76 research outputs found
Electric Field Conjugation with the Project 1640 coronagraph
The Project 1640 instrument on the 200-inch Hale telescope at Palomar
Observatory is a coronagraphic instrument with an integral field spectrograph
at the back end, designed to find young, self-luminous planets around nearby
stars. To reach the necessary contrast for this, the PALM-3000 adaptive optics
system corrects for fast atmospheric speckles, while CAL, a phase-shifting
interferometer in a Mach-Zehnder configuration, measures the quasistatic
components of the complex electric field in the pupil plane following the
coronagraphic stop. Two additional sensors measure and control low-order modes.
These field measurements may then be combined with a system model and data
taken separately using a white-light source internal to the AO system to
correct for both phase and amplitude aberrations. Here, we discuss and
demonstrate the procedure to maintain a half-plane dark hole in the image plane
while the spectrograph is taking data, including initial on-sky performance.Comment: 9 pages, 7 figures, in Proceedings of SPIE, 8864-19 (2013
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Integrative functional genomics identifies RINT1 as a novel GBM oncogene
Large-scale cancer genomics efforts are identifying hundreds of somatic genomic alterations in glioblastoma (GBM). Distinguishing between active driver and neutral passenger alterations requires functional assessment of each gene; therefore, integrating biological weight of evidence with statistical significance for each genomic alteration will enable better prioritization for downstream studies. Here, we demonstrate the feasibility and potential of in vitro functional genomic screens to rapidly and systematically prioritize high-probability candidate genes for in vivo validation. Integration of low-complexity gain- and loss-of-function screens designed on the basis of genomic data identified 6 candidate GBM oncogenes, and RINT1 was validated as a novel GBM oncogene based on its ability to confer tumorigenicity to primary nontransformed murine astrocytes in vivo. Cancer genomics-guided low-complexity genomic screens can quickly provide a functional filter to prioritize high-value targets for further downstream mechanistic and translational studies
Spectral Typing of Late Type Stellar Companions to Young Stars from Low Dispersion Near-Infrared Integral Field Unit Data
We used the Project 1640 near-infrared coronagraph and integral field
spectrograph to observe 19 young solar type stars. Five of these stars are
known binary stars and we detected the late-type secondaries and were able to
measure their JH spectra with a resolution of R\sim30. The reduced, extracted,
and calibrated spectra were compared to template spectra from the IRTF spectral
library. With this comparison we test the accuracy and consistency of spectral
type determination with the low-resolution near-infrared spectra from P1640.
Additionally, we determine effective temperature and surface gravity of the
companions by fitting synthetic spectra calculated with the PHOENIX model
atmosphere code. We also present several new epochs of astrometry of each of
the systems. Together these data increase our knowledge and understanding of
the stellar make up of these systems. In addition to the astronomical results,
the analysis presented helps validate the Project 1640 data reduction and
spectral extraction processes and the utility of low-resolution, near-infrared
spectra for characterizing late-type companions in multiple systems.Comment: Accepted to Astronomical Journal, 25 pages, 8 figure
Somatic Mutations of PIK3R1 Promote Gliomagenesis
The phosphoinositide 3-kinase (PI3K) pathway is targeted for frequent alteration in glioblastoma (GBM) and is one of the core GBM pathways defined by The Cancer Genome Atlas. Somatic mutations of PIK3R1 are observed in multiple tumor types, but the tumorigenic activity of these mutations has not been demonstrated in GBM. We show here that somatic mutations in the iSH2 domain of PIK3R1 act as oncogenic driver events. Specifically, introduction of a subset of the mutations identified in human GBM, in the nSH2 and iSH2 domains, increases signaling through the PI3K pathway and promotes tumorigenesis of primary normal human astrocytes in an orthotopic xenograft model. Furthermore, we show that cells that are dependent on mutant P85α-mediated PI3K signaling exhibit increased sensitivity to a small molecule inhibitor of AKT. Together, these results suggest that GBM patients whose tumors carry mutant PIK3R1 alleles may benefit from treatment with inhibitors of AKT
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Genomic sequencing of meningiomas identifies oncogenic SMO and AKT1 mutations
Meningiomas are the most common primary nervous system tumor. The tumor suppressor NF2 is disrupted in approximately half of meningiomas1 but the complete spectrum of genetic changes remains undefined. We performed whole-genome or whole-exome sequencing on 17 meningiomas and focused sequencing on an additional 48 tumors to identify and validate somatic genetic alterations. Most meningiomas exhibited simple genomes, with fewer mutations, rearrangements, and copy-number alterations than reported in other adult tumors. However, several meningiomas harbored more complex patterns of copy-number changes and rearrangements including one tumor with chromothripsis. We confirmed focal NF2 inactivation in 43% of tumors and found alterations in epigenetic modifiers among an additional 8% of tumors. A subset of meningiomas lacking NF2 alterations harbored recurrent oncogenic mutations in AKT1 (E17K) and SMO (W535L) and exhibited immunohistochemical evidence of activation of their pathways. These mutations were present in therapeutically challenging tumors of the skull base and higher grade. These results begin to define the spectrum of genetic alterations in meningiomas and identify potential therapeutic targets
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Exome sequencing identifies BRAF mutations in papillary craniopharyngiomas
PLEKHA7 Is an Adherens Junction Protein with a Tissue Distribution and Subcellular Localization Distinct from ZO-1 and E-Cadherin
The pleckstrin-homology-domain-containing protein PLEKHA7 was recently identified as a protein linking the E-cadherin-p120 ctn complex to the microtubule cytoskeleton. Here we characterize the expression, tissue distribution and subcellular localization of PLEKHA7 by immunoblotting, immunofluorescence microscopy, immunoelectron microscopy, and northern blotting in mammalian tissues. Anti-PLEKHA7 antibodies label the junctional regions of cultured kidney epithelial cells by immunofluorescence microscopy, and major polypeptides of Mr âŒ135 kDa and âŒ145 kDa by immunoblotting of lysates of cells and tissues. Two PLEKHA7 transcripts (âŒ5.5 kb and âŒ6.5 kb) are detected in epithelial tissues. PLEKHA7 is detected at epithelial junctions in sections of kidney, liver, pancreas, intestine, retina, and cornea, and its tissue distribution and subcellular localization are distinct from ZO-1. For example, PLEKHA7 is not detected within kidney glomeruli. Similarly to E-cadherin, p120 ctn, ÎČ-catenin and α-catenin, PLEKHA7 is concentrated in the apical junctional belt, but unlike these adherens junction markers, and similarly to afadin, PLEKHA7 is not localized along the lateral region of polarized epithelial cells. Immunoelectron microscopy definitively establishes that PLEKHA7 is localized at the adherens junctions in colonic epithelial cells, at a mean distance of 28 nm from the plasma membrane. In summary, we show that PLEKHA7 is a cytoplasmic component of the epithelial adherens junction belt, with a subcellular localization and tissue distribution that is distinct from that of ZO-1 and most AJ proteins, and we provide the first description of its distribution and localization in several tissues
Civil society leadership in the struggle for AIDS treatment in South Africa and Uganda
Includes abstract.Includes bibliographical references.This thesis is an attempt to theorise and operationalise empirically the notion of âcivil society leadershipâ in Sub-Saharan Africa. âAIDS leadership,â which is associated with the intergovernmental institutions charged with coordinating the global response to HIV/AIDS, is both under-theorised and highly context-specific. In this study I therefore opt for an inclusive framework that draws on a range of approaches, including the literature on âleadershipâ, institutions, social movements and the ânetworkâ perspective on civil society mobilisation. This framework is employed in rich and detailed empirical descriptions (âthick descriptionâ) of civil society mobilisation around AIDS, including contentious AIDS activism, in the key case studies of South Africa and Uganda. South Africa and Uganda are widely considered key examples of poor and good leadership (from national political leaders) respectively, while the Treatment Action Campaign (TAC) and The AIDS Support Organisation (TASO) are both seen as highly effective civil society movements. These descriptions emphasise âtransnational networks of influenceâ in which civil society leaders participated (and at times actively constructed) in order to mobilise both symbolic and material resources aimed at exerting influence at the transnational, national and local levels
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