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Infection Exposure Promotes ETV6-RUNX1 Precursor B-cell Leukemia via Impaired H3K4 Demethylases
(2017)
ETV6-RUNX1 is associated with the most common subtype of childhood leukemia. As few ETV6-RUNX1 carriers develop precursor B cell acute lymphocytic leukemia (pB-ALL), the underlying genetic basis for development of full-blown leukemia remains to be identified, but the appearance of leukemia cases in time-space clusters keeps infection as a potential causal factor. Here we present in vivo genetic evidence mechanistically connecting preleukemic ETV6-RUNX1 expression in hematopoetic stem cells/peripheral cells (HSC/PC) and postnatal infections for human-like pB-ALL. In our model, ETV6-RUNX1 conferred a low risk of developing pB-ALL after exposure to common pathogens, corroborating the low incidence observed in humans. Murine preleukemic ETV6-RUNX1 pro/preB cells showed high Rag1/2 expression, known for human ETV6-RUNX1 pB-ALL. Murine and human ETV6-RUNX1 pB-ALL revealed recurrent genomic alterations, with a relevant proportion affecting genes of the lysine demethylase (KDM) family. KDM5C loss-of-function resulted in increased levels of H3K4me3, which co-precipitated with RAG2 in a human cell line model, laying the molecular basis for recombination activity. We conclude that alterations of KDM family members represent a disease-driving mechanism and an explanation for RAG off-target cleavage observed in humans. Our results explain the genetic basis for clonal evolution of an ETV6-RUNX1 preleukemic clone to pB-ALL after infection exposure and offer the possibility of novel therapeutic approaches.
OpenDaylight (ODL) is a commercial, collaborative, open-source platform to accelerate the adoption and innovation of Software Defined Networking (SDN) and Network Function Visualization. This paper describes the novel ODL architecture in a simplified way to grasp a better understanding of such architecture. ODL architecture intends to foster new innovation and accelerate adoption of programming the network. The innovation of Model-Driven Service Abstraction Layer (MD-SAL) in the architecture leads to developing models for automatic management and configuration of the networks. MD-SAL provides ODL with the ability to support any protocol talking to the network elements as well as any network application. The flexibility inherent in ODL architecture could enable ODL to shape the next generation networks.
We present a new interface for interactive comparisons of more than two alternative documents in the context of a generative design system that uses generative data-flow networks defined via directed acyclic graphs. To better show differences between such networks, we emphasize added, deleted, (un)changed nodes and edges. We emphasize differences in the output as well as parameters using highlighting and enable post-hoc merging of the state of a parameter across a selected set of alternatives. To minimize visual clutter, we introduce new difference visualizations for selected nodes and alternatives using additive and subtractive encodings, which improve readability and keep visual clutter low. We analyzed similarities in networks from a set of alternative designs produced by architecture students and found that the number of similarities outweighs the differences, which motivates use of subtractive encoding. We ran a user study to evaluate the two main proposed difference visualization encodings and found that they are equally effective.
Studienverläufe von Studenten weichen nicht selten vom offiziell geplanten Curriculum ab. Für eine den Studienerfolg verbessernde Planung und Weiterentwicklung von Studiengängen und Curricula fehlen den Verantwortlichen häufig Erkenntnisse über tatsächliche sowie typischerweise erfolgreiche und weniger erfolgreiche Studienverlaufsmuster. Process-Mining-Techniken können helfen, mehr Transparenz bei der Auswertung von Studienverläufen zu schaffen und so die Erkennung typischer Studienverlaufsmuster, die Überprüfung der Übereinstimmung der konkreten Studienverläufe mit dem vorgegebenen Curriculum sowie eine zielgerechte Verbesserung des Curriculums zu unterstützen.
Maßgefertigte Abläufe
(2017)
A deployment of the Vehicle-2-Vehicle communication technology according to ETSI is in preparation in Europe. Currently, a policy for a necessary Public Key Infrastructure to enrol cryptographic keys and certificates for vehicles and infrastructure component is in discussion to enable an interoperable Vehicle-2-Vehicle communication. Vehicle-2-Vehicle communication means that vehicles periodically send Cooperative Awareness Messages. These messages contain the current geographic position, driving direction, speed, acceleration, and the current time of a vehicle. To protect privacy (location privacy, “speed privacy”) of vehicles and drivers ETSI provides a specific pseudonym concept. We show that the Vehicle-2-Vehicle communication can be misused by an attacker to plot a trace of sequent Cooperative Awareness Messages and to link this trace to a specific vehicle. Such a trace is non-disputable due to the cryptographic signing of the messages. So, the periodically sending of Cooperative Awareness Messages causes privacy problems even if the pseudonym concept is applied.