644 research outputs found

    Growing Income Inequality Threatens American Education

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    The first of two articles in consecutive months describes the origins and nature of growing income inequality, and some of its consequences for American children. It documents the increased family income inequality that's occurred over the past 40 years and shows that the increased income disparity has been more than matched by an expanding gap between the amounts of money that low- and high-income parents spend on enrichment activities for their children. It also shows that the growth in income inequality has been accompanied by increasing gaps in academic achievement. The article draws from the first part of the author's recent book, Restoring Opportunity: The Crisis of Inequality and the Challenge for American Education (Harvard Education Press and the Russell Sage Foundation, 2014). The second part to the series, also drawn from Restoring Opportunity, describes ideas based on proven policy approaches that will enable the country to make progress on the enormous task of restoring the educational opportunities that children from low-income families need if they are to lead productive and fulfilling lives. © 2014

    Metabolite profiles of medulloblastoma for rapid and non-invasive detection of molecular disease groups

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    BackgroundThe malignant childhood brain tumour, medulloblastoma, is classified clinically into molecular groups which guide therapy. DNA-methylation profiling is the current classification ‘gold-standard’, typically delivered 3–4 weeks post-surgery. Pre-surgery non-invasive diagnostics thus offer significant potential to improve early diagnosis and clinical management. Here, we determine tumour metabolite profiles of the four medulloblastoma groups, assess their diagnostic utility using tumour tissue and potential for non-invasive diagnosis using in vivo magnetic resonance spectroscopy (MRS).MethodsMetabolite profiles were acquired by high-resolution magic-angle spinning NMR spectroscopy (MAS) from 86 medulloblastomas (from 59 male and 27 female patients), previously classified by DNA-methylation array (WNT (n = 9), SHH (n = 22), Group3 (n = 21), Group4 (n = 34)); RNA-seq data was available for sixty. Unsupervised class-discovery was performed and a support vector machine (SVM) constructed to assess diagnostic performance. The SVM classifier was adapted to use only metabolites (n = 10) routinely quantified from in vivo MRS data, and re-tested. Glutamate was assessed as a predictor of overall survival.FindingsGroup-specific metabolite profiles were identified; tumours clustered with good concordance to their reference molecular group (93%). GABA was only detected in WNT, taurine was low in SHH and lipids were high in Group3. The tissue-based metabolite SVM classifier had a cross-validated accuracy of 89% (100% for WNT) and, adapted to use metabolites routinely quantified in vivo, gave a combined classification accuracy of 90% for SHH, Group3 and Group4. Glutamate predicted survival after incorporating known risk-factors (HR = 3.39, 95% CI 1.4–8.1, p = 0.025).InterpretationTissue metabolite profiles characterise medulloblastoma molecular groups. Their combination with machine learning can aid rapid diagnosis from tissue and potentially in vivo. Specific metabolites provide important information; GABA identifying WNT and glutamate conferring poor prognosis

    The Science of Sungrazers, Sunskirters, and Other Near-Sun Comets

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    This review addresses our current understanding of comets that venture close to the Sun, and are hence exposed to much more extreme conditions than comets that are typically studied from Earth. The extreme solar heating and plasma environments that these objects encounter change many aspects of their behaviour, thus yielding valuable information on both the comets themselves that complements other data we have on primitive solar system bodies, as well as on the near-solar environment which they traverse. We propose clear definitions for these comets: We use the term near-Sun comets to encompass all objects that pass sunward of the perihelion distance of planet Mercury (0.307 AU). Sunskirters are defined as objects that pass within 33 solar radii of the Sun’s centre, equal to half of Mercury’s perihelion distance, and the commonly-used phrase sungrazers to be objects that reach perihelion within 3.45 solar radii, i.e. the fluid Roche limit. Finally, comets with orbits that intersect the solar photosphere are termed sundivers. We summarize past studies of these objects, as well as the instruments and facilities used to study them, including space-based platforms that have led to a recent revolution in the quantity and quality of relevant observations. Relevant comet populations are described, including the Kreutz, Marsden, Kracht, and Meyer groups, near-Sun asteroids, and a brief discussion of their origins. The importance of light curves and the clues they provide on cometary composition are emphasized, together with what information has been gleaned about nucleus parameters, including the sizes and masses of objects and their families, and their tensile strengths. The physical processes occurring at these objects are considered in some detail, including the disruption of nuclei, sublimation, and ionisation, and we consider the mass, momentum, and energy loss of comets in the corona and those that venture to lower altitudes. The different components of comae and tails are described, including dust, neutral and ionised gases, their chemical reactions, and their contributions to the near-Sun environment. Comet-solar wind interactions are discussed, including the use of comets as probes of solar wind and coronal conditions in their vicinities. We address the relevance of work on comets near the Sun to similar objects orbiting other stars, and conclude with a discussion of future directions for the field and the planned ground- and space-based facilities that will allow us to address those science topics

    Quantitative PCR tissue expression profiling of the human SGLT2 gene and related family members

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    SGLT2 (for “Sodium GLucose coTransporter” protein 2) is the major protein responsible for glucose reabsorption in the kidney and its inhibition has been the focus of drug discovery efforts to treat type 2 diabetes. In order to better clarify the human tissue distribution of expression of SGLT2 and related members of this cotransporter class, we performed TaqMan™ (Applied Biosystems, Foster City, CA, USA) quantitative polymerase chain reaction (PCR) analysis of SGLT2 and other sodium/glucose transporter genes on RNAs from 72 normal tissues from three different individuals. We consistently observe that SGLT2 is highly kidney specific while SGLT5 is highly kidney abundant; SGLT1, sodium-dependent amino acid transporter (SAAT1), and SGLT4 are highly abundant in small intestine and skeletal muscle; SGLT6 is expressed in the central nervous system; and sodium myoinositol cotransporter is ubiquitously expressed across all human tissues

    An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

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    For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types

    Search for lepton-flavor violation at HERA

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    A search for lepton-flavor-violating interactions epμXe p \to \mu X and epτXe p\to \tau X has been performed with the ZEUS detector using the entire HERA I data sample, corresponding to an integrated luminosity of 130 pb^{-1}. The data were taken at center-of-mass energies, s\sqrt{s}, of 300 and 318 GeV. No evidence of lepton-flavor violation was found, and constraints were derived on leptoquarks (LQs) that could mediate such interactions. For LQ masses below s\sqrt{s}, limits were set on λeq1βq\lambda_{eq_1} \sqrt{\beta_{\ell q}}, where λeq1\lambda_{eq_1} is the coupling of the LQ to an electron and a first-generation quark q1q_1, and βq\beta_{\ell q} is the branching ratio of the LQ to the final-state lepton \ell (μ\mu or τ\tau) and a quark qq. For LQ masses much larger than s\sqrt{s}, limits were set on the four-fermion interaction term λeqαλqβ/MLQ2\lambda_{e q_\alpha} \lambda_{\ell q_\beta} / M_{\mathrm{LQ}}^2 for LQs that couple to an electron and a quark qαq_\alpha and to a lepton \ell and a quark qβq_\beta, where α\alpha and β\beta are quark generation indices. Some of the limits are also applicable to lepton-flavor-violating processes mediated by squarks in RR-Parity-violating supersymmetric models. In some cases, especially when a higher-generation quark is involved and for the process epτXe p\to \tau X , the ZEUS limits are the most stringent to date.Comment: 37 pages, 10 figures, Accepted by EPJC. References and 1 figure (Fig. 6) adde

    Observation of Scaling Violations in Scaled Momentum Distributions at HERA

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    Charged particle production has been measured in deep inelastic scattering (DIS) events over a large range of xx and Q2Q^2 using the ZEUS detector. The evolution of the scaled momentum, xpx_p, with Q2,Q^2, in the range 10 to 1280 GeV2GeV^2, has been investigated in the current fragmentation region of the Breit frame. The results show clear evidence, in a single experiment, for scaling violations in scaled momenta as a function of Q2Q^2.Comment: 21 pages including 4 figures, to be published in Physics Letters B. Two references adde

    D* Production in Deep Inelastic Scattering at HERA

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    This paper presents measurements of D^{*\pm} production in deep inelastic scattering from collisions between 27.5 GeV positrons and 820 GeV protons. The data have been taken with the ZEUS detector at HERA. The decay channel D+(D0Kπ+)π+D^{*+}\to (D^0 \to K^- \pi^+) \pi^+ (+ c.c.) has been used in the study. The e+pe^+p cross section for inclusive D^{*\pm} production with 5<Q2<100GeV25<Q^2<100 GeV^2 and y<0.7y<0.7 is 5.3 \pms 1.0 \pms 0.8 nb in the kinematic region {1.3<pT(D±)<9.01.3<p_T(D^{*\pm})<9.0 GeV and η(D±)<1.5| \eta(D^{*\pm}) |<1.5}. Differential cross sections as functions of p_T(D^{*\pm}), η(D±),W\eta(D^{*\pm}), W and Q2Q^2 are compared with next-to-leading order QCD calculations based on the photon-gluon fusion production mechanism. After an extrapolation of the cross section to the full kinematic region in p_T(D^{*\pm}) and η\eta(D^{*\pm}), the charm contribution F2ccˉ(x,Q2)F_2^{c\bar{c}}(x,Q^2) to the proton structure function is determined for Bjorken xx between 2 \cdot 104^{-4} and 5 \cdot 103^{-3}.Comment: 17 pages including 4 figure

    Multijet production in neutral current deep inelastic scattering at HERA and determination of alpha_s

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    Multijet production rates in neutral current deep inelastic scattering have been measured in the range of exchanged boson virtualities 10 < Q2 < 5000 GeV2. The data were taken at the ep collider HERA with centre-of-mass energy sqrt(s) = 318 GeV using the ZEUS detector and correspond to an integrated luminosity of 82.2 pb-1. Jets were identified in the Breit frame using the k_T cluster algorithm in the longitudinally invariant inclusive mode. Measurements of differential dijet and trijet cross sections are presented as functions of jet transverse energy E_{T,B}{jet}, pseudorapidity eta_{LAB}{jet} and Q2 with E_{T,B}{jet} > 5 GeV and -1 < eta_{LAB}{jet} < 2.5. Next-to-leading-order QCD calculations describe the data well. The value of the strong coupling constant alpha_s(M_Z), determined from the ratio of the trijet to dijet cross sections, is alpha_s(M_Z) = 0.1179 pm 0.0013(stat.) {+0.0028}_{-0.0046}(exp.) {+0.0064}_{-0.0046}(th.)Comment: 22 pages, 5 figure

    Observation of hard scattering in photoproduction events with a large rapidity gap at HERA

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    Events with a large rapidity gap and total transverse energy greater than 5 GeV have been observed in quasi-real photoproduction at HERA with the ZEUS detector. The distribution of these events as a function of the γp\gamma p centre of mass energy is consistent with diffractive scattering. For total transverse energies above 12 GeV, the hadronic final states show predominantly a two-jet structure with each jet having a transverse energy greater than 4 GeV. For the two-jet events, little energy flow is found outside the jets. This observation is consistent with the hard scattering of a quasi-real photon with a colourless object in the proton.Comment: 19 pages, latex, 4 figures appended as uuencoded fil
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