Anticancer metallohelices: nanomolar potency and high selectivity

A range of new helicate-like architectures have been prepared via highly diastereoselective self-assembly using readily accessible starting materials. Six pairs of enantiomers [Fe2L3]Cl4.nH2O (L = various bidentate ditopic ligands NN–NN) show very good water solubility and stability. Their activity against a range of cancer cell lines in vitro is structure-dependent and gives IC50 values as low as 40 nM. In an isogenic pair of HCT116 colorectal cancer cells, preferential activity was observed against cell lines that lack functional p53. Selectivity is also excellent, and against healthy human retinal pigment epithelial (ARPE19) and lung fibroblast (WI38) cells IC50 values are nearly three orders of magnitude higher. Cisplatin is unselective in the same tests. The compounds also appear to have low general toxicity in a number of models: there is little if any antimicrobial activity against Methicillin-resistant Staphylococcus aureus and Escherichia coli.; Acanthamoeba polyphaga is unaffected at 25 μg ml-1 (12.5 μM); Manduca sexta larvae showed clear evidence of systemic distribution of the drug, and rather than any observation of adverse effects they exhibited a significant mean weight gain vs controls. Investigation of the mode of action revealed no significant interaction of the molecules with DNA, and stimulation of substantial cell death by apoptosis

David Hume's no-miracles argument begets a valid No-Miracles Argument

Hume's essay ‘Of Miracles’ has been a focus of controversy ever since its publication. The challenge to Christian orthodoxy was only too evident, but the balance-of-probabilities criterion advanced by Hume for determining when testimony justifies belief in miracles has also been a subject of contention among philosophers. The temptation for those familiar with Bayesian methodology to show that Hume's criterion determines a corresponding balance-of-posterior probabilities in favour of miracles is understandable, but I will argue that their attempts fail. However, I show that his criterion generates a valid form of the so-called No-Miracles Argument appealed to by modern realist philosophers, whose own presentation of it, despite their possession of the probabilistic machinery Hume himself lacked, is invalid

What probability probably isn't

Joyce and others have claimed that degrees of belief are estimates of truth-values and that the probability axioms are conditions of admissibility for these estimates with respect to a scoring rule penalising inaccuracy. In this paper I argue that the claim that the rules of probability are truth-directed in this way depends on an assumption which is both implausible and lacks any supporting evidence, strongly suggesting that the probability axioms have nothing intrinsically to do with truth-directedness

Exotic structures on magnetic multilayers

To characterize the possible magnetic structures created on magnetic multilayers a model has been formulated and studied. The interlayer inhomogeneous structures found indicate either (i) a regular periodic, (ii) a quasiperiodic change in the magnetization or (iii) spatially chaotic glass states. The magnetic structures created depend mainly on the ratio of the magnetic anisotropy constant to the exchange constant. With the increase of this ratio the periodic structures first transform into the quasiperiodic and then into the chaotic glass states. The same tendency arises with the depolarization of the magnetic moments of the first layer deposited on the substrate.Comment: 4 pages, 1 figur

Does information inform confirmation?

In a recent survey of the literature on the relation between information and confirmation, Crupi and Tentori (Stud Hist Philos Sci 47:81–90, 2014) claim that the former is a fruitful source of insight into the latter, with two well-known measures of confirmation being definable purely information-theoretically. I argue that of the two explicata of semantic information (due originally to Bar Hillel and Carnap) which are considered by the authors, the one generating a popular Bayesian confirmation measure is a defective measure of information, while the other, although an admissible measure of information, generates a defective measure of confirmation. Some results are proved about the representation of measures on consequence-classes

Cinema of the dark side, atrocity and the ethics of spectatorship.

Book Review

Integrity in business: is it optional or necessary for NGOs

Globalisation has created difficulties and success for organisations and corporations alike. International economic governance is in a crisis as proposals for reform are divisive. The rise in NGOs is due to MNCs entering foreign markets for further business opportunities which has outpaced regulation from international government agencies or suitable state regulatory powers. The changing balance of power between NGOs and MNCs is heavily contested, however it is deemed that NGOs ascertain more people power as they conduct business in the will of the people rather than conducting business to make a profit without caring about societal needs. Multinational Corporations have adapted to the cultural, social and environmental differences in each country that they operate. The power of corporations runs deep to as they control the emerging international investment in developing countries. This has brought with it its challenges, especially calling into question the integrity and ethical practices of organisations operating across borders. Now that these organisations are being scrutinised more deeply due to their CSR procedures they must find a way to create value with their products or services. This research paper will analyse the literature surrounding business integrity, nongovernmental organizations and multinational corporations with a view to finding out if NGOs can collectively form partnerships with MNCs without sacrificing their integrity values for the other. There will also be an analysis of Creating Shared Value to help solve societal problems by having multinationals, non-governmental organisations and international organisations work coherently together using their individual strengths to achieve economic growth.A globalização criou dificuldades e sucesso para organizações e corporações. A governação económica internacional está em crise, uma vez que as propostas de reforma são divisórias. O aumento das ONGs deve-se ao fato de as multinacionais entrarem em mercados externos para oportunidades de negócios adicionais, que ultrapassaram a regulamentação de agências governamentais internacionais ou de poderes regulatórios estaduais adequados. A mudança no equilíbrio de poder entre as ONGs e as multinacionais é fortemente contestada, mas considera-se que as ONGs determinam mais poder das pessoas enquanto conduzem negócios na vontade do povo, em vez de realizarem negócios para obter lucros sem se preocuparem com as necessidades da sociedade. As corporações multinacionais se adaptaram às diferenças culturais, sociais e ambientais em cada país em que operam. O poder das corporações é profundo, pois controlam o emergente investimento internacional nos países em desenvolvimento. Isto trouxe consigo os seus desafios, especialmente pondo em causa a integridade e as práticas éticas das organizações que operam através das fronteiras. Agora que estas organizações estão sendo examinadas mais profundamente devido a seus procedimentos do CSR devem encontrar uma maneira criar o valor com seus produtos ou serviços. Este trabalho de investigação irá analisar a literatura em torno da integridade das empresas, organizações não-governamentais e corporações multinacionais, a fim de descobrir se as ONGs podem coletivamente formar parcerias com as multinacionais sem sacrificar seus valores de integridade para o outro. Haverá também uma análise de Criação de Valor Partilhado para ajudar a resolver problemas societais por ter multinacionais, organizações não-governamentais e organizações internacionais trabalhar coerentemente juntos usando suas forças individuais para alcançar o crescimento econômic

ViewPoint: Upper Gastrointestinal Endoscopy in Malawi: An opportunity

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