680 research outputs found
Development of a conformational histamine H(3) receptor biosensor for the synchronous screening of agonists and inverse agonists
The histamine H(3) receptor (H(3)R) represents a highly attractive drug target for the treatment of various central nervous system disorders, but the discovery of novel H(3)R targeting compounds relies on the assessment of highly amplified intracellular signaling events that do not only reflect H(3)R modulation and carry the risk of high false-positive and -negative screening rates. To address these limitations, we designed an intramolecular H(3)R biosensor based on the principle of bioluminescence resonance energy transfer (BRET) that reports the receptor's real-time conformational dynamics and provides an advanced tool to screen for both H(3)R agonists and inverse agonists in a live cell screening-compatible assay format. This conformational G-protein-coupled receptor (GPCR) sensor allowed us to characterize the pharmacological properties of known and new H(3) receptor ligands with unprecedented accuracy. Interestingly, we found that one newly developed H(3) receptor ligand possesses even stronger inverse agonistic activity than reference H(3)R inverse agonists including the current gold standard pitolisant. Taken together, we describe here the design and validation of the first screening-compatible H(3)R conformational biosensor that will aid in the discovery of novel H(3)R ligands and can be employed to gain deeper insights into the (in-)activation mechanism of this highly attractive drug target
Fire and plant evolution
3 páginas, 1 figura.Peer reviewe
Model study of adsorbed metallic quantum dots: Na on Cu(111)
We model electronic properties of the second monolayer Na adatom islands
(quantum dots) on the Cu(111) surface covered homogeneously by the first Na
monolayer. An axially-symmetric three-dimensional jellium model, taking into
account the effects due to the first Na monolayer and the Cu substrate, has
been developed. The electronic structure is solved within the local-density
approximation of the density-functional theory using a real-space multigrid
method. The model enables the study of systems consisting of thousands of
Na-atoms. The results for the local density of states are compared with
differential conductance () spectra and constant current topographs from
Scanning Tunneling Microscopy.Comment: 10 pages, 8 figures. For better quality figures, download
http://www.fyslab.hut.fi/~tto/cylart1.pd
Fluoride supplements (tablets, drops, lozenges or chewing gums) for preventing dental caries in children.
BACKGROUND: Dietary fluoride supplements were first introduced to provide systemic fluoride in areas where water fluoridation is not available. Since 1990, the use of fluoride supplements in caries prevention has been re-evaluated in several countries.
OBJECTIVES: To evaluate the efficacy of fluoride supplements for preventing dental caries in children.
SEARCH METHODS: We searched the Cochrane Oral Health Group's Trials Register (to 12 October 2011), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 3), MEDLINE via OVID (1950 to 12 October 2011), EMBASE via OVID (1980 to 12 October 2011), WHOLIS/PAHO/MEDCARIB/LILACS/BBO via BIREME (1982 to 12 October 2011), and Current Controlled Trials (to 12 October 2011). We handsearched reference lists of articles and contacted selected authors.
SELECTION CRITERIA: We included randomised or quasi-randomised controlled trials comparing, with minimum follow-up of 2 years, fluoride supplements (tablets, drops, lozenges) with no fluoride supplement or with other preventive measures such as topical fluorides in children less than 16 years of age at the start. The main outcome was caries increment measured by the change in decayed, missing and filled tooth surfaces (DMFS).
DATA COLLECTION AND ANALYSIS: Two review authors, independently and in duplicate, assessed the eligibility of studies for inclusion, and carried out risk of bias assessment and data extraction. In the event of disagreement, we sought consensus and consulted a third review author. We contacted trial authors for missing information. We used the prevented fraction (PF) as a metric for evaluating the efficacy of the intervention. The PF is defined as the mean caries increment in controls minus mean caries increment in the treated group divided by mean caries increment in controls. We conducted random-effects meta-analyses when data could be pooled. We assessed heterogeneity in the results of the studies by examining forest plots and by using formal tests for homogeneity. We recorded adverse effects (fluorosis) when the studies provided relevant data.
MAIN RESULTS: We included 11 studies in the review involving 7196 children.In permanent teeth, when fluoride supplements were compared with no fluoride supplement (three studies), the use of fluoride supplements was associated with a 24% (95% confidence interval (CI) 16 to 33%) reduction in decayed, missing and filled surfaces (D(M)FS). The effect of fluoride supplements was unclear on deciduous or primary teeth. In one study, no caries-inhibiting effect was observed on deciduous teeth while in another study, the use of fluoride supplements was associated with a substantial reduction in caries increment.When fluoride supplements were compared with topical fluorides or with other preventive measures, there was no differential effect on permanent or deciduous teeth.The review found limited information on the adverse effects associated with the use of fluoride supplements.
AUTHORS' CONCLUSIONS: This review suggests that the use of fluoride supplements is associated with a reduction in caries increment when compared with no fluoride supplement in permanent teeth. The effect of fluoride supplements was unclear on deciduous teeth. When compared with the administration of topical fluorides, no differential effect was observed. We rated 10 trials as being at unclear risk of bias and one at high risk of bias, and therefore the trials provide weak evidence about the efficacy of fluoride supplements
Schwinger boson theory of anisotropic ferromagnetic ultrathin films
Ferromagnetic thin films with magnetic single-ion anisotropies are studied
within the framework of Schwinger bosonization of a quantum Heisenberg model.
Two alternative bosonizations are discussed. We show that qualitatively correct
results are obtained even at the mean-field level of the theory, similar to
Schwinger boson results for other magnetic systems. In particular, the
Mermin-Wagner theorem is satisfied: a spontaneous magnetization at finite
temperatures is not found if the ground state of the anisotropic system
exhibits a continuous degeneracy. We calculate the magnetization and effective
anisotropies as functions of exchange interaction, magnetic anisotropies,
external magnetic field, and temperature for arbitrary values of the spin
quantum number. Magnetic reorientation transitions and effective anisotropies
are discussed. The results obtained by Schwinger boson mean-field theory are
compared with the many-body Green's function technique.Comment: 14 pages, including 7 EPS figures, minor changes, final version as
publishe
An improved method for measuring muon energy using the truncated mean of dE/dx
The measurement of muon energy is critical for many analyses in large
Cherenkov detectors, particularly those that involve separating
extraterrestrial neutrinos from the atmospheric neutrino background. Muon
energy has traditionally been determined by measuring the specific energy loss
(dE/dx) along the muon's path and relating the dE/dx to the muon energy.
Because high-energy muons (E_mu > 1 TeV) lose energy randomly, the spread in
dE/dx values is quite large, leading to a typical energy resolution of 0.29 in
log10(E_mu) for a muon observed over a 1 km path length in the IceCube
detector. In this paper, we present an improved method that uses a truncated
mean and other techniques to determine the muon energy. The muon track is
divided into separate segments with individual dE/dx values. The elimination of
segments with the highest dE/dx results in an overall dE/dx that is more
closely correlated to the muon energy. This method results in an energy
resolution of 0.22 in log10(E_mu), which gives a 26% improvement. This
technique is applicable to any large water or ice detector and potentially to
large scintillator or liquid argon detectors.Comment: 12 pages, 16 figure
All-particle cosmic ray energy spectrum measured with 26 IceTop stations
We report on a measurement of the cosmic ray energy spectrum with the IceTop
air shower array, the surface component of the IceCube Neutrino Observatory at
the South Pole. The data used in this analysis were taken between June and
October, 2007, with 26 surface stations operational at that time, corresponding
to about one third of the final array. The fiducial area used in this analysis
was 0.122 km^2. The analysis investigated the energy spectrum from 1 to 100 PeV
measured for three different zenith angle ranges between 0{\deg} and 46{\deg}.
Because of the isotropy of cosmic rays in this energy range the spectra from
all zenith angle intervals have to agree. The cosmic-ray energy spectrum was
determined under different assumptions on the primary mass composition. Good
agreement of spectra in the three zenith angle ranges was found for the
assumption of pure proton and a simple two-component model. For zenith angles
{\theta} < 30{\deg}, where the mass dependence is smallest, the knee in the
cosmic ray energy spectrum was observed between 3.5 and 4.32 PeV, depending on
composition assumption. Spectral indices above the knee range from -3.08 to
-3.11 depending on primary mass composition assumption. Moreover, an indication
of a flattening of the spectrum above 22 PeV were observed.Comment: 38 pages, 17 figure
The exposure of the hybrid detector of the Pierre Auger Observatory
The Pierre Auger Observatory is a detector for ultra-high energy cosmic rays.
It consists of a surface array to measure secondary particles at ground level
and a fluorescence detector to measure the development of air showers in the
atmosphere above the array. The "hybrid" detection mode combines the
information from the two subsystems. We describe the determination of the
hybrid exposure for events observed by the fluorescence telescopes in
coincidence with at least one water-Cherenkov detector of the surface array. A
detailed knowledge of the time dependence of the detection operations is
crucial for an accurate evaluation of the exposure. We discuss the relevance of
monitoring data collected during operations, such as the status of the
fluorescence detector, background light and atmospheric conditions, that are
used in both simulation and reconstruction.Comment: Paper accepted by Astroparticle Physic
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