267 research outputs found

    Partially spin polarized quantum Hall effect in the filling factor range 1/3 < nu < 2/5

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    The residual interaction between composite fermions (CFs) can express itself through higher order fractional Hall effect. With the help of diagonalization in a truncated composite fermion basis of low-energy many-body states, we predict that quantum Hall effect with partial spin polarization is possible at several fractions between ν=1/3\nu=1/3 and ν=2/5\nu=2/5. The estimated excitation gaps are approximately two orders of magnitude smaller than the gap at ν=1/3\nu=1/3, confirming that the inter-CF interaction is extremely weak in higher CF levels.Comment: 4 pages, 3 figure

    DNA methylation is required to maintain both DNA replication timing precision and 3D genome organization integrity

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    DNA replication timing and three-dimensional (3D) genome organization are associated with distinct epigenome patterns across large domains. However, whether alterations in the epigenome, in particular cancer-related DNA hypomethylation, affects higher-order levels of genome architecture is still unclear. Here, using Repli-Seq, single-cell Repli-Seq, and Hi-C, we show that genome-wide methylation loss is associated with both concordant loss of replication timing precision and deregulation of 3D genome organization. Notably, we find distinct disruption in 3D genome compartmentalization, striking gains in cell-to-cell replication timing heterogeneity and loss of allelic replication timing in cancer hypomethylation models, potentially through the gene deregulation of DNA replication and genome organization pathways. Finally, we identify ectopic H3K4me3-H3K9me3 domains from across large hypomethylated domains, where late replication is maintained, which we purport serves to protect against catastrophic genome reorganization and aberrant gene transcription. Our results highlight a potential role for the methylome in the maintenance of 3D genome regulation

    The Nell-1 Growth Factor Stimulates Bone Formation by Purified Human Perivascular Cells

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    The search for novel sources of stem cells other than bone marrow mesenchymal stem cells (MSCs) for bone regeneration and repair has been a critical endeavor. We previously established an effective protocol to homogeneously purify human pericytes from multiple fetal and adult tissues, including adipose, bone marrow, skeletal muscle, and pancreas, and identified pericytes as a primitive origin of human MSCs. In the present study, we further characterized the osteogenic potential of purified human pericytes combined with a novel osteoinductive growth factor, Nell-1. Purified pericytes grown on either standard culture ware or human cancellous bone chip (hCBC) scaffolds exhibited robust osteogenic differentiation in vitro. Using a nude mouse muscle pouch model, pericytes formed significant new bone in vivo as compared to scaffold alone (hCBC). Moreover, Nell-1 significantly increased pericyte osteogenic differentiation, both in vitro and in vivo. Interestingly, Nell-1 significantly induced pericyte proliferation and was observed to have pro-angiogenic effects, both in vitro and in vivo. These studies suggest that pericytes are a potential new cell source for future efforts in skeletal regenerative medicine, and that Nell-1 is a candidate growth factor able to induce pericyte osteogenic differentiation

    No evidence that protein truncating variants in BRIP1 are associated with breast cancer risk: implications for gene panel testing.

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    BACKGROUND: BRCA1 interacting protein C-terminal helicase 1 (BRIP1) is one of the Fanconi Anaemia Complementation (FANC) group family of DNA repair proteins. Biallelic mutations in BRIP1 are responsible for FANC group J, and previous studies have also suggested that rare protein truncating variants in BRIP1 are associated with an increased risk of breast cancer. These studies have led to inclusion of BRIP1 on targeted sequencing panels for breast cancer risk prediction. METHODS: We evaluated a truncating variant, p.Arg798Ter (rs137852986), and 10 missense variants of BRIP1, in 48 144 cases and 43 607 controls of European origin, drawn from 41 studies participating in the Breast Cancer Association Consortium (BCAC). Additionally, we sequenced the coding regions of BRIP1 in 13 213 cases and 5242 controls from the UK, 1313 cases and 1123 controls from three population-based studies as part of the Breast Cancer Family Registry, and 1853 familial cases and 2001 controls from Australia. RESULTS: The rare truncating allele of rs137852986 was observed in 23 cases and 18 controls in Europeans in BCAC (OR 1.09, 95% CI 0.58 to 2.03, p=0.79). Truncating variants were found in the sequencing studies in 34 cases (0.21%) and 19 controls (0.23%) (combined OR 0.90, 95% CI 0.48 to 1.70, p=0.75). CONCLUSIONS: These results suggest that truncating variants in BRIP1, and in particular p.Arg798Ter, are not associated with a substantial increase in breast cancer risk. Such observations have important implications for the reporting of results from breast cancer screening panels.The COGS project is funded through a European Commission's Seventh Framework Programme grant (agreement number 223175 - HEALTH-F2-2009-223175). BCAC is funded by Cancer Research UK [C1287/A10118, C1287/A12014] and by the European Community´s Seventh Framework Programme under grant agreement number 223175 (grant number HEALTH-F2-2009-223175) (COGS). Funding for the iCOGS infrastructure came from: the European Community's Seventh Framework Programme under grant agreement n° 223175 (HEALTH-F2-2009-223175) (COGS), Cancer Research UK (C1287/A10118, C1287/A 10710, C12292/A11174, C1281/A12014, C5047/A8384, C5047/A15007, C5047/A10692, C8197/A16565), the National Institutes of Health (CA128978) and Post-Cancer GWAS initiative (1U19 CA148537, 1U19 16 CA148065 and 1U19 CA148112 - the GAME-ON initiative), the Department of Defense (W81XWH-10-1- 0341), the Canadian Institutes of Health Research (CIHR) for the CIHR Team in Familial Risks of Breast Cancer, Komen Foundation for the Cure, the Breast Cancer Research Foundation, and the Ovarian Cancer Research Fund. This study made use of data generated by the Wellcome Trust Case Control consortium. Funding for the project was provided by the Wellcome Trust under award 076113. The results published here are in part based upon data generated by The Cancer Genome Atlas Project established by the National Cancer Institute and National Human Genome Research Institute.This is the author accepted manuscript. The final version is available from BMJ Group at http://dx.doi.org/10.1136/jmedgenet-2015-103529

    Fine-Scale Mapping of the 4q24 Locus Identifies Two Independent Loci Associated with Breast Cancer Risk

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    Background: A recent association study identified a common variant (rs9790517) at 4q24 to be associated with breast cancer risk. Independent association signals and potential functional variants in this locus have not been explored. Methods: We conducted a fine-mapping analysis in 55,540 breast cancer cases and 51,168 controls from the Breast Cancer Association Consortium. Results: Conditional analyses identified two independent association signals among women of European ancestry, represented by rs9790517 [conditional P = 2.51 × 10−4; OR, 1.04; 95% confidence interval (CI), 1.02–1.07] and rs77928427 (P = 1.86 × 10−4; OR, 1.04; 95% CI, 1.02–1.07). Functional annotation using data from the Encyclopedia of DNA Elements (ENCODE) project revealed two putative functional variants, rs62331150 and rs73838678 in linkage disequilibrium (LD) with rs9790517 (r2 ≥ 0.90) residing in the active promoter or enhancer, respectively, of the nearest gene, TET2. Both variants are located in DNase I hypersensitivity and transcription factor–binding sites. Using data from both The Cancer Genome Atlas (TCGA) and Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), we showed that rs62331150 was associated with level of expression of TET2 in breast normal and tumor tissue. Conclusion: Our study identified two independent association signals at 4q24 in relation to breast cancer risk and suggested that observed association in this locus may be mediated through the regulation of TET2. Impact: Fine-mapping study with large sample size warranted for identification of independent loci for breast cancer risk

    Determination of the Form Factors for the Decay B0 --> D*-l+nu_l and of the CKM Matrix Element |Vcb|

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    We present a combined measurement of the Cabibbo-Kobayashi-Maskawa matrix element Vcb|V_{cb}| and of the parameters ρ2\rho^2, R1R_1, and R2R_2, which fully characterize the form factors of the B0D+νB^0 \to D^{*-}\ell^{+}\nu_\ell decay in the framework of HQET, based on a sample of about 52,800 B0D+νB^0 \to D^{*-}\ell^{+}\nu_\ell decays recorded by the BABAR detector. The kinematical information of the fully reconstructed decay is used to extract the following values for the parameters (where the first errors are statistical and the second systematic): ρ2=1.156±0.094±0.028\rho^2 = 1.156 \pm 0.094 \pm 0.028, R1=1.329±0.131±0.044R_1 = 1.329 \pm 0.131 \pm 0.044, R2=0.859±0.077±0.022R_2 = 0.859 \pm 0.077 \pm 0.022, F(1)Vcb=(35.03±0.39±1.15)×103\mathcal{F}(1)|V_{cb}| = (35.03 \pm 0.39 \pm 1.15) \times 10^{-3}. By combining these measurements with the previous BABAR measurements of the form factors which employs a different technique on a partial sample of the data, we improve the statistical accuracy of the measurement, obtaining: ρ2=1.179±0.048±0.028,R1=1.417±0.061±0.044,R2=0.836±0.037±0.022,\rho^2 = 1.179 \pm 0.048 \pm 0.028, R_1 = 1.417 \pm 0.061 \pm 0.044, R_2 = 0.836 \pm 0.037 \pm 0.022, and F(1)Vcb=(34.68±0.32±1.15)×103. \mathcal{F}(1)|V_{cb}| = (34.68 \pm 0.32 \pm 1.15) \times 10^{-3}. Using the lattice calculations for the axial form factor F(1)\mathcal{F}(1), we extract Vcb=(37.74±0.35±1.25±1.441.23)×103|V_{cb}| =(37.74 \pm 0.35 \pm 1.25 \pm ^{1.23}_{1.44}) \times 10^{-3}, where the third error is due to the uncertainty in F(1)\mathcal{F}(1)

    Study of the Exclusive Initial-State Radiation Production of the DDˉD \bar D System

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    A study of exclusive production of the DDˉD \bar D system through initial-state r adiation is performed in a search for charmonium states, where D=D0D=D^0 or D+D^+. The D0D^0 mesons are reconstructed in the D0Kπ+D^0 \to K^- \pi^+, D0Kπ+π0D^0 \to K^- \pi^+ \pi^0, and D0Kπ+π+πD^0 \to K^- \pi^+ \pi^+ \pi^- decay modes. The D+D^+ is reconstructed through the D+Kπ+π+D^+ \to K^- \pi^+ \pi^+ decay mode. The analysis makes use of an integrated luminosity of 288.5 fb1^{-1} collected by the BaBar experiment. The DDˉD \bar D mass spectrum shows a clear ψ(3770)\psi(3770) signal. Further structures appear in the 3.9 and 4.1 GeV/c2c^2 regions. No evidence is found for Y(4260) decays to DDˉD \bar D, implying an up per limit \frac{\BR(Y(4260)\to D \bar D)}{\BR(Y(4260)\to J/\psi \pi^+ \pi^-)} < 7.6 (95 % confidence level)

    Search for Tensor, Vector, and Scalar Polarizations in the Stochastic Gravitational-Wave Background

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    The detection of gravitational waves with Advanced LIGO and Advanced Virgo has enabled novel tests of general relativity, including direct study of the polarization of gravitational waves. While general relativity allows for only two tensor gravitational-wave polarizations, general metric theories can additionally predict two vector and two scalar polarizations. The polarization of gravitational waves is encoded in the spectral shape of the stochastic gravitational-wave background, formed by the superposition of cosmological and individually unresolved astrophysical sources. Using data recorded by Advanced LIGO during its first observing run, we search for a stochastic background of generically polarized gravitational waves. We find no evidence for a background of any polarization, and place the first direct bounds on the contributions of vector and scalar polarizations to the stochastic background. Under log-uniform priors for the energy in each polarization, we limit the energy densities of tensor, vector, and scalar modes at 95% credibility to Ω0T<5.58×10-8, Ω0V<6.35×10-8, and Ω0S<1.08×10-7 at a reference frequency f0=25 Hz. © 2018 American Physical Society

    Search for gravitational waves from Scorpius X-1 in the second Advanced LIGO observing run with an improved hidden Markov model

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    We present results from a semicoherent search for continuous gravitational waves from the low-mass x-ray binary Scorpius X-1, using a hidden Markov model (HMM) to track spin wandering. This search improves on previous HMM-based searches of LIGO data by using an improved frequency domain matched filter, the J-statistic, and by analyzing data from Advanced LIGO's second observing run. In the frequency range searched, from 60 to 650 Hz, we find no evidence of gravitational radiation. At 194.6 Hz, the most sensitive search frequency, we report an upper limit on gravitational wave strain (at 95% confidence) of h095%=3.47×10-25 when marginalizing over source inclination angle. This is the most sensitive search for Scorpius X-1, to date, that is specifically designed to be robust in the presence of spin wandering. © 2019 American Physical Society
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