The Computer Misuse Act 1990: lessons from its past and predictions for its future

The age of the internet has thrown down some real challenges to the Computer Misuse Act 1990. Recently, the Government made changes to this piece of legislation, in an attempt to meet two of those challenges--the proliferation of “ Denial of Service” (DoS) attacks, and the creation and dissemination of “ Hackers' tools” --and to fulfil international commitments on cybercrime. Yet some of these new measures invite criticisms of policy, form and content, and bring doubts about how easy to interpret, and how enforceable, they will be

Suppression of steady-state, but not stimulus-induced NF-kappaB activity inhibits alphavirus-induced apoptosis.

Recent studies have established cell type- specific, proapoptotic, or antiapoptotic functions for the transcription factor NF-kappaB. In each of these studies, inhibitors of NF-kappaB activity have been present before the apoptotic stimulus, and so the role of stimulus- induced NF-kappaB activation in enhancing or inhibiting survival could not be directly assessed. Sindbis virus, an alphavirus, induces NF-kappaB activation and apoptosis in cultured cell lines. To address whether Sindbis virus- induced NF-kappaB activation is required for apoptosis, we used a chimeric Sindbis virus that expresses a superrepressor of NF-kappaB activity. Complete suppression of virus-induced NF-kappaB activity neither prevents nor potentiates Sindbis virus-induced apoptosis. In contrast, inhibition of NF-kappaB activity before infection inhibits Sindbis virus-induced apoptosis. Our results demonstrate that suppression of steady-state, but not stimulus-induced NF-kappaB activity, regulates expression of gene products required for Sindbis virus-induced death. Furthermore, we show that in the same cell line, NF-kappaB can be proapoptotic or antiapoptotic depending on the death stimulus. We propose that the role of NF-kappaB in regulating apoptosis is determined by the death stimulus and by the timing of modulating NF-kappaB activity relative to the death stimulus

Regulation of NF-κB by PML and PML-RARα

Promyelocytic Leukemia (PML) is a nuclear protein that forms sub-nuclear structures termed nuclear bodies associated with transcriptionally active genomic regions. PML is a tumour suppressor and regulator of cell differentiation. We demonstrate that PML promotes TNFα-induced transcriptional responses by promoting NF-κB activity. TNFα-treated PML−/− cells show normal IκBα degradation and NF-κB nuclear translocation but significantly reduced NF-κB DNA binding and phosphorylation of NF-κB p65. We also demonstrate that the PML retinoic acid receptor-α (PML-RARα) oncofusion protein, which causes acute promyelocytic leukemia, inhibits TNFα induced gene expression and phosphorylation of NF-κB. This study establishes PML as an important regulator of NF-κB and demonstrates that PML-RARα dysregulates NF-κB

Oscillation dynamics underlie functional switching of NF-κB for B-cell activation.

Transcription factor nuclear factor kappa B (NF-κB) shows cooperative switch-like activation followed by prolonged oscillatory nuclear translocation in response to extracellular stimuli. These dynamics are important for activation of the NF-κB transcriptional machinery, however, NF-κB activity regulated by coordinated actions of these dynamics has not been elucidated at the system level. Using a variety of B cells with artificially rewired NF-κB signaling networks, we show that oscillations and switch-like activation of NF-κB can be dissected and that, under some conditions, these two behaviors are separated upon antigen receptor activation. Comprehensive quantitative experiments and mathematical analysis showed that the functional role of switch activation in the NF-κB system is to overcome transient IKK (IκB kinase) activity to amplify nuclear translocation of NF-κB, thereby inducing the prolonged NF-κB oscillatory behavior necessary for target gene expression and B-cell activation

Intégration de l’Opéra de Lausanne dans l’offre touristique régionale

Établi il y a 145 ans, l’Opéra de Lausanne est un établissement historique de la capitale vaudoise. Actuellement, la clientèle est très fidèle et à 92% vaudoise. L’idée de ce travail est d’intégrer l’opéra dans l’offre touristique régionale afin de diversifier et de renouveler le public de l’opéra. Pour ce faire, une enquête qualitative a été menée auprès de professionnels du tourisme dans le but de déterminer les attentes et de connaître les comportements des touristes fortunés à Lausanne. De plus, un Benchmark a été réalisé afin de tirer les bonnes pratiques de ce qui est mis en place dans d’autres opéras européens

Evidence linking exposure of fish primary macrophages to antibiotics activates the NF-kB pathway.

Low doses of antibiotics are ubiquitous in the marine environment and may exert negative effects on non-target aquatic organisms. Using primary macrophages of common carp, we investigated the mechanisms of action following exposure to several common antibiotics; cefotaxime, enrofloxacin, tetracycline, sulfamonomethoxine, and their mixtures, and explored the immunomodulatory effects associated with the nuclear factor-κB (NF-κB) signaling pathway. A KEGG pathway analysis was conducted using the sixty-six differentially expressed genes found in all treatments, and showed that exposure to 100 μg/L of antibiotics could affect regulation of the NF-κB signaling pathway, suggesting that activation of NF-κB is a common response in all four classes of antibiotics. In addition, the four antibiotics induced nf-κb and NF-κB-associated cytokines expression, as verified by qPCR, however, these induction responses by four antibiotics were minor when compared to the same concentration of LPS treatment (100 μg/L). Antagonists of NF-κB blocked many of the immune effects of the antibiotics, providing evidence that NF-κB pathways mediate the actions of all four antibiotics. Moreover, exposure to environmentally relevant, low levels (0.01-100 μg/L) of antibiotics induced a NF-κB-mediated immune response, including endogenous generation of ROS, activity of antioxidant enzymes, as well as expression of cytokine and apoptosis. Moreover, exposure to mixtures of antibiotics presented greater effects on most tested immunological parameters than exposure to a single antibiotic, suggesting additive effects from multiple antibiotics in the environment. This study demonstrates that exposure of fish primary macrophages to low doses of antibiotics activates the NF-kB pathway

The laminA/NF-Y protein complex reveals an unknown transcriptional mechanism on cell proliferation

Lamin A is a component of the nuclear matrix that also controls proliferation by largely unknown mechanisms. NF-Y is a ubiquitous protein involved in cell proliferation composed of three subunits (-YA -YB -YC) all required for the DNA binding and transactivation activity. To get clues on new NF-Y partner(s) we performed a mass spectrometry screening of proteins that co-precipitate with the regulatory subunit of the complex, NF-YA. By this screening we identified lamin A as a novel putative NF-Y interactor. Co-immunoprecipitation experiments and confocal analysis confirmed the interaction between the two endogenous proteins. Interestingly, this association occurs on euchromatin regions, too. ChIP experiments demonstrate lamin A enrichment in several promoter regions of cell cycle related genes in a NF-Y dependent manner. Gain and loss of function experiments reveal that lamin A counteracts NF-Y transcriptional activity. Taking advantage of a recently generated transgenic reporter mouse, called MITO-Luc, in which an NF-Y–dependent promoter controls luciferase expression, we demonstrate that lamin A counteracts NF-Y transcriptional activity not only in culture cells but also in living animals. Altogether, our data demonstrate the occurrence of lamin A/NF-Y interaction and suggest a possible role of this protein complex in regulation of NF-Y function in cell proliferatio

Transferts culturels et déclinaisons de la pédagogie européenne: le cas franco-romand au travers de l'itinéraire d'Alexandre Daguet (1816-1894)

Cette thèse vise à réévaluer la circulation des savoirs pédagogiques dans l’espace francosuisse. Méthodologiquement, nous nous proposons d’insister sur les modalités de passage de ces savoirs d’un contexte culturel à l’autre, en étudiant les acteurs, les vecteurs, ainsi que les inévitables transformations sémantiques qui accompagnent nécessairement ces échanges transnationaux. Cette recherche, articulée sous la forme d’une Gesellschaftsbiographie, prend pour guide le théoricien des idées éducatives, Alexandre Daguet (1816-1894). Il s’agit d’éclairer son rôle de médiateur privilégié dans le transfert de savoirs pédagogiques entre la Suisse romande et la France, en étudiant notamment son rôle de passeur via la revue L’Éducateur. Bien qu’il ait décliné l’appel de Ferdinand Buisson à édifier avec lui une « oeuvre internationale d’éducation », il n’en a pas pour le moins joué un rôle de « courtier » dans la diffusion de savoirs spécifiques, véhiculés notamment par les proscrits français réfugiés en Suisse romande dès 1852. Cette thèse permet de souligner comment les savoirs pédagogiques européens, élaborés de manière collective, sont diversement déclinés selon des spécificités locales. Dans ce sens, il s’agit de montrer qu’à mesure que les identités se solidifient, les spécificités nationales sont de plus en plus exaltées lors des Expositions universelles et les « exotismes » bientôt dévalorisés, voire même dissimulés au profit d’un certain génie national. Cette recherche souhaite donc contextualiser cette apparence trompeuse de Sonderfälle, pour mettre davantage de relief dans la construction collective d’une pédagogie européenne métissée. Mots clés : Alexandre Daguet, Suisse, transferts culturels, transformation sémantique, circulation des savoirs, histoire de la pédagogie, Ferdinand Buisson, Troisième RépubliqueThis thesis seeks to reassess the way in which pedagogical knowledge circulated between France and Switzerland. In terms of method, we have chosen to focus on the way in which this knowledge passed from one cultural context to another by studying the related actors and vectors, as well as the inevitable semantic transformations which, of necessity, accompany transnational exchanges of this nature. The research takes the form of a Gesellschaftsbiographie, with a guide in the person of educational theorist Alexandre Daguet (1816-1894). It aims to shed light on his role as a key mediator in the transfer of pedagogical expertise between French-speaking Switzerland and France, with a special emphasis on the way he used the review L’Éducateur to take this knowledge across borders. Although Daguet turned down the proposal by Ferdinand Buisson to work with the latter to create an “international treatise on education”, he nevertheless acted as a ‘broker’ in the trade of specific knowledge, passed on in particular by the French political exiles that took refuge in French-speaking Switzerland from 1852 onwards. The thesis also highlights the way in which European pedagogical knowledge, developed collectively, was applied in a variety of ways depending on local particularities. The issue here is to show the way in which, as identities became more firmly established, distinctive national features were increasingly honoured at Universal Expositions, while the various forms of “exoticism” soon fell out of favour, sometimes even to the point of being concealed in favour of national genius. This research therefore seeks to contextualise the deceptive semblance of Sonderfälle and provide a clearer picture of the collective emergence of a multifaceted European pedagogy. Key words : Alexandre Daguet, Switzerland, cultural transfer, semantic transformation, circulation of knowledge, history of pedagogy, Ferdinand Buisson, French Third Republi