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Conformational analysis provides further insight into the SA
2021-11-03
Conformational analysis provides further insight into the SAR trends apparent in . Acyclic precursors – are 25–50-fold less active than their macrocyclic counterparts – against Pyk2. The global minima for – are conformations in which the –NHCH– linker between the pyrimidine and pyridine rings is st
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br Application of TIRFM to visualizing
2021-11-03
Application of TIRFM to visualizing exocytosis TIRFM was first used to visualize exocytosis from large secretory granules from chromaffin CBR-5884 sale (Steyer et al., 1997). Before that, visualization of secretory organelle was strictly limited to a few exceptions, such as mast cell of mutant m
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We sought to deduce the
2021-11-03
We sought to deduce the role of membrane lipid determinants on endo- and exocytosis by applying a combination of metabolic (lipid) engineering approaches and biophysical methods, e.g. classical optical imaging technologies and high-resolution time-resolved patch-clamp/capacitance measurements. The l
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It has been known for some time that an oral
2021-11-02
It has been known for some time that an oral salt load given to mammals induces a much greater natriuresis than the intravenous administration of an equivalent amount of saline (Carey et al., 1976, Singer et al., 1998). In addition, oral administration of salt to rats has been reported to augmented
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The calculations for the R substrate
2021-11-02
The calculations for the R substrate showed that, like the S substrate, the coordination shell of the Zn mu receptors is more symmetric than in the HIC-SG crystal structure. This symmetry indicates that the enzyme could use the same reaction mechanisms as for the S substrate, but with exchanged role
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In experiments using D to displace binding of specific
2021-11-02
In experiments using D22 to displace binding of specific high-affinity radioligands for DAT, NET, and SERT in mouse α-mangostin tissue, we observed a ranking with D22 displacement efficiency in the order of DAT > SERT > NET (IC50 values being ~ 11 (DAT), 26 (SERT), and 101 (NET) µM; Fig. 1, Fig. 2,
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Two excellent GSMs with clear pharmacological effect across
2021-11-02
Two excellent GSMs with clear pharmacological effect across rats, dogs, monkeys, and human subjects are BMS-932481 and BMS-986133 with IC50 at 6.6 and 3.5 nM to reduce Aβ42, respectively. Both GSMs exhibit dose- and time-dependent activity in vivo by decreasing Aβ1-42 and Aβ1-40 levels while increas
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br Acknowledgments The authors gratefully acknowledge
2021-11-02
Acknowledgments The authors gratefully acknowledge the support provide by National Natural Science Foundation of China (Number 31301415). Introduction β-Galactosidases (EC 3.2.1.23), frequently known as lactases, are widely used in lactose hydrolysis. This disaccharide is present in mammalian
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Two types of processes intrinsic and extrinsic contribute sy
2021-11-02
Two types of processes, intrinsic and extrinsic, contribute synergistically to the age-related change on structural integrity and physiological function of the skin (Farage, Miller, Elsner, & Maibach, 2008). Intrinsic aging arise from genetically programmed cell aging, normal metabolic activities, a
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br Materials and methods br Acknowledgments We are
2021-11-02
Materials and methods Acknowledgments We are grateful for financial support from the National Natural Science Foundation of China (Grants No. 81661148046 and 81773762, China) and the “Personalized Medicines—Molecular Signature-based Drug Discovery and Development”, Strategic Priority Research
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We reviewed the results of comprehensive genomic
2021-11-02
We reviewed the results of comprehensive genomic profiling (CGP) in 26,054 cases of NSCLC and examined the frequency and clinical characteristics of patients whose tumors harbor FGFR fusions. To our knowledge, this is the most in-depth evaluation of FGFR fusions exclusively in NSCLC. Here we will de
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br Acknowledgments We apologize to the researchers who were
2021-11-02
Acknowledgments We apologize to the researchers who were not referenced due to space limitations. We thank Dave Primm (Department of Surgery, University of Texas Southwestern Medical Center) for his critical reading of the manuscript. This work was supported by grants from the US National Institu
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Over decades a deeper understanding of terpene
2021-11-02
Over decades, a deeper understanding of terpene synthases has also permitted enzyme engineering for unnatural substrate acceptance. Novel terpenoids have been successfully synthesized from substrate analogues as by-products from mechanistic investigation (Faraldos et al., 2012; Miller, Yu, & Alleman
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In conclusion the present study
2021-11-01
In conclusion, the present study shows that the endothelin system is of importance in the cardiopulmonary vascular pathophysiology of porcine endotoxin shock. In this model, combination of a selective endothelin ETA and a selective endothelin ETB receptor antagonist markedly improved pulmonary circu
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A repertoire of cytotoxic payloads is
2021-11-01
A repertoire of cytotoxic payloads is increasing; among those, MMAE has been utilized for the highly effective ADC brentuximab vedotin. However, the ADCs which utilized MMAE to target GCC in solid tumors have shown a poor efficacy suggesting that various tumor types respond differently to a given to
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