NF-KB protein purification from bovine spleen: Nucleotide stimulation and binding site specificity

The activity of the enhancer for the κ immunoglobulin light chain gene critically depends on the presence in the nucleus of the NF-κB protein. We purified NF-κB over 50,000-fold and identified two protein species, 42 and 44 kDa, that could be eluted and renatured from a sodium dodecyl sulfate/polyacrylamide gel to give specific DNA-binding activity. Binding of the purified bovine NF-κB as well as that from human and murine B- or T-lymphoid cell extracts was dramatically stimulated by nucleoside triphosphates. This effect distinguished NF-κB from a related factor, H2-TF1. Purified NF-κB interacted efficiently with regulatory sequences that function during either B- or T-lymphocyte activation, including the human immunodeficiency virus enhancer and a NF-κB binding site we detected in the interleukin 2 enhancer

Co-option of an endogenous retrovirus envelope for host defense in hominid ancestors

Endogenous retroviral sequences provide a molecular fossil record of ancient infections whose analysis might illuminate mechanisms of viral extinction. A close relative of gammaretroviruses, HERV-T, circulated in primates for ~25 million years (MY) before apparent extinction within the past ~8 MY. Construction of a near-complete catalog of HERV-T fossils in primate genomes allowed us to estimate a ~32 MY old ancestral sequence and reconstruct a functional envelope protein (ancHTenv) that could support infection of a pseudotyped modern gammaretrovirus. Using ancHTenv, we identify monocarboxylate transporter-1 (MCT-1) as a receptor used by HERV-T for attachment and infection. A single HERV-T provirus in hominid genomes includes an env gene (hsaHTenv) that has been uniquely preserved. This apparently exapted HERV-T env could not support virion infection but could block ancHTenv mediated infection, by causing MCT-1 depletion from cell surfaces. Thus, hsaHTenv may have contributed to HERV-T extinction, and could also potentially regulate cellular metabolism

Non-uniform vortex lattices in inhomogeneous rotating Bose-Einstein condensates

We derive a general framework, in terms of elastic theory, for describing the distortion of the vortex lattice in a rotating Bose-Einstein condensate at arbitrary rotation speed and determining the dependence of the distortion on the density inhomogeneity of the system. In the rapidly rotating limit, we derive the energetics in terms of Landau levels, including excitation to higher levels; the distortion depends on the excitation of higher levels as well as on the density gradient. As we show, the dominant effect of higher Landau levels in a distorted lattice in equilibrium is simply to renormalize the frequency entering the lowest Landau level condensate wave function -- from the transverse trap frequency, $\omega$, to the rotational frequency, $\Omega$, of the system. Finally, we show how the equilibrium lattice distortion emerges from elastohydrodynamic theory for inhomogeneous systems.Comment: 6 pages, no figure

How Do the Social Benefits and Costs of the Patent System Stack Up in Pharmaceuticals?

This paper explores the workings of the patent system in the context of the generation of new pharmaceutical products. First it identifies the relevant characteristics of the patent system and its relation to the market. The paper concedes that, in general, the patent system is probably the best way of generating new technology, in substantial part because that system uses the market to provide both incentives and rewards. The paper also identifies downsides of this patent/market system: deadweight loss and the unresponsiveness of that patent/market system to the needs of the poor. The paper then explores the social costs and benefits of the patent system, drawing from analyses by Arrow and Kaplow. Drawing from a format developed by Kaplow, the paper develops a linear (and constant cost) model in which social costs and benefits are compared. Under the linear model, social costs remain low relative to social benefits for a substantial time period. Then the linear model is made more complex by abandoning the earlier assumptions of constant costs and linear demand. It shows how some nonlinear demand might result in very large deadweight losses, producing results significantly different from those of the linear model. The paper then considers price discrimination as a means by which producers might both increase their profits and reduce deadweight losses. The paper then explores the possibility that pharmaceutical producers might reduce global deadweight losses through price discrimination that favored third-world nations. Because international price discrimination might be discouraged by the prospect of arbitrage, the paper considers the extent to which existing laws provide means of protection against arbitrage. The paper considers contract law, patent law, and the lawfulness of potential governmental arrangements providing protection against arbitrage under the WTO and the Doha Declaration. Finally, the paper considers the possibility that global welfare would be maximized through an international treaty providing for the public and international funding of a limited class of pharmaceutical products

The Antitrust State-Action Doctrine After Fisher v. Berkeley

In February 1986 the United States Supreme Court in Fisher v. Berkeley\u27 upheld the validity of a municipal rent control ordinance against a contention that the Sherman Act preempted the ordinance. In an eight-to-one decision, the Court effectively gave the coup de grace to its earlier attempt to apply the federal antitrust laws to municipalities and political subdivisions. It also may have finally ended the remarkable series of disingenuous state-action decisions that had become an almost regular part of the Court\u27s calendar since Goldfarb v. Virginia State Bar\u27 in 1975.Fisher holds a promise of restoring to the state-action exemption a simplicity and predictability not seen since Parker v. Brown. This Article examines the origin, history, and scope of the state-action doctrine of federal antitrust law-a doctrine exempting state legislation and other (generally regulatory) activity from invalidation by the federal antitrust laws. The Article describes the ways in which the Court increasingly confused and elaborated that doctrine. The Article examines in particular how the Court\u27s recent decisions involving the relation of federal antitrust law to municipal legislation spun a web of confusion and uncertainty from which the Court itself has been forced to withdraw; how the lower federal courts refused to apply the Court\u27s state-action precedents with which they disagreed; and how even the Congress was provoked into action to undo some of the uncertainties engendered by these decisions. The examination of the state-action doctrine attempts to identify the concerns underlying the Court\u27s recent state-action decisions and to show why the series of state-action decisions since 1975 has been a failure. The Article also attempts to delineate the proper reach of federal antitrust law and to provide a reasoned basis for its conclusions. The analysis includes an assessment of Fisher v. Berkeley and its ramifications for the relation between federal antitrust law and the regulatory laws of states and local governments. Finally, the Article proposes legislation that provides an optimum reconciliation of the free market policies underlying the federal antitrust laws and the internal governing autonomy to which the states are entitled