4,426 research outputs found
Modification of pharmacokinetic and abuse-related effects of cocaine by human-derived cocaine hydrolase in monkeys
Although substantial research effort has focused on developing pharmacological treatments for
cocaine abuse, no effective medications have been developed. Recent studies show that enzymes
that metabolize cocaine in the periphery, forestalling its entry into the brain, can prevent cocaine
toxicity and its behavioral effects in rodents. Here we report on effects of one such enzyme (Albu-
CocH) on the pharmacokinetic and behavioral effects of cocaine in squirrel monkeys. Albu-CocH
was developed from successive mutations of human butyrylcholinesterase (BChE) and has 1000-
fold greater catalytic activity against cocaine than naturally occurring BChE. Pharmacokinetic
studies showed that Albu-CocH (5 mg/kg) had a half-life of 56.6 hours in squirrel monkeys. In
these studies, plasma levels of cocaine following i.v. 1 mg/kg cocaine were reduced two hours
after administration of Albu-CocH, whereas plasma levels of the cocaine metabolite ecgonine
methyl ester were increased. These effects were still evident 72 hrs following Albu-CocH
administration. In behavioral experiments in monkeys, pretreatment with 5 mg/kg Albu-CocH
dramatically decreased self-administration of a reinforcing dose of i.v. cocaine (30 μg/kg/
injection) for over 24 hours. Pretreatment with 5 mg/kg Albu-CocH also attenuated the
reinstatement of extinguished cocaine self-administration by an i.v. priming injection of cocaine
(0.1 or 0.3 mg/kg) and, in separate studies, attenuated the discriminative stimulus effects of
cocaine. The ability of Albu-CocH to attenuate the abuse-related effects of cocaine in squirrel monkeys indicates that further investigation of BChE mutants as potential treatment for cocaine
abuse and toxicity is warranted.This research was supported in part by the Intramural Research Program of the NIH, National Institute on Drug
Abuse
Hard x-ray optics for the HEFT balloon-borne payload: prototype design and status
We report on the current status and performance of prototype hard x-ray optics we are producing for use on the high energy focusing telescope (HEFT) experiment. The baseline substrates are thermally formed glass mirrors that are overcoated with multilayers to provide good performance throughout the 20-80 keV bandpass. Progress made in the thermal forming process as well as in the multilayer performance has allowed production of optics that meet or exceed all HEFT requirements. We present metrology on the substrates and result from x-ray characterization. A novel mounting scheme for the individual telescope shells is currently being tested. If successful the mounting technique will produce a monolithic, extremely stiff and robust optic
Semen-Derived Amyloid Fibrils Drastically Enhance HIV Infection
SummarySexual intercourse is the major route of HIV transmission. To identify endogenous factors that affect the efficiency of sexual viral transmission, we screened a complex peptide/protein library derived from human semen. We show that naturally occurring fragments of the abundant semen marker prostatic acidic phosphatase (PAP) form amyloid fibrils. These fibrils, termed Semen-derived Enhancer of Virus Infection (SEVI), capture HIV virions and promote their attachment to target cells, thereby enhancing the infectious virus titer by several orders of magnitude. Physiological concentrations of SEVI amplified HIV infection of T cells, macrophages, ex vivo human tonsillar tissues, and transgenic rats in vivo, as well as trans-HIV infection of T cells by dendritic or epithelial cells. Amyloidogenic PAP fragments are abundant in seminal fluid and boost semen-mediated enhancement of HIV infection. Thus, they may play an important role in sexual transmission of HIV and could represent new targets for its prevention
LSST Science Book, Version 2.0
A survey that can cover the sky in optical bands over wide fields to faint
magnitudes with a fast cadence will enable many of the exciting science
opportunities of the next decade. The Large Synoptic Survey Telescope (LSST)
will have an effective aperture of 6.7 meters and an imaging camera with field
of view of 9.6 deg^2, and will be devoted to a ten-year imaging survey over
20,000 deg^2 south of +15 deg. Each pointing will be imaged 2000 times with
fifteen second exposures in six broad bands from 0.35 to 1.1 microns, to a
total point-source depth of r~27.5. The LSST Science Book describes the basic
parameters of the LSST hardware, software, and observing plans. The book
discusses educational and outreach opportunities, then goes on to describe a
broad range of science that LSST will revolutionize: mapping the inner and
outer Solar System, stellar populations in the Milky Way and nearby galaxies,
the structure of the Milky Way disk and halo and other objects in the Local
Volume, transient and variable objects both at low and high redshift, and the
properties of normal and active galaxies at low and high redshift. It then
turns to far-field cosmological topics, exploring properties of supernovae to
z~1, strong and weak lensing, the large-scale distribution of galaxies and
baryon oscillations, and how these different probes may be combined to
constrain cosmological models and the physics of dark energy.Comment: 596 pages. Also available at full resolution at
http://www.lsst.org/lsst/sciboo
Measurement of the Branching Fraction for B- --> D0 K*-
We present a measurement of the branching fraction for the decay B- --> D0
K*- using a sample of approximately 86 million BBbar pairs collected by the
BaBar detector from e+e- collisions near the Y(4S) resonance. The D0 is
detected through its decays to K- pi+, K- pi+ pi0 and K- pi+ pi- pi+, and the
K*- through its decay to K0S pi-. We measure the branching fraction to be
B.F.(B- --> D0 K*-)= (6.3 +/- 0.7(stat.) +/- 0.5(syst.)) x 10^{-4}.Comment: 7 pages, 1 postscript figure, submitted to Phys. Rev. D (Rapid
Communications
Measurement of the quasi-elastic axial vector mass in neutrino-oxygen interactions
The weak nucleon axial-vector form factor for quasi-elastic interactions is
determined using neutrino interaction data from the K2K Scintillating Fiber
detector in the neutrino beam at KEK. More than 12,000 events are analyzed, of
which half are charged-current quasi-elastic interactions nu-mu n to mu- p
occurring primarily in oxygen nuclei. We use a relativistic Fermi gas model for
oxygen and assume the form factor is approximately a dipole with one parameter,
the axial vector mass M_A, and fit to the shape of the distribution of the
square of the momentum transfer from the nucleon to the nucleus. Our best fit
result for M_A = 1.20 \pm 0.12 GeV. Furthermore, this analysis includes updated
vector form factors from recent electron scattering experiments and a
discussion of the effects of the nucleon momentum on the shape of the fitted
distributions.Comment: 14 pages, 10 figures, 6 table
Measurement of Branching Fraction and Dalitz Distribution for B0->D(*)+/- K0 pi-/+ Decays
We present measurements of the branching fractions for the three-body decays
B0 -> D(*)-/+ K0 pi^+/-B0 -> D(*)-/+ K*+/- using
a sample of approximately 88 million BBbar pairs collected by the BABAR
detector at the PEP-II asymmetric energy storage ring.
We measure:
B(B0->D-/+ K0 pi+/-)=(4.9 +/- 0.7(stat) +/- 0.5 (syst)) 10^{-4}
B(B0->D*-/+ K0 pi+/-)=(3.0 +/- 0.7(stat) +/- 0.3 (syst)) 10^{-4}
B(B0->D-/+ K*+/-)=(4.6 +/- 0.6(stat) +/- 0.5 (syst)) 10^{-4}
B(B0->D*-/+ K*+/-)=(3.2 +/- 0.6(stat) +/- 0.3 (syst)) 10^{-4}
From these measurements we determine the fractions of resonant events to be :
f(B0-> D-/+ K*+/-) = 0.63 +/- 0.08(stat) +/- 0.04(syst) f(B0-> D*-/+ K*+/-) =
0.72 +/- 0.14(stat) +/- 0.05(syst)Comment: 7 pages, 3 figures submitted to Phys. Rev. Let
A Study of Time-Dependent CP-Violating Asymmetries and Flavor Oscillations in Neutral B Decays at the Upsilon(4S)
We present a measurement of time-dependent CP-violating asymmetries in
neutral B meson decays collected with the BABAR detector at the PEP-II
asymmetric-energy B Factory at the Stanford Linear Accelerator Center. The data
sample consists of 29.7 recorded at the
resonance and 3.9 off-resonance. One of the neutral B mesons,
which are produced in pairs at the , is fully reconstructed in
the CP decay modes , , , () and , or in flavor-eigenstate
modes involving and (). The flavor of the other neutral B meson is tagged at the time of
its decay, mainly with the charge of identified leptons and kaons. The proper
time elapsed between the decays is determined by measuring the distance between
the decay vertices. A maximum-likelihood fit to this flavor eigenstate sample
finds . The value of the asymmetry amplitude is determined from
a simultaneous maximum-likelihood fit to the time-difference distribution of
the flavor-eigenstate sample and about 642 tagged decays in the
CP-eigenstate modes. We find , demonstrating that CP violation exists in the neutral B meson
system. (abridged)Comment: 58 pages, 35 figures, submitted to Physical Review
Search for the W-exchange decays B0 --> Ds(*)- Ds(*)+
We report a search for the decays , , in a sample of 232
million decays to \BBb ~pairs collected with the \babar detector
at the PEP-II asymmetric-energy storage ring. We find no significant
signal and set upper bounds for the branching fractions: and at 90% confidence level.Comment: 8 pages, 2 figures, submitted to PRD-R
- …