100,658 research outputs found
Commercial Use of WS-PGRADE/gUSE
No full textAlthough originally an academic and research product, the WS-PGRADE/gUSE framework is increasingly applied by commercial institutions too. Within the SCI-BUS project, several commercial gateways have been developed by various companies. WS-PGRADE/gUSE is also intensively used within another European research project, CloudSME (Cloud-based Simulation Platform for Manufacturing and Engineering). This chapter provides an overview and de-scribes in detail some commercial WS-PGRADE/gUSE based gateway implemen-tations. Two representative case studies from the SCI-BUS project, the Build and Test portal and the eDOX Archiver Gateway are introduced. An overview of WS-PGRADE/gUSE based gateways for running simulation applications in the cloud within the CloudSME project is also provided
WS-PGRADE/gUSE-Based Science Gateways in Teaching
No full textVarious WS-PGRADE/gUSE science gateways have been extensively used in educational contexts, supporting courses offered by different European universities and organizations. This chapter presents some examples of how WS-PGRADE/gUSE generic and customized gateways have been used in such cours-es. These examples include practical cases from a variety of scientific fields and educational styles. For each case, the educational context and the course organization are presented, with emphasis on how the respective portal has been adopted for the practical exercises. A summary of experiences are also reported, including advantages and difficulties faced for using these gateways in teaching
Developing Science Gateways at Various Levels of Granularity Using WS-PGRADE/gUSE
No full textScience gateways can provide access to distributed computing resources and applications at very different levels of granularity. Some gateways do not even hide the details of the underlying infrastructure, while on the other end some provide completely customized high-level interfaces to end-users. In this chapter the different granularity levels at which science gateways can be developed with WS-PGRADE/gUSE are analysed. The differences between these various granu-larity levels are also illustrated via the example of a molecular docking gateway and its four different implementations
WS-PGRADE/gUSE in European Projects
No full textBesides core project partners, the SCI-BUS project also supported several external user communities in developing and setting up customized science gateways. The focus was on large communities typically represented by other European research projects. However, smaller local efforts with the potential of generalizing the solution to wider communities were also supported. This chapter gives an overview of support activities related to user communities external to the SCI-BUS project. A generic overview of such activities is provided followed by the detailed description of three gateways developed in collaboration with European projects: the agINFRA Science Gateway for Workflows for agricultural research, the VERCE Science Gateway for seismology, and the DRIHM Science Gateway for weather research and forecasting
Letter, [Author unclear] to Paulina T. Merritt
No full textHandwritten letter to Paulina Merritt from an unknown author, October 1, 1876.
The role of NAADP for Ca2+-signaling in T cells of the rat and ventricular cardiomyocytes of the mouse
No full textCalcium Signalling Triggered by NAADP in T Cells Determines Cell Shape and Motility During Immune Synapse Formation
No full textNicotinic acid adenine dinucleotide phosphate (NAADP) has been implicated as an initial Ca2+ trigger in T cell Ca2+ signalling, but its role in formation of the immune synapse in CD4+ effector T cells has not been analysed. CD4+ T cells are activated by the interaction with peptide-MHCII complexes on the surface of antigen-presenting cells. Establishing a two-cell system including primary rat CD4+ T cells specific for myelin basic protein and rat astrocytes enabled us to mirror this activation process in vitro and to analyse Ca2+ signalling, cell shape changes and motility in T cells during formation and maintenance of the immune synapse. After immune synapse formation, T cells showed strong, antigen-dependent increases in free cytosolic calcium concentration ([Ca2+] i ). Analysis of cell shape and motility revealed rounding and immobilization of T cells depending on the amplitude of the Ca2+ signal. NAADP-antagonist BZ194 effectively blocked Ca2+ signals in T cells evoked by the interaction with antigen-presenting astrocytes. BZ194 reduced the percentage of T cells showing high Ca2+ signals thereby supporting the proposed trigger function of NAADP for global Ca2+ signalling. Taken together, the NAADP signalling pathway is further confirmed as a promising target for specific pharmacological intervention to modulate T cell activation
Adhäsionsvermittelte Voraktivierung von T-Zellen
No full textT cells are an essential part of the adaptive immune system and play a central role in cell-mediated immune response. Their activation leads to an increase of the free cytosolic Ca2+ concentration ([Ca2+]i), which can be described by two main pathways: (i) the release of Ca2+ from intracellular Ca2+ stores into the cytosol and (ii) Ca2+ influx from the extracellular space through Ca2+ channels located at the plasma membrane (PM). Once activated, T cells proliferate and migrate into the inflamed tissue, thereby binding to other cells or extracellular matrix (ECM) proteins via integrins.
Already in 2018, our lab observed formation of local Ca2+ microdomains in the absence of TCR stimulation. However, up to now their detailed molecular mechanism could not be fully elucidated.
In this thesis, the involvement of various components (such as FAK, IP3R, and SOCE proteins) in adhesion-induced pre-activation of T cells was investigated.
Therefore, we utilized three different advanced optical methods: fluorescence resonance energy transfer (FRET), Super Resolution via Optical Re-assignment (SoRa) and Stimulated Emission Depletion (STED) microscopy. Overall, STED microscopy provided the most accurate information for protein localization due to the achievable spatial resolution of up to 40 nm. Furthermore, the formation of clusters could be determined and it was even possible to dissect them into loose and tight clusters. Here, a tight cluster is defined as an interaction between proteins that is visible as a single spot due to its tight localization. Loose clusters, on the other hand, display an accumulation of these spots in a defined region. Based on the existent crystal structures of individual proteins, we were able to examine individual clusters in more detail. Therefore, it was possible to estimate the number of proteins that accumulate at a site.
Next, for the first time, adhesion-dependent co-localization with ORAI1, as well as clustering of FAK, the three IP3R subtypes and SOCE proteins (ORAI1 and STIM1/2) could be determined. The increased co-localization and cluster formation of ORAI1, STIM1, FAK and IP3R1, due to adhesion, suggests an essential role of these proteins in pre-activation of T cells. In addition, the data supports the hypothesis that SOCE activation by STIM1 is critical after adhesion, whereas STIM2 serves to regulate Ca2+ levels.
In conclusion, these results demonstrate a pre-activation state of T cells evoked by adhesion to ECM proteins, involving FAK, IP3R1, and activation of SOCE. Therefore, our findings can be summarized in a three-state model of T cells: (i) quiescent state, (ii) adhesion pre-activated state and (iii) fully activated state upon TCR stimulation
Monolithic triglyceride matrices: a controlled-release system for proteins
No full textMatrices made of glyceryl trimyristate as a bioerodible and biocompatible material were manufactured by compression in dimensions that would still allow an application via injection. Pyranine, as a low molecular hydrophilic compound with a low detection limit, and tetramethylrhodamine labeled bovine serum albumin (TAMRA-BSA), as a high molecular weight (66 kDa) protein compound, served as model drugs for release investigations. In vitro studies with pyranine revealed that release depends substantially on the gelatin content of the matrices, which proved to be a useful tool as a release modifier. The duration of the drug release period can be adjusted to a desired time interval ranging from days to weeks by choosing the right gelatin content. Moreover, results illustrated the importance of the molecular weight and the nature of the compound to be incorporated into such matrices, since investigations with TAMRA-BSA showed a more pronounced burst release and altered release profiles and periods. Experiments with hyaluronidase, which served as a model enzyme to assess the problem of protein integrity in such matrices, suggested that proteins may display sufficient stability during the manufacturing procedure of the cylinders or while in contact with the triglyceride matrices. In addition to in vitro investigations, a study in mice revealed that after 15 days of subcutaneous implantation the matrices showed a good in vivo stability. The main conclusion that could be drawn from these results was that triglycerides are a promising alternative to biodegradable polymers for the development of parenteral release systems for protein and peptide drugs
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