bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Preclinical Pharmacology and Therapeutic Activity of the Novel CHK1 Inhibitor SAR-020106
Authors: Walton Michael I. , Eve Paul D. , Hayes Angela , Valenti Melanie , De Haven Brandon Alexis , Box Gary , Boxall Kathy J. , Aherne G. Wynne , Eccles Suzanne A. , Raynaud Florence I. , Williams David H. , Reader John C. , Collins Ian , Garrett Michelle D. 
Published: January 2010

AbstractGenotoxic antitumor agents continue to be the mainstay of current cancer chemotherapy. These drugs cause DNA damage and activate numerous cell cycle checkpoints facilitating DNA repair and the maintenance of genomic integrity. Most human tumors lack functional p53 and consequently have compromised G1-S checkpoint control. This has led to the hypothesis that S and G2-M checkpoint abrogation may selectively enhance genotoxic cell killing in a p53-deficient background, as normal cells would be rescued at the G1-S checkpoint. CHK1 is a serine/threonine kinase associated with DNA damage–linked S and G2-M checkpoint control. SAR-020106 is an ATP-competitive, potent, and selective CHK1 inhibitor with an IC50 of 13.3 nmol/L on the isolated human enzyme. This compound abrogates an etoposide-induced G2 arrest with an IC50 of 55 nmol/L in HT29 cells, and significantly enhances the cell killing of gemcitabine and SN38 by 3.0- to 29-fold in several colon tumor lines in vitro and in a p53-dependent fashion. Biomarker studies have shown that SAR-020106 inhibits cytotoxic drug–induced autophosphorylation of CHK1 at S296 and blocks the phosphorylation of CDK1 at Y15 in a dose-dependent fashion both in vitro and in vivo. Cytotoxic drug combinations were associated with increased γH2AX and poly ADP ribose polymerase cleavage consistent with the SAR-020106–enhanced DNA damage and tumor cell death. Irinotecan and gemcitabine antitumor activity was enhanced by SAR-020106 in vivo with minimal toxicity. SAR-020106 represents a novel class of CHK1 inhibitors that can enhance antitumor activity with selected anticancer drugs in vivo and may therefore have clinical utility. Mol Cancer Ther; 9(1); 89–100
Structure Activity Analysis of 2-Methoxyestradiol Analogues Reveals Targeting of Microtubules as the Major Mechanism of Antiproliferative and Proapoptotic Activity
Authors: Chua Yee Shin , Chua Yee Liu , Hagen Thilo 
Published: January 2010

Abstract
2-Methoxyestradiol (2ME2) is an anticancer agent with antiproliferative, antiangiogenic, and proapoptotic effects. A major proposed mechanism of drug action is the disruption of the microtubule skeleton, leading to the induction of cell cycle arrest and apoptosis. In addition, other mechanisms of action have been proposed, including the generation of reactive oxygen species (ROS), inhibition of hypoxia-inducible factor (HIF), and interference with mitochondrial function. In this study, we used a selection of 2ME2 analogues to conduct structure activity analysis and correlated the antiproliferative and proapoptotic activity of the various analogues with their effects on different drug targets. A good correlation was observed between drug activity and effects on microtubule function. In contrast, our results indicate that effects on ROS, HIF, and mitochondria are unlikely to contribute significantly to the cellular activity of 2ME2. Thus, our data indicate that the structural requirements for inducing ROS and inhibition of complex I of the mitochondrial electron transport chain were different from those required for proapoptotic drug activity. Furthermore, antioxidant treatment or overexpression of catalase did not inhibit the cellular activity of 2ME2 in epithelial cancer cells. Inhibition of HIF required much higher concentrations of 2ME2 analogues compared with concentrations that inhibited cell proliferation and induced apoptosis. Our results thus provide a better insight into the mechanism of action of 2ME2 and reveal structural requirements that confer high cellular activity, which may aid future drug development. Mol Cancer Ther; 9(1); 224–35
Proteomic and functional characterisation of platelet microparticle size classes
Authors: Dean William L. , Lee Menq J. , Cummins Timothy D. , Schultz David J. , Powell David W. 
Published: January 2010

SummaryActivated platelets release large lipid-protein complexes termed microparticles. These platelet microparticles (PMP) are composed of vesicular fragments of the plasma membrane and α-granules. PMP facilitate coagulation, promote platelet and leukocyte adhesion to the subendothelial matrix, support angiogenesis and stimulate vascular smooth muscle proliferation. Objectives: PMP were separated into 4 size classes to facilitate identification of active protein and lipid components. PMP were obtained from activated human platelets and separated into 4 size classes by gel filtration chromatography. Proteins were identified using 2-dimensional, liquid chromatography tandem mass spectrometry. Functional effects on platelets were determined using the PFA-100→ and on endothelial cells by measuring transendothelial cell electrical resistance. PMP size classes differed significantly in their contents of plasma membrane receptors and adhesion molecules, chemokines, growth factors and protease inhibitors. The two smallest size classes (3 and 4) inhibited collagen/adenosine-diphosphate-mediated platelet thrombus formation, while fractions 2 and 4 stimulated barrier formation by endothelial cells. Heat denaturation blocked the effect of fraction 4 on endothelial cell function, but not fraction 2 implying that the active component in fraction 4 is a protein and in fraction 2 is a heat-stable protein or lipid but not sphingosine-1-phosphate. Proteomic and functional analysis of PMP size fractions has shown that PMP can be separated into different size classes that differ in protein components, protein/lipid ratio, and functional effects on platelets and endothelial cells. This analysis will facilitate identification of active components in the PMP and clarify their involvement in diseases such as atherosclerosis and cancer.
The origins of the rebellion in the Punjab
Authors: Bhushan Bharat 
Published: January 2010

At the beginning of June, the Indian government used 70,000 troops to put down rebellion in the Punjab. At the height of the operation, tanks, artillery and hundreds of commandos engaged in 3 days and nights of warfare to gain control of the Golden Temple, the holiest shrine of the Sikh religion, which had been heavily fortified by the leaders of the rebellion. In the taking of the Golden Temple more than 100 soldiers, 350 pilgrims and 350 rebels lost their lives - amongst them Sant Jarnail Singh Bhindranwale the most prominent leader of the rebellion. The Punjab is India's most advanced State. New technologies and capitalist relations have transformed agricultural productivity to the extent that the State now produces over fifty percent of the national marketed surplus of both wheat and rice. But the rebellion raised economic demands alongside those of religious identity – in a land claimed as a model of the success of modern Western technology were reborn the Middle Ages with their springtime of superstitions, prejudices, aggressiveness, religious witch-hunt'. Whilst reporting the rebellion for Business India, Bharat Bhushan was able to interview the main leaders of the Akali Dal, the political party expressing many Sikh and Punjabi demands, including Bhindranwale. Here he analyses the main strands in the agitation, showing how its economic demands are primarily those of rich capitalist farmers but how popular support was ensured by an alliance with the religious identity of the whole Sikh community.
Nationalised industry policies and the destruction of communities: Some evidence from North East England
Authors: Beynon Huw , Hudson Ray , Sadler David 
Published: January 2010

This article examines the operation of three nationalised industries—coal, steel and water—in the North East of England. It looks at the links between them and assesses the impact of their policies on the economy and the environment of the local communities. In addition, it explores the relationship between the private and public sectors by examining the effects of private sector open cast coal production upon the National Coal Board's deep-mined output. The authors conclude by pointing to a ‘new politics of production’.
A Survival Analysis of Australian Equity Mutual Funds
Authors: Cameron A. Colin , Hall Anthony D. 
Published: January 2010

Determining which types of mutual (or managed) investment funds are good financial investments is complicated by potential survivorship biases. This project adds to a small recent international literature on the patterns and determinants of mutual fund survivorship. We use statistical techniques for survival data that are rarely applied in finance. Of specific interest is the hazard rate of fund closure, which gives the variation over time in the conditional probability of fund closure given fund survival to date. For a sample of 251 retail investment funds in Australia from 1980 to 1999 we identify a hump-shaped hazard function that reaches its maximum after about five or six years, a pattern similar to the UK findings of Lunde, Timmermann and Blake (1999). We also consider the impact of monthly and annual fund performance (gross and relative to a market benchmark). Returns relative to the benchmark are much more important than gross returns, with higher relative returns associated with lower hazard of fund closure. There appears to be an asymmetric response to performance, with positive shocks having a larger impact on the hazard rate than negative shocks.
Progressive Income Taxes, Tax-Favoured Investments and Investment Behaviour
Authors: Chisholm Anthony H. 
Published: January 2010

The current debate on the taxation of business income highlights the need for the tax to not distort investment decisions. A tax on business income that permits immediate expensing of all outlays (including investment outlays) is shown to be a tax on pure profits, whereas a true income tax that allows the write-off of economic depreciation (Samuelson tax) is shown to be a tax on both pure profits and the ‘normal’ interest earned on investments. Neither tax distorts investment decisions, though the latter distorts consumption/investment decisions. Under existing progressive income taxes, which roughly approximate the Samuelson type of tax but which provide tax-concessions to favoured investment activities, pre-tax rates of return on the favoured investment activities will tend toward equilibrium levels below those for non-favoured investments. The tax-favoured investment areas eventually will be dominated by high tax-bracket investors.
The Progress of the Interstate Banking Movement in the United States and Effects on Owners of Banking Organisations
Authors: Peavler Rosemary C. 
Published: January 2010

This study details the evolution of the interstate banking movement in the United States and the resultant effect on the wealth of shareholders of the affected banking organisations. State regulations regarding interstate banking are being relaxed at an increasing rate. Using an event-study methodology, this study investigates the resultant wealth positions of shareholders affected by the passage of liberalised interstate banking laws. Results indicate that shareholders do gain, although modestly, when regulations regarding interstate banking are relaxed. Thus, there seems to be some benefit to owners of these regulated firms when geographic expansion is permitted.
Corporate social responsibility, what's in a name? A critical appraisal of the Green Paper
Authors: Dorssemont Filip 
Published: January 2010

In July 2001 the European Commission issued a Green Paper entitled Promoting a European Framework for Corporate Social Responsibility. The paper was elaborated by the Directorate-General for Employment and Social Affairs. It focused on companies’ responsibilities in the social field. The term ‘corporate social responsibility (CSR) emerged from discourses and statements delivered by companies reflecting upon, even praising, their own functioning. The European Union's concern with the topic is rooted in the expressed conviction that CSR can be a positive contribution to the strategic goal set in Lisbon ‘to become the most competitive and dynamic knowledge-based economy in the world, capable of sustainable economic growth with more and better jobs and greater social cohesion’ (European Commission 2001: 4). This article seeks to examine the Green Paper's ‘new speech’ from the conceptual angle of collective labour law. It assesses the legal nature of the concept of corporate social responsibility (CSR) as well as its implications, in particular for human and fundamental workers’ rights, and for the trade union movement. It also addresses the question of whether CSR amounts to a new understanding of the freedom of enterprise.
Meetings on European multinationals: the experience so far
Authors: Fulton Lionel 
Published: January 2010

This article looks at the experience to date of meetings on European multinational companies, precursors to European works councils, using information from the main organisers, the European Industry Committees, and the participants. It finds that: there are now at least 290 European multinationals where employee representatives have met to talk about the prospect of a European works council. Overwhelmingly it is the national unions who decide who participates in the European level meetings and that, while non-UK unions draw on the statutory representative structures, such as works councils, to select their participants, in the UK the situation is more fluid. Overall around two-thirds of those attending are lay representatives. There are three issues which most meetings cover: the financial structure and plans of the company; a comparison of working conditions and trade union representation in the company's European locations; and the prospects of establishing a European works council. The meetings are about both exchanging information and building a European Works Council, although some Industry Committees focus more clearly on establishing a European Works Council than others. Participants report progress towards works councils, although they also welcome the links made and information shared at meetings. There are difficulties in maintaining links outside the meetings. The biggest single problem is language; people cannot communicate outside the formal sessions. There is also a general feeling among participants that they would like more information and among the organisers that they would like more resources. The key training needs are identified as language training followed by more training on the industrial relations systems in other countries.
Rapprochement based on common interests between the ETUC and the trade unions in Central and Eastern Europe
Authors: Seideneck Peter 
Published: January 2010

Many people in Eastern Europe found that their living conditions actually worsened during the transition from one old régime to another old-established - but pretty sound and adaptable- system. For the most part, the anticipated and in some cases publicised direct benefits of the free market economy failed to materialise. The governments of the Eastern European countries are all faced with inescapable dilemmas in the short term. Even those governments which claim to have close links with trade unions are implementing an economic and monetary policy that will inevitably lead to confrontations with the unions. Some governments regard the tripartite system as an instrument for appeasement, but not as a starting point for autonomous social relations. Their interest lies more with short-term conflict management and less with the development of independent interest-oriented structures. The ideal path that could be taken by the trade unions will have no other milestones than representativeness, the strength embodied in high numbers of members, the ability to mobilise them, and high acceptance among the public. The process of integration has not yet been concluded. The fundamental changes in Europe demand that the states in Central and Eastern Europe be involved in this process. The enlargement of the ETUC to include trade unions from Eastern Europe is no act of charity; it is in the direct interests of the ETUC and its affiliates. No longer can the developments in Eastern Europe be regarded as external affairs - they must now be integrated into the ETUC's policy.
European Monetary Union - a quantum leap
Authors: Jacobi Otto 
Published: January 2010

The main statements contained in this paper can be summed up as follows: 1. The single market created a supranational economic area. It is only logical from an economic point of view that the single market should also give rise to a single currency. 2. In order to improve Europe's competitive position vis-à-vis Japan and the USA, the dollar must be rivalled by a European currency having equivalent clout. 3. The convergence criteria are economically justified. Stable prices, low interest rates, the reduction of dramatically inflated national debts and the elimination of competitive devaluations stimulate investment, jobs and growth. 4. The European Central Bank will assume the status of a European monetary government. If an equal effort is to be made to achieve employment and social policy objectives, then an economic government and a social government are also required. 5. The task of an economic government, in the form of a harmonised economic policy for the EU Member States, is to promote job-creating investment in new technologies and modern infrastructure projects. 6. The task of a social government, in the form of Union-wide coordinated trade union representation, is to safeguard social standards, participation rights and wage claims. 7. Only the trio of Monetary, Employment and Social Union make sense and entail genuine legitimacy. 8. In the light of the ongoing trend towards globalisation, the cost of failure and the associated re-establishment of putatively wholly sovereign nation states would be counter-productive for all countries in Europe.
Trade unions in Greece: change and continuity1
Authors: Ioannou Christos A. 
Published: January 2010

Trade unions in the Greek system of industrial relations (the system of wage and employment regulation, the bargaining structure and behaviour) have shown signs of change and modernisation since the late 80s and the early 90s. The question is whether the model of industrial relations that was dominant in the 70s and 80s, (state-controlled compulsory arbitration, conflict-oriented collective bargaining, political-party-dominated trade-unionism) has given way to a modem model of industrial relations (development of bipartite regulation, consensus-oriented collective bargaining, more union independence vs. the state and the party rivalries). To explore the prospects of modernisation of Greek trade unions we will discuss changes in the bargaining behaviour (content of collective agreements, strike activity, performance etc.) and the bargaining structure at the national, branch and company level. The role of new labour legislation in modernisation is also discussed. The influence of the Delors initiative for European social dialogue is taken into account as a factor that shaped the behaviour of the major social partners in Greece. The prospects for modernisation are finally evaluated in the context of the restructuring of the Greek labour market and the difficult convergence criteria for Economic and Monetary Union (EMU). The process of modernisation is taking place in conditions of rising unemployment, increasing labour market segmentation, real wage cuts and deindustrialisation, which may buttress elements of continuity in Greek industrial relations.
Atypical work in the European experience
Authors: Meulders Danièle , Plasman Olivier , Plasman Robert 
Published: January 2010

The persistent employment crisis that dogged all of the countries of the European Community, with the exception of Luxembourg, throughout the 1980s has led to the spread of all sorts of jobs which cannot be compared with full-time, life-time work: part-time employment; temporary employment; jobs created by the public authorities; and work experience schemes for young people, as well as jobs with varied or unusual schedules. The present study follows the evolution of the principal forms of atypical employment during three periods (1983–1985, 1985–1990 and 1990–1994), revealing the constants and the variations, as well as the national divergences in the development of the methods of flexibility and of organisation of working time. The first part looks at divergences and convergences, whilst a second highlights the localisation of the types of atypical employment in certain segments of the labour market
The presence of occupational pension schemes within the overall pension scene
Authors: Bruni Raffaele 
Published: January 2010

Normally the studies concerning the development of pension funds focus on the quantitative dimensions of the phenomenon. Supplementary pensions include a plurality of instruments and various types of pensions. Thus to modify this situation, we need redirect reflection towards a more qualitative approach. Quantitative approach is the consequence of the existence of an ideological clash between a liberal and a social view of welfare problems. Social and economic framework has been modified in the last decades and so there is no reason for keeping the terms of the conflict unaltered. It suggests the need to develop an empirical and flexible approach to the matter. Pension funds will be one of the pivot of a mixed pension system. involving both public and private players with capitalisation and pay-as-you-go system. Defining this process requires a major planning effort by the social partners. Pension funds offer opportunities for shifting relations between social parties onto a level which has never been achieved, but at the same time they require a long-term strategy which also presupposes that different national situations will move towards convergence. The experience of the European Union may perhaps offer a suitable occasion for achieving this objective.