In this scenario, neither the computers with GE Digital products to be licensed nor the Local License Server are connected to the Internet. Using a flash drive or other portable media device, files are transferred between the offline Local License Server and an online computer that can connect to the GE License Server. Intranet computers then connect to the Local License Server to obtain activation.
In this scenario, a computer with GE Digital products to be licensed is not connected to the Internet. Using a flash drive or other portable media device, files are transferred between the offline computer and an online computer that can connect to the GE License Server to complete activation.
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The CODESYS Development System allows for the development of professional control applications. Numerous standard functions are included, such as integrated compilers and a fully developed library design, as well as all IEC 61131-3-compliant editors.
The license number is a 25-digit number which is needed to activate the licenses purchased in the CODESYS Store. The activation can be done directly in the CODESYS Development System via the integrated License Manager or via the CODESYS License Central - an online platform under
The licenses can be stored on a server in the local network and used there by all connected users. The number of licenses determines the number of users possible at the same time. The license activation itself takes place via the CODESYS soft container, which is permanently bound on the server. Alternatively, the license can be stored on a CODESYS key. By changing the CODESYS key, the license can be used on another server.
(A) In humans, the TCR is comprised of predominately ÎÎ heterodimers (but also ÎÎ chains) that assemble into the TCR (i. PDB 1TCR) [96]. Crucial for the ability of the adaptive immune system to respond to novel antigens, each T cell possesses a TCR with unique pMHC binding properties (ii. PDB 2AK4). In cells the ÎÎ TCR is associated with the CD3εÎ, CD3εÎ, and a Î chain homodimer (ÎÎ) in a 1:1:1:1 stoichiometry (iii.) [97, 98]. Binding of the TCR to antigen causes T cell activation and leads to the initiation of a T cell response. Upon activation, a naive T cell undergoes expansion and differentiation into effector subsets. These effector subsets carry out specialized functions that are responsible for coordinating the adaptive immune response. (B) When TCR:pMHC binding occurs it is communicated across the T cell plasma membrane when the TCR complex is phosphorylated by the kinase Lck. Phosphorylated signaling motifs within the TCR complex recruit the Zap70 kinase. Recruitment of Zap70, and its phosphorylation by Lck, causes its activation. Zap70 then phosphorylates the adaptor protein LAT which recruits additional signaling effectors that become activated (BOX 1). In this way, the binding of the TCR to pMHC antigen is converted into a biochemical signal. A TCR signal causes global cellular changes within the T cell ranging from the activation of transcriptional regulators and protein synthesis to the reorganization of the cytoskeleton and altered metabolism and are necessary for a naive T cell to undergo clonal expansion and differentiation into effector subsets.
(A) Lck is a Src family kinase (SFK) and is localized to the inner leaflet of the plasma membrane through lipidation of its N-terminus where it associates with the cytoplasmic domain of the CD4/CD8 coreceptors. Lck possess a catalytic kinase domain, two regulatory domains, and several sites of phosphorylation. The activity of the catalytic kinase domain is controlled by regulating its conformation. Conformational control is achieved through phosphorylation of Lck regulatory sites. The C-terminal tail of Lck, when phosphorylated, is bound by the SH2 regulatory domain through an intramolecular interaction to stabilize the inactive autoinhibited conformation. In contrast, the active conformation of Lck is stabilized by trans-autophosphorylation of the activation loop within the kinase domain. (B) Recent studies have indicated that a pool of Lck is basally active in resting T cells. Increasing the abundance of active Lck molecules can alter affinity discrimination and potentiate T cell activation in response to low affinity ligands. (C) Inhibitory feedback pathways are proposed to regulate the abundance of active Lck molecules in a T cell. Phosphorylation of Y192 within the SH2 domain of Lck is proposed to disrupt the activation of Lck by CD45 and therefore reduce the abundance of active Lck and TCR sensitivity. (D) Because the inhibitory kinase Csk is cytoplasmic, recruitment of Csk to the plasma membrane through the Lckdependent phosphorylation of inhibitory adaptor proteins (e.g., PAG) can decrease active Lck abundance.
(A) Lck and Zap70 exist in a strict signaling hierarchy. (B) Zap70 undergoes stepwise activation which requires its recruitment to phosphorylated ITAMs within the TCR complex and its phosphorylation by Lck. (C) Zap70 contains a highly basic region that is important for its rigid substrate specificity. The basic region of Zap70 acts as an electrostatic filter to ensure specificity for phosphosites within LAT and SLP-76 and prevents phosphorylation of ITAMs and the Zap70 activation loop. (D) Phosphorylation of Zap70 Y126 is proposed to cause its release from the TCR complex such that it can migrate and encounter LAT to phosphorylate it. Meanwhile, additional Zap70 molecules are able to bind the TCR complex and become activated suggesting a mode of TCR signal amplification.
(A) In vitro reconstitution studies have revealed that multivalent interactions between adaptors such as Grb2/Gads and SOS1 molecules can bridge LAT adaptors to assemble liquid-like phase separated clusters. These clusters are dynamic and can be reversed through dephosphorylation by protein tyrosine phosphatases. Interestingly, these LAT clusters have been observed to enrich Zap70 and exclude the phosphatase CD45. (B) The assembly of distinct LAT signalosomes has been observed to occur upon crosslinking of the LFA-1 integrin. These LAT signalosomes are formed through the activation of FAK kinase which phosphorylates only LAT Y171 which recruits a Grb2/SKAP1 complex. These LAT-Grb2-SKAP1 signalosomes are reported to mediate de-adhesion of LFA-1 and regulate cell motility.
Product activation is a quick and anonymous process that confirms the authenticity of your software. This is done toprotect you from the adverse effects of pirated software. The process also verifies that AdminStudio has not been activatedon more machines than allowed by the AdminStudio End-User License Agreement (EULA).
After you first launch AdminStudio, the activation wizard opens. After a few seconds, the activation wizard disappears ifyou have not clicked on it, and AdminStudio is launched as a trial product. If you want to activate AdminStudio right away,you can select the Activate or Purchase AdminStudio option, and then click the Next button. The wizard guides youthrough the activation process, and in seconds, AdminStudio is activated.
Product reactivation is the process by which an activated product is checked to verify that it is still installed according tothe AdminStudio EULA, and that it has not been activated on more machines than allowed.
Reactivation is required on each machine on which AdminStudio has been successfully installed and activated.Reactivation must occur a certain number of months after the last activation or reactivation occurred; otherwise,AdminStudio stops working.
Reactivation offers more flexibility than licensing models that do not require it. With the reactivation model that is used forAdminStudio, a license is not permanently tied to a specific machine; this allows users to periodically update and replacehardware and the machines on which AdminStudio is installed.
Reactivation typically occurs automatically, without any interaction on your part. Several weeks before reactivation isrequired, the activation wizard sends a reactivation request for your activation code to the activation server silently (thatis, without displaying any user interface). The server receives the reactivation request, and it validates the request. If thereactivation request is successful, the server automatically notifies the activation wizard about the status, enabling thewizard to reactivate AdminStudio for you.
If reactivation cannot be automatically performed when needed (for example, if you do not have an Internet connection),the activation wizard is displayed when you launch AdminStudio. At that point, the activation wizard lets you reactivateAdminStudio using the same wizard that is used for activation. The wizard first attempts an online reactivation. If onlinereactivation is unsuccessful, the wizard enables you to use the offline method.
After purchasing AdminStudio (and subsequently receiving your activation code), you simply enter the activation code inthe designated field that is displayed in the activation wizard when you launch AdminStudio, and then click the Activatebutton.
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