Unsupervised learning of pharmacokinetic responses

Pharmacokinetics (PK) is a branch of pharmacology dedicated to the study of the time course of drug concentrations, from absorption to excretion from the body. PK dynamic models are often based on homogeneous, multi-compartment assumptions, which allow to identify the PK parameters and further predict the time evolution of drug concentration for a given subject. One key characteristic of these time series is their high variability among patients, which may hamper their correct stratification. In the present work, we address this variability by estimating the PK parameters and simultaneously clustering the corresponding subjects using the time series. We propose an expectation maximization algorithm that clusters subjects based on their PK drug responses, in an unsupervised way, collapsing clusters that are closer than a given threshold. Experimental results show that the proposed algorithm converges fast and leads to meaningful results in synthetic and real scenarios.     

TRIFLUOROMETHYLTHIOLATION OF NORBORNENE

Treatment of norbornene with trifluoromethylsulfenyl chloride at ?80°C furnishes, in addition to trifluoromethylthionortricyclane, four isomeric (chloro) (trifluoromethylthio)-norbornanes and bis-(2, 6-trifluoromethylthio)norbornane. The probable mechanism of the formation of the various compounds via free radical intermediates and their mass spectral characterization are described in this communication.     

Dynamical Bifurcation in Gas‐Phase XH− + CH3Y SN2 Reactions: The Role of Energy Flow and Redistribution in Avoiding the Minimum Energy Path

The gas‐phase reactions of XH^? (X=O, S) + CH₃Y (Y=F, Cl, Br) span nearly the whole range of S_N2 pathways, and show an intrinsic reaction coordinate (IRC) (minimum energy path) with a deep well owing to the CH₃XH???Y^? (or CH₃S^????HF) hydrogen‐bonded postreaction complex. MP2 quasiclassical‐type direct dynamics starting at the [HX???CH₃???Y]^? transition‐state (TS) structure reveal distinct mechanistic behaviors. Trajectories that yield the separated CH₃XH+Y^? (or CH₃S^?+HF) products directly are non‐IRC, whereas those that sample the CH₃XH???Y^? (or CH₃S^????HF) complex are IRC. The IRCIRC/non‐IRC ratios of 90:10, 40:60, 25:75, 2:98, 0:100, and 0:100 are obtained for (X, Y)=(S, F), (O, F), (S, Cl), (S, Br), (O, Cl), and (O, Br), respectively. The properties of the energy profiles after the TS cannot provide a rationalization of these results. Analysis of the energy flow in dynamics shows that the trajectories cross a dynamical bifurcation, and that the inability to follow the minimum energy path arises from long vibration periods of the X?C???Y bending mode. The partition of the available energy to the products into vibrational, rotational, and translational energies reveals that if the vibrational contribution is more than 80 %, non‐IRC behavior dominates, unless the relative fraction of the rotational and translational components is similar, in which case a richer dynamical mechanism is shown, with an IRC/non‐IRC ratio that correlates to this relative fraction.     

Microwave Induced Reaction of H-Dimethylphosphonate with Styrene Oxide

Microwave catalyzed reaction of a neat mixture of styrene oxide and H-dimethylphosphonate furnished dimethyl methylphosphonate, trimethylphosphate, phenylacetaldehyde, 1-methoxy-2-phenylethanol, 1-phenylethleneglycol, cis- and trans-1,3-diphenylcyclobutanes, hydrogen 1-(2-phenylethyl)methylphosphinate, (1-phenylethyl)dimethylphosphonate, and (1-phenylethyl)dimethylphosphonate via free radical processes.     

A Combined Experimental and Theoretical Study on the Formation of Ag Filaments on β‐Ag2MoO4 Induced by Electron Irradiation

A combined experimental and theoretical study is presented to understand the novel observed nucleation and early evolution of Ag filaments on β‐Ag₂MoO₄ crystals, driven by an accelerated electron beam from an electronic microscope under high vacuum. The growth process, chemical composition, and the element distribution in these filaments are analyzed in depth at the nanoscale level using field‐emission scanning electron microscopy (FE‐SEM) and transmission electron microscopy (TEM) with energy‐dispersive spectroscopy (EDS) characterization. To complement experimental results, chemical stability, structural and electronic aspects have been studied systematically using first‐principles electronic structure theory within a quantum theory of atoms in molecules (QTAIM) framework. The Ag nucleation and formation on β‐Ag₂MoO₄ are a result of structural and electronic changes of the AgO₄ tetrahedral cluster as a constituent building block of β‐Ag₂MoO₄, consistent with Ag metallic formation. The formation of Ag filament transforms the β‐Ag₂MoO₄ semiconductor from n‐ to p‐type concomitant with the appearance of Ag defects.     

Rapid calcination of ferrite Ni0.75Zn0.25Fe2O4 by microwave energy

Ferrites Ni_0.75Zn_0.25Fe₂O₄ were obtained by polymeric precursor method and calcined in a short time with microwave energy to assess the morphological and microstructural characteristics. Samples were calcined at 500, 650, 800, and 950 °C for 30 min in a microwave oven. The resulting powders were characterized by thermal analysis (TG/DSC), X-ray diffraction (XRD), Fourier transform infrared spectrometer, field-emission gun scanning electron microscope (FEG-SEM), and energy-dispersive X-ray spectroscopy. The XRD results showed the formation of single ferrite phase at temperature of 500 °C for 30 min. The FEG-SEM analysis showed agglomerated particles with formation of non-dense longitudinal plates, with interparticle porosity and agglomerated fine particles. The rapid calcination by microwave energy demonstrated satisfactory results in relatively low temperature of 500 °C for 30 min and appeared to be a promising technique for obtaining nickel–zinc ferrite powders.     

Microwave hydrothermal synthesis,characterisation, and catalytic performance of Zn1−x Mn x O in cellulose conversion

Wurtzite-type Zn_1?x Mn _x O (x = 0, 0.03, 0.05, 0.07) nanostructures were successfully synthesised using a simple microwave-assisted hydrothermal route and their catalytic properties were investigated in the cellulose conversion. The morphology of the nanocatalysts is dopant-dependent. Pure ZnO presented multi-plate morphology with a flower-like shape of nanometric sizes, while the Zn_0.97Mn_0.03O sample is formed by nanoplates with the presence of spherical nanoparticles; the Zn_0.95Mn_0.05O and Zn_0.93Mn_0.07O samples are mainly formed by nanorods with the presence of a small quantity of spherical nanoparticles. The catalyst without Mn did not show any catalytic activity in the cellulose conversion. The Mn doping promoted an increase in the density of weak acid sites which, according to the catalytic results, favoured promotion of the reaction.     

N−H Bond Formation at a Diiron Bridging Nitride

Despite their connection to ammonia synthesis, little is known about the ability of iron-bound, bridging nitrides to form N−H bonds. Herein we report a linear diiron bridging nitride complex supported by a redox-active macrocycle. The unique ability of the ligand scaffold to adapt to the geometric preference of the bridging species was found to facilitate the formation of N−H bonds via proton-coupled electron transfer to generate a μ-amide product. The structurally analogous μ-silyl- and μ-borylamide complexes were shown to form from the net insertion of the nitride into the E−H bonds (E=B, Si). Protonation of the parent bridging amide produced ammonia in high yield, and treatment of the nitride with PhSH was found to liberate NH₃ in high yield through a reaction that engages the redox-activity of the ligand during PCET.