ABSTRACT
Cement production causes 7.5% of global anthropogenic CO2 emissions, arising from limestone decarbonation and fossil-fuel combustion1-3. Current decarbonation strategies include substituting Portland clinker with supplementary materials, but these mainly arise in emitting processes, developing alternative binders but none yet promises scale, or adopting carbon capture and storage that still releases some emissions4-8. However, used cement is potentially an abundant, decarbonated feedstock. Here we show that recovered cement paste can be reclinkered if used as a partial substitute for the lime-dolomite flux used in steel recycling nowadays. The resulting slag can meet existing specifications for Portland clinker and can be blended effectively with calcined clay and limestone. The process is sensitive to the silica content of the recovered cement paste, and silica and alumina that may come from the scrap, but this can be adjusted easily. We show that the proposed process may be economically competitive, and if powered by emissions-free electricity, can lead to zero emissions cement while also reducing the emissions of steel recycling by reducing lime flux requirements. The global supply of scrap steel for recycling may treble by 2050, and it is likely that more slag can be made per unit of steel recycled. With material efficiency in construction9,10, future global cement requirements could be met by this route.
ABSTRACT
BACKGROUND: Elagolix is a gonadotropin-releasing hormone (GnRH) modulator and used for pain relief from endometriosis. OBJECTIVE: The present research was performed to develop and validate a simple, novel, fast, sensitive, and cost-effective LC-MS-compatible chromatographic method for quantification of all prominent organic impurities of elagolix sodium in tablet formulation with identification of major degradation products. METHODS: The optimum separation of the organic impurities of elagolix sodium was achieved on an ACE C18-PFP (250 mm × 4.6 mm, 5 µm) column by employing pH 5.6 acetate buffer-acetonitrile (95 + 5, by volume) as mobile phase A, and acetonitrile-methanol (90 + 10, by volume) as mobile phase B. UV detection of the drug and impurities was carried out at 210 nm. A forced degradation study was carried out by employing acid, alkali, oxidative, thermal, and photolytic stress conditions on elagolix sodium drug substance and its drug product. The major degradation products observed during the stress study were identified by using mass spectrometry. RESULTS: Elagolix sodium and its prominent organic impurities were resolved in the developed method through a gradient elution program of 46 min at a flow rate of 1.3 mL/min. Significant degradation was observed during alkali hydrolysis and oxidative stress conditions with a mass balance of more than 97.0%. The method was validated in line with present International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) Q2(R1) guidelines. CONCLUSION: The forced degradation study suggested that the developed method is specific and stability-indicating and can be used for related substance analysis of elagolix drug substance and its dosage forms. HIGHLIGHTS: This is the first research paper which describes a simple and sensitive (LOD 0.08 µg/mL) HPLC method for quantification of all probable impurities of elagolix in tablet dosage forms. The noticeable feature of the developed method is resolution of impurities of similar structures in a short time using routine solvents which are easily available in the QC laboratory.
Subject(s)
Tandem Mass Spectrometry , Humans , Chromatography, Liquid , Drug Stability , Tandem Mass Spectrometry/methods , Chromatography, High Pressure Liquid/methods , Tablets , Reproducibility of ResultsABSTRACT
Verotoxin-producing Escherichia coli (VTEC) O157:H7 inhibits interferon-gamma-stimulated tyrosine phosphorylation of signal transducer and activator of transcription (Stat)-1 in epithelial cells, independent of Verotoxins and the locus of enterocyte effacement pathogenicity island. Although E. coli O157:H7 is the major cause of disease in humans, non-O157:H7 VTEC also cause human disease. However, the virulence properties of non-O157:H7 VTEC are less well characterized. The aims of this study were to define the ability of VTEC strains of differing seropathotypes (classified as A-E) to inhibit interferon-gamma stimulated Stat1-phosphorylation and to further characterize the bacterial-derived inhibitory factor. Confluent T84 and HEp-2 cells were infected with VTEC strains (MOI 100:1, 6h, 37 degrees C), and then stimulated with interferon-gamma (50 ng/mL) for 0.5h at 37 degrees C. Whole-cell protein extracts of infected cells were collected and prepared for immunoblotting to detect tyrosine phosphorylation of Stat1. The effects of E. coli O55 strains, the evolutionary precursors of VTEC, on Stat1-tyrosine phosphorylation were also determined. The effects of isogenic mutants of O-islands 47 and 122 were tested to determine the role of genes encoded on these putative pathogenicity islands in mediating VTEC inhibition of the interferon-gamma-Stat1 signaling cascade. To evaluate potential mechanism(s) of inhibition, VTEC O157:H7-infected cells were treated with pharmacological inhibitors, including, wortmannin and LY294002. Relative to uninfected cells, Stat1-tyrosine phosphorylation was significantly reduced after 6h infection of both T84 and HEp-2 cells by VTEC strains of all five seropathotypes. E. coli O55 strains, but not enteropathogenic E. coli (EPEC), also caused inhibition of Stat1-tyrosine phosphorylation, suggesting that this effect was acquired early in the evolution of VTEC. Stat1-activation did not recover in epithelial cells infected with isogenic mutants of O-islands 47 and 122, indicating that the inhibitory factor was not contained in these genomic regions. Stat1-phosphorylation remained intact when VTEC-infected cells were treated with wortmannin (0-100 nM), but not by treatment with the more specific PI3-kinase inhibitor, LY294002. Inhibition of interferon-gamma stimulated Stat1-tyrosine phosphorylation by VTEC of multiple seropathotypes indicates the presence of a common inhibitory factor that is independent of bacterial virulence in humans. The results of treatment with wortmannin suggest that the bacterial-derived inhibitory factor employs host cell signal transduction to mediate inhibition of Stat1-activation.
