Cofilin is a pH sensor for actin free barbed end formation: role of phosphoinositide binding

Newly generated actin free barbed ends at the front of motile cells provide sites for actin filament assembly driving membrane protrusion. Growth factors induce a rapid biphasic increase in actin free barbed ends, and we found both phases absent in fibroblasts lacking H+ efflux by the Na-H exchanger NHE1. The first phase is restored by expression of mutant cofilin-H133A but not unphosphorylated cofilin-S3A. Constant pH molecular dynamics simulations and nuclear magnetic resonance (NMR) reveal pH-sensitive structural changes in the cofilin C-terminal filamentous actin binding site dependent on His133. However, cofilin-H133A retains pH-sensitive changes in NMR spectra and severing activity in vitro, which suggests that it has a more complex behavior in cells. Cofilin activity is inhibited by phosphoinositide binding, and we found that phosphoinositide binding is pH-dependent for wild-type cofilin, with decreased binding at a higher pH. In contrast, phosphoinositide binding by cofilin-H133A is attenuated and pH insensitive. These data suggest a molecular mechanism whereby cofilin acts as a pH sensor to mediate a pH-dependent actin filament dynamics

Supercurrent flow through an effective double barrier structure

Supercurrent flow is studied in a structure that in the Ginzburg-Landau regime can be described in terms of an effective double barrier potential. In the limit of strongly reflecting barriers, the passage of Cooper pairs through such a structure may be viewed as a realization of resonant tunneling with a rigid wave function. For interbarrier distances smaller than $d_0=\pi\xi(T)$ no current-carrying solutions exist. For distances between $d_0$ and $2d_0$, four solutions exist. The two symmetric solutions obey a current-phase relation of $\sin(\Delta\varphi/2)$, while the two asymmetric solutions satisfy $\Delta\varphi=\pi$ for all allowed values of the current. As the distance exceeds $nd_0$, a new group of four solutions appears, each contaning $(n-1)$ soliton-type oscillations between the barriers. We prove the inexistence of a continuous crossover between the physical solutions of the nonlinear Ginzburg-Landau equation and those of the corresponding linearized Schr\"odinger equation. We also show that under certain conditions a repulsive delta function barrier may quantitatively describe a SNS structure. We are thus able to predict that the critical current of a SNSNS structure vanishes as $\sqrt{T'_c-T}$, where $T'_c$ is lower than the bulk critical temperature.Comment: 20 pages, RevTex, to appear in Phys. Rev. B, 6 figures on request at [email protected]

On "Non-Geometric" Contribution To The Entropy Of Black Hole Due To Quantum Corrections

The quantum corrections to the entropy of charged black holes are calculated. The Reissner-Nordstrem and dilaton black holes are considered. The appearance of logarithmically divergent terms not proportional to the horizon area is demonstrated. It is shown that the complete entropy which is sum of classical Bekenstein-Hawking entropy and the quantum correction is proportional to the area of quantum-corrected horizon.Comment: Latex, 9 page

Entanglement entropy in curved spacetimes with event horizons

We consider the computation of the entanglement entropy in curved backgrounds with event horizons. We use a Hamiltonian approach to the problem and perform numerical computations on a spherical lattice of spacing $a$. We study the cosmological case and make explicit computations for the Friedmann-Robertson-Walker universe. Our results for a massless, minimally coupled scalar field can be summarized by $S_{ent}=0.30 r_H^2/a^2$,which resembles the flat space formula, although here the horizon radius, $r_H$, is time-dependent.Comment: 12 pages, RevTex 3.0, 2 figures as uuencoded compressed Postscript file

Graph Invariants of Vassiliev Type and Application to 4D Quantum Gravity

We consider a special class of Kauffman's graph invariants of rigid vertex isotopy (graph invariants of Vassiliev type). They are given by a functor from a category of colored and oriented graphs embedded into a 3-space to a category of representations of the quasi-triangular ribbon Hopf algebra $U_q(sl(2,\bf C))$. Coefficients in expansions of them with respect to $x$ ($q=e^x$) are known as the Vassiliev invariants of finite type. In the present paper, we construct two types of tangle operators of vertices. One of them corresponds to a Casimir operator insertion at a transverse double point of Wilson loops. This paper proposes a non-perturbative generalization of Kauffman's recent result based on a perturbative analysis of the Chern-Simons quantum field theory. As a result, a quantum group analog of Penrose's spin network is established taking into account of the orientation. We also deal with the 4-dimensional canonical quantum gravity of Ashtekar. It is verified that the graph invariants of Vassiliev type are compatible with constraints of the quantum gravity in the loop space representation of Rovelli and Smolin.Comment: 34 pages, AMS-LaTeX, no figures,The proof of thm.5.1 has been improve

Efficacy of Maternal Choline Supplementation During Pregnancy in Mitigating Adverse Effects of Prenatal Alcohol Exposure on Growth and Cognitive Function: A Randomized, Double-Blind, Placebo-Controlled Clinical Trial

Background: We recently demonstrated the acceptability and feasibility of a randomized, double-blind choline supplementation intervention for heavy drinking women during pregnancy. In this study, we report our results relating to the efficacy of this intervention in mitigating adverse effects of prenatal alcohol exposure (PAE) on infant growth and cognitive function. Methods: Sixty-nine Cape Coloured (mixed ancestry) heavy drinkers in Cape Town, South Africa, recruited in mid-pregnancy, were randomly assigned to receive a daily oral dose of either 2 g of choline or placebo from time of enrollment until delivery. Each dose consisted of an individually wrapped packet of powder that, when mixed with water, produced a sweet tasting grape-flavored drink. The primary outcome, eyeblink conditioning (EBC), was assessed at 6.5 months. Somatic growth was measured at birth, 6.5, and 12 months, recognition memory and processing speed on the Fagan Test of Infant Intelligence, at 6.5 and 12 months. Results: Infants born to choline-treated mothers were more likely to meet criterion for conditioning on EBC than the placebo group. Moreover, within the choline arm, degree of maternal adherence to the supplementation protocol strongly predicted EBC performance. Both groups were small at birth, but choline-treated infants showed considerable catch-up growth in weight and head circumference at 6.5 and 12 months. At 12 months, the infants in the choline treatment arm had higher novelty preference scores, indicating better visual recognition memory. Conclusions: This exploratory study is the first to provide evidence that a high dose of choline administered early in pregnancy can mitigate adverse effects of heavy PAE on EBC, postnatal growth, and cognition in human infants. These findings are consistent with studies of alcohol-exposed animals that have demonstrated beneficial effects of choline supplementation on classical conditioning, learning, and memory

Dark Energy and Gravity

I review the problem of dark energy focusing on the cosmological constant as the candidate and discuss its implications for the nature of gravity. Part 1 briefly overviews the currently popular `concordance cosmology' and summarises the evidence for dark energy. It also provides the observational and theoretical arguments in favour of the cosmological constant as the candidate and emphasises why no other approach really solves the conceptual problems usually attributed to the cosmological constant. Part 2 describes some of the approaches to understand the nature of the cosmological constant and attempts to extract the key ingredients which must be present in any viable solution. I argue that (i)the cosmological constant problem cannot be satisfactorily solved until gravitational action is made invariant under the shift of the matter lagrangian by a constant and (ii) this cannot happen if the metric is the dynamical variable. Hence the cosmological constant problem essentially has to do with our (mis)understanding of the nature of gravity. Part 3 discusses an alternative perspective on gravity in which the action is explicitly invariant under the above transformation. Extremizing this action leads to an equation determining the background geometry which gives Einstein's theory at the lowest order with Lanczos-Lovelock type corrections. (Condensed abstract).Comment: Invited Review for a special Gen.Rel.Grav. issue on Dark Energy, edited by G.F.R.Ellis, R.Maartens and H.Nicolai; revtex; 22 pages; 2 figure

Thermodynamic Gravity and the Schrodinger Equation

We adopt a 'thermodynamical' formulation of Mach's principle that the rest mass of a particle in the Universe is a measure of its long-range collective interactions with all other particles inside the horizon. We consider all particles in the Universe as a 'gravitationally entangled' statistical ensemble and apply the approach of classical statistical mechanics to it. It is shown that both the Schrodinger equation and the Planck constant can be derived within this Machian model of the universe. The appearance of probabilities, complex wave functions, and quantization conditions is related to the discreetness and finiteness of the Machian ensemble.Comment: Minor corrections, the version accepted by Int. J. Theor. Phy

Clinical observations on interferences of early father absence in the achievement of femininity

In clinical work, we have observed that the loss of the father through divorce has a significant effect on the young girl's developing sense of feminity. This paper briefly reviews the research findings from sex-role development theory and psychoanalytic theory, and presents clinical discussions of latency aged girls whose parents divorced during their daughter's early and oedipal years. The most common defensive or coping patterns seen in these child patients during latency are identified, with clinical material presented to illustrate both the existence of these patterns and implications for treatment.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44356/1/10615_2004_Article_BF00756561.pd

Cosmological evolution of interacting dark energy in Lorentz violation

The cosmological evolution of an interacting scalar field model in which the scalar field interacts with dark matter, radiation, and baryon via Lorentz violation is investigated. We propose a model of interaction through the effective coupling $\bar{\beta}$. Using dynamical system analysis, we study the linear dynamics of an interacting model and show that the dynamics of critical points are completely controlled by two parameters. Some results can be mentioned as follows. Firstly, the sequence of radiation, the dark matter, and the scalar field dark energy exist and baryons are sub dominant. Secondly, the model also allows the possibility of having a universe in the phantom phase with constant potential. Thirdly, the effective gravitational constant varies with respect to time through $\bar{\beta}$. In particular, we consider a simple case where $\bar{\beta}$ has a quadratic form and has a good agreement with the modified $\Lambda$CDM and quintessence models. Finally, we also calculate the first post--Newtonian parameters for our model.Comment: 14 pages, published versio