Microtubule disrupting N-phenyl-N’-(2-chloroethyl) ureas display anticancer activity on cell adhesion, P-glycoprotein and BCL-2-mediated drug resistance.

Objective: Our research program has focused on the development of promising, soft alkylating N-phenyl-N’-(2-chloroethyl)urea (CEU) compounds which acylate the glutamic acid-198 of β-tubulin, near the binding site of colchicum alkaloids. CEUs inhibit the motility of cancerous cells in vitro and, interestingly, exhibit antiangiogenic and anticancer activity in vivo. Mitotic arrest induced by microtubule-interfering agents such as CEUs remains the major mechanism of their anticancer activity, leading to apoptosis. However, we recently demonstrated that microtubule disruption by CEUs and other common antimicrotubule agents greatly alters the integrity and organization of microtubule-associated structures, the focal adhesion contact, thereby initiating anoikis, an apoptosis-like cell death mechanism caused by the loss of cell contact with the extracellular matrix. Methods: To ascertain the activated signaling pathway profile of CEUs, flow cytometry, Western blot, immunohistochemistry and transfection experiments were performed. Wound-healing and chick embryo assays were carried out to evaluate the antiangiogenic potency of CEUs. Results: CEU-induced apoptosis involved early cell cycle arrest in G2/M and increased level of CDK1/cycline B proteins. These signaling events were followed by the specific activation of the intrinsic apoptosis pathway, involving loss of mitochondrial membrane potential (Δψm) and ROS production, cytochrome c release from mitochondria, caspase activation, AIF nuclear translocation, PARP cleavage and nuclear fragmentation. CEUs maintained their efficacy on cells plated on pro-survival extracellular matrices or exhibiting overexpression of P-glycoprotein or the anti-apoptotic protein Bcl-2. Conclusion: Our results suggest that CEUs represent a promising new class of antimicrotubule, antiangiogenic and pro-anoikis agents.

Self adhesion of short Kevlar fibre -thermoplastic polyurethane composite

The self adhesion behaviour of thermoplastic polyurethane (TPU) in itself and its composite with short Kevlar fibre with respect to contact time, temperature, pressure, and fibre loading has been studied. The adhesion strength showed two linear increments of different slopes with respect to the square root of time: with temperature and pressure of contact, the adhesion strength was improved. The maximum strength was obtained with 20 phr of short fibre in only one of the mating substrates in the peel test sample. The duration for wetting and diffusion was shifted to longer time intervals with fibres loaded in both the substrates.

Psychological contract breach and outcomes : Combining meta-analysis and structural equation models. 'Ruptura de contrato psicol??gico : combinando meta-an??lisis y modelos de ecuaciones estructurales'

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Alps Workshop 1 p23 learning contract

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Freedom of contract and the coexistence of trademark registrations in Colombia

In trademark systems such as the Andean Community, a state authority verifiesthat the marks are distinctive, lawful and do not affect third parties, and after that,given their ownership. In this context, particular interest has sparked the possibilityof individuals by agreements or statements of co-existence, are who ensure that theirsigns meet the conditions for simultaneous registrations.Such agreements for the coexistence of marks are problematic if one thinks thatthe holders of interests that would be available also seem to matter to consumers,competitors and the market. Therefore, define the scope of contractual freedom inthe field of trademark law, whose rules are considered imperative, acquire practicaland theoretical importance because its realization i) recognizes the risks that maybe relevant to evaluating trade agreements and ii) contributes to debates on the roleof private autonomy in areas reserved for non-derogable norms. Thus, this researchputs the declarations of consent for the coexistence of registrations in Colombia, ina larger scope of the limits of freedom of contract.

Indirect expropriation in concession contract

 The work aims to demonstrate that an indirect expropriation of rights occurs when mining concession agreements are made for subsoil exploitation. The article looks at examples such as when administrative divesture for public utilities or for social interest is decreed to implement projects or environmental works; when any regulation or administrative action is taken determining protected areas or environment control of type; and when environmental control plans are implemented. The indirect expropriation occurs because a conflict exists between general interests and equality principles of the burdens, the contractual right of adherence to agreed upon provisions and the legality of prior legal regulations for the carrying out of such expropriation. 

Industrial Organization: a Contract Based approach

Industrial Organization, a Contract Based approach (aka IOCB) offers an extensive and an up-to-date panorama of Industrial Organization. It is aimed at advanced undergraduates, graduates, academics and practitioners with an interest in the field. The analysis of market interactions, business strategies and public policy is performed using the standard framework of game theory and the recent advances of contract theory and information economics