2,948 research outputs found

    Femtosecond x-ray absorption spectroscopy of spin and orbital angular momentum in photoexcited Ni films during ultrafast demagnetization

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    We follow for the first time the evolution of the spin and orbital angular momentum of a thin Ni film during ultrafast demagnetization, by means of x-ray magnetic circular dichroism. Both components decrease with a 130 +/- 40 fs time constant upon excitation with a femtosecond laser pulse. Additional x-ray absorption measurements reveal an increase in the spin-orbit interaction by 6 +/- 2 % during this process. This is the experimental demonstration quantifying the importance of spin-orbit mediated processes during the demagnetization

    Canning study: Impact of new public buying habits

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    Role of critical spin fluctuations in ultrafast demagnetization of transition-metal rare-earth alloys

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    Ultrafast magnetization dynamics induced by femtosecond laser pulses have been measured in ferrimagnetic Co0.8Gd0.2, Co.74Tb.26 and Co.86Tb.14 alloys. Using element sensitivity of X-ray magnetic circular dichroism at the Co L3, Tb M5 and Gd M5 edges we evidence that the demagnetization dynamics is element dependent. We show that a thermalization time as fast as 280 fs is observed for the rare-earth in the alloy, when the laser excited state temperature is below the compensation temperature. It is limited to 500 fs when the laser excited state temperature is below the Curie temperature (Tc). We propose critical spin fluctuations in the vicinity of TC as the mechanism which reduces the demagnetization rates of the 4f electrons in transition-metal rare-earth alloys whereas at any different temperature the limited demagnetization rates could be avoided.Comment: 11 pages, 4 figure

    Human gene copy number spectra analysis in congenital heart malformations

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    The clinical significance of copy number variants (CNVs) in congenital heart disease (CHD) continues to be a challenge. Although CNVs including genes can confer disease risk, relationships between gene dosage and phenotype are still being defined. Our goal was to perform a quantitative analysis of CNVs involving 100 well-defined CHD risk genes identified through previously published human association studies in subjects with anatomically defined cardiac malformations. A novel analytical approach permitting CNV gene frequency “spectra” to be computed over prespecified regions to determine phenotype-gene dosage relationships was employed. CNVs in subjects with CHD (n = 945), subphenotyped into 40 groups and verified in accordance with the European Paediatric Cardiac Code, were compared with two control groups, a disease-free cohort (n = 2,026) and a population with coronary artery disease (n = 880). Gains (≄200 kb) and losses (≄100 kb) were determined over 100 CHD risk genes and compared using a Barnard exact test. Six subphenotypes showed significant enrichment (P ≀ 0.05), including aortic stenosis (valvar), atrioventricular canal (partial), atrioventricular septal defect with tetralogy of Fallot, subaortic stenosis, tetralogy of Fallot, and truncus arteriosus. Furthermore, CNV gene frequency spectra were enriched (P ≀ 0.05) for losses at: FKBP6, ELN, GTF2IRD1, GATA4, CRKL, TBX1, ATRX, GPC3, BCOR, ZIC3, FLNA and MID1; and gains at: PRKAB2, FMO5, CHD1L, BCL9, ACP6, GJA5, HRAS, GATA6 and RUNX1. Of CHD subjects, 14% had causal chromosomal abnormalities, and 4.3% had likely causal (significantly enriched), large, rare CNVs. CNV frequency spectra combined with precision phenotyping may lead to increased molecular understanding of etiologic pathways

    Impact of \u3cem\u3eMYH6\u3c/em\u3e Variants in Hypoplastic Left Heart Syndrome

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    Hypoplastic left heart syndrome (HLHS) is a clinically and anatomically severe form of congenital heart disease (CHD). Although prior studies suggest that HLHS has a complex genetic inheritance, its etiology remains largely unknown. The goal of this study was to characterize a risk gene in HLHS and its effect on HLHS etiology and outcome. We performed next-generation sequencing on a multigenerational family with a high prevalence of CHD/HLHS, identifying a rare variant in the α-myosin heavy chain (MYH6) gene. A case-control study of 190 unrelated HLHS subjects was then performed and compared with the 1000 Genomes Project. Damaging MYH6 variants, including novel, missense, in-frame deletion, premature stop, de novo, and compound heterozygous variants, were significantly enriched in HLHS cases (P \u3c 1 × 10−5). Clinical outcomes analysis showed reduced transplant-free survival in HLHS subjects with damaging MYH6 variants (P \u3c 1 × 10−2). Transcriptome and protein expression analyses with cardiac tissue revealed differential expression of cardiac contractility genes, notably upregulation of the ÎČ-myosin heavy chain (MYH7) gene in subjects with MYH6 variants (P \u3c 1 × 10−3). We subsequently used patient-specific induced pluripotent stem cells (iPSCs) to model HLHS in vitro. Early stages of in vitro cardiomyogenesis in iPSCs derived from two unrelated HLHS families mimicked the increased expression of MYH7 observed in vivo (P \u3c 1 × 10−2), while revealing defective cardiomyogenic differentiation. Rare, damaging variants in MYH6 are enriched in HLHS, affect molecular expression of contractility genes, and are predictive of poor outcome. These findings indicate that the etiology of MYH6-associated HLHS can be informed using iPSCs and suggest utility in future clinical applications

    Insights on Water Interaction at the Interface of Nitrogen Functionalized Hydrothermal Carbons

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    Hydrothermal carbon (HTC) derived from biomass is a class of cost-efficient, eco-friendly functional carbon materials with various potential applications. In this work, solid-state nuclear magnetic resonance (NMR), longitudinal (T1) relaxation time and diffusion NMR were employed to investigate the structure and water dynamics for HTC and nitrogen-functionalized hydrothermal carbon (N-HTC) samples ((N)-HTC). Results showed that the presence of N-functional groups influences the water interaction with (N)-HTC more strongly than surface area, pore size distribution or oxygenated functional groups. Furthermore, the degree of water interaction can be tuned by adjusting the synthesis temperature and the precursor ratio. Water motion was more strongly inhibited in N-HTC than in N-free HTC, thereby suggesting the existence of a differently structured hydration shell around N-HTC particles. In addition, the diffusion data of water in the N-HTC material shows two components that do not exchange on the time scale of the experiment (tens of milliseconds), indicating a significant fraction of slow mobile water that exists inside the structure of N-HTC. 1H–2H isotope exchange and cross-polarization NMR results show this internal water only in a near-surface layer of the N-HTC particles. Based on these findings, a model for water interaction with (N)-HTC particles is proposed

    Dipolar interaction between two-dimensional magnetic particles

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    We determine the effective dipolar interaction between single domain two-dimensional ferromagnetic particles (islands or dots), taking into account their finite size. The first correction term decays as 1/D^5, where D is the distance between particles. If the particles are arranged in a regular two-dimensional array and are magnetized in plane, we show that the correction term reinforces the antiferromagnetic character of the ground state in a square lattice, and the ferromagnetic one in a triangular lattice. We also determine the dipolar spin-wave spectrum and evaluate how the Curie temperature of an ensemble of magnetic particles scales with the parameters defining the particle array: height and size of each particle, and interparticle distance. Our results show that dipolar coupling between particles might induce ferromagnetic long range order at experimentally relevant temperatures. However, depending on the size of the particles, such a collective phenomenon may be disguised by superparamagnetism.Comment: 11 pages, 5 figure

    Spatial relationships between land-use, habitat, water quality and lotic macroinvertebrates in two Swiss catchments

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    We examined the influence of land-use, habitat, and water quality on the spatial distribution of aquatic macroinvertebrates in two human-dominated catchments in the Swiss Plateau (GĂŒrbe, Mönchaltorfer Aa). Land-use in the GĂŒrbe catchment was dominated by agriculture, whereas urban land-use was more common in the Mönchaltorfer Aa. Study sites in each catchment were characterized using measures of local habitat conditions, water quality parameters including water temperature, and organic matter resources. A strong longitudinal gradient in temperature, conductivity and nitrogen was evident among sites in the GĂŒrbe catchment, although sites on a main tributary had a strong agricultural signature and deviated from this pattern. Percentage agricultural land-use in the GĂŒrbe was strongly correlated with algal biomass and the water quality PCA axes associated with conductivity, nitrogen (axis-1) and temperature (axis-3). Spatial grouping of sites by water quality was less evident in the Mönchaltorfer Aa, except for a strong signal by wastewater treatment plant effluents and partial differences between upper and lower basin sites. Percentage forest and agricultural land-use in the Mönchaltorfer Aa were correlated with water quality PCA axis-2, being associated with phosphorus and temperature. Macroinvertebrate densities, taxonomic richness, and axis-1 from a non-metric multidimensional scaling analysis (NMDS) of taxonomic composition were significantly correlated with water quality PCA axis-1 in the GĂŒrbe catchment. Here, macroinvertebrate densities and NMDS axis-1 scores based on taxon relative abundances and densities were correlated with land-use features. Spatial distances between sites also were related to site differences in macroinvertebrates, reflecting the strong longitudinal environmental gradient in the GĂŒrbe. Taxonomic differences between water quality PCA site groups were less pronounced in the Mönchaltorfer Aa, although differences were significant for trichopterans, ephemeropterans, chironomids, gastropods and coleopterans. Here, NMDS axis-1 based on taxon relative abundances and densities was correlated with forest land-use. Spatial distances between sites were not evident in macroinvertebrate site differences, reflecting the less pronounced spatial and longitudinal patterns in environmental attributes in this catchment. Our results support the hypothesis that spatial distributions of macroinvertebrates are related to spatial relationships among environmental attributes like land-use, habitat, and water quality in human-dominated catchments that depend on river network complexity, a habitat-filtering template in line with ecological niche theory

    Involvement of PARP1 in the Regulation of Alternative Splicing

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    Specialized chromatin structures such as nucleosomes with specific histone modifications decorate exons in eukaryotic genomes, suggesting a functional connection between chromatin organization and the regulation of pre-mRNA splicing. Through profiling the functional location of Poly (ADP) ribose polymerase, we observed that it is associated with the nucleosomes at exon/intron boundaries of specific genes, suggestive of a role for this enzyme in alternative splicing. Poly (ADP) ribose polymerase has previously been implicated in the PARylation of splicing factors as well as regulation of the histone modification H3K4me3, a mark critical for co-transcriptional splicing. In light of these studies, we hypothesized that interaction of the chromatin-modifying factor, Poly (ADP) ribose polymerase with nucleosomal structures at exon–intron boundaries, might regulate pre-mRNA splicing. Using genome-wide approaches validated by gene-specific assays, we show that depletion of PARP1 or inhibition of its PARylation activity results in changes in alternative splicing of a specific subset of genes. Furthermore, we observed that PARP1 bound to RNA, splicing factors and chromatin, suggesting that Poly (ADP) ribose polymerase serves as a gene regulatory hub to facilitate co-transcriptional splicing. These studies add another function to the multi-functional protein, Poly (ADP) ribose polymerase, and provide a platform for further investigation of this protein’s function in organizing chromatin during gene regulatory processes

    Sudemycin E Influences Alternative Splicing and Changes Chromatin Modifications

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    Sudemycin E is an analog of the pre-messenger RNA splicing modulator FR901464 and its derivative spliceostatin A. Sudemycin E causes the death of cancer cells through an unknown mechanism. We found that similar to spliceostatin A, sudemycin E binds to the U2 small nuclear ribonucleoprotein (snRNP) component SF3B1. Native chromatin immunoprecipitations showed that U2 snRNPs physically interact with nucleosomes. Sudemycin E induces a dissociation of the U2 snRNPs and decreases their interaction with nucleosomes. To determine the effect on gene expression, we performed genome-wide array analysis. Sudemycin E first causes a rapid change in alternative pre-messenger RNA splicing, which is later followed by changes in overall gene expression and arrest in the G2 phase of the cell cycle. The changes in alternative exon usage correlate with a loss of the H3K36me3 modification in chromatin encoding these exons. We propose that sudemycin E interferes with the ability of U2 snRNP to maintain an H3K36me3 modification in actively transcribed genes. Thus, in addition to the reversible changes in alternative splicing, sudemycin E causes changes in chromatin modifications that result in chromatin condensation, which is a likely contributing factor to cancer cell death
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