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Expansion of an initial population of T cells is essential for cellular immunotherapy. In Chronic Lymphocytic Leukemia (CLL), expansion is often complicated by lack of T cell proliferation, as these cells frequently show signs of exhaustion. This report seeks to identify specific biomarkers or measures of cell function that capture the proliferative potential of a starting population of cells. Mixed CD4+/CD8+ T cells from healthy donors and individuals previously treated for CLL were characterized on the basis of proliferative potential and in vitro cellular functions. Single-factor analysis found little correlation between the number of populations doublings reached during expansion and either Rai stage (a clinical measure of CLL spread) or PD-1 expression. However, inclusion of in vitro IL-2 secretion and the propensity of cells to align onto micropatterned features of activating proteins as factors identified three distinct groups of donors. Notably, these group assignments provided an elegant separation of donors with regards to proliferative potential. Furthermore, these groups exhibited different motility characteristics, suggesting a mechanism that underlies changes in proliferative potential. This study describes a new set of functional readouts that augment surface marker panels to better predict expansion outcomes and clinical prognosis. 

Hydrogen peroxide (H₂O₂) and methyl hydroperoxide (MHP, CH₃OOH) serve as HO_x(OH and HO₂radicals) reservoirs and therefore as useful tracers of HO_xchemistry. Both hydroperoxides were measured during the 2016–2018 Atmospheric Tomography Mission as part of a global survey of the remote troposphere over the Pacific and Atlantic Ocean basins conducted using the NASA DC‐8 aircraft. To assess the relative contributions of chemical and physical processes to the global hydroperoxide budget and their impact on atmospheric oxidation potential, we compare the observations with two models, a diurnal steady‐state photochemical box model and the global chemical transport model Goddard Earth Observing System (GEOS)‐Chem. We find that the models systematically under‐predict H₂O₂by 5%–20% and over‐predict MHP by 40%–50% relative to measurements. In the marine boundary layer, over‐predictions of H₂O₂in a photochemical box model are used to estimate H₂O₂boundary‐layer mean deposition velocities of 1.0–1.32 cm s⁻¹, depending on season; this process contributes to up to 5%–10% of HO_xloss in this region. In the upper troposphere and lower stratosphere, MHP is under‐predicted and H₂O₂is over‐predicted by a factor of 2–3 on average. The differences between the observations and predictions are associated with recent convection: MHP is under‐estimated and H₂O₂is over‐estimated in air parcels that have experienced recent convective influence.

 

Atmospheric hydroperoxides are a significant component of the atmosphere's oxidizing capacity. Two of the most abundant hydroperoxides, hydrogen peroxide (H₂O₂) and methyl hydroperoxide (MHP, CH₃OOH), were measured in the remote atmosphere using chemical ionization mass spectrometry aboard the NASA DC‐8 aircraft during the Atmospheric Tomography Mission. These measurements present a seasonal investigation into the global distribution of these two hydroperoxides, with near pole‐to‐pole coverage across the Pacific and Atlantic Ocean basins and from the marine boundary layer to the upper troposphere and lower stratosphere. H₂O₂mixing ratios are highest between 2 and 4 km altitude in the equatorial region of the Atlantic Ocean basin, where they reach global maximums of 3.6–6.5 ppbv depending on season. MHP mixing ratios reach global maximums of 4.3–8.6 ppbv and are highest between 1 and 3 km altitude, but peak in different regions depending on season. A major factor contributing to the global H₂O₂distribution is the influence of biomass burning emissions in the Atlantic Ocean basin, encountered in all four seasons, where the highest H₂O₂mixing ratios were found to correlate strongly with increased mixing ratios of the biomass burning tracers hydrogen cyanide (HCN) and carbon monoxide (CO). This biomass burning enhanced H₂O₂by a factor of 1.3–2.2, on average, in the Atlantic compared with the Pacific Ocean basin.

 

The mammalian sex chromosome system (XX female/XY male) is ancient and highly conserved. The sex chromosome karyotype of the creeping vole (Microtus oregoni) represents a long-standing anomaly, with an X chromosome that is unpaired in females (X0) and exclusively maternally transmitted. We produced a highly contiguous male genome assembly, together with short-read genomes and transcriptomes for both sexes. We show thatM. oregonihas lost an independently segregating Y chromosome and that the male-specific sex chromosome is a second X chromosome that is largely homologous to the maternally transmitted X. Both maternally inherited and male-specific sex chromosomes carry fragments of the ancestral Y chromosome. Consequences of this recently transformed sex chromosome system include Y-like degeneration and gene amplification on the male-specific X, expression of ancestral Y-linked genes in females, and X inactivation of the male-specific chromosome in male somatic cells. The genome ofM. oregonielucidates the processes that shape the gene content and dosage of mammalian sex chromosomes and exemplifies a rare case of plasticity in an ancient sex chromosome system.

 

Cloud condensation nuclei (CCN) are mediators of aerosol‐cloud interactions, which contribute to the largest uncertainty in climate change prediction. Here, we present a machine learning (ML)/artificial intelligence (AI) model that quantifies CCN from model‐simulated aerosol composition, atmospheric trace gas, and meteorological variables. Comprehensive multi‐campaign airborne measurements, covering varied physicochemical regimes in the troposphere, confirm the validity of and help probe the inner workings of this ML model: revealing for the first time that different ranges of atmospheric aerosol composition and mass correspond to distinct aerosol number size distributions. ML extracts this information, important for accurate quantification of CCN, additionally from both chemistry and meteorology. This can provide a physicochemically explainable, computationally efficient, robust ML pathway in global climate models that only resolve aerosol composition; potentially mitigating the uncertainty of effective radiative forcing due to aerosol‐cloud interactions (ERF_aci) and improving confidence in assessment of anthropogenic contributions and climate change projections.