Cytotoxicity of half sandwich ruthenium(II) complexes with strong hydrogen bond acceptor ligands and their mechanism of action

Neutral and cationic organometallic ruthenium(II) piano stool complexes of the type [(eta(6)-cymene)R-uCl(X)(Y)] (complexes R1-R8) has been synthesized and characterized. In cationic complexes, X, Y is either a eta(2) phosphorus ligand such as 1,1-bis(diphenylphosphino)methane (DPPM) and 1,2-bis(diphenylphosphino)ethane (DPPE) or partially oxidized ligands such as 1,2-bis(diphenylphosphino)methane monooxide (DPPMO) and 1,2-bis(diphenylphosphino)ethane monooxide (DPPEO) which are strong hydrogen bond acceptors. In neutral complexes. X is chloride and Y is a monodentate phosphorous donor. Complexes with DPPM and DPPMO ligands ([(eta(6)-cymene)Ru(eta(2)-DPPM)Cl]PF6 (R2), [(eta(6)-cymene)Ru(eta(2)-DPPMO)Cl]PF6 (R3), [(eta(6)-cymene)Ru(eta(1)-DPPM)Cl-2] (R5) and [(eta(6)-cymene)Ru(eta(1)-DPPMO)Cl-2] (R6) show good cytotoxicity. Growth inhibition study of several human cancer cell lines by these complexes has been carried out. Mechanistic studies for R5 and R6 show that inhibition of cancer cell growth involves both cell cycle arrest and apoptosis induction. Using an apoptosis PCR array, we identified the sets of antiapoptotic genes that were down regulated and pro-apoptotic genes that were up regulated. These complexes were also found to be potent metastasis inhibitors as they prevented cell invasion through matrigel. The complexes were shown to bind DNA in a non intercalative fashion and cause unwinding of plasmid DNA in cell-free medium by competitive ethidium bromide binding, viscosity measurements, thermal denaturation and gel mobility shift assays.

Assessing the effectiveness of school-based sexual abuse prevention programs

This article highlights the importance of systematic reviews for research synthesis, with the strength of this approach demonstrated through the authors’ recent Cochrane review into the effectiveness of school-based programs for the prevention of child sexual abuse. It describes the features of evaluation studies and the differences between systematic reviews and more traditional literature reviews, before summarising the findings of their recent Cochrane review.

Accuracy of absorbed dose in external photon beam radiotherapy : what level is sufficient and how to approach it?

Radiation therapy (RT) plays currently significant role in curative treatments of several cancers. External beam RT is carried out mostly by using megavoltage beams of linear accelerators. Tumor eradication and normal tissue complications correlate to dose absorbed in tissues. Normally this dependence is steep and it is crucial that actual dose within patient accurately correspond to the planned dose. All factors in a RT procedure contain uncertainties requiring strict quality assurance. From hospital physicist´s point of a view, technical quality control (QC), dose calculations and methods for verification of correct treatment location are the most important subjects. Most important factor in technical QC is the verification that radiation production of an accelerator, called output, is within narrow acceptable limits. The output measurements are carried out according to a locally chosen dosimetric QC program defining measurement time interval and action levels. Dose calculation algorithms need to be configured for the accelerators by using measured beam data. The uncertainty of such data sets limits for best achievable calculation accuracy. All these dosimetric measurements require good experience, are workful, take up resources needed for treatments and are prone to several random and systematic sources of errors. Appropriate verification of treatment location is more important in intensity modulated radiation therapy (IMRT) than in conventional RT. This is due to steep dose gradients produced within or close to healthy tissues locating only a few millimetres from the targeted volume. The thesis was concentrated in investigation of the quality of dosimetric measurements, the efficacy of dosimetric QC programs, the verification of measured beam data and the effect of positional errors on the dose received by the major salivary glands in head and neck IMRT. A method was developed for the estimation of the effect of the use of different dosimetric QC programs on the overall uncertainty of dose. Data were provided to facilitate the choice of a sufficient QC program. The method takes into account local output stability and reproducibility of the dosimetric QC measurements. A method based on the model fitting of the results of the QC measurements was proposed for the estimation of both of these factors. The reduction of random measurement errors and optimization of QC procedure were also investigated. A method and suggestions were presented for these purposes. The accuracy of beam data was evaluated in Finnish RT centres. Sufficient accuracy level was estimated for the beam data. A method based on the use of reference beam data was developed for the QC of beam data. Dosimetric and geometric accuracy requirements were evaluated for head and neck IMRT when function of the major salivary glands is intended to be spared. These criteria are based on the dose response obtained for the glands. Random measurement errors could be reduced enabling lowering of action levels and prolongation of measurement time interval from 1 month to even 6 months simultaneously maintaining dose accuracy. The combined effect of the proposed methods, suggestions and criteria was found to facilitate the avoidance of maximal dose errors of up to even about 8 %. In addition, their use may make the strictest recommended overall dose accuracy level of 3 % (1SD) achievable.

The generalized anomeric effect in the 1,3-thiazolidines: Evidence forboth sulphur and nitrogen as electron donors. Crystal structures of various N-acylthiazolidines including mercury(II) complexes. Possible relevance to penicillin action

Evidence for the generalized anomeric effect (GAE) in the N-acyl-1,3-thiazolidines, an important structural motif in the penicillins, was sought in the crystal structures of N-(4-nitrobenzoyl)-1,3-thiazolidine and its (2:1) complex with mercuric chloride, N-acetyl-2-phenyl-1,3-thiazolidine, and the (2:1) complex of N-benzoyl-1,3-thiazolidine with mercuric bromide. An inverse relationship was generally observed between the. C-2-N and C-2-S bond lengths of the thiazolidine ring, supporting the existence of the GAE. (Maximal bond length changes were similar to 0.04 angstrom for C-2-N-3, S-1-C-2, and similar to 0.08 angstrom for N-3-C-6.) Comparison with N-acylpyrrolidines and tetrahydrothiophenes indicates that both the nitrogen-to-sulphur and sulphur-to-nitrogen GAE's operate simultaneously in the 1,3-thiazolidines, the former being dominant. (This is analogous to the normal and exo-anomeric effects in pyranoses, and also leads to an interesting application of Baldwin's rules.) The nitrogen-to-sulphur GAE is generally enhanced in the mercury(II) complexes (presumably via coordination at the sulphur); a 'competition' between the GAE and the amide resonance of the N-acyl moiety is apparent. There is evidence for a 'push-pull' charge transfer between the thiazolidine moieties in the mercury(II) complexes, and for a 'back-donation' of charge from the bromine atoms to the thiazolidine moieties in the HgBr2 complex. (The sulphur atom appears to be sp(2) hybridised in the mercury(II) complexes, possibly for stereoelectronic reasons.) These results are apparently relevant to the mode of action of the penicillins. (c) 2006 Elsevier B.V. All rights reserved.

Software Pipelined Execution of Stream Programs on GPUs

The StreamIt programming model has been proposed to exploit parallelism in streaming applications on general purpose multi-core architectures. This model allows programmers to specify the structure of a program as a set of filters that act upon data, and a set of communication channels between them. The StreamIt graphs describe task, data and pipeline parallelism which can be exploited on modern Graphics Processing Units (GPUs), as they support abundant parallelism in hardware. In this paper, we describe the challenges in mapping StreamIt to GPUs and propose an efficient technique to software pipeline the execution of stream programs on GPUs. We formulate this problem - both scheduling and assignment of filters to processors - as an efficient Integer Linear Program (ILP), which is then solved using ILP solvers. We also describe a novel buffer layout technique for GPUs which facilitates exploiting the high memory bandwidth available in GPUs. The proposed scheduling utilizes both the scalar units in GPU, to exploit data parallelism, and multiprocessors, to exploit task and pipelin parallelism. Further it takes into consideration the synchronization and bandwidth limitations of GPUs, and yields speedups between 1.87X and 36.83X over a single threaded CPU.

Reforming technology company incentive programs for achieving knowledge-based economic development:a Brazil-Australia comparative study

This doctoral thesis aims to demonstrate the importance of incentives to technology-based firms as a strategy to promote knowledge-based economic development (KBED). To remain competitive, technology-based firms must innovate and seek new markets; therefore, this study aims to propose an incentive model to technology-based firms as a strategy to promote knowledge-based urban development, according to framework described by Yigitcanlar (2011). This is an exploratory and descriptive research with a qualitative approach. Surveys were carried out with national trade associations that represented technology-based firms both in Brazil and Australia. After analysing the surveys, structured interviews were conducted with government representatives, trade associations and businessmen who had used financial support by the federal government. When comparing both countries, the study found the importance of direct incentives through tax incentives, for it is a less bureaucratic, quicker and more direct process for firms. We suggest to include the terms incentives in the framework of knowledge-based urban development, as one of the pillars that contribute to knowledge-based economic development.

Structural plasticity and enzyme action: Crystal structures of Mycobacterium tuberculosis peptidyl-tRNA hydrolase

Peptidyl-tRNA hydrolase cleaves the ester bond between tRNA and the attached peptide in peptidyl-tRNA in order to avoid the toxicity resulting from its accumulation and to free the tRNA available for further rounds in protein synthesis. The structure of the enzyme from Mycobacteritan tuberculosis has been determined in three crystal forms. This structure and the structure of the enzyme frorn Escherichia coli in its crystal differ substantially on account of the binding of the C terminus of the E. coli enzyme to the peptide-binding site of a neighboring molecule in the crystal. A detailed examination of this difference led to an elucidation of the plasticity of the binding site of the enzyme. The peptide-binding site of the enzyme is a cleft between the body, of the molecule and a polypepticle Y stretch involving a loop and a helix. This stretch is in the open conformation when the enzyme is in the free state as in the crystals of M. tuberculosis peptidyl-tRNA hydrolase. Furthermore, there is no physical continuity between the tRNA and the peptide-binding sites. The molecule in the E. coli crystal mimics the peptide-bound enzyme molecule. The peptide stretch referred to earlier now closes on the bound peptide. Concurrently, a channel connecting the tRNA and the peptide-binding site opens primarily through the concerted movement of two residues. Thus, the crystal structure of M. tuberculosis peptidyl-tRNA hydrolase when compared with the crystal structure of the E. coli enzyme, leads to a model of structural changes associated with enzyme action on the basis of the plasticity of the molecule. (c) 2007 Elsevier Ltd. All rights reserved.

Youth programs in remote Indigenous communities: Context matters

A diversity of programs oriented to young people seek to develop their capacities and their connection to the communities in which they live. Some focus on ameliorating a particular issue or ‘deficit’ whilst others, such as sporting, recreation and youth groups are more grounded in the community. This article reports a qualitative study undertaken in three remote Indigenous communities in Central Australia. Sixty interviews were conducted with a range of stakeholders involved in a diversity of youth programs. A range of critical challenges for and characteristics of remote Indigenous youth programs are identified if such programs are to be ‘fit for context’. ‘Youth centred-context specific’ provides a positive frame for the delivery of youth programs in remote Central Australia, encouraging an explicit focus on program logic; program content and processes; and relational, temporal, and, spatial aspects of the practice context. These provide lenses with which youth program planning and delivery may be enhanced in remote communities. Culturally safe service planning and delivery suggests locally determined processes for decision-making and community ownership. In some cases, this may mean a community preference for all ages to access the service to engage in culturally relevant activities. Where activities are targeted at young people, yet open to and inclusive of all ages, they provide a medium for cross-generational interaction that requires a high degree of flexibility on the part of staff and funding programs. Although the findings are focused in Central Australia, they may be relevant to similar contexts elsewhere.

Human Rights in Action

In the post-World War II era human rights have emerged as an enormous global phenomenon. In Finland human rights have particularly in the 1990s moved from the periphery to the center of public policy making and political rhetoric. Human rights education is commonly viewed as the decisive vehicle for emancipating individuals of oppressive societal structures and rendering them conscious of the equal value of others; both core ideals of the abstract discourse. Yet little empirical research has been conducted on how these goals are realized in practice. These factors provide the background for the present study which, by combining anthropological insights with critical legal theory, has analyzed the educational activities of a Scandinavian and Nordic network of human rights experts and PhD students in 2002-2005. This material has been complemented by data from the proceedings of UN human rights treaty bodies, hearings organized by the Finnish Foreign Ministry, the analysis of different human rights documents as well as the manner human rights are talked of in the Finnish media. As the human rights phenomenon has expanded, human rights experts have acquired widespread societal influence. The content of human rights remains, nevertheless, ambiguous: on the one hand they are law, on the other, part of a moral discourse. By educating laymen on what human rights are, experts act both as intermediaries and activists who expand the scope of rights and simultaneously exert increasing political influence. In the educational activities of the analyzed network these roles were visible in the rhetorics of legality and legitimacy . Among experts both of these rhetorics are subject to ongoing professional controversy, yet in the network they are presented as undisputable facts. This contributes to the impression that human rights knowledge is uncontested. This study demonstrates how the network s activities embody and strengthen a conception of expertise as located in specific, structurally determined individuals. Simultaneously its conception of learning emphasizes the adoption of knowledge by students, emphasizing the power of experts over them. The majority of the network s experts are Nordic males, whereas its students are predominantly Nordic females and males from East-European and developing countries. Contrary to the ideals of the discourse the network s activities do not create dialogue, but instead repeat power structures which are themselves problematic.

'Getting started, getting feedback, and getting finished'- practice research in action

This article outlines the purpose, definition and usefulness of social work practice research and then describes a training program conducted by a group of social workers in the Australian Association of Social Workers (Victorian Branch) Practice Research Special Interest Group. These workshops offered practitioners the opportunity to explore a research idea with a group of colleagues which acted as a reference group over a period of six months. Two models of practice research workshops are described and their outcomes presented.

Action regulation across the adult lifespan (ARAL): A metatheory of work and aging

The goals of this article are to integrate action regulation theory (ART) with the lifespan developmental perspective and to outline tenets of a new metatheory of work and aging. The action regulation across the adult lifespan (ARAL) theory explains how workers influence, and are influenced by, their environment across different time spans. First, the basic concepts of ART are described, including the sequential and hierarchical structure of actions, complete tasks and actions, foci of action regulation, and the action-regulating mental model. Second, principles of the lifespan developmental perspective are delineated, including development as a lifelong and multidirectional process, the joint occurrence of gains and losses, intraindividual plasticity, historical embeddedness, and contextualism. Third, propositions of ARAL theory are derived by analyzing workers’ action regulation from a lifespan developmental perspective (i.e., effects of aging on action regulation), and by analyzing aging and development in the work context from an ART perspective (i.e., effects of action regulation on age-related changes in cognition and personality). Fourth, we develop further propositions to integrate ART with lifespan theories of motivation and socioemotional experience. Finally, we discuss implications for future research and practice based on ARAL theory.

Conformation of the flexible bent helix of Leu1-zervamicin in crystal C and a possible gating action for ion passage

The membrane channel-forming polypeptide, Leu(1)-zervamicin, Ac-Leu-Ile-Gln-Iva-Ile(5)-Thr-Aib-Leu-Aib-Hyp(10) -Gln-Aib-Hyp-Aib-Pro(15)-Phol (Aib: alpha-aminoisobutyric acid; Iva: isovaline; Hyp: 4-hydroxyproline; Phol: phenylalininol) has been analyzed by x-ray diffraction in a third crystal form. Although the bent helix is quite similar to the conformations found in crystals A and B, the amount of bending is more severe with a bending angle approximate to 47 degrees, The water channel formed by the convex polar faces of neighboring helices is larger at the mouth than in crystals A and B, and the water sites have become disordered. The channel is interrupted in the middle by a hydrogen bond between the OH of Hyp(10) and the NH2 of the Gln(11) of a neighboring molecule. The side chain of Gln(11) is wrapped around the helix backbone in an unusual fashion in order that it can augment the polar side of the helix. In the present crystal C there appears to be an additional conformation for the Gln(11) side chain (with approximate to 20% occupancy) that opens the channel for possible ion passage. Structure parameters for C85H140N18O22.xH(2)O.C2H5OH are space group P2(1)2(1)2(1), a = 10.337 (2) Angstrom, b = 28.387 (7) Angstrom, c = 39.864 (11) Angstrom, Z = 4, agreement factor R = 12.99% for 3250 data observed > 3 sigma(F), resolution = 1.2 Angstrom. (C) 1994 John Wiley & Sons, Inc.