CORRECTIONS TO BOTTOM PRESSURE RECORDS FOR DYNAMIC TEMPERATURE RESPONSE
JOURNAL OF ATMOSPHERIC AND OCEANIC TECHNOLOGY
Authors: BOSS, EF; GONZALEZ, FI
Abstract
Factory calibration of Digiquartz(TM) transducers allows for static temperature corrections, assuming that the temperature changes slowly enough during deployment that the gauge is always in thermal equilibrium. Deep ocean bottom pressure recorders used by the NOAA/PMEL Tsunami Project are sometimes deployed in environments where assumptions of thermal equilibrium do not hold. In these cases the static temperature correction is not sufficient; pressure signals arise that are due purely to dynamic changes in the temperature of the gauge itself. Previous authors have determined the dynamic response of a transducer by subjecting it to known temperature-forcing functions in the laboratory and measuring the pressure response. The authors have developed a method of estimating the temperature response by relating the pressure signal to the time derivative of temperature. This relationship has been explored both with field and laboratory data. Once the parameters describing this relationship have been determined, pressure records can be corrected for dynamic temperature effects. For one particular deployment at the Loihi Seamount in Hawaii, pressure ''noise'' in the 2-120-min period band has been reduced from 8 mb to less than 1 mb.
N-acetyl cysteine protects anti-melanoma cytotoxic T cells from exhaustion induced by rapid expansion via the downmodulation of Foxo1 in an Akt-dependent manner
CANCER IMMUNOLOGY IMMUNOTHERAPY
Authors: Scheffel, Matthew J.; Scurti, Gina; Wyatt, Megan M.; Garrett-Mayer, Elizabeth; Paulos, Chrystal M.; Nishimura, Michael I.; Voelkel-Johnson, Christina
Abstract
Therapeutic outcomes for adoptive cell transfer (ACT) therapy are constrained by the quality of the infused T cells. The rapid expansion necessary to obtain large numbers of cells results in a more terminally differentiated phenotype with decreased durability and functionality. N-acetyl cysteine (NAC) protects against activation-induced cell death (AICD) and improves anti-tumor efficacy of Pmel-1 T cells in vivo. Here, we show that these benefits of NAC can be extended to engineered T cells and significantly increases T-cell survival within the tumor microenvironment. The addition of NAC to the expansion protocol of human TIL13838I TCR-transduced T cells that are under evaluation in a Phase I clinical trial, demonstrated that findings in murine cells extend to human cells. Expansion of TIL13838I TCR-transduced T cells in NAC also increased their ability to kill target cells in vitro. Interestingly, NAC did not affect memory subsets, but diminished up-regulation of senescence (CD57) and exhaustion (PD-1) markers and significantly decreased expression of the transcription factors EOMES and Foxo1. Pharmacological inhibition of the PI3K/Akt pathway ablates the decrease in Foxo1 induced by NAC treatment of activated T cells. This suggests a model in which NAC through PI3K/Akt activation suppresses Foxo1 expression, thereby impacting its transcriptional targets EOMES, PD-1, and granzyme B. Taken together, our results indicate that NAC exerts pleiotropic effects that impact the quality of TCR-transduced T cells and suggest that the addition of NAC to current clinical protocols should be considered.
COA
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