International Union of Basic and Clinical Pharmacology. CXII: adenosine receptors: a further update

Our previous International Union of Basic and Clinical Pharmacology report on the nomenclature and classification of adenosine receptors (2011) contained a number of emerging developments with respect to this G protein-coupled receptor subfamily, including protein structure, protein oligomerization, protein diversity, and allosteric modulation by small molecules. Since then, a wealth of new data and results has been added, allowing us to explore novel concepts such as target binding kinetics and biased signaling of adenosine receptors, to examine a multitude of receptor structures and novel ligands, to gauge new pharmacology, and to evaluate clinical trials with adenosine receptor ligands. This review should therefore be considered a further update of our previous reports from 2001 and 2011.Significance Statement-Adenosine receptors (ARs) are of continuing interest for future treatment of chronic and acute disease conditions, including inflammatory diseases, neurodegenerative afflictions, and cancer. The design of AR agonists ("biased" or not) and antagonists is largely structure based now, thanks to the tremendous progress in AR structural biology. The A2A and A2BAR appear to modulate the immune response in tumor biology. Many clinical trials for this indication are ongoing, whereas an A2AAR antagonist (istradefylline) has been approved as an anti-Parkinson agent.Medicinal Chemistr

Unified N=2 Maxwell-Einstein and Yang-Mills-Einstein Supergravity Theories in Four Dimensions

We study unified N=2 Maxwell-Einstein supergravity theories (MESGTs) and unified Yang-Mills Einstein supergravity theories (YMESGTs) in four dimensions. As their defining property, these theories admit the action of a global or local symmetry group that is (i) simple, and (ii) acts irreducibly on all the vector fields of the theory, including the ``graviphoton''. Restricting ourselves to the theories that originate from five dimensions via dimensional reduction, we find that the generic Jordan family of MESGTs with the scalar manifolds [SU(1,1)/U(1)] X [SO(2,n)/SO(2)X SO(n)] are all unified in four dimensions with the unifying global symmetry group SO(2,n). Of these theories only one can be gauged so as to obtain a unified YMESGT with the gauge group SO(2,1). Three of the four magical supergravity theories defined by simple Euclidean Jordan algebras of degree 3 are unified MESGTs in four dimensions. Two of these can furthermore be gauged so as to obtain 4D unified YMESGTs with gauge groups SO(3,2) and SO(6,2), respectively. The generic non-Jordan family and the theories whose scalar manifolds are homogeneous but not symmetric do not lead to unified MESGTs in four dimensions. The three infinite families of unified five-dimensional MESGTs defined by simple Lorentzian Jordan algebras, whose scalar manifolds are non-homogeneous, do not lead directly to unified MESGTs in four dimensions under dimensional reduction. However, since their manifolds are non-homogeneous we are not able to completely rule out the existence of symplectic sections in which these theories become unified in four dimensions.Comment: 47 pages; latex fil

Unified Maxwell-Einstein and Yang-Mills-Einstein Supergravity Theories in Five Dimensions

Unified N=2 Maxwell-Einstein supergravity theories (MESGTs) are supergravity theories in which all the vector fields, including the graviphoton, transform in an irreducible representation of a simple global symmetry group of the Lagrangian. As was established long time ago, in five dimensions there exist only four unified Maxwell-Einstein supergravity theories whose target manifolds are symmetric spaces. These theories are defined by the four simple Euclidean Jordan algebras of degree three. In this paper, we show that, in addition to these four unified MESGTs with symmetric target spaces, there exist three infinite families of unified MESGTs as well as another exceptional one. These novel unified MESGTs are defined by non-compact (Minkowskian) Jordan algebras, and their target spaces are in general neither symmetric nor homogeneous. The members of one of these three infinite families can be gauged in such a way as to obtain an infinite family of unified N=2 Yang-Mills-Einstein supergravity theories, in which all vector fields transform in the adjoint representation of a simple gauge group of the type SU(N,1). The corresponding gaugings in the other two infinite families lead to Yang-Mills-Einstein supergravity theories coupled to tensor multiplets.Comment: Latex 2e, 28 pages. v2: reference added, footnote 14 enlarge

Limb Spicules from the Ground and from Space

We amassed statistics for quiet-sun chromosphere spicules at the limb using ground-based observations from the Swedish 1-m Solar Telescope on La Palma and simultaneously from NASA's Transition Region and Coronal Explorer (TRACE) spacecraft. The observations were obtained in July 2006. With the 0.2 arcsecond resolution obtained after maximizing the ground-based resolution with the Multi-Object Multi-Frame Blind Deconvolution (MOMFBD) program, we obtained specific statistics for sizes and motions of over two dozen individual spicules, based on movies compiled at 50-second cadence for the series of five wavelengths observed in a very narrow band at H-alpha, on-band and in the red and blue wings at 0.035 nm and 0.070 nm (10 s at each wavelength) using the SOUP filter, and had simultaneous observations in the 160 nm EUV continuum from TRACE. The MOMFBD restoration also automatically aligned the images, facilitating the making of Dopplergrams at each off-band pair. We studied 40 H-alpha spicules, and 14 EUV spicules that overlapped H-alpha spicules; we found that their dynamical and morphological properties fit into the framework of several previous studies. From a preliminary comparison with spicule theories, our observations are consistent with a reconnection mechanism for spicule generation, and with UV spicules being a sheath region surrounding the H-alpha spicules

Toward a 21st-century health care system: Recommendations for health care reform

The coverage, cost, and quality problems of the U.S. health care system are evident. Sustainable health care reform must go beyond financing expanded access to care to substantially changing the organization and delivery of care. The FRESH-Thinking Project (www.fresh-thinking.org) held a series of workshops during which physicians, health policy experts, health insurance executives, business leaders, hospital administrators, economists, and others who represent diverse perspectives came together. This group agreed that the following 8 recommendations are fundamental to successful reform: 1. Replace the current fee-for-service payment system with a payment system that encourages and rewards innovation in the efficient delivery of quality care. The new payment system should invest in the development of outcome measures to guide payment. 2. Establish a securely funded, independent agency to sponsor and evaluate research on the comparative effectiveness of drugs, devices, and other medical interventions. 3. Simplify and rationalize federal and state laws and regulations to facilitate organizational innovation, support care coordination, and streamline financial and administrative functions. 4. Develop a health information technology infrastructure with national standards of interoperability to promote data exchange. 5. Create a national health database with the participation of all payers, delivery systems, and others who own health care data. Agree on methods to make de-identified information from this database on clinical interventions, patient outcomes, and costs available to researchers. 6. Identify revenue sources, including a cap on the tax exclusion of employer-based health insurance, to subsidize health care coverage with the goal of insuring all Americans. 7. Create state or regional insurance exchanges to pool risk, so that Americans without access to employer-based or other group insurance could obtain a standard benefits package through these exchanges. Employers should also be allowed to participate in these exchanges for their employees' coverage. 8. Create a health coverage board with broad stakeholder representation to determine and periodically update the affordable standard benefit package available through state or regional insurance exchanges