Design of synthetic materials for intracellular delivery of RNAs: From siRNA-mediated gene silencing to CRISPR/Cas gene editing

Ribonucleic acids (RNAs) possess great therapeutic potential and can be used to treat a variety of diseases. The unique biophysical properties of RNAs, such as high molecular weight, negative charge, hydrophilicity, low stability, and potential immunogenicity, require chemical modification and development of carriers to enable intracellular delivery of RNAs for clinical use. A variety of nanomaterials have been developed for the effective in vivo delivery of short/ small RNAs, messenger RNAs, and RNAs required for gene editing technologies including clustered regularly interspaced palindromic repeat (CRISPR)/Cas. This review outlines the challenges of delivering RNA therapeutics, explores the chemical synthesis of RNA modifications and carriers, and describes the efforts to design nanomaterials that can be used for a variety of clinical indications.     

Biomedical applications of mRNA nanomedicine

As an attractive alternative to plasmid DNA, messenger RNA (mRNA) has recently emerged as a promising class of nucleic acid therapeutics for biomedical applications. Advances in addressing the inherent shortcomings of mRNA and in the development of nanoparticle-based delivery systems have prompted the development and clinical translation of mRNA-based medicines. In this review, we discuss the chemical modification strategies of mRNA to improve its stability, minimize immune responses, and enhance translational efficacy. We also highlight recent progress in nanoparticle-based mRNA delivery. Considerable attention is given to the increasingly widespread applications of mRNA nanomedicine in the biomedical fields of vaccination, protein-replacement therapy, gene editing, and cellular reprogramming and engineering.     

Module embedding e]radenski@ga.unc.edu

This paper proposes a code reuse mechanism called module embedding that enables the building of new modules from existing ones through inheritance, overriding of procedures, and overriding of types; the paper also describes an implementation scheme for this mechanism. Module embedding is beneficial when modules and classes are used in combination and need to be extended together, or when modules are a more appropriate medium than classes.     

Fractional-Fourier-transform calculation through the fast-Fourier-transform algorithm

A method for the calculation of the fractional Fourier transform (FRT) by means of the fast Fourier transform (FFT) algorithm is presented. The process involves mainly two FFT's in cascade; thus the process has the same complexity as this algorithm. The method is valid for fractional orders varying from -1 to 1. Scaling factors for the FRT and Fresnel diffraction when calculated through the FFT are discussed.     

Endoscopic sclerotherapy is useful in Dieulafoy''s disease

1.5% Capsaicin (Cap) or Vehicle was respectively used to treat the right or left sciatic nerve in 20 Sprague-Dawley rats. On the seventh day, the 20 rats were at random divided into electroacupuncture (EA) group and non-EA group, the spinal cord corresponding to the afferent segments of sciatic nerve was taken out for observing the changes of acetylcholinesterase (AChE) activity and [3H]-quinuelidinylbenzylate (QNB) binding sites in the spinal dorsal horn (SDH). The results were as follows: (1) EA "Huantiao" could enhance AChE activity in the SDH and decrease [3H]-QNB binding sites; (2) Cap treating sciatice nerve could weaken AChE activity in the SDH and merease [3H]-QNB binding sites; (3) Cap treatment could inhibit or partially inhibit the actions of EA as above. The results indicated that ACh participated in the primary afferent of acupuncture information and might exist in Cap-sensitive neurons.     

Design sensitivity analysis of acoustical damping and its application to design of musical bells

Damping characteristics of a musical bell plays an important role in characterizing the musical sound. The total damping consists of acoustical damping and internal damping. Acoustical damping depends upon resonating frequencies and vibration patterns while internal damping is a material property. The acoustical damping of a vibrating structure is formulated via boundary element method and finite element method using eigenmode decomposition. The design sensitivity of acoustical damping is derived using an adjoint variable method of the eigenvalue problem. Design optimization of a musical bell is then performed in terms of acoustical parameters. The goal of the optimization problem is to design a harmonically tuned bell with given acoustical damping values. The proposed automated design process integrates finite element analysis, boundary element analysis, design sensitivity analysis, mode-tracking algorithm and optimization module, seamlessly. It is demonstrated by numerical examples to show practical applications.     

Study of delay-independent decentralized guaranteed cost control for large scale systems

This study introduces delay independent decentralized guaranteed cost control design method based on two controller structures for nonlinear uncertain interconnected large scale systems with time delays. First, a set of equivalent Takagi-Sugeno (T-S) fuzzy models are extended to represent the systems. Then a decentralized state-feedback guaranteed cost performance controller is proposed for the fuzzy systems. Based on delay independent Lyapunov functional approach, some sufficient conditions for the existence of the controller can be cast into the feasible problem of LMIs irrespective of the sizes of the time delays so that the system can be asymptotically stabilized for all considered uncertainties whose sizes are not larger than their bounds. Finally, the minimizing approach is proposed to search the suboptimal upper bound value of guaranteed cost function. Moreover, the corresponding conditions are extended into the generalized dynamic output-feedback close-loop system. Finally, the better control performances of the proposed methods are shown by the simulation examples.     

A study of a new data association and track initiation method with normalized distance squared ordering

In an underwater environment, measurements regarding true targets and false targets (clutter) can be made. Therefore, a suitable data association method to exactly detect and track a target and an efficient track initiation method for judging tracks formed by the target should be selected in this environment. This paper attempts to propose a new data association method and track initiation method to detect and track targets more effectively. Also, the performance of the new method is tested in a series of Monte Carlo simulation runs and is compared with the existing data association and track initiation methods in a cluttered environment.     

Adaptive control of uncertain port-controlled Hamiltonian systems subject to actuator saturation

This paper deals with the problem of adaptive control of uncertain nonlinear port-controlled Hamiltonian systems subject to actuator saturation, and proposes a number of results on the control design. Firstly, the adaptive stabilization problem is studied, and a control design method is developed by using both the dissipative Hamiltonian structural and saturated actuator properties. Secondly, for the case that there are both parametric uncertainties and external disturbances in the AS systems, an adaptive H _∞ control design approach is presented. Finally, study of an example of power systems with simulations shows that the adaptive controller proposed in this paper is effective.     

An internet of things–based personal device for diabetes therapy management in ambient assisted living (AAL)

Diabetes therapy management in AAL environments, such as old people and diabetes patients homes, is a very difficult task since many factors affect a patient’s blood sugar levels. Factors such as illness, treatments, physical and psychological stress, physical activity, drugs, intravenous fluids and change in the meal plan cause unpredictable and potentially dangerous fluctuations in blood sugar levels. Right now, operations related to dosage are based on insulin infusion protocol boards, which are provided by physicians to the patients. These boards are not considering very influential factors such as glycemic index from the diet, consequently patients need to estimate the dosage leading to dose error, which culminates in hyperglycemia and hypoglycemia episode. Therefore, right insulin infusion calculation needs to be supported by the next generation of personal-care devices. For this reason, a personal device has been developed to assist and consider more factors in the insulin therapy dosage calculation. The proposed solution is based on Internet of things in order to, on the one hand, support a patient’s profile management architecture based on personal RFID cards and, on the other hand, provide global connectivity between the developed patient’s personal device based on 6LoWPAN, nurses/physicians desktop application to manage personal health cards, glycemic index information system, and patient’s web portal. This solution has been evaluated by a multidisciplinary group formed by patients, physicians, and nurses.