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Objective(s): Gene therapy is a hopeful approach for treatment of a wide range of life threatening disease from infectious and inherited diseases to cancer. Multifunctional Envelope-type Nano Device (MEND) is a new carrier as non-viral genetic vector. Moreover, associating peptide structures with the nuclear localization signals (NLSs), which contains various functional groups enables them to condense DNA and specifically transfer genetic material to the nucleus. Materials and Methods: In this study, two forms of low molecular weight protamine (LMWP) were used for preparation of MEND carrier. The MEND carriers were then targeted with GE11 ligand to obtain T-MEND structure. The size distribution of the resulting nanoparticles, as well as their transfection efficiency and cytotoxicity, were investigated on the A549 cell line. Results: Results demonstrated that the size of polyplex carrier's formulation by both peptides (VV45 and VV32) was below 200 nm and MEND formulations were between 200-300 nm. T-MEND formulations contained VV32 and VV45 peptides showed slightly higher transfection than similar MEND formulations. Also, MEND formulation showed increased transfection efficiency compared to similar PD complexes. The result of metabolic activity test showed that MEND lipopolyplex did not represent any remarkable cytotoxicity. Conclusion: It can be concluded that multifunctional carriers designed based on LMWP are considered as the safe carrier for gene delivery. Presence of protamine and targeted ligand in the nanoparticulate structure did not increase the risk of cytotoxicity of carriers. So, MEND and T-MEND lipoplexes showed low cytotoxicity and acceptable transfection efficiency at the level of PEI 25 kDa. [ABSTRACT FROM AUTHOR]

Estimating the parameters (or characteristics) of a distribution, from the availability of censored samples, is one of the most important topics in statistical inference over the past decades. This study is concerned about the E-Bayesian estimation method to compute the estimates of the parameter, the hazard rate function and the reliability function of the Weibull distribution when the progressive type-2 censored samples are available. The estimations are obtained based on the Squared error loss function (as a symmetric loss) and General Entropy and LINEX loss functions (as asymmetric losses). In addition, the asymptotic behaviour of the derived E-Bayesian estimators is discussed. Moreover, the E-Bayesian estimators under the different loss functions have been compared through Monte Carlo simulation studies by calculating the E-MSE of the resulting estimators, which is a new measure to compare the E-Bayesian estimators. As an application, we analyzed two real data sets that follow from the Weibull distribution. [ABSTRACT FROM AUTHOR]

In this paper, a hybrid flow shop scheduling problem with a new approach considering time lags and sequence-dependent setup time in realistic situations is presented. Since few works have been implemented in this field, the necessity of finding better solutions is a motivation to extend heuristic or meta-heuristic algorithms. This type of production system is found in industries such as food processing, chemical, textile, metallurgical, printed circuit board, and automobile manufacturing. A mixed integer linear programming (MILP) model is proposed to minimize the makespan. Since this problem is known as NP-Hard class, a meta-heuristic algorithm, named Genetic Algorithm (GA), and three heuristic algorithms (Johnson, SPTCH and Palmer) are proposed. Numerical experiments of different sizes are implemented to evaluate the performance of presented mathematical programming model and the designed GA in compare to heuristic algorithms and a benchmark algorithm. Computational results indicate that the designed GA can produce near optimal solutions in a short computational time for different size problems.

In piezoelectric materials and at the nano-scale, there is a coupling between electrical polarization and strain gradients fields, which is called flexoelectricity. The effects of this phenomenon seem to be negligible in micro/macro scales. The current study has attempted to have a cohesive concentration on the buckling behaviors of sandwich plates. To achieve the abovementioned aim with a higher accuracy, the flexoelectric effect assumes to be existing on the top and bottom face sheets and the core is a composite plate. Also, based on statistics, the first-order shear deformation theory seems to lead to more accurate results. Therefore, in the present research we follow this method to obtain results. The analytical method is applied to solve higher order governing equations. In addition, the critical buckling voltage is calculated considering the flexoelectricity, and it is found that the effects of flexoelectricity play significant roles in determining the critical buckling voltage. Moreover, it is revealed that the thickness of the flexoelectric face sheets and the aspect ratio of the sandwich plate play the same role in critical buckling load variations. It means that the critical buckling load decreases when the thickness of the flexoelectric face sheets or the aspect ratio of the sandwich plate increases and vice versa. The results of the present work can be used for the optimum design and control of similar systems such as micro-electro-mechanical and nano-electromechanical devices. [ABSTRACT FROM AUTHOR]

In the present study, free vibration of sandwich flexoelectric plates resting on Pasternak foundation is investigated. The top and bottom layers are under applied voltage based on flexoelectricity considerations and core is a nanocomposite plate where reinforced by carbon nanotubes. Based on first-order shear deformation theory, flexoelectricity considerations and Hamilton's principle, the governing equations are derived for the first time. Navier's method is used to solve the governing equations analytically in the case of simply supported sandwich plate. Finally, the effects of different parameters are discussed in details. It is found when thickness of flexoelectric face sheets increase, the frequency of nano-sandwich plate decrease. The results of this study can be useful in design and manufacturing of flexoelectric systems as sensor and actuator. [ABSTRACT FROM AUTHOR]

Due to large surface area, tunable pore size, easy surface manipulation, and low-toxicity mesoporous silica nanoparticles (MSNs) may act as a suitable vector for gene delivery. In order to make MSNs as a suitable gene delivery system, we modified the surface of phosphonated MSNs (PMSN) with polyethyleneimine (PEI) 10 and 25 KDa. Then nanoparticles were loaded with chloroquine (CQ) (a lysosomotropic agent) and complexed with plasmid DNA. The transfection efficiency and cytotoxicity of these nanoparticles was examined using green fluorescent protein plasmid (pGFP) and cytotoxicity assay. All PEI coated nanoparticles showed positive zeta potential and mean size was ranged between 170 and 215 nm with polydispersity index bellow 0.35. PEI-coated MSNs significiantly enhanced GFP gene expression in Neuro-2 A cells compared to PEI 10 and 25 KDa. The results of the cytotoxicity assays showed that these nanoparticles have an acceptable level of viability but CQ loaded nanoparticles showed higher cytotoxicity and lower transfection activity than CQ free nanoparticles. [ABSTRACT FROM AUTHOR]

In this study, the antigenotoxic effects of diversin, a prenylated coumarin obtained from Ferula diversivittata roots were evaluated using comet assay. Isolated lymphocytes from healthy volunteers' blood samples were incubated with diversin (10, 25, 50, 100, 200 and 400 µM) alone, or in the presence of H2O2 (25 µM). DNA break was measured based on the %tail DNA and compared with different concentrations of curcumin (10, 25 and 50 µM) as the positive control. It was shown that all concentrations of diversin significantly reduce DNA damage caused by H2O2. [ABSTRACT FROM AUTHOR]

The present study proposes a fuzzy mathematical model of HIV infection consisting of a linear fuzzy differential equations (FDEs) system describing the ambiguous immune cells level and the viral load which are due to the intrinsic fuzziness of the immune system's strength in HIV-infected patients. The immune cells in question are considered CD4+ T-cells and cytotoxic T-lymphocytes (CTLs). The dynamic behavior of the immune cells level and the viral load within the three groups of patients with weak, moderate, and strong immune systems are analyzed and compared. Moreover, the approximate explicit solutions of the proposed model are derived using a fitting-based method. In particular, a fuzzy control function indicating the drug dosage is incorporated into the proposed model and a fuzzy optimal control problem (FOCP) minimizing both the viral load and the drug costs is constructed. An optimality condition is achieved as a fuzzy boundary value problem (FBVP). In addition, the optimal fuzzy control function is completely characterized and a numerical solution for the optimality system is computed. [ABSTRACT FROM AUTHOR]

Let Xn, n≥1 be a stationary sequence of m-dependent random variables with survival function F(x) = P X1 > x . The empirical survival function Fn(x) based on X1,X2,…,Xn is proposed as an estimator for Fn(x). Strong consistency and pointwise as well as uniform of Fn(x) are discussed. [ABSTRACT FROM AUTHOR]