Connected sum decompositions of high-dimensional manifolds

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

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 s$^{-1}$) the GW packet has a slow vertical group velocity of 0.05–0.2 m s$^{-1}$. 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

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

Increased cranio-caudal spinal cord oscillations are the cardinal pathophysiological change in degenerative cervical myelopathy.

INTRODUCTION Degenerative cervical myelopathy (DCM) is the most common cause of non-traumatic incomplete spinal cord injury, but its pathophysiology is poorly understood. As spinal cord compression observed in standard MRI often fails to explain a patient's status, new diagnostic techniques to assess DCM are one of the research priorities. Minor cardiac-related cranio-caudal oscillations of the cervical spinal cord are observed by phase-contrast MRI (PC-MRI) in healthy controls (HCs), while they become pathologically increased in patients suffering from degenerative cervical myelopathy. Whether transversal oscillations (i.e., anterior-posterior and right-left) also change in DCM patients is not known. METHODS We assessed spinal cord motion simultaneously in all three spatial directions (i.e., cranio-caudal, anterior-posterior, and right-left) using sagittal PC-MRI and compared physiological oscillations in 18 HCs to pathological changes in 72 DCM patients with spinal canal stenosis. The parameter of interest was the amplitude of the velocity signal (i.e., maximum positive to maximum negative peak) during the cardiac cycle. RESULTS Most patients suffered from mild DCM (mJOA score 16 (14-18) points), and the majority (68.1%) presented with multisegmental stenosis. The spinal canal was considerably constricted in DCM patients in all segments compared to HCs. Under physiological conditions in HCs, the cervical spinal cord oscillates in the cranio-caudal and anterior-posterior directions, while right-left motion was marginal [e.g., segment C5 amplitudes: cranio-caudal: 0.40 (0.27-0.48) cm/s; anterior-posterior: 0.18 (0.16-0.29) cm/s; right-left: 0.10 (0.08-0.13) cm/s]. Compared to HCs, DCM patients presented with considerably increased cranio-caudal oscillations due to the cardinal pathophysiologic change in non-stenotic [e.g., segment C5 amplitudes: 0.79 (0.49-1.32) cm/s] and stenotic segments [.g., segment C5 amplitudes: 0.99 (0.69-1.42) cm/s]). In contrast, right-left [e.g., segment C5 amplitudes: non-stenotic segment: 0.20 (0.13-0.32) cm/s; stenotic segment: 0.11 (0.09-0.18) cm/s] and anterior-posterior oscillations [e.g., segment C5 amplitudes: non-stenotic segment: 0.26 (0.15-0.45) cm/s; stenotic segment: 0.11 (0.09-0.18) cm/s] remained on low magnitudes comparable to HCs. CONCLUSION Increased cranio-caudal oscillations of the cervical cord are the cardinal pathophysiologic change and can be quantified using PC-MRI in DCM patients. This study addresses spinal cord oscillations as a relevant biomarker reflecting dynamic mechanical cord stress in DCM patients, potentially contributing to a loss of function

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

This study investigated the effects of irrigation frequency on N$_{2}$ and N$_{2}$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 N$_{2}$ + N$_{2}$O-N ha$^{-1}$ was emitted on average regardless of irrigation frequency, with N$_{2}$O accounting for 25% of overall N$_{2}$ + N$_{2}$O. Repeated, small amounts of irrigation produced an equal amount of N$_{2}$ + N$_{2}$O losses as a single, large irrigation event. The increase in N$_{2}$O emissions after the large rainfall event was smaller in the high-frequency treatment, shifting the N$_{2}$O/(N$_{2}$O + N$_{2}$) ratio towards N$_{2}$, indicating a treatment legacy effect. Cumulative losses of N$_{2}$O and N$_{2}$ did not differ between treatments, but higher CO$_{2}$ emissions were observed in the high-frequency treatment. Our results suggest that the increase in microbial activity and related O$_{2}$ 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 N$_{2}$O and N$_{2}$ 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 (N$_{2}$O), but not overall magnitude of N$_{2}$O and N$_{2}$ 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

Nitrification inhibitors (NIs) have been shown to reduce emissions of the greenhouse gas nitrous oxide (N$_{2}$O) from agricultural soils. However, their N$_{2}$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 N$_{2}$ and N$_{2}$O emissions with $^{15}$N tracing analysis and the quantification of the N$_{2}$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 N$_{2}$O is responsible for large pulses of N$_{2}$O after the fertilization of agricultural soils. DMPP attenuated this effect only in the horticultural soil, reducing nitrification while increasing nosZ abundance. DMPP reduced N$_{2}$O emissions from the horticultural soil by >50% but did not affect overall N$_{2}$ + N$_{2}$O losses, demonstrating the shift in the N$_{2}$O:N$_{2}$ ratio towards N$_{2}$ as a key mechanism of N$_{2}$O mitigation by NIs. Under non-limiting NO$_{3}$$^{-}$ availability, the efficacy of NIs to mitigate N$_{2}$O emissions therefore depends on their ability to reduce the suppression of the N$_{2}$O reductase by high NO$_{3}$$^{-}$ concentrations in the soil, enabling complete denitrification to N$_{2}$

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

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

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)

Molecular evidence for a diverse green algal community growing in the hair of sloths and a specific association with Trichophilus welckeri (Chlorophyta, Ulvophyceae)

Peer reviewe

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

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