Records Of The Late Glacial Influx Of Ice-Rafted Detritus On The Orphan Knoll, Northwest Atlantic Ocean

The top 110 centimeters of IRD records for GVY002 reveal 5 distinct peaks in IRD input, each between 4000-6500 lithics/gram. Three of these peaks coincide with three peaks in the Ca/Sr ratios in the upper meter indicative of dolomite rich IRD from the Canadian margin. The IRD record and Ca/Sr ratio record generated in this study, when compared to the previously generated similar records in GVY001, reveals a similar pattern but over a much longer downcore sediment interval (over the upper 4.5 meters in GVY001 versus the upper 1.8 meters in GVY002). This is due to the higher sedimentation rate in GVY001. Hendry, et al. (2019) tentatively correlated the shallowest peaks in Ca/Sr ratios with Heinrich Events H0 - H4 by correlating the Ca/Sr ratio records in GVY001 to the δ18O record of N. pachyderma (s.). An IRD peak in GVY001 corresponds to each of the Heinrich Events identified in Hendry, et al. (2019). Subsequent comparison of GVY002 IRD records with those of GVY001 suggest that Heinrich Events H0, H1, and H2 can be identified over the first meter. Both GVY002 and GVY001 display two additional IRD peaks of at least 4000 lithics/gram between H1 and H2 during intervals of very low Ca/Sr ratios

Non-thermal Atmospheric Plasma Induces ROS-independent Cell Death in U373MG Glioma Cells and Augments the Cytotoxicity of Temozolomide

Non-thermal atmospheric plasma (NTAP) is an ionised gas produced under high voltage that can generate short-lived chemically active species and induce a cytotoxic insult in cancer cells. Cell-specific resistance to NTAP-mediated cytotoxicity has been reported in the literature. The aim of this study was to determine whether resistance against NTAP could be overcome using the human glioma cell line U373MG. Methods: Non-thermal atmospheric plasma was generated using a Dielectric Barrier Device (DBD) system with a maximum voltage output of 120 kV at 50 Hz. The viability of U373MG GBM cells and HeLa cervical carcinoma cells was determined using morphology, flow cytometry and cytotoxicity assays. Fluorescent probes and inhibitors were used to determine the mechanisms of cytotoxicity of cells exposed to the plasma field. Combinational therapy with temozolomide (TMZ) and multi-dose treatments were explored as mechanisms to overcome resistance to NTAP. Results: Non-thermal atmospheric plasma decreased cell viability in a dose (time)-dependent manner. U373MG cells were shown to be resistant to NTAP treatment when compared with HeLa cells, and the levels of intracellular reactive oxygen species (ROS) quantified in U373MG cells were much lower than in HeLa cells following exposure to the plasma field. Reactive oxygen species inhibitor N-acetyl cysteine (NAC) only alleviated the cytotoxic effects in HeLa cells and not in the relatively NTAP-resistant cell line U373MG. Longer exposures to NTAP induced a cell death independent of ROS, JNK and caspases in U373MG. The relative resistance of U373MG cells to NTAP could be overcome when used in combination with low concentrations of the GBM chemotherapy TMZ or exposure to multiple doses. Conclusions: For the very first time, we report that NTAP induces an ROS-, JNK- and caspase-independent mechanism of cell death in the U373MG GBM cell line that can be greatly enhanced when used in combination with low doses of TMZ. Further refinement of the technology may facilitate localised activation of cytotoxicity against GBM when used in combination with new and existing chemotherapeutic regimens

Non-thermal Atmospheric Plasma Induces ROS-independent Cell Death in U373MG Glioma Cells and Augments the Cytotoxicity of Temozolomide

Non-thermal atmospheric plasma (NTAP) is an ionised gas produced under high voltage that can generate short-lived chemically active species and induce a cytotoxic insult in cancer cells. Cell-specific resistance to NTAP-mediated cytotoxicity has been reported in the literature. The aim of this study was to determine whether resistance against NTAP could be overcome using the human glioma cell line U373MG. Methods: Non-thermal atmospheric plasma was generated using a Dielectric Barrier Device (DBD) system with a maximum voltage output of 120 kV at 50 Hz. The viability of U373MG GBM cells and HeLa cervical carcinoma cells was determined using morphology, flow cytometry and cytotoxicity assays. Fluorescent probes and inhibitors were used to determine the mechanisms of cytotoxicity of cells exposed to the plasma field. Combinational therapy with temozolomide (TMZ) and multi-dose treatments were explored as mechanisms to overcome resistance to NTAP. Results: Non-thermal atmospheric plasma decreased cell viability in a dose (time)-dependent manner. U373MG cells were shown to be resistant to NTAP treatment when compared with HeLa cells, and the levels of intracellular reactive oxygen species (ROS) quantified in U373MG cells were much lower than in HeLa cells following exposure to the plasma field. Reactive oxygen species inhibitor N-acetyl cysteine (NAC) only alleviated the cytotoxic effects in HeLa cells and not in the relatively NTAP-resistant cell line U373MG. Longer exposures to NTAP induced a cell death independent of ROS, JNK and caspases in U373MG. The relative resistance of U373MG cells to NTAP could be overcome when used in combination with low concentrations of the GBM chemotherapy TMZ or exposure to multiple doses. Conclusions: For the very first time, we report that NTAP induces an ROS-, JNK- and caspase-independent mechanism of cell death in the U373MG GBM cell line that can be greatly enhanced when used in combination with low doses of TMZ. Further refinement of the technology may facilitate localised activation of cytotoxicity against GBM when used in combination with new and existing chemotherapeutic regimens

North Atlantic Intermediate to Deep Water circulation and chemical stratification during the past 1 Myr

Benthic foraminiferal carbon isotope records from a suite of drill sites in the North Atlantic are used to trace variations in the relative strengths of Lower North Atlantic Deep Water (LNADW), Upper North Atlantic Deep Water (UNADW), and Southern Ocean Water (SOW) over the past 1 Myr. During glacial intervals, significant increases in intermediate-to-deep δ13C gradients (commonly reaching >1.2‰) are consistent with changes in deep water circulation and associated chemical stratification. Bathymetric δ13C gradients covary with benthic foraminiferal δ18O and covary inversely with Vostok CO2, in agreement with chemical stratification as a driver of atmospheric CO2 changes. Three deep circulation indices based on δ13C show a phasing similar to North Atlantic sea surface temperatures, consistent with a Northern Hemisphere control of NADW/SOW variations. However, lags in the precession band indicate that factors other than deep water circulation control ice volume variations at least in this band

The First Robust Constraints on the Relationship Between Dust-to-Gas Ratio and Metallicity in Luminous Star-forming Galaxies at High Redshift

We present rest-optical spectroscopic properties of a sample of four galaxies in the Atacama Large Millimeter/submillimeter Array Hubble Ultra Deep Field (ALMA HUDF). These galaxies span the redshift range $1.41 \leq z \leq 2.54$ and the stellar mass range $10.36\leq\log(M_*/{\rm M}_{\odot})\leq10.91$. They have existing far-infrared and radio measurements of dust-continuum and molecular gas emission from which bolometric star-formation rates (SFRs), dust masses, and molecular gas masses have been estimated. We use new $H$- and $K$-band near-infrared spectra from the Keck/MOSFIRE spectrograph to estimate SFRs from dust-corrected H$\alpha$ emission (SFR(H$\alpha$)) and gas-phase oxygen abundances from the ratio [NII]$\lambda 6584$/H$\alpha$. We find that the dust-corrected SFR(H$\alpha$) is systematically lower than the bolometric SFR by a factor of several, and measure gas-phase oxygen abundances in a narrow range, 12+\log(\mbox{O/H})=8.59-8.69 (0.8-1.0\: (\mbox{O/H})_{\odot}). Relative to a large $z\sim 2$ comparison sample from the MOSDEF survey, the ALMA HUDF galaxies scatter roughly symmetrically around the best-fit linear mass-metallicity relation, providing tentative evidence for a flattening in the SFR dependence of metallicity at high stellar mass. Combining oxygen abundances with estimates of dust and molecular gas masses, we show that there is no significant evolution in the normalization of the dust-to-gas ratio DGR vs. metallicity relation from $z\sim0$ to $z\sim2$. This result is consistent with some semi-analytic models and cosmological simulations describing the evolution of dust in galaxies. Tracing the actual form of the DGR vs. metallicity relation at high redshift now requires combined measurements of dust, gas, and metallicity over a significantly wider range in metallicity.Comment: 6 pages, 3 figures, accepted to ApJ Letter

Cold Atmospheric Plasma Induces Accumulation of Lysosomes and Caspase-independent Cell Death in U373MG Glioblastoma Multiforme Cells

Room temperature Cold Atmospheric Plasma (CAP) has shown promising efficacy for the treatment of cancer but the exact mechanisms of action remain unclear. Both apoptosis and necrosis have been implicated as the mode of cell death in various cancer cells. We have previously demonstrated a caspase-independent mechanism of cell death in p53-mutated glioblastoma multiforme (GBM) cells exposed to plasma. The purpose of this study was to elucidate the molecular mechanisms involved in caspase-independent cell death induced by plasma treatment. We demonstrate that plasma induces rapid cell death in GBM cells, independent of caspases. Accumulation of vesicles was observed in plasma treated cells that stained positive with acridine orange. Western immunoblotting confirmed that autophagy is not activated following plasma treatment. Acridine orange intensity correlates closely with the lysosomal marker Lyso TrackerTM Deep Red. Further investigation using isosurface visualisation of confocal imaging confirmed that lysosomal accumulation occurs in plasma treated cells. The accumulation of lysosomes was associated with concomitant cell death following plasma treatment. In conclusion, we observed rapid accumulation of acidic vesicles and cell death following CAP treatment in GBM cells. We found no evidence that either apoptosis or autophagy, however, determined that a rapid accumulation of late stage endosomes/lysosomes precedes membrane permeabilisation, mitochondrial membrane depolarisation and caspase independent cell death