ROCK2/rasHa cooperation induce malignant conversion via p53 loss, elevated NF-κβ and tenascin C-associated rigidity but p21 inhibits ROCK2/NF-κβ-mediated progression

To study ROCK2 activation in carcinogenesis, mice expressing 4-hydroxytamoxifen (4HT)- activated ROCK2 [K14.ROCKer] were crossed to mice expressing epidermal activated ras Ha [HK1.ras1205]. At 8 weeks, 4HT-treated K14.ROCKer-HK1.ras1205 cohorts exhibited papillomas similar to HK1.ras1205 controls; however, K14.ROCKer-HK1.ras1205 histotypes comprised a mixed papilloma/well-differentiated squamous cell carcinoma [wdSCC], exhibiting p53 loss, increased proliferation, and novel NF-κβ expression. By 12 weeks, K14.ROCKer-HK1.ras1205 wdSCCs exhibited increased NF-κβ and novel tenascin C, indicative of elevated rigidity; yet despite continued ROCK2 activities /p-Mypt1 inactivation, progression to SCC required loss of compensatory p21 expression. K14.ROCKer -HK1.ras1205 papillomatogenesis also required a wound-promotion stimulus, confirmed by breeding K14.ROCKer into promotion-insensitive HK1.ras1276 mice, suggesting a permissive K14.ROCKer-HK1.ras1205 papilloma context [wound-promoted/NF-κβ+ve/p53-ve/p21+ve] preceded K14.ROCKer-mediated [p-Mypt1/tenascin C/rigidity] malignant conversion. Malignancy depended on ROCKer/p-Mypt1 expression, as cessation of 4HT-treatment induced disorganised tissue architecture and p21-associated differentiation in wdSCCs; yet tenascin C retention in connective tissue ECM suggests the rigidity laid down for conversion persists. Novel papilloma outgrowths appeared expressing intense, basal-layer p21 which confined endogenous ROCK2/p-Mypt1/NF-κβ to supra-basal layers, and was paralleled by restored basal-layer p53. In later SCCs, 4HT-cessation became irrelevant as endogenous ROCK2 expression increased, driving progression via p21 loss, elevated NF-κβ expression and tenascin C-associated rigidity; with p-Mypt1 inactivation/actinomyosin-mediated contractility to facilitate invasion. However, p21-associated inhibition of early-stage malignant progression and the intense expression in papilloma outgrowths, identifies a novel, significant antagonism between p21 and ras Ha/ROCK2/NF-κβ signalling in skin 3 carcinogenesis. Collectively these data show that ROCK2 activation induces malignancy in rasHa-initiated/promoted papillomas in the context of p53 loss and novel NF-κβ expression;whilst increased tissue rigidity and cell motility/contractility help mediate tumour progression

S and D Wave Mixing in High TcT_c Superconductors

For a tight binding model with nearest neighbour attraction and a small orthorhombic distortion, we find a phase diagram for the gap at zero temperature which includes three distinct regions as a function of filling. In the first, the gap is a mixture of mainly $d$-wave with a smaller extended $s$-wave part. This is followed by a region in which there is a rapid increase in the $s$-wave part accompanied by a rapid increase in relative phase between $s$ and $d$ from 0 to $\pi$. Finally, there is a region of dominant $s$ with a mixture of $d$ and zero phase. In the mixed region with a finite phase, the $s$-wave part of the gap can show a sudden increase with decreasing temperature accompanied with a rapid increase in phase which shows many of the characteristics measured in the angular resolved photoemission experiments of Ma {\em et al.} in $\rm Bi_2Sr_2CaCu_2O_8$Comment: 12 pages, RevTeX 3.0, 3 PostScript figures uuencoded and compresse

Effect of Interband Transitions on the c axis Penetration Depth of Layered Superconductors

The electromagnetic response of a system with two planes per unit cell involves, in addition to the usual intraband contribution, an added interband term. These transitions affect the temperature dependence and the magnitude of the zero temperature c-axis penetration depth. When the interplane hopping is sufficiently small, the interband transitions dominate the low temperature behaviour of the penetration depth which then does not reflect the linear temperature dependence of the intraband term and in comparison becomes quite flat even for a d-wave gap. It is in this regime that the pseudogap was found in our previous normal state calculations of the c-axis conductivity, and the effects are connected.Comment: 8 pages, 5 figure

Numerical studies of the two- and three-dimensional gauge glass at low temperature

We present results from Monte Carlo simulations of the two- and three-dimensional gauge glass at low temperature using the parallel tempering Monte Carlo method. Our results in two dimensions strongly support the transition being at T_c=0. A finite-size scaling analysis, which works well only for the larger sizes and lower temperatures, gives the stiffness exponent theta = -0.39 +/- 0.03. In three dimensions we find theta = 0.27 +/- 0.01, compatible with recent results from domain wall renormalization group studies.Comment: 7 pages, 10 figures, submitted to PR

Nature of the vortex-glass order in strongly type-II superconductors

The stability and the critical properties of the three-dimensional vortex-glass order in random type-II superconductors with point disorder is investigated in the unscreened limit based on a lattice {\it XY} model with a uniform field. By performing equilibrium Monte Carlo simulations for the system with periodic boundary conditions, the existence of a stable vortex-glass order is established in the unscreened limit. Estimated critical exponents are compared with those of the gauge-glass model.Comment: Error in the reported value of the exponent eta is correcte

Zero Temperature Glass Transition in the Two-Dimensional Gauge Glass Model

We investigate dynamic scaling properties of the two-dimensional gauge glass model for the vortex glass phase in superconductors with quenched disorder. From extensive Monte Carlo simulations we obtain static and dynamic finite size scaling behavior, where the static simulations use a temperature exchange method to ensure convergence at low temperatures. Both static and dynamic scaling of Monte Carlo data is consistent with a glass transition at zero temperature. We study a dynamic correlation function for the superconducting order parameter, as well as the phase slip resistance. From the scaling of these two functions, we find evidence for two distinct diverging correlation times at the zero temperature glass transition. The longer of these time scales is associated with phase slip fluctuations across the system that lead to finite resistance at any finite temperature, while the shorter time scale is associated with local phase fluctuations.Comment: 8 pages, 10 figures; v2: some minor correction

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Nature of the Spin-glass State in the Three-dimensional Gauge Glass

We present results from simulations of the gauge glass model in three dimensions using the parallel tempering Monte Carlo technique. Critical fluctuations should not affect the data since we equilibrate down to low temperatures, for moderate sizes. Our results are qualitatively consistent with earlier work on the three and four dimensional Edwards-Anderson Ising spin glass. We find that large scale excitations cost only a finite amount of energy in the thermodynamic limit, and that those excitations have a surface whose fractal dimension is less than the space dimension, consistent with a scenario proposed by Krzakala and Martin, and Palassini and Young.Comment: 5 pages, 7 figure

Conceptual design of mechanisms based on computational synthesis and simulation of kinematic building blocks

Although many ingenious mechanisms have been designed, the fundamental task of conceptualizing these devices is, to a great extent, still an art. While sophisticated computational tools for dynamic analysis of mechanisms exist, hardly any computational methods exist for generalized synthesis. To develop a computational model for synthesis, a formal foundation for mechanisms design must be laid by rationalizing the process of mechanical synthesis. Rationalization in synthesis implies that complex mechanical motions can be described in terms of primitives or building blocks. In this paper, we present a matrix methodology that forms the basis for a computable approach to design synthesis. In this methodology, the continuous design space of a mechanisms domain is discretized into functional subspaces, and each subspace is represented uniquely by a conceptual building block. The matrix scheme serves as a formal means to (a) represent and reason with the building blocks at different levels of abstraction, (b) generate alternate conceptual design configurations, and (c) facilitate rapid simulation of design concepts by connecting a series of building blocks.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45878/1/163_2005_Article_BF01580146.pd

Phase Behavior of Bent-Core Molecules

Recently, a new class of smectic liquid crystal phases (SmCP phases) characterized by the spontaneous formation of macroscopic chiral domains from achiral bent-core molecules has been discovered. We have carried out Monte Carlo simulations of a minimal hard spherocylinder dimer model to investigate the role of excluded volume interations in determining the phase behavior of bent-core materials and to probe the molecular origins of polar and chiral symmetry breaking. We present the phase diagram as a function of pressure or density and dimer opening angle $\psi$. With decreasing $\psi$, a transition from a nonpolar to a polar smectic phase is observed near $\psi = 167^{\circ}$, and the nematic phase becomes thermodynamically unstable for $\psi < 135^{\circ}$. No chiral smectic or biaxial nematic phases were found.Comment: 4 pages Revtex, 3 eps figures (included