Images of Self: A Study of Feminine and Feminist Subjectivity in the Poetry of Sylvia Plath, Anne Sexton, Margaret Atwood and Adrienne Rich, 1950-1980

PhDThe thesis explores the poetry (and some prose) of Plath, Sexton, Atwood and Rich in terms of the changing constructions of self-image predicated upon the female role between approx. 1950-1980.1 am particularly concerned with the question of how the discourses of femininity and feminism contribute to the scope of the images of the self which are presented. The period was chosen because it involved significant upheaval and change in terms of women's role and gender identity. The four poets' work spans this period of change and appears to some extent generally characteristic of its social, political and cultural contexts in America, Britain and Canada. (Other poets' work, for example Rukeyser, Lorde, Levertov, is included too. ) The poets were not chosen to illustrate a pre-feminist vs. feminist opposition since a major concern is to explore what I see to be the symbiotic relation between femininity and feminism (as also between orthodoxy and heresy). However the thesis is organised chronologically because periodisation is important for a consideration of the poetry's social setting. In wanting to connect the poetry with cultural and political circumstances as much as possible I have taken Edward Said's assertion of a text's position of 'being in the world', its potential as a cultural product to help reshape reality, and its value as a 'powerful weapon of both materialism and consciousness'. This is the starting point for the study which is circular and cumulative in shape, fundamentally thematic, though each chapter is a chronological exploration of the work of one specific poet, beginning with Plath and completing with Rich. A conclusion attempts to pull the strands of each together and consider the implications raised. The thesis has four general concerns which run through its particular focus on each poet. The first involves the relations between cultural practice and ideology; the second involves the ideology of gender (through exploration of femininity and feminism); the third involves authorial ideology (through the construction of self-image in relation to femininity and feminism) while the fourth involves these concerns in terms of the overall arena of women's struggle for meaning and selfdetermination in cultural practice. More specific elements of the study include collating and comparing self-images and attempting to make connections or chart changes where images such as witch, queen, handmaid, shamaness, goddess, earth mother, whore, madwoman, etc., re-occur. Usage of myth (particularly Persephone). the Gothic, 'and articulation of lesbian desire are also explored. The emergence of a female 'hero' self-image, in opposition to 'victim', seems to be a corollary of the impact , of feminism in Rich's poetry particularly, but this tendency can be traced back through Plath. I explore the celebration of nature and the power of essentialism in the construction of heroic female images, particularly in the figure of the mother flowing with milk at the centre of 'ecriture feminine'. The concluding chapter suggests that femininity did not constitute such a repressive constraint on self-image and writing practice for women as perhaps might be supposed; and that feminism, while opening up many empowering changes for women, has raised further disturbing and unresolved questions about identity, and even helped, in some of its aspects, to create a new 'orthodoxy' in which various aspects of experience cannot easily be articulated. My example is Rich's later work where it seems to admit itself limited by its own initially liberating strategies and looks further on towards new 'heresies.

HIV-specific Cytotoxic T Cells from Long-Term Survivors Select a Unique T Cell Receptor

HIV-specific cytotoxic T lymphocytes (CTL) are important in controlling HIV replication, but the magnitude of the CTL response does not predict clinical outcome. In four donors with delayed disease progression we identified Vβ13.2 T cell receptors (TCRs) with very similar and unusually long β-chain complementarity determining region 3 (CDR3) regions in CTL specific for the immunodominant human histocompatibility leukocyte antigens (HLA)-B8–restricted human immunodeficiency virus-1 (HIV-1) nef epitope, FLKEKGGL (FL8). CTL expressing Vβ13.2 TCRs tolerate naturally arising viral variants in the FL8 epitope that escape recognition by other CTL. In addition, they expand efficiently in vitro and are resistant to apoptosis, in contrast to FL8–specific CTL using other TCRs. Selection of Vβ13.2 TCRs by some patients early in the FL8-specific CTL response may be linked with better clinical outcome

Immune Activation and CD8(+) T-Cell Differentiation towards Senescence in HIV-1 Infection

Progress in the fight against the HIV/AIDS epidemic is hindered by our failure to elucidate the precise reasons for the onset of immunodeficiency in HIV-1 infection. Increasing evidence suggests that elevated immune activation is associated with poor outcome in HIV-1 pathogenesis. However, the basis of this association remains unclear. Through ex vivo analysis of virus-specific CD8(+) T-cells and the use of an in vitro model of naïve CD8(+) T-cell priming, we show that the activation level and the differentiation state of T-cells are closely related. Acute HIV-1 infection induces massive activation of CD8(+) T-cells, affecting many cell populations, not only those specific for HIV-1, which results in further differentiation of these cells. HIV disease progression correlates with increased proportions of highly differentiated CD8(+) T-cells, which exhibit characteristics of replicative senescence and probably indicate a decline in T-cell competence of the infected person. The differentiation of CD8(+) and CD4(+) T-cells towards a state of replicative senescence is a natural process. It can be driven by excessive levels of immune stimulation. This may be part of the mechanism through which HIV-1-mediated immune activation exhausts the capacity of the immune system

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

CD8⁺ T-Cell Differentiation and HIV-1 Disease Progression

<div><p>(A) Distribution of the CD8⁺ T-cell population in differentiated subsets (CD28⁺/CD27⁺ early, CD28⁻/CD27⁺ intermediate, and CD28⁻/CD27⁻ late) through the course of HIV-1 infection. Abbreviations: H, healthy (<i>n</i> = 15); A, acute HIV infection (<i>n</i> = 11); C, chronic HIV infection nonprogressor (no ART; <i>n</i> = 14); P, chronic HIV infection with signs of disease progression (no ART; <i>n</i> = 10). Statistics: * <i>p</i> < 0.0001 with the ANOVA test and <i>p</i> < 0.005 between each group.</p> <p>(B) Percentages of CD27⁻ CD8⁺ T-cells that are specific for HLA-B8 HIV (nef) or HLA-A2 CMV in HIV-1-infected individuals at different stages of infection. Statistics: ** <i>p</i> < 0.005 with the nonparametric Mann–Whitney test.</p> <p>(C) Inverse correlation between CD4⁺ T-cell counts and percentage of highly differentiated CD27⁻ cells in the whole CD8⁺ T-cell population of HIV-1-infected donors during chronic infection (untreated nonprogressors and progressors). The <i>p</i> value was obtained using the nonparametric Spearman rank correlation test.</p></div

CD8⁺ T-Cell Differentiation and Senescence

<div><p>(A) Expression of the replicative senescence-associated marker CD57 on antigen-experienced CD8⁺ T-cell subsets. The percentage and mean fluorescence intensity for the CD57⁺ cells are shown for one single donor. Data on several donors (HIV-1-infected or healthy) are also shown (<i>n</i> = 24).</p> <p>(B) Expression of CD57 on CD8⁺ T-cells (whole population or antigen-specific) from acute to postacute (on ART) HIV-1 infection.</p> <p>(C) CD69 expression and CFSE proliferation profile for CD8⁺ T-cell subsets gated on the basis of CD57 and CD27 expression following stimulation with anti-CD3 antibodies. PBMCs were analysed for CD69 expression after 18 h and CFSE labeling after 6 d. Percentages of proliferating cells (with background subtracted) are indicated. Representative results from three experiments (one HIV-infected and two healthy donors) are shown.</p> <p>(D) Telomere length measurement by flow FISH on naïve and antigen-experienced CD8⁺ T-cell subsets FACS-sorted on the basis of CD57, CD27, CCR7, and CD45RA expression. The average length of telomeres was obtained by substracting the mean fluorescence of the background control (no probe; open histogram) from the mean fluorescence obtained from cells hybridised with the FITC-labeled telomere probe (gray histogram). Representative results from two experiments (on healthy donors) are shown.</p> <p>(E) CD57 and perforin expression in the CD8⁺ T-cell population dissected into naïve (CD27^+high, perforin-negative), antigen-experienced CD27⁺ (perforin^low), and antigen-experienced CD27⁻ perforin^low or perforin^high subsets. The percentage and mean fluorescence intensity for the CD57⁺ cells are indicated.</p> <p>(F) Representative staining for perforin and CD57 in CD8⁺ T-cells from a HIV-1-infected or a healthy donor. Percentages of cells present in the top quadrants are shown.</p> <p>(G) Representative staining for perforin and CD57 in CD4⁺ T-cells from an HIV-1-infected or a healthy donor. Percentages of cells present in the top quadrants are shown.</p></div

CD8⁺ T-Cell Activation during Acute HIV-1 Infection

<div><p>(A) Percentages of activated CD38⁺ cells (gated on whole CD8⁺ T-cells, HIV tetramer-positive CD8⁺ T-cells, or whole CD4⁺ T-cells) in donors during acute HIV-1 infection and later postacute on ART (<i>n</i> = 12); healthy donors (<i>n</i> = 11) and untreated donors with nonprogressing chronic infection (<i>n</i> = 12) are also shown.</p> <p>(B and C) CD38 and Ki67 expression on CD8⁺ T-cell subsets defined by CD45RA/CD62L (B) or CD28/CD27 (C) expression, shown in one single donor from acute to postacute (on ART) HIV-1 infection. Percentages of positive cells are shown. Means (± SEM) of CD38⁺ and Ki67⁺ CD8⁺ T-cells for ten patients are also shown; statistics concern CD38 expression.</p> <p>(D) Staining for the activation marker CD38 on CMV-, EBV-, or influenza A virus-specific CD8⁺ T-cells during acute and postacute (on ART) HIV-1 infection in a single donor. Percentages of CD38⁺ tetramer-positive CD8⁺ T-cells are shown. Data on all donors (see <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.0020020#pbio-0020020-t001" target="_blank">Table 1</a>) are also shown.</p> <p>(E) Activation (CD38 and Ki67 staining) of CMV-specific CD8⁺ T-cells or whole CD8⁺ T-cell population during acute and postacute (on ART) HIV-1 infection in a single donor. Percentages of cells present in quadrants are shown.</p> <p>Statistics: * <i>p</i> < 0.002, ** <i>p</i> < 0.01, NS = nonsignificant, with the nonparametric Mann–Whitney test.</p></div

Memory CD8+ T cells vary in differentiation phenotype in different persistent virus infections.

The viruses HIV-1, Epstein-Barr virus (EBV), cytomegalovirus (CMV) and hepatitis C virus (HCV) are characterized by the establishment of lifelong infection in the human host, where their replication is thought to be tightly controlled by virus-specific CD8+ T cells. Here we present detailed studies of the differentiation phenotype of these cells, which can be separated into three distinct subsets based on expression of the costimulatory receptors CD28 and CD27. Whereas CD8+ T cells specific for HIV, EBV and HCV exhibit similar characteristics during primary infection, there are significant enrichments at different stages of cellular differentiation in the chronic phase of persistent infection according to the viral specificity, which suggests that distinct memory T-cell populations are established in different virus infections. These findings challenge the current definitions of memory and effector subsets in humans, and suggest that ascribing effector and memory functions to subsets with different differentiation phenotypes is no longer appropriate