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8,672 results on '"Hurst, D."'

1. Pediatric Resource Allocation, Triage, and Rationing Decisions in Public Health Emergencies and Disasters: How Do We Fairly Meet Health Needs?

Author

Hurst, D. J., Padilla, L. A., Cooley, Dennis R., Series Editor, Weisstub, David N., Advisory Editor, Thomasma, David C., Founding Editor, Kimbrough Kushner, Thomasine, Founding Editor, Carney, Terry, Editorial Board Member, Düwell, Marcus, Editorial Board Member, Holm, Søren, Editorial Board Member, Kimsma, Gerrit, Editorial Board Member, Novak, David, Editorial Board Member, Sulmasy, Daniel P., Editorial Board Member, Hodge, David Augustin, Editorial Board Member, Jones, Nora L., Editorial Board Member, Nortjé, Nico, editor, and Bester, Johan C., editor

Published
2022
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2. Non-Reciprocal Transmission and Reflection of a Chirally-Coupled Quantum Dot

Author

Hurst, D. L., Price, D. M., Bentham, C., Makhonin, M. N., Royall, B., Clarke, E., Kok, P., Wilson, L. R., Skolnick, M. S., and Fox, A. M.

Subjects
Quantum Physics, Condensed Matter - Mesoscale and Nanoscale Physics
Abstract

We report strongly non-reciprocal behaviour for quantum dot exciton spins coupled to nano-photonic waveguides under resonant laser excitation. A clear dependence of the transmission spectrum on the propagation direction is found for a chirally-coupled quantum dot, with spin up and spin down exciton spins coupling to the left and right propagation directions respectively. The reflection signal shows an opposite trend to the transmission, which a numerical model indicates is due to direction-selective saturation of the quantum dot. The chiral spin-photon interface we demonstrate breaks reciprocity of the system and opens the way to spin-based quantum optical components such as optical diodes and circulators in a chip-based solid-state environment., Comment: 19 pages, 4 figures, supplemental information available on request

Published
2018
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3. Electrical control of nonlinear quantum optics in a nano-photonic waveguide

Author

Hallett, D., Foster, A. P., Hurst, D. L., Royall, B., Kok, P., Clarke, E., Itskevich, I. E., Fox, A. M., Skolnick, M. S., and Wilson, L. R.

Subjects
Quantum Physics, Condensed Matter - Mesoscale and Nanoscale Physics, Physics - Optics
Abstract

Local control of the generation and interaction of indistinguishable single photons is a key requirement for photonic quantum networks. Waveguide-based architectures, in which embedded quantum emitters act as both highly coherent single photon sources and as nonlinear elements to mediate photon-photon interactions, offer a scalable route to such networks. However, local electrical control of a quantum optical nonlinearity has yet to be demonstrated in a waveguide geometry. Here, we demonstrate local electrical tuning and switching of single photon generation and nonlinear interaction by embedding a quantum dot in a nano-photonic waveguide with enhanced light-matter interaction. A power-dependent transmission extinction as large as 40$\pm$2% and clear, voltage-controlled bunching in the photon statistics of the transmitted light demonstrate the single photon character of the nonlinearity. The deterministic nature of the nonlinearity is particularly attractive for the future realization of photonic gates for scalable nano-photonic waveguide-based quantum information processing., Comment: 21 pages, 4 figures

Published
2017
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5. Effectiveness of a Home-Based Pulmonary Rehabilitation Program in Veterans.

Author

Drwal KR, Hurst D, and Wakefield BJ

Subjects
Humans, Male, Aged, Female, Middle Aged, United States, Quality of Life, United States Department of Veterans Affairs organization & administration, Exercise Tolerance, Dyspnea rehabilitation, Veterans, Home Care Services organization & administration, Pulmonary Disease, Chronic Obstructive rehabilitation
Abstract

Purpose: This study examined the effectiveness and safety of a home-based pulmonary rehabilitation (HBPR) program in Veterans. Methods: Patients were evaluated from five Veteran Affairs facilities that enrolled in the 12-week program. Pre- to postchanges were completed on clinical outcomes using paired t -tests and the Wilcoxon signed rank sum test. Descriptive statistics were used for patient demographics, emergency room visits, and hospitalizations. Results: Two hundred eighty-five patients with a mean age of 69.6 ± 8.3 years enrolled in the HBPR program from October 2018 to March 2020. There was a 62% ( n  = 176) completion rate of both pre- and post assessments. Significant improvements were detected after completion of the HBPR program in dyspnea (modified Medical Research Council: 3.1 ± 1.1 vs. 1.9 ± 1.1; p  < 0.0001); exercise capacity (six-minute walk distance: 263.1 m ± 96.6 m vs. 311.0 m ± 103.6 m; p < 0.0001; Duke Activity Status Index: 13.8 ± 9.6 vs. 20.0 ± 12.7; p < 0.0001; self-reported steps per day: 1514.5 ± 1360.4 vs. 3033.8 ± 2716.2; p  < 0.0001); depression (patient health questionnaire-9: 8.3 ± 5.7 vs. 6.4 ± 5.1); nutrition habits (rate your plate, heart: 45.3 ± 9.0 vs. 48.9 ± 9.2; p < 0.0001); multicomponent assessment tools (BODE Index: 5.1 ± 2.5 vs. 3.4 ± 2.4; p < 0.0001), GOLD ABCD Assessment: p < 0.0009); and quality of life (chronic obstructive pulmonary disease assessment test: 25.4 ± 7.7 vs. 18.7 ± 8.5; p < 0.0001). No adverse events were reported due to participation in HBPR. Conclusions: The HBPR program is a safe and effective model and provides an additional option to address the gap in pulmonary rehabilitation access and utilization in the Veterans Affairs.

Published
2024
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7. Use of collagen powder in secondary intention healing after Mohs surgery or excisional surgery: a retrospective study.

Author

Kendall L, Hurst D, Monahan J, and Smith Iii SP

Subjects
Humans, Retrospective Studies, Female, Male, Middle Aged, Aged, Patient Satisfaction, Aged, 80 and over, Treatment Outcome, Adult, Mohs Surgery methods, Wound Healing drug effects, Collagen therapeutic use, Powders, Skin Neoplasms surgery
Abstract

Background: Little is known about the usefulness of collagen powder in secondary intention healing in patients undergoing cutaneous surgery., Objective: To investigate the clinical outcomes associated with application of collagen powder in cutaneous surgery and patients' perceptions of the procedure., Methods: A retrospective chart review of 266 patients who underwent Mohs surgery or excisional surgery at a single institution between January 2020 and January 2022, and who had secondary intention healing of wounds assisted by powdered collagen was conducted. Personal interviews were conducted with 63 of those patients (23.7%). Tumor characteristics, estimated healing times, and patient satisfaction were scored. The Vancouver Scar Scale and the Patient and Observer Scar Assessment Scale were used to assess the resulting wound bed. All data underwent statistical analysis., Results: Of 266 granulating wounds with an average defect size of 6.0 cm2, excisional surgery was performed in 143 (54%) and Mohs surgery in 123 (46%). Most procedures (92.1%) were undertaken for nonmelanoma skin cancers. The average healing time was 6.3 weeks. The mean patient score for ease of use and overall impression of collagen application was 8.2 on a scale of 1 to 10, with 10 being most favorable., Conclusion: When clinically appropriate, granulation assisted by collagen powder should be considered for augmenting secondary intention healing.

Published
2024
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8. Switzerland -determination of kinetic constants for the interaction between the platelet glycoprotein IIb-IIla and fibrinogen by means of surface plasmon resonance In EUR. J. BIOCHEM. (227/3 (647–656) 1995) W. Huber, J. Hurst, D. Schlatter, R. Barner, J. Hubscher, W.C. Kouns, B. Steiner of F. Hoffmann-La Roche report “Determination of kinetic constants for the interaction between the platelet glycoprotein IIb-IIla and fibrinogen by means of surface plasmon resonance”.

Author

Owen, V, primary

Published
1995
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9. Switzerland -determination of kinetic constants for the interaction between the platelet glycoprotein IIb-IIla and fibrinogen by means of surface plasmon resonance In EUR. J. BIOCHEM. (227/3 (647–656) 1995) W. Huber, J. Hurst, D. Schlatter, R. Barner, J. Hubscher, W.C. Kouns, B. Steiner of F. Hoffmann-La Roche report 'Determination of kinetic constants for the interaction between the platelet glycoprotein IIb-IIla and fibrinogen by means of surface plasmon resonance'

Author

V Owen

Subjects
Electrochemistry, Biomedical Engineering, Biophysics, General Medicine, Biotechnology
Published
1995
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10. Bridge-to-transplant temporary mechanical circulatory support and risk of allosensitization.

Author

Sideris K, Lázár-Molnár E, Kyriakopoulos CP, Taleb I, Hurst D, Ugolini S, Selzman CH, Brinker L, Drakos SG, Tonna JE, Geer L, Goodwin ML, Wever-Pinzon O, Hanff TC, Fang JC, Carter S, and Stehlik J

Subjects
Humans, Male, Female, Middle Aged, Follow-Up Studies, Adult, Risk Factors, Prognosis, Retrospective Studies, Heart Failure surgery, Heart Failure therapy, Graft Rejection etiology, Heart-Assist Devices, Heart Transplantation, Isoantibodies immunology, Isoantibodies blood
Abstract

Introduction: Since the 2018 change in the US adult heart allocation policy, more patients are bridged-to-transplant on temporary mechanical circulatory support (tMCS). Previous studies indicate that durable left ventricular assist devices (LVAD) may lead to allosensitization. The goal of this study was to assess whether tMCS implantation is associated with changes in sensitization., Methods: We included patients evaluated for heart transplants between 2015 and 2022 who had alloantibody measured before and after MCS implantation. Allosensitization was defined as development of new alloantibodies after tMCS implant., Results: A total of 41 patients received tMCS before transplant. Nine (22.0%) patients developed alloantibodies following tMCS implantation: 3 (12.0%) in the intra-aortic balloon pump group (n = 25), 2 (28.6%) in the microaxial percutaneous LVAD group (n = 7), and 4 (44.4%) in the veno-arterial extra-corporeal membrane oxygenation group (n = 9)-p = .039. Sensitized patients were younger (44.7 ± 11.6 years vs. 54.3 ± 12.5 years, p = .044), were more likely to be sensitized at baseline - 3 of 9 (33.3%) compared to 2 out of 32 (6.3%) (p = .028) and received more transfusions with red blood cells (6 (66.6%) vs. 8 (25%), p = .02) and platelets (6 (66.6%) vs. 5 (15.6%), p = .002). There was no significant difference in tMCS median duration of support (4 [3,15] days vs. 8.5 [5,14.5] days, p = .57). Importantly, out of the 11 patients who received a durable LVAD after tMCS, 5 (45.5%) became sensitized, compared to 4 out of 30 patients (13.3%) who only had tMCS-p = .028., Conclusions: Our findings suggest that patients bridged-to-transplant with tMCS, without significant blood product transfusions and a subsequent durable LVAD implant, have a low risk of allosensitization. Further studies are needed to confirm our findings and determine whether risk of sensitization varies by type of tMCS and duration of support., (© 2024 The Authors. Clinical Transplantation published by John Wiley & Sons Ltd.)

Published
2024
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12. REFERENCE UPPER-AIR OBSERVATIONS FOR CLIMATE : From Concept to Reality

Author

Bodeker, G. E., Bojinski, S., Cimini, D., Dirksen, R. J., Haeffelin, M., Hannigan, J. W., Hurst, D. F., Leblanc, T., Madonna, F., Maturilli, M., Mikalsen, A. C., Philipona, R., Reale, T., Seidel, D. J., Tan, D. G. H., Thorne, P. W., Vömel, H., and Wang, J.

Published
2016

13. Diagnosis and treatment of coagulopathy using thromboelastography with platelet mapping is associated with decreased risk of pulmonary failure in COVID-19 patients.

Author

Hranjec T, Mayhew M, Rogers B, Solomon R, Hurst D, Estreicher M, Augusten A, Nunez A, Green M, Malhotra S, Katz R, Rosenthal A, Hennessy S, Pepe P, Sawyer R, and Arenas J

Subjects
Humans, Adolescent, Thrombelastography, Retrospective Studies, Prospective Studies, COVID-19 Testing, Anticoagulants therapeutic use, Hemorrhage drug therapy, COVID-19 complications, Blood Coagulation Disorders complications, Thrombosis drug therapy
Abstract

Introduction: Treatment of coronavirus disease 2019 (COVID-19) patients may require antithrombotic and/or anti-inflammatory medications. We hypothesized that individualized anticoagulant (AC) management, based on diagnosis of coagulopathy using thromboelastography with platelet mapping (TEG-PM), would decrease the frequency of pulmonary failure (PF) requiring mechanical ventilation (MV), mitigate thrombotic and hemorrhagic events, and, in-turn, reduce mortality., Methods: Hospital-admitted COVID-19 patients, age 18 or older, with escalating oxygen requirements were included. Prospective and supplemental retrospective chart reviews were conducted during a 2-month period. Patients were stratified into two groups based on clinician-administered AC treatment: TEG-PM guided vs. non-TEG guided., Results: Highly-elevated inflammatory markers (D-dimer, C-reactive protein, ferritin) were associated with poor prognosis but did not distinguish coagulopathic from noncoagulopathic patients. TEG-guided AC treatment was used in 145 patients vs. 227 treated without TEG-PM guidance. When managed by TEG-PM, patients had decreased frequency of PF requiring MV (45/145 [31%] vs. 152/227 [66.9%], P  < 0.0001), fewer thrombotic events (2[1.4%] vs. 39[17.2%], P  = 0.0019) and fewer hemorrhagic events (6[4.1%] vs. 24[10.7%], P  = 0.0240), and had markedly reduced mortality (43[29.7%] vs. 142[62.6%], P  < 0.0001). Platelet hyperactivity, indicating the need for antiplatelet medications, was identified in 75% of TEG-PM patients. When adjusted for confounders, empiric, indiscriminate AC treatment (not guided by TEG-PM) was shown to be an associated risk factor for PF requiring MV, while TEG-PM guided management was associated with a protective effect (odds ratio = 0.18, 95% confidence interval 0.08-0.4)., Conclusions: Following COVID-19 diagnosis, AC therapies based on diagnosis of coagulopathy using TEG-PM were associated with significantly less respiratory decompensation, fewer thrombotic and hemorrhagic complications, and improved likelihood of survival., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2023
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15. Observational evidence for interhemispheric hydroxyl-radical parity

Author

Patra, P. K., Krol, M. C., Montzka, S. A., Arnold, T., Atlas, E. L., Lintner, B. R., Stephens, B. B., Xiang, B., Elkins, J. W., Fraser, P. J., Ghosh, A., Hintsa, E. J., Hurst, D. F., Ishijima, K., Krummel, P. B., Miller, B. R., Miyazaki, K., Moore, F. L., Mühle, J., O’Doherty, S., Prinn, R. G., Steele, L. P., Takigawa, M., Wang, H. J., Weiss, R. F., Wofsy, S. C., and Young, D.

Published
2014
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24. Therapeutic Exploitation of GPR18: Beyond the Cannabinoids?

Author

Morales, Paula, Lago-Fernandez, Ana, Hurst, D. P., Sotudeh, N., Brailoiu, E., Reggio, P. H., Abood, Mary E., Jagerovic, Nadine, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Comunidad de Madrid, and Consejo Superior de Investigaciones Científicas (España)

Subjects
Cannabinoids, Protein Conformation, Drug Design, Humans, Article, Receptors, G-Protein-Coupled
Abstract

GPR18 is a G-protein-coupled receptor that belongs to the orphan class A family. Even though it shares low sequence homology with the cannabinoid receptors CBR and CBR, a growing body of research suggests its relationship with the endocannabinoid system, not only because it is able to recognize cannabinoid ligands but also because of its expression and ability to heteromerize with CBRs. In this review, we aim to analyze the biological relevance, reported modulators, and structural features of GPR18. In order to guide future drug design in this field, highlights from molecular modeling of GPR18 will be provided., P.M., A.L.-F., and N.J. are supported by the Ministry of Science, Innovation, and Universities, Spain (MCIU)/FEDER Grant RTI2018-095544-B-I00, and the Spanish National Research Council (CSIC) Grant PIE-201580E033. M.E.A., P.H.R., and N.J. are supported by National Institutes of Health Grant R01 DA0455698-01. P.M. acknowledges the Comunidad de Madrid (CM) program “Atraccion de Talento” Grant 2018-T2/BMD10819.

Published
2020

25. Metalloenzymes

Author

Pollard, J. W., Danilkovitch-Miagkova, A., Minaguchi, T., Waite, K. A., Buys, T. P. H., Lam, W. L., Müller-Hermelink, H. K., Ott, G., Robb, V. A., Henske, E. P., Lynge, E., Boyd, N., Geisler, C., Seger, R., De Wolf-Peeters, C., Sagaert, X., Sheng, S., Ribatti, D., Verstovsek, S., Akin, C., Stack, M. S., Kitada, S., Gartenhaus, R., Moretti, F., Frühwald, Michael C., Mooi, W. J., Krausz, T., Kefford, R., Peikert, T., Specks, U., Tueting, T., Pföhler, C., Blask, D. E., Stevens, R. G., Nies, A. T., Gotoh, N., Tsuchida, N., Escriba, P., Singh, V., Hickey, M., Saunders, C., Xiao, G.-H., Testa, J. R., Furtwängler, R., Scholler, N., Carbone, M., Furge, K., Woude, G. F. V., Roland, W. C., Muschel, R., Hunter, K., Welch, D. R., Vaidya, K. S., Hurst, D. R., Silveira, A. C., Zang, X. A., Bari, R., Silveira, A., Szmulewitz, R., Taylor, J., Rinker-Schaffer, C., Shim, H., Plass, C., Lindsey, J. C., Clifford, S. C., Holdenrieder, S., Steinle, A., Salih, H., Brown, D. A., Breit, S. N., Bauskin, A. R., Mousses, S., Lung, M. L., Alix-Panabieres, C., Pantel, K., Djuzenova, C. S., Dalmay, T., Ahlquist, T., Lothe, R. A., Bhat, K., Setaluri, V., Rutka, J. T., Salhia, B., Cockell, K. A., Radich, J. P., Yamagishi, S.-I., Bignami, M., Verma, M., Kumar, D., Brenner, C., Zhang, Y.-W., Jamieson, D., Chi, Y.-H., Jeang, K.-T., Roninson, I., Dragani, T., Sobolev, A. S., Powers, M. V., Workmann, P., Evans, M. F., Cooper, K., Kausch, I., Doehn, C., Janz, S., Huang, C.-L., Toland, A. E., Osinaga, E., Kaye, F., Lemos, M. C., Thakker, R. V., Teh, B. T., Ponder, B. A. J., Mulligan, L. M., Gullo, C., Klein, G., Wu, X., Araten, D. J., Loeb, L. A., Cheadle, J. P., Lipsick, J., Albihn, A., Henriksson, M., Kremens, B., Germing, U., Zangemeister-Wittke, U., Simon, H.-U., Yu, Y. P., Luo, J., and Aman, P.

Published
2020

26. Metallothionein enzymes

Author

Pollard, J. W., Danilkovitch-Miagkova, A., Minaguchi, T., Waite, K. A., Buys, T. P. H., Lam, W. L., Müller-Hermelink, H. K., Ott, G., Robb, V. A., Henske, E. P., Lynge, E., Boyd, N., Geisler, C., Seger, R., De Wolf-Peeters, C., Sagaert, X., Sheng, S., Ribatti, D., Verstovsek, S., Akin, C., Stack, M. S., Kitada, S., Gartenhaus, R., Moretti, F., Frühwald, Michael C., Mooi, W. J., Krausz, T., Kefford, R., Peikert, T., Specks, U., Tueting, T., Pföhler, C., Blask, D. E., Stevens, R. G., Nies, A. T., Gotoh, N., Tsuchida, N., Escriba, P., Singh, V., Hickey, M., Saunders, C., Xiao, G.-H., Testa, J. R., Furtwängler, R., Scholler, N., Carbone, M., Furge, K., Woude, G. F. V., Roland, W. C., Muschel, R., Hunter, K., Welch, D. R., Vaidya, K. S., Hurst, D. R., Silveira, A. C., Zang, X. A., Bari, R., Silveira, A., Szmulewitz, R., Taylor, J., Rinker-Schaffer, C., Shim, H., Plass, C., Lindsey, J. C., Clifford, S. C., Holdenrieder, S., Steinle, A., Salih, H., Brown, D. A., Breit, S. N., Bauskin, A. R., Mousses, S., Lung, M. L., Alix-Panabieres, C., Pantel, K., Djuzenova, C. S., Dalmay, T., Ahlquist, T., Lothe, R. A., Bhat, K., Setaluri, V., Rutka, J. T., Salhia, B., Cockell, K. A., Radich, J. P., Yamagishi, S.-I., Bignami, M., Verma, M., Kumar, D., Brenner, C., Zhang, Y.-W., Jamieson, D., Chi, Y.-H., Jeang, K.-T., Roninson, I., Dragani, T., Sobolev, A. S., Powers, M. V., Workmann, P., Evans, M. F., Cooper, K., Kausch, I., Doehn, C., Janz, S., Huang, C.-L., Toland, A. E., Osinaga, E., Kaye, F., Lemos, M. C., Thakker, R. V., Teh, B. T., Ponder, B. A. J., Mulligan, L. M., Gullo, C., Klein, G., Wu, X., Araten, D. J., Loeb, L. A., Cheadle, J. P., Lipsick, J., Albihn, A., Henriksson, M., Kremens, B., Germing, U., Zangemeister-Wittke, U., Simon, H.-U., Yu, Y. P., Luo, J., and Aman, P.

Published
2020

27. Exploring the thienopyrimidine scaffold for GPR55

Author

Figuerola-Asencio, Laura, Morales, Paula, Hurst, D. P., Zhao, Pingwei, Reggio, Patricia H., Abood, Mary E., and Jagerovic, Nadine

Abstract

GPR55 is an orphan Class A G-protein coupled receptor that recognizes a sub-set of cannabinoid CB1 and CB2 ligands, suggesting that GPR55 could belong to the endocannabinoid system. Lysophosphatidylinositol (LPI) has been proposed to be endogenous ligand for GPR55. However, GPR55 is still considered orphan receptor due to the lack of in vivo efficacy. The interest of GPR55 ligands as therapeutic agents is supported by the fact that this receptor is involved in diverse physiological and pathological processes such as inflammatory and neuropathic pain, metabolic disorder, bone and neuronal development, and cancer. Few potent GPR55 ligands have been identified to date due to an absence of information about salient features of GPR55, such as residues importance for binding and residues implicated in the GPR55 signaling cascade. High throughput screening of a large library of compounds from the Molecular Libraries Probe Production Centers Network (MLPCN) allowed the identification of different GPR55 chemical scaffolds, including ML192, a GPR55 antagonist. However, their potency and selectivity needs to be optimized in order to develop appropriate pharmacological tools or novel drugs to continue with the challenging goal of the validation of this receptor.

Published
2020

29. Exploring the Orphan GPCR GPR18 through Novel Synthetic Cannabidiol Derivatives

Author

Lago-Fernández, Ana, Zhao, Pingwei, Sotudeh, N., Leo, L. M., Brailoiu, E., Hurst, D. P., Morales, Paula, Reggio, P. H., Abood, M. E., Jagerovic, Nadine, Lago-Fernández, Ana, Zhao, Pingwei, Sotudeh, N., Leo, L. M., Brailoiu, E., Hurst, D. P., Morales, Paula, Reggio, P. H., Abood, M. E., and Jagerovic, Nadine

Abstract

GPR18 is an orphan GPCR highly expressed in lymphoid tissues and the central nervous system that regulates cellular migration, proliferation, nociociception, and immunomodulation. The endocannabinoid derivative N-Arachidonoylglycine (NAGly) has been proposed as the putative ligand. Several other cannabinoids also interact with GPR18, such as Abn-CBD and ¿9-THC. However, very few potent synthetic GPR18 ligands have been described so far. A new family of compounds with a cannabidiol scaffold were designed to target GPR18. Calcium mobilization imaging studies1 and docking studies in a in silico model2 were used to evaluate the activity of compounds and their mechanism of action. Here, two of the best compounds are exemplified: S5, a GPR18 agonist, and S4, a GPR18 antagonist.

Published
2020

30. LIGAND-BASED DRUG DESIGN APPROACHES FOR THE IDENTIFICATION OF NOVEL GPR55 MODULATORS

Author

Figuerola-Asencio, Laura, Morales, Paula, Hurst, D. P., Zhao, Pingwei, Reggio, Patricia H., Abood, Mary E., Jagerovic, Nadine, Figuerola-Asencio, Laura, Morales, Paula, Hurst, D. P., Zhao, Pingwei, Reggio, Patricia H., Abood, Mary E., and Jagerovic, Nadine

Abstract

GPR55 is an orphan Class A G-protein coupled receptor that recognizes a sub-set of cannabinoid CB1 and CB2 ligands, suggesting that GPR55 could belong to the endocannabinoid system. Lysophosphatidylinositol (LPI) has been proposed to be endogenous ligand for GPR55. This receptor is involved in diverse physiological and pathological processes such as inflammatory and neuropathic pain, metabolic disorder, bone and neuronal development, and cancer. Few potent GPR55 ligands have been identified to date. High throughput screening of a large library of compounds from the Molecular Libraries Probe Production Centers Network (MLPCN) allowed the identification of different GPR55 chemical scaffolds, including ML192, a GPR55 antagonist. However, their potency and selectivity needs to be optimized in order to develop appropriate pharmacological tools or novel drugs to continue with the challenging goal of the validation of this receptor

Published
2020

31. Therapeutic Exploitation of GPR18: Beyond the Cannabinoids?

Author

Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Comunidad de Madrid, Consejo Superior de Investigaciones Científicas (España), Morales, Paula, Lago-Fernández, Ana, Hurst, D. P., Sotudeh, N., Brailoiu, E., Reggio, P. H., Abood, Mary E., Jagerovic, Nadine, Ministerio de Ciencia, Innovación y Universidades (España), European Commission, Comunidad de Madrid, Consejo Superior de Investigaciones Científicas (España), Morales, Paula, Lago-Fernández, Ana, Hurst, D. P., Sotudeh, N., Brailoiu, E., Reggio, P. H., Abood, Mary E., and Jagerovic, Nadine

Abstract

GPR18 is a G-protein-coupled receptor that belongs to the orphan class A family. Even though it shares low sequence homology with the cannabinoid receptors CBR and CBR, a growing body of research suggests its relationship with the endocannabinoid system, not only because it is able to recognize cannabinoid ligands but also because of its expression and ability to heteromerize with CBRs. In this review, we aim to analyze the biological relevance, reported modulators, and structural features of GPR18. In order to guide future drug design in this field, highlights from molecular modeling of GPR18 will be provided.

Published
2020

32. GPR6 structural insights: Homology model construction and docking studies

Author

Comunidad de Madrid, Isawi, I. H., Morales, Paula, Sotudeh, Noori, Hurst, D. P., Lynch, Diane L., Reggio, Patricia H., Comunidad de Madrid, Isawi, I. H., Morales, Paula, Sotudeh, Noori, Hurst, D. P., Lynch, Diane L., and Reggio, Patricia H.

Abstract

GPR6 is an orphan G protein-coupled receptor that has been associated with the cannabinoid family because of its recognition of a sub-set of cannabinoid ligands. The high abundance of GPR6 in the central nervous system, along with high constitutive activity and a link to several neurodegenerative diseases make GPR6 a promising biological target. In fact, diverse research groups have demonstrated that GPR6 represents a possible target for the treatment of neurodegenerative disorders such as Parkinson’s disease, Alzheimer’s disease, and Huntington’s disease. Several patents have claimed the use of a wide range of pyrazine derivatives as GPR6 inverse agonists for the treatment of Parkinson’s disease symptoms and other dyskinesia syndromes. However, the full pharmacological importance of GPR6 has not yet been fully explored due to the lack of high potency, readily available ligands targeting GPR6. The long-term goal of the present study is to develop such ligands. In this paper, we describe our initial steps towards this goal. A human GPR6 homology model was constructed using a suite of computational techniques. This model permitted the identification of unique GPR6 structural features and the exploration of the GPR6 binding crevice. A subset of patented pyrazine analogs were docked in the resultant GPR6 inactive state model to validate the model, rationalize the structure-activity relationships from the reported patents and identify the key residues in the binding crevice for ligand recognition. We will take this structural knowledge into the next phase of GPR6 project, in which scaffold hopping will be used to design new GPR6 ligands.

Published
2020

33. Validation of SAGE III/ISS Solar Water Vapor Data With Correlative Satellite and Balloon‐Borne Measurements

Author

Davis, S. M., primary, Damadeo, R., additional, Flittner, D., additional, Rosenlof, K. H., additional, Park, M., additional, Randel, W. J., additional, Hall, E. G., additional, Huber, D., additional, Hurst, D. F., additional, Jordan, A. F., additional, Kizer, S., additional, Millan, L. F., additional, Selkirk, H., additional, Taha, G., additional, Walker, K. A., additional, and Vömel, H., additional

Published
2021
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34. Endurance training increases LKB1 and MO25 protein but not AMP-activated protein kinase kinase activity in skeletal muscle

Author

Taylor, E.B., Hurst, D., Greenwood, L.J., Lamb, J.D., Cline, T.D., Sudweeks, S.N., and Winder, W.W.

Subjects
Diabetes -- Research, Adenosine -- Research, Endurance sports -- Research, Biological sciences
Abstract

LKB1 complexed with MO25 and STRAD has been identified as an AMP-activated protein kinase kinase (AMPKK). We measured relative LKB1 protein abundance and AMPKK activity in liver (LV), heart (HT), soleus (SO), red quadriceps (RQ), and white quadriceps (WQ) from sedentary and endurance-trained rats. We examined trained RQ for altered levels of MO25 protein and LKB 1, STRAD, and MO25 mRNA. LKB 1 protein levels normalized to HT ([+ or -] 0.03) were LV (0.50 [+ or -] 0.03), SO (0.28 [+ or -] 0.02), RQ (0.32 [+ or -] 0.01), and WQ (0.12 [+ or -] 0.03). AMPKK activities in nanomoles per gram per minute were HT (79 [+ or -] 6), LV (220 [+ or -] 9), SO (22 [+ or -] 2), RQ (29 [+ or -] 2), and WQ (42 [+ or -] 4). Training increased LKB1 protein in SO, RQ, and WQ (P < 0.05). LKBI protein levels after training (%controls) were SO (158 [+ or -] 17), RQ (316 [+ or -] 17), WQ (191 [+ or -] 27), HT (106 [+ or -] 2), and LV (104 [+ or -] 7). MO25 protein after training (%controls) was 595 [+ or -] 71. Training did not affect AMPKK activity. MO25 but not LKB1 or STRAD mRNA increased with training (P < 0.05). Trained values (%controls) were MO25 (164 [+ or -] 22), LKB1 (120 [+ or -] 16), and STRAD (112 [+ or -] 17). LKB1 protein content strongly correlated (r = 0.93) with citrate synthase activity in skeletal muscle (P < 0.05). In conclusion, endurance training markedly increased skeletal muscle LKB 1 and MO25 protein without increasing AMPKK activity. LKB1 may be playing multiple roles in skeletal muscle adaptation to endurance training. adenosine 5'-monophosphate-activated protein kinase; diabetes; serine-threonine kinase-11 ; Ste20-related adaptor protein

Published
2004

37. The Relation Between Atmospheric Humidity and Temperature Trends for Stratospheric Water

Author

Fueglistaler, S, Liu, Y. S, Flannaghan, T. J, Haynes, P. H, Dee, D. P, Read, W. J, Remsberg, E. E, Thomason, L. W, Hurst, D. F, Lanzante, J. R, and Bernath, P. F

Subjects
Meteorology And Climatology
Abstract

We analyze the relation between atmospheric temperature and water vapor-a fundamental component of the global climate system-for stratospheric water vapor (SWV). We compare measurements of SWV (and methane where available) over the period 1980-2011 from NOAA balloon-borne frostpoint hygrometer (NOAA-FPH), SAGE II, Halogen Occultation Experiment (HALOE), Microwave Limb Sounder (MLS)/Aura, and Atmospheric Chemistry Experiment Fourier Transform Spectrometer (ACE-FTS) to model predictions based on troposphere-to-stratosphere transport from ERA-Interim, and temperatures from ERA-Interim, Modern Era Retrospective-Analysis (MERRA), Climate Forecast System Reanalysis (CFSR), Radiosonde Atmospheric Temperature Products for Assessing Climate (RATPAC), HadAT2, and RICHv1.5. All model predictions are dry biased. The interannual anomalies of the model predictions show periods of fairly regular oscillations, alternating with more quiescent periods and a few large-amplitude oscillations. They all agree well (correlation coefficients 0.9 and larger) with observations for higherfrequency variations (periods up to 2-3 years). Differences between SWV observations, and temperature data, respectively, render analysis of the model minus observation residual difficult. However, we find fairly well-defined periods of drifts in the residuals. For the 1980s, model predictions differ most, and only the calculation with ERA-Interim temperatures is roughly within observational uncertainties. All model predictions show a drying relative to HALOE in the 1990s, followed by a moistening in the early 2000s. Drifts to NOAA-FPH are similar (but stronger), whereas no drift is present against SAGE II. As a result, the model calculations have a less pronounced drop in SWV in 2000 than HALOE. From the mid-2000s onward, models and observations agree reasonably, and some differences can be traced to problems in the temperature data. These results indicate that both SWV and temperature data may still suffer from artifacts that need to be resolved in order to answer the question whether the large-scale flow and temperature field is sufficient to explain water entering the stratosphere.

Published
2013
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40. Informed Consent for Potential Recipients of Pig Kidney Xenotransplantation in the United States.

Author

Padilla LA, Hurst D, Maxwell K, Gawlowicz K, Paris W, Cleveland D, and Cooper DKC

Subjects
Animals, Female, Humans, Male, Swine, Transplantation, Heterologous, United States, Informed Consent, Kidney
Abstract

Clinical trials of kidney xenotransplantation are being considered in the United States. Before this novel procedure can take place, investigators will have to obtain approval from the institutional review board. The consent form that will be used for such a trial and that will receive approval from the institutional review board will be complex. Informed consent-the process by which a research participant provides his/her permission to participate in a clinical trial-is a staple of the research process and most commonly is in the form of a physical document. In the case of a novel procedure with uncertain benefits and risks and a participant population in acute need of a transplant, the consent process is crucial. These complexities may raise several ethical considerations for the initial pig kidney xenotransplantation recipients in the United States that will require adaptations of the required elements of the informed consent process by the US Department of Human and Health Services. The ethical issues include (1) a subject's ability to withdraw from the trial, (2) restrictions on their reproductive rights, and (3) the possibility of the need for quarantine if there is a perceived risk of xenozoonosis. This article aims to discuss ethical considerations that may challenge the general required elements of the informed consent form stipulated by the 45 Code of Federal Regulations 46 of the US Department of Health and Human Services and to suggest recommendations for deliberation., Competing Interests: D.K.C.C. is a consultant to eGenesis Bio (Cambridge, MA). The other authors declare no conflicts of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)

Published
2022
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41. Correction Technique for Raman Water Vapor Lidar Signal-Dependent Bias and Suitability for Water Wapor Trend Monitoring in the Upper Troposphere

Author

Whiteman, D. N, Cadirola, M, Venable, D, Calhoun, M, Miloshevich, L, Vermeesch, K, Twigg, L, Dirisu, A, Hurst, D, Hall, E, Jordan, A, and Voemel, H

Subjects
Geosciences (General), Instrumentation And Photography
Abstract

The MOHAVE-2009 campaign brought together diverse instrumentation for measuring atmospheric water vapor. We report on the participation of the ALVICE (Atmospheric Laboratory for Validation, Interagency Collaboration and Education) mobile laboratory in the MOHAVE-2009 campaign. In appendices we also report on the performance of the corrected Vaisala RS92 radiosonde measurements during the campaign, on a new radiosonde based calibration algorithm that reduces the influence of atmospheric variability on the derived calibration constant, and on other results of the ALVICE deployment. The MOHAVE-2009 campaign permitted the Raman lidar systems participating to discover and address measurement biases in the upper troposphere and lower stratosphere. The ALVICE lidar system was found to possess a wet bias which was attributed to fluorescence of insect material that was deposited on the telescope early in the mission. Other sources of wet biases are discussed and data from other Raman lidar systems are investigated, revealing that wet biases in upper tropospheric (UT) and lower stratospheric (LS) water vapor measurements appear to be quite common in Raman lidar systems. Lower stratospheric climatology of water vapor is investigated both as a means to check for the existence of these wet biases in Raman lidar data and as a source of correction for the bias. A correction technique is derived and applied to the ALVICE lidar water vapor profiles. Good agreement is found between corrected ALVICE lidar measurments and those of RS92, frost point hygrometer and total column water. The correction is offered as a general method to both quality control Raman water vapor lidar data and to correct those data that have signal-dependent bias. The influence of the correction is shown to be small at regions in the upper troposphere where recent work indicates detection of trends in atmospheric water vapor may be most robust. The correction shown here holds promise for permitting useful upper tropospheric water vapor profiles to be consistently measured by Raman lidar within NDACC (Network for the Detection of Atmospheric Composition Change) and elsewhere, despite the prevalence of instrumental and atmospheric effects that can contaminate the very low signal to noise measurements in the UT.

Published
2012
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42. Validation of MIPAS IMK-IAA Temperature, Water Vapor, and Ozone Profiles with MOHAVE-2009 Campaign Measurements

Author

Stiller, Gabrielle, Kiefer, M, Eckert, E, von Clarmann, T, Kellmann, S, Garcia-Comas, M, Funke, B, Leblanc, T, Fetzer, E, Froidevaux, L, Gomez, M, Hall, E, Hurst, D, Jordan, A, Kampfer, N, Lambert, A, McDermid, I. S, McGee, T, Miloshevich, L, Nedoluha, G, Read, W, Schneider, M, Schwartz, M, Straub, C, Toon, G, Twigg, L. W, Walker, K, and Whiteman, D. N

Subjects
Earth Resources And Remote Sensing, Meteorology And Climatology
Abstract

MIPAS observations of temperature, water vapor, and ozone in October 2009 as derived with the scientific level-2 processor run by Karlsruhe Institute of Technology (KIT), Institute for Meteorology and Climate Research (IMK) and CSIC, Instituto de Astrofısica de Andalucıa (IAA) and retrieved from version 4.67 level-1b data have been compared to co-located field campaign observations obtained during the MOHAVE-2009 campaign at the Table Mountain Facility near Pasadena, California in October 2009. The MIPAS measurements were validated regarding any potential biases of the profiles, and with respect to their precision estimates. The MOHAVE-2009 measurement campaign provided measurements of atmospheric profiles of temperature, water vapor/relative humidity, and ozone from the ground to the mesosphere by a suite of instruments including radiosondes, ozonesondes, frost point hygrometers, lidars, microwave radiometers and Fourier transform infrared (FTIR) spectrometers. For MIPAS temperatures (version V4O_T_204), no significant bias was detected in the middle stratosphere; between 22 km and the tropopause MIPAS temperatures were found to be biased low by up to 2 K, while below the tropopause, they were found to be too high by the same amount. These findings confirm earlier comparisons of MIPAS temperatures to ECMWF data which revealed similar differences. Above 12 km up to 45 km, MIPAS water vapor (version V4O_H2O_203) is well within 10% of the data of all correlative instruments. The well-known dry bias of MIPAS water vapor above 50 km due to neglect of non-LTE effects in the current retrievals has been confirmed. Some instruments indicate that MIPAS water vapor might be biased high by 20 to 40% around 10 km (or 5 km below the tropopause), but a consistent picture from all comparisons could not be derived. MIPAS ozone (version V4O_O3_202) has a high bias of up to +0.9 ppmv around 37 km which is due to a non-identified continuum like radiance contribution. No further significant biases have been detected. Cross-comparison to co-located observations of other satellite instruments (Aura/MLS, ACE-FTS, AIRS) is provided as well.

Published
2012
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44. State of the climate in 2016

Author

Aaron-Morrison, A. P., Ackerman, S. A., Adams, N. G., Adler, R. F., Albanil, A., Alfaro, E. J., Allan, R., Alves, L. M., Amador, J. A., Andreassen, L. M., Arendt, A., Arévalo, J., Arndt, D. S., Arzhanova, N. M., Aschan, M. M., Azorin-Molina, C., Banzon, V., Bardin, M. U., Barichivich, J., Baringer, M. O., Barreira, S., Baxter, S., Bazo, J., Becker, A., Bedka, K. M., Behrenfeld, M. J., Bell, G. D., Belmont, M., Benedetti, A., Bernhard, G., Berrisford, P., Berry, D. I., Bettolli, M. L., Bhatt, U. S., Bidegain, M., Bill, B. D., Billheimer, S., Bissolli, P., Blake, E. S., Blunden, J., Bosilovich, M. G., Boucher, O., Boudet, D., Box, J. E., Boyer, T., Braathen, G. O., Bromwich, D. H., Brown, R., Bulygina, O. N., Burgess, D., Calderón, B., Camargo, S. J., Campbell, J. D., Cappelen, J., Carrasco, G., Carter, B. R., Chambers, D. P., Chandler, E., Christiansen, H. H., Christy, J. R., Chung, D., Chung, E. S., Cinque, K., Clem, K. R., Coelho, C. A., Cogley, J. G., Coldewey-Egbers, M., Colwell, S., Cooper, O. R., Copland, L., Cosca, C. E., Cross, J. N., Crotwell, M. J., Crouch, J., Davis, S. M., Eyto, E., Jeu, R. A. M., Laat, J., Degasperi, C. L., Degenstein, D., Demircan, M., Derksen, C., Destin, D., Di Girolamo, L., Di Giuseppe, F., Diamond, H. J., Dlugokencky, E. J., Dohan, K., Dokulil, M. T., Dolgov, A. V., Dolman, A. J., Domingues, C. M., Donat, M. G., Dong, S., Dorigo, W. A., Dortch, Q., Doucette, G., Drozdov, D. S., Ducklow, H., Dunn, R. J. H., Durán-Quesada, A. M., Dutton, G. S., Ebrahim, A., Elkharrim, M., Elkins, J. W., Espinoza, J. C., Etienne-Leblanc, S., Evans, T. E., Famiglietti, J. S., Farrell, S., Fateh, S., Fausto, R. S., Fedaeff, N., Feely, R. A., Feng, Z., Fenimore, C., Fettweis, X., Fioletov, V. E., Flemming, J., Fogarty, C. T., Fogt, R. L., Folland, C., Fonseca, C., Fossheim, M., Foster, M. J., Fountain, A., Francis, S. D., Franz, B. A., Frey, R. A., Frith, S. M., Froidevaux, L., Ganter, C., Garzoli, S., Gerland, S., Gobron, N., Goldenberg, S. B., Gomez, R. S., Goni, G., Goto, A., Grooß, J. U., Gruber, A., Guard, C. C., Gugliemin, M., Gupta, S. K., Gutiérrez, J. M., Hagos, S., Hahn, S., Haimberger, L., Hakkarainen, J., Hall, B. D., Halpert, M. S., Hamlington, B. D., Hanna, E., Hansen, K., Hanssen-Bauer, I., Harris, I., Heidinger, A. K., Heikkilä, A., Heil, A., Heim, R. R., Hendricks, S., Hernández, M., Hidalgo, H. G., Hilburn, K., Ho, S. P. B., Holmes, R. M., Hu, Z. Z., Huang, B., Huelsing, H. K., Huffman, G. J., Hughes, C., Hurst, D. F., Ialongo, I., Ijampy, J. A., Ingvaldsen, R. B., Inness, A., Isaksen, K., Ishii, M., Jevrejeva, S., Jiménez, C., Jin, X., Johannesen, E., John, V., Johnsen, B., Johnson, B., Johnson, G. C., Jones, P. D., Joseph, A. C., Jumaux, G., Kabidi, K., Kaiser, J. W., Kato, S., Kazemi, A., Keller, L. M., Kendon, M., Kennedy, J., Kerr, K., Kholodov, A. L., Khoshkam, M., Killick, R., Kim, H., Kim, S. J., Kimberlain, T. B., Klotzbach, P. J., Knaff, J. A., Kobayashi, S., Kohler, J., Korhonen, J., Korshunova, N. N., Kovacs, K. M., Kramarova, N., Kratz, D. P., Kruger, A., Kruk, M. C., Kudela, R., Kumar, A., Lakatos, M., Lakkala, K., Lander, M. A., Landsea, C. W., Lankhorst, M., Lantz, K., Lazzara, M. A., Lemons, P., Leuliette, E., L’heureux, M., Lieser, J. L., Lin, I. I., Liu, H., Liu, Y., Locarnini, R., Loeb, N. G., Lo Monaco, C., Long, C. S., López Álvarez, L. A., Lorrey, A. M., Loyola, D., Lumpkin, R., Luo, J. J., Luojus, K., Lydersen, C., Lyman, J. M., Maberly, S. C., Maddux, B. C., Malheiros Ramos, A., Malkova, G. V., Manney, G., Marcellin, V., Marchenko, S. S., Marengo, J. A., Marra, J. J., Marszelewski, W., Martens, B., Martínez-Güingla, R., Massom, R. A., Mata, M. M., Mathis, J. T., May, L., Mayer, M., Mazloff, M., Mcbride, C., Mccabe, M. F., Mccarthy, M., Mcclelland, J. W., Mcgree, S., Mcvicar, T. R., Mears, C. A., Meier, W., Meinen, C. S., Mekonnen, A., Menéndez, M., Mengistu Tsidu, G., Menzel, W. P., Merchant, C. J., Meredith, M. P., Merrifield, M. A., Metzl, N., Minnis, P., Miralles, D. G., Mistelbauer, T., Mitchum, G. T., Monselesan, D., Monteiro, P., Montzka, S. A., Morice, C., Mote, T., Mudryk, L., Mühle, J., Mullan, A. B., Nash, E. R., Naveira-Garabato, A. C., Nerem, R. S., Newman, P. A., Nieto, J. J., Noetzli, J., O’neel, S., Osborn, T. J., Overland, J., Oyunjargal, L., Parinussa, R. M., Park, E. H., Parker, D., Parrington, M., Parsons, A. R., Pasch, R. J., Pascual-Ramírez, R., Paterson, A. M., Paulik, C., Pearce, P. R., Pelto, M. S., Peng, L., Perkins-Kirkpatrick, S. E., Perovich, D., Petropavlovskikh, I., Pezza, A. B., Phillips, D., Pinty, B., Pitts, M. C., Pons, M. R., Porter, A. O., Primicerio, R., Proshutinsky, A., Quegan, S., Quintana, J., Rahimzadeh, F., Rajeevan, M., Randriamarolaza, L., Razuvaev, V. N., Reagan, J., Reid, P., Reimer, C., Rémy, S., Renwick, J. A., Revadekar, J. V., Richter-Menge, J., Riffler, M., Rimmer, A., Rintoul, S., Robinson, D. A., Rodell, M., Rodríguez Solís, J. L., Romanovsky, V. E., Ronchail, J., Rosenlof, K. H., Roth, C., Rusak, J. A., Sabine, C. L., Sallée, J. B., Sánchez-Lugo, A., Santee, M. L., Sawaengphokhai, P., Sayouri, A., Scambos, T. A., Schemm, J., Schladow, S. G., Schmid, C., Schmid, M., Schmidtko, S., Schreck, C. J., Selkirk, H. B., Send, U., Sensoy, S., Setzer, A., Sharp, M., Shaw, A., Shi, L., Shiklomanov, A. I., Shiklomanov, N. I., Siegel, D. A., Signorini, S. R., Sima, F., Simmons, A. J., Smeets, C. J. P. P., Smith, S. L., Spence, J. M., Srivastava, A. K., Stackhouse, P. W., Stammerjohn, S., Steinbrecht, W., Stella, J. L., Stengel, M., Stennett-Brown, R., Stephenson, T. S., Strahan, S., Streletskiy, D. A., Sun-Mack, S., Swart, S., Sweet, W., Talley, L. D., Tamar, G., Tank, S. E., Taylor, M. A., Tedesco, M., Teubner, K., Thoman, R. L., Thompson, P., Thomson, L., Timmermans, M. L., Maxim Timofeyev, Tirnanes, J. A., Tobin, S., Trachte, K., Trainer, V. L., Tretiakov, M., Trewin, B. C., Trotman, A. R., Tschudi, M., As, D., Wal, R. S. W., A, R. J., Schalie, R., Schrier, G., Werf, G. R., Meerbeeck, C. J., Velicogna, I., Verburg, P., Vigneswaran, B., Vincent, L. A., Volkov, D., Vose, R. S., Wagner, W., Wåhlin, A., Wahr, J., Walsh, J., Wang, C., Wang, J., Wang, L., Wang, M., Wang, S. H., Wanninkhof, R., Watanabe, S., Weber, M., Weller, R. A., Weyhenmeyer, G. A., Whitewood, R., Wijffels, S. E., Wilber, A. C., Wild, J. D., Willett, K. M., Williams, M. J. M., Willie, S., Wolken, G., Wong, T., Wood, E. F., Woolway, R. I., Wouters, B., Xue, Y., Yamada, R., Yim, S. Y., Yin, X., Young, S. H., Yu, L., Zahid, H., Zambrano, E., Zhang, P., Zhao, G., Zhou, L., Ziemke, J. R., Love-Brotak, S. E., Gilbert, K., Maycock, T., Osborne, S., Sprain, M., Veasey, S. W., Ambrose, B. J., Griffin, J., Misch, D. J., Riddle, D. B., Young, T., Macias Fauria, M, Blunden, J, Arndt, D, Earth and Climate, Faculty of Earth and Life Sciences, Clinical Developmental Psychology, Climate Change and Landscape Dynamics, and Molecular Cell Physiology

Subjects
Meteor (satellite), Atmospheric Science, 010504 meteorology & atmospheric sciences, 0208 environmental biotechnology, 02 engineering and technology, 01 natural sciences, 020801 environmental engineering, Geography, 13. Climate action, Climatology, SDG 13 - Climate Action, SDG 14 - Life Below Water, 0105 earth and related environmental sciences
Abstract

In 2016, the dominant greenhouse gases released into Earth's atmosphere-carbon dioxide, methane, and nitrous oxide-continued to increase and reach new record highs. The 3.5 +/- 0.1 ppm rise in global annual mean carbon dioxide from 2015 to 2016 was the largest annual increase observed in the 58-year measurement record. The annual global average carbon dioxide concentration at Earth's surface surpassed 400 ppm (402.9 +/- 0.1 ppm) for the first time in the modern atmospheric measurement record and in ice core records dating back as far as 800000 years. One of the strongest El Nino events since at least 1950 dissipated in spring, and a weak La Nina evolved later in the year. Owing at least in part to the combination of El Nino conditions early in the year and a long-term upward trend, Earth's surface observed record warmth for a third consecutive year, albeit by a much slimmer margin than by which that record was set in 2015. Above Earth's surface, the annual lower troposphere temperature was record high according to all datasets analyzed, while the lower stratospheric temperature was record low according to most of the in situ and satellite datasets. Several countries, including Mexico and India, reported record high annual temperatures while many others observed near-record highs. A week-long heat wave at the end of April over the northern and eastern Indian peninsula, with temperatures surpassing 44 degrees C, contributed to a water crisis for 330 million people and to 300 fatalities. In the Arctic the 2016 land surface temperature was 2.0 degrees C above the 1981-2010 average, breaking the previous record of 2007, 2011, and 2015 by 0.8 degrees C, representing a 3.5 degrees C increase since the record began in 1900. The increasing temperatures have led to decreasing Arctic sea ice extent and thickness. On 24 March, the sea ice extent at the end of the growth season saw its lowest maximum in the 37-year satellite record, tying with 2015 at 7.2% below the 1981-2010 average. The September 2016 Arctic sea ice minimum extent tied with 2007 for the second lowest value on record, 33% lower than the 1981-2010 average. Arctic sea ice cover remains relatively young and thin, making it vulnerable to continued extensive melt. The mass of the Greenland Ice Sheet, which has the capacity to contribute similar to 7 m to sea level rise, reached a record low value. The onset of its surface melt was the second earliest, after 2012, in the 37-year satellite record. Sea surface temperature was record high at the global scale, surpassing the previous record of 2015 by about 0.01 degrees C. The global sea surface temperature trend for the 21st century-to-date of +0.162 degrees C decade(-1) is much higher than the longer term 1950-2016 trend of +0.100 degrees C decade(-1). Global annual mean sea level also reached a new record high, marking the sixth consecutive year of increase. Global annual ocean heat content saw a slight drop compared to the record high in 2015. Alpine glacier retreat continued around the globe, and preliminary data indicate that 2016 is the 37th consecutive year of negative annual mass balance. Across the Northern Hemisphere, snow cover for each month from February to June was among its four least extensive in the 47-year satellite record. Continuing a pattern below the surface, record high temperatures at 20-m depth were measured at all permafrost observatories on the North Slope of Alaska and at the Canadian observatory on northernmost Ellesmere Island. In the Antarctic, record low monthly surface pressures were broken at many stations, with the southern annular mode setting record high index values in March and June. Monthly high surface pressure records for August and November were set at several stations. During this period, record low daily and monthly sea ice extents were observed, with the November mean sea ice extent more than 5 standard deviations below the 1981-2010 average. These record low sea ice values contrast sharply with the record high values observed during 2012-14. Over the region, springtime Antarctic stratospheric ozone depletion was less severe relative to the 1991-2006 average, but ozone levels were still low compared to pre-1990 levels. Closer to the equator, 93 named tropical storms were observed during 2016, above the 1981-2010 average of 82, but fewer than the 101 storms recorded in 2015. Three basins-the North Atlantic, and eastern and western North Pacific-experienced above-normal activity in 2016. The Australian basin recorded its least active season since the beginning of the satellite era in 1970. Overall, four tropical cyclones reached the Saffir-Simpson category 5 intensity level. The strong El Nino at the beginning of the year that transitioned to a weak La Nina contributed to enhanced precipitation variability around the world. Wet conditions were observed throughout the year across southern South America, causing repeated heavy flooding in Argentina, Paraguay, and Uruguay. Wetter-than-usual conditions were also observed for eastern Europe and central Asia, alleviating the drought conditions of 2014 and 2015 in southern Russia. In the United States, California had its first wetter-than-average year since 2012, after being plagued by drought for several years. Even so, the area covered by drought in 2016 at the global scale was among the largest in the post-1950 record. For each month, at least 12% of land surfaces experienced severe drought conditions or worse, the longest such stretch in the record. In northeastern Brazil, drought conditions were observed for the fifth consecutive year, making this the longest drought on record in the region. Dry conditions were also observed in western Bolivia and Peru; it was Bolivia's worst drought in the past 25 years. In May, with abnormally warm and dry conditions already prevailing over western Canada for about a year, the human-induced Fort McMurray wildfire burned nearly 590000 hectares and became the costliest disaster in Canadian history, with $3 billion (U.S. dollars) in insured losses.

Published
2017
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46. Why don't general dental practitioners test for diabetes in periodontitis patients? How infrastructure, role identity and self-efficacy can prevent effective shared care.

Author

Rattu V and Hurst D

Subjects
Attitude of Health Personnel, Dentists, General Practice, Dental, Humans, Professional Role, Self Efficacy, Diabetes Mellitus diagnosis, Periodontitis
Abstract

Aim To explore the attitudes of general dental practitioners (GDPs) towards testing for diabetes in periodontitis patients amid recommendations from professional organisations that dentists and oral health professionals are well-positioned to support the diagnosis of diabetes in primary dental care.Method GDPs were selected based on purposeful sampling. The number of GDPs recruited was dependent on thematic saturation. Semi-structured telephone interviews were conducted with all recruited GDPs. Interviews were audio recorded and transcribed verbatim. Thematic analysis was utilised to generate initial codes and subsequent themes.Results Fifteen GDPs participated in this qualitative study. Three main interrelated themes emerged: 1) there is an inadequate infrastructure within the current NHS; 2) the difference in the definition and threshold of the social and professional roles and identities of GDPs; and 3) there is a low self-efficacy to testing due to a perceived lack of knowledge.Conclusions This qualitative study has identified the barriers to and enablers for testing for diabetes in patients with periodontitis attending general dental practices in England. The findings have the potential to influence interventions and policies going forward to improve the co-management of diabetes and periodontitis within primary healthcare., (© 2022. The Author(s), under exclusive licence to the British Dental Association.)

Published
2022
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48. State of the Climate in 2018

Author

Arndt, D. S., Blunden, J., Dunn, R. J. H., Stanitski, D. M., Gobron, N., Willett, K. M., Sanchez-lugo, A., Berrisford, P., Morice, C., Nicolas, Jp, Carrea, L., Woolway, R. I., Merchant, C. J., Dokulil, M. T., De Eyto, E., Degasperi, C. L., Korhonen, J., Marszelewski, W., May, L., Paterson, A. M., Rusak, J. A., Schladow, S. G., Schmid, M., Verburg, P., Watanabe, S., Weyhenmeyer, G. A., King, A. D., Donat, M. G., Christy, J. R., Po-chedley, S., Mears, C. R., Haimberger, L., Covey, C., Randel, W., Noetzli, J., Biskaborn, B. K., Christiansen, H. H., Isaksen, K., Schoeneich, P., Smith, S., Vieira, G., Zhao, L., Streletskiy, D. A., Robinson, D. A., Pelto, M., Berry, D. I., Bosilovich, M. G., Simmons, A. J., Mears, C., Ho, S. P., Bock, O., Zhou, X., Nicolas, J, Vose, R. S., Adler, R., Gu, G., Becker, A., Yin, X, Tye, M. R., Blenkinsop, S., Durre, I., Ziese, M., Collow, A. B. Marquardt, Rustemeier, E., Foster, M. J., Di Girolamo, L., Frey, R. A., Heidinger, A. K., Sun-mack, S., Phillips, C., Menzel, W. P., Stengel, M., Zhao, G., Kim, H., Rodell, M., Li, B., Famiglietti, J. S., Scanlon, T., Van Der Schalie, R., Preimesberger, W., Reimer, C., Hahn, S., Gruber, A., Kidd, R., De Jeu, R. A. M., Dorigo, W. A., Barichivich, J., Osborn, T. J., Harris, I., Van Der Schrier, G., Jones, P. D., Miralles, D. G., Martens, B., Beck, H. E., Dolman, A. J., Jimenez, C., Mccabe, M. F., Wood, E. F., Allan, R., Azorin-molina, C., Mears, C. A., Mcvicar, T. R., Mayer, M., Schenzinger, V., Hersbach, H., Stackhouse, P. W., Jr., Wong, T., Kratz, D. P., Sawaengphokhai, P., Wilber, A. C., Gupta, S. K., Loeb, N. G., Dlugokencky, E. J., Hall, B. D., Montzka, S. A., Dutton, G., Muhle, J., Elkins, J. W., Miller, Br, Remy, S., Bellouin, N., Kipling, Z., Ades, M., Benedetti, A., Boucher, O., Weber, M., Steinbrecht, W., Arosio, C., Van Der A, R., Frith, S. M., Anderson, J., Coldewey-egbers, M., Davis, S., Degenstein, D., Fioletov, V. E., Froidevaux, L., Hubert, D., Long, C. S., Loyola, D., Rozanov, A., Roth, C., Sofieva, V., Tourpali, K., Wang, R., Wild, J. D., Davis, S. M., Rosenlof, K. H., Hurst, D. F., Selkirk, H. B., Vomel, H., Ziemke, J. R., Cooper, O. R., Flemming, J., Inness, A., Pinty, B., Kaiser, J. W., Van Der Werf, G. R., Hemming, D. L., Garforth, J., Park, T., Richardson, A. D., Rutishauser, T., Sparks, T. H., Thackeray, S. J., Myneni, R., Lumpkin, R., Huang, B., Kennedy, J., Xue, Y., Zhang, H. -m., Hu, C., Wang, M., Johnson, G. C., Lyman, J. M., Boyer, T., Cheng, L., Domingues, C. M., Gilson, J., Ishii, M., Killick, R. E., Monselesan, D., Purkey, S. G., Wijffels, S. E., Locarnini, R., Yu, L., Jin, X., Stackhouse, P. W., Kato, S., Weller, R. A., Thompson, P. R., Widlansky, M. J., Leuliette, E., Sweet, W., Chambers, D. P., Hamlington, B. D., Jevrejeva, S., Marra, J. J., Merrifield, M. A., Mitchum, G. T., Nerem, R. S., Kelble, C., Karnauskas, M., Hubbard, K., Goni, G., Streeter, C., Dohan, K., Franz, B. A., Cetinic, I., Karakoylu, E. M., Siegel, D. A., Westberry, T. K., Feely, R. A., Wanninkhof, R., Carter, B. R., Landschutzer, P., Sutton, A. J., Cosca, C., Trinanes, J. A., Baxter, S., Schreck, C., Bell, G. D., Mullan, A. B., Pezza, A. B., Coelho, C. A. S., Wang, B., He, Q., Diamond, H. J., Schreck, C. J., Blake, E. S., Landsea, C. W., Wang, H., Goldenberg, S. B., Pasch, R. J., Klotzbach, P. J., Kruk, M. C., Camargo, S. J., Trewin, B. C., Pearce, P. R., Lorrey, A. M., Domingues, R., Goni, G. J., Knaff, J. A., Lin, I. -i., Bringas, F., Richter-menge, J., Osborne, E., Druckenmiller, M., Jeffries, M. O., Overland, J. E., Hanna, E., Hanssen-bauer, I., Kim, S. -j., Walsh, J. E., Bhatt, U. S., Timmermans, M. -l., Ladd, C., Perovich, D., Meier, W., Tschudi, M., Farrell, S., Hendricks, S., Gerland, S., Haas, C., Krumpen, T., Polashenski, C., Ricker, R, Webster, M., Stabeno, P. J., Tedesco, M., Box, J. E., Cappelen, J., Fausto, R. S., Fettweis, X., Andersen, J. K., Mote, T., Smeets, C. J. P. P., Van As, D., Van De Wal, R. S. W., Romanovsky, V. E., Smith, S. L., Shiklomanov, N. I., Kholodov, A. L., Drozdov, D. S., Malkova, G. V., Marchenko, S. S., Jella, K. B., Mudryk, L., Brown, R., Derksen, C., Luojus, K., Decharme, B., Holmes, R. M., Shiklomanov, A. I., Suslova, A., Tretiakov, M., Mcclelland, J. W., Spencer, R. G. M., Tank, S. E., Epstein, H., Bhatt, U., Raynolds, M., Walker, D., Forbes, B., Phoenix, G., Bjerke, J., Tommervik, H., Karlsen, S. -r., Goetz, S., Jia, G., Bernhard, G. H., Grooss, J. -u., Ialongo, I., Johnsen, B., Lakkala, K., Manney, G. L., Mueller, R., Scambos, T., Stammerjohn, S., Clem, K. R., Barreira, S., Fogt, R. L., Colwell, S., Keller, L. M., Lazzara, M. A., Reid, P., Massom, R. A., Lieser, J. L., Meijers, A., Sallee, J. -b., Grey, A., Johnson, K., Arrigo, K., Swart, S., King, B., Meredith, M., Mazloff, M., Scardilli, A., Claus, F., Shuman, C. A., Kramarova, N., Newman, P. A., Nash, E. R., Strahan, S. E., Johnson, B., Pitts, M., Santee, M. L., Petropavlovskikh, I., Braathen, G. O., Coy, L., De Laat, J., Bissolli, P., Ganter, C., Li, T., Mekonnen, A., Gleason, K., Smith, A., Fenimore, C., Heim, R. R., Jr., Nauslar, N. J., Brown, T. J., Mcevoy, D. J., Lareau, N. P., Amador, J. A., Hidalgo, H. G., Alfaro, E. J., Calderon, B., Mora, N., Stephenson, T. S., Taylor, M. A., Trotman, A. R., Van Meerbeeck, C. J., Campbell, J. D., Brown, A., Spence, J., Martinez, R., Diaz, E., Marin, D., Hernandez, R., Caceres, L., Zambrano, E., Nieto, J., Marengo, J. A., Espinoza, J. C., Alves, L. M., Ronchail, J., Lavado-casimiro, J. W., Ramos, I., Davila, C., Ramos, A. M., Diniz, F. A., Aliaga-nestares, V., Castro, A. Y., Stella, J. L., Aldeco, L. S., Diaz, D. A. Campos, Misevicius, N., Kabidi, K., Sayouri, A., Elkharrim, M., Mostafa, A. E., Hagos, S., Feng, Z., Ijampy, J. A., Sima, F., Francis, S. D., Tsidu, G. Mengistu, Kruger, A. C., Mcbride, C., Jumaux, G., Dhurmea, K. R., Belmont, M., Rakotoarimalala, C. L., Labbe, L., Rosner, B., Benedict, I., Van Heerwaarden, C., Weerts, A., Hazeleger, W., Trachte, K., Zhu, Z., Zhang, P., Lee, T. C., Ripaldi, A., Mochizuki, Y., Lim, J. -y, Oyunjargal, L., Timbal, B., Srivastava, A. K., Revadekar, J. V., Rajeevan, M., Shimpo, A., Khoshkam, M., Kazemi, A. Fazl, Zeyaeyan, S., Lander, M. A., Mcgree, S., Tobin, S., Bettio, L., Arndt, D. S., Blunden, J., Dunn, R. J. H., Stanitski, D. M., Gobron, N., Willett, K. M., Sanchez-lugo, A., Berrisford, P., Morice, C., Nicolas, Jp, Carrea, L., Woolway, R. I., Merchant, C. J., Dokulil, M. T., De Eyto, E., Degasperi, C. L., Korhonen, J., Marszelewski, W., May, L., Paterson, A. M., Rusak, J. A., Schladow, S. G., Schmid, M., Verburg, P., Watanabe, S., Weyhenmeyer, G. A., King, A. D., Donat, M. G., Christy, J. R., Po-chedley, S., Mears, C. R., Haimberger, L., Covey, C., Randel, W., Noetzli, J., Biskaborn, B. K., Christiansen, H. H., Isaksen, K., Schoeneich, P., Smith, S., Vieira, G., Zhao, L., Streletskiy, D. A., Robinson, D. A., Pelto, M., Berry, D. I., Bosilovich, M. G., Simmons, A. J., Mears, C., Ho, S. P., Bock, O., Zhou, X., Nicolas, J, Vose, R. S., Adler, R., Gu, G., Becker, A., Yin, X, Tye, M. R., Blenkinsop, S., Durre, I., Ziese, M., Collow, A. B. Marquardt, Rustemeier, E., Foster, M. J., Di Girolamo, L., Frey, R. A., Heidinger, A. K., Sun-mack, S., Phillips, C., Menzel, W. P., Stengel, M., Zhao, G., Kim, H., Rodell, M., Li, B., Famiglietti, J. S., Scanlon, T., Van Der Schalie, R., Preimesberger, W., Reimer, C., Hahn, S., Gruber, A., Kidd, R., De Jeu, R. A. M., Dorigo, W. A., Barichivich, J., Osborn, T. J., Harris, I., Van Der Schrier, G., Jones, P. D., Miralles, D. G., Martens, B., Beck, H. E., Dolman, A. J., Jimenez, C., Mccabe, M. F., Wood, E. F., Allan, R., Azorin-molina, C., Mears, C. A., Mcvicar, T. R., Mayer, M., Schenzinger, V., Hersbach, H., Stackhouse, P. W., Jr., Wong, T., Kratz, D. P., Sawaengphokhai, P., Wilber, A. C., Gupta, S. K., Loeb, N. G., Dlugokencky, E. J., Hall, B. D., Montzka, S. A., Dutton, G., Muhle, J., Elkins, J. W., Miller, Br, Remy, S., Bellouin, N., Kipling, Z., Ades, M., Benedetti, A., Boucher, O., Weber, M., Steinbrecht, W., Arosio, C., Van Der A, R., Frith, S. M., Anderson, J., Coldewey-egbers, M., Davis, S., Degenstein, D., Fioletov, V. E., Froidevaux, L., Hubert, D., Long, C. S., Loyola, D., Rozanov, A., Roth, C., Sofieva, V., Tourpali, K., Wang, R., Wild, J. D., Davis, S. M., Rosenlof, K. H., Hurst, D. F., Selkirk, H. B., Vomel, H., Ziemke, J. R., Cooper, O. R., Flemming, J., Inness, A., Pinty, B., Kaiser, J. W., Van Der Werf, G. R., Hemming, D. L., Garforth, J., Park, T., Richardson, A. D., Rutishauser, T., Sparks, T. H., Thackeray, S. J., Myneni, R., Lumpkin, R., Huang, B., Kennedy, J., Xue, Y., Zhang, H. -m., Hu, C., Wang, M., Johnson, G. C., Lyman, J. M., Boyer, T., Cheng, L., Domingues, C. M., Gilson, J., Ishii, M., Killick, R. E., Monselesan, D., Purkey, S. G., Wijffels, S. E., Locarnini, R., Yu, L., Jin, X., Stackhouse, P. W., Kato, S., Weller, R. A., Thompson, P. R., Widlansky, M. J., Leuliette, E., Sweet, W., Chambers, D. P., Hamlington, B. D., Jevrejeva, S., Marra, J. J., Merrifield, M. A., Mitchum, G. T., Nerem, R. S., Kelble, C., Karnauskas, M., Hubbard, K., Goni, G., Streeter, C., Dohan, K., Franz, B. A., Cetinic, I., Karakoylu, E. M., Siegel, D. A., Westberry, T. K., Feely, R. A., Wanninkhof, R., Carter, B. R., Landschutzer, P., Sutton, A. J., Cosca, C., Trinanes, J. A., Baxter, S., Schreck, C., Bell, G. D., Mullan, A. B., Pezza, A. B., Coelho, C. A. S., Wang, B., He, Q., Diamond, H. J., Schreck, C. J., Blake, E. S., Landsea, C. W., Wang, H., Goldenberg, S. B., Pasch, R. J., Klotzbach, P. J., Kruk, M. C., Camargo, S. J., Trewin, B. C., Pearce, P. R., Lorrey, A. M., Domingues, R., Goni, G. J., Knaff, J. A., Lin, I. -i., Bringas, F., Richter-menge, J., Osborne, E., Druckenmiller, M., Jeffries, M. O., Overland, J. E., Hanna, E., Hanssen-bauer, I., Kim, S. -j., Walsh, J. E., Bhatt, U. S., Timmermans, M. -l., Ladd, C., Perovich, D., Meier, W., Tschudi, M., Farrell, S., Hendricks, S., Gerland, S., Haas, C., Krumpen, T., Polashenski, C., Ricker, R, Webster, M., Stabeno, P. J., Tedesco, M., Box, J. E., Cappelen, J., Fausto, R. S., Fettweis, X., Andersen, J. K., Mote, T., Smeets, C. J. P. P., Van As, D., Van De Wal, R. S. W., Romanovsky, V. E., Smith, S. L., Shiklomanov, N. I., Kholodov, A. L., Drozdov, D. S., Malkova, G. V., Marchenko, S. S., Jella, K. B., Mudryk, L., Brown, R., Derksen, C., Luojus, K., Decharme, B., Holmes, R. M., Shiklomanov, A. I., Suslova, A., Tretiakov, M., Mcclelland, J. W., Spencer, R. G. M., Tank, S. E., Epstein, H., Bhatt, U., Raynolds, M., Walker, D., Forbes, B., Phoenix, G., Bjerke, J., Tommervik, H., Karlsen, S. -r., Goetz, S., Jia, G., Bernhard, G. H., Grooss, J. -u., Ialongo, I., Johnsen, B., Lakkala, K., Manney, G. L., Mueller, R., Scambos, T., Stammerjohn, S., Clem, K. R., Barreira, S., Fogt, R. L., Colwell, S., Keller, L. M., Lazzara, M. A., Reid, P., Massom, R. A., Lieser, J. L., Meijers, A., Sallee, J. -b., Grey, A., Johnson, K., Arrigo, K., Swart, S., King, B., Meredith, M., Mazloff, M., Scardilli, A., Claus, F., Shuman, C. A., Kramarova, N., Newman, P. A., Nash, E. R., Strahan, S. E., Johnson, B., Pitts, M., Santee, M. L., Petropavlovskikh, I., Braathen, G. O., Coy, L., De Laat, J., Bissolli, P., Ganter, C., Li, T., Mekonnen, A., Gleason, K., Smith, A., Fenimore, C., Heim, R. R., Jr., Nauslar, N. J., Brown, T. J., Mcevoy, D. J., Lareau, N. P., Amador, J. A., Hidalgo, H. G., Alfaro, E. J., Calderon, B., Mora, N., Stephenson, T. S., Taylor, M. A., Trotman, A. R., Van Meerbeeck, C. J., Campbell, J. D., Brown, A., Spence, J., Martinez, R., Diaz, E., Marin, D., Hernandez, R., Caceres, L., Zambrano, E., Nieto, J., Marengo, J. A., Espinoza, J. C., Alves, L. M., Ronchail, J., Lavado-casimiro, J. W., Ramos, I., Davila, C., Ramos, A. M., Diniz, F. A., Aliaga-nestares, V., Castro, A. Y., Stella, J. L., Aldeco, L. S., Diaz, D. A. Campos, Misevicius, N., Kabidi, K., Sayouri, A., Elkharrim, M., Mostafa, A. E., Hagos, S., Feng, Z., Ijampy, J. A., Sima, F., Francis, S. D., Tsidu, G. Mengistu, Kruger, A. C., Mcbride, C., Jumaux, G., Dhurmea, K. R., Belmont, M., Rakotoarimalala, C. L., Labbe, L., Rosner, B., Benedict, I., Van Heerwaarden, C., Weerts, A., Hazeleger, W., Trachte, K., Zhu, Z., Zhang, P., Lee, T. C., Ripaldi, A., Mochizuki, Y., Lim, J. -y, Oyunjargal, L., Timbal, B., Srivastava, A. K., Revadekar, J. V., Rajeevan, M., Shimpo, A., Khoshkam, M., Kazemi, A. Fazl, Zeyaeyan, S., Lander, M. A., Mcgree, S., Tobin, S., and Bettio, L.

Published
2019

49. GCOS reference upper air network (GRUAN) : Steps towards assuring future climate records

Author

Thorne, P. W., Vömel, H., Bodeker, G., Sommer, M., Apituley, A., Berger, F., Bojinski, S., Braathen, G., Calpini, B., Demoz, B., Diamond, H. J., Dykema, J., Fassò, A., Fujiwara, M., Gardiner, T., Hurst, D., Leblanc, T., Madonna, F., Merlone, A., Mikalsen, A., Miller, C. D., Reale, T., Rannat, K., Richter, C., Seidel, D. J., Shiotani, M., Sisterson, D., Tan, D. G. H., Vose, R. S., Voyles, J., Wang, J., Whiteman, D. N., Williams, S., Thorne, P. W., Vömel, H., Bodeker, G., Sommer, M., Apituley, A., Berger, F., Bojinski, S., Braathen, G., Calpini, B., Demoz, B., Diamond, H. J., Dykema, J., Fassò, A., Fujiwara, M., Gardiner, T., Hurst, D., Leblanc, T., Madonna, F., Merlone, A., Mikalsen, A., Miller, C. D., Reale, T., Rannat, K., Richter, C., Seidel, D. J., Shiotani, M., Sisterson, D., Tan, D. G. H., Vose, R. S., Voyles, J., Wang, J., Whiteman, D. N., and Williams, S.

Published
2019

50. Design of Novel GPR6 Inverse Agonists Using a Fragment Replacement Scaffold Hopping Approach

Author

Isawi, Israa, Morales, Paula, Hurst, D. P., Jagerovic, Nadine, Reggio, Patricia H., Isawi, Israa, Morales, Paula, Hurst, D. P., Jagerovic, Nadine, and Reggio, Patricia H.

Abstract

The orphan G protein coupled receptor 6 (GPR6) is a cannabinoid-related Class A GPCR. It is highly expressed in the central nervous system and exhibits high constitutive activation of adenylyl cyclase. Several research groups have demonstrated that GPR6 represents a possible target for the treatment of neurodegenerative disorders such as Parkinson’s, Alzheimer’s, and Huntington’s diseases. Several patents claim the use of a wide range of pyrazine derivatives as GPR6 inverse agonists for the treatment of Parkinson’s disease and other dyskinesia syndromes. Using cyclic AMP accumulation assays in hGPR6-CHO cells as a readout, the most potent GPR6 pyridopyrazine inverse agonist compounds identified thus far have been found to display IC50 values in the low nanomolar range. A subset of these compounds was used here as starting points for the design of novel potent GPR6 inverse agonists using a core hopping approach. In parallel with the core hopping studies, we employed a recently constructed homology model of the GPR6 inactive state. The X-ray crystal structure of the Sphingosine-1-phosphate receptor 1 (S1P1) receptor structure was used as the template and the conformational memories technique was used to explore the conformational consequences of sequence differences between S1P1 and GPR6. The most potent GPR6 pyridopyrazine inverse agonists were docked in the resultant GPR6 inactive state model, first as tests of the model. Once we had identified the binding site of each inverse agonist, we used this site to identify amino acid sites in proximity that we can use to build additional interactions for ligands output from core hopping studies above. ADME properties and the absence of PAINS will also be considered for the hit selection process. These potential GPR6 chemotypes may serve as research tools for further understanding the biological role of this orphan receptor.

Published
2019

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