Injunctions against Innocent Third Parties: The Case of Website Blocking

The paper discusses the phenomenon of injunctions against third parties that are innocent from the tort law perspective. One such type of injunction, website blocking, is currently appearing in the spotlight around various European jurisdictions as a consequence of the implementation of Article 8(3) of the Information Society Directive and Article 11 of the Enforcement Directive. Website-blocking injunctions are used in this paper only as a plastic and perhaps also canonical example of the paradigmatic shift we are facing: the shift from tort-law-centric injunctions to in rem injunctions. The author of this paper maintains that the theoretical framework for the latter injunctions is not in the law of civil wrongs, but in an old Roman law concept of ‘in rem actions��� (actio in rem negatoria). Thus the term ‘in rem injunctions’ is coined to describe this paradigm of injunctions. Besides the theoretical foundations, this paper explains how a system of injunctions against innocent third parties fits into the private law regulation of negative externalities of online technology and explores the expected dangers of derailing injunctions from the tracks of tort law. The author’s PhD project – the important question of the justification of an extension of the intellectual property entitlements by the in rem paradigm, along with its limits or other solutions – is left out from the paper.

MECHANISM-BASED STRATEGIES TO ENHANCE THE ACTIONS OF A

Heat shock protein 90 (HSP90) is an abundant molecular chaperone that regulates the functional stability of client oncoproteins, such as STAT3, Raf-1 and Akt, which play a role in the survival of malignant cells. The chaperone function of HSP90 is driven by the binding and hydrolysis of ATP. The geldanamycin analog, 17-AAG, binds to the ATP pocket of HSP90 leading to the degradation of client proteins. However, treatment with 17-AAG results in the elevation of the levels of antiapoptotic proteins HSP70 and HSP27, which may lead to cell death resistance. The increase in HSP70 and HSP27 protein levels is due to the activation of the transcription factor HSF-1 binding to the promoter region of HSP70 and HSP27 genes. HSF-1 binding subsequently promotes HSP70 and HSP27 gene expression. Based on this, I hypothesized that inhibition of transcription/translation of HSP or client proteins would enhance 17-AAG-mediated cytotoxicity. Multiple myeloma (MM) cell lines MM.1S, RPMI-8226, and U266 were used as a model. To test this hypothesis, two different strategies were used. For the first approach, a transcription inhibitor was combined with 17-AAG. The established transcription inhibitor Actinomycin D (Act D), used in the clinic, intercalates into DNA and blocks RNA elongation. Stress inducible (HSP90á, HSP70 and HSP27) and constitutive (HSP90â and HSC70) mRNA and protein levels were measured using real time RT-PCR and immunoblot assays. Treatment with 0.5 µM 17-AAG for 8 hours resulted in the induction of all HSP transcript and protein levels in the MM cell lines. This induction of HSP mRNA levels was diminished by 0.05 µg/mL Act D for 12 hours in the combination treatment, except for HSP70. At the protein level, Act D abrogated the 17-AAG-mediated induction of all HSP expression levels, including HSP70. Cytotoxic evaluation (Annexin V/7-AAD assay) of Act D in combination with 17-AAG suggested additive or more than additive interactions. For the second strategy, an agent that affected bioenergy production in addition to targeting transcription and translation was used. Since ATP is necessary for the proper folding and maturation of client proteins by HSP90, ATP depletion should lead to a decrease in client protein levels. The transcription and translation inhibitor 8-Chloro-Adenosine (8-Cl-Ado), currently in clinical trials, is metabolized into its cytotoxic form 8-Cl-ATP causing a parallel decrease of the cellular ATP pool. Treatment with 0.5 µM 17-AAG for 8 hours resulted in the induction of all HSP transcript and protein levels in the three MM cell lines evaluated. In the combination treatment, 10 µM 8-Cl-Ado for 20 hours did not abrogate the induction of HSP mRNA or protein levels. Since cellular bioenergy is necessary for the stabilization of oncoproteins by HSP90, immunoblot assays analyzing for expression levels of client proteins such as STAT3, Raf-1, and Akt were performed. Immunoblot assays detecting for the phosphorylation status of the translation repressor 4E-BP1, whose activity is modulated by upstream kinases sensitive to changes in ATP levels, were also performed. The hypophosphorylated state of 4E-BP1 leads to translation repression. Data indicated that treatment with 17-AAG alone resulted in a minor (<10%) change in STAT3, Raf-1, and Akt protein levels, while no change was observed for 4E-BP1. The combination treatment resulted in more than 50% decrease of the client protein levels and hypophosphorylation of 4E-BP1 in all MM cell lines. Treatment with 8-Cl-Ado alone resulted in less than 30% decrease in client protein levels as well as a decrease in 4E-BP1 phosphorylation. Cytotoxic evaluation of 8-Cl-Ado in combination with 17-AAG resulted in more than additive cytotoxicity when drugs were combined in a sequential manner. In summary, these data suggest that the mechanism-based combination of agents that target transcription, translation, or decrease cellular bioenergy with 17-AAG results in increase cytotoxicity when compared to the single agents. Such combination strategies may be applied in the clinic since these drugs are established chemotherapeutic agents or currently in clinical trials.

The Experience of the National Rainbow Coalition (NARC) : Political Parties in Kenya from 1991 to 2007

This paper first examines splits and mergers among Kenya’s political parties (and inner-party factions) from the restoration of a multi-party system in 1991 until 2007, before the turbulent 10th general elections were conducted. It then considers what functions “political parties” have in Kenya with special reference to the period since 2002, the year in which President Moi announced his intention to retire. A look back at NARC’s five years of rule reveals that, although it succeeded in changing the government, NARC, as a “political party,” remained throughout an organization without any real substance. The paper looks at (1) NARC’s de facto split after its overwhelming win in the ninth general election, (2) malfunctions of the anti-defection laws that were introduced in the 1960s, and (3) Kenya’s election rules that require candidates to be nominated by registered political parties in general elections. The paper proceeds to argue that as a result of the operation of these three elements, Kenya’s political parties, and especially the victorious coalition sides, tend to end up being nothing more than temporary vehicles for political elites angling for post-election posts.

Modifications in the Dynamic Properties of a Structure due to Human Actions

The interest for modelling of human actions acting on structures has been recurrent since the first accidents on suspension bridges in the nineteenth century such as Broughton (1831) in the U.K. or Angers (1850) in France. Stadiums, gymnasiums are other types of structure where human induced vibration is very important. In these structures a particular phenomenon appears such as the interaction personstructure (lock-in), the person-person synchronization, and the influence of the mass and damping of the people in the structural behaviour. This paper focuses on the latter topic. In order to evaluate these property modifications several tests have been carried out on a stand-alone building. For the test an electro-dynamic shaker was installed at a fixed point of the gym slab and different groups of people were located around the shaker. The dynamic characteristics of the structure without people inside have been calculated by two methods: using a three-dimensional finite element model of the building and by operational modal analysis. These calculated experimental and numerical values are the reference values used to evaluate the modifications in the dynamic properties of the structure.

Structures subjected to Human Actions

In this paper we present the tests on a structure designed to be a gymnasium, which has natural frequencies within that range. In these tests the gym slab was instrumented with acceleration sensors and different people jumped on a force plate installed on the floor. The test results have been compared with predictions based on the two existing load modelling alternatives (Sim and SCI Guide) and two new methodologies for modelling jumping loads has been proposed. The results of the force plate trials were analysed in an attempt to better characterize the profile of the jump force and determine how best to approximate it. In the first proposed methodology the study is carried out in the frequency domain using an average power spectral density of the jumps. In the second proposed methodology, the jump force is decomposed into the summation of one peak with a large period and a number of peaks with smaller periods. Utilizing a similar model to that of the Sim model, the approximation will still be comprised of the summation of two quadratic cosine functions.

Assessment of University External Internships. Towards a Mixed Model for Measuring the Acquisition of Skills and the Satisfaction of Parties Involved

The continuous improvement of management and assessment processes for curricular external internships has led a group of university teachers specialised in this area to develop a mixed model of measurement that combines the verification of skill acquisition by those students choosing external internships with the satisfaction of the parties involved in that process. They included academics, educational tutors of companies and organisations and administration and services personnel in the latter category. The experience, developed within University of Alicante, has been carried out in the degrees of Business Administration and Management, Business Studies, Economics, Advertising and Public Relations, Sociology and Social Work, all part of the Faculty of Economics and Business. By designing and managing closed standardised interviews and other research tools, validated outside the centre, a system of continuous improvement and quality assurance has been created, clearly contributing to the gradual increase in the number of students with internships in this Faculty, as well as to the improvement in satisfaction, efficiency and efficacy indicators at a global level. As this experience of educational innovation has shown, the acquisition of curricular knowledge, skills, abilities and competences by the students is directly correlated with the satisfaction of those parties involved in a process that takes the student beyond the physical borders of a university campus. Ensuring the latter is a task made easier by the implementation of a mixed assessment method, combining continuous and final assessment, and characterised by its rigorousness and simple management. This report presents that model, subject in turn to a persistent and continuous control, a model all parties involved in the external internships are taking part of. Its short-term results imply an increase, estimated at 15% for the last course, in the number of students choosing curricular internships and, for the medium and long-term, a major interweaving between the academic world and its social and productive environment, both in the business and institutional areas. The potentiality of this assessment model does not lie only in the quality of its measurement tools, but also in the effects from its use in the various groups and in the actions that are carried out as a result of its implementation and which, without any doubt and as it is shown below, are the real guarantee of a continuous improvement.

Who performs a stronger response to whom? Detecting individual competitive actions and reactions

This study analyzes the degree of competition through individual actions and reactions. Empirical support for this analysis has derived mainly from structural econometric models describing the nature of competition. This analysis extends the existing literature by empirically considering a direct measurement of competition through the analysis of the competitive actions and responses, and describing how firms compete within and between strategic groups. We estimate the firms’ conduct in the Spanish deposits market with 146 firms and 18,888 observations. This is a specially compelling context for the banking industry, in which a deregulation process gives rise to the adoption of aggressive strategies seeking to increase the market shares of deposit accounts; thus, producing a turbulent situation of increasing rivalry. Our results offer a deeper understanding of the firms’ competitive behavior, since we identify different patterns of actions and reactions depending upon the strategic group the firm belongs to.