The neutral amino acid transporter alanine serine cysteine transporter 2 (ASCT2) belongs to the solute carrier 1 (SLC1) family of transport proteins and transports neutral amino acids, such as alanine and glutamine, into the cell in exchange with intracellular amino acids. This amino acid transport is sodium dependent, but not driven by the transmembrane Na+ concentration gradient. Glutamine transport by ASCT2 is proposed to be important for glutamine homoeostasis in rapidly growing cancer cells to fulfill the energy and nitrogen demands of these cells. Thus, ASCT2 is thought to be a potential anticancer drug target. However, the pharmacology of the amino acid binding site is not well established. Here, we report on the synthesis and characterization of a novel class of ASCT2 inhibitors based on an amino acid scaffold with a sulfonamide/sulfonic acid ester linker to a hydrophobic group. The compounds were designed based on an improved ASCT2 homology model using the human glutamate transporter hEAAT1 crystal structure as a modeling template. The compounds were shown to inhibit with a competitive mechanism and a potency that scales with the hydrophobicity of the side chain. The most potent compound binds with an apparent affinity, Ki, of 8 ± 4 µM and can block the alanine response with a Ki of 40 ± 23 µM at 200 µM alanine concentration. Computational analysis predicts inhibitor interactions with the binding site through molecular docking. In conclusion, the sulfonamide/sulfonic acid ester scaffold provides facile synthetic access to ASCT2 inhibitors with a potentially large variability in chemical space of the hydrophobic side chain. These inhibitors will be useful chemical tools to further characterize the role of ASCT2 in disease as well as improve our understanding of inhibition mechanisms of this transporter.

• the identification of types of systems that perform, or support human agents in performing, the activities within a given domain, and• the identification of the nature and content of the interfaces required among those systems. Accordingly, the reference architecture has three parts:• Part 1 -the Activity Model -provides a model of the generic activities involved in the manufacturing process, and the information flows required to support those activities.• Part 2 -the Systems Model -identifies the manufacturing application systems, both human and automated, which perform these activities, and the interfaces required for those systems to support the identified information flows.• Part 3 -the Information Models -define formally and in detail the objects and information which appear in the interfaces.This document is Part 1 -the Activity Model. It represents the first step toward the goal of the SIMA architecture project -to identify the functions and interfaces required of manufacturing applications software systems. It is intended to provide a frame of reference for SIMA projects and similar industrial projects, which are developing "standard interface specifications". As a frame of reference, it permits such specification projects to name and "locate" the interfaces they intend to specify and assists those projects in defining the scope of those interface specifications, by identifying the functions the interface is intended to support.Companion documents will provide the other parts of the reference architecture and define a corresponding "engineering architecture" specifying for each interface the means of information exchange to be used and the representation forms for the information. Multiple engineering architectures which correspond to the reference architecture, but use different mechanisms or forms for interchange, are possible.

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The current industrial revolution is said to be driven by the digitization that exploits connected information across all aspects of manufacturing. Standards have been recognized as an important enabler. Ontology-based information standard may provide benefits not offered by current information standards. Although there have been ontologies developed in the industrial manufacturing domain, they have been fragmented and inconsistent, and little has received a standard status. With successes in developing coherent ontologies in the biological, biomedical, and financial domains, an effort called Industrial Ontologies Foundry (IOF) has been formed to pursue the same goal for the industrial manufacturing domain. However, developing a coherent ontology covering the entire industrial manufacturing domain has been known to be a mountainous challenge because of the multidisciplinary nature of manufacturing. To manage the scope and expectations, the IOF community kicked-off its effort with a proof-of-concept (POC) project. This paper describes the developments within the project. It also provides a brief update on the IOF organizational set up.

Abstract. This paper presents an approach for visually modeling OWL DL and OWL Full ontologies based on the well-established visual modeling language UML. We discuss a metamodel for OWL based on the Meta-Object Facility, an associated UML profile as visual syntax, and transformations between both. The work we present supports modeldriven development of OWL ontologies and is currently undergoing the standardization process of the Object Management Group. After describing our approach, we present the implementation of our approach and an example, showing how the metamodel and UML profile can be used to improve developing Semantic Web applications.