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The main aim of the paper is to demonstrate an approach for post-processing of the Dobson spectrophotometers' total ozone columns (TOCs) in order to compensate for their known stratospheric effective temperature (Teff) dependency and its resulting effect on the usage of the Dobson TOCs for satellite TOCs' validation. The Dobson observations employed are those routinely submitted to the World Ozone and Ultraviolet Data Centre (WOUDC) of the World Meteorological Organization, whereas the effective temperatures have been extracted from two sources: the European Space Agency, ESA, Ozone Climate Change Initiative, Ozone-CCI, GODFIT version 3 (GOME-type Direct FITting) algorithm applied to the GOME2/MetopA, GOME2A, observations as well as the one derived from the European Centre for Medium-Range Weather Forecasts (ECMWF) outputs. Both temperature sources are evaluated utilizing co-located ozonesonde measurements also retrieved from the WOUDC database. Both GODFIT_v3 and ECMWF Teffs are found to be unbiased against the ozonesonde observations and to agree with high correlation coefficients, especially for latitudes characterized by high seasonal variability in Teff. The validation analysis shows that, when applying the GODFIT_v3 effective temperatures in order to post-process the Dobson TOC, the mean difference between Dobson and GOME2A GODFIT_v3 TOCs moves from 0.63±0.66 to 0.26±0.46% in the Northern Hemisphere and from 1.25±1.20 to 0.80±0.71% in the Southern Hemisphere. The existing solar zenith angle dependency of the differences has been smoothed out, with near-zero dependency up to the 60-65° bin and the highest deviation decreasing from 2.38±6.6 to 1.37±6.4% for the 80-85° bin. We conclude that the global-scale validation of satellite TOCs against collocated Dobson measurements benefits from a post-correction using suitably estimated Teffs. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitor (ICI) associated diabetes is a harmful adverse event (AE) in patients with cancer following anti-programmed (cell) death protein-1 (PD-1) treatment. There are no available biomarkers able to predict this AE. The primary aim of this study was to investigate C-peptide levels as potential predictor for the occurrence of ICI-related diabetes. The secondary aim was to describe the presence of islet autoantibodies and course of pancreatic enzymes in patients with and without ICI-related diabetes. From a total of 1318 patients with cancer who started anti-PD-1 treatment 8 cases and 16 controls were studied in this nested case-control study. C-peptide levels, islet autoantibodies, and pancreatic enzymes were measured in prospectively collected blood serum. In cases versus controls, median C-peptide levels were comparable at baseline and before toxicity or at the corresponding time point in controls. No patient had C-peptide levels below reference range before toxicity onset. Two out of eight patients in the ICI-related diabetes group had positive islet autoantibodies, whereas one out of 16 patients in the control group had positive islet autoantibodies. Pancreatic enzymes were elevated before diabetes onset in one patient (13%) and in one control (6%) at the corresponding time point. In patients developing ICI-related diabetes, changes in C-peptide levels, islet autoantibody positivity, and pancreatic enzymes before ICI-related diabetes onset seem comparable to patients without ICI-related diabetes. (NTR: NL6828) [Display omitted] • Diabetes is a potentially life-threatening adverse event of ICI treatment. • There was no decline in C-peptide levels prior to onset of ICI-related diabetes. • Islet autoantibodies did not differ between ICI-related diabetes cases and controls. • Pancreatic enzymes did not differ between ICI-related diabetes cases and controls. [ABSTRACT FROM AUTHOR]

Background and Purpose: Niacin can effectively treat dyslipidaemic disorders. However, its clinical use is limited due to the cutaneous flushing mediated by the nicotinic acid receptor HCA(2) . In the current study, we evaluated two partial agonists for HCA(2) , LUF6281 and LUF6283, with respect to their anti-dyslipidaemic potential and cutaneous flushing effect.Experimental Approach: In vitro potency and efficacy studies with niacin and the two HCA(2) partial agonists were performed using HEK293T cells stably expressing human HCA(2) . Normolipidaemic C57BL/6 mice received either niacin or the HCA(2) partial agonists (400 mg·kg(-1) ·day(-1) ) once a day for 4 weeks for evaluation of their effects in vivo.Key Results: Radioligand competitive binding assay showed K(i) values for LUF6281 and LUF6283 of 3 and 0.55 µM. [(35) S]-GTPγS binding revealed the rank order of their potency as niacin > LUF6283 > LUF6281. All three compounds reduced plasma VLDL-triglyceride concentrations similarly, while LUF6281 and LUF6283, in contrast to niacin, did not also exhibit the unwanted flushing side effect in C57BL/6 mice. Niacin reduced the expression of lipolytic genes HSL and ATGL in adipose tissue by 50%, whereas LUF6281 and LUF6283 unexpectedly did not. In contrast, the decrease in VLDL-triglyceride concentration induced by LUF6281 and LUF6283 was associated with a parallel >40% reduced expression of APOB within the liver.Conclusions and Implications: The current study identifies LUF6281 and LUF6283, two HCA(2) partial agonists of the pyrazole class, as promising drug candidates to achieve the beneficial lipid lowering effect of niacin without producing the unwanted flushing side effect. [ABSTRACT FROM AUTHOR]

Abstract: By encompassing four centuries of solar evolution, the sunspot number provides the longest available record of solar activity. Nowadays, it is widely used as the main reference solar index on which hundreds of published studies are based, in various fields of science. In this review, we will retrace the history of this crucial solar index, from its roots at the Zürich Observatory up to the current multiple indices established and distributed by the Solar Influences Data Analysis Center (SIDC), World Data Center for the International Sunspot Index, which was founded in 1981, exactly 25 years ago. We describe the principles now in use for the statistical processing of input data coming from the worldwide observing network (∼80 stations). Among the various SIDC data products and innovations, we highlight some recent ones, including the daily Estimated International Sunspot Number. Taking a wider perspective, we show how the sunspot index stands the test of time versus more recent quantitative indices, but we also consider the prospects and possible options for a future transition from the visual sunspot index heritage towards an equivalent global activity index. Based on past historical flaws, we conclude on the key requirements involved in the maintenance of any robust long-term solar activity index. [Copyright &y& Elsevier]

Following avulsion of a spinal ventral root, motoneurons that project through the avulsed root are axotomized. Avulsion between, for example, L2 and L6 leads to denervation of hind limb muscles. Reimplantation of an avulsed root directed to the motoneuron pool resulted in re-ingrowth of some motor axons. However, most motoneurons display retrograde atrophy and subsequently die. Two neurotrophic factors, glial cell line-derived neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), promote the survival of motoneurons after injury. The long-term delivery of these neurotrophic factors to the motoneurons in the ventral horn of the spinal cord is problematic. One strategy to improve the outcome of the neurosurgical reinsertion of the ventral root following avulsion would involve gene transfer with adeno-associated viral (AAV) vectors encoding these neurotrophic factors near the denervated motoneuron pool. Here, we show that AAV-mediated overexpression of GDNF and BDNF in the spinal cord persisted for at least 16 weeks. At both 1 and 4 months post-lesion AAV-BDNF- and -GDNF-treated animals showed an increased survival of motoneurons, the effect being more prominent at 1 month. AAV vector-mediated overexpression of neurotrophins also promoted the formation of a network of motoneuron fibers in the ventral horn at the avulsed side, but motoneurons failed to extent axons into the reinserted L4 root towards the sciatic nerve nor to improve functional recovery of the hind limbs. This suggests that high levels of neurotrophic factors in the ventral horn promote sprouting, but prevent directional growth of axons of a higher number of surviving motoneurons into the implanted root. [Copyright &y& Elsevier]

Presents a study which determined the role of CD44 cell receptor in controlling Mycobacterium tuberculosis leukocyte migration and phagocytosis. Characteristics of Mycobacterium tuberculosis; Methods used; Accumulation of CD44[sub+] cells in the pulmonary compartment during Mycobacterium tuberculosis infection; Reduction of cytokine concentrations in the absence of CD44.

Scavenger receptor BI (SR-BI) has been suggested to modulate adipocyte function. To uncover the potential relevance of SR-BI for the development of obesity and associated metabolic complications, we compared the metabolic phenotype of wild-type and SR-BI deficient mice fed an obesogenic diet enriched in fat. Both male and female SR-BI knockout mice gained significantly more weight as compared to their wild-type counterparts in response to 12 weeks high fat diet feeding (1.5-fold; P < .01 for genotype). Plasma free cholesterol levels were ~2-fold higher (P < .001) in SR-BI knockout mice of both genders, whilst plasma cholesteryl ester and triglyceride concentrations were only significantly elevated in males. Strikingly, the exacerbated obesity in SR-BI knockout mice was paralleled by a better glucose handling. In contrast, only SR-BI knockout mice developed atherosclerotic lesions in the aortic root, with a higher predisposition in females. Biochemical and histological studies in male mice revealed that SR-BI deficiency was associated with a reduced hepatic steatosis degree as evident from the 29% lower (P < .05) liver triglyceride levels. Relative mRNA expression levels of the glucose uptake transporter GLUT4 were increased (+47%; P < .05), whilst expression levels of the metabolic PPARgamma target genes CD36, HSL, ADIPOQ and ATGL were reduced 39%-58% (P < .01) in the context of unchanged PPARgamma expression levels in SR-BI knockout gonadal white adipose tissue. In conclusion, we have shown that SR-BI deficiency is associated with a decrease in adipocyte PPARgamma activity and a concomitant uncoupling of obesity development from hepatic steatosis and glucose intolerance development in high fat diet-fed mice. [ABSTRACT FROM AUTHOR]

This study aims to generate a satellite-based qualitative emission source characterization for the heavily polluted eastern part of China in the 2010-2016 time period. The applied source identification technique relies on satellite-based NO x and SO 2 emission estimates by OMI, their SO 2 :NO x ratio, and the MIX anthropogenic emission inventory to distinguish emissions from different emission categories (urban, industrial, natural) and characterize the dominant source per 0.25° × 0.25° grid cell in East China. Overall, we find good agreement between the satellite- and emission inventory-based spatiotemporal distribution and characterization of the dominant emission sources in East China in 2010-2016. In 2010, the satellite measurements suggest an emission distribution less dominated by industrial areas, a somewhat larger role for urban/transportation areas and agricultural activities, and more natural emissions in the southern part compared to the bottom-up emission categorization. In 2016, more than half of the classified emission categories over East China have remained the same. At the same time, there is a notable increase of agricultural lands and decrease of areas dominated by industry/transportation in 2016, suggestive of an overall decrease in heavy air pollution in East China over the course of 7 years. This is likely attributed to the sustained efforts of the Chinese government to drastically improve the air quality, especially since 2013 when the National Air Pollution Prevention and Control Action Plan was enacted. However, signs of urban expansion (urbanization) and rural-urban migration ("Go West" motion) stemmed from China's rapid economic growth and labour demand are evident; escalating industrialization (even with cleaner means) and the urban population growth in East China resulted in stronger emissions from sources representing consumption and transportation which are strongly related to NO 2 and PM 10 pollution (rather than SO 2 ) and are directly influenced by the population size. This resulted to a shift of the emissions from the east mainly to the north and northwest of East China. Overall, although the effectiveness of the Chinese environmental control policies has been successful, the air pollution problem remains an important concern., (© 2024. The Author(s).)

Response actions to the coronavirus disease 2019 perturbed economies and carbon dioxide (CO 2 ) emissions. The Omicron variant that emerged in 2022 caused more substantial infections than in 2020 and 2021 but it has not yet been ascertained whether Omicron interrupted the temporary post-2021 rebound of CO 2 emissions. Here, using satellite nitrogen dioxide observations combined with atmospheric inversion, we show a larger decline in China's CO 2 emissions between January and April 2022 than in those months during the first wave of 2020. China's CO 2 emissions are estimated to have decreased by 15% (equivalent to -244.3 million metric tons of CO 2 ) during the 2022 lockdown, greater than the 9% reduction during the 2020 lockdown. Omicron affected most of the populated and industrial provinces in 2022, hindering China's CO 2 emissions rebound starting from 2021. China's emission variations agreed with downstream CO 2 concentration changes, indicating a potential to monitor CO 2 emissions by integrating satellite and ground measurements.

The Arctic region is experiencing notable warming as well as more lightning. Lightning is the dominant source of upper tropospheric nitrogen oxides (NO x ), which are precursors for ozone and hydroxyl radicals. In this study, we combine the nitrogen dioxide (NO 2 ) observations from the TROPOspheric Monitoring Instrument (TROPOMI) with Vaisala Global Lightning Dataset 360 to evaluate lightning NO 2 (LNO 2 ) production in the Arctic. By analyzing consecutive TROPOMI NO 2 observations, we determine the lifetime and production efficiency of LNO 2 during the summers of 2019-2021. Our results show that the LNO 2 production efficiency over the ocean is ∼6 times higher than over continental regions. Additionally, we find that a higher LNO 2 production efficiency is often correlated with lower lightning rates. The summertime lightning NO x emission in the Arctic (north of 70° N) is estimated to be 219 ± 116 Mg of N, which is equal to 5% of anthropogenic NO x emissions. However, for the span of a few hours, the Arctic LNO 2 density can even be comparable to anthropogenic NO 2 emissions in the region. These new findings suggest that LNO 2 can play an important role in the upper-troposphere/lower-stratosphere atmospheric chemical processes in the Arctic, particularly during the summer.

Changes in CO 2 emissions during the COVID-19 pandemic have been estimated from indicators on activities like transportation and electricity generation. Here, we instead use satellite observations together with bottom-up information to track the daily dynamics of CO 2 emissions during the pandemic. Unlike activity data, our observation-based analysis deploys independent measurement of pollutant concentrations in the atmosphere to correct misrepresentation in the bottom-up data and can provide more detailed insights into spatially explicit changes. Specifically, we use TROPOMI observations of NO 2 to deduce 10-day moving averages of NO x and CO 2 emissions over China, differentiating emissions by sector and province. Between January and April 2020, China's CO 2 emissions fell by 11.5% compared to the same period in 2019, but emissions have since rebounded to pre-pandemic levels before the coronavirus outbreak at the beginning of January 2020 owing to the fast economic recovery in provinces where industrial activity is concentrated., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).)

China's policy interventions to reduce the spread of the coronavirus disease 2019 have environmental and economic impacts. Tropospheric nitrogen dioxide indicates economic activities, as nitrogen dioxide is primarily emitted from fossil fuel consumption. Satellite measurements show a 48% drop in tropospheric nitrogen dioxide vertical column densities from the 20 days averaged before the 2020 Lunar New Year to the 20 days averaged after. This decline is 21 ± 5% larger than that from 2015 to 2019. We relate this reduction to two of the government's actions: the announcement of the first report in each province and the date of a province's lockdown. Both actions are associated with nearly the same magnitude of reductions. Our analysis offers insights into the unintended environmental and economic consequences through reduced economic activities., (Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution NonCommercial License 4.0 (CC BY-NC).)

Satellite NO 2 observations have been widely used to evaluate emission changes. To determine trends in NO x emission over China, we used a method independent of chemical transport models to quantify the NO x emissions from 48 cities and 7 power plants over China, on the basis of Ozone Monitoring Instrument (OMI) NO 2 observations during 2005 to 2015. We found that NO x emissions over 48 Chinese cities increased by 52% from 2005 to 2011 and decreased by 21% from 2011 to 2015. The decrease since 2011 could be mainly attributed to emission control measures in power sector; while cities with different dominant emission sources (i.e. power, industrial and transportation sectors) showed variable emission decline timelines that corresponded to the schedules for emission control in different sectors. The time series of the derived NO x emissions was consistent with the bottom-up emission inventories for all power plants (r=0.8 on average), but not for some cities (r=0.4 on average). The lack of consistency observed for cities was most probably due to the high uncertainty of bottom-up urban emissions used in this study, which were derived from downscaling the regional-based emission data to cities by using spatial distribution proxies.