γ-secretase inhibitors and modulators induce distinct conformational changes in the active sites of γ-secretase and signal peptide peptidase

γ-Secretase inhibitors (GSIs) and modulators (GSMs) are at the frontline of cancer and Alzheimer’s disease research, respectively. While both are therapeutically promising, not much is known about their interactions with proteins other than γ-secretase. Signal peptide peptidase (SPP), like γ-secretase, is a multispan transmembrane aspartyl protease that catalyzes regulated intramembrane proteolysis. We used active site-directed photophore walking probes to study the effects of different GSIs and GSMs on the active sites of γ-secretase and SPP and found that nontransition state GSIs inhibit labeling of γ-secretase by activity-based probes but enhance labeling of SPP. The opposite is true of GSMs, which have little effect on the labeling of γ-secretase but diminish labeling of SPP. These results demonstrate that GSIs and GSMs are altering the structure of not only γ-secretase but also SPP, leading to potential changes in enzyme activity and specificity that may impact the clinical outcomes of these molecules

Some remarks on weighted logarithmic Sobolev inequality

We give here a simple proof of weighted logarithmic Sobolev inequality, for example for Cauchy type measures, with optimal weight, sharpening results of Bobkov-Ledoux. Some consequences are also discussed

A Note on Normal Forms of Quantum States and Separability

We study the normal form of multipartite density matrices. It is shown that the correlation matrix (CM) separability criterion can be improved from the normal form we obtained under filtering transformations. Based on CM criterion the entanglement witness is further constructed in terms of local orthogonal observables for both bipartite and multipartite systems.Comment: 8 page

Numerical Simulation of Water Mist Fire Suppression Technology

AbstractThe paper introduced the progress in research and application of electronic ultrasonic water mist fire suppression technology. Several researches showed that the electronic ultrasonic water mist can be as effective as the now-banned gaseous fire suppressant halon 1301. With the further research about electronic ultrasonic water mist technology, there must be more and more electronic ultrasonic water mist extinguishment tools applied in the fire suppression

Cationic Porphyrins with Large Side Arm Substituents as Resonance Light Scattering Ratiometric Probes for Specific Recognition of Nucleic Acid G-quadruplexes

Specific G-quadruplex-probing is crucial for both biological sciences and biosensing applications. Most reported probes are focused on fluorescent or colorimetric recognition of G-quadruplexes. Herein, for the first time, we reported a new specific G-quadruplex-probing technique—resonance light scattering (RLS)-based ratiometric recognition. To achieve the RLS probing of G-quadruplexes in the important physiological pH range of 7.4-6.0, four water soluble cationic porphyrin derivatives, including an unreported octa-cationic porphyrin, with large side arm substituents were synthesized and developed as RLS probes. These RLS probes were demonstrated to work well for ratiometric recognition of G-quadruplexes with high specificity against single- and double-stranded DNAs, including long double-stranded ones. The working mechanism was speculated to be based on the RLS signal changes caused by porphyrin protonation that was promoted by the end-stacking of porphyrins on Gquadruplexes. This work adds an important member in G-quadruplex probe family, thus providing a useful tool for studies on G-quadruplex-related events concerning G-quadruplex formation, destruction and changes in size, shape and aggregation. As a proofof-concept example of applications, the RLS probes were demonstrated to work well for label-free and sequence-specific sensing of microRNA. This work also provides a simple and useful way for the preparation of cationic porphyrins with high charges