Clinical reasoning in pragmatic trial randomization: a qualitative interview study.

Background: Pragmatic trials, because they study widely used treatments in settings of routine practice, require intensive participation from clinicians who determine whether patients can be enrolled. Clinicians are often conflicted between their therapeutic obligation to patients and their willingness to enroll them in trials in which treatments are randomly determined and thus potentially suboptimal. Refusal to enroll eligible patients can hinder trial completion and damage generalizability.

A new coarse-grained model for E. coli cytoplasm: accurate calculation of the diffusion coefficient of proteins and observation of anomalous diffusion.

A new coarse-grained model of the E. coli cytoplasm is developed by describing the proteins of the cytoplasm as flexible units consisting of one or more spheres that follow Brownian dynamics (BD), with hydrodynamic interactions (HI) accounted for by a mean-field approach. Extensive BD simulations were performed to calculate the diffusion coefficients of three different proteins in the cellular environment.

The free energy profile of tubulin straight-bent conformational changes, with implications for microtubule assembly and drug discovery.

αβ-tubulin dimers need to convert between a 'bent' conformation observed for free dimers in solution and a 'straight' conformation required for incorporation into the microtubule lattice. Here, we investigate the free energy landscape of αβ-tubulin using molecular dynamics simulations, emphasizing implications for models of assembly, and modulation of the conformational landscape by colchicine, a tubulin-binding drug that inhibits microtubule polymerization. Specifically, we performed molecular dynamics, potential-of-mean force simulations to obtain the free energy profile for unpolymerized GDP-bound tubulin as a function of the ∼12° intradimer rotation differentiating the straight and bent conformers.

Angiotensin-I converting enzyme inhibitory activity of hydrolysates from oat (Avena sativa) proteins by in silico and in vitro analyses.

The potential for producing antihypertensive peptides from oat proteins through enzymatic hydrolysis was assessed in silico and confirmed in vitro. Thermolysin (EC 3.4.