Energy dependence of processing and breakdown properties of Cu and Mo

Peer reviewe

HCMV pUL135 remodels the actin cytoskeleton to impair immune recognition of infected cells

Immune evasion genes help human cytomegalovirus (HCMV) establish lifelong persistence. Without immune pressure, laboratory-adapted HCMV strains have undergone genetic alterations. Among these, the deletion of the UL/b’ domain is associated with loss of virulence. In a screen of UL/b’, we identified pUL135 as a protein responsible for the characteristic cytopathic effect of clinical HCMV strains that also protected from natural killer (NK) and T cell attack. pUL135 interacted directly with abl interactor 1 (ABI1) and ABI2 to recruit the WAVE2 regulatory complex to the plasma membrane, remodel the actin cytoskeleton and dramatically reduce the efficiency of immune synapse (IS) formation. An intimate association between F-actin filaments in target cells and the IS was dispelled by pUL135 expression. Thus, F-actin in target cells plays a critical role in synaptogenesis, and this can be exploited by pathogens to protect against cytotoxic immune effector cells. An independent interaction between pUL135 and talin disrupted cell contacts with the extracellular matrix

Compactlight design study

H2020 CompactLight Project aims at designing the next generation of compact hard X-Rays Free-Electron Lasers, relying on very high accelerating gradients and on novel undulator concepts. CompactLight intends to design a compact Hard X-ray FEL facility based on very high-gradient acceleration in the X band of frequencies, on a very bright photo injector, and on short-period/superconductive undulators to enable smaller electron beam energy. If compared to existing facilities, the proposed facility will benefit from a lower electron beam energy, due to the enhanced undulators performance, be significantly more compact, as a consequence both of the lower energy and of the high-gradient X-band structures, have lower electrical power demand and a smaller footprint. CompactLight is a consortium of 24 institutes (21 European + 3 extra Europeans), gathering the world-leading experts both in the domains of X-band acceleration and undulator design

Two novel human cytomegalovirus NK cell evasion functions target MICA for lysosomal degradation

NKG2D plays a major role in controlling immune responses through the regulation of natural killer (NK) cells, αβ and γδ T-cell function. This activating receptor recognizes eight distinct ligands (the MHC Class I polypeptide-related sequences (MIC) A andB, and UL16-binding proteins (ULBP)1–6) induced by cellular stress to promote recognition cells perturbed by malignant transformation or microbial infection. Studies into human cytomegalovirus (HCMV) have aided both the identification and characterization of NKG2D ligands (NKG2DLs). HCMV immediate early (IE) gene up regulates NKGDLs, and we now describe the differential activation of ULBP2 and MICA/B by IE1 and IE2 respectively. Despite activation by IE functions, HCMV effectively suppressed cell surface expression of NKGDLs through both the early and late phases of infection. The immune evasion functions UL16, UL142, and microRNA(miR)-UL112 are known to target NKG2DLs. While infection with a UL16 deletion mutant caused the expected increase in MICB and ULBP2 cell surface expression, deletion of UL142 did not have a similar impact on its target, MICA. We therefore performed a systematic screen of the viral genome to search of addition functions that targeted MICA. US18 and US20 were identified as novel NK cell evasion functions capable of acting independently to promote MICA degradation by lysosomal degradation. The most dramatic effect on MICA expression was achieved when US18 and US20 acted in concert. US18 and US20 are the first members of the US12 gene family to have been assigned a function. The US12 family has 10 members encoded sequentially through US12–US21; a genetic arrangement, which is suggestive of an ‘accordion’ expansion of an ancestral gene in response to a selective pressure. This expansion must have be an ancient event as the whole family is conserved across simian cytomegaloviruses from old world monkeys. The evolutionary benefit bestowed by the combinatorial effect of US18 and US20 on MICA may have contributed to sustaining the US12 gene family

A primary electron beam facility at CERN -- eSPS Conceptual design report

The design of a primary electron beam facility at CERN is described. The study has been carried out within the framework of the wider Physics Beyond Colliders study. It re-enables the Super Proton Synchrotron (SPS) as an electron accelerator, and leverages the development invested in Compact Linear Collider (CLIC) technology for its injector and as an accelerator research and development infrastructure. The facility would be relevant for several of the key priorities in the 2020 update of the European Strategy for Particle Physics, such as an electron-positron Higgs factory, accelerator R\&D, dark sector physics, and neutrino physics. In addition, it could serve experiments in nuclear physics. The electron beam delivered by this facility would provide access to light dark matter production significantly beyond the targets predicted by a thermal dark matter origin, and for natures of dark matter particles that are not accessible by direct detection experiments. It would also enable electro-nuclear measurements crucial for precise modelling the energy dependence of neutrino-nucleus interactions, which is needed to precisely measure neutrino oscillations as a function of energy. The implementation of the facility is the natural next step in the development of X-band high-gradient acceleration technology, a key technology for compact and cost-effective electron/positron linacs. It would also become the only facility with multi-GeV drive bunches and truly independent electron witness bunches for plasma wakefield acceleration. A second phase capable to deliver positron witness bunches would make it a complete facility for plasma wakefield collider studies. [...

Status of the compactlight design study*

CompactLight (XLS) is an International Collaboration of 24 partners and 5 third parties, funded by the European Union through the Horizon 2020 Research and Innovation Programme. The main goal of the project, which started in January 2018 with a duration of 36 months, is the design of an hard X-ray FEL facility beyond today’s state of the art, using the latest concepts for bright electron photo-injectors, high-gradient accelerating structures, and innovative short-period undulators. The specifications of the facility and the parameters of the future FEL are driven by the demands of potential users and the associated science cases. In this paper we will give an overview on the ongoing activities and the major results achieved until now