Zinc Binding Properties of Engineered RING Finger Domain of Arkadia E3 Ubiquitin Ligase

Human Arkadia is a nuclear protein consisted of 989 amino acid residues, with a characteristic RING domain in its C-terminus. The RING domain harbours the E3 ubiquitin ligase activity needed by Arkadia to ubiquitinate its substrates such as negative regulators of TGF-β signaling. The RING finger domain of Arkadia is a RING-H2 type and its structure and stability is strongly dependent on the presence of two bound Zn(II) ions attached to the protein frame through a defined Cys3-His2-Cys3 motif. In the present paper we transform the RING-H2 type of Arkadia finger domain to nonnative RING sequence, substituting the zinc-binding residues Cys955 or His960 to Arginine, through site-directed mutagenesis. The recombinant expression, in Escherichia coli, of the mutants C955R and H960R reveal significant lower yield in respect with the native polypeptide of Arkadia RING-H2 finger domain. In particular, only the C955R mutant exhibits expression yield sufficient for recombinant protein isolation and preliminary studies. Atomic absorption measurements and preliminary NMR data analysis reveal that the C955R point mutation in the RING Finger domain of Arkadia diminishes dramatically the zinc binding affinity, leading to the breakdown of the global structural integrity of the RING construct

TaskGenX: A Hardware-Software Proposal for Accelerating Task Parallelism

As chip multi-processors (CMPs) are becoming more and more complex, software solutions such as parallel programming models are attracting a lot of attention. Task-based parallel programming models offer an appealing approach to utilize complex CMPs. However, the increasing number of cores on modern CMPs is pushing research towards the use of fine grained parallelism. Task-based programming models need to be able to handle such workloads and offer performance and scalability. Using specialized hardware for boosting performance of task-based programming models is a common practice in the research community. Our paper makes the observation that task creation becomes a bottleneck when we execute fine grained parallel applications with many task-based programming models. As the number of cores increases the time spent generating the tasks of the application is becoming more critical to the entire execution. To overcome this issue, we propose TaskGenX. TaskGenX offers a solution for minimizing task creation overheads and relies both on the runtime system and a dedicated hardware. On the runtime system side, TaskGenX decouples the task creation from the other runtime activities. It then transfers this part of the runtime to a specialized hardware. We draw the requirements for this hardware in order to boost execution of highly parallel applications. From our evaluation using 11 parallel workloads on both symmetric and asymmetric multicore systems, we obtain performance improvements up to 15×, averaging to 3.1× over the baseline.This work has been supported by the RoMoL ERC Advanced Grant (GA 321253), by the European HiPEAC Network of Excellence, by the Spanish Ministry of Science and Innovation (contracts TIN2015-65316-P), by the Generalitat de Catalunya (contracts 2014-SGR-1051 and 2014-SGR-1272), and by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 671697 and No. 779877. M. Moretó has been partially supported by the Ministry of Economy and Competitiveness under Ramon y Cajal fellowship number RYC-2016-21104. Finally, the authors would like to thank Thomas Grass for his valuable help with the simulator.Peer ReviewedPostprint (author's final draft

Effective Viscosity, Resistivity, and Reynolds Number in Weakly Collisional Plasma Turbulence

We examine dissipation and energy conversion in weakly collisional plasma turbulence, employing in situ observations from the Magnetospheric Multiscale (MMS) mission and kinetic Particle-in-Cell (PIC) simulations of proton-electron plasma. A previous result indicated the presence of viscous-like and resistive-like scaling of average energy conversion rates -- analogous to scalings characteristic of collisional systems. This allows for extraction of collisional-like coefficients of effective viscosity and resistivity, and thus also determination of effective Reynolds numbers based on these coefficients. The effective Reynolds number, as a measure of the available bandwidth for turbulence to populate various scales, links macro turbulence properties with kinetic plasma properties in a novel way.Comment: 9 pages, 2 figures, 5 table

Transition from ion-coupled to electron-only reconnection: Basic physics and implications for plasma turbulence

Using kinetic particle-in-cell (PIC) simulations, we simulate reconnection conditions appropriate for the magnetosheath and solar wind, i.e., plasma beta (ratio of gas pressure to magnetic pressure) greater than 1 and low magnetic shear (strong guide field). Changing the simulation domain size, we find that the ion response varies greatly. For reconnecting regions with scales comparable to the ion Larmor radius, the ions do not respond to the reconnection dynamics leading to ''electron-only'' reconnection with very large quasi-steady reconnection rates. The transition to more traditional ''ion-coupled'' reconnection is gradual as the reconnection domain size increases, with the ions becoming frozen-in in the exhaust when the magnetic island width in the normal direction reaches many ion inertial lengths. During this transition, the quasi-steady reconnection rate decreases until the ions are fully coupled, ultimately reaching an asymptotic value. The scaling of the ion outflow velocity with exhaust width during this electron-only to ion-coupled transition is found to be consistent with a theoretical model of a newly reconnected field line. In order to have a fully frozen-in ion exhaust with ion flows comparable to the reconnection Alfv\'en speed, an exhaust width of at least several ion inertial lengths is needed. In turbulent systems with reconnection occurring between magnetic bubbles associated with fluctuations, using geometric arguments we estimate that fully ion-coupled reconnection requires magnetic bubble length scales of at least several tens of ion inertial lengths