Tradition- and science-based quality control of Chinese medicines--introducing the Phyto-True system

The current QC practice of quantifying presumed active chemicals or arbitrarily selected chemical markers is of doubtful value in assessing multicomponent complex traditional Chinese medicines (CMs) and often leads to an inconsistent or irreproducible research and clinical outcome. Consequently, the first and most important step in the QC of CMs (or other botanical medicines) whose exact active chemical components are unknown is to use analytical techniques that can comprehensively define the totality of the components/attributes making up their identity and quality. One of the most versatile techniques is HPTLC. Using HPTLC, along with other simple techniques such as FTIR spectroscopy and UV-Vis spectroscopy combined with complementary gene expression profiling, we have been able to correctly identify CM materials, detect adulterants, and differentiate closely related materials and botanical species. Our research has resulted in the introduction of the concept and specimens of Phyto-True Reference Material (PTRM), aka Representative Botanical Reference/Research Material (RBRM), now commercially available, and a novel patent-pending technology (Phyto-True system) that can serve as a starting point for the meaningful QC of traditional CMs so far not possible for these complex materials. Examples will be highlighted to demonstrate this new concept.     

Selection of aptamers for signal transduction proteins by capillary electrophoresis

High‐affinity aptamers for important signal transduction proteins, i.e. Cdc42‐GTP, p21‐activated kinase1 (PAK1) and MRCK (myotonic dystrophy kinase‐related Cdc42‐binding kinase) α were successfully selected in the low micro‐ to nanomolar range using non‐systematic evolution of ligands by exponential enrichment (SELEX) with at least three orders of magnitude enhancement from their respective bulk affinity of naïve DNA library. In the non‐SELEX procedure, CE was used as a highly efficient affinity method to select aptamers for the desired molecular target through a process that involved repetitive steps of partitioning, known as non‐equilibrium CE of equilibrium mixtures with no PCR amplification between successive steps. Various non‐SELEX conditions including the type, concentration and pH of the run buffer were optimized. Other considerations such as salt composition of selection buffer, protein concentration and sample injection size were also studied for high stringency during selection. After identifying the best enriched aptamer pool, randomly selected clones from the aptamer pool were sequenced to obtain the individual DNA sequences. The dissociation constants (K_d) of these sequences were in the low micromolar to nanomolar range, indicating high affinity to the respective proteins. The best binders were also subjected to sequence alignment to generate a phylogenetic tree. No significant consensus region based on approximately 50 sequences for each protein was observed, suggesting the high efficiency of non‐SELEX for the selection of numerous unique sequences with high selectivity.     

Manufacturer’s revenue-sharing contract and retail competition

This paper investigates a revenue-sharing contract for coordinating a supply chain comprising one manufacturer and two competing retailers. The manufacturer, as a Stackelberg leader, offers a revenue-sharing contract to two competing retailers who face stochastic demand before the selling season. Under the offered contract terms, the competing retailers are to determine the quantities to be ordered from the manufacturer, prior to the season, and the retail price at which to sell the items during the season. The process of pricing and ordering is expected to result in an equilibrium as in the Bayesian Nash game. On the basis of anticipated responses and actions of the retailers, the manufacturer designs the revenue-sharing contract. Adopting the classic newsvendor problem model framework and using numerical methods, the study finds that the provision of revenue-sharing in the contract can obtain better performance than a price-only contract. However, the benefits earned under the revenue-sharing contract by different supply chain partners differ because of the impact of demand variability and price-sensitivity factors. The paper also analyses the impact of demand variability on decisions about optimal retail price, order quantity and profit sharing between the manufacturer and the retailers. Lastly, it investigates how the competition (between retailers) factor influences the decision-making of supply chain members in response to uncertain demand and profit variability.     

Photo-activated pheophorbide a inhibits the growth of prostate cancer cells

Pheophorbide a (PhA) was identified as a photosensitizer to exert cytotoxicity on tumor cells. However, the efficacy of this compound on the treatment of prostate cancer remains unknown. The aim of this study was to evaluate the photodynamic effect of PhA on prostate cancer cells. Cellular uptake of PhA and cell viability after photo-activation was studied in LNCaP prostate cancer cells. The corresponding production of reactive oxygen species within cells was determined after photodynamic therapy (PDT). Our results showed that the uptake of PhA into LNCaP cells was in a time-dependent manner and the cytotoxicity of PhA-PDT was photosensitizer dose- and light dose-dependent. The intracellular reactive oxygen species was remarkably induced after PDT treatment, which was responsible for the inhibition effect on prostate cancer cells. This is the first report to evaluate the photodynamic effect of PhA on prostate cancer. Our findings demonstrate that PhA-PDT may be a potentially promising treatment for localized prostate cancer, which can be a therapeutic option after the failures of radiotherapy and hormone therapy.     

An Eulerian approach for computing the finite time Lyapunov exponent

We propose efficient Eulerian methods for approximating the finite-time Lyapunov exponent (FTLE). The idea is to compute the related flow map using the Level Set Method and the Liouville equation. There are several advantages of the proposed approach. Unlike the usual Lagrangian-type computations, the resulting method requires the velocity field defined only at discrete locations. No interpolation of the velocity field is needed. Also, the method automatically stops a particle trajectory in the case when the ray hits the boundary of the computational domain. The computational complexity of the algorithm is O(Δx^?(d+1)) with d the dimension of the physical space. Since there are the same number of mesh points in the x–t space, the computational complexity of the proposed Eulerian approach is optimal in the sense that each grid point is visited for only O(1) time. We also extend the algorithm to compute the FTLE on a co-dimension one manifold. The resulting algorithm does not require computation on any local coordinate system and is simple to implement even for an evolving manifold.     

A grid based particle method for solving partial differential equations on evolving surfaces and modeling high order geometrical motion

We develop numerical methods for solving partial differential equations (PDE) defined on an evolving interface represented by the grid based particle method (GBPM) recently proposed in [S. Leung, H.K. Zhao, A grid based particle method for moving interface problems, J. Comput. Phys. 228 (2009) 7706–7728]. In particular, we develop implicit time discretization methods for the advection–diffusion equation where the time step is restricted solely by the advection part of the equation. We also generalize the GBPM to solve high order geometrical flows including surface diffusion and Willmore-type flows. The resulting algorithm can be easily implemented since the method is based on meshless particles quasi-uniformly sampled on the interface. Furthermore, without any computational mesh or triangulation defined on the interface, we do not require remeshing or reparametrization in the case of highly distorted motion or when there are topological changes. As an interesting application, we study locally inextensible flows governed by energy minimization. We introduce tension force via a Lagrange multiplier determined by the solution to a Helmholtz equation defined on the evolving interface. Extensive numerical examples are also given to demonstrate the efficiency of the proposed approach.     

Transport properties of Pr0.7Ca0.3MnO3/Nb:SrTiO3 heterojunctions

Current–voltage (J–V) characteristics of epitaxial hetero-junctions composed of Pr_0.7Ca_0.3MnO₃ and Nb:SrTiO₃ were studied under forward and reversed bias conditions. Detailed analysis showed that the J–V characteristics of these heterojunctions can be well-fitted by the thermally-assisted tunnelling model. While the dielectric constant of Nb:SrTiO₃ extracted under the forward bias was about one order of magnitude smaller than that of bulk SrTiO₃, the value obtained under reverse bias was very close to that of the bulk SrTiO₃. The result can be explained by the existence of an interface layer on the Nb:SrTiO₃ substrate with a smaller effective dielectric constant. The current finding suggested that the properties of interface layer should be taken into account in order to accurately simulate the J–V characteristics of such heterojunctions.     

Characterization of silicon nanophotonic devices using the finite element method

The Poynting vector and the full-vectorial H and E-field profiles are considered for use in nanoscale silicon waveguides in this article. This paper reveals that the mode profile of a circular silicon nanowire is not circular and also has a strong axial field component. From the analysis, the characteristics of single mode operation and the vector field profiles of both circular and planar silicon nanowires are presented. The modal birefringence of rectangular silicon nanowires and power density in low-index region of a slot-type waveguide and designs of a compact polarization rotator are also presented in this work.     

First synthesis of dioxadithiaporphycene with a benzene ring fused onto the double bond

Dioxadithiaporphycenes 5 and 5′ were synthesized by using the Suzuki cross-coupling and McMurry coupling reactions as the key steps. This approach provided an access to the first dioxadithiaporphycene derivative 15 with a benzene ring fused onto the double bond.