Distinct stages in the recognition, sorting, and packaging of proTGFα into COPII-coated transport vesicles.

In addition to its role in forming vesicles from the endoplasmic reticulum (ER), the coat protein complex II (COPII) is also responsible for selecting specific cargo proteins to be packaged into COPII transport vesicles. Comparison of COPII vesicle formation in mammalian systems and in yeast suggested that the former uses more elaborate mechanisms for cargo recognition, presumably to cope with a significantly expanded repertoire of cargo that transits the secretory pathway. Using proTGFα, the transmembrane precursor of transforming growth factor α (TGFα), as a model cargo protein, we demonstrate in cell-free assays that at least one auxiliary cytosolic factor is specifically required for the efficient packaging of proTGFα into COPII vesicles. Using a knockout HeLa cell line generated by CRISPR/Cas9, we provide functional evidence showing that a transmembrane protein, Cornichon-1 (CNIH), acts as a cargo receptor of proTGFα. We show that both CNIH and the auxiliary cytosolic factor(s) are required for efficient recruitment of proTGFα to the COPII coat in vitro. Moreover, we provide evidence that the recruitment of cargo protein by the COPII coat precedes and may be distinct from subsequent cargo packaging into COPII vesicles

Requirement driven knowledge management system design to support automotive product development

Nowadays, New Product Development (NPD) has become a business priority in manufacturing companies due to international competition in terms of meeting higher and changing customer requirements, generating high profit at low cost, and maintaining sustainable development and growth. Through literature review and industrial investigations, it has been recognised that NPD is an information and knowledge intensive process. However, in current practice, enterprise knowledge is not properly managed or easily accessible. Many service providers have not followed the good practice of considering business objectives and end users’ requirements as main drivers of knowledge management system development and implementation. This doctoral thesis presents a methodology for the design and development of Knowledge Management (KM) systems to support NPD based on Enterprise Architecture Frameworks (EAFs). The project focuses on IT system specifications generation driven by business and knowledge users’ requirements in the automotive industry. Current EAFs have been developed by researchers and practitioners to help enterprises to design their information systems based on business objectives and user requirements. However, these frameworks are mainly proposed to manage information and data such as finances, resources, management and engineering documents, not for the increasingly important enterprise knowledge, especially tacit and unstructured knowledge. This project aims to extend the capabilities of the latest enterprise architecture frameworks so that not only data and information, but also enterprise knowledge can be managed. A guideline in the form of a flowchart has been developed, which provides a process that can be followed and used by system developers and implementation. The extended EAF has been implemented as easy-to-use folders for the development of a structured knowledge base. A case study in an automotive company proved that the methodology can be used to produce the functional specifications of their IT systems to include knowledge management capability. The system specification can then be used, either to assess a company’s existing information systems and direct its future system development and implementation; or to develop/implement a complete new information system from scratch

Homogeneous and Isotropic Cosmology, the Schwarzschild Solution, and Applications

Classically, the physics of the universe is described by Newton\u27s Laws of Motion and Newton\u27s Law of Universal Gravitation. In most cases, the results predicted by Newton\u27s theories accurately agree with experimental observations. However, under certain limitations, classical theories may yield slight deviation from observations, such as when the speed of an object approaches the speed of light. At the extreme, classical theory completely fails to explain the motion of photons, which are massless particles of light. In 1915, Albert Einstein published the General Theory of Relativity. Einstein\u27s theory provides a new perspective to a better understanding of the physics describing this universe. In this paper, we attempt to introduce some of the prerequisite material in differential geometry and investigate the general theory of relativity, along with some of its solutions from a mathematical point of view. We study homogeneous and isotropic cosmology, and the Schwarzschild solution. Finally, we will discuss some of their applications and significance