156 research outputs found

    0-pi oscillations in nanostructured Nb/Fe/Nb Josephson junctions

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    The physics of the Ο€\pi phase shift in ferromagnetic Josephson junctions may enable a range of applications for spin-electronic devices and quantum computing. We investigate transitions from ``0'' to ``Ο€\pi'' states in Nb/Fe/Nb Josephson junctions by varying the Fe barrier thickness from 0.5 nm to 5.5 nm. From magnetic measurements we estimate for Fe a magnetic dead layer of about 1.1 nm. By fitting the characteristic voltage oscillations with existing theoretical models we extrapolate an exchange energy of 256 meV, a Fermi velocity of 1.98Γ—1051.98 \times 10^5 m/s and an electron mean free path of 6.2 nm, in agreement with other reported values. From the temperature dependence of the ICRNI_CR_N product we show that its decay rate exhibits a nonmonotonic oscillatory behavior with the Fe barrier thickness.Comment: 7 pages, 5 figures, accepted for publication in Eur. Phys. J.

    High-Resolution Genome-Wide Analysis of Irradiated (UV and Ξ³-Rays) Diploid Yeast Cells Reveals a High Frequency of Genomic Loss of Heterozygosity (LOH) Events

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    In diploid eukaryotes, repair of double-stranded DNA breaks by homologous recombination often leads to loss of heterozygosity (LOH). Most previous studies of mitotic recombination in Saccharomyces cerevisiae have focused on a single chromosome or a single region of one chromosome at which LOH events can be selected. In this study, we used two techniques (single-nucleotide polymorphism microarrays and high-throughput DNA sequencing) to examine genome-wide LOH in a diploid yeast strain at a resolution averaging 1 kb. We examined both selected LOH events on chromosome V and unselected events throughout the genome in untreated cells and in cells treated with either Ξ³-radiation or ultraviolet (UV) radiation. Our analysis shows the following: (1) spontaneous and damage-induced mitotic gene conversion tracts are more than three times larger than meiotic conversion tracts, and conversion tracts associated with crossovers are usually longer and more complex than those unassociated with crossovers; (2) most of the crossovers and conversions reflect the repair of two sister chromatids broken at the same position; and (3) both UV and Ξ³-radiation efficiently induce LOH at doses of radiation that cause no significant loss of viability. Using high-throughput DNA sequencing, we also detected new mutations induced by Ξ³-rays and UV. To our knowledge, our study represents the first high-resolution genome-wide analysis of DNA damage-induced LOH events performed in any eukaryote

    Gentle Masking of Low-Complexity Sequences Improves Homology Search

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    Detection of sequences that are homologous, i.e. descended from a common ancestor, is a fundamental task in computational biology. This task is confounded by low-complexity tracts (such as atatatatatat), which arise frequently and independently, causing strong similarities that are not homologies. There has been much research on identifying low-complexity tracts, but little research on how to treat them during homology search. We propose to find homologies by aligning sequences with β€œgentle” masking of low-complexity tracts. Gentle masking means that the match score involving a masked letter is , where is the unmasked score. Gentle masking slightly but noticeably improves the sensitivity of homology search (compared to β€œharsh” masking), without harming specificity. We show examples in three useful homology search problems: detection of NUMTs (nuclear copies of mitochondrial DNA), recruitment of metagenomic DNA reads to reference genomes, and pseudogene detection. Gentle masking is currently the best way to treat low-complexity tracts during homology search

    High-Resolution Genome-Wide Analysis of Irradiated (UV and Β -Rays) Diploid Yeast Cells Reveals a High Frequency of Genomic Loss of Heterozygosity (LOH) Events

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    In diploid eukaryotes, repair of double-stranded DNA breaks by homologous recombination often leads to loss of heterozygosity (LOH). Most previous studies of mitotic recombination in Saccharomyces cerevisiae have focused on a single chromosome or a single region of one chromosome at which LOH events can be selected. In this study, we used two techniques (single-nucleotide polymorphism microarrays and high-throughput DNA sequencing) to examine genome-wide LOH in a diploid yeast strain at a resolution averaging 1 kb. We examined both selected LOH events on chromosome V and unselected events throughout the genome in untreated cells and in cells treated with either Ξ³-radiation or ultraviolet (UV) radiation. Our analysis shows the following: (1) spontaneous and damage-induced mitotic gene conversion tracts are more than three times larger than meiotic conversion tracts, and conversion tracts associated with crossovers are usually longer and more complex than those unassociated with crossovers; (2) most of the crossovers and conversions reflect the repair of two sister chromatids broken at the same position; and (3) both UV and Ξ³-radiation efficiently induce LOH at doses of radiation that cause no significant loss of viability. Using high-throughput DNA sequencing, we also detected new mutations induced by Ξ³-rays and UV. To our knowledge, our study represents the first high-resolution genome-wide analysis of DNA damage-induced LOH events performed in any eukaryote

    Molecular Poltergeists: Mitochondrial DNA Copies (numts) in Sequenced Nuclear Genomes

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    The natural transfer of DNA from mitochondria to the nucleus generates nuclear copies of mitochondrial DNA (numts) and is an ongoing evolutionary process, as genome sequences attest. In humans, five different numts cause genetic disease and a dozen human loci are polymorphic for the presence of numts, underscoring the rapid rate at which mitochondrial sequences reach the nucleus over evolutionary time. In the laboratory and in nature, numts enter the nuclear DNA via non-homolgous end joining (NHEJ) at double-strand breaks (DSBs). The frequency of numt insertions among 85 sequenced eukaryotic genomes reveal that numt content is strongly correlated with genome size, suggesting that the numt insertion rate might be limited by DSB frequency. Polymorphic numts in humans link maternally inherited mitochondrial genotypes to nuclear DNA haplotypes during the past, offering new opportunities to associate nuclear markers with mitochondrial markers back in time

    HIGH CURRENT BEAM EXTRACTION FROM THE 88-INCH CYCLOTRON AT LBNL

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    Abstract The low energy beam transport system and the inflector of the 88-Inch Cyclotron have been improved to provide more intense heavy-ion beams, especially for experiments requiring 48 Ca beams. In addition to a new spiral inflector [1] and increased injection voltage, the injection line beam transport and beam orbit dynamics in the cyclotron have been analyzed, new diagnostics have been developed, and extensive measurements have been performed to improve the transmission efficiency. By coupling diagnostics, such as emittance scanners in the injection line and a radially-adjustable beam viewing scintillator within the cyclotron, with computer simulations we have been able to identify loss mechanisms. The diagnostics used and their findings will be presented. We will discuss the solutions we have employed to address losses, such as changing our approach to tuning VENUS and running the cyclotron's central trim coil asymmetrically

    Genome Digging: Insight into the Mitochondrial Genome of Homo

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    A fraction of the Neanderthal mitochondrial genome sequence has a similarity with a 5,839-bp nuclear DNA sequence of mitochondrial origin (numt) on the human chromosome 1. This fact has never been interpreted. Although this phenomenon may be attributed to contamination and mosaic assembly of Neanderthal mtDNA from short sequencing reads, we explain the mysterious similarity by integration of this numt (mtAncestor-1) into the nuclear genome of the common ancestor of Neanderthals and modern humans not long before their reproductive split.Exploiting bioinformatics, we uncovered an additional numt (mtAncestor-2) with a high similarity to the Neanderthal mtDNA and indicated that both numts represent almost identical replicas of the mtDNA sequences ancestral to the mitochondrial genomes of Neanderthals and modern humans. In the proteins, encoded by mtDNA, the majority of amino acids distinguishing chimpanzees from humans and Neanderthals were acquired by the ancestral hominins. The overall rate of nonsynonymous evolution in Neanderthal mitochondrial protein-coding genes is not higher than in other lineages. The model incorporating the ancestral hominin mtDNA sequences estimates the average divergence age of the mtDNAs of Neanderthals and modern humans to be 450,000-485,000 years. The mtAncestor-1 and mtAncestor-2 sequences were incorporated into the nuclear genome approximately 620,000 years and 2,885,000 years ago, respectively.This study provides the first insight into the evolution of the mitochondrial DNA in hominins ancestral to Neanderthals and humans. We hypothesize that mtAncestor-1 and mtAncestor-2 are likely to be molecular fossils of the mtDNAs of Homo heidelbergensis and a stem Homo lineage. The d(N)/d(S) dynamics suggests that the effective population size of extinct hominins was low. However, the hominin lineage ancestral to humans, Neanderthals and H. heidelbergensis, had a larger effective population size and possessed genetic diversity comparable with those of chimpanzee and gorilla

    Essential Factors for Incompatible DNA End Joining at Chromosomal DNA Double Strand Breaks In Vivo

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    Non-homologous end joining (NHEJ) is a major pathway for the repair of DNA double strand break (DSBs) with incompatible DNA ends, which are often generated by ionizing irradiation. In vitro reconstitution studies have indicated that NHEJ of incompatible DNA ends requires not only the core steps of synapsis and ligation, employing KU80/DNA-PKcs and LIG4, but also additional DNA end processing steps, such as DNA end resection by Artemis and gap-filling by POLΞ» and POLΞΌ. It seems that DNA end processing steps are important for joining of incompatible DNA ends rather than compatible ends. Despite the fact that DNA end processing is important for incompatible DNA end joining in vitro, the role of DNA processing in NHEJ of incompatible DSBs in vivo has not yet been demonstrated. Here we investigated the in vivo roles of proteins implicated in each step of NHEJ using an assay in which NHEJ of incompatible DNA ends on chromosomal DNA can be assessed in living human cells. siRNA- or inhibitor-mediated impairment of factors in each NHEJ step resulted in a reduction in joining efficiency. Strikingly, stronger effects were observed when DNA end resection and ligation protein functions were impaired. Disruption of synapsis by KU80 and DNA-PKcs impairment, or the disruption of gap filling by POLΞ» and POLΞΌ depletion, resulted in higher levels of microhomology-mediated joining. The present study indicates that DNA end resection and ligation factors are critical for the efficient joining of incompatible ends in vivo, further emphasizing the importance of synapsis and gap-filling factors in preventing illegitimate joining
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