Electrical properties of methane hydrate + sediment mixtures

Knowledge of the electrical properties of multicomponent systems with gas hydrate, sediments, and pore water is needed to help relate electromagnetic (EM) measurements to specific gas hydrate concentration and distribution patterns in nature. Toward this goal, we built a pressure cell capable of measuring in situ electrical properties of multicomponent systems such that the effects of individual components and mixing relations can be assessed. We first established the temperature-dependent electrical conductivity (?) of pure, single-phase methane hydrate to be ~5 orders of magnitude lower than seawater, a substantial contrast that can help differentiate hydrate deposits from significantly more conductive water-saturated sediments in EM field surveys. Here we report ? measurements of two-component systems in which methane hydrate is mixed with variable amounts of quartz sand or glass beads. Sand by itself has low ? but is found to increase the overall ? of mixtures with well-connected methane hydrate. Alternatively, the overall ? decreases when sand concentrations are high enough to cause gas hydrate to be poorly connected, indicating that hydrate grains provide the primary conduction path. Our measurements suggest that impurities from sand induce chemical interactions and/or doping effects that result in higher electrical conductivity with lower temperature dependence. These results can be used in the modeling of massive or two-phase gas-hydrate-bearing systems devoid of conductive pore water. Further experiments that include a free water phase are the necessary next steps toward developing complex models relevant to most natural systems

CAR T Cells in Solid Tumors: Blueprints for Building Effective Therapies

Genetic redirection of T lymphocytes with chimeric antigen receptors (CARs) has soared from treating cancers preclinically to FDA approval for hematologic malignancies and commercial-grade production scale in under 30 years. To date, solid tumors are less susceptible to CAR therapies and instead have been treated more successfully with immune checkpoint blockade or tumor-infiltrating lymphocyte therapy. Here, we discuss the current challenges in treating solid tumors with CAR T cells, and the obstacles within the host and tumor microenvironment hindering their efficacy. We present a novel three-pronged approach for enhancing the efficacy of CAR T cells whereby a single infusion product can synergize the power of an optimal CAR construct, a highly potent T cell subset, and rejuvenate the endogenous immune response to conquer therapeutically-resistant solid tumors

Fueling Cancer Immunotherapy With Common Gamma Chain Cytokines

Adoptive T cell transfer therapy (ACT) using tumor infiltrating lymphocytes or lymphocytes redirected with antigen receptors (CAR or TCR) has revolutionized the field of cancer immunotherapy. Although CAR T cell therapy mediates robust responses in patients with hematological malignancies, this approach has been less effective for treating patients with solid tumors. Additionally, toxicities post T cell infusion highlight the need for safer ACT protocols. Current protocols traditionally expand T lymphocytes isolated from patient tumors or from peripheral blood to large magnitudes in the presence of high dose IL-2 prior to infusion. Unfortunately, this expansion protocol differentiates T cells to a full effector or terminal phenotype in vitro, consequently reducing their long-term survival and antitumor effectiveness in vivo. Post-infusion, T cells face further obstacles limiting their persistence and function within the suppressive tumor microenvironment. Therapeutic manipulation of T cells with common γ chain cytokines, which are critical growth factors for T cells, may be the key to bypass such immunological hurdles. Herein, we discuss the primary functions of the common γ chain cytokines impacting T cell survival and memory and then elaborate on how these distinct cytokines have been used to augment T cell-based cancer immunotherapy

Management of Obstructive Sleep Apnea and Comorbid Insomnia: A Mixed-Methods Evaluation

The purpose of this study was to examine the process of care in an interdisciplinary sleep clinic for patients with obstructive sleep apnea (OSA) and comorbid insomnia. A mixed-methods approach was used to examine clinical and patient-centered measures for 34 patients who received positive-airway pressure for OSA or cognitive-behavior therapy for insomnia. The results revealed baseline-to-follow-up improvements on several self-reported sleep parameters and measures of daytime functioning. Qualitative analyses from patient interviews revealed three themes: conceptual distinctions about each sleep disorder, importance of treating both sleep disorders, and preferences with regard to the sequence of treatment. These findings indicate that patients with OSA and comorbid insomnia encounter unique challenges. A dimensional approach to assessment and treatment is proposed for future research

SN 2022jox: An extraordinarily ordinary Type II SN with Flash Spectroscopy

We present high cadence optical and ultraviolet observations of the Type II supernova (SN), SN 2022jox which exhibits early spectroscopic high ionization flash features of \ion{H}{1}, \ion{He}{2}, \ion{C}{4}, and \ion{N}{4} that disappear within the first few days after explosion. SN 2022jox was discovered by the Distance Less than 40 Mpc (DLT40) survey $\sim$0.75 days after explosion with followup spectra and UV photometry obtained within minutes of discovery. The SN reached a peak brightness of M$_V \sim$ $-$17.3 mag, and has an estimated $^{56}$Ni mass of 0.04 M$_{\odot}$, typical values for normal Type II SNe. The modeling of the early lightcurve and the strong flash signatures present in the optical spectra indicate interaction with circumstellar material (CSM) created from a progenitor with a mass loss rate of $\dot{M} \sim 10^{-3}-10^{-2}\ M_\odot\ \mathrm{yr}^{-1}$. There may also be some indication of late-time CSM interaction in the form of an emission line blueward of H$\alpha$ seen in spectra around 200 days. The mass-loss rate is much higher than the values typically associated with quiescent mass loss from red supergiants, the known progenitors of Type II SNe, but is comparable to inferred values from similar core collapse SNe with flash features, suggesting an eruptive event or a superwind in the progenitor in the months or years before explosion.Comment: Submitted to Ap

An in situ gas chromatograph with automatic detector switching between PTR- and EI-TOF-MS: isomer-resolved measurements of indoor air

We have developed a field-deployable gas chromatograph (GC) with thermal desorption preconcentration (TDPC), which is demonstrated here with automatic detector switching between two high-resolution time-of-flight mass spectrometers (TOF-MSs) for in situ measurements of volatile organic compounds (VOCs). This system provides many analytical advances, including acquisition of fast time&ndash;response data in tandem with molecular speciation and two types of mass spectral information for each resolved GC peak: molecular ion identification from Vocus proton transfer reaction (PTR) TOF-MS and fragmentation pattern from electron ionization (EI) TOF-MS detection. This system was deployed during the 2018 ATHLETIC campaign at the University of Colorado Dal Ward Athletic Center in Boulder, Colorado, where it was used to characterize VOC emissions in the indoor environment. The addition of the TDPC-GC increased the Vocus sensitivity by a factor of 50 due to preconcentration over a 6&thinsp;min GC sample time versus direct air sampling with the Vocus, which was operated with a time resolution of 1&thinsp;Hz. The GC-TOF methods demonstrated average limits of detection of 1.6&thinsp;ppt across a range of monoterpenes and aromatics. Here, we describe the method to use the two-detector system to conclusively identify a range of VOCs including hydrocarbons, oxygenates, and halocarbons, along with detailed results including the quantification of anthropogenic monoterpenes, where limonene accounted for 47&thinsp;%&ndash;80&thinsp;% of the indoor monoterpene composition. We also report the detection of dimethylsilanediol (DMSD), an organosiloxane degradation product, which was observed with dynamic temporal behavior distinct from volatile organosiloxanes (e.g., decamethylcyclopentasiloxane, D5 siloxane). Our results suggest DMSD is produced from humidity-dependent heterogeneous reactions occurring on surfaces in the indoor environment, rather than formed through gas-phase oxidation of volatile siloxanes. &nbsp;</p

Identification of human CD4+ T cell populations with distinct antitumor activity

How naturally arising human CD4+ T helper subsets affect cancer immunotherapy is unclear. We reported that human CD4+CD26high T cells elicit potent immunity against solid tumors. As CD26high T cells are often categorized as TH17 cells for their IL-17 production and high CD26 expression, we posited these populations would have similar molecular properties. Here, we reveal that CD26high T cells are epigenetically and transcriptionally distinct from TH17 cells. Of clinical importance, CD26high and TH17 cells engineered with a chimeric antigen receptor (CAR) regressed large human tumors to a greater extent than enriched TH1 or TH2 cells. Only human CD26high T cells mediated curative responses, even when redirected with a suboptimal CAR and without aid by CD8+ CAR T cells. CD26high T cells cosecreted effector cytokines, produced cytotoxic molecules, and persisted long term. Collectively, our work underscores the promise of CD4+ T cell populations to improve durability of solid tumor therapies

A randomized controlled trial of CBT-I and PAP for obstructive sleep apnea and comorbid insomnia : main outcomes from the MATRICS study

Study Objectives -- To investigate treatment models using cognitive behavioral therapy for insomnia (CBT-I) and positive airway pressure (PAP) for people with obstructive sleep apnea (OSA) and comorbid insomnia. Methods -- 121 adults with OSA and comorbid insomnia were randomized to receive CBT-I followed by PAP, CBT-I concurrent with PAP, or PAP only. PAP was delivered following standard clinical procedures for in-lab titration and home setup and CBT-I was delivered in four individual sessions. The primary outcome measure was PAP adherence across the first 90 days, with regular PAP use (≥4 h on ≥70% of nights during a 30-day period) serving as the clinical endpoint. The secondary outcome measures were the Pittsburgh Sleep Quality Index (PSQI) and Insomnia Severity Index (ISI) with good sleeper (PSQI 7) serving as the clinical endpoints. Results -- No significant differences were found between the concomitant treatment arms and PAP only on PAP adherence measures, including the percentage of participants who met the clinical endpoint. Compared to PAP alone, the concomitant treatment arms reported a significantly greater reduction from baseline on the ISI (p = .0009) and had a greater percentage of participants who were good sleepers (p = .044) and remitters (p = .008). No significant differences were found between the sequential and concurrent treatment models on any outcome measure. Conclusions -- The findings from this study indicate that combining CBT-I with PAP is superior to PAP alone on insomnia outcomes but does not significantly improve adherence to PAP

Early Spectroscopy and Dense Circumstellar Medium Interaction in SN~2023ixf

We present the optical spectroscopic evolution of SN~2023ixf seen in sub-night cadence spectra from 1.18 to 14 days after explosion. We identify high-ionization emission features, signatures of interaction with material surrounding the progenitor star, that fade over the first 7 days, with rapid evolution between spectra observed within the same night. We compare the emission lines present and their relative strength to those of other supernovae with early interaction, finding a close match to SN~2020pni and SN~2017ahn in the first spectrum and SN~2014G at later epochs. To physically interpret our observations we compare them to CMFGEN models with confined, dense circumstellar material around a red supergiant progenitor from the literature. We find that very few models reproduce the blended \NC{} emission lines observed in the first few spectra and their rapid disappearance thereafter, making this a unique diagnostic. From the best models, we find a mass-loss rate of $10^{-3}-10^{-2}$ \mlunit{}, which far exceeds the mass-loss rate for any steady wind, especially for a red supergiant in the initial mass range of the detected progenitor. These mass-loss rates are, however, similar to rates inferred for other supernovae with early circumstellar interaction. Using the phase when the narrow emission features disappear, we calculate an outer dense radius of circumstellar material $R_\mathrm{CSM, out}\sim5\times10^{14}~\mathrm{cm}$ and a mean circumstellar material density of $\rho=5.6\times10^{-14}~\mathrm{g\,cm^{-3}}$. This is consistent with the lower limit on the outer radius of the circumstellar material we calculate from the peak \Halpha{} emission flux, $R_\text{CSM, out}\gtrsim9\times10^{13}~\mathrm{cm}$.Comment: Submitted to ApJ