Ciprofloxacin and Compulsory Licensing of Pharmaceutical Patents

The recent threat of biological terrorism involving the Anthrax virus incited a debate about whether the United States government should use its powers under 28 USC §1498 to take a compulsory license on the drug ciprofloxacin in order to stockpile it. Negotiating a deal with Bayer allowed the United States to stockpile ciprofloxacin at a substantial discount while avoiding the negative consequences of issuing a compulsory license. Under 35 U.S.C. 1498, the United States government has the authority to issue a compulsory license; however, the government may not have the authority under the TRIPs agreement. In fact, under the interpretation of the TRIPs agreement that the United States has adopted in previous situations when other countries wanted to issue compulsory licenses on pharmaceuticals, the United States most likely would have violated TRIPs if it had issued a compulsory license for ciprofloxacin. Furthermore, the policy decision to have strong patent protection and to not have price controls on pharmaceuticals in the United States has led to the development of a very strong pharmaceutical industry that leads the world in the development of innovative drugs

Evaluation of effective resistances in pseudo-distance-regular resistor networks

In Refs.[1] and [2], calculation of effective resistances on distance-regular networks was investigated, where in the first paper, the calculation was based on the stratification of the network and Stieltjes function associated with the network, whereas in the latter one a recursive formula for effective resistances was given based on the Christoffel-Darboux identity. In this paper, evaluation of effective resistances on more general networks called pseudo-distance-regular networks [21] or QD type networks \cite{obata} is investigated, where we use the stratification of these networks and show that the effective resistances between a given node such as $\alpha$ and all of the nodes $\beta$ belonging to the same stratum with respect to $\alpha$ ($R_{\alpha\beta^{(m)}}$, $\beta$ belonging to the $m$-th stratum with respect to the $\alpha$) are the same. Then, based on the spectral techniques, an analytical formula for effective resistances $R_{\alpha\beta^{(m)}}$ such that $L^{-1}_{\alpha\alpha}=L^{-1}_{\beta\beta}$ (those nodes $\alpha$, $\beta$ of the network such that the network is symmetric with respect to them) is given in terms of the first and second orthogonal polynomials associated with the network, where $L^{-1}$ is the pseudo-inverse of the Laplacian of the network. From the fact that in distance-regular networks, $L^{-1}_{\alpha\alpha}=L^{-1}_{\beta\beta}$ is satisfied for all nodes $\alpha,\beta$ of the network, the effective resistances $R_{\alpha\beta^{(m)}}$ for $m=1,2,...,d$ ($d$ is diameter of the network which is the same as the number of strata) are calculated directly, by using the given formula.Comment: 30 pages, 7 figure

Molecular basis of fosmidomycin's action on the human malaria parasite Plasmodium falciparum

The human malaria parasite Plasmodium falciparum is responsible for the deaths of more than a million people each year. Fosmidomycin has been proven to be efficient in the treatment of P. falciparum malaria by inhibiting 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an enzyme of the non-mevalonate pathway, which is absent in humans. However, the structural details of DXR inhibition by fosmidomycin in P. falciparum are unknown. Here, we report the crystal structures of fosmidomycin-bound complete quaternary complexes of PfDXR. Our study revealed that (i) an intrinsic flexibility of the PfDXR molecule accounts for an induced-fit movement to accommodate the bound inhibitor in the active site and (ii) a cis arrangement of the oxygen atoms of the hydroxamate group of the bound inhibitor is essential for tight binding of the inhibitor to the active site metal. We expect the present structures to be useful guides for the design of more effective antimalarial compounds

Microstructure and Phase Formation in a Rapidly Solidified Laser-Deposited Ni-Cr-B-Si-C Hardfacing Alloy

In this study, microstructural evolutions and phase selection phenomena during laser deposition of a hardfacing Ni-Cr-B-Si-C alloy at different processing conditions are experimentally investigated. The results show that even minor variations in the thermal conditions during solidification can modify the type and morphology of the phases. Higher undercoolings obtained at faster cooling rates suppressed the primary borides and encouraged floret-shape mixtures of Ni and Cr5B3 via a metastable reaction. Variations in the boride phases are discussed in terms of nucleation-and growth-controlled phase selection mechanisms. These selection processes also influenced the nature and proportion of the Ni-B-Si eutectics by changing the amount of the boron available for the final eutectic reactions. The results of this work emphasize the importance of controlling the cooling rate during deposition of these industrially important alloys using laser beam or other rapid solidification techniques. (C) The Minerals, Metals & Materials Society and ASM International 201

Diffusion-limited aggregation: A relationship between surface thermodynamics and crystal morphology

We have combined the original diffusion-limited aggregation model introduced by Witten and Sander with the surface thermodynamics of the growing solid aggregate. The theory is based on the consideration of the surface chemical potential as a thermodynamic function of the temperature and nearest-neighbor configuration. The Monte Carlo simulations on a two-dimensional square lattice produce the broad range of shapes such as fractal dendritic structures, densely branching patterns, and compact aggregates. The morphology diagram illustrating the relationship between the model parameters and cluster geometry is presented and discussed.Comment: 5 pages, 6 figure