Kinetic proofreading models for cell signaling predict ways to escape kinetic proofreading

In the context of cell signaling, kinetic proofreading was introduced to explain how cells can discriminate among ligands based on a kinetic parameter, the ligand-receptor dissociation rate constant. In the kinetic proofreading model of cell signaling, responses occur only when a bound receptor undergoes a complete series of modifications. If the ligand dissociates prematurely, the receptor returns to its basal state and signaling is frustrated. We extend the model to deal with systems where aggregation of receptors is essential to signal transduction, and present a version of the model for systems where signaling depends on an extrinsic kinase. We also investigate the kinetics of signaling molecules, “messengers,” that are generated by aggregated receptors but do not remain associated with the receptor complex. We show that the extended model predicts modes of signaling that exhibit kinetic discrimination for some range of parameters but for other parameter values show little or no discrimination and thus escape kinetic proofreading. We compare model predictions with experimental data.

Remembering Liberal Feminism In Radical Ways: Locating Conservative Strategies In The Narratives Of Dr. Christina Hoff Sommers, Tammy Bruce, And Dr. Laura Schlessinger

This dissertation identifies and challenges post-feminist narratives that remember the second wave or 1960s and 1970s liberal feminism as a radical form of activism. The narratives of three prominent post-feminist authors: Dr. Christina Hoff Sommers, Tammy Bruce and Dr. Laura Schlessinger are used as examples of how identification works as a rhetorical device that motivates individual actors to join in a struggle against liberal and radical feminist ideologies. I argue that each author draws on classically liberal and politically conservative virtues to define a "true" feminism that is at odds with alternative feminist commitments. I demonstrate how these authors create a subject position of a "true feminist" that is reminiscent of the classically liberal suffragist. In Burkean terms, each author constitutes the suffragist as a friend and juxtaposes her with the enemy--modern liberal and radical feminists. I articulate the consequences of such dialectical portrayals of feminist activism and further suggest that these authors' visions of feminism reinforce patriarchal practices, urging women to assimilate into a classically liberal society at the cost of social justice. In opposition to their memories of feminism, I offer a radical democratic approach of remembering feminism that is less concerned with the definition of feminism or feminist than it is with holistically addressing oppression and what oppression means to subjugated populations.

A strongly magnetized pulsar within the grasp of the milky way’s supermassive black hole

The center of our Galaxy hosts a supermassive black hole, Sagittarius (Sgr) A∗. Young, massive stars within 0.5 pc of Sgr A∗ are evidence of an episode of intense star formation near the black hole a few million years ago, which might have left behind a young neutron star traveling deep into Sgr A∗’s gravitational potential. On 2013 April 25, a short X-ray burst was observed from the direction of the Galactic center. With a series of observations with the Chandra and the Swift satellites, we pinpoint the associated magnetar at an angular distance of 2.4±0.3 arcsec from Sgr A∗, and refine the source spin period and its derivative (P = 3.7635537(2) s and ˙ P = 6.61(4) × 10−12 s s−1), confirmed by quasi simultaneous radio observations performed with the Green Bank Telescope and Parkes Radio Telescope, which also constrain a dispersion measure of DM = 1750 ± 50 pc cm−3, the highest ever observed for a radio pulsar. We have found that this X-ray source is a young magnetar at ≈0.07–2 pc from Sgr A∗. Simulations of its possible motion around Sgr A∗ show that it is likely (∼90% probability) in a bound orbit around the black hole. The radiation front produced by the past activity from the magnetar passing through the molecular clouds surrounding the Galactic center region might be responsible for a large fraction of the light echoes observed in the Fe fluorescence features.