2,291 research outputs found
Craniopharyngioma
Craniopharyngiomas are rare malformational tumours of low histological malignancy arising along the craniopharyngeal duct. The two histological subtypes, adamantinomatous craniopharyngioma (ACP) and papillary craniopharyngioma (PCP), differ in genesis and age distribution. ACPs are diagnosed with a bimodal peak of incidence (5-15 years and 45-60 years), whereas PCPs are restricted to adults mainly in the fifth and sixth decades of life. ACPs are driven by somatic mutations in CTNNB1 (encoding ÎČ-catenin) that affect ÎČ-catenin stability and are predominantly cystic in appearance. PCPs frequently harbour somatic BRAFV600E mutations and are typically solid tumours. Clinical manifestations due to increased intracranial pressure, visual impairment and endocrine deficiencies should prompt imaging investigations, preferentially MRI. Treatment comprises neurosurgery and radiotherapy; intracystic chemotherapy is used in monocystic ACP. Although long-term survival is high, quality of life and neuropsychological function are frequently impaired due to the close anatomical proximity to the optic chiasm, hypothalamus and pituitary gland. Indeed, hypothalamic involvement and treatment-related hypothalamic lesions frequently result in hypothalamic obesity, physical fatigue and psychosocial deficits. Given the rarity of these tumours, efforts to optimize infrastructure and international collaboration should be research priorities
Learning from cases: Analysis of two cases of craniopharyngioma from the 19th to the 21st centuries. [version 1; peer review: 2 approved]
This manuscript describes the study of two cases of craniopharyngioma, which have been examined repeatedly over three separate centuries. This includes analysis by Josef Engel in 1839, who sought to uncover the physiological role of the pituitary gland; Jacob Erdheim in 1904, who initially described the disease we now call craniopharyngioma, and recent high resolution MRI and micro-CT imaging and attempted DNA analyses of the tumours. The cases highlight how, rightly or wrongly, our interpretation of data is shaped by the technologies, methodologies and prevailing theories of a given time
mTOR regulates MAPKAPK2 translation to control the senescence-associated secretory phenotype
Senescent cells secrete a combination of factors collectively known as the senescence-associated secretory phenotype (SASP). The SASP reinforces senescence and activates an immune surveillance response, but it can also show pro-tumorigenic properties and contribute to age-related pathologies. In a drug screen to find new SASP regulators, we uncovered the mTOR inhibitor rapamycin as a potent SASP suppressor. Here we report a mechanism by which mTOR controls the SASP by differentially regulating the translation of the MK2 (also known as MAPKAPK2) kinase through 4EBP1. In turn, MAPKAPK2 phosphorylates the RNA-binding protein ZFP36L1 during senescence, inhibiting its ability to degrade the transcripts of numerous SASP components. Consequently, mTOR inhibition or constitutive activation of ZFP36L1 impairs the non-cell-autonomous effects of senescent cells in both tumour-suppressive and tumour-promoting contexts. Altogether, our results place regulation of the SASP as a key mechanism by which mTOR could influence cancer, age-related diseases and immune responses
The major upgrade of the MAGIC telescopes, Part II: A performance study using observations of the Crab Nebula
MAGIC is a system of two Imaging Atmospheric Cherenkov Telescopes located in
the Canary island of La Palma, Spain. During summer 2011 and 2012 it underwent
a series of upgrades, involving the exchange of the MAGIC-I camera and its
trigger system, as well as the upgrade of the readout system of both
telescopes. We use observations of the Crab Nebula taken at low and medium
zenith angles to assess the key performance parameters of the MAGIC stereo
system. For low zenith angle observations, the standard trigger threshold of
the MAGIC telescopes is ~50GeV. The integral sensitivity for point-like sources
with Crab Nebula-like spectrum above 220GeV is (0.66+/-0.03)% of Crab Nebula
flux in 50 h of observations. The angular resolution, defined as the sigma of a
2-dimensional Gaussian distribution, at those energies is < 0.07 degree, while
the energy resolution is 16%. We also re-evaluate the effect of the systematic
uncertainty on the data taken with the MAGIC telescopes after the upgrade. We
estimate that the systematic uncertainties can be divided in the following
components: < 15% in energy scale, 11-18% in flux normalization and +/-0.15 for
the energy spectrum power-law slope.Comment: 21 pages, 25 figures, accepted for publication in Astroparticle
Physic
Multi-Wavelength Observations of the Blazar 1ES 1011+496 in Spring 2008
The BL Lac object 1ES 1011+496 was discovered at Very High Energy gamma-rays
by MAGIC in spring 2007. Before that the source was little studied in different
wavelengths. Therefore a multi-wavelength (MWL) campaign was organized in
spring 2008. Along MAGIC, the MWL campaign included the Metsahovi radio
observatory, Bell and KVA optical telescopes and the Swift and AGILE
satellites. MAGIC observations span from March to May, 2008 for a total of 27.9
hours, of which 19.4 hours remained after quality cuts. The light curve showed
no significant variability. The differential VHE spectrum could be described
with a power-law function. Both results were similar to those obtained during
the discovery. Swift XRT observations revealed an X-ray flare, characterized by
a harder when brighter trend, as is typical for high synchrotron peak BL Lac
objects (HBL). Strong optical variability was found during the campaign, but no
conclusion on the connection between the optical and VHE gamma-ray bands could
be drawn. The contemporaneous SED shows a synchrotron dominated source, unlike
concluded in previous work based on nonsimultaneous data, and is well described
by a standard one zone synchrotron self Compton model. We also performed a
study on the source classification. While the optical and X-ray data taken
during our campaign show typical characteristics of an HBL, we suggest, based
on archival data, that 1ES 1011+496 is actually a borderline case between
intermediate and high synchrotron peak frequency BL Lac objects.Comment: 13 pages, accepted for publication in MNRA
Probing the very-high-energy gamma-ray spectral curvature in the blazar PG 1553+113 with the MAGIC telescopes
PG 1553+113 is a very-high-energy (VHE, ) -ray
emitter classified as a BL Lac object. Its redshift is constrained by
intergalactic absorption lines in the range . The MAGIC telescopes
have monitored the source's activity since 2005. In early 2012, PG 1553+113 was
found in a high-state, and later, in April of the same year, the source reached
its highest VHE flux state detected so far. Simultaneous observations carried
out in X-rays during 2012 April show similar flaring behaviour. In contrast,
the -ray flux at observed by Fermi-LAT is
compatible with steady emission. In this paper, a detailed study of the flaring
state is presented. The VHE spectrum shows clear curvature, being well fitted
either by a power law with an exponential cut-off or by a log-parabola. A
simple power-law fit hypothesis for the observed shape of the PG 1553+113 VHE
-ray spectrum is rejected with a high significance (fit probability
P=2.6 ). The observed curvature is compatible with the
extragalactic background light (EBL) imprint predicted by current generation
EBL models assuming a redshift . New constraints on the redshift are
derived from the VHE spectrum. These constraints are compatible with previous
limits and suggest that the source is most likely located around the optical
lower limit, , based on the detection of Ly absorption. Finally,
we find that the synchrotron self-Compton (SSC) model gives a satisfactory
description of the observed multi-wavelength spectral energy distribution
during the flare.Comment: 13 pages, 7 figures, accepted for publication in MNRA
Observation of Pulsed Gamma-rays Above 25 GeV from the Crab Pulsar with MAGIC
One fundamental question about pulsars concerns the mechanism of their pulsed
electromagnetic emission. Measuring the high-end region of a pulsar's spectrum
would shed light on this question. By developing a new electronic trigger, we
lowered the threshold of the Major Atmospheric gamma-ray Imaging Cherenkov
(MAGIC) telescope to 25 GeV. In this configuration, we detected pulsed
gamma-rays from the Crab pulsar that were greater than 25 GeV, revealing a
relatively high cutoff energy in the phase-averaged spectrum. This indicates
that the emission occurs far out in the magnetosphere, hence excluding the
polar-cap scenario as a possible explanation of our measurement. The high
cutoff energy also challenges the slot-gap scenario.Comment: Slight modification of the analysis: Fitting a more general function
to the combined data set of COMPTEL, EGRET and MAGIC. Final result and
conclusion is unchange
Multiplicity dependence of jet-like two-particle correlations in p-Pb collisions at = 5.02 TeV
Two-particle angular correlations between unidentified charged trigger and
associated particles are measured by the ALICE detector in p-Pb collisions at a
nucleon-nucleon centre-of-mass energy of 5.02 TeV. The transverse-momentum
range 0.7 5.0 GeV/ is examined,
to include correlations induced by jets originating from low
momen\-tum-transfer scatterings (minijets). The correlations expressed as
associated yield per trigger particle are obtained in the pseudorapidity range
. The near-side long-range pseudorapidity correlations observed in
high-multiplicity p-Pb collisions are subtracted from both near-side
short-range and away-side correlations in order to remove the non-jet-like
components. The yields in the jet-like peaks are found to be invariant with
event multiplicity with the exception of events with low multiplicity. This
invariance is consistent with the particles being produced via the incoherent
fragmentation of multiple parton--parton scatterings, while the yield related
to the previously observed ridge structures is not jet-related. The number of
uncorrelated sources of particle production is found to increase linearly with
multiplicity, suggesting no saturation of the number of multi-parton
interactions even in the highest multiplicity p-Pb collisions. Further, the
number scales in the intermediate multiplicity region with the number of binary
nucleon-nucleon collisions estimated with a Glauber Monte-Carlo simulation.Comment: 23 pages, 6 captioned figures, 1 table, authors from page 17,
published version, figures at
http://aliceinfo.cern.ch/ArtSubmission/node/161
Multi-particle azimuthal correlations in p-Pb and Pb-Pb collisions at the CERN Large Hadron Collider
Measurements of multi-particle azimuthal correlations (cumulants) for charged
particles in p-Pb and Pb-Pb collisions are presented. They help address the
question of whether there is evidence for global, flow-like, azimuthal
correlations in the p-Pb system. Comparisons are made to measurements from the
larger Pb-Pb system, where such evidence is established. In particular, the
second harmonic two-particle cumulants are found to decrease with multiplicity,
characteristic of a dominance of few-particle correlations in p-Pb collisions.
However, when a gap is placed to suppress such correlations,
the two-particle cumulants begin to rise at high-multiplicity, indicating the
presence of global azimuthal correlations. The Pb-Pb values are higher than the
p-Pb values at similar multiplicities. In both systems, the second harmonic
four-particle cumulants exhibit a transition from positive to negative values
when the multiplicity increases. The negative values allow for a measurement of
to be made, which is found to be higher in Pb-Pb collisions at
similar multiplicities. The second harmonic six-particle cumulants are also
found to be higher in Pb-Pb collisions. In Pb-Pb collisions, we generally find
which is indicative of a Bessel-Gaussian
function for the distribution. For very high-multiplicity Pb-Pb
collisions, we observe that the four- and six-particle cumulants become
consistent with 0. Finally, third harmonic two-particle cumulants in p-Pb and
Pb-Pb are measured. These are found to be similar for overlapping
multiplicities, when a gap is placed.Comment: 25 pages, 11 captioned figures, 3 tables, authors from page 20,
published version, figures at http://aliceinfo.cern.ch/ArtSubmission/node/87
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