Search

Therapeutic agents acting on RNA, including RNA modification, RNA editing and RNA interference (RNAi), play a vital role in gene function study, signaling pathway, drug discovery, disease treatment, vaccine development and so on. Therein, RNAi as an emerging gene therapy has been widely applied in many cancer studies by silencing oncogenes or specific mRNA in malignant tumor cells. Mechanism and efficiency of RNAi are the key issues of RNAi technology. RNA silencing involves dynamic modeling, analyses and optimal control of RNAi gene system. Physiological delay and Hill response describing off-target are considerable elements involving RNAi efficiency. In this paper, we first formulate a four-dimensional RNAi model with time delays and Hill functions, and then investigate the complex dynamic behaviors including the number, existence and stability of internal equilibria and Hopf bifurcations of single delay and two delays. Furthermore, based on the specific mRNA degradation adopted in impulsive patterns, we build an optimal problem by adding exogenous dsRNA at alterable time points in variable dosages in a treatment session. By the method of gradient formula, we can find the optimal impulsive time and proportion of dsRNA. Finally, simulation indicates that (1) physiological lags not only raise the oscillations of mRNA but also cut down the levels of cost; (2) smaller delays and larger rates of siRNA–mRNA complex formation and dsRNA synthesis imply the rapid composition of RISC and fast synthesis of dsRNA leading to more desirable therapeutic schedule, which affords evidence for gene regulation and RNAi; (3) a larger half-saturation coefficient characterizes a unique and stable higher targeted mRNA, whereas a smaller half-saturation coefficient generates bistability in which the higher and lower targeted mRNAs simultaneously emerge; and (4) the bistability will provide a good guidance to control, suppress and degrade targeted mRNA. [ABSTRACT FROM AUTHOR]

Identifying proteins is crucial for disease diagnosis and treatment. With the increase of known proteins, large-scale batch predictions are essential. However, traditional biological experiments being time-consuming and expensive are difficult to accomplish this task efficiently. Nevertheless, deep learning algorithms based on big data analysis have manifested potential in this aspect. In recent years, language representation models, especially BERT, have made significant advancements in natural language processing. In this paper, using three protein segmentation methods and three encoder numbers, nine BERT models with different sizes are constructed to predict whether known proteins are DNA-binding proteins or not. Furthermore, based on the concept of protein motifs, multi-scale convolutional networks are fused into the models to extract the local features of DNA-binding proteins. Finally, we find that the larger the number of encoders, the better the model predictions under the condition of considering each amino acid in the protein as a word. Our proposed algorithm achieves 81.88% sensitivity and 0.39 MCC value on the test set. Furthermore, it achieves 62.41% accuracy on the independent test set PDB2272. It is evident that our proposed method can be a tool to assist in the identification of DNA-binding proteins. [ABSTRACT FROM AUTHOR]

Aphids, the sap-sucking insects, often feeding in clusters on new plant growth, have resulted in large amounts of resources and efforts being spent attempting to control their activities. Taking cotton aphids as an example, this paper presents optimal control problems governed by stochastic models with impulsive interferences. Differing from the moment closure equation methods which are computationally intractable when the model contains excessive species, a new computational approach is employed to solve this problem. The key of the approach is to establish a functional relationship between the control variables involving the releasing rates of sterile insects and the spraying rates of pesticide and corresponding states on aphids and sterile aphids. Then the log-linear regression model is proposed to link the control variables with the moments (including the mean and variance) of states. Using training sample simulated from Gillespie algorithm, the regression coefficients for constraints and the objective function are estimated by least squares method. Simulation shows the error of the prediction of this model is relatively low and control results based on regression model are superior to the method based on the moment closure equations in terms of the control cost. Finally, the relative impacts of the prices and area of the field on optimal tactics are explored. [ABSTRACT FROM AUTHOR]

Based on literature [J. Q. Li, Z. E. Ma and F. Q. Zhang, Stability analysis for an epidemic model with stage structure, J. Appl. Math. Comput. 9 (2008) 1672-1679], incorporating the recovery of the infected population with the length of the infectious periods, a modified epidemic disease SIS model with delay and stage was investigated. First, the criteria keeping stability with delay were given. Next, in order to lower the level of the infected individuals and minimize the cost of treatment, mixed, early and late therapeutic strategies were introduced into our model, respectively. Then we investigated the existence and uniqueness of optimal controls. And then, we expressed the unique optimal control in terms of the solution of the optimality systems. Finally, by numerical simulations, several important results were acquired: (1) The terminal time influenced the early optimal control largely. In detail, for a shorter terminal time it was optimal to initiate treatment with maximal effort at the start of the epidemic and continue treatment with maximal effort until the switch time was arrived. But for a longer terminal time, the maximal treatment effort need not be a prerequisite at the start or end of the epidemic but it was obligatory at the metaphase of the epidemic. (2) For our SIS model, minimizing the total infectious burden of the disease can be achieved by only early optimal treatment tactics. (3) For a disease with a shorter infectious period time, more cost would be spent to control the disease in order to achieve the optimal control objective. Otherwise, a relative lower cost would be to control the disease with a longer infectious period. [ABSTRACT FROM AUTHOR]

In this work, we consider a logistic fishery model and discuss the selective impulsive harvesting of fish above a certain age or size by incorporating a time delay in the impulsive harvesting term. It is proved that there exists an asymptotically stable positive periodic solution $x^*_{l1}(t)$ when the catchability coefficient h is less than some critical value $h^*_{l}$. It is concluded that $h^*_{l}$ and $x^*_{l1}$ are increasing with respect to l. Simulations shows that the delayed harvesting is advantageous to the sustainability of the population. [ABSTRACT FROM AUTHOR]

This work investigates the dynamic behaviors of one-prey multi-predator model with defensive ability of the prey by introducing impulsive biological control strategy. By using the Floquent theorem and the small amplitude perturbation method, it is proved that there exists an asymptotically stable pest-eradication periodic solution when the impulsive period is less than some critical value, and a permanence condition is established via the method of comparison involving multiple Liapunov functions. It is shown that the multi-predator impulsive control strategy is more effective than the classical one and makes the behavior dynamics of the system more complex. [ABSTRACT FROM AUTHOR]