Downregulation of genes with a function in axon outgrowth and synapse formation in motor neurones of the VEGF(delta/delta) mouse model of amyotrophic lateral sclerosis

Background: Vascular endothelial growth factor (VEGF) is an endothelial cell mitogen that stimulates vasculogenesis. It has also been shown to act as a neurotrophic factor in vitro and in vivo. Deletion of the hypoxia response element of the promoter region of the gene encoding VEGF in mice causes a reduction in neural VEGF expression, and results in adult-onset motor neurone degeneration that resembles amyotrophic lateral sclerosis (ALS). Investigating the molecular pathways to neurodegeneration in the VEGF(delta/delta) mouse model of ALS may improve understanding of the mechanisms of motor neurone death in the human disease. Results: Microarray analysis was used to determine the transcriptional profile of laser captured spinal motor neurones of transgenic and wild-type littermates at 3 time points of disease. 324 genes were significantly differentially expressed in motor neurones of presymptomatic VEGF(delta/delta) mice, 382 at disease onset, and 689 at late stage disease. Massive transcriptional downregulation occurred with disease progression, associated with downregulation of genes involved in RNA processing at late stage disease. VEGF(delta/delta) mice showed reduction in expression, from symptom onset, of the cholesterol synthesis pathway, and genes involved in nervous system development, including axonogenesis, synapse formation, growth factor signalling pathways, cell adhesion and microtubule-based processes. These changes may reflect a reduced capacity of VEGF(delta/delta) mice for maintenance and remodelling of neuronal processes in the face of demands of neural plasticity. The findings are supported by the demonstration that in primary motor neurone cultures from VEGF(delta/delta) mice, axon outgrowth is significantly reduced compared to wild-type littermates. Conclusions: Downregulation of these genes involved in axon outgrowth and synapse formation in adult mice suggests a hitherto unrecognized role of VEGF in the maintenance of neuronal circuitry. Dysregulation of VEGF may lead to neurodegeneration through synaptic regression and dying-back axonopathy

Анизотропно-пучковая неустойчивость лазерной плазмы

При распространении мощного лазерного импульса вдоль внешнего магнитного поля в плазме возбуждается широкий спектр вистлерных мод с частотами ниже электронной циклотронной частоты, что приводит к появлению надтепловых электронов и установлению плато на первоначально максвелловской функции распределения. В результате развивается анизотропно-пучковая неустойчивость и происходит трансформация энергии быстрых электронов в энергию электростатических колебаний плазмы.При розповсюдженні потужного лазерного імпульсу вздовж зовнішнього магнітного поля в плазмі збуджується широкий спектр вістлерних мод з частотами нижче електронної циклотроної частоти, що призводить до появи надтеплових електронів і встановленню плато на первісно максвеллівській функції розподілу. У результаті розвивається анізотропно-пучкова нестійкість і відбувається трансформація енергії швидких електронів в енергію електростатичних коливань плазми.In the propagation of intense laser pulse along the external magnetic field in a plasma excited a wide range of whistler modes with frequencies below the electron cyclotron frequency, which leads to the suprathermal electrons and the establishment of a plateau on the original Maxwellian distribution functions. As a result, develops anisotropically-stream instability and a transformation of fast electron energy in the energy of electrostatic plasma oscillations

Endovascular Treatment of the Descending Thoracic Aorta

AbstractObjectives: to report our initial experience with endovascular stent graft repair of a variety of thoracic aortic pathology.Design: retrospective single center study.Material and methods: between February 2000 and January 2002, endovascular stent graft repair was performed in 26 patients: traumatic aortic isthmus rupture (n=3), Type B dissection (n=11) and descending thoracic aortic aneurysm (n=12). The deployed stent graft systems were AneuRx-Medtronic (n=1), Talent-Medtronic (n=13) and Excluder-Gore (n=12).Results: successful deployment of the stent grafts in the intended position was achieved in all patients. No hospital mortality neither paraplegia were observed. Late, non procedure related, death occurred in four patients (15%). Access artery complications with rupture of the iliac artery occurred in two patients and were managed by iliac-femoral bypass. The left subclavian artery was overstented in seven patients (27%). Only the first patient received a carotido-subclavian bypass. The mean maximal aortic diameter decreased significantly in patients treated for descending thoracic aneurysm. Only one patient had an endoleak type II after 6 months without enlargement of the aneurysm. Complete thrombosis of the thoracic false lumen occurred in all but one patient treated for Type B dissection 6 months postoperatively. Two patients underwent a consecutive stent graft placement, due to a large re-entry tear distal to the first stent graft.Conclusions: endovascular stent graft repair for Type B dissection, descending thoracic aneurysm and aortic isthmus rupture is a promising less-invasive alternative to surgical repair. Further studies are mandatory to determine its long-term efficacy

M. Kontsevich's graph complex and the Grothendieck-Teichmueller Lie algebra

We show that the zeroth cohomology of M. Kontsevich's graph complex is isomorphic to the Grothendieck-Teichmueller Lie algebra grt_1. The map is explicitly described. This result has applications to deformation quantization and Duflo theory. We also compute the homotopy derivations of the Gerstenhaber operad. They are parameterized by grt_1, up to one class (or two, depending on the definitions). More generally, the homotopy derivations of the (non-unital) E_n operads may be expressed through the cohomology of a suitable graph complex. Our methods also give a second proof of a result of H. Furusho, stating that the pentagon equation for grt_1-elements implies the hexagon equation

Comparative susceptibility of mosquito populations in North Queensland, Australia to oral infection with dengue virus.

Dengue is the most prevalent arthropod-borne virus, with at least 40% of the world's population at risk of infection each year. In Australia, dengue is not endemic, but viremic travelers trigger outbreaks involving hundreds of cases. We compared the susceptibility of Aedes aegypti mosquitoes from two geographically isolated populations to two strains of dengue virus serotype 2. We found, interestingly, that mosquitoes from a city with no history of dengue were more susceptible to virus than mosquitoes from an outbreak-prone region, particularly with respect to one dengue strain. These findings suggest recent evolution of population-based differences in vector competence or different historical origins. Future genomic comparisons of these populations could reveal the genetic basis of vector competence and the relative role of selection and stochastic processes in shaping their differences. Lastly, we show the novel finding of a correlation between midgut dengue titer and titer in tissues colonized after dissemination

Wear of human teeth: a tribological perspective

The four main types of wear in teeth are attrition (enamel-on-enamel contact), abrasion (wear due to abrasive particles in food or toothpaste), abfraction (cracking in enamel and subsequent material loss), and erosion (chemical decomposition of the tooth). They occur as a result of a number of mechanisms including thegosis (sliding of teeth into their lateral position), bruxism (tooth grinding), mastication (chewing), toothbrushing, tooth flexure, and chemical effects. In this paper the current understanding of wear of enamel and dentine in teeth is reviewed in terms of these mechanisms and the major influencing factors are examined. In vitro tooth wear simulation and in vivo wear measurement and ranking are also discussed

Fibrin structural and diffusional analysis suggests that fibers are permeable to solute transport

Fibrin hydrogels are promising carrier materials in tissue engineering. They are biocompatible and easy to prepare, they can bind growth factors and they can be prepared from a patient’s own blood. While fibrin structure and mechanics have been extensively studied, not much is known about the relation between structure and diffusivity of solutes within the network. This is particularly relevant for solutes with a size similar to that of growth factors. A novel methodological approach has been used in this study to retrieve quantitative structural characteristics of fibrin hydrogels, by combining two complementary techniques, namely confocal fluorescence microscopy with a fiber extraction algorithm and turbidity measurements. Bulk rheological measurements were conducted to determine the impact of fibrin hydrogel structure on mechanical properties. From these measurements it can be concluded that variations in the fibrin hydrogel structure have a large impact on the rheological response of the hydrogels (up to two orders of magnitude difference in storage modulus) but only a moderate influence on the diffusivity of dextran solutes (up to 25% difference). By analyzing the diffusivity measurements by means of the Ogston diffusion model we further provide evidence that individual fibrin fibers can be semi-permeable to solute transport, depending on the average distance between individual protofibrils. This can be important for reducing mass transport limitations, for modulating fibrinolysis and for growth factor binding, which are all relevant for tissue engineering

Open Posterior Reduction and Stabilization of AO Spine C3 Sacral Fractures.

AO Spine C3 sacral fractures are defined by separation of the spine including S1 from the pelvic ring and are usually result of a high-energy injury. Besides their high biomechanical instability and high rate of associated neurological impairment, these fractures are often extremely difficult to reduce due to severe bony impaction and dislocation. Additional difficulties in management of these fractures arise from only a thin-layer of soft-tissue coverage overlying the injured area

Combining Exploration and Exploitation in Active Learning

This thesis investigates the active learning in the presence of model bias. State of the art approaches advocate combining exploration and exploitation in active learning. However, they suffer from premature exploitation or unnecessary exploration in the later stages of learning. We propose to combine exploration and exploitation in active learning by discarding instances outside a sampling window that is centered around the estimated decision boundary and uniformly draw sample from this window. Initially the window spans the entire feature space and is gradually constricted, where the rate of constriction models the exploration-exploitation tradeoff. The desired effect of this approach (CExp) is that we get an increasing sampling density in informative regions as active learning progresses, resulting in a continuous and natural transition from exploration to exploitation, limiting both premature exploitation and unnecessary exploration. We show that our approach outperforms state of the art on real world multiclass datasets. We also extend our approach to spatial mapping problems where the standard active learning assumption of uniform costs is violated. We show that we can take advantage of \emph{spatial continuity} in the data by geographically partitioning the instances in the sampling window and choosing a single partition (region) for sampling, as opposed to taking a random sample from the entire window, resulting in a novel spatial active learning algorithm that combines exploration and exploitation. We demonstrate that our approach (CExp-Spatial) can generate cost-effective sampling trajectories over baseline sampling methods. Finally, we present the real world problem of mapping benthic habitats where bathymetry derived features are typically not strong enough to discriminate the fine details between classes identified from high-resolution imagery, increasing the possiblity of model bias in active learning. We demonstrate, under such conditions, that CExp outperforms state of the art and that CExp-Spatial can generate more cost-effective sampling trajectories for an Autonomous Underwater Vehicle in contrast to baseline sampling strategies

Dynamics of pebbles in the vicinity of a growing planetary embryo: hydro-dynamical simulations

Understanding the growth of the cores of giant planets is a difficult problem. Recently, Lambrechts and Johansen (2012; LJ12) proposed a new model in which the cores grow by the accretion of pebble-size objects, as the latter drift towards the star due to gas drag. Here, we investigate the dynamics of pebble-size objects in the vicinity of planetary embryos of 1 and 5 Earth masses and the resulting accretion rates. We use hydrodynamical simulations, in which the embryo influences the dynamics of the gas and the pebbles suffer gas drag according to the local gas density and velocities. The pebble dynamics in the vicinity of the planetary embryo is non-trivial, and it changes significantly with the pebble size. Nevertheless, the accretion rate of the embryo that we measure is within an order of magnitude of the rate estimated in LJ12 and tends to their value with increasing pebble-size. We conclude that the model by LJ12 has the potential to explain the rapid growth of giant planet cores. The actual accretion rates however, depend on the surface density of pebble size objects in the disk, which is unknown to date.Comment: In press in Astronomy and Astrophysic