Study of the enhancement effect of cyclopentadecanolide on protein permeation through lipid membranes

Intranasal drug delivery has been a topic of increasing interest for a decade as a convenient and reliable method for the systemic administration of drugs. The low bioavailability of simple formulation of protein drugs, such as insulin, can be greatly improved by using permeation enhancers. We studied the effect of cyclopentadecanolide (CPE-215RTM) as a permeation enhancer in protein release through lipid bilayer membranes. We successfully designed a novel in-vitro membrane permeability model using liposomes and performed a series of transmembrane protein release experiments. These were carried out under a wide range of conditions in the presence of different permeation enhancer combinations. The experimental results showed that CPE-215RTM is an effective membrane permeation enhancer for proteins and a phase transfer agent, for example, cyclodextrins, can further enhance the effect of CPE-215RTM. Besides the release experiments, studies on insulin solution properties (self-diffusion and self-association states), the interaction between insulin and liposome and the interaction between CPE-215RTM and liposomes were carried out. Based on the mechanistic study and release data, we hypothesized that CPE-215RTM can form transient pores in the lipid bilayer that dissolve when CPE-215RTM distributes homogeneously within the bilayer and restore the barrier function of the lipid bilayer. We performed several experiments that corroborate our hypothesis. A mathematical model was developed based on our hypothesized release mechanism. A semi-empirical nonlinear equation involving four parameters effectively fits the protein release profiles. The quality of the data fit with this model is good supporting evidence for the validity of our mechanistic model. Finally we used a neural network approach to correlate the different release condition parameters and the four semi-empirical fitting parameters based on our limited data sets. Reasonable neural networks were formed for the three major parameters of the mathematical model and provided acceptable prediction results

On the pinning strategy of complex networks

In pinning control of complex networks, a tacit believing is that the system dynamics will be better controlled by pinning the large-degree nodes than the small-degree ones. Here, by changing the number of pinned nodes, we find that, when a significant fraction of the network nodes are pinned, pinning the small-degree nodes could generally have a higher performance than pinning the large-degree nodes. We demonstrate this interesting phenomenon on a variety of complex networks, and analyze the underlying mechanisms by the model of star networks. By changing the network properties, we also find that, comparing to densely connected homogeneous networks, the advantage of the small-degree pinning strategy is more distinct in sparsely connected heterogenous networks

Direct evidences for inner-shell electron-excitation by laser induced electron recollision

Extreme ultraviolet (XUV) attosecond pulses, generated by a process known as laser-induced electron recollision, are a key ingredient for attosecond metrology, providing a tool to precisely initiate and probe sub-femtosecond dynamics in the microcosms of atoms, molecules and solids[1]. However, with the current technology, extending attosecond metrology to scrutinize the dynamics of the inner-shell electrons is a challenge, that is because of the lower efficiency in generating the required soft x-ray \hbar\omega>300 eV attosecond bursts and the lower absorption cross-sections in this spectral range. A way around this problem is to use the recolliding electron to directly initiate the desired inner-shell process, instead of using the currently low flux x-ray attosecond sources.Such an excitation process occurs in a sub-femtosecond timescale, and may provide the necessary "pump" step in a pump-probe experiment[2]. Here we used a few cycle infrared \lambda_{0}~1800nm source[3] and observed direct evidences for inner-shell excitations through the laser-induced electron recollision process. It is the first step toward time-resolved core-hole studies in the keV energy range with sub-femtosecond time resolution.Comment: 6 pages, 4 figure

A Mixed-Integer SDP Solution Approach to Distributionally Robust Unit Commitment with Second Order Moment Constraints

A power system unit commitment (UC) problem considering uncertainties of renewable energy sources is investigated in this paper, through a distributionally robust optimization approach. We assume that the first and second order moments of stochastic parameters can be inferred from historical data, and then employed to model the set of probability distributions. The resulting problem is a two-stage distributionally robust unit commitment with second order moment constraints, and we show that it can be recast as a mixed-integer semidefinite programming (MI-SDP) with finite constraints. The solution algorithm of the problem comprises solving a series of relaxed MI-SDPs and a subroutine of feasibility checking and vertex generation. Based on the verification of strong duality of the semidefinite programming (SDP) problems, we propose a cutting plane algorithm for solving the MI-SDPs; we also introduce a SDP relaxation for the feasibility checking problem, which is an intractable biconvex optimization. Experimental results on a IEEE 6-bus system are presented, showing that without any tunings of parameters, the real-time operation cost of distributionally robust UC method outperforms those of deterministic UC and two-stage robust UC methods in general, and our method also enjoys higher reliability of dispatch operation