Site-directed mutagenesis of recombinant human beta 2-glycoprotein I identifies a cluster of lysine residues that are critical for phospholipid binding and anti-cardiolipin antibody activity

beta2-Glycoprotein I (beta2GPI) is a phospholipid-binding serum protein with anticoagulant properties. It plays a vital role in the binding of anti-cardiolipin Abs purified from patients with autoimmune disease when assayed in a cardiolipin (CL) ELISA. Based on a three-dimensional model of beta2GPI, electrostatic calculations, and earlier peptide studies, a highly positively charged amino acid sequence, Lys282-Asn-Lys-Glu-Lys-Lys287, located in the fifth domain of beta2GPI, has been predicted to be the phospholipid binding site. We tested this hypothesis by site-directed mutagenesis of residues in the predicted phospholipid binding site and by assessing the mutants for phospholipid binding and anti-beta2GPI activity. A single amino acid change from Lys286 to Glu significantly decreased the binding of beta2GPI to CL. Double and triple mutants 2k (from Lys286, 287 to Glu286, 287), 2ka (from Lys284, 287 to Glu284, 287), and 3k (from Lys284, 286, 287 to Glu284, 286, 287) possessed no binding of Ab to beta2GPI in a CL ELISA, as well as no inhibitory activity on the binding of iodinated native beta2GPI to CL. These results indicate that the residues Lys284, Lys286, and Lys287 in the fifth domain of beta2GPI are critical for its binding to anionic phospholipids and its subsequent capture for binding of anti-beta2GPI Abs.     

信息处理用维语词汇标注标记集的确定

介绍了研究和制定信息处理用维语标注标记集的研究进展。讨论了研究与制订“维语标注标记集”必要性,说明了只靠语法角度提出的词汇一级“维语标注标记集”的有限性,论述国内外英语、汉语层次分析研究的最新成果,结合维语的本身特点研究维语语义分类体系迫切性,给出了“维语标注标记集”的工作思路、标记集制定的原则和语法语义词汇一级词性标记集的内容,比较了标记集两个版本的特点,展望了其发展。     

Global solar radiation estimation from relative sunshine hours in Yemen

The existing measurements of global solar radiation and sunshine duration for Yemen are examined. The errors of estimating solar radiation from sunshine hour measurements using Angstrom's relation are evaluated. As a simple predictor for global radiation, an average Ansgtrom relations in the form

Full-size image (<1K)

for all stations is evaluated. Other Angstrom correlation relations are also proposed by classifying the stations under into four groups. The estimated results are compared and seem to be satisfactory in the latter case.     

In-vitro and in-vivo comparison of T-OA microemulsions and solid dispersions based on EPDC

The goal of this study was to enhance the absorption of a new water-insoluble antitumor lead compound, T-OA (3β-hydroxyolea-12-en-28-oic acid-3, 5, 6-trimethylpyrazin-2-methyl ester). Early-stage preparation discovery concept (EPDC) was employed in this study. Based on this concept, a microemulsion system was chosen as the method of improving bioavailability. The solubility of T-OA was checked in different oils, surfactants and cosurfactants. Ternary phase diagrams were constructed to evaluate the microemulsion domain. Developed high-performance liquid chromatography method was used to determine drug content. The transparent o/w microemulsion formulation composed of oleic acid (oil), Tween 80 (surfactant), ethanol (co-surfactant) and water enhanced the solubility of T-OA up to 20?mg/mL. It was characterized in terms of appearance, content, viscosity, zeta potential, conductivity, morphology and particle size. The particle size distribution, viscosity, conductivity and zeta potential were found to be 70?nm, 15.57?MPa?s, 44.1?μS?cm^?1 and ?0.174, respectively. Oral bioavailability of T-OA microemulsion and oleic acid solution were checked by using rat model. Contrast to the solid dispersion and proto drug, the area-under-the-curve (AUC) of T-OA microemulsion and oleic acid solution were significantly enhanced. The relative bioavailability of T-OA microemulsion was found to be 5654.7%, which is 57-fold higher than the pure drug. Improved T-OA solubility in microemulsion was found sustained 48?h in dilution study. While the solid dispersion may precipitate under the gastrointestinal circumstance based on dilution results. The in-vivo and in-vitro results indicated that, compare to improve the solubility, it is more important to maintain and prolong the T-OA dissolved status, for improvement of the in-vivo absorption.     

On the distance of databases

In the present paper a distance concept of databases is investigated. Two database instances are of distance 0, if they have the same number of attributes and satisfy exactly the same set of functional dependencies. This naturally leads to the poset of closures as a model of changing database. The distance of two databases (closures) is defined to be the distance of the two closures in the Hasse diagram of that poset. We determine the diameter of the poset and show that the distance of two closures is equal to the natural lower bound, that is to the size of the symmetric difference of the collections of closed sets. We also investigate the diameter of the set of databases with a given system of keys. Sharp upper bounds are given in the case when the minimal keys are 2 (or r)-element sets.     

Reactive Magnetron Sputter Deposition of Titanium Oxynitride TiNxOy Coatings: Influence of Substrate Bias Voltage on the Structure,Composition, and Properties

Protection of Metals and Physical Chemistry of Surfaces - TiOxNy films were grown onto 316L stainless steel substrate using radiofrequency (rf) magnetron sputtering from a pure titanium nitride...     

Analysis of Integrin αIIb Subunit Dynamics Reveals Long-Range Effects of Missense Mutations on Calf Domains

Integrin α_IIbβ₃, a glycoprotein complex expressed at the platelet surface, is involved in platelet aggregation and contributes to primary haemostasis. Several integrin α_IIbβ₃ polymorphisms prevent the aggregation that causes haemorrhagic syndromes, such as Glanzmann thrombasthenia (GT). Access to 3D structure allows understanding the structural effects of polymorphisms related to GT. In a previous analysis using Molecular Dynamics (MD) simulations of α_IIb Calf-1 domain structure, it was observed that GT associated with single amino acid variation affects distant loops, but not the mutated position. In this study, experiments are extended to Calf-1, Thigh, and Calf-2 domains. Two loops in Calf-2 are unstructured and therefore are modelled expertly using biophysical restraints. Surprisingly, MD revealed the presence of rigid zones in these loops. Detailed analysis with structural alphabet, the Proteins Blocks (PBs), allowed observing local changes in highly flexible regions. The variant P741R located at C-terminal of Calf-1 revealed that the Calf-2 presence did not affect the results obtained with isolated Calf-1 domain. Simulations for Calf-1 + Calf-2, and Thigh + Calf-1 variant systems are designed to comprehend the impact of five single amino acid variations in these domains. Distant conformational changes are observed, thus highlighting the potential role of allostery in the structural basis of GT.     

Effects of a new saccharose-containing powder on the indicators of carbohydrate and lipid metabolism in animals

Experimental animals were fed with semisynthetic rations with sugar-containing powder (40% of carbohydrate energy value) during 10 months. It has been found that this ration does not influence the levels of glucose in the blood, glycogen in the liver, and the content of triglycerides, total cholesterol and alpha-lipoprotein cholesterol in the blood serum. Similar quantity of refined sugar in the ration led to elevation of the levels of glucose in the blood, of triglycerides and total cholesterol in the blood serum by the end of the experiment. Correlation between biochemical and morphological investigation data has been recorded.     

An Efficient Backoff Algorithm for IEEE 802.15.4 Wireless Sensor Networks

IEEE 802.15.4 is one of the most prominent MAC protocol standard designed to achieve low-power, low-cost, and low-rate wireless personal area networks. The contention access period of IEEE 802.15.4 employs carrier sense multiple access with collision avoidance (CSMA/CA) algorithm. A long random backoff time causes longer average delay, while a small one gives a high collision rate. In this paper, we propose an efficient backoff algorithm, called EBA-15.4MAC that enhances the performance of slotted CSMA/CA algorithm. EBA-15.4MAC is designed based on two new techniques; firstly, it updates the contention window size based on the probability of collision parameter. Secondly, EBA-15.4MAC resolves the problem of access collision via the deployment of a novel Temporary Backoff (TB) and Next Temporary Backoff (NTB). In this case, the nodes not choose backoff exponent randomly as mentioned in the standard but they select TB and NTB values which can be 10–50 % of the actual backoff delay selected by the node randomly. By using these two new methods, EBA-15.4MAC minimizes the level of collision since the probability of two nodes selecting the same backoff period will be low. To evaluate the performance of EBA-15.4MAC mechanism, the network simulator has been conducted. Simulation results demonstrate that the proposed scheme significantly improves the throughput, delivery ratio, power consumption and average delay.