Pre-compacted bentonite bricks are often considered as sealing/backfill elements in deep geological repositories for high level radioactive waste. A good understanding of their microstructure changes ...upon hydration is essential as the microstructure changes are directly related to the macroscopic hydro-mechanical behaviour. In this study, the microstructure features of the compacted MX80 bentonite used as a sealing material in a field experiment were characterized by means of both mercury intrusion porosimetry (MIP) and scanning electron microscopy (SEM). Emphasis was put on the effects of final dry density (density after swelling) and hydration time. The results obtained show that the changes in soil porosity upon swelling are mainly due to the increase in large-pores of about 50µm diameter and medium-pores of 1µm diameter. In addition, the microstructure changed over time due to the water re-distribution that occurred among each level of pores: the volume of both the large-pores and small-pores decreased along as the volume of the medium-pores increased. A uniform microstructure can be then expected in the long term. Furthermore, it was observed that the higher the final dry density, the slower the microstructure changes.
It is of great significance to depolymerize used or waste polymers to recover the starting monomers suitable for repolymerization reactions that reform recycled materials no different from the virgin ...polymer. Herein, we report a novel recyclable plastic: degradable polycarbonate synthesized by dinuclear chromium‐complex‐mediated copolymerization of CO2 with 1‐benzyloxycarbonyl‐3,4‐epoxy pyrrolidine, a meso‐epoxide. Notably, the novel polycarbonate with more than 99 % carbonate linkages could be recycled back into the epoxide monomer in quantitative yield under mild reaction conditions. Remarkably, the copolymerization/depolymerization processes can be achieved by the ON/OFF reversible temperature switch, and recycled several times without any change in the epoxide monomer and copolymer. These characteristics accord well with the concept of perfectly sustainable polymers.
A sustainable plastic was synthesized by dinuclear chromium‐complex‐mediated copolymerization of CO2 with an epoxide that could be recycled back into the monomer in quantitative yield under mild conditions. Temperature was used as a reversible switch in the recycle process. These characteristics are in accordance with the concept of perfectly sustainable polymers.
Synthesis of stereoregular polyesters with main-chain chirality was achieved for the first time by the asymmetric copolymerization of meso-epoxides and cyclic anhydrides using catalyst systems based ...on enantiopure bimetallic complexes. The combination of the biphenol-linked dinuclear aluminum complex with tert-butyl groups in the phenolate ortho-positions and a nucleophilic co-catalyst was found to be more efficient in catalyzing this asymmetric copolymerization, affording enantiomerically enriched polyesters (up to 91% ee) with completely alternating structure and narrow molecular weight distribution. It was discovered that the isotactic-enriched poly(cyclopentene phthalate) is a typical semicrystalline material with a melting endothermic peak at 221 °C. This study is expected to provide a promising route to prepare various stereoregular polyesters having a wide variety of physical properties and degradability.
Limestone calcined clay cement (LC3) has gained attention in the research paradigm, and useful data is available in scattered form, necessitates comprehensive review to provide global insight into ...important research questions, i.e., micro-macro response, and environmental implications, keeping in view the future research directions. In this regard, the current article provides a comprehensive insight into LC3, focusing on its micro-macro mechanisms and critically examining different aspects such as chemical composition, hydration chemistry with special attention on phase assemblage, impacts of various salts and carbonation, rheological properties, mechanical behavior, high-temperature exposure, and compatibility with different admixtures. Additionally, this article explores the sustainable and environmentally friendly applications of LC3, with an emphasis on its economic and environmental advantages highlighted by pertinent data and lifecycle assessments (LCA). Comprehensive data was gathered from a micro-macro perspective considering SCMs from different regional sources, and comparisons were drawn with Ordinary Portland Cement (OPC). Further, comparative economic and environmental aspects for different grades of LC3 and OPC were evaluated and analyzed considering energy demand, cost-effectiveness, and energy efficiency. The micro-macro characteristics of LC3 are found to be majorly dependent on its constituent, particularly clinker composition and alumina content in SCMs, which varies regionally. This review study outlines the critical research directions, i.e., enhancement of mechanical behavior and rheology, incorporation of super plasticizers and waste materials for resource conservation, and improvement of carbonation resistance for durability to make LC3 a sustainable and first-choice cement.
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•Hydration chemistry and phase assemblage of SCMs were critically discussed.•Effect of SCMs on rheological, mechanical, and durability properties•Environmental implications and potential research areas were discussed.•Potential application of LC3 in various fields of construction was determined.•LCA showed LC3 a cost-effective blend with low carbon footprints.
Regioselective ring opening of three-membered heterocyclic compounds (epoxides or N-substituted aziridines) at various temperatures was observed in coupling reactions with CO2 by the use of an ...aluminum–salen catalyst in conjunction with intramolecular quaternary ammonium salts as cocatalysts, affording the corresponding five-membered cyclic products with complete configuration retention at the methine carbon. Notably, this bifunctional aluminum-based catalyst exhibited nearly 100% regioselectivity for the ring opening at the methylene C–O bond for various terminal epoxides. This was true for those bearing an electron-withdrawing group, such as styrene oxide or epichlorohydrin, thereby affording the synthesis of various enantiopure cyclic carbonates that have previously been obtained only rarely by other methods. An intramolecular cooperative catalysis is suggested to contribute to the high activity and excellent stereochemistry control observed. Surprisingly, the highly selective ring opening at the methine carbon of N-substituted aziridines was found in the coupling with CO2, predominantly giving 5-substituted oxazolininones with retention of configuration as a result of double inversion at the methine carbon.
Hot spot gene mutations in splicing factor 3b subunit 1 (SF3B1) are observed in many types of cancer and create abundant aberrant mRNA splicing, which is profoundly implicated in tumorigenesis. Here, ...we identified that the SF3B1 K700E (SF3B1K700E) mutation is strongly associated with tumor growth in pancreatic ductal adenocarcinoma (PDAC). Knockdown of SF3B1 significantly retarded cell proliferation and tumor growth in a cell line (Panc05.04) with the SF3B1K700E mutation. However, SF3B1 knockdown had no notable effect on cell proliferation in two cell lines (BxPC3 and AsPC1) carrying wild‐type SF3B1. Ectopic expression of SF3B1K700E but not SF3B1WT in SF3B1‐knockout Panc05.04 cells largely restored the inhibitory role induced by SF3B1 knockdown. Introduction of the SF3B1K700E mutation in BxPC3 and AsPC1 cells also boosted cell proliferation. Gene set enrichment analysis demonstrated a close correlation between SF3B1 mutation and aerobic glycolysis. Functional analyses showed that the SF3B1K700E mutation promoted tumor glycolysis, as evidenced by glucose consumption, lactate release, and extracellular acidification rate. Mechanistically, the SF3B1 mutation promoted the aberrant splicing of PPP2R5A and led to the activation of the glycolytic regulator c‐Myc via post‐translational regulation. Pharmacological activation of PP2A with FTY‐720 markedly compromised the growth advantage induced by the SF3B1K700E mutation in vitro and in vivo. Taken together, our data suggest a novel function for SF3B1 mutation in the Warburg effect, and this finding may offer a potential therapeutic strategy against PDAC with the SF3B1K700E mutation.
SF3B1 mutations have been previously implicated in tumorigenesis. Here, we investigate the role of SF3B1K700E mutation in pancreatic ductal adenocarcinoma (PDAC). SF3B1K700E led to aberrant splicing of PPP2R5A, coupled with c‐Myc activation higher aerobic glycolysis rate and growth advantage of tumor cells. Taken together, our data describe a novel function for SF3B1 K700E mutations in the Warburg effect. Inhibition of SF3B1 K700E mutation may potentially serve as a novel therapeutic strategy for patients with PDAC.
Unprecedented enantioselectivity and catalytic activity was observed in the asymmetric copolymerization of CO2 with meso‐epoxides (including the less reactive cyclopentene oxide) mediated by the ...dinuclear CoIII complex (S,S,S,S)‐1 under mild conditions. The resultant copolymers possess more than 99 % carbonate linkages and a perfectly isotactic structure.
During the long-term operation of a deep geological repository, the buffer/backfill properties of compacted bentonite could be affected by the chemistry of the infiltrated porewater. In this study, ...swelling tests and microstructural analyses were conducted on the compacted GMZ bentonite specimens with an initial dry density of 1.5 or 1.7 Mg/m3 with infiltration of distilled water, as well as, KCl and KOH solutions (0.1 and 1.0 M). Influences of K+ solutions on the swelling behavior of compacted GMZ bentonite were investigated. Results show that swelling properties of compacted GMZ bentonite specimens could be significantly influenced by concentration of K+ solutions and dry density of specimens. Swelling pressure of compacted GMZ bentonite specimens was significantly attenuated by infiltration of K+ salt/alkaline solutions. For swelling strain tests with infiltration of KCl or KOH solutions, instead of a secondary swelling stage, a volumetric collapse stage was observed. Micro-structural test results demonstrate that the attenuation of swelling behavior could be attributed to the K+ exchange or silica dissolution.
•Influences of K+ solutions on the swelling behavior of compacted GMZ bentonite were investigated•Swelling pressures of compacted GMZ bentonite were significantly attenuated by K+ salt/alkaline solutions•Swelling attenuation could be attributed to the K+ fixation, ion exchange, smectite dissolution and mineral transformation.
Aberrant activation of Bruton’s tyrosine kinase (BTK) plays an important role in pathogenesis of B-cell lymphomas, suggesting that inhibition of BTK is useful in the treatment of hematological ...malignancies. The discovery of a more selective on-target covalent BTK inhibitor is of high value. Herein, we disclose the discovery and preclinical characterization of a potent, selective, and irreversible BTK inhibitor as our clinical candidate by using in vitro potency, selectivity, pharmacokinetics (PK), and in vivo pharmacodynamic for prioritizing compounds. Compound BGB-3111 (31a, Zanubrutinib) demonstrates (i) potent activity against BTK and excellent selectivity over other TEC, EGFR and Src family kinases, (ii) desirable ADME, excellent in vivo pharmacodynamic in mice and efficacy in OCI-LY10 xenograft models.
The rostromedial tegmental nucleus (RMTg), also called the GABAergic tail of the ventral tegmental area, projects to the midbrain dopaminergic system, dorsal raphe nucleus, locus coeruleus, and other ...regions. Whether the RMTg is involved in sleep-wake regulation is unknown. In the present study, pharmacogenetic activation of rat RMTg neurons promoted non-rapid eye movement (NREM) sleep with increased slow-wave activity (SWA). Conversely, rats after neurotoxic lesions of 8 or 16 days showed decreased NREM sleep with reduced SWA at lights on. The reduced SWA persisted at least 25 days after lesions. Similarly, pharmacological and pharmacogenetic inactivation of rat RMTg neurons decreased NREM sleep. Electrophysiological experiments combined with optogenetics showed a direct inhibitory connection between the terminals of RMTg neurons and midbrain dopaminergic neurons. The bidirectional effects of the RMTg on the sleep-wake cycle were mimicked by the modulation of ventral tegmental area (VTA)/substantia nigra compacta (SNc) dopaminergic neuronal activity using a pharmacogenetic approach. Furthermore, during the 2-hour recovery period following 6-hour sleep deprivation, the amount of NREM sleep in both the lesion and control rats was significantly increased compared with baseline levels; however, only the control rats showed a significant increase in SWA compared with baseline levels. Collectively, our findings reveal an essential role of the RMTg in the promotion of NREM sleep and homeostatic regulation.
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Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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