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排序方式: 共有536条查询结果,搜索用时 15 毫秒
1.
Bokyung Kim Young Ho Ko Massimiliano Runfola Simona Rapposelli Gabriella Ortore Grazia Chiellini Jin Hae Kim 《International journal of molecular sciences》2021,22(7)
Thyromimetics, whose physicochemical characteristics are analog to thyroid hormones (THs) and their derivatives, are promising candidates as novel therapeutics for neurodegenerative and metabolic pathologies. In particular, sobetirome (GC-1), one of the initial halogen-free thyromimetics, and newly synthesized IS25 and TG68, with optimized ADME-Tox profile, have recently attracted attention owing to their superior therapeutic benefits, selectivity, and enhanced permeability. Here, we further explored the functional capabilities of these thyromimetics to inhibit transthyretin (TTR) amyloidosis. TTR is a homotetrameric transporter protein for THs, yet it is also responsible for severe amyloid fibril formation, which is facilitated by tetramer dissociation into non-native monomers. By combining nuclear magnetic resonance (NMR) spectroscopy, computational simulation, and biochemical assays, we found that GC-1 and newly designed diphenyl-methane-based thyromimetics, namely IS25 and TG68, are TTR stabilizers and efficient suppressors of TTR aggregation. Based on these observations, we propose the novel potential of thyromimetics as a multi-functional therapeutic molecule for TTR-related pathologies, including neurodegenerative diseases. 相似文献
2.
Gökelma Mertol Einarsrud Kristian Etienne Tranell Gabriella Friedrich Bernd 《Metallurgical and Materials Transactions B》2020,51(2):850-860
Metallurgical and Materials Transactions B - The quality requirements of aluminum products are steadily increasing, and the presence of non-metallic inclusions have a large impact on the quality of... 相似文献
3.
4.
Roberto Leoni Bruno Buonomo Gabriella Castellano Francesco Mattioli Guido Torrioli Luciana Di Gaspare Florestano Evangelisti 《Nuclear instruments & methods in physics research. Section A, Accelerators, spectrometers, detectors and associated equipment》2004,520(1-3):44-47
We discuss the performance, of a normal metal hot electron bolometer (NHEB) that we have measured at 0.3 K. We found that the noise equivalent power was limited by the amplifier noise. To improve the NHEB power response and to make it more robust and reliable we propose to substitute the normal metal with heavily doped silicon. The heavily doped silicon behaves like a metal with lower carrier concentration and has a smaller electron–phonon thermal coupling. We have fabricated superconductor-doped silicon-superconductor contacts (S-Sm-S) and we have used them as thermometers and coolers. 相似文献
5.
In this work a new class of numerical methods for the BGK model of kinetic equations is presented. In principle, schemes of
any order of accuracy in both space and time can be constructed with this technique. The methods proposed are based on an
explicit–implicit time discretization. In particular the convective terms are treated explicitly, while the source terms are
implicit. In this fashion even problems with infinite stiffness can be integrated with relatively large time steps. The conservation
properties of the schemes are investigated. Numerical results are shown for schemes of order 1, 2 and 5 in space, and up to
third-order accurate in time. 相似文献
6.
Gabriella Tranell Oleg Ostrovski Sharif Jahanshahi 《Metallurgical and Materials Transactions B》2002,33(1):61-67
The redox behavior of titanium in CaO-SiO2-TiO
x
melts was investigated using a slag-gas equilibrium technique. Titanium partitioning between Ti3+ and Ti4+ valency states and the ratio of activity coefficients of TiO1.5 and TiO2 were determined as functions of oxygen partial pressure, temperature, and slag composition. The equilibrium experiments were
carried out at temperatures between 1783 and 1903 K under CO-CO2-Ar gas atmosphere with oxygen partial pressure ranging from 10−12 to 10−7 atm (1.01×10−10 kPa to 1.01×10−5 kPa). The slags had CaO/SiO2 ratios between 0.55 and 1.35 and total titanium oxide concentrations from 7 to 50 mass pct. Experimental results showed that
the Ti3+/Ti4+ ratio in CaO-SiO2-TiO
x
slags, containing up to 50 mass pct TiO
x
, increased with decreasing oxygen partial pressure and decreased with increasing CaO/SiO2 ratio and decreasing temperature. Measured variation of the redox ratio Ti3+/Ti4+ with oxygen partial pressure closely followed the ideal behavior. Increasing the CaO/SiO2 ratio increased the ratio of activity coefficients of TiO1.5 and TiO2. The effect of total titania content on this ratio was more complex and in accord with Raman spectroscopy data. 相似文献
7.
Impedance spectroscopy and gravimetry were employed to characterize alkyd-acrylate and styrene-acrylate water-borne resin film properties during wetting-through (i.e. during water uptake). 相似文献
8.
Davide Barbagallo Angela Caponnetto Cristina Barbagallo Rosalia Battaglia Federica Mirabella Duilia Brex Michele Stella Giuseppe Broggi Roberto Altieri Francesco Certo Rosario Caltabiano Giuseppe Maria Vincenzo Barbagallo Carmelina Daniela Anfuso Gabriella Lupo Marco Ragusa Cinzia Di Pietro Thomas Birkballe Hansen Michele Purrello 《International journal of molecular sciences》2021,22(4)
Circular RNAs (circRNAs) are a large class of RNAs with regulatory functions within cells. We recently showed that circSMARCA5 is a tumor suppressor in glioblastoma multiforme (GBM) and acts as a decoy for Serine and Arginine Rich Splicing Factor 1 (SRSF1) through six predicted binding sites (BSs). Here we characterized RNA motifs functionally involved in the interaction between circSMARCA5 and SRSF1. Three different circSMARCA5 molecules (Mut1, Mut2, Mut3), each mutated in two predicted SRSF1 BSs at once, were obtained through PCR-based replacement of wild-type (WT) BS sequences and cloned in three independent pcDNA3 vectors. Mut1 significantly decreased its capability to interact with SRSF1 as compared to WT, based on the RNA immunoprecipitation assay. In silico analysis through the “Find Individual Motif Occurrences” (FIMO) algorithm showed GAUGAA as an experimentally validated SRSF1 binding motif significantly overrepresented within both predicted SRSF1 BSs mutated in Mut1 (q-value = 0.0011). U87MG and CAS-1, transfected with Mut1, significantly increased their migration with respect to controls transfected with WT, as revealed by the cell exclusion zone assay. Immortalized human brain microvascular endothelial cells (IM-HBMEC) exposed to conditioned medium (CM) harvested from U87MG and CAS-1 transfected with Mut1 significantly sprouted more than those treated with CM harvested from U87MG and CAS-1 transfected with WT, as shown by the tube formation assay. qRT-PCR showed that the intracellular pro- to anti-angiogenic Vascular Endothelial Growth Factor A (VEGFA) mRNA isoform ratio and the amount of total VEGFA mRNA secreted in CM significantly increased in Mut1-transfected CAS-1 as compared to controls transfected with WT. Our data suggest that GAUGAA is the RNA motif responsible for the interaction between circSMARCA5 and SRSF1 as well as for the circSMARCA5-mediated control of GBM cell migration and angiogenic potential. 相似文献
9.
Aneta Kaczor Nikoletta Szemerédi Dr. Katarzyna Kucwaj-Brysz Dr. Monika Dąbrowska Dr. Małgorzata Starek Dr. Gniewomir Latacz Dr. Gabriella Spengler Prof. Jadwiga Handzlik 《ChemMedChem》2021,16(15):2386-2401
ABCB1 modulation is an interesting strategy in the search for new anticancer agents that can overcome multidrug resistance (MDR). Hence, 17 new 5-arylideneimidazolones containing an amine moiety, as potential ABCB1 inhibitors, were designed, synthesized, and investigated. The series was tested in both parental (PAR) and multidrug-resistant (MDR) ABCB1-overexpressing T-lymphoma cancer cells using cytotoxicity assays. The ABCB1-modulating activity was examined in rhodamine 123 accumulation tests, followed by Pgp-Glo™ Assay to determine the influence of the most active compounds on ATPase activity. Lipophilic properties were assessed both, in silico and experimentally (RP-TLC). Pharmacophore-based molecular modelling toward ABCB1 modulation was performed. The studies allowed the identification of anticancer agents (p-fluorobenzylidene derivatives) more potent than doxorubicin, with highly selective action on MDR T-lymphoma cells (selectivity index >40). Most of the investigated compounds showed ABCB1-modulating action; in particular, two 5-benzyloxybenzylidene derivatives displayed activity nearly as strong as that of tariquidar. 相似文献
10.