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

Faster k-Medoids Clustering: Improving the PAM, CLARA, and CLARANS Algorithms

Clustering non-Euclidean data is difficult, and one of the most used algorithms besides hierarchical clustering is the popular algorithm Partitioning Around Medoids (PAM), also simply referred to as k-medoids. In Euclidean geometry the mean-as used in k-means-is a good estimator for the cluster center, but this does not hold for arbitrary dissimilarities. PAM uses the medoid instead, the object with the smallest dissimilarity to all others in the cluster. This notion of centrality can be used with any (dis-)similarity, and thus is of high relevance to many domains such as biology that require the use of Jaccard, Gower, or more complex distances. A key issue with PAM is its high run time cost. We propose modifications to the PAM algorithm to achieve an O(k)-fold speedup in the second SWAP phase of the algorithm, but will still find the same results as the original PAM algorithm. If we slightly relax the choice of swaps performed (at comparable quality), we can further accelerate the algorithm by performing up to k swaps in each iteration. With the substantially faster SWAP, we can now also explore alternative strategies for choosing the initial medoids. We also show how the CLARA and CLARANS algorithms benefit from these modifications. It can easily be combined with earlier approaches to use PAM and CLARA on big data (some of which use PAM as a subroutine, hence can immediately benefit from these improvements), where the performance with high k becomes increasingly important. In experiments on real data with k=100, we observed a 200-fold speedup compared to the original PAM SWAP algorithm, making PAM applicable to larger data sets as long as we can afford to compute a distance matrix, and in particular to higher k (at k=2, the new SWAP was only 1.5 times faster, as the speedup is expected to increase with k)

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

Tilting instability and other anomalies in the flux-lattice in some magnetic superconductors

The flux-line lattice in the compound $ErNi_2B_2C$, which has a tendency to ferromagnetic order in the a-b plane is studied with external magnetic field direction close to the c-axis. We show the existence of an instability where the direction of flux-lines spontaneously tilts away from that of the applied field near the onset of ferromagnetic order. The enhanced fluctuations in the flux lattice and the square flux lattice recently observed are explained and further experiments suggested.Comment: 12 pages, Latex file, no figur

Recent progress in Hamiltonian light-front QCD

Hamiltonian light-front quantum field theory constitutes a framework for the non-perturbative solution of invariant masses and correlated parton amplitudes of self-bound systems. By choosing light-front gauge and adopting a basis function representation, we obtain a large, sparse, Hamiltonian matrix for mass eigenstates of gauge theories that is solvable by adapting the ab initio no-core methods of nuclear many-body theory. Full covariance is recovered in the continuum limit, the infinite matrix limit. We outline our approach and discuss the computational challenges.Comment: Invited paper at Light Cone 2008, Mulhouse, Franc

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

Entangled light from Bose-Einstein condensates

We propose a method to generate entangled light with a Bose-Einstein condensate trapped in a cavity, a system realized in recent experiments. The atoms of the condensate are trapped in a periodic potential generated by a cavity mode. The condensate is continuously pumped by a laser and spontaneously emits a pair of photons of different frequencies in two distinct cavity modes. In this way, the condensate mediates entanglement between two cavity modes which leak out and can be separated and exhibit continuous variable entanglement. The scheme exploits the experimentally demonstrated strong, steady and collective coupling of condensate atoms to a cavity field.Comment: 5 pages and 5 figure

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