Agonist and antagonist effects of diadenosine tetraphosphate, a platelet dense granule constituent, on platelet P2Y1, P2Y12 and P2X1 receptors

INTRODUCTION: Diadenosine 5',5'''-P(1),P(4)- tetraphosphate (Ap(4)A) is stored in platelet dense granules, but its effects on platelet function are not well understood. METHODS AND RESULTS: We examined the effects of Ap(4)A on platelet purinergic receptors P2Y(1), P2Y(12) and P2X(1). Flow cytometry was used to measure the effects of Ap(4)A in the presence or absence of ADP on: a) P2Y(12)-mediated decrease in intraplatelet phosphorylated vasodilator stimulated phosphoprotein (VASP), b) P2Y(1)-mediated increase in platelet cytosolic Ca(2+), and c) P2X(1)-mediated intraplatelet entry of extracellular Ca(2+). ADP-stimulated platelet shape change (P2Y(1)-mediated) and aggregation (P2Y(1)- and P2Y(12)-mediated) were measured optically. Ap(4)A inhibited 3 microM ADP-induced: a) platelet aggregation (IC(50) 9.8+/-2.8 microM), b) P2Y(1)-mediated shape change, c) P2Y(1)-mediated increase in platelet cytosolic Ca(2+) (IC(50) 40.8+/-12.3 microM), and d) P2Y(12)-mediated decrease in VASP phosphorylation (IC(50)>250 microM). In the absence of added ADP, Ap(4)A had agonist effects on platelet P2X(1) and P2Y(12), but not P2Y(1), receptors. CONCLUSION: Ap(4)A, a constituent of platelet dense granules, is a) an antagonist of platelet P2Y(1) and P2Y(12) receptors, where it inhibits the effects of ADP, and b) an agonist of platelet P2X(1) and P2Y(12) receptors

Double-slit interference pattern from single-slit screen and its gravitational analogues

The double slit experiment (DSE) is known as an important cornerstone in the foundations of physical theories such as Quantum Mechanics and Special Relativity. A large number of different variants of it were designed and performed over the years. We perform and discuss here a new verion with the somewhat unexpected results of obtaining interference pattern from single-slit screen. This outcome, which shows that the routes of the photons through the array were changed, leads one to discuss it, using the equivalence principle, in terms of geodesics mechanics. We show using either the Brill's version of the canonical formulation of general relativity or the linearized version of it that one may find corresponding and analogous situations in the framework of general relativity.Comment: 51 pages, 12 Figures five of them contain two subfigures and thus the number of figures is 17, 1 Table. Some minor changes introduced, especially, in the reference

Rapid And Durable Responses With The Syk/Jak Inhibitor Cerdulatinib In A Phase 2 Study In Relapsed/Refractory Follicular Lymphoma—Alone Or In Combination With Rituximab

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/149541/1/hon30_2629.pd

Chiral 4d string vacua with D-branes and NSNS and RR fluxes

We discuss type IIB orientifolds with D-branes, and NSNS and RR field strength fluxes. The D-brane sectors lead to open string spectra with non-abelian gauge symmetry and charged chiral fermions. The closed string field strengths generate a scalar potential stabilizing most moduli. We describe the construction of N=1 supersymmetric models in the context of orientifolds of IIB theory on T^6/Z_2 x Z_2, containing D9-branes with world-volume magnetic fluxes, and illustrate model building possibilities with several explicit examples. We comment on a T-dual picture with D8-branes on non-Calabi-Yau half-flat geometries, and discuss some of the topological properties of such configurations. We also explore the construction of models with fluxes and with D3-branes at singularities and present a non-supersymmetric 3-family SU(5) model.Comment: latex, 49 pages, 2 figure

Supersymmetric Intersections of M-branes and pp-waves

We study supersymmetric intersections of M2 and M5 branes with different pp-waves of M-theory. We consider first M-brane probes in the background of pp-waves and determine under which conditions the embedding is supersymmetric. We particularize our formalism to the case of pp-waves with 32, 24 and 20 supersymmetries. We also construct supergravity solutions for the brane-wave system. Generically these solutions are delocalised along some directions transverse to the brane and preserve the same number of supersymmetries as in the brane probe approach.Comment: 41 pages, LaTeX; v2 references adde

Flux Compactifications on Calabi-Yau Threefolds

The presence of RR and NS three-form fluxes in type IIB string compactification on a Calabi-Yau orientifold gives rise to a nontrivial superpotential W for the dilaton and complex structure moduli. This superpotential is computable in terms of the period integrals of the Calabi-Yau manifold. In this paper, we present explicit examples of both supersymmetric and nonsupersymmetric solutions to the resulting 4d N=1 supersymmetric no-scale supergravity, including some nonsupersymmetric solutions with relatively small values of W. Our examples arise on orientifolds of the hypersurfaces in $WP^{4}_{1,1,1,1,4}$ and $WP^{4}_{1,1,2,2,6}$. They serve as explicit illustrations of several of the ingredients which have played a role in the recent proposals for constructing de Sitter vacua of string theory.Comment: 30 pages, harvmac big; refs and minor comments adde

State sampling dependence of the Hopfield network inference

The fully connected Hopfield network is inferred based on observed magnetizations and pairwise correlations. We present the system in the glassy phase with low temperature and high memory load. We find that the inference error is very sensitive to the form of state sampling. When a single state is sampled to compute magnetizations and correlations, the inference error is almost indistinguishable irrespective of the sampled state. However, the error can be greatly reduced if the data is collected with state transitions. Our result holds for different disorder samples and accounts for the previously observed large fluctuations of inference error at low temperatures.Comment: 4 pages, 1 figure, further discussions added and relevant references adde

Open Strings in Exactly Solvable Model of Curved Spacetime and PP-Wave Limit

In this paper we study the superstring version of the exactly solvable string model constructed by Russo and Tseytlin. This model represents superstring theory in a curved spacetime and can be seen as a generalization of the Melvin background. We investigate D-branes in this model as probes of the background geometry by constructing the boundary states. We find that spacetime singularities in the model become smooth at high energy from the viewpoint of open string. We show that there always exist bulk (movable) D-branes by the effect of electric flux. The model also includes Nappi-Witten model as the Penrose limit and supersymmetry is enhanced in the limit. We examine this phenomenon in the open string spectrum. We also find the similar enhancement of supersymmetry can be occurred in several coset models.Comment: Latex, 32 pages, typos corrected, references added, to appear in JHEP, eq.(2.22) correcte

Collective perspective on advances in Dyson-Schwinger Equation QCD

We survey contemporary studies of hadrons and strongly interacting quarks using QCD's Dyson-Schwinger equations, addressing: aspects of confinement and dynamical chiral symmetry breaking; the hadron spectrum; hadron elastic and transition form factors, from small- to large-Q^2; parton distribution functions; the physics of hadrons containing one or more heavy quarks; and properties of the quark gluon plasma.Comment: 56 pages. Summary of lectures delivered by the authors at the "Workshop on AdS/CFT and Novel Approaches to Hadron and Heavy Ion Physics," 2010-10-11 to 2010-12-03, hosted by the Kavli Institute for Theoretical Physics, China, at the Chinese Academy of Science