ABSTRACT The need to characterize the oxidative capacity of the atmosphere in the vast region of ... more ABSTRACT The need to characterize the oxidative capacity of the atmosphere in the vast region of East Antarctica motivated the OPALE initiative with investigations both at the top of the high plateau (Concordia) and at the East coast (Dumont d'Urville). The top of the East Antarctic plateau is a region where processes are suspected to differ from those already identified at the South Pole, in particular the photo-denitrification of the surface snow. For instance, in contrast to the South Pole experiencing 24-hour sunlight, the solar irradiance at Concordia has a strong diurnal cycle. Concordia is also the inland site where the longest sulfur derived aerosol record has been extracted from deep ice cores. Regarding coastal site observations, it is suspected that the oxidative capacity of the atmosphere is different in Eastern Antarctica due to the frequent occurrence of katabatic flow. This has to be considered in studies dealing with year-round observations carried out at coastal Antarctic regions where large oceanic DMS emissions take place. The first OPALE field campaign took place in January 2011 at the coastal site of Dumont d'Urville. Measurements of OH, the sum of HO2+RO2, HONO, O3, H2O2, CH3OOH, and HCHO, were done. Logistical problems, which followed a helicopter accident (occurred 28thOctober 2010), obliged us to cancel NOx measurement at the coast. The major finding of this campaign is related to the observed high HOx levels. With 24 h means of 2 106 and 3 108 molecule cm-3 for OH and RO2, respectively, the OH and RO2 concentrations observed at DDU are the highest ever seen at the Antarctic coast. The OH level observed at DDU cannot be simply explained by the relatively high level of ozone observed at this site in relation with an efficient transport of air masses coming from inland Antarctica. The steady state calculations suggest a RO2 to OH conversion mechanism equivalent to 30 pptv of NO to explain observed HOx concentrations. Such rather high NO levels were confirmed by NO2 measurements made in January 2012. During the second campaign carried out at Concordia in December 2011-January 2012, investigations included OH and HO2+RO2 together with species relevant to discuss their sources and sinks (NO, NO2, HONO, O3, H2O2, HCHO), surface meteorological parameters and physic of the boundary layer, and photolysis rates. It has to be noted that HONO was measured for the first time in Antarctica by using the long path absorption photometer (LOPAP) technique. A few balloon experiments documented ozone and NOx changes with height. These data for which a well-marked diurnal cycle was often observed will allow a better understanding of the role of snow-pack emissions on the oxidative properties of the atmosphere overlying the East Antarctic plateau.
The spatial and temporal (event and seasonal timescale) variability of major runoff components in... more The spatial and temporal (event and seasonal timescale) variability of major runoff components in the mountainous Brugga basin (Black Forest, Germany) were examined. The mesoscale (40 km2) study basin represented an extraordinary challenge as comparable studies have been undertaken mainly in smaller headwater basins. Discharge data, tracer concentrations of 18O, 3H, CFCs, and dissolved silica, and major anions and cations
ABSTRACT White mica from the Liassic black shales and slates in Central Switzerland was analysed ... more ABSTRACT White mica from the Liassic black shales and slates in Central Switzerland was analysed by transmission electron microscopy (TEM) and electron microprobe to determine its textural and compositional evolution during very low-grade prograde metamorphism. Samples were studied from the diagenetic zone, anchizone and epizone (T ≈100°–450 °C). Phyllosilicate minerals analysed include illite/smectite (I/S), phengite, muscovite, brammallite, paragonite, margarite and glauconite. Textural evolution primarily is towards larger, more defect-free grains with compositions that approach those of their respective end-members. The smectite-to-illite transformation reduced the amounts of the exchange components SiK−1Al−1, MgSiAl−2, and Fe3+Al−1. These trends continue to a lesser degree in the anchizone and epizone. Correlations between the proportion of smectite in I/S and the composition of I/S indicate that smectite layers may contain a high layer charge. Illite in I/S bears a compositional resemblance to macrocrystalline phengite in some samples, but is different in others. Paragonite first appears in the upper diagenetic zone or lower anchizone as an interlayer-deficient brammallite, and it may be mixed with muscovite on the nanometre scale. Owing to the small calculated structure factor for paragonite-muscovite superstructures, conventional X-ray powder diffraction cannot distinguish between mixed-layer structures and a homogeneous compositionally intermediate solid solutions. However, indirect TEM evidence shows that irregularly shaped domains of Na- and K-rich mica exist below 10 nm. Subsequent coarsening of domains at higher grades produced discrete paragonite grains at the margins of muscovite crystals or in laths parallel to the basal plane of the host muscovite. Margarite appears in the epizone and follows a textural evolution similar to paragonite in that mixtures of margarite, paragonite, and muscovite may initially occur on the nanometre scale. However, no evidence of interlayer-poor margarite has been found.
Bacterial DNA containing motifs of unmethylated CpG dinucleotides (CpG-DNA) triggers innate immun... more Bacterial DNA containing motifs of unmethylated CpG dinucleotides (CpG-DNA) triggers innate immune cells through the pattern recognition receptor Toll-like receptor 9 (TLR-9). CpG-DNA possesses potent immunostimulatory effects on macrophages, dendritic cells, and B lymphocytes. Therefore, CpG-DNA contributes to inflammation during the course of bacterial infections. In contrast to other TLR-dependent microbial patterns, CpG-DNA is a strong inductor of IL-12. Thus, it acts as a Th1-polarizing agent that can be utilized as potent vaccine adjuvant. To assess the role of CpG-DNA in immune reactions in the CNS, we analyzed the effects of CpG-DNA on microglial cells in vitro and in vivo. Primary microglial cells as well as microglial cell lines express TLR-9 mRNA. Consequently, CpG-DNA activated microglial cells in vitro and induced TNF-alpha, IL-12p40, IL-12p70, and NO. Furthermore, MHC class II, B7-1, B7-2, and CD40 molecules were up-regulated. In addition, phagocytic activity of microglia was enhanced. After intracerebroventricular injection of CpG-DNA, microglial cells were activated and produced TNF-alpha and IL-12p40 transcripts, as shown by in situ hybridization. These results indicate that microglia is sensitive to CpG-DNA. Thus, bacterial DNA containing CpG motifs could not only play an important role during infections of the CNS, but also might trigger and sustain Th1-dominated immunopathogenic reactions.
ABSTRACT The comprehensive isotopic composition of atmospheric nitrate (i.e., the simultaneous me... more ABSTRACT The comprehensive isotopic composition of atmospheric nitrate (i.e., the simultaneous measurement of all its stable isotope ratios: 15N/14N, 17O/16O and 18O/16O) has been determined for aerosol samples collected in the marine boundary layer (MBL) over the Atlantic Ocean from 65°S (Weddell Sea) to 79°N (Svalbard), along a ship-borne latitudinal transect. In nonpolar areas, the δ15N of nitrate mostly deriving from anthropogenically emitted NOx is found to be significantly different (from 0 to 6‰) from nitrate sampled in locations influenced by natural NOx sources (−4 ± 2)‰. The effects on δ15N(NO3−) of different NOx sources and nitrate removal processes associated with its atmospheric transport are discussed. Measurements of the oxygen isotope anomaly (Δ17O = δ17O − 0.52 × δ18O) of nitrate suggest that nocturnal processes involving the nitrate radical play a major role in terms of NOx sinks. Different Δ17O between aerosol size fractions indicate different proportions between nitrate formation pathways as a function of the size and composition of the particles. Extremely low δ15N values (down to −40‰) are found in air masses exposed to snow-covered areas, showing that snowpack emissions of NOx from upwind regions can have a significant impact on the local surface budget of reactive nitrogen, in conjunction with interactions with active halogen chemistry. The implications of the results are discussed in light of the potential use of the stable isotopic composition of nitrate to infer atmospherically relevant information from nitrate preserved in ice cores.
Impaired host defense mechanisms may crucially modulate the pathogenesis of atopic dermatitis (AD... more Impaired host defense mechanisms may crucially modulate the pathogenesis of atopic dermatitis (AD). More than 10% of patients with AD are heterozygous for the Toll-like receptor 2 (TLR-2) R753Q single nucleotide polymorphism (SNP) and exhibit severe eczema. To elucidate the functional effect of the TLR-2 mutation and its putative relevance for AD. Using the human embryonic kidney 293 transfection system, we characterized the properties of the TLR-2 R753Q SNP. Moreover, TLR-2 expression, IL-8 production, and cytokine secretion were analyzed in monocytes and CD4+ T cells of patients with AD with and without the mutant TLR-2 gene. Human embryonic kidney 293 transfectants mimicking this heterozygous mutation produced less IL-8 when stimulated with lipoteichoic acid (LTA), heat-inactivated Staphylococcus aureus or triacylated lipopeptides requiring the TLR-2/1 heterodimer. Suppressed production of IL-8 was confirmed in monocytes from patients with mutant AD after stimulation with peptidoglycan. Cell surface TLR-2 expression was severely impaired in CD3/CD28 activated CD4+ T cells of patients with AD bearing the mutant receptor, which could be restored on LTA stimulation. In contrast, LTA decreased TLR-2 expression among nonatopic individuals and patients with AD with the TLR-2 wild-type gene. T cells from patients with AD exhibited markedly suppressed IL-2 production after macrophage-activating lipopeptide-2 activation. However, no difference was found between mutant and wild-type patients with AD for IL-5, TNF-alpha, IFN-gamma, and IL-2 production. Collectively, the outcome of innate and adaptive immune responses in AD is modulated by the TLR-2 R753Q SNP.
The innate immune system recognizes pathogen-associated molecular patterns (PAMP) to cope with ev... more The innate immune system recognizes pathogen-associated molecular patterns (PAMP) to cope with evolving infections. Toll-like receptors (TLRs) play a pivotal role in recognition of PAMPs. In the course of infection not a single but rather a full panel of different microbial components interacts with distinct TLRs simultaneously. Only limited information is available on effects of combinations of TLR agonists. Here, we have analyzed the effects of lipoteichoic acid (LTA), CpG-DNA and combinations thereof on innate immune cells in vitro. Although proinflammatory cytokines like TNF-alpha were induced by these agonists in quite similar amounts, CpG DNA was superior in its potency to induce IL-12p40 reflecting important differences in the biological valence of LTA and CpG-DNA. When given in combination, LTA and CpG-DNA were additive in induction of TNF-alpha, IL-6 and nitric oxide in RAW 264 macrophages, peritoneal macrophages and dendritic cells. Additive effects were also observed in regard to TNF-alpha mRNA. In contrast, LTA suppressed IL12p40 secretion induced by CpG-DNA in RAW cells and peritoneal macrophages but not in dendritic cells. Intracellular signal cascades (NFkappaB and p38 MAP kinase) showed additive effects after simultaneous triggering. mRNA expression ofTLRs showed only minor regulation after CpG or LTA application and thus does not account for the additive/suppressive effects observed. These results indicate that the consequences of interaction of innate immune cells with microbial pattern depend on the responding cell type and might be differential for certain effector mechanisms. Thus, the pathogen-characteristic panel of TLR ligands will induce pathogen-specific innate responses decisive for the inflammatory reactions.
INTRODUCTION The technique of fission-track analysis has been widely applied to Alpine rocks in o... more INTRODUCTION The technique of fission-track analysis has been widely applied to Alpine rocks in order to unravel the cooling and exhumation history either in connection with other dating systems, such as K-Ar, Ar-Ar, and Rb-Sr, or by comparison of the variation of apatite ...
Toll-like receptors (TLRs) mediate recognition of microbial components. Despite activation of a s... more Toll-like receptors (TLRs) mediate recognition of microbial components. Despite activation of a shared set of signal transduction molecules, the biological effects of certain TLR agonists differ considerably. In macrophages and dendritic cells, stimulation by the prototypical stimuli CpG-DNA (TLR9), lipopolysaccharide (LPS; TLR4) and lipoteichoic acid (LTA; TLR2) resulted in striking differences in expression of IL-12. However, these stimuli induced similar amounts of the common proinflammatory cytokine TNFalpha. Surprisingly, an IL-12p40 promoter reporter construct was activated equally by CpG-DNA, LPS and LTA. Examinations of the chromatin structure of the endogenous IL-12p40 promoter revealed that nucleosome remodelling contributed to differential IL-12 induction. Upon stimulation, nucleosome architecture was changed to provide increased access to the IL-12p40 promoter. In dendritic cells, a differential induction of nucleosome remodelling at the IL-12p40 promoter was observed upon triggering with different TLR agonists. These results identify nucleosome remodelling as an additional restriction point in differential TLR signalling.
ABSTRACT The need to characterize the oxidative capacity of the atmosphere in the vast region of ... more ABSTRACT The need to characterize the oxidative capacity of the atmosphere in the vast region of East Antarctica motivated the OPALE initiative with investigations both at the top of the high plateau (Concordia) and at the East coast (Dumont d'Urville). The top of the East Antarctic plateau is a region where processes are suspected to differ from those already identified at the South Pole, in particular the photo-denitrification of the surface snow. For instance, in contrast to the South Pole experiencing 24-hour sunlight, the solar irradiance at Concordia has a strong diurnal cycle. Concordia is also the inland site where the longest sulfur derived aerosol record has been extracted from deep ice cores. Regarding coastal site observations, it is suspected that the oxidative capacity of the atmosphere is different in Eastern Antarctica due to the frequent occurrence of katabatic flow. This has to be considered in studies dealing with year-round observations carried out at coastal Antarctic regions where large oceanic DMS emissions take place. The first OPALE field campaign took place in January 2011 at the coastal site of Dumont d'Urville. Measurements of OH, the sum of HO2+RO2, HONO, O3, H2O2, CH3OOH, and HCHO, were done. Logistical problems, which followed a helicopter accident (occurred 28thOctober 2010), obliged us to cancel NOx measurement at the coast. The major finding of this campaign is related to the observed high HOx levels. With 24 h means of 2 106 and 3 108 molecule cm-3 for OH and RO2, respectively, the OH and RO2 concentrations observed at DDU are the highest ever seen at the Antarctic coast. The OH level observed at DDU cannot be simply explained by the relatively high level of ozone observed at this site in relation with an efficient transport of air masses coming from inland Antarctica. The steady state calculations suggest a RO2 to OH conversion mechanism equivalent to 30 pptv of NO to explain observed HOx concentrations. Such rather high NO levels were confirmed by NO2 measurements made in January 2012. During the second campaign carried out at Concordia in December 2011-January 2012, investigations included OH and HO2+RO2 together with species relevant to discuss their sources and sinks (NO, NO2, HONO, O3, H2O2, HCHO), surface meteorological parameters and physic of the boundary layer, and photolysis rates. It has to be noted that HONO was measured for the first time in Antarctica by using the long path absorption photometer (LOPAP) technique. A few balloon experiments documented ozone and NOx changes with height. These data for which a well-marked diurnal cycle was often observed will allow a better understanding of the role of snow-pack emissions on the oxidative properties of the atmosphere overlying the East Antarctic plateau.
The spatial and temporal (event and seasonal timescale) variability of major runoff components in... more The spatial and temporal (event and seasonal timescale) variability of major runoff components in the mountainous Brugga basin (Black Forest, Germany) were examined. The mesoscale (40 km2) study basin represented an extraordinary challenge as comparable studies have been undertaken mainly in smaller headwater basins. Discharge data, tracer concentrations of 18O, 3H, CFCs, and dissolved silica, and major anions and cations
ABSTRACT White mica from the Liassic black shales and slates in Central Switzerland was analysed ... more ABSTRACT White mica from the Liassic black shales and slates in Central Switzerland was analysed by transmission electron microscopy (TEM) and electron microprobe to determine its textural and compositional evolution during very low-grade prograde metamorphism. Samples were studied from the diagenetic zone, anchizone and epizone (T ≈100°–450 °C). Phyllosilicate minerals analysed include illite/smectite (I/S), phengite, muscovite, brammallite, paragonite, margarite and glauconite. Textural evolution primarily is towards larger, more defect-free grains with compositions that approach those of their respective end-members. The smectite-to-illite transformation reduced the amounts of the exchange components SiK−1Al−1, MgSiAl−2, and Fe3+Al−1. These trends continue to a lesser degree in the anchizone and epizone. Correlations between the proportion of smectite in I/S and the composition of I/S indicate that smectite layers may contain a high layer charge. Illite in I/S bears a compositional resemblance to macrocrystalline phengite in some samples, but is different in others. Paragonite first appears in the upper diagenetic zone or lower anchizone as an interlayer-deficient brammallite, and it may be mixed with muscovite on the nanometre scale. Owing to the small calculated structure factor for paragonite-muscovite superstructures, conventional X-ray powder diffraction cannot distinguish between mixed-layer structures and a homogeneous compositionally intermediate solid solutions. However, indirect TEM evidence shows that irregularly shaped domains of Na- and K-rich mica exist below 10 nm. Subsequent coarsening of domains at higher grades produced discrete paragonite grains at the margins of muscovite crystals or in laths parallel to the basal plane of the host muscovite. Margarite appears in the epizone and follows a textural evolution similar to paragonite in that mixtures of margarite, paragonite, and muscovite may initially occur on the nanometre scale. However, no evidence of interlayer-poor margarite has been found.
Bacterial DNA containing motifs of unmethylated CpG dinucleotides (CpG-DNA) triggers innate immun... more Bacterial DNA containing motifs of unmethylated CpG dinucleotides (CpG-DNA) triggers innate immune cells through the pattern recognition receptor Toll-like receptor 9 (TLR-9). CpG-DNA possesses potent immunostimulatory effects on macrophages, dendritic cells, and B lymphocytes. Therefore, CpG-DNA contributes to inflammation during the course of bacterial infections. In contrast to other TLR-dependent microbial patterns, CpG-DNA is a strong inductor of IL-12. Thus, it acts as a Th1-polarizing agent that can be utilized as potent vaccine adjuvant. To assess the role of CpG-DNA in immune reactions in the CNS, we analyzed the effects of CpG-DNA on microglial cells in vitro and in vivo. Primary microglial cells as well as microglial cell lines express TLR-9 mRNA. Consequently, CpG-DNA activated microglial cells in vitro and induced TNF-alpha, IL-12p40, IL-12p70, and NO. Furthermore, MHC class II, B7-1, B7-2, and CD40 molecules were up-regulated. In addition, phagocytic activity of microglia was enhanced. After intracerebroventricular injection of CpG-DNA, microglial cells were activated and produced TNF-alpha and IL-12p40 transcripts, as shown by in situ hybridization. These results indicate that microglia is sensitive to CpG-DNA. Thus, bacterial DNA containing CpG motifs could not only play an important role during infections of the CNS, but also might trigger and sustain Th1-dominated immunopathogenic reactions.
ABSTRACT The comprehensive isotopic composition of atmospheric nitrate (i.e., the simultaneous me... more ABSTRACT The comprehensive isotopic composition of atmospheric nitrate (i.e., the simultaneous measurement of all its stable isotope ratios: 15N/14N, 17O/16O and 18O/16O) has been determined for aerosol samples collected in the marine boundary layer (MBL) over the Atlantic Ocean from 65°S (Weddell Sea) to 79°N (Svalbard), along a ship-borne latitudinal transect. In nonpolar areas, the δ15N of nitrate mostly deriving from anthropogenically emitted NOx is found to be significantly different (from 0 to 6‰) from nitrate sampled in locations influenced by natural NOx sources (−4 ± 2)‰. The effects on δ15N(NO3−) of different NOx sources and nitrate removal processes associated with its atmospheric transport are discussed. Measurements of the oxygen isotope anomaly (Δ17O = δ17O − 0.52 × δ18O) of nitrate suggest that nocturnal processes involving the nitrate radical play a major role in terms of NOx sinks. Different Δ17O between aerosol size fractions indicate different proportions between nitrate formation pathways as a function of the size and composition of the particles. Extremely low δ15N values (down to −40‰) are found in air masses exposed to snow-covered areas, showing that snowpack emissions of NOx from upwind regions can have a significant impact on the local surface budget of reactive nitrogen, in conjunction with interactions with active halogen chemistry. The implications of the results are discussed in light of the potential use of the stable isotopic composition of nitrate to infer atmospherically relevant information from nitrate preserved in ice cores.
Impaired host defense mechanisms may crucially modulate the pathogenesis of atopic dermatitis (AD... more Impaired host defense mechanisms may crucially modulate the pathogenesis of atopic dermatitis (AD). More than 10% of patients with AD are heterozygous for the Toll-like receptor 2 (TLR-2) R753Q single nucleotide polymorphism (SNP) and exhibit severe eczema. To elucidate the functional effect of the TLR-2 mutation and its putative relevance for AD. Using the human embryonic kidney 293 transfection system, we characterized the properties of the TLR-2 R753Q SNP. Moreover, TLR-2 expression, IL-8 production, and cytokine secretion were analyzed in monocytes and CD4+ T cells of patients with AD with and without the mutant TLR-2 gene. Human embryonic kidney 293 transfectants mimicking this heterozygous mutation produced less IL-8 when stimulated with lipoteichoic acid (LTA), heat-inactivated Staphylococcus aureus or triacylated lipopeptides requiring the TLR-2/1 heterodimer. Suppressed production of IL-8 was confirmed in monocytes from patients with mutant AD after stimulation with peptidoglycan. Cell surface TLR-2 expression was severely impaired in CD3/CD28 activated CD4+ T cells of patients with AD bearing the mutant receptor, which could be restored on LTA stimulation. In contrast, LTA decreased TLR-2 expression among nonatopic individuals and patients with AD with the TLR-2 wild-type gene. T cells from patients with AD exhibited markedly suppressed IL-2 production after macrophage-activating lipopeptide-2 activation. However, no difference was found between mutant and wild-type patients with AD for IL-5, TNF-alpha, IFN-gamma, and IL-2 production. Collectively, the outcome of innate and adaptive immune responses in AD is modulated by the TLR-2 R753Q SNP.
The innate immune system recognizes pathogen-associated molecular patterns (PAMP) to cope with ev... more The innate immune system recognizes pathogen-associated molecular patterns (PAMP) to cope with evolving infections. Toll-like receptors (TLRs) play a pivotal role in recognition of PAMPs. In the course of infection not a single but rather a full panel of different microbial components interacts with distinct TLRs simultaneously. Only limited information is available on effects of combinations of TLR agonists. Here, we have analyzed the effects of lipoteichoic acid (LTA), CpG-DNA and combinations thereof on innate immune cells in vitro. Although proinflammatory cytokines like TNF-alpha were induced by these agonists in quite similar amounts, CpG DNA was superior in its potency to induce IL-12p40 reflecting important differences in the biological valence of LTA and CpG-DNA. When given in combination, LTA and CpG-DNA were additive in induction of TNF-alpha, IL-6 and nitric oxide in RAW 264 macrophages, peritoneal macrophages and dendritic cells. Additive effects were also observed in regard to TNF-alpha mRNA. In contrast, LTA suppressed IL12p40 secretion induced by CpG-DNA in RAW cells and peritoneal macrophages but not in dendritic cells. Intracellular signal cascades (NFkappaB and p38 MAP kinase) showed additive effects after simultaneous triggering. mRNA expression ofTLRs showed only minor regulation after CpG or LTA application and thus does not account for the additive/suppressive effects observed. These results indicate that the consequences of interaction of innate immune cells with microbial pattern depend on the responding cell type and might be differential for certain effector mechanisms. Thus, the pathogen-characteristic panel of TLR ligands will induce pathogen-specific innate responses decisive for the inflammatory reactions.
INTRODUCTION The technique of fission-track analysis has been widely applied to Alpine rocks in o... more INTRODUCTION The technique of fission-track analysis has been widely applied to Alpine rocks in order to unravel the cooling and exhumation history either in connection with other dating systems, such as K-Ar, Ar-Ar, and Rb-Sr, or by comparison of the variation of apatite ...
Toll-like receptors (TLRs) mediate recognition of microbial components. Despite activation of a s... more Toll-like receptors (TLRs) mediate recognition of microbial components. Despite activation of a shared set of signal transduction molecules, the biological effects of certain TLR agonists differ considerably. In macrophages and dendritic cells, stimulation by the prototypical stimuli CpG-DNA (TLR9), lipopolysaccharide (LPS; TLR4) and lipoteichoic acid (LTA; TLR2) resulted in striking differences in expression of IL-12. However, these stimuli induced similar amounts of the common proinflammatory cytokine TNFalpha. Surprisingly, an IL-12p40 promoter reporter construct was activated equally by CpG-DNA, LPS and LTA. Examinations of the chromatin structure of the endogenous IL-12p40 promoter revealed that nucleosome remodelling contributed to differential IL-12 induction. Upon stimulation, nucleosome architecture was changed to provide increased access to the IL-12p40 promoter. In dendritic cells, a differential induction of nucleosome remodelling at the IL-12p40 promoter was observed upon triggering with different TLR agonists. These results identify nucleosome remodelling as an additional restriction point in differential TLR signalling.
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