112 research outputs found

    A single-label phenylpyrrolocytidine provides a molecular beacon-like response reporting HIV-1 RT RNase H activity

    Get PDF
    6-Phenylpyrrolocytidine (PhpC), a structurally conservative and highly fluorescent cytidine analog, was incorporated into oligoribonucleotides. The PhpC-containing RNA formed native-like duplex structures with complementary DNA or RNA. The PhpC-modification was found to act as a sensitive reporter group being non-disruptive to structure and the enzymatic activity of RNase H. A RNA/DNA hybrid possessing a single PhpC insert was an excellent substrate for HIV-1 RT Ribonuclease H and rapidly reported cleavage of the RNA strand with a 14-fold increase in fluorescence intensity. The PhpC-based assay for RNase H was superior to the traditional molecular beacon approach in terms of responsiveness, rapidity and ease (single label versus dual). Furthermore, the PhpC-based assay is amenable to high-throughput microplate assay format and may form the basis for a new screen for inhibitors of HIV-RT RNase H

    The Long-Baseline Neutrino Experiment: Exploring Fundamental Symmetries of the Universe

    Get PDF
    The preponderance of matter over antimatter in the early Universe, the dynamics of the supernova bursts that produced the heavy elements necessary for life and whether protons eventually decay --- these mysteries at the forefront of particle physics and astrophysics are key to understanding the early evolution of our Universe, its current state and its eventual fate. The Long-Baseline Neutrino Experiment (LBNE) represents an extensively developed plan for a world-class experiment dedicated to addressing these questions. LBNE is conceived around three central components: (1) a new, high-intensity neutrino source generated from a megawatt-class proton accelerator at Fermi National Accelerator Laboratory, (2) a near neutrino detector just downstream of the source, and (3) a massive liquid argon time-projection chamber deployed as a far detector deep underground at the Sanford Underground Research Facility. This facility, located at the site of the former Homestake Mine in Lead, South Dakota, is approximately 1,300 km from the neutrino source at Fermilab -- a distance (baseline) that delivers optimal sensitivity to neutrino charge-parity symmetry violation and mass ordering effects. This ambitious yet cost-effective design incorporates scalability and flexibility and can accommodate a variety of upgrades and contributions. With its exceptional combination of experimental configuration, technical capabilities, and potential for transformative discoveries, LBNE promises to be a vital facility for the field of particle physics worldwide, providing physicists from around the globe with opportunities to collaborate in a twenty to thirty year program of exciting science. In this document we provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess.Comment: Major update of previous version. This is the reference document for LBNE science program and current status. Chapters 1, 3, and 9 provide a comprehensive overview of LBNE's scientific objectives, its place in the landscape of neutrino physics worldwide, the technologies it will incorporate and the capabilities it will possess. 288 pages, 116 figure

    Cardiomyocytes from human pluripotent stem cells: from laboratory curiosity to industrial biomedical platform

    Get PDF
    Cardiomyocytes from human pluripotent stem cells (hPSCs-CMs) could revolutionise biomedicine. Global burden of heart failure will soon reach USD $90bn, while unexpected cardiotoxicity underlies 28% of drug withdrawals. Advances in hPSC isolation, Cas9/CRISPR genome engineering and hPSC-CM differentiation have improved patient care, progressed drugs to clinic and opened a new era in safety pharmacology. Nevertheless, predictive cardiotoxicity using hPSC-CMs contrasts from failure to almost total success. Since this likely relates to cell immaturity, efforts are underway to use biochemical and biophysical cues to improve many of the ~ 30 structural and functional properties of hPSC-CMs towards those seen in adult CMs. Other developments needed for widespread hPSC-CM utility include subtype specification, cost reduction of large scale differentiation and elimination of the phenotyping bottleneck. This review will consider these factors in the evolution of hPSC-CM technologies, as well as their integration into high content industrial platforms that assess structure, mitochondrial function, electrophysiology, calcium transients and contractility. This article is part of a Special Issue entitled: Cardiomyocyte Biology: Integration of Developmental and Environmental Cues in the Heart edited by Marcus Schaub and Hughes Abriel

    Antineutrino Oscillations in the Atmospheric Sector

    Get PDF
    This thesis presents measurements of the oscillations of muon antineutrinos in the atmospheric sector, where world knowledge of antineutrino oscillations lags well behind the knowledge of neutrinos, as well as a search for νμ \to ν̅ μ transitions. Differences between neutrino and antineutrino oscillations could be a sign of physics beyond the Standard Model, including non-standard matter interactions or the violation of CPT symmetry. These measurements leverage the sign-selecting capabilities of the magnetized steel-scintillator MINOS detectors to analyze antineutrinos from the NuMI beam, both when it is in FHC and when it is in RHC. Antineutrino oscillations are observed at |Δm̅2atm| = (3.36+0.46-0.40(stat)±0.06(syst)) x 10- eV2 and sin2(2θ̅23 = 0.860+0.11-0.12(stat)± 0.01(syst). The oscillation parameters measured for antineutrinos and those measured by MINOS for neutrinos differ by a large enough margin that the chance of obtaining two values as discrepant as those observed is only 2%, assuming the two measurements arise from the same underlying mechanism, with the same parameter values. No evidence is seen for neutrino-to-antineutrino transitions

    New neutrino oscillation results from NOVA

    No full text
    Neutrinos oscillate among flavors as they travel because a neutrino of a particular flavor is also a superposition of multiple neutrinos with slightly different masses.&nbsp; The interferometric nature of oscillations allows these tiny mass differences to be measured, along with the parameters of the PMNS matrix which governs the mixing. However, since neutrinos only interact weakly, a powerful neutrino source and massive detectors are required to measure them. In this talk I will show recently updated results from NOvA, a long-baseline neutrino oscillation experiment at Fermilab with two functionally identical scintillator detectors. I will present measurements of muon neutrino disappearance and electron neutrino appearance, and what constraints those measurements put on the remaining open questions in neutrino oscillations: Is the neutrino mass hierarchy "normal" or "inverted?" Do neutrino oscillations violate CP symmetry? Is the mixing in the atmospheric sector maximal? The recent update includes 50% more data than previous results as well as simulation and analysis improvements.</p

    PHYSTAT-nu 2019

    No full text

    The transmission of water through snow

    No full text
    corecore