771 research outputs found
An Oral Selective Alpha-1A Adrenergic Receptor Agonist Prevents Doxorubicin Cardiotoxicity
Alpha-1 adrenergic receptors (α1-ARs) play adaptive and protective roles in the heart. Dabuzalgron is an oral selective α1A-AR agonist that was well tolerated in multiple clinical trials of treatment for urinary incontinence, but has never been used to treat heart disease in humans or animal models. In this study, the authors administered dabuzalgron to mice treated with doxorubicin (DOX), a widely used chemotherapeutic agent with dose-limiting cardiotoxicity that can lead to heart failure (HF). Dabuzalgron protected against DOX-induced cardiotoxicity, likely by preserving mitochondrial function. These results suggest that activating cardiac α1A-ARs with dabuzalgron, a well-tolerated oral agent, might represent a novel approach to treating HF
Structural Ordering and Symmetry Breaking in Cd_2Re_2O_7
Single crystal X-ray diffraction measurements have been carried out on
Cd_2Re_2O_7 near and below the phase transition it exhibits at Tc' ~195 K.
Cd_2Re_2O_7 was recently discovered as the first, and to date only,
superconductor with the cubic pyrochlore structure. Superlattice Bragg peaks
show an apparently continuous structural transition at Tc', however the order
parameter displays anomalously slow growth to ~Tc'/10, and resolution limited
critical-like scattering is seen above Tc'. High resolution measurements show
the high temperature cubic Bragg peaks to split on entering the low temperature
phase, indicating a (likely tetragonal) lowering of symmetry below Tc'.Comment: 4 pages, 4 figure
Momentum-Transfer to and Elementary-Excitations of a Bose-Einstein Condensate by a Time-Dependent Optical Potential
We present results of calculations on Bose-Einstein condensed Rb atoms
subjected to a moving standing-wave light-potential of the form . We calculate the mean-field dynamics (the order
paramter) of the condensate and determine the resulting condensate momentum in
the direction, , where is the peak optical
potential strength and is the pulse duration. Although the local density
approximation for the Bogoliubov excitation spectral distribution is a good
approximation for very low optical intensities, long pulse duration and
sufficiently large values of the wavevector of the light-potential, for
small , short duration pulses, or for not-so-low intensities, the local
density perturbative description of the excitation spectrum breaks down badly,
as shown by our results.Comment: 8 pages, 7 figure
Temperature-induced resonances and Landau damping of collective modes in Bose-Einstein condensed gases in spherical traps
Interaction between collective monopole oscillations of a trapped
Bose-Einstein condensate and thermal excitations is investigated by means of
perturbation theory. We assume spherical symmetry to calculate the matrix
elements by solving the linearized Gross-Pitaevskii equations. We use them to
study the resonances of the condensate induced by temperature when an external
perturbation of the trapping frequency is applied and to calculate the Landau
damping of the oscillations.Comment: revtex, 9 pages, 5 figure
Detecting new microRNAs in human osteoarthritic chondrocytes identifies miR-3085 as a human, chondrocyte-selective, microRNA
Objective: To use deep sequencing to identify novel microRNAs in human osteoarthritic cartilage which have a functional role in chondrocyte phenotype or function. Design: A small RNA library was prepared from human osteoarthritic primary chondrocytes using in-house adaptors and analysed by Illumina sequencing. Novel candidate microRNAs were validated by northern blot and qRT-PCR. Expression was measured in cartilage models. Targets of novel candidates were identified by microarray and computational analysis, validated using 3’-UTR-luciferase reporter plasmids. Protein levels were assessed by western blot and functional analysis by cell adhesion. Results: We identified 990 known microRNAs and 1621 potential novel microRNAs in human osteoarthritic chondrocytes, 60 of the latter were expressed in all samples assayed. MicroRNA-140-3p was the most highly expressed microRNA in osteoarthritic cartilage. Sixteen novel candidate microRNAs were analysed further, of which 6 remained after northern blot analysis. Three novel microRNAs were regulated across models of chondrogenesis, chondrocyte differentiation or cartilage injury. One sequence (novel #11), annotated in rodents as microRNA-3085-3p, was preferentially expressed in cartilage, dependent on chondrocyte differentiation and, in man, is located in an intron of the cartilage-expressed gene CRTAC-1. This microRNA was shown to target the ITGA5 gene directly (which encodes integrin alpha5) and inhibited adhesion to fibronectin (dependent on alpha5beta1 integrin). Conclusion: Deep sequencing has uncovered many potential microRNA candidates expressed in human cartilage. At least three of these show potential functional interest in cartilage homeostasis and osteoarthritis. Particularly, novel #11 (microRNA-3085-3p) which has been identified for the first time in man
Design, Synthesis, and Characterization of Ogerin-Based Positive Allosteric Modulators for G Protein-Coupled Receptor 68 (GPR68)
G protein-coupled receptor 68 (GPR68) is an understudied orphan G protein-coupled receptor (GPCR). It is expressed most abundantly in the brain, potentially playing important roles in learning and memory. Pharmacological studies with GPR68 have been hindered by lack of chemical tools that can selectively modulate its activity. We previously reported the first small-molecule positive allosteric modulator (PAM), ogerin (1), and showed that 1 can potentiate proton activity at the GPR68-Gs pathway. Here, we report the first comprehensive structure-activity relationship (SAR) study on the scaffold of 1. Our lead compound resulted from this study, MS48107 (71), displayed 33-fold increased allosteric activity compared to 1. Compound 71 demonstrated high selectivity over closely related proton GPCRs and 48 common drug targets, and was bioavailable and brain-penetrant in mice. Thus, our SAR study has resulted in an improved GPR68 PAM for investigating the physiological and pathophysiological roles of GPR68 in vitro and in vivo
Enhancement of Sm3+emission by SnO2nanocrystals in the silica matrix
Silica xerogels containing Sm3+ions and SnO2nanocrystals were prepared in a sol–gel process. The image of transmission electron microscopy (TEM) shows that the SnO2nanocrystals are dispersed in the silica matrix. The X-ray diffraction (XRD) of the sample confirms the tetragonal phase of SnO2. The xerogels containing SnO2nanocrystals and Sm3+ions display the characteristic emission of Sm3+ions (4G5/2 → 6HJ(J = 5/2, 7/2, 9/2)) at the excitation of 335 nm which energy corresponds to the energy gap of the SnO2nanocrystals, while no emission of Sm3+ions can be observed for the samples containing Sm3+ions. The enhancement of the Sm3+emission is probably due to the energy transfer from SnO2nanocrystals to Sm3+ions
Measurements of J/psi Decays into 2(pi+pi-)eta and 3(pi+pi-)eta
Based on a sample of 5.8X 10^7 J/psi events taken with the BESII detector,
the branching fractions of J/psi--> 2(pi+pi-)eta and J/psi-->3(pi+pi-)eta are
measured for the first time to be (2.26+-0.08+-0.27)X10^{-3} and
(7.24+-0.96+-1.11)X10^{-4}, respectively.Comment: 11 pages, 6 figure
BESII Detector Simulation
A Monte Carlo program based on Geant3 has been developed for BESII detector
simulation. The organization of the program is outlined, and the digitization
procedure for simulating the response of various sub-detectors is described.
Comparisons with data show that the performance of the program is generally
satisfactory.Comment: 17 pages, 14 figures, uses elsart.cls, to be submitted to NIM
Measurement of branching fractions for the inclusive Cabibbo-favored ~K*0(892) and Cabibbo-suppressed K*0(892) decays of neutral and charged D mesons
The branching fractions for the inclusive Cabibbo-favored ~K*0 and
Cabibbo-suppressed K*0 decays of D mesons are measured based on a data sample
of 33 pb-1 collected at and around the center-of-mass energy of 3.773 GeV with
the BES-II detector at the BEPC collider. The branching fractions for the
decays D+(0) -> ~K*0(892)X and D0 -> K*0(892)X are determined to be BF(D0 ->
\~K*0X) = (8.7 +/- 4.0 +/- 1.2)%, BF(D+ -> ~K*0X) = (23.2 +/- 4.5 +/- 3.0)% and
BF(D0 -> K*0X) = (2.8 +/- 1.2 +/- 0.4)%. An upper limit on the branching
fraction at 90% C.L. for the decay D+ -> K*0(892)X is set to be BF(D+ -> K*0X)
< 6.6%
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