Pathways and Mechanisms that Prevent Genome Instability in Saccharomyces cerevisiae.

Genome rearrangements result in mutations that underlie many human diseases, and ongoing genome instability likely contributes to the development of many cancers. The tools for studying genome instability in mammalian cells are limited, whereas model organisms such as Saccharomyces cerevisiae are more amenable to these studies. Here, we discuss the many genetic assays developed to measure the rate of occurrence of Gross Chromosomal Rearrangements (called GCRs) in S. cerevisiae These genetic assays have been used to identify many types of GCRs, including translocations, interstitial deletions, and broken chromosomes healed by de novo telomere addition, and have identified genes that act in the suppression and formation of GCRs. Insights from these studies have contributed to the understanding of pathways and mechanisms that suppress genome instability and how these pathways cooperate with each other. Integrated models for the formation and suppression of GCRs are discussed

Bowen Measure From Heteroclinic Points

We present a new construction of the entropy-maximizing, invariant probability measure on a Smale space (the Bowen measure). Our construction is based on points that are unstably equivalent to one given point, and stably equivalent to another: heteroclinic points. The spirit of the construction is similar to Bowen's construction from periodic points, though the techniques are very different. We also prove results about the growth rate of certain sets of heteroclinic points, and about the stable and unstable components of the Bowen measure. The approach we take is to prove results through direct computation for the case of a Shift of Finite type, and then use resolving factor maps to extend the results to more general Smale spaces

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

Electrolytic pretreatment unit gaseous effluent conditioning

The electrolytic pretreatment of urine is an advanced process that eliminates the need for handling and storing the highly corrosive chemicals that are normally used in water reclamation systems. The electrolytic pretreatment process also converts the organic materials in urine to gases (N2 and O2) that can be used to replenish those lost to space by leakage, venting, and air lock operations. The electrolytic process is more than a pretreatment, since it decreases the urine solids content by approximately one third, thus reducing the load and eventual solids storage requirements of the urine processing system. The evolved gases from the pretreatment step cannot, however, be returned directly to the atmosphere of a spacecraft without first removing several impurities including hydrogen, chlorine, and certain organic compounds. A treatment concept was developed that would decrease the impurities in the gas stream that emanates from an electrolysis unit to levels sufficiently low to allow the conditioned gas stream to be safely discharged to a spacecraft atmosphere. Two methods were experimentally demonstrated that can accomplish the desired cleanup. The bases of the two methods are, repectively: (1) raw urine scrubbing and (2) silica gel sorption

Education and Social Capital

Education is usually the most important predictor of political and social engagement. Over the last half century, educational levels in the United States have risen sharply, yet levels of political and social participation have not. Norman Nie, Jane Junn, and Kenneth Stehlik-Barry (NJS-B) have offered an elegant resolution to this paradox based on a distinction between the relative education having positive effects on participation. Using a broad range of evidence, including the data used by NJS-B, this paper shows that increases in average education levels improve trust and do not reduce participation levels. The contrast with the NJS-B participation results is found to be due to the definition of the educational environment. We use a changing regional comparison group, theoretically preferable to NJS-B's static national measure. Our results point to a more optimistic conclusion about the consequences of increases in average education levels, while leaving open the puzzle of sluggish participation.

An experimental and analytical investigation of effect on isolated boattail drag of varying Reynolds numbers up to 130,000,000

An investigation was conducted to determine whether large Reynolds number effects occur on isolated boattails, including an analytical study and tests in a 1/3-meter transonic cryogenic tunnel. This investigation was conducted at an angle of attack of 0 deg at Mach numbers from 0.6 to 0.9 for Reynolds numbers up to 130 million. Results indicate that as the Reynolds number was increased, the static pressure coefficients in the expansion region of the boattail became more negative whereas those in the recompression region became more positive. These two trends were compensating and, as a result, there was only a small effect (if any) of Reynolds numbers on boattail pressure drag

Education and Social Capital

Education is usually the most important predictor of political and social engagement. Over the last half Century, educational levels in the United States have risen sharply, yet levels of political and social participation have not. Norman Nie, Jane Junn and Kenneth Stehlik-Barry (NJS-B) have offered a resolution to this paradox based on the distinction between absolute and relative education, with only relative education having positive effects on education. Using a broad range of data, including that used by NJS-B, this paper shows that increases in average education levels increases trust and does not reduce average participation levels. These results are found when we use a dynamic regional comparison group, theoretically preferable to NJS-B’s static national measure. Our results provide an optimistic conclusion about the effects of increases in education levels, while leaving open the explanation of declining participation levels. Our results suggest that exposure to television during childhood may play an important role in that story.