Proteolysis-inducing factor core peptide mediates dermcidin-induced proliferation of hepatic cells through multiple signalling networks

Dermcidin is a candidate oncogene capable of increasing the number of cultured neuronal, breast cancer and prostate cancer cells and improving the survival of hepatic cells. The dermcidin gene encodes the proteolysis-inducing factor core peptide (PIF-CP) and the skin antimicrobial peptide DCD-1. The peptide responsible for inducing proliferation of cells and the mechanisms involved are unknown. In this study, we confirmed a proliferative effect of dermcidin over-expression of 20% (p<0.02) in the HuH7 human hepatic cell line. Proliferation was abrogated by prevention of PIF-CP translation or inactivation of its calcineurin-like phosphatase domain by site-directed mutagenesis. Prevention of DCD-1 translation had no effect. Treatment of cells with a 30 amino acid synthetic PIF-CP induced an analogous increase in proliferation of 14%. Microarray analysis of PIF-CP-treated cells revealed low but significant changes in 111 potential mediator genes. Pathway analysis revealed several gene networks involved in the cellular response to the peptide, one with VEGFB as a hub and two other networks converging on FOS and MYC. Quantitative PCR confirmed direct upregula-tion of VEGFB. These data reveal PIF-CP as the key mediator of dermcidin-induced proliferation and demonstrate induction of key oncogenic pathways

Design approach for the development of a cryomodule for compact crab cavities for Hi-Lumi LHC

A prototype Superconducting RF (SRF) cryomodule, comprising multiple compact crab cavities is foreseen to realise a local crab crossing scheme for the “Hi-Lumi LHC”, a project launched by CERN to increase the luminosity performance of LHC. A cryomodule with two cavities will be initially installed and tested on the SPS drive accelerator at CERN to evaluate performance with high-intensity proton beams. A series of boundary conditions influence the design of the cryomodule prototype, arising from; the complexity of the cavity design, the requirement for multiple RF couplers, the close proximity to the second LHC beam pipe and the tight space constraints in the SPS and LHC tunnels. As a result, the design of the helium vessel and the cryomodule has become extremely challenging. This paper assesses some of the critical cryogenic and engineering design requirements and describes an optimised cryomodule solution for the evaluation tests on SPS

Key Design Features of Crab-Cavity Cryomodule for HiLumi LHC

A prototype Superconducting RF (SRF) cryomodule, comprising multiple compact crab cavities is foreseen to realise a local crab crossing scheme for the “Hi-Lumi LHC”, a project launched by CERN to increase the luminosity performance of LHC. A cryomodule with two cavities will be initially installed and tested on the SPS drive accelerator at CERN to evaluate performance with high-intensity proton beams. STFC in collaboration with, University of Lancaster, CERN and FNAL has developed a concept cryomodule that has overcome most of the critical challenges imposed by a series of boundary conditions arising from; the complexity of the cavity design, the requirement for multiple RF couplers, the close proximity to the second LHC beam pipe and the tight space constraints in the SPS tunnel. This paper highlights some of the key design features of the cryomodule with the results of the associated mechanical and thermal analysis

Architectural Considerations for Recirculated and Energy-Recovered Hard XFEL Drivers

A confluence of events motivates discussion of design options for hard XFEL driver accelerators. Firstly, multiple superconducting radio-frequency (SRF) driven systems are now online (European XFEL), in construction (LCLS-II), or in design (MARIE); these provide increasing evidence of the transformational potential they offer for fundamental science with its concomitant benefits. Secondly, operation of 12 GeV CEBAF* validates use of recirculation in high energy SRF linacs. Thirdly, advances in the analysis and control of effects such as coherent synchrotron radiation (CSR) and the microbunching instability (uBI) have been recently achieved. Collectively, these developments offer insights providing extended facility science reach, reduced costs, multiplicity (i.e., support of numerous FELs operating over a range of wavelengths), and enhanced scalability and upgradability (to higher powers and energies). We will discuss the relationship amongst the various threads, and indicate how they inform design choices for the system architecture of an option for the UK-XFEL** - that of a staged multi-user X-ray FEL and nuclear physics facility based on a multi-pass recirculating SRF CW linac

Testing and Dressed Cavity Design for the HL-LHC 4R Crab Cavity

The High luminosity upgrade to the LHC (HL-LHC) calls for crab cavities to reduce the luminosity loss due to the crossing angle and help provide luminosity levelling. The 4 Rod Crab Cavity (4RCC) is one of three proposed options under consideration. A bare cavity has been prototyped and has undergone recent vertical tests and the results are presented. The dressed cavity includes a power coupler, a lower order mode coupler and two HOM couplers will be presented and discussed

ESS Superconducting RF Collaboration

International audienceThe European Spallation Source (ESS) project is a neutron-scattering facility, currently under construction by a partnership of at least 17 European countries, with Sweden and Denmark as host nations. The ESS was designated a European Research Infrastructure Consortium, or ERIC, by the European Commission in October of 2015. Scientists and engineers from 50 different countries are members of the workforce in Lund who participate in the design and construction of the European Spallation Source. In complement to the local workforce, the superconducting RF linear accelerator is being prototyped and will be constructed based on a collaboration with European institutions: CEA-Saclay, CNRS-IPN Orsay, INFN-LASA, STFC-Daresbury, Uppsala and Lund Universities. After a description of the ESS collaborative project and its in-kind model for the SRF linac, this article will introduce the linac component first results

RF Measurement and Characterization of European Spallation Source Cavities at UKRI-STFC Daresbury Laboratory and DESY

The Accelerator and Science and Technology Centre (ASTeC) is responsible for delivering 88 High Beta (HB) cavities as part of the European Spallation Source (ESS) facility in Sweden. The bulk Niobium Superconducting Radio Frequency (SRF) cavities operate at 704 MHz. They have been fabricated in industry and are currently being tested at Daresbury Laboratory and Deutsches Elektronen-Synchrotron (DESY). They will then be delivered to Commissariat à l’énergie atomique et aux énergies alternatives (CEA) Saclay, France for integration into cryomodules. To date, 50 cavities have been conditioned and evaluated and 36 cavities have been delivered to CEA. This paper discusses the experiences and testing of the cavities performed to date at both sites

The EMMA Non-scaling FFAG

The Elec­tron Model for Many Ap­pli­ca­tions (EMMA) will be the World's first non-scal­ing FFAG and is under con­struc­tion at the STFC Dares­bury Lab­o­ra­to­ry in the UK. Con­struc­tion is due for com­ple­tion in March 2010 and will be fol­lowed by com­mis­sion­ing with beam and a de­tailed ex­per­i­men­tal pro­gramme to study the func­tion­ing of this type of ac­cel­er­a­tor. This paper will give an overview of the mo­ti­va­tion for the pro­ject and de­scribe the EMMA de­sign and hard­ware. The first re­sults from com­mis­sion­ing will be pre­sent­ed in a sep­a­rate paper