143 research outputs found
Non-linear effects and Joule heating in I-V curves in manganites
We study the influence of the Joule effect on the non-linear behavior of the
transport I-V curves in polycrystalline samples of the manganite Pr0.8Ca0.2MnO3
by using the crystalline unit cell parameters as an internal thermometer in
X-ray and neutron diffraction. We develop a simple analytical model to estimate
the temperature profile in the samples. Under the actual experimental
conditions we show that the internal temperature gradient or the difference
between the temperature of the sample and that of the thermal bath are at the
origin of the non-linearity observed in the I-V curves. Consequences on other
compounds with colossal magnetoresistance are also discussed.Comment: accepted in Journal of Applied Physic
Diagnostic challenges in a child with early onset desmoplastic medulloblastoma and homozygous variants in MSH2 and MSH6
International audienceConstitutional mismatch repair deficiency (CMMRD) is an autosomal recessively inherited childhood cancer susceptibility syndrome caused by biallelic germline mutations in one of the mismatch repair (MMR
Nerve Injury Evoked Loss of Latexin Expression in Spinal Cord Neurons Contributes to the Development of Neuropathic Pain
Nerve injury leads to sensitization mechanisms in the peripheral and central
nervous system which involve transcriptional and post-transcriptional
modifications in sensory nerves. To assess protein regulations in the spinal
cord after injury of the sciatic nerve in the Spared Nerve Injury model (SNI) we
performed a proteomic analysis using 2D-difference gel electrophoresis (DIGE)
technology. Among approximately 2300 protein spots separated on each gel we
detected 55 significantly regulated proteins after SNI whereof 41 were
successfully identified by MALDI-TOF MS. Out of the proteins which were
regulated in the DIGE analyses after SNI we focused on the carboxypeptidase A
inhibitor latexin because protease dysfunctions contribute to the development of
neuropathic pain. Latexin protein expression was reduced after SNI which could
be confirmed by Western Blot analysis, quantitative RT-PCR and in-situ
hybridisation. The decrease of latexin was associated with an increase of the
activity of carboxypeptidase A indicating that the balance between latexin and
carboxypeptidase A was impaired in the spinal cord after peripheral nerve injury
due to a loss of latexin expression in spinal cord neurons. This may contribute
to the development of cold allodynia because normalization of neuronal latexin
expression in the spinal cord by AAV-mediated latexin transduction or
administration of a small molecule carboxypeptidase A inhibitor significantly
reduced acetone-evoked nociceptive behavior after SNI. Our results show the
usefulness of proteomics as a screening tool to identify novel mechanisms of
nerve injury evoked hypernociception and suggest that carboxypeptidase A
inhibition might be useful to reduce cold allodynia
High prevalence of BRCA1 stop mutation c.4183C>T in the Tyrolean population: implications for genetic testing
Screening for founder mutations in BRCA1 and BRCA2 has been discussed as a cost-effective testing strategy in certain populations. In this study, comprehensive BRCA1 and BRCA2 testing was performed in a routine diagnostic setting. The prevalence of the BRCA1 stop mutation c.4183C>T, p.(Gln1395Ter), was determined in unselected breast and ovarian cancer patients from different regions in the Tyrol. Cancer registry data were used to evaluate the impact of this mutation on regional cancer incidence. The mutation c.4183C>T was detected in 30.4% of hereditary BRCA1-associated breast and ovarian cancer patients in our cohort. It was also identified in 4.1% of unselected (26% of unselected triple negative) Tyrolean breast cancer patients and 6.8% of unselected ovarian cancer patients from the Lower Inn Valley (LIV) region. Cancer incidences showed a region-specific increase in age-stratified breast and ovarian cancer risk with standardized incidence ratios of 1.23 and 2.13, respectively. We, thus, report a Tyrolean BRCA1 founder mutation that correlates to a local increase in the breast and ovarian cancer risks. On the basis of its high prevalence, we suggest that targeted genetic analysis should be offered to all women with breast or ovarian cancer and ancestry from the LIV region
Three-Dimensional Maps of All Chromosomes in Human Male Fibroblast Nuclei and Prometaphase Rosettes
Studies of higher-order chromatin arrangements are an essential part of ongoing attempts to explore changes in epigenome structure and their functional implications during development and cell differentiation. However, the extent and cell-type-specificity of three-dimensional (3D) chromosome arrangements has remained controversial. In order to overcome technical limitations of previous studies, we have developed tools that allow the quantitative 3D positional mapping of all chromosomes simultaneously. We present unequivocal evidence for a probabilistic 3D order of prometaphase chromosomes, as well as of chromosome territories (CTs) in nuclei of quiescent (G0) and cycling (early S-phase) human diploid fibroblasts (46, XY). Radial distance measurements showed a probabilistic, highly nonrandom correlation with chromosome size: small chromosomes—independently of their gene density—were distributed significantly closer to the center of the nucleus or prometaphase rosette, while large chromosomes were located closer to the nuclear or rosette rim. This arrangement was independently confirmed in both human fibroblast and amniotic fluid cell nuclei. Notably, these cell types exhibit flat-ellipsoidal cell nuclei, in contrast to the spherical nuclei of lymphocytes and several other human cell types, for which we and others previously demonstrated gene-density-correlated radial 3D CT arrangements. Modeling of 3D CT arrangements suggests that cell-type-specific differences in radial CT arrangements are not solely due to geometrical constraints that result from nuclear shape differences. We also found gene-density-correlated arrangements of higher-order chromatin shared by all human cell types studied so far. Chromatin domains, which are gene-poor, form a layer beneath the nuclear envelope, while gene-dense chromatin is enriched in the nuclear interior. We discuss the possible functional implications of this finding
Measurement of the cosmic ray spectrum above eV using inclined events detected with the Pierre Auger Observatory
A measurement of the cosmic-ray spectrum for energies exceeding
eV is presented, which is based on the analysis of showers
with zenith angles greater than detected with the Pierre Auger
Observatory between 1 January 2004 and 31 December 2013. The measured spectrum
confirms a flux suppression at the highest energies. Above
eV, the "ankle", the flux can be described by a power law with
index followed by
a smooth suppression region. For the energy () at which the
spectral flux has fallen to one-half of its extrapolated value in the absence
of suppression, we find
eV.Comment: Replaced with published version. Added journal reference and DO
Energy Estimation of Cosmic Rays with the Engineering Radio Array of the Pierre Auger Observatory
The Auger Engineering Radio Array (AERA) is part of the Pierre Auger
Observatory and is used to detect the radio emission of cosmic-ray air showers.
These observations are compared to the data of the surface detector stations of
the Observatory, which provide well-calibrated information on the cosmic-ray
energies and arrival directions. The response of the radio stations in the 30
to 80 MHz regime has been thoroughly calibrated to enable the reconstruction of
the incoming electric field. For the latter, the energy deposit per area is
determined from the radio pulses at each observer position and is interpolated
using a two-dimensional function that takes into account signal asymmetries due
to interference between the geomagnetic and charge-excess emission components.
The spatial integral over the signal distribution gives a direct measurement of
the energy transferred from the primary cosmic ray into radio emission in the
AERA frequency range. We measure 15.8 MeV of radiation energy for a 1 EeV air
shower arriving perpendicularly to the geomagnetic field. This radiation energy
-- corrected for geometrical effects -- is used as a cosmic-ray energy
estimator. Performing an absolute energy calibration against the
surface-detector information, we observe that this radio-energy estimator
scales quadratically with the cosmic-ray energy as expected for coherent
emission. We find an energy resolution of the radio reconstruction of 22% for
the data set and 17% for a high-quality subset containing only events with at
least five radio stations with signal.Comment: Replaced with published version. Added journal reference and DO
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