Cytotoxic Activities of Bis-cyclometalated M(III) Complexes (M=Rh, Ir) Containing 5-substituted 1,10-Phenanthroline or 4,4'-substituted 2,2'-Bipyridine Ligands

The synthesis and characterization of eight new bis-cyclometalated compounds [M(ptpy)(2)(NN)]PF6 (ptpy=2-(p-tolyl)pyridinato;NN=5-chloro-1,10-phenanthroline: M=Rh, 1;M=Ir, 2);NN=5-methyl-1,10-phenanthroline: M=Rh, 3;M=Ir, 4;NN=4,4'-diphenyl-2,2'-bipyridine: M=Rh, 5;M=Ir, 6;NN=4,4'-diamino-2,2'-bipyridine: M=Rh, 7;M=Ir, 8) are described. All compounds were characterized by spectroscopic means. Additionally, the molecular structures of compounds 4, 5, 6, and 8 in the crystal were determined by single-crystal X-ray diffraction studies. To explore the cytotoxic properties of all new eight compounds, colorimetric assays (MTT assay) against prominent cancer cell lines, MCF-7 and HT-29, were performed. The determined IC50 values are in the low micromolar range, between 1.3-5.6 mu M. The most effective compounds are 1 and 2 with 5-chloro-substituted phenanthroline ligands, whereas the diamino-substituted bipyridine ligands (5 and 6) are the least cytotoxic compounds. The tested complexes showed a significant increase in cytotoxicity, up to 25-fold increase in MCF-7 cancer cells, and up to 60-fold increase in the HT-29 cell line compared to the established anticancer compound cisplatin under identical conditions

Inhibition of CRISPR-Cas9 ribonucleoprotein complex assembly by anti-CRISPR AcrIIC2

CRISPR-Cas adaptive immune systems function to protect bacteria from invasion by foreign genetic elements. The CRISPR-Cas9 system has been widely adopted as a powerful genome-editing tool, and phage-encoded inhibitors, known as anti-CRISPRs, offer a means of regulating its activity. Here, we report the crystal structures of anti-CRISPR protein AcrIIC2Nme alone and in complex with Nme1Cas9. We demonstrate that AcrIIC2Nme inhibits Cas9 through interactions with the positively charged bridge helix, thereby preventing sgRNA loading. In vivo phage plaque assays and in vitro DNA cleavage assays show that AcrIIC2Nme mediates its activity through a large electronegative surface. This work shows that anti-CRISPR activity can be mediated through the inhibition of Cas9 complex assembly

Cytotoxic Activities of Bis-cyclometalated Iridium(III) Complexes Containing Chloro-substituted kappa N-2-terpyridines

The synthesis and characterization of two new bis-cyclometalated compounds [Ir(ptpy)(2)(kappa N-2-terpy-C6H4Cl-p)]PF6 [terpy-C6H4Cl-p=4'-(4-chlorophenyl)-2,2':6',2''-terpyridine, (1)], and [Ir(ptpy)(2)(kappa N-2-terpy-Cl)]PF6 [terpy-Cl=4'-chloro-2,2':6',2''-terpyridine, (2);ptpy=2-(p-tolyl)pyridinato)] are described. The molecular structures of compounds 1 and 2 in the crystal were determined by single-crystal X-ray diffraction. 1 crystallized from dichloromethane/methanol/iso-hexane in the monoclinic space group P2/(n) and 2 from the same mixture of solvents in the triclinic space group P(-)1. Photophysical investigations on 1 and 2 revealed broad unstructured luminescence in the red spectral region with the emission maxima in dichloromethane at 620 and 630 nm respectively. To explore cytotoxic properties of compounds 1 and 2, a colorimetric assay (MTT assay) against prominent cancer cell lines, MCF-7 and HT-29, was performed. The determined IC50 values are in the low micromolar range (2-3 mu M). In comparison to cisplatin, the tested complexes 1 and 2 exhibit up to >20-fold (MCF-7) and >40-fold (HT-29) increase in biological activity

Strengthening double curved arch bridges by using extrados section augmentation method

Double curved arch bridges have played an important role in the history of bridge construction in China. The strengthening or retrofitting of this type of bridge has attracted a great deal of research attention in the Chinese bridge engineering community. In this paper, a novel strengthening method, i.e. the extrados section augmentation strengthening method (ESASM), has been reported. Firstly, the rationale behind this new method and the changes in internal forces after strengthening have been studied in details. A numerical optimization analysis was then performed to derive a strengthening design solution based on these results. Secondly, a trial use of this novel strengthening method in a double curved arch bridge has been reported. A numerical simulation was carried out to analyze the internal forces in the bridge both before and after it was strengthened. Results show that internal forces have been favourably redistributed after the bridge has been strengthened by using ESASM. Lastly, the adopted construction method and the strengthening effect for that project were described

On the performance of non-conforming finite elements for the upper bound limit analysis of plates

This is a preprint version of an article accepted for publication in International Journal for Numerical Methods in Engineering Copyright © 2012 John Wiley & Sons, Ltd.International audienceIn this paper, the upper bound limit analysis of thin plates in bending is addressed using various types of triangular finite elements for the generation of velocity fields and second order cone programming (SOCP) for the minimization problem. Three different C1-discontinuous finite elements are considered : the quadratic 6 node Lagrange triangle (T6), an enhanced T6 element with a cubic bubble function at centroid (T6b) and the cubic Hermite triangle (H3). Through numerical examples involving Johansen and von Mises yield criteria, it is shown that cubic elements (H3) give far better results in terms of convergence rate and precision than fully conforming elements found in the literature, especially for problems involving clamped boundaries

Comparison of in-plane and out-of-plane failure modes of masonry arch bridges using discontinuum analysis

This research aims to provide a better understanding of the structural behavior of masonry arch bridges using advanced modeling strategies. Two main contributions are achieved in this article; first, triggering mechanisms for the out of plane failure of spandrel walls are established; second, the influence of soil backfill on the behavior and strength of the bridges is presented through a comprehensive parametric study. Here, masonry arch bridges are modeled using a discontinuum approach, composed of discrete blocks, including also a continuum mesh to replicate infill material, adopting a framework of discrete element modeling. The equations of motion for each block are solved by an explicit finite-difference method, using the commercial software 3DEC. The results of the preliminary analyses are compared with analytical solutions and limit state analysis for validation purposes. Different arch bridge models, representing common geometrical properties in the northwest Iberian Peninsula are analyzed. Transverse effects, damage patterns and collapse mechanisms are discussed under different types of loading. The analysis demonstrated the severe capacity reduction due to spandrel wall failures and the importance of soil backfill in results, only possible by taking advantage of the performed numerical modeling strategy

Shaking table tests and numerical analyses on a scaled dry-joint arch undergoing windowed sine pulses

The damages occurred during recent seismic events have emphasised the vulnerability of vaulted masonry structures, one of the most representative elements of worldwide cultural heritage. Although a certain consensus has been reached regarding the static behaviour of masonry arches, still more efforts are requested to investigate their dynamic behaviour. In this regard, the present paper aims to investigate the performance of a scaled dry-joint arch undergoing windowed sine pulses. A feature tracking based measuring technique was employed to evaluate the displacement of selected points, shading light on the failure mechanisms and gathering data for the calibration of the numerical model. This was built according to a micro-modelling approach of the finite element method, with voussoirs assumed very stiff and friction interface elements. Comparisons with existing literature are also stressed, together with comments about scale effects.This work was partly financed by FEDER funds through the Competitivity Factors Operational Programme-COMPETE and by national funds through FCT-Foundation for Science and Technology within the scope of the Project POCI-01-0145-FEDER-007633.info:eu-repo/semantics/publishedVersio

Communicating data quality in a GIS environment

The GIS database is a digital representation of the real world. Any abstract of reality will contain discrepancies from its source. With traditional methods many of the problems are visible and the skilled map analyst makes the necessary adjustments and knows how far the information can be relied upon. With a Geographic Information System the equivalent operations are not transparent (the black box effect), usually the operators are no longer so skilled and the problems are largely invisible. The digital modelling has the potential to dramatically increase both the magnitude and importance of errors in the models. The results may be used for decision making and planning despite possessing levels of uncertainty that are completely unknown and usually cannot even be guessed. That is why the accuracy analysis is one of the most important problems in the development and applications of the system. Currently there are several demands from users of data to include quality parameters in the related GIS databases. A number of researchers have done work on the derivation of data quality especially on positional or geometrical accuracies. However there has been little work done on qualitative or semantic accuracies and ways of communicating them. A major contribution toward standardizing the definition, assessment and reporting of GIS data quality has been made by the Data Set Quality Working Group of the National Committee for Digital Cartographic Data Standards. This research, provides an overview of the data quality factors that should be considered when using geographic information, and is intended to explore the possibility of generating and communicating data quality in various ways in a GIS environment. Suitable algorithms, .mainly concerning positional and attribute accuracy assessments, were adopted from relevant literature to determine the data quality parameters at different levels of abstraction, for different data types. The levels of abstraction. considered were overall accuracy parameters at coverage level and specific accuracy parameters referring to entity level. To communicate the data quality to the user different methods such as numerical, graphical and textual messages were adopted .The area for the case study is located in Kegalle district. The feasibility of the reported implementation was assessed by means of the referred case study. The results obtained with this case study were used to draw some conclusions and recommendations regarding the communication of, data quality in a GIS environment