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"Christensen, K"
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Di-n-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) metabolism in a human volunteer after single oral doses
by
Brüning, T.
,
Lorber, M.
,
Christensen, K. L. Y.
in
Adult
,
Biomedical and Life Sciences
,
Biomedicine
2012
An individual (male, 36 years, 87 kg) ingested two separate doses of di-
n
-butyl phthalate (DnBP) and diisobutyl phthalate (DiBP) at a rate of ~60 μg/kg. Key monoester and oxidized metabolites were identified and quantified in urine continuously collected until 48 h post-dose. For both DnBP and DiBP, the majority of the dose was excreted in the first 24 h (92.2 % of DnBP, 90.3 % of DiBP), while only <1 % of the dose was excreted in urine on day 2. In each case, the simple monoesters were the major metabolites (MnBP, 84 %; MiBP, 71 %). For DnBP, ~8 % was excreted as various side chain oxidized metabolites. For DiBP, approximately 20 % was excreted mainly as the oxidized side chain metabolite 2OH-MiBP, indicating that the extent of oxidative modification is around 2.5 times higher for DiBP than for DnBP. All DnBP and DiBP metabolites reached peak concentrations between 2 and 4 h post-exposure, followed by a monotonic decline. For DnBP metabolites, the elimination halftime of MnBP was 2.6 h; longer elimination halftimes were estimated for the oxidized metabolites (2.9–6.9 h). For DiBP metabolites, MiBP had the shortest halftime (3.9 h), and the oxidized metabolites had somewhat longer halftimes (4.1 and 4.2 h). Together with the simple monoesters, secondary oxidized metabolites are additional and valuable biomarkers of phthalate exposure. This study provides basic human metabolism and toxicokinetic data for two phthalates that have to be considered human reproductive toxicants and that have been shown to be omnipresent in humans.
Journal Article
UbiSite approach for comprehensive mapping of lysine and N-terminal ubiquitination sites
by
Olsen, Jesper V
,
Hallenborg, Philip
,
Pedersen, Anna-Kathrine
in
Acetylation
,
Amino acids
,
Cell lines
2018
Ubiquitination is a post-translational modification (PTM) that is essential for balancing numerous physiological processes. To enable delineation of protein ubiquitination at a site-specific level, we generated an antibody, denoted UbiSite, recognizing the C-terminal 13 amino acids of ubiquitin, which remain attached to modified peptides after proteolytic digestion with the endoproteinase LysC. Notably, UbiSite is specific to ubiquitin. Furthermore, besides ubiquitination on lysine residues, protein N-terminal ubiquitination is readily detected as well. By combining UbiSite enrichment with sequential LysC and trypsin digestion and high-accuracy MS, we identified over 63,000 unique ubiquitination sites on 9,200 proteins in two human cell lines. In addition to uncovering widespread involvement of this PTM in all cellular aspects, the analyses reveal an inverse association between protein N-terminal ubiquitination and acetylation, as well as a complete lack of correlation between changes in protein abundance and alterations in ubiquitination sites upon proteasome inhibition.
Journal Article
Spatial structure of a turbulent boundary layer with irregular surface roughness
by
WU, Y.
,
CHRISTENSEN, K. T.
in
Boundary layer
,
Boundary layer and shear turbulence
,
Boundary layers
2010
Particle image velocimetry experiments were performed to study the impact of realistic roughness on the spatial structure of wall turbulence at moderate Reynolds number. This roughness was replicated from an actual turbine blade damaged by deposition of foreign materials and its features are quite distinct from most roughness characterizations previously considered as it is highly irregular and embodies a broad range of topographical scales. The spatial structure of flow over this rough surface near the outer edge of the roughness sublayer is contrasted with that of smooth-wall flow to identify any structural modifications due to roughness. Hairpin vortex packets are observed in the outer layer of the rough-wall flow and are found to contribute heavily to the Reynolds shear stress, consistent with smooth-wall flow. While similar qualitative consistency is observed in comparisons of smooth- and rough-wall two-point correlations, some quantitative differences are also apparent. In particular, a reduction in the streamwise extent of two-point correlations of streamwise velocity is noted which could be indicative of a roughness-induced modification of outer-layer vortex organization. Proper orthogonal decomposition analysis reveals the streamwise coherence of the larger scales to be most sensitive to roughness while the spatial characteristics of the smaller scales appear relatively insensitive to such effects.
Journal Article
The Effects of Public Service Motivation on Job Choice Decisions: Disentangling the Contributions of Person-Organization Fit and Person-Job Fit
2011
Although most research focuses on person-organization fit to explain public service motivation (PSM)' s influence on job choice, this study investigates the independent effects of both person-organization fit and person-job fit using a policy capturing research design and a sample of first-year law students. Our findings suggest that PSM may play a more important role in person-job fit than person-organization fit. Consistent across three sectors of employment, individuals with stronger PSM were more likely to accept jobs that emphasize service to others-whether that be pro bono work (private sector), client interaction (public sector), or client representation (nonprofit sector). After controlling for characteristics that influence person-job fit, PSM neither increased the likelihood that individuals would accept a public sector job nor decreased the likelihood that they would accept a private sector job. Among other things, our findings suggest that sector may be an inaccurate proxy for values that are often taken for granted in PSM studies.
Journal Article
Population trends of spanwise vortices in wall turbulence
by
WU, Y.
,
CHRISTENSEN, K. T.
in
Boundary layer and shear turbulence
,
Boundary layers
,
Channel flow
2006
The present effort documents the population trends of prograde and retrograde spanwise vortex cores in wall turbulence outside the buffer layer. Large ensembles of instantaneous velocity fields are acquired by particle-image velocimetry in the streamwise–wall-normal plane of both turbulent channel flow at $\\hbox{\\it Re}_\\tau\\equiv u_*\\delta/\\nu=570$, 1185 and 1760 and a zero-pressure-gradient turbulent boundary layer at $\\hbox{\\it Re}_\\tau=1400$, 2350 and 3450. Substantial numbers of prograde spanwise vortices are found to populate the inner boundary of the log layer of both flows and most of these vortices have structural signatures consistent with the heads of hairpin vortices. In contrast, retrograde vortices are most prominent at the outer edge of the log layer, often nesting near clusters of prograde vortices. Appropriate Reynolds-number scalings for outer- and inner-scaled population densities of prograde and retrograde vortices are determined. However, the Re$_\\tau=570$ channel-flow case deviates from these scalings, indicating that it suffers from low-Re effects. When the population densities are recast in terms of fractions of resolved prograde and retrograde spanwise vortices, similarity is observed for $100\\,{<}\\,y^+\\,{<}\\,0.8\\delta^+$ in channel flow and in both flows for $100\\,{<}\\,y^+\\,{<}\\,0.3\\delta^+$ over the Re$_\\tau$ range studied. The fraction of retrograde vortices increases slightly with $Re_\\tau$ beyond the log layer in both flows, suggesting that they may play an increasingly important role at higher Reynolds numbers. Finally, while the overall prograde and retrograde population trends of channel flow and the boundary layer show little difference for $y\\,{<}\\,0.45\\delta$, the retrograde populations differ considerably beyond this point, highlighting the influence of the opposing wall in channel flow.
Journal Article
Prokaryotic toxin–antitoxin stress response loci
by
Løbner-Olesen, Anders
,
Gerdes, Kenn
,
Christensen, Susanne K.
in
Antitoxins
,
Antitoxins - genetics
,
Apoptosis
2005
Key Points
Prokaryotic toxin–antitoxin (TA) loci, such as
relBE
and
mazEF
, encode mRNA-cleaving enzymes that are activated by nutritional stress.
Slowly growing bacteria and Archaea have numerous TA loci. For example,
Mycobacterium tuberculosis
has 38 and
Sulfolobus tokodaii
has 32 TA loci.
Free-living bacteria have many TA loci whereas obligate intracellular organisms have none, consistent with a hypothesis that TA loci function as part of the cellular stress response.
RelE cleaves mRNA codons positioned at the ribosomal A-site, between the 2nd and 3rd nucleotide. RelE does not cleave naked mRNA
in vitro
if ribosomes aren't present.
Whereas mRNA cleavage by RelE is strictly dependent on the presence of ribosomes, MazF cleaves mRNAs site-specifically at ACA sites independently of the ribosomes. Whether the ribosomes have a role in MazF-mediated mRNA cleavage during physiological conditions is not resolved.
TA loci function as stress response elements that help the cells cope with nutritional stress, possibly by reducing the production of defective proteins during scarce conditions.
Although toxin–antitoxin gene cassettes were first found in plasmids, recent database mining has shown that these loci are abundant in free-living prokaryotes, including many pathogenic bacteria. For example,
Mycobacterium tuberculosis
has 38 chromosomal toxin–antitoxin loci, including 3
relBE
and 9
mazEF
loci. RelE and MazF are toxins that cleave mRNA in response to nutritional stress. RelE cleaves mRNAs that are positioned at the ribosomal A-site, between the second and third nucleotides of the A-site codon. It has been proposed that toxin–antitoxin loci function in bacterial programmed cell death, but evidence now indicates that these loci provide a control mechanism that helps free-living prokaryotes cope with nutritional stress.
Journal Article
Understanding the anthropogenic influence on formation of biogenic secondary organic aerosols in Denmark via analysis of organosulfates and related oxidation products
2014
Anthropogenic emissions of sulfur dioxide (SO2) and nitrogen oxides (NOx) may affect concentration levels and composition of biogenic secondary organic aerosols (BSOA) through photochemical reactions with biogenic organic precursors to form organosulfates and nitrooxy organosulfates. We investigated this influence in a field study from 19 May to 22 June, 2011 at two sampling sites in Denmark. Within the study, we identified a substantial number of organic acids, organosulfates and nitrooxy organosulfates in the ambient urban curbside and semi-rural background air. A high degree of correlation in concentrations was found among a group of specific organic acids, organosulfates and nitrooxy organosulfates, which may originate from various precursors, suggesting a common mechanism or factor affecting their concentration levels at the sites. It was proposed that the formation of those species most likely occurred on a larger spatial scale, with the compounds being long-range transported to the sites on the days with the highest concentrations. The origin of the long-range transported aerosols was investigated using the Hybrid Single Particle Lagrangian Integrated Trajectory (HYSPLIT) model in addition to modeled emissions of related precursors, including isoprene and monoterpenes using the global Model of Emissions of Gases and Aerosols from Nature (MEGAN) and SO2 emissions using the European Monitoring and Evaluation Program (EMEP) database. The local impacts were also studied by examining the correlation between selected species, which showed significantly enhanced concentrations at the urban curbside site and the local concentrations of various gases, including SO2, ozone (O3), NOx, aerosol acidity and other meteorological conditions. This investigation showed that an inter-play of the local parameters such as the aerosol acidity, NOx, SO2, relative humidity (RH), temperature and global radiation seemed to affect the concentration level of those species, suggesting the influence of aqueous aerosol chemistry. The local impacts, however, seemed minor compared to the regional impacts. The total concentrations of organosulfates and nitrooxy organosulfates, on average, contributed to approximately 0.5–0.8% of PM1 mass at the two sampling sites.
Journal Article
Cross-stream stereoscopic particle image velocimetry of a modified turbulent boundary layer over directional surface pattern
by
Hutchins, N.
,
Monty, J. P.
,
Barros, J. M.
in
Boundary layer
,
Boundary layer transition
,
Boundary layers
2017
A turbulent boundary layer developed over a herringbone patterned riblet surface is investigated using stereoscopic particle image velocimetry in the cross-stream plane at
$Re_{\\unicode[STIX]{x1D70F}}\\approx 3900$
. The three velocity components resulting from this experiment reveal a pronounced spanwise periodicity in all single-point velocity statistics. Consistent with previous hot-wire studies over similar-type riblets, we observe a weak time-average secondary flow in the form of
$\\unicode[STIX]{x1D6FF}$
-filling streamwise vortices. The observed differences in the surface and secondary flow characteristics, compared to other heterogeneous-roughness studies, may suggest that different mechanisms are responsible for the flow modifications in this case. Observations of instantaneous velocity fields reveal modified and rearranged turbulence structures. The instantaneous snapshots also suggest that the time-average secondary flow may be an artefact arising from superpositions of much stronger instantaneous turbulent events enhanced by the surface texture. In addition, the observed instantaneous secondary motions seem to have promoted a free-stream-engulfing behaviour in the outer layer, which would indicate an increase turbulent/non-turbulent flow mixing. It is overall demonstrated that the presence of large-scale directionality in transitional surface roughness can cause a modification throughout the entire boundary layer, even when the roughness height is 0.5 % of the layer thickness.
Journal Article
Field Evidence for the Initiation of Isolated Aeolian Sand Patches
2023
Sand patches are one of the precursors to early stage protodunes and occur widely in both desert and coastal aeolian environments. Here we show field evidence of a mechanism to explain the initiation of sand patches on non‐erodible surfaces, such as desert gravels and moist beaches. Changes in sand transport dynamics, directly associated with the height of the saltation layer and variable transport law, observed at the boundary between non‐erodible and erodible surfaces lead to sand deposition on the erodible surface. This explains how sand patches can form on surfaces with limited sand availability where linear stability of dune theory does not apply. This new mechanism is supported by field observations that evidence both the change in transport rate over different surfaces and in situ patch formation that leads to modification of transport dynamics at the surface boundary.
Plain Language Summary
Sand patches can be observed in various environments such as beaches and gravel plains in deserts. Expected to be precursors of dunes when sediment supply is limited, these bedforms are typically a few centimeters high and present a reverse longitudinal elevation profile, with a sharp upwind edge and a smooth downwind tail. Based on field measurements, we propose a formation mechanism for these patches associated with the sensitive nature of wind‐blown sand transport to changing bed conditions: sand saltation is reduced at the transition from a solid to an erodible surface, hence favoring deposition on the patches. This allows us to explain their typical meter‐scale length as well as their asymmetric shapes.
Key Points
Sand patches can emerge on non‐erodible surfaces
Differing surfaces characteristics control particle behavior
Field measurements demonstrate the key role of sand transport in bedform initiation
Journal Article