William Sanday

n/

Mice lacking NF-κB1 exhibit marked DNA damage responses and more severe gastric pathology in response to intraperitoneal tamoxifen administration

Tamoxifen (TAM) has recently been shown to cause acute gastric atrophy and metaplasia in mice. We have previously demonstrated that the outcome of Helicobacter felis infection, which induces similar gastric lesions in mice, is altered by deletion of specific NF-κB subunits. Nfkb1-/- mice developed more severe gastric atrophy than wild-type (WT) mice 6 weeks after H. felis infection. In contrast, Nfkb2-/- mice were protected from this pathology. We therefore hypothesized that gastric lesions induced by TAM may be similarly regulated by signaling via NF-κB subunits. Groups of five female C57BL/6 (WT), Nfkb1-/-, Nfkb2-/- and c-Rel-/- mice were administered 150 mg/kg TAM by IP injection. Seventy-two hours later, gastric corpus tissues were taken for quantitative histological assessment. In addition, groups of six female WT and Nfkb1-/- mice were exposed to 12 Gy γ-irradiation. Gastric epithelial apoptosis was quantified 6 and 48 h after irradiation. TAM induced gastric epithelial lesions in all strains of mice, but this was more severe in Nfkb1-/- mice than in WT mice. Nfkb1-/- mice exhibited more severe parietal cell loss than WT mice, had increased gastric epithelial expression of Ki67 and had an exaggerated gastric epithelial DNA damage response as quantified by γH2AX. To investigate whether the difference in gastric epithelial DNA damage response of Nfkb1-/- mice was unique to TAM-induced DNA damage or a generic consequence of DNA damage, we also assessed gastric epithelial apoptosis following γ-irradiation. Six hours after γ-irradiation, gastric epithelial apoptosis was increased in the gastric corpus and antrum of Nfkb1-/- mice. NF-κB1-mediated signaling regulates the development of gastric mucosal pathology following TAM administration. This is associated with an exaggerated gastric epithelial DNA damage response. This aberrant response appears to reflect a more generic sensitization of the gastric mucosa of Nfkb1-/- mice to DNA damage

The Body Dances: Carnival Dance and Organization

Building on the work of Pierre Bourdieu and Maurice Merleau-Ponty we seek to open up traditional categories of thought surrounding the relation `body-organization' and elicit a thought experiment: What happens if we move the body from the periphery to the centre? We pass the interlocking theoretical concepts of object-body/subject-body and habitus through the theoretically constructed empirical case of `carnival dance' in order to re-evaluate such key organizational concepts as knowledge and learning. In doing so, we connect with an emerging body of literature on `sensible knowledge'; knowledge that is produced and preserved within bodily practices. The investigation of habitual appropriation in carnival dance also allows us to make links between repetition and experimentation, and reflect on the mechanism through which the principles of social organization, whilst internalized and experienced as natural, are embodied so that humans are capable of spontaneously generating an infinite array of appropriate actions. This perspective on social and organizational life, where change and permanence are intricately interwoven, contrasts sharply with the dominant view in organization studies which juxtaposes change/ creativity and stability

Epithelial cell shedding and barrier function: a matter of life and death at the small intestinal villus tip

The intestinal epithelium is a critical component of the gut barrier. Composed of a single layer of intestinal epithelial cells (IECs) held together by tight junctions, this delicate structure prevents the transfer of harmful microorganisms, antigens, and toxins from the gut lumen into the circulation. The equilibrium between the rate of apoptosis and shedding of senescent epithelial cells at the villus tip, and the generation of new cells in the crypt, is key to maintaining tissue homeostasis. However, in both localized and systemic inflammation, this balance may be disturbed as a result of pathological IEC shedding. Shedding of IECs from the epithelial monolayer may cause transient gaps or microerosions in the epithelial barrier, resulting in increased intestinal permeability. Although pathological IEC shedding has been observed in mouse models of inflammation and human intestinal conditions such as inflammatory bowel disease, understanding of the underlying mechanisms remains limited. This process may also be an important contributor to systemic and intestinal inflammatory diseases and gut barrier dysfunction in domestic animal species. This review aims to summarize current knowledge about intestinal epithelial cell shedding, its significance in gut barrier dysfunction and host-microbial interactions, and where research in this field is directed

Staggered versus overlap fermions: a study in the Schwinger model with Nf=0,1,2N_f=0,1,2

We study the scalar condensate and the topological susceptibility for a continuous range of quark masses in the Schwinger model with $N_f=0,1,2$ dynamical flavors, using both the overlap and the staggered discretization. At finite lattice spacing the differences between the two formulations become rather dramatic near the chiral limit, but they get severely reduced, at the coupling considered, after a few smearing steps.Comment: 15 pages, 7 figures, v2: 1 ref corrected, minor change

Unravelling social constructionism

Social constructionist research is an area of rapidly expanding influence that has brought together theorists from a range of different disciplines. At the same time, however, it has fuelled the development of a new set of divisions. There would appear to be an increasing uneasiness about the implications of a thoroughgoing constructionism, with some regarding it as both theoretically parasitic and politically paralysing. In this paper I review these debates and clarify some of the issues involved. My main argument is that social constructionism is not best understood as a unitary paradigm and that one very important difference is between what Edwards (1997) calls its ontological and epistemic forms. I argue that an appreciation of this distinction not only exhausts many of the disputes that currently divide the constructionist community, but also takes away from the apparent radicalism of much of this work

Series Expansions for three-dimensional QED

Strong-coupling series expansions are calculated for the Hamiltonian version of compact lattice electrodynamics in (2+1) dimensions, with 4-component fermions. Series are calculated for the ground-state energy per site, the chiral condensate, and the masses of `glueball' and positronium states. Comparisons are made with results obtained by other techniques.Comment: 13 figure

Expressivity in children's drawings of themselves for adult audiences with varied authority and familiarity

This study investigated whether children’s expressive drawings of themselves vary as a function of audience authority and familiarity. One hundred and seventy-five children, 85 boys and 90 girls, aged between 8 years 1 months and 9 years 2 months (M= 8 years 5 months) were allocated into seven groups; a reference group (n=25) where no audience was specified, and six audience groups (n=25 per group) varying by audience type (policeman vs. teacher vs. man) and familiarity (familiar vs. unfamiliar). They drew baseline then happy and sad drawings of themselves, rated affect towards drawings type, and rated perceived audience authority. Audience familiarity and authority impacted expressive drawing strategy use and this varied by gender. There was higher overall expressive strategy use for happy drawings and for girls, and influences of affect type, familiarity and authority were found. The implications of children’s perceptions of audience type on their expressive drawings are discussed

Some approximate analytical methods in the study of the self-avoiding loop model with variable bending rigidity and the critical behaviour of the strong coupling lattice Schwinger model with Wilson fermions

Some time ago Salmhofer demonstrated the equivalence of the strong coupling lattice Schwinger model with Wilson fermions to a certain 8-vertex model which can be understood as a self-avoiding loop model on the square lattice with bending rigidity $\eta = 1/2$ and monomer weight $z = (2\kappa)^{-2}$. The present paper applies two approximate analytical methods to the investigation of critical properties of the self-avoiding loop model with variable bending rigidity, discusses their validity and makes comparison with known MC results. One method is based on the independent loop approximation used in the literature for studying phase transitions in polymers, liquid helium and cosmic strings. The second method relies on the known exact solution of the self-avoiding loop model with bending rigidity $\eta = 1/\sqrt{2}$. The present investigation confirms recent findings that the strong coupling lattice Schwinger model becomes critical for $\kappa_{cr} \simeq 0.38-0.39$. The phase transition is of second order and lies in the Ising model universality class. Finally, the central charge of the strong coupling Schwinger model at criticality is discussed and predicted to be $c = 1/2$.Comment: 22 pages LaTeX, 6 Postscript figure

Four-dimensional pure compact U(1) gauge theory on a spherical lattice

We investigate the confinement-Coulomb phase transition in the four-dimensional (4D) pure compact U(1) gauge theory on spherical lattices. The action contains the Wilson coupling beta and the double charge coupling gamma. The lattice is obtained from the 4D surface of the 5D cubic lattice by its radial projection onto a 4D sphere, and made homogeneous by means of appropriate weight factors for individual plaquette contributions to the action. On such lattices the two-state signal, impeding the studies of this theory on toroidal lattices, is absent for gamma le 0. Furthermore, here a consistent finite-size scaling behavior of several bulk observables is found, with the correlation length exponent nu in the range nu = 0.35 - 40. These observables include Fisher zeros, specific-heat and cumulant extrema as well as pseudocritical values of beta at fixed gamma. The most reliable determination of nu by means of the Fisher zeros gives nu = 0.365(8). The phase transition at gamma le 0 is thus very probably of 2nd order and belongs to the universality class of a non-Gaussian fixed point.Comment: 40 pages, LaTeX, 12 figure