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Numerical models of blood regulation provide
2021-09-14
Numerical models of blood regulation provide insight into the interaction of the cellular-level and macro-scale phenomena studied in silico, a term referring to computer simulations of the dynamics of complex biological systems as opposed to in vivo or in vitro experimental studies. These in silico
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The focused set of additional pyrazole analogs allowed the i
2021-09-14
The focused set of additional pyrazole analogs allowed the identification of three additional moderately potent γ-secretase modulators, , and which were subsequently screened in a kinetic solubility assay. Unfortunately, neither the architectural changes in analog nor the integration of trifluoro
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94535 sale br FGF FGFR pathway as predictive
2021-09-14
FGF/FGFR pathway as predictive factor Several studies have identified FGFR1 amplification as the major predictive factor of response to FGFR inhibitors [26], [27]. However, in a recent study on lung cancer cell lines with ponatinib, FGFR1 mRNA and protein expression, together with FGF2 and FGF9 m
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During the activation of the
2021-09-14
During the activation of the coagulation cascade, factor Xa (FXa) forms a complex with activated factor V and calcium L-161,982 synthesis on the surface of platelet membrane (so called prothrombinase complex) and converts prothrombin to thrombin [5], [6]. Selective FXa inhibitors do not directly in
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Dysregulation of the HPA axis resulting in alteration to bot
2021-09-14
Dysregulation of the HPA axis, resulting in alteration to both baseline and stress-induced glucocorticoid levels (e.g., cortisol and corticosterone), has been implicated in several diseases and psychopathologies, including anxiety (McEwen et al., 2015, 2016; Shin and Liberzon, 2010). For example, ba
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In addition to the regulation
2021-09-14
In addition to the regulation of SV exo- and calcium ionophore by Ca2+ influx retrieval of SV membranes depends on the exocytic insertion of SV components into the presynaptic membrane: If exocytic SV fusion in neurons is abrogated by genetic inactivation of the core release machinery (e.g. knockout
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br Characterization of quantal exocytosis by amperometry
2021-09-14
Characterization of quantal exocytosis by amperometry A secretory vesicle experiences four phases during exocytosis: (i) cargo packaging & translocation, (ii) vesicle docking & priming; (iii) fusion pore formation; (iv) fusion pore expansion and cargo secretion (Fig. 1a). The release of monoamine
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br Materials and methods br Results br Discussion
2021-09-14
Materials and methods Results Discussion mmLDL is an important risk factor for cardiovascular disease, but its mechanism is still unclear. Previously, we co-cultured mmLDL with the coronary artery and basilar artery and found that mmLDL could upregulate ETB receptor expression in both [16],
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RS testing has been extensively validated in patients with e
2021-09-14
RS testing has been extensively validated in patients with early stage, ER+, HER2− patients. TAILORx, a randomized controlled trial to evaluate the role of adjuvant chemotherapy by RS, found no recurrence or survival benefit to the addition of chemotherapy to endocrine therapy in patients with inter
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OS has a key role in the pathogenesis
2021-09-14
OS has a key role in the pathogenesis of micro- and macrovascular diabetic complications [3]. There is now convincing evidence that the enzymes that generate ROS and gasotransmitters, such as nitric oxide (NO) and CO, are redox regulated at both the transcription and activity levels, and are also im
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We demonstrated that bilirubin the product of heme
2021-09-14
We demonstrated that bilirubin, the product of heme metabolism by HO-1, exerted a potent suppression of NADPH oxidase activity (Fig. 2B). Different from the down-regulation of NADPH oxidase subunit by HO-1 induction in macrophages [24], the protein levels of the NADPH oxidase subunits in vascular en
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To test this concept we
2021-09-14
To test this concept, we took advantage of our large supply of various 2-pyridyl containing [3.1.0] cores (inactive with alkyl or aryl sulfonamides) and prepared the -methylimidazole sulfonamide analogs and (), as work form Merck demonstrated that the 2-pyridyl moiety was superior to the original 4-
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Acknowledgments We would like to
2021-09-13
Acknowledgments We would like to thank Dr. Greg Morriello, Mr. Lehua Chang, Mr. Chris Moyes and Mr. Nam Fung Kar for intermediate 3 syntheses. Cheng Zhu would like to thank Dr. Milana Maletic, Mr. Kake Zhao and Mrs. Wanying Sun for helpful discussions. Introduction Glucagon-like peptide-1 (GLP-
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SAR around amino derivative revealed a
2021-09-13
SAR around amino-derivative revealed a number of interesting trends related to the serum shift and in vitro activity (). A comparison of derivative , and its epimer , showed that the stereochemistry had little effect on the serum shift and the intrinsic affinity for the receptor. In contrast, re-po
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The fact that KNDy neurons activity is
2021-09-13
The fact that KNDy neurons activity is sensitive for circulating hormones related with control of sq 22 homeostasis was demonstrated in other studies (Cejudo Roman et al., 2012; Navarro et al., 2011). It is well documented that leptin plays an important role in the regulation of the gonadotrophic a
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