Preclinical anticancer activity of DNA-based cleavage molecules

Deoxyribozymes (DNAzymes) are DNA residue-based molecules capable of specific cleavage of complementary mRNA. As such, they are more stable counterparts for the earlier discovered ribozymes. A handful of studies have shown the potential of DNAzymes against cancer both in cell culture and importantly in vivo models. This relatively new molecular entity may progress to clinical trials provided that more extensive testing is carried out at the preclinical stage. While a significant amount of work has gone into chemically stabilizing the molecule, delivery is one area that needs particular attention.     

Cooperative enhancement of deoxyribozyme activity by chemical modification and added cationic copolymer

Deoxyribozymes (DNAzymes) having RNA-cleaving activity have widely been explored as tools for therapeutic and diagnostic purposes. Both the chemical cleaving step and the turnover step should be improved for enhancing overall activity of DNAzymes. We have shown that cationic copolymer enhanced DNAzyme activity by increasing turnover efficacy. In this paper, effectｓ of the copolymer on DNAzymes modified with locked nucleic acids (LNA) or 2′-O-methylated (2′-OMe) nucleic acids were studied. The copolymer increased activity of these chemically modified DNAzymes. More than 30-fold enhancement in multiple-turnover catalytic activity was observed with 2′-OMe-modified DNAzyme in the presence of the copolymer. DNAzyme catalytic activity was successfully enhanced by cooperation of the added copolymer and chemical modification of DNAzyme.     

Artificial Engineered Natural Killer Cells Combined with Antiheat Endurance as a Powerful Strategy for Enhancing Photothermal‐Immunotherapy Efficiency of Solid Tumors

Although photothermal therapy (PTT) is preclinically applied in solid tumor treatment, incomplete tumor removal of PTT and heat endurance of tumor cells induces significant tumor relapse after treatment, therefore lowering the therapeutic efficiency of PTT. Herein, a programmable therapeutic strategy that integrates photothermal therapeutic agents (PTAs), DNAzymes, and artificial engineered natural killer (A‐NK) cells for immunotherapy of hepatocellular carcinoma (HCC) is designed. The novel PTAs, termed as Mn‐CONASHs, with 2D structure are synthesized by the coordination of tetrahydroxyanthraquinone and Mn²⁺ ions. By further adsorbing polyetherimide/DNAzymes on the surface, the DNAzymes@Mn‐CONASHs exhibit excellent light‐to‐heat conversion ability, tumor microenvironment enhanced T₁‐MRI guiding ability, and antiheat endurance ability. Furthermore, the artificial engineered NK cells with HCC specific targeting TLS11a‐aptamer decoration are constructed for specifically eliminating any possible residual tumor cells after PTT, to systematically enhance the therapeutic efficacy of PTT and avoid tumor relapse. Taken together, the potential of A‐NK cells combined with antiheat endurance as a powerful strategy for immuno‐enhancing photothermal therapy efficiency of solid tumors is highlighted, and the current strategy might provide promising prospects for cancer therapy.     

Functional DNAzymes organized into two-dimensional arrays

DNAzymes are catalytically active DNA molecules, which have previously been described in solution. Here, we organize these molecules into a series of two-dimensional (2D) arrays using a periodic arrangement of DNA structures based on the DNA double crossover motif. We demonstrate by means of atomic force microscopy that the DNAzymes are organized according to the design and that they retain their activity when attached in linear strings within the context of the 2D array.     

Entrapment of fluorescence signaling DNA enzymes in sol-gel-derived materials for metal ion sensing

Three fluorescence signaling DNA enzymes (deoxyribozymes or DNAzymes) were successfully immobilized within a series of sol-gel-derived matrixes and used for sensing of various metal ions. The DNAzymes are designed such that binding of appropriate metal ions induces the formation of a catalytic site that cleaves a ribonucleotide linkage within a DNA substrate. A fluorophore (fluorescein) and a quencher (DABCYL, [4-(4-dimethylaminophenylazo)benzoic acid]) were placed on the two deoxythymidines flanking the ribonucleotide to allow the generation of fluorescence upon the catalytic cleavage at the RNA linkage. In general, all DNAzymes retained at least partial catalytic function when entrapped in either hydrophilic or hydrophobic silica-based materials, but displayed slower response times and lower overall signal changes relative to solution. Interestingly, it was determined that maximum sensitivity toward metal ions was obtained when DNAzymes were entrapped into composite materials containing approximately 40% of methyltrimethoxysilane (MTMS) and approximately 60% tetramethoxysilane (TMOS). Highly polar materials derived from sodium silicate, diglycerylsilane, or TMOS had relatively low signal enhancements, while materials with very high levels of MTMS showed significant leaching and low signal enhancements. Entrapment into the hybrid silica material also reduced signal interferences that were related to metal-induced quenching; such interferences were a significant problem for solution-based assays and for polar materials. Extension of the solid-phase DNAzyme assay toward a multiplexed assay format for metal detection is demonstrated, and shows that sol-gel technology can provide new opportunities for the development of DNAzyme-based biosensors.     

Gelation theory for solutions of polymers with loci of strong interaction

This paper presents a statistical mechanical analysis of gelation in certain solutions ofA/B copolymers. Repeat unitsA, the major units, must constitute about 90 mole% or more of the copolymer, and are compatible with the solvent. Repeat unitsB, the minor units, must be totally incompatible with the solvent and represent loci of strong interaction between the macromolecular chains. If these interactions are sufficiently strong they can lead to gelation of the mixture. The following simplifications of the model afford results that can be expressed in simple, closed form: (1) TheB units are uniformly distributed along the chain backbone. (2) Polymer concentration must be greater then that for chain overlap. (3)B–B interactions lead to dimerization ofB units only. Examples include: (1) Any aqueous polymer solution where theA repeat units are hydrophilic and theB repeat units are hydrophobic;B–B interactions are thus by hydrophobic bonding. (2) Neutralized acrylic acid/acrylamide copolymers where theB are acrylamide repeat units which associate by hydrogen bonds. (3) Ionomer solutions whereB–B bonding is by dipole-dipole interaction. The results show that there is a critical copolymer concentration for gel formation, C _c . It turns out that C _c decreases withB content for low dimerization energies and increases withB content for higher dimerization energies. At intermediate dimerization energies, C _c is insensitive to theB content. The two extreme regimes of behavior are similar to contradictory predictions of previously published theories. Received: 18 September 2000 / Reviewed and accepted: 20 September 2000     

Load–bearing behaviour and simulation of textile reinforced concrete

The new composite material Textile Reinforced Concrete (TRC) is a promising development which may open up entirely new fields for the application of the construction material concrete. The possible more filigree structures with high quality surfaces make TRC an attractive choice for the architect and give the engineer more freedom in design. However, the use of TRC requires design rules which are currently being developed at RWTH Aachen University, Germany. In this article, recent experimental results as well as modeling techniques are described.     

Some Comments on Designs for Cox's Mixture Polynomial

Designs are suggested for estimating the restricted parameters in Cox's mixture polynomial. The variances of the restricted estimates of the parameters are minimum when using the simplex-lattice designs suggested by Scheffé The precision of the estimates, in terms of their variances, as affected by the location of the design points as well as the location of the standard mixture s is also discussed. It is shown for the vertex design centered at s that if s is positioned on the axis of an individual component, the closer s lies to the vertex of the simplex representing the individual component, the more precise will be the parameter estimates associated with the individual component relative to the other components. A numerical example is presented to illustrate the difference in the interpretations given to the parameter estimates associated with the Cox polynomial and the Scheffé polynomial.     

Thermodynamic Characteristics of Uranyl Benzenesulfonate and p-Toluenesulfonate

The enthalpies of solution of anhydrous and hydrated uranyl benzenesulfonate (I) and p-toluenesulfonate II) in 4 M HCl were determined. The standard enthalpies of formation of I and II and their crystal hydrates from uranium trioxide, sulfonic acids, and water and enthalpies of water addition to anhydrous salts and lower hydrates of II were calculated. The enthalpy of addition of water molecule to II·H₂O is about half that of addition to II·3H₂O. With regard to all approximations in calculations, the enthalpy of formation of II from amorphous uranium trioxide and aqueous solution of the corresponding acid is by approximately 20 kJ mol^{- 1} more negative as compared to I. It was concluded that the electron-donor power of the p-toluenesulfonate ion is noticeably greater than that of the benzenesulfonate ion, which determines the difference in the properties of II and I.     

Identification of singular interfaces with Δ<Emphasis Type="Bold">g</Emphasis>s and its basis of the O-lattice

This article identifies singular interfaces according to singularity in terms of structural defects, including dislocations and ledges. Defect singularities are defined by the elimination of one or more classes of defects, which must be present in the vicinal interfaces. In addition to the three commonly classified structural interfaces, a new type of interface—the CS-coherent interface—is introduced. Singularities in dislocation and ledge structures have been integrated in the study of orientation relationships (OR). The dislocation structures are determined through the O-lattice theory, originally proposed by Bollmann. The basic concepts of the O-lattice and related formulas from the original theory and extended studies are briefly reviewed. According to the theory, singular interfaces exhibiting singularity in the dislocation structures have been identified. An interface that is singular with respect to the interface orientation must be normal to at least one Δg, a vector connecting two reciprocal points from different lattices. An interface that is singular also with respect to the OR must obey one or more Δg parallelism rules. The selection of proper Δgs for different preferred states of interfaces are explained. Identification of singular interfaces with measurable Δgs provides a convenient and effective approach to the interpretation of the observed facets and ORs. The ambiguity about the selection of the deformation matrix (A) for the O-lattice calculation and the advantage of the O-lattice approach over the approach using the Frank–Bilby equation for the calculation of the interfacial dislocations are clarified. Limitations of the present approach and further study are discussed.     

A methodology for fatigue crack growth and residual strength prediction with applications to aircraft fuselages

The FRANC3D/STAGS software system has been developed to model curvilinear crack growth in aircraft fuselages. Simulations of fatigue crack growth have been reported previously (Potyondy et al. 1995). This paper presents two enhancements to this system. One is the generalization of the representation of cracks that allows the system to represent realistic damaged structures more accurately. With this capability, parameters that may affect the trajectory of a fatigue crack are studied. Results are compared with measurements from a full-scale test. The second enhancement is to model stable tearing for residual strength prediction. A stable tearing simulation along a crack path that captures the material nonlinearities inherent at the crack tip is performed. The CTOA (Crack Tip Opening Angle) is used as a crack growth criterion to characterize the fracture process under conditions of general yielding. Residual strength of cracked structures is predicted.     

Scheduling flexible manufacturing cells using Tabu Search

Scheduling is an important aspect in the overall control of a flexible manufacturing system. The research presented focuses on production scheduling of jobs within a flexible manufacturing cell (FMC)–one type of flexible manufacturing system. Due to the complexity of the FMC scheduling problem, a 0–1 mixed-integer linear programming (MILP) model is formulated for M machines and N jobs with alternative routings. Although small instances of the problem can be solved optimally with MILP models, a two-stage Tabu Search (TS² ) algorithm that minimises the manufacturing makespan (MS) is proposed to solve medium-to-large-scale problems more efficiently. During Stage I (construction phase), two heuristics are utilised to generate an initial feasible sequence and an initial MS solution. In Stage II (improvement phase), the acquired initial solutions from Stage I are combined with a Tabu Search meta-heuristic procedure that provides improved MS solutions. The TS² algorithm provides tremendous savings in computational time for medium/large-sized multi-machine FMC problems.     

IR and Raman spectroscopic studies of sol–gel derived alkaline-earth silicate glasses

IR and Raman spectroscopies have been utilized to study the structure and vibrational modes of sol–gel-derived binary silicate glasses. The present study is motivated by the immense geological significance and focuses on the MO–SiO ₂ (M = Ca, Mg) binary systems in an effort to unveil the role of the CaO and MgO modifiers when incorporated to the 3D silica structure. Glasses in the composition range x =0, 0·1, 0·2, 0·3 and 0·4 prepared by the sol–gel method were compared with the corresponding glasses formed by appropriate mixing of SiO ₂ and MO powders through melting and fast cooling. The vibrational spectra of the sol–gel-derived glasses have revealed considerable changes in relative intensities as a function of the MO mole fraction. These changes signify structural modifications on the silica network. The population of the Q ³ species was found to increase for both modified silicate systems. The rate of increase is more pronounced in the CaO–SiO ₂ glasses. The extent of network depolymerization in the porous glass is higher at the same content of alkaline earth oxide compared to the bulk glass. The results are indicative of a more ‘defective’ nature of the sol–gel glasses compared to the corresponding melt-quenched ones.     

Total energy calculation of perovskite,BaTiO<Subscript>3</Subscript>, by self-consistent tight binding method

We present results of numerical computation on some characteristics of BaTiO3 such as total energy, lattice constant, density of states, band structure etc using self-consistent tight binding method. Besides strong Ti-O bond between 3 d on titanium and 2 p orbital on oxygen states, we also include weak hybridization between the Ba 6 s and O 2 p tates. The results are compared with those of other more sophisticated methods.     

On foundational aspects of optical quantum communication

ABSTRACT

Using a simple model of the quantized photon field in an optical fibre we suggest a model of quantum teleportation of continuous variables which is more realistic than the usual one in the sense that the localization properties of the quantities to be teleported are taken into account.     

Biaxial buckling analysis of double-orthotropic microplate-systems including in-plane magnetic field based on strain gradient theory

Background/purposeThis paper deals with analysis of biaxial buckling behavior of double-orthotropic microplate system including in-plane magnetic field, using strain gradient theory.MethodsTwo Kirchhoff microplates are coupled by an internal elastic medium and also are limited to the external Pasternak elastic foundation. Utilizing the principle of total potential energy, the equilibrium equations of motion for three cases (out-of-phase buckling, in-phase buckling and buckling with a plate) are acquired. In this study, we assumed boundary conditions of all the edges are simply supported. In order to get exact solution for buckling load of system, Navier approach which satisfies the simply supported boundary conditions is applied.ResultsVariations of the buckling load of double-microplate system subjected to biaxial compression corresponding to various values of the thickness, length scale parameter, magnetic field, stiffness of internal and external elastic medium, aspect ratio, shear stiffness of the Pasternak foundation and biaxial compression ratio are investigated. Furthermore, influence of higher modes on buckling load is shown. By comparing the numerical results, it is found that dimensionless buckling load ratio for in-phase mode is more than those of out of phase and one microplate fixed. Also it is shown that the value of buckling load ratio reduces, when non-dimensional length scale parameter increases.ConclusionHowever, we found when properties of plate are orthotropic the buckling load ratio is more than isotropic state. Also, by considering the effect of magnetic field, non-dimensional buckling load ratio reduces.     

Statistical Analysis for Decision Making

In this article we consider a generalization of the univariate g-and-h distribution to the multivariate situation with the aim of providing a flexible family of multivariate distributions that incorporate skewness and kurtosis. The approach is to modify the underlying random variables and their quantiles, directly giving rise to a family of distributions in which the quantiles rather than the densities are the foci of attention. Using the ideas of multivariate quantiles, we show how to fit multivariate data to our multivariate g-and-h distribution. This provides a more flexible family than the skew-normal and skew-elliptical distributions when quantiles are of principal interest. Unlike those families, the distribution of quadratic forms from the multivariate g-and-h distribution depends on the underlying skewness. We illustrate our methods on Australian athletes data, as well as on some wind speed data from the northwest Pacific.     

The dynamic characteristics of taper seals

Abstract

The dynamic characteristics of taper seal has been investigated. The approach is similar to Black's analysis; the stiffness and damping coefficients are derived. The results showed that the taper seals presented more stable characteristics comparing with plain seals. The practical application of this theory is increasingly used in industry.     

Computation of X-ray powder diffractograms of cement components and its application to phase analysis and hydration performance of OPC cement

The importance of computed X-ray diffraction patterns of various polymorphs of alite (M₃, T₁, R{\bf \emph{M}_{3}, \emph{T}_{1}, \emph{R}}), belite (b\boldsymbol{\beta}, g\boldsymbol{\gamma}), aluminate (cubic, orthorhombic), aluminoferrite, gypsum and hemihydrate in the quantitative phase analysis of cement and its early stage hydration performance is highlighted in this work with three OPC samples. The analysis shows that the predominant silicate phases present in all the samples are M₃{\bf \emph{M}_{3}}-alite phase and b\boldsymbol{\beta}-belite phase, respectively. Both cubic and orthorhombic phases of C ₃ A, brownmillerite, gypsum and hemihydrates are present at different levels. Quantitative phase analysis of cement by Rietveld refinement method provides more accurate and comprehensive data of the phase composition compared to Bogue method. The comparative hydration performance of these samples was studied with w/c{\bf \emph{w/c}} ratio, 0·5 and the results are interpreted in the light of difference in phase compositions viz. b\boldsymbol{\beta}-C ₂ S/C ₃ S ratio, fraction of finer cement particles present in the samples and theoretical modeling of C ₃ S hydration.     

1,3-dimethyl-6-nitroacridine derivatives induce apoptosis in human breast cancer cells by targeting DNA

The acridine derivatives can interact with the double-stranded DNA, which is regarded as the biological target of the anticancer drugs in cancer treatment. We designed and synthesized a new series of 1,3-dimethyl-6-nitroacridine derivatives as potential DNA-targeted anticancer agents. These compounds could partially intercalate into the calf thymus DNA, differing from the parent acridine. The results showed that the substitutions of the acridine ring had great effect on DNA binding affinity. The binding constants determined by UV-vis spectroscopy were found to be 10⁵?M^?1 grade. Anticancer activity of these compounds was screened using MTT assay. Most compounds inhibited 50% cancer cell growth at concentration below 30?μM, the results were consistent with the DNA binding ability. Compounds 1 and 6 were found to have more effective cytotoxicity, especially in human breast cancer cell lines. To investigate the action mechanism, we studied cell apoptosis, morphological changes, and cell cycle distribution in MCF-7 and MDA-MB-231 cells. Compounds 1 and 6 caused MCF-7 and MDA-MB-231 cells death due to apoptosis, and induced cell apoptosis in a dose-dependent manner. They also had significant effect on cell cycle progression and arrested cell cycle at G2/M phase. The results demonstrated that compounds 1 and 6 are promising candidates for cancer treatment.