119 research outputs found
Detecting a stochastic gravitational wave background with the Laser Interferometer Space Antenna
The random superposition of many weak sources will produce a stochastic
background of gravitational waves that may dominate the response of the LISA
(Laser Interferometer Space Antenna) gravitational wave observatory. Unless
something can be done to distinguish between a stochastic background and
detector noise, the two will combine to form an effective noise floor for the
detector. Two methods have been proposed to solve this problem. The first is to
cross-correlate the output of two independent interferometers. The second is an
ingenious scheme for monitoring the instrument noise by operating LISA as a
Sagnac interferometer. Here we derive the optimal orbital alignment for
cross-correlating a pair of LISA detectors, and provide the first analytic
derivation of the Sagnac sensitivity curve.Comment: 9 pages, 11 figures. Significant changes to the noise estimate
Calibration and Characterization of the IceCube Photomultiplier Tube
Over 5,000 PMTs are being deployed at the South Pole to compose the IceCube
neutrino observatory. Many are placed deep in the ice to detect Cherenkov light
emitted by the products of high-energy neutrino interactions, and others are
frozen into tanks on the surface to detect particles from atmospheric cosmic
ray showers. IceCube is using the 10-inch diameter R7081-02 made by Hamamatsu
Photonics. This paper describes the laboratory characterization and calibration
of these PMTs before deployment. PMTs were illuminated with pulses ranging from
single photons to saturation level. Parameterizations are given for the single
photoelectron charge spectrum and the saturation behavior. Time resolution,
late pulses and afterpulses are characterized. Because the PMTs are relatively
large, the cathode sensitivity uniformity was measured. The absolute photon
detection efficiency was calibrated using Rayleigh-scattered photons from a
nitrogen laser. Measured characteristics are discussed in the context of their
relevance to IceCube event reconstruction and simulation efforts.Comment: 40 pages, 12 figure
Efficacy of a Non-Hypercalcemic Vitamin-D2 Derived Anti-Cancer Agent (MT19c) and Inhibition of Fatty Acid Synthesis in an Ovarian Cancer Xenograft Model
BACKGROUND:Numerous vitamin-D analogs exhibited poor response rates, high systemic toxicities and hypercalcemia in human trials to treat cancer. We identified the first non-hypercalcemic anti-cancer vitamin D analog MT19c by altering the A-ring of ergocalciferol. This study describes the therapeutic efficacy and mechanism of action of MT19c in both in vitro and in vivo models. METHODOLOGY/PRINCIPAL FINDING:Antitumor efficacy of MT19c was evaluated in ovarian cancer cell (SKOV-3) xenografts in nude mice and a syngenic rat ovarian cancer model. Serum calcium levels of MT19c or calcitriol treated animals were measured. In-silico molecular docking simulation and a cell based VDR reporter assay revealed MT19c-VDR interaction. Genomewide mRNA analysis of MT19c treated tumors identified drug targets which were verified by immunoblotting and microscopy. Quantification of cellular malonyl CoA was carried out by HPLC-MS. A binding study with PPAR-Y receptor was performed. MT19c reduced ovarian cancer growth in xenograft and syngeneic animal models without causing hypercalcemia or acute toxicity. MT19c is a weak vitamin-D receptor (VDR) antagonist that disrupted the interaction between VDR and coactivator SRC2-3. Genome-wide mRNA analysis and western blot and microscopy of MT19c treated xenograft tumors showed inhibition of fatty acid synthase (FASN) activity. MT19c reduced cellular levels of malonyl CoA in SKOV-3 cells and inhibited EGFR/phosphoinositol-3kinase (PI-3K) activity independently of PPAR-gamma protein. SIGNIFICANCE:Antitumor effects of non-hypercalcemic agent MT19c provide a new approach to the design of vitamin-D based anticancer molecules and a rationale for developing MT19c as a therapeutic agent for malignant ovarian tumors by targeting oncogenic de novo lipogenesis
Molecular evolution of the LNX gene family
<p>Abstract</p> <p>Background</p> <p>LNX (Ligand of Numb Protein-X) proteins typically contain an amino-terminal RING domain adjacent to either two or four PDZ domains - a domain architecture that is unique to the LNX family. LNX proteins function as E3 ubiquitin ligases and their domain organisation suggests that their ubiquitin ligase activity may be targeted to specific substrates or subcellular locations by PDZ domain-mediated interactions. Indeed, numerous interaction partners for LNX proteins have been identified, but the <it>in vivo </it>functions of most family members remain largely unclear.</p> <p>Results</p> <p>To gain insights into their function we examined the phylogenetic origins and evolution of the <it>LNX </it>gene family. We find that a <it>LNX1/LNX2</it>-like gene arose in an early metazoan lineage by gene duplication and fusion events that combined a RING domain with four PDZ domains. These PDZ domains are closely related to the four carboxy-terminal domains from multiple PDZ domain containing protein-1 (MUPP1). Duplication of the <it>LNX1/LNX2</it>-like gene and subsequent loss of PDZ domains appears to have generated a gene encoding a LNX3/LNX4-like protein, with just two PDZ domains. This protein has novel carboxy-terminal sequences that include a potential modular LNX3 homology domain. The two ancestral <it>LNX </it>genes are present in some, but not all, invertebrate lineages. They were, however, maintained in the vertebrate lineage, with further duplication events giving rise to five LNX family members in most mammals. In addition, we identify novel interactions of LNX1 and LNX2 with three known MUPP1 ligands using yeast two-hybrid asssays. This demonstrates conservation of binding specificity between LNX and MUPP1 PDZ domains.</p> <p>Conclusions</p> <p>The <it>LNX </it>gene family has an early metazoan origin with a LNX1/LNX2-like protein likely giving rise to a LNX3/LNX4-like protein through the loss of PDZ domains. The absence of LNX orthologs in some lineages indicates that LNX proteins are not essential in invertebrates. In contrast, the maintenance of both ancestral <it>LNX </it>genes in the vertebrate lineage suggests the acquisition of essential vertebrate specific functions. The revelation that the LNX PDZ domains are phylogenetically related to domains in MUPP1, and have common binding specificities, suggests that LNX and MUPP1 may have similarities in their cellular functions.</p
Measurement of acoustic attenuation in South Pole ice
Using the South Pole Acoustic Test Setup (SPATS) and a retrievable transmitter deployed in holes drilled for the IceCube experiment, we have measured the attenuation of acoustic signals by South Pole ice at depths between 190 m and 500 m. Three data sets, using different acoustic sources, have been analyzed and give consistent results. The method with the smallest systematic uncertainties yields an amplitude attenuation coefficient α = 3.20 ± 0.57 kmâ1 between 10 and 30 kHz, considerably larger than previous theoretical estimates. Expressed as an attenuation length, the analyses give a consistent result for λ ⥠1/α of âŒ300 m with 20% uncertainty. No significant depth or frequency dependence has been found
Solar Energetic Particle Spectrum on 13 December 2006 Determined by IceTop
On 13 December 2006 the IceTop air shower array at the South Pole detected a
major solar particle event. By numerically simulating the response of the
IceTop tanks, which are thick Cherenkov detectors with multiple thresholds
deployed at high altitude with no geomagnetic cut-off, we determined the
particle energy spectrum in the energy range 0.6 to 7.6 GeV. This is the first
such spectral measurement using a single instrument with a well defined viewing
direction. We compare the IceTop spectrum and its time evolution with
previously published results and outline plans for improved resolution of
future solar particle spectra.Comment: To appear in Astrophysical Journal Letters, 6 pages, 4 figure
The IceCube Data Acquisition System: Signal Capture, Digitization, and Timestamping
IceCube is a km-scale neutrino observatory under construction at the South
Pole with sensors both in the deep ice (InIce) and on the surface (IceTop). The
sensors, called Digital Optical Modules (DOMs), detect, digitize and timestamp
the signals from optical Cherenkov-radiation photons. The DOM Main Board (MB)
data acquisition subsystem is connected to the central DAQ in the IceCube
Laboratory (ICL) by a single twisted copper wire-pair and transmits packetized
data on demand. Time calibration is maintained throughout the array by regular
transmission to the DOMs of precisely timed analog signals, synchronized to a
central GPS-disciplined clock. The design goals and consequent features,
functional capabilities, and initial performance of the DOM MB, and the
operation of a combined array of DOMs as a system, are described here.
Experience with the first InIce strings and the IceTop stations indicates that
the system design and performance goals have been achieved.Comment: 42 pages, 20 figures, submitted to Nuclear Instruments and Methods
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