Grounding Deliberative Contractualism

Contractualism is often seen as a kind of self-interested bargaining in which individuals engage to preserve their own desired outcome. If individuals are only out for themselves, then no one achieves his or her desired end. Yet, if individuals constrain some of their desires and are assured that others will do the same, then, the contractors can avoid mutual destruction. It is not hard to see why Contractualism is often viewed as a way to explain the origins of morality within civil society. In this paper, I take up a version of Contractualism espoused by Nicholas Southwood called Deliberative Contractualism. The outcome of a perfectly deliberative rational process is what grounds morality or says Southwood. I consider two objections against Southwood’s account. I first consider the way Southwood criticizes a nearby Contractualist view and demonstrate that the same criticisms that Southwood levels against that account apply to Southwood’s. I end with a modest conclusion. While I don’t resolve the problems in either account, I do think I give more clarity to the debate about what it takes to ground morality

Improving Vaccine Design For Viral Diseases Using Modified Antigens And Vectors

Two of the principal challenges facing vaccine design today are how to generate protective antibody responses against viruses that have evolved sophisticated strategies to evade the humoral immune system and how to more rapidly and effectively produce vaccines to address emerging epidemics. In this regard, we explored multiple strategies to improve vaccine design for HIV-1 and Zika virus. In one approach, we derived CD4-independent variants of HIV-1 envelope (Env) with the hypothesis that such Envs would expose conserved epitopes that may be targets of protective, non-neutralizing antibodies. We characterized the biological and structural properties of two CD4-independent Env clones and found that they exhibited significantly greater exposure of a relatively conserved, linear epitope in the second variable loop (V2) that had previously been associated with decreased risk of infection in a clinical HIV-1 vaccine trial. This epitope was significantly more immunogenic in mice and nonhuman primates and, intriguingly, was associated with more rapid development of antibody-dependent cell-mediated cytotoxicity. In another approach, we designed mutations in the cytoplasmic tail of HIV-1 Env that were predicted to increase its cell surface expression and thus its immunogenicity in a vaccinia prime-protein boost vaccine protocol. We found that the highest level of surface expression was mediated by Envs with truncated cytoplasmic tails, and this was associated with higher levels of binding and neutralizing antibodies after vaccinia primes and protein boosts, respectively. These two studies revealed that modifications to HIV-1 Env immunogens are able to influence both the quality and magnitude of desirable antibody responses. Finally, we used a newly developed vaccine platform based on nucleoside-modified mRNA to design a vaccine against Zika virus. This vaccine, encoding the surface prM and E proteins, was potently immunogenic and elicited high and sustained titers of neutralizing antibodies in mice and nonhuman primates following a single intradermal immunization. We observed rapid and durable protection from Zika virus infection in mice and a high level of protection in monkeys challenged five weeks after vaccination. This vaccine thus represents a promising candidate for clinical use in controlling the spread of Zika virus

Gender and Fluid: A Reconsideration of the Stain in the Painting of Helen Frankenthaler

This paper explores the stain technique of Helen Frankenthaler through a reconsideration of its novelty and innovation. Recent scholarship has assessed the technique and its critical acceptance through a primarily feminist lens, focused on either assessment of the gendered language utilized by critics or application of a uniquely feminist approach in determining its meaning. The singular focus applied in recent criticism is consistent with past approaches that have typically isolated a particular methodology – formalistic, technical, comparative, or historical – to the exclusion of broader consideration of other methodologies. Moreover, prior critical efforts frequently limited analytical consideration to her groundbreaking work Mountains and Sea and the extent of Jackson Pollock’s influence on it. Yet Frankenthaler’s oeuvre is rich with formal and technical nuances that create a denser and more complex art than these approaches individually expose. Through consideration of a multiplicity of critical methodologies, this paper will reveal the complexity of Frankenthaler’s work broadly and the uniqueness of her approach specifically in Mountains and Sea when considered on its own as well as in comparison to the work of other artists. The paper will suggest a different reading of the stain that recognizes the implicit calm yet intense power of water and liquid as a metaphor for the intensity of the artist as a woman painter undeterred in her professional aspirations to create a place for herself in a man’s world

The Radio Properties of Brightest Cluster Galaxies

Energetic feedback from the Active Galactic Nucleus (AGN) of the Brightest Cluster Galaxy (BCG) is required to prevent catastrophic cooling of the intra-cluster medium (ICM) in galaxy clusters. Evidence for this is seen through the inflation of cavities in the ICM by AGN-launched, radio-emitting jets, and understanding this process is an active area of research. Radio observations play an integral role in this, as they trace the active stages of the feedback cycle. Understanding the radio properties of BCGs is therefore paramount for understanding both galaxy clusters and AGN feedback processes globally. Within this thesis, the BCGs in a large ($>$700) sample of X-ray selected clusters are studied. We observe these BCGs with a wide variety of facilities, building a census of their radio properties across a range of frequencies, timescales and angular resolutions. Radio spectral energy distributions (SEDs) are built for over 200 BCGs, and then decomposed into two components; a core, attributable to ongoing nuclear activity, and a non-core, attributable to historical accretion. Both components are not only more common, but also significantly more powerful in cool-core (CC) clusters than non-cool core (NCC) clusters. However, it is the presence of an {\em active} core that shows BCGs in CC clusters are constantly `on' - explaining how they regulate their environments over gigayear timescales. We observe 35 currently active BCGs at high (15~--~353~GHz) radio frequencies, and monitor their variability. Self-absorbed, active components are found to be common at high frequency. Little variability is seen on $<$year timescales, although longer term variation of $\approx$10\% annually over few-decade timescales is observed. Evidence is presented for a hitherto unseen component in BCG spectra that may be attributable to a naked Advection Dominated Accretion Flow (ADAF). The milli-arcsecond scale radio properties of 59 sources are studied, with a large range of morphologies recovered although no evidence is found for dual AGN being common in BCGs. Finally, we present a study that has more than doubled the number of HI absorption systems known in BCGs. We show that both the detection rate and column densities observed are strongly affected by the multi-scale properties of the radio continuum. All our clear detections are redshifted or at the systemic velocity. Most HI appears to be located in a clumpy torus that is replenished by residual material cooling from the ICM, linking the environment to the central engine and completing the feedback cycle