scholarly journals Efficient fidelity control by stepwise nucleotide selection in polymerase elongation Abstract: Polymerases select nucleotides

2014 ◽  
Vol 2 (1) ◽  
pp. 141-160 ◽  
Author(s):  
Jin Yu

Abstract Polymerases select nucleotides according to a template before incorporating them for chemical synthesis during gene replication or transcription. Efficient selection to achieve sufficiently high fidelity and speed is essential for polymerase function. Due to multiple kinetic steps detected in a polymerase elongation cycle, there exist multiple selection checkpoints to allow different strategies of fidelity control. In our current work, we examined step-by-step selections in an elongation cycle that have conformational transition rates tuned one at a time, with a controlled differentiation free energy between the right and wrong nucleotides at each checkpoint. The elongation is sustained at non-equilibrium steady state with constant free energy input and heat dissipation. It is found that a selection checkpoint in the later stage of a reaction path has less capability for error reduction. Hence, early selection is essential to achieve an efficient fidelity control. In particular, for an intermediate state, the selection through the forward transition inhibition has the same capacity for error reduction as the selection through the backward rejection. As with respect to the elongation speed, an initial screening is indispensible for maintaining high speed, as the wrong nucleotides can be removed quickly and replaced by the right ones at the entry. Overall, the elongation error rate can be repeatedly reduced through multiple selection checkpoints. This study provides a theoretical framework to guide more detailed structural dynamics studies, and to support rational redesign of related enzymes and devices.

2020 ◽  
Vol 43 ◽  
Author(s):  
Robert Mirski ◽  
Mark H. Bickhard ◽  
David Eck ◽  
Arkadiusz Gut

Abstract There are serious theoretical problems with the free-energy principle model, which are shown in the current article. We discuss the proposed model's inability to account for culturally emergent normativities, and point out the foundational issues that we claim this inability stems from.


2019 ◽  
Vol 118 (6) ◽  
pp. 145-149
Author(s):  
A. Ekanthalingam ◽  
Dr. A. Gopinath

‘Marketing’ is not just an activity. It is a process, a philosophy and a phenomenon. The evolution of marketing has produced tremendous benefits to business and end consumers. The innovation in this field has been steady and yet at high speed. From ‘word of mouth advertising’ which was the only option earlier we are now at the mercy of what consumers are sharing about their experience on the internet. Social Media has become more powerful than what we think and this article shows how we can leverage this to benefit the top-line and customer delight. We dive deep to understand the influence Social Media can create towards purchase of residential property. As much complex it is to make the purchase decision of a property, it is equally difficult for marketers to send the right message to their target audience. Through this article, we are trying to see how marketers have transformed their traditional marketing strategies to address the needs of the millennial population, who are the most potential customers for property purchase.


2007 ◽  
Vol 567-568 ◽  
pp. 185-188 ◽  
Author(s):  
Miroslav Piska

Modern trends in metal cutting, high speed/feed machining, dry cutting and hard cutting set more demanding characteristics for cutting tool materials. The exposed parts of the cutting edges must be protected against the severe loading conditions and wear. The most significant coatings methods for cutting tools are PVD and CVD/MTCVD today. The choice of the right substrate or the right protective coating in the specific machining operation can have serious impact on machining productivity and economy. In many cases the deposition of the cutting tool with a hard coating increases considerably its cutting performance and tool life. The coating protects the tool against abrasion, adhesion, diffusion, formation of comb cracks and other wear phenomena.


Author(s):  
Feng Wang ◽  
Mauro Carnevale ◽  
Luca di Mare ◽  
Simon Gallimore

Computational Fluid Dynamics (CFD) has been widely used for compressor design, yet the prediction of performance and stage matching for multi-stage, high-speed machines remain challenging. This paper presents the authors’ effort to improve the reliability of CFD in multistage compressor simulations. The endwall features (e.g. blade fillet and shape of the platform edge) are meshed with minimal approximations. Turbulence models with linear and non-linear eddy viscosity models are assessed. The non-linear eddy viscosity model predicts a higher production of turbulent kinetic energy in the passages, especially close to the endwall region. This results in a more accurate prediction of the choked mass flow and the shape of total pressure profiles close to the hub. The non-linear viscosity model generally shows an improvement on its linear counterparts based on the comparisons with the rig data. For geometrical details, truncated fillet leads to thicker boundary layer on the fillet and reduced mass flow and efficiency. Shroud cavities are found to be essential to predict the right blockage and the flow details close to the hub. At the part speed the computations without the shroud cavities fail to predict the major flow features in the passage and this leads to inaccurate predictions of massflow and shapes of the compressor characteristic. The paper demonstrates that an accurate representation of the endwall geometry and an effective turbulence model, together with a good quality and sufficiently refined grid result in a credible prediction of compressor matching and performance with steady state mixing planes.


2017 ◽  
Author(s):  
Mizuki Takemoto ◽  
Yongchan Lee ◽  
Ryuichiro Ishitani ◽  
Osamu Nureki

AbstractSecondary active transporters translocate their substrates using the electrochemical potentials of other chemicals, undergoing large-scale conformational changes. Despite extensive structural studies, the atomic details of the transport mechanism still remain elusive. Here we performed a series of all-atom molecular dynamics simulations of the triose-phosphate/phosphate translocator (TPT), which exports organic phosphates in the chloroplast stroma in strict counter exchange with inorganic phosphate (Pi). Biased sampling methods, including string method and umbrella sampling, successfully reproduced the conformational changes between the inward– and outward-facing states, along with the substrate binding. The free energy landscape of this entire TPT transition pathway demonstrated the alternating access and substrate translocation mechanisms, which revealed Pi is relayed by positively charged residues along the transition pathway. Furthermore, the conserved Glu207 functions as a “molecular switch”, linking the local substrate binding and the global conformational transition. Our results provide atomic-detailed insights into the energy coupling mechanism of antiporter.


Polymers ◽  
2021 ◽  
Vol 13 (22) ◽  
pp. 4006
Author(s):  
Qinlong Wang ◽  
Hao Wang ◽  
Caixia Zhang ◽  
Qilong Zhang ◽  
Hui Yang

High-frequency communication equipment urgently needs substrate materials with lower dielectric loss, better heat dissipation, and higher stability, to ensure real-time low-loss and high-speed signal transmission. The core-shell structure of Sr2CeO4@SiO2 was prepared by the sol-gel method, and the modified powders with different volume contents were introduced into the cyclic olefin copolymer (COC) to prepare hydrocarbon resin-based composites. Due to the protective effect of the SiO2 shell, the stability of the powders is significantly improved, and the moisture barrier and corrosion resistance of the composites are enhanced, which is conducive to the normal operation of electronic equipment in harsh and complex environments. When the filler content is 20 vol%, the composite has a dielectric loss of 0.0023 at 10 GHz, a dielectric constant of 3.5, a thermal conductivity of 0.9 W·m−1·K−1, a water absorption of 0.32% and a coefficient of thermal expansion of 37.7 ppm/℃. The COC/Sr2CeO4@SiO2 composites exhibit excellent dielectric properties and thermal conductivity, while maintaining good moisture resistance and dimensional stability, which shows potential application prospects in the field of high-frequency substrates.


Author(s):  
Iryna Vorotnykova

The article defines the conditions for the formation of a teacher's digital competence in postgraduate education. The analysis of the international standards of UNESCO, the European digital competence framework for citizens (DigComp 2.1 and educators (Digcompedu), and the generalization of the criteria for the definition and assessment of digital competence among teachers. The results of the study are based on the experience of improving the skills of teachers of the city of Kyiv using empirical methods: observation, survey (questionnaires, interviews). The questionnaire allowed to identify the main inquiries of teachers regarding the formation of individual trajectories of professional development, including in The conditions of the formation of the digital competence of teachers in the system of postgraduate pedagogical education are determined: the digitalization of education, the availability of legal documents on standards and requirements for the teacher's digital competency (international, institutional, national), the need to develop and implement the criteria for the development of digital competency teachers (tests, questionnaires, etc.), introduction of international, domestic projects on the use of ICT, readiness of postgraduate students Go to ensure the formation of the digital competency of teachers (IT infrastructure, availability of scientific, educational and environmental resources), IT infrastructure of the educational institutions in which the teacher works (hardware, software, including digital laboratories, connection to high-speed Internet, personalized informational and educational environments, etc.). In addition, an important condition is determined by the teacher's motivation to continuous professional development and self-assessment of his digital competence. It is proved that the development and implementation of national standards for teacher's digital competence, giving him the right to decide for themselves in which institutions to improve their qualifications, promote the introduction of new approaches to constructing individual paths for developing digital competency of teachers.


2013 ◽  
Vol 579-580 ◽  
pp. 568-572
Author(s):  
Da Guo Ma ◽  
Xin Bo Jiang

The structure and composition of the air-cooled high speed motorized spindle for wood-working machine and some features relative to the metal cutting motorized spindle are introduced briefly. Then the main heat sources and heat dissipation mechanism of the air-cooled motorized spindle are thoroughly analyzed, finite element model of the air-cooled motorized spindle is built, the motorized spindles temperature distribution under thermal steady state and the influence of speed are analyzed. The results show that air cooling relative to the water or oil cooling has many advantages and reasonable heat dissipation structure design of air-cooled motorized spindle could meet the requirements of the high-speed motorized spindle for wood-working machine.


2004 ◽  
Vol 126 (31) ◽  
pp. 9492-9493 ◽  
Author(s):  
Bernd Ensing ◽  
Alessandro Laio ◽  
Francesco L. Gervasio ◽  
Michele Parrinello ◽  
Michael L. Klein

2020 ◽  
Vol 830 ◽  
pp. 93-100
Author(s):  
Jae Dong Yoo ◽  
Tae Min Hwang ◽  
Man Soo Joun

Investigation into behaviors of aluminum alloy to be metal formed at the room temperature is conducted in this study. An index is used to evaluate the sensitivity of temperature, that is, index of relative normalized temperature rise to steel called normalized temperature rise index per steel which helps researchers to obtain some insight on new materials based on experiences of steel forging. An investigation to an aluminum alloy shows that the index is quite high, implying that temperature effect as well as rate-dependence effect on the forming processes of aluminum alloy at the room temperature cannot be neglected. Some details of thermomechanical predictions of a relatively high-speed automatic multi-stage forging process of a yoke with highly deformed region are given to reveal the importance of temperature and/or strain rate even in cold forging of aluminum alloy parts with high speed and high strain. All manuscripts must be in English, also the table and figure texts, otherwise we cannot publish your paper. Please keep a second copy of your manuscript in your office. When receiving the paper, we assume that the corresponding authors grant us the copyright to use the paper for the book or journal in question. Should authors use tables or figures from other Publications, they must ask the corresponding publishers to grant them the right to publish this material in their paper. Use italic for emphasizing a word or phrase. Do not use boldface typing or capital letters except for section headings (cf. remarks on section headings, below).


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