851 research outputs found
The Human Papillomavirus Type 11 E1∧E4 Protein Is Phosphorylated in Genital Epithelium
AbstractThe most abundant viral transcript in human papillomavirus (HPV) 11-infected xenograft tissue has been shown to encode the E1∧E4 protein. The function of E1∧E4 protein has not been determined. Several potential phosphorylation sequence motifs were identified in the HPV 11 E1∧E4 protein, including potential sites of phosphorylation by mitogen-activated protein kinase (MAPK), cAMP-dependent protein kinase (PKA), casein kinase II, and protein kinase C. To test phosphorylation of the HPV 11 E1∧E4 protein, a soluble maltose binding protein (MBP) fusion was produced in Escherichia coli. Only MAPK and PKA phosphorylated the E1∧E4 protein. Phosphoamino acid analysis showed that one or more threonine residues were phosphorylated by MAPK, and both serine and threonine residues were phosphorylated by PKA. MBP–E1∧E4 mutant proteins were designed to delineate the E1∧E4 phosphoacceptor residues. MAPK was shown to phosphorylate E1∧E4 on threonine 53 within a MAPK consensus phorphorylation sequence motif. PKA was shown to phosphorylate E1∧E4 at two residues: threonine 36 within a consensus motif and serine 44 within a variant of the PKA consensus phosphorylation sequence motif. HPV 11-infected human genital tissue grown as a xenograft in an athymic mouse was labeled with [32P]orthophosphate. Phosphoamino acid analysis of E1∧E4 protein immunoprecipitated from 32P-labeled tissue revealed that both serine and threonine residues were phosphorylated. Analysis by liquid chromatography–mass spectrophotometry was consistent with phosphorylation of residues within the PKA and MAPK phosphorylation sequence motifs. Expression of E1∧E4 protein containing phosphorylation substitution mutations showed that the PKA mutant did not differ from wild-type E1∧E4 protein in intracellular distribution. In contrast, the MAPK mutant did not localize exclusively to the cytoplasm nor did it colocalize with wild-type E1∧E4 protein. We conclude that HPV 11 E1∧E4 protein is phosphorylated in vitro and in vivo. Our data are consistent with phosphorylation of HPV 11 E1∧E4 protein by MAPK and PKA in infected tissue
Dynamical mechanism of atrial fibrillation: a topological approach
While spiral wave breakup has been implicated in the emergence of atrial
fibrillation, its role in maintaining this complex type of cardiac arrhythmia
is less clear. We used the Karma model of cardiac excitation to investigate the
dynamical mechanisms that sustain atrial fibrillation once it has been
established. The results of our numerical study show that spatiotemporally
chaotic dynamics in this regime can be described as a dynamical equilibrium
between topologically distinct types of transitions that increase or decrease
the number of wavelets, in general agreement with the multiple wavelets
hypothesis. Surprisingly, we found that the process of continuous excitation
waves breaking up into discontinuous pieces plays no role whatsoever in
maintaining spatiotemporal complexity. Instead this complexity is maintained as
a dynamical balance between wave coalescence -- a unique, previously
unidentified, topological process that increases the number of wavelets -- and
wave collapse -- a different topological process that decreases their number.Comment: 15 pages, 14 figure
Finite to infinite steady state solutions, bifurcations of an integro-differential equation
We consider a bistable integral equation which governs the stationary
solutions of a convolution model of solid--solid phase transitions on a circle.
We study the bifurcations of the set of the stationary solutions as the
diffusion coefficient is varied to examine the transition from an infinite
number of steady states to three for the continuum limit of the
semi--discretised system. We show how the symmetry of the problem is
responsible for the generation and stabilisation of equilibria and comment on
the puzzling connection between continuity and stability that exists in this
problem
On well-posedness, stability, and bifurcation for the axisymmetric surface diffusion flow
In this article, we study the axisymmetric surface diffusion flow (ASD), a
fourth-order geometric evolution law. In particular, we prove that ASD
generates a real analytic semiflow in the space of (2 + \alpha)-little-H\"older
regular surfaces of revolution embedded in R^3 and satisfying periodic boundary
conditions. We also give conditions for global existence of solutions and prove
that solutions are real analytic in time and space. Further, we investigate the
geometric properties of solutions to ASD. Utilizing a connection to
axisymmetric surfaces with constant mean curvature, we characterize the
equilibria of ASD. Then, focusing on the family of cylinders, we establish
results regarding stability, instability and bifurcation behavior, with the
radius acting as a bifurcation parameter for the problem.Comment: 37 pages, 6 figures, To Appear in SIAM J. Math. Ana
Domain Walls in Non-Equilibrium Systems and the Emergence of Persistent Patterns
Domain walls in equilibrium phase transitions propagate in a preferred
direction so as to minimize the free energy of the system. As a result, initial
spatio-temporal patterns ultimately decay toward uniform states. The absence of
a variational principle far from equilibrium allows the coexistence of domain
walls propagating in any direction. As a consequence, *persistent* patterns may
emerge. We study this mechanism of pattern formation using a non-variational
extension of Landau's model for second order phase transitions. PACS numbers:
05.70.Fh, 42.65.Pc, 47.20.Ky, 82.20MjComment: 12 pages LaTeX, 5 postscript figures To appear in Phys. Rev.
The Speed of Fronts of the Reaction Diffusion Equation
We study the speed of propagation of fronts for the scalar reaction-diffusion
equation \, with . We give a new integral
variational principle for the speed of the fronts joining the state to
. No assumptions are made on the reaction term other than those
needed to guarantee the existence of the front. Therefore our results apply to
the classical case in , to the bistable case and to cases in
which has more than one internal zero in .Comment: 7 pages Revtex, 1 figure not include
Application of elastostatic Green function tensor technique to electrostriction in cubic, hexagonal and orthorhombic crystals
The elastostatic Green function tensor approach, which was recently used to
treat electrostriction in numerical simulation of domain structure formation in
cubic ferroelectrics, is reviewed and extended to the crystals of hexagonal and
orthorhombic symmetry. The tensorial kernels appearing in the expressions for
effective nonlocal interaction of electrostrictive origin are derived
explicitly and their physical meaning is illustrated on simple examples. It is
argued that the bilinear coupling between the polarization gradients and
elastic strain should be systematically included in the Ginzburg-Landau free
energy expansion of electrostrictive materials.Comment: 4 page
Insulin-induced remission in new-onset NOD mice is maintained by the PD-1–PD-L1 pathway
The past decade has seen a significant increase in the number of potentially tolerogenic therapies for treatment of new-onset diabetes. However, most treatments are antigen nonspecific, and the mechanism for the maintenance of long-term tolerance remains unclear. In this study, we developed an antigen-specific therapy, insulin-coupled antigen-presenting cells, to treat diabetes in nonobese diabetic mice after disease onset. Using this approach, we demonstrate disease remission, inhibition of pathogenic T cell proliferation, decreased cytokine production, and induction of anergy. Moreover, we show that robust long-term tolerance depends on the programmed death 1 (PD-1)–programmed death ligand (PD-L)1 pathway, not the distinct cytotoxic T lymphocyte–associated antigen 4 pathway. Anti–PD-1 and anti–PD-L1, but not anti–PD-L2, reversed tolerance weeks after tolerogenic therapy by promoting antigen-specific T cell proliferation and inflammatory cytokine production directly in infiltrated tissues. PD-1–PD-L1 blockade did not limit T regulatory cell activity, suggesting direct effects on pathogenic T cells. Finally, we describe a critical role for PD-1–PD-L1 in another powerful immunotherapy model using anti-CD3, suggesting that PD-1–PD-L1 interactions form part of a common pathway to selectively maintain tolerance within the target tissues
Traveling wave solutions in the Burridge-Knopoff model
The slider-block Burridge-Knopoff model with the Coulomb friction law is
studied as an excitable medium. It is shown that in the continuum limit the
system admits solutions in the form of the self-sustained shock waves traveling
with constant speed which depends only on the amount of the accumulated stress
in front of the wave. For a wide class of initial conditions the behavior of
the system is determined by these shock waves and the dynamics of the system
can be expressed in terms of their motion. The solutions in the form of the
periodic wave trains and sources of counter-propagating waves are analyzed. It
is argued that depending on the initial conditions the system will either tend
to synchronize or exhibit chaotic spatiotemporal behavior.Comment: 12 pages (ReVTeX), 7 figures (Postscript) to be published in Phys.
Rev.
One-dimensional symmetry and Liouville type results for the fourth order Allen-Cahn equation in R
In this paper, we prove an analogue of Gibbons' conjecture for the extended
fourth order Allen-Cahn equation in R N , as well as Liouville type results for
some solutions converging to the same value at infinity in a given direction.
We also prove a priori bounds and further one-dimensional symmetry and rigidity
results for semilinear fourth order elliptic equations with more general
nonlinearities
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