A functional high throughput screen identified a novel chemotype for the positive allosteric modulation (PAM) of the muscarinic acetylcholine receptor (mAChR) subtype 5 (M5). Application of rapid analog, iterative parallel synthesis efficiently optimized M5 potency to arrive at the most potent M5 PAMs prepared to date and provided tool compound 8n (ML380) demonstrating modest CNS penetration (h...

Papers published in Hydrology and Earth System Sciences Discussions are under open-access review for the journal Hydrology and Earth System Sciences Abstract Introduction Conclusions References Tables Figures Back Close Full Screen / Esc Printer-friendly Version Interactive Discussion EGU Abstract A data mining, regression tree algorithm M5 was used to review the understanding of mutual hydrolo...

We determined the antigenic specificity and protective immunogenicity of two chemically synthesized peptides of type 5 streptococcal M protein. The synthetic peptides, designated S-M5(1-20) and S-M5(20-40), represent the amino-terminal amino acid sequence of the native pepsin-extracted M5 molecule, which is known to contain at least one heart cross-reactive epitope. Initial studies showed that ...

Intrinsically photosensitive retinal ganglion cells (ipRGCs) mediate both image-forming vision and non-image-forming visual responses such as pupillary constriction and circadian photoentrainment. Five types of ipRGCs, named M1-M5, have been discovered in rodents. To further investigate their photoresponse properties, we made multielectrode array spike recordings from rat ipRGCs, classified the...

Prourokinase (proUK) is a zymogenic plasminogen activator that at pharmacological doses is prone to nonspecific activation to urokinase. This has handicapped therapeutic exploitation of its fibrin-specific physiological properties. To attenuate this susceptibility without compromising specific activation of proUK on a fibrin clot, a Lys300-->His mutation (M5) was developed. M5 had a lower intri...

This paper investigates the effectiveness of four different soft computing methods, namely radial basis neural network (RBNN), adaptive neuro fuzzy inference system (ANFIS) with subtractive clustering (ANFIS-SC), ANFIS with fuzzy c-means clustering (ANFIS-FCM) and M5 model tree (M5Tree), for predicting the ultimate strength and strain of concrete cylinders confined with fiber-reinforced polymer...

assessing seismic hazards involves specifying the likelihood, magnitude and location of earthquakes in a region. predicting the seismic hazards is the first step in reducing the impact of the damage caused by an earthquake.  in this study, to fully utilize all the known parameters which may possibly affect the occurrence of earthquakes (mb ≥ 4.5); a data-driven rule-extraction method called the...

Myosin V is a double-headed unconventional myosin that has been implicated in organelle transport. To perform this role, myosin V may have a high duty cycle. To test this hypothesis and understand the properties of this molecule at the molecular level, we used the laser trap and in vitro motility assay to characterize the mechanics of heavy meromyosin-like fragments of myosin V (M5(HMM)) expres...

The surface-localized M protein of Streptococcus pyogenes is a major virulence factor that inhibits phagocytosis, as determined ex vivo. Because little is known about the role of M protein in vivo we analyzed the contribution of different M protein regions to virulence, using the fibrinogen (Fg)-binding M5 protein and a mouse model of acute invasive infection. This model was suitable, because M...

Two voltage-dependent potassium channels, KCNQ1 and KCNH2, are expressed in the taste buds and were identified as strong candidates involved in the repolarization of taste receptor cells expressing phospholipase C-beta2 and TRPM5 (beta2/M5-TRCs). In cell type-specific expression, KCNQ1 was expressed in most taste bud cells, including beta2/M5-TRCs, whereas KCNH2 was expressed in a subset of bet...