Microtubule plus-end binding protein CLASP2 in neural development

Normal brain function is dependent on the correct positioning and connectivity of neurons established during development. The Reelin signaling pathway plays a crucial role in cortical lamination. Reelin is a secreted glycoprotein that exerts its function by binding to lipoprotein receptors and inducing tyrosine phosphorylation of the intracellular adaptor protein Dab1. Mutations in genes of the Reelin signaling pathway lead to profound defects in neuronal positioning during brain development in both mice and humans. However, the molecular mechanisms by which Reelin controls neuronal morphology and migration are unknown. We have used a systems analysis approach to identify genes perturbed in the Reelin signaling pathway and identified microtubule stabilizing CLIP-associated protein 2 (CLASP2) as a key cytoskeletal modifier of Reelin mutant phenotypes. Currently, little is known about the role of CLASP2 in the developing brain. We propose that CLASP2 is a key effector in the Reelin signaling pathway controlling basic aspects of cortical layering, neuronal morphology, and function. CLASP2 is a plus-end tracking protein and this localization places CLASP2 in a strategic position to control neurite outgrowth, directionality, and responsiveness to extracellular cues. Our results demonstrate that CLASP2 expression correlates with neurite length and synaptic activity in primary neuron cultures; however, the role of CLASP2 during brain development was unknown. In this dissertation, we have characterized the role of CLASP2 during cortical development by in utero electroporation of shRNA plasmids and found that silencing CLASP2 in migrating neurons leads to mislocalized cells at deeper cortical layers, abnormal positioning of the centrosome-Golgi complex, and aberrant length/orientation of the leading process. In addition, we found that GSK3β-mediated phosphorylation of CLASP2 controls Dab1 binding and is required for regulating CLASP2 effects on neuron morphology and migration. This dissertation provides the first steps in gaining insight into how Reelin signaling affects cytoskeletal reorganization to regulate fundamental features of neuronal migration, positioning and morphogenesis

Semantic web support for open-source software development

Open-source software is unique in that the development of the product is performed in public over the Internet by developers who elect to contribute to the project and rarely if ever meet face-to-face. Software development is a knowledge intensive process and the information generated in open-source software development projects is typically housed in a central Internet repository. Open-source repositories typically contains vast amounts of information, much of it unstructured, meaning that even if a question has previously been discussed and dealt with it is not a trivial task to locate it, leading to rework, confusion amongst developers and possibly deterring new developers from getting involved.This paper develops an ontology based software development architecture for open-source software development. Such an architecture would enable better categorisation of information, communication, co-ordination and the development of sophisticated search agents

Targeting Kinase Networks in Glioblastoma

Nanoparticles with same core size and shell thickness were made. Samples with low, medium, and high gradients were compared with a control with no gradient. TEM (Transmission Electron Microscopy) results showed a well-controlled size with a mean diameter of 10 nm and standard deviation of 1 nm. The elemental distribution throughout the particle was analyzed by EELS (Electron Energy Loss Spectroscopy) to confirm the existence of core-gradient shell structure. Physical properties, such as saturation magnetization, blocking temperature, and effective anisotropy were then measured and calculated based on VSM (Vibration Sampling Magnetometry) and ZFC-FC (Zero Field Cooling-Field Cooling) measurements

A New Metric for Quantifying Burn Severity: The Relativized Burn Ratio

Satellite-inferred burn severity data have become increasingly popular over the last decade for management and research purposes. These data typically quantify spectral change between pre-and post-fire satellite images (usually Landsat). There is an active debate regarding which of the two main equations, the delta normalized burn ratio (dNBR) and its relativized form (RdNBR), is most suitable for quantifying burn severity; each has its critics. In this study, we propose and evaluate a new Landsat-based burn severity metric, the relativized burn ratio (RBR), that provides an alternative to dNBR and RdNBR. For 18 fires in the western US, we compared the performance of RBR to both dNBR and RdNBR by evaluating the agreement of these metrics with field-based burn severity measurements. Specifically, we evaluated (1) the correspondence between each metric and a continuous measure of burn severity (the composite burn index) and (2) the overall accuracy of each metric when classifying into discrete burn severity classes (i.e., unchanged, low, moderate, and high). Results indicate that RBR corresponds better to field-based measurements (average R2 among 18 fires = 0.786) than both dNBR (R2 = 0.761) and RdNBR (R2 = 0.766). Furthermore, the overall classification accuracy achieved with RBR (average among 18 fires = 70.5%) was higher than both dNBR (68.4%) and RdNBR (69.2%). Consequently, we recommend RBR as a robust alternative to both dNBR and RdNBR for measuring and classifying burn severity

A Fire Severity Mapping System for Real-Time Fire Management Applications and Long-Term Planning: The FIRESEV project

Accurate, consistent, and timely fire severity maps are needed in all phases of fire management including planning, managing, and rehabilitating wildfires. The problem is that fire severity maps are commonly developed from satellite imagery that is difficult to use for planning wildfire responses before a fire has actually happened and can’t be used for real-time wildfire management because of the timing of the imagery delivery. Moreover, imagery is difficult to use for controlled fires such as prescribed burning. This study, called FIRESEV (FIRE SEVerity Mapping Tools) created a comprehensive set of tools and protocols to deliver, create, and evaluate fire severity maps for all phases of fire management. The first tool is a Severe Fire Potential Map (SFPM) that quantifies the potential for fires to burn with high severity, should they occur, for any 30m x 30m piece of ground across the western United States. This map was developed using empirical models that related topographic, vegetation, and fire weather variables to burn severity as mapped using the Monitoring Trends in Burn Severity (MTBS) digital products. This SFPM map is currently available on the Fire Research and Management Exchange System (FRAMES, http://www.frames.gov/firesev) web site and can be used to plan for future wildfires or for managing wildfires in real time, e.g. by including it as a layer in Wildland Fire Decision Support System or other GIS analysis. The next tool was the inclusion of a fire severity mapping algorithm in the Wildland Fire Assessment Tool (WFAT) developed by the National Interagency Fuels Technology Transfer (NIFTT) team. WFAT is used for fuel treatment planning to predict potential fire effects under prescribed fire weather conditions (http://www.frames.gov/partner-sites/niftt/tools/niftt-current-resources/). Now, fire severity can be mapped explicitly from fire effects simulation models (FOFEM, Consume) for real-time and planning wildfire applications. Next, the FIRESEV project showed how results from the WFAT simulated fire severity can be integrated with satellite imagery to improve fire severity mapping. And last, the FIRESEV project produced a suite of research studies, synthesis papers, and popular articles designed to improve the description, interpretation, and mapping of fire severity for wildland fire management: (1) a research study created a completely objective method of quantifying fire severity from fire effects to obtain nine unique classes of fire severity, (2) a research study comprehensively contrasted all current classifications of fire severity using Composite Burn Index (CBI) as measured on over 300 plots across the western United States to determine commonalities and differences, and (3) a synthesis paper was written discussing the problems involved in measuring, describing, and quantifying fire severity. This FIRESEV project yielded over 15 deliverables that we feel provides a comprehensive suite of products to create useful fire severity maps, along with current satellite imagery products, and also FIRESEV provides a thorough background on how to measure, interpret, and apply fire severity in fire management

Lack of Tryptophan Hydroxylase-1 in Mice Results in Gait Abnormalities

The role of peripheral serotonin in nervous system development is poorly understood. Tryptophan hydroxylase-1 (TPH1) is expressed by non-neuronal cells including enterochromaffin cells of the gut, mast cells and the pineal gland and is the rate-limiting enzyme involved in the biosynthesis of peripheral serotonin. Serotonin released into circulation is taken up by platelets via the serotonin transporter and stored in dense granules. It has been previously reported that mouse embryos removed from Tph1-deficient mothers present abnormal nervous system morphology. The goal of this study was to assess whether Tph1-deficiency results in behavioral abnormalities. We did not find any differences between Tph1-deficient and wild-type mice in general motor behavior as tested by rotarod, grip-strength test, open field and beam walk. However, here we report that Tph1 (−/−) mice display altered gait dynamics and deficits in rearing behavior compared to wild-type (WT) suggesting that tryptophan hydroxylase-1 expression has an impact on the nervous system

Granular Media-Based Tunable Passive Vibration Suppressor

and vibration suppression device is composed of statically compressed chains of spherical particles. The device superimposes a combination of dissipative damping and dispersive effects. The dissipative damping resulting from the elastic wave attenuation properties of the bulk material selected for the granular media is independent of particle geometry and periodicity, and can be accordingly designed based on the dissipative (or viscoelastic) properties of the material. For instance, a viscoelastic polymer might be selected where broadband damping is desired. In contrast, the dispersive effects result from the periodic arrangement and geometry of particles composing a linear granular chain. A uniform (monatomic) chain of statically compressed spherical particles will have a low-pass filter effect, with a cutoff frequency tunable as a function of particle mass, elastic modulus, Poisson fs ratio, radius, and static compression. Elastic waves with frequency content above this cutoff frequency will exhibit an exponential decay in amplitude as a function of propagation distance. System design targeting a specific application is conducted using a combination of theoretical, computational, and experimental techniques to appropriately select the particle radii, material (and thus elastic modulus and Poisson fs ratio), and static compression to satisfy estimated requirements derived for shock and/or vibration protection needs under particular operational conditions. The selection of a chain of polymer spheres with an elastic modulus .3 provided the appropriate dispersive filtering effect for that exercise; however, different operational scenarios may require the use of other polymers, metals, ceramics, or a combination thereof, configured as an array of spherical particles. The device is a linear array of spherical particles compressed in a container with a mechanism for attachment to the shock and/or vibration source, and a mechanism for attachment to the article requiring isolation (Figure 1). This configuration is referred to as a single-axis vibration suppressor. This invention also includes further designs for the integration of the single-axis vibration suppressor into a six-degree-of-freedom hexapod "Stewart"mounting configuration (Figure 2). By integrating each singleaxis vibration suppressor into a hexapod formation, a payload will be protected in all six degrees of freedom from shock and/or vibration. Additionally, to further enable the application of this device to multiple operational scenarios, particularly in the case of high loads, the vibration suppressor devices can be used in parallel in any array configuration

Effective field theory and the quark model

We analyze the connections between the quark model (QM) and the description of hadrons in the low-momentum limit of heavy-baryon effective field theory in QCD. By using a three-flavor-index representation for the effective baryon fields, we show that the ``nonrelativistic'' constituent QM for baryon masses and moments is completely equivalent through O(m_s) to a parametrization of the relativistic field theory in a general spin--flavor basis. The flavor and spin variables can be identified with those of effective valence quarks. Conversely, the spin-flavor description clarifies the structure and dynamical interpretation of the chiral expansion in effective field theory, and provides a direct connection between the field theory and the semirelativistic models for hadrons used in successful dynamical calculations. This allows dynamical information to be incorporated directly into the chiral expansion. We find, for example, that the striking success of the additive QM for baryon magnetic moments is a consequence of the relative smallness of the non-additive spin-dependent corrections.Comment: 25 pages, revtex, no figure