Computational Investigations on Polymerase Actions in Gene Transcription and Replication Combining Physical Modeling and Atomistic Simulations

Polymerases are protein enzymes that move along nucleic acid chains and catalyze template-based polymerization reactions during gene transcription and replication. The polymerases also substantially improve transcription or replication fidelity through the non-equilibrium enzymatic cycles. We briefly review computational efforts that have been made toward understanding mechano-chemical coupling and fidelity control mechanisms of the polymerase elongation. The polymerases are regarded as molecular information motors during the elongation process. It requires a full spectrum of computational approaches from multiple time and length scales to understand the full polymerase functional cycle. We keep away from quantum mechanics based approaches to the polymerase catalysis due to abundant former surveys, while address only statistical physics modeling approach and all-atom molecular dynamics simulation approach. We organize this review around our own modeling and simulation practices on a single-subunit T7 RNA polymerase, and summarize commensurate studies on structurally similar DNA polymerases. For multi-subunit RNA polymerases that have been intensively studied in recent years, we leave detailed discussions on the simulation achievements to other computational chemical surveys, while only introduce very recently published representative studies, including our own preliminary work on structure-based modeling on yeast RNA polymerase II. In the end, we quickly go through kinetic modeling on elongation pauses and backtracking activities. We emphasize the fluctuation and control mechanisms of the polymerase actions, highlight the non-equilibrium physical nature of the system, and try to bring some perspectives toward understanding replication and transcription regulation from single molecular details to a genome-wide scale

Control of a lane-drop bottleneck through variable speed limits

In this study, we formulate the VSL control problem for the traffic system in a zone upstream to a lane-drop bottleneck based on two traffic flow models: the Lighthill-Whitham-Richards (LWR) model, which is an infinite-dimensional partial differential equation, and the link queue model, which is a finite-dimensional ordinary differential equation. In both models, the discharging flow-rate is determined by a recently developed model of capacity drop, and the upstream in-flux is regulated by the speed limit in the VSL zone. Since the link queue model approximates the LWR model and is much simpler, we first analyze the control problem and develop effective VSL strategies based on the former. First for an open-loop control system with a constant speed limit, we prove that a constant speed limit can introduce an uncongested equilibrium state, in addition to a congested one with capacity drop, but the congested equilibrium state is always exponentially stable. Then we apply a feedback proportional-integral (PI) controller to form a closed-loop control system, in which the congested equilibrium state and, therefore, capacity drop can be removed by the I-controller. Both analytical and numerical results show that, with appropriately chosen controller parameters, the closed-loop control system is stable, effect, and robust. Finally, we show that the VSL strategies based on I- and PI-controllers are also stable, effective, and robust for the LWR model. Since the properties of the control system are transferable between the two models, we establish a dual approach for studying the control problems of nonlinear traffic flow systems. We also confirm that the VSL strategy is effective only if capacity drop occurs. The obtained method and insights can be useful for future studies on other traffic control methods and implementations of VSL strategies.Comment: 31 pages, 14 figure

Training Students for Critical Thinking in an Electrical Engineering Core Course

Analysis and Design of Control Systems is a core course in most Electrical Engineering programs in the United States. This course is the first course that provides a systemic view of engineering designs and links classroom knowledge to real-world applications. Training students for critical thinking (CT) skills in this class is essential to their career success. However, a high D and F grades and withdraw (DFW) rate has been observed in this course for years. The goal of this study is to redesign the course components to integrate critical thinking training into classroom activities and reform students’ habits in problem-solving. The new course components include a series of lectures on cognition, critical thinking, examples of famous engineering projects with critical thinking, and decomposition of critical thinking skills in classroom examples. Evaluation of the new course module was conducted based on critical thinking assessment test, two student surveys through the semester, three classroom observations, and students’ performance comparing against an untrained control group in the previous semester. Our results illustrated an effective way to improve critical thinking with this training module.Cockrell School of Engineerin

Credit Termination and the Technology Bubbles

We study the role of firms' credit histories in a business cycle model. Loans are dynamic contracts between banks and firms, and credit terminations are used as an incentive device. Banks deny future loans to an entrepreneur according to his credit histories in order to affect his choice of project ex ante. This will generate fluctuations from technology shocks to the riskiness of different types of projects as occurred during the technology bubbles. The model is used to explain the boom-and-bust of the dot-com bubble, one leading example of technology bubbles in the economy, in the late 1990s.credit terminations; technology bubbles

Z-pole test of effective dark matter diboson interactions at the CEPC

In this paper we investigate the projected sensitivity to effective dark matter (DM) - diboson interaction during the high luminosity $Z$-pole and 240 GeV runs at the proposed Circular Electron Positron Collider (CEPC). The proposed runs at the 91.2 GeV $e^+e^-$ center of mass energy offers an interesting opportunity to probe effective dark matter couplings to the $Z$ boson, which can be less stringently tested in non-collider searches. We investigate the prospective sensitivity for dimension 6 and dimension 7 effective diboson operators to scalar and fermion dark matter. These diboson operators can generate semi-visible $Z$ boson decay, and high missing transverse momentum mono-photon signals that can be test efficiently at the CEPC, with a small and controllable Standard Model $\gamma\bar{\nu}\nu$ background. A projected sensitivity for effective $\gamma Z$ coupling efficient $\kappa_{\gamma Z}< (1030$ GeV$)^{-3}$, $(1970$ GeV$)^{-3}$ for scalar DM, $\kappa_{\gamma Z}< (360$ GeV$)^{-3}$, $(540$ GeV$)^{-3}$ for fermion DM are obtain for 25 fb$^{-1}$ and 2.5 ab$^{-1}$ $Z$-pole luminosities assuming the optimal low dark matter mass range. In comparison the effective DM-diphoton coupling sensitivity $\kappa_{\gamma \gamma}< (590$ GeV$)^{-3}$ for scalar DM, $\kappa_{\gamma \gamma}< (360$ GeV$)^{-3}$ for fermion DM are also obtained for a 5 ab$^{-1}$ 240 GeV Higgs run. We also compare the CEPC sensitivities to current direct and indirect search limits on these effective DM-diboson operators.Comment: 10 pages, 7 figures. Dimension-6 diboson operators include