MAPK phosphorylation of connexin 43 promotes binding of cyclin E and smooth muscle cell proliferation

<p>Rationale: Dedifferentiation of vascular smooth muscle cells (VSMC) leading to a proliferative cell phenotype significantly contributes to the development of atherosclerosis. Mitogen-activated protein kinase (MAPK) phosphorylation of proteins including connexin 43 (Cx43) has been associated with VSMC proliferation in atherosclerosis.</p> <p>Objective: To investigate whether MAPK phosphorylation of Cx43 is directly involved in VSMC proliferation.</p> <p>Methods and Results: We show in vivo that MAPK-phosphorylated Cx43 forms complexes with the cell cycle control proteins cyclin E and cyclin-dependent kinase 2 (CDK2) in carotids of apolipoprotein-E receptor null (ApoE−/−) mice and in C57Bl/6 mice treated with platelet-derived growth factor–BB (PDGF). We tested the involvement of Cx43 MAPK phosphorylation in vitro using constructs for full-length Cx43 (Cx43) or the Cx43 C-terminus (Cx43CT) and produced null phosphorylation Ser>Ala (Cx43MK4A/Cx43CTMK4A) and phospho-mimetic Ser>Asp (Cx43MK4D/Cx43CTMK4D) mutations. Coimmunoprecipitation studies in primary VSMC isolated from Cx43 wild-type (Cx43+/+) and Cx43 null (Cx43−/−) mice and analytic size exclusion studies of purified proteins identify that interactions between cyclin E and Cx43 requires Cx43 MAPK phosphorylation. We further demonstrate that Cx43 MAPK phosphorylation is required for PDGF-mediated VSMC proliferation. Finally, using a novel knock-in mouse containing Cx43-MK4A mutation, we show in vivo that interactions between Cx43 and cyclin E are lost and VSMC proliferation does not occur after treatment of carotids with PDGF and that neointima formation is significantly reduced in carotids after injury.</p> <p>Conclusions: We identify MAPK-phosphorylated Cx43 as a novel interacting partner of cyclin E in VSMC and show that this interaction is critical for VSMC proliferation. This novel interaction may be important in the development of atherosclerotic lesions.</p&gt

Social Factors Related to Smoking among Rural, Low-Income Women: Findings from a Systematic Review

Objective: This systematic review of the literature assesses congruency of findings from descriptive, qualitative, and association studies focusing on factors influencing smoking and smoking cessation with findings from smoking cessation interventions that included low-income rural women. Design and Sample: Six databases relevant to the health and social sciences were searched in this systematic review using combinations of select keyword terms, specific inclusion criteria, and studies between 1997 and 2012. Results: Descriptive studies on this population of smokers provide economic, environmental, and social factors related to smoking patterns. Qualitative studies found social support received from an individual's social network was viewed as most beneficial when considering or maintaining smoking cessation while randomized controlled trials included in this review implemented social support through peripheral resources or resources with little personal connection to the sample and failed to produce significant results. Conclusions: Few studies have focused on the specific needs and difficulties of smoking cessation among rural low-income women and interventions have not targeted the complex social network of this population. Incongruence in study findings supports the need for smoking assessment and cessation interventions that incorporates the unique social and cultural meanings of smoking in rural low-income women

First electron beam polarization measurements with a Compton polarimeter at Jefferson Laboratory

A Compton polarimeter has been installed in Hall A at Jefferson Laboratory. This letter reports on the first electron beam polarization measurements performed during the HAPPEX experiment at an electron energy of 3.3 GeV and an average current of 40 $\mu$A. The heart of this device is a Fabry-Perot cavity which increased the luminosity for Compton scattering in the interaction region so much that a 1.4% statistical accuracy could be obtained within one hour, with a 3.3% total error

Approximating a Behavioural Pseudometric without Discount for<br> Probabilistic Systems

Desharnais, Gupta, Jagadeesan and Panangaden introduced a family of behavioural pseudometrics for probabilistic transition systems. These pseudometrics are a quantitative analogue of probabilistic bisimilarity. Distance zero captures probabilistic bisimilarity. Each pseudometric has a discount factor, a real number in the interval (0, 1]. The smaller the discount factor, the more the future is discounted. If the discount factor is one, then the future is not discounted at all. Desharnais et al. showed that the behavioural distances can be calculated up to any desired degree of accuracy if the discount factor is smaller than one. In this paper, we show that the distances can also be approximated if the future is not discounted. A key ingredient of our algorithm is Tarski's decision procedure for the first order theory over real closed fields. By exploiting the Kantorovich-Rubinstein duality theorem we can restrict to the existential fragment for which more efficient decision procedures exist

Strategic responses to global challenges: The case of European banking, 1973–2000

In applying a strategy, structure, ownership and performance (SSOP) framework to three major clearing banks (ABN AMRO, UBS, Barclays), this article debates whether the conclusions generated by Whittington and Mayer about European manufacturing industry can be applied to the financial services sector. While European integration plays a key role in determining strategy, it is clear that global factors were far more important in determining management actions, leading to significant differences in structural adaptation. The article also debates whether this has led to improved performance, given the problems experienced with both geographical dispersion and diversification, bringing into question the quality of decision-making over the long term

Towards hierarchical blackboard mapping on a whiskered robot

The paradigm case for robotic mapping assumes large quantities of sensory information which allow the use of relatively weak priors. In contrast, the present study considers the mapping problem for a mobile robot, CrunchBot, where only sparse, local tactile information from whisker sensors is available. To compensate for such weak likelihood information, we make use of low-level signal processing and strong hierarchical object priors. Hierarchical models were popular in classical blackboard systems but are here applied in a Bayesian setting as a mapping algorithm. The hierarchical models require reports of whisker distance to contact and of surface orientation at contact, and we demonstrate that this information can be retrieved by classifiers from strain data collected by CrunchBot's physical whiskers. We then provide a demonstration in simulation of how this information can be used to build maps (but not yet full SLAM) in an zero-odometry-noise environment containing walls and table-like hierarchical objects. © 2012 Elsevier B.V. All rights reserved

Cross Section Measurements of Charged Pion Photoproduction in Hydrogen and Deuterium from 1.1 to 5.5 GeV

The differential cross section for the gamma +n --> pi- + p and the gamma + p --> pi+ n processes were measured at Jefferson Lab. The photon energies ranged from 1.1 to 5.5 GeV, corresponding to center-of-mass energies from 1.7 to 3.4 GeV. The pion center-of-mass angles varied from 50 degree to 110 degree. The pi- and pi+ photoproduction data both exhibit a global scaling behavior at high energies and high transverse momenta, consistent with the constituent counting rule prediction and the existing pi+ data. The data suggest possible substructure of the scaling behavior, which might be oscillations around the scaling value. The data show an enhancement in the scaled cross section at center-of-mass energy near 2.2 GeV. The differential cross section ratios at high energies and high transverse momenta can be described by calculations based on one-hard-gluon-exchange diagrams.Comment: 18 pages, 19 figure

Probing the high momentum component of the deuteron at high Q^2

The d(e,e'p) cross section at a momentum transfer of 3.5 (GeV/c)^2 was measured over a kinematical range that made it possible to study this reaction for a set of fixed missing momenta as a function of the neutron recoil angle theta_nq and to extract missing momentum distributions for fixed values of theta_nq up to 0.55 GeV/c. In the region of 35 (deg) <= theta_nq <= 45 (deg) recent calculations, which predict that final state interactions are small, agree reasonably well with the experimental data. Therefore these experimental reduced cross sections provide direct access to the high momentum component of the deuteron momentum distribution in exclusive deuteron electro-disintegration.Comment: 5 pages, 2 figure

Recoil Polarization for Delta Excitation in Pion Electroproduction

We measured angular distributions of recoil-polarization response functions for neutral pion electroproduction for W=1.23 GeV at Q^2=1.0 (GeV/c)^2, obtaining 14 separated response functions plus 2 Rosenbluth combinations; of these, 12 have been observed for the first time. Dynamical models do not describe quantities governed by imaginary parts of interference products well, indicating the need for adjusting magnitudes and phases for nonresonant amplitudes. We performed a nearly model-independent multipole analysis and obtained values for Re(S1+/M1+)=-(6.84+/-0.15)% and Re(E1+/M1+)=-(2.91+/-0.19)% that are distinctly different from those from the traditional Legendre analysis based upon M1+ dominance and sp truncation.Comment: 5 pages, 2 figures, for PR

Simulated Optimisation of Disordered Structures with negative Poisson’s ratios

Copyright © 2009 Elsevier. NOTICE: this is the author’s version of a work that was accepted for publication in Mechanics of Materials. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Mechanics of Materials, Vol. 41 Issue 8 (2009). DOI: 10.1016/j.mechmat.2009.04.008Two-dimensional regular theoretical units that give a negative Poisson’s ratio (NPR) are well documented and well understood. Predicted mechanical properties resulting from these models are reasonably accurate in two dimensions but fall down when used for heterogeneous real-world materials. Manufacturing processes are seldom perfect and some measure of heterogeneity is therefore required to account for the deviations from the regular unit cells in this real-life situation. Analysis of heterogeneous materials in three dimensions is a formidable problem; we must first understand heterogeneity in two dimensions. This paper approaches the problem of finding a link between heterogeneous networks and its material properties from a new angle. Existing optimisation tools are used to create random two-dimensional topologies that display NPR, and the disorder in the structure and its relationship with NPR is investigated