Budding and vesiculation are prominent shape transformations of fluid lipid-bilayer vesicles. We discuss these transitions within the context of a curvature model which contains two types of bending energy. In addition to the usual local curvature elasticity~, we include the effect of a relative areal stretching of the two monolayers. This area-difFerence elasticity leads to an effective nonlocal curvature energy characterized by another parameter K We argue that the two contributions to the curvature energy are typically comparable in magnitude.The

Cholesterol is an important molecular component of the plasma membranes of mammalian cells. Its precursor in the sterol biosynthetic pathway, lanosterol, has been argued by Konrad Bloch (Bloch, K. 1965. Science. 150:19-28; 1983. CRC Crit. Rev. Biochem. 14:47-92; 1994. Blonds in Venetian Paintings, the Nine-Banded Armadillo, and Other Essays in Biochemistry. Yale University Press, New Haven, CT.) to also be a precursor in the molecular evolution of cholesterol. We present a comparative study of the effects of cholesterol and lanosterol on molecular conformational order and phase equilibria of lipid-bilayer membranes. By using deuterium NMR spectroscopy on multilamellar lipid-sterol systems in combination with Monte Carlo simulations of microscopic models of lipid-sterol interactions, we demonstrate that the evolution in the molecular chemistry from lanosterol to cholesterol is manifested in the model lipid-sterol membranes by an increase in the ability of the sterols to promote and stabilize a particular membrane phase, the liquid-ordered phase, and to induce collective order in the acyl-chain conformations of lipid molecules. We also discuss the biological relevance of our results, in particular in the context of membrane domains and rafts.

This study shows that age, weight and the VKORC1 and CYP2C9 polymorphism affect warfarin dose requirements in our sample of Chinese patients receiving long-term therapy and showing stable control of anticoagulation. It is anticipated that the use of dosing regimens modified by taking into account the contribution of age, weight, and the CYP2C9 and VKORC1 genotypes has the potential to improve the safety of warfarin therapy.

We have studied the conformation of a polymer brush in equilibrium with a solvent that is subject to a shear flow. The interplay between the polymer brush and the hydrodynamic flow of the solvent has been modeled, with simple but largely justifiable approximations. The main technique used in our study is a Monte-Carlo simulation algorithm that is distinct from many standard numerical methods used in studies of polymer brushes in that it combines an off-lattice description of polymer brushesthe Edwards Hamiltonianwith a modification of the standard Metropolis Monte-Carlo transition probability to take into account the effective force acting upon the polymer molecules by the moving solvent. The conformation of the polymer brush, the configurations of each individual chain in particular, is investigated in detail. It is found that the significant response of the brush to the solvent shear flow manifests principally in the form of the chain tilting toward and stretching along the direction of the flow, whereas the overall conformational properties, such as the averaged local monomer density, and the linear span of the brush in the direction normal to that of the flow remain essentially unaffected by the flow. Such response can be understood both qualitatively and semiquantitatively in terms of a notion of the mechanical balance of the different physical forces involved, which was used in the theory of Rabin and Alexander (Rabin, Y.; Alexander, S. Europhys. Lett. 1990, 13, 49). The relevance of our study to some recent experiments is briefly discussed.

Background Clinical practice guidelines or recommendations often require timely and regular updating as new evidence emerges, because this can alter the risk-benefit trade-off. The scientific process of developing and updating guidelines accompanied by adequate implementation can improve outcomes. To promote better management of patients receiving vancomycin therapy, we updated the guideline for the therapeutic drug monitoring (TDM) of vancomycin published in 2015. Methods Our updated recommendations complied with standards for developing trustworthy guidelines, including timeliness and rigor of the updating process, as well as the use of the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. We also followed the methodology handbook published by the National Institute for Health and Clinical Excellence and the Spanish National Health System. Results We partially updated the 2015 guideline. Apart from adults, the updated guideline also focuses on pediatric patients and neonates requiring intravenous vancomycin therapy. The guideline recommendations involve a broadened range of patients requiring TDM, modified index of TDM (both 24-hour area under the curve and trough concentration), addition regarding the necessity and timing of repeated TDM, and initial dose for specific subpopulations. Overall, 1 recommendation was deleted and 3 recommendations were modified. Eleven new recommendations were added, and no recommendation was made for 2 clinical questions. Conclusions We updated an evidence-based guideline regarding the TDM of vancomycin using a rigorous and multidisciplinary approach. The updated guideline provides more comprehensive recommendations to inform rational and optimized vancomycin use and is thus of greater applicability.