Low-Level HIV-I Replication and the Dynamics of the Resting CD4(+) T Cell Reservoir for HIV-I in the Setting of HAART

In the setting of highly active antiretroviral therapy (HAART), plasma levels of human immunodeficiency type-I (HIV-I) rapidly decay to below the limit of detection of standard clinical assays. However, reactivation of remaining latently infected memory CD4(+) T cells is a source of continued virus production, forcing patients to remain on HAART despite clinically undetectable viral loads. Unfortunately, the latent reservoir decays slowly, with a half-life of up to 44 months, making it the major known obstacle to the eradication of HIV-I infection. However, the mechanism underlying the long half-life of the latent reservoir is unknown. The most likely potential mechanisms are low-level viral replication and the intrinsic stability of latently infected cells. Methods: Here we use a mathematical model of T cell dynamics in the setting of HIV-I infection to probe the decay characteristics of the latent reservoir upon initiation of HAART. We compare the behavior of this model to patient derived data in order to gain insight into the role of low-level viral replication in the setting of HAART. Results: By comparing the behavior of our model to patient derived data, we find that the viral dynamics observed in patients on HAART could be consistent with low-level viral replication but that this replication would not significantly affect the decay rate of the latent reservoir. Rather than low-level replication, the intrinsic stability of latently infected cells and the rate at which they are reactivated primarily determine the observed reservoir decay rate according to the predictions of our model. Conclusion: The intrinsic stability of the latent reservoir has important implications for efforts to eradicate HIV-I infection and suggests that intensified HAART would not accelerate the decay of the latent reservoir.NIH AI 065960, AI 143222, AI 51178Doris Duke Charitable FoundationThe Howard Hughes Medical InstituteIntegrative Biolog

Constructing Mobius Transformations with Spheres

Every Mobius transformation can be constructed by stereographic projection of the complex plane onto a sphere, followed by a rigid motion of the sphere and projection back onto the plane, illustrated in the video Mobius Transformations Revealed. In this article we show that, for a given Mobius transformation and sphere, this representation is unique

Corporate Behavior and the Social Efficiency of Tort Law

This article examines this dissonance between accepted theory and observed reality, between what the model envisions and what the tort system seems to deliver. After sketching the model in greater detail, the first section of the article reviews restraints within tort law on the achievement of efficient outcomes. The analysis then turns to the broader legal environment, and describes how legally sanctioned means of liability evasion - such as the corporate law doctrine of limited liability and the bankruptcy rules permitting discharge of obligations - may further undermine the practical utility of the social efficiency model of tort. The final section of the article examines tort reform\u27s potential for overcoming such barriers to efficiency, and, in light of its pessimistic conclusion, suggests that rethinking the efficiency norm may be a more appropriate response

Negligent Accounting and the Limits of Instrumental Tort Reform

This article first explores the relationship between the accountant and the reliant third party, and recounts the mounting judicial hostility to the accountant\u27s traditional privity defense. Next, the article critically examines the arguments that have supported traditional privity-based regimes. The third section turns to the reform courts and tests whether the rationales offered for reform justify abandoning the privity requirement. Concluding that a convincing case for reform has yet to be made and - given the complexity of a properly executed instrumental analysis - may never be made, the article\u27s final section reconsiders the utility of instrumental reasoning as a self-sustaining basis for tort reform. It suggests that, if the negligent accounting cases are any indication, the viability of tort reforms based on instrumental rationales may ultimately depend on how well the outcome in such cases corresponds to more traditional notions of fairness between the parties. In situations where this subtext of fairness concerns yields no obvious answer, the analysis suggests that courts armed with an instrumental agenda should proceed with considerably more caution than they currently exercise

Corporate Behavior and the Social Efficiency of Tort Law

This article examines this dissonance between accepted theory and observed reality, between what the model envisions and what the tort system seems to deliver. After sketching the model in greater detail, the first section of the article reviews restraints within tort law on the achievement of efficient outcomes. The analysis then turns to the broader legal environment, and describes how legally sanctioned means of liability evasion - such as the corporate law doctrine of limited liability and the bankruptcy rules permitting discharge of obligations - may further undermine the practical utility of the social efficiency model of tort. The final section of the article examines tort reform\u27s potential for overcoming such barriers to efficiency, and, in light of its pessimistic conclusion, suggests that rethinking the efficiency norm may be a more appropriate response