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Article ; Online: Critical Signaling Events in the Mechanoactivation of Human Mast Cells through p.C492Y-ADGRE2.

Naranjo, Andrea N / Bandara, Geethani / Bai, Yun / Smelkinson, Margery G / Tobío, Araceli / Komarow, Hirsh D / Boyden, Steven E / Kastner, Daniel L / Metcalfe, Dean D / Olivera, Ana

The Journal of investigative dermatology

2020 Volume 140, Issue 11, Page(s) 2210–2220.e5

Abstract: ... by the finding of a missense substitution (p.C492Y) associated with familial vibratory urticaria ... In these patients, friction of the skin induces mast cell hyper-degranulation through p.C492Y-ADGRE2, causing ... signals elicited by mechanical activation in human mast cells expressing p.C492Y-ADGRE2 and attached ...

Abstract	A role for the adhesion G-protein coupled receptor ADGRE2 or EMR2 in mechanosensing was revealed by the finding of a missense substitution (p.C492Y) associated with familial vibratory urticaria. In these patients, friction of the skin induces mast cell hyper-degranulation through p.C492Y-ADGRE2, causing localized hives, flushing, and hypotension. We have now characterized the responses and intracellular signals elicited by mechanical activation in human mast cells expressing p.C492Y-ADGRE2 and attached to dermatan sulfate, a ligand for ADGRE2. The presence of p.C492Y-ADGRE2 reduced the threshold to activation and increased the extent of degranulation along with the percentage of mast cells responding. Vibration caused phospholipase C activation, transient increases in cytosolic calcium, and downstream activation of phosphoinositide 3-kinase and extracellular signal-regulated kinases 1 and 2 by Gβγ, Gα
MeSH term(s)	Calcium/metabolism ; Cell Degranulation ; Cells, Cultured ; Extracellular Signal-Regulated MAP Kinases/physiology ; Humans ; Mast Cells/physiology ; Mechanotransduction, Cellular ; Mutation, Missense ; Phosphatidylinositol 3-Kinases/physiology ; Prostaglandin D2/physiology ; Protein Kinase C/physiology ; Receptors, G-Protein-Coupled/genetics ; Receptors, G-Protein-Coupled/physiology ; Signal Transduction/physiology ; Tetraspanin 30/physiology ; Type C Phospholipases/physiology ; Urticaria/etiology ; Urticaria/genetics ; Vibration/adverse effects
Chemical Substances	ADGRE2 protein, human ; CD63 protein, human ; Receptors, G-Protein-Coupled ; Tetraspanin 30 ; Protein Kinase C (EC 2.7.11.13) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24) ; Type C Phospholipases (EC 3.1.4.-) ; Prostaglandin D2 (RXY07S6CZ2) ; Calcium (SY7Q814VUP)
Language	English
Publishing date	2020-03-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	80136-7
ISSN	1523-1747 ; 0022-202X
ISSN (online)	1523-1747
ISSN	0022-202X
DOI	10.1016/j.jid.2020.03.936
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Article ; Online: Homozygous variant p. Arg90His in NCF1 is associated with early-onset Interferonopathy: a case report.

Schnappauf, Oskar / Heale, Liane / Dissanayake, Dilan / Tsai, Wanxia L / Gadina, Massimo / Leto, Thomas L / Kastner, Daniel L / Malech, Harry L / Kuhns, Douglas B / Aksentijevich, Ivona / Laxer, Ronald M

Pediatric rheumatology online journal

2021 Volume 19, Issue 1, Page(s) 54

Abstract: ... and chronic granulomatous disease (CGD). Heterozygosity for the p.Arg90His variant in NCF1 has been ... in adult patients. This study demonstrates the association of the homozygous p.Arg90His variant ... elevated antinuclear, anti-Ro, and anti-La antibodies was found to carry the homozygous p.Arg90His variant ...

Abstract	Background: Biallelic loss-of-function variants in NCF1 lead to reactive oxygen species deficiency and chronic granulomatous disease (CGD). Heterozygosity for the p.Arg90His variant in NCF1 has been associated with susceptibility to systemic lupus erythematosus, rheumatoid arthritis, and Sjögren's syndrome in adult patients. This study demonstrates the association of the homozygous p.Arg90His variant with interferonopathy with features of autoinflammation and autoimmunity in a pediatric patient. Case presentation: A 5-year old female of Indian ancestry with early-onset recurrent fever and headache, and persistently elevated antinuclear, anti-Ro, and anti-La antibodies was found to carry the homozygous p.Arg90His variant in NCF1 through exome sequencing. Her unaffected parents and three other siblings were carriers for the mutant allele. Because the presence of two NCF1 pseudogenes, this variant was confirmed by independent genotyping methods. Her intracellular neutrophil oxidative burst and NCF1 expression levels were normal, and no clinical features of CGD were apparent. Gene expression analysis in peripheral blood detected an interferon gene expression signature, which was further supported by cytokine analyses of supernatants of cultured patient's cells. These findings suggested that her inflammatory disease is at least in part mediated by type I interferons. While her fever episodes responded well to systemic steroids, treatment with the JAK inhibitor tofacitinib resulted in decreased serum ferritin levels and reduced frequency of fevers. Conclusion: Homozygosity for p.Arg90His in NCF1 should be considered contributory in young patients with an atypical systemic inflammatory antecedent phenotype that may evolve into autoimmunity later in life. The complex genomic organization of NCF1 poses a difficulty for high-throughput genotyping techniques and variants in this gene should be carefully evaluated when using the next generation and Sanger sequencing technologies. The p.Arg90His variant is found at a variable allele frequency in different populations, and is higher in people of South East Asian ancestry. In complex genetic diseases such as SLE, other rare and common susceptibility alleles might be necessary for the full disease expressivity.
MeSH term(s)	Autoimmune Diseases/genetics ; Child, Preschool ; Female ; Homozygote ; Humans ; Interferons ; NADPH Oxidases/genetics ; Pedigree
Chemical Substances	Interferons (9008-11-1) ; NADPH Oxidases (EC 1.6.3.-) ; neutrophil cytosolic factor 1 (EC 1.6.3.1)
Language	English
Publishing date	2021-04-23
Publishing country	England
Document type	Case Reports ; Journal Article
ZDB-ID	2279468-2
ISSN	1546-0096 ; 1546-0096
ISSN (online)	1546-0096
ISSN	1546-0096
DOI	10.1186/s12969-021-00536-y
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Article ; Online: Influence of the environment on the oxidative deamination of p-substituted benzylamines in monoamine oxidase.

Zenn, Roland K / Abad, Enrique / Kästner, Johannes

The journal of physical chemistry. B

2015 Volume 119, Issue 9, Page(s) 3678–3686

Abstract: ... the role of the enzymatic environment for the reaction mechanism of human MAO-B with different p ...

Abstract	The flavin-containing enzyme monoamine oxidase (MAO) is essential for the enzymatic decomposition of amine neurotransmitters. The exact mechanism of the oxidative deamination of amines to aldehydes by the enzyme has not yet been fully understood despite extensive research on the area. The rate limiting step is the reductive half-reaction where the Hα together with two electrons of the amine substrate is transferred to the flavin cofactor. However, it is still not known whether the hydrogen is transferred as a proton or a hydride. Experimental results cannot be fully explained by either of those mechanisms. In our previous work, theoretical results based on QM/MM calculations of the full enzyme show an intermediate situation between these two cases. In this paper, we report on an in-depth computational analysis concerning the role of the enzymatic environment for the reaction mechanism of human MAO-B with different p-substituted benzylamines as substrates. Our results show that steric and electrostatic effects from the active site environment turn the mechanism closer to an asynchronous polar nucleophilic mechanism. We found indications that the protein environment of MAO-A enhances the polar nucleophilic character of the mechanism compared to that of MAO-B.
MeSH term(s)	Benzylamines/chemistry ; Benzylamines/metabolism ; Deamination ; Humans ; Molecular Dynamics Simulation ; Monoamine Oxidase/chemistry ; Monoamine Oxidase/metabolism ; Oxidation-Reduction ; Protein Conformation ; Quantum Theory
Chemical Substances	Benzylamines ; Monoamine Oxidase (EC 1.4.3.4)
Language	English
Publishing date	2015-03-05
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	1520-5207
ISSN (online)	1520-5207
DOI	10.1021/jp512470a
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Article: From humic substances to soil organic matter–microbial contributions. In honour of Konrad Haider and James P. Martin for their outstanding research contribution to soil science

Schaeffer, Andreas / Nannipieri, Paolo / Kästner, Matthias / Schmidt, Burkhard / Botterweck, Jens

Journal of soils and sediments. 2015 Sept., v. 15, no. 9

2015

Abstract: ... of the soil organic matter (SOM) are essential for the stability and ecosystem services of soils. James P. Martin and Konrad ...

Abstract	PURPOSE: Many decades of research have shown that humic compounds as part of the soil organic matter (SOM) are essential for the stability and ecosystem services of soils. James P. Martin and Konrad Haider based on several pioneers in humus research improved the basis for the current knowledge of key processes in the soil environment, in particular structure and formation of humus triggered mainly by soil fungi. Other major contributions are briefly described but not in the focus of this article, such as their innovative tracer experiments with isotope-labelled xenobiotic chemicals and natural litter to study their fate. Both scientists inspired generations of younger researchers to advance their approaches and laid the cornerstone of the current understanding of soil organic matter formation. RESULTS AND DISCUSSION: This article values the key experiments of Martin and Haider in this field and the related follow-up research finally resulting in the current view on formation mechanisms of SOM and non-extractable residues (NER) of xenobiotics. The improved understanding of these processes considering necromass with tissue residues of plants, microbes and animals challenges the traditional views of humic matter as macromolecular organic matrix, which according to the research of the last years represents only a variable part of the total organic matter besides associates of low molecular weight molecules. We discuss views on soil organic matter and humic substances that are nowadays considered not to differ in molecular diversity. We will start by demonstrating the understanding of humus characteristics and humus formation three decades ago closely related to the findings of Martin and Haider. Methodological approaches to characterize relevant structural and mechanistic pictures of SOM such as the priming effect, clay mineral catalysed reactions and the various mechanisms by which natural and xenobiotic chemicals are protected in soil are briefly illustrated by examples. Fungal activities in producing secondary metabolites like polyketides and their probably minor contributions to SOM formation are presented. CONCLUSIONS AND PERSPECTIVES: Open research questions stimulated by these two soil scientists are sketched which are nowadays possible to address by new sophisticated high-resolution techniques.
Keywords	clay ; ecosystem services ; edaphic factors ; humic substances ; humus ; methodology ; molecular weight ; polyketides ; researchers ; scientists ; secondary metabolites ; soil ; soil fungi ; xenobiotics
Language	English
Dates of publication	2015-09
Size	p. 1865-1881.
Publishing place	Springer Berlin Heidelberg
Document type	Article
ZDB-ID	2050898-0
ISSN	1614-7480 ; 1439-0108
ISSN (online)	1614-7480
ISSN	1439-0108
DOI	10.1007/s11368-015-1177-4
Database	NAL-Catalogue (AGRICOLA)

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Article: Mechanistic inquiry and scientific pursuit: The case of visual processing.

Haueis, Philipp / Kästner, Lena

Studies in history and philosophy of science

2022 Volume 93, Page(s) 123–135

Abstract: Why is it rational for scientists to pursue multiple models of a phenomenon at the same time? The literatures on mechanistic inquiry and scientific pursuit each develop answers to a version of this question which is rarely discussed by the other. The ... ...

Abstract	Why is it rational for scientists to pursue multiple models of a phenomenon at the same time? The literatures on mechanistic inquiry and scientific pursuit each develop answers to a version of this question which is rarely discussed by the other. The mechanistic literature suggests that scientists pursue different complementary models because each model provides detailed insights into different aspects of the phenomenon under investigation. The pursuit literature suggests that scientists pursue competing models because alternative models promise to solve outstanding empirical and conceptual problems. Looking into research on visual processing as a case study, we suggest an integrated account of why it is rational for scientists to pursue both complementary and competing models of the same mechanism in scientific practice.
MeSH term(s)	Cognition ; Visual Perception
Language	English
Publishing date	2022-04-12
Publishing country	England
Document type	Journal Article
ZDB-ID	202358-1
ISSN	1879-2510 ; 0039-3681
ISSN (online)	1879-2510
ISSN	0039-3681
DOI	10.1016/j.shpsa.2022.03.007
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Book ; Thesis: Untersuchungen zur Messgenauigkeit der endoskopischen Trachealvermessung mit dem ENDOSCAN-System

Kästner, Peter

2002

Author's details	vorgelegt von Peter Kästner
Language	German
Size	71 Bl. : Ill. graph. Darst.
Publishing country	Germany
Document type	Book ; Thesis
Thesis / German Habilitation thesis	Jena, Univ., Diss., 2003
HBZ-ID	HT013634467
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2003 E 1258	order for loan	Magazin

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Article: Purification of cytochromes P-450 derived from liver microsomes of untreated and 2,3,7,8-tetrachlorodibenzo-p-dioxin-treated marmoset monkeys.

Kastner, M / Neubert, D

Journal of chromatography

2002 Volume 625, Issue 1, Page(s) 55–66

Abstract: The purification of multiple forms of cytochrome P-450 (P450) from 2,3,7,8-tetrachlorodibenzo-p ...

Abstract	The purification of multiple forms of cytochrome P-450 (P450) from 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)-treated marmosets using fast protein liquid chromatography (FPLC) is described. The main aim was to achieve a better separation of certain closely related P450 sub-forms from each other than that previously obtained using conventional chromatography. An 8-aminooctyl-Sepharose fraction of cholate-solubilized microsomes was obtained first and, after fast desalting on Sephadex G-25, loaded on to a preparative Mono Q column. Five of the six gradient peaks contained P450 and were each rechromatographed on an analytical Mono Q column. The pass-through peak was fractionated further using a Mono S column. Other HPLC-quality anion- and cation-exchange gels were compared. For removal of excess of non-ionic detergent, five types of hydroxyapatite gels were compared. Seven purified forms of P450 and cytochrome b5 and P420 were isolated and characterized according to PHAST sodium dodecylsulphate-polyacrylamide gel electrophoretic apparent molecular masses, catalytic, spectral and magnetic properties and also TCDD-binding capacity (molar ratio of [14C]TCDD to P450). There are at least two sub-forms which appear to be TCDD inducible, one showing a substantial ethoxyresorufin-O-deethylase activity and the other having a high TCDD-binding molar ratio. Two other forms appear to be constitutive, as deduced from comparisons with forms purified from untreated animals.
MeSH term(s)	Animals ; Callithrix ; Chromatography, High Pressure Liquid ; Chromatography, Ion Exchange ; Cytochrome P-450 Enzyme System/isolation & purification ; Electrophoresis, Polyacrylamide Gel ; Microsomes, Liver/enzymology ; Polychlorinated Dibenzodioxins/administration & dosage
Chemical Substances	Polychlorinated Dibenzodioxins ; Cytochrome P-450 Enzyme System (9035-51-2)
Language	English
Publishing date	2002-06-25
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	218139-3
ISSN	0021-9673 ; 0378-4355 ; 0376-737X
ISSN	0021-9673 ; 0378-4355 ; 0376-737X
DOI	10.1016/0021-9673(92)87221-s
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Article ; Online: Inactive nurses' willingness to return to active nursing during the COVID-19 pandemic: A qualitative study.

Lücker, Petra / Henning, Esther / Kästner, Anika / Hoffmann, Wolfgang

Journal of advanced nursing

2023 Volume 80, Issue 3, Page(s) 1043–1057

Abstract: Aims: To investigate factors that influence the willingness of inactive nurses to return to nursing in a crisis situation and to identify aspects that need to be considered with regard to a possible deployment.: Design: A deductive and inductive ... ...

Abstract	Aims: To investigate factors that influence the willingness of inactive nurses to return to nursing in a crisis situation and to identify aspects that need to be considered with regard to a possible deployment. Design: A deductive and inductive qualitative content analysis of semi-structured focus group interviews. Methods: Semi-structured focus group interviews with inactive or marginally employed nurses, nurses who have been inactive for some time and nursing home managers in October and November 2021. The participating inactive nurses had declared their willingness for a deployment during the COVID-19 pandemic or not. Data were analysed using qualitative content analysis. Results: Communication was seen as essential by the participants for an informed decision for or against a temporary return to nursing and to potential or actual deployments. To make them feel safe, inactive nurses need to know what to expect and what is expected of them, for example, regarding required training and responsibilities. Considering their current employment status, some flexibility in terms of deployment conditions is needed. A remaining attachment to care can trigger a sense of duty. Knowledge of (regular) working conditions in nursing can lead to both a desire to support former colleagues and a refusal to be exposed to these conditions again. Conclusion: Past working experiences and the current employment situation play a major role in the willingness of inactive nurses to return to nursing in a crisis situation. Unbureaucratic arrangements must be provided for those who are willing to return. Summary statement: What already is known - In crisis situations, not every inactive nurse is willing or able to return to nursing and therefore, the 'silent reserve' may not be as large as suspected. What this paper adds - Inactive nurses need to know what to expect and what is expected of them for their decision regarding a return to active patient care during a crisis situation. Implications for practice/policy - Inactive nurses need to be informed and should be offered free training and refresher courses to ensure patient safety. Impact: This research shows that the group of inactive nurses are not a silent workforce which can be activated anytime. Those who are able and willing to return to direct patient care in crisis situations need the best possible support - during and between crises. Reporting method: This study adhered to COREQ guidelines. No patient or public contribution: The involvement of patients or members of the public did not apply for the study, as the aim was to gain insight into the motivations and attitudes of the group of inactive nurses.
MeSH term(s)	Humans ; COVID-19 ; Pandemics ; Qualitative Research ; Nursing Homes ; Nurses
Language	English
Publishing date	2023-09-29
Publishing country	England
Document type	Journal Article
ZDB-ID	197634-5
ISSN	1365-2648 ; 0309-2402
ISSN (online)	1365-2648
ISSN	0309-2402
DOI	10.1111/jan.15881
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Article: NAD(P)H oxidase activity in cultured human podocytes: effects of adenosine triphosphate.

Greiber, S / Münzel, T / Kästner, S / Müller, B / Schollmeyer, P / Pavenstädt, H

Kidney international

1998 Volume 53, Issue 3, Page(s) 654–663

Abstract: ... Activation of the plasma-membrane bound NAD(P)H oxidases by ATP was time and dose dependent ... enzyme activity at the transcriptional and translational levels. In conclusion, NAD(P)H dependent, membrane ... associated oxidases represent the major superoxide source in human podocytes. Activation of NAD(P ...

Abstract	Reactive oxygen species contribute to glomerular damage and proteinuria. In this study, we show that cultured human podocytes produce superoxide in response to extracellular adenosine triphosphate (ATP), and we identified the oxidases involved in this process. Adenosine triphosphate (10-4 M for 4 hr) raised superoxide production from 1.28 +/- 0.15 to 2.67 &/- 0.34 nmol/mg protein/min. Studies with podocyte homogenates revealed activation of both nicotinamide adenine dinucleotide (NADH; from 2.65 +/- 0.23 to 7.43 +/- 0.57) and nicotinamide adenine dinucleotide phosphate (NADPH) dependent oxidases [from 1.74 +/- 0.13 to 4.05 +/- 0.12 (nmol O2/mg protein/min)] by ATP. Activity of xanthine-oxidases was low and unchanged by ATP. Activation of the plasma-membrane bound NAD(P)H oxidases by ATP was time and dose dependent. Reverse transcribed-polymerase chain reaction (RT-PCR) studies with primers derived from monocyte sequences amplified mRNA for the NADPH oxidase subunits p22phox, p47phox, gp91phox, and p67phox, and the latter was transiently increased by ATP. Experiments with actinomycin D and cycloheximide suggested that ATP modulates enzyme activity at the transcriptional and translational levels. In conclusion, NAD(P)H dependent, membrane associated oxidases represent the major superoxide source in human podocytes. Activation of NAD(P)H oxidase by ATP might be secondary to increased mRNA expression of the NADPH oxidase subunit gp67phox.
MeSH term(s)	Adenosine Triphosphate/pharmacology ; Cell Membrane/enzymology ; Cells, Cultured ; Gene Expression Regulation, Enzymologic/drug effects ; Humans ; Kidney Glomerulus/cytology ; Kidney Glomerulus/drug effects ; Kidney Glomerulus/metabolism ; Membrane Glycoproteins/genetics ; Membrane Transport Proteins ; Monocytes/metabolism ; NADH, NADPH Oxidoreductases/genetics ; NADH, NADPH Oxidoreductases/metabolism ; NADPH Dehydrogenase/genetics ; NADPH Oxidase 2 ; NADPH Oxidases ; Phosphoproteins/genetics ; Polymerase Chain Reaction ; RNA, Messenger/genetics ; RNA, Messenger/metabolism ; Reactive Oxygen Species/metabolism ; Superoxides/metabolism
Chemical Substances	Membrane Glycoproteins ; Membrane Transport Proteins ; Phosphoproteins ; RNA, Messenger ; Reactive Oxygen Species ; neutrophil cytosol factor 67K ; Superoxides (11062-77-4) ; Adenosine Triphosphate (8L70Q75FXE) ; NADH, NADPH Oxidoreductases (EC 1.6.-) ; CYBB protein, human (EC 1.6.3.-) ; NADPH Oxidase 2 (EC 1.6.3.-) ; NADPH Oxidases (EC 1.6.3.-) ; CYBA protein, human (EC 1.6.3.1) ; neutrophil cytosolic factor 1 (EC 1.6.3.1) ; NADPH Dehydrogenase (EC 1.6.99.1)
Language	English
Publishing date	1998-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	120573-0
ISSN	1523-1755 ; 0085-2538
ISSN (online)	1523-1755
ISSN	0085-2538
DOI	10.1046/j.1523-1755.1998.00796.x
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Article: Untersuchungen zum P-Phänomen bei progressiv chronischer Polyarthritis.

Kästner, P

Zeitschrift fur die gesamte innere Medizin und ihre Grenzgebiete

1973 Volume 28, Issue 15, Page(s) 450–454

Title translation	P-phenomenon in progressive chronic polyarthritis.
MeSH term(s)	Animals ; Antineoplastic Agents/therapeutic use ; Arthritis, Rheumatoid/blood ; Arthritis, Rheumatoid/immunology ; Chloroquine/therapeutic use ; Cortisone/therapeutic use ; Gold/therapeutic use ; Gout/immunology ; Immunoglobulin Fragments/analysis ; Immunoglobulin G ; Immunoglobulin M ; Immunosuppressive Agents/therapeutic use ; Indomethacin/therapeutic use ; Osteoarthritis/immunology ; Pyrazoles/therapeutic use ; Rats ; Spondylitis, Ankylosing/immunology ; Synovial Fluid/analysis ; Tuberculosis, Osteoarticular/immunology
Chemical Substances	Antineoplastic Agents ; Immunoglobulin Fragments ; Immunoglobulin G ; Immunoglobulin M ; Immunosuppressive Agents ; Pyrazoles ; Gold (7440-57-5) ; Chloroquine (886U3H6UFF) ; Cortisone (V27W9254FZ) ; Indomethacin (XXE1CET956)
Language	German
Publishing date	1973-08-01
Publishing country	Germany
Document type	Journal Article
ZDB-ID	509068-4
ISSN	0044-2542
ISSN	0044-2542
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