Nse2, a component of the Smc5-6 complex, is a SUMO ligase required for the response to DNA damage

The Schizosaccharomyces pombe SMC proteins Rad18 (Smc6) and Spr18 (Smc5) exist in a high-M(r) complex which also contains the non-SMC proteins Nse1, Nse2, Nse3, and Rad62. The Smc5-6 complex, which is essential for viability, is required for several aspects of DNA metabolism, including recombinational repair and maintenance of the DNA damage checkpoint. We have characterized Nse2 and show here that it is a SUMO ligase. Smc6 (Rad18) and Nse3, but not Smc5 (Spr18) or Nse1, are sumoylated in vitro in an Nse2-dependent manner, and Nse2 is itself autosumoylated, predominantly on the C-terminal part of the protein. Mutations of C195 and H197 in the Nse2 RING-finger-like motif abolish Nse2-dependent sumoylation. nse2.SA mutant cells, in which nse2.C195S-H197A is integrated as the sole copy of nse2, are viable, whereas the deletion of nse2 is lethal. Smc6 (Rad18) is sumoylated in vivo: the sumoylation level is increased upon exposure to DNA damage and is drastically reduced in the nse2.SA strain. Since nse2.SA cells are sensitive to DNA-damaging agents and to exposure to hydroxyurea, this implicates the Nse2-dependent sumoylation activity in DNA damage responses but not in the essential function of the Smc5-6 complex

Editorial for FGCS Special issue on “Time-critical Applications on Software-defined Infrastructures”

Performance requirements in many applications can often be modelled as constraints related to time, for example, the span of data processing for disaster early warning [1], latency in live event broadcasting [2], and jitter during audio/video conferences [3]. These time constraints are often treated either in an “as fast as possible” manner, such as sensitive latencies in high-performance computing or communication tasks, or in a “timeliness” way where tasks have to be finished within a given window in real-time systems, as classified in [4]. To meet the required time constraints, one has to carefully analyse time constraints, engineer and integrate system components, and optimise the scheduling for computing and communication tasks. The development of a time-critical application is thus time-consuming and costly. During the past decades, the infrastructure technologies of computing, storage and networking have made tremendous progress. Besides the capacity and performance of physical devices, the virtualisation technologies offer effective resource management and isolation at different levels, such as Java Virtual Machines at the application level, Dockers at the operating system level, and Virtual Machines at the whole system level. Moreover, the network embedding [5] and software-defined networking [6] provide network-level virtualisation and control that enable a new paradigm of infrastructure, where infrastructure resources can be virtualised, isolated, and dynamically customised based on application needs. The software-defined infrastructures, including Cloud, Fog, Edge, software-defined networking and network function virtualisation, emerge nowadays as new environments for distributed applications with time-critical application requirements, but also face challenges in effectively utilising the advanced infrastructure features in system engineering and dynamic control. This special issue on “time-critical applications and software-defined infrastructures” focuses on practical aspects of the design, development, customisation and performance-oriented operation of such applications for Clouds and other distributed environments

Birationality of \'etale morphisms via surgery

We use a counting argument and surgery theory to show that if $D$ is a sufficiently general algebraic hypersurface in $\Bbb C^n$, then any local diffeomorphism $F:X \to \Bbb C^n$ of simply connected manifolds which is a $d$-sheeted cover away from $D$ has degree $d=1$ or $d=\infty$ (however all degrees $d > 1$ are possible if $F$ fails to be a local diffeomorphism at even a single point). In particular, any \'etale morphism $F:X \to \Bbb C^n$ of algebraic varieties which covers away from such a hypersurface $D$ must be birational.Comment: 17 pages. Replaced to add further references and make language more consistent with the literatur

The clinical application of PET/CT: a contemporary review

The combination of positron emission tomography (PET) scanners and x-ray computed tomography (CT) scanners into a single PET/CT scanner has resulted in vast improvements in the diagnosis of disease, particularly in the field of oncology. A decade on from the publication of the details of the first PET/CT scanner, we review the technology and applications of the modality. We examine the design aspects of combining two different imaging types into a single scanner, and the artefacts produced such as attenuation correction, motion and CT truncation artefacts. The article also provides a discussion and literature review of the applications of PET/CT to date, covering detection of tumours, radiotherapy treatment planning, patient management, and applications external to the field of oncology

Reply to "Comment on 'Fano resonance for Anderson Impurity Systems' "

In a recent Comment, Kolf et al. (cond-mat/0503669) state that our analysis of the Fano resonance for Anderson impurity systems [Luo et al., Phys. Rev. Lett 92, 256602 (2004)] is incorrect. Here we want to point out that their comments are not based on firm physical results and their criticisms are unjustified and invalid.Comment: 1 page, 1 figure, to appear in PR

Supermassive Black-hole Demographics & Environments With Pulsar Timing Arrays

Precision timing of large arrays (>50) of millisecond pulsars will detect the nanohertz gravitational-wave emission from supermassive binary black holes within the next ~3-7 years. We review the scientific opportunities of these detections, the requirements for success, and the synergies with electromagnetic instruments operating in the 2020s.Comment: Submitted to the Astro2020 Decadal Survey. One of 5 core white-papers authored by members of the NANOGrav Collaboration. 9 pages, 2 figure

A sharp stability criterion for the Vlasov-Maxwell system

We consider the linear stability problem for a 3D cylindrically symmetric equilibrium of the relativistic Vlasov-Maxwell system that describes a collisionless plasma. For an equilibrium whose distribution function decreases monotonically with the particle energy, we obtained a linear stability criterion in our previous paper. Here we prove that this criterion is sharp; that is, there would otherwise be an exponentially growing solution to the linearized system. Therefore for the class of symmetric Vlasov-Maxwell equilibria, we establish an energy principle for linear stability. We also treat the considerably simpler periodic 1.5D case. The new formulation introduced here is applicable as well to the nonrelativistic case, to other symmetries, and to general equilibria