Recombinant protein-based polymers for advanced drug delivery

Advances in recombinant techniques have led to the development of genetically engineered polymers with exquisite control over monomer sequence and polymer length. The ability to study how precise structures correlate with function has provided opportunities for the utility of these polymers in drug delivery. Chemically derived and developed methods of synthesis have yielded many useful polymers for drug delivery to-date, including those currently used in patients. However they have drawbacks, including limitations involved in statistical characterization of conventional polymer synthetic techniques. Encoding at the genetic level and production of such recombinant polymers in organisms allow for precise order and accuracy of amino acid residues and production of monodisperse polymers with specific function and physicochemical properties. Research into elastin-like, silk-like, and silk-elastinlike protein polymers for example has led to the development of delivery systems based on natural motifs of structural proteins to take advantage of their physicochemical properties. Additionally, protein based polymers on other natural motifs and de novo designs are starting to produce promising constructs for drug and gene delivery applications where precise control over structure promises correlation with function and guides the development of new and improved constructs. Clinical applications based on recombinant polymers for delivery of bioactive agents have not been realized at this point. However lessons learned from fundamental research with these polymers can be used to guide design of safe and effective systems for use in the clinic. This tutorial review summarizes progress made in the design and utility of recombinant polymers in drug and gene delivery and discusses challenges and future directions of such polymers for this purpose.     

Practical copper-catalyzed N-arylation of amines with 20% aqueous solution of n-Bu4NOH

N-Arylation of a wide variety of amines with phenylboronic acid catalyzed by copper acetate under 20%aqueous solution of n-Bu₄NOH was accomplished in good to excellent yields（up to 92%） and substrate conversions（up to 96%）.     

Influence of Solute Charge and Hydrophobicity on Partitioning and Diffusion in a Genetically Engineered Silk‐Elastin‐Like Protein Polymer Hydrogel

The influence of solute hydrophobicity and charge on partitioning and diffusion in physically crosslinked networks of a genetically engineered SELP polymer was investigated. A series of fluorescent dyes were used to assess the impact of solute charge and hydrophobicity on release behavior. The mechanism of solute release from the SELP hydrogel appeared to vary as a function of dye hydrophobicity. The extent of FITC attachment to amine‐terminated G4 dendrimers influenced SELP hydrogel partitioning more than dendrimer diffusion properties. Results suggest the possibility of controlling solute release from SELP hydrogels by modifying the hydrophobicity and surface charge of drugs and drug/polymer conjugates as well as the possibility of “designing‐in” solute‐specific interactions.

     

The generalized cubic functional equation and the stability of cubic Jordan *-derivations

In the current work, we obtain the general solution of the following generalized cubic functional equation $$\begin{aligned}&f(x+my)+f(x-my)\\&\quad =2\left( 2\cos \left( \frac{m\pi }{2}\right) +m^2-1\right) f(x)-\frac{1}{2}\left( \cos \left( \frac{m\pi }{2}\right) +m^2-1\right) f(2x)\\&\qquad +m^2\{f(x+y)+f(x-y)\} \end{aligned}$$ for an integer $m \ge 1$ . We prove the Hyers–Ulam stability and the superstability for this cubic functional equation by the directed method and a fixed point approach. We also employ the mentioned functional equation to establish the stability of cubic Jordan $*$ -derivations on $C^*$ -algebras and $JC^*$ -algebras.     

Numerical analysis of SOA performance over a wide optical bandwidth in a CO-OFDM transmission system

We present a numerical analysis of the impact of the optical amplification by semiconductor optical amplifiers (SOAs) in a Coherent Optical-Orthogonal Frequency Division Multiplexing transmission link at 100 Gb/s. The numerical modeling of SOA is developed to be able to simulate all of nonlinear effects of the SOA, particularly four-wave mixing effect. This model is integrated into a co-simulation platform to perform a simulation at a system level. Error Vector Magnitude (EVM) measurement is given with respect to the number of subcarriers and phase-amplitude coupling. We show also the dependence of the EVM at the signal wavelength by performing our simulations on a wide optical bandwidth, taking into account the main parameters of the SOA—such as the phase-amplitude coupling factor, the saturation power and the noise figure—that influence the non-linear effects.

     

Tunneling Conductance in a Normal Metal/Ferromagnetic Superconductor Nano-Junction at a Finite Temperature

In this study, we investigate the tunneling conductance at a finite temperature in a normal metal/ferromagnetic superconductor nano-junction where the ferromagnetic superconductor (FS) is in three different cooper pairing states: spin singlet s-wave pairing (SWP), spin triplet opposite spin pairing (OSP), and spin triplet equal spin pairing (ESP) while including Fermiwave mismatch (FWM) and effective mass mismatch (EMM) in two sides of the nano-junction. We find that the conductance shows clearly different behaviors all depending on the symmetries of cooper pairing in a mannerthat the conductance spectra shows a gap-like structure, two interior dipsstructure and zero bias peak for SWP, OSP, and ESP, respectively. Also, theeffective FS gap (δ_eff) is a linear and decreasing function of exchange field. The slope of (δ_eff) versus exchange field for OSP is twice the SWP. Thus, we can determine the spin polarization of N/FS nano-junction based on the dependence of (δ_eff) to exchange field.     

Simulation of Solute Transport Through Fractured Rock: A Higher-Order Accurate Finite-Element Finite-Volume Method Permitting Large Time Steps

Discrete-fracture and rock matrix (DFM) modelling necessitates a physically realistic discretisation of the large aspect ratio fractures and the dissected material domains. Using unstructured spatially adaptively refined finite-element meshes, we find that the fastest flow often occurs in the smallest elements. Flow velocity and element size vary over many orders of magnitude, disqualifying global Courant number (CFL)-dependent transport schemes because too many time steps would be necessary to investigate displacements of interest. Here, we present a higher-order accurate implicit pressure–(semi)-implicit transport scheme for the advection–diffusion equation that overcomes this CFL limitation for DFM models. Using operator splitting, we solve the pressure and the transport equations on finite-element, node-centred finite-volume meshes, respectively, using algebraic multigrid methods. We apply this approach to field data-based DFM models where the fracture flow velocity and mesh refinement is 2–4 orders of magnitude greater than that of the matrix. For a global CFL of ≤10,000, this implies sub-CFL, second-order accurate behaviour in the matrix, and super-CFL, at least first-order accurate, transports in fast-flowing fractures. Their greater refinement, however, largely offsets this numerical dispersion, promoting a highly accurate overall solution. Numerical and fracture-related mechanical dispersions are compared in the realistic DFM models using second-order accurate runs as reference cases. With a CFL histogram, we establish target error criteria for CFL overstepping. This analysis indicates that for extreme fracture heterogeneity, only a few transport steps can be sufficient to analyse macro-dispersion. This makes our implicit method attractive for quick analysis of transport properties on multiple realisations of DFM models.     

Upscaling in Vertically Fractured Oil Reservoirs Using Homogenization

Flow modeling in fractured reservoirs is largely confined to the so-called sugar cube model. Here, however, we consider vertically fractured reservoirs, i.e., the situation that the reservoir geometry can be approximated by fractures enclosed columns running from the base rock to the cap rock (aggregated columns). This article deals with the application of the homogenization method to derive an upscaled equation for fractured reservoirs with aggregated columns. It turns out that vertical flow in the columns plays an important role, whereas it can be usually disregarded in the sugar cube model. The vertical flow is caused by coupling of the matrix and fracture pressure along the vertical faces of the columns. We formulate a fully implicit three-dimensional upscaled numerical model. Furthermore, we develop a computationally efficient numerical approach. As found previously for the sugar cube model, the Peclet number, i.e., the ratio between the capillary diffusion time in the matrix and the residence time of the fluids in the fracture, plays an important role. The gravity number plays a secondary role. For low Peclet numbers, the results are sensitive to gravity, but relatively insensitive to the water injection rate, lateral matrix column size, and reservoir geometry, i.e., sugar cube versus aggregated column. At a low Peclet number and sufficiently low gravity number, the effective permeability model gives good results, which agree with the solution of the aggregated column model. However, ECLIPSE simulations (Barenblatt or Warren and Root (BWR) approach) show deviations at low Peclet numbers, but show good agreement at intermediate Peclet numbers. At high Peclet numbers, the results are relatively insensitive to gravity, but sensitive to the other conditions mentioned above. The ECLIPSE simulations and the effective permeability model show large deviations from the aggregated column model at high Peclet numbers. We conclude that at low Peclet numbers, it is advantageous to increase the water injection rate to improve the net present value. However, at high Peclet numbers, increasing the flow rate may lead to uneconomical water cuts.     

Electrochemical and theoretical study of novel functional porous graphene aerogel-supported Sm2O3 nanoparticles for supercapacitor applications

Journal of Solid State Electrochemistry - A graphene aerogel cross-linked by p-phenylenediamine (PPDA) composite with Sm2O3 nanoparticles (AP.Sm) was synthesized as a novel nanocomposite via a...