Overlap Distribution of the Three-Dimensional Ising Model

We study the Parisi overlap probability density P_L(q) for the three-dimensional Ising ferromagnet by means of Monte Carlo (MC) simulations. At the critical point P_L(q) is peaked around q=0 in contrast with the double peaked magnetic probability density. We give particular attention to the tails of the overlap distribution at the critical point, which we control over up to 500 orders of magnitude by using the multi-overlap MC algorithm. Below the critical temperature interface tension estimates from the overlap probability density are given and their approach to the infinite volume limit appears to be smoother than for estimates from the magnetization.Comment: 7 pages, RevTex, 9 Postscript figure

Involution of the mouse mammary gland is associated with an immune cascade and an acute-phase response, involving LBP, CD14 and STAT3

INTRODUCTION: Involution of the mammary gland is a complex process of controlled apoptosis and tissue remodelling. The aim of the project was to identify genes that are specifically involved in this process. METHODS: We used Affymetrix oligonucleotide microarrays to perform a detailed transcript analysis on the mechanism of controlled involution after withdrawal of the pups at day seven of lactation. Some of the results were confirmed by semi-quantitative reverse transcriptase polymerase chain reaction, Western blotting or immunohistochemistry. RESULTS: We identified 145 genes that were specifically upregulated during the first 4 days of involution; of these, 49 encoded immunoglobulin genes. A further 12 genes, including those encoding the signal transducer and activator of transcription 3 (STAT3), the lipopolysaccharide receptor (CD14) and lipopolysaccharide-binding protein (LBP), were involved in the acute-phase response, demonstrating that the expression of acute-phase response genes can occur in the mammary gland itself and not only in the liver. Expression of LBP and CD14 was upregulated, at both the RNA and protein level, immediately after pup withdrawal; CD14 was strongly expressed in the luminal epithelial cells. Other genes identified suggested neutrophil activation early in involution, followed by macrophage activation late in the process. Immunohistochemistry and histological staining confirmed the infiltration of the involuting mammary tissue with neutrophils, plasma cells, macrophages and eosinophils. CONCLUSION: Oligonucleotide microarrays are a useful tool for identifying genes that are involved in the complex developmental process of mammary gland involution. The genes identified are consistent with an immune cascade, with an early acute-phase response that occurs in the mammary gland itself and resembles a wound healing process

In situ conditions affecting the ductility capacity of lightly reinforced concrete wall structures in the Canterbury earthquake sequence

Following the 2010-2011 Canterbury (New Zealand) earthquake sequence, lightly reinforced wall structures in the Christchurch central business district were observed to form undesirable crack patterns in the plastic hinge region, while yield penetration either side of cracks and into development zones was less than predicted using empirical expressions. To some extent this structural behaviour was unexpected and has therefore demonstrated that there may be less confidence in the seismic performance of conventionally designed reinforced concrete (RC) structures than previously anticipated. This paper provides an observation-based comparison between the behaviour of RC structural components in laboratory testing and the unexpected structural behaviour of some case study buildings in Christchurch that formed concentrated inelastic deformations. The unexpected behaviour and poor overall seismic performance of ‘real’ buildings (compared to the behaviour of laboratory test specimens) was due to the localization of peak inelastic strains, which in some cases has arguably led to: (i) significantly less ductility capacity; (ii) less hysteretic energy dissipation; and (iii) the fracture of the longitudinal reinforcement. These observations have raised concerns about whether lightly reinforced wall structures can satisfy the performance objective of “Life Safety” at the Ultimate Limit State. The significance of these issues and potential consequences has prompted a review of potential problems with the testing conditions and procedures that are commonly used in seismic experimentations on RC structures. This paper attempts to revisit the principles of RC mechanics, in particular, the influence of loading history, concrete tensile strength, and the quantity of longitudinal reinforcement on the performance of real RC structures. Consideration of these issues in future research on the seismic performance of RC might improve the current confidence levels in newly designed conventional RC structures

Studies of Prototype CsI(Tl) Crystal Scintillators for Low-Energy Neutrino Experiments

Crystal scintillators provide potential merits for the pursuit of low-energy low-background experiments. A CsI(Tl) scintillating crystal detector is being constructed to study low-energy neutrino physics at a nuclear reactor, while projects are underway to adopt this technique for dark matter searches. The choice of the geometrical parameters of the crystal modules, as well as the optimization of the read-out scheme, are the results of an R&D program. Crystals with 40 cm in length were developed. The detector requirements and the achieved performance of the prototypes are presented. Future prospects for this technique are discussed.Comment: 32 pages, 14 figure

A framework for modelling whole-lung and regional TLCO using hyperpolarised 129Xe lung MRI

Background: Pulmonary gas exchange is assessed by the transfer factor of the lungs (TL) for carbon monoxide (TLCO), and can also be measured with inhaled xenon-129 (129Xe) MRI. A model has been proposed to estimate TL from 129Xe MRI metrics, but this approach has not been fully validated and does not utilise the spatial information provided by 3D 129Xe MRI. Methods: Three models for predicting TL from 129Xe MRI metrics were compared; (1) a previously-published physiology-based model, (2) multivariable linear regression and (3) random forest regression. Models were trained on data from 150 patients with asthma and/or chronic obstructive pulmonary disease. The random forest model was applied voxel-wise to 129Xe images to yield regional TL maps. Results: Coefficients of the physiological model were found to differ from previously reported values. All models had good prediction accuracy with small mean absolute error (MAE); (1) 1.24±0.15 mmol·min−1·kPa−1, (2) 1.01±0.06 mmol·min−1·kPa−1, (3) 0.995±0.129 mmol·min−1·kPa−1. The random forest model performed well when applied to a validation group of post-COVID-19 patients and healthy volunteers (MAE=0.840 mmol·min−1·kPa−1), suggesting good generalisability. The feasibility of producing regional maps of predicted TL was demonstrated and the whole-lung sum of the TL maps agreed with measured TLCO (MAE=1.18 mmol·min−1·kPa−1). Conclusion: The best prediction of TLCO from 129Xe MRI metrics was with a random forest regression framework. Applying this model on a voxel-wise level to create parametric TL maps provides a useful tool for regional visualisation and clinical interpretation of 129Xe gas exchange MRI

Glucocorticoids regulate AKR1D1 activity in human liver in vitro and in vivo

Steroid 5β-reductase (AKR1D1) is highly expressed in human liver where it inactivates endogenous glucocorticoids and catalyses an important step in bile acid synthesis. Endogenous and synthetic glucocorticoids are potent regulators of metabolic phenotype and play a crucial role in hepatic glucose metabolism. However, the potential of synthetic glucocorticoids to be metabolised by AKR1D1 as well as to regulate its expression and activity has not been investigated. The impact of glucocorticoids on AKR1D1 activity was assessed in human liver HepG2 and Huh7 cells; AKR1D1 expression was assessed by qPCR and Western blotting. Genetic manipulation of AKR1D1 expression was conducted in HepG2 and Huh7 cells and metabolic assessments were made using qPCR. Urinary steroid metabolite profiling in healthy volunteers was performed pre- and post-dexamethasone treatment, using gas chromatography-mass spectrometry. AKR1D1 metabolised endogenous cortisol, but cleared prednisolone and dexamethasone less efficiently. In vitro and in vivo, dexamethasone decreased AKR1D1 expression and activity, further limiting glucocorticoid clearance and augmenting action. Dexamethasone enhanced gluconeogenic and glycogen synthesis gene expression in liver cell models and these changes were mirrored by genetic knockdown of AKR1D1 expression. The effects of AKR1D1 knockdown were mediated through multiple nuclear hormone receptors, including the glucocorticoid, pregnane X and farnesoid X receptors. Glucocorticoids down-regulate AKR1D1 expression and activity and thereby reduce glucocorticoid clearance. In addition, AKR1D1 down-regulation alters the activation of multiple nuclear hormone receptors to drive changes in gluconeogenic and glycogen synthesis gene expression profiles, which may exacerbate the adverse impact of exogenous glucocorticoids

Manageable creativity

This article notes a perception in mainstream management theory and practice that creativity has shifted from being disruptive or destructive to 'manageable'. This concept of manageable creativity in business is reflected in a similar rhetoric in cultural policy, especially towards the creative industries. The article argues that the idea of 'manageable creativity' can be traced back to a 'heroic' and a 'structural' model of creativity. It is argued that the 'heroic' model of creativity is being subsumed within a 'structural' model which emphasises the systems and infrastructure around individual creativity rather than focusing on raw talent and pure content. Yet this structured approach carries problems of its own, in particular a tendency to overlook the unpredictability of creative processes, people and products. Ironically, it may be that some confusion in our policies towards creativity is inevitable, reflecting the paradoxes and transitions which characterise the creative process

Characterisation of GLUT4 trafficking in HeLa cells: comparable kinetics and orthologous trafficking mechanisms to 3T3-L1 adipocytes

Insulin-stimulated glucose transport is a characteristic property of adipocytes and muscle cells and involves the regulated delivery of glucose transporter (GLUT4)-containing vesicles from intracellular stores to the cell surface. Fusion of these vesicles results in increased numbers of GLUT4 molecules at the cell surface. In an attempt to overcome some of the limitations associated with both primary and cultured adipocytes, we expressed an epitope- and GFP-tagged version of GLUT4 (HA–GLUT4–GFP) in HeLa cells. Here we report the characterisation of this system compared to 3T3-L1 adipocytes. We show that insulin promotes translocation of HA–GLUT4–GFP to the surface of both cell types with similar kinetics using orthologous trafficking machinery. While the magnitude of the insulin-stimulated translocation of GLUT4 is smaller than mouse 3T3-L1 adipocytes, HeLa cells offer a useful, experimentally tractable, human model system. Here, we exemplify their utility through a small-scale siRNA screen to identify GOSR1 and YKT6 as potential novel regulators of GLUT4 trafficking in human cells

Curvature correction to the mobility of fluid membrane inclusions

For the first time, using rigorous low-Reynolds-number hydrodynamic theory on curved surfaces via a Stokeslet-type approach, we provide a general and concise expression for the leading-order curvature correction to the canonical, planar, Saffman-Delbrück value of the diffusion constant for a small inclusion embedded in an arbitrarily (albeit weakly) curved fluid membrane. In order to demonstrate the efficacy and utility of this wholly general result, we apply our theory to the specific case of calculating the diffusion coefficient of a locally curvature inducing membrane inclusion. By including both the effects of inclusion and membrane elasticity, as well as their respective thermal shape fluctuations, excellent agreement is found with recently published experimental data on the surface tension dependent mobility of membrane bound inclusions