Trans-dichlorooxovandium (IV) complex as a novel photoinducible DNA interstrand crosslinker for cancer therapy

Although DNA interstrand crosslinking (ICL) agents such as mitomycin C, cisplatin and psoralen serve as potent anticancer drugs, these agents are known to have dose-limiting toxic effects on normal cells. Moreover, tumor resistance to these agents has been reported. Here, we show that trans-dichlorooxovanadium (IV) complex of pyrenyl terpyridine (VDC) is a novel photoinducible DNA crosslinking agent. By a combination of in vitro and ex vivo experiments including plasmid-based assays, we find that VDC forms monoadducts on the DNA and can be activated by UV-A and visible light to generate DNA interstrand crosslinks. VDC efficiently activates Fanconi anemia (FA) pathway of DNA interstrand crosslink repair. Strikingly, photoinduction of VDC induces prolonged activation of cell cycle checkpoint and a high degree of cell death in homologous recombination (HR)/ICL repair defective cells. Moreover, VDC specifically targets cells that express pathological RAD51C mutants. These data imply that VDC can be potentially used for cancer therapy and suggest that tumors arising in patients with gene mutations in FA and HR repair pathway can be specifically targeted by a photoactivatable VDC.

Mitochondrial selectivity and remarkable photocytotoxicity of a ferrocenyl neodymium(III) complex of terpyridine and curcumin in cancer cells

A series of four novel neodymium(III) complexes of the formulation Nd(R-tpy)(O-O)(NO3)(2)] (1-4), where R-tpy is 4'-phenyl-2,2': 6', 2''-terpyridine (Ph-tpy; 1, 2) and 4'-ferrocenyl-2,2': 6', 2''-terpyridine (Fc-tpy; 3, 4); O-O is the conjugate base of acetylacetone (Hacac; 1, 3) or curcumin (Hcurc; 2, 4), are synthesized and characterized. The single crystal structure of 1 shows that the complex is a discrete mononuclear species with the Nd(III) centre in a nine coordinate environment provided by a set of O6N3 donor atoms. Complexes 1 and 3 having the simple acac ligand are prepared as control compounds. Complex 4, possessing an appended ferrocenyl (Fc) and the curcumin moiety, is remarkably photocytotoxic to HeLa and MCF-7 cancer cells in visible light giving respective IC50 values of 0.7 mu M and 2.1 mu M while being significantly less toxic to MCF-10A normal cells (IC50 = 34 mu M) and in the dark (IC50 > 50 mu M). The phenyl appended complex 2, lacking a ferrocenyl moiety, is significantly less toxic to both the cell lines when compared with 4. Complexes 1 and 3, lacking the photoactive curcumin moiety, do not show any apparent toxicity both in light and in the dark. The cell death is apoptotic in nature and is mediated by the light-induced formation of reactive oxygen species (ROS). Fluorescence imaging experiment with HeLa cells reveals mitochondrial accumulation of complex 4 within 4 h of incubation. The complexes bind to calf thymus (ct) DNA with moderate affinity giving K-b values in the range of 10(4)-10(5) M-1. The curcumin complexes 2 and 4 cleave plasmid supercoiled DNA to its nicked circular form in visible light via O-1(2) and (OH)-O-center dot pathways. The presence of the ferrocenyl moiety is likely to be responsible for the enhanced cellular uptake and photocytotoxicity of complex 4. Thus, the mitochondria targeting complex 4, being remarkably cytotoxic in light but non-toxic in the dark and to normal cells, is a potential candidate for photochemotherapeutic applications.

Complex potentials and singular integral equation for curve crack problem in antiplane elasticity

Four types of the fundamental complex potential in antiplane elasticity are introduced: (a) a point dislocation, (b) a concentrated force, (c) a dislocation doublet and (d) a concentrated force doublet. It is proven that if the axis of the concentrated force doublet is perpendicular to the direction of the dislocation doublet, the relevant complex potentials are equivalent. Using the obtained complex potentials, a singular integral equation for the curve crack problem is introduced. Some particular features of the obtained singular integral equation are discussed, and numerical solutions and examples are given.

Anisotropic thermopiezoelectric solids with an elliptic inclusion or a hole under uniform heat flow

The two-dimensional problem of a thermopiezoelectric material containing an elliptic inclusion or a hole subjected to a remote uniform heat flow is studied. Based on the extended Lekhnitskii formulation for thermopiezoelectricity, conformal mapping and Laurent series expansion, the explicit and closed-form solutions are obtained both inside and outside the inclusion (or hole). For a hole problem, the exact electric boundary conditions on the hole surface are used. The results show that the electroelastic fields inside the inclusion or the electric field inside the hole are linear functions of the coordinates. When the elliptic hole degenerates into a slit crack, the electroelastic fields and the intensity factors are obtained. The effect of the heat how direction and the dielectric constant of air inside the crack on the thermal electroelastic fields are discussed. Comparison is made with two special cases of which the closed solutions exist and it is shown that our results are valid.

Large Eddy Simulation of Complex Turbulent Flows: Physical Aspects and Research Trends

In the current paper, we have primarily addressed one powerful simulation tool developed during the last decades-Large Eddy Simulation (LES), which is most suitable for unsteady three-dimensional complex turbulent flows in industry and natural environment. The main point in LES is that the large-scale motion is resolved while the small-scale motion is modeled or, in geophysical terminology, parameterized. With a view to devising a subgrid-scale(SGS) model of high quality, we have highlighted analyzing physical aspects in scale interaction and-energy transfer such as dissipation, backscatter, local and non-local interaction, anisotropy and resolution requirement. They are the factors responsible for where the advantages and disadvantages in existing SGS models come from. A case study on LES of turbulence in vegetative canopy is presented to illustrate that LES model is more based on physical arguments. Then, varieties of challenging complex turbulent flows in both industry and geophysical fields in the near future-are presented. In conclusion; we may say with confidence that new century shall see the flourish in the research of turbulence with the aid of LES combined with other approaches.

Copper homeostasis in Salmonella is atypical and copper-CueP is a major periplasmic metal complex.

Salmonella enterica sv. typhimurium (S. enterica sv. Typhimurium) has two metal-transporting P(1)-type ATPases whose actions largely overlap with respect to growth in elevated copper. Mutants lacking both ATPases over-accumulate copper relative to wild-type or either single mutant. Such duplication of ATPases is unusual in bacterial copper tolerance. Both ATPases are under the control of MerR family metal-responsive transcriptional activators. Analyses of periplasmic copper complexes identified copper-CueP as one of the predominant metal pools. Expression of cueP was recently shown to be controlled by the same metal-responsive activator as one of the P(1)-type ATPase genes (copA), and copper-CueP is a further atypical feature of copper homeostasis in S. enterica sv. Typhimurium. Elevated copper is detected by a reporter construct driven by the promoter of copA in wild-type S. enterica sv. Typhimurium during infection of macrophages. Double mutants missing both ATPases also show reduced survival inside cultured macrophages. It is hypothesized that elevated copper within macrophages may have selected for specialized copper-resistance systems in pathogenic microorganism such as S. enterica sv. Typhimurium.

Enhanced 10-Gbit/s link performance for directly Modulated complex-coupled DFB lasers via resonance frequency, damping rate, and chirp

This paper demonstrates the respective roles that combined index- and gain-coupling play in the overall link performance of distributed feedback (DFB) lasers. Their impacts on both static and dynamic properties such as slope efficiency, resonance frequency, damping rate, and chirp are investigated. Simulation results are compared with experimental data with good agreement. Transmission-oriented optimization is then demonstrated based on a targeted specification. The design tradeoffs are revealed, and it is shown that a modest combination of index- and gain-coupling enables optimum transmission at 10 Gbit/s.

Multiscale Coupling in Complex Mechanical Systems

Multiscale coupling attracts broad interests from mechanics, physics and chemistry to biology. The diversity and coupling of physics at different scales are two essential features of multiscale problems in far-from-equilibrium systems. The two features present fundamental difficulties and are great challenges to multiscale modeling and simulation. The theory of dynamical system and statistical mechanics provide fundamental tools for the multiscale coupling problems. The paper presents some closed multiscale formulations, e.g., the mapping closure approximation, multiscale large-eddy simulation and statistical mesoscopic damage mechanics, for two typical multiscale coupling problems in mechanics, that is, turbulence in fluids and failure in solids. It is pointed that developing a tractable, closed nonequilibrium statistical theory may be an effective approach to deal with the multiscale coupling problems. Some common characteristics of the statistical theory are discussed.

Pattern Recognition With Weighted Complex Networks

In this paper we introduce a weighted complex networks model to investigate and recognize structures of patterns. The regular treating in pattern recognition models is to describe each pattern as a high-dimensional vector which however is insufficient to express the structural information. Thus, a number of methods are developed to extract the structural information, such as different feature extraction algorithms used in pre-processing steps, or the local receptive fields in convolutional networks. In our model, each pattern is attributed to a weighted complex network, whose topology represents the structure of that pattern. Based upon the training samples, we get several prototypal complex networks which could stand for the general structural characteristics of patterns in different categories. We use these prototypal networks to recognize the unknown patterns. It is an attempt to use complex networks in pattern recognition, and our result shows the potential for real-world pattern recognition. A spatial parameter is introduced to get the optimal recognition accuracy, and it remains constant insensitive to the amount of training samples. We have discussed the interesting properties of the prototypal networks. An approximate linear relation is found between the strength and color of vertexes, in which we could compare the structural difference between each category. We have visualized these prototypal networks to show that their topology indeed represents the common characteristics of patterns. We have also shown that the asymmetric strength distribution in these prototypal networks brings high robustness for recognition. Our study may cast a light on understanding the mechanism of the biologic neuronal systems in object recognition as well.