A Conformation-Sensitive Monoclonal Antibody against the A2 Domain of von Willebrand Factor Reduces Its Proteolysis by ADAMTS13

The size of von Willebrand factor (VWF), controlled by ADAMTS13-dependent proteolysis, is associated with its hemostatic activity. Many factors regulate ADAMTS13-dependent VWF proteolysis through their interaction with VWF. These include coagulation factor VIII, platelet glycoprotein 1bα, and heparin sulfate, which accelerate the cleavage of VWF. Conversely, thrombospondin-1 decreases the rate of VWF proteolysis by ADAMTS13 by competing with ADAMTS13 for the A3 domain of VWF. To investigate whether murine monoclonal antibodies (mAbs) against human VWF affect the susceptibility of VWF to proteolysis by ADAMTS13 in vitro, eight mAbs to different domains of human VWF were used to evaluate the effects on VWF cleavage by ADAMTS13 under fluid shear stress and static/denaturing conditions. Additionally, the epitope of anti-VWF mAb (SZ34) was mapped using recombinant proteins in combination with enzyme-linked immunosorbent assay and Western blot analysis. The results indicate that mAb SZ34 inhibited proteolytic cleavage of VWF by ADAMTS13 in a concentration-dependent manner under fluid shear stress, but not under static/denaturing conditions. The binding epitope of SZ34 mAb is located between A1555 and G1595 in the central A2 domain of VWF. These data show that an anti-VWF mAb against the VWF-A2 domain (A1555-G1595) reduces the proteolytic cleavage of VWF by ADAMTS13 under shear stress, suggesting the role of this region in interaction with ADAMTS13

PPCS:a progressive popularity-aware caching scheme for edge-based cache redundancy avoidance in information-centric networks

Abstract This article proposes a novel chunk-based caching scheme known as the Progressive Popularity-Aware Caching Scheme (PPCS) to improve content availability and eliminate the cache redundancy issue of Information-Centric Networking (ICN). Particularly, the proposal considers both entire-object caching and partial-progressive caching for popular and non-popular content objects, respectively. In the case that the content is not popular enough, PPCS first caches initial chunks of the content at the edge node and then progressively continues caching subsequent chunks at upstream Content Nodes (CNs) along the delivery path over time, according to the content popularity and each CN position. Therefore, PPCS efficiently avoids wasting cache space for storing on-path content duplicates and improves cache diversity by allowing no more than one replica of a specified content to be cached. To enable a complete ICN caching solution for communication networks, we also propose an autonomous replacement policy to optimize the cache utilization by maximizing the utility of each CN from caching content items. By simulation, we show that PPCS, utilizing edge-computing for the joint optimization of caching decision and replacement policies, considerably outperforms relevant existing ICN caching strategies in terms of latency (number of hops), cache redundancy, and content availability (hit rate), especially when the CN’s cache size is small