"Napsterizing" Pharmaceuticals: Access, Innovation, and Consumer Welfare

We analyze the effects on consumers of an extreme policy experiment -- Napsterizing' pharmaceuticals -- whereby all patent rights on branded prescription drugs are eliminated for both existing and future prescription drugs without compensation to the patent holders. The question of whether this policy maximizes consumer welfare cannot be resolved on an a priori basis due to an obvious tradeoff: While accelerating generic entry will yield substantial gains in consumer surplus associated with greater access to the current stock of pharmaceuticals, future consumers will be harmed by reducing the flow of new pharmaceuticals to the market. Our estimates of the consumer surpluses at stake are based on the stylized facts concerning how generic entry has affected prices, outputs, and market shares. We find that providing greater access to the current stock of prescription drugs yields large benefits to existing consumers. However, realizing those benefits has a substantially greater cost in terms of lost consumer benefits from reductions in the flow of new drugs. Specifically, the model yields the result that for every dollar in consumer benefit realized from providing greater access to the current stock, future consumers would be harmed at a rate of three dollars in present value terms from reduced future innovation. We obtain this result even accounting for the stylized fact that after generic entry branded drugs continue to earn significant price premia over generic products and hence recognizing that Napsterizing does not completely eliminate the incentives to innovate.

Omnidirectional Sensory and Motor Volumes in Electric Fish

Active sensing organisms, such as bats, dolphins, and weakly electric fish, generate a 3-D space for active sensation by emitting self-generated energy into the environment. For a weakly electric fish, we demonstrate that the electrosensory space for prey detection has an unusual, omnidirectional shape. We compare this sensory volume with the animal's motor volume—the volume swept out by the body over selected time intervals and over the time it takes to come to a stop from typical hunting velocities. We find that the motor volume has a similar omnidirectional shape, which can be attributed to the fish's backward-swimming capabilities and body dynamics. We assessed the electrosensory space for prey detection by analyzing simulated changes in spiking activity of primary electrosensory afferents during empirically measured and synthetic prey capture trials. The animal's motor volume was reconstructed from video recordings of body motion during prey capture behavior. Our results suggest that in weakly electric fish, there is a close connection between the shape of the sensory and motor volumes. We consider three general spatial relationships between 3-D sensory and motor volumes in active and passive-sensing animals, and we examine hypotheses about these relationships in the context of the volumes we quantify for weakly electric fish. We propose that the ratio of the sensory volume to the motor volume provides insight into behavioral control strategies across all animals

Electrostatic potential on human leukocyte antigen: implications for putative mechanism of chronic beryllium disease.

The pathobiology of chronic beryllium disease (CBD) involves the major histocompatibility complex class II human leukocyte antigen (HLA). Although occupational exposure to beryllium is the cause of CBD, molecular epidemiologic studies suggest that specific (Italic)HLA-DPB1(/Italic) alleles may be genetic susceptibility factors. We have studied three-dimensional structural models of HLA-DP proteins encoded by these genes. The extracellular domains of HLA-DPA1*0103/B1*1701, *1901, *0201, and *0401, and HLA-DPA1*0201/B1*1701, *1901, *0201, and *0401 were modeled from the X-ray coordinates of an HLA-DR template. Using these models, the electrostatic potential at the molecular surface of each HLA-DP was calculated and compared. These comparisons identify specific characteristics in the vicinity of the antigen-binding pocket that distinguish the different HLA-DP allotypes. Differences in electrostatics originate from the shape, specific disposition, and variation in the negatively charged groups around the pocket. The more negative the pocket potential, the greater the odds of developing CBD estimated from reported epidemiologic studies. Adverse impact is caused by charged substitutions in positions 55, 56, 69, 84, and 85, namely, the exact same loci identified as genetic markers of CBD susceptibility as well as cobalt-lung hard metal disease. These findings suggest that certain substitutions may promote an involuntary cation-binding site within a putatively metal-free peptide-binding pocket and therefore change the innate specificity of antigen recognition

The Antiferromagnetic Band Structure of La2CuO4 Revisited

Using the Becke-3-LYP functional, we have performed band structure calculations on the high temperature superconductor parent compound, La2CuO4. Under the restricted spin formalism (rho(alpha) equal to rho(beta)), the R-B3LYP band structure agrees well with the standard LDA band structure. It is metallic with a single Cu x2-y2/O p(sigma) band crossing the Fermi level. Under the unrestricted spin formalism (rho(alpha) not equal to rho(beta)), the UB3LYP band structure has a spin polarized antiferromagnetic solution with a band gap of 2.0 eV, agreeing well with experiment. This state is 1.0 eV (per formula unit) lower than that calculated from the R-B3LYP. The apparent high energy of the spin restricted state is attributed to an overestimate of on-site Coulomb repulsion which is corrected in the unrestricted spin calculations. The stabilization of the total energy with spin polarization arises primarily from the stabilization of the x2-y2 band, such that the character of the eigenstates at the top of the valence band in the antiferromagnetic state becomes a strong mixture of Cu x2-y2/O p(sigma) and Cu z2/O' p(z). Since the Hohenberg-Kohn theorem requires the spin restricted and spin unrestricted calculations give exactly the same ground state energy and total density for the exact functionals, this large disparity in energy reflects the inadequacy of current functionals for describing the cuprates. This calls into question the use of band structures based on current restricted spin density functionals (including LDA) as a basis for single band theories of superconductivity in these materials.Comment: 13 pages, 8 figures, to appear in Phys. Rev. B, for more information see http://www.firstprinciples.co

Temperature Affects Hatching Success of Cocoons in the Invasive Asian Earthworm Amynthas agrestis from the Southern Appalachians

Invasive Asian earthworms are increasingly common in the eastern USA where they are a major cause of terrestrial ecosystem disturbance. Among these, Amynthas agrestis (Crazy Worm, Alabama Jumper, and other common names) has been shown to alter above- and belowground food webs. Life-history traits of these earthworms are largely unknown, particularly in their invaded range. Here, we sought to answer questions about temperature effects on hatching success for cocoons of this species, using specimens collected from the southern Appalachian Mountains. We conducted 2 experiments investigating the effects of incubation temperature and the effect of varying the duration of cold temperature on hatching success. Of the temperatures tested, we found that cocoons hatched with greatest success at 10 °C, but our tests indicate a long duration at that temperature may be needed to result in an increase in hatching success. These results indicate that temperature and the duration of temperature exposure affect hatching success in this species. While our results contribute to the growing body of knowledge about the life-history traits of invasive Asian earthworms in the eastern US, more research is needed to provide a finer-resolution understanding of the optimum level and duration of temperatures for hatching success of A. agrestis

Development of a Tuned Interfacial Force Field Parameter Set for the Simulation of Protein Adsorption to Silica Glass

Adsorption free energies for eight host–guest peptides (TGTG-X-GTGT, with X = N, D, G, K, F, T, W, and V) on two different silica surfaces [quartz (100) and silica glass] were calculated using umbrella sampling and replica exchange molecular dynamics and compared with experimental values determined by atomic force microscopy. Using the CHARMM force field, adsorption free energies were found to be overestimated (i.e., too strongly adsorbing) by about 5–9 kcal/mol compared to the experimental data for both types of silica surfaces. Peptide adsorption behavior for the silica glass surface was then adjusted using a modified version of the CHARMM program, which we call dual force-field CHARMM, which allows separate sets of nonbonded parameters (i.e., partial charge and Lennard-Jones parameters) to be used to represent intra-phase and inter-phase interactions within a given molecular system. Using this program, interfacial force field (IFF) parameters for the peptide-silica glass systems were corrected to obtain adsorption free energies within about 0.5 kcal/mol of their respective experimental values, while IFF tuning for the quartz (100) surface remains for future work. The tuned IFF parameter set for silica glass will subsequently be used for simulations of protein adsorption behavior on silica glass with greater confidence in the balance between relative adsorption affinities of amino acid residues and the aqueous solution for the silica glass surface

The Extrapolation of High Altitude Solar Cell I(V) Characteristics to AM0

The high altitude aircraft method has been used at NASA GRC since the early 1960's to calibrate solar cell short circuit current, ISC, to Air Mass Zero (AMO). This method extrapolates ISC to AM0 via the Langley plot method, a logarithmic extrapolation to 0 air mass, and includes corrections for the varying Earth-Sun distance to 1.0 AU and compensating for the non-uniform ozone distribution in the atmosphere. However, other characteristics of the solar cell I(V) curve do not extrapolate in the same way. Another approach is needed to extrapolate VOC and the maximum power point (PMAX) to AM0 illumination. As part of the high altitude aircraft method, VOC and PMAX can be obtained as ISC changes during the flight. These values can then the extrapolated, sometimes interpolated, to the ISC(AM0) value. This approach should be valid as long as the shape of the solar spectra in the stratosphere does not change too much from AMO. As a feasibility check, the results are compared to AMO I(V) curves obtained using the NASA GRC X25 based multi-source simulator. This paper investigates the approach on both multi-junction solar cells and sub-cells