Systems analysis of host-parasite interactions.

Parasitic diseases caused by protozoan pathogens lead to hundreds of thousands of deaths per year in addition to substantial suffering and socioeconomic decline for millions of people worldwide. The lack of effective vaccines coupled with the widespread emergence of drug-resistant parasites necessitates that the research community take an active role in understanding host-parasite infection biology in order to develop improved therapeutics. Recent advances in next-generation sequencing and the rapid development of publicly accessible genomic databases for many human pathogens have facilitated the application of systems biology to the study of host-parasite interactions. Over the past decade, these technologies have led to the discovery of many important biological processes governing parasitic disease. The integration and interpretation of high-throughput -omic data will undoubtedly generate extraordinary insight into host-parasite interaction networks essential to navigate the intricacies of these complex systems. As systems analysis continues to build the foundation for our understanding of host-parasite biology, this will provide the framework necessary to drive drug discovery research forward and accelerate the development of new antiparasitic therapies

Managing Risk in an Athletic Training Education Program

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The Effect of Platelet-Derived Growth Factor on Cell Division and Glycosaminoglycan Synthesis by Human Skin and Scar Fibroblasts

The effect of platelet-derived growth factor (PDGF) on cell division and glycosaminoglycan (GAG) synthesis by fibroblasts isolated from skin and scar was measured. We found that PDGF stimulates cell division more efficiently in normal skin fibroblasts than in scar fibroblasts and decreases GAG synthesis in skin and scar fibroblasts. Using a 4-h pulse label with [3H]thymidine ([3H]Thd) following a 20-h incubation of confluent monolayer cultures with 0–5 units PDGF/ml Dulbecco's modified Eagle's medium, WC found a concentration-dependent increase in [3H]Thd incorporation. After incubation of fibroblasts with [3H]glucosamine and 35SO4 in the presence or absence of PDGF, labeled constituents were isolated from the extracellular, pericellular, and cellular fractions by pronase digestion and column chromatography on Sepharose CL4B or DEAE-cellulose and analyzed by cellulose acetate electrophoresis. The presence of PDGF decreased the total amount of 35S incorporated into macromolecules by skin and scar fibroblasts and resulted in an altered distribution of labeled GAGs. Dermatan fibroblasts exposed to PDGF for 24h incorporated a greater percentage of radiolabeled 35S into dermatan sulfate prime (DS') and less into dermatan sulfate (DS) in the extracellular fractions and a greater percentage of 35S into heparan sulfate (HS) in the pericellular fractions than did parallel cultures grown in the absence of PDGF. It is thought than PDGF may have an effect on scar formation by increasing the fibroblast population in the wound tissue and by affecting the total amount and types of matrix components synthesized

Relationships between mental toughness, barriers to exercise, and exercise behaviour in undergraduate students

The present study explored relationships between mental toughness (MT), barriers to exercise, and self-reported exercise behaviour in university students. Perceived barriers to exercise are important since previous work has identified barriers as strong predictors of exercise behaviour. MT was hypothesised to predict exercise barriers and self-reported exercise behaviour. Participants were 173 undergraduate students (45 men, 128 women) from 10 United Kingdom universities. Questionnaires were used to assess MT, exercise levels, and exercise barriers. Path analysis identified that MT predicted barriers to exercise, with higher MT associated with weaker perceived barriers. Regular exercisers were found to have significantly higher MT than non-regular exercisers, with commitment identified as a key difference. These findings support the proposed hypotheses and provide further evidence of the importance of MT in exercise / physical activity contexts. Future research that adopts longitudinal designs and tests targeted interventions to reduce perceptions of barriers and enhance exercise participation are encouraged

Observing the earliest moments of supernovae using strong gravitational lenses

We determine the viability of exploiting lensing time delays to observe strongly gravitationally lensed supernovae (gLSNe) from first light. Assuming a plausible discovery strategy, the Legacy Survey of Space and Time (LSST) and the Zwicky Transient Facility (ZTF) will discover $\sim$ 110 and $\sim$ 1 systems per year before the supernova (SN) explosion in the final image respectively. Systems will be identified $11.7^{+29.8}_{-9.3}$ days before the final explosion. We then explore the possibility of performing early-time observations for Type IIP and Type Ia SNe in LSST-discovered systems. Using a simulated Type IIP explosion, we predict that the shock breakout in one trailing image per year will peak at $\lesssim$ 24.1 mag ($\lesssim$ 23.3) in the $B$-band ($F218W$), however evolving over a timescale of $\sim$ 30 minutes. Using an analytic model of Type Ia companion interaction, we find that in the $B$-band we should observe at least one shock cooling emission event per year that peaks at $\lesssim$ 26.3 mag ($\lesssim$ 29.6) assuming all Type Ia gLSNe have a 1 M$_\odot$ red giant (main sequence) companion. We perform Bayesian analysis to investigate how well deep observations with 1 hour exposures on the European Extremely Large Telescope would discriminate between Type Ia progenitor populations. We find that if all Type Ia SNe evolved from the double-degenerate channel, then observations of the lack of early blue flux in 10 (50) trailing images would rule out more than 27% (19%) of the population having 1 M$_\odot$ main sequence companions at 95% confidence.Comment: 17 pages, 15 figures (including appendices). Accepted by MNRAS 3rd May 202

'The Apish Art': Taste in Early Modern England

The recent burgeoning of sensory history has produced much valuable work. The sense of taste, however, remains neglected. Focusing on the early modern period, my thesis remedies this deficit. I propose that the eighteenth-century association of ‘taste’ with aesthetics constitutes a restriction, not an expansion, of its scope. Previously, taste’s epistemological jurisdiction was much wider: the word was frequently used to designate trial and testing, experiential knowledge, and mental judgement. Addressing sources ranging across manuscript commonplace books, drama, anatomical textbooks, devotional poetry, and ecclesiastical polemic, I interrogate the relation between taste as a mode of knowing, and contemporary experiences of the physical sense, arguing that the two are inextricable in this period. I focus in particular on four main areas of enquiry: early uses of ‘taste’ as a term for literary discernment; taste’s utility in the production of natural philosophical data and its rhetorical efficacy in the valorisation of experimental methodologies; taste’s role in the experience and articulation of religious faith; and a pervasive contemporary association between sweetness and erotic experience. Poised between acclaim and infamy, the sacred and the profane, taste in the seventeenth century is, as a contemporary iconographical print representing ‘Gustus’ expresses it, an ‘Apish Art’. My thesis illuminates the pivotal role which this ambivalent sense played in the articulation and negotiation of early modern obsessions including the nature and value of empirical knowledge, the attainment of grace, and the moral status of erotic pleasure, attesting in the process to a very real contiguity between different ways of knowing – experimental, empirical, textual, and rational – in the period

Self-ideal, Self-discrepancy and Sociometric Choice Status

This study hypothesized a relationship between self-acceptance and acceptance by others. The hypothesis was that patients chosen frequently by other persons on a friendship criterion would have lower self-ideal, self-discrepancy scores than patients chosen infrequently by other persons on a friendship criterion. The study also hypothesized that depressed patients would have higher discrepancy scores than either the psychopathic or situational stress groups

Characterising the B-cell response to Hepatitis C virus infection in patient cohorts: impact on clinical outcomes and implications for vaccine design

Hepatitis C virus (HCV) infection is one of the major causes of liver morbidity and mortality worldwide. While effective therapies are now available, if eradication of this virus is to be achieved globally, an effective vaccine is still necessary. During hepatitis C virus (HCV) infection, broadly neutralizing antibody (bNAb) responses targeting E1E2 envelope glycoproteins are generated in many individuals. It is unclear if these antibodies play a protective or a pathogenic role during chronic infection or if they could prevent infection or reinfection with the virus. I investigated the presence and clinical associations of bNAb responses in three cohorts of individuals infected with or exposed to HCV infection. One with chronic HCV infection at differing disease states, one with chronic HCV infection at an early disease state and one group of individuals at high risk of HCV exposure who remained uninfected by conventional testing. I also studied bNAb responses in an individual from a HCV-HIV co-infected cohort who experienced spontaneous clearance of HCV after a post-therapy relapse (‘secondary spontaneous clearance’). I found a proportion of individuals when exposed to or infected with HCV produce a polyclonal bNAb response which may contribute to viral clearance in some cases. Host genetics and the ability to target multiple neutralising epitopes on the envelope protein are associated with such responses, although resistance mutations to bNAbs do exist in vivo. The presence of bNAbs is associated with lower levels of liver fibrosis. Using next generation sequencing technology in the study of B cell receptors in HCV infection revealed subtle changes in the B cell repertoire on HCV infection, this technology may be used in future to gain insight into the generation of bNAb responses

Large Five State Health System Standardizes Stroke Patient Education While Significantly Improving Health Literacy

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Cost Analysis of Implementing Standardized Stroke Patient Education Materials in a Large Five State Health System

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