2,010 research outputs found
Inflammation and Hypoxia: HIF and PHD Isoform Selectivity
Get PDFCells sense and respond to hypoxia through the activity of the transcriptionfactor HIF (hypoxia-inducible factor) and its regulatory hydroxylases, the prolylhydroxylase domain enzymes (PHDs). Multiple isoforms of HIFs and PHDsexist, and isoform-selective roles have been identified in the context of theinflammatory environment, which is itself frequently hypoxic. Recent advancesin the field have highlighted the complexity of this system, particularly withregards to the cell and context-specific activity of HIFs and PHDs. Becausenovel therapeutic agents which regulate this pathway are nearing the clinic,understanding the role of HIFs and PHDs in inflammation outcomes is anessential step in avoiding off-target effects and, crucially, in developing newanti-inflammatory strategies
The 'true use of reading' : Sarah Fielding and mid eighteenth-century literary strategies.
No full textPhDThe aim of this thesis is to explore, by examining her life and
works, how Sarah Fielding (1710-68) established her identity as an author.
The definition of her role involves her notions of the functions of
writing and reading.
Sarah Fielding attempts to invite readers to form a sense of ties
by tacit understanding of her messages. As she believes that a work
of literature is produced through collaboration between the writer and
the reader, it is an important task in her view to show her attentiveness
toward reading practice. In her consideration of reading, she has two
distinct, even opposite views of her audience: on the one hand a familiar
and limited circle of readers with shared moral and cultural values and
on the other potential readers among the unknown mass of people. The
dual targets direct her to devise various strategies. She tries to
appeal to those who can endorse and appreciate her moral values as well
as her learning. Her writings and letters testify that she is sensitive
to the demands of the literary market, trying to lead the taste of readers
by inventing new forms.
The thesis opens with an overview of Sarah Fielding's career,
followed by a consideration of her critical attention to the roles of
reading. I go on to examine the narrative structures and strategies
she deploys, with a particular emphasis on her use of the epistolary
method. The following chapter deals with her attention to the reading
of the moral message tangibly embodied in her educational writing. It
is followed by an analysis of the activity which earned her a reputation
as a learned woman. Various as the forms of her works are, they invariably
reflect her attempt to balance herself between the two demands of
inventiveness and familiarity
Sarah Fielding: Satire and Subversion in the Eighteenth-Century Novel
No full textThis study of Sarah Fielding (1710―68) is an original contribution to Fielding scholarship that has a dual purpose: to support those who are striving to re-introduce her to the modern literary landscape in an effort to restore her eighteenth-century literary standing, and to firmly establish Fielding as an early feminist writer. It is argued here that throughout her oeuvre Fielding challenged prevailing traditions that denied women a choice, particularly in education, employment and marriage. These themes are also considered in the political treatises of Mary Astell (1666―1731) and Mary Wollstonecraft (1759―97), who are now widely recognised as feminist writers.
It is further argued that Fielding’s subversion in fiction of the English patriarchal system is underscored by her unorthodox performance in the literary arena. This is fully explored alongside her use of sentimentalism as a literary tool with which she challenges her seemingly inhumane society. Fielding’s interest in ‘the Labyrinths of the Mind’ (in modern terms, human psychology) will also be addressed as will her placement in the history of feminism and her placement in the sentimental novel tradition. Fielding’s performance as a literary critic will be compared with the few female authors who, like her, dared to publish literary criticism during her writing career. Accordingly, extracts from Fielding’s novels and her two critical pamphlets will be thoroughly examined.
An updated biography of Fielding that is also included here will provide evidence for a further claim, that her fiction is autobiographical in part. A comprehensive account of Fielding’s performance as a literary critic forms the final chapter of this work. It is the first full-length examination of her contribution to the genre and includes an appraisal of her recently unearthed critical pamphlet entitled A Comparison Between the Horace of Corneille and The Roman Father of Mr. Whitehead (1750) that is yet to be formerly attributed to her. Ultimately this study of Fielding will go far beyond what has previously been written about this remarkable eighteenth-century author, particularly regarding her feminist activity
'F- F- Felt it': Breathing Feminist, Queer and Clown Thinking into the Practice and Study of Sarah Kane’s Cleansed and Blasted
No full textThis thesis uses studio practice, scholarly research, close reading of text, performance observation and conversation with practitioners to establish diverse readings of Sarah Kane’s Cleansed. It includes original material from the 2012 productions of Cleansed in Japan (Kamome-za Fringe Theatre), and in Ireland (Bare Cheek Theatre). It notes practice on Cleansed in gallery spaces (Cast-Off Drama, UK). It offers a dramaturgical approach to workshopping the play from a feminist and queer position, informed by theories of gender and transgender, and the marginalised, loving and delinquent practice of clowning. The research discusses principles of breath, voice and sexuate difference drawing primarily on the philosophies of Luce Irigaray, on the voice practice of Cicely Berry and the clown teaching of Sue Morrison.
The work challenges the ‘in-yer-face’ theatre discourse on Kane arguing that it represents a McDonaldization of its subject matter, and an insidious trivialisation of her texts. It offers new thinking on the opening night of Blasted (1995), suggesting that the ‘furore’ was fuelled by collective male hysteria and superstition; its roots centred in mourning. Analysing Cleansed in relation to Edward Bond’s Saved and Lear, it explores tropes of ghosts, stitching and the silent scream, and argues that Kane militates for gynocentric time and becoming. It analyses the symbol of the perimeter fence as a feature of 1980s Britain, noting the strength of binary associations configured in it with reference to both English football hooliganism (male) and the Greenham Common Women’s Peace Camp (female). It argues that Kane sets up heteronormative binaries in Cleansed to debate and contest them.
A key conclusion of the thesis is that Cleansed politically addresses and dramatises issues of transgender experience presenting accounts of gender violence, mutability, transitioning, the sharp fractures and silences of gender dysphoria, but also, ultimately, queer desire, love and optimism
Data and R Code for Analyses in "Grassland birds demonstrate delayed response to large-scale tree removal in central North America"
No full textThe csv file documents the species observed at various point count stations in 14 Waterfowl Production Area sites. Measurements about the surrounding vegetation were included. Each of the 18493 rows is a record for a particular SPECIES observed at specified time and location. The R code file runs on R and imports the CSV file. The R code was written in R version 3.1.2.These files contain R code and data required for analsyes detailed within "Grassland birds demonstrate delayed response to large-scale tree removal in central North America" in the Journal of Applied Ecology. The lead author wrote this code to analyze multi-year point count data collected in west-central Minnesota. The purpose of the study was to assess the success of habitat restoration activities aimed at removal of encroaching trees and shrubs.The United States Fish and Wildlife ServiceThompson, Sarah, J. (2015). Data and R Code for Analyses in "Grassland birds demonstrate delayed response to large-scale tree removal in central North America". Retrieved from the University Digital Conservancy, http://dx.doi.org/10.13020/D6C88M
A critical analysis of the plays of Sarah Daniels.
Get PDFAs one of the forerunners of 'second wave' feminist playwriting, Sarah Daniels has for the
past fifteen years been one of Britain's most prolific writers for the stage. This thesis is the
first to offer a detailed critical analysis of all her published plays along with a developmental
account of her career. My approach throughout is text-based and non-prescriptive,
although I do at certain points indicate where Daniels reflects or voices differing feminist
perspectives. I also consider, beginning in Chapter Three, the critical reception and
'gendered' reviewing the playwright has received over the years.
The thesis is organised into five chapters with an Afterword. Chapter One, the
Introduction, offers an overview of Daniels' career as well as certain key characteristics of
her work. In Chapter Two I analyse the early plays, Ripen Our Darkness, The Devil's
Gateway and Neaptide, and consider in particular how they reflect, along with other
women's playwriting at the time, certain ideals of the Women's Liberation Movement.
Chapter Three is devoted entirely to Masterpieces, Daniels' most controversial and, on
many levels, successful play to date. Chapter Four is an analysis of the 'history plays',
Byrthrite and The Gut Girls. In addition to giving voice to women traditionally silenced in
and by history, these plays (especially Byrthrite) also echo particular strands of modern
feminist debate. Chapter Five examines Daniels' plays of the 1990s (Beside Herself, Head-
Rot Holiday and The Madness of Esme and Shaz) with their central theme of 'women and
madness'. This is also a fitting theme with which to conclude the thesis as it brings together
and expands on the most significant motif running throughout the playwright's work. In the
Afterword I consider the effect of Esme and Shaz's critical reception on Daniels, as well as
her current 'work in progress'. Finally, the two Appendices provide a chronological table of
Daniels' productions and a list of subsequent professional productions as well as awards
Editorial. Inclusive research in education: contributions to method and debate
Get PDFEducation is not necessarily associated with inclusive research and the label of inclusive research is little used in our discipline. It is an umbrella term encompassing participatory, emancipatory and community/peer-led research. This is research in which those (such as learners and teachers) who tend to be the objects of other people’s research become agents in the conduct of research, ensuring that such research addresses issues that are important to them and includes their views and experiences (see Walmsley & Johnson, 2003 and Nind, 2014 for more on definitions). Conceptualising some research as inclusive is part of a concern with the democratization of the research process and with social justice - in and through - research; it represents an interest in the people outside of academia being active and credible producers of knowledge
Hypoxia, reactive oxygen species and glucose metabolism in the regulation of the innate immune system
Get PDFINTRODUCTION:
Neutrophils are the most abundant innate immune cells, essential for
clearing pathogens from injured or infected sites and directing the ensuing
inflammatory response. Sites of inflammation tend to be hypoxic due to rapid tissue
volume expansion, loss of vascular integrity and oxygen consumption by infiltrating
immune cells. Neutrophils are well suited to the hypoxic niche and have metabolic
adaptations that enable them to exist in hypoxia, including a reliance on anaerobic
respiration, despite possessing a mitochondrial network. The role of neutrophil
mitochondria is unclear, and relatively few studies have examined what role the
mitochondria play in regulating neutrophil apoptosis and function, and how hypoxia
modulates anaerobic and aerobic neutrophil metabolism.
METHODS:
Neutrophils isolated from healthy volunteers were cultured in normoxia
(21% O2) and hypoxia (1% O2) in vitro and neutrophil function and metabolic flux
interrogated ex vivo. Functional consequences of hypoxic response pathway
manipulation were investigated in infection models carried out in mice with myeloid
specific PHD3 knockout.
RESULTS:
Neutrophil mitochondrial membrane potential and reactive oxygen species
production are enhanced in hypoxia through a mechanism independent of oxidative
phosphorylation. Neutrophil mitochondrial reactive oxygen species are capable of
stabilising HIF-1α and enhancing hypoxic survival of neutrophils. Manipulation of
the hypoxic response pathway and neutrophil metabolism through knockout of
PHD3 enhances control of bacterial infection through changes in neutrophil
metabolic flux.
CONCLUSION:
We describe a signalling role for the neutrophil mitochondria in
hypoxic conditions that is independent of oxidative phosphorylation activity.
Neutrophil anaerobic metabolism is also linked closely to antioxidant production
through the pentose phosphate pathway that compensates for mitochondrial oxidant
signalling from the mitochondria. Regulation of glycolysis is therefore required for
both reactive oxygen signalling and for managing oxidative stress in hypoxic
conditions. These pathways are also regulated by the activity of PHD3, in a manner
capable of modulating neutrophil bactericidal function
“And Abram listened to the voice of Sarai”: R. Crumb’s pro-feminist interpretation of Sarah in the Bible
No full textIn 2009, R. Crumb produced a singular work: The Book of Genesis, Illustrated by R. Crumb, which purports to be a faithful, graphical interpretation of the book of Genesis from the Hebrew Bible. Among other sources, Crumb states that he used Robert Alter’s translation and commentary on Genesis to inform his work, along with the King James Version (KJV), the Jewish Publication Society Version (JPS) and Sarah the Priestess: The First Matriarch of Genesis by Savina J. Teubal; from those, he produced his own interpretation together with annotations to explain his interpretive decisions.
Remediating or adapting ancient texts into modern graphical comic books affects the reception of the text in many ways, but also offers both comics creators and readers different interpretive spaces within which they can allow different readings of texts to emerge. Such spaces are arguably affected by the way in which creators read and interpret original sources, as well as by the understanding and application of comics’ tools and resources employed to create the comic book remediations.
This paper will investigate Crumb’s utilisation of various comics tools and resources in his remediation of Genesis, arguing that his interpretation of the biblical text is presented through careful visual and textual decisions. I argue that these decisions in turn present the matriarchs (Sarah, Rebekah, Rachel and Leah) in Genesis, Illustrated as strong, dominant characters who are cast as potential leaders in an otherwise patriarchal world. This is a characterisation which subverts both biblically-traditional readings of the women of Genesis, as well as expectations of Crumb as an author. Accusations of misogyny and sexism have followed Crumb throughout his career, but, I argue, do not stand when the reader is presented with his pro-feminist matriarchal remediation of the biblical text
Hypoxia and the regulation of host responses to acute bacterial pulmonary infections
No full textIntroduction – Severe pulmonary bacterial infections are frequently complicated by
systemic hypoxaemia and, in the context of acute respiratory distress syndrome
(ARDS), inappropriately prolonged neutrophilic inflammation. This combination of
acute hypoxaemia and persistent inflammatory response carries significant morbidity
and mortality. However, patients with chronic lung disease function in the
community with chronic systemic hypoxaemia and bacterial colonisation with much
lower acute mortality. The HIF/PHD pathway tightly regulates neutrophilic
responses to hypoxia and bacteria. Here, using acute bacterial pneumonia models, I
have dissected the differences in innate immune responses to infection in acute
hypoxia and following exposure to hypoxia prior to infection (‘preconditioning’).
Methods – C57BL/6 mice were housed in room air or ‘preconditioned’ by exposure
to 10% ambient hypoxia for seven days. They were then instilled with intratracheal
Streptococcus pneumoniae (1x104 or 1x107 cfu to assess macrophage and neutrophil
function respectively) under recovery anaesthesia and housed in normoxia (21% O2)
or hypoxia (10% O2). At pre-determined time-points, the animals were assessed
clinically for sickness and rectal temperature. Blood, bronchoalveolar lavage and
tissues were taken for analysis. Transcriptome analysis by RNA-sequencing and
functional glycolysis by Seahorse was performed on blood leucocytes.
Results – Concurrent exposure to hypoxia and infection resulted in neutrophil-mediated
morbidity and mortality. Acute hypoxia caused rapid utilisation of glucose,
glycogen and fat stores resulting in systemic hypoglycaemia and death.
Preconditioning with exposure to hypoxia prior to infection completely protected the
host against hypoxia-induced morbidity and mortality by suppressing leucocyte
glycolysis, through suppression of HIF1α, and resultant rescue from the negative
energy state and cardiovascular compromise.
Conclusion – Hypoxia preconditions the innate immune response by suppression of
HIF1α and glycolysis in leucocytes, thereby protecting against acute hypoxia-induced
mortality outcomes in acute bacterial pulmonary infection
- …
