The properties of Msh2-Msh6 ATP binding mutants suggest a signal amplification mechanism in DNA mismatch repair.

DNA mismatch repair (MMR) corrects mispaired DNA bases and small insertion/deletion loops generated by DNA replication errors. After binding a mispair, the eukaryotic mispair recognition complex Msh2-Msh6 binds ATP in both of its nucleotide-binding sites, which induces a conformational change resulting in the formation of an Msh2-Msh6 sliding clamp that releases from the mispair and slides freely along the DNA. However, the roles that Msh2-Msh6 sliding clamps play in MMR remain poorly understood. Here, using Saccharomyces cerevisiae, we created Msh2 and Msh6 Walker A nucleotide-binding site mutants that have defects in ATP binding in one or both nucleotide-binding sites of the Msh2-Msh6 heterodimer. We found that these mutations cause a complete MMR defect in vivo The mutant Msh2-Msh6 complexes exhibited normal mispair recognition and were proficient at recruiting the MMR endonuclease Mlh1-Pms1 to mispaired DNA. At physiological (2.5 mm) ATP concentration, the mutant complexes displayed modest partial defects in supporting MMR in reconstituted Mlh1-Pms1-independent and Mlh1-Pms1-dependent MMR reactions in vitro and in activation of the Mlh1-Pms1 endonuclease and showed a more severe defect at low (0.1 mm) ATP concentration. In contrast, five of the mutants were completely defective and one was mostly defective for sliding clamp formation at high and low ATP concentrations. These findings suggest that mispair-dependent sliding clamp formation triggers binding of additional Msh2-Msh6 complexes and that further recruitment of additional downstream MMR proteins is required for signal amplification of mispair binding during MMR

A Universe Without Weak Interactions

A universe without weak interactions is constructed that undergoes big-bang nucleosynthesis, matter domination, structure formation, and star formation. The stars in this universe are able to burn for billions of years, synthesize elements up to iron, and undergo supernova explosions, dispersing heavy elements into the interstellar medium. These definitive claims are supported by a detailed analysis where this hypothetical "Weakless Universe" is matched to our Universe by simultaneously adjusting Standard Model and cosmological parameters. For instance, chemistry and nuclear physics are essentially unchanged. The apparent habitability of the Weakless Universe suggests that the anthropic principle does not determine the scale of electroweak breaking, or even require that it be smaller than the Planck scale, so long as technically natural parameters may be suitably adjusted. Whether the multi-parameter adjustment is realized or probable is dependent on the ultraviolet completion, such as the string landscape. Considering a similar analysis for the cosmological constant, however, we argue that no adjustments of other parameters are able to allow the cosmological constant to raise up even remotely close to the Planck scale while obtaining macroscopic structure. The fine-tuning problems associated with the electroweak breaking scale and the cosmological constant therefore appear to be qualitatively different from the perspective of obtaining a habitable universe.Comment: 27 pages; 4 figure

Laser diode initiated detonators for space applications

Ensign Bickford Aerospace Company (EBAC) has over ten years of experience in the design and development of laser ordnance systems. Recent efforts have focused on the development of laser diode ordnance systems for space applications. Because the laser initiated detonators contain only insensitive secondary explosives, a high degree of system safety is achieved. Typical performance characteristics of a laser diode initiated detonator are described in this paper, including all-fire level, function time, and output. A finite difference model used at EBAC to predict detonator performance, is described and calculated results are compared to experimental data. Finally, the use of statistically designed experiments to evaluate performance of laser initiated detonators is discussed

Experimental Design for the Gemini Planet Imager

The Gemini Planet Imager (GPI) is a high performance adaptive optics system being designed and built for the Gemini Observatory. GPI is optimized for high contrast imaging, combining precise and accurate wavefront control, diffraction suppression, and a speckle-suppressing science camera with integral field and polarimetry capabilities. The primary science goal for GPI is the direct detection and characterization of young, Jovian-mass exoplanets. For plausible assumptions about the distribution of gas giant properties at large semi-major axes, GPI will be capable of detecting more than 10% of gas giants more massive than 0.5 M_J around stars younger than 100 Myr and nearer than 75 parsecs. For systems younger than 1 Gyr, gas giants more massive than 8 M_J and with semi-major axes greater than 15 AU are detected with completeness greater than 50%. A survey targeting young stars in the solar neighborhood will help determine the formation mechanism of gas giant planets by studying them at ages where planet brightness depends upon formation mechanism. Such a survey will also be sensitive to planets at semi-major axes comparable to the gas giants in our own solar system. In the simple, and idealized, situation in which planets formed by either the "hot-start" model of Burrows et al. (2003) or the core accretion model of Marley et al. (2007), a few tens of detected planets are sufficient to distinguish how planets form.Comment: 15 pages, 9 figures, revised after referee's comments and resubmitted to PAS

Configurational factors in the perception of unfamiliar faces

Young et al (1987) have demonstrated that the juxtaposition of top and bottom halves of different faces produces a powerful impression of a novel face. It is difficult to isolate perceptually either half of the 'new' face. Inversion of the stimulus, however, makes this task easier. Upright chimeric faces appear to evoke strong and automatic configurational processing mechanisms which interfere with selective piecemeal processing. In this paper three experiments are described in which a matching paradigm was used to show that Young et al's findings apply to unfamiliar as well as to familiar faces. The results highlight the way in which minor procedural differences may alter the way in which subjects perform face-recognition tasks