931 research outputs found
Transplanting intact donor tissue enhances dopamine cell survival and the predictability of motor improvements in a rat model of Parkinson's disease
Primary cell transplantation is currently the gold standard for cell replacement in Parkinson's disease. However, the number of donors needed to treat a single patient is high, and the functional outcome is sometimes variable. The present work explores the possibility of enhancing the viability and/or functionality of small amounts of ventral mesencephalic (VM) donor tissue by reducing its perturbation during preparation and implantation. Briefly, unilaterally lesioned rats received either: (1) an intact piece of half an embryonic day 13 (E13) rat VM; (2) dissociated cells from half an E13 rat VM; or (3) no transplant. D-amphetamine- induced rotations revealed that animals receiving pieces of VM tissue or dissociated cells showed significant improvement in ipsilateral rotation 4 weeks post transplantation. By 6 weeks post transplantation, animals receiving pieces of VM tissue showed a trend for further improvement, while those receiving dissociated cells remained at their 4 week scores. Postmortem cell counts showed that the number of dopaminergic neurons in dissociated cell transplants was significantly lower than that surviving in transplants of intact tissue. When assessing the correlation between the number of dopamine cells in each transplant, and the improvement in rotation bias in experimental animals, it was shown that transplants of whole pieces of VM tissue offered greater predictability of graft function based on their dopamine cell content. Such results suggest that maintaining the integrity of VM tissue during implantation improves dopamine cell content, and that the dopamine cell content of whole tissue grafts offers a more predictable outcome of graft function in an animal model of Parkinson's disease
Spá:A Web-Based Viewer for Text Mining in Evidence Based Medicine
Summarizing the evidence about medical interventions is an immense undertaking, in part because unstructured Portable Document Format (PDF) documents remain the main vehicle for disseminating sci- entific findings. Clinicians and researchers must therefore manually ex- tract and synthesise information from these PDFs. We introduce Spá,12 a web-based viewer that enables automated annotation and summari- sation of PDFs via machine learning. To illustrate its functionality, we use Spá to semi-automate the assessment of bias in clinical trials. Spá has a modular architecture, therefore the tool may be widely useful in other domains with a PDF-based literature, including law, physics, and biology
Estrogen activation of microglia underlies the sexually dimorphic differences in Nf1 optic glioma-induced retinal pathology
Children with neurofibromatosis type 1 (NF1) develop low-grade brain tumors throughout the optic pathway. Nearly 50% of children with optic pathway gliomas (OPGs) experience visual impairment, and few regain their vision after chemotherapy. Recent studies have revealed that girls with optic nerve gliomas are five times more likely to lose vision and require treatment than boys. To determine the mechanism underlying this sexually dimorphic difference in clinical outcome, we leveraged Nf1 optic glioma (Nf1-OPG) mice. We demonstrate that female Nf1-OPG mice exhibit greater retinal ganglion cell (RGC) loss and only females have retinal nerve fiber layer (RNFL) thinning, despite mice of both sexes harboring tumors of identical volumes and proliferation. Female gonadal sex hormones are responsible for this sexual dimorphism, as ovariectomy, but not castration, of Nf1-OPG mice normalizes RGC survival and RNFL thickness. In addition, female Nf1-OPG mice have threefold more microglia than their male counterparts, and minocycline inhibition of microglia corrects the retinal pathology. Moreover, pharmacologic inhibition of microglial estrogen receptor-β (ERβ) function corrects the retinal abnormalities in female Nf1-OPG mice. Collectively, these studies establish that female gonadal sex hormones underlie the sexual dimorphic differences in Nf1 optic glioma–induced retinal dysfunction by operating at the level of tumor-associated microglial activation
A SINFONI view of flies in the Spiderweb: a galaxy cluster in the making
The environment of the high-z radio galaxy PKS 1138-262 at z~2.2 is a prime
example of a forming galaxy cluster. We use deep SINFONI data to perform a
detailed study of the kinematics of the galaxies within 60 kpc of the radio
core and we link this to the kinematics of the protocluster on the megaparsec
scale. Identification of optical emission lines shows that 11 galaxies are at
the redshift of the protocluster. The density of line emitters is more than an
order of magnitude higher in the core of the protocluster than the larger scale
environment. This implies a matter overdensity in the core of delta_m~70 which
is similar to the outskirts of local galaxy clusters. The velocity distribution
of the confirmed satellite galaxies shows a broad, double-peaked velocity
structure with sigma=1360+/-206 km/s. A similar broad, double-peaked
distribution was found in a previous study targeting the large scale
protocluster structure, indicating that a common process is acting on both
small and large scales. Including all spectroscopically confirmed protocluster
galaxies, a velocity dispersion of 1013+/-87 km/s is found. We show that the
protocluster has likely decoupled from the Hubble flow and is a dynamically
evolved structure. Comparison to the Millenium simulation indicates that the
protocluster velocity distribution is consistent with that of the most massive
haloes at z~2, but we rule out that the protocluster is a fully virialized
structure based on dynamical arguments and its X-ray luminosity. Comparison to
merging haloes in the Millennium simulation shows that the structure as
observed in and around the Spiderweb galaxy is best interpreted as being the
result of a merger between two massive haloes. We propose that this merger can
result in an increase in star formation and AGN activity in the protocluster
core and is possibly an important stage in the evolution of massive cD
galaxies.Comment: 12 pages, 7 figures. Accepted for publication in MNRA
Gamma Ray Pulsars: Multiwavelength Observations
High-energy gamma rays are a valuable tool for studying particle acceleration
and radiation in the magnetospheres of energetic pulsars. The seven or more
pulsars seen by instruments on the Compton Gamma Ray Observatory (CGRO) show
that: the light curves usually have double-peak structures (suggesting a broad
cone of emission); gamma rays are frequently the dominant component of the
radiated power; and all the spectra show evidence of a high-energy turnover.
For all the known gamma-ray pulsars, multiwavelength observations and
theoretical models based on such observations offer the prospect of gaining a
broad understanding of these rotating neutron stars. The Gamma-ray Large Area
Space Telescope (GLAST), now in planning for a launch in 2007, will provide a
major advance in sensitivity, energy range, and sky coverage.Comment: To appear in Cosmic Gamma Ray Sources, Kluwer ASSL Series, Edited by
K.S. Cheng and G.E. Romer
Voltage-programmable liquid optical interface
Recently, there has been intense interest in photonic devices based on microfluidics, including displays and refractive tunable microlenses and optical beamsteerers, that work using the principle of electrowetting. Here, we report a novel approach to optical devices in which static wrinkles are produced at the surface of a thin film of oil as a result of dielectrophoretic forces. We have demonstrated this voltage-programmable surface wrinkling effect in periodic devices with pitch lengths of between 20 and 240 µm and with response times of less than 40 µs. By a careful choice of oils, it is possible to optimize either for high-amplitude sinusoidal wrinkles at micrometre-scale pitches or more complex non-sinusoidal profiles with higher Fourier components at longer pitches. This opens up the possibility of developing rapidly responsive voltage-programmable, polarization-insensitive transmission and reflection diffraction devices and arbitrary surface profile optical devices
Validating module network learning algorithms using simulated data
In recent years, several authors have used probabilistic graphical models to
learn expression modules and their regulatory programs from gene expression
data. Here, we demonstrate the use of the synthetic data generator SynTReN for
the purpose of testing and comparing module network learning algorithms. We
introduce a software package for learning module networks, called LeMoNe, which
incorporates a novel strategy for learning regulatory programs. Novelties
include the use of a bottom-up Bayesian hierarchical clustering to construct
the regulatory programs, and the use of a conditional entropy measure to assign
regulators to the regulation program nodes. Using SynTReN data, we test the
performance of LeMoNe in a completely controlled situation and assess the
effect of the methodological changes we made with respect to an existing
software package, namely Genomica. Additionally, we assess the effect of
various parameters, such as the size of the data set and the amount of noise,
on the inference performance. Overall, application of Genomica and LeMoNe to
simulated data sets gave comparable results. However, LeMoNe offers some
advantages, one of them being that the learning process is considerably faster
for larger data sets. Additionally, we show that the location of the regulators
in the LeMoNe regulation programs and their conditional entropy may be used to
prioritize regulators for functional validation, and that the combination of
the bottom-up clustering strategy with the conditional entropy-based assignment
of regulators improves the handling of missing or hidden regulators.Comment: 13 pages, 6 figures + 2 pages, 2 figures supplementary informatio
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