Diatomite was used as the main material and sodium silicate as the alkali activating solution in this paper. Diatomite light-weigh material was made by chemical foaming method. Compressive strength, density and heat conductivity were used to measure its performances. Results showed that density, compressive strength showed a growth trend while coefficient of thermal conductivity showed the opposite trend with increasing rapid hardening cement and senior gypsum.
Gain-of-function mutations in the KCNT1 gene, which encodes the sodium-activated potassium channel known as SLACK, are associated with the rare but devastating developmental and epileptic encephalopathy known as epilepsy of infancy with migrating focal seizures (EIMFS). The design of small molecule inhibitors of SLACK channels represents a potential therapeutic approach to the treatment of EIMFS, other childhood epilepsies, and developmental disorders. Herein, we describe a hit optimization effort centered on a xanthine SLACK inhibitor (8) discovered via a high-throughput screen. Across three distinct regions of the chemotype, we synthesized 58 new analogs and tested each one in a whole-cell automated patch-clamp assay to develop structure–activity relationships for inhibition of SLACK channels. We further evaluated selected analogs for their selectivity versus a variety of other ion channels and for their activity versus clinically relevant SLACK mutants. Selectivity within the series was quite good, including versus hERG. Analog 80 (VU0948578) was a potent inhibitor of WT, A934T, and G288S SLACK, with IC50 values between 0.59 and 0.71 µM across these variants. VU0948578 represents a useful in vitro tool compound from a chemotype that is distinct from previously reported small molecule inhibitors of SLACK channels.
IGS is abundant in polymorphism, which is widely used in the analysis of intraspecific genetic diversity and phylogenetic relationships among geographical populations. In this study, the 45S rDNA repeat unit of Saccharina japonica was obtained for the first time by BAC clone sequencing. The total length of the 45S rDNA repeat unit of S. japonica was 8 995 bp, including 5 420 bp of 18S-5.8S–25S rDNA, and 3 575 bp of IGS (Intergenic Spacer), with the GC content of 51.4 %. The IGS was composed of a 465 bp of 3′-outer transcribed spacer (ETS), an 874 bp 5′-ETS, and a 2 236 bp non-transcribed spacer (NTS), with the GC content of 50.1 %. Fiber-FISH (fiber-fluorescence in situ hybridization) analysis of the distribution of 45S rDNA repeat units on the bacterial artificial chromosome illustrated that each fiber had at least five continuously moniliform hybridization signal points. This study provided a new candidate molecular marker for detecting intraspecific polymorphisms of S. japonica. In addition, the successful fiber-FISH analysis of the 45S rDNA on BAC molecule would contribute to the construction of the physical map and map-based cloning of this kelp.
The G-protein activated, inward-rectifying potassium (K+) channels, "GIRKs", are a family of ion channels (Kir3.1-Kir3.4) that has been the focus of intense research interest for nearly two decades. GIRKs are comprised of various homo- and heterotetrameric combinations of four different subunits. These subunits are expressed in different combinations in a variety of regions throughout the central nervous system and in the periphery. The body of GIRK research implicates GIRK in processes as diverse as controlling heart rhythm, to effects on reward/addiction, to modulation of response to analgesics. Despite years of GIRK research, very few tools exist to selectively modulate GIRK channels' activity and until now no tools existed that potently and selectively activated GIRKs. Here we report the development and characterization of the first truly potent, effective, and selective GIRK activator, ML297 (VU0456810). We further demonstrate that ML297 is active in two in vivo models of epilepsy, a disease where up to 40% of patients remain with symptoms refractory to present treatments. The development of ML297 represents a truly significant advancement in our ability to selectively probe GIRK's role in physiology as well as providing the first tool for beginning to understand GIRK's potential as a target for a diversity of therapeutic indications.
An entry from the Cambridge Structural Database, the world’s repository for small molecule crystal structures. The entry contains experimental data from a crystal diffraction study. The deposited dataset for this entry is freely available from the CCDC and typically includes 3D coordinates, cell parameters, space group, experimental conditions and quality measures.
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