197 research outputs found
Disease-specific, neurosphere-derived cells as models for brain disorders
There is a pressing need for patient-derived cell models of brain diseases that are relevant and robust enough to produce the large quantities of cells required for molecular and functional analyses. We describe here a new cell model based on patient-derived cells from the human olfactory mucosa, the organ of smell, which regenerates throughout life from neural stem cells. Olfactory mucosa biopsies were obtained from healthy controls and patients with either schizophrenia, a neurodevelopmental psychiatric disorder, or Parkinson's disease, a neurodegenerative disease. Biopsies were dissociated and grown as neurospheres in defined medium. Neurosphere-derived cell lines were grown in serum-containing medium as adherent monolayers and stored frozen. By comparing 42 patient and control cell lines we demonstrated significant disease-specific alterations in gene expression, protein expression and cell function, including dysregulated neurodevelopmental pathways in schizophrenia and dysregulated mitochondrial function, oxidative stress and xenobiotic metabolism in Parkinson's disease. The study has identified new candidate genes and cell pathways for future investigation. Fibroblasts from schizophrenia patients did not show these differences. Olfactory neurosphere-derived cells have many advantages over embryonic stem cells and induced pluripotent stem cells as models for brain diseases. They do not require genetic reprogramming and they can be obtained from adults with complex genetic diseases. They will be useful for understanding disease aetiology, for diagnostics and for drug discovery
Neutral weak currents in pion electroproduction on the nucleon
Parity violating asymmetry in inclusive scattering of longitudinally
polarized electrons by unpolarized protons with or meson
production, is calculated as a function of the momentum transfer squared
and the total energy of the -system. This asymmetry, which is
induced by the interference of the one-photon exchange amplitude with the
parity-odd part of the -exchange amplitude, is calculated for the
processes ( is a virtual photon and
a virtual Z-boson) considering the -contribution in the channel,
the standard Born contributions and vector meson ( and )
exchanges in the channel. Taking into account the known isotopic properties
of the hadron electromagnetic and neutral currents, we show that the P-odd term
is the sum of two contributions. The main term is model independent and it can
be calculated exactly in terms of fundamental constants. It is found to be
linear in . The second term is a relatively small correction which is
determined by the isoscalar component of the electromagnetic current. Near
threshold and in the -region, this isoscalar part is much smaller (in
absolute value) than the isovector one: its contribution to the asymmetry
depend on the polarization state (longitudinal or transverse) of the virtual
photon.Comment: 30 pages 9 figure
Large-scale pathways-based association study in amyotrophic lateral sclerosis
Sporadic amyotrophic lateral sclerosis (ALS), a devastating neurodegenerative disease, most likely results from complex genetic and environmental interactions. Although a number of association studies have been performed in an effort to find genetic components of sporadic ALS, most of them resulted in inconsistent findings due to a small number of genes investigated in relatively small sample sizes, while the replication of results was rarely attempted. Defects in retrograde axonal transport, vesicle trafficking and xenobiotic metabolism have been implicated in neurodegeneration and motor neuron death both in human disease and animal models. To assess the role of common genetic variation in these pathways in susceptibility to sporadic ALS, we performed a pathway-based candidate gene case-control association study with replication. Furthermore, we determined reliability of whole genome amplified DNA in a large-scale association study. In the first stage of the study, 1277 putative functional and tagging SNPs in 134 genes spanning 8.7 Mb were genotyped in 822 British sporadic ALS patients and 872 controls using whole genome amplified DNA. To detect variants with modest effect size and discriminate among false positive findings 19 SNPs showing a trend of association in the initial screen were genotyped in a replication sample of 580 German sporadic ALS patients and 361 controls. We did not detect strong evidence of association with any of the genes investigated in the discovery sample (lowest uncorrected P-value 0.00037, lowest permutation corrected P-value 0.353). None of the suggestive associations was replicated in a second sample, further excluding variants with moderate effect size. We conclude that common variation in the investigated pathways is unlikely to have a major effect on susceptibility to sporadic ALS. The genotyping efficiency was only slightly decreased (âŒ1%) and genotyping quality was not affected using whole genome amplified DNA. It is reliable for large scale genotyping studies of diseases such as ALS, where DNA sample collections are limited because of low disease prevalence and short survival time. © 2007 The Author(s)
On the selection of AGN neutrino source candidates for a source stacking analysis with neutrino telescopes
The sensitivity of a search for sources of TeV neutrinos can be improved by
grouping potential sources together into generic classes in a procedure that is
known as source stacking. In this paper, we define catalogs of Active Galactic
Nuclei (AGN) and use them to perform a source stacking analysis. The grouping
of AGN into classes is done in two steps: first, AGN classes are defined, then,
sources to be stacked are selected assuming that a potential neutrino flux is
linearly correlated with the photon luminosity in a certain energy band (radio,
IR, optical, keV, GeV, TeV). Lacking any secure detailed knowledge on neutrino
production in AGN, this correlation is motivated by hadronic AGN models, as
briefly reviewed in this paper.
The source stacking search for neutrinos from generic AGN classes is
illustrated using the data collected by the AMANDA-II high energy neutrino
detector during the year 2000. No significant excess for any of the suggested
groups was found.Comment: 43 pages, 12 figures, accepted by Astroparticle Physic
An improved method for measuring muon energy using the truncated mean of dE/dx
The measurement of muon energy is critical for many analyses in large
Cherenkov detectors, particularly those that involve separating
extraterrestrial neutrinos from the atmospheric neutrino background. Muon
energy has traditionally been determined by measuring the specific energy loss
(dE/dx) along the muon's path and relating the dE/dx to the muon energy.
Because high-energy muons (E_mu > 1 TeV) lose energy randomly, the spread in
dE/dx values is quite large, leading to a typical energy resolution of 0.29 in
log10(E_mu) for a muon observed over a 1 km path length in the IceCube
detector. In this paper, we present an improved method that uses a truncated
mean and other techniques to determine the muon energy. The muon track is
divided into separate segments with individual dE/dx values. The elimination of
segments with the highest dE/dx results in an overall dE/dx that is more
closely correlated to the muon energy. This method results in an energy
resolution of 0.22 in log10(E_mu), which gives a 26% improvement. This
technique is applicable to any large water or ice detector and potentially to
large scintillator or liquid argon detectors.Comment: 12 pages, 16 figure
All-particle cosmic ray energy spectrum measured with 26 IceTop stations
We report on a measurement of the cosmic ray energy spectrum with the IceTop
air shower array, the surface component of the IceCube Neutrino Observatory at
the South Pole. The data used in this analysis were taken between June and
October, 2007, with 26 surface stations operational at that time, corresponding
to about one third of the final array. The fiducial area used in this analysis
was 0.122 km^2. The analysis investigated the energy spectrum from 1 to 100 PeV
measured for three different zenith angle ranges between 0{\deg} and 46{\deg}.
Because of the isotropy of cosmic rays in this energy range the spectra from
all zenith angle intervals have to agree. The cosmic-ray energy spectrum was
determined under different assumptions on the primary mass composition. Good
agreement of spectra in the three zenith angle ranges was found for the
assumption of pure proton and a simple two-component model. For zenith angles
{\theta} < 30{\deg}, where the mass dependence is smallest, the knee in the
cosmic ray energy spectrum was observed between 3.5 and 4.32 PeV, depending on
composition assumption. Spectral indices above the knee range from -3.08 to
-3.11 depending on primary mass composition assumption. Moreover, an indication
of a flattening of the spectrum above 22 PeV were observed.Comment: 38 pages, 17 figure
The Rise and Fall, and the Rise (Again) of Feminist Research in Music: 'What Goes Around Comes Around'
This article reports from a two-phase study that involved an analysis of the extant literature followed by a three-part survey answered by seventy-one women composers. Through these theoretical and empirical data, the authors explore the relationship between gender and musicâs symbolic and cultural capital. Bourdieuâs theory of the habitus is employed to understand the gendered experiences of the female composers who participated in the survey. The article suggests that these female composers have different investments in gender but that, overall, they reinforce the male habitus given that the female habitus occupies a subordinate position in relation to that of the male. The findings of the study also suggest a connection between contemporary feminism and the attitudes towards gender held by the participants. The article concludes that female composers classify themselves, and others, according to gendered norms and that these perpetuate the social order in music in which the male norm dominates
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