| 4031. |
- Tissot, Heloise, et al.
(författare)
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Acetic acid conversion to ketene on Cu2O(100) : Reaction mechanism deduced from experimental observations and theoretical computations
- 2021
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Ingår i: Journal of Catalysis. - : Elsevier BV. - 0021-9517 .- 1090-2694. ; 402, s. 154-165
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Tidskriftsartikel (refereegranskat)abstract
- Ketene, a versatile reagent in production of fine and specialty chemicals, is produced from acetic acid. We investigate the synthesis of ketene from acetic acid over the (3,0;1,1) surface of Cu2O(1 0 0) through analysis of the adsorption and desorption characteristics of formic and acetic acids. The results allow us to establish a reaction mechanism for ketene formation. Observations from x-ray photoelectron spectroscopy (XPS), scanning tunneling microscopy, and temperature programmed desorption (TPD), supported by a comparison with formic acid results, suggest that acetic acid reacts with Cu2O through deprotonation to form acetate species coordinated to copper sites and hydroxylation of nearby surface oxygen sites. For formic acid the decomposition of adsorbed formate species results in desorption of CO2 and CO while, for acetic acid, high yields of ketene are observed at temperature >500 K. Modeling by density functional theory (DFT) confirms the strong interaction of acetic acid with the (3,0;1,1) surface and the spontaneous dissociation into adsorbed acetate and hydrogen atom species, the latter forming an OH-group. In an identified reaction intermediate ketene binds via all C and O atoms to Cu surface sites, in agreement with interpretations from XPS. In the vicinity of the adsorbate the surface experiences a local reorganization into a c(2 × 2) reconstruction. The total computed energy barrier for ketene formation is 1.81 eV in good agreement with the 1.74 eV obtained from TPD analysis. Our experimental observations and mechanistic DFT studies suggests that Cu2O can operate as an efficient catalyst for the green generation of ketene from acetic acid.
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| 4032. |
- Tobias, Deirdre K, et al.
(författare)
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Second international consensus report on gaps and opportunities for the clinical translation of precision diabetes medicine
- 2023
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Ingår i: Nature Medicine. - 1546-170X. ; 29:10, s. 2438-2457
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Forskningsöversikt (refereegranskat)abstract
- Precision medicine is part of the logical evolution of contemporary evidence-based medicine that seeks to reduce errors and optimize outcomes when making medical decisions and health recommendations. Diabetes affects hundreds of millions of people worldwide, many of whom will develop life-threatening complications and die prematurely. Precision medicine can potentially address this enormous problem by accounting for heterogeneity in the etiology, clinical presentation and pathogenesis of common forms of diabetes and risks of complications. This second international consensus report on precision diabetes medicine summarizes the findings from a systematic evidence review across the key pillars of precision medicine (prevention, diagnosis, treatment, prognosis) in four recognized forms of diabetes (monogenic, gestational, type 1, type 2). These reviews address key questions about the translation of precision medicine research into practice. Although not complete, owing to the vast literature on this topic, they revealed opportunities for the immediate or near-term clinical implementation of precision diabetes medicine; furthermore, we expose important gaps in knowledge, focusing on the need to obtain new clinically relevant evidence. Gaps include the need for common standards for clinical readiness, including consideration of cost-effectiveness, health equity, predictive accuracy, liability and accessibility. Key milestones are outlined for the broad clinical implementation of precision diabetes medicine.
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| 4033. |
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| 4034. |
- Togo, S, et al.
(författare)
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PDE4 inhibitors roflumilast and rolipram augment PGE2 inhibition of TGF-{beta}1-stimulated fibroblasts
- 2009
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Ingår i: American journal of physiology. Lung cellular and molecular physiology. - : American Physiological Society. - 1040-0605 .- 1522-1504. ; 296:6, s. L959-L969
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Tidskriftsartikel (refereegranskat)abstract
- Fibrotic diseases are characterized by the accumulation of extracellular matrix together with distortion and disruption of tissue architecture. Phosphodiesterase (PDE)4 inhibitors, by preventing the breakdown of cAMP, can inhibit fibroblast functions and may be able to mitigate tissue remodeling. Transforming growth factor (TGF)-β1, a mediator of fibrosis, can potentially modulate cAMP by altering PGE2 metabolism. The present study assessed whether PDE4 inhibitors functionally antagonize the profibrotic activity of fibroblasts stimulated by TGF-β1. The PDE4 inhibitors roflumilast and rolipram both inhibited fibroblast-mediated contraction of three-dimensional collagen gels and fibroblast chemotaxis toward fibronectin in the widely studied human fetal lung fibroblast strain HFL-1 and several strains of fibroblasts from adult human lung. Roflumilast was ∼10-fold more potent than rolipram. There was a trend for PDE4 inhibitors to inhibit more in the presence of TGF-β1 (0.05 < P < 0.08). The effect of the PDE4 inhibitors was mediated through cAMP-stimulated protein kinase A (PKA), although a PKA-independent effect on gel contraction was also observed. The effect of PDE4 inhibitors depended on fibroblast production of PGE2 and TGF-β1-induced PGE2 production. PDE4 inhibitors together with TGF-β1 resulted in augmented PGE2 production together with increased expression of COX mRNA and protein. The present study supports the concept that PDE4 inhibitors may attenuate fibroblast activities that can lead to fibrosis and that PDE4 inhibitors may be particularly effective in the presence of TGF-β1-induced fibroblast stimulation.
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| 4035. |
- Toh, Soo Ting, et al.
(författare)
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Deep sequencing of the hepatitis B virus in hepatocellular carcinoma patients reveals enriched integration events, structural alterations and sequence variations
- 2013
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Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 34:4, s. 787-798
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Tidskriftsartikel (refereegranskat)abstract
- Chronic hepatitis B virus (HBV) infection is epidemiologically associated with hepatocellular carcinoma (HCC), but its role in HCC remains poorly understood due to technological limitations. In this study, we systematically characterize HBV in HCC patients. HBV sequences were enriched from 48 HCC patients using an oligo-bead-based strategy, pooled together and sequenced using the FLX-Genome-Sequencer. In the tumors, preferential integration of HBV into promoters of genes (P < 0.001) and significant enrichment of integration into chromosome 10 (P < 0.01) were observed. Integration into chromosome 10 was significantly associated with poorly differentiated tumors (P < 0.05). Notably, in the tumors, recurrent integration into the promoter of the human telomerase reverse transcriptase (TERT) gene was found to correlate with increased TERT expression. The preferred region within the HBV genome involved in integration and viral structural alteration is at the 3'-end of hepatitis B virus X protein (HBx), where viral replication/transcription initiates. Upon integration, the 3'-end of the HBx is often deleted. HBxhuman chimeric transcripts, the most common type of chimeric transcripts, can be expressed as chimeric proteins. Sequence variation resulting in non-conservative amino acid substitutions are commonly observed in HBV genome. This study highlights HBV as highly mutable in HCC patients with preferential regions within the host and virus genome for HBV integration/structural alterations.
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| 4036. |
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| 4037. |
- Tomata, Y, et al.
(författare)
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Fatty Acids and Frailty: A Mendelian Randomization Study
- 2021
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 13:10
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Tidskriftsartikel (refereegranskat)abstract
- Background: Observational studies have suggested that fatty acids such as higher levels of n-3 polyunsaturated fatty acids (PUFAs) may prevent frailty. By using Mendelian randomization analysis, we examined the relationship between fatty acids and frailty. Methods: We used summary statistics data for single-nucleotide polymorphisms associated with plasma levels of saturated fatty acids (palmitic acid, stearic acid), mono-unsaturated fatty acids (MUFAs) (palmitoleic acid, oleic acid), n-6 PUFAs (linoleic acid, arachidonic acid), and n-3 PUFAs (alpha-linolenic acid, eicosapentaenoic acid, docosapentaenoic acid, docosahexaenoic acid), and the corresponding data for frailty index (FI) in 356,432 individuals in the UK Biobank. Results: Although there were no robust associations on the MUFAs or the PUFAs, genetically predicted higher plasma stearic acid level (one of saturated fatty acids) was statistically significantly associated with higher FI (β = 0.178; 95% confidence interval = −0.050 to 0.307; p = 0.007). Such a relationship was also observed in a multivariate MR (β = 0.361; 95% confidence interval = 0.155 to 0.567; p = 0.001). Genetically predicted higher palmitic acid was also significantly associated with higher FI (β = 0.288; 95% confidence interval = 0.128 to 0.447; p < 0.001) in the multivariate MR analysis. Conclusions: The present MR study implies that saturated fatty acids, especially stearic acid, is a risk factor of frailty.
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| 4038. |
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| 4039. |
- Toohey, M., et al.
(författare)
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Characterizing sampling biases in the trace gas climatologies of the SPARC Data Initiative
- 2013
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Ingår i: Journal of Geophysical Research. - : American Geophysical Union (AGU). - 0148-0227 .- 2156-2202 .- 2169-897X .- 2169-8996. ; 118:20, s. 11847-11862
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Tidskriftsartikel (refereegranskat)abstract
- Monthly zonal mean climatologies of atmospheric measurements from satellite instruments can have biases due to the nonuniform sampling of the atmosphere by the instruments. We characterize potential sampling biases in stratospheric trace gas climatologies of the Stratospheric Processes and Their Role in Climate (SPARC) Data Initiative using chemical fields from a chemistry climate model simulation and sampling patterns from 16 satellite-borne instruments. The exercise is performed for the long-lived stratospheric trace gases O3 and H2O. Monthly sampling biases for O3 exceed 10% for many instruments in the high-latitude stratosphere and in the upper troposphere/lower stratosphere, while annual mean sampling biases reach values of up to 20% in the same regions for some instruments. Sampling biases for H2O are generally smaller than for O3, although still notable in the upper troposphere/lower stratosphere and Southern Hemisphere high latitudes. The most important mechanism leading to monthly sampling bias is nonuniform temporal sampling, i.e., the fact that for many instruments, monthly means are produced from measurements which span less than the full month in question. Similarly, annual mean sampling biases are well explained by nonuniformity in the month-to-month sampling by different instruments. Nonuniform sampling in latitude and longitude are shown to also lead to nonnegligible sampling biases, which are most relevant for climatologies which are otherwise free of biases due to nonuniform temporal sampling.
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| 4040. |
- Topuz, G., et al.
(författare)
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Carboniferous mafic-ultramafic intrusions in the Eastern Pontides (Pulur Complex): Implications for the source of coeval voluminous granites
- 2023
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Ingår i: Lithos. - : Elsevier BV. - 0024-4937. ; 436-437
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Tidskriftsartikel (refereegranskat)abstract
- This study deals with the age and petrogenesis of mafic-ultramafic intrusions ranging in size from a few meters to 10 km within the Early Carboniferous high-grade gneisses of the Pulur Complex in the Eastern Pontides. The intrusions comprise dunite, wehrlite, gabbronorite, leucogabbro, anorthosite and ilmenite-bearing gabbronorite of cumulus origin, and are crosscut by dikes of ilmenite-bearing gabbronorite, leucogranite and microdiorite. U–Pb dating on zircons from gabbronorite, anorthosite and leucogranite yielded igneous crystallization ages of 322–326 Ma, indicating that the intrusions were emplaced ca. 5–7 Ma after the peak of high-grade metamorphism, and form part of the Late Carboniferous high-volume magmatism in the region. In most cumulate rocks, Cr–Al spinel, olivine and plagioclase were early crystallizing phases, followed by orthopyroxene, clinopyroxene and hornblende. Whole rock geochemical data suggest that wehrlite, gabbronorite, leucogabbro and anorthosite stem from a common magma, and ilmenite-bearing gabbronorite and dikes of leucogranite and microdiorite from different magmas. Application of mineral/melt partition coefficients to trace element compositions of clinopyroxene and hornblende in cumulate rocks suggests that the main cumulate body was derived from middle- to high-K calc-alkaline basic melts, and relatively late ilmenite-bearing gabbronorites from hypersthene-normative Ca-rich melts. All the rock types display radiogenic Sr and Pb isotopic signatures, and unradiogenic Nd isotopic ratios, which are indistinguishable from those of the coeval voluminous high-K calc-alkaline I-type granites in the region; the isotopic ratios are probably related to the metasomatism of the lithospheric mantle by sediment-derived melts. We suggest that the parental melts of the mafic-ultramafic intrusions and those of the high-K calc-alkaline granites were genetically related, and melts of the high-K calc-alkaline granites were probably derived from the melting of newly underplated calc-alkaline basic material at lower crustal depths, that were compositionally comparable to the parental magmas of the mafic-ultramafic intrusions.
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