Revisiting the IIoT Platform Graveyard: Key Learnings from Failed IIoT Platform Initiatives

The Industrial Internet of Things (IIoT) has led to a competitive race among digital and incumbent players to establish IIoT platforms. However, despite the undisputed potential of the IIoT, a first wave of IIoT platforms failed around 2018, with GE’s Predix being the most prominent one. Nevertheless, building upon valuable lessons learned, the IIoT platform market continued to grow significantly. We now experience a second wave of IIoT platform failures, with companies like Siemens, Google, and SAP divesting or restructuring significant parts of their IIoT platform. Acknowledging this, we revisited the IIoT platform graveyard to challenge and extend existing lessons learned. Hence, we interviewed major IIoT platforms and customers that were impacted by IIoT platform failures. We identified six key learnings that we integrated into a preliminary model for IIoT platform growth, highlighting evolutionary steps for successful platform growth. These findings provide practitioners strategic orientation for establishing IIoT platforms long-term

Advanced Numerical Simulation of Organic Light-emitting Devices

Materials scienc

Chapter Advanced Numerical Simulation of Organic Light-emitting Devices

Materials scienc

Spin-Parity Analysis of the Centrally produced KsKs system at 800 GeV

Results are presented of the spin-parity analysis on a sample of centrally produced mesons in the reaction (p p -> p_{slow} K_s K_s p_{fast}) with 800 GeV protons on liquid hydrogen. The spin-parity analysis in the mass region between threshold and 1.58 GeV/c^2 shows that the (K_s K_s) system is produced mainly in S-wave. The f_0(1500) is clearly observed in this region. Above 1.58 GeV/c^2 two solutions are possible, one with mainly S-wave and another with mainly D-wave. This ambiguity prevents a unique determination of the spin of the f_J(1710) meson.Comment: 6 pages, including 6 figures. LaTex, uses 'espcrc2.sty'. To appear in LEAP'96 proceeding

Automated Real-Time Control of Fluidic Self-Assembly of Microparticles

Self-assembly is a key coordination mechanism for large multi-unit systems and a powerful bottom-up technology for micro/nanofabrication. Controlled self-assembly and dynamic reconfiguration of large ensembles of microscopic particles can effectively bridge these domains to build innovative systems. In this perspective, we present SelfSys, a novel platform for the automated control of the fluidic self-assembly of microparticles. SelfSys centers around a water-filled microfluidic chamber whose agitation modes, induced by a coupled ultrasonic actuator, drive the assembly. Microparticle dynamics is imaged, tracked and analyzed in real-time by an integrated software framework, which in turn algorithmically controls the agitation modes of the microchamber. The closed control loop is fully automated and can direct the stochastic assembly of microparticle clusters of preset dimension. Control issues specific to SelfSys implementation are discussed, and its potential applications presented. The SelfSys platform embodies at microscale the automated self-assembly control paradigm we first demonstrated in an earlier platform

Nanobodies as allosteric modulators of Parkinson’s disease-associated LRRK2

Mutations in the gene coding for Leucine-Rich Repeat Kinase 2 (LRRK2) are a leading cause of the inherited form of Parkinson’s disease (PD), while LRRK2 overactivation is also associated with the more common idiopathic form of PD. LRRK2 is a large multi-domain protein, including a GTPase as well as a Ser/Thr protein kinase domain. Common disease-causing mutations increase LRRK2 kinase activity, presenting LRRK2 as an attractive target for inhibitory drug design. Currently, drug development has mainly focused on ATP-competitive kinase inhibitors. Here, we report the identification and characterization of a variety of Nanobodies that bind to different LRRK2 domains and inhibit or activate LRRK2 activity in cells and in vitro. Importantly, diverse groups of Nanobodies were identified that inhibit LRRK2 kinase activity through a mechanism that does not involve binding to the ATP pocket or even to the kinase domain. Moreover, while certain Nanobodies completely inhibit the LRRK2 kinase activity, we also identified Nanobodies that specifically inhibit the phosphorylation of Rab protein substrates. Finally, in contrast to current type-I kinase inhibitors, the studied kinase-inhibitory Nanobodies did not induce LRRK2 microtubule association. These comprehensively characterized Nanobodies represent versatile tools to study the LRRK2 function and mechanism, and can pave the way toward novel diagnostic and therapeutic strategies for PD

Nanobodies as allosteric modulators of Parkinson's disease-associated LRRK2

Mutations in the gene coding for leucine-rich repeat kinase 2 (LRRK2) are a leading cause of the inherited form of Parkinson’s disease (PD), while LRRK2 overactivation is also associated with the more common idiopathic form of PD. LRRK2 is a large multidomain protein, including a GTPase as well as a Ser/Thr protein kinase domain. Common, disease-causing mutations increase LRRK2 kinase activity, presenting LRRK2 as an attractive target for drug discovery. Currently, drug development has mainly focused on ATP-competitive kinase inhibitors. Here, we report the identification and characterization of a variety of nanobodies that bind to different LRRK2 domains and inhibit or activate LRRK2 in cells and in in vitro. Importantly, nanobodies were identified that inhibit LRRK2 kinase activity while binding to a site that is topographically distinct from the active site and thus act through an allosteric inhibitory mechanism that does not involve binding to the ATP pocket or even to the kinase domain. Moreover, while certain nanobodies completely inhibit the LRRK2 kinase activity, we also identified nanobodies that specifically inhibit the phosphorylation of Rab protein substrates. Finally, in contrast to current type I kinase inhibitors, the studied kinase-inhibitory nanobodies did not induce LRRK2 microtubule association. These comprehensively characterized nanobodies represent versatile tools to study the LRRK2 function and mechanism and can pave the way toward novel diagnostic and therapeutic strategies for PD