Journal Staff

BACKGROUND: It has been hypothesised that an upregulation of the neuropeptide substance P (SP) and its preferred receptor, the neurokinin-1 receptor (NK-1 R), is a causative factor in inducing tenocyte hypercellularity, a characteristic of tendinosis, through both proliferative and antiapoptotic stimuli. We have demonstrated earlier that SP stimulates proliferation of human tenocytes in culture. AIM: The aim of this study was to investigate whether SP can mediate an antiapoptotic effect in tumour necrosis factor-α (TNF-α)-induced apoptosis of human tenocytes in vitro. RESULTS: A majority (approximately 75%) of tenocytes in culture were immunopositive for TNF Receptor-1 and TNF Receptor-2. Exposure of the cells to TNF-α significantly decreased cell viability, as shown with crystal violet staining. TNF-α furthermore significantly increased the amount of caspase-10 and caspase-3 mRNA, as well as both BID and cleaved-poly ADP ribosome polymerase (c-PARP) protein. Incubation of SP together with TNF-α resulted in a decreased amount of BID and c-PARP, and in a reduced lactate dehydrogenase release, as compared to incubation with TNF-α alone. The SP effect was blocked with a NK-1 R inhibitor. DISCUSSION: This study shows that SP, through stimulation of the NK-1 R, has the ability to reduce TNF-α-induced apoptosis of human tenocytes. Considering that SP has previously been shown to stimulate tenocyte proliferation, the study confirms SP as a potent regulator of cell-turnover in tendon tissue, capable of stimulating hypercellularity through different mechanisms. This gives further support for the theory that the upregulated amount of SP seen in tendinosis could contribute to hypercellularity

Decomposing the Yang-Mills Field

Recently we have proposed a set of variables for describing the physical parameters of SU(N) Yang--Mills field. Here we propose an off-shell generalization of our Ansatz. For this we envoke the Darboux theorem to decompose arbitrary one-form with respect to some basis of one-forms. After a partial gauge fixing we identify these forms with the preimages of holomorphic and antiholomorphic forms on the coset space $SU(N)/U(1)^{N-1}$, identified as a particular coadjoint orbit. This yields an off-shell gauge fixed decomposition of the Yang-Mills connection that contains our original variables in a natural fashion.Comment: 5 pages, latex, no figure

Dissimilar bouncy walkers

We consider the dynamics of a one-dimensional system consisting of dissimilar hardcore interacting (bouncy) random walkers. The walkers' (diffusing particles') friction constants xi_n, where n labels different bouncy walkers, are drawn from a distribution rho(xi_n). We provide an approximate analytic solution to this recent single-file problem by combining harmonization and effective medium techniques. Two classes of systems are identified: when rho(xi_n) is heavy-tailed, rho(xi_n)=A xi_n^(-1-\alpha) (0<alpha<1) for large xi_n, we identify a new universality class in which density relaxations, characterized by the dynamic structure factor S(Q,t), follows a Mittag-Leffler relaxation, and the the mean square displacement of a tracer particle (MSD) grows as t^delta with time t, where delta=alpha/(1+\alpha). If instead rho is light-tailedsuch that the mean friction constant exist, S(Q,t) decays exponentially and the MSD scales as t^(1/2). We also derive tracer particle force response relations. All results are corroborated by simulations and explained in a simplified model.Comment: 11 pages, to appear in Journal of Chemical Physic

First-passage dynamics of obstructed tracer particle diffusion in one-dimensional systems

The standard setup for single-file diffusion is diffusing particles in one dimension which cannot overtake each other, where the dynamics of a tracer (tagged) particle is of main interest. In this article we generalise this system and investigate first-passage properties of a tracer particle when flanked by crowder particles which may, besides diffuse, unbind (rebind) from (to) the one-dimensional lattice with rates $k_{\rm off}$ ($k_{\rm on}$). The tracer particle is restricted to diffuse with rate $k_D$ on the lattice. Such a model is relevant for the understanding of gene regulation where regulatory proteins are searching for specific binding sites ona crowded DNA. We quantify the first-passage time distribution, $f(t)$ ($t$ is time), numerically using the Gillespie algorithm, and estimate it analytically. In terms of our key parameter, the unbinding rate $k_{\rm off}$, we study the bridging of two known regimes: (i) when unbinding is frequent the particles may effectively pass each other and we recover the standard single particle result $f(t)\sim t^{-3/2}$ with a renormalized diffusion constant, (ii) when unbinding is rare we recover well-known single-file diffusion result $f(t)\sim t^{-7/4}$. The intermediate cases display rich dynamics, with the characteristic $f(t)$-peak and the long-time power-law slope both being sensitive to $k_{\rm off}$

Single-file dynamics with different diffusion constants

We investigate the single-file dynamics of a tagged particle in a system consisting of N hardcore interacting particles (the particles cannot pass each other) which are diffusing in a one-dimensional system where the particles have different diffusion constants. For the two particle case an exact result for the conditional probability density function (PDF) is obtained for arbitrary initial particle positions and all times. The two-particle PDF is used to obtain the tagged particle PDF. For the general N-particle case (N large) we perform stochastic simulations using our new computationally efficient stochastic simulation technique based on the Gillespie algorithm. We find that the mean square displacement for a tagged particle scales as the square root of time (as for identical particles) for long times, with a prefactor which depends on the diffusion constants for the particles; these results are in excellent agreement with very recent analytic predictions in the mathematics literature.Comment: 9 pages, 5 figures. Journal of Chemical Physics (in press

Habits without values

Habits form a crucial component of behavior. In recent years, key computational models have conceptualized habits as arising from model-free reinforcement learning (RL) mechanisms, which typically select between available actions based on the future value expected to result from each. Traditionally, however, habits have been understood as behaviors that can be triggered directly by a stimulus, without requiring the animal to evaluate expected outcomes. Here, we develop a computational model instantiating this traditional view, in which habits develop through the direct strengthening of recently taken actions rather than through the encoding of outcomes. We demonstrate that this model accounts for key behavioral manifestations of habits, including insensitivity to outcome devaluation and contingency degradation, as well as the effects of reinforcement schedule on the rate of habit formation. The model also explains the prevalent observation of perseveration in repeated-choice tasks as an additional behavioral manifestation of the habit system. We suggest that mapping habitual behaviors onto value-free mechanisms provides a parsimonious account of existing behavioral and neural data. This mapping may provide a new foundation for building robust and comprehensive models of the interaction of habits with other, more goal-directed types of behaviors and help to better guide research into the neural mechanisms underlying control of instrumental behavior more generally

Shafranov's virial theorem and magnetic plasma confinement

Shafranov's virial theorem implies that nontrivial magnetohydrodynamical equilibrium configurations must be supported by externally supplied currents. Here we extend the virial theorem to field theory, where it relates to Derrick's scaling argument on soliton stability. We then employ virial arguments to investigate a realistic field theory model of a two-component plasma, and conclude that stable localized solitons can exist in the bulk of a finite density plasma. These solitons entail a nontrivial electric field which implies that purely magnetohydrodynamical arguments are insufficient for describing stable, nontrivial structures within the bulk of a plasma.Comment: 9 pages no figure

Human tenocytes are stimulated to proliferate by acetylcholine through an EGFR signalling pathway

Studies of human patellar and Achilles tendons have shown that primary tendon fibroblasts (tenocytes) not only have the capacity to produce acetylcholine (ACh) but also express muscarinic ACh receptors (mAChRs) through which ACh can exert its effects. In patients with tendinopathy (chronic tendon pain) with tendinosis, the tendon tissue is characterised by hypercellularity and angiogenesis, both of which might be influenced by ACh. In this study, we have tested the hypothesis that ACh increases the proliferation rate of tenocytes through mAChR stimulation and have examined whether this mechanism operates via the extracellular activation of the epidermal growth factor receptor (EGFR), as shown in other fibroblastic cells. By use of primary human tendon cell cultures, we identified cells expressing vimentin, tenomodulin and scleraxis and found that these cells also contained enzymes related to ACh synthesis and release (choline acetyltransferase and vesicular acetylcholine transporter). The cells furthermore expressed mAChRs of several subtypes. Exogenously administered ACh stimulated proliferation and increased the viability of tenocytes in vitro. When the cells were exposed to atropine (an mAChR antagonist) or the EGFR inhibitor AG1478, the proliferative effect of ACh decreased. Western blot revealed increased phosphorylation, after ACh stimulation, for both EGFR and the extracellular-signal-regulated kinases 1 and 2. Given that tenocytes have been shown to produce ACh and express mAChRs, this study provides evidence of a possible autocrine loop that might contribute to the hypercellularity seen in tendinosis tendon tissue

Aspects of Electric and Magnetic Variables in SU(2) Yang-Mills Theory

We introduce a novel decomposition of the four dimensional SU(2) gauge field. This decomposition realizes explicitely a symmetry between electric and magnetic variables, suggesting a duality picture between the corresponding phases. It also indicates that at large distances the Yang-Mills theory involves a three component unit vector field, a massive Lorentz vector field, and a neutral scalar field that condenses which yields the mass scale. Our results are consistent with the proposal that the physical spectrum of the theory contains confining strings which are tied into stable knotted solitons.Comment: we have made substantial improvement