Discrete CO2-System Measurements in the Chesapeake Bay Mainstem between 2016 and 2018

These are discrete observations of total dissolved inorganic carbon (DIC) and alkalinity (TA), and associated computed CO2-system parameters, from samples collected throughout the Chesapeake Bay mainstem between 2016 and 2018. Samples were collected on board the R/V Kerhin in Maryland and the R/V Fay Slover in Virginia at a subset of fixed stations in collaboration with the Chesapeake Bay Water Quality Monitoring Program. Samples were analyzed following standard procedures at the Virginia Institute of Marine Science. The DIC and TA data were then used to compute the remaining CO2-system parameters (pH, CO2 partial pressure (pCO2), and carbonate saturation state). A detailed description of sample collection and analytical methods is given Friedman et al., 2019

High-frequency CO2-system variability over the winter-to-spring transition in a large coastal plain estuary

Understanding the vulnerability of estuarine ecosystems to anthropogenic impacts requires a quantitative assessment of the dynamic drivers of change to the carbonate (CO2) system. Here we present new high‐frequency pH data from a moored sensor. These data are combined with discrete observations to create continuous time series of total dissolved inorganic carbon (TCO2), CO2 partial pressure (pCO2), and carbonate saturation state. We present two deployments over the winter‐to‐spring transition in the lower York River (where it meets the Chesapeake Bay mainstem) in 2016/2017 and 2017/2018. TCO2 budgets with daily resolution are constructed, and contributions from circulation, air‐sea CO2 exchange, and biology are quantified. We find that TCO2 is most strongly influenced by circulation and biological processes; pCO2 and pH also respond strongly to changes in temperature. The system transitions from autotrophic to heterotrophic conditions multiple times during both deployments; the conventional view of a spring bloom and subsequent summer production followed by autumn and winter respiration may not apply to this region. Despite the dominance of respiration in winter and early spring, surface waters were undersaturated with respect to atmospheric CO2 for the majority of both deployments with mean fluxes ranging from −9 to −5 mmol C·m−2·day−1. Deployments a year apart indicate that the seasonal transition in the CO2 system differs significantly from one year to the next and highlights the necessity of sustained monitoring in dynamic nearshore environments

Seasonal Variability of the CO2 System in a Large Coastal Plain Estuary

The Chesapeake Bay, a large coastal plain estuary, has been studied extensively in terms of its water quality, and yet, comparatively less is known about its carbonate system. Here we present discrete observations of dissolved inorganic carbon (DIC) and total alkalinity from four seasonal cruises in 2016–2017. These new observations are used to characterize the regional CO2 system and to construct a DIC budget of the mainstem. In all seasons, elevated DIC concentrations were observed at the mouth of the bay associated with inflowing Atlantic Ocean waters, while minimum concentrations of DIC were associated with fresher waters at the head of the bay. Significant spatial variability of the partial pressure of CO2 was observed throughout the mainstem, with net uptake of atmospheric CO2 during each season in the upper mainstem and weak seasonal outgassing of CO2 near the outflow to the Atlantic Ocean. During the time frame of this study, the Chesapeake Bay mainstem was (1) net autotrophic in the mixed layer (net community production of 0.31‐mol C m−2·year−1) and net heterotrophic throughout the water column (net community production of −0.48‐mol C m−2·year−1), (2) a sink of 0.38‐mol C m−2·year−1 for atmospheric CO2, and (3) significantly seasonally and spatially variable with respect to biologically driven changes in DIC. DATA available at: https://doi.org/10.25773/rntn‐ez1

Challenges in Quantifying Air‐Water Carbon Dioxide Flux Using Estuarine Water Quality Data: Case Study for Chesapeake Bay

Estuaries play an uncertain but potentially important role in the global carbon cycle via CO2 outgassing. The uncertainty mainly stems from the paucity of studies that document the full spatial and temporal variability of estuarine surface water partial pressure of carbon dioxide ( p CO2). Here, we explore the potential of utilizing the abundance of pH data from historical water quality monitoring programs to fill the data void via a case study of the mainstem Chesapeake Bay (eastern United States). We calculate p CO2 and the air‐water CO2 flux at monthly resolution from 1998 to 2018 from tidal fresh to polyhaline waters, paying special attention to the error estimation. The biggest error is due to the pH measurement error, and errors due to the gas transfer velocity, temporal sampling, the alkalinity mixing model, and the organic alkalinity estimation are 72%, 27%, 15%, and 5%, respectively, of the error due to pH. Seasonal, interannual, and spatial variability in the air‐water flux and surface p CO2 is high, and a correlation analysis with oxygen reveals that this variability is driven largely by biological processes. Averaged over 1998–2018, the mainstem bay is a weak net source of CO2 to the atmosphere of 1.2 (1.1, 1.4) mol m−2 yr−1 (best estimate and 95% confidence interval). Our findings suggest that the abundance of historical pH measurements in estuaries around the globe should be mined in order to constrain the large spatial and temporal variability of the CO2 exchange between estuaries and the atmosphere

Challenges in Quantifying Air‐Water Carbon Dioxide Flux Using Estuarine Water Quality Data: Case Study for Chesapeake Bay

Estuaries play an uncertain but potentially important role in the global carbon cycle via CO2 outgassing. The uncertainty mainly stems from the paucity of studies that document the full spatial and temporal variability of estuarine surface water partial pressure of carbon dioxide ( pCO2). Here, we explore the potential of utilizing the abundance of pH data from historical water quality monitoring programs to fill the data void via a case study of the mainstem Chesapeake Bay (eastern United States). We calculate pCO2 and the air-water CO2 flux at monthly resolution from 1998 to 2018 from tidal fresh to polyhaline waters, paying special attention to the error estimation. The biggest error is due to the pH measurement error, and errors due to the gas transfer velocity, temporal sampling, the alkalinity mixing model, and the organic alkalinity estimation are 72%, 27%, 15%, and 5%, respectively, of the error due to pH. Seasonal, interannual, and spatial variability in the air-water flux and surface pCO2 is high, and a correlation analysis with oxygen reveals that this variability is driven largely by biological processes. Averaged over 1998–2018, the mainstem bay is a weak net source of CO2 to the atmosphere of 1.2 (1.1, 1.4) mol m−2 yr−1 (best estimate and 95% confidence interval). Our findings suggest that the abundance of historical pH measurements in estuaries around the globe should be mined in order to constrain the large spatial and temporal variability of the CO2 exchange between estuaries and the atmosphere

Bioreactor technologies to support liver function in vitro

Liver is a central nexus integrating metabolic and immunologic homeostasis in the human body, and the direct or indirect target of most molecular therapeutics. A wide spectrum of therapeutic and technological needs drives efforts to capture liver physiology and pathophysiology in vitro, ranging from prediction of metabolism and toxicity of small molecule drugs, to understanding off-target effects of proteins, nucleic acid therapies, and targeted therapeutics, to serving as disease models for drug development. Here we provide perspective on the evolving landscape of bioreactor-based models to meet old and new challenges in drug discovery and development, emphasizing design challenges in maintaining long-term liver-specific function and how emerging technologies in biomaterials and microdevices are providing new experimental models.National Institutes of Health (U.S.) (R01 EB010246)National Institutes of Health (U.S.) (P50-GM068762-08)National Institutes of Health (U.S.) (R01-ES015241)National Institutes of Health (U.S.) (P30-ES002109)5UH2TR000496-02National Science Foundation (U.S.). Emergent Behaviors of Integrated Cellular Systems (CBET-0939511)United States. Defense Advanced Research Projects Agency. Microphysiological Systems Program (W911NF-12-2-0039

Retrospective evaluation of whole exome and genome mutation calls in 746 cancer samples

Funder: NCI U24CA211006Abstract: The Cancer Genome Atlas (TCGA) and International Cancer Genome Consortium (ICGC) curated consensus somatic mutation calls using whole exome sequencing (WES) and whole genome sequencing (WGS), respectively. Here, as part of the ICGC/TCGA Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium, which aggregated whole genome sequencing data from 2,658 cancers across 38 tumour types, we compare WES and WGS side-by-side from 746 TCGA samples, finding that ~80% of mutations overlap in covered exonic regions. We estimate that low variant allele fraction (VAF < 15%) and clonal heterogeneity contribute up to 68% of private WGS mutations and 71% of private WES mutations. We observe that ~30% of private WGS mutations trace to mutations identified by a single variant caller in WES consensus efforts. WGS captures both ~50% more variation in exonic regions and un-observed mutations in loci with variable GC-content. Together, our analysis highlights technological divergences between two reproducible somatic variant detection efforts

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival

Alkalinity in Tidal Tributaries of the Chesapeake Bay

Despite the important role of alkalinity in estuarine carbon cycling, the seasonal and decadal variability of alkalinity, particularly within multiple tidal tributaries of the same estuary, is poorly understood. Here we analyze more than 25,000 alkalinity measurements, mostly from the 1980s and 1990s,in the major tidal tributaries of the Chesapeake Bay, a large, coastal‐plain estuary of eastern North America.The long‐term means of alkalinity in tidal‐fresh waters vary by a factor of 6 among seven tidal tributaries,reflecting the alkalinity of nontidal rivers draining to these estuaries. At 25 stations, mostly in the Potomac River Estuary, wefind significant long‐term increasing trends that exceed the trends in the nontidal rivers upstream of those stations. Box model calculations in the Potomac River Estuary indicate that the main cause of the estuarine trends is a declining alkalinity sink. The magnitude of this sink is consistent with a simple model of calcification by the invasive bivalve Corbicula fluminea. More generally, in tidal tributaries fed by high‐alkalinity nontidal rivers, alkalinity is consumed, with sinks ranging from 8% to 27% of the upstream input. In contrast, tidal tributaries that are fed by low‐alkalinity nontidal rivers have sources of alkalinity amounting to 34% to 171% of the upstream input. For a single estuarine system, the Chesapeake Bay has diverse alkalinity dynamics and can thus serve as a laboratory for studying the numerous processes influencing alkalinity among the world\u27s estuaries