The Model of Emissions of Gases and Aerosols from Nature (MEGANv2.1) together with the Modern-Era Retrospective Analysis for Research and Applications (MERRA) meteorological fields were used to ...create a global emission data set of biogenic volatile organic compounds (BVOC) available on a monthly basis for the time period of 1980–2010. This data set, developed under the Monitoring Atmospheric Composition and Climate project (MACC), is called MEGAN–MACC. The model estimated mean annual total BVOC emission of 760 Tg (C) yr−1 consisting of isoprene (70%), monoterpenes (11%), methanol (6%), acetone (3%), sesquiterpenes (2.5%) and other BVOC species each contributing less than 2%. Several sensitivity model runs were performed to study the impact of different model input and model settings on isoprene estimates and resulted in differences of up to ±17% of the reference isoprene total. A greater impact was observed for a sensitivity run applying parameterization of soil moisture deficit that led to a 50% reduction of isoprene emissions on a global scale, most significantly in specific regions of Africa, South America and Australia. MEGAN–MACC estimates are comparable to results of previous studies. More detailed comparison with other isoprene inventories indicated significant spatial and temporal differences between the data sets especially for Australia, Southeast Asia and South America. MEGAN–MACC estimates of isoprene, α-pinene and group of monoterpenes showed a reasonable agreement with surface flux measurements at sites located in tropical forests in the Amazon and Malaysia. The model was able to capture the seasonal variation of isoprene emissions in the Amazon forest.
The glucagon-like peptide-1 (GLP-1) is a multifaceted hormone with broad pharmacological potential. Among the numerous metabolic effects of GLP-1 are the glucose-dependent stimulation of insulin ...secretion, decrease of gastric emptying, inhibition of food intake, increase of natriuresis and diuresis, and modulation of rodent β-cell proliferation. GLP-1 also has cardio- and neuroprotective effects, decreases inflammation and apoptosis, and has implications for learning and memory, reward behavior, and palatability. Biochemically modified for enhanced potency and sustained action, GLP-1 receptor agonists are successfully in clinical use for the treatment of type-2 diabetes, and several GLP-1-based pharmacotherapies are in clinical evaluation for the treatment of obesity.
In this review, we provide a detailed overview on the multifaceted nature of GLP-1 and its pharmacology and discuss its therapeutic implications on various diseases.
Since its discovery, GLP-1 has emerged as a pleiotropic hormone with a myriad of metabolic functions that go well beyond its classical identification as an incretin hormone. The numerous beneficial effects of GLP-1 render this hormone an interesting candidate for the development of pharmacotherapies to treat obesity, diabetes, and neurodegenerative disorders
Ponatinib is a potent oral tyrosine kinase inhibitor of unmutated and mutated BCR-ABL, including BCR-ABL with the tyrosine kinase inhibitor-refractory threonine-to-isoleucine mutation at position 315 ...(T315I). We conducted a phase 2 trial of ponatinib in patients with chronic myeloid leukemia (CML) or Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph-positive ALL).
We enrolled 449 heavily pretreated patients who had CML or Ph-positive ALL with resistance to or unacceptable side effects from dasatinib or nilotinib or who had the BCR-ABL T315I mutation. Ponatinib was administered at an initial dose of 45 mg once daily. The median follow-up was 15 months.
Among 267 patients with chronic-phase CML, 56% had a major cytogenetic response (51% of patients with resistance to or unacceptable side effects from dasatinib or nilotinib and 70% of patients with the T315I mutation), 46% had a complete cytogenetic response (40% and 66% in the two subgroups, respectively), and 34% had a major molecular response (27% and 56% in the two subgroups, respectively). Responses were observed regardless of the baseline BCR-ABL kinase domain mutation status and were durable; the estimated rate of a sustained major cytogenetic response of at least 12 months was 91%. No single BCR-ABL mutation conferring resistance to ponatinib was detected. Among 83 patients with accelerated-phase CML, 55% had a major hematologic response and 39% had a major cytogenetic response. Among 62 patients with blast-phase CML, 31% had a major hematologic response and 23% had a major cytogenetic response. Among 32 patients with Ph-positive ALL, 41% had a major hematologic response and 47% had a major cytogenetic response. Common adverse events were thrombocytopenia (in 37% of patients), rash (in 34%), dry skin (in 32%), and abdominal pain (in 22%). Serious arterial thrombotic events were observed in 9% of patients; these events were considered to be treatment-related in 3%. A total of 12% of patients discontinued treatment because of an adverse event.
Ponatinib had significant antileukemic activity across categories of disease stage and mutation status. (Funded by Ariad Pharmaceuticals and others; PACE ClinicalTrials.gov number, NCT01207440 .).
There is growing interest in the therapeutic utility of psychedelic substances, like psilocybin, for disorders characterized by distortions of the self-experience, like depression. Accumulating ...preclinical evidence emphasizes the role of the glutamate system in the acute action of the drug on brain and behavior; however this has never been tested in humans. Following a double-blind, placebo-controlled, parallel group design, we utilized an ultra-high field multimodal brain imaging approach and demonstrated that psilocybin (0.17 mg/kg) induced region-dependent alterations in glutamate, which predicted distortions in the subjective experience of one's self (ego dissolution). Whereas higher levels of medial prefrontal cortical glutamate were associated with negatively experienced ego dissolution, lower levels in hippocampal glutamate were associated with positively experienced ego dissolution. Such findings provide further insights into the underlying neurobiological mechanisms of the psychedelic, as well as the baseline, state. Importantly, they may also provide a neurochemical basis for therapeutic effects as witnessed in ongoing clinical trials.
Quantifying signals and uncertainties in climate models is essential for the detection, attribution, prediction and projection of climate change
. Although inter-model agreement is high for ...large-scale temperature signals, dynamical changes in atmospheric circulation are very uncertain
. This leads to low confidence in regional projections, especially for precipitation, over the coming decades
. The chaotic nature of the climate system
may also mean that signal uncertainties are largely irreducible. However, climate projections are difficult to verify until further observations become available. Here we assess retrospective climate model predictions of the past six decades and show that decadal variations in North Atlantic winter climate are highly predictable, despite a lack of agreement between individual model simulations and the poor predictive ability of raw model outputs. Crucially, current models underestimate the predictable signal (the predictable fraction of the total variability) of the North Atlantic Oscillation (the leading mode of variability in North Atlantic atmospheric circulation) by an order of magnitude. Consequently, compared to perfect models, 100 times as many ensemble members are needed in current models to extract this signal, and its effects on the climate are underestimated relative to other factors. To address these limitations, we implement a two-stage post-processing technique. We first adjust the variance of the ensemble-mean North Atlantic Oscillation forecast to match the observed variance of the predictable signal. We then select and use only the ensemble members with a North Atlantic Oscillation sufficiently close to the variance-adjusted ensemble-mean forecast North Atlantic Oscillation. This approach greatly improves decadal predictions of winter climate for Europe and eastern North America. Predictions of Atlantic multidecadal variability are also improved, suggesting that the North Atlantic Oscillation is not driven solely by Atlantic multidecadal variability. Our results highlight the need to understand why the signal-to-noise ratio is too small in current climate models
, and the extent to which correcting this model error would reduce uncertainties in regional climate change projections on timescales beyond a decade.
Robust skill of decadal climate predictions Smith, D. M.; Eade, R.; Scaife, A. A. ...
NPJ climate and atmospheric science,
05/2019, Letnik:
2, Številka:
1
Journal Article, Publication
Recenzirano
Odprti dostop
Abstract
There is a growing need for skilful predictions of climate up to a decade ahead. Decadal climate predictions show high skill for surface temperature, but confidence in forecasts of ...precipitation and atmospheric circulation is much lower. Recent advances in seasonal and annual prediction show that the signal-to-noise ratio can be too small in climate models, requiring a very large ensemble to extract the predictable signal. Here, we reassess decadal prediction skill using a much larger ensemble than previously available, and reveal significant skill for precipitation over land and atmospheric circulation, in addition to surface temperature. We further propose a more powerful approach than used previously to evaluate the benefit of initialisation with observations, improving our understanding of the sources of skill. Our results show that decadal climate is more predictable than previously thought and will aid society to prepare for, and adapt to, ongoing climate variability and change.
Global tropospheric ozone distributions, budgets, and radiative forcings from an ensemble of 26 state‐of‐the‐art atmospheric chemistry models have been intercompared and synthesized as part of a ...wider study into both the air quality and climate roles of ozone. Results from three 2030 emissions scenarios, broadly representing “optimistic,” “likely,” and “pessimistic” options, are compared to a base year 2000 simulation. This base case realistically represents the current global distribution of tropospheric ozone. A further set of simulations considers the influence of climate change over the same time period by forcing the central emissions scenario with a surface warming of around 0.7K. The use of a large multimodel ensemble allows us to identify key areas of uncertainty and improves the robustness of the results. Ensemble mean changes in tropospheric ozone burden between 2000 and 2030 for the 3 scenarios range from a 5% decrease, through a 6% increase, to a 15% increase. The intermodel uncertainty (±1 standard deviation) associated with these values is about ±25%. Model outliers have no significant influence on the ensemble mean results. Combining ozone and methane changes, the three scenarios produce radiative forcings of −50, 180, and 300 mW m−2, compared to a CO2 forcing over the same time period of 800–1100 mW m−2. These values indicate the importance of air pollution emissions in short‐ to medium‐term climate forcing and the potential for stringent/lax control measures to improve/worsen future climate forcing. The model sensitivity of ozone to imposed climate change varies between models but modulates zonal mean mixing ratios by ±5 ppbv via a variety of feedback mechanisms, in particular those involving water vapor and stratosphere‐troposphere exchange. This level of climate change also reduces the methane lifetime by around 4%. The ensemble mean year 2000 tropospheric ozone budget indicates chemical production, chemical destruction, dry deposition and stratospheric input fluxes of 5100, 4650, 1000, and 550 Tg(O3) yr−1, respectively. These values are significantly different to the mean budget documented by the Intergovernmental Panel on Climate Change (IPCC) Third Assessment Report (TAR). The mean ozone burden (340 Tg(O3)) is 10% larger than the IPCC TAR estimate, while the mean ozone lifetime (22 days) is 10% shorter. Results from individual models show a correlation between ozone burden and lifetime, and each model's ozone burden and lifetime respond in similar ways across the emissions scenarios. The response to climate change is much less consistent. Models show more variability in the tropics compared to midlatitudes. Some of the most uncertain areas of the models include treatments of deep tropical convection, including lightning NOx production; isoprene emissions from vegetation and isoprene's degradation chemistry; stratosphere‐troposphere exchange; biomass burning; and water vapor concentrations.
The accuracy of state‐of‐the‐art global barotropic tide models is assessed using bottom pressure data, coastal tide gauges, satellite altimetry, various geodetic data on Antarctic ice shelves, and ...independent tracked satellite orbit perturbations. Tide models under review include empirical, purely hydrodynamic (“forward”), and assimilative dynamical, i.e., constrained by observations. Ten dominant tidal constituents in the diurnal, semidiurnal, and quarter‐diurnal bands are considered. Since the last major model comparison project in 1997, models have improved markedly, especially in shallow‐water regions and also in the deep ocean. The root‐sum‐square differences between tide observations and the best models for eight major constituents are approximately 0.9, 5.0, and 6.5 cm for pelagic, shelf, and coastal conditions, respectively. Large intermodel discrepancies occur in high latitudes, but testing in those regions is impeded by the paucity of high‐quality in situ tide records. Long‐wavelength components of models tested by analyzing satellite laser ranging measurements suggest that several models are comparably accurate for use in precise orbit determination, but analyses of GRACE intersatellite ranging data show that all models are still imperfect on basin and subbasin scales, especially near Antarctica. For the M2 constituent, errors in purely hydrodynamic models are now almost comparable to the 1980‐era Schwiderski empirical solution, indicating marked advancement in dynamical modeling. Assessing model accuracy using tidal currents remains problematic owing to uncertainties in in situ current meter estimates and the inability to isolate the barotropic mode. Velocity tests against both acoustic tomography and current meters do confirm that assimilative models perform better than purely hydrodynamic models.
Key Points
Tide model accuracy assessmentImproved accuraciesTidal current estimates
Formic (HCOOH) and acetic acids (
CH3COOH) are the most abundant carboxylic acids in the Earth's atmosphere and key compounds to aqueous‐phase chemistry. Here we present the first distributions of
...CH3COOH retrieved from the 2007–2018 satellite observations of the nadir‐looking infrared atmospheric sounding interferometer (IASI), using a neural network‐based retrieval approach. A joint analysis with the IASI HCOOH product reveals that the two species exhibit similar distributions, seasonality, and atmospheric burden, pointing to major common sources. We show that their abundance is highly correlated to isoprene and monoterpenes emissions, as well as to biomass burning. Over Africa, evidence is provided that residual smoldering combustion might be a major driver of the HCOOH and
CH3COOH seasonality. Earlier seasonal enhancement of HCOOH at Northern Hemisphere middle and high latitudes and late seasonal secondary peaks of
CH3COOH in the tropics suggest that sources and production pathways specific to each species are also at play.
Key Points
First atmospheric distributions of acetic acid are obtained from IASI/Metop observations
In emission regions, formic and acetic acids highly correlate with each other and with biogenic hydrocarbon emissions and biomass burning
Residual smoldering combustion appears to be a major driver of the formic and acetic acids seasonality in Africa
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