The role of novel Rydberg-valence behaviour in the non-adiabatic dynamics of tertiary aliphatic amines

Time-resolved photoelectron imaging was used to study non-adiabatic relaxation dynamics in N,N-dimethylisopropylamine, N,N-dimethylpropylamine and N-methylpyrrolidine following excitation at 200 nm.</p

Orchestration of the S-phase and DNA damage checkpoint pathways by replication forks from early origins

The S-phase checkpoint activated at replication forks coordinates DNA replication when forks stall because of DNA damage or low deoxyribonucleotide triphosphate pools. We explore the involvement of replication forks in coordinating the S-phase checkpoint using dun1Δ cells that have a defect in the number of stalled forks formed from early origins and are dependent on the DNA damage Chk1p pathway for survival when replication is stalled. We show that providing additional origins activated in early S phase and establishing a paused fork at a replication fork pause site restores S-phase checkpoint signaling to chk1Δ dun1Δ cells and relieves the reliance on the DNA damage checkpoint pathway. Origin licensing and activation are controlled by the cyclin–Cdk complexes. Thus, oncogene-mediated deregulation of cyclins in the early stages of cancer development could contribute to genomic instability through a deficiency in the forks required to establish the S-phase checkpoint

Decay of isolated surface features driven by the Gibbs-Thomson effect in analytic model and simulation

A theory based on the thermodynamic Gibbs-Thomson relation is presented which provides the framework for understanding the time evolution of isolated nanoscale features (i.e., islands and pits) on surfaces. Two limiting cases are predicted, in which either diffusion or interface transfer is the limiting process. These cases correspond to similar regimes considered in previous works addressing the Ostwald ripening of ensembles of features. A third possible limiting case is noted for the special geometry of "stacked" islands. In these limiting cases, isolated features are predicted to decay in size with a power law scaling in time: A is proportional to (t0-t)^n, where A is the area of the feature, t0 is the time at which the feature disappears, and n=2/3 or 1. The constant of proportionality is related to parameters describing both the kinetic and equilibrium properties of the surface. A continuous time Monte Carlo simulation is used to test the application of this theory to generic surfaces with atomic scale features. A new method is described to obtain macroscopic kinetic parameters describing interfaces in such simulations. Simulation and analytic theory are compared directly, using measurements of the simulation to determine the constants of the analytic theory. Agreement between the two is very good over a range of surface parameters, suggesting that the analytic theory properly captures the necessary physics. It is anticipated that the simulation will be useful in modeling complex surface geometries often seen in experiments on physical surfaces, for which application of the analytic model is not straightforward.Comment: RevTeX (with .bbl file), 25 pages, 7 figures from 9 Postscript files embedded using epsf. Submitted to Phys. Rev. B A few minor changes made on 9/24/9

N-body simulations of gravitational dynamics

We describe the astrophysical and numerical basis of N-body simulations, both of collisional stellar systems (dense star clusters and galactic centres) and collisionless stellar dynamics (galaxies and large-scale structure). We explain and discuss the state-of-the-art algorithms used for these quite different regimes, attempt to give a fair critique, and point out possible directions of future improvement and development. We briefly touch upon the history of N-body simulations and their most important results.Comment: invited review (28 pages), to appear in European Physics Journal Plu

The DNA Damage Response Pathway Contributes to the Stability of Chromosome III Derivatives Lacking Efficient Replicators

In eukaryotic chromosomes, DNA replication initiates at multiple origins. Large inter-origin gaps arise when several adjacent origins fail to fire. Little is known about how cells cope with this situation. We created a derivative of Saccharomyces cerevisiae chromosome III lacking all efficient origins, the 5ORIΔ-ΔR fragment, as a model for chromosomes with large inter-origin gaps. We used this construct in a modified synthetic genetic array screen to identify genes whose products facilitate replication of long inter-origin gaps. Genes identified are enriched in components of the DNA damage and replication stress signaling pathways. Mrc1p is activated by replication stress and mediates transduction of the replication stress signal to downstream proteins; however, the response-defective mrc1AQ allele did not affect 5ORIΔ-ΔR fragment maintenance, indicating that this pathway does not contribute to its stability. Deletions of genes encoding the DNA-damage-specific mediator, Rad9p, and several components shared between the two signaling pathways preferentially destabilized the 5ORIΔ-ΔR fragment, implicating the DNA damage response pathway in its maintenance. We found unexpected differences between contributions of components of the DNA damage response pathway to maintenance of ORIΔ chromosome derivatives and their contributions to DNA repair. Of the effector kinases encoded by RAD53 and CHK1, Chk1p appears to be more important in wild-type cells for reducing chromosomal instability caused by origin depletion, while Rad53p becomes important in the absence of Chk1p. In contrast, RAD53 plays a more important role than CHK1 in cell survival and replication fork stability following treatment with DNA damaging agents and hydroxyurea. Maintenance of ORIΔ chromosomes does not depend on homologous recombination. These observations suggest that a DNA-damage-independent mechanism enhances ORIΔ chromosome stability. Thus, components of the DNA damage response pathway contribute to genome stability, not simply by detecting and responding to DNA template damage, but also by facilitating replication of large inter-origin gaps

Ash agglomeration and deposition during combustion of poultry litter in a bubbling fluidized-bed combustor

peer-reviewedn this study, we have characterized the ash resulting from fluidized bed combustion of poultry litter as being dominated by a coarse fraction of crystalline ash composed of alkali-Ca-phosphates and a fine fraction of particulate K2SO4 and KCl. Bed agglomeration was found to be coating-induced with two distinct layers present. The inner layer (0.05–0.09 mm thick) was formed due to the reaction of gaseous potassium with the sand (SiO2) surface forming K-silicates with low melting points. Further chemical reaction on the surface of the bed material strengthened the coating forming a molten glassy phase. The outer layer was composed of loosely bound, fine particulate ash originating from the char. Thermodynamic equilibrium calculations showed slag formation in the combustion zone is highly temperature-dependent, with slag formation predicted to increase from 1.8 kg at 600 °C to 7.35 kg at 1000 °C per hour of operation (5.21 kg of ash). Of this slag phase, SiO2 and K2O were the dominant phases, accounting for almost 95%, highlighting the role of K-silicates in initiating bed agglomeration. The remaining 5% was predicted to consist mainly of Al2O3, K2SO4, and Na2O. Deposition downstream in the low-temperature regions was found to occur mostly through the vaporization–condensation mechanism, with equilibrium decreasing significantly with decreasing temperatures. The dominant alkali chloride-containing gas predicted to form in the combustion zone was KCl, which corresponds with the high KCl content in the fine baghouse ash

The Origin Recognition Complex Interacts with a Subset of Metabolic Genes Tightly Linked to Origins of Replication

The origin recognition complex (ORC) marks chromosomal sites as replication origins and is essential for replication initiation. In yeast, ORC also binds to DNA elements called silencers, where its primary function is to recruit silent information regulator (SIR) proteins to establish transcriptional silencing. Indeed, silencers function poorly as chromosomal origins. Several genetic, molecular, and biochemical studies of HMR-E have led to a model proposing that when ORC becomes limiting in the cell (such as in the orc2-1 mutant) only sites that bind ORC tightly (such as HMR-E) remain fully occupied by ORC, while lower affinity sites, including many origins, lose ORC occupancy. Since HMR-E possessed a unique non-replication function, we reasoned that other tight sites might reveal novel functions for ORC on chromosomes. Therefore, we comprehensively determined ORC “affinity” genome-wide by performing an ORC ChIP–on–chip in ORC2 and orc2-1 strains. Here we describe a novel group of orc2-1–resistant ORC–interacting chromosomal sites (ORF–ORC sites) that did not function as replication origins or silencers. Instead, ORF–ORC sites were comprised of protein-coding regions of highly transcribed metabolic genes. In contrast to the ORC–silencer paradigm, transcriptional activation promoted ORC association with these genes. Remarkably, ORF–ORC genes were enriched in proximity to origins of replication and, in several instances, were transcriptionally regulated by these origins. Taken together, these results suggest a surprising connection among ORC, replication origins, and cellular metabolism

Pain coping skills training for African Americans with osteoarthritis (STAART): study protocol of a randomized controlled trial

Background: African Americans bear a disproportionate burden of osteoarthritis (OA), with higher prevalence rates, more severe pain, and more functional limitations. One key barrier to addressing these disparities has been limited engagement of African Americans in the development and evaluation of behavioral interventions for management of OA. Pain Coping Skills Training (CST) is a cognitive-behavioral intervention with shown efficacy to improve OA-related pain and other outcomes. Emerging data indicate pain CST may be a promising intervention for reducing racial disparities in OA symptom severity. However, there are important gaps in this research, including incorporation of stakeholder perspectives (e.g. cultural appropriateness, strategies for implementation into clinical practice) and testing pain CST specifically among African Americans with OA. This study will evaluate the effectiveness of a culturally enhanced pain CST program among African Americans with OA. Methods/Design: This is a randomized controlled trial among 248 participants with symptomatic hip or knee OA, with equal allocation to a pain CST group and a wait list (WL) control group. The pain CST program incorporated feedback from patients and other stakeholders and involves 11 weekly telephone-based sessions. Outcomes are assessed at baseline, 12 weeks (primary time point), and 36 weeks (to assess maintenance of treatment effects). The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index, and secondary outcomes include self-efficacy, pain coping, pain interference, quality of life, depressive symptoms, and global assessment of change. Linear mixed models will be used to compare the pain CST group to the WL control group and explore whether participant characteristics are associated with differential improvement in the pain CST program. This research is in compliance with the Helsinki Declaration and was approved by the Institutional Review Boards of the University of North Carolina at Chapel Hill, Durham Veterans Affairs Medical Center, East Carolina University, and Duke University Health System. Discussion: This culturally enhanced pain CST program could have a substantial impact on outcomes for African Americans with OA and may be a key strategy in the reduction of racial health disparities.Funded by Patient-Centered Outcomes Research Institute (PCORI) Award (AD-1408-19519)

Pentavalent HIV-1 vaccine protects against simian-human immunodeficiency virus challenge

The RV144 Thai trial HIV-1 vaccine of recombinant poxvirus (ALVAC) and recombinant HIV-1 gp120 subtype B/subtype E (B/E) proteins demonstrated 31% vaccine efficacy. Here we design an ALVAC/Pentavalent B/E/E/E/E vaccine to increase the diversity of gp120 motifs in the immunogen to elicit a broader antibody response and enhance protection. We find that immunization of rhesus macaques with the pentavalent vaccine results in protection of 55% of pentavalent-vaccine-immunized macaques from simian–human immunodeficiency virus (SHIV) challenge. Systems serology of the antibody responses identifies plasma antibody binding to HIV-infected cells, peak ADCC antibody titres, NK cell-mediated ADCC and antibody-mediated activation of MIP-1β in NK cells as the four immunological parameters that best predict decreased infection risk that are improved by the pentavalent vaccine. Thus inclusion of additional gp120 immunogens to a pox-prime/protein boost regimen can augment antibody responses and enhance protection from a SHIV challenge in rhesus macaques