Statin pharmacogenomics: pursuing biomarkers for predicting clinical outcomes

Indicated for treating hyperlipidemias and for the prevention of cardiovascular disease (CVD), statins rank among the most commonly prescribed drug classes. While statins are considered to be highly effective in preventing atherosclerotic events, a substantial portion of treated patients still progress to overt CVD. Genetic factors are thought to contribute substantially to treatment outcome. Several candidate genes have been associated with statin dose requirements and treatment outcomes, but a clinically relevant pharmacogenomics test to guide statin therapy has not yet emerged. Here we define basic pharmacogenomics terminology, present strong candidate genes (CETP, HMGCR, SLCO1B1, ABCB1, and CYP3A4/5), and discuss the challenges in developing much-needed statin pharmacogenomics biomarkers for predicting treatment outcomes

Symmetry breaking in the Hubbard model at weak coupling

The phase diagram of the Hubbard model is studied at weak coupling in two and three spatial dimensions. It is shown that the Neel temperature and the order parameter in d=3 are smaller than the Hartree-Fock predictions by a factor of q=0.2599. For d=2 we show that the self-consistent (sc) perturbation series bears no relevance to the behavior of the exact solution of the Hubbard model in the symmetry-broken phase. We also investigate an anisotropic model and show that the coupling between planes is essential for the validity of mean-field-type order parameters

Biomarcatori farmacogenomici per la predizione di efficacia e sicurezza delle statine

Le statine, indicate per il trattamento delle iperlipidemie e per la prevenzione delle malattie cardiovascolari, sono fra le classi di farmaci pi\uf9 frequentemente prescritte. A dispetto della loro ormai riconosciuta efficacia, una percentuale rilevante dei pazienti trattati con questi farmaci continua a progredire verso la malattia cardiovascolare conclamata. \uc8 quindi pensiero comune che diversi fattori genetici possano contribuire sostanzialmente al risultato di questo trattamento terapeutico. Effettivamente, diversi geni candidati sono stati associati al dosaggio di statina necessario e al risultato terapeutico. Ci\uf2 nonostante, non esiste ad oggi alcun test farmacogenomico specifico che permetta di guidare il medico nelle scelte riguardanti la terapia con questi farmaci. Nel presente articolo, oltre a definire la terminologia di base della farmacogenomica, saranno descritti i geni candidati di maggior interesse (CETP, HMGCR, SLCO1B1, ABCB1 e CYP3A4/5) e i pi\uf9 recenti studi effettuati al fine di soddisfare la crescente richiesta di nuovi marcatori farmacogenomici capaci di predire la risposta al trattamento con una statina.Statins have high efficacy for treating hyperlipidemia and are widely prescribed. While most patients benefit from statins, some experience cardiovascular events despite statin pharmacotherapy and others experience adverse effects. Patient response to statins is genetically influenced, and polymorphisms in many genes have been associated with statin dose requirements and clinical outcomes. However, a clinically relevant pharmacogenomics test to guide statin therapy has not yet materialized. This article provides a basic overview of pharmacogenomics, describes several key genes (CETP, HMGCR, SLCO1B1, ABCB1, and CYP3A4/5) influencing the pharmacology of statins, and highlights the difficulties in developing actionable genetic assays to help guide statin pharmacotherapy

Atmospheric Heating and Wind Acceleration: Results for Cool Evolved Stars based on Proposed Processes

A chromosphere is a universal attribute of stars of spectral type later than ~F5. Evolved (K and M) giants and supergiants (including the zeta Aurigae binaries) show extended and highly turbulent chromospheres, which develop into slow massive winds. The associated continuous mass loss has a significant impact on stellar evolution, and thence on the chemical evolution of galaxies. Yet despite the fundamental importance of those winds in astrophysics, the question of their origin(s) remains unsolved. What sources heat a chromosphere? What is the role of the chromosphere in the formation of stellar winds? This chapter provides a review of the observational requirements and theoretical approaches for modeling chromospheric heating and the acceleration of winds in single cool, evolved stars and in eclipsing binary stars, including physical models that have recently been proposed. It describes the successes that have been achieved so far by invoking acoustic and MHD waves to provide a physical description of plasma heating and wind acceleration, and discusses the challenges that still remain.Comment: 46 pages, 9 figures, 1 table; modified and unedited manuscript; accepted version to appear in: Giants of Eclipse, eds. E. Griffin and T. Ake (Berlin: Springer

One particle spectral weight of the three dimensional single band Hubbard model

Dynamic properties of the three-dimensional single-band Hubbard model are studied using Quantum Monte Carlo combined with the maximum entropy technique. At half-filling, there is a clear gap in the density of states and well-defined quasiparticle peaks at the top (bottom) of the lower (upper) Hubbard band. We find an antiferromagnetically induced weight above the naive Fermi momentum. Upon hole doping, the chemical potential moves to the top of the lower band where a robust peak is observed. Results are compared with spin-density-wave (SDW) mean-field and self consistent Born approximation results, and also with the infinite dimensional Hubbard model, and experimental photoemission (PES) for three dimensional transition-metal oxides.Comment: 11 pages, REVTeX, 16 figures included using psfig.sty. Ref.30 correcte

Dynamic nuclear polarization and spin-diffusion in non-conducting solids

There has been much renewed interest in dynamic nuclear polarization (DNP), particularly in the context of solid state biomolecular NMR and more recently dissolution DNP techniques for liquids. This paper reviews the role of spin diffusion in polarizing nuclear spins and discusses the role of the spin diffusion barrier, before going on to discuss some recent results.Comment: submitted to Applied Magnetic Resonance. The article should appear in a special issue that is being published in connection with the DNP Symposium help in Nottingham in August 200

High-Order Coupled Cluster Method (CCM) Calculations for Quantum Magnets with Valence-Bond Ground States

In this article, we prove that exact representations of dimer and plaquette valence-bond ket ground states for quantum Heisenberg antiferromagnets may be formed via the usual coupled cluster method (CCM) from independent-spin product (e.g. N\'eel) model states. We show that we are able to provide good results for both the ground-state energy and the sublattice magnetization for dimer and plaquette valence-bond phases within the CCM. As a first example, we investigate the spin-half $J_1$--$J_2$ model for the linear chain, and we show that we are able to reproduce exactly the dimerized ground (ket) state at $J_2/J_1=0.5$. The dimerized phase is stable over a range of values for $J_2/J_1$ around 0.5. We present evidence of symmetry breaking by considering the ket- and bra-state correlation coefficients as a function of $J_2/J_1$. We then consider the Shastry-Sutherland model and demonstrate that the CCM can span the correct ground states in both the N\'eel and the dimerized phases. Finally, we consider a spin-half system with nearest-neighbor bonds for an underlying lattice corresponding to the magnetic material CaV$_4$O$_9$ (CAVO). We show that we are able to provide excellent results for the ground-state energy in each of the plaquette-ordered, N\'eel-ordered, and dimerized regimes of this model. The exact plaquette and dimer ground states are reproduced by the CCM ket state in their relevant limits.Comment: 34 pages, 13 figures, 2 table

Interstellar MHD Turbulence and Star Formation

This chapter reviews the nature of turbulence in the Galactic interstellar medium (ISM) and its connections to the star formation (SF) process. The ISM is turbulent, magnetized, self-gravitating, and is subject to heating and cooling processes that control its thermodynamic behavior. The turbulence in the warm and hot ionized components of the ISM appears to be trans- or subsonic, and thus to behave nearly incompressibly. However, the neutral warm and cold components are highly compressible, as a consequence of both thermal instability in the atomic gas and of moderately-to-strongly supersonic motions in the roughly isothermal cold atomic and molecular components. Within this context, we discuss: i) the production and statistical distribution of turbulent density fluctuations in both isothermal and polytropic media; ii) the nature of the clumps produced by thermal instability, noting that, contrary to classical ideas, they in general accrete mass from their environment; iii) the density-magnetic field correlation (or lack thereof) in turbulent density fluctuations, as a consequence of the superposition of the different wave modes in the turbulent flow; iv) the evolution of the mass-to-magnetic flux ratio (MFR) in density fluctuations as they are built up by dynamic compressions; v) the formation of cold, dense clouds aided by thermal instability; vi) the expectation that star-forming molecular clouds are likely to be undergoing global gravitational contraction, rather than being near equilibrium, and vii) the regulation of the star formation rate (SFR) in such gravitationally contracting clouds by stellar feedback which, rather than keeping the clouds from collapsing, evaporates and diperses them while they collapse.Comment: 43 pages. Invited chapter for the book "Magnetic Fields in Diffuse Media", edited by Elisabete de Gouveia dal Pino and Alex Lazarian. Revised as per referee's recommendation

First Measurement of Z/gamma* Production in Compton Scattering of Quasi-real Photons

We report the first observation of Z/gamma* production in Compton scattering of quasi-real photons. This is a subprocess of the reaction e+e- to e+e-Z/gamma*, where one of the final state electrons is undetected. Approximately 55 pb-1 of data collected in the year 1997 at an e+e- centre-of-mass energy of 183 GeV with the OPAL detector at LEP have been analysed. The Z/gamma* from Compton scattering has been detected in the hadronic decay channel. Within well defined kinematic bounds, we measure the product of cross-section and Z/gamma* branching ratio to hadrons to be (0.9+-0.3+-0.1) pb for events with a hadronic mass larger than 60 GeV, dominated by (e)eZ production. In the hadronic mass region between 5 GeV and 60 GeV, dominated by (e)egamma* production, this product is found to be (4.1+-1.6+-0.6) pb. Our results agree with the predictions of two Monte Carlo event generators, grc4f and PYTHIA.Comment: 18 pages, LaTeX, 5 eps figures included, submitted to Physics Letters

Search for Higgs Bosons in e+e- Collisions at 183 GeV

The data collected by the OPAL experiment at sqrts=183 GeV were used to search for Higgs bosons which are predicted by the Standard Model and various extensions, such as general models with two Higgs field doublets and the Minimal Supersymmetric Standard Model (MSSM). The data correspond to an integrated luminosity of approximately 54pb-1. None of the searches for neutral and charged Higgs bosons have revealed an excess of events beyond the expected background. This negative outcome, in combination with similar results from searches at lower energies, leads to new limits for the Higgs boson masses and other model parameters. In particular, the 95% confidence level lower limit for the mass of the Standard Model Higgs boson is 88.3 GeV. Charged Higgs bosons can be excluded for masses up to 59.5 GeV. In the MSSM, mh > 70.5 GeV and mA > 72.0 GeV are obtained for tan{beta}>1, no and maximal scalar top mixing and soft SUSY-breaking masses of 1 TeV. The range 0.8 < tanb < 1.9 is excluded for minimal scalar top mixing and m{top} < 175 GeV. More general scans of the MSSM parameter space are also considered.Comment: 49 pages. LaTeX, including 33 eps figures, submitted to European Physical Journal