The future is genome-wide

A report of the annual meeting of the European Society of Human Genetics, Amsterdam, 6-9 May 2006

Sure success partial search

Partial search has been proposed recently for finding the target block containing a target element with fewer queries than the full Grover search algorithm which can locate the target precisely. Since such partial searches will likely be used as subroutines for larger algorithms their success rate is important. We propose a partial search algorithm which achieves success with unit probability

Modeling DNA beacons at the mesoscopic scale

We report model calculations on DNA single strands which describe the equilibrium dynamics and kinetics of hairpin formation and melting. Modeling is at the level of single bases. Strand rigidity is described in terms of simple polymer models; alternative calculations performed using the freely rotating chain and the discrete Kratky-Porod models are reported. Stem formation is modeled according to the Peyrard-Bishop-Dauxois Hamiltonian. The kinetics of opening and closing is described in terms of a diffusion-controlled motion in an effective free energy landscape. Melting profiles, dependence of melting temperature on loop length, and kinetic time scales are in semiquantitative agreement with experimental data obtained from fluorescent DNA beacons forming poly(T) loops. Variation in strand rigidity is not sufficient to account for the large activation enthalpy of closing and the strong loop length dependence observed in hairpins forming poly(A) loops. Implications for modeling single strands of DNA or RNA are discussed.Comment: 15 pages, 17 figures, submitted to Eur. J. Phys.

Teleportation as a quantum computation

An explicit quantum circuit is given to implement quantum teleportation. This circuit makes teleportation straightforward to anyone who believes that quantum computation is a reasonable proposition. It could also be genuinely used inside a quantum computer if teleportation is needed to move quantum information around. An unusual feature of this circuit is that there are points in the computation at which the quantum information can be completely disrupted by a measurement (or some types of interaction with the environment) without ill effects: the same final result is obtained whether or not these measurements takes place.Comment: 3 pages, LaTeX2e, PhysComp 96 submissio

Genomic determinants of the efficiency of internal ribosomal entry sites of viral and cellular origin

Variation in cellular gene expression levels has been shown to be inherited. Expression is controlled at transcriptional and post-transcriptional levels. Internal ribosome entry sites (IRES) are used by viruses to bypass inhibition of cap-dependent translation, and by eukaryotic cells to control translation under conditions when protein synthesis is inhibited. We aimed at identifying genomic determinants of variability in IRES-mediated translation of viral [Encephalomyocarditis virus (EMCV)] and cellular IRES [X-linked inhibitor-of-apoptosis (XIAP) and c-myc]. Bicistronic lentiviral constructs expressing two fluorescent reporters were used to transduce laboratory and B lymphoblastoid cell lines [15 CEPH pedigrees (n = 205) and 50 unrelated individuals]. IRES efficiency varied according to cell type and among individuals. Control of IRES activity has a significant genetic component (h2 of 0.47 and 0.36 for EMCV and XIAP, respectively). Quantitative linkage analysis identified a suggestive locus (LOD 2.35) on chromosome 18q21.2, and genome-wide association analysis revealed of a cluster of SNPs on chromosome 3, intronic to the FHIT gene, marginally associated (P = 5.9E-7) with XIAP IRES function. This study illustrates the in vitro generation of intermediate phenotypes by using cell lines for the evaluation of genetic determinants of control of elements such as IRE

Quantum computation over continuous variables

This paper provides necessary and sufficient conditions for constructing a universal quantum computer over continuous variables. As an example, it is shown how a universal quantum computer for the amplitudes of the electromagnetic field might be constructed using simple linear devices such as beam-splitters and phase shifters, together with squeezers and nonlinear devices such as Kerr-effect fibers and atoms in optical cavities. Such a device could in principle perform `quantum floating point' computations. Problems of noise, finite precision, and error correction are discussed.Comment: 9 pages, Te

Gene expression variation and expression quantitative trait mapping of human chromosome 21 genes

Inter-individual differences in gene expression are likely to account for an important fraction of phenotypic differences, including susceptibility to common disorders. Recent studies have shown extensive variation in gene expression levels in humans and other organisms, and that a fraction of this variation is under genetic control. We investigated the patterns of gene expression variation in a 25 Mb region of human chromosome 21, which has been associated with many Down syndrome (DS) phenotypes. Taqman real-time PCR was used to measure expression variation of 41 genes in lymphoblastoid cells of 40 unrelated individuals. For 25 genes found to be differentially expressed, additional analysis was performed in 10 CEPH families to determine heritabilities and map loci harboring regulatory variation. Seventy-six percent of the differentially expressed genes had significant heritabilities, and genomewide linkage analysis led to the identification of significant eQTLs for nine genes. Most eQTLs were in trans, with the best result (P=7.46×10−8) obtained for TMEM1 on chromosome 12q24.33. A cis-eQTL identified for CCT8 was validated by performing an association study in 60 individuals from the HapMap project. SNP rs965951 located within CCT8 was found to be significantly associated with its expression levels (P=2.5×10−5) confirming cis-regulatory variation. The results of our study provide a representative view of expression variation of chromosome 21 genes, identify loci involved in their regulation and suggest that genes, for which expression differences are significantly larger than 1.5-fold in control samples, are unlikely to be involved in DS-phenotypes present in all affected individual

Casimir Effect on the Worldline

We develop a method to compute the Casimir effect for arbitrary geometries. The method is based on the string-inspired worldline approach to quantum field theory and its numerical realization with Monte-Carlo techniques. Concentrating on Casimir forces between rigid bodies induced by a fluctuating scalar field, we test our method with the parallel-plate configuration. For the experimentally relevant sphere-plate configuration, we study curvature effects quantitatively and perform a comparison with the ``proximity force approximation'', which is the standard approximation technique. Sizable curvature effects are found for a distance-to-curvature-radius ratio of a/R >~ 0.02. Our method is embedded in renormalizable quantum field theory with a controlled treatment of the UV divergencies. As a technical by-product, we develop various efficient algorithms for generating closed-loop ensembles with Gaussian distribution.Comment: 27 pages, 10 figures, Sect. 2.1 more self-contained, improved data for Fig. 6, minor corrections, new Refs, version to be published in JHE