This study aimed to investigate the validity and reliability of global (GPS) and local (LPS) positioning systems for measuring distances covered and sprint mechanical properties in team sports. Here, ...we evaluated two recently released 18 Hz GPS and 20 Hz LPS technologies together with one established 10 Hz GPS technology. Six male athletes (age: 27±2 years; VO2max: 48.8±4.7 ml/min/kg) performed outdoors on 10 trials of a team sport-specific circuit that was equipped with double-light timing gates. The circuit included various walking, jogging, and sprinting sections that were performed either in straight-lines or with changes of direction. During the circuit, athletes wore two devices of each positioning system. From the reported and filtered velocity data, the distances covered and sprint mechanical properties (i.e., the theoretical maximal horizontal velocity, force, and power output) were computed. The sprint mechanical properties were modeled via an inverse dynamic approach applied to the center of mass. The validity was determined by comparing the measured and criterion data via the typical error of estimate (TEE), whereas the reliability was examined by comparing the two devices of each technology (i.e., the between-device reliability) via the coefficient of variation (CV). Outliers due to measurement errors were statistically identified and excluded from validity and reliability analyses. The 18 Hz GPS showed better validity and reliability for determining the distances covered (TEE: 1.6-8.0%; CV: 1.1-5.1%) and sprint mechanical properties (TEE: 4.5-14.3%; CV: 3.1-7.5%) than the 10 Hz GPS (TEE: 3.0-12.9%; CV: 2.5-13.0% and TEE: 4.1-23.1%; CV: 3.3-20.0%). However, the 20 Hz LPS demonstrated superior validity and reliability overall (TEE: 1.0-6.0%; CV: 0.7-5.0% and TEE: 2.1-9.2%; CV: 1.6-7.3%). For the 10 Hz GPS, 18 Hz GPS, and 20 Hz LPS, the relative loss of data sets due to measurement errors was 10.0%, 20.0%, and 15.8%, respectively. This study shows that 18 Hz GPS has enhanced validity and reliability for determining movement patterns in team sports compared to 10 Hz GPS, whereas 20 Hz LPS had superior validity and reliability overall. However, compared to 10 Hz GPS, 18 Hz GPS and 20 Hz LPS technologies had more outliers due to measurement errors, which limits their practical applications at this time.
The potential interactive effects of iron (Fe) limitation and Ocean Acidification in the Southern Ocean (SO) are largely unknown. Here we present results of a long-term incubation experiment ...investigating the combined effects of CO2 and Fe availability on natural phytoplankton assemblages from the Weddell Sea, Antarctica. Active Chl a fluorescence measurements revealed that we successfully cultured phytoplankton under both Fe-depleted and Fe-enriched conditions. Fe treatments had significant effects on photosynthetic efficiency (Fv/Fm; 0.3 for Fe-depleted and 0.5 for Fe-enriched conditions), non-photochemical quenching (NPQ), and relative electron transport rates (rETR). pCO2 treatments significantly affected NPQ and rETR, but had no effect on Fv/Fm. Under Fe limitation, increased pCO2 had no influence on C fixation whereas under Fe enrichment, primary production increased with increasing pCO2 levels. These CO2-dependent changes in productivity under Fe-enriched conditions were accompanied by a pronounced taxonomic shift from weakly to heavily silicified diatoms (i.e. from Pseudo-nitzschia sp. to Fragilariopsis sp.). Under Fe-depleted conditions, this functional shift was absent and thinly silicified species dominated all pCO2 treatments (Pseudo-nitzschia sp. and Synedropsis sp. for low and high pCO2, respectively). Our results suggest that Ocean Acidification could increase primary productivity and the abundance of heavily silicified, fast sinking diatoms in Fe-enriched areas, both potentially leading to a stimulation of the biological pump. Over much of the SO, however, Fe limitation could restrict this possible CO2 fertilization effect.
Novel treatment options for human papillomavirus (HPV)‐induced cancers are urgently required. The oncogenic transcription factor signal transducer and activator of transcription 3 (STAT3) is ...considered to be constitutively active in HPV‐positive cervical cancer cells and essential for their proliferation. Moreover, STAT3 was reported to undergo mutually stimulatory interactions with the HPV E6/E7 oncogenes. Thus, inhibiting STAT3 in HPV‐positive cancer cells is under discussion to provide a powerful novel therapeutic strategy. We here show that the antifungal drug ciclopirox destabilizes the STAT3 protein by acting as an iron chelator. However, by exploring the functional consequences of STAT3 inhibition in HPV‐positive cancer cells, we obtained several unexpected results. Chemical STAT3 inhibitors heterogeneously affect cervical cancer cell proliferation and those which act antiproliferative also block the growth of STAT3 knockout cells, indicating induction of off‐target effects. In contrast to several chemical inhibitors, genetic inhibition of STAT3 expression by either RNA interference or the CRISPR/Cas9 method does not appreciably affect cervical cancer cell proliferation. Transcriptome analyses indicate that blocking STAT3 expression in HPV‐positive cancer cells has very limited effects on putative STAT3 target genes. Although the targeted inhibition of specific growth‐promoting signaling pathways leads to a feedback activation of STAT3 in cervical cancer cells via Janus kinase 1/2, this does not lead to treatment resistance. Moreover, we did not obtain experimental evidence for a STAT3‐linked activation of HPV E6/E7 oncogene expression or, vice versa, an E6/E7‐dependent activation of STAT3, at endogenous conditions in cervical cancer cells. Collectively, these findings question the essential role of STAT3 in cervical cancer cell proliferation and the strategy to inhibit STAT3 in these cells for therapeutic purposes.
Cycling hypoxia (cycH) is a prevalent form of tumor hypoxia that is characterized by exposure of tumor cells to recurrent phases of hypoxia and reoxygenation. CycH has been associated with a ...particularly aggressive cellular phenotype of tumor cells and increased therapy resistance. By performing comparative analyses under normoxia, physoxia, chronic hypoxia, and cycH, we here uncover distinct effects of cycH on the phenotype of human papillomavirus (HPV)‐positive cervical cancer cells. We show that—other than under chronic hypoxia—viral E6/E7 oncogene expression is largely maintained under cycH as is the E6/E7‐dependent regulation of p53 and retinoblastoma protein. Further, cycH enables HPV‐positive cancer cells to evade prosenescent chemotherapy, similar to chronic hypoxia. Moreover, cells under cycH exhibit a particularly pronounced resistance to the proapoptotic effects of Cisplatin. Quantitative proteome analyses reveal that cycH induces a unique proteomic signature in cervical cancer cells, which includes a significant downregulation of luminal lysosomal proteins. These encompass the potentially proapoptotic cathepsins B and cathepsin L, which, however, appear not to affect the response to Cisplatin under any of the O2 conditions tested. Rather, we show that the proapoptotic Caspase 8/BH3‐interacting domain death agonist (BID) cascade plays a pivotal role for the efficiency of Cisplatin‐induced apoptosis in HPV‐positive cancer cells under all investigated O2 conditions. In addition, we provide evidence that BID activation by Cisplatin is impaired under cycH, which could contribute to the high resistance to the proapoptotic effects of Cisplatin. Collectively, this study provides the first insights into the profound phenotypic alterations induced by cycH in HPV‐positive cancer cells, with implications for their therapeutic susceptibility.
Oncogenic types of human papillomaviruses (HPVs) are major human carcinogens. The viral E6/E7 oncogenes maintain the malignant growth of HPV‐positive cancer cells. Targeted E6/E7 inhibition results ...in efficient induction of cellular senescence, which could be exploited for therapeutic purposes. Here we show that viral E6/E7 expression is strongly downregulated by Metformin in HPV‐positive cervical cancer and head and neck cancer cells, both at the transcript and protein level. Metformin‐induced E6/E7 repression is glucose and PI3K‐dependent but—other than E6/E7 repression under hypoxia—AKT‐independent. Proteome analyses reveal that Metformin‐induced HPV oncogene repression is linked to the downregulation of cellular factors associated with E6/E7 expression in HPV‐positive cancer biopsies. Notably, despite efficient E6/E7 repression, Metformin induces only a reversible proliferative stop in HPV‐positive cancer cells and enables them to evade senescence. Metformin also efficiently blocks senescence induction in HPV‐positive cancer cells in response to targeted E6/E7 inhibition by RNA interference. Moreover, Metformin treatment enables HPV‐positive cancer cells to escape from chemotherapy‐induced senescence. These findings uncover profound effects of Metformin on the virus/host cell interactions and the phenotype of HPV‐positive cancer cells with implications for therapy‐induced senescence, for attempts to repurpose Metformin as an anticancer agent and for the development of E6/E7‐inhibitory therapeutic strategies.
What's new?
Inhibition of the viral E6/E7 oncogenes in human papillomavirus (HPV)‐positive cancer cells leads to cellular senescence, thus representing an attractive anti‐cancer therapeutic strategy. The antidiabetic drug Metformin has shown anti‐tumorigenic potential in HPV‐positive cancer cells, but whether Metformin affects the HPV oncogenes or the virus/host cell crosstalk remains unknown. Here, the authors show that Metformin efficiently inhibits viral E6/E7 expression. Metformin however protects HPV‐positive cancer cells against the pro‐senescent effects of E6/E7 inhibition and chemotherapy‐induced senescence. These results reveal profound effects of Metformin on the virus/host cell crosstalk in HPV‐positive cancer cells, with potential implications for their therapeutic susceptibility.
Abstract
The Arctic is warming faster than anywhere else on Earth, prompting glacial melt, permafrost thaw, and sea ice decline. These severe consequences induce feedbacks that contribute to ...amplified warming, affecting weather and climate globally. Aerosols and clouds play a critical role in regulating radiation reaching the Arctic surface. However, the magnitude of their effects is not adequately quantified, especially in the central Arctic where they impact the energy balance over the sea ice. Specifically, aerosols called ice nucleating particles (INPs) remain understudied yet are necessary for cloud ice production and subsequent changes in cloud lifetime, radiative effects, and precipitation. Here, we report observations of INPs in the central Arctic over a full year, spanning the entire sea ice growth and decline cycle. Further, these observations are size-resolved, affording valuable information on INP sources. Our results reveal a strong seasonality of INPs, with lower concentrations in the winter and spring controlled by transport from lower latitudes, to enhanced concentrations of INPs during the summer melt, likely from marine biological production in local open waters. This comprehensive characterization of INPs will ultimately help inform cloud parameterizations in models of all scales.
Poisson surface reconstruction creates watertight surfaces from oriented point sets. In this work we extend the technique to explicitly incorporate the points as interpolation constraints. The ...extension can be interpreted as a generalization of the underlying mathematical framework to a screened Poisson equation. In contrast to other image and geometry processing techniques, the screening term is defined over a sparse set of points rather than over the full domain. We show that these sparse constraints can nonetheless be integrated efficiently. Because the modified linear system retains the same finite-element discretization, the sparsity structure is unchanged, and the system can still be solved using a multigrid approach. Moreover we present several algorithmic improvements that together reduce the time complexity of the solver to linear in the number of points, thereby enabling faster, higher-quality surface reconstructions.
•The Me−O coordination numbers are six in the MeP4O11 crystals and the respective glasses.•The same Me2+ cations have coordination numbers 4, 5, 6, and 7 at Me(PO3)2 composition.•There is a great ...similarity in the short-range order of these crystals and glasses.•Non-bridging and bridging oxygens must have an equivalent use in crystals and glasses.•The heterogeneities of 1 nm in Mg(PO3)2 glasses are explained by clusters of MgO6/MgO5.
Besides the PO4-based networks, the structure of phosphate glasses is determined much by the modifier cations. The consideration is focused on glasses (MeO)x(P2O5)1-x with divalent modifiers with concentrations x = 0.33 and 0.50. The packing densities and Me−O coordination numbers of the glasses and the related crystals are compared. The MeP4O11 crystals and the glasses at x = 0.33 have MeO6 octahedra for all Me dimensions from Zn to Ca. At x = 0.50, the structures of crystals and glasses show a large variability with different Me−O coordination numbers of 4, 5, 6, and 7 for the Me = Zn, Mg, Fe, Co, Mn, Cd, and Ca. Several factors beyond the ionic radii influence the MeOm polyhedra. Heterogeneities of 1 nm dimension known from small-angle X-ray scattering experiments of the Mg(PO3)2 glass are explained by small clusters of interconnected MgO6 units within a matrix of isolated MgO5 pairs.
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