,Receptor ,Multiple Sclerosis ,Lymphoid Tissue ,Knockout ,1.1 Normal biological development and functioning ,T cell ,Immunology ,CX3C Chemokine Receptor 1 ,Bone Marrow Cells ,Biology ,Autoimmune Disease ,Experimental ,Interferon-gamma ,Immune system ,Underpinning research ,medicine ,Animals ,Antigens ,Cytokine ,Cell Proliferation ,Inflammation ,Chimera ,Macrophage Colony-Stimulating Factor ,Inflammatory and immune system ,Neurosciences ,HIV ,Dendritic Cells ,medicine.disease ,Peptide Fragments ,CD11c Antigen ,Brain Disorders ,Ly ,biology.protein ,Myelin-Oligodendrocyte Glycoprotein ,Autoimmune ,Demyelinating Diseases ,Interleukin-1 - Abstract
Fractalkine, a chemokine anchored to neurons or peripheral endothelial cells, serves as an adhesion molecule or as a soluble chemoattractant. Fractalkine binds CX3CR1 on microglia and circulating monocytes, dendritic cells, and NK cells. The aim of this study is to determine the role of CX3CR1 in the trafficking and function of myeloid cells to the CNS during experimental autoimmune encephalomyelitis (EAE). Our results show that, in models of active EAE, Cx3cr1−/− mice exhibited more severe neurologic deficiencies. Bone marrow chimeric mice confirmed that CX3CR1 deficiency in bone marrow enhanced EAE severity. Notably, CX3CR1 deficiency was associated with an increased accumulation of CD115+Ly6C−CD11c+ dendritic cells into EAE-affected brains that correlated with enhanced demyelination and neuronal damage. Furthermore, higher IFN-γ and IL-17 levels were detected in cerebellar and spinal cord tissues of CX3CR1-deficient mice. Analyses of peripheral responses during disease initiation revealed a higher frequency of IFN-γ– and IL-17–producing T cells in lymphoid tissues of CX3CR1-deficient as well as enhanced T cell proliferation induced by CX3CR1-deficient dendritic cells. In addition, adoptive transfer of myelin oligodendrocyte glycoprotein35–55-reactive wild-type T cells induced substantially more severe EAE in CX3CR1-deficient recipients when compared with wild-type recipients. Collectively, the data demonstrate that besides its role in chemoattraction, CX3CR1 is a key regulator of myeloid cell activation contributing to the establishment of adaptive immune responses.
- Published
- 2013
49. Characterization of Pharmacologic and Pharmacokinetic Properties of CCX168, a Potent and Selective Orally Administered Complement 5a Receptor Inhibitor, Based on Preclinical Evaluation and Randomized Phase 1 Clinical Study
- Author
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Daniel J. Dairaghi, Jay P. Powers, Juan C. Jaen, Trageen Baumgart, Yu Wang, Israel F. Charo, Ton Dang, Sarah Shugarts, Lisa Seitz, Daniel Johnson, Yibin Zeng, Lisa Lohr, Linda S. Ertl, Penglie Zhang, Pingchen Fan, Pirow Bekker, Manmohan Reddy Leleti, Thomas J. Schall, and Shichang Miao
- Subjects
0301 basic medicine ,Neutrophils ,Physiology ,Complement System ,Nipecotic Acids ,lcsh:Medicine ,Phases of clinical research ,Administration, Oral ,Drug research and development ,Monkeys ,Pharmacology ,Biochemistry ,C5a receptor ,White Blood Cells ,Mice ,Clinical trials ,0302 clinical medicine ,Animal Cells ,Immune Physiology ,Medicine and Health Sciences ,Medicine ,lcsh:Science ,Receptor ,Mammals ,Immune System Proteins ,Multidisciplinary ,Aniline Compounds ,Phase I clinical investigation ,Chemotaxis ,Hematology ,U937 Cells ,Healthy Volunteers ,Body Fluids ,Cell Motility ,Blood ,Tolerability ,Vertebrates ,Cellular Types ,Anatomy ,Research Article ,Primates ,Immune Cells ,Immunology ,Mice, Transgenic ,Blood Plasma ,03 medical and health sciences ,Pharmacokinetics ,In vivo ,Potency ,Animals ,Humans ,Receptor, Anaphylatoxin C5a ,Blood Cells ,business.industry ,lcsh:R ,Organisms ,Biology and Life Sciences ,Proteins ,Correction ,Cell Biology ,Research and analysis methods ,Macaca fascicularis ,030104 developmental biology ,Clinical medicine ,Immune System ,Amniotes ,lcsh:Q ,business ,030217 neurology & neurosurgery ,Ex vivo - Abstract
The complement 5a receptor has been an attractive therapeutic target for many autoimmune and inflammatory disorders. However, development of a selective and potent C5aR antagonist has been challenging. Here we describe the characterization of CCX168 (avacopan), an orally administered selective and potent C5aR inhibitor. CCX168 blocked the C5a binding, C5a-mediated migration, calcium mobilization, and CD11b upregulation in U937 cells as well as in freshly isolated human neutrophils. CCX168 retains high potency when present in human blood. A transgenic human C5aR knock-in mouse model allowed comparison of the in vitro and in vivo efficacy of the molecule. CCX168 effectively blocked migration in in vitro and ex vivo chemotaxis assays, and it blocked the C5a-mediated neutrophil vascular endothelial margination. CCX168 was effective in migration and neutrophil margination assays in cynomolgus monkeys. This thorough in vitro and preclinical characterization enabled progression of CCX168 into the clinic and testing of its safety, tolerability, pharmacokinetic, and pharmacodynamic profiles in a Phase 1 clinical trial in 48 healthy volunteers. CCX168 was shown to be well tolerated across a broad dose range (1 to 100 mg) and it showed dose-dependent pharmacokinetics. An oral dose of 30 mg CCX168 given twice daily blocked the C5a-induced upregulation of CD11b in circulating neutrophils by 94% or greater throughout the entire day, demonstrating essentially complete target coverage. This dose regimen is being tested in clinical trials in patients with anti-neutrophil cytoplasmic antibody-associated vasculitis. Trial Registration ISRCTN registry with trial ID ISRCTN13564773.
- Published
- 2016
50. Mechanoluminescence of Coordination Compounds
- Author
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Wagner M. Faustino, Ercules E.S. Teotonio, Jandeilson de Lima Moura, Maria C.F.C. Felinto, Israel F. Costa, Paulo R.S. Santos, and Hermi F. Brito
- Subjects
Lanthanide ,chemistry.chemical_classification ,Materials science ,Antenna effect ,Nanotechnology ,02 engineering and technology ,010402 general chemistry ,021001 nanoscience & nanotechnology ,01 natural sciences ,0104 chemical sciences ,Rubbing ,Coordination complex ,chemistry ,0210 nano-technology ,Luminescence ,Static loading ,Mechanoluminescence - Abstract
Mechanoluminescence (ML) involves all luminescence phenomena induced by mechanical action on solids. In this case, a wide varieties of mechanical stimuli, such as compressing, stretching, static loading (pressure-step), pressure pulse, cleaving, rubbing, and grinding, might induce the excitation of solids, yielding luminescence phenomena. The present chapter discusses on mechanoluminescent properties of transition metal and lanthanide coordination compounds. The principal aim of this chapter is to describe the recent facts about the mechanisms of mechanoluminescence and their correlation with structural properties. It will be also presented a concise overview on the latest progress made on the current variety of ML coordination compounds or materials based on transition and lanthanide metals. The recent studies in this area may lead to the development of ML materials for smart optical sensors for real-time damage detections, monitoring civil and military structures, luminescent probes for biological applications, and lightning systems.
- Published
- 2016
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