Binding of tissue plasminogen activator to endothelial cells. The effect on functional properties. Localization of a ligand in the B-chain of tPA

The binding of 125I-labelled tissue plasminogen activator (tPA), the tPA A- or B-chain to endothelial cells (EC) were studied in suspensions of cultured human umbilical vein EC (HUVEC) or immortalized microvascular EC (HMEC). By determinations of the concentration-dependent binding it was shown that both the A-chain and the B-chain, which were isolated after partial reduction of two-chain tPA, contain ligands for binding to EC. The affinity for the B-chain was much higher than for the A-chain according to Scatchard analysis (Kd 24 and 515 nM, respectively), whereas the number of binding sites was higher for the A-chain than for the B-chain (Bmax 8 x 10(5) and 1.2 x 10(5), respectively). There were no cross interactions between the A- and B-chains and their binding sites. The binding of tPA to EC induced an almost 100-fold increase of the activation rate when compared to the same amount of enzyme in free solution, which in contrast to the fibrin-induced stimulation was not inhibited by antibodies against fibrin. The enzymatic activity of the B-chain was much less affected by the association to the cells. Both tPA and the tPA B-chain were largely protected against inhibition by an excess plasminogen activator type-1 (PAI-1) when bound to EC, whereas the same amount of free tPA was totally inactivated. The competition studies strongly indicated that an N-terminal segment in the B-chain, AKHRRSPGER, may be the ligand part of the B-chain. It is interesting to note that this polypeptide segment also participates in a binding site for PAI-1, necessary for effective inhibition. This implies a possible competition between PAI-1 and a tPA-receptor for binding of tPA. High molecular weight urokinase had no quenching effect on the binding of the B-chain to EC.     

Designing circuits with partial scan

In this scan design methodology, only selected faults are targeted for detection. These faults are those not detected by the designer's functional vectors. The test generator decides exactly which flip-flops should be scanned using one of two methods. In the first method, all possible tests are generated for each target fault, and the set of tests requiring the fewest flip-flops is selected. In the second method, only one test is generated for each fault, and the use of flip-flops is avoided as much as possible during test generation. Examples of actual VLSI circuits show a savings of at least a 40% in full-scan overhead     

Landmark-based spatial memory in birds (Parus atricapillus and Columba livia): The use of edges and distances to represent spatial positions.

Birds' use of landmarks to identify spatial locations was examined. Black-capped chickadees (Parus atricapillus) and pigeons (Columba livia) searched for hidden food on a 120-cm–2 tray. In each task the target was near an edge with a nearby landmark. On occasional unrewarded tests the landmark was either left in its usual position, shifted parallel to the edge, shifted perpendicular to the edge, or shifted diagonally. On diagonal landmark shifts the birds shifted their searching more in the parallel direction than in the perpendicular, which violates the predictions of the vector sum model (K. Cheng, 1989). In some cases the birds maintained their searching at a constant perpendicular distance under all landmark shifts. This suggests that perpendicular distance to an edge forms an element in determining where to search on the basis of landmarks. Chickadees and pigeons performed similarly, which suggests similarity in the way they encode locations. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

近程地对地战术导弹的作用与问题

海湾战争中,“爱国者”导弹成功地拦截了“飞毛腿”导弹,给近程地对地战术导弹的作用、发展与装备方向提出了值得思考的问题。本文着重讨论在局部战争中,近程地对地战术导弹的作用、使用场合及其技术发展方向。     

刊首语

今天本刊以全新的面貌呈现于广大读者面前,这是杂志成长过程中的羽化新生。2006年9月,经国家新闻出版总署批准,《中国农村水电及电气化》杂志正式更名为《中国水能及电气化》。作为水利部主管的行业期刊,杂志的更名是主办单位水利部水电局贯彻落实科学发展观和《可再生能源法》     

SIDAC双向开关触发器的典型应用

详细介绍了SIDAC作为一种高压双向触发器的工作特点及其典型的应用电路。     

Managing Clinical Use of High-Alert Drugs: A Supervised Learning Approach to Pharmacokinetic Data Analysis

Drug-related problems, particularly those that result from sub- or overtherapeutic doses of high-alert medications, have become a growing concern in clinical medicine. In this paper, we use a model-tree-based regression technique (namely, M5) and support vector machine (SVM) for regression to develop learning-based systems for predicting the adequacy of a vancomycin regimen. We empirically evaluate each system's accuracy in predicting patients' peak and trough concentrations in different clinical scenarios characterized by renal functions and regimen types. Our data consist of 1099 clinical cases that were collected from a major tertiary medical center in southern Taiwan. We also examine the use of bagging for enhancing the prediction power of the respective systems and include in our evaluation a salient one-compartment model for performance benchmark purposes. Overall, our evaluation results suggest that both M5 and SVM are significantly more accurate than the benchmark one-compartment model in predicting patients' peak and trough concentrations across all investigated clinical scenarios. M5 appears to benefit considerably from bagging, which has a positive but seemingly smaller effect on SVM. Taken together, our findings indicate supervised learning techniques that are capable of effectively supporting clinicians' use of vancomycin or similar high-alert drugs in their patient care and management.     

Thin film deposition on a corrugated surface: A molecular dynamics approach

This paper presents the use of molecular dynamics (MD) simulation in the investigation of the surface topography of early-stage film growth on a GMR (giant-magnetoresistance) corrugated structure. The size of the simulated system is limited in order to reduce the computational workload. The numerical model adopts the Morse potential and the Verlet-leapfrog time evolution scheme [R.W. Hockney, 1970; D. Potter, 1972 (Chapter 5). [1]] to describe the atomic interactions which take place between the atoms. The impact energy transferred from the incident atoms to the substrate is modeled by rescaling the atoms within the upper substrate layers. It is found that the important properties of the film-substrate system may be obtained after the deposition of just several atomic layers. The influence of the impact velocity upon the coating parameters is investigated by varying the incident energy of the deposited atoms. The current results indicate that the surface coverage is poor, when atoms are deposited at low incident energies upon a low temperature substrate. At a higher incident energy, the deposited film tends to exhibit a quasi-layer-by-layer growth mechanism, which results in an improved surface coverage. Finally, it is demonstrated that a distinct quasi-fluid behavior is evident on the substrate when the atoms are deposited at high incident energies.     

Linearly many faults in Cayley graphs generated by transposition trees

We prove that when linearly many vertices are deleted in a Cayley graph generated by a transposition tree, the resulting graph has a large connected component containing almost all remaining vertices.     

Shear-induced crystallization of poly(phenylene sulfide)

The crystalline morphology of poly(phenylene sulfide) (PPS) isothermally crystallized from the melt under shear has been observed by polarized optical microscope (POM) equipped with a CSS450 hot-stage. The shish–kebab-like fibrillar crystal structure is formed at a higher shear rate or for a longer shear time, which is ascribed to the tight aggregation of numerous oriented nuclei in the direction of shear. The crystallization induction time of PPS decreases with the shear time, indicating that the shear accelerates the formation of stable crystal nuclei. Under shear, the increase of spherulite growth rate results from highly oriented chains. The melting behavior of shear-induced crystallized PPS performed by differential scanning calorimetry (DSC) shows multiple melting peaks. The lower melting peak corresponds to melting of imperfect crystal, and the degree of crystal perfection decreases as the shear rate increases. The higher melting peak is related to the orientation of molecular chains. These oriented molecular chains form the orientation nuclei which have higher thermal stability than the kebab-like lamellae that are developed later. A new model based on the above observation has been proposed to explain the mechanism of shish–kebab-like fibrillar crystal formation under shear flow.