Towards a Pharmacophore for Amyloid

Diagnosing and treating Alzheimer's and other diseases associated with amyloid fibers remains a great challenge despite intensive research. To aid in this effort, we present atomic structures of fiber-forming segments of proteins involved in Alzheimer's disease in complex with small molecule binders, determined by X-ray microcrystallography. The fiber-like complexes consist of pairs of β-sheets, with small molecules binding between the sheets, roughly parallel to the fiber axis. The structures suggest that apolar molecules drift along the fiber, consistent with the observation of nonspecific binding to a variety of amyloid proteins. In contrast, negatively charged orange-G binds specifically to lysine side chains of adjacent sheets. These structures provide molecular frameworks for the design of diagnostics and drugs for protein aggregation diseases

Application of GIS-Based Construction Engineering: An Electronic Document Management System

This paper describes the implementation of a GIS to provide decision support for successfully monitoring the movements and storage of materials, hence ensuring that finished products travel from the point of origin to the destination construction site through the supply-chain management (SCM) system. This system ensures the efficient operation of suppliers, manufacturers, and distributors by determining the shortest path from the point of origin to the final destination to reduce construction costs, minimize time, and enhance productivity. These systems are essential to the construction industry because they reduce costs and save time, thereby improve productivity and effectiveness. This study describes a typical supply-chain model and a geographical information system (GIS)-based SCM that focuses on implementing an electronic document management system, which maps the application framework to integrate geodetic support with the supply-chain system. This process provides guidance for locating the nearest suppliers to fill the information needs of project members in different locations. Moreover, this study illustrates the use of a GIS-based SCM as a collaborative tool in innovative methods for implementing Web mapping services, as well as aspects of their integration by generating an interactive GIS for the construction industry platform