The Critical Role of Passive Permeability in Designing Successful Drugs

Passive permeability is a key property in drug disposition and delivery. It is critical for gastrointestinal absorption, brain penetration, renal reabsorption, defining clearance mechanisms and drug-drug interactions. Passive diffusion rate is translatable across tissues and animal species, while the extent of absorption is dependent on drug properties, as well as in vivo physiology/pathophysiology. Design principles have been developed to guide medicinal chemistry to enhance absorption, which combine the balance of aqueous solubility, permeability and the sometimes unfavorable compound characteristic demanded by the target. Permeability assays have been implemented that enable rapid development of structure-permeability relationships for absorption improvement. Future advances in assay development to reduce nonspecific binding and improve mass balance will enable more accurately measurement of passive permeability. Design principles that integrate potency, selectivity, passive permeability and other ADMET properties facilitate rapid advancement of successful drug candidates to patients.     

Distributed learning consensus control based on neural networks for heterogeneous nonlinear multiagent systems

This paper considers a novel distributed iterative learning consensus control algorithm based on neural networks for the control of heterogeneous nonlinear multiagent systems. The system's unknown nonlinear function is approximated by suitable neural networks; the approximation error is countered by a robust term in the control. Two types of control algorithms, both of which utilize distributed learning laws, are provided to achieve consensus. In the provided control algorithms, the desired reference is considered to be an unknown factor and then estimated using the associated learning laws. The consensus convergence is proven by the composite energy function method. A numerical simulation is ultimately presented to demonstrate the efficacy of the proposed control schemes.     

我公司延长耐火砖寿命的工艺管理措施

正0引言我公司有两条2 500 t/d的熟料生产线,于2000年先后投产,现正常生产,随着近年来对耐火材料使用的技术攻关和精心管控,烧成带窑砖使用寿命超过40个月。下面就我公司的延长耐火砖寿命的工艺管理措施进行介绍,供借鉴研讨。     

Alloy optimisation of bainitic steel for large plastic mould

Based on the phase transformation theories, especially the T₀ concept of bainite transformation, alloy optimisation of bainitic steel with carbides has been carried out aiming at the produce of plastic mould with large cross-section. The effect of manganese and silicon on proeutectoid ferrite and bainite transformation is explored by dilatometric analysis, XRD and different microscopy techniques. The results show that after the alloy optimisation, the transformation of proeutectoid ferrite is suppressed and when the cooling rate is lower than 0·1°C?s^??1, the new lower bainite transformation appears by decreasing carbon capacity of austenite and promoting carbide precipitation. Industrial production proves that the optimised alloy SDP1 can meet the demand for the plastic mould with the thickness of 1050?mm.     

Single-Crystalline TiO2(B) Nanobelts with Unusual Large Exposed {100} Facets and Enhanced Li-Storage Capacity

The {100} facet of single-crystalline TiO₂(B) is an ideal platform for inserting Li ions, but it is hard to be obtained due to its high surface energy. Here, the single-crystalline TiO₂(B) nanobelts from H₂Ti₃O₇ with nearly 70% {100} facets exposed are synthesized, which significantly enhances Li-storage capacity. The first-principle calculations demonstrate an ab in-plane 2D diffusion through the exposed {100} facets. As a consequence, the nanobelts can significantly accommodate Li ions in LiTiO₂ formula with specific capacity up to 335 mAh g⁻¹, which is in good agreement with the electrochemical characterizations. Coating with conductive and protective poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate), the cut-off discharge voltage is as low as 0.5 V, leading to a capacity of 160.7 mAh g⁻¹ after 1500 cycles with a retention rate of 66% at 1C. This work provides a practical strategy to increase the Li-ion capacity and cycle stability by tailoring the crystal orientation and nanostructures.     

Improving weld formability by a novel dual-rotation bobbin tool friction stir welding

A novel dual-rotation bobbin tool friction stir welding (DBT-FSW) was developed, in which the upper shoulder (US) and lower shoulder (LS) have different rotational speeds. This process was tried to weld 3.2 mm thick aluminum-lithium alloy sheets. The metallographic analysis and torque measurement were carried out to characterize the weld formability. Experimental results show that compared to conventional bobbin tool friction stir welding, the DBT-FSW has an excellent process stability, and can produce the defect-free joints in a wider range of welding parameters. These can be attributed to the significant improvement of material flow caused by the formation of a staggered layer structure and the unbalanced force between the US and LS during the DBT-FSW process.     

The origin of the modulated structure in Sr2CuO3+δ (δ = 0.4): [CuO2] in-plane oxygen vacancy or apical oxygen vacancy?

We propose the question of the modulated structures of copper oxide is caused by the [CuO₂] in-plane oxygen vacancy or apical oxygen vacancy. Sr₂CuO_3+δ single-crystal samples were prepared using high-temperature and high-pressure methods. The major phase of Sr₂CuO_3+δ (δ = 0.4) single-crystal system is found to be constituted by the 5 a modulated structure with the Fmmm space group, which originates from the [CuO₂] in-plane oxygen vacancy appearing in octahedral Cu-O. Besides, the presence of the [CuO₂] in-plane oxygen vacancy may obliterate the superconductivity of the system. Experimental results deduce that the oxygen vacancy may appear in the apical oxygen sites in high-temperature copper oxide superconductors.     

Unsteady free convection of second‐grade nanofluid with a new time‐space fractional heat conduction

The Caputo and Caputo–Fabrizio derivative are applied to study a second‐grade nanofluid over a vertical plate. A comparative analysis is presented to study the unsteady free convection of a second‐grade nanofluid with a new time–space fractional heat conduction. The governing equations with mixed time–space fractional derivatives are non‐dimensionalized and solved numerically, and a comparison between the Caputo and the Caputo–Fabrizio models is made. It is found that the temperature is higher for the Caputo–Fabrizio fractional model than the Caputo model, but the higher velocity only exists near the vertical plate for the Caputo–Fabrizio model than the Caputo model. Moreover, the velocity for the Caputo model will exceed the Caputo–Fabrizio model as y evolves.