MACE: Deliverable JD8 - Report on training

The objective of the MACE project is to interlink repositories to provide simplified access to digital, architectural learning resources. Gaps resulting from autonomous design, implementation, funding, and maintenance are bridged by implementing conceptual tools (ontologies, glossaries, and standards), interfaces and metadata agglomeration. Consequently, MACE will create innovative e-learning tools that help both expert users and laypeople to find, tag, acquire, use, and discuss contents from many architectural repositories that previously had limited accessibility. Even though the MACE software is designed to be as self explanatory as possible, it offers a variety of services and tools. In this context, this document reports on how users of MACE are trained to use MACE tools and to integrate with MACE tools

MACE: Joint Deliverable "Evaluation of the MACE system"

Stefaner, M., Wolpers, M., Memmel, M., Duval, E., Specht, M., Börner, D., Gruber, M., De Jong, T., Giretti, A., & Klemke, R. (2009). MACE: Joint Deliverable "Evaluation of the MACE system". MACE-project.This deliverable presents the evaluation results of the MACE project1. MACE integrates large amounts of technology enhanced learning contents and metadata in the domain of architecture, in order to create a framework for the integration of multiple content sources, content enrichment with different metadata types, and improved access to these existing contents.MAC

A Role for P21-Activated Kinase in Endothelial Cell Migration

The serine/threonine p21-activated kinase (PAK) is an effector for Rac and Cdc42, but its role in regulating cytoskeletal organization has been controversial. To address this issue, we investigated the role of PAK in migration of microvascular endothelial cells. We found that a dominant negative (DN) mutant of PAK significantly inhibited cell migration and in-creased stress fibers and focal adhesions. The DN effect mapped to the most NH2-terminal proline-rich SH3-binding sequence. Observation of a green fluorescent protein-tagged α-actinin construct in living cells revealed that the DN construct had no effect on membrane ruffling, but dramatically inhibited stress fiber and focal contact motility and turnover. Constitutively active PAK inhibited migration equally well and also increased stress fibers and focal adhesions, but had a somewhat weaker effect on their dynamics. In contrast to their similar effects on motility, DN PAK decreased cell contractility, whereas active PAK increased contractility. Active PAK also increased myosin light chain (MLC) phosphorylation, as indicated by staining with an antibody to phosphorylated MLC, whereas DN PAK had little effect, despite the increase in actin stress fibers. These results demonstrate that although PAK is not required for extension of lamellipodia, it has substantial effects on cell adhesion and contraction. These data suggest a model in which PAK plays a role coordinating the formation of new adhesions at the leading edge with contraction and detachment at the trailing edge

Towards Design Patterns for Augmented Reality Serious Games

For professional workers today, keeping up with knowledge and the continuous technology progress is challenging. Increased innovation speed and dynamic work situations shorten preparation times for new tasks significantly. Traditional professional training approaches preparing employees for new tasks are becoming inappropriate. Thus new educational means are needed. These would help employees get acquainted with new situations faster and more efficiently. According to learning theories such as action learning and situated learning, which embed the learning process in the application context and challenge the learner to be actively involved help to improve the learning process. These theories are the basis for mobile learning and serious games. From research in Serious Games we know that games have the potential to actively involve learners and to immerse them in a learning situation and increase their engagement. With Augmented Reality (AR) and wearable devices a new generation of tools and applications becomes available, which inherently are mobile, contextualized and personalized. First successful application scenarios show the potential of these new technologies for education and training. While the application of game-design patterns to learning processes help to systematically design learning games supporting specific learning outcomes, an empirically tested, systematic approach towards the design of AR-based learning solutions is still missing. Based on the state of the art in AR research and in applying design patterns for serious games, we consequently propose a research methodology to apply game design patterns to augmented reality-based learning games for the training of professionals in dynamic situations

Trihydrophobin 1 Phosphorylation by c-Src Regulates MAPK/ERK Signaling and Cell Migration

c-Src activates Ras-MAPK/ERK signaling pathway and regulates cell migration, while trihydrophobin 1 (TH1) inhibits MAPK/ERK activation and cell migration through interaction with A-Raf and PAK1 and inhibiting their kinase activities. Here we show that c-Src interacts with TH1 by GST-pull down assay, coimmunoprecipitation and confocal microscopy assay. The interaction leads to phosphorylation of TH1 at Tyr-6 in vivo and in vitro. Phosphorylation of TH1 decreases its association with A-Raf and PAK1. Further study reveals that Tyr-6 phosphorylation of TH1 reduces its inhibition on MAPK/ERK signaling, enhances c-Src mediated cell migration. Moreover, induced tyrosine phosphorylation of TH1 has been found by EGF and estrogen treatments. Taken together, our findings demonstrate a novel mechanism for the comprehensive regulation of Ras/Raf/MEK/ERK signaling and cell migration involving tyrosine phosphorylation of TH1 by c-Src

Postnatal Changes in the Expression Pattern of the Imprinted Signalling Protein XLαs Underlie the Changing Phenotype of Deficient Mice

The alternatively spliced trimeric G-protein subunit XLαs, which is involved in cAMP signalling, is encoded by the Gnasxl transcript of the imprinted Gnas locus. XLαs deficient mice show neonatal feeding problems, leanness, inertia and a high mortality rate. Mutants that survive to weaning age develop into healthy and fertile adults, which remain lean despite elevated food intake. The adult metabolic phenotype can be attributed to increased energy expenditure, which appears to be caused by elevated sympathetic nervous system activity. To better understand the changing phenotype of Gnasxl deficient mice, we compared XLαs expression in neonatal versus adult tissues, analysed its co-localisation with neural markers and characterised changes in the nutrient-sensing mTOR1-S6K pathway in the hypothalamus. Using a newly generated conditional Gnasxl lacZ gene trap line and immunohistochemistry we identified various types of muscle, including smooth muscle cells of blood vessels, as the major peripheral sites of expression in neonates. Expression in all muscle tissues was silenced in adults. While Gnasxl expression in the central nervous system was also developmentally silenced in some midbrain nuclei, it was upregulated in the preoptic area, the medial amygdala, several hypothalamic nuclei (e.g. arcuate, dorsomedial, lateral and paraventricular nuclei) and the nucleus of the solitary tract. Furthermore, expression was detected in the ventral medulla as well as in motoneurons and a subset of sympathetic preganglionic neurons of the spinal cord. In the arcuate nucleus of Gnasxl-deficient mice we found reduced activity of the nutrient sensing mTOR1-S6K signalling pathway, which concurs with their metabolic status. The expression in these brain regions and the hypermetabolic phenotype of adult Gnasxl-deficient mice imply an inhibitory function of XLαs in energy expenditure and sympathetic outflow. By contrast, the neonatal phenotype of mutant mice appears to be due to a transient role of XLαs in muscle tissues

Genomic loss of the putative tumor suppressor gene E2A in human lymphoma

The transcription factor E2A is essential for lymphocyte development. In this study, we describe a recurrent E2A gene deletion in at least 70% of patients with Sézary syndrome (SS), a subtype of T cell lymphoma. Loss of E2A results in enhanced proliferation and cell cycle progression via derepression of the protooncogene MYC and the cell cycle regulator CDK6. Furthermore, by examining the gene expression profile of SS cells after restoration of E2A expression, we identify several E2A-regulated genes that interfere with oncogenic signaling pathways, including the Ras pathway. Several of these genes are down-regulated or lost in primary SS tumor cells. These data demonstrate a tumor suppressor function of E2A in human lymphoid cells and could help to develop new treatment strategies for human lymphomas with altered E2A activity