Genome-wide organization of eukaryotic pre-initiation complex is influenced by nonconsensus protein-DNA binding

Genome-wide binding preferences of the key components of eukaryotic pre-initiation complex (PIC) have been recently measured with high resolution in Saccharomyces cerevisiae by Rhee and Pugh (Nature (2012) 483:295-301). Yet the rules determining the PIC binding specificity remain poorly understood. In this study we show that nonconsensus protein-DNA binding significantly influences PIC binding preferences. We estimate that such nonconsensus binding contribute statistically at least 2-3 kcal/mol (on average) of additional attractive free energy per protein, per core promoter region. The predicted attractive effect is particularly strong at repeated poly(dA:dT) and poly(dC:dG) tracts. Overall, the computed free energy landscape of nonconsensus protein-DNA binding shows strong correlation with the measured genome-wide PIC occupancy. Remarkably, statistical PIC binding preferences to both TFIID-dominated and SAGA-dominated genes correlate with the nonconsensus free energy landscape, yet these two groups of genes are distinguishable based on the average free energy profiles. We suggest that the predicted nonconsensus binding mechanism provides a genome-wide background for specific promoter elements, such as transcription factor binding sites, TATA-like elements, and specific binding of the PIC components to nucleosomes. We also show that nonconsensus binding influences transcriptional frequency genome-wide

Online Dispute Resolution Through the Lens of Bargaining and Negotiation Theory: Toward an Integrated Model

[Excerpt] In this article we apply negotiation and bargaining theory to the analysis of online dispute resolution. Our principal objective is to develop testable hypotheses based on negotiation theory that can be used in ODR research. We have not conducted the research necessary to test the hypotheses we develop; however, in a later section of the article we suggest a possible methodology for doing so. There is a vast literature on negotiation and bargaining theory. For the purposes of this article, we realized at the outset that we could only use a small part of that literature in developing a model that might be suitable for empirical testing. We decided to use the behavioral theory of negotiation developed by Richard Walton and Robert McKersie, which was initially formulated in the 1960s. This theory has stood the test of time. Initially developed to explain union-management negotiations, it has proven useful in analyzing a wide variety of disputes and conflict situations. In constructing their theory, Walton and McKersie built on the contributions and work of many previous bargaining theorists including economists, sociologists, game theorists, and industrial relations scholars. In this article, we have incorporated a consideration of the foundations on which their theory was based. In the concluding section of the article we discuss briefly how other negotiation and bargaining theories might be applied to the analysis of ODR

Sequence correlations shape protein promiscuity

We predict analytically that diagonal correlations of amino acid positions within protein sequences statistically enhance protein propensity for nonspecific binding. We use the term 'promiscuity' to describe such nonspecific binding. Diagonal correlations represent statistically significant repeats of sequence patterns where amino acids of the same type are clustered together. The predicted effect is qualitatively robust with respect to the form of the microscopic interaction potentials and the average amino acid composition. Our analytical results provide an explanation for the enhanced diagonal correlations observed in hubs of eukaryotic organismal proteomes [J. Mol. Biol. 409, 439 (2011)]. We suggest experiments that will allow direct testing of the predicted effect

Organizational Conflict Resolution and Strategic Choice: Evidence from a Survey of Fortune 1000 Companies

In this paper we develop the argument that a firm’s ADR strategies are likely to be associated with a firm’s use of one conflict resolution option or the other. More specifically, we examine whether a firm’s use of either arbitration or mediation is a function of (1) the extent to which the use of either of these dispute resolution processes aligns with the goals and objectives management is seeking to advance, and (2) the extent of the firm’s commitment to the use of these practices. We expect to find that an organization’s use of either mediation or arbitration may be governed by different underlying strategic objectives as well as the firm’s broader commitment to ADR. In what follows, we further develop this strategic choice argument

Organizational Strategies for the Adoption of Electronic Medical Records: Toward an Understanding of Outcome Variation in Nursing Homes

[Excerpt] An important element in president-elect Obama\u27s economic stimulus proposal is his plan to invest a significant proportion of federal dollars in installing electronic medical records (EMR) in U.S. healthcare institutions. In emphasizing the need for EMR, Obama is following the advice of numerous healthcare experts who have pointed out that the healthcare sector lags behind other industries in the use of computer technology. They believe the widespread use of EMR would help reduce medical errors, control the costs of healthcare, and lead to significant improvements in the quality of care Americans receive. In this paper we present preliminary results of an ongoing study of the introduction of EMR in 20 nursing homes in the New York City area. Although most observers believe EMR holds great promise for the improvement of healthcare, in fact recent studies have found mixed evidence regarding the effect of EMR on patient outcomes. The evidence we have gathered to date suggests that whether EMR has beneficial effects on the costs and quality of healthcare depends very much on the purposes and objectives nursing home managers and administrators intend to achieve through its use. That is, management strategy and style, we believe, strongly influences healthcare outcomes associated with technological innovation

From the Negotiating Arena to Conflict Management

Richard Walton and Robert McKersie’s A Behavioral Theory of Labor Negotiations has influenced generations of scholars who have studied conflict resolution and negotiations, as well as countless negotiation practitioners (Walton and McKersie 1991; for an assessment of Walton and McKersie’s influence on research and practice, see Kochan and Lipsky 2003). In this article, we extend Walton and McKersie’s theory, which focused on the negotiations between unions and employers, to consider its implications for the strategic choices made by organizations as they develop conflict management policies.We begin by discussing Walton and McKersie’s influence on the language that both scholars and practitioners use to describe not only negotiating behavior but also the strategies organizations pursue to manage workplace conflict

Deconfinement Phase Transition in Hot and Dense QCD at Large N

We conjecture that the confinement- deconfinement phase transition in QCD at large number of colors $N$ and $N_f\ll N$ at $T\neq 0$ and $\mu\neq 0$ is triggered by the drastic change in $\theta$ behavior. The conjecture is motivated by the holographic model of QCD where confinement -deconfinement phase transition indeed happens precisely at $T=T_c$ where $\theta$ dependence experiences a sudden change in behavior. The conjecture is also supported by quantum field theory arguments when the instanton calculations (which trigger the $\theta$ dependence) are under complete theoretical control for $T>T_c$, suddenly break down immediately below $T<T_c$ with sharp changes in the $\theta$ dependence. Finally, the conjecture is supported by a number of numerical lattice results. We employ this conjecture to study confinement -deconfinement phase transition of hot and dense QCD in large $N$ limit by analyzing the $\theta$ dependence. We estimate the critical values for $T_c$ and $\mu_c$ where the phase transition happens by approaching the critical values from the hot and/or dense regions where the instanton calculations are under complete theoretical control. We also describe some defects of various codimensions within a holographic model of QCD by focusing on their role around the phase transition point.Comment: Talk at the Workshop honoring 60th anniversary of Misha Shifma

Possible Signatures Of Dissipation From Time-Series Analysis Techniques Using A Turbulent Laboratory Magnetohydrodynamic Plasma

The frequency spectrum of magnetic fluctuations as measured on the Swarthmore Spheromak Experiment is broadband and exhibits a nearly Kolmogorov 5/3 scaling. It features a steepening region which is indicative of dissipation of magnetic fluctuation energy similar to that observed in fluid and magnetohydrodynamic turbulence systems. Two non-spectrum based time-series analysis techniques are implemented on this data set in order to seek other possible signatures of turbulent dissipation beyond just the steepening of fluctuation spectra. Presented here are results for the flatness, permutation entropy, and statistical complexity, each of which exhibits a particular character at spectral steepening scales which can then be compared to the behavior of the frequency spectrum

Contact Term, its Holographic Description in QCD and Dark Energy

In this work we study the well known contact term, which is the key element in resolving the so-called $U(1)_A$ problem in QCD. We study this term using the dual Holographic Description. We argue that in the dual picture the contact term is saturated by the D2 branes which can be interpreted as the tunnelling events in Minkowski space-time. We quote a number of direct lattice results supporting this identification. We also argue that the contact term receives a Casimir -like correction \sim (\Lqcd R)^{-1} rather than naively expected \exp(-\Lqcd R) when the Minkowski space-time ${\cal R}_{3,1}$ is replaced by a large but finite manifold with a size $R$. Such a behaviour is consistent with other QFT-based computations when power like corrections are due to nontrivial properties of topological sectors of the theory. In holographic description such a behaviour is due to massless Ramond-Ramond (RR) field living in the bulk of multidimensional space when power like corrections is a natural outcome of massless RR field. In many respects the phenomenon is similar to the Aharonov -Casher effect when the "modular electric field" can penetrate into a superconductor where the electric field is exponentially screened. The role of "modular operator" from Aharonov -Casher effect is played by large gauge transformation operator $\cal{T}$ in 4d QCD, resulting the transparency of the system to topologically nontrivial pure gauge configurations. We discuss some profound consequences of our findings. In particular, we speculate that a slow variation of the contact term in expanding universe might be the main source of the observed Dark Energy.Comment: Final version to appear in Phys. Rev. D. Comments added on interpretation of the "topological Casimir effect" from 5d viewpoint where it can be thought as conventional Casimir effec