In vivo targeting of acute myocardial infarction with negative-charge, polymer-modified antimyosin antibody: use of different cross-linkers

BACKGROUND: Cell surfaces and intercellular matrixes contain acidic residues, making them negatively charged. Antibodies are basic, positively charged glycoproteins. Therefore the potential for nonspecific ionic interaction exists, which could increase the background activity. Modification of antibodies with negatively charge-modified polymers have been shown to reduce this nonspecific background activity. This study was performed to investigate the appropriateness of different cross-linkers used covalently to link the chelating negatively charge-modified polylysine to antimyosin Fab (AM-Fab). The cross-linking was performed through peptide (AM-I) or thioether (AM-II) bonds. The in vitro evaluation of the immunointegrity and the in vivo assessment were performed to investigate the potential for reduction of nontarget background activity. Furthermore, the role of the charge of the polymers (whether completely negatively charge modified by succinylation [AM-IIs] or only partially negatively charge modified [AM-IIns]) was also assessed. METHODS AND RESULTS: All polymer-modified preparations (AM-I, AM-IIs, and AM-IIns) retained the immunoreactivities relative to the unmodified or conventional diethylenetriaminepentaacetic acid-coupled AM-Fab as assessed by radioimmunoassay or enzyme-linked immunosorbent assay. These polymer-modified preparations labeled with 111In were assessed in 13 rabbits with acute experimental myocardial infarction. Acute infarcts were produced by 40 minutes of left anterior descending coronary artery occlusion followed by reperfusion. At between 10 and 30 minutes of reperfusion, 10.4 +/- 1.8 mBq 111In-AM-I (10 to 20 micrograms; n = 7) or 11.4 +/- 2.3 mBq 111In-AM-II (n or ns) (20 to 25 micrograms; n = 6) was administered intravenously. Gamma imaging was performed in the left lateral position and arterial blood samples were withdrawn serially for the next 3 hours. At the end of the final imaging session, AM-I uptake was determined to be 1.09% +/- 0.11% (mean percent injected dose per gram myocardium +/- SEM) in 20 infarcted myocardial segments from seven rabbits, compared with 0.031% +/- 0.003% in 20 normal myocardial segments (infarct/normal myocardial ratio 53.9 +/- 18.41). The mean percent injected dose of 111In-labeled thioether-linked AM-Fab preparations in nine infarcted myocardial segments from each group was 0.067% +/- 0.008% (infarct/normal myocardial ratio 9.0 +/- 1.5) and 0.144% +/- 0.011% (infarct/normal myocardial ratio 10.2 +/- 1.9) with AM-IIs (n = 3) and AM-IIns (n = 3), respectively (p < 0.0001). The non-target organ distribution of the AM-I and AM-IIs was similar. AM-IIns preparation resulted in high non-target organ activities. CONCLUSIONS: This study shows that the charge of the antibody can be manipulated favorably by cross-linking with negatively charged polymers, which results in the reduced in vivo non-target organ activities. Charge modification does not adversely affect the apparent affinity of the antibody. However, the type of cross-linkers used may significantly influence the in vivo stability of the modified antibody preparations for target organ visualization. These data may find potential application in future clinical imaging protocols.     

New model of conjunctival scarring in the mouse eye

AIMS: To establish a simple model of conjunctival wound healing in the mouse eye. METHODS: 4 week old BABL/c mouse eyes were studied over a 14 day period. Surgical procedure under general anaesthesia involved a blunt dissection of the conjunctiva performed by injection of 25 microliters of PBS via a 27 gauge needle into one eye, while the contralateral eye was used as control. Mice were assessed clinically and sacrificed at 1, 2, 3, 7, and 14 days after surgery. Enucleated eyes were prepared for histological analysis. Development of scar tissue was studied with haematoxylin and eosin, oxidation aldehyde fuchsin, and van Gieson stains, with assessment of cellularity, extracellular matrix formation, and wound characterisation. RESULTS: Histological analysis revealed a marked and characteristic healing response initiated by a predominantly granulocytic inflammatory reaction at day 1 with peak fibroblast activity 3 days after surgery. Oxytalan fibres and newly laid collagen fibres were detected early in the subconjunctival wound area and up to 7 days after surgery. Remodelling and complete organisation of scar tissue was evident by day 14. CONCLUSION: A single subconjunctival injection in the mouse eye results in a marked and consistent healing response. This represents a simple, inexpensive, and reliable animal model of conjunctival scarring. The mouse is a biologically well characterised animal model and allows the use of a wide variety of molecular tools. There are potentially significant clinical applications, in particular in investigating the effects of modulating agents such as antimetabolites, growth factors, and their antagonists on conjunctival scarring.     

Electron spin resonance studies of some Canadian coals

Nine Canadian coals of different rank and composition were studied by electron spin resonance. For percentage of fixed carbon in the range of 43 to 78 wt%, the free radical g values were found to increase with decreasing carbon content, and did not level off for the low rank coals. The free radical linewidths are attributed to atomic species such as oxygen and not to protons of hydrogen.     

Preparation of bovine serum albumin surface-imprinted submicrometer particles with magnetic susceptibility through core-shell miniemulsion polymerization

Molecular imprinting is a state-of-the-art technique for preparing mimics of natural, biological receptors. Nevertheless, the imprinting of macromolecules like proteins remains a challenge due to their bulkiness and sensitivity to denaturation. In this work, a surface imprinting strategy based on covalently immobilized template molecules was adopted for protein imprinting. Bovine serum albumin (BSA) surface-imprinted submicrometer particles (500-600 nm) with magnetic susceptibility were prepared through a two-stage core-shell miniemulsion polymerization system using methyl methacrylate and ethylene glycol dimethacrylate as functional and cross-linking monomers, respectively. The particles possessed a novel red blood cell-like structure and exhibited a very favorable recognition property toward the template BSA molecules in aqueous medium. In a two-protein system, the particles had shown a very high specific recognition of the template proteins over the nontemplate proteins. The magnetic susceptibility was imparted through the successful encapsulation of Fe3O4 nanoparticles. Their superparamagnetic nature increases their potential applications in the fields such as magnetic bioseparation, cell labeling, and bioimaging. In addition, the importance of template immobilization for successful protein imprinting had also been illustrated to demonstrate the potential of this approach as a general methodology for protein imprinting.     

生态之脉朝阳之魂--温榆河生态走廊(朝阳段)规划方案

温榆河生态走廊的总体规划为其地域的未来发展提供了一个清晰的策略性框架,并为沿着河岸的重点区域提供了概念性景观设计内容,希望能藉此创造一个世界级的生态生活环境.方案的设计致力体现对温榆河流域生态环境、社会形态以及当地文化的深刻理解,探讨基地与周边区域所面临的主要的城市设计与生态环境议题,通过土地利用配置、开放空间框架、交通网络,采用科学分析为基础的旅游策略与生态环境策略以及关于生态保育的原则,提供了一个真正的生态走廊设计,建设温榆河走廊成为一个最具强大生态价值与经济价值的世界级河岸走廊.     

Mechanistic study on hydration and drug release behavior of sodium alginate compacts

The influence of sodium alginate viscosity on the dynamics of matrix hydration, solvent front movement, swelling, erosion, and drug release from alginate matrix tablets were examined. The solvent front showed preferential penetration from the radial direction even though matrix swelling showed axial predominance. This study proposed alternative views for the anisotropic behavior of hydrating alginate compacts, namely, formation of gel barrier with different permeability characteristics, tension at the gel-core interface and preferential radial erosion, in addition to an in-depth examination on the contribution of stress relaxation of hydrated polymer as well as core expansion. Alginate matrices demonstrated pH-dependent hydration, swelling and erosion behavior, resulting in pH-dependent drug release mechanisms. Dissolution profiles for alginate matrices of different viscosities were similar in acid but differed upon increase of pH. This was due to the influence of alginate viscosity grade on liquid uptake, erosion and pronounced swelling at near neutral pH.     

Graphite flake self-retraction response based on potential seeking

ABSTRACT: The high elastic modulus and interlayer strengths of graphite flakes make them a durable solid superlubricant. Apart from this, they have configurable electrical properties, exhibit quantum Hall effects, and possess a myriad of useful photonic properties. The self-retraction behavior of graphite flakes can have significant impact on the creation of ordered stacks for various applications because any accidental or intentional displacement of the top flake over the stacks below may result in a misalignment of the carbon-carbon atomic arrangement which, in turn, can have influence over the electrical and photonic properties. It has also been revealed that there was a tendency of the displaced microflake to fail at times to return to its original starting position and orientation. Here, we elucidate this behavior by considering the influence of the interlayer potential forces based on minimal potential energy seeking. The maps of the parameters interrogated here provide the ability for precautions to be undertaken. They also potentially permit the creation of an array of microflake stacks in which the metastable states permit different information to be encoded by virtue of the differentiated photonic or electrical characteristics readable from each array site.     

Electrocoagulation versus chemical coagulation: coagulation/flocculation mechanisms and resulting floc characteristics

Electrocoagulation (EC) and chemical coagulation (CC) are employed in water treatment for particle removal. Although both are used for similar purposes, they differ in their dosing method - in EC the coagulant is added by electrolytic oxidation of an appropriate anode material, while in CC dissolution of a chemical coagulant is used. These different methods in fact induce different chemical environments, which should impact coagulation/flocculation mechanisms and subsequent floc formation. Hence, the process implications when choosing which to apply should be significant. This study elucidates differences in coagulation/flocculation mechanisms in EC versus CC and their subsequent effect on floc growth kinetics and structural evolution. A buffered kaolin suspension served as a representative solution that underwent EC and CC by applying aluminum via additive dosing regime in batch mode. In EC an aluminum anode generated the active species while in CC, commercial alum was used. Aluminum equivalent doses were applied, at initial pH values of 5, 6.5 and 8, while samples were taken over pre-determined time intervals, and analyzed for pH, particle size distribution, ζ potential, and structural properties. EC generated fragile flocs, compared to CC, over a wider pH range, at a substantially higher growth rate, that were prone to restructuring and compaction. The results suggest that the flocculation mechanism governing EC in sweep floc conditions is of Diffusion Limited Cluster Aggregation (DCLA) nature, versus a Reaction Limited Cluster Aggregation (RLCA) type in CC. The implications of these differences are discussed.     

Phase equilibria and electrical properties of pyrochlore and zirconolite phases in the Bi2O3-ZnO-Ta2O5 system

The complete subsolidus phase diagram of the system Bi₂O₃-ZnO-Ta₂O₅, including cubic pyrochlore and monoclinic zirconolite phases, has been determined at 950-1050 °C. Through systematic heat treatment and X-ray diffraction of over 100 compositions, the layout of compatibility triangles (both 2-phase and 3-phase) and single phase solid solution areas has been determined. Pyrochlore and zirconolite phases have ideal nominal compositions Bi_1.5Zn_1.0Ta_1.5O₇ and Bi₂(Zn_1/3Ta_2/3)₂O₇ respectively, but both form solid solution areas. The sintering condition of pyrochlore pellets has been optimised to obtain high density ceramics with minimal weight loss: optimised condition is 1100 °C for pellets covered with sacrificial powder. Permittivity, ?′ dielectric loss and temperature coefficient of capacitance, TCC, of single phase materials were measured using impedance spectroscopy; ?′ and TCC show little variation with composition but the losses are higher for Zn-deficient compositions.