Single-cell recording and stimulation with a 16k micro-nail electrode array integrated on a 0.18 μm CMOS chip

To cope with the growing needs in research towards the understanding of cellular function and network dynamics, advanced micro-electrode arrays (MEAs) based on integrated complementary metal oxide semiconductor (CMOS) circuits have been increasingly reported. Although such arrays contain a large number of sensors for recording and/or stimulation, the size of the electrodes on these chips are often larger than a typical mammalian cell. Therefore, true single-cell recording and stimulation remains challenging. Single-cell resolution can be obtained by decreasing the size of the electrodes, which inherently increases the characteristic impedance and noise. Here, we present an array of 16,384 active sensors monolithically integrated on chip, realized in 0.18 μm CMOS technology for recording and stimulation of individual cells. Successful recording of electrical activity of cardiac cells with the chip, validated with intracellular whole-cell patch clamp recordings are presented, illustrating single-cell readout capability. Further, by applying a single-electrode stimulation protocol, we could pace individual cardiac cells, demonstrating single-cell addressability. This novel electrode array could help pave the way towards solving complex interactions of mammalian cellular networks.     

The design and synthesis of novel IBiox N-heterocyclic carbene ligands derived from substituted amino-indanols

A synthetic route towards a number of novel IBiox N-heterocyclic carbene (NHC) ligands has been developed. The resulting ligands have restricted flexibility and high steric demand. Preliminary studies have shown these ligands to give high levels of asymmetric induction in the copper-free allylic alkylation of cinnamyl bromide.     

Effective interaction between two ion-adsorbing plates: Hofmeister series and salting-in/salting-out phase diagrams from a global mean-field analysis

Interactions between ions and solutes are key to ion-specificity. A generic model in which ions interact via square well potentials of finite range with charged plates is solved analytically on the Poisson-Boltzmann level and analyzed globally for varying surface charge, salt concentration, and ion-surface affinity. Ion adsorption as well as depletion can lead to stably bound plates at finite separation, relevant for the equilibrium salting-out of small solutes such as proteins. The interplate pressure at large plate separation, relevant for aggregation kinetics of large solutes, exhibits direct as well as indirect Hofmeister ordering, depending on surface charge and salt concentration. A simple method for mapping explicit ion-surface potentials of mean force as obtained from solvent-explicit molecular dynamics simulations onto square-well potential parameters is demonstrated.     

Building large supramolecular nanocapsules with europium cations

A new tripodal ligand has been designed by connecting pyridine-based coordination units to a rigid triptycene moiety. Its reaction with europium(III) provides three-dimensional tetranuclear edifices, whose structural and photophysical characteristics as well as host-guest interactions are discussed in this contribution.     

Phosphate starvation as an antimicrobial strategy: the controllable toxicity of lanthanum oxide nanoparticles

Lanthanum oxide nanoparticles were utilized to scavenge phosphate from microbial growth media for the use of targeted nutrient starvation as an antimicrobial strategy. Only in phosphate poor environments a toxic effect was observed. The effect was shown on Escherichia coli, Staphylococcus carnosus, Penicillium roqueforti, and Chlorella vulgaris.     

Substantial improvements in large-scale redocking and screening using the novel HYDE scoring function

The HYDE scoring function consistently describes hydrogen bonding, the hydrophobic effect and desolvation. It relies on HYdration and DEsolvation terms which are calibrated using octanol/water partition coefficients of small molecules. We do not use affinity data for calibration, therefore HYDE is generally applicable to all protein targets. HYDE reflects the Gibbs free energy of binding while only considering the essential interactions of protein-ligand complexes. The greatest benefit of HYDE is that it yields a very intuitive atom-based score, which can be mapped onto the ligand and protein atoms. This allows the direct visualization of the score and consequently facilitates analysis of protein-ligand complexes during the lead optimization process. In this study, we validated our new scoring function by applying it in large-scale docking experiments. We could successfully predict the correct binding mode in 93% of complexes in redocking calculations on the Astex diverse set, while our performance in virtual screening experiments using the DUD dataset showed significant enrichment values with a mean AUC of 0.77 across all protein targets with little or no structural defects. As part of these studies, we also carried out a very detailed analysis of the data that revealed interesting pitfalls, which we highlight here and which should be addressed in future benchmark datasets.     

Organocatalysis of CN/CN and CC/CN Exchange in Dynamic Covalent Chemistry

The reversibly formed C?N bond plays a very important role in dynamic covalent chemistry and the C?N/C?N exchange of components between different imine constituents to create dynamic covalent libraries has been extensively used. To facilitate diversity generation, we have investigated an organocatalyzed approach, using L ‐proline as catalyst, to accelerate the formation of dynamic libraries of [n×n] imine components. The organocatalysis methodology has also been extended, under somewhat modified conditions, to reversible C?C/C?N exchange processes between Knoevenagel derivatives of barbituric acid and imines, allowing for the generation of increased diversity.     

Heat Convection Between Two Confocal Elliptic Tubes Placed at Different Orientations

In this paper, transient and steady natural convection heat transfer in an elliptical annulus has been investigated. The annulus occupies the space between two horizontal concentric tubes of elliptic cross-section. The resulting velocity and thermal fields are predicted at different annulus orientations assuming isothermal surfaces. The full governing equations of mass, momentum and energy are solved numerically using the Fourier Spectral method. The heat convection process between the two tubes depends on Rayleigh number, Prandtl number, angle of inclination of tube axes and the geometry and dimensions of both tubes. The Prandtl number and inner tube axis ratio are fixed at 0.7 and 0.5, respectively. The problem is solved for the two Rayleigh numbers of $10^4$ and $10^5$ considering a ratio between the two major axes up to 3 while the angle of orientation of the minor axes varies from $0^\circ$ to $90^\circ$. The results for local and average Nusselt numbers are obtained and discussed together with the details of both flow and thermal fields. For isothermal heating conditions, the study has shown an optimum value for major axes ratio that minimizes the rate of heat transfer between the two tubes. Another important aspect of this paper is to prove the successful use of the Fourier Spectral Method in solving confined flow and heat convection problems.     

基于小型电磁动力驱动器的微流道混合控制研究

对于许多微流体应用系统来说,流体的混合是至关重要的.本文研究了基于电磁流体动力混合器的微流道主动混合控制方法,建立了该微流道混合系统的理论模型并进行了数值模拟.在交变Lorentz驱动下,流经混合器流道的流体及其分界面在混合器流道内往复运动,流体界面的反复折叠与流体局部流动使流体混合,流体的横向往复运动使流体分界面反复折叠从而使流体间的接触面积大大增加.对流体混合过程进行了讨论并给出了漉体混合程度评价方法.     

Adaptive policies for time-varying stochastic systems under discounted criterion

We consider a class of time-varying stochastic control systems, with Borel state and action spaces, and possibly unbounded costs. The processes evolve according to a discrete-time equation x _{n + 1}=G _n (x _n , a _n , ξ_n), n=0, 1, … , where the ξ_n are i.i.d. ℜ^k-valued random vectors whose common density is unknown, and the G _n are given functions converging, in a restricted way, to some function G _∞ as n→∞. Assuming observability of ξ_n, we construct an adaptive policy which is asymptotically discounted cost optimal for the limiting control system x _n+1=G _∞ (x _n , a _n , ξ_n).