Combined Chondroitinase and KLF7 Expression Reduce Net Retraction of Sensory and CST Axons from Sites of Spinal Injury

Axon regeneration in the central nervous system is limited both by inhibitory extracellular cues and by an intrinsically low capacity for axon growth in some CNS populations. Chondroitin sulfate proteoglycans (CSPGs) are well-studied inhibitors of axon growth in the CNS, and degradation of CSPGs by chondroitinase has been shown to improve the extension of injured axons. Alternatively, axon growth can be improved by targeting the neuron-intrinsic growth capacity through forced expression of regeneration-associated transcription factors. For example, a transcriptionally active chimera of Krüppel-like Factor 7 (KLF7) and a VP16 domain improves axon growth when expressed in corticospinal tract neurons. Here we tested the hypothesis that combined expression of chondroitinase and VP16-KLF7 would lead to further improvements in axon growth after spinal injury. Chondroitinase was expressed by viral transduction of cells in the spinal cord, while VP16-KLF7 was virally expressed in sensory neurons of the dorsal root ganglia or corticospinal tract (CST) neurons. After transection of the dorsal columns, both chondroitinase and VP16-KLF7 increased the proximity of severed sensory axons to the injury site. Similarly, after complete crush injuries, VP16-KLF7 expression increased the approach of CST axons to the injury site. In neither paradigm however, did single or combined treatment with chondroitinase or VP16-KLF7 enable regenerative growth distal to the injury. These results substantiate a role for CSPG inhibition and low KLF7 activity in determining the net retraction of axons from sites of spinal injury, while suggesting that additional factors act to limit a full regenerative response

Investigation of a pulsed electrothermal thruster system

The performance of an ablative wall Pulsed Electrothermal (PET) thruster is accurately characterized on a calibrated thrust stand, using polyethylene propellant. The thruster is tested for four configurations of capillary length and pulse length. The exhaust velocity is determined with twin time-of-flight photodiode stagnation probes, and the ablated mass is measured from the loss over ten shots. Based on the measured thrust impulse and the ablated mass, the specific impulse varies from 1000 to 1750 seconds. The thrust to power varies from .05 N/kW (quasi-steady mode) to .10 N/kW (unsteady mode). The thruster efficiency varies from .56 at 1000 seconds to .42 at 1750 seconds. A conceptual design is presented for a 40 kW PET propulsion system. The point design system performance is .62 system efficiency at 1000 seconds specific impulse. The system's reliability is enhanced by incorporating 20, 20 kW thruster modules which are fired in pairs. The thruster design is non-ablative, and uses water propellant, from a central storage tank, injected through the cathode

Methods for removing inertial force from measured wave impact force signals

This report discusses the implementation of three methods for removing or mitigating the so-called inertial force from measured signals resulting from wave impact on components of offshore structure models. The wave impact causes vibration or acceleration in the modeted component. The acceleration is perceived as a force by the measurement transducers. This inertial force component is not scaleable, and must be removed in order to obtain the actual applied force. -- A mitigation method based on the solution of the system equation of motion using normalized coordinates, known as the normal mode method, is investigated. A technique based on the division of the fast Fourier transform of the measured force by the system frequency response, known as the inverse Fourier transform method, is implemented. Finally, the use of digital low pass and band reject filters is examined. -- These techniques are applied to wave impact and decay test measurements from experiments conducted on jacket type fixed offshore structure models. -- The results prove to be less than ideal. The reasons for this are discussed, and recommendations are made for future investigations

The Tumor Suppressor HHEX Inhibits Axon Growth when Prematurely Expressed in Developing Central Nervous System Neurons

Neurons in the embryonic and peripheral nervoussystem respond to injury by activating transcriptional programs supportive of axon growth, ultimately resulting in functional recovery. In contrast, neurons in the adult central nervous system (CNS) possess a limited capacity to regenerate axons after injury, fundamentally constraining repair. Activating pro-regenerative gene expression in CNS neurons is a promising therapeutic approach, but progress is hampered by incomplete knowledge of the relevant transcription factors. An emerging hypothesis is that factors implicated in cellular growth and motility outside the nervous system may also control axon growth in neurons. We therefore tested sixty-nine transcription factors, previously identified as possessing tumor suppressive or oncogenic properties in non-neuronal cells, in assays of neurite outgrowth. This screen identified YAP1 and E2F1 as enhancers of neurite outgrowth, and PITX1, RBM14, ZBTB16, and HHEX as inhibitors. Follow-up experiments are focused on the tumor suppressor HHEX, one of the strongest growth inhibitors. HHEX is widely expressed in adult CNS neurons, including corticospinal tract neurons after spinal injury, but is present only in trace amounts in immature cortical neurons and adult peripheral neurons. HHEX overexpression in early postnatal cortical neurons reduced both initial axonogenesis and the rate of axon elongation, and domain deletion analysis strongly implicated transcriptional repression as the underlying mechanism. These findings suggest a role for HHEX in restricting axon growth in the developing CNS, and substantiate the hypothesis that previously identified oncogenes and tumor suppressors can play conserved roles in axon extension

Condensation of microturbulence-generated shear flows into global modes

In full flux-surface computer studies of tokamak edge turbulence, a spectrum of shear flows is found to control the turbulence level and not just the conventional (0,0)-mode flows. Flux tube domains too small for the large poloidal scale lengths of the continuous spectrum tend to overestimate the flows, and thus underestimate the transport. It is shown analytically and numerically that under certain conditions dominant (0,0)-mode flows independent of the domain size develop, essentially through Bose-Einstein condensation of the shear flows.Comment: 5 pages, 4 figure

Investigation of a repetitive pulsed electrothermal thruster

A pulsed electrothermal (PET) thruster with 1000:1 ratio nozzle is tested in a repetitive mode on water propellant. The thruster is driven by a 60J pulse forming network at repetition rates up to 10 Hz (600W). The pulse forming network has a .31 ohm impedance, well matched to the capillary discharge resistance of .40 ohm, and is directly coupled to the thruster electrodes without a switch. The discharge is initiated by high voltage breakdown, typically at 2500V, through the water vapor in the interelectrode gap. Water is injected as a jet through a .37 mm orifice on the thruster axis. Thruster voltage, current and impulse bit are recorded for several seconds at various power supply currents. Thruster to power ratio is typically T/P = .07 N/kW. Tank background pressure precludes direct measurement of exhaust velocity which is inferred from calculated pressure and temperature in the discharge to be about 14 km/sec. Efficiency, based on this velocity and measured T/P is .54 + or - .07. Thruster ablation is zero at the throat and becomes measurable further upstream, indicating that radiative ablation is occurring late in the pulse

A Summary of Fault Recurrence and Strain Rates in the Vicinity of the Hanford Site--Topical Report

This document is one in a series of topical reports compiled by the Pacific Northwest National Laboratory to summarize technical information on selected topics important to the performance of a probabilistic seismic hazard analysis of the Hanford Site. The purpose of this report is to summarize available data and analyses relevant to fault recurrence and strain rates within the Yakima Fold Belt. Strain rates have met with contention in the expert community and may have a significant potential for impact on the seismic hazard estimate at the Hanford Site. This report identifies the alternative conceptual models relevant to this technical issue and the arguments and data that support those models. It provides a brief description of the technical issue and principal uncertainties; a general overview on the nature of the technical issue, along with alternative conceptual models, supporting arguments and information, and uncertainties; and finally, suggests some prospective approaches to reducing uncertainties about earthquake recurrence rates for the Yakima Fold Belt

Linking the 8.2 ka Event and its Freshwater Forcing in the Labrador Sea

The 8.2 ka event was the last deglacial abrupt climate event. A reduction in the Atlantic meridional overturning circulation (AMOC) attributed to the drainage of glacial Lake Agassiz may have caused the event, but the freshwater signature of Lake Agassiz discharge has yet to be identified in (delta)18O of foraminiferal calcite records from the Labrador Sea, calling into question the connection between freshwater discharge to the North Atlantic and AMOC strength. Using Mg/Ca-paleothermometry, we demonstrate that approx. 3 C of near-surface ocean cooling masked an 1.0 % decrease in western Labrador Sea (delta)18O of seawater concurrent with Lake Agassiz drainage. Comparison with North Atlantic (delta)18O of seawater records shows that the freshwater discharge was transported to regions of deep-water formation where it could perturb AMOC and force the 8.2 ka event

Evidence for the Gompertz Curve in the Income Distribution of Brazil 1978-2005

This work presents an empirical study of the evolution of the personal income distribution in Brazil. Yearly samples available from 1978 to 2005 were studied and evidence was found that the complementary cumulative distribution of personal income for 99% of the economically less favorable population is well represented by a Gompertz curve of the form $G(x)=\exp [\exp (A-Bx)]$, where $x$ is the normalized individual income. The complementary cumulative distribution of the remaining 1% richest part of the population is well represented by a Pareto power law distribution $P(x)= \beta x^{-\alpha}$. This result means that similarly to other countries, Brazil's income distribution is characterized by a well defined two class system. The parameters $A$, $B$, $\alpha$, $\beta$ were determined by a mixture of boundary conditions, normalization and fitting methods for every year in the time span of this study. Since the Gompertz curve is characteristic of growth models, its presence here suggests that these patterns in income distribution could be a consequence of the growth dynamics of the underlying economic system. In addition, we found out that the percentage share of both the Gompertzian and Paretian components relative to the total income shows an approximate cycling pattern with periods of about 4 years and whose maximum and minimum peaks in each component alternate at about every 2 years. This finding suggests that the growth dynamics of Brazil's economic system might possibly follow a Goodwin-type class model dynamics based on the application of the Lotka-Volterra equation to economic growth and cycle.Comment: 22 pages, 15 figures, 4 tables. LaTeX. Accepted for publication in "The European Physical Journal B

Pseudomonas Genome Database: improved comparative analysis and population genomics capability for Pseudomonas genomes

Pseudomonas is a metabolically-diverse genus of bacteria known for its flexibility and leading free living to pathogenic lifestyles in a wide range of hosts. The Pseudomonas Genome Database (http://www.pseudomonas.com) integrates completely-sequenced Pseudomonas genome sequences and their annotations with genome-scale, high-precision computational predictions and manually curated annotation updates. The latest release implements an ability to view sequence polymorphisms in P. aeruginosa PAO1 versus other reference strains, incomplete genomes and single gene sequences. This aids analysis of phenotypic variation between closely related isolates and strains, as well as wider population genomics and evolutionary studies. The wide range of tools for comparing Pseudomonas annotations and sequences now includes a strain-specific access point for viewing high precision computational predictions including updated, more accurate, protein subcellular localization and genomic island predictions. Views link to genome-scale experimental data as well as comparative genomics analyses that incorporate robust genera-geared methods for predicting and clustering orthologs. These analyses can be exploited for identifying putative essential and core Pseudomonas genes or identifying large-scale evolutionary events. The Pseudomonas Genome Database aims to provide a continually updated, high quality source of genome annotations, specifically tailored for Pseudomonas researchers, but using an approach that may be implemented for other genera-level research communities