The field theoretic derivation of the contact value theorem in planar geometries and its modification by the Casimir effect

The contact value theorem for Coulomb gases in planar or film-like geometries is derived using a Hamiltonian field theoretic representation of the system. The case where the film is enclosed by a material of different dielectric constant to that of the film is shown to contain an additional Casimir-like term which is generated by fluctuations of the electric potential about its mean-field value.Comment: Link between Sine-Gordon and Coulomb gas pressures via subtraction of self interaction terms included. Discussion of results within Debye-Huckel approximation included. Added reference

Steady State Behavior of Mechanically Perturbed Spin Glasses and Ferromagnets

A zero temperature dynamics of Ising spin glasses and ferromagnets on random graphs of finite connectivity is considered, like granular media these systems have an extensive entropy of metastable states. We consider the problem of what energy a randomly prepared spin system falls to before becoming stuck in a metastable state. We then introduce a tapping mechanism, analogous to that of real experiments on granular media, this tapping, corresponding to flipping simultaneously any spin with probability $p$, leads to stationary regime with a steady state energy $E(p)$. We explicitly solve this problem for the one dimensional ferromagnet and $\pm J$ spin glass and carry out extensive numerical simulations for spin systems of higher connectivity. The link with the density of metastable states at fixed energy and the idea of Edwards that one may construct a thermodynamics with a flat measure over metastable states is discussed. In addition our simulations on the ferromagnetic systems reveal a novel first order transition, whereas the usual thermodynamic transition on these graphs is second order.Comment: 11 pages, 7 figure

Mechanism of high-mobility group protein B enhancement of progesterone receptor sequence-specific DNA binding

The DNA-binding domain (DBD) of progesterone receptor (PR) is bipartite containing a zinc module core that interacts with progesterone response elements (PRE), and a short flexible carboxyl terminal extension (CTE) that interacts with the minor groove flanking the PRE. The chromosomal high-mobility group B proteins (HMGB), defined as DNA architectural proteins capable of bending DNA, also function as auxiliary factors that increase the DNA-binding affinity of PR and other steroid receptors by mechanisms that are not well defined. Here we show that the CTE of PR contains a specific binding site for HMGB that is required for stimulation of PR-PRE binding, whereas the DNA architectural properties of HMGB are dispensable. Specific PRE DNA inhibited HMGB binding to the CTE, indicating that DNA and HMGB–CTE interactions are mutually exclusive. Exogenous CTE peptide increased PR-binding affinity for PRE as did deletion of the CTE. In a PR-binding site selection assay, A/T sequences flanking the PRE were enriched by HMGB, indicating that PR DNA-binding specificity is also altered by HMGB. We conclude that a transient HMGB–CTE interaction alters a repressive conformation of the flexible CTE enabling it to bind to preferred sequences flanking the PRE

On random graphs and the statistical mechanics of granular matter

The dynamics of spins on a random graph with ferromagnetic three-spin interactions is used to model the compaction of granular matter under a series of taps. Taps are modelled as the random flipping of a small fraction of the spins followed by a quench at zero temperature. We find that the density approached during a logarithmically slow compaction - the random-close-packing density - corresponds to a dynamical phase transition. We discuss the the role of cascades of successive spin-flips in this model and link them with density-noise power fluctuations observed in recent experiments.Comment: minor changes, to appear in EP

Ignition Delay Times of Kerosene (Jet-A)/Air Mixtures

Ignition of Jet-A/air mixtures was studied behind reflected shock waves. Heating of shock tube at temperature of 150 C was used to prepare a homogeneous fuel mixture. Ignition delay times were measured from OH emission at 309 nm and from absorption of He-Ne laser radiation at 3.3922 micrometers. The conditions behind shock waves were calculated by one-dimensional shock wave theory from initial conditions T1, P1, mixture composition and incident shock wave velocity. The ignition delay times were obtained at two fixed pressures 10, 20 atm for lean, stoichiometric and rich mixtures (ER=0.5, 1, 2) at an overall temperature range of 1040-1380 K.Comment: V.P. Zhukov, V.A. Sechenov, and A.Yu. Starikovskii, Ignition Delay Times of Kerosene(Jet-A)/Air Mixtures, 31st Symposium on Combustion, Heidelberg, Germany, August 6-11, 200

The progestin receptor interactome in the female mouse hypothalamus: Interactions with synaptic proteins are isoform specific and ligand dependent

Progestins bind to the progestin receptor (PR) isoforms, PR-A and PR-B, in brain to influence development, female reproduction, anxiety, and stress. Hormone-activated PRs associate with multiple proteins to form functional complexes. In the present study, proteins from female mouse hypothalamus that associate with PR were isolated using affinity pull-down assays with glutathione S-transferase–tagged mouse PR-A and PR-B. Using complementary proteomics approaches, reverse phase protein array (RPPA) and mass spectrometry, we identified hypothalamic proteins that interact with PR in a ligand-dependent and isoform-specific manner and were confirmed by Western blot. Synaptic proteins, including synapsin-I and synapsin-II, interacted with agonist-bound PR isoforms, suggesting that both isoforms function in synaptic plasticity. In further support, synaptogyrin-III and synapsin-III associated with PR-A and PR-B, respectively. PR also interacted with kinases, including c-Src, mTOR, and MAPK1, confirming phosphorylation as an integral process in rapid effects of PR in the brain. Consistent with a role in transcriptional regulation, PR associated with transcription factors and coactivators in a ligand-specific and isoform-dependent manner. Interestingly, both PR isoforms associated with a key regulator of energy homeostasis, FoxO1, suggesting a novel role for PR in energy metabolism. Because many identified proteins in this PR interactome are synaptic proteins, we tested the hypothesis that progestins function in synaptic plasticity. Indeed, progesterone enhanced synaptic density, by increasing synapsin-I–positive synapses, in rat primary cortical neuronal cultures. This novel combination of RPPA and mass spectrometry allowed identification of PR action in synaptic remodeling and energy homeostasis and reveals unique roles for progestins in brain function and disease

Binding-Folding Induced Regulation of AF1 Transactivation Domain of the Glucocorticoid Receptor by a Cofactor That Binds to Its DNA Binding Domain

Intrinsically disordered (ID) regions of proteins commonly exist within transcription factors, including the N-terminal domain (NTD) of steroid hormone receptors (SHRs) that possesses a powerful activation function, AF1 region. The mechanisms by which SHRs pass signals from a steroid hormone to control gene expression remain a central unresolved problem. The role of N-terminal activation function AF1, which exists in an intrinsically disordered (ID) conformation, in this process is of immense importance. It is hypothesized that under physiological conditions, ID AF1 undergoes disorder/order transition via inter- and intra-molecular communications, which allows AF1 surfaces to interact with specific co-regulatory proteins, critical for the final outcome of target gene expression regulated by SHRs. However, the means by which AF1 acquires functionally folded conformations is not well understood. In this study, we tested whether binding of jun dimerization protein 2 (JDP2) within the DNA binding domain (DBD) of the glucocorticoid receptor (GR) leads to acquisition of functionally active structure in its AF1/NTD. Our results show that signals mediated from GR DBD:JDP2 interactions in a two domain GR fragment, consisting of the entire NTD and little beyond DBD, significantly increased secondary/tertiary structure formation in the NTD/AF1. This increased structure formation facilitated AF1’s interaction with specific co-regulatory proteins and subsequent glucocorticoid response element-mediated AF1 promoter:reporter activity. These results support the hypothesis that inter- and intra-molecular signals give a functionally active structure(s) to the GR AF1, which is important for its transcriptional activity

Hinge and Amino-Terminal Sequences Contribute to Solution Dimerization of Human Progesterone Receptor

We and others have shown previously that progesterone receptors (PR) form homodimers in solution in the absence of DNA and that dimers are the preferential form of receptor that binds with high affinity to target DNA. To determine the sequence regions involved in solution homodimerization, wild type PR and truncated PR proteins were expressed in an insect baculovirus system. The expression constructs included the ligand-binding domain [LBD, amino acids (aa) 688–933], the LBD plus hinge (hLBD, aa 634–933), the hLBD plus the DNA-binding domain (DhLBD, aa 538–933), and the full- length A and B isoforms of PR. PR-PR interactions were detected by three methods, coimmunoprecipitation of the PR fragments with full-length PR-A, pull-down of PR-polypeptides with polyhistidine-tagged versions of the same polypeptides immobilized to metal affinity columns and cooperative ligand-binding assays (Hill coefficient, nH \u3e 1 indicating PR-PR interaction). By all three assays, the LBD alone was not sufficient to mediate protein-protein interaction. However, the LBD did exhibit other properties ascribed to this domain, including binding to steroids with a relatively good affinity and specificity, ligand-induced conformational changes at the carboxyl terminus tail and binding of heat shock protein 90 and its dissociation in response to hormone. Thus, failure of the expressed LBD to mediate dimerization does not appear to be due to an extensively misfolded or unstable polypeptide. The minimal carboxyl-terminal fragment capable of mediating PR-PR interaction was the hLBD construct. However, by immobilized metal affinity chromatography assay, self-association of PR-A was 3.5-fold more efficient than that of either the DhLBD or hLBD constructs. An expressed amino-terminal domain (aa 165–535) lacking the DNA-binding domain, hinge, and LBD was found to physically associate with PR-A or with another amino-terminal fragment lacking the LBD, but retaining the DNA-binding domain. These results provide evidence for direct amino-terminal interactions in the more efficient PR-PR interaction exhibited by wild-type PR-A, as compared with DhLBD and hLBD constructs. The overall results of this paper are consistent with the conclusion that the carboxyl-terminal LBD is not sufficient for mediating PR dimerization and that multiple regions, including the hinge and amino-terminal sequences, contribute either directly or indirectly to homodimerization of PR

Ethical and methodological issues in engaging young people living in poverty with participatory research methods

This paper discusses the methodological and ethical issues arising from a project that focused on conducting a qualitative study using participatory techniques with children and young people living in disadvantage. The main aim of the study was to explore the impact of poverty on children and young people's access to public and private services. The paper is based on the author's perspective of the first stage of the fieldwork from the project. It discusses the ethical implications of involving children and young people in the research process, in particular issues relating to access and recruitment, the role of young people's advisory groups, use of visual data and collection of data in young people's homes. The paper also identifies some strategies for addressing the difficulties encountered in relation to each of these aspects and it considers the benefits of adopting participatory methods when conducting research with children and young people

Glassy dynamics in granular compaction: sand on random graphs

We discuss the use of a ferromagnetic spin model on a random graph to model granular compaction. A multi-spin interaction is used to capture the competition between local and global satisfaction of constraints characteristic for geometric frustration. We define an athermal dynamics designed to model repeated taps of a given strength. Amplitude cycling and the effect of permanently constraining a subset of the spins at a given amplitude is discussed. Finally we check the validity of Edwards' hypothesis for the athermal tapping dynamics.Comment: 13 pages Revtex, minor changes, to appear in PR