Temperature dependence of circular DNA topological states

Circular double stranded DNA has different topological states which are defined by their linking numbers. Equilibrium distribution of linking numbers can be obtained by closing a linear DNA into a circle by ligase. Using Monte Carlo simulation, we predict the temperature dependence of the linking number distribution of small circular DNAs. Our predictions are based on flexible defect excitations resulted from local melting or unstacking of DNA base pairs. We found that the reduced bending rigidity alone can lead to measurable changes of the variance of linking number distribution of short circular DNAs. If the defect is accompanied by local unwinding, the effect becomes much more prominent. The predictions can be easily investigated in experiments, providing a new method to study the micromechanics of sharply bent DNAs and the thermal stability of specific DNA sequences. Furthermore, the predictions are directly applicable to the studies of binding of DNA distorting proteins that can locally reduce DNA rigidity, form DNA kinks, or introduce local unwinding.Comment: 15 pages in preprint format, 4 figure

Sequence Dependent Structural Transition of Short DNA by Tensile Force

Del 25 de novembre de 2013 al 3 de febrer de 201

Prediction of superconducting properties of materials based on machine learning models

The application of superconducting materials is becoming more and more widespread. Traditionally, the discovery of new superconducting materials relies on the experience of experts and a large number of "trial and error" experiments, which not only increases the cost of experiments but also prolongs the period of discovering new superconducting materials. In recent years, machine learning has been increasingly applied to materials science. Based on this, this manuscript proposes the use of XGBoost model to identify superconductors; the first application of deep forest model to predict the critical temperature of superconductors; the first application of deep forest to predict the band gap of materials; and application of a new sub-network model to predict the Fermi energy level of materials. Compared with our known similar literature, all the above algorithms reach state-of-the-art. Finally, this manuscript uses the above models to search the COD public dataset and identify 50 candidate superconducting materials with possible critical temperature greater than 90 K

Drug repositioning for Alzheimer's disease with transfer learning

Deep Learning and DRUG-seq (Digital RNA with perturbation of genes) have attracted attention in drug discovery. However, the public DRUG-seq dataset is too small to be used for directly training a deep learning neural network from scratch. Inspired by the transfer learning technique, we pretrain a drug efficacy prediction neural network model with the Library of Integrated Network-based Cell-Signature (LINCS) L1000 data and then use human neural cell DRUG-seq data to fine-tune it. After training, the model is used for virtual screening to find potential drugs for Alzheimer's disease (AD) treatment. Finally, we find 27 potential drugs for AD treatment including Irsogladine (PDE4 inhibitor), Tasquinimod (HDAC4 selective inhibitor), Suprofen (dual COX-1/COX-2 inhibitor) et al.Comment: 13 pages, 1 figur

Effects of kink and flexible hinge defects on mechanical responses of short double stranded DNA molecules

We predict various detectable mechanical responses to the presence of local DNA defects which are defined as short DNA segments exhibiting mechanical properties obviously different from the 50 nm persistence length based semiflexible polymer model. The defects discussed are kinks and flexible hinges either permanently fixed on DNA or thermally excited. Their effects on extension shift, the effective persistence length, the end-to-end distance distribution, and the cyclization probability are computed using a transfer-matrix method. Our predictions will be useful in future experimental designs to study DNA nicks or mismatch base pairs, mechanics of specific DNA sequences, and specific DNA-protein interaction using magnetic tweezer, fluorescence resonance energy transfer or plasmon resonance technique, and the traditional biochemistry cyclization probability measurements.Comment: 9 pages with 9 figures. Theoretical calculation based on transfer matrix. Minor updates, a new figure and more discussions are adde

A Bayesian Network Based Adaptability Design of Product Structures for Function Evolution

Structure adaptability design is critical for function evolution in product families, in which many structural and functional design factors are intertwined together with manufacturing cost, customer satisfaction, and final market sales. How to achieve a delicate balance among all of these factors to maximize the market performance of the product is too complicated to address based on traditional domain experts’ knowledge or some ad hoc heuristics. Here, we propose a quantitative product evolution design model that is based on Bayesian networks to model the dynamic relationship between customer needs and product structure design. In our model, all of the structural or functional features along with customer satisfaction, manufacturing cost, sale price, market sales, and indirect factors are modeled as random variables denoted as nodes in the Bayesian networks. The structure of the Bayesian model is then determined based on the historical data, which captures the dynamic sophisticated relationship of customer demands of a product, structural design, and market performance. Application of our approach to an electric toothbrush product family evolution design problem shows that our model allows for designers to interrogate with the model and obtain theoretical and decision support for dynamic product feature design process