Oncolytic herpes viruses, chemotherapeutics, and other cancer drugs

Oncolytic viruses are emerging as a potential new way of treating cancers. They are selectively replication-competent viruses that propagate only in actively dividing tumor cells but not in normal cells and, as a result, destroy the tumor cells by consequence of lytic infection. At least six different oncolytic herpes simplex viruses (oHSVs) have undergone clinical trials worldwide to date, and they have demonstrated an excellent safety profile and intimations of efficacy. The first pivotal Phase III trial with an oHSV, talimogene laherparepvec (T-Vec [OncoVex<sup>GM-CSF</sup>]), is almost complete, with extremely positive early results reported. Intuitively, therapeutically beneficial interactions between oHSV and chemotherapeutic and targeted therapeutic drugs would be limited as the virus requires actively dividing cells for maximum replication efficiency and most anticancer agents are cytotoxic or cytostatic. However, combinations of such agents display a range of responses, with antagonistic, additive, or, perhaps most surprisingly, synergistic enhancement of antitumor activity. When synergistic interactions in cancer cell killing are observed, chemotherapy dose reductions that achieve the same overall efficacy may be possible, resulting in a valuable reduction of adverse side effects. Therefore, the combination of an oHSV with “standard-of-care” drugs makes a logical and reasonable approach to improved therapy, and the addition of a targeted oncolytic therapy with “standard-of-care” drugs merits further investigation, both preclinically and in the clinic. Numerous publications report such studies of oncolytic HSV in combination with other drugs, and we review their findings here. Viral interactions with cellular hosts are complex and frequently involve intracellular signaling networks, thus creating diverse opportunities for synergistic or additive combinations with many anticancer drugs. We discuss potential mechanisms that may lead to synergistic interactions

Iain Banks, James Kelman and the art of engagement: an application of Jean Paul Sartre's theories of literature and existentialism to two modern Scottish novelists

This thesis is a study of the key novels of Iain Banks and James Kelman in the light of Jean Paul Sartre’s theories of existentialism and literature as set out in his 1949 literary manifesto Literature and Existentialism. By comparing and contrasting these two contemporary Scottish writers with reference to Sartre’s ideas, valuable insights into their fiction and their Scottish literary context may be gained. Sartre’s existentialism is primarily concerned with the potential of the apparently alienated subjective individual to influence and affect wider society. His theory of literature focuses specifically on the relationship between the writer, the reader and the social context of both, so the thesis will consider not only the novels of Banks and Kelman but also the social context of their writing and the critical reaction to it. The thesis is structured as an examination of Kelman and Banks in terms of their depictions of class, politics (both economic and social), gender, religion and ideas of morality. The introduction explains the reasons for choosing Sartre’s Literature and Existentialism as the critical basis of the thesis and the context in which his theories were formed. A brief overview of existentialism precedes consideration of the specific argument that Sartre proffers in terms of the relationship between his existentialist thought and literature. As a novelist himself, as well as a politically committed intellectual and existential philosopher, Sartre believed that there was a strong connection between literature and philosophy. His ideas about literature and existentialism therefore have the authority of a novelist’s experience of writing as well as those of a philosopher and critical thinker. I subsequently explain why I have chosen Iain Banks and James Kelman as the literary focus of the thesis. Both are pre-eminently novelists who have expressed political and, in some senses, philosophical, ideas that link them implicitly to Sartre’s writings. Neither makes extensive or overt acknowledgement of Sartre, but approaching them and their work from the Sartrean perspective is illuminating because it highlights what drives their main protagonists as well as their own motivation for writing. Using Sartre’s claims for the importance of literature as my starting point I consider not only their writing but also what has inspired their work in terms of their political, social and ethical beliefs, examining the reaction to their work, both from critics and in their own self-reflective comment. Chapter One examines in greater detail the ideas set out in the introduction, with reference to the idea of the ‘engaged writer’. This is a specific term which derives from Sartre’s claim that the ‘engaged writer knows his words are actions’. The chapter examines Sartre’s definition of the writer and the writer’s role in society. This definition is applied to Iain Banks and James Kelman with reference to their artistic reaction to the world post 9/11 in Banks’ novels Dead Air and The Steep Approach to Garbadale and Kelman’s You Have to Be Careful in the Land of the Free. The chapter analyses what can be gleaned from their differences and similarities when writing about the same subject and concludes that both writers, for all their apparent contrasts in terms of style and aesthetic, understand that the relationship between reader and writer is one which can promote social and political change, thus fulfilling Sartre’s definition. Chapter Two focuses on Banks’ and Kelman’s reaction to a specific political situation and widens the scope to look at the political climate that both Banks and Kelman deal with in their fiction. Kelman (born 1946) and Banks (born 1954) are of a generation of Scottish artists who have reacted to a particularly volatile time in Scottish politics. By looking at their personal comment upon it I investigate the culture that produced their writing, and how relevant their respective reactions were. For this, particular attention is paid to Banks’ Complicity and Kelman’s How Late it Was, How Late in a discussion of the role of the writer in political debate and in wider society. In these and other novels both writers not only provide reportage on the politics of the time, but, through their fiction, as ‘engaged writers’, directly challenge the mainstream contemporary political ideology. Chapter Three moves on from questions of politics to consider the writer and morality. For Sartre, the question of personal morality is central to the writer’s reason for writing. He believed not only that an individual writer’s moral sense is evident in their fiction, but also that the reader likewise learns about the environment that created that moral sensibility, specifically in their respective community. In this chapter questions are therefore asked about the transmission of ideas and ideals through the act of Banks’ and Kelman’s writing, as well as questioning what the nature of morality is. In their fiction Banks and Kelman deal with the individual, the collective (with reference to religion, art, class and philosophy) and further related questions of social and political morality by placing their characters outside the socially accepted norm, and offering a critique of those norms in their depiction of those characters’ circumstances and actions. In ways that invite comparison with Sartre’s stated ideas about the link between an individual’s writing and personal morality, both writers offer considered moral, social and political ideas and ideals that they believe will change the individual reader, and the wider collective, for the better. Chapter Four examines the question of Scottish masculinity and femininity as expressed in the novels of Banks and Kelman. This examination is related to the ideas discussed in the previous two chapters with reference to how portrayals of men and women in literature reflect the connection between gender and a nation’s political and social systems in a Scottish context. Said depictions interrogate the politics, morals and aesthetics of the writers’ work. Banks and Kelman offer different, but related, critiques of the masculine and feminine stereotypes in Scottish, British, and Anglo-American conventions. Their creation of male and female characters thus exemplifies the politics and aesthetics of their writing and the nature of their ‘engagement’. Chapter Five looks more closely at Sartre’s theories with specific reference to the individual writer’s aesthetic, the individual reader’s aesthetic and the idea of shared aesthetic values between both. This is done with close analysis of how Banks’ and Kelman’s writing has changed over the years, and in doing so this analysis asks to what extent one writer can be said to be ‘artistically superior to’, or more ‘aesthetically pleasing than’, another. The expectations of the reader and the writer are discussed with reference to Sartre’s specific definition of the writer’s aesthetic, and this definition is applied to Banks and Kelman to ascertain what we can learn from their respective aesthetics. Both writer and reader are required to create an ‘objective reality’, a process by which Banks, Kelman and Sartre implicitly, and sometimes explicitly, propose the recognition of ‘human freedom’ as its ultimate aim. Chapter Six posits that comparison with a number of their contemporaries will demonstrate that, while Banks and Kelman are novelists who notably benefit from such critical exposition, Sartre’s ideas are perennially relevant and insightful when considering writers in a political, social and ethical context. Amongst modern Scottish writers Banks and Kelman are pre-eminently ‘engaged’ writers with moral responsibilities, as Sartre believes all writers should be, and their engagement remains morally, politically and aesthetically committed and challenging, yet open to further revision and development. Over and above applying Sartrean literary philosophy to Banks and Kelman this thesis therefore also offers a model of literary criticism that can be applied to a number of other contemporary Scottish authors. In conclusion, this thesis suggests that Sartre’s theories of literature can assist in the attempt to better understand the value of the writer in society, and of Kelman and Banks in particular. The comparison and contrast between Banks and Kelman makes clear the importance of contextualising the individual writer not only with the work of their contemporaries, but with the time, place and position in which they are writing. The intention of the thesis is to discover how Sartre’s ideas of existentialism and literature can be applied to writers and their work in a way that allows ‘the critic’ to analyse both the novelist’s fictional technique and to gauge the value of their role in society – in other words, how Sartre’s theories allow us to better understand the individual writer in a social, political and moral context, both nationally and internationally

Sub_Merge

This work takes as its starting point recorded sounds and measurements of water from North America, the Arctic, and Antarctica. Using field recordings, data measurements, and multiple temporalities as a factor for composition, we decode the recordings and measurements to make audible the various forms of ecological memory and story held within water. These include water quality data, sea-ice thickness, glacial weather data, and recordings made underwater and on the land.   Sub_Merge is a space and time for active listening consistent with a meditative practice, a mediation on the collective experiences possible within water. The embedded performance creates a boundary for shared listening, while the 6-channel installation is amorphous, unfolding over the 12-hour installation - a timescale allowing for engaged listener participation. Sub_Merge is a speculative soundscape for listeners to emerge with stories and new understandings of water in all its myriad forms. It creates a new collective listening experience built from an historical record of water’s Listening Pasts, and new knowledge for Listening Futures, from the memories held within water.&nbsp

Table of Contents: The first governor – A bicentenary symposium on Arthur Phillip.

The first governor – A bicentenary symposium on Arthur Phillip. A selection of papers presented to commemorate the bicentenary of Arthur Phillip's death at Sydney Living Museums