Systematic approach to developing splice modulating antisense oligonucleotides

The process of pre-mRNA splicing is a common and fundamental step in the expression of most human genes. Alternative splicing, whereby different splice motifs and sites are recognised in a developmental and/or tissue-specific manner, contributes to genetic plasticity and diversity of gene expression. Redirecting pre-mRNA processing of various genes has now been validated as a viable clinical therapeutic strategy, providing treatments for Duchenne muscular dystrophy (inducing specific exon skipping) and spinal muscular atrophy (promoting exon retention). We have designed and evaluated over 5000 different antisense oligonucleotides to alter splicing of a variety of pre-mRNAs, from the longest known human pre-mRNA to shorter, exon-dense primary gene transcripts. Here, we present our guidelines for designing, evaluating and optimising splice switching antisense oligomers in vitro. These systematic approaches assess several critical factors such as the selection of target splicing motifs, choice of cells, various delivery reagents and crucial aspects of validating assays for the screening of antisense oligonucleotides composed of 2′-O-methyl modified bases on a phosphorothioate backbone

ALICE: The Ultraviolet Imaging Spectrograph aboard the New Horizons Pluto-Kuiper Belt Mission

The New Horizons ALICE instrument is a lightweight (4.4 kg), low-power (4.4 Watt) imaging spectrograph aboard the New Horizons mission to Pluto/Charon and the Kuiper Belt. Its primary job is to determine the relative abundances of various species in Pluto's atmosphere. ALICE will also be used to search for an atmosphere around Pluto's moon, Charon, as well as the Kuiper Belt Objects (KBOs) that New Horizons hopes to fly by after Pluto-Charon, and it will make UV surface reflectivity measurements of all of these bodies as well. The instrument incorporates an off-axis telescope feeding a Rowland-circle spectrograph with a 520-1870 angstroms spectral passband, a spectral point spread function of 3-6 angstroms FWHM, and an instantaneous spatial field-of-view that is 6 degrees long. Different input apertures that feed the telescope allow for both airglow and solar occultation observations during the mission. The focal plane detector is an imaging microchannel plate (MCP) double delay-line detector with dual solar-blind opaque photocathodes (KBr and CsI) and a focal surface that matches the instrument's 15-cm diameter Rowland-circle. In what follows, we describe the instrument in greater detail, including descriptions of its ground calibration and initial in flight performance.Comment: 24 pages, 29 figures, 2 tables; To appear in a special volume of Space Science Reviews on the New Horizons missio

ϵ′/ϵ\epsilon'/\epsilon And Anomalous Gauge Boson Couplings

We study $\epsilon'/\epsilon$ in the Standard Model and $\epsilon'/\epsilon$ due to anomalous $WW\gamma$ and $WWZ$ interactions %using recent result on the top quark mass from CDF. as a function of the top quark mass. In the Standard Model, $\epsilon'/\epsilon$ is in the range $10^{-3} \sim 10^{-4}$ for the central value of top quark mass reported by CDF. The anomalous gauge couplings can have large contributions to the $CP$ violating $I=2$ amplitude in $K \rightarrow \pi\pi$. Within the allowed regions for the anomalous gauge couplings, $\epsilon'/\epsilon$ can be dramatically different from the standard model prediction.Comment: 17 pages plus one figure (available from the author upon request), Revtex, OITS-541, UM-P-94/4

Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study

A41 Use of SMS texts for facilitating access to online alcohol interventions: a feasibility study In: Addiction Science & Clinical Practice 2017, 12(Suppl 1): A4

TRY plant trait database – enhanced coverage and open access

Plant traits—the morphological, anatomical, physiological, biochemical and phenological characteristics of plants—determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait‐based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits—almost complete coverage for ‘plant growth form’. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait–environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

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

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

Erratum: "A Gravitational-wave Measurement of the Hubble Constant Following the Second Observing Run of Advanced LIGO and Virgo" (2021, ApJ, 909, 218)

[no abstract available

Track A Basic Science

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/138319/1/jia218438.pd