Flat SAR of P3-methylsulphonamide based small molecule legumain inhibitors

This letter describes the design, development and SAR exploration of a novel series of small legumain inhibitors. The SAR of a new small molecule legumain inhibitor chemotype was explored and found to have improved physiochemical properties compared to previously developed inhibitors within our group. However, further development of this series was found to be limited as the SAR was observed to be relatively flat.

Quantum chaos in ultracold collisions between Yb(¹S0) and Yb(³P2)

We calculate and analyze Feshbach resonance spectra for ultracold Yb(1S0)+Yb(3P2) collisions as a function of an interatomic potential scaling factor λ and external magnetic field. We show that, at zero field, the resonances are distributed randomly in λ, but that signatures of quantum chaos emerge as a field is applied. The random zero-field distribution arises from superposition of structured spectra associated with individual total angular momenta. In addition, we show that the resonances with respect to magnetic field in the experimentally accessible range of 400 to 2000 G are chaotically distributed, with strong level repulsion that is characteristic of quantum chaos.

The 2p interloper resonances in collisions

Ab initio electron scattering calculations using the R -matrix approach have been performed for within a three-state valence configuration-interaction model (VCI). The lowest three electronic target states ( , and the ) of this molecular nitrogen cation are included in the close-coupling method, with each state being represented by a valence CI approximation. From a detailed analysis of the resonance structure found in our work for the symmetries we find four prominent Rydberg series of the type , , , and a interloper resonance. This interloper molecular resonance associated with the B state of is seen to cause distortions of the resulting resonance spectra. A comparison of our total cross sections for the X - B transition shows excellent agreement with the available experimental data.

A gene-signature progression approach to identifying candidate small-molecule cancer therapeutics with connectivity mapping

Gene expression connectivity mapping has gained much popularity recently with a number of successful applications in biomedical research testifying its utility and promise. Previously methodological research in connectivity mapping mainly focused on two of the key components in the framework, namely, the reference gene expression profiles and the connectivity mapping algorithms. The other key component in this framework, the query gene signature, has been left to users to construct without much consensus on how this should be done, albeit it has been an issue most relevant to end users. As a key input to the connectivity mapping process, gene signature is crucially important in returning biologically meaningful and relevant results. This paper intends to formulate a standardized procedure for constructing high quality gene signatures from a user’s perspective.