541 research outputs found

    Klauder's coherent states for the radial Coulomb problem in a uniformly curved space and their flat-space limits

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    First a set of coherent states a la Klauder is formally constructed for the Coulomb problem in a curved space of constant curvature. Then the flat-space limit is taken to reduce the set for the radial Coulomb problem to a set of hydrogen atom coherent states corresponding to both the discrete and the continuous portions of the spectrum for a fixed \ell sector.Comment: 10 pages, no figure

    Cancer-Associated noncoding mutations affect RNA G-quadruplex-mediated regulation of gene expression

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    © 2017 The Author(s). Cancer is a multifactorial disease driven by a combination of genetic and environmental factors. Many cancer driver mutations have been characterised in protein-coding regions of the genome. However, mutations in noncoding regions associated with cancer have been less investigated. G-quadruplex (G4) nucleic acids are four-stranded secondary structures formed in guanine-rich sequences and prevalent in the regulatory regions. In this study, we used published whole cancer genome sequence data to find mutations in cancer patients that overlap potential RNA G4-forming sequences in 5ⲠUTRs. Using RNAfold, we assessed the effect of these mutations on the thermodynamic stability of predicted RNA G4s in the context of full-length 5ⲠUTRs. Of the 217 identified mutations, we found that 33 are predicted to destabilise and 21 predicted to stabilise potential RNA G4s. We experimentally validated the effect of destabilising mutations in the 5ⲠUTRs of BCL2 and CXCL14 and one stabilising mutation in the 5ⲠUTR of TAOK2. These mutations resulted in an increase or a decrease in translation of these mRNAs, respectively. These findings suggest that mutations that modulate the G4 stability in the noncoding regions could act as cancer driver mutations, which present an opportunity for early cancer diagnosis using individual sequencing information.Link_to_subscribed_fulltex

    SYMBIOSIS: Development, Implementation, and Assessment of a Model Curriculum across Biology and Mathematics at the Introductory Level

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    “It takes a lot of courage to release the familiar and seemingly secure, to embrace the new. But there is no real security in what is no longer meaningful. There is more security in the adventurous and exciting, for in movement there is life, and in change there is power.”Alan Cohen (Used by permission. All rights reserved. For more information on Alan Cohen's books and programs, see (www.alancohen.com.

    Global analysis of the mammalian RNA degradome reveals widespread miRNA-dependent and miRNA-independent endonucleolytic cleavage

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    The Ago2 component of the RNA-induced silencing complex (RISC) is an endonuclease that cleaves mRNAs that base pair with high complementarity to RISC-bound microRNAs. Many examples of such direct cleavage have been identified in plants, but not in vertebrates, despite the conservation of catalytic capacity in vertebrate Ago2. We performed parallel analysis of RNA ends (PAREs), a deep sequencing approach that identifies 5′-phosphorylated, polyadenylated RNAs, to detect potential microRNA-directed mRNA cleavages in mouse embryo and adult tissues. We found that numerous mRNAs are potentially targeted for cleavage by endogenous microRNAs, but at very low levels relative to the mRNA abundance, apart from miR-151-5p-guided cleavage of the N4BP1 mRNA. We also find numerous examples of non-miRNA-directed cleavage, including cleavage of a group of mRNAs within a CA-repeat consensus sequence. The PARE analysis also identified many examples of adenylated small non-coding RNAs, including microRNAs, tRNA processing intermediates and various other small RNAs, consistent with adenylation being part of a widespread proof-reading and/or degradation pathway for small RNAs

    Quality of Private Ground-Water Supplies in Kentucky

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    About 3.7 million people live in Kentucky, of which 1.9 million (52 percent) live in urban areas (roughly defined as any community with 2,500 or more people) and 1.8 million (48 percent) live in rural areas (University of Kentucky, 1993). Figure 1 summarizes sources of drinking water for Kentucky residents. About 70 percent of Kentuckians get their daily supply of water from surface-water sources - lakes and streams; about 25 percent get their water from ground-water wells; and about 5 percent get their water from other sources - springs, cisterns, ponds, or hauled water

    The long noncoding RNA MALAT1 promotes tumor-driven angiogenesis by up-regulating pro-angiogenic gene expression

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    Neuroblastoma is the most common solid tumor during early childhood. One of the key features of neuroblastoma is extensive tumor-driven angiogenesis due to hypoxia. However, the mechanism through which neuroblastoma cells drive angiogenesis is poorly understood. Here we show that the long noncoding RNA MALAT1 was upregulated in human neuroblastoma cell lines under hypoxic conditions. Conditioned media from neuroblastoma cells transfected with small interfering RNAs (siRNA) targeting MALAT1, compared with conditioned media from neuroblastoma cells transfected with control siRNAs, induced significantly less endothelial cell migration, invasion and vasculature formation. Microarray-based differential gene expression analysis showed that one of the genes most significantly downregulated following MALAT1 suppression in human neuroblastoma cells under hypoxic conditions was fibroblast growth factor 2 (FGF2). RT-PCR and immunoblot analyses confirmed that MALAT1 suppression reduced FGF2 expression, and Enzyme-Linked Immunosorbent Assays revealed that transfection with MALAT1 siRNAs reduced FGF2 protein secretion from neuroblastoma cells. Importantly, addition of recombinant FGF2 protein to the cell culture media reversed the effects of MALAT1 siRNA on vasculature formation. Taken together, our data suggest that up-regulation of MALAT1 expression in human neuroblastoma cells under hypoxic conditions increases FGF2 expression and promotes vasculature formation, and therefore plays an important role in tumor-driven angiogenesis

    A boron-coated CCD camera for direct detection of Ultracold Neutrons (UCN)

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    A new boron-coated CCD camera is described for direct detection of ultracold neutrons (UCN) through the capture reactions 10^{10}B (n,α\alpha0γ\gamma)7^7Li (6%) and 10^{10}B(n,α\alpha1γ\gamma)7^7Li (94%). The experiments, which extend earlier works using a boron-coated ZnS:Ag scintillator, are based on direct detections of the neutron-capture byproducts in silicon. The high position resolution, energy resolution and particle ID performance of a scientific CCD allows for observation and identification of all the byproducts α\alpha, 7^7Li and γ\gamma (electron recoils). A signal-to-noise improvement on the order of 104^4 over the indirect method has been achieved. Sub-pixel position resolution of a few microns is demonstrated. The technology can also be used to build UCN detectors with an area on the order of 1 m2^2. The combination of micrometer scale spatial resolution, few electrons ionization thresholds and large area paves the way to new research avenues including quantum physics of UCN and high-resolution neutron imaging and spectroscopy.Comment: 10 pages, 8 figure

    Quantum Theory and Time Asymmetry

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    The relation between quantum measurement and thermodynamically irreversible processes is investigated. The reduction of the state vector is fundamentally asymmetric in time and shows an observer-relatedness which may explain the double interpretation of the state vector as a representation of physical states as well as of information about them. The concept of relevance being used in all statistical theories of irreversible thermodynamics is shown to be based on the same observer-relatedness. Quantum theories of irreversible processes implicitly use an objectivized process of state vector reduction. The conditions for the reduction are discussed, and I speculate that the final (subjective) observer system might even be carried by a spacetime point.Comment: Latex version of a paper published in 1979 (with minor revisions), 18 page

    Protein-coding and non-coding gene expression analysis in differentiating human keratinocytes using a three-dimensional epidermal equivalent

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    The epidermal compartment is complex and organized into several strata composed of keratinocytes (KCs), including basal, spinous, granular, and corniWed layers. The continuous process of self-renewal and barrier formation is dependent on a homeostatic balance achieved amongst KCs involving proliferation, diVerentiation, and cell death. To determine genes responsible for initiating and maintaining a corniWed epidermis, organotypic cultures comprised entirely of stratiWed KCs creating epidermal equivalents (EE) were raised from a submerged state to an air/liquid (A/L) interface. Compared to the array proWle of submerged cultures containing KCs predominantly in a proliferative (relatively undiVerentiated) state, EEs raised to an A/L interface displayed a remarkably consistent and distinct proWle of mRNAs. Cultures lifted to an A/L interface triggered the induction of gene groups that regulate proliferation, diVerentiation, and cell death. Next, diVerentially expressed microRNAs (miRNAs) and long noncoding (lncRNA) RNAs were identiWed in EEs. Several diVerentially expressed miRNAs were validated by qRT-PCR and Northern blots. miRNAs 203, 205 and Let-7b were up-regulated at early time points (6, 18 and 24 h) but downregulated by 120 h. To study the lncRNA regulation in EEs, we proWled lncRNA expression by microarray and validated the results by qRT-PCR. Although the diVerential expression of several lncRNAs is suggestive of a role in epidermal diVerentiation, their biological functions remain to be elucidated. The current studies lay the foundation for relevant model systems to address such fundamentally important biological aspects of epidermal structure and function in normal and diseased human skin

    Prediction of Anisotropic Single-Dirac-Cones in Bi1x{}_{1-x}Sbx{}_{x} Thin Films

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    The electronic band structures of Bi1x{}_{1-x}Sbx{}_{x} thin films can be varied as a function of temperature, pressure, stoichiometry, film thickness and growth orientation. We here show how different anisotropic single-Dirac-cones can be constructed in a Bi1x{}_{1-x}Sbx{}_{x} thin film for different applications or research purposes. For predicting anisotropic single-Dirac-cones, we have developed an iterative-two-dimensional-two-band model to get a consistent inverse-effective-mass-tensor and band-gap, which can be used in a general two-dimensional system that has a non-parabolic dispersion relation as in a Bi1x{}_{1-x}Sbx{}_{x} thin film system
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