213 research outputs found
Dual dopamine D2 receptor and β2-adrenoceptor agonists for the treatment of chronic obstructive pulmonary disease: the pre-clinical rationale
AbstractThis paper describes the rationale for the development of dual dopamine D2-receptor and β2-adrenoceptor agonists as potential treatments for the symptoms of chronic obstructive pulmonary disease (COPD). The putative involvement of pulmonary sensory afferent nerves in mediating the key COPD symptoms of breathlessness, cough and excess sputum production is outlined and the hypothesis that activation of D2-receptors on such nerves would modulate their activity is developed. This premise was tested, in a range of animal models, using the first of a novel class of dual dopamine D2-receptor and β2-adrenoceptor agonists, sibenadet HCI (Viozan™, AR-C68397AA). In the course of these studies it was demonstrated that sibenadet, through activation of D2-receptors, inhibited discharge of rapidly adapting receptors and was effective in reducing reflex-induced tachypnoea, mucus production and cough in the dog. Sibenadet, through its activation of β2-adrenoceptors, was also shown to be an effective bronchodilator with a prolonged duration of action following topical administration to the lungs. These studies also indicated that sibenadet had a wide therapeutic ratio with respect to expected undesirable side-effects such as emesis and cardiovascular disturbances. These results provided a compelling rationale for the initiation of a clinical development programme with sibenadet for the treatment of COPD
Electron self-trapping in intermediate-valent SmB6
SmB6 exhibits intermediate valence in the ground state and unusual behaviour
at low temperatures. The resistivity and the Hall effect cannot be explained
either by conventional sf-hybridization or by hopping transport in an impurity
band. At least three different energy scales determine three temperature
regimes of electron transport in this system. We consider the ground state
properties, the soft valence fluctuations and the spectrum of band carriers in
n-doped SmB6. The behaviour of excess conduction electrons in the presence of
soft valence fluctuations and the origin of the three energy scales in the
spectrum of elementary excitations is discussed. The carriers which determine
the low-temperature transport in this system are self-trapped electron-polaron
complexes rather than simply electrons in an impurity band. The mechanism of
electron trapping is the interaction with soft valence fluctuations.Comment: 12 pages, 3 figure
Physics Opportunities with the 12 GeV Upgrade at Jefferson Lab
This white paper summarizes the scientific opportunities for utilization of
the upgraded 12 GeV Continuous Electron Beam Accelerator Facility (CEBAF) and
associated experimental equipment at Jefferson Lab. It is based on the 52
proposals recommended for approval by the Jefferson Lab Program Advisory
Committee.The upgraded facility will enable a new experimental program with
substantial discovery potential to address important topics in nuclear,
hadronic, and electroweak physics.Comment: 64 page
Quasinormal modes from potentials surrounding the charged dilaton black hole
We clarify the purely imaginary quasinormal frequencies of a massless scalar
perturbation on the 3D charged-dilaton black holes. This case is quite
interesting because the potential-step appears outside the event horizon
similar to the case of the electromagnetic perturbations on the large
Schwarzschild-AdS black holes. It turns out that the potential-step type
provides the purely imaginary quasinormal frequencies, while the
potential-barrier type gives the complex quasinormal modes.Comment: 19 pages, 8 figure
Some general properties of the renormalized stress-energy tensor for static quantum states on (n+1)-dimensional spherically symmetric black holes
We study the renormalized stress-energy tensor (RSET) for static quantum
states on (n+1)-dimensional, static, spherically symmetric black holes. By
solving the conservation equations, we are able to write the stress-energy
tensor in terms of a single unknown function of the radial co-ordinate, plus
two arbitrary constants. Conditions for the stress-energy tensor to be regular
at event horizons (including the extremal and ``ultra-extremal'' cases) are
then derived using generalized Kruskal-like co-ordinates. These results should
be useful for future calculations of the RSET for static quantum states on
spherically symmetric black hole geometries in any number of space-time
dimensions.Comment: 9 pages, no figures, RevTeX4, references added, accepted for
publication in General Relativity and Gravitatio
Extreme Ultra-Violet Spectroscopy of the Lower Solar Atmosphere During Solar Flares
The extreme ultraviolet portion of the solar spectrum contains a wealth of
diagnostic tools for probing the lower solar atmosphere in response to an
injection of energy, particularly during the impulsive phase of solar flares.
These include temperature and density sensitive line ratios, Doppler shifted
emission lines and nonthermal broadening, abundance measurements, differential
emission measure profiles, and continuum temperatures and energetics, among
others. In this paper I shall review some of the advances made in recent years
using these techniques, focusing primarily on studies that have utilized data
from Hinode/EIS and SDO/EVE, while also providing some historical background
and a summary of future spectroscopic instrumentation.Comment: 34 pages, 8 figures. Submitted to Solar Physics as part of the
Topical Issue on Solar and Stellar Flare
Observing Supermassive Black Holes across cosmic time: from phenomenology to physics
In the last decade, a combination of high sensitivity, high spatial
resolution observations and of coordinated multi-wavelength surveys has
revolutionized our view of extra-galactic black hole (BH) astrophysics. We now
know that supermassive black holes reside in the nuclei of almost every galaxy,
grow over cosmological times by accreting matter, interact and merge with each
other, and in the process liberate enormous amounts of energy that influence
dramatically the evolution of the surrounding gas and stars, providing a
powerful self-regulatory mechanism for galaxy formation. The different
energetic phenomena associated to growing black holes and Active Galactic
Nuclei (AGN), their cosmological evolution and the observational techniques
used to unveil them, are the subject of this chapter. In particular, I will
focus my attention on the connection between the theory of high-energy
astrophysical processes giving rise to the observed emission in AGN, the
observable imprints they leave at different wavelengths, and the methods used
to uncover them in a statistically robust way. I will show how such a combined
effort of theorists and observers have led us to unveil most of the SMBH growth
over a large fraction of the age of the Universe, but that nagging
uncertainties remain, preventing us from fully understating the exact role of
black holes in the complex process of galaxy and large-scale structure
formation, assembly and evolution.Comment: 46 pages, 21 figures. This review article appears as a chapter in the
book: "Astrophysical Black Holes", Haardt, F., Gorini, V., Moschella, U and
Treves A. (Eds), 2015, Springer International Publishing AG, Cha
Pion Freeze-Out Time in Pb+Pb Collisions at 158 A GeV/c Studied via pi-/pi+ and K-/K+ Ratios
The effect of the final state Coulomb interaction on particles produced in
Pb+Pb collisions at 158 A GeV/c has been investigated in the WA98 experiment
through the study of the pi-/pi+ and K-/K+ ratios measured as a function of
transverse mass. While the ratio for kaons shows no significant transverse mass
dependence, the pi-/pi+ ratio is enhanced at small transverse mass values with
an enhancement that increases with centrality. A silicon pad detector located
near the target is used to estimate the contribution of hyperon decays to the
pi-/pi+ ratio. The comparison of results with predictions of the RQMD model in
which the Coulomb interaction has been incorporated allows to place constraints
on the time of the pion freeze-out.Comment: 9 pages, 12 figure
Proximity effect at superconducting Sn-Bi2Se3 interface
We have investigated the conductance spectra of Sn-Bi2Se3 interface junctions
down to 250 mK and in different magnetic fields. A number of conductance
anomalies were observed below the superconducting transition temperature of Sn,
including a small gap different from that of Sn, and a zero-bias conductance
peak growing up at lower temperatures. We discussed the possible origins of the
smaller gap and the zero-bias conductance peak. These phenomena support that a
proximity-effect-induced chiral superconducting phase is formed at the
interface between the superconducting Sn and the strong spin-orbit coupling
material Bi2Se3.Comment: 7 pages, 8 figure
Centrality Dependence of the High p_T Charged Hadron Suppression in Au+Au collisions at sqrt(s_NN) = 130 GeV
PHENIX has measured the centrality dependence of charged hadron p_T spectra
from central Au+Au collisions at sqrt(s_NN)=130 GeV. The truncated mean p_T
decreases with centrality for p_T > 2 GeV/c, indicating an apparent reduction
of the contribution from hard scattering to high p_T hadron production. For
central collisions the yield at high p_T is shown to be suppressed compared to
binary nucleon-nucleon collision scaling of p+p data. This suppression is
monotonically increasing with centrality, but most of the change occurs below
30% centrality, i.e. for collisions with less than about 140 participating
nucleons. The observed p_T and centrality dependence is consistent with the
particle production predicted by models including hard scattering and
subsequent energy loss of the scattered partons in the dense matter created in
the collisions.Comment: 7 pages text, LaTeX, 6 figures, 2 tables, 307 authors, resubmitted to
Phys. Lett. B. Revised to address referee concerns. Plain text data tables
for the points plotted in figures for this and previous PHENIX publications
are publicly available at
http://www.phenix.bnl.gov/phenix/WWW/run/phenix/papers.htm
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