Inclusive meson production in peripheral collisions of ultrarelativistic heavy ions

There exist several proposals to use Weizs\"{a}cker-Williams photons generated by ultrarelativistic heavy ions to produce exotic particles in $\gamma\gamma$ fusion reactions. To estimate the background conditions for such reactions we analyze various mechanisms of meson production in very peripheral collisions of ultrarelativistic heavy ions at RHIC and LHC energies. Besides $\gamma\gamma$ fusion they include also electromagnetic $\gamma A$ interactions and strong nucleon-nucleon interactions in grazing $AA$ collisions. All these processes are characterised by low multiplicities of produced particles. $\gamma A$ and $AA$ events are simulated by corresponding Monte Carlo codes, RELDIS and FRITIOF. In each of these processes a certain fraction of pions is produced close to the mid-rapidity region that gives a background for the $\gamma\gamma$ events. The possibility of selecting mesons produced in $\gamma\gamma$ fusion events via different $p_t$ cut procedures is demonstrated.Comment: 27 pages with 4 eps-figures included, uses axodraw.sty Tab.2 and 3 correcte

Development of a thermal ionizer as ion catcher

An effective ion catcher is an important part of a radioactive beam facility that is based on in-flight production. The catcher stops fast radioactive products and emits them as singly charged slow ions. Current ion catchers are based on stopping in He and H$_2$ gas. However, with increasing intensity of the secondary beam the amount of ion-electron pairs created eventually prevents the electromagnetic extraction of the radioactive ions from the gas cell. In contrast, such limitations are not present in thermal ionizers used with the ISOL production technique. Therefore, at least for alkaline and alkaline earth elements, a thermal ionizer should then be preferred. An important use of the TRI$\mu$P facility will be for precision measurements using atom traps. Atom trapping is particularly possible for alkaline and alkaline earth isotopes. The facility can produce up to 10$^9$ s$^{-1}$ of various Na isotopes with the in-flight method. Therefore, we have built and tested a thermal ionizer. An overview of the operation, design, construction, and commissioning of the thermal ionizer for TRI$\mu$P will be presented along with first results for $^{20}$Na and $^{21}$Na.Comment: 10 pages, 4 figures, XVth International Conference on Electromagnetic Isotope Separators and Techniques Related to their Applications (EMIS 2007

Particle emission following Coulomb excitation in ultrarelativistic heavy-ion collisions

We study nuclear reactions induced by virtual photons associated with Lorentz-boosted Coulomb fields of ultrarelativistic heavy ions. Evaporation, fission and multifragmentation mechanisms are included in a new RELDIS code, which describes the deexcitation of residual nuclei formed after single and double photon absorption in peripheral heavy-ion collisions. Partial cross sections for different dissociation channels, including the multiple neutron emission ones, are calculated and compared with data when available. Rapidity and transverse momentum distributions of nucleons, nuclear fragments and pions, produced electromagnetically, are also calculated. These results provide important information for designing large-rapidity detectors and zero-degree calorimeters at RHIC and LHC. The electromagnetic dissociation of nuclei imposes some constrains on the investigation of exotic particle production in gamma-gamma fusion reactions.Comment: 26 LaTeX pages including 8 figures, uses epsf.st

Coherent radiation from neutral molecules moving above a grating

We predict and study the quantum-electrodynamical effect of parametric self-induced excitation of a molecule moving above the dielectric or conducting medium with periodic grating. In this case the radiation reaction force modulates the molecular transition frequency which results in a parametric instability of dipole oscillations even from the level of quantum or thermal fluctuations. The present mechanism of instability of electrically neutral molecules is different from that of the well-known Smith-Purcell and transition radiation in which a moving charge and its oscillating image create an oscillating dipole. We show that parametrically excited molecular bunches can produce an easily detectable coherent radiation flux of up to a microwatt.Comment: 4 page

Variants in PCSK7, PNPLA3 and TM6SF2 are risk factors for the development of cirrhosis in hereditary haemochromatosis

BACKGROUND: Cirrhosis develops in <10% of individuals homozygous for the C282Y variant in the homeostatic iron regulator (HFE) gene. Carriage of PCSK7:rs236918 is associated with an increased risk of cirrhosis in this population. AIM: To determine if genetic variants significantly associated with the risk of alcohol- and NAFLD-related cirrhosis also modulate the cirrhosis risk in C282Y homozygotes. METHODS: Variants in PCSK7, PNPLA3, TM6SF2, MBOAT7 and HSD17B13 were genotyped in 1319 C282Y homozygotes, from six European countries, of whom 171 (13.0%) had cirrhosis. Genotypic and allelic associations with the risk for developing cirrhosis were assessed, adjusting for age and sex. Fixed effects meta-analyses of the adjusted summary data for each country were performed. Post hoc association testing was undertaken in the 131 (76.6%) cases and 299 (26.0%) controls with available liver histology. RESULTS: Significant associations were observed between PCSK7:rs236918 (OR = 1.52 [95% CI 1.06-2.19]; P = 0.022; I2  = 0%); PNPLA3:rs738409 (OR = 1.60 [95% CI 1.22-2.11]; P = 7.37 × 10-4 ; I2  = 45.5%) and TM6SF2:rs58542926 (OR = 1.94 [95% CI 1.28-2.95]; P = 1.86 × 10-3 ; I2  = 0%) and the cirrhosis risk in C282Y homozygotes. These findings remained significant in the subpopulation with available liver histology. The population-attributable fractions were 5.6% for PCSK7:rs236918, 13.8% for PNPLA3:rs738409, 6.5% for TM6SF2:rs58542926 and 24.0% for carriage of all three variants combined. CONCLUSIONS: The risk of cirrhosis associated with carriage of PCSK7:rs236918 was confirmed in this much larger population of C282Y homozygotes. In addition, PNPLA3:rs738409 and TM6SF2:rs58542926 were established as significant additional risk factors. More detailed genetic testing of C282Y homozygotes would allow risk stratification and help guide future management

Genetic variation in HSD17B13 reduces the risk of developing cirrhosis and hepatocellular carcinoma in alcohol misusers

BACKGROUND & AIMS: Carriage of rs738409:G in patatin-like phospholipase domain-containing 3 (PNPLA3) is associated with an increased risk for developing alcohol-related cirrhosis and hepatocellular carcinoma (HCC). Recently, rs72613567:TA in hydroxysteroid 17-beta dehydrogenase 13 (HSD17B13) was shown to be associated with a reduced risk for developing alcohol-related liver disease and to attenuate the risk associated with PNPLA3 rs738409:G. This study explores the risk-associations between these two genetic variants and the development of alcohol-related cirrhosis and HCC. APPROACH AND RESULTS: Variants in HSD17B13 and PNPLA3 were genotyped in 6,171 participants, including: 1,031 with alcohol-related cirrhosis and HCC; 1,653 with alcohol-related cirrhosis without HCC; 2,588 alcohol misusers with no liver disease; and 899 healthy controls. Genetic associations with the risks for alcohol-related cirrhosis and HCC were determined using logistic regression analysis. Carriage of HSD17B13 rs72613567:TA was associated with a lower risk for both cirrhosis (OR 0.79 [95% CI 0.72-0.88], p=8.13×10-6) and HCC (OR 0.77 [95% CI 0.68-0.89], p=2.27×10-4), while carriage of PNPLA3 rs738409:G was associated with an increased risk for developing cirrhosis (OR 1.70 [95% CI 1.54-1.88], p=1.52x10-26) and HCC (OR 1.77 [95% CI 1.58-1.98], p=2.31×10-23). These associations remained significant after adjusting for age, sex, body mass index, type II diabetes mellitus and country. Carriage of HSD17B13 rs72613567:TA attenuated the risk for developing cirrhosis associated with PNPLA3 rs738409:G in both men and women but the protective effect against the subsequent development of HCC was only observed in men (p=1.72×10-4; ORallelic, 0.75; 95% CI, 0.64-0.87). CONCLUSIONS: Carriage of variants in PNPLA3 and HSD17B13 differentially affect the risk for developing advanced alcohol-related liver disease. A genotypic/phenotypic risk score might facilitate earlier diagnosis of HCC in this population

Genome-wide association analysis of diverticular disease points towards neuromuscular, connective tissue and epithelial pathomechanisms.

This is the author accepted manuscript.OBJECTIVE: Diverticular disease is a common complex disorder characterised by mucosal outpouchings of the colonic wall that manifests through complications such as diverticulitis, perforation and bleeding. We report the to date largest genome-wide association study (GWAS) to identify genetic risk factors for diverticular disease. DESIGN: Discovery GWAS analysis was performed on UK Biobank imputed genotypes using 31 964 cases and 419 135 controls of European descent. Associations were replicated in a European sample of 3893 cases and 2829 diverticula-free controls and evaluated for risk contribution to diverticulitis and uncomplicated diverticulosis. Transcripts at top 20 replicating loci were analysed by real-time quatitative PCR in preparations of the mucosal, submucosal and muscular layer of colon. The localisation of expressed protein at selected loci was investigated by immunohistochemistry. RESULTS: We discovered 48 risk loci, of which 12 are novel, with genome-wide significance and consistent OR in the replication sample. Nominal replication (p<0.05) was observed for 27 loci, and additional 8 in meta-analysis with a population-based cohort. The most significant novel risk variant rs9960286 is located near CTAGE1 with a p value of 2.3×10-10 and 0.002 (ORallelic=1.14 (95% CI 1.05 to 1.24)) in the replication analysis. Four loci showed stronger effects for diverticulitis, PHGR1 (OR 1.32, 95% CI 1.12 to 1.56), FAM155A-2 (OR 1.21, 95% CI 1.04 to 1.42), CALCB (OR 1.17, 95% CI 1.03 to 1.33) and S100A10 (OR 1.17, 95% CI 1.03 to 1.33). CONCLUSION: In silico analyses point to diverticulosis primarily as a disorder of intestinal neuromuscular function and of impaired connective fibre support, while an additional diverticulitis risk might be conferred by epithelial dysfunction.German Research CouncilAustrian Science FundFaculty of Medicine, Saarland UniversityResearch Council of LithuaniaSwedish Research CouncilMedical Research Counci

Determinants of Bacteriophage 933W Repressor DNA Binding Specificity

We reported previously that 933W repressor apparently does not cooperatively bind to adjacent sites on DNA and that the relative affinities of 933W repressor for its operators differ significantly from that of any other lambdoid bacteriophage. These findings indicate that the operational details of the lysis-lysogeny switch of bacteriophage 933W are unique among lambdoid bacteriophages. Since the functioning of the lysis-lysogeny switch in 933W bacteriophage uniquely and solely depends on the order of preference of 933W repressor for its operators, we examined the details of how 933W repressor recognizes its DNA sites. To identify the specificity determinants, we first created a molecular model of the 933W repressor-DNA complex and tested the predicted protein-DNA interactions. These results of these studies provide a picture of how 933W repressor recognizes its DNA sites. We also show that, opposite of what is normally observed for lambdoid phages, 933W operator sequences have evolved in such a way that the presence of the most commonly found base sequences at particular operator positions serves to decrease, rather than increase, the affinity of the protein for the site. This finding cautions against assuming that a consensus sequence derived from sequence analysis defines the optimal, highest affinity DNA binding site for a protein