Demonstration of mixed properties of RU486 in progesterone receptor (PR)-transfected MDA-MB-231 cells: a model for studying the functions of progesterone analogues

Progesterone antagonist RU486 (mifepristone) has been implicated for many anti-neoplastic and obstetrical applications. But the compound has demonstrated undesired agonist-like effect depending on cell, tissue and species studied. Using PR-transfected breast cancer cells MDA-MB-231, this report describes the similarities and differences between progesterone- and RU486-mediated effects on cell growth, cell differentiation and, at the molecular level, on the activation of p44/p42 MAP kinases (MAPK). Like progesterone, RU486 inhibited cells growth by arresting the cells in G0/G1 phase of the cell cycle. In contrast to progesterone that induced cell spreading, RU486 induced a multipolar, stellate morphology. RU486-treated cells showed no increase of stress fibers, nor was there any increase of focal adhesions as progesterone-treated cells did. Furthermore, despite of the fact that both compounds inhibited cell growth, RU486 significantly stimulated the activation of p44/p42 MAP kinases whereas progesterone markedly inhibited the activation. Nonetheless, the effects of RU486 were PR-mediated and RU486 was able to antagonize the effect of progesterone on cell growth and focal adhesion. In conclusion, RU486 can act not only as a progesterone antagonist, a progesterone agonist but also induced morphological and molecular changes that were distinct from progesterone-mediated effects in PR-transfected MDA-MB-231 cells. The non-progesterone-like effect of RU486 may be mediated through a pathway that is different from the progesterone-mediated pathway, or it is the result of a blockade of certain critical step(s) in the progesterone-mediated pathway. In any case, undesired side effects of antiprogestin may create clinical complications. PR-transfected MDA-MB-231 breast cancer cells provide a model for studying the functions of progesterone analogues.© 2001 Cancer Research Campaign http://www.bjcancer.co

Advanced flight control system study

A fly by wire flight control system architecture designed for high reliability includes spare sensor and computer elements to permit safe dispatch with failed elements, thereby reducing unscheduled maintenance. A methodology capable of demonstrating that the architecture does achieve the predicted performance characteristics consists of a hierarchy of activities ranging from analytical calculations of system reliability and formal methods of software verification to iron bird testing followed by flight evaluation. Interfacing this architecture to the Lockheed S-3A aircraft for flight test is discussed. This testbed vehicle can be expanded to support flight experiments in advanced aerodynamics, electromechanical actuators, secondary power systems, flight management, new displays, and air traffic control concepts

Health status of older adults with Type 2 diabetes mellitus after aerobic or resistance training: A randomised trial

10.1186/1477-7525-9-59Health and Quality of Life Outcomes9

Stochastic Spacetime and Brownian Motion of Test Particles

The operational meaning of spacetime fluctuations is discussed. Classical spacetime geometry can be viewed as encoding the relations between the motions of test particles in the geometry. By analogy, quantum fluctuations of spacetime geometry can be interpreted in terms of the fluctuations of these motions. Thus one can give meaning to spacetime fluctuations in terms of observables which describe the Brownian motion of test particles. We will first discuss some electromagnetic analogies, where quantum fluctuations of the electromagnetic field induce Brownian motion of test particles. We next discuss several explicit examples of Brownian motion caused by a fluctuating gravitational field. These examples include lightcone fluctuations, variations in the flight times of photons through the fluctuating geometry, and fluctuations in the expansion parameter given by a Langevin version of the Raychaudhuri equation. The fluctuations in this parameter lead to variations in the luminosity of sources. Other phenomena which can be linked to spacetime fluctuations are spectral line broadening and angular blurring of distant sources.Comment: 15 pages, 3 figures. Talk given at the 9th Peyresq workshop, June 200

Secondary aerosol formation from atmospheric reactions of aliphatic amines

Although aliphatic amines have been detected in both urban and rural atmospheric aerosols, little is known about the chemistry leading to particle formation or the potential aerosol yields from reactions of gas-phase amines. We present here the first systematic study of aerosol formation from the atmospheric reactions of amines. Based on laboratory chamber experiments and theoretical calculations, we evaluate aerosol formation from reaction of OH, ozone, and nitric acid with trimethylamine, methylamine, triethylamine, diethylamine, ethylamine, and ethanolamine. Entropies of formation for alkylammonium nitrate salts are estimated by molecular dynamics calculations enabling us to estimate equilibrium constants for the reactions of amines with nitric acid. Though subject to significant uncertainty, the calculated dissociation equilibrium constant for diethylammonium nitrate is found to be sufficiently small to allow for its atmospheric formation, even in the presence of ammonia which competes for available nitric acid. Experimental chamber studies indicate that the dissociation equilibrium constant for triethylammonium nitrate is of the same order of magnitude as that for ammonium nitrate. All amines studied form aerosol when photooxidized in the presence of NOx with the majority of the aerosol mass present at the peak of aerosol growth consisting of aminium (R3NH+) nitrate salts, which repartition back to the gas phase as the parent amine is consumed. Only the two tertiary amines studied, trimethylamine and triethylamine, are found to form significant non-salt organic aerosol when oxidized by OH or ozone; calculated organic mass yields for the experiments conducted are similar for ozonolysis (15% and 5% respectively) and photooxidation (23% and 8% respectively). The non-salt organic aerosol formed appears to be more stable than the nitrate salts and does not quickly repartition back to the gas phase

From computation to black holes and space-time foam

We show that quantum mechanics and general relativity limit the speed $\tilde{\nu}$ of a simple computer (such as a black hole) and its memory space $I$ to \tilde{\nu}^2 I^{-1} \lsim t_P^{-2}, where $t_P$ is the Planck time. We also show that the life-time of a simple clock and its precision are similarly limited. These bounds and the holographic bound originate from the same physics that governs the quantum fluctuations of space-time. We further show that these physical bounds are realized for black holes, yielding the correct Hawking black hole lifetime, and that space-time undergoes much larger quantum fluctuations than conventional wisdom claims -- almost within range of detection with modern gravitational-wave interferometers.Comment: A misidentification of computer speeds is corrected. Our results for black hole computation now agree with those given by S. Lloyd. All other conclusions remain unchange

The Complex Wind Torus and Jets of PSR B1706-44

We report on Chandra ACIS imaging of the pulsar wind nebula (PWN) of the young Vela-like PSR B1706-44, which shows the now common pattern of an equatorial wind and polar jets. The structure is particularly rich, showing a relativistically boosted termination shock, jets with strong confinement, a surrounding radio/X-ray PWN and evidence for a quasi-static `bubble nebula'. The structures trace the pulsar spin geometry and illuminate its possible relation to SNR G343.1-2.3. We also obtain improved estimates of the pulsar flux and nebular spectrum, constraining the system age and energetics.Comment: To appear in the Astrophysical Journal. 15pp, 4 figures in 7 file

Gravity Waves from Quantum Stress Tensor Fluctuations in Inflation

We consider the effects of the quantum stress tensor fluctuations of a conformal field in generating gravity waves in inflationary models. We find a non-scale invariant, non-Gaussian contribution which depends upon the total expansion factor between an initial time and the end of inflation. This spectrum of gravity wave perturbations is an illustration of a negative power spectrum, which is possible in quantum field theory. We discuss possible choices for the initial conditions. If the initial time is taken to be sufficiently early, the fluctuating gravity waves are potentially observable both in the CMB radiation and in gravity wave detectors, and could offer a probe of transplanckian physics. The fact that they have not yet been observed might be used to constrain the duration and energy scale of inflation.Comment: 17 -pages, no figure

Quantum Stress Tensor Fluctuations of a Conformal Field and Inflationary Cosmology

We discuss the additional perturbation introduced during inflation by quantum stress tensor fluctuations of a conformally invariant field such as the photon. We consider both a kinematical model, which deals only with the expansion fluctuations of geodesics, and a dynamical model which treats the coupling of the stress tensor fluctuations to a scalar inflaton. In neither model do we find any growth at late times, in accordance with a theorem due to Weinberg. What we find instead is a correction which becomes larger the earlier one starts inflation. This correction is non-Gaussian and highly scale dependent, so the absence of such effects from the observed power spectra may imply a constraint on the total duration of inflation. We discuss different views about the validity of perturbation theory at very early times during which currently observable modes are transplanckian.Comment: 31 pages, 1 figure, uses LaTeX2epsilo

Spin polarized liquid 3He

We have employed the constrained variational method to study the influence of spin polarization on the ground state properties of liquid $^3{\rm He}$. The spin polarized phase, we have found, has stronger correlation with respect to the unpolarized phase. It is shown that the internal energy of liquid $^3{\rm He}$ increases by increasing polarization with no crossing point between polarized and unpolarized energy curves over the liquid density range. The obtained internal energy curves show a bound state, even in the case of fully spin polarized matter. We have also investigated the validity of using a parabolic formula for calculating the energy of spin polarized liquid $^3{\rm He}$. Finally, we have compared our results with other calculations.Comment: 16 pages, 6 figure