The development of character presentation in Elizabethan prose fiction, with some particular reference to the works of Thomas Deloney

This thesis sets out to demonstrate the gradual growth of interest in, and successful presentation of, character traceable during the Elizabethan period. It attempts to show: (a) the lack both of conscious interest in character and of the tools for its portrayal in the early years; (b) the effects of the period of apprenticeship -the assimilation of new character-types and the development of the methods of presentation; (c) the emergence of certain writers, notably Gascoigne, Greene, Nashe and Deloney, who made original advances in the field of characterisation. It has proved necessary to investigate the origins of English Renaissance fiction in order to reveal the paucity of the story-teller's stock-in-trade at the beginning of the period. Interest in character is to-day taken so much for granted that the lack of satisfying characterisation in early fiction may be wrongly ascribed to failure on the writer's part successfully to fulfil his aims. In fact, the depiction of human personalities and relationships was little part of his aim, and conscious interestin character, except under its moral aspect, was rare. Against this background, the successes of a few writers stand out in their true perspective. The most successful creators of character were, with the possible exception of Robert Greene, innovators rather than perfecters of others' techniques. It has been possible, by concentrating on their achievements in characterisation alone, and by measuring these against the achievements of the average fiction-writer of the day, to shed new light on the work of Gascoigne, Greene, Nashe and Deloney. In particular, a reassessment of the relative merits of Greene's various works of fiction has been arrived at, and the detailed analysis of Deloney's methods of characterisation has shown how he achieved the considerable success now generally conceded to him.<p

Narrow Line Cooling: Finite Photon Recoil Dynamics

We present an extensive study of the unique thermal and mechanical dynamics for narrow-line cooling on the 1S0 - 3P1 88Sr transition. For negative detuning, trap dynamics reveal a transition from the semiclassical regime to the photon-recoil-dominated quantum regime, yielding an absolute minima in the equilibrium temperature below the single-photon recoil limit. For positive detuning, the cloud divides into discrete momentum packets whose alignment mimics lattice points on a face-centered-cubic crystal. This novel behavior arises from velocity selection and "positive feedback" acceleration due to a finite number of photon recoils. Cooling is achieved with blue-detuned light around a velocity where gravity balances the radiative force.Comment: 4 pages, 3 figures, Phys. Rev. Lett., in pres

Specific protein-protein binding in many-component mixtures of proteins

Proteins must bind to specific other proteins in vivo in order to function. The proteins must bind only to one or a few other proteins of the of order a thousand proteins typically present in vivo. Using a simple model of a protein, specific binding in many component mixtures is studied. It is found to be a demanding function in the sense that it demands that the binding sites of the proteins be encoded by long sequences of bits, and the requirement for specific binding then strongly constrains these sequences. This is quantified by the capacity of proteins of a given size (sequence length), which is the maximum number of specific-binding interactions possible in a mixture. This calculation of the maximum number possible is in the same spirit as the work of Shannon and others on the maximum rate of communication through noisy channels.Comment: 13 pages, 3 figures (changes for v2 mainly notational - to be more in line with notation in information theory literature

Superoxide dismutase downregulation in osteoarthritis progression and end-stage disease

Oxidative stress is proposed as an important factor in osteoarthritis (OA). To investigate the expression of the three superoxide dismutase (SOD) antioxidant enzymes in OA. SOD expression was determined by real-time PCR and immunohistochemistry using human femoral head cartilage. SOD2 expression in Dunkin–Hartley guinea pig knee articular cartilage was determined by immunohistochemistry. The DNA methylation status of the SOD2 promoter was determined using bisulphite sequencing. RNA interference was used to determine the consequence of SOD2 depletion on the levels of reactive oxygen species (ROS) using MitoSOX and collagenases, matrix metalloproteinase 1 (MMP-1) and MMP-13, gene expression. All three SOD were abundantly expressed in human cartilage but were markedly downregulated in end-stage OA cartilage, especially SOD2. In the Dunkin–Hartley guinea pig spontaneous OA model, SOD2 expression was decreased in the medial tibial condyle cartilage before, and after, the development of OA-like lesions. The SOD2 promoter had significant DNA methylation alterations in OA cartilage. Depletion of SOD2 in chondrocytes increased ROS but decreased collagenase expression. This is the first comprehensive expression profile of all SOD genes in cartilage and, importantly, using an animal model, it has been shown that a reduction in SOD2 is associated with the earliest stages of OA. A decrease in SOD2 was found to be associated with an increase in ROS but a reduction of collagenase gene expression, demonstrating the complexities of ROS function

Application of a stochastic modeling to evaluate tuberculosis onset in patients treated with tumor necrosis factor inhibitors

In this manuscript we apply stochastic modeling to investigate the risk of reactivation of latent mycobacterial infections in patients undergoing treatment with tumor necrosis factor inhibitors. First, we review the perspective proposed by one of the authors in a previous work and which consists in predicting the occurrence of reactivation of latent tuberculosis infection or newly acquired tuberculosis during treatment; this is based on variational procedures on a simple set of parameters (e.g. rate of reactivation of a latent infection). Then, we develop a full analytical study of this approach through a Markov chain analysis and we find an exact solution for the temporal evolution of the number of cases of tuberculosis infection (re)activation. The analytical solution is compared with Monte Carlo simulations and with experimental data, showing overall excellent agreement. The generality of this theoretical framework allows to investigate also the case of non-tuberculous mycobacteria infections; in particular, we show that reactivation in that context plays a minor role. This may suggest that, while the screening for tuberculous is necessary prior to initiating biologics, when considering non-tuberculous mycobacteria only a watchful monitoring during the treatment is recommended. The framework outlined in this paper is quite general and could be extremely promising in further researches on drug-related adverse events.Comment: 26 pages, 7 figure

Direct Observation of Site-specific Valence Electronic Structure at Interface: SiO2/Si Interface

Atom specific valence electronic structures at interface are elucidated successfully using soft x-ray absorption and emission spectroscopy. In order to demonstrate the versatility of this method, we investigated SiO2/Si interface as a prototype and directly observed valence electronic states projected at the particular atoms of the SiO2/Si interface; local electronic structure strongly depends on the chemical states of each atom. In addition we compared the experimental results with first-principle calculations, which quantitatively revealed the interfacial properties in atomic-scale.Comment: 4 pages, 3 figure

Interference of Bose-Einstein condensates in momentum space

We suggest an experiment to investigate the linear superposition of two spatially separated Bose-Einstein condensates. Due to the coherent combination of the two wave functions, the dynamic structure factor, measurable through inelastic photon scattering at high momentum transfer $q$, is predicted to exhibit interference fringes with frequency period $\Delta\nu = q/md$ where $d$ is the distance between the condensates. We show that the coherent configuration corresponds to an eigenstate of the physical observable measured in the experiment and that the relative phase of the condensates is hence created through the measurement process.Comment: 4 pages and 2 eps figure

Intimin, tir, and Shiga toxin 1 do not influence enteropathogenic responses to Shiga toxin-producing Escherichia coli in bovine ligated intestinal loops

Shiga toxin-producing Escherchia coli (STEC) comprises a group of attaching and effacing (A/E) enteric pathogens of animals and humans. Natural and experimental infection of calves with STEC may result in acute enteritis or subclinical infection, depending on serotype- and host-specific factors. To quantify intestinal secretory and inflammatory responses to STEC in the bovine intestine, serotypes that are associated with human disease (O103:H2 and O157:H7) were introduced into ligated mid-ileal loops in gnotobiotic and conventional calves, and fluid accumulation and recruitment of radiolabeled neutrophils were measured after 12 h. STEC serotype O103:H2, but not serotype O157:H7, elicited strong enteropathogenic responses. To determine if the inflammatory response to STEC O103:H2 in calves requires Shiga toxin 1 or intimate bacterial attachment to the intestinal epithelium, defined mutations were made in the stx1, eae, and tir genes. Our data indicate that some STEC induce intestinal inflammatory responses in calves by a mechanism that is independent of A/E-lesion formation, intimin, or Shiga toxin 1. This may have implications for strategies to reduce STEC carriage in cattle

Patterns of care and survival for patients aged under 40 years with bone sarcoma in Britain, 1980–1994

The purpose of the study was to calculate population-based survival rates for osteosarcoma (OS) and Ewing's sarcoma (ES) in Great Britain during 1980–1994, determine proportions of patients treated at specialist centres or entered in national and international clinical trials, and investigate effects of these factors on survival. Data on a population-based series of 1349 patients with OS and 849 with ES were compiled from regional and national cancer registries, UK Children's Cancer Study Group, regional bone tumour registries and clinical trials. Follow-up was through population registers. Survival was analysed by actuarial analysis with log-rank tests and by Cox's proportional hazards analysis. Five-year survival rates during 1980–1984, 1985–1989 and 1990–1994 were 42% (95% CI: 37, 46), 54% (95% CI: 50, 59) and 53% (95% CI: 48, 57), respectively, for OS and 31% (95% CI: 26, 37), 46% (95% CI: 40, 51) and 51% (95% CI: 45, 57) for ES. Proportions of patients treated at a supraregional bone tumour centre or a paediatric oncology centre in the three quinquennia were 36, 56 and 67% for OS and 41, 60 and 69% for ES. In 1983–1992, 48% of OS patients were entered in a national trial; for ES, 27% were entered in 1980–1986 and 54% in 1987–1994. Survival was similar for trial and nontrial patients with OS. For ES, trial patients had consistently higher 5-year survival than nontrial patients: 1980–1986, 42 vs 30%; 1987–1992, 59 vs 42%; 1993–1994, 54 vs 43%. During 1985–1994, patients with OS or ES whose main treatment centre was a nonteaching hospital had lower survival rates. In multivariate analyses of patients diagnosed during 1985–1994 that also included age, sex, primary site, surgical treatment centre, the results relating to main treatment centre for both OS and ES retained significance but the survival advantage of trial entry for ES became nonsignificant. For both OS and ES diagnosed since 1985, patients whose main treatment centre was a nonspecialist hospital had a lower survival rate