1,136 research outputs found

    Connected sum decompositions of high-dimensional manifolds

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    The classical Kneser-Milnor theorem says that every closed oriented connected 3-dimensional manifold admits a unique connected sum decomposition into manifolds that cannot be decomposed any further. We discuss to what degree such decompositions exist in higher dimensions and we show that in many settings uniqueness fails in higher dimensions.Comment: 25 pages, fixed several minor mistakes, final versio

    Orographically induced spontaneous imbalance within the jet causing a large-scale gravity wave event

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    To better understand the impact of gravity waves (GWs) on the middle atmosphere in the current and future climate, it is essential to understand their excitation mechanisms and to quantify their basic properties. Here a new process for GW excitation by orography–jet interaction is discussed. In a case study, we identify the source of a GW observed over Greenland on 10 March 2016 during the POLSTRACC (POLar STRAtosphere in a Changing Climate) aircraft campaign. Measurements were taken with the Gimballed Limb Observer for Radiance Imaging of the Atmosphere (GLORIA) instrument deployed on the High Altitude Long Range (HALO) German research aircraft. The measured infrared limb radiances are converted into a 3D observational temperature field through the use of inverse modelling and limited-angle tomography. We observe GWs along a transect through Greenland where the GW packet covers ≈ 1/3 of the Greenland mainland. GLORIA observations indicate GWs between 10 and 13 km of altitude with a horizontal wavelength of 330 km, a vertical wavelength of 2 km and a large temperature amplitude of 4.5 K. Slanted phase fronts indicate intrinsic propagation against the wind, while the ground-based propagation is with the wind. The GWs are arrested below a critical layer above the tropospheric jet. Compared to its intrinsic horizontal group velocity (25–72 m s1^{-1}) the GW packet has a slow vertical group velocity of 0.05–0.2 m s1^{-1}. This causes the GW packet to propagate long distances while spreading over a large area and remaining constrained to a narrow vertical layer. A plausible source is not only orography, but also out-of-balance winds in a jet exit region and wind shear. To identify the GW source, 3D GLORIA observations are combined with a gravity wave ray tracer, ERA5 reanalysis and high-resolution numerical experiments. In a numerical experiment with a smoothed orography, GW activity is quite weak, indicating that the GWs in the realistic orography experiment are due to orography. However, analysis shows that these GWs are not mountain waves. A favourable area for spontaneous GW emission is identified in the jet by the cross-stream ageostrophic wind, which indicates when the flow is out of geostrophic balance. Backwards ray-tracing experiments trace into the jet and regions where the Coriolis and the pressure gradient forces are out of balance. The difference between the full and a smooth-orography experiment is investigated to reveal the missing connection between orography and the out-of-balance jet. We find that this is flow over a broad area of elevated terrain which causes compression of air above Greenland. The orography modifies the wind flow over large horizontal and vertical scales, resulting in out-of-balance geostrophic components. The out-of-balance jet then excites GWs in order to bring the flow back into balance. This is the first observational evidence of GW generation by such an orography–jet mechanism

    MMP13 mediates cell cycle progression in melanocytes and melanoma cells: in vitro studies of migration and proliferation

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    Contains fulltext : 87376.pdf (publisher's version ) (Open Access)BACKGROUND: Melanoma cells are usually characterized by a strong proliferative potential and efficient invasive migration. Among the multiple molecular changes that are recorded during progression of this disease, aberrant activation of receptor tyrosine kinases (RTK) is often observed. Activation of matrix metalloproteases goes along with RTK activation and usually enhances RTK-driven migration. The purpose of this study was to examine RTK-driven three-dimensional migration of melanocytes and the pro-tumorigenic role of matrix metalloproteases for melanocytes and melanoma cells. RESULTS: Using experimental melanocyte dedifferentiation as a model for early melanomagenesis we show that an activated EGF receptor variant potentiates migration through three-dimensional fibrillar collagen. EGFR stimulation also resulted in a strong induction of matrix metalloproteases in a MAPK-dependent manner. However, neither MAPK nor MMP activity were required for migration, as the cells migrated in an entirely amoeboid mode. Instead, MMPs fulfilled a function in cell cycle regulation, as their inhibition resulted in strong growth inhibition of melanocytes. The same effect was observed in the human melanoma cell line A375 after stimulation with FCS. Using sh- and siRNA techniques, we could show that MMP13 is the protease responsible for this effect. Along with decreased proliferation, knockdown of MMP13 strongly enhanced pigmentation of melanocytes. CONCLUSIONS: Our data show for the first time that growth stimuli are mediated via MMP13 in melanocytes and melanoma, suggesting an autocrine MMP13-driven loop. Given that MMP13-specific inhibitors are already developed, these results support the evaluation of these inhibitors in the treatment of melanoma

    Amplitude and frequency of wetting and drying cycles drive N2_{2} and N2_{2}O emissions from a subtropical pasture

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    This study investigated the effects of irrigation frequency on N2_{2} and N2_{2}O emissions from an intensively managed pasture in the subtropics. Irrigation volumes were estimated to replace evapotranspiration and were applied either once (low frequency) or split into four applications (high frequency). To test for legacy effects, a large rainfall event was simulated at the end of the experiment. Over 15 days, 7.9 ± 2.7 kg N2_{2} + N2_{2}O-N ha1^{-1} was emitted on average regardless of irrigation frequency, with N2_{2}O accounting for 25% of overall N2_{2} + N2_{2}O. Repeated, small amounts of irrigation produced an equal amount of N2_{2} + N2_{2}O losses as a single, large irrigation event. The increase in N2_{2}O emissions after the large rainfall event was smaller in the high-frequency treatment, shifting the N2_{2}O/(N2_{2}O + N2_{2}) ratio towards N2_{2}, indicating a treatment legacy effect. Cumulative losses of N2_{2}O and N2_{2} did not differ between treatments, but higher CO2_{2} emissions were observed in the high-frequency treatment. Our results suggest that the increase in microbial activity and related O2_{2} consumption in response to small and repeated wetting events can offset the effects of increased soil gas diffusivity on denitrification, explaining the lack of treatment effect on cumulative N2_{2}O and N2_{2} emissions and the abundance of N cycling marker genes. The observed legacy effect may be linked to increased mineralisation and subsequent increased dissolved organic carbon availability, suggesting that increased irrigation frequency can reduce the environmental impact (N2_{2}O), but not overall magnitude of N2_{2}O and N2_{2} emissions from intensively managed pastures

    Effect of the nitrification inhibitor 3,4-dimethylpyrazole phosphate (DMPP) on N-turnover, the N2_{2}O reductase-gene nosZ and N2_{2}O:N2_{2} partitioning from agricultural soils

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    Nitrification inhibitors (NIs) have been shown to reduce emissions of the greenhouse gas nitrous oxide (N2_{2}O) from agricultural soils. However, their N2_{2}O reduction efficacy varies widely across different agro-ecosystems, and underlying mechanisms remain poorly understood. To investigate effects of the NI 3,4-dimethylpyrazole-phosphate (DMPP) on N-turnover from a pasture and a horticultural soil, we combined the quantification of N2_{2} and N2_{2}O emissions with 15^{15}N tracing analysis and the quantification of the N2_{2}O-reductase gene (nosZ) in a soil microcosm study. Nitrogen fertilization suppressed nosZ abundance in both soils, showing that high nitrate availability and the preferential reduction of nitrate over N2_{2}O is responsible for large pulses of N2_{2}O after the fertilization of agricultural soils. DMPP attenuated this effect only in the horticultural soil, reducing nitrification while increasing nosZ abundance. DMPP reduced N2_{2}O emissions from the horticultural soil by >50% but did not affect overall N2_{2} + N2_{2}O losses, demonstrating the shift in the N2_{2}O:N2_{2} ratio towards N2_{2} as a key mechanism of N2_{2}O mitigation by NIs. Under non-limiting NO3_{3}^{-} availability, the efficacy of NIs to mitigate N2_{2}O emissions therefore depends on their ability to reduce the suppression of the N2_{2}O reductase by high NO3_{3}^{-} concentrations in the soil, enabling complete denitrification to N2_{2}

    Comparison of axial and sagittal spinal cord motion measurements in degenerative cervical myelopathy.

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    BACKGROUND AND PURPOSE The timing of decision-making for a surgical intervention in patients with mild degenerative cervical myelopathy (DCM) is challenging. Spinal cord motion phase contrast MRI (PC-MRI) measurements can reveal the extent of dynamic mechanical strain on the spinal cord to potentially identify high-risk patients. This study aims to determine the comparability of axial and sagittal PC-MRI measurements of spinal cord motion with the prospect of improving the clinical workup. METHODS Sixty-four DCM patients underwent a PC-MRI scan assessing spinal cord motion. The agreement of axial and sagittal measurements was determined by means of intraclass correlation coefficients (ICCs) and Bland-Altman analyses. RESULTS The comparability of axial and sagittal PC-MRI measurements was good to excellent at all cervical levels (ICCs motion amplitude: .810-.940; p < .001). Significant differences between axial and sagittal amplitude values could be found at segments C3 and C4, while its magnitude was low (C3: 0.07 ± 0.19 cm/second; C4: -0.12 ± 0.30 cm/second). Bland-Altman analysis showed a good agreement between axial and sagittal PC-MRI scans (coefficients of repeatability: minimum -0.23 cm/second at C2; maximum -0.58 cm/second at C4). Subgroup analysis regarding anatomic conditions (stenotic vs. nonstenotic segments) and different velocity encoding (2 vs. 3 cm/second) showed comparable results. CONCLUSIONS This study demonstrates good comparability between axial and sagittal spinal cord motion measurements in DCM patients. To this end, axial and sagittal PC-MRI are both accurate and sensitive in detecting pathologic cord motion. Therefore, such measures could identify high-risk patients and improve clinical decision-making (ie, timing of decompression)

    Comparison of axial and sagittal spinal cord motion measurements in degenerative cervical myelopathy

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    BACKGROUND AND PURPOSE The timing of decision-making for a surgical intervention in patients with mild degenerative cervical myelopathy (DCM) is challenging. Spinal cord motion phase contrast MRI (PC-MRI) measurements can reveal the extent of dynamic mechanical strain on the spinal cord to potentially identify high-risk patients. This study aims to determine the comparability of axial and sagittal PC-MRI measurements of spinal cord motion with the prospect of improving the clinical workup. METHODS Sixty-four DCM patients underwent a PC-MRI scan assessing spinal cord motion. The agreement of axial and sagittal measurements was determined by means of intraclass correlation coefficients (ICCs) and Bland-Altman analyses. RESULTS The comparability of axial and sagittal PC-MRI measurements was good to excellent at all cervical levels (ICCs motion amplitude: .810-.940; p < .001). Significant differences between axial and sagittal amplitude values could be found at segments C3 and C4, while its magnitude was low (C3: 0.07 ± 0.19 cm/second; C4: -0.12 ± 0.30 cm/second). Bland-Altman analysis showed a good agreement between axial and sagittal PC-MRI scans (coefficients of repeatability: minimum -0.23 cm/second at C2; maximum -0.58 cm/second at C4). Subgroup analysis regarding anatomic conditions (stenotic vs. nonstenotic segments) and different velocity encoding (2 vs. 3 cm/second) showed comparable results. CONCLUSIONS This study demonstrates good comparability between axial and sagittal spinal cord motion measurements in DCM patients. To this end, axial and sagittal PC-MRI are both accurate and sensitive in detecting pathologic cord motion. Therefore, such measures could identify high-risk patients and improve clinical decision-making (ie, timing of decompression)

    In vivo imaging and quantitative analysis of leukocyte directional migration and polarization in inflamed tissue

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    Directional migration of transmigrated leukocytes to the site of injury is a central event in the inflammatory response. Here, we present an in vivo chemotaxis assay enabling the visualization and quantitative analysis of subtype-specific directional motility and polarization of leukocytes in their natural 3D microenvironment. Our technique comprises the combination of i) semi-automated in situ microinjection of chemoattractants or bacteria as local chemotactic stimulus, ii) in vivo near-infrared reflected-light oblique transillumination (RLOT) microscopy for the visualization of leukocyte motility and morphology, and iii) in vivo fluorescence microscopy for the visualization of different leukocyte subpopulations or fluorescence-labeled bacteria. Leukocyte motility parameters are quantified off-line in digitized video sequences using computer-assisted single cell tracking. Here, we show that perivenular microinjection of chemoattractants [macrophage inflammatory protein-1alpha (MIP-1alpha/Ccl3), platelet-activating factor (PAF)] or E. coli into the murine cremaster muscle induces target-oriented intravascular adhesion and transmigration as well as polarization and directional interstitial migration of leukocytes towards the locally administered stimuli. Moreover, we describe a crucial role of Rho kinase for the regulation of directional motility and polarization of transmigrated leukocytes in vivo. Finally, combining in vivo RLOT and fluorescence microscopy in Cx3CR1(gfp/gfp) mice (mice exhibiting green fluorescent protein-labeled monocytes), we are able to demonstrate differences in the migratory behavior of monocytes and neutrophils.Taken together, we propose a novel approach for investigating the mechanisms and spatiotemporal dynamics of subtype-specific motility and polarization of leukocytes during their directional interstitial migration in vivo

    Post-acute sequelae after SARS-CoV-2 infection by viral variant and vaccination status: a multicenter cross-sectional study.

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    BACKGROUND Disentangling the effects of SARS-CoV-2 variants and vaccination on the occurrence of post-acute sequelae of SARS-CoV-2 (PASC) is crucial to estimate and reduce the burden of PASC. METHODS We performed a cross-sectional analysis (May/June 2022) within a prospective multicenter healthcare worker (HCW) cohort in North-Eastern Switzerland. HCW were stratified by viral variant and vaccination status at time of their first positive SARS-CoV-2 nasopharyngeal swab. HCW without positive swab and with negative serology served as controls. The sum of eighteen self-reported PASC symptoms was modeled with univariable and multivariable negative-binomial regression to analyse the association of mean symptom number with viral variant and vaccination status. RESULTS Among 2'912 participants (median age 44 years, 81.3% female), PASC symptoms were significantly more frequent after wild-type infection (estimated mean symptom number 1.12, p<0.001; median time since infection 18.3 months), after Alpha/Delta infection (0.67 symptoms, p<0.001; 6.5 months), and after Omicron BA.1 infections (0.52 symptoms, p=0.005; 3.1 months) compared to uninfected controls (0.39 symptoms). After Omicron BA.1 infection, the estimated mean symptom number was 0.36 for unvaccinated individuals, compared to 0.71 with 1-2 vaccinations (p=0.028) and 0.49 with ≥3 prior vaccinations (p=0.30). Adjusting for confounders, only wild-type (adjusted rate ratio [aRR] 2.81, 95% confidence interval [CI] 2.08-3.83) and Alpha/Delta infection (aRR 1.93, 95% CI 1.10-3.46) were significantly associated with the outcome. CONCLUSIONS Previous infection with pre-Omicron variants was the strongest risk factor for PASC symptoms among our HCW. Vaccination prior to Omicron BA.1 infection was not associated with a clear protective effect against PASC symptoms in this population
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