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Article ; Online: Correction: Disseminated intravascular coagulation phenotype is regulated by the TRPM7 channel during sepsis.

Jiménez-Dinamarca, Ivanka / Prado, Yolanda / Tapia, Pablo / Gatica, Sebastian / Alt, Clemens / Lin, Charles P / Reyes-Martínez, Cristian / Feijóo, Carmen G / Aravena, Cristobal / González-Canacer, Alejandra / Correa, Simón / Varela, Diego / Cabello-Verrugio, Claudio / Simon, Felipe

Biological research

2023 Volume 56, Issue 1, Page(s) 24

Language	English
Publishing date	2023-05-11
Publishing country	England
Document type	Published Erratum
ZDB-ID	1138990-4
ISSN	0717-6287 ; 0716-9760
ISSN (online)	0717-6287
ISSN	0716-9760
DOI	10.1186/s40659-023-00433-6
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Article ; Online: Correction

Ivanka Jiménez-Dinamarca / Yolanda Prado / Pablo Tapia / Sebastian Gatica / Clemens Alt / Charles P. Lin / Cristian Reyes-Martínez / Carmen G. Feijóo / Cristobal Aravena / Alejandra González-Canacer / Simón Correa / Diego Varela / Claudio Cabello-Verrugio / Felipe Simon

Biological Research, Vol 56, Iss 1, Pp 1-

Disseminated intravascular coagulation phenotype is regulated by the TRPM7 channel during sepsis

2023 Volume 3

Keywords	Biology (General) ; QH301-705.5
Language	English
Publishing date	2023-05-01T00:00:00Z
Publisher	BMC
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels.

Jiménez-Dinamarca, Ivanka / Reyes-Lizana, Rachel / Lemunao-Inostroza, Yordan / Cárdenas, Kevin / Castro-Lazo, Raimundo / Peña, Francisca / Lucero, Claudia M / Prieto-Villalobos, Juan / Retamal, Mauricio Antonio / Orellana, Juan Andrés / Stehberg, Jimmy

International journal of molecular sciences

2022 Volume 23, Issue 21

Abstract: Gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. It is produced by interneurons and recycled by astrocytes. In neurons, GABA activates the influx of ... ...

Abstract	Gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. It is produced by interneurons and recycled by astrocytes. In neurons, GABA activates the influx of Cl
MeSH term(s)	Rats ; Animals ; Connexin 43/metabolism ; Astrocytes/metabolism ; Receptors, GABA-A ; Bicuculline/pharmacology ; Animals, Newborn ; Cells, Cultured ; Glutamic Acid/pharmacology ; gamma-Aminobutyric Acid/pharmacology ; Adenosine Triphosphate/pharmacology
Chemical Substances	Connexin 43 ; Receptors, GABA-A ; Bicuculline (Y37615DVKC) ; Glutamic Acid (3KX376GY7L) ; gamma-Aminobutyric Acid (56-12-2) ; Adenosine Triphosphate (8L70Q75FXE)
Language	English
Publishing date	2022-11-07
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232113625
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Article ; Online: Disseminated intravascular coagulation phenotype is regulated by the TRPM7 channel during sepsis.

Biological research

2023 Volume 56, Issue 1, Page(s) 8

Abstract: Background: Sepsis is an uncontrolled inflammatory response against a systemic infection that results in elevated mortality, mainly induced by bacterial products known as endotoxins, producing endotoxemia. Disseminated intravascular coagulation (DIC) is ...

Abstract	Background: Sepsis is an uncontrolled inflammatory response against a systemic infection that results in elevated mortality, mainly induced by bacterial products known as endotoxins, producing endotoxemia. Disseminated intravascular coagulation (DIC) is frequently observed in septic patients and is associated with organ failure and death. Sepsis activates endothelial cells (ECs), promoting a prothrombotic phenotype contributing to DIC. Ion channel-mediated calcium permeability participates in coagulation. The transient reception potential melastatin 7 (TRPM7) non-selective divalent cation channel that also contains an α-kinase domain, which is permeable to divalent cations including Ca Results: The results showed that TRPM7 regulated endotoxin-induced platelet and neutrophil adhesion to ECs, dependent on the TRPM7 ion channel activity and by the α-kinase function. Endotoxic animals showed that TRPM7 mediated neutrophil rolling on blood vessels and intravascular coagulation. TRPM7 mediated the increased expression of the adhesion proteins, von Willebrand factor (vWF), intercellular adhesion molecule 1 (ICAM-1), and P-selectin, which were also mediated by the TRPM7 α-kinase function. Notably, endotoxin-induced expression of vWF, ICAM-1 and P-selectin were required for endotoxin-induced platelet and neutrophil adhesion to ECs. Endotoxemic rats showed increased endothelial TRPM7 expression associated with a procoagulant phenotype, liver and kidney dysfunction, increased death events and an increased relative risk of death. Interestingly, circulating ECs (CECs) from septic shock patients (SSPs) showed increased TRPM7 expression associated with increased DIC scores and decreased survival times. Additionally, SSPs with a high expression of TRPM7 in CECs showed increased mortality and relative risk of death. Notably, CECs from SSPs showed significant results from the AUROC analyses for predicting mortality in SSPs that were better than the Acute Physiology and Chronic Health Evaluation II (APACHE II) and the Sequential Organ Failure Assessment (SOFA) scores. Conclusions: Our study demonstrates that sepsis-induced DIC is mediated by TRPM7 in ECs. TRPM7 ion channel activity and α-kinase function are required by DIC-mediated sepsis-induced organ dysfunction and its expression are associated with increased mortality during sepsis. TRPM7 appears as a new prognostic biomarker to predict mortality associated to DIC in SSPs, and as a novel target for drug development against DIC during infectious inflammatory diseases.
MeSH term(s)	Animals ; Rats ; Intercellular Adhesion Molecule-1 ; P-Selectin ; TRPM Cation Channels ; Endothelial Cells ; Endotoxemia ; Calcium ; Disseminated Intravascular Coagulation ; von Willebrand Factor ; Sepsis ; Endotoxins
Chemical Substances	Intercellular Adhesion Molecule-1 (126547-89-5) ; P-Selectin ; TRPM Cation Channels ; Calcium (SY7Q814VUP) ; von Willebrand Factor ; Endotoxins ; Trpm7 protein, rat (EC 2.7.11.1)
Language	English
Publishing date	2023-03-03
Publishing country	England
Document type	Journal Article
ZDB-ID	1138990-4
ISSN	0717-6287 ; 0716-9760
ISSN (online)	0717-6287
ISSN	0716-9760
DOI	10.1186/s40659-023-00419-4
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Article ; Online: GABAergic Regulation of Astroglial Gliotransmission through Cx43 Hemichannels

Ivanka Jiménez-Dinamarca / Rachel Reyes-Lizana / Yordan Lemunao-Inostroza / Kevin Cárdenas / Raimundo Castro-Lazo / Francisca Peña / Claudia M. Lucero / Juan Prieto-Villalobos / Mauricio Antonio Retamal / Juan Andrés Orellana / Jimmy Stehberg

International Journal of Molecular Sciences, Vol 23, Iss 13625, p

2022 Volume 13625

Abstract	Gamma-Aminobutyric acid (GABA) is the primary inhibitory neurotransmitter in the brain. It is produced by interneurons and recycled by astrocytes. In neurons, GABA activates the influx of Cl - via the GABA A receptor or efflux or K + via the GABA B receptor, inducing hyperpolarization and synaptic inhibition. In astrocytes, the activation of both GABA A and GABA B receptors induces an increase in intracellular Ca 2+ and the release of glutamate and ATP. Connexin 43 (Cx43) hemichannels are among the main Ca 2+ -dependent cellular mechanisms for the astroglial release of glutamate and ATP. However, no study has evaluated the effect of GABA on astroglial Cx43 hemichannel activity and Cx43 hemichannel-mediated gliotransmission. Here we assessed the effects of GABA on Cx43 hemichannel activity in DI NCT1 rat astrocytes and hippocampal brain slices. We found that GABA induces a Ca 2+ -dependent increase in Cx43 hemichannel activity in astrocytes mediated by the GABA A receptor, as it was blunted by the GABA A receptor antagonist bicuculline but unaffected by GABA B receptor antagonist CGP55845. Moreover, GABA induced the Cx43 hemichannel-dependent release of glutamate and ATP, which was also prevented by bicuculline, but unaffected by CGP. Gliotransmission in response to GABA was also unaffected by pannexin 1 channel blockade. These results are discussed in terms of the possible role of astroglial Cx43 hemichannel-mediated glutamate and ATP release in regulating the excitatory/inhibitory balance in the brain and their possible contribution to psychiatric disorders.
Keywords	GABA ; GABA A receptors ; astrocytes ; Cx43 hemichannels ; astroglia ; connexin 43 ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	333
Language	English
Publishing date	2022-11-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: TRPM Channels in Human Diseases.

Jimenez, Ivanka / Prado, Yolanda / Marchant, Felipe / Otero, Carolina / Eltit, Felipe / Cabello-Verrugio, Claudio / Cerda, Oscar / Simon, Felipe

Cells

2020 Volume 9, Issue 12

Abstract: The transient receptor potential melastatin (TRPM) subfamily belongs to the TRP cation channels family. Since the first cloning of TRPM1 in 1989, tremendous progress has been made in identifying novel members of the TRPM subfamily and their functions. ... ...

Abstract	The transient receptor potential melastatin (TRPM) subfamily belongs to the TRP cation channels family. Since the first cloning of TRPM1 in 1989, tremendous progress has been made in identifying novel members of the TRPM subfamily and their functions. The TRPM subfamily is composed of eight members consisting of four six-transmembrane domain subunits, resulting in homomeric or heteromeric channels. From a structural point of view, based on the homology sequence of the coiled-coil in the C-terminus, the eight TRPM members are clustered into four groups: TRPM1/M3, M2/M8, M4/M5 and M6/M7. TRPM subfamily members have been involved in several physiological functions. However, they are also linked to diverse pathophysiological human processes. Alterations in the expression and function of TRPM subfamily ion channels might generate several human diseases including cardiovascular and neurodegenerative alterations, organ dysfunction, cancer and many other channelopathies. These effects position them as remarkable putative targets for novel diagnostic strategies, drug design and therapeutic approaches. Here, we review the current knowledge about the main characteristics of all members of the TRPM family, focusing on their actions in human diseases.
MeSH term(s)	Animals ; Cardiovascular Diseases/metabolism ; Cell Line, Tumor ; Humans ; Hydrogen Peroxide/chemistry ; Ions ; Neoplasms/metabolism ; Neurodegenerative Diseases/metabolism ; Neurons/metabolism ; Phosphorylation ; Phylogeny ; Protein Domains ; Reactive Oxygen Species ; Retina/metabolism ; Signal Transduction ; Synapses/metabolism ; TRPM Cation Channels/metabolism
Chemical Substances	Ions ; Reactive Oxygen Species ; TRPM Cation Channels ; Hydrogen Peroxide (BBX060AN9V)
Language	English
Publishing date	2020-12-04
Publishing country	Switzerland
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	2661518-6
ISSN	2073-4409 ; 2073-4409
ISSN (online)	2073-4409
ISSN	2073-4409
DOI	10.3390/cells9122604
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Article ; Online: TRPM Channels in Human Diseases

Ivanka Jimenez / Yolanda Prado / Felipe Marchant / Carolina Otero / Felipe Eltit / Claudio Cabello-Verrugio / Oscar Cerda / Felipe Simon

Cells, Vol 9, Iss 2604, p

2020 Volume 2604

Abstract	The transient receptor potential melastatin (TRPM) subfamily belongs to the TRP cation channels family. Since the first cloning of TRPM1 in 1989, tremendous progress has been made in identifying novel members of the TRPM subfamily and their functions. The TRPM subfamily is composed of eight members consisting of four six-transmembrane domain subunits, resulting in homomeric or heteromeric channels. From a structural point of view, based on the homology sequence of the coiled-coil in the C-terminus, the eight TRPM members are clustered into four groups: TRPM1/M3, M2/M8, M4/M5 and M6/M7. TRPM subfamily members have been involved in several physiological functions. However, they are also linked to diverse pathophysiological human processes. Alterations in the expression and function of TRPM subfamily ion channels might generate several human diseases including cardiovascular and neurodegenerative alterations, organ dysfunction, cancer and many other channelopathies. These effects position them as remarkable putative targets for novel diagnostic strategies, drug design and therapeutic approaches. Here, we review the current knowledge about the main characteristics of all members of the TRPM family, focusing on their actions in human diseases.
Keywords	TRPM channels ; human diseases ; ion channels ; Biology (General) ; QH301-705.5
Subject code	572
Language	English
Publishing date	2020-12-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Astroglial gliotransmitters released via Cx43 hemichannels regulate NMDAR-dependent transmission and short-term fear memory in the basolateral amygdala.

Linsambarth, Sergio / Carvajal, Francisco J / Moraga-Amaro, Rodrigo / Mendez, Luis / Tamburini, Giovanni / Jimenez, Ivanka / Verdugo, Daniel Antonio / Gómez, Gonzalo I / Jury, Nur / Martínez, Pablo / van Zundert, Brigitte / Varela-Nallar, Lorena / Retamal, Mauricio A / Martin, Claire / Altenberg, Guillermo A / Fiori, Mariana C / Cerpa, Waldo / Orellana, Juan A / Stehberg, Jimmy

FASEB journal : official publication of the Federation of American Societies for Experimental Biology

2022 Volume 36, Issue 2, Page(s) e22134

Abstract: Astrocytes release gliotransmitters via connexin 43 (Cx43) hemichannels into neighboring synapses, which can modulate synaptic activity and are necessary for fear memory consolidation. However, the gliotransmitters released, and their mechanisms of ... ...

Abstract	Astrocytes release gliotransmitters via connexin 43 (Cx43) hemichannels into neighboring synapses, which can modulate synaptic activity and are necessary for fear memory consolidation. However, the gliotransmitters released, and their mechanisms of action remain elusive. Here, we report that fear conditioning training elevated Cx43 hemichannel activity in astrocytes from the basolateral amygdala (BLA). The selective blockade of Cx43 hemichannels by microinfusion of TAT-Cx43L2 peptide into the BLA induced memory deficits 1 and 24 h after training, without affecting learning. The memory impairments were prevented by the co-injection of glutamate and D-serine, but not by the injection of either alone, suggesting a role for NMDA receptors (NMDAR). The incubation with TAT-Cx43L2 decreased NMDAR-mediated currents in BLA slices, effect that was also prevented by the addition of glutamate and D-serine. NMDARs in primary neuronal cultures were unaffected by TAT-Cx43L2, ruling out direct effects of the peptide on NMDARs. Finally, we show that D-serine permeates through purified Cx43 hemichannels reconstituted in liposomes. We propose that the release of glutamate and D-serine from astrocytes through Cx43 hemichannels is necessary for the activation of post-synaptic NMDARs during training, to allow for the formation of short-term and subsequent long-term memory, but not for learning per se.
MeSH term(s)	Animals ; Astrocytes/metabolism ; Basolateral Nuclear Complex/metabolism ; Connexin 43/metabolism ; Fear/physiology ; Glutamic Acid/metabolism ; Male ; Memory, Short-Term/physiology ; Neurons/metabolism ; Neurotransmitter Agents/metabolism ; Rats ; Rats, Sprague-Dawley ; Receptors, N-Methyl-D-Aspartate/metabolism ; Serine/metabolism
Chemical Substances	Connexin 43 ; Gja1 protein, rat ; Neurotransmitter Agents ; Receptors, N-Methyl-D-Aspartate ; Glutamic Acid (3KX376GY7L) ; Serine (452VLY9402)
Language	English
Publishing date	2022-01-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	639186-2
ISSN	1530-6860 ; 0892-6638
ISSN (online)	1530-6860
ISSN	0892-6638
DOI	10.1096/fj.202100798RR
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Book ; Online: Evaluation of the NAQFC driven by the NOAA Global Forecast System (version 16)

Tang, Youhua / Campbell, Patrick C. / Lee, Pius / Saylor, Rick / Yang, Fanglin / Baker, Barry / Tong, Daniel / Stein, Ariel / Huang, Jianping / Huang, Ho-Chun / Pan, Li / McQueen, Jeff / Stajner, Ivanka / Tirado-Delgado, Jose / Jung, Youngsun / Yang, Melissa / Bourgeois, Ilann / Peischl, Jeff / Ryerson, Tom /

Blake, Donald / Schwarz, Joshua / Jimenez, Jose-Luis / Crawford, James / Diskin, Glenn / Moore, Richard / Hair, Johnathan / Huey, Greg / Rollins, Andrew / Dibb, Jack / Zhang, Xiaoyang

eISSN: 1991-9603

comparison with the WRF-CMAQ during the summer 2019 FIREX-AQ campaign

2022

Abstract: The latest operational National Air Quality Forecast Capability (NAQFC) has been advanced to use the Community Multiscale Air Quality (CMAQ) model (version 5.3.1) with the CB6r3 (Carbon Bond 6 revision 3) AERO7 (version 7 of the aerosol module) chemical ... ...

Abstract	The latest operational National Air Quality Forecast Capability (NAQFC) has been advanced to use the Community Multiscale Air Quality (CMAQ) model (version 5.3.1) with the CB6r3 (Carbon Bond 6 revision 3) AERO7 (version 7 of the aerosol module) chemical mechanism and is driven by the Finite-Volume Cubed-Sphere (FV3) Global Forecast System, version 16 (GFSv16). This update has been accomplished via the development of the meteorological preprocessor, NOAA-EPA Atmosphere–Chemistry Coupler (NACC), adapted from the existing Meteorology–Chemistry Interface Processor (MCIP). Differing from the typically used Weather Research and Forecasting (WRF) CMAQ system in the air quality research community, the interpolation-based NACC can use various meteorological outputs to drive the CMAQ model (e.g., FV3-GFSv16), even though they are on different grids. In this study, we compare and evaluate GFSv16-CMAQ and WRFv4.0.3-CMAQ using observations over the contiguous United States (CONUS) in summer 2019 that have been verified with surface meteorological and AIRNow observations. During this period, the Fire Influence on Regional to Global Environments and Air Quality (FIREX-AQ) field campaign was performed, and we compare the two models with airborne measurements from the NASA DC-8 aircraft. The GFS-CMAQ and WRF-CMAQ systems show similar performance overall with some differences for certain events, species and regions. The GFSv16 meteorology tends to have a stronger diurnal variability in the planetary boundary layer height (higher during daytime and lower at night) than WRF over the US Pacific coast, and it also predicted lower nighttime 10 m winds. In summer 2019, the GFS-CMAQ system showed better surface ozone (O 3 ) than WRF-CMAQ at night over the CONUS domain; however, the models' fine particulate matter (PM 2.5 ) predictions showed mixed verification results: GFS-CMAQ yielded better mean biases but poorer correlations over the Pacific coast. These results indicate that using global GFSv16 meteorology with NACC to directly ...
Subject code	333
Language	English
Publishing date	2022-11-07
Publishing country	de
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Book ; Online: Evaluation of the NAQFC Driven by the NOAA Global Forecast System Version 16

Tang, Youhua / Campbell, Patrick / Lee, Pius / Saylor, Rick / Yang, Fanglin / Baker, Barry / Tong, Daniel / Stein, Ariel / Huang, Jianping / Huang, Ho-Chun / Pan, Li / McQueen, Jeff / Stajner, Ivanka / Tirado-Delgado, Jose / Jung, Youngsun / Yang, Melissa / Bourgeois, Ilann / Peischl, Jeff / Ryerson, Tom /

Blake, Donald / Schwarz, Joshua / Jimenez, Jose-Luis / Crawford, James / Diskin, Glenn / Moore, Richard / Hair, Johnathan / Huey, Greg / Rollins, Andrew / Dibb, Jack / Zhang, Xiaoyang

eISSN:

Comparison with the WRF-CMAQ Downscaling Method During the Summer 2019 FIREX-AQ Campaign

2022

Abstract	The latest operational National Air Quality Forecast Capability (NAQFC) has been advanced to use the Community Multiscale Air Quality (CMAQ) model (version 5.3.1) with the CB6r3 (Carbon Bond 6 revision 3) AERO7 (version 7 of the aerosol module) chemical mechanism and is driven by the Finite-Volume Cubed-Sphere (FV3) Global Forecast System, version 16 (GFSv16). This update has been accomplished via the development of the meteorological preprocessor, NOAA-EPA Atmosphere–Chemistry Coupler (NACC), adapted from the existing Meteorology–Chemistry Interface Processor (MCIP). Differing from the typically used Weather Research and Forecasting (WRF) CMAQ system in the air quality research community, the interpolation-based NACC can use various meteorological outputs to drive the CMAQ model (e.g., FV3-GFSv16), even though they are on different grids. In this study, we compare and evaluate GFSv16-CMAQ and WRFv4.0.3-CMAQ using observations over the contiguous United States (CONUS) in summer 2019 that have been verified with surface meteorological and AIRNow observations. During this period, the Fire Influence on Regional to Global Environments and Air Quality (FIREX-AQ) field campaign was performed, and we compare the two models with airborne measurements from the NASA DC-8 aircraft. The GFS-CMAQ and WRF-CMAQ systems show similar performance overall with some differences for certain events, species and regions. The GFSv16 meteorology tends to have a stronger diurnal variability in the planetary boundary layer height (higher during daytime and lower at night) than WRF over the US Pacific coast, and it also predicted lower nighttime 10 m winds. In summer 2019, the GFS-CMAQ system showed better surface ozone (O 3 ) than WRF-CMAQ at night over the CONUS domain; however, the models' fine particulate matter (PM 2.5 ) predictions showed mixed verification results: GFS-CMAQ yielded better mean biases but poorer correlations over the Pacific coast. These results indicate that using global GFSv16 meteorology with NACC to directly ...
Subject code	333
Language	English
Publishing date	2022-11-07
Publishing country	de
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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