The Large Hadron-Electron Collider at the HL-LHC

The Large Hadron-Electron Collider (LHeC) is designed to move the field of deep inelastic scattering (DIS) to the energy and intensity frontier of particle physics. Exploiting energy-recovery technology, it collides a novel, intense electron beam with a proton or ion beam from the High-Luminosity Large Hadron Collider (HL-LHC). The accelerator and interaction region are designed for concurrent electron-proton and proton-proton operations. This report represents an update to the LHeC's conceptual design report (CDR), published in 2012. It comprises new results on the parton structure of the proton and heavier nuclei, QCD dynamics, and electroweak and top-quark physics. It is shown how the LHeC will open a new chapter of nuclear particle physics by extending the accessible kinematic range of lepton-nucleus scattering by several orders of magnitude. Due to its enhanced luminosity and large energy and the cleanliness of the final hadronic states, the LHeC has a strong Higgs physics programme and its own discovery potential for new physics. Building on the 2012 CDR, this report contains a detailed updated design for the energy-recovery electron linac (ERL), including a new lattice, magnet and superconducting radio-frequency technology, and further components. Challenges of energy recovery are described, and the lower-energy, high-current, three-turn ERL facility, PERLE at Orsay, is presented, which uses the LHeC characteristics serving as a development facility for the design and operation of the LHeC. An updated detector design is presented corresponding to the acceptance, resolution, and calibration goals that arise from the Higgs and parton-density-function physics programmes. This paper also presents novel results for the Future Circular Collider in electron-hadron (FCC-eh) mode, which utilises the same ERL technology to further extend the reach of DIS to even higher centre-of-mass energies.Peer reviewe

Extensive germline-somatic interplay contributes to prostate cancer progression through HNF1B co-option of TMPRSS2-ERG

Abstract Genome-wide association studies have identified 270 loci conferring risk for prostate cancer (PCa), yet the underlying biology and clinical impact remain to be investigated. Here we observe an enrichment of transcription factor genes including HNF1B within PCa risk-associated regions. While focused on the 17q12/HNF1B locus, we find a strong eQTL for HNF1B and multiple potential causal variants involved in the regulation of HNF1B expression in PCa. An unbiased genome-wide co-expression analysis reveals PCa-specific somatic TMPRSS2-ERG fusion as a transcriptional mediator of this locus and the HNF1B eQTL signal is ERG fusion status dependent. We investigate the role of HNF1B and find its involvement in several pathways related to cell cycle progression and PCa severity. Furthermore, HNF1B interacts with TMPRSS2-ERG to co-occupy large proportion of genomic regions with a remarkable enrichment of additional PCa risk alleles. We finally show that HNF1B co-opts ERG fusion to mediate mechanistic and biological effects of the PCa risk-associated locus 17p13.3/VPS53/FAM57A/GEMIN4. Taken together, we report an extensive germline-somatic interaction between TMPRSS2-ERG fusion and genetic variations underpinning PCa risk association and progression

Genome-wide 3′-UTR single nucleotide polymorphism association study identifies significant prostate cancer risk-associated functional loci at 8p21.2 in Chinese population

Abstract MicroRNAs (miRNAs) are involved in the regulation of gene expression via incomplete base pairing to sequence motifs at the three prime untranslated regions (3′-UTRs) of mRNAs and play critical roles in the etiology of cancers. Single nucleotide polymorphisms (SNPs) in the 3′-UTR miRNA-binding regions may influence the miRNA affinity. However, this biological mechanism in prostate cancer (PCa) remains unclear. Here, a three-stage genome-wide association study of 3′-UTR SNPs (n=33 117) is performed in 5515 Chinese men. Three genome-wide significant variants are discovered at 8p21.2 (rs1567669, rs4872176, and rs4872177), which are all located in a linkage disequilibrium region of the NKX3–1 gene. Phenome-wide association analysis using the FinnGen data reveals a specific association of rs1567669 with PCa over 2,264 disease endpoints. Expression quantitative trait locus analyses based on both Chinese PCa cohort and the GTEx database show that risk alleles of these SNPs are significantly associated with low expression of NKX3–1. Based on the MirSNP database, dual-luciferase reporter assays show that risk alleles of these SNPs downregulate the expression of NKX3–1 via increased miRNA binding. These results indicate that the SNPs at the 3′-UTR of NKX3–1 significantly downregulate NKX3–1 expression by influencing the affinity of miRNA and increase the PCa risk

The Large Hadron-Electron Collider at the HL-LHC

The Large Hadron electron Collider (LHeC) is designed to move the field of deep inelastic scattering (DIS) to the energy and intensity frontier of particle physics. Exploiting energy recovery technology, it collides a novel, intense electron beam with a proton or ion beam from the High Luminosity--Large Hadron Collider (HL-LHC). The accelerator and interaction region are designed for concurrent electron-proton and proton-proton operation. This report represents an update of the Conceptual Design Report (CDR) of the LHeC, published in 2012. It comprises new results on parton structure of the proton and heavier nuclei, QCD dynamics, electroweak and top-quark physics. It is shown how the LHeC will open a new chapter of nuclear particle physics in extending the accessible kinematic range in lepton-nucleus scattering by several orders of magnitude. Due to enhanced luminosity, large energy and the cleanliness of the hadronic final states, the LHeC has a strong Higgs physics programme and its own discovery potential for new physics. Building on the 2012 CDR, the report represents a detailed updated design of the energy recovery electron linac (ERL) including new lattice, magnet, superconducting radio frequency technology and further components. Challenges of energy recovery are described and the lower energy, high current, 3-turn ERL facility, PERLE at Orsay, is presented which uses the LHeC characteristics serving as a development facility for the design and operation of the LHeC. An updated detector design is presented corresponding to the acceptance, resolution and calibration goals which arise from the Higgs and parton density function physics programmes. The paper also presents novel results on the Future Circular Collider in electron-hadron mode, FCC-eh, which utilises the same ERL technology to further extend the reach of DIS to even higher centre-of-mass energies

The Large Hadron-Electron Collider at the HL-LHC

The Large Hadron electron Collider (LHeC) is designed to move the field of deep inelastic scattering (DIS) to the energy and intensity frontier of particle physics. Exploiting energy recovery technology, it collides a novel, intense electron beam with a proton or ion beam from the High Luminosity--Large Hadron Collider (HL-LHC). The accelerator and interaction region are designed for concurrent electron-proton and proton-proton operation. This report represents an update of the Conceptual Design Report (CDR) of the LHeC, published in 2012. It comprises new results on parton structure of the proton and heavier nuclei, QCD dynamics, electroweak and top-quark physics. It is shown how the LHeC will open a new chapter of nuclear particle physics in extending the accessible kinematic range in lepton-nucleus scattering by several orders of magnitude. Due to enhanced luminosity, large energy and the cleanliness of the hadronic final states, the LHeC has a strong Higgs physics programme and its own discovery potential for new physics. Building on the 2012 CDR, the report represents a detailed updated design of the energy recovery electron linac (ERL) including new lattice, magnet, superconducting radio frequency technology and further components. Challenges of energy recovery are described and the lower energy, high current, 3-turn ERL facility, PERLE at Orsay, is presented which uses the LHeC characteristics serving as a development facility for the design and operation of the LHeC. An updated detector design is presented corresponding to the acceptance, resolution and calibration goals which arise from the Higgs and parton density function physics programmes. The paper also presents novel results on the Future Circular Collider in electron-hadron mode, FCC-eh, which utilises the same ERL technology to further extend the reach of DIS to even higher centre-of-mass energies

The Large Hadron–Electron Collider at the HL-LHC

The Large Hadron–Electron Collider (LHeC) is designed to move the field of deep inelastic scattering (DIS) to the energy and intensity frontier of particle physics. Exploiting energy-recovery technology, it collides a novel, intense electron beam with a proton or ion beam from the High-Luminosity Large Hadron Collider (HL-LHC). The accelerator and interaction region are designed for concurrent electron–proton and proton–proton operations. This report represents an update to the LHeC's conceptual design report (CDR), published in 2012. It comprises new results on the parton structure of the proton and heavier nuclei, QCD dynamics, and electroweak and top-quark physics. It is shown how the LHeC will open a new chapter of nuclear particle physics by extending the accessible kinematic range of lepton–nucleus scattering by several orders of magnitude. Due to its enhanced luminosity and large energy and the cleanliness of the final hadronic states, the LHeC has a strong Higgs physics programme and its own discovery potential for new physics. Building on the 2012 CDR, this report contains a detailed updated design for the energy-recovery electron linac (ERL), including a new lattice, magnet and superconducting radio-frequency technology, and further components. Challenges of energy recovery are described, and the lower-energy, high-current, three-turn ERL facility, PERLE at Orsay, is presented, which uses the LHeC characteristics serving as a development facility for the design and operation of the LHeC. An updated detector design is presented corresponding to the acceptance, resolution, and calibration goals that arise from the Higgs and parton-density-function physics programmes. This paper also presents novel results for the Future Circular Collider in electron–hadron (FCC-eh) mode, which utilises the same ERL technology to further extend the reach of DIS to even higher centre-of-mass energies