593 research outputs found
Explosivity : an unusual challenge in drug development
There remains an urgent global need for new drugs to combat diseases such as malaria, tuberculosis and cancer, as well as overcoming increasing antibiotic resistance. Chemists are moving into ‘new chemical space’ for drug design (1,2) and with this comes the possibility of traditional (and stable) ‘carbon-carbon’ bond structures being replaced by more ‘exotic’ bonding arrangements. While the implication of this on pharmaceutical stability can often be mitigated by suitable formulation and storage strategies, we came across an unusual case of chemical stability: the possibility that the drug was an explosive! By pushing drug designing into uncharted chemical space it could be argued that the possibility of finding explosive molecules of pharmaceutical interest will increase
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
The Birmingham Boron Neutron Capture Therapy (BNCT) project : developments towards selective internal particle therapy
This paper will review progress on two aspects of the Birmingham BNCT project. Firstly on evaluation of the effects of high and low LET radiations when delivered simultaneously, and secondly on attempts to optimise delivery of the boron carrier compound BPA through pharmacokinetic studies. Simultaneous or non-simultaneous irradiations of V79 cells with alpha-particle and X-ray irradiations were performed. Alpha doses of 2 and 2.5 Gy were chosen and the impact on survival when delivered separately or simultaneously with variable doses of X-rays was evaluated. The pharmacokinetics of the delivery of a new formulation of BPA (BPA-mannitol) are being investigated in brain tumour patients through a study with 2 × 2 design featuring intravenous and intracarotid artery infusion of BPA, with or without a mannitol bolus. On the combined effect of low and high LET radiations, a synergistic effect was observed when alpha and X-ray doses are delivered simultaneously. The effect is only present at the 2.5 Gy alpha dose and is a very substantial effect on both the shape of the survival curve and the level of cell killing. This indicates that the alpha component may have the effect of inhibiting the repair of damage from the low LET radiation dose delivered simultaneously. On the pharmacokinetics of BPA, data on the first three cohorts indicate that bioavailability of BPA in brain ECF is increased substantially through the addition of a mannitol bolus, as well as by the use of intracarotid artery route of infusion. In both cases, for some patients the levels after infusion approach those seen in blood, whereas the ECF levels for intravenous infusion without mannitol are typically less than 10% of the blood values
The brain tumor experience from the relatives' perspective
Article describes the clinical optimization of uptake parameters of Boronophenylalanin
Looking backward, looking forward: the city region of the mid-21st century
Emerging as a serious tool of analysis in the United States around 1950, the city region concept was increasingly applied in a European context after 1980. Since 2000, it has evolved further with recognition of the polycentric mega-city region, first recognised in Eastern Asia but now seen as an emerging urban form both in Europe and the United States. The paper speculates on the main changes that may impact on the growth and development of such complex urban regions in the first half of the 21st century, concluding that achieving the goal of polycentric urban development may prove more complex than at first it may seem
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
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
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Study of spin-temperature effects using energy-ordered continuum gamma-ray spectroscopy technique
We have investigated a new continuum {gamma}-ray spectroscopy technique which is based on the detection of all emitted {gamma} rays in a 4{pi} detector system, and ordering them according to their energies on an event-by-event basis. The technique allows determination of gamma strength functions, and rotational damping width as a function of spin and temperature. Thus, it opens up the possibility of studying the onset of motional narrowing, order-to-chaos transition, and the mapping of the evolution of nuclear collectivity with a spin and temperature. Application of the technique for preferential entry-state population, exit-channel selection, and feeding of the discrete states via selective pathways will be discussed. 20 refs., 4 figs
Shape coexistence and disappearance of pairing correlations in 82Sr
Extensive high-spin band structures in 82Sr have been established using proton-[gamma]-[gamma] coincidence techniques. On the basis of the Woods-Saxon cranking calculations with pairing, four of these bands are interpreted to have prolate, oblate, or triaxial shapes. Pairing correlations are predicted to be very weak at high spins in this nucleus, and calculations with no static pairing successfully reproduce the experimentally observed crossing frequencies and alignments despite the fact that none of the bands displays a rigid-rotor behavior. It is concluded that observation of rigid-rotor behavior is neither necessary nor sufficient for the disappearance of static pairing in nuclei.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/29458/1/0000540.pd
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