Transient-mediated fate determination in a transcriptional circuit of HIV

Steady-state behavior and bistability have been proposed as mechanisms for decision-making in gene circuits. However, transient gene expression has also been proposed to control cell fate with the decision arbitrated by the lifetime of the expression transient. Here, we report that transcriptional positive-feedback plays a critical role in determining HIV infected cell-fate by extending the duration of Tat expression transients far beyond what protein half-life modulation can achieve. To directly quantify feedback strength and its effects on the duration of Tat transcriptional pulses, we exploit the noise inherent to gene-expression and measure shifts in the autocorrelation of expression noise. The results indicate that transcriptional positive-feedback extends the single-cell Tat expression lifetime by ~6-fold for both minimal Tat circuits and full-length, actively-replicating HIV-1. Importantly, artificial weakening of Tat positive-feedback shortened the duration of Tat expression transients and biased the probability in favor of latency. Thus, transcriptional positive-feedback appears to modulate transient expression lifetime and thereby control cell-fate in HIV

A Theory of Pragmatic Information and Its Application to the Quasispecies Model of Biological Evolution

"Standard" information theory says nothing about the semantic content of information. Nevertheless, applications such as evolutionary theory demand consideration of precisely this aspect of information, a need that has motivated a largely unsuccessful search for a suitable measure of an "amount of meaning". This paper represents an attempt to move beyond this impasse, based on the observation that the meaning of a message can only be understood relative to its receiver. Positing that the semantic value of information is its usefulness in making an informed decision, we define pragmatic information as the information gain in the probability distributions of the receiver's actions, both before and after receipt of a message in some pre-defined ensemble. We then prove rigorously that our definition is the only one that satisfies obvious desiderata, such as the additivity of information from logically independent messages. This definition, when applied to the information "learned" by the time evolution of a process, defies the intuitions of the few previous researchers thinking along these lines by being monotonic in the uncertainty that remains after receipt of the message, but non-monotonic in the Shannon entropy of the input ensemble. It then follows that the pragmatic information of the genetic "messages" in an evolving population is a global Lyapunov function for Eigen's quasi-species model of biological evolution. A concluding section argues that a theory such as ours must explicitly acknowledge purposeful action, or "agency", in such diverse fields as evolutionary theory and finance.Comment: as published in BIOSYSTEMS (I fixed an error in the proof of Theorem 2

Detecting the Dusty Debris of Terrestrial Planet Formation

We use a multiannulus accretion code to investigate debris disks in the terrestrial zone, at 0.7-1.3 AU around a 1 solar mass star. Terrestrial planet formation produces a bright dusty ring of debris with a lifetime of at least 1 Myr. The early phases of terrestrial planet formation are observable with current facilities; the late stages require more advanced instruments with adaptive optics.Comment: 11 pages of text, 3 figures, accepted for ApJ Letters, additional info at http://cfa-www.harvard.edu/~kenyon/pf/terra/td

Planetary environment simulation - Martian sand and dust storm simulation and evaluation, volume 2

Particle behavior in simulated Martian sand and dust stor