Genetic modifiers of lung disease in cystic fibrosis

BACKGROUND: Polymorphisms in genes other than the cystic fibrosis transmembrane conductance regulator (CFTR) gene may modify the severity of pulmonary disease in patients with cystic fibrosis. METHODS: We performed two studies with different patient samples. We first tested 808 patients who were homozygous for the ΔF508 mutation and were classified as having either severe or mild lung disease, as defined by the lowest or highest quartile of forced expiratory volume in one second (FEV 1), respectively, for age. We genotyped 16 polymorphisms in 10 genes reported by others as modifiers of disease severity in cystic fibrosis and tested for an association in patients with severe disease (263 patients) or mild disease (545). In the replication (second) study, we tested 498 patients, with various CFTR genotypes and a range of FEV 1 values, for an association of the TGFβ1 codon 10 CC genotype with low FEV 1. RESULTS: In the initial study, significant allelic and genotypic associations with phenotype were seen only for TGFβ1 (the gene encoding transforming growth factor β1), particularly the -509 and codon 10 polymorphisms (with P values obtained with the use of Fisher's exact test and logistic regression ranging from 0.006 to 0.0002). The odds ratio was about 2.2 for the highest-risk TGFβ1 genotype (codon 10 CC) in association with the phenotype for severe lung disease. The replication study confirmed the association of the TGFβ1 codon 10 CC genotype with more severe lung disease in comparisons with the use of dichotomized FEV 1 for severity status (P=0.0002) and FEV 1 values directly (P=0.02). CONCLUSIONS: Genetic variation in the 5′ end of TGFβ1 or a nearby upstream region modifies disease severity in cystic fibrosis

On Born approximation in black hole scattering

A massless field propagating on spherically symmetric black hole metrics such as the Schwarzschild, Reissner-Nordstr\"{o}m and Reissner-Nordstr\"{o}m-de Sitter backgrounds is considered. In particular, explicit formulae in terms of transcendental functions for the scattering of massless scalar particles off black holes are derived within a Born approximation. It is shown that the conditions on the existence of the Born integral forbid a straightforward extraction of the quasi normal modes using the Born approximation for the scattering amplitude. Such a method has been used in literature. We suggest a novel, well defined method, to extract the large imaginary part of quasinormal modes via the Coulomb-like phase shift. Furthermore, we compare the numerically evaluated exact scattering amplitude with the Born one to find that the approximation is not very useful for the scattering of massless scalar, electromagnetic as well as gravitational waves from black holes

Study of ttbar Production in ppbar Collisions Using Total Transverse Energy

We analyze a sample of W + jet events collected with the Collider Detector at Fermilab (CDF) in ppbar collisions at sqrt(s) = 1.8 TeV to study ttbar production. We employ a simple kinematical variable "H", defined as the scalar sum of the transverse energies of the lepton, neutrino and jets. For events with a W boson and four or more jets, the shape of the "H" distribution deviates by 3.8 standard deviations from that expected from known backgrounds to ttbar production. However this distribution agrees well with a linear combination of background and ttbar events, the agreement being best for a top mass of 180 GeV/c^2.Comment: Postscript file (gzip+uuencode). 5-page, two-column PRL format (RevTex). Submitted to Phys. Rev. Lett. 09 June 199