Carbon emissions from the 2023 Canadian wildfires.

The 2023 Canadian forest fires have been extreme in scale and intensity with more than seven times the average annual area burned compared to the previous four decades. Here, we quantify the carbon emissions from these fires from May to September 2023 on the basis of inverse modelling of satellite carbon monoxide observations. We find that the magnitude of the carbon emissions is 647 TgC (570-727 TgC), comparable to the annual fossil fuel emissions of large nations, with only India, China and the USA releasing more carbon per year.

The reduced net carbon uptake over Northern Hemisphere land causes the close-to-normal CO growth rate in 2021 La Niña.

La Niña climate anomalies have historically been associated with substantial reductions in the atmospheric CO growth rate. However, the 2021 La Niña exhibited a unique near-neutral impact on the CO growth rate. In this study, we investigate the underlying mechanisms by using an ensemble of net CO fluxes constrained by CO observations from the Orbiting Carbon Observatory-2 in conjunction with estimates of gross primary production and fire carbon emissions.

The worldwide COVID-19 lockdown impacts on global secondary inorganic aerosols and radiative budget.

Global lockdown measures to prevent the spread of the coronavirus disease 2019 (COVID-19) led to air pollutant emission reductions. While the COVID-19 lockdown impacts on both trace gas and total particulate pollutants have been widely investigated, secondary aerosol formation from trace gases remains unclear. To that end, we quantify the COVID-19 lockdown impacts on NO and SO emissions and sulfate-nitrate-ammonium aerosols using multiconstituent satellite data assimilation and model simulations.

Predictability of fossil fuel CO from air quality emissions.

Quantifying the coevolution of greenhouse gases and air quality pollutants can provide insight into underlying anthropogenic processes enabling predictions of their emission trajectories. Here, we classify the dynamics of historic emissions in terms of a modified Environmental Kuznets Curve (MEKC), which postulates the coevolution of fossil fuel CO (FFCO) and NOx emissions as a function of macroeconomic development. The MEKC broadly captures the historic FFCO-NO dynamical regimes for countries including the US, China, and India as well as IPCC scenarios.

Attribution of Space-Time Variability in Global-Ocean Dissolved Inorganic Carbon.

The inventory and variability of oceanic dissolved inorganic carbon (DIC) is driven by the interplay of physical, chemical, and biological processes. Quantifying the spatiotemporal variability of these drivers is crucial for a mechanistic understanding of the ocean carbon sink and its future trajectory. Here, we use the Estimating the Circulation and Climate of the Ocean-Darwin ocean biogeochemistry state estimate to generate a global-ocean, data-constrained DIC budget and investigate how spatial and seasonal-to-interannual variability in three-dimensional circulation, air-sea CO flux, and biological processes have modulated the ocean sink for 1995-2018.

Amazonian terrestrial water balance inferred from satellite-observed water vapor isotopes.

Atmospheric humidity and soil moisture in the Amazon forest are tightly coupled to the region's water balance, or the difference between two moisture fluxes, evapotranspiration minus precipitation (ET-P). However, large and poorly characterized uncertainties in both fluxes, and in their difference, make it challenging to evaluate spatiotemporal variations of water balance and its dependence on ET or P. Here, we show that satellite observations of the HDO/HO ratio of water vapor are sensitive to spatiotemporal variations of ET-P over the Amazon.

Discovery of Pemigatinib: A Potent and Selective Fibroblast Growth Factor Receptor (FGFR) Inhibitor.

Aberrant activation of FGFR has been linked to the pathogenesis of many tumor types. Selective inhibition of FGFR has emerged as a promising approach for cancer treatment. Herein, we describe the discovery of compound (INCB054828, pemigatinib), a highly potent and selective inhibitor of FGFR1, FGFR2, and FGFR3 with excellent physiochemical properties and pharmacokinetic profiles.

Changes in global terrestrial live biomass over the 21st century.

Live woody vegetation is the largest reservoir of biomass carbon, with its restoration considered one of the most effective natural climate solutions. However, terrestrial carbon fluxes remain the largest uncertainty in the global carbon cycle. Here, we develop spatially explicit estimates of carbon stock changes of live woody biomass from 2000 to 2019 using measurements from ground, air, and space.

Global tropospheric ozone responses to reduced NO emissions linked to the COVID-19 worldwide lockdowns.

Efforts to stem the transmission of coronavirus disease 2019 (COVID-19) led to rapid, global ancillary reductions in air pollutant emissions. Here, we quantify the impact on tropospheric ozone using a multiconstituent chemical data assimilation system. Anthropogenic NO emissions dropped by at least 15% globally and 18 to 25% regionally in April and May 2020, which decreased free tropospheric ozone by up to 5 parts per billion, consistent with independent satellite observations.

Impacts of Degradation on Water, Energy, and Carbon Cycling of the Amazon Tropical Forests.

Selective logging, fragmentation, and understory fires directly degrade forest structure and composition. However, studies addressing the effects of forest degradation on carbon, water, and energy cycles are scarce. Here, we integrate field observations and high-resolution remote sensing from airborne lidar to provide realistic initial conditions to the Ecosystem Demography Model (ED-2.

INCB054828 (pemigatinib), a potent and selective inhibitor of fibroblast growth factor receptors 1, 2, and 3, displays activity against genetically defined tumor models.

Alterations in fibroblast growth factor receptor (FGFR) genes have been identified as potential driver oncogenes. Pharmacological targeting of FGFRs may therefore provide therapeutic benefit to selected cancer patients, and proof-of-concept has been established in early clinical trials of FGFR inhibitors. Here, we present the molecular structure and preclinical characterization of INCB054828 (pemigatinib), a novel, selective inhibitor of FGFR 1, 2, and 3, currently in phase 2 clinical trials.

Fire decline in dry tropical ecosystems enhances decadal land carbon sink.

The terrestrial carbon sink has significantly increased in the past decades, but the underlying mechanisms are still unclear. The current synthesis of process-based estimates of land and ocean sinks requires an additional sink of 0.6 PgC yr in the last decade to explain the observed airborne fraction.

Quantifying the Impact of Atmospheric Transport Uncertainty on CO Surface Flux Estimates.

We show that transport differences between two commonly used global chemical transport models, GEOS-Chem and TM5, lead to systematic space-time differences in modeled distributions of carbon dioxide and sulfur hexafluoride. The distribution of differences suggests inconsistencies between the transport simulated by the models, most likely due to the representation of vertical motion. We further demonstrate that these transport differences result in systematic differences in surface CO flux estimated by a collection of global atmospheric inverse models using TM5 and GEOS-Chem and constrained by in situ and satellite observations.

Effects of Epacadostat on Brain Extracellular Fluid Concentrations of Serotonin-an Intracerebral Microdialysis Study in Sprague-Dawley Rats.

Epacadostat (EPAC) is an indoleamine 2,3-dioxygenase 1 (IDO1) inhibitor that has been examined in multiple clinical trials. The substrate for IDO1 is tryptophan and there is a theoretical concern that inhibition of IDO1 may increase the concentrations of tryptophan and subsequently serotonin, potentially leading to serotonin syndrome (SS). The objective of this study was to evaluate the effect of EPAC, either alone or with linezolid, a monoamine oxidase inhibitor (MAOI), on brain extracellular fluid (ECF) concentrations of serotonin in rats, using microdialysis.

Response to Comment on "Contrasting carbon cycle responses of the tropical continents to the 2015-2016 El Niño".

Chevallier showed a column CO ([Formula: see text]) anomaly of ±0.5 parts per million forced by a uniform net biosphere exchange (NBE) anomaly of 2.5 gigatonnes of carbon over the tropical continents within a year, so he claimed that the inferred NBE uncertainties should be larger than presented in Liu We show that a much concentrated NBE anomaly led to much larger [Formula: see text] perturbations.

Preclinical characterization of INCB053914, a novel pan-PIM kinase inhibitor, alone and in combination with anticancer agents, in models of hematologic malignancies.

The Proviral Integration site of Moloney murine leukemia virus (PIM) serine/threonine protein kinases are overexpressed in many hematologic and solid tumor malignancies and play central roles in intracellular signaling networks important in tumorigenesis, including the Janus kinase-signal transducer and activator of transcription (JAK/STAT) and phosphatidylinositol 3-kinase (PI3K)/AKT pathways. The three PIM kinase isozymes (PIM1, PIM2, and PIM3) share similar downstream substrates with other key oncogenic kinases and have differing but mutually compensatory functions across tumors. This supports the therapeutic potential of pan-PIM kinase inhibitors, especially in combination with other anticancer agents chosen based on their role in overlapping signaling networks.

Impact of intercontinental pollution transport on North American ozone air pollution: an HTAP phase 2 multi-model study.

The recent update on the US National Ambient Air Quality Standards (NAAQS) of the ground-level ozone (O/ can benefit from a better understanding of its source contributions in different US regions during recent years. In the Hemispheric Transport of Air Pollution experiment phase 1 (HTAP1), various global models were used to determine the O source-receptor (SR) relationships among three continents in the Northern Hemisphere in 2001. In support of the HTAP phase 2 (HTAP2) experiment that studies more recent years and involves higher-resolution global models and regional models' participation, we conduct a number of regional-scale Sulfur Transport and dEposition Model (STEM) air quality base and sensitivity simulations over North America during May-June 2010.

Leveraging benefit design for better diabetes self-management and A1C control.

Objectives: To evaluate the relationship between cost sharing for blood glucose testing strips and glycemic control rates.

Study Design: A retrospective observational study using medical and pharmacy claims data integrated with laboratory glycated hemoglobin (A1C) values for patients using insulin and testing strips. A new user study design was utilized to identify individuals from 14 commercial US health plans who filled testing strips with assumed intention to monitor blood glucose.

Contrasting carbon cycle responses of the tropical continents to the 2015-2016 El Niño.

The 2015-2016 El Niño led to historically high temperatures and low precipitation over the tropics, while the growth rate of atmospheric carbon dioxide (CO) was the largest on record. Here we quantify the response of tropical net biosphere exchange, gross primary production, biomass burning, and respiration to these climate anomalies by assimilating column CO, solar-induced chlorophyll fluorescence, and carbon monoxide observations from multiple satellites. Relative to the 2011 La Niña, the pantropical biosphere released 2.

Lowering Cost Share May Improve Rates of Home Glucose Monitoring Among Patients with Diabetes Using Insulin.

Background: Not much is known about the extent to which lower cost share for blood glucose strips is associated with persistent filling.

Objective: To evaluate the relationship between cost sharing for blood glucose testing strips and continued use of testing strips.

Methods: This is a retrospective observational study using medical and pharmacy claims data integrated with laboratory hemoglobin A1c (A1c) values for patients using insulin and blood glucose testing strips.

INCB24360 (Epacadostat), a Highly Potent and Selective Indoleamine-2,3-dioxygenase 1 (IDO1) Inhibitor for Immuno-oncology.

A data-centric medicinal chemistry approach led to the invention of a potent and selective IDO1 inhibitor , INCB24360 (epacadostat). The molecular structure of INCB24360 contains several previously unknown or underutilized functional groups in drug substances, including a hydroxyamidine, furazan, bromide, and sulfamide. These moieties taken together in a single structure afford a compound that falls outside of "drug-like" space.

First-in-Human Phase I Study of the Oral Inhibitor of Indoleamine 2,3-Dioxygenase-1 Epacadostat (INCB024360) in Patients with Advanced Solid Malignancies.

Indoleamine 2,3-dioxygenase-1 (IDO1) catalyzes the degradation of tryptophan to N-formyl-kynurenine. Overexpressed in many solid malignancies, IDO1 can promote tumor escape from host immunosurveillance. This first-in-human phase I study investigated the maximum tolerated dose, safety, pharmacokinetics, pharmacodynamics, and antitumor activity of epacadostat (INCB024360), a potent and selective inhibitor of IDO1.