Tailoring therapy for heart failure: the pharmacogenomics of adrenergic receptor signaling.

Heart failure is one of the leading causes of mortality in Western countries, and β-blockers are a cornerstone of its treatment. However, the response to these drugs is variable among individuals, which might be explained, at least in part, by genetic differences. Pharmacogenomics is the study of genetic contributions to drug response variability in order to provide evidence for a tailored therapy in an individual patient. Several studies have investigated the pharmacogenomics of the adrenergic receptor system and its role in the context of the use of β-blockers in treating heart failure. In this review, we will focus on the most significant polymorphisms described in the literature involving adrenergic receptors and adrenergic receptor-related proteins, as well as genetic variations influencing β-blocker metabolism

Simulating cosmic metal enrichment by the first galaxies

We study cosmic metal enrichment via AMR hydrodynamical simulations in a (10 Mpc/h)$^3$ volume following the Pop III-Pop II transition and for different Pop III IMFs. We have analyzed the joint evolution of metal enrichment on galactic and intergalactic scales at z=6 and z=4. Galaxies account for <9% of the baryonic mass; the remaining gas resides in the diffuse phases: (a) voids, i.e. regions with extremely low density ($\Delta$<1), (b) the true intergalactic medium (IGM, 1<$\Delta$<10) and (c) the circumgalactic medium (CGM, 10<$\Delta<10^{2.5}$), the interface between the IGM and galaxies. By z=6 a galactic mass-metallicity relation is established. At z=4, galaxies with a stellar mass $M_*=10^{8.5}M_\odot$ show log(O/H)+12=8.19, consistent with observations. The total amount of heavy elements rises from $\Omega^{SFH}_Z=1.52\, 10^{-6}$ at z=6 to 8.05 $10^{-6}$ at z=4. Metals in galaxies make up to ~0.89 of such budget at z=6; this fraction increases to ~0.95 at z=4. At z=6 (z=4) the remaining metals are distributed in CGM/IGM/voids with the following mass fractions: 0.06/0.04/0.01 (0.03/0.02/0.01). Analogously to galaxies, at z=4 a density-metallicity ($\Delta$-Z) relation is in place for the diffuse phases: the IGM/voids have a spatially uniform metallicity, Z~$10^{-3.5}$Zsun; in the CGM Z steeply rises with density up to ~$10^{-2}$Zsun. In all diffuse phases a considerable fraction of metals is in a warm/hot (T>$10^{4.5}$K) state. Due to these physical conditions, CIV absorption line experiments can probe only ~2% of the total carbon present in the IGM/CGM; however, metal absorption line spectra are very effective tools to study reionization. Finally, the Pop III star formation history is almost insensitive to the chosen Pop III IMF. Pop III stars are preferentially formed in truly pristine (Z=0) gas pockets, well outside polluted regions created by previous star formation episodes.Comment: 23 pages, 18 figures, 3 tables, Accepted for publication in MNRA

Production of atomic hydrogen by cosmic rays in dark clouds

The presence of small amounts of atomic hydrogen, detected as absorption dips in the 21 cm line spectrum, is a well-known characteristic of dark clouds. The abundance of hydrogen atoms measured in the densest regions of molecular clouds can be only explained by the dissociation of H$_2$ due to cosmic rays. We want to assess the role of Galactic cosmic rays in the formation of atomic hydrogen, by using recent developments in the characterisation of the low-energy spectra of cosmic rays and advances in the modelling of their propagation in molecular clouds. We model the attenuation of the interstellar cosmic rays entering a cloud and compute the dissociation rate of molecular hydrogen due to collisions with cosmic-ray protons and electrons as well as fast hydrogen atoms. We compare our results with the available observations. The cosmic-ray dissociation rate is entirely determined by secondary electrons produced in primary ionisation collisions. These secondary particles constitute the only source of atomic hydrogen at column densities above $\sim10^{21}$ cm$^{-2}$. We also find that the dissociation rate decreases with column density, while the ratio between the dissociation and ionisation rates varies between about 0.6 and 0.7. From comparison with observations we conclude that a relatively flat spectrum of interstellar cosmic-ray protons, as the one suggested by the most recent Voyager 1 data, can only provide a lower bound for the observed atomic hydrogen fraction. An enhanced spectrum of low-energy protons is needed to explain most of the observations. Our findings show that a careful description of molecular hydrogen dissociation by cosmic rays can explain the abundance of atomic hydrogen in dark clouds. An accurate characterisation of this process at high densities is crucial for understanding the chemical evolution of star-forming regions.Comment: 7 pages, 7 figures, accepted by Astronomy and Astrophysic

Positive energy unitary irreducible representations of D=6 conformal supersymmetry

We give a constructive classification of the positive energy (lowest weight) unitary irreducible representations of the D=6 superconformal algebras osp(8*/2N). Our results confirm all but one of the conjectures of Minwalla (for N=1,2) on this classification. Our main tool is the explicit construction of the norms of the states that has to be checked for positivity. We give also the reduction of the exceptional UIRs.Comment: 27 pages, TeX with harvmac, amssym.def, amssym.tex; v.2: minor corrections and references added; v.3: minor corrections; v.4: to appear in J. Phys.

Supersymmetric Sum Rules for Electromagnetic Multipoles

We derive model independent, non-perturbative supersymmetric sum rules for the magnetic and electric multipole moments of any theory with N=1 supersymmetry. We find that in any irreducible N=1 supermultiplet the diagonal matrix elements of the l-multipole moments are completely fixed in terms of their off-diagonal matrix elements and the diagonal (l-1)-multipole moments.Comment: 10 pages, plain Te

D3-branes dynamics and black holes

Using the D3-brane as the fundamental tool, we adress two aspects of D-branes physics. The first regards the interaction between two electromagnetic dual D-branes in 10 dimensions. In particular, we give a meaning to {\it both} even and odd spin structure contributions, the latter being non vanishing for non zero relative velocity $v$ (and encoding the Lorentz-like contribution). The second aspect regards the D-brane/black holes correspondence. We show how the 4 dimensional configuration corresponding to a {\it single} D3-brane wrapped on the orbifold T^6/Z_3 represents a regular Reissner-Nordstrom solution of d=4 N=2 supergravityComment: 8 pages, latex, 1 eps figure. Talk presented by M. Bertolini at the conference "Quantum aspects of gauge theories, supergravity and unification" in Corfu`; to appear in the proceeding

Generalized Green-Schwarz mechanism in F theory

We derive the anomaly 8-form of 6-dimensional gauge theories arising in F theory compactifications on elliptic Calabi-Yau threefolds. The result allows to determine the matter content of certain such theories in terms of intersection numbers on the base of elliptic fibration. We also discuss gauge theories on 7-branes with double point singularities on the worldvolume. Applications to Type II compactifications on Hirzebruch surfaces and $P^2$ are outlined.Comment: 11 pages, harvmac. Normalization of (tr R^2)^2 term correcte

Thread-Modular Static Analysis for Relaxed Memory Models

We propose a memory-model-aware static program analysis method for accurately analyzing the behavior of concurrent software running on processors with weak consistency models such as x86-TSO, SPARC-PSO, and SPARC-RMO. At the center of our method is a unified framework for deciding the feasibility of inter-thread interferences to avoid propagating spurious data flows during static analysis and thus boost the performance of the static analyzer. We formulate the checking of interference feasibility as a set of Datalog rules which are both efficiently solvable and general enough to capture a range of hardware-level memory models. Compared to existing techniques, our method can significantly reduce the number of bogus alarms as well as unsound proofs. We implemented the method and evaluated it on a large set of multithreaded C programs. Our experiments showthe method significantly outperforms state-of-the-art techniques in terms of accuracy with only moderate run-time overhead.Comment: revised version of the ESEC/FSE 2017 pape

g = 2 as a Gauge Condition

Charged matter spin-1 fields enjoy a nonelectromagnetic gauge symmetry when interacting with vacuum electromagnetism, provided their gyromagnetic ratio is 2.Comment: 5 pages, REVTeX, submitted to Phys Rev D Brief Report

Focusing and imaging with increased numerical apertures through multimode fibers with micro-fabricated optics

The use of individual multimode optical fibers in endoscopy applications has the potential to provide highly miniaturized and noninvasive probes for microscopy and optical micromanipulation. A few different strategies have been proposed recently, but they all suffer from intrinsically low resolution related to the low numerical aperture of multimode fibers. Here, we show that two-photon polymerization allows for direct fabrication of micro-optics components on the fiber end, resulting in an increase of the numerical aperture to a value that is close to 1. Coupling light into the fiber through a spatial light modulator, we were able to optically scan a submicrometer spot (300 nm FWHM) over an extended region, facing the opposite fiber end. Fluorescence imaging with improved resolution is also demonstrated.Comment: 5 pages, 3 figure