The redoxomics of PTEN: walking a fine line between damage and signaling:mass spectrometry-based approaches to study the effect of oxidation on PTEN function, structure, and protein-protein interactions

The research described in this PhD thesis focuses on proteomics approaches to study the effect of oxidation on the modification status and protein-protein interactions of PTEN, a redox-sensitive phosphatase involved in a number of cellular processes including metabolism, apoptosis, cell proliferation, and survival. While direct evidence of a redox regulation of PTEN and its downstream signaling has been reported, the effect of cellular oxidative stress or direct PTEN oxidation on PTEN structure and interactome is still poorly defined. In a first study, GST-tagged PTEN was directly oxidized over a range of hypochlorous acid (HOCl) concentration, assayed for phosphatase activity, and oxidative post-translational modifications (oxPTMs) were quantified using LC-MS/MS-based label-free methods. In a second study, GSTtagged PTEN was prepared in a reduced and reversibly H2O2-oxidized form, immobilized on a resin support and incubated with HCT116 cell lysate to capture PTEN interacting proteins, which were analyzed by LC-MS/MS and comparatively quantified using label-free methods. In parallel experiments, HCT116 cells transfected with a GFP-tagged PTEN were treated with H2O2 and PTENinteracting proteins immunoprecipitated using standard methods. Several high abundance HOCl-induced oxPTMs were mapped, including those taking place at amino acids known to be important for PTEN phosphatase activity and protein-protein interactions, such as Met35, Tyr155, Tyr240 and Tyr315. A PTEN redox interactome was also characterized, which identified a number of PTEN-interacting proteins that vary with the reversible inactivation of PTEN caused by H2O2 oxidation. These included new PTEN interactors as well as the redox proteins peroxiredoxin-1 (Prdx1) and thioredoxin (Trx), which are known to be involved in the recycling of PTEN active site following H2O2-induced reversible inactivation. The results suggest that the oxidative modification of PTEN causes functional alterations in PTEN structure and interactome, with fundamental implications for the PTEN signaling role in many cellular processes, such as those involved in the pathophysiology of disease and ageing.

Enterprise management and ERP development:case study of Zoomlion using dynamic enterprise reference grid

The enterprise management approach provides a holistic view of organizations and their related information systems. In order to cope with the globalization, virtualization, and volatile competitive environment, traditional firms are seeking to reconstruct their organizational structures and establish new IS architectures to transform from single autonomous entities into more open enterprises supported by new Enterprise Resource Planning (ERP) systems. This paper reports on ERP engage-abilities within three different enterprise management patterns based on the theoretical foundations of the "Dynamic Enterprise Reference Grid". An exploratory inductive study in Zoomlion using the narrative research approach has been conducted. Also, this research delivers a conceptual framework to demonstrate the adoption of ERP in the three enterprise management structures and points to a new architectural type (ERPIII) for operating in the virtual enterprise paradigm. © 2010 Springer-Verlag.

Jointly event extraction and visualization on Twitter via probabilistic modelling

Event extraction from texts aims to detect structured information such as what has happened, to whom, where and when. Event extraction and visualization are typically considered as two different tasks. In this paper, we propose a novel approach based on probabilistic modelling to jointly extract and visualize events from tweets where both tasks benefit from each other. We model each event as a joint distribution over named entities, a date, a location and event-related keywords. Moreover, both tweets and event instances are associated with coordinates in the visualization space. The manifold assumption that the intrinsic geometry of tweets is a low-rank, non-linear manifold within the high-dimensional space is incorporated into the learning framework using a regularization. Experimental results show that the proposed approach can effectively deal with both event extraction and visualization and performs remarkably better than both the state-of-the-art event extraction method and a pipeline approach for event extraction and visualization.