816 research outputs found
Calibration of a single atom detector for atomic micro chips
We experimentally investigate a scheme for detecting single atoms
magnetically trapped on an atom chip. The detector is based on the
photoionization of atoms and the subsequent detection of the generated ions. We
describe the characterization of the ion detector with emphasis on its
calibration via the correlation of ions with simultaneously generated
electrons. A detection efficiency of 47.8% (+-2.6%) is measured, which is
useful for single atom detection, and close to the limit allowing atom counting
with sub-Poissonian uncertainty
Laser frequency locking by direct measurement of detuning
We present a new method of laser frequency locking in which the feedback
signal is directly proportional to the detuning from an atomic transition, even
at detunings many times the natural linewidth of the transition. Our method is
a form of sub-Doppler polarization spectroscopy, based on measuring two Stokes
parameters ( and ) of light transmitted through a vapor cell. This
extends the linear capture range of the lock loop by up to an order of
magnitude and provides equivalent or improved frequency discrimination as other
commonly used locking techniques.Comment: 4 pages, 4 figures Revte
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cGMP via PKG activates 26S proteasomes and enhances degradation of proteins, including ones that cause neurodegenerative diseases.
Because raising cAMP enhances 26S proteasome activity and the degradation of cell proteins, including the selective breakdown of misfolded proteins, we investigated whether agents that raise cGMP may also regulate protein degradation. Treating various cell lines with inhibitors of phosphodiesterase 5 or stimulators of soluble guanylyl cyclase rapidly enhanced multiple proteasome activities and cellular levels of ubiquitinated proteins by activating protein kinase G (PKG). PKG stimulated purified 26S proteasomes by phosphorylating a different 26S component than is modified by protein kinase A. In cells and cell extracts, raising cGMP also enhanced within minutes ubiquitin conjugation to cell proteins. Raising cGMP, like raising cAMP, stimulated the degradation of short-lived cell proteins, but unlike cAMP, also markedly increased proteasomal degradation of long-lived proteins (the bulk of cell proteins) without affecting lysosomal proteolysis. We also tested if raising cGMP, like cAMP, can promote the degradation of mutant proteins that cause neurodegenerative diseases. Treating zebrafish models of tauopathies or Huntington's disease with a PDE5 inhibitor reduced the levels of the mutant huntingtin and tau proteins, cell death, and the resulting morphological abnormalities. Thus, PKG rapidly activates cytosolic proteasomes, protein ubiquitination, and overall protein degradation, and agents that raise cGMP may help combat the progression of neurodegenerative diseases
Rilmenidine attenuates toxicity of polyglutamine expansions in a mouse model of Huntington's disease
Huntington's disease (HD) is an autosomal dominant neurodegenerative disease caused by a polyglutamine expansion in huntingtin. There are no treatments that are known to slow the neurodegeneration caused by this mutation. Mutant huntingtin causes disease via a toxic gain-of-function mechanism and has the propensity to aggregate and form intraneuronal inclusions. One therapeutic approach for HD is to enhance the degradation of the mutant protein. We have shown that this can be achieved by upregulating autophagy, using the drug rapamycin. In order to find safer ways of inducing autophagy for clinical purposes, we previously screened United States Food and Drug Administration-approved drugs for their autophagy-stimulating potential. This screen suggested that rilmenidine, a well tolerated, safe, centrally acting anti-hypertensive drug, could induce autophagy in cell culture via a pathway that was independent of the mammalian target of rapamycin. Here we have shown that rilmenidine induces autophagy in mice and in primary neuronal culture. Rilmenidine administration attenuated the signs of disease in a HD mouse model and reduced levels of the mutant huntingtin fragment. As rilmenidine has a long safety record and is designed for chronic use, our data suggests that it should be considered for the treatment of HD and related conditions
Growth dynamics of a Bose-Einstein condensate in a dimple trap without cooling
We study the formation of a Bose-Einstein condensate in a cigar-shaped
three-dimensional harmonic trap, induced by the controlled addition of an
attractive "dimple" potential along the weak axis. In this manner we are able
to induce condensation without cooling due to a localized increase in the phase
space density. We perform a quantitative analysis of the thermodynamic
transformation in both the sudden and adiabatic regimes for a range of dimple
widths and depths. We find good agreement with equilibrium calculations based
on self-consistent semiclassical Hartree-Fock theory describing the condensate
and thermal cloud. We observe there is an optimal dimple depth that results in
a maximum in the condensate fraction. We also study the non-equilibrium
dynamics of condensate formation in the sudden turn-on regime, finding good
agreement for the observed time dependence of the condensate fraction with
calculations based on quantum kinetic theory.Comment: v1: 9 pages, 7 figures, submitted to Phys. Rev. A; v2: 10 pages, 8
figures, fixed typos, added references, additional details on experimental
procedure, values of phase-space density, new figure and discussion on
effects of three-body loss in Appendix B (replaced with published version
Observation of shock waves in a large Bose-Einstein condensate
We observe the formation of shock waves in a Bose-Einstein condensate
containing a large number of sodium atoms. The shock wave is initiated with a
repulsive, blue-detuned light barrier, intersecting the BEC, after which two
shock fronts appear. We observe breaking of these waves when the size of these
waves approaches the healing length of the condensate. At this time, the wave
front splits into two parts and clear fringes appear. The experiment is modeled
using an effective 1D Gross-Pitaevskii-like equation and gives excellent
quantitative agreement with the experiment, even though matter waves with
wavelengths two orders of magnitude smaller than the healing length are
present. In these experiments, no significant heating or particle loss is
observed.Comment: 7 pages, 7 figure
Analysis of dynamical tunnelling experiments with a Bose-Einstein condensate
Dynamical tunnelling is a quantum phenomenon where a classically forbidden
process occurs, that is prohibited not by energy but by another constant of
motion. The phenomenon of dynamical tunnelling has been recently observed in a
sodium Bose-Einstein condensate. We present a detailed analysis of these
experiments using numerical solutions of the three dimensional Gross-Pitaevskii
equation and the corresponding Floquet theory. We explore the parameter
dependency of the tunnelling oscillations and we move the quantum system
towards the classical limit in the experimentally accessible regime.Comment: accepted for publication in Physical Review
Improved theory of laser-enhanced ionization in flames: comparison with experiment
An improved theory for laser enhanced ionization in flames has been developed for one‐ and two‐step laser excitations. The model gives an analytical expression for the sensitivity of the method for a given transition of any element. The theoretical expression is compared with experimentally measured signals for a number of elements and the agreement is found to be generally good
Latent cluster analysis of ALS phenotypes identifies prognostically differing groups
BACKGROUND
Amyotrophic lateral sclerosis (ALS) is a degenerative disease predominantly affecting motor neurons and manifesting as several different phenotypes. Whether these phenotypes correspond to different underlying disease processes is unknown. We used latent cluster analysis to identify groupings of clinical variables in an objective and unbiased way to improve phenotyping for clinical and research purposes.
METHODS
Latent class cluster analysis was applied to a large database consisting of 1467 records of people with ALS, using discrete variables which can be readily determined at the first clinic appointment. The model was tested for clinical relevance by survival analysis of the phenotypic groupings using the Kaplan-Meier method.
RESULTS
The best model generated five distinct phenotypic classes that strongly predicted survival (p<0.0001). Eight variables were used for the latent class analysis, but a good estimate of the classification could be obtained using just two variables: site of first symptoms (bulbar or limb) and time from symptom onset to diagnosis (p<0.00001).
CONCLUSION
The five phenotypic classes identified using latent cluster analysis can predict prognosis. They could be used to stratify patients recruited into clinical trials and generating more homogeneous disease groups for genetic, proteomic and risk factor research
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