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.     

The use of mindmapping software for patent search and management

Modern information technologies and in particular the internet have revolutionized the patent information professionals' work in terms of speed of access and information comprehensiveness from both company internal and external digital sources. Here, I describe how the digital mindmapping technique can be used to complement existing intellectual property management software solutions to meet the challenge of optimizing and managing patent search workflows as well as to rapidly organise and access highly dynamic, heterogeneous and scattered patent information sources. Both eye catching and highly memorable and at the same time self-explanatory mindmapping examples are presented. These were designed to include basic and advanced level digital mindmapping features tailored to significantly speed up and maintain a high work quality level of patent search professionals. A special emphasis is put on the great benefit of organising and accessing the plethora of internet-based worldwide online patent registers through mindmapping, both in terms of managing the constantly changing deep links to the actual search options for e.g., legal status information, and keeping track of the offered level of content.     

Information for Authors

正General Journal of Beijing Institute of Technology(JBIT),an English language journal sponsored by Beijing Institute of Technology,was established in 1992.JBIT mainly publishes research articles that reflect the latest achievements in basic theory and experimental studies in various engineering fields and in applied mathematics,mechanics,physics,chemistry,and so on.JBIT is listed in Ei,CA,SA,AJ,CSA,MR,ZM and many other abstracting indexes.     

VxWorks5.5 平台下矢量字体显示的实现

VxWorks5.5采用点阵字库实现字体显示,这种字库设计简洁,应用广泛,但一个字库只能对应一种字体的一种大小,在不确定使用何种字体的情况下,这种传统的字体显示方式便不能够满足需求。通过使用TrueType字库和FreeType字体引擎相结合的方式,能实现多种字体、任意大小的显示功能。主要介绍了TrueType、FreeType技术的基本原理,以及在VxWorks5.5下如何将WindML、FreeType和TrueType三者相结合实现矢量字体显示的方法。     

Fuel properties of Brassica juncea oil methyl esters blended with ultra-low sulfur diesel fuel

Brassica juncea is a drought-tolerant member of the Brassicaceae plant family with high oil content and a short growing season that is tolerant of low quality soils. It was investigated as a feedstock for production of biodiesel along with evaluation of subsequent fuel properties, both neat and in blends with petroleum diesel fuel. These results were compared against relevant fuel standards such as ASTM D6751, EN 14214, ASTM D975, EN 590, and ASTM D7467. Crude B. juncea oil was extracted from unconditioned seeds utilizing a continuous tubular radial expeller. The oil was then chemically refined via degumming, neutralization and bleaching to render it amenable to direct homogeneous sodium methoxide-catalyzed transesterification. The principal fatty acid detected in B. juncea oil was erucic acid (44.1%). The resulting biodiesel yielded fuel properties compliant with the biodiesel standards with the exception of oxidative stability and kinematic viscosity in the case of EN 14214. Addition of tert-butylhydroquinone and blending with soybean oil-derived biodiesel ameliorated these deficiencies. The fuel properties of B5 and B20 blends of B. juncea oil methyl esters (BJME) in ultra-low sulfur (<15 ppm S) diesel (ULSD) fuel were within the ranges specified in the petrodiesel standards ASTM D975, EN 590 and ASTM D7467 with the exception of derived cetane number in the case of EN 590. This deficiency was attributed to the inherently low cetane number of the certification-grade ULSD, as it did not contain performance-enhancing additives. In summary, this study reports new fuel property data for BJME along with properties of B5 and B20 blends in ULSD. Such results will be useful for the development of B. juncea as an alternative source of biodiesel fuel.     

Conformation–function relationships for the comb-shaped polymer pOEGMA

Poly(oligo(ethylene glycol) methyl ether methacrylate) (pOEGMA) is a highly versatile polymer because manipulation of the dimensions of its comb-type structure has a predictable effect on the conformation of its main-chain and side-chains which can, together or independently, be either extended or collapsed. This control, and the distinctive physical–chemical characteristics of pOEGMA, are the common driving forces behind its tunable thermosensitivity properties, supramolecular assembly characteristics, and efficient protein repellency. Because of these interesting properties, pOEGMA is increasingly being used within functional coatings, biosensors, drug delivery systems, biomaterials, etc. This Trend article highlights the how to control (and factors influencing) pOEGMA main/side-chain conformations, and consequently exploit this polymer in several emerging areas of importance. This discussion integrates all current areas of application (i.e., in solution, within complex (bio)conjugates, and grafted to solids), in order to provide a common and general perspective on how this polymer can be most efficiently used in future applications.     

High pressure enhances activity and selectivity of Candida rugosa lipase immobilized onto silica nanoparticles in organic solvent

High hydrostatic pressure has been increasingly utilized to improve functions of enzymes, and most of such studies are currently focused on free enzymes in aqueous solution or organic solvent. In this work, Candida rugosa lipase (CRL) was immobilized onto silica nanoparticles and its activity and enantioselectivity in organic solvent were evaluated at high pressures under different water activities. The application of high hydrostatic pressures (50–200 MPa) led to improved activities of immobilized CRL for transesterification of (R)-1-phenylpropan-2-ol with vinyl acetate by 4–6 folds. Additionally the immobilization of CRL resulted in a significant change of selectivities, shifting the enantiomeric excess from the (R)- towards (S)-1-phenylpropan-2-yl acetate product at atmospheric pressure. The application of high pressures led to either enantiomeric excess towards (R)-1-phenylpropan-2-yl or no enantiomeric selectivity, depending on the water activities in the organic solvent and the level of pressures. The interesting behaviour of immobilized CRL under high pressures offers new opportunities to modulate enzyme functions through combination of high pressures and enzyme immobilization.     

Continuous distance-based skyline queries in road networks

In recent years, the research community has introduced various methods for processing skyline queries in road networks. A skyline query retrieves the skyline points that are not dominated by others in terms of static and dynamic attributes (i.e., the road distance). This paper addresses the issue of efficiently processing continuous skyline queries in road networks. Two novel and important distance-based skyline queries are presented, namely, the continuous  _dε-skylinequery   (_Cdε-SQ) and the continuous k nearest neighbor-skyline query (Cknn-SQ  ). A grid index is first designed to effectively manage the information of data objects and then two algorithms are proposed, the _Cdε-SQalgorithm   and the _Cdε-SQ⁺algorithm  , which are combined with the grid index to answer the _Cdε-SQ. Similarly, the Cknn-SQ algorithm and the Cknn-SQ⁺algorithm are developed to efficiently process the Cknn-SQ. Extensive experiments using real road network datasets demonstrate the effectiveness and the efficiency of the proposed algorithms.