ALOHA: a novel probability fusion approach for scoring multi-parameter drug-likeness during the lead optimization stage of drug discovery

Automated lead optimization helper application (ALOHA) is a novel fitness scoring approach for small molecule lead optimization. ALOHA employs a series of generalized Bayesian models trained from public and proprietary pharmacokinetic, absorption, distribution, metabolism, and excretion, and toxicology data to determine regions of chemical space that are likely to have excellent drug-like properties. The input to ALOHA is a list of molecules, and the output is a set of individual probabilities as well as an overall probability that each of the molecules will pass a panel of user selected assays. In addition to providing a summary of how and when to apply ALOHA, this paper will discuss the validation of ALOHA’s Bayesian models and probability fusion approach. Most notably, ALOHA is demonstrated to discriminate between members of the same chemical series with strong statistical significance, suggesting that ALOHA can be used effectively to select compound candidates for synthesis and progression at the lead optimization stage of drug discovery.     

Innovation diffusion model with interactions and delays in adoption for two competitive products in two different patches

Ricerche di Matematica - The aim of the present paper, how the people behave towards the offer of two products in two different patches. In this work, an innovation diffusion model with...     

Ion irradiation effects on conduction in single-wall carbon nanotube networks

We have measured how irradiation by Ar⁺ and N⁺ ions modifies electronic conduction in single-wall carbon nanotube (SWNT) networks, finding dramatically different effects for different thicknesses. For very thin transparent networks, ion irradiation increases localization of charge carriers and reduces the variable-range hopping conductivity, especially at low temperatures. However, for thick networks (SWNT paper) showing metallic conductivity, we find a relatively sharp peak in conductivity as a function of irradiation dose. Our investigation of this peak reveals the important role of thermal annealing extending beyond the range of the irradiating ions, and shows the dependence on the morphology of the samples. We propose a simple model that accounts for the temperature-dependent conductivity. PACS 73.63.Fg; 61.80.-x     

The role of defects in chemical sensing properties of carbon nanotube films

The electrical resistance of 24 different carbon nanotube (CNT) thin film samples in blowing ambient air and 10 different analyte vapor environments was measured. The effects of the CNT growth method, different chemical treatments, ball milling, sample preparation conditions and Ar⁺-ion irradiation are compared. Significant differences in the response signal curves as a function of time in the case of the studied sensor/vapor combinations show the important role of the defect structure and attached functional groups in the chemical sensing properties of CNTs.     

Rate mechanisms of a novel thiol-ene photopolymerization reaction

A novel thiol-ene photopolymerization reaction involving copolymerization of tetrathiol monomer with vinyl silazane is experimentally characterized and is modeled successfully. The overall polymerization rate is found to be controlled by the ratio of the propagation to chain transfer kinetic parameters. The polymerization rate of this mixture, in the presence of added photoinitiator, is approximately first order in ene functionality and is independent of thiol functional group concentration. Initiation rates in this system, when cured utilizing a light centered around 365 nm light, and in the presence of no added photoinitiator, are shown to be proportional to the ene monomer concentration. When the mixture is polymerized utilizing light centered at 254 nm light, and without photoinitiator, the initiation rates are proportional to the thiol monomer concentrations. This novel reaction scheme is further utilized to form ultra rapidly polymerizable polymer derived ceramic structures with high aspect ratios.