Public-Private Litigation for Health

Public health litigation can be a powerful mechanism for addressing public health harms where alternative interventions have failed. It can draw public attention to corporate misconduct and create a public record of the actions taken and the harms done. In an ideal world, it could achieve compensation for past harms and incentivize deterrence of future misconduct. But the full public health potential of these lawsuits is rarely achieved, even when the suits are brought on behalf of federal, state, and local governments with the ostensible goal of protecting the health of the citizens. The increasing involvement of private attorneys in public litigation only adds to the challenges of using litigation to achieve public health goals. While there are continuing debates over the desirability of litigation partnerships between state attorneys general (AGs) and private counsel, as a practical matter, the involvement of private law firms in public litigation is unlikely to disappear any time soon. This Article fills a critical gap in the literature on the privatization of public litigation by showing why, despite their shortcomings, arrangements between state and private lawyers have the potential to satisfy public health goals that might otherwise remain out of reach. It provides a theory of legal research and development to show why these arrangements are not only likely to persist but are also most likely to occur in high-impact public health litigation. This Article then examines how the incentives of both state AGs and private law firms influence choices along the litigation pathway in ways that may undermine the potential to achieve public health value. It concludes by proposing a novel impact-based approach to public-private litigation, providing a decision-making framework that AGs can adopt to increase the role of public health objectives in the litigation process

X-Ray Scattering at FeCo(001) Surfaces and the Crossover between Ordinary and Normal Transitions

In a recent experiment by Krimmel et al. [PRL 78, 3880 (1997)], the critical behavior of FeCo near a (001) surface was studied by x-ray scattering. Here the experimental data are reanalyzed, taking into account recent theoretical results on order-parameter profiles in the crossover regime between ordinary and normal transitions. Excellent agreement between theoretical expectations and the experimental results is found.Comment: 9 pages, Latex, 1 PostScript figure, to be published in Phys.Rev.

Typing and Compositionality for Security Protocols::A Generalization to the Geometric Fragment

We integrate, and improve upon, prior relative soundness results of two kinds. The first kind are typing results showing that any security protocol that fulfils a number of sufficient conditions has an attack if it has a well-typed attack. The second kind considers the parallel composition of protocols, showing that when running two protocols in parallel allows for an attack, then at least one of the protocols has an attack in isolation. The most important generalization over previous work is the support for all security properties of the geometric fragment

Thermal Impact on Spiking Properties in Hodgkin-Huxley Neuron with Synaptic Stimulus

The effect of environmental temperature on neuronal spiking behaviors is investigated by numerically simulating the temperature dependence of spiking threshold of the Hodgkin-Huxley neuron subject to synaptic stimulus. We find that the spiking threshold exhibits a global minimum in a "comfortable temperature" range where spike initiation needs weakest synaptic strength, indicating the occurrence of optimal use of synaptic transmission in neural system. We further explore the biophysical origin of this phenomenon in ion channel gating kinetics and also discuss its possible biological relevance in information processing in neural systems.Comment: 10 pages, 4 figure

Palladin Compensates for the Arp2/3 Complex and Supports Actin Structures during Listeria Infections

Palladin is an important component of motile actin-rich structures and nucleates branched actin filament arrays in vitro. Here we examine the role of palladin during Listeria monocytogenes infections in order to tease out novel functions of palladin. We show that palladin is co-opted by L. monocytogenes during its cellular entry and intracellular motility. Depletion of palladin resulted in shorter and misshapen comet tails, and when actin- or VASP-binding mutants of palladin were overexpressed in cells, comet tails disintegrated or became thinner. Comet tail thinning resulted in parallel actin bundles within the structures. To determine whether palladin could compensate for the Arp2/3 complex, we overexpressed palladin in cells treated with the Arp2/3 inhibitor CK-666. In treated cells, bacterial motility could be initiated and maintained when levels of palladin were increased. To confirm these findings, we utilized a cell line depleted of multiple Arp2/3 complex subunits. Within these cells, L. monocytogenes failed to generate comet tails. When palladin was overexpressed in this Arp2/3 functionally null cell line, the ability of L. monocytogenes to generate comet tails was restored. Using purified protein components, we demonstrate that L. monocytogenes actin clouds and comet tails can be generated (in a cell-free system) by palladin in the absence of the Arp2/3 complex. Collectively, our results demonstrate that palladin can functionally replace the Arp2/3 complex during bacterial actin-based motility

BigWig and BigBed: enabling browsing of large distributed datasets

Summary: BigWig and BigBed files are compressed binary indexed files containing data at several resolutions that allow the high-performance display of next-generation sequencing experiment results in the UCSC Genome Browser. The visualization is implemented using a multi-layered software approach that takes advantage of specific capabilities of web-based protocols and Linux and UNIX operating systems files, R trees and various indexing and compression tricks. As a result, only the data needed to support the current browser view is transmitted rather than the entire file, enabling fast remote access to large distributed data sets

Statistical model-based testing to evaluate the recurrence of genomic aberrations

Motivation: In cancer genomes, chromosomal regions harboring cancer genes are often subjected to genomic aberrations like copy number alteration and loss of heterozygosity. Given this, finding recurrent genomic aberrations is considered an apt approach for screening cancer genes. Although several permutation-based tests have been proposed for this purpose, none of them are designed to find recurrent aberrations from the genomic dataset without paired normal sample controls. Their application to unpaired genomic data may lead to false discoveries, because they retrieve pseudo-aberrations that exist in normal genomes as polymorphisms

Distribution of CD147 During Enteropathogenic Escherichia coli and Salmonella enterica Serovar Typhimurium Infections

Enteropathogenic Escherichia coli (EPEC) and Salmonella enterica serovar Typhimurium (S. Typhimurium) are highly infectious gastrointestinal human pathogens. These microbes inject bacterial-derived effector proteins directly into the host cell cytosol as part of their disease processes. A common host subcellular target of these pathogens is the actin cytoskeleton, which is commandeered by the bacteria and is used during their attachment onto (EPEC) or invasion into (S. Typhimurium) the host cells. We previously demonstrated that the host enzyme cyclophilin A (CypA) is recruited to the actin-rich regions of EPEC pedestals and S. Typhimurium membrane ruffles. To further expand the growing catalogue of host proteins usurped by actin-hijacking bacteria, we examined the host plasma membrane protein and cognate receptor of CypA, CD147, during EPEC and S. Typhimurium infections. Here, we show that CD147 is enriched at the basolateral regions of pedestals but, unlike CypA, it is absent from their actin-rich core. We show that the CD147 recruitment to these areas requires EPEC pedestal formation and not solely bacteria-host cell contact. Additionally, we demonstrate that the depletion of CD147 by siRNA does not alter the formation of pedestals. Finally, we show that CD147 is also a component of actin-rich membrane ruffles generated during S. Typhimurium invasion of host cells. Collectively, our findings establish CD147 as another host component present at dynamic actin-rich structures formed during bacterial infections

Aharonov-Bohm-Type Oscillations of Thermopower in a Quantum Dot Ring Geometry

We investigate Aharonov-Bohm-type oscillations of the thermopower of a quantum dot embedded in a ring for the case when the interaction between electrons can be neglected. The thermopower is shown to be strongly flux dependent, and typically the amplitude of oscillations exceeds the background value. It is also shown to be essentially dependent on the phase of the scattering matrix which is determined by the experimental geometry and is not known in the given experiment. Two procedures to compare theory and experiment are proposed.Comment: Revtex, 5 figures include