In accordance with the present invention, there are provided compns. and methods useful for the in vivo delivery of substantially water insol. pharmacol. active agents (such as the anticancer drug paclitaxel) in which the pharmacol. active agent is delivered in the form of suspended particles coated with protein (which acts as a stabilizing agent). In particular, protein and pharmacol. active agent in a biocompatible dispersing medium are subjected to high shear, in the absence of any conventional surfactants, and also in the absence of any polymeric core material for the particles. The procedure yields particles with a diam. of less than about 1 μ. The use of specific compn. and prepn. conditions (e.g., addn. of a polar solvent to the org. phase), and careful election of the proper org. phase and phase fraction, enables the reproducible prodn. of unusually small nanoparticles of less than 200 nm diam., which can be sterile-filtered. The particulate system produced according to the invention can be converted into a redispersible dry powder comprising nanoparticles of water-insol. drug coated with a protein, and free protein to which mols. of the pharmacol. agent are bound. This results in a unique delivery system, in which part of the pharmacol. active agent is readily bioavailable (in the form of mols. bound to the protein), and part of the agent is present within particles without any polymeric matrix therein. [on SciFinder(R)]
The asymptotic value, introduced by Kannai in 1966, is an asymptotic approach to the notion of the Shapley value for games with infinitely many players. A vector measure game is a game v where the worth v(S) of a coalition S is a function f of u(S) where u is a vector measure. Special classes of vector measure games are the weighted majority games and the two-house weighted majority games, where a two-house weighted majority game is a game in which a coalition is winning if and only if it is winning in two given weighted majority games. All weighted majority games have an asymptotic value. However, not all two-house weighted majority games have an asymptotic value. In this paper, we prove that the existence of infinitely many atoms with sufficient variety suffice for the existence of the asymptotic value in a general class of nonsmooth vector measure games that includes in particular two-house weighted majority games.
Electropolymn. of medical devices such as cardiovascular stents may possess advantages including a simple and reproducible process with the ability to control the thickness, adherence, and compn. of the coating by the duration and intensity of the applied current, the monomer compn. and concn., the solvent, and the reaction conditions. The properties of the polymer can also be controlled by copolymn. of different monomers, grafting substituents to a functionalized polymer, and by entrapping biomols. This article describes the synthesis of a range of pyrrole-based monomers and their electrocoating onto stainless steel surfaces. N-substituted pyrrole monomers with C1-C18 alkyl chains and polyethylene glycol chains were synthesized in good yields and purity. Electropolymn. of these monomers provided uniform coatings with different hydrophobicities. Studies now focus on the incorporation of drugs in the coated device for release from the surface. [on SciFinder(R)]
Margarida D Amaral, Luka A Clarke, Anabela S Ramalho, Sebastian Beck, Fiona Broackes-Carter, Rebecca Rowntree, Nathalie Mouchel, Sarah H Williams, Ann Harris, Maria Tzetis, Bernhard Steiner, Javier Sanz, Sabina Gallati, Malka Nissim-Rafinifa, Batsheva Kerem, Timothy Hefferon, Garry R Cutting, Elisa Goina, and Franco Pagani. 2004. “Quantitative methods for the analysis of CFTR transcripts/splicing variants..” J Cyst Fibros, 3 Suppl 2, Pp. 17-23. Abstract
In cystic fibrosis (CF), transcript analysis and quantification are important for diagnosis, prognosis and also as surrogate markers for some therapies including gene therapy. Classical RNA-based methods require significant expression levels in target samples for appropriate analysis, thus PCR-based methods are evolving towards reliable quantification. Various protocols for the quantitative analysis of CFTR transcripts (including those resulting from splicing variants) are described and discussed here.
The construction of devices based on molecular components depends upon the development of molecular wires with adaptable current-voltage characteristics. Here, we report that quantum interference effects could lead to substantial differences in conductance in molecular wires which include some simple polycyclic aromatic hydrocarbons (PAHs). For molecular wires containing a single benzene. anthracene or tetracene molecule a large peak appears in the electron transmission probability spectrum at an energy just above the lowest unoccupied orbital (LUMO). For a molecular wire containing a single naphthalene molecule, however, this same peak essentially vanishes. Furthermore, the peak can be re-established by altering the attachment points of the molecular leads to the naphthalene molecule. A breakdown of the individual terms contributing the relevant peak confirms that these results are in fact due to quantum interference effects. (C) 2004 Elsevier B.V. All rights reserved.
F Remacle and RD LEVINE. 2004. “Quasiclassical computation.” PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 101, Pp. 12091-12095. Abstract
The chemical kinetic description of time evolution where the phase is random but the states are discrete is discussed as a basis for a computational approach. This proposed scheme uses numbers in the entire range of 0 to 1 to represent Boolean propositions. In the implementation by chemical kinetics these numbers are the mole fractions of different species. Vibrational relaxation in a mixture of HCI and DCI is the physical system that is used to illustrate the approach. Energy exchange in such a mixture corresponds to two strongly coupled two-level systems. A search problem, previously discussed in the quantum computing literature, is solved as an example. The solution requires the same number of function evaluations as in the quantal case. The action of the oracle is described in detail.
The present work aims at demonstrating that visual training associated with the act of reading modifies the way we perceive printed words. As reading does not train all parts of the retina in the same way but favors regions on the side in the direction of scanning, visual word recognition should be better at retinal locations that are frequently used during reading. In two studies that probed word and letter discriminations we provided evidence for a correlation between eye fixation pattern during reading and performance. We showed that effects of reading-related visual training were stimulus-specific in the sense that it [...]
We present a linear-response approach for time-dependent density-functional theories using time-adiabatic functionals. The resulting theory can be performed both in the time and in the frequency domain. The derivation considers an impulsive perturbation after which the Kohn-Sham orbitals develop in time autonomously. The equation describing the evolution is not strictly linear in the wave function representation. Only after going into a symplectic real-spinor representation does the linearity make itself explicit. For performing the numerical integration of the resulting equations, yielding the linear response in time, we develop a modified Chebyshev expansion approach. The frequency domain is easily accessible as well by changing the coefficients of the Chebyshev polynomial, yielding the expansion of a formal symplectic Green's operator. (C) 2004 American Institute of Physics.
BACKGROUND: Head lice move easily from head to head. The lack of safe, effective repellents leads to reinfestation. OBJECTIVES: To test the efficacy of a slow-release citronella formulation as a repellent against the head louse. METHODS: During 4 months in 2003 a randomized, placebo-controlled double-blind clinical study was conducted in four elementary schools; 103 children were treated with the test formulation and 95 with a placebo. RESULTS: A significant difference was observed during the second examination 2 months later, when 12.0% of the children treated with the test repellent and 50.5% of those treated with placebo were infested with lice. A significant difference was also observed at the third examination 2 months later, when 12.4% of the children treated with the test repellent and 33.7% treated with placebo were infested. Overall, there were significant differences between those treated with the repellent and those treated with the placebo (15.4% and 55.1% respectively, P < 0.0001). Side effects were observed in 4.4% of children who disliked the odor of the formulation, and an additional 1.0% who complained of a slight itching and burning sensation. CONCLUSIONS: Use of an effective repellent could significantly lower the incidence of reinfestations, which would lower expenditure on lice control, including pediculicides, combs and products for nit removal, and the time spent on treatment and removal of the nits.[on SciFinder (R)]
A significant fraction of disease-causing mutations affects pre-mRNA splicing. These mutations can generate both aberrant and correct transcripts, the level of which varies among different patients. An inverse correlation was found between this level and disease severity, suggesting a role for splicing regulation as a genetic modifier. Overexpression of splicing factors increased the level of correctly spliced RNA, transcribed from minigenes carrying disease-causing splicing mutations. However, whether this increase could restore the protein function was unknown. Here, we demonstrate that overexpression of Htra2-beta1 and SC35 increases the level of normal cystic fibrosis transmembrane conductance regulator (CFTR) transcripts in cystic-fibrosis-derived epithelial cells carrying the 3849+10 kb C --> T splicing mutation. This led to activation of the CFTR channel and restoration of its function. Restoration was also obtained by sodium butyrate, a histone deacetylase inhibitor, known to upregulate the expression of splicing factors. These results highlight the therapeutic potential of splicing modulation for genetic diseases caused by splicing mutations.
