133 research outputs found
MEMS 411: Dressmaker Pin Dispenser
The goal of this project was to design, manufacture, and test a machine which can dispense dressmaker pins in a consistent orientation, allowing the user can easily, and safely remove them one at a time. The purpose of the machine is to increase the efficiency and safety of sewers who may use dressmaker pins daily
The Atacama Cosmology Telescope: Cosmology from Galaxy Clusters Detected via the Sunyaev-Zel'dovich Effect
We present constraints on cosmological parameters based on a sample of
Sunyaev-Zel'dovich-selected galaxy clusters detected in a millimeter-wave
survey by the Atacama Cosmology Telescope. The cluster sample used in this
analysis consists of 9 optically-confirmed high-mass clusters comprising the
high-significance end of the total cluster sample identified in 455 square
degrees of sky surveyed during 2008 at 148 GHz. We focus on the most massive
systems to reduce the degeneracy between unknown cluster astrophysics and
cosmology derived from SZ surveys. We describe the scaling relation between
cluster mass and SZ signal with a 4-parameter fit. Marginalizing over the
values of the parameters in this fit with conservative priors gives sigma_8 =
0.851 +/- 0.115 and w = -1.14 +/- 0.35 for a spatially-flat wCDM cosmological
model with WMAP 7-year priors on cosmological parameters. This gives a modest
improvement in statistical uncertainty over WMAP 7-year constraints alone.
Fixing the scaling relation between cluster mass and SZ signal to a fiducial
relation obtained from numerical simulations and calibrated by X-ray
observations, we find sigma_8 = 0.821 +/- 0.044 and w = -1.05 +/- 0.20. These
results are consistent with constraints from WMAP 7 plus baryon acoustic
oscillations plus type Ia supernoava which give sigma_8 = 0.802 +/- 0.038 and w
= -0.98 +/- 0.053. A stacking analysis of the clusters in this sample compared
to clusters simulated assuming the fiducial model also shows good agreement.
These results suggest that, given the sample of clusters used here, both the
astrophysics of massive clusters and the cosmological parameters derived from
them are broadly consistent with current models.Comment: 12 pages, 7 figures. Submitted to Ap
Fluorescent probing for RNA molecules by an unnatural base-pair system
Fluorescent labeling of nucleic acids is widely used in basic research and medical applications. We describe the efficient site-specific incorporation of a fluorescent base analog, 2-amino-6-(2-thienyl)purine (s), into RNA by transcription mediated by an unnatural base pair between s and pyrrole-2-carbaldehyde (Pa). The ribonucleoside 5′-triphosphate of s was site-specifically incorporated into RNA, by T7 RNA polymerase, opposite Pa in DNA templates. The fluorescent intensity of s in RNA molecules changes according to the structural environment. The site-specific s labeling of RNA hairpins and tRNA molecules provided characteristic fluorescent profiles, depending on the labeling sites, temperature and Mg2+ concentration. The Pa-containing DNA templates can be amplified by PCR using 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds), another pairing partner of Pa. This site-specific fluorescent probing by the unnatural pair system including the s-Pa and Ds-Pa pairs provides a powerful tool for studying the dynamics of the local structural features of 3D RNA molecules and their intra- and intermolecular interactions
Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders.
Genetic variants in chromatin regulators are frequently found in neurodevelopmental disorders, but their effect in disease etiology is rarely determined. Here, we uncover and functionally define pathogenic variants in the chromatin modifier EZH1 as the cause of dominant and recessive neurodevelopmental disorders in 19 individuals. EZH1 encodes one of the two alternative histone H3 lysine 27 methyltransferases of the PRC2 complex. Unlike the other PRC2 subunits, which are involved in cancers and developmental syndromes, the implication of EZH1 in human development and disease is largely unknown. Using cellular and biochemical studies, we demonstrate that recessive variants impair EZH1 expression causing loss of function effects, while dominant variants are missense mutations that affect evolutionarily conserved aminoacids, likely impacting EZH1 structure or function. Accordingly, we found increased methyltransferase activity leading to gain of function of two EZH1 missense variants. Furthermore, we show that EZH1 is necessary and sufficient for differentiation of neural progenitor cells in the developing chick embryo neural tube. Finally, using human pluripotent stem cell-derived neural cultures and forebrain organoids, we demonstrate that EZH1 variants perturb cortical neuron differentiation. Overall, our work reveals a critical role of EZH1 in neurogenesis regulation and provides molecular diagnosis for previously undefined neurodevelopmental disorders
Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders
Genetic variants in chromatin regulators are frequently found in neurodevelopmental disorders, but their effect in disease etiology is rarely determined. Here, we uncover and functionally define pathogenic variants in the chromatin modifier EZH1 as the cause of dominant and recessive neurodevelopmental disorders in 19 individuals. EZH1 encodes one of the two alternative histone H3 lysine 27 methyltransferases of the PRC2 complex. Unlike the other PRC2 subunits, which are involved in cancers and developmental syndromes, the implication of EZH1 in human development and disease is largely unknown. Using cellular and biochemical studies, we demonstrate that recessive variants impair EZH1 expression causing loss of function effects, while dominant variants are missense mutations that affect evolutionarily conserved aminoacids, likely impacting EZH1 structure or function. Accordingly, we found increased methyltransferase activity leading to gain of function of two EZH1 missense variants. Furthermore, we show that EZH1 is necessary and sufficient for differentiation of neural progenitor cells in the developing chick embryo neural tube. Finally, using human pluripotent stem cell-derived neural cultures and forebrain organoids, we demonstrate that EZH1 variants perturb cortical neuron differentiation. Overall, our work reveals a critical role of EZH1 in neurogenesis regulation and provides molecular diagnosis for previously undefined neurodevelopmental disorders
Bird-Like Anatomy, Posture, and Behavior Revealed by an Early Jurassic Theropod Dinosaur Resting Trace
BACKGROUND: Fossil tracks made by non-avian theropod dinosaurs commonly reflect the habitual bipedal stance retained in living birds. Only rarely-captured behaviors, such as crouching, might create impressions made by the hands. Such tracks provide valuable information concerning the often poorly understood functional morphology of the early theropod forelimb. METHODOLOGY/PRINCIPAL FINDINGS: Here we describe a well-preserved theropod trackway in a Lower Jurassic ( approximately 198 million-year-old) lacustrine beach sandstone in the Whitmore Point Member of the Moenave Formation in southwestern Utah. The trackway consists of prints of typical morphology, intermittent tail drags and, unusually, traces made by the animal resting on the substrate in a posture very similar to modern birds. The resting trace includes symmetrical pes impressions and well-defined impressions made by both hands, the tail, and the ischial callosity. CONCLUSIONS/SIGNIFICANCE: The manus impressions corroborate that early theropods, like later birds, held their palms facing medially, in contrast to manus prints previously attributed to theropods that have forward-pointing digits. Both the symmetrical resting posture and the medially-facing palms therefore evolved by the Early Jurassic, much earlier in the theropod lineage than previously recognized, and may characterize all theropods
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