Drug self-assembly: A phenomenon at the nanometer scale with major impact in the structure–biological properties relationship and the treatment of disease

Under water-rich conditions, small amphiphilic and hydrophobic drug molecules self-assemble into supramolecular nanostructures. Thus, substantial modifications in their interaction with cellular structures and the ability to reach intracellular targets could happen. Additionally, drug aggregates could be more toxic than the non-aggregated counterparts, or vice versa. Moreover, since self-aggregation reduces the number of effective “monomeric” molecules that interact with the target, the drug potency could be underestimated. In other cases, the activity could be ascribed to the non-aggregated molecule while it stems from its aggregates. Thus, drug self-assembly could mislead from drug throughput screening assays to advanced preclinical and clinical trials. Finally, aggregates could serve as crystallization nuclei. The impact that this phenomenon has on the biological performance of active compounds, the inconsistent and often controversial nature of the published data and the need for recommendations/guidelines as preamble of more harmonized research protocols to characterize drug self-aggregation were main motivations for this review. First, the key molecular and environmental parameters governing drug self-aggregation, the main drug families for which this phenomenon and the methods used for its characterization are described. Then, promising nanotechnology platforms investigated to prevent/control it towards a more efficient drug development process are briefly discussed.     

Improved robust exponential stability for Takagi–Sugeno fuzzy uncertain systems with time-varying delays

This paper concerns managing the robust exponential stability problem of uncertain Takagi–Sugeno fuzzy systems with time-varying delay by employing a further improved integral inequality matrix approach. Based on the linear matrix inequality (LMI) approach, delay-dependent robust exponential stability criteria have been developed. By taking the relationship among the time-varying delay, its upper bound and their difference into account, some less conservative LMI-based delay-dependent robust exponential stability criteria are obtained without ignoring any useful terms in the derivative of Lyapunov–Krasovskii functionals. Maximum allowable upper bound for time-varying delays is determined. Numerical examples are provided to show that the obtained results significantly improve the allowed upper bounds of delay size over some methods existing in the literature.     

Mechanical properties of concrete containing phase-change material

This study aimed to investigate the mechanical properties of concrete containing solid–liquid phase-change material (PCM) and focused on two key factors. First, a systematic study on the mechanical performance of PCM-modified concretes was conducted, including compressive, elastic modulus, and shrinkage tests. Second, because PCM provides high latent heat during the solid–liquid phase change, the effects of the solid phase and liquid phase on the mechanical properties of concrete were also explored. Results of this study showed that the solid–liquid phase of PCM affected the mechanical properties of concrete. For example, the compressive strength of 10% PCM concrete in solid phase (23 °C) and liquid phase (40 °C) at 28 days was 29.30 and 19.57 MPa, respectively. In addition, with increasing PCM content, the mechanical properties were degraded. For example, 10, 20, and 30% of PCM content lowered the compressive strength by 35.4, 58.4, and 74.3%, respectively. Therefore, concrete with PCM may not be suitable for structural elements. However, PCM is an important solution for optimizing energy consumption in modern buildings. It can absorb or emit large amounts of heat to store or release thermal energy. These properties can be used to control building temperatures resulting in energy saving and carbon reduction.     

The lateral load-deformation response of RC walls with a consideration of the height–length ratio

Reinforced concrete (RC) walls play an important role in resisting earthquakes, so understanding the lateral load-deformation response of an RC wall subjected to an axial load, shear, and moment is essential to nonlinear structural analysis. In this study, the moment-bending deformation response of an RC wall under an axial load and moment is obtained from moment–curvature analysis using the wall’s proper plastic hinge length. Furthermore, modified compression-field theory, adjusted according to the height–length ratio of the wall, is used to calculate the shear–shear deformation response of the wall under an axial load and shear. By integrating the moment-bending deformation and the shear–shear deformation responses, the lateral load-deformation response of the RC wall under axial load–moment–shear interaction can be reasonably determined. To confirm the reliability of the proposed method, experimental results for 67 RC walls are compared with analysis results from the proposed method. The statistical results show that the proposed method accurately predicts the lateral ultimate load but somewhat underestimates the lateral ultimate deformation. Finally, this paper gives an example using an equivalent column to simulate an RC wall using SAP2000 pushover analysis.     

Thermal,mechanical and drug release characteristics of an acrylic film using active pharmaceutical ingredient as non-traditional plasticizer

Abstract

The objective of this study was to investigate thermal and mechanical properties as well as in vitro drug release of Eudragit® RL (ERL) film using chlorpheniramine maleate (CPM) as either active pharmaceutical ingredient or non-traditional plasticizer. Differential scanning calorimeter was used to measure the glass transition temperature (T_g) of 0–100% w/w CPM in ERL physical mixture. Instron testing machine was used to investigate Young’s modulus, tensile stress and tensile strain (%) of ERL film containing 20–60% w/w CPM. Finally, a Franz diffusion cell was used to study drug release from ERL films obtained from four formulations, i.e. CRHP0/0, CRHP0/5, CRHP2/0 and CRHP2/5. The T_g of ERL was decreased when the weight percentage of CPM increased. The reduction of the T_g could be described by Kwei equation, indicating the interaction between CPM and ERL. Modulus and tensile stress decreased whereas tensile strain (%) increased when weight percentage of CPM increased. The change of mechanical properties was associated with the reduction of the T_g when weight percentage of CPM increased. ERL films obtained from four formulations could release the drug in no less than 10?h. Cumulative amount of drug release per unit area of ERL film containing only CPM (CRHP0/0) was lower than those obtained from the formulations containing traditional plasticizer (CRHP0/5), surfactant (CRHP2/0) or both of them (CRHP2/5). The increase of drug release was a result of the increase of drug permeability through ERL film and drug solubility based on traditional plasticizer and surfactant, respectively.     

Development of a water-in-oil-in-water multiple emulsion system integrating biomimetic aqueous-core lipid nanodroplets for protein entity stabilization. Part II: process and product characterization

The aqueous-core enclosed in lipid nanoballoons integrating multiple emulsions of the type water-in-oil-in-water mimic, at least in theory, the environment within viable cells, thus being suitable for housing hydrophilic protein entities such as bioactive proteins, peptides and bacteriophage particles. This study reports a complete physicochemical characterization of optimized biomimetic aqueous-core lipid nanoballoons housing hydrophilic (BSA) protein entities, evolved from a statistical 2³×3¹ factorial design study (three variables at two levels and one variable at three levels) that was the subject of the first paper of a series of three, aiming at complete stabilization of the three-dimensional structure of protein entities attempted via housing the said molecular entities within biomimetic aqueous-core lipid nanoballoons integrating a multiple (W/O/W) emulsion. The statistical factorial design followed led to the production of an optimum W/O/W multiple emulsion possessing quite homogeneous particles with an average hydrodynamic size of (186.2?±?2.6) nm and average Zeta potential of (?36.5?±?0.9) mV, and exhibiting a polydispersity index of 0.206?±?0.014. Additionally, the results obtained for the diffusion coefficient of the lipid nanoballoons integrating the optimized W/O/W multiple emulsion were comparable and of the same order of magnitude (10^?12 m² s^?1) as those published by other authors since, typically, diffusion coefficients for molecules range from 10^?10 to 10^?7 m² s^?1, but diffusion coefficients for nanoparticles are typically of the order of magnitude of 10^?12 m² s^?1.     

Prediction of color changes in acetaminophen solution using the time–temperature superposition principle

A prediction method for color changes based on the time–temperature superposition principle (TTSP) was developed for acetaminophen solution. Color changes of acetaminophen solution are caused by the degradation of acetaminophen, such as hydrolysis and oxidation. In principle, the TTSP can be applied to only thermal aging. Therefore, the impact of oxidation on the color changes of acetaminophen solution was verified. The results of our experiment suggested that the oxidation products enhanced the color changes in acetaminophen solution. Next, the color changes of acetaminophen solution samples of the same head space volume after accelerated aging at various temperatures were investigated using the Commission Internationale de l’Eclairage (CIE) LAB color space (a*, b*, L* and ΔE*ab), following which the TTSP was adopted to kinetic analysis of the color changes. The apparent activation energies using the time–temperature shift factor of a*, b*, L* and ΔE*ab were calculated as 72.4, 69.2, 72.3 and 70.9 (kJ/mol), respectively, which are similar to the values for acetaminophen hydrolysis reported in the literature. The predicted values of a*, b*, L* and ΔE*ab at 40?°C were obtained by calculation using Arrhenius plots. A comparison between the experimental and predicted values for each color parameter revealed sufficiently high R² values (>0.98), suggesting the high reliability of the prediction. The kinetic analysis using TTSP was successfully applied to predicting the color changes under the controlled oxygen amount at any temperature and for any length of time.     

Photo Noise

Like past avant-garde movements, glitch and noise in the twenty-first century are used to reveal the materiality of the medium. But instead of providing insight or clarity into the politics or social conditions of a technology, they demarcate broader conditions of opacity and blockage, contributing to what Jodi Dean has called ‘communicative capitalism’. The work of German photographer Thomas Ruff alongside the Düsseldorf School, New Photography and JPEG technology are used in this article to illustrate this tendency as a move away from meaning and toward visual noise and communicative breakdown. I use three core analytic registers: the deliberate failure to adhere to visual norms, communicative failure and machine failure and breakdown. Ruff’s work uses visual noise as art to at once reaffirm pervasive conditions of breakdown, failure and decline in high-tech global capitalism, while simultaneously providing a temporary reprieve from these conditions through an emergent form of visual beauty.     

Precise identification of moving vehicular parameters based on improved glowworm swarm optimization algorithm

This paper proposes an indirect method for the identification of moving vehicular parameters using the dynamic responses of the vehicle. The moving vehicle is modelled as 2-DOF system with 5 parameters and 4-DOF system with 12 parameters, respectively. Finite element method is used to establish the equation of the coupled bridge–vehicle system. The dynamic responses of the system are calculated by Newmark direct integration method. The parameter identification problem is transformed into an optimization problem by minimizing errors between the calculated dynamic responses of the moving vehicle and those of the simulated measured responses. Glowworm swarm optimization algorithm (GSO) is used to solve the objective function of the optimization problem. A local search method is introduced into the movement phase of GSO to enhance the accuracy and convergence rate of the algorithm. Several test cases are carried out to verify the efficiency of the proposed method and the results show that the vehicular parameters can be identified precisely with the present method and it is not sensitive to artificial measurement noise.