441 research outputs found
Confronting eternity : strange (im)mortalities, and states of undying in popular fiction.
When the meritless scrabble for the bauble of deity, they ironically set their human lives at the âpinâs feeâ to which Shakespeareâs Hamlet refers. This thesis focuses on these undeserving individuals in premillennial and postmillennial fiction, who seek immortality at the expense of both their humanities, and their natural mortalities.
I will analyse an array of popular modern characters, paying particular attention to the precursors of immortal personages. I will inaugurate these analyses with an examination of fan favourite serie
Global Transcriptional Response to Hfe Deficiency and Dietary Iron Overload in Mouse Liver and Duodenum
Iron is an essential trace element whose absorption is usually tightly regulated in the duodenum. HFE-related hereditary hemochromatosis (HH) is characterized by abnormally low expression of the iron-regulatory hormone, hepcidin, which results in increased iron absorption. The liver is crucial for iron homeostasis as it is the main production site of hepcidin. The aim of this study was to explore and compare the genome-wide transcriptome response to Hfe deficiency and dietary iron overload in murine liver and duodenum. Illuminaâą arrays containing over 47,000 probes were used to study global transcriptional changes. Quantitative RT-PCR (Q-RT-PCR) was used to validate the microarray results. In the liver, the expression of 151 genes was altered in Hfeâ/â mice while dietary iron overload changed the expression of 218 genes. There were 173 and 108 differentially expressed genes in the duodenum of Hfeâ/â mice and mice with dietary iron overload, respectively. There was 93.5% concordance between the results obtained by microarray analysis and Q-RT-PCR. Overexpression of genes for acute phase reactants in the liver and a strong induction of digestive enzyme genes in the duodenum were characteristic of the Hfe-deficient genotype. In contrast, dietary iron overload caused a more pronounced change of gene expression responsive to oxidative stress. In conclusion, Hfe deficiency caused a previously unrecognized increase in gene expression of hepatic acute phase proteins and duodenal digestive enzymes
On the effect of image denoising on galaxy shape measurements
Weak gravitational lensing is a very sensitive way of measuring cosmological
parameters, including dark energy, and of testing current theories of
gravitation. In practice, this requires exquisite measurement of the shapes of
billions of galaxies over large areas of the sky, as may be obtained with the
EUCLID and WFIRST satellites. For a given survey depth, applying image
denoising to the data both improves the accuracy of the shape measurements and
increases the number density of galaxies with a measurable shape. We perform
simple tests of three different denoising techniques, using synthetic data. We
propose a new and simple denoising method, based on wavelet decomposition of
the data and a Wiener filtering of the resulting wavelet coefficients. When
applied to the GREAT08 challenge dataset, this technique allows us to improve
the quality factor of the measurement (Q; GREAT08 definition), by up to a
factor of two. We demonstrate that the typical pixel size of the EUCLID optical
channel will allow us to use image denoising.Comment: Accepted for publication in A&A. 8 pages, 5 figure
Effects of iron loading on muscle: genome-wide mRNA expression profiling in the mouse
Background
Hereditary hemochromatosis (HH) encompasses genetic disorders of iron overload characterized by deficient expression or function of the iron-regulatory hormone hepcidin. Mutations in 5 genes have been linked to this disease: HFE, TFR2 (encoding transferrin receptor 2), HAMP (encoding hepcidin), SLC40A1 (encoding ferroportin) and HJV (encoding hemojuvelin). Hepcidin inhibits iron export from cells into plasma. Hemojuvelin, an upstream regulator of hepcidin expression, is expressed in mice mainly in the heart and skeletal muscle. It has been suggested that soluble hemojuvelin shed by the muscle might reach the liver to influence hepcidin expression. Heart muscle is one of the target tissues affected by iron overload, with resultant cardiomyopathy in some HH patients. Therefore, we investigated the effect of iron overload on gene expression in skeletal muscle and heart using Illuminaâą arrays containing over 47,000 probes. The most apparent changes in gene expression were confirmed using real-time RT-PCR.
Results
Genes with up-regulated expression after iron overload in both skeletal and heart muscle included angiopoietin-like 4, pyruvate dehydrogenase kinase 4 and calgranulin A and B. The expression of transferrin receptor, heat shock protein 1B and DnaJ homolog B1 were down-regulated by iron in both muscle types. Two potential hepcidin regulatory genes, hemojuvelin and neogenin, showed no clear change in expression after iron overload.
Conclusion
Microarray analysis revealed iron-induced changes in the expression of several genes involved in the regulation of glucose and lipid metabolism, transcription and cellular stress responses. These may represent novel connections between iron overload and pathological manifestations of HH such as cardiomyopathy and diabetes.BioMed Central Open acces
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A Randomized, Controlled, Phase 2 Study of Maralixibat in the Treatment of Itching Associated With Primary Biliary Cholangitis.
Primary biliary cholangitis (PBC) is typically associated with elevated serum bile acid levels and pruritus, but pruritus is often refractory to treatment with existing therapies. This phase 2 study assessed the efficacy and safety of maralixibat, a selective, ileal, apical, sodium-dependent, bile acid transporter inhibitor, in adults with PBC and pruritus. Adults with PBC and pruritus who had received ursodeoxycholic acid (UDCA) for â„6 months or were intolerant to UDCA were randomized 2:1 to maralixibat (10 or 20 mg/day) or placebo for 13 weeks in combination with UDCA (when tolerated). The primary outcome was change in Adult Itch Reported Outcome (ItchROâą) average weekly sum score (0, no itching; 70, maximum itching) from baseline to week 13/early termination (ET). The study enrolled 66 patients (maralixibat [both doses combined], n = 42; placebo, n = 24). Mean ItchROâą weekly sum scores decreased from baseline to week 13/ET with maralixibat (-26.5; 95% confidence interval [CI], -31.8, -21.2) and placebo (-23.4; 95% CI, -30.3, -16.4). The difference between groups was not significant (P = 0.48). In the maralixibat and placebo groups, adverse events (AEs) were reported in 97.6% and 70.8% of patients, respectively. Gastrointestinal disorders were the most frequently reported AEs (maralixibat, 78.6%; placebo, 50.0%). Conclusion: Reductions in pruritus did not differ significantly between maralixibat and placebo. However, a large placebo effect may have confounded assessment of pruritus. Lessons learned from this rigorously designed and executed trial are indispensable for understanding how to approach trials assessing pruritus as the primary endpoint and the therapeutic window of bile acid uptake inhibition as a therapeutic strategy in PBC
Real time simulation using position sensing
An interactive exercise system including exercise equipment having a resistance system, a speed sensor, a controller that varies the resistance setting of the exercise equipment, and a playback device for playing pre-recorded video and audio. The controller, operating in conjunction with speed information from the speed sensor and terrain information from media table files, dynamically varies the resistance setting of the exercise equipment in order to simulate varying degrees of difficulty while the playback device concurrently plays back the video and audio to create the simulation that the user is exercising in a natural setting such as a real-world exercise course
Expression of iron-related genes in human brain and brain tumors
<p>Abstract</p> <p>Background</p> <p>Defective iron homeostasis may be involved in the development of some diseases within the central nervous system. Although the expression of genes involved in normal iron balance has been intensively studied in other tissues, little is known about their expression in the brain. We investigated the mRNA levels of hepcidin (<it>HAMP</it>), HFE, neogenin (<it>NEO1</it>), transferrin receptor 1 (<it>TFRC</it>), transferrin receptor 2 (<it>TFR2</it>), and hemojuvelin (<it>HFE2</it>) in normal human brain, brain tumors, and astrocytoma cell lines. The specimens included 5 normal brain tissue samples, 4 meningiomas, one medulloblastoma, 3 oligodendrocytic gliomas, 2 oligoastrocytic gliomas, 8 astrocytic gliomas, and 3 astrocytoma cell lines.</p> <p>Results</p> <p>Except for hemojuvelin, all genes studied had detectable levels of mRNA. In most tumor types, the pattern of gene expression was diverse. Notable findings include high expression of transferrin receptor 1 in the hippocampus and medulla oblongata compared to other brain regions, low expression of HFE in normal brain with elevated HFE expression in meningiomas, and absence of hepcidin mRNA in astrocytoma cell lines despite expression in normal brain and tumor specimens.</p> <p>Conclusion</p> <p>These results indicate that several iron-related genes are expressed in normal brain, and that their expression may be dysregulated in brain tumors.</p
Peginterferon Alfa-2a and Ribavirin for 16 or 24 Weeks in HCV Genotype 2 or 3
Background
Patients infected with hepatitis C virus (HCV) genotype 2 or 3 have sustained virologic response rates of approximately 80% after receiving treatment with peginterferon and ribavirin for 24 weeks. We conducted a large, randomized, multinational, noninferiority trial to determine whether similar efficacy could be achieved with only 16 weeks of treatment with peginterferon alfa-2a and ribavirin.
Methods
We randomly assigned 1469 patients with HCV genotype 2 or 3 to receive 180 ÎŒg of peginterferon alfa-2a weekly, plus 800 mg of ribavirin daily, for either 16 or 24 weeks. A sustained virologic response was defined as an undetectable serum HCV RNA level (milliliter) 24 weeks after the end of treatment.
Results
The study failed to demonstrate that the 16-week regimen was noninferior to the 24-week regimen. The sustained virologic response rate was significantly lower in patients treated for 16 weeks than in patients treated for 24 weeks (62% vs. 70%; odds ratio for 16 weeks vs. 24 weeks, 0.67; 95% confidence interval, 0.54 to 0.84; P
Conclusions
Treatment with peginterferon and ribavirin for 16 weeks in patients infected with HCV genotype 2 or 3 results in a lower overall sustained virologic response rate than treatment with the standard 24-week regimen. (ClinicalTrials.gov number, NCT00077636.
HST STIS spectroscopy of the triple nucleus of M31: two nested disks in Keplerian rotation around a Supermassive Black Hole
We present HST spectroscopy of the nucleus of M31 obtained with STIS. Spectra
taken around the CaT lines at 8500 see only the red giants in the double
bright- ness peaks P1 and P2. In contrast, spectra taken at 3600-5100 A are
sensitive to the tiny blue nucleus embedded in P2, the lower surface brightness
red nucleus. P2 has a K-type spectrum, but the embedded blue nucleus has an
A-type spectrum with strong Balmer absorption lines. Given the small likelihood
for stellar collisions, a 200 Myr old starburst appears to be the most
plausible origin of the blue nucleus. In stellar population, size, and velocity
dispersion, the blue nucleus is so different from P1 and P2 that we call it P3.
The line-of-sight velocity distributions of the red stars in P1+P2 strengthen
the support for Tremaine s eccentric disk model. The kinematics of P3 is
consistent with a circular stellar disk in Keplerian rotation around a
super-massive black hole with M_bh = 1.4 x 10^8 M_sun. The P3 and the P1+P2
disks rotate in the same sense and are almost coplanar. The observed velocity
dispersion of P3 is due to blurred rotation and has a maximum value of sigma =
1183+-201 km/s. The observed peak rotation velocity of P3 is V = 618+-81 km/s
at radius 0.05" = 0.19 pc corresponding to a circular rotation velocity at this
radius of ~1700 km/s. Any dark star cluster alternative to a black hole must
have a half-mass radius <= 0.03" = 0.11 pc. We show that this excludes clusters
of brown dwarfs or dead stars on astrophysical grounds.Comment: Astrophysical Journal, Sep 20, 2005, 21 pages including 20 figure
MeerKLASS: MeerKAT Large Area Synoptic Survey
We discuss the ground-breaking science that will be possible with a wide area
survey, using the MeerKAT telescope, known as MeerKLASS (MeerKAT Large Area
Synoptic Survey). The current specifications of MeerKAT make it a great fit for
science applications that require large survey speeds but not necessarily high
angular resolutions. In particular, for cosmology, a large survey over for hours will potentially provide the first
ever measurements of the baryon acoustic oscillations using the 21cm intensity
mapping technique, with enough accuracy to impose constraints on the nature of
dark energy. The combination with multi-wavelength data will give unique
additional information, such as exquisite constraints on primordial
non-Gaussianity using the multi-tracer technique, as well as a better handle on
foregrounds and systematics. Such a wide survey with MeerKAT is also a great
match for HI galaxy studies, providing unrivalled statistics in the pre-SKA era
for galaxies resolved in the HI emission line beyond local structures at z >
0.01. It will also produce a large continuum galaxy sample down to a depth of
about 5\,Jy in L-band, which is quite unique over such large areas and
will allow studies of the large-scale structure of the Universe out to high
redshifts, complementing the galaxy HI survey to form a transformational
multi-wavelength approach to study galaxy dynamics and evolution. Finally, the
same survey will supply unique information for a range of other science
applications, including a large statistical investigation of galaxy clusters as
well as produce a rotation measure map across a huge swathe of the sky. The
MeerKLASS survey will be a crucial step on the road to using SKA1-MID for
cosmological applications and other commensal surveys, as described in the top
priority SKA key science projects (abridged).Comment: Larger version of the paper submitted to the Proceedings of Science,
"MeerKAT Science: On the Pathway to the SKA", Stellenbosch, 25-27 May 201
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