406 research outputs found
Approximate Analysis of an Unreliable M/M/2 Retrial Queue
This thesis considers the performance evaluation of an M/M/2 retrial queue for which both servers are subject to active and idle breakdowns. Customers may abandon service requests if they are blocked from service upon arrival, or if their service is interrupted by a server failure. Customers choosing to remain in the system enter a retrial orbit for a random amount of time before attempting to re-access an available server. We assume that each server has its own dedicated repair person, and repairs begin immediately following a failure. Interfailure times, repair times and times between retrials are exponentially distributed, and all processes are assumed to be mutually independent. Modeling the number of customers in the orbit and status of the servers as a continuous-time Markov chain, we employ a phase-merging algorithm to approximately analyze the limiting behavior. Subsequently, we derive approximate expressions for several congestion and delay measures. Using a benchmark simulation model, we assess the accuracy of the approximations and show that, when the algorithm assumptions are met, the approximation procedure yields favorable results. However, as the rate of abandonment for blocked arrivals decreases, the performance declines while the results are insensitive to the rate of abandonment of customers preempted by a server failure
Assessing the Accuracy and Power of Population Genetic Inference from Low-Pass Next-Generation Sequencing Data
Next-generation sequencing (NGS) technologies have made it possible to address population genetic questions in almost any system, but high error rates associated with such data can introduce significant biases into downstream analyses, necessitating careful experimental design and interpretation in studies based on short-read sequencing. Exploration of population genetic analyses based on NGS has revealed some of the potential biases, but previous work has emphasized parameters relevant to human population genetics and further examination of parameters relevant to other systems is necessary, including situations where sample sizes are small and genetic variation is high. To assess experimental power to address several principal objectives of population genetic studies under these conditions, we simulated population samples under selective sweep, population growth, and population subdivision models and tested the power to accurately infer population genetic parameters from sequence polymorphism data obtained through simulated 4×, 8×, and 15× read depth sequence data. We found that estimates of population genetic differentiation and population growth parameters were systematically biased when inference was based on 4× sequencing, but biases were markedly reduced at even 8× read depth. We also found that the power to identify footprints of positive selection depends on an interaction between read depth and the strength of selection, with strong selection being recovered consistently at all read depths, but weak selection requiring deeper read depths for reliable detection. Although we have explored only a small subset of the many possible experimental designs and population genetic models, using only one SNP-calling approach, our results reveal some general patterns and provide some assessment of what biases could be expected under similar experimental structures
Upper Limits on Pulsed Radio Emission from the 6.85 s X-ray Pulsar XTE J0103-728 in the Small Magellanic Cloud
X-ray pulsations with a 6.85 s period were recently detected in the SMC and
were subsequently identified as originating from the Be/X-ray binary system XTE
J0103-728. The recent localization of the source of the X-ray emission has made
a targeted search for radio pulsations from this source possible. The detection
of pulsed radio emission from XTE J0103-728 would make it only the second
system after PSR B1259-63 that is both a Be/X-ray binary and a radio pulsar. We
observed XTE J0103-728 in Feb 2008 with the Parkes 64-m radio telescope soon
after the identification of the source of X-ray pulsations was reported in
order to search for corresponding radio pulsations. We used a continuous 6.4
hour observation with a 256 MHz bandwidth centered at 1390 MHz using the center
beam of the Parkes multibeam receiver. In the subsequent data analysis, which
included a folding search, a Fourier search, a fast-folding algorithm search,
and a single-pulse search, no pulsed signals were found for trial dispersion
measures (DMs) between 0 and 800 pc cm^-3. This DM range easily encompasses the
expected values for sources in the SMC. We place an upper limit of ~45 mJy
kpc^2 on the luminosity of periodic radio emission from XTE J0103-728 at the
epoch of our observation, and we compare this limit to a range of luminosities
measured for PSR B1259-63, the only Be/X-ray binary currently known to emit
radio pulses. We also compare our limit to the radio luminosities of neutron
stars having similarly long spin periods to XTE J0103-728. Since the radio
pulses from PSR B1259-63 are eclipsed and undetectable during the portion of
the orbit near periastron, repeated additional radio search observations of XTE
J0103-728 may be valuable if it is undergoing similar eclipsing and if such
observations are able to sample the orbital phase of this system well.Comment: 16 pages, including 1 table. Accepted for publication in Ap
The Extended Blue Continuum and Line Emission around the Central Radio Galaxy in Abell 2597
We present results from detailed imaging of the centrally dominant radio
elliptical galaxy in the cooling flow cluster Abell 2597, using data obtained
with the Wide Field and Planetary Camera 2 (WFPC2) on the Hubble Space
Telescope (HST). This object is one of the archetypal "blue-lobed" cooling flow
radio elliptical galaxies, also displaying a luminous emission-line nebula, a
compact radio source, and a significant dust lane and evidence of molecular gas
in its center. We show that the radio source is surrounded by a complex network
of emission-line filaments, some of which display a close spatial association
with the outer boundary of the radio lobes. We present a detailed analysis of
the physical properties of ionized and neutral gas associated with the radio
lobes, and show that their properties are strongly suggestive of direct
interactions between the radio plasma and ambient gas. We resolve the blue
continuum emission into a series of knots and clumps, and present evidence that
these are most likely due to regions of recent star formation. We investigate
several possible triggering mechanisms for the star formation, including direct
interactions with the radio source, filaments condensing from the cooling flow,
or the result of an interaction with a gas-rich galaxy, which may also have
been responsible for fueling the active nucleus. We propose that the properties
of the source are plausibly explained in terms of accretion of gas by the cD
during an interaction with a gas-rich galaxy, which combined with the fact that
this object is located at the center of a dense, high-pressure ICM can account
for the high rates of star formation and the strong confinement of the radio
source.Comment: Astrophysical Journal, in press, 34 pages, includes 6 PostScript
figures. Latex format, uses aaspp4.sty and epsf.sty file
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Gut inflammation provides a respiratory electron acceptor for Salmonella.
Salmonella enterica serotype Typhimurium (S. Typhimurium) causes acute gut inflammation by using its virulence factors to invade the intestinal epithelium and survive in mucosal macrophages. The inflammatory response enhances the transmission success of S. Typhimurium by promoting its outgrowth in the gut lumen through unknown mechanisms. Here we show that reactive oxygen species generated during inflammation react with endogenous, luminal sulphur compounds (thiosulphate) to form a new respiratory electron acceptor, tetrathionate. The genes conferring the ability to use tetrathionate as an electron acceptor produce a growth advantage for S. Typhimurium over the competing microbiota in the lumen of the inflamed gut. We conclude that S. Typhimurium virulence factors induce host-driven production of a new electron acceptor that allows the pathogen to use respiration to compete with fermenting gut microbes. Thus the ability to trigger intestinal inflammation is crucial for the biology of this diarrhoeal pathogen
A Bitter Taste Receptor as a Novel Molecular Target on Cancer-Associated Fibroblasts in Pancreatic Ductal Adenocarcinoma
Cancer-associated fibroblasts (CAFs) execute diverse and complex functions in cancer progression. While reprogramming the crosstalk between CAFs and cancer epithelial cells is a promising avenue to evade the adverse effects of stromal depletion, drugs are limited by their suboptimal pharmacokinetics and off-target effects. Thus, there is a need to elucidate CAF-selective cell surface markers that can improve drug delivery and efficacy. Here, functional proteomic pulldown with mass spectrometry was used to identify taste receptor type 2 member 9 (TAS2R9) as a CAF target. TAS2R9 target characterization included binding assays, immunofluorescence, flow cytometry, and database mining. Liposomes conjugated to a TAS2R9-specific peptide were generated, characterized, and compared to naked liposomes in a murine pancreatic xenograft model. Proof-of-concept drug delivery experiments demonstrate that TAS2R9-targeted liposomes bind with high specificity to TAS2R9 recombinant protein and exhibit stromal colocalization in a pancreatic cancer xenograft model. Furthermore, the delivery of a CXCR2 inhibitor by TAS2R9-targeted liposomes significantly reduced cancer cell proliferation and constrained tumor growth through the inhibition of the CXCL-CXCR2 axis. Taken together, TAS2R9 is a novel cell-surface CAF-selective target that can be leveraged to facilitate small-molecule drug delivery to CAFs, paving the way for new stromal therapies
The Chandrayaan-1 X-ray spectrometer
The Chandrayaan-1 X-ray Spectrometer (C1XS) is a
compact X-ray spectrometer for the Chandrayaan-1
lunar mission. It exploits heritage from the D-C1XS
instrument on ESA’s SMART-1 mission. C1XS is
designed to measure absolute and relative abundances
of major rock-forming elements (principally Mg, Al,
Si, Ti, Ca and Fe) over the lunar surface. The baseline
design consists of 24 nadir pointing Swept Charge Device
detectors, which provide high detection efficiency
in the 1–7 keV range, which contains the X-ray fluorescence
lines of the above elements of interest. Micromachined
collimators provide a 14 degree FWHM FOV,
equivalent to 25 km from 100 km altitude. A deployable
door protects the instrument during launch and
cruise, and also provides a 55Fe calibration X-ray source
for detector calibration. Additional refinements compared
to D-C1XS will result in a significantly improved
energy resolution. To record the incident solar X-ray
flux at the Moon, C1XS carries an X-ray Solar Monitor
(XSM). C1XS will arrive at the Moon in the run
up to the maximum of the solar cycle 24, and the expected
high incident X-ray flux coupled to a 100 km
circular polar orbit, will provide composition data
accurate to better than 10% of major elemental abundances
over the lunar surface
D'Annunzio sulla scena lirica: libretto o "Poema"?
Australia Direct Action climate change policy relies on purchasing greenhouse gas abatement from projects undertaking approved abatement activities. Management of soil organic carbon (SOC) in agricultural soils is an approved activity, based on the expectation that land use change can deliver significant changes in SOC. However, there are concerns that climate, topography and soil texture will limit changes in SOC stocks. This work analyses data from 1482 sites surveyed across the major agricultural regions of Eastern Australia to determine the relative importance of land use vs. other drivers of SOC. Variation in land use explained only 1.4% of the total variation in SOC, with aridity and soil texture the main regulators of SOC stock under different land uses. Results suggest the greatest potential for increasing SOC stocks in Eastern Australian agricultural regions lies in converting from cropping to pasture on heavy textured soils in the humid regions
Using comparative genomics to reorder the human genome sequence into a virtual sheep genome
Using BAC-end sequences, a sparse marker map and the sequences of the human, dog and cow genomes, an accurate and detailed sub-gene level map of the sheep genome has been constructed
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Pan-viral serology implicates enteroviruses in acute flaccid myelitis.
Since 2012, the United States of America has experienced a biennial spike in pediatric acute flaccid myelitis (AFM)1-6. Epidemiologic evidence suggests non-polio enteroviruses (EVs) are a potential etiology, yet EV RNA is rarely detected in cerebrospinal fluid (CSF)2. CSF from children with AFM (n = 42) and other pediatric neurologic disease controls (n = 58) were investigated for intrathecal antiviral antibodies, using a phage display library expressing 481,966 overlapping peptides derived from all known vertebrate and arboviruses (VirScan). Metagenomic next-generation sequencing (mNGS) of AFM CSF RNA (n = 20 cases) was also performed, both unbiased sequencing and with targeted enrichment for EVs. Using VirScan, the viral family significantly enriched by the CSF of AFM cases relative to controls was Picornaviridae, with the most enriched Picornaviridae peptides belonging to the genus Enterovirus (n = 29/42 cases versus 4/58 controls). EV VP1 ELISA confirmed this finding (n = 22/26 cases versus 7/50 controls). mNGS did not detect additional EV RNA. Despite rare detection of EV RNA, pan-viral serology frequently identified high levels of CSF EV-specific antibodies in AFM compared with controls, providing further evidence for a causal role of non-polio EVs in AFM
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