882 research outputs found
Liquid-filled hard gelatin capsules : excipient/capsule compatibility studies
Encapsulation of pharmaceutical formulations as liquids or semisolids, within hard gelatin capsules, presents an important oral dosage strategy for poorly water-soluble drugs, resulting in good bioavailability and reproducible drug absorption. In addition, this technology offers an inherently safer process than powder filled capsules and tablets for highly potent or cytotoxic drugs by avoiding dust generation. Here we present a compatibility study of hard gelatin capsules with common excipients in absence of active pharmaceutical
Expression in Yeast Links Field Polymorphisms in PfATP6 to in Vitro Artemisinin Resistance and Identifies New Inhibitor Classes
Background.âThe mechanism of action of artemisinins against malaria is unclear, despite their widespread use in combination therapies and the emergence of resistance. Results.âHere, we report expression of PfATP6 (a SERCA pump) in yeast and demonstrate its inhibition by artemisinins. Mutations in PfATP6 identified in field isolates (such as S769N) and in laboratory clones (such as L263E) decrease susceptibility to artemisinins, whereas they increase susceptibility to unrelated inhibitors such as cyclopiazonic acid. As predicted from the yeast model, Plasmodium falciparum with the L263E mutation is also more susceptible to cyclopiazonic acid. An inability to knockout parasite SERCA pumps provides genetic evidence that they are essential in asexual stages of development. Thaperoxides are a new class of potent antimalarial designed to act by inhibiting PfATP6. Results in yeast confirm this inhibition. Conclusions.âThe identification of inhibitors effective against mutated PfATP6 suggests ways in which artemisinin resistance may be overcom
Removing exogenous information using pedigree data
Management of certain populations requires the preservation of its pure genetic background. When, for different reasons, undesired alleles are introduced, the original genetic conformation must be recovered. The present study tested, through computer simulations, the power of recovery (the ability for removing the foreign information) from genealogical data. Simulated scenarios comprised different numbers of exogenous individuals taking partofthe founder population anddifferent numbers of unmanaged generations before the removal program started. Strategies were based on variables arising from classical pedigree analyses such as founders? contribution and partial coancestry. The ef?ciency of the different strategies was measured as the proportion of native genetic information remaining in the population. Consequences on the inbreeding and coancestry levels of the population were also evaluated. Minimisation of the exogenous founders? contributions was the most powerful method, removing the largest amount of genetic information in just one generation.However, as a side effect, it led to the highest values of inbreeding. Scenarios with a large amount of initial exogenous alleles (i.e. high percentage of non native founders), or many generations of mixing became very dif?cult to recover, pointing out the importance of being careful about introgression events in populatio
Elastic scattering and breakup of 17^F at 10 MeV/nucleon
Angular distributions of fluorine and oxygen produced from 170 MeV 17^F
incident on 208^Pb were measured. The elastic scattering data are in good
agreement with optical model calculations using a double-folding potential and
parameters similar to those obtained from 16^O+208^Pb. A large yield of oxygen
was observed near \theta_lab=36 deg. It is reproduced fairly well by a
calculation of the (17^F,16^O) breakup, which is dominated by one-proton
stripping reactions. The discrepancy between our previous coincidence
measurement and theoretical predictions was resolved by including core
absorption in the present calculation.Comment: 9 pages, 5 figure
Delays Associated with Elementary Processes in Nuclear Reaction Simulations
Scatterings, particularly those involving resonances, and other elementary
processes do not happen instantaneously. In the context of semiclassical
nuclear reaction simulations, we consider delays associated with an interaction
for incident quantum wave-packets. As a consequence, we express delays
associated with elementary processes in terms of elements of the scattering
matrix and phase shifts for elastic scattering. We show that, to within the
second order in density, the simulation must account for delays in scattering
consistently with the mean field in order to properly model thermodynamic
properties such as pressure and free-energy density. The delays associated with
nucleon-nucleon and pion-nucleon scattering in free space are analysed with
their nontrivial energy dependence. Finally, an example of s-channel scattering
of massless partons is studied, and scattering schemes in nuclear reaction
simulations are investigated in the context of scattering delays.Comment: 45 pages, 5 uuencoded Postscript figure
Collective Flow from the Intranuclear Cascade Model
The phenomenon of collective flow in relativistic heavy ion collisions is
studied using the hadronic cascade model ARC. Direct comparison is made to data
gathered at the Bevalac, for Au+Au at GeV/c. In contrast to the
standard lore about the cascade model, collective flow is well described
quantitatively without the need for explicit mean field terms to simulate the
nuclear equation of state. Pion collective flow is in the opposite direction to
nucleon flow as is that of anti-nucleons and other produced particles. Pion and
nucleon flow are predicted at AGS energies also, where, in light of the higher
baryon densities achieved, we speculate that equation of state effects may be
observable.Comment: 9 pages, 2 figures include
Measurements of (p,p) and (p,p'Îł) Observables for 1+ States in 12-C at 200 MeV
This research was sponsored by the National Science Foundation Grant NSF PHY-931478
Quantum Tunneling in Nuclear Fusion
Recent theoretical advances in the study of heavy ion fusion reactions below
the Coulomb barrier are reviewed. Particular emphasis is given to new ways of
analyzing data, such as studying barrier distributions; new approaches to
channel coupling, such as the path integral and Green function formalisms; and
alternative methods to describe nuclear structure effects, such as those using
the Interacting Boson Model. The roles of nucleon transfer, asymmetry effects,
higher-order couplings, and shape-phase transitions are elucidated. The current
status of the fusion of unstable nuclei and very massive systems are briefly
discussed.Comment: To appear in the January 1998 issue of Reviews of Modern Physics. 13
Figures (postscript file for Figure 6 is not available; a hard copy can be
requested from the authors). Full text and figures are also available at
http://nucth.physics.wisc.edu/preprints
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