263 research outputs found
Recommended from our members
Asymmetric crowders and membrane morphology at the nexus of intracellular trafficking and oncology.
A definitive understanding of the interplay between protein binding/migration and membrane curvature evolution is emerging but needs further study. The mechanisms defining such phenomena are critical to intracellular transport and trafficking of proteins. Among trafficking modalities, exosomes have drawn attention in cancer research as these nano-sized naturally occurring vehicles are implicated in intercellular communication in the tumor microenvironment, suppressing anti-tumor immunity and preparing the metastatic niche for progression. A significant question in the field is how the release and composition of tumor exosomes are regulated. In this perspective article, we explore how physical factors such as geometry and tissue mechanics regulate cell cortical tension to influence exosome production by co-opting the biophysics as well as the signaling dynamics of intracellular trafficking pathways and how these exosomes contribute to the suppression of anti-tumor immunity and promote metastasis. We describe a multiscale modeling approach whose impact goes beyond the fundamental investigation of specific cellular processes toward actual clinical translation. Exosomal mechanisms are critical to developing and approving liquid biopsy technologies, poised to transform future non-invasive, longitudinal profiling of evolving tumors and resistance to cancer therapies to bring us one step closer to the promise of personalized medicine
Evryscope Science: Exploring the Potential of All-Sky Gigapixel-Scale Telescopes
Low-cost mass-produced sensors and optics have recently made it feasible to build telescope arrays which observe the entire accessible sky simultaneously. In this article, we discuss the scientific motivation for these telescopes, including exoplanets, stellar variability, and extragalactic transients. To provide a concrete example we detail the goals and expectations for the Evryscope, an under-construction 780 MPix telescope which covers 8660 sq. deg. in each 2-minute exposure; each night, 18,400 sq. deg. will be continuously observed for an average of ≈6 hr. Despite its small 61 mm aperture, the system's large field of view provides an étendue which is ∼10% of LSST. The Evryscope, which places 27 separate individual telescopes into a common mount which tracks the entire accessible sky with only one moving part, will return 1%-precision, many-year-length, high-cadence light curves for every accessible star brighter than ∼16th magnitude. The camera readout times are short enough to provide near-continuous observing, with a 97% survey time efficiency. The array telescope will be capable of detecting transiting exoplanets around every solar-type star brighter than mV = 12, providing at least few-millimagnitude photometric precision in long-term light curves. It will be capable of searching for transiting giant planets around the brightest and most nearby stars, where the planets are much easier to characterize; it will also search for small planets nearby M-dwarfs, for planetary occultations of white dwarfs, and will perform comprehensive nearby microlensing and eclipse-timing searches for exoplanets inaccessible to other planet-finding methods. The Evryscope will also provide comprehensive monitoring of outbursting young stars, white dwarf activity, and stellar activity of all types, along with finding a large sample of very-long-period M-dwarf eclipsing binaries. When relatively rare transients events occur, such as gamma-ray bursts (GRBs), nearby supernovae, or even gravitational wave detections from the Advanced LIGO/Virgo network, the array will return minute-by-minute light curves without needing pointing toward the event as it occurs. By coadding images, the system will reach V ∼ 19 in 1-hr integrations, enabling the monitoring of faint objects. Finally, by recording all data, the Evryscope will be able to provide pre-event imaging at 2-minute cadence for bright transients and variable objects, enabling the first high-cadence searches for optical variability before, during and after all-sky events
The Hydrogen Epoch of Reionization Array Dish I: Beam Pattern Measurements and Science Implications
The Hydrogen Epoch of Reionization Array (HERA) is a radio interferometer
aiming to detect the power spectrum of 21 cm fluctuations from neutral hydrogen
from the Epoch of Reionization (EOR). Drawing on lessons from the Murchison
Widefield Array (MWA) and the Precision Array for Probing the Epoch of
Reionization (PAPER), HERA is a hexagonal array of large (14 m diameter) dishes
with suspended dipole feeds. Not only does the dish determine overall
sensitivity, it affects the observed frequency structure of foregrounds in the
interferometer. This is the first of a series of four papers characterizing the
frequency and angular response of the dish with simulations and measurements.
We focus in this paper on the angular response (i.e., power pattern), which
sets the relative weighting between sky regions of high and low delay, and
thus, apparent source frequency structure. We measure the angular response at
137 MHz using the ORBCOMM beam mapping system of Neben et al. We measure a
collecting area of 93 m^2 in the optimal dish/feed configuration, implying
HERA-320 should detect the EOR power spectrum at z~9 with a signal-to-noise
ratio of 12.7 using a foreground avoidance approach with a single season of
observations, and 74.3 using a foreground subtraction approach. Lastly we study
the impact of these beam measurements on the distribution of foregrounds in
Fourier space.Comment: 13 pages, 9 figures. Replaced to match accepted ApJ versio
Very Low Mass Stellar and Substellar Companions to Solar-Like Stars From MARVELS V: A Low Eccentricity Brown Dwarf from the Driest Part of the Desert, MARVELS-6b
We describe the discovery of a likely brown dwarf (BD) companion with a
minimum mass of 31.7 +/- 2.0 M_Jup to GSC 03546-01452 from the MARVELS radial
velocity survey, which we designate as MARVELS-6b. For reasonable priors, our
analysis gives a probability of 72% that MARVELS-6b has a mass below the
hydrogen-burning limit of 0.072 M_Sun, and thus it is a high-confidence BD
companion. It has a moderately long orbital period of 47.8929 +0.0063/-0.0062
days with a low eccentricty of 0.1442 +0.0078/-0.0073, and a semi-amplitude of
1644 +12/-13 m/s. Moderate resolution spectroscopy of the host star has
determined the following parameters: T_eff = 5598 +/- 63, log g = 4.44 +/-
0.17, and [Fe/H] = +0.40 +/- 0.09. Based upon these measurements, GSC
03546-01452 has a probable mass and radius of M_star = 1.11 +/- 0.11 M_Sun and
R_star = 1.06 +/- 0.23 R_Sun with an age consistent with less than ~6 Gyr at a
distance of 219 +/- 21 pc from the Sun. Although MARVELS-6b is not observed to
transit, we cannot definitively rule out a transiting configuration based on
our observations. There is a visual companion detected with Lucky Imaging at
7.7 arcsec from the host star, but our analysis shows that it is not bound to
this system. The minimum mass of MARVELS-6b exists at the minimum of the mass
functions for both stars and planets, making this a rare object even compared
to other BDs.Comment: 15 pages, 15 figures, 5 tables. Accepted for publication in The
Astronomical Journa
1965: Abilene Christian College Bible Lectures - Full Text
LIFT UP YOUR EYES”
Being the Abilene Christian College Annual Bible Lectures 1965
Price: $3.95
Published by
ABILENE CHRISTIAN COLLEGE STUDENTS EXCHANGE
ACC Station Abilene. Texa
InterPro, progress and status in 2005
InterPro, an integrated documentation resource of protein families, domains and functional sites, was created to integrate the major protein signature databases. Currently, it includes PROSITE, Pfam, PRINTS, ProDom, SMART, TIGRFAMs, PIRSF and SUPERFAMILY. Signatures are manually integrated into InterPro entries that are curated to provide biological and functional information. Annotation is provided in an abstract, Gene Ontology mapping and links to specialized databases. New features of InterPro include extended protein match views, taxonomic range information and protein 3D structure data. One of the new match views is the InterPro Domain Architecture view, which shows the domain composition of protein matches. Two new entry types were introduced to better describe InterPro entries: these are active site and binding site. PIRSF and the structure-based SUPERFAMILY are the latest member databases to join InterPro, and CATH and PANTHER are soon to be integrated. InterPro release 8.0 contains 11 007 entries, representing 2573 domains, 8166 families, 201 repeats, 26 active sites, 21 binding sites and 20 post-translational modification sites. InterPro covers over 78% of all proteins in the Swiss-Prot and TrEMBL components of UniProt. The database is available for text- and sequence-based searches via a webserver (http://www.ebi.ac.uk/interpro), and for download by anonymous FTP (ftp://ftp.ebi.ac.uk/pub/databases/interpro)
Pan-cancer Alterations of the MYC Oncogene and Its Proximal Network across the Cancer Genome Atlas
Although theMYConcogene has been implicated incancer, a systematic assessment of alterations ofMYC, related transcription factors, and co-regulatoryproteins, forming the proximal MYC network (PMN),across human cancers is lacking. Using computa-tional approaches, we define genomic and proteo-mic features associated with MYC and the PMNacross the 33 cancers of The Cancer Genome Atlas.Pan-cancer, 28% of all samples had at least one ofthe MYC paralogs amplified. In contrast, the MYCantagonists MGA and MNT were the most frequentlymutated or deleted members, proposing a roleas tumor suppressors.MYCalterations were mutu-ally exclusive withPIK3CA,PTEN,APC,orBRAFalterations, suggesting that MYC is a distinct onco-genic driver. Expression analysis revealed MYC-associated pathways in tumor subtypes, such asimmune response and growth factor signaling; chro-matin, translation, and DNA replication/repair wereconserved pan-cancer. This analysis reveals insightsinto MYC biology and is a reference for biomarkersand therapeutics for cancers with alterations ofMYC or the PMN
Genomic, Pathway Network, and Immunologic Features Distinguishing Squamous Carcinomas
This integrated, multiplatform PanCancer Atlas study co-mapped and identified distinguishing
molecular features of squamous cell carcinomas (SCCs) from five sites associated with smokin
Pan-Cancer Analysis of lncRNA Regulation Supports Their Targeting of Cancer Genes in Each Tumor Context
Long noncoding RNAs (lncRNAs) are commonly dys-regulated in tumors, but only a handful are known toplay pathophysiological roles in cancer. We inferredlncRNAs that dysregulate cancer pathways, onco-genes, and tumor suppressors (cancer genes) bymodeling their effects on the activity of transcriptionfactors, RNA-binding proteins, and microRNAs in5,185 TCGA tumors and 1,019 ENCODE assays.Our predictions included hundreds of candidateonco- and tumor-suppressor lncRNAs (cancerlncRNAs) whose somatic alterations account for thedysregulation of dozens of cancer genes and path-ways in each of 14 tumor contexts. To demonstrateproof of concept, we showed that perturbations tar-geting OIP5-AS1 (an inferred tumor suppressor) andTUG1 and WT1-AS (inferred onco-lncRNAs) dysre-gulated cancer genes and altered proliferation ofbreast and gynecologic cancer cells. Our analysis in-dicates that, although most lncRNAs are dysregu-lated in a tumor-specific manner, some, includingOIP5-AS1, TUG1, NEAT1, MEG3, and TSIX, synergis-tically dysregulate cancer pathways in multiple tumorcontexts
- …