Review and outlook of accelerator-related codes and their interplay with the experiments software

Powerful flexible computer codes are essential for the design and optimisation of accelerator and experiments. We briefly review what already exists and what is needed in terms of accelerator codes. For the FCC-ee, it will be important to include the effects of beamstrahlung and beam–beam interaction as well as machine imperfections and sources of beam-induced backgrounds relevant for the experiments and consider the possibility of beam polarisation. The experiment software Key4hep, which aims to provide a common software stack for future experiments, is described, and the possibility of extending this concept to machine codes is discussed. We analyse how to interface and connect the accelerator and experiment codes in an efficient and flexible way for optimisation of the FCC-ee interaction region design and discuss the possibility of using shared data formats as an interface.

FANCA Variants in Exons 27-30 Are Associated with Solid Tumors in Fanconi Anemia

Fanconi anemia (FA) is predominantly an autosomal recessive inherited bone marrow failure syndrome (IBMFS) characterized by congenital anomalies, bone marrow failure (BMF) and an increased cancer risk. It is caused by pathogenic variants in more than 22 genes in the FA/BRCA DNA repair pathway. Approximately 60% of patients have biallelic variants in FANCA. We sought to identify phenotypic differences and clinical outcomes of patients with diverse FANCA variants. We analyzed data from 86 patients with variants in FANCA enrolled in the National Cancer Institute (NCI) IBMFS study (ClinicalTrials.gov identifier 00027274). FANCA variants were determined through review of genetic test reports or whole exome sequencing done as part of the study. The variants were plotted using the online tool ProteinPaint (https://proteinpaint.stjude.org, Figure 1A). Clinical data were extracted from review of medical records and/or evaluations at the NIH. We compared patients with: 1) hypomorphic (hypomorphic variant on one or both alleles) versus null genotype (null variants on both alleles), 2) single nucleotide variant (SNV)/small insertions/deletions (indels) on both alleles versus SNV/small indels on one allele plus large multi-exon deletion on the other allele versus large multi-exon deletions on both alleles. We further compared patients with one or biallelic variants involving the BRCA1 interaction region in the N-terminal domain, FAAP20-binding domain, and variants in exons 27 to 30 where we saw an accumulation of variants, with patients who did not have variants in these regions. We evaluated physical abnormalities that are part of VACTERL-H (Vertebral, Anal, Cardiac, Tracheo-esophageal fistula, Esophageal or duodenal atresia, Renal, upper Limb abnormalities, Hydrocephalus) association and PHENOS (skin Pigmentation abnormalities, small Head, small Eyes, central Nervous system, Otologic abnormalities, Short stature). We focused on the presence, severity and age at BMF, and development of cancers and age at first solid tumor. Frequencies were compared by Fisher's exact test, and a multiple Cox regression model was used to estimate hazard ratio of solid tumors in patients with variants in different regions of FANCA, adjusting for age and hematopoietic cell transplant status of patients with cancer. Analyses were performed using Excel and RStudio, p-value <0.05 was considered significant. The phenotypes, BMF and cancer outcomes were similar between patients with hypomorphic and null genotypes. Similarly, comparison between patients with SNV/small indels, SNV/small indel plus large deletion, and biallelic large deletions did not reveal significant associations. Comparison according the location of the variants on FANCA protein showed that VACTERL-H and VACTERL-H plus PHENOS were less common in patients with at least one SNV/small indel in the BRCA1 interaction region of FANCA compared with patients without variants in this region (2/33 vs 12/51, p= 0.04; 1/33 vs 11/51, p= 0.024, respectively). These associations were not observed when we included patients with large deletions encompassing the BRCA1 interaction region. Eighteen of the 86 patients developed solid tumors; 15/45 patients with an SNV/small indel and/or large deletion within or including exons 27-30 region developed solid tumors compared with 3/41 patients without variants in this region (p= 0.003). Cox regression analysis showed that patients with variants within or involving exons 27-30 were at higher risk of developing solid tumors compared with those without variants in this region (HR: 6.2, 95% CI: 1.36-28.2, Figure 1B). There was no difference between the age at first cancer or type of solid tumors in patients with and without the variant involving this region. The frequency, severity, and age of BMF were also similar between the groups. Our data highlight the possibility that variants involving exons 27-30 within the C-terminal domain of FANCA may be associated with solid tumor development. FANCA forms a homodimer through the interaction between C-terminal domains; variants in this region may affect dimerization and further protein function. Functional analysis and in vivo studies of individual variants in this region and effects of the variants in trans might provide new insights into oncogenesis in FA and may have implications in personalized cancer screening. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Heat load in IR from synchrotron radiation and beam loss for CEPC double ring scheme

With the discovery of the Higgs boson at around 125 GeV, a circular Higgs factory design with high luminosity [Formula: see text] is becoming more popular in the accelerator world. The CEPC project in China is one of them. Machine Detector Interface (MDI) is the key research area in electron–positron colliders, especially in CEPC, since the synchrotron radiation (SR) photons can contribute to the heat load of the beam pipe and radiation dose may damage the components. And the heat load can cause the temperature rise in some part, and if the temperature rise is too high, the beryllium pipe in the interaction region will melt and the superconducting magnet may quench. Thus, the heat load distribution from synchrotron radiation and beam loss in the interaction region are analyzed carefully and results are given in this paper.

Steepening of magnetosonic waves in the inner coma of comet 67P/Churyumov–Gerasimenko

We present a statistical survey of large-amplitude, asymmetric plasma and magnetic field enhancements detected outside the diamagnetic cavity at comet 67P/Churyumov–Gerasimenko from December 2014 to June 2016. Based on the concurrent observations of plasma and magnetic field enhancements, we interpret them to be magnetosonic waves. The aim is to provide a general overview of these waves' properties over the mission duration. As the first mission of its kind, the ESA Rosetta mission was able to study the plasma properties of the inner coma for a prolonged time and during different stages of activity. This enables us to study the temporal evolution of these waves and their characteristics. In total, we identified ∼ 70 000 steepened waves in the magnetic field data by means of machine learning. We observe that the occurrence of these steepened waves is linked to the activity of the comet, where steepened waves are primarily observed at high outgassing rates. No clear indications of a relationship between the occurrence rate and solar wind conditions were found. The waves are found to propagate predominantly perpendicular to the background magnetic field, which indicates their compressional nature. Characteristics like amplitude, skewness, and width of the waves were extracted by fitting a skew normal distribution to the magnetic field magnitude of individual steepened waves. With increasing mass loading, the average amplitude of the waves decreases, while the skewness increases. Using a modified 1D magnetohydrodynamic (MHD) model, we investigated if the waves can be described by the combination of nonlinear and dissipative effects. By combining the model with observations of amplitude, width and skewness, we obtain an estimate of the effective plasma diffusivity in the comet–solar wind interaction region and compare it with suitable reference values as a consistency check. At 67P/Churyumov–Gerasimenko, these steepened waves are of particular importance as they dominate the innermost interaction region for intermediate to high activity.

Superconducting quadrupole magnet R&D in the interaction region of CEPC

To obtain high luminosity, compact high gradient quadrupole magnets QD0 and QF1 are required on both sides of the interaction points of the proposed Circular Electron Positron Collider (CEPC). QD0 is a double aperture superconducting quadrupole closest to the interaction point with a crossing angle between two aperture centerlines of 33 mrad. Magnetic field crosstalk between two apertures of QD0 is negligible using iron yoke, and the 3D coil end is optimized by ROXIE. In the design study, both NbTi conductor and HTS conductor are taken into account. The first step of the R&D is to design and manufacture a QD0 short model magnet with a magnetic length of 0.5 m. In this paper, the R&D status of QD0 short model magnet is described, and the design study of quadrupole magnet including NbTi technology and HTS Bi-2212 technology is presented.

Substituent Effects on the σ···π Interactions Between Au6 Cluster and Substituted Benzene

The σ···π interactions in the Au6···PhX (X=H, CH3, OH, OCH3, NH2, F, Cl, Br, CN, NO2) complexes are studied using quantum chemical methods. The present study focuses on the different effects of electron-donating and -withdrawing substituent. The structure and binding strength of the complexes are examined. The interactions between Au6 cluster and various substituted benzene become strengthened relative to the Au6···benzene complex. The interaction region indicator analysis was performed, and the interaction region and interaction between the substituent and Au6 cluster are discussed. It is found that the substituent effects on the σ···π interactions between Au6 cluster and substituted benzene are different from π···π interactions of benzene dimer. Energy decomposition analysis was carried out to study the nature of σ···π interactions, and the substituent effects are mainly reflected on the electrostatic interaction and dispersion.

Overlapping regions of Caf20 mediate its interactions with the mRNA-5′cap-binding protein eIF4E and with ribosomes

By interacting with the mRNA 5′ cap, the translation initiation factor eIF4E plays a critical role in selecting mRNAs for protein synthesis in eukaryotic cells. Caf20 is a member of the family of proteins found across eukaryotes termed 4E-BPs, which compete with eIF4G for interaction with eIF4E. Caf20 independently interacts with ribosomes. Thus, Caf20 modulates the mRNA selection process via poorly understood mechanisms. Here we performed unbiased mutagenesis across Caf20 to characterise which regions of Caf20 are important for interaction with eIF4E and with ribosomes. Caf20 binding to eIF4E is entirely dependent on a canonical motif shared with other 4E-BPs. However, binding to ribosomes is weakened by mutations throughout the protein, suggesting an extended binding interface that partially overlaps with the eIF4E-interaction region. By using chemical crosslinking, we identify a potential ribosome interaction region on the ribosome surface that spans both small and large subunits and is close to a known interaction site of eIF3. The function of ribosome binding by Caf20 remains unclear.