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.     

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.     

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.     

Design and synthesis of a diverse morpholine template library

Efficient and general procedures have been developed for the solution-phase preparation of substituted morpholine derivatives, and a library has been produced around generic structure 1. This library was designed with proprietary modeling software for use as a general screening library. The 30 R1 reagents were phenols, and the 275 R2 reagents were taken from five different reagent classes, giving a variety of product classes in the final library of 8250 potential products. All of the library members were generated from a common intermediate, mesylate (5), which was synthesized efficiently, in bulk, in three steps from N-benzylethanolamine (2). High-throughput chemistry using robotics was carried out to produce the 7907 library members, which were individually characterized by reversed-phase LC/MS analysis.     

A Poly(cobaloxime)/Carbon Nanotube Electrode: Freestanding Buckypaper with Polymer‐Enhanced H2‐Evolution Performance

A freestanding H₂‐evolution electrode consisting of a copolymer‐embedded cobaloxime integrated into a multiwall carbon nanotube matrix by π–π interactions is reported. This electrode is straightforward to assemble and displays high activity towards hydrogen evolution in near‐neutral pH solution under inert and aerobic conditions, with a cobalt‐based turnover number (TON_Co) of up to 420. An analogous electrode with a monomeric cobaloxime showed less activity with a TON_Co of only 80. These results suggest that, in addition to the high surface area of the porous network of the buckypaper, the polymeric scaffold provides a stabilizing environment to the catalyst, leading to further enhancement in catalytic performance. We have therefore established that the use of a multifunctional copolymeric architecture is a viable strategy to enhance the performance of molecular electrocatalysts.     

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.     

Ruthenium(II) ammine and hydrazine complexes with [N(Ph2PQ)2]- (Q = S, Se) ligands

Reactions of coordinatively unsaturated Ru[N(Ph2PQ)2]2(PPh3) (Q = S (1), Se (2)) with pyridine (py), SO2, and NH3 afford the corresponding 18e adducts Ru[N(Ph2PQ)2]2(PPh3)(L) (Q = S, L = NH3 (5); Q = Se, L = py (3), SO2 (4), NH3 (6)). The molecular structures of complexes 2 and 6 are determined. The geometry around Ru in 2 is pseudo square pyramidal with PPh3 occupying the apical position, while that in 6 is pseudooctahedral with PPh3 and NH3 mutually cis. The Ru-P distances in 2 and 6 are 2.2025(11) and 2.2778(11) A, respectively. The Ru-N bond length in 6 is 2.185(3) A. Treatment of 1 or 2 with substituted hydrazines L or NH2OH yields the respective adducts Ru[N(Ph2PQ)2]2(PPh3)(L) (Q = S, L = NH2NH2 (12), t-BuNHNH2 (14), l-aminopiperidine (C5H10NNH2) (15); Q = Se, L = PhCONHNH2 (7), PhNHNH2 (8), NH2OH (9), t-BuNHNH2 (10), C5H10NNH2 (11), NH2NH2 (13)), which are isolated as mixtures of their trans and cis isomers. The structures of cis-14 and cis-15 are characterized by X-ray crystallography. In both molecular structures, the ruthenium adopts a pseudooctahedral arrangement with PPh3 and hydrazine mutually cis. The Ru-N bond lengths in cis-14.CH2Cl2 and cis-15 are 2.152(3) and 2.101(3) A, respectively. The Ru-N-N bond angles in cis-14.CH2Cl2 and cis-15 are 120.5(4) and 129.0(2) degrees, respectively. Treatment of 1 with hydrazine monohydrate leads to the isolation of yellow 5 and red trans-Ru[N(Ph2PS)2]2(NH3)(H2O) (16), which are characterized by mass spectrometry, 1H NMR spectroscopy, and elemental analyses. The geometry around ruthenium in 16 is pseudooctahedral with the NH3 and H2O ligands mutually trans. The Ru-O and Ru-N bond distances are 2.118(4) and 2.142(6) A, respectively. Oxidation reactions of the above ruthenium hydrazine complexes are also studied.     

Periodic optimal control for parabolic Volterra-Lotka type equations

This paper considers the optimal harvesting control of a biological species, whose growth is governed by the parabolic diffusive Volterra-Lotka equation. We prove that such equation with L^∞ periodic coefficients has an unique positive periodic solution. We show the existence and uniqueness of an optimal control, and under certain conditions, we characterize the optimal control in terms of a parabolic optimality system. A monotone sequence which converges to the optimal control is constructed.     

Carbazole-oxadiazole containing polyurethanes as phosphorescent host for organic light emitting diodes

New types of polyurethanes (PUs) were prepared from condensation polymerization of isophorone diisocyanate (IPDI) with various combination of 9-butyl-3,6-bis(4-hydroxyphenyl)carbazole (Cz) and 2,5-bis(4-hydroxyphenyl)-1,3,4-oxadiazole (OXD), and end-capped with 4-tert-butyl phenol. The Cz-OXD PUs can also be used as host for phosphorescent dye. Red EL emission was obtained when Ir(btp)₂(acac) or Ir(2-phq)₂(acac) was used as the phosphorescent dyes in Cz-OXD (3:1) PU. Maximum brightness of 394 cd/m² and EL efficiency of 1 cd/A were achieved for the Ir(2-phq)₂(acac) base device. In addition, white light PLED was demonstrated when co-dopant of Ir(btp)₂(acac) and Firpic were used.