Smc5/6 is required for repair at collapsed replication forks.

In eukaryotes, three pairs of structural-maintenance-of-chromosome (SMC) proteins are found in conserved multisubunit protein complexes required for chromosomal organization. Cohesin, the Smc1/3 complex, mediates sister chromatid cohesion while two condensin complexes containing Smc2/4 facilitate chromosome condensation. Smc5/6 scaffolds an essential complex required for homologous recombination repair. We have examined the response of smc6 mutants to the inhibition of DNA replication. We define homologous recombination-dependent and -independent functions for Smc6 during replication inhibition and provide evidence for a Rad60-independent function within S phase, in addition to a Rad60-dependent function following S phase. Both genetic and physical data show that when forks collapse (i.e., are not stabilized by the Cds1Chk2 checkpoint), Smc6 is required for the effective repair of resulting lesions but not for the recruitment of recombination proteins. We further demonstrate that when the Rad60-dependent, post-S-phase Smc6 function is compromised, the resulting recombination-dependent DNA intermediates that accumulate following release from replication arrest are not recognized by the G2/M checkpoint

Smc5/6 maintains stalled replication forks in a recombination-competent conformation

The Smc5/6 structural maintenance of chromosomes complex is required for efficient homologous recombination (HR). Defects in Smc5/6 result in chromosome missegregation and fragmentation. By characterising two Schizosaccharomyces pombe smc6 mutants, we define two separate functions for Smc5/6 in HR. The first represents the previously described defect in processing recombination-dependent DNA intermediates when replication forks collapse, which leads to increased rDNA recombination. The second novel function defines Smc5/6 as a positive regulator of recombination in the rDNA and correlates mechanistically with a requirement to load RPA and Rad52 onto chromatin genome-wide when replication forks are stably stalled by nucleotide depletion. Rad52 is required for all HR repair, but Rad52 loading in response to replication fork stalling is unexpected and does not correlate with damage-induced foci. We propose that Smc5/6 is required to maintain stalled forks in a stable recombination-competent conformation primed for replication restart

Regulation of Chk1

Chk1 is a serine/threonine protein kinase that is the effector of the G2 DNA damage checkpoint. Chk1 homologs have a highly conserved N-terminal kinase domain, and a less conserved C-terminal regulatory domain of ~200 residues. In response to a variety of genomic lesions, a number of proteins collaborate to activate Chk1, which in turn ensures that the mitotic cyclin-dependent kinase Cdc2 remains in an inactive state until DNA repair is completed. Chk1 activation requires the phosphorylation of residues in the C-terminal domain, and this is catalyzed by the ATR protein kinase. How phosphorylation of the C-terminal regulatory domain activates the N-terminal kinase domain has not been elucidated, though some studies have suggested that this phosphorylation relieves an inhibitory intramolecular interaction between the N- and C-termini. However, recent studies in the fission yeast Schizosaccharomyces pombe have revealed that there is more to Chk1 regulation than this auto-inhibition model, and we review these findings and their implication to the biology of this genome integrity determinant

A bioclimatic approach to integrated design : form, technology, and architectural knowledge

Thesis (M. Arch.)--Massachusetts Institute of Technology, Dept. of Architecture, 1996.Includes bibliographical references (p. 173-175).This thesis explores a holistic design process through which architectural elements can engage the dynamic forces of natural phenomena and integrate the spatial and temporal experience of building form with its physical environment. The framework for this exploration is a contextual mapping of dynamical systems and complexity theory to the processes of architectural design. By incorporating concepts and methods from the study of non-linear dynamics, a broad base of scientific knowledge aimed at understanding physical behavior in nature, this thesis proposes a synthetic relationship between architectural elements, their physical performance in the context of natural phenomena, and their contribution to a coherent spatial structure. Modern technological imperatives have rephrased the sensible relationships between architecture, climate, and inhabited space as a problem for "environmental controls". The contemporary urban office building, under economic pretenses, exhibits a particular over-dependence on external machinery for light, ventilation, and thermal comfort, often to the detriment of physical experience. This thesis emphasizes the use of scientific knowledge and computational tools in the early processes of design in an attempt to investigate the manifestations of physical energy -- light, air, and heat --in the building's final form. By addressing these physical performance criteria as spatial influences during preliminary design, this thesis supports an integrated framework for professional collaboration and examines a cultural context for the application of architectural knowledge. A bioclimatic approach to design, therefore, is a synthetic response to the dialectic between the tectonics of physical experience and the dynamics of the natural environment.by Matthew J. O'Connell.M.Arch

The PHASES Differential Astrometry Data Archive. I. Measurements and Description

The Palomar High-precision Astrometric Search for Exoplanet Systems (PHASES) monitored 51 sub-arcsecond binary systems to determine precision binary orbits, study the geometries of triple and quadruple star systems, and discover previously unknown faint astrometric companions as small as giant planets. PHASES measurements made with the Palomar Testbed Interferometer (PTI) from 2002 until PTI ceased normal operations in late 2008 are presented. Infrared differential photometry of several PHASES targets were measured with Keck Adaptive Optics and are presented.Comment: 33 pages emulateapj, Accepted to A

Designing hollow nano gold golf balls.

Hollow/porous nanoparticles, including nanocarriers, nanoshells, and mesoporous materials have applications in catalysis, photonics, biosensing, and delivery of theranostic agents. Using a hierarchical template synthesis scheme, we have synthesized a nanocarrier mimicking a golf ball, consisting of (i) solid silica core with a pitted gold surface and (ii) a hollow/porous gold shell without silica. The template consisted of 100 nm polystyrene beads attached to a larger silica core. Selective gold plating of the core followed by removal of the polystyrene beads produced a golf ball-like nanostructure with 100 nm pits. Dissolution of the silica core produced a hollow/porous golf ball-like nanostructure

T-infinity: The Dependency Inversion Principle for Rapid and Sustainable Multidisciplinary Software Development

The CFD Vision 2030 Study recommends that, NASA should develop and maintain an integrated simulation and software development infrastructure to enable rapid CFD technology maturation.... [S]oftware standards and interfaces must be emphasized and supported whenever possible, and open source models for noncritical technology components should be adopted. The current paper presents an approach to an open source development architecture, named T-infinity, for accelerated research in CFD leveraging the Dependency Inversion Principle to realize plugins that communicate through collections of functions without exposing internal data structures. Steady state flow visualization, mesh adaptation, fluid-structure interaction, and overset domain capabilities are demonstrated through compositions of plugins via standardized abstract interfaces without the need for source code dependencies between disciplines. Plugins interact through abstract interfaces thereby avoiding N 2 direct code-to-code data structure coupling where N is the number of codes. This plugin architecture enhances sustainable development by controlling the interaction between components to limit software complexity growth. The use of T-infinity abstract interfaces enables multidisciplinary application developers to leverage legacy applications alongside newly-developed capabilities. While rein, a description of interface details is deferred until the are more thoroughly tested and can be closed to modification

Baryon Acoustic Oscillations in the Ly{\alpha} forest of BOSS DR11 quasars

We report a detection of the baryon acoustic oscillation (BAO) feature in the flux-correlation function of the Ly{\alpha} forest of high-redshift quasars with a statistical significance of five standard deviations. The study uses 137,562 quasars in the redshift range $2.1\le z \le 3.5$ from the Data Release 11 (DR11) of the Baryon Oscillation Spectroscopic Survey (BOSS) of SDSS-III. This sample contains three times the number of quasars used in previous studies. The measured position of the BAO peak determines the angular distance, $D_A(z=2.34)$ and expansion rate, $H(z=2.34)$, both on a scale set by the sound horizon at the drag epoch, $r_d$. We find $D_A/r_d=11.28\pm0.65(1\sigma)^{+2.8}_{-1.2}(2\sigma)$ and $D_H/r_d=9.18\pm0.28(1\sigma)\pm0.6(2\sigma)$ where $D_H=c/H$. The optimal combination, $\sim D_H^{0.7}D_A^{0.3}/r_d$ is determined with a precision of $\sim2\%$. For the value $r_d=147.4~{\rm Mpc}$, consistent with the CMB power spectrum measured by Planck, we find $D_A(z=2.34)=1662\pm96(1\sigma)~{\rm Mpc}$ and $H(z=2.34)=222\pm7(1\sigma)~{\rm km\,s^{-1}Mpc^{-1}}$. Tests with mock catalogs and variations of our analysis procedure have revealed no systematic uncertainties comparable to our statistical errors. Our results agree with the previously reported BAO measurement at the same redshift using the quasar-Ly{\alpha} forest cross-correlation. The auto-correlation and cross-correlation approaches are complementary because of the quite different impact of redshift-space distortion on the two measurements. The combined constraints from the two correlation functions imply values of $D_A/r_d$ and $D_H/r_d$ that are, respectively, 7% low and 7% high compared to the predictions of a flat $\Lambda$CDM cosmological model with the best-fit Planck parameters. With our estimated statistical errors, the significance of this discrepancy is $\approx 2.5\sigma$.Comment: Accepted for publication in A&A. 17 pages, 18 figure

Chemical Cartography with APOGEE: Large-scale Mean Metallicity Maps of the Milky Way

We present Galactic mean metallicity maps derived from the first year of the SDSS-III APOGEE experiment. Mean abundances in different zones of Galactocentric radius (0 < R < 15 kpc) at a range of heights above the plane (0 < |z| < 3 kpc), are derived from a sample of nearly 20,000 stars with unprecedented coverage, including stars in the Galactic mid-plane at large distances. We also split the sample into subsamples of stars with low and high-[{\alpha}/M] abundance ratios. We assess possible biases in deriving the mean abundances, and find they are likely to be small except in the inner regions of the Galaxy. A negative radial gradient exists over much of the Galaxy; however, the gradient appears to flatten for R < 6 kpc, in particular near the Galactic mid-plane and for low-[{\alpha}/M] stars. At R > 6 kpc, the gradient flattens as one moves off of the plane, and is flatter at all heights for high-[{\alpha}/M] stars than for low-[{\alpha}/M] stars. Alternatively, these gradients can be described as vertical gradients that flatten at larger Galactocentric radius; these vertical gradients are similar for both low and high-[{\alpha}/M] populations. Stars with higher [{\alpha}/M] appear to have a flatter radial gradient than stars with lower [{\alpha}/M]. This could suggest that the metallicity gradient has grown steeper with time or, alternatively, that gradients are washed out over time by migration of stars.Comment: 16 pages, 12 figures, submitted to A