Northern China harbored the world's earliest complex societies based on millet farming, in two major centers in the Yellow (YR) and West Liao (WLR) River basins. Until now, their genetic histories have remained largely unknown. Here we present 55 ancient genomes dating to 7500-1700 BP from the YR, WLR, and Amur River (AR) regions. Contrary to the genetic stability in the AR, the YR and WLR genetic profiles substantially changed over time. The YR populations show a monotonic increase over time in their genetic affinity with present-day southern Chinese and Southeast Asians. In the WLR, intensification of farming in the Late Neolithic is correlated with increased YR affinity while the inclusion of a pastoral economy in the Bronze Age was correlated with increased AR affinity. Our results suggest a link between changes in subsistence strategy and human migration, and fuel the debate about archaeolinguistic signatures of past human migration.

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When micron-scale compositional heterogeneity develops in membranes, the distribution of lipids on one face of the membrane strongly affects the distribution on the other. Specifically, when lipid membranes phase separate into coexisting liquid phases, domains in each monolayer leaflet of the membrane are colocalized with domains in the opposite leaflet. Colocalized domains have never been observed to spontaneously move out of registry. This result indicates that the lipid compositions in one leaflet are strongly coupled to compositions in the opposing leaflet. Predictions of the interleaflet coupling parameter, Λ, vary by a factor of 50. We measure the value of Λ by applying high shear forces to supported lipid bilayers. This causes the upper leaflet to slide over the lower leaflet, moving domains out of registry. We find that the threshold shear stress required to deregister domains in the upper and lower leaflets increases with the inverse length of domains. We derive a simple, closed-form expression relating the threshold shear to Λ, and find Λ = 0.016 ± 0.004 kBT/nm2.

Citation: HAN, T. and DAS, D.B., 2015. Potential of combined ultrasound and microneedles for enhanced transdermal drug permeation: a review. European Journal of Pharmaceutics and Biopharmaceutics,89, Additional Information:• NOTICE: this is the author's version of a work that was accepted for publication in European Journal of Pharmaceutics and Biopharmaceutics. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive ver- have been developed to overcome the resistance of the stratum corneum to molecular 10 diffusion. In particular, researchers have started to consider the possibility of combining the 11 TDD technologies in order to have further increase in drug permeability. Microneedles (MNs) 12 and ultrasound are both promising technologies. They achieve enhancement in drug 13 permeation via different mechanisms and therefore give a good potential for combining with 14 each other. This review will focus on discussing the potential of this combinational technique 15 along with other important issues, e.g., the mechanisms of ultrasound and MNs as it is these 16 mechanisms which are coupled via the two systems (i.e. MNs and ultrasound). We discuss 17 the possible ways to achieve this combination as well as how this combination would 18 increase the permeability. Some of the undeveloped (weaker) research areas of MNs and 19 sonophoresis are also discussed in order to understand the true potential of combining the two 20 technologies when they are developed further in the future. We propose several hypothetical 21 combinations based on the possible mechanisms involved in MNs and ultrasound. 22Furthermore, we carry out a cluster analysis by which we determine the significance of this 23Page 2 of 54 combinational method in comparison with some other selected combinational methods for 24 TDD (e.g., MNs and iontophoresis). Using a time series analysis tool (ARIMA model), the 25 current trend and the future development of combined MNs and ultrasound are also analysed. 26Overall, the review in this paper indicates that combining MNs and ultrasound is a promising 27 TDD method for the future. 28

The formation and dynamics of spatially extended compositional domains in multicomponent lipid membranes lie at the heart of many important biological and biophysical phenomena. While the thermodynamic basis for domain formation has been explored extensively in the past, domain growth in the presence of hydrodynamic interactions both within the (effectively) two-dimensional membrane and in the three-dimensional solvent in which the membrane is immersed has received little attention. In this work, we explore the role of hydrodynamic effects on spinodal decomposition kinetics via continuum simulations of a convective Cahn-Hilliard equation for membrane composition coupled to the Stokes equation. Our approach explicitly includes hydrodynamics both within the planar membrane and in the three-dimensional solvent in the viscously dominated flow regime. Numerical simulations reveal that dynamical scaling breaks down for critical lipid mixtures due to distinct coarsening mechanisms for elongated versus more isotropic compositional lipid domains. The breakdown in scaling should be readily observable in experiments on model membrane systems.