Impact of template backbone heterogeneity on RNA polymerase II transcription.

Variations in the sugar component (ribose or deoxyribose) and the nature of the phosphodiester linkage (3'-5' or 2'-5' orientation) have been a challenge for genetic information transfer from the very beginning of evolution. RNA polymerase II (pol II) governs the transcription of DNA into precursor mRNA in all eukaryotic cells. How pol II recognizes DNA template backbone (phosphodiester linkage and sugar) and whether it tolerates the backbone heterogeneity remain elusive. Such knowledge is not only important for elucidating the chemical basis of transcriptional fidelity but also provides new insights into molecular evolution. In this study, we systematically and quantitatively investigated pol II transcriptional behaviors through different template backbone variants. We revealed that pol II can well tolerate and bypass sugar heterogeneity sites at the template but stalls at phosphodiester linkage heterogeneity sites. The distinct impacts of these two backbone components on pol II transcription reveal the molecular basis of template recognition during pol II transcription and provide the evolutionary insight from the RNA world to the contemporary 'imperfect' DNA world. In addition, our results also reveal the transcriptional consequences from ribose-containing genomic DNA

Lift-Based Bidding in Ad Selection

Real-time bidding (RTB) has become one of the largest online advertising markets in the world. Today the bid price per ad impression is typically decided by the expected value of how it can lead to a desired action event (e.g., registering an account or placing a purchase order) to the advertiser. However, this industry standard approach to decide the bid price does not consider the actual effect of the ad shown to the user, which should be measured based on the performance lift among users who have been or have not been exposed to a certain treatment of ads. In this paper, we propose a new bidding strategy and prove that if the bid price is decided based on the performance lift rather than absolute performance value, advertisers can actually gain more action events. We describe the modeling methodology to predict the performance lift and demonstrate the actual performance gain through blind A/B test with real ad campaigns in an industry-leading Demand-Side Platform (DSP). We also discuss the relationship between attribution models and bidding strategies. We prove that, to move the DSPs to bid based on performance lift, they should be rewarded according to the relative performance lift they contribute.Comment: AAAI 201

STUDY ON EARTHQUAKE DAMAGE MECHANISM OF AQUEDUCT STRUCTURE BASED ON DIFFERENT BOUNDARY

Numerically simulating an infinite domain foundation is an important method for solving structural dynamics problems. This paper introduces several artificial dynamic boundaries commonly used in the study of structural dynamics, and elaborates the theory and methods of the dynamic infinite element method boundary (IEMB) and viscous–spring artificial boundary (VSAB). The capacity of different boundary effects on seismic waves energy absorption is verified by establishing a layered half-space model. An irrigation aqueduct is taken as a research object. The IEMB, VSAB, and fixed boundary (FB) models are established and the Concrete Damaged Plasticity (CDP) constitutive is introduced, which is aimed at studying the dynamic failure mechanism and the rules of damage development to the aqueduct structure during the seismic duration. The results for the IEMB and VSAB show better energy absorption for the incident waves and a better simulation result for the damping effect of the far field foundation than that of the FB. Comparing the maximum displacement response rules of the three boundaries, it is seen that the maximum displacement response values of the VSAB and dynamic IEMB increased by 6%–48% and 9%–35%, respectively, over the FB. The calculation results of the VSAB are similar to that of the IEMB. The difference between the maximum acceleration response values is 2%–17% whereas the difference between the maximum displacement response values is 0.4%–19%. The IEMB studied in this paper provides a theoretical reference for large–scale building boundary treatment in structural dynamics calculations

Ce3+, Mn2+ Co-doped Red–light Long–Lasting Phosphor: BaMg2Si2O7 Through Energy Transfer

AbstractThe red light long-lasting phosphors BaMg2Si2O7: Ce3+, Mn2+, Dy3+ were synthesized by solid-state reactions under a weak reductive atmosphere. The energy transfer between Ce3+ and Mn2+ in BaMg2Si2O7 was systematically investigated. Through co-dope with Ce3+ in BaMg2Si2O7:Mn2+, Dy3+, the red phosphorescence of Mn2+ can prolong to more than 2h. Two types of traps were existed in BaMg2Si2O7

Bridge helix bending promotes RNA polymerase II backtracking through a critical and conserved threonine residue.

The dynamics of the RNA polymerase II (Pol II) backtracking process is poorly understood. We built a Markov State Model from extensive molecular dynamics simulations to identify metastable intermediate states and the dynamics of backtracking at atomistic detail. Our results reveal that Pol II backtracking occurs in a stepwise mode where two intermediate states are involved. We find that the continuous bending motion of the Bridge helix (BH) serves as a critical checkpoint, using the highly conserved BH residue T831 as a sensing probe for the 3'-terminal base paring of RNA:DNA hybrid. If the base pair is mismatched, BH bending can promote the RNA 3'-end nucleotide into a frayed state that further leads to the backtracked state. These computational observations are validated by site-directed mutagenesis and transcript cleavage assays, and provide insights into the key factors that regulate the preferences of the backward translocation

STUDY ON EARTHQUAKE DESTRUCTION MODE OF THE LARGEST CANAL CROSSING HIGHWAY BRIDGE BASED ON IEM BOUNDARY IN SOUTH-TO-NORTH WATER DIVERSION

  To study the dynamic failure mechanism and damage development law of highway bridge structure under the boundary effect in the process of seismic dynamic duration, the Wenchang Highway Bridge with the largest canal crossing in the South-to-North Water Diversion is taken as an example for seismic design analysis. Based on the finite element and infinite element coupling theory, the infinite element method boundary is introduced, the concrete damage plasticity is introduced, and the half-space free field model is established to study the energy dispersion phenomenon of waves in the boundary and the absorption effect of the infinite element method boundary on wave energy is verified. Under different peak acceleration intensities, the seismic response analysis of the bridge structure was carried out. The results show that: Under the action of selected artificial waves, the damage location of the bridge mainly concentrated in the junction of the box girder supported by the pier, the bottom of the pier and the junction of the pier and beam. The damage tends to develop downward near the bottom of the box girder. The damage at both ends of the beam extends from both ends to the middle. And the bottom and top of the pier have penetrating damage. These are weak points in seismic design. At a horizontal peak acceleration of 0.6g, in addition to damage to the pier column, damage also occurred to the bottom of the box girder. Therefore, when the horizontal peak acceleration of the seismic wave is greater than 0.6g, the failure of the bottom of the box girder is paid attention to. Moreover, the IEM boundary has a good control effect on the far-field energy dissipation of the wave, which is simpler and more efficient than the viscous–spring boundary

Functional interplay between NTP leaving group and base pair recognition during RNA polymerase II nucleotide incorporation revealed by methylene substitution.

RNA polymerase II (pol II) utilizes a complex interaction network to select and incorporate correct nucleoside triphosphate (NTP) substrates with high efficiency and fidelity. Our previous 'synthetic nucleic acid substitution' strategy has been successfully applied in dissecting the function of nucleic acid moieties in pol II transcription. However, how the triphosphate moiety of substrate influences the rate of P-O bond cleavage and formation during nucleotide incorporation is still unclear. Here, by employing β,γ-bridging atom-'substituted' NTPs, we elucidate how the methylene substitution in the pyrophosphate leaving group affects cognate and non-cognate nucleotide incorporation. Intriguingly, the effect of the β,γ-methylene substitution on the non-cognate UTP/dT scaffold (∼3-fold decrease in kpol) is significantly different from that of the cognate ATP/dT scaffold (∼130-fold decrease in kpol). Removal of the wobble hydrogen bonds in U:dT recovers a strong response to methylene substitution of UTP. Our kinetic and modeling studies are consistent with a unique altered transition state for bond formation and cleavage for UTP/dT incorporation compared with ATP/dT incorporation. Collectively, our data reveals the functional interplay between NTP triphosphate moiety and base pair hydrogen bonding recognition during nucleotide incorporation