197 research outputs found
Magnocellular and parvocellular influences on reflexive attention
AbstractPrevious studies have provided conflicting evidence regarding whether the magnocellular (M) or parvocellular (P) visual pathway is primarily responsible for triggering involuntary orienting. Here, we used event-related potentials (ERPs) to provide new evidence that both the M and P pathways can trigger attentional capture and bias visual processing at multiple levels. Specifically, cued-location targets elicited enhanced activity, relative to uncued-location targets, at both early sensory processing levels (indexed by the P1 component) and later higher-order processing stages (as indexed by the P300 component). Furthermore, the present results show these effects of attentional capture were not contingent on the feature congruency between the cue and expected target, providing evidence that this biasing of visual processing was not dependant on top-down expectations or within-pathway priming
Intrareef variations in Li/Mg and Sr/Ca sea surface temperature proxies in the Caribbean reefâbuilding coral Siderastrea siderea
Caribbean sea surface temperatures (SSTs) have increased at a rate of 0.2°C per decade since 1971, a rate double that of the mean global change. Recent investigations of the coral Siderastrea siderea on the Belize Mesoamerican Barrier Reef System (MBRS) have demonstrated that warming over the last 30âyears has had a detrimental impact on calcification. Instrumental temperature records in this region are sparse, making it necessary to reconstruct longer SST records indirectly through geochemical temperature proxies. Here we investigate the skeletal Sr/Ca and Li/Mg ratios of S. siderea from two distinct reef zones (forereef and backreef) of the MBRS. Our field calibrations of S. siderea show that Li/Mg and Sr/Ca ratios are well correlated with temperature, although both ratios are 3 times more sensitive to temperature change in the forereef than in the backreef. These differences suggest that a secondary parameter also influences these SST proxies, highlighting the importance for siteâ and speciesâspecific SST calibrations. Application of these paleothermometers to downcore samples reveals highly uncertain reconstructed temperatures in backreef coral, but wellâmatched reconstructed temperatures in forereef coral, both between Sr/CaâSSTs and Li/MgâSSTs, and in comparison to the Hadley Centre Sea Ice and Sea Surface Temperature record. Reconstructions generated from a combined Sr/Ca and Li/Mg multiproxy calibration improve the precision of these SST reconstructions. This result confirms that there are circumstances in which both Li/Mg and Sr/Ca are reliable as standâalone and combined proxies of sea surface temperature. However, the results also highlight that highâprecision, siteâspecific calibrations remain critical for reconstructing accurate SSTs from coralâbased elemental proxies
Intrareef variations in Li/Mg and Sr/Ca sea surface temperature proxies in the Caribbean reef-building coral Siderastrea siderea
Caribbean sea surface temperatures (SSTs) have increased at a rate of 0.2°C per decade since 1971, a rate double that of the mean global change. Recent investigations of the coral Siderastrea siderea on the Belize Mesoamerican Barrier Reef System (MBRS) have demonstrated that warming over the last 30âyears has had a detrimental impact on calcification. Instrumental temperature records in this region are sparse, making it necessary to reconstruct longer SST records indirectly through geochemical temperature proxies. Here we investigate the skeletal Sr/Ca and Li/Mg ratios of S. siderea from two distinct reef zones (forereef and backreef) of the MBRS. Our field calibrations of S. siderea show that Li/Mg and Sr/Ca ratios are well correlated with temperature, although both ratios are 3 times more sensitive to temperature change in the forereef than in the backreef. These differences suggest that a secondary parameter also influences these SST proxies, highlighting the importance for siteâ and speciesâspecific SST calibrations. Application of these paleothermometers to downcore samples reveals highly uncertain reconstructed temperatures in backreef coral, but wellâmatched reconstructed temperatures in forereef coral, both between Sr/CaâSSTs and Li/MgâSSTs, and in comparison to the Hadley Centre Sea Ice and Sea Surface Temperature record. Reconstructions generated from a combined Sr/Ca and Li/Mg multiproxy calibration improve the precision of these SST reconstructions. This result confirms that there are circumstances in which both Li/Mg and Sr/Ca are reliable as standâalone and combined proxies of sea surface temperature. However, the results also highlight that highâprecision, siteâspecific calibrations remain critical for reconstructing accurate SSTs from coralâbased elemental proxies
Measuring and Correcting Wind-Induced Pointing Errors of the Green Bank Telescope Using an Optical Quadrant Detector
Wind-induced pointing errors are a serious concern for large-aperture
high-frequency radio telescopes. In this paper, we describe the implementation
of an optical quadrant detector instrument that can detect and provide a
correction signal for wind-induced pointing errors on the 100m diameter Green
Bank Telescope (GBT). The instrument was calibrated using a combination of
astronomical measurements and metrology. We find that the main wind-induced
pointing errors on time scales of minutes are caused by the feedarm being blown
along the direction of the wind vector. We also find that wind-induced
structural excitation is virtually non-existent. We have implemented offline
software to apply pointing corrections to the data from imaging instruments
such as the MUSTANG 3.3 mm bolometer array, which can recover ~70% of
sensitivity lost due to wind-induced pointing errors. We have also performed
preliminary tests that show great promise for correcting these pointing errors
in real-time using the telescope's subreflector servo system in combination
with the quadrant detector signal.Comment: 17 pages, 11 figures; accepted for publication in PAS
Boron isotope sensitivity to seawater pH change in a species of Neogoniolithon coralline red alga
The increase in atmospheric carbon dioxide (CO2) observed since the industrial revolution has reduced surface ocean pH by âŒ0.1 pH units, with further change in the oceanic system predicted in the coming decades. Calcareous organisms can be negatively affected by extreme changes in seawater pH (pHsw) such as this due to the associated changes in the oceanic carbonate system. The boron isotopic composition (ÎŽ11B) of biogenic carbonates has been previously used to monitor pH at the calcification site (pHcf) in scleractinian corals, providing mechanistic insights into coral biomineralisation and the impact of variable pHsw on this process. Motivated by these investigations, this study examines the ÎŽ11B of the high-Mg calcite skeleton of the coralline red alga Neogoniolithon sp. to constrain pHcf, and investigates how this taxonâs pHcf is impacted by ocean acidification. ÎŽ11B was measured in multiple algal replicates (n = 4â5) cultured at four different pCO2 scenarios â averaging (±1Ï) 409 (±6), 606 (±7), 903 (±12) and 2856 (±54) ÎŒatm, corresponding to average pHsw (±1Ï) of 8.19 (±0.03), 8.05 (±0.06), 7.91 (±0.03) and 7.49 (±0.02) respectively. Results show that skeletal ÎŽ11B is elevated relative to the ÎŽ11B of seawater borate at all pHsw treatments by up to 18â°. Although substantial variability in ÎŽ11B exists between replicate samples cultured at a given pHsw (smallest range = 2.32â° at pHsw 8.19, largest range = 6.08â° at pHsw 7.91), strong correlations are identified between ÎŽ11B and pHsw (R2 = 0.72, p < 0.0001, n = 16) and between ÎŽ11B and B/Ca (R2 = 0.72, p < 0.0001, n = 16). Assuming that skeletal ÎŽ11B reflects pHcf as previously observed for scleractinian corals, the average pHcf across all experiments was 1.20 pH units (0.79 to 1.56) higher than pHsw, with the magnitude of this offset varying parabolically with decreasing pHsw, with a maximum difference between pHsw and pHcf at a pHsw of 7.91. Observed relationships between pHsw and calcification rate, and between pHsw and pHcf, suggest that coralline algae exhibit some resilience to moderate ocean acidification via increase of pHcf relative to pHsw in a similar manner to scleractinian corals. However, these results also indicate that pHcf cannot be sufficiently increased by algae exposed to a larger reduction in pHsw, adversely impacting calcification rates of coralline red algae
Development and characterization of CD22-targeted pegylated-liposomal doxorubicin (IL-PLD)
Non-Hodgkinâs lymphoma (NHL) is the sixth most common cause of cancer deaths in the U.S. Most NHLs initially respond well to chemotherapy, but relapse is common and treatment is often limited due to the toxicity of chemotherapeutic agents. Pegylated-liposomal doxorubicin (PLD, Ben Venue Laboratories, Inc), a produces less myelotoxicity than non-liposomal (NL) doxorubicin. To further enhance efficacy and NHL targeting and to decrease toxicity, we conjugated an anti-CD22 monoclonal antibody (HB22.7) to the surface of PLD, thereby creating CD22-targeted immunoliposomal PLD (IL-PLD). HB22.7 was successfully conjugated to PLD and the resulting IL-PLD exhibits specific binding to CD22-expressing cells as assessed by immunofluorescence staining. IL-PLD exhibits more cytotoxicity than PLD in CD22 positive cell lines but does not increase killing of CD22 negative cells. The IC50 of IL-PLD is 3.1 to 5.4 times lower than that of PLD in CD22+ cell lines while the IC50 of IL-PLD is equal to that of PLD in CD22- cells. Furthermore, IL-PLD remained bound to the CD22+ cells after washing and continued to exert cytotoxic effects, while PLD and NL- doxorubicin could easily be washed from these cells
T Cell Cancer Therapy Requires CD40-CD40L Activation of Tumor Necrosis Factor and Inducible Nitric-Oxide-Synthase-Producing Dendritic Cells
Effective cancer immunotherapy requires overcoming immunosuppressive tumor microenvironments. We\ua0found that local nitric oxide (NO) production by tumor-infiltrating myeloid cells is important for adoptively transferred CD8(+) cytotoxic T\ua0cells to destroy tumors. These myeloid cells are phenotypically similar to inducible nitric oxide synthase (NOS2)- and tumor necrosis factor (TNF)-producing dendritic cells (DC), or Tip-DCs. Depletion of immunosuppressive, colony stimulating factor 1 receptor (CSF-1R)-dependent arginase 1(+) myeloid cells enhanced NO-dependent tumor killing. Tumor elimination via NOS2 required the CD40-CD40L pathway. We also uncovered a strong correlation between survival of colorectal cancer patients and NOS2, CD40, and TNF expression in their tumors. Our results identify a network of pro-tumor factors that can be targeted to boost cancer immunotherapies
The Bs20x22 anti-CD20-CD22 bispecific antibody has more lymphomacidal activity than do the parent antibodies alone
Previous studies have shown that bispecific antibodies that target both CD20 and CD22 have in vivo lymphomacidal properties. We developed a CD20-CD22 bispecific antibody (Bs20x22) from anti-CD20 and the anti-CD22 monoclonal antibodies (mAb), rituximab and HB22.7, respectively. Bs20x22 was constructed using standard methods and was shown to specifically bind CD20 and CD22. In vitro cytotoxicity assays showed that Bs20x22 was three times more effective than either parent mAb alone and twice as effective as a combination of both parent mAb used at equimolar concentrations. Bs20x22 was also nearly four times more effective at inducing apoptosis than either mAb alone. Examination of the MAPK and SAPK signaling cascades revealed that Bs20x22 induced significantly more p38 phosphorylation than either mAb alone. In an in vivo human NHL xenograft model, treatment with Bs20x22 resulted in significantly greater tumor shrinkage and improved overall survival when compared to either mAb alone or treatment with a combination of HB22.7 and rituximab. The effect of the initial tumor volume was assessed by comparing the efficacy of Bs20x22 administered before xenografts grew versus treatment of established tumors; significantly, greater efficacy was found when treatment was initiated before tumors could become established
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