Antithrombotic actions of statins involve PECAM-1 signalling

Statins are widely prescribed cholesterol-lowering drugs that are a first-line treatment for coronary artery disease and atherosclerosis, reducing the incidence of thrombotic events such as myocardial infarction and stroke. Statins have been shown to reduce platelet activation, although the mechanism(s) through which this occurs is unclear. Since several of the characteristic effects of statins on platelets are shared with those elicited by the inhibitory platelet adhesion receptor PECAM-1, we investigated a potential connection between the influence of statins on platelet function and PECAM-1 signalling. Statins were found to inhibit a range of platelet functional responses and thrombus formation in vitro and in vivo. Notably, these effects of statins on platelet function in vitro and in vivo were diminished in PECAM-1-/- platelets. Activation of PECAM-1 signalling results in its tyrosine phosphorylation, the recruitment and activation of tyrosine phosphatase SHP-2, the subsequent binding of phosphoinositol 3-kinase (PI3-K) and diminished PI3-K signalling. Statins resulted in the stimulation of these events, leading to the inhibition of Akt activation. Together, these data provides evidence for a fundamental role of PECAM-1 in the inhibitory effects of statins on platelet activation, which may explain some of the pleiotropic actions of these drugs.

Aluminium and breast cancer: sources of exposure, tissue measurements and mechanisms of toxicological actions on breast biology

This review examines recent evidence linking exposure to aluminium with the aetiology of breast cancer. The human population is exposed to aluminium throughout daily life including through diet, application of antiperspirants, use of antacids and vaccination. Aluminium has now been measured in a range of human breast structures at higher levels than in blood serum and experimental evidence suggests that the tissue concentrations measured have the potential to adversely influence breast epithelial cells including generation of genomic instability, induction of anchorage-independent proliferation and interference in oestrogen action. The presence of aluminium in the human breast may also alter the breast microenvironment causing disruption to iron metabolism, oxidative damage to cellular components, inflammatory responses and alterations to the motility of cells. The main research need is now to investigate whether the concentrations of aluminium measured in the human breast can lead in vivo to any of the effects observed in cells in vitro and this would be aided by the identification of biomarkers specific for aluminium action.

Cities’ low carbon plans in an ‘age of austerity’: an analysis of UK local authority actions, attitudes and responses

Background: Cities play a significant role globally in creating carbon emissions but, as centers of major population, innovation and social practice, they also offer important opportunities to tackle climate change. The new challenges faced by cities in an ‘age of austerity’ and decentralist agendas present substantial challenges for coordinated multilevel governance. Results: Based on research carried out in 2011–2012, this paper examines the attitudes and responses of sustainability and climate change officers in UK cities that have prepared low carbon and climate change plans, in the context of these challenges. Using a conceptual framework that analyses ‘awareness’, ‘analysis’ and ‘actions’ (in the context of spending cuts and a new ‘decentralized’ policy agenda) this research suggests that progress on low-carbon futures for cities continues to be fragmented, with increased funding constraints, short-termism and lack of leadership acting as key barriers to progress. Conclusion: Recent UK national policies (including localism, austerity measures and new economic incentives) have not only created further uncertainties, but also scope for cities’ local innovation through policy leverage and self-governing actions.

From Rio to Copenhagen: multilateral agreements, disagreements and situated actions

Governing climate change is arguably one of the most complex problems, environmental or otherwise, that the global community has had to contend with. This chapter highlights the innovations in governance that have characterized the global climate change regime as it sought to respond to and manage these complexities, political imperatives and competing interests. We suggest that the key contestations and innovations within climate governance can be understood in terms of four themes/questions all of which relate to issues of justice and equity.

Military targeting in the context of self-defence actions

In order to bring conceptual clarity to a particular dimension of the relationship between the jus ad bellum and the jus in bello regimes, this article explores the independent sources of a military targeting rule in both branches of international law. The aim is not to displace the jus in bello as the ‘lead’ regime on how targeting decisions must be made, or to undermine the traditional separation between these regimes. Rather, conceptual light is shed on a sometimes assumed but generally neglected dimension of the jus ad bellum’s necessity and proportionality criteria that may, in limited circumstances, have significance for our understanding of human protection during war, by covering possible gaps in the jus in bello targeting rules.

The Article 51 reporting requirement for self-defense actions

This article examines one legal criterion for the exercise of the right of self-defense that has been significantly overlooked by commentators: the so-called “reporting requirement.” Article 51 of the United Nations (UN) Charter provides, inter alia, that “[m]easures taken by members in the exercise of this right of self-defense shall be immediately reported to the Security Council.” Although the requirement to report all self-defense actions to the Council is clearly set out in Article 51, the Charter offers no further guidance with regard to this obligation. Reference to the practice of states since the UN’s inception in 1945 is therefore essential to understanding the scope and nature of the reporting requirement. As such, this article is underpinned by an extensive original dataset of reporting practice covering the period from January 1, 1998 to December 31, 2013. We know from Article 51 that states “shall” report, but do they, and—if so—in what manner? What are the various implications of reporting, of failing to report, and of the way in which states report? How are reports used, and by whom? Most importantly, this article questions the ultimate value of states reporting their self-defense actions to the Security Council in modern interstate relations.

A unified approach to the recognition of complex actions from sequences of zone-crossings

We present a method for the recognition of complex actions. Our method combines automatic learning of simple actions and manual definition of complex actions in a single grammar. Contrary to the general trend in complex action recognition that consists in dividing recognition into two stages, our method performs recognition of simple and complex actions in a unified way. This is performed by encoding simple action HMMs within the stochastic grammar that models complex actions. This unified approach enables a more effective influence of the higher activity layers into the recognition of simple actions which leads to a substantial improvement in the classification of complex actions. We consider the recognition of complex actions based on person transits between areas in the scene. As input, our method receives crossings of tracks along a set of zones which are derived using unsupervised learning of the movement patterns of the objects in the scene. We evaluate our method on a large dataset showing normal, suspicious and threat behaviour on a parking lot. Experiments show an improvement of ~ 30% in the recognition of both high-level scenarios and their composing simple actions with respect to a two-stage approach. Experiments with synthetic noise simulating the most common tracking failures show that our method only experiences a limited decrease in performance when moderate amounts of noise are added.

Pharmacological actions of nobiletin in the modulation of platelet function

Background and Purpose The discovery that flavonoids are capable of inhibiting platelet function has led to their investigation as potential antithrombotic agents. However, despite the range of studies on the antiplatelet properties of flavonoids, little is known about the mechanisms by which flavonoids inhibit platelet function. In this study, we aimed to explore the pharmacological effects of a polymethoxy flavonoid, nobiletin in the modulation of platelet function. Experimental Approach The ability of nobiletin to modulate platelet function was explored by using a range of in vitro and in vivo experimental approaches. Aggregation, dense granule secretion and spreading assays were performed using washed platelets. The fibrinogen binding, α-granule secretion and calcium mobilisation assays were performed using platelet-rich plasma and whole blood was used in impedance aggregometry and thrombus formation experiments. The effect of nobiletin in vivo was assessed by measuring tail bleeding time using C57BL/6 mice. Key Results Nobiletin was shown to supress a range of well-established activatory mechanisms, including platelet aggregation, granule secretion, integrin modulation, calcium mobilisation and thrombus formation. Nobiletin was shown to extend bleeding time in mice and reduce the phosphorylation of Akt and PLCγ2 within the collagen receptor (GPVI) - stimulated pathway, in addition to increasing the levels of cGMP and phosphorylation of VASP, a protein whose activity is associated with inhibitory cyclic nucleotide signalling. Conclusions and Implications This study provides insight into the underlying molecular mechanisms through which nobiletin modulates haemostasis and thrombus formation. Therefore nobiletin may represent a potential antithrombotic agent of dietary origins.

Women’s Popular Cinema in Greece: the case of Olga Malea

This thesis examines the film comedies directed by Olga Malea and released between 1997 and 2007 in Greece, in order to make a claim for the study of women’s popular cinema in Greece and beyond. Women’s popular cinema refers to films which are thematically associated with women’s cinema while operating in popular forms, such as genre. Olga Malea and her work make for a useful case study, in that they encapsulate the relationship between these two broad categories of women’s cinema and popular cinema. In addition, this thesis claims that the two categories inflect one another in interesting ways, and their intersections act as a productive framework for the analysis of women’s cinema as popular cinema, effecting a popularisation of usually marginalised themes. The introduction to this work primarily outlines the theoretical frameworks for the argument that follows, namely: women’s cinema and feminist theory; discussions around popular cinema; and considerations about authorship. The concept of national film cultures and its possible meaning in relation to Greece is also alluded to as a contextual factor. Each subsequent chapter advances the argument for women’s popular cinema through close textual analysis of the films in chronological order of their release. In particular, the analysis identifies recurrent strands and motifs in the director’s oeuvre, such as tensions between tradition and modernity, and the pervasive nature of patriarchy in informing national gender discourses. Having established the argument that women’s popular cinema is productive in popularising women’s cinema itself, the thesis concludes that, in the work of Olga Malea, its themes are conceived of, represented and perceived as prominent in the country during the period examined – and one can finally address women’s cinema as popular.

Is there a Rhythm Of The Rain? An analysis of weather in popular music

Weather is frequently used in music to frame events and emotions, yet quantitative analyses are rare. From a collated base set of 759 weather-related songs, 419 were analysed based on listings from a karaoke database. This article analyses the 20 weather types described, frequency of occurrence, genre, keys, mimicry, lyrics and songwriters. Vocals were the principal means of communicating weather: sunshine was the most common, followed by rain, with weather depictions linked to the emotions of the song. Bob Dylan, John Lennon and Paul McCartney wrote the most weather-related songs, partly following their experiences at the time of writing.

Parliamentary sovereignty, popular sovereignty, and Henry Parker's adjudicative standpoint

Discussions of popular sovereignty in early modern England have usually been premised upon a sharp distinction between ‘legal/constitutional’ forms of discourse (which merely interpret the law) and ‘political’ ones (which focus upon the right to make it). In such readings of the period, Henry Parker has a pivotal position as a writer who abandoned merely legalistic thinking. This chapter takes a different view. It argues that Parker’s major intellectual achievement was not so much to abandon legal/constitutional discourse as to offer a theorisation of its most distinctive features: he offered an account of a new kind of politics in which concern for ‘interests’ in property and in self-preservation replaced humanist concern with promotion of virtue. Parker drew upon ideas about representation best expressed by Sir Thomas Smith and ideas about law best expressed by Oliver St John. The theory he developed was not intended as a justification of legislative sovereignty, but of adjudicative supremacy. His picture of the two Houses as supreme adjudicators was meant to block the path to direct democracy. But the adjudicative standpoint they came to occupy presupposed that freeborn adults had ‘interests’ in life, liberty, and possessions. This had democratising implications.

L'effet de compensation morale ou comment les 'bonnes actions' peuvent aboutir à une situation indésirable

Des recherches récentes arguent qu’une « bonne action » pourrait contribuer à « désinhiber » l’individu en lui permettant d’entreprendre des actions « moins souhaitables » par la suite. Cet effet de compensation morale reste un domaine peu étudié, en dépit des conséquences potentielles considérables sur l’efficacité des politiques publiques. L’objectif de notre contribution est de définir et de caractériser cet effet tout en soulignant les risques d’effets pervers associés. Nous utilisons à cet effet des études et des exemples tirés de divers domaines, comme la consommation alimentaire ou les comportements prosociaux, et identifions des pistes de recherche visant à mieux comprendre les conséquences directes et indirectes de cet effet, tout en mentionnant quelques stratégies envisageables afin d’atténuer ce biais.