Enhancement of the immunoregulatory potency of mesenchymal stromal cells by treatment with immunosuppressive drugs

Background aims Multipotent mesenchymal stromal cells (MSCs) are distinguished by their ability to differentiate into a number of stromal derivatives of interest for regenerative medicine, but they also have immunoregulatory properties that are being tested in a number of clinical settings. Methods We show that brief incubations with rapamycin, everolimus, FK506 or cyclosporine A increase the immunosuppressive potency of MSCs and other cell types. Results The treated MSCs are up to 5-fold more potent at inhibiting the induced proliferation of T lymphocytes in vitro. We show that this effect probably is due to adsorption of the drug by the MSCs during pre-treatment, with subsequent diffusion into co-cultures at concentrations sufficient to inhibit T-cell proliferation. MSCs contain measurable amounts of rapamycin after a 15-min exposure, and the potentiating effect is blocked by a neutralizing antibody to the drug. With the use of a pre-clinical model of acute graft-versus-host disease, we demonstrate that a low dose of rapamycin-treated but not untreated umbilical cord–derived MSCs significantly inhibit the onset of disease. Conclusions The use of treated MSCs may achieve clinical end points not reached with untreated MSCs and allow for infusion of fewer cells to reduce costs and minimize potential side effects

On vacuum gravitational collapse in nine dimensions

We consider the vacuum gravitational collapse for cohomogeneity-two solutions of the nine dimensional Einstein equations. Using combined numerical and analytical methods we give evidence that within this model the Schwarzschild-Tangherlini black hole is asymptotically stable. In addition, we briefly discuss the critical behavior at the threshold of black hole formation.Comment: 4 pages, 4 figure

Quasinormal Modes, the Area Spectrum, and Black Hole Entropy

The results of canonical quantum gravity concerning geometric operators and black hole entropy are beset by an ambiguity labelled by the Immirzi parameter. We use a result from classical gravity concerning the quasinormal mode spectrum of a black hole to fix this parameter in a new way. As a result we arrive at the Bekenstein - Hawking expression of $A/4 l_P^2$ for the entropy of a black hole and in addition see an indication that the appropriate gauge group of quantum gravity is SO(3) and not its covering group SU(2).Comment: 4 pages, 2 figure

Stability of bicontinuous cubic phases in ternary amphiphilic systems with spontaneous curvature

We study the phase behavior of ternary amphiphilic systems in the framework of a curvature model with non-vanishing spontaneous curvature. The amphiphilic monolayers can arrange in different ways to form micellar, hexagonal, lamellar and various bicontinuous cubic phases. For the latter case we consider both single structures (one monolayer) and double structures (two monolayers). Their interfaces are modeled by the triply periodic surfaces of constant mean curvature of the families G, D, P, C(P), I-WP and F-RD. The stability of the different bicontinuous cubic phases can be explained by the way in which their universal geometrical properties conspire with the concentration constraints. For vanishing saddle-splay modulus $\bar \kappa$, almost every phase considered has some region of stability in the Gibbs triangle. Although bicontinuous cubic phases are suppressed by sufficiently negative values of the saddle-splay modulus $\bar \kappa$, we find that they can exist for considerably lower values than obtained previously. The most stable bicontinuous cubic phases with decreasing $\bar \kappa < 0$ are the single and double gyroid structures since they combine favorable topological properties with extreme volume fractions.Comment: Revtex, 23 pages with 10 Postscript files included, to appear in J. Chem. Phys. 112 (6) (February 2000

Single polymer dynamics in elongational flow and the confluent Heun equation

We investigate the non-equilibrium dynamics of an isolated polymer in a stationary elongational flow. We compute the relaxation time to the steady-state configuration as a function of the Weissenberg number. A strong increase of the relaxation time is found around the coil-stretch transition, which is attributed to the large number of polymer configurations. The relaxation dynamics of the polymer is solved analytically in terms of a central two-point connection problem for the singly confluent Heun equation.Comment: 9 pages, 6 figure

Unconventional Gravitational Excitation of a Schwarzschild Black Hole

Besides the well-known quasinormal modes, the gravitational spectrum of a Schwarzschild black hole also has a continuum part on the negative imaginary frequency axis. The latter is studied numerically for quadrupole waves. The results show unexpected striking behavior near the algebraically special frequency $\Omega=-4i$. This reveals a pair of unconventional damped modes very near $\Omega$, confirmed analytically.Comment: REVTeX4, 4pp, 6 EPS figure files. N.B.: "Alec" is my first, and "Maassen van den Brink" my family name. v2: better pole placement in Fig. 1. v3: fixed Refs. [9,20]. v4: added context on "area quantum" research; trimmed one Fig.; textual clarification

A note on quasinormal modes: A tale of two treatments

There is an apparent discrepancy in the literature with regard to the quasinormal mode frequencies of Schwarzschild-de Sitter black holes in the degenerate-horizon limit. On the one hand, a Poschl-Teller-inspired method predicts that the real part of the frequencies will depend strongly on the orbital angular momentum of the perturbation field whereas, on the other hand, the degenerate limit of a monodromy-based calculation suggests there should be no such dependence (at least, for the highly damped modes). In the current paper, we provide a possible resolution by critically re-assessing the limiting procedure used in the monodromy analysis.Comment: 11 pages, Revtex format; (v2) new addendum in response to reader comments, also references, footnote and acknowledgments adde

Semi-analytic results for quasi-normal frequencies

The last decade has seen considerable interest in the quasi-normal frequencies [QNFs] of black holes (and even wormholes), both asymptotically flat and with cosmological horizons. There is wide agreement that the QNFs are often of the form omega_n = (offset) + i n (gap), though some authors have encountered situations where this behaviour seems to fail. To get a better understanding of the general situation we consider a semi-analytic model based on a piecewise Eckart (Poeschl-Teller) potential, allowing for different heights and different rates of exponential falloff in the two asymptotic directions. This model is sufficiently general to capture and display key features of the black hole QNFs while simultaneously being analytically tractable, at least for asymptotically large imaginary parts of the QNFs. We shall derive an appropriate "quantization condition" for the asymptotic QNFs, and extract as much analytic information as possible. In particular, we shall explicitly verify that the (offset)+ i n (gap) behaviour is common but not universal, with this behaviour failing unless the ratio of rates of exponential falloff on the two sides of the potential is a rational number. (This is "common but not universal" in the sense that the rational numbers are dense in the reals.) We argue that this behaviour is likely to persist for black holes with cosmological horizons.Comment: V1: 28 pages, no figures. V2: 3 references added, no physics changes. V3: 29 pages, 9 references added, no physics changes; V4: reformatted, now 27 pages. Some clarifications, comparison with results obtained by monodromy techniques. This version accepted for publication in JHEP. V5: Minor typos fixed. Compatible with published versio

Quasinormal modes of a black hole surrounded by quintessence

Using the third-order WKB approximation, we evaluate the quasinormal frequencies of massless scalar field perturbation around the black hole which is surrounded by the static and spherically symmetric quintessence. Our result shows that due to the presence of quintessence, the scalar field damps more rapidly. Moreover, we also note that the quintessential state parameter $\epsilon$ (the ratio of pressure $p_q$ to the energy density $\rho_q$) play an important role for the quasinormal frequencies. As the state parameter $\epsilon$ increases the real part increases and the absolute value of the imaginary part decreases. This means that the scalar field decays more slowly in the larger $\epsilon$ quintessence case.Comment: 7 pages, 3 figure