Modes of action of antibacterial agents

This chapter describes the modes of action of the major antibiotics and synthetic agents used to treat bacterial infections. Particular attention is given to the biochemical mechanisms by which the agents interfere with biosynthetic processes and the basis for their selective antibacterial action. Interference with the biosynthesis and assembly of structural components of the bacterial cell wall provides the basis for many important groups of antibiotics, including the agents targeting steps in peptidoglycan synthesis. Other agents exploit more subtle differences between bacteria and mammalian cells in fundamental processes such as DNA, RNA and protein synthesis.

Válságkezelés Európában: új gazdaságfilozófia felé? (Towards a New Philosophy of Crisis Management in Europe?)

Az évek óta tartó európai válságkezelés leírása és a részletek bemutatása helyett a rögtönzött, politikai alapon hozott lépések gazdaságelméleti értelmezésére törekszünk. Kutatási alapkérdésünk a következő: igaz-e még a 70-es évek végének felismerése, ami szerint sem szerkezeti, sem szabályozási eredetű válságot nem lehet keresletélénkítéssel leküzdeni? Igaz-e, hogy a szuverén EU-tagállamokon belül bármi okból hiányzó belső elköteleződést nem lehet pótolni a külső fegyelmezéssel? Ennek fényében vizsgáljuk a költségvetési és a bankunió 2012 októberében körvonalazott és jóváhagyott tervezetét is. _____ This paper attempts to provide a theoretical interpretation of new policy initiatives in the EU culminating in the launching of a fiscal and banking union in June, 2012. This step is reinforced by the new ECB strategy launched in September 2012. These measures were a result of a series of policy improvisations rather than of any secret master plan, still they add up to a new model of European integration. Our research question is if, and to what degrees the insights from the crisis of the 1970s hold. Accordingly no amount of easy money may remedy ills deriving from regulatory and structural inefficiencies. Second, we contend that no amount of external straightjacket/disciplining may replace domestic commitment of national governments in implementing structural reforms rather than fiscal adjustments on the margin.

On the new economic philosophy of crisis management in the European Union

This essay attempts to go beyond presenting the bits and pieces of still ongoing crisis management in the EU. Instead it attempts at finding the ‘red thread’ behind a series of politically improvised decisions. Our fundamental research question asks whether basic economic lessons learned in the 1970s are still valid. Namely, that a crises emanating from either structural or regulatory weaknesses cannot and should not be remedied by demand management. Our second research question is the following: Can lacking internal commitment and conviction in any member state be replaced or substituted by external pressure or formalized procedures and sanctions? Under those angles we analyze the project on establishing a fiscal and banking union in the EU, as approved by the Council in December 2012.

From theory-inspired to theory-based interventions : A protocol for developing and testing a methodology for linking behaviour change techniques to theoretical mechanisms of action

This research is funded by UK Medical Research Council grant number MR/L011115/1

From Theory-Inspired to Theory-Based Interventions : A Protocol for Developing and Testing a Methodology for Linking Behaviour Change Techniques to Theoretical Mechanisms of Action

This research is funded by UK Medical Research Council grant number MR/L011115/1. We would like to thank the 105 experts in behaviour change who have committed their time and offered their expertise for study 2 of this research. We are also very grateful to all those who sent us peer-reviewed behaviour change intervention descriptions for study 1. Finally, we would like thank Dr. Emma Beard and Dr. Dan Dediu for their statistical input and to all the researchers, particularly Holly Walton, who have assisted in the coding of papers for study 1.

Vagal blocking for obesity control : a possible mechanism-of-action

Peer reviewed

Plato's Cretan Colony: Theology and Religion in the Political Philosophy of the Laws

The Laws is generally regarded as Plato’s attempt to engage with the practical realities of political life, as opposed to the more idealistic, or utopian, vision of the Republic. Yet modern scholars have often felt disquieted at the central role of religion in the Laws’ second-best city and regime. There are essentially the two dominant interpretations on offer today: either religion supports a repressive theocracy, which controls every aspect of the citizens’ lives to such an extent that even philosophy itself is discouraged, or religion is an example of the kind of noble lie, which the philosopher must deceive the citizens into believing—viz., that a god, not a man, is the author of the regime’s laws. I argue that neither of these interpretations do justice to the dialogue’s intricately dramatic structure, and therefore to Plato’s treatment of civil religion. What I propose is a third position in which Plato both takes seriously the social and political utility of religion, and views theology as a legitimate, and even necessary, subject of philosophical inquiry without going so far as to advocate theocracy as the second best form of regime.

I conclude that a proper focus on the dialogue form, combined with a careful historical analysis of Plato’s use of social and political institutions, reveals an innovative yet traditional form of civil religion, purified of the harmful influence of the poets, based on the authority of the oracle at Delphi, and grounded on a philosophical conception of god as the eternal source of order, wisdom, and all that is good. Through a union of traditional Delphic theology and Platonic natural theology, Plato gives the city of the Laws a common cult acceptable to philosopher and non-philosopher alike, and thus, not only bridges the gap between religion and philosophy, but also creates a sense of community, political identity, and social harmony—the prerequisites for political order and stability. The political theology of the Laws, therefore, provides a rational defense of the rule of law (νόμος) re-conceived as the application of divine Reason (νοῦς) to human affairs.

Akrasia and the Aesthetic: Human Agency and the Site of Literature, 1760-1820

This study focuses on a series of foundational stylistic and formal innovations in eighteenth-century and Romantic literature, and argues that they can be cumulatively attributed to the distinct challenges authors faced in representing human action and the will. The study focuses in particular on cases of “acting against better judgment” or “failing to do what one knows one ought to do” – concepts originally theorized as “akrasia” and “weakness of the will” in ancient Greek and Scholastic thought. During the Enlightenment, philosophy increasingly conceives of human minds and bodies like systems and machines, and consequently fails to address such cases except as intractable or incoherent. Yet eighteenth-century and Romantic narratives and poetry consistently engage the paradoxes and ambiguities of action and volition in representations of akrasia. As a result, literature develops representational strategies that distinguish the epistemic capacities of literature as privileged over those of philosophy.

The study begins by centering on narratives of distempered selves from the 1760s. Jean-Jacques Rousseau’s Confessions and Laurence Sterne’s A Sentimental Journey narrate cases of knowingly and weakly acting against better judgment, and in so doing, reveal the limitations of the “philosophy of the passions” that famously informed sentimental literature at the time. These texts find that the interpretive difficulties of action demand a non-systematic and hermeneutic approach to interpreting a self through the genre of narrative. Rousseau’s narrative in particular informs William Godwin’s realist novels of distempered subjects. Departing from his mechanistic philosophy of mind and action, Godwin develops the technique of free indirect discourse in his third novel Fleetwood (1805) as a means of evoking the ironies and self-deceptions in how we talk about willing.

Romantic poetry employs the literary trope of weakness of will primarily through the problem of regretted inaction – a problem which I argue motivates the major poetic innovations of William Wordsworth and John Keats. While Samuel Taylor Coleridge sought to characterize his weakness of will in philosophical writing, Wordsworth turns to poetry with The Prelude (1805), revealing poetry itself to be a self-deceiving and disappointing form of procrastination. More explicitly than Wordsworth, John Keats identifies indolence as the prime symbol and basis of what he calls “negative capability.” In his letters and poems such as “On Seeing the Elgin Marbles” (1817) and “Ode on Indolence” (1819), Keats reveals how the irreducibly contradictory qualities of human agency speak to the particular privilege of “disinterested aesthetics” – a genre fitted for the modern era for its ability to disclose contradictions without seeking to resolve or explain them in terms of component parts.

A Philosophy of Operatic Storytelling

This dissertation presents the first theoretical model for understanding narration and point of view in opera, examining repertoire from Richard Wagner to Benjamin Britten. Prior music scholarship on musical narratives and narrativity has drawn primarily on continental literary theory and philosophy of the 1960s to the middle of the 1980s. This study, by contrast, engages with current debates in the analytic branch of aesthetic philosophy. One reason why the concept of point of view has not been more extensively explored in opera studies is the widespread belief that operas are not narratives. This study questions key premises on which this assumption rests. In so doing, it presents a new definition of narrative. Arguably, a narrative is an utterance intended to communicate a story, where "story" is understood to involve the representation of a particular agent or agents exercising their agency. This study explores the role of narrators in opera, introducing the first taxonomy of explicit fictional operatic narrators. Through a close analysis of Britten and Myfanwy Piper's Owen Wingrave, it offers an explanation of music's power to orient spectators to the points of view of opera characters by providing audiences with access to characters' perceptual experiences and cognitive, affective, and psychological states. My analysis also helps account for how our subjective access to fictional characters may engender sympathy for them. The second half of the dissertation focuses on opera in performance. Current thinking in music scholarship predominantly holds that fidelity is an outmoded concern. I argue that performing a work-for-performance is a matter of intentionally modelling one's performance on the work-for-performance's features and achieving a moderate degree of fidelity or matching between the two. Finally, this study investigates how the creative decisions of the performers and director impact the point of view from which an opera is told.

A philosophy of performance, politics and composition

This thesis discusses socio-political issues worldwide through philosophical approaches to performance, politics and composition. My research also discuss sound decisions which I regard to be simultaneously an outlet for personal expression, as well as a practical tool to inspire a socio-political change in society. Although the latter is paramount to the methodology of the project, the sound cannot be regarded in isolation as a “political composition”. It can only become truly functional in a political sense through interaction with other art forms, within the context of a specific place and time. My portfolio for this project is of two socio-political projects which are my chief concern. The first project concerns the Israeli-Palestinian conflict. I named this project PATH. PATH aims to foster and expand peaceful thought between Jewish and Palestinian civilians in Israel-Palestine. Through performance art, PATH spreads a message of acceptance, unity and brotherhood between our peoples. Above all, PATH demands and end to intolerance, hatred and violence among all the inhabitants of the State of Israel. The second project concerns women’s rights globally. I have realised that although we have come a long way in our struggle for rights for women, great challenges remain. There is a need to unite women and men against a form of oppression that discriminates against 50% of the world’s population. I called this project, For Utopia.

The Kyoto School and Confucianism: a Confucian reading of the philosophy of history and political thought of Masaaki Kosaka

This dissertation examines the philosophy of Masaaki Kōsaka (1900-1969) from the East Asian perspective of Confucianism, which I believe is the most appropriate moral paradigm for comprehending his political speculations. Although largely neglected in post-war scholarship, Kōsaka was a prominent member of the Kyoto School during the 1930s and 40s. This was a group of Japanese thinkers strongly associated with the philosophies of Kitarō Nishida and Hajime Tanabe. Kōsaka is now best known for his participation in the three Chūō Kōron symposia held in 1941 and 1942. These meetings have been routinely denounced by liberal historians due to the participants’ support for the Pacific War and the Co-Prosperity Sphere. However, many of these liberal portrayals have failed to take into account the full extent of the group’s resistance to the military junta of Hideki Tōjō. Adopting the methods and techniques of the empirical disciplines of academic history and Orientalism, I develop an interpretative framework that is more receptive to the political values that mattered to Kōsaka as a Confucian inspired intellectual. This has necessitated the rejection of moral history, which typically prioritises modern liberal values brought a priori to the historical record of wartime Japan, as well as recognition of the different ontological foundations that inform the unique political theories of the East Asian intellectual tradition. Reinforced by the prior research of Michel Dalissier and Graham Parkes, as well as my own reading of the Confucian canon, I adopt David Williams’s thesis of ‘Confucian Revolution’ as my principle schema of interpretation. This, I believe, is better able to reconcile Kōsaka’s support for the war with his strong condemnation of the imperialist practices of the Japanese military. Moreover, acknowledging the importance of Confucianism allows us to fully appreciate Kōsaka’s strong affinity for Kant’s practical metaphysics, Hegel’s political philosophy and Ranke’s historiography.

Metaphysics of love in the religious philosophy of Pável Florensky

This article focuses on the analysis of the concept of love in the religious philosophy of Pavel Florensky, who shares the ontological approach to the consideration of love with other representatives of Russian religious philosophy (N. berdyaev and S. bulgakov). We pay more careful attention to the understanding of love-άγαπαν by Florensky. We have drawn the conclusion that, in the philosophy of P. Florensky, Love, closely connected with truth and beauty, is considered an ontological basis existence of personality. We develop the ideas of Pavel Florensky, and accordingly assume that it is possible to synthesise love-agape and love-eros around the idea of sacrificial love. Agapelogical and erotical ‘bezels’ of one jewel of love is aspects of united love, which is given by God. this gift of God, the gift of united love, is kept by humans through prayer and deeds of love.

Plato’s Parmenides and understanding the One in the philosophy of Plotinus: an oversight by Heidegger?

The present article focuses on the study of the exegesis by Plotinus with regard to the meaning of the ineffability of the one provided in Plato’s Parmenides in the first hypothesis. He places this first ineffable one at the very centre of his system, which would have important implications from both an ontological point of view and with regard to understanding the language. The conception of reality that derives from the ineffability of the first principle and the implications for the nature of philosophical language that this postulate raises will be the centre of our reflections. To shed light on the position set down in the Enneads, we will review the key points based on the original texts that deal with this issue and related critical works. We will also look at the contemporary relevance of this position and its ability to go beyond the Heideggerian critique of metaphysics.

Attenuation of monocyte chemotaxis--a novel anti-inflammatory mechanism of action for the cardio-protective hormone B-type natriuretic peptide

B-type natriuretic peptide (BNP) is a prognostic and diagnostic marker for heart failure (HF). An anti-inflammatory, cardio-protective role for BNP was proposed. In cardiovascular diseases including pressure overload-induced HF, perivascular inflammation and cardiac fibrosis are, in part, mediated by monocyte chemoattractant protein (MCP)1-driven monocyte migration. We aimed to determine the role of BNP in monocyte motility to MCP1. A functional BNP receptor, natriuretic peptide receptor-A (NPRA) was identified in human monocytes. BNP treatment inhibited MCP1-induced THP1 (monocytic leukemia cells) and primary monocyte chemotaxis (70 and 50 %, respectively). BNP did not interfere with MCP1 receptor expression or with calcium. BNP inhibited activation of the cytoskeletal protein RhoA in MCP1-stimulated THP1 (70 %). Finally, BNP failed to inhibit MCP1-directed motility of monocytes from patients with hypertension (n = 10) and HF (n = 6) suggesting attenuation of this anti-inflammatory mechanism in chronic heart disease. We provide novel evidence for a direct role of BNP/NPRA in opposing human monocyte migration and support a role for BNP as a cardio-protective hormone up-regulated as part of an adaptive compensatory response to combat excess inflammation.

The Importance of Learning History and Philosophy of Computing

Computers have invaded our offices, our homes, cars and coffee-pots; they have become ubiquitous. However, the advance of computing technologies is associated with an increasing lack of “visibility” of the underlying software and hardware technologies. While we use and accept the computer, we neither know its history nor functionality. In this paper, we argue that this is not a healthy situation. Also, recruitment onto UK Computing degree courses is steadily falling; these courses are appearing less attractive to school-leavers. This may be associated with the increasing ubiquity. In this paper we reflect on an MSc. module of instruction, Concepts and Philosophy of Computing, and a BSc. module Computer Games Development developed at the University of Worcester which address these issues. We propose that the elements of these modules form a necessary part of the education of all citizens, and we suggest how this may be realized. We also suggest how to re-enthuse our youth about computing as a discipline and halt the drop in recruitment.