Making the At Work for Nebraska Report work for IANR: Next Steps

Folks, I am so pleased to have this opportunity to talk with you about the "At Work for Nebraska" report we recently received from Battelle of Columbus, Ohio.

Defibrotide Interferes With Several Steps of the Coagulation-Inflammation Cycle and Exhibits Therapeutic Potential to Treat Severe Malaria

Objective-The coagulation-inflammation cycle has been implicated as a critical component in malaria pathogenesis. Defibrotide (DF), a mixture of DNA aptamers, displays anticoagulant, anti-inflammatory, and endothelial cell (EC)-protective activities and has been successfully used to treat comatose children with veno-occlusive disease. DF was investigated here as a drug to treat cerebral malaria. Methods and Results-DF blocks tissue factor expression by ECs incubated with parasitized red blood cells and attenuates prothrombinase activity, platelet aggregation, and complement activation. In contrast, it does not affect nitric oxide bioavailability. We also demonstrated that Plasmodium falciparum glycosylphosphatidylinositol (Pf-GPI) induces tissue factor expression in ECs and cytokine production by dendritic cells. Notably, dendritic cells, known to modulate coagulation and inflammation systemically, were identified as a novel target for DF. Accordingly, DF inhibits Toll-like receptor ligand-dependent dendritic cells activation by a mechanism that is blocked by adenosine receptor antagonist (8-p-sulfophenyltheophylline) but not reproduced by synthetic poly-A, -C, -T, and -G. These results imply that aptameric sequences and adenosine receptor mediate dendritic cells responses to the drug. DF also prevents rosetting formation, red blood cells invasion by P. falciparum and abolishes oocysts development in Anopheles gambiae. In a murine model of cerebral malaria, DF affected parasitemia, decreased IFN-gamma levels, and ameliorated clinical score (day 5) with a trend for increased survival. Conclusion-Therapeutic use of DF in malaria is proposed. (Arterioscler Thromb Vasc Biol. 2012; 32:786-798.)

Influence of the magnetization damping on dynamic hysteresis loops in single domain particles

This article reports on the influence of the magnetization damping on dynamic hysteresis loops in single-domain particles with uniaxial anisotropy. The approach is based on the Neel-Brown theory and the hierarchy of differential recurrence relations, which follow from averaging over the realizations of the stochastic Landau-Lifshitz equation. A new method of solution is proposed, where the resulting system of differential equations is solved directly using optimized algorithms to explore its sparsity. All parameters involved in uniaxial systems are treated in detail, with particular attention given to the frequency dependence. It is shown that in the ferromagnetic resonance region, novel phenomena are observed for even moderately low values of the damping. The hysteresis loops assume remarkably unusual shapes, which are also followed by a pronounced reduction of their heights. Also demonstrated is that these features remain for randomly oriented ensembles and, moreover, are approximately independent of temperature and particle size. (C) 2012 American Institute of Physics. [doi:10.1063/1.3684629]

Essential steps to providing reliable results using the Analytical Quality Assurance Cycle

Considering how demand for quality assurance (QA) has grown in analytical laboratories, we show the trends in analytical science, illustrated through international standard ISO/IEC 17025, validation, measurements of uncertainty, and quality-control (QC) measures. A detailed review of the history of analytical chemistry indicates that these concepts are consistently used in laboratories to demonstrate their traceabilities and competences to provide reliable results. We propose a new approach for laboratory QA, which also develops a diagram to support routine laboratories (which generally apply a quality system, such as ISO/IEC 17025) or research laboratories (that have some difficult applying this international standard). This approach, called the Analytical Quality Assurance Cycle (AQAC), presents the major QA concepts and the relationships between these concepts in order to provide traceability and reliable results. The AQAC is a practical tool to support the trend towards QA in analytical laboratories. (C) 2012 Elsevier Ltd. All rights reserved.

Early and One-Year Stroke Case Fatality in Sao Paulo, Brazil: Applying the World Health Organization's Stroke STEPS

Case fatality rate is considered a main determinant of stroke mortality trends. We applied the World Health Organization's Stroke STEPS to identify case fatality rates in a community hospital in Brazil. We evaluated all patients with first-ever stroke seeking acute care at the hospital's emergency ward between April 2006 and December 2008 to verify early and late case fatality according to stroke subtype. We used years of formal education as a surrogate for socioeconomic status. Of 430 first-ever stroke events, 365 (84.9%) were ischemic and 65 (15.1%) were intracerebral hemorrhage. After 1 year, we adjudicated 108 deaths (86 ischemic; 22 hemorrhagic). Age-adjusted case fatality rates for ischemic stroke and intracerebral hemorrhage were 6.0% v 19.8% at 10 days, 10.6% v 22.1% at 28 days, 17.6% v 29.1% at 6 months, and 21.0% v 31.5% at 1 year. Illiteracy or no formal education was a predictor of death at 6 months (odds ratio [OR], 4.31; 95% confidence interval [CI] 1.34-13.91) and 1 year (OR, 4.21; 95% CI, 1.45-12.28) in patients with ischemic stroke, as well as at 6 months (OR, 3.19; 95% CI, 1.17-8.70) and 1 year (OR, 3.30; 95% CI, 1.30-8.45) for all stroke patients. Other variables, including previous cardiovascular risk factors and acute medical care, did not change this association to a statistically significant degree. In conclusion, case fatality, particularly up to 6 months, was higher in hemorrhagic stroke, and lack of formal education was associated with increased stroke mortality.

Expanding the horizontal capabilities of CRT monitors using artificial inter-pixel steps for neuroscience experiments

This article describes the development of a visual stimulus generator to be used in neuroscience experiments with invertebrates such as flies. The experiment consists in the visualization of a fixed image that is displaced horizontally according to the stimulus data. The system is capable of displaying 640 x 480 pixels with 256 intensity levels at 200 frames per second (FPS) on conventional raster monitors. To double the possible horizontal positioning possibilities from 640 to 1280, a novel technique is presented introducing artificial inter-pixel steps. The implementation consists in using two video frame buffers containing each a distinct view of the desired image pattern. This implementation generates a visual effect capable of doubling the horizontal positioning capabilities of the visual stimulus generator allowing more precise and movements more contiguous. (C) 2011 Elsevier Inc. All rights reserved.

Following the steps of spanish mathematical analysis: from Cauchy to Weierstrass between 1880 and 1914

[EN] Rigorous Mathematical Analysis in the Cauchy style was not accepted in a straightforward manner by the European mathematical community of the central years of the 19th Century. In average, only around forty years after the 1821 Cours d'Analyse did Cauchy's treatment become a standard in the more mathematically advanced countries, as a paradigm that remained in use until the arithmetisation of Analysis by Weierstrass replaced it before the end of the century. ln this paper the authors show how rigorous Mathematical Analysis à la Cauchy was adopted in Spain quite late -around 1880- and how in sorne more forty years, the Weierstrassian formulation became the usual presentation in Spanish texts

Magnetic properties of selected 3d- and 4f-systems on alpha-Al 2 O 3 substrates

In this work the growth and the magnetic properties of the transition metals molybdenum, niobium, and iron and of the highly-magnetostrictive C15 Laves phases of the RFe2 compounds (R: Rare earth metals: here Tb, Dy, and Tb{0.3}Dy{0.7} deposited on alpha-Al2O3 (sapphire) substrates are analyzed. Next to (11-20) (a-plane) oriented sapphire substrates mainly (10-10) (m-plane) oriented substrates were used. These show a pronounced facetting after high temperature annealing in air. Atomic force microscopy (AFM) measurements reveal a dependence of the height, width, and angle of the facets with the annealing temperature. The observed deviations of the facet angles with respect to the theoretical values of the sapphire (10-1-2) and (10-11) surfaces are explained by cross section high resolution transmission electron microscopy (HR-TEM) measurements. These show the plain formation of the (10-11) surface while the second, energy reduced (10-1-2) facet has a curved shape given by atomic steps of (10-1-2) layers and is formed completely solely at the facet ridges and valleys. Thin films of Mo and Nb, respectively, deposited by means of molecular beam epitaxy (MBE) reveal a non-twinned, (211)-oriented epitaxial growth as well on non-faceted as on faceted sapphire m-plane, as was shown by X-Ray and TEM evaluations. In the case of faceted sapphire the two bcc crystals overgrow the facets homogeneously. Here, the bcc (111) surface is nearly parallel to the sapphire (10-11) facet and the Mo/Nb (100) surface is nearly parallel to the sapphire (10-1-2) surface. (211)-oriented Nb templates on sapphire m-plane can be used for the non-twinned, (211)-oriented growth of RFe2 films by means of MBE. Again, the quality of the RFe2 films grown on faceted sapphire is almost equal to films on the non-faceted substrate. For comparison thin RFe2 films of the established (110) and (111) orientation were prepared. Magnetic and magnetoelastic measurements performed in a self designed setup reveal a high quality of the samples. No difference between samples with undulated and flat morphology can be observed. In addition to the preparation of covering, undulating thin films on faceted sapphire m-plane nanoscopic structures of Nb and Fe were prepared by shallow incidence MBE. The formation of the nanostructures can be explained by a shadowing of the atomic beam due to the facets in addition to de-wetting effects of the metals on the heated sapphire surface. Accordingly, the nanostructures form at the facet ridges and overgrow them. The morphology of the structures can be varied by deposition conditions as was shown for Fe. The shape of the structures vary from pearl-necklet strung spherical nanodots with a diameter of a few 10 nm to oval nanodots of a few 100 nm length to continuous nanowires. Magnetization measurements reveal uniaxial magnetic anisotropy with the easy axis of magnetization parallel to the facet ridges. The shape of the hysteresis is depending on the morphology of the structures. The magnetization reversal processes of the spherical and oval nanodots were simulated by micromagnetic modelling and can be explained by the formation of magnetic vortices.

Magnetization dynamics in spin valves

Key technology applications like magnetoresistive sensors or the Magnetic Random Access Memory (MRAM) require reproducible magnetic switching mechanisms. i.e. predefined remanent states. At the same time advanced magnetic recording schemes push the magnetic switching time into the gyromagnetic regime. According to the Landau-Lifschitz-Gilbert formalism, relevant questions herein are associated with magnetic excitations (eigenmodes) and damping processes in confined magnetic thin film structures.rnObjects of study in this thesis are antiparallel pinned synthetic spin valves as they are extensively used as read heads in today’s magnetic storage devices. In such devices a ferromagnetic layer of high coercivity is stabilized via an exchange bias field by an antiferromagnet. A second hard magnetic layer, separated by a non-magnetic spacer of defined thickness, aligns antiparallel to the first. The orientation of the magnetization vector in the third ferromagnetic NiFe layer of low coercivity - the freelayer - is then sensed by the Giant MagnetoResistance (GMR) effect. This thesis reports results of element specific Time Resolved Photo-Emission Electron Microscopy (TR-PEEM) to image the magnetization dynamics of the free layer alone via X-ray Circular Dichroism (XMCD) at the Ni-L3 X-ray absorption edge.rnThe ferromagnetic systems, i.e. micron-sized spin valve stacks of typically deltaR/R = 15% and Permalloy single layers, were deposited onto the pulse leading centre stripe of coplanar wave guides, built in thin film wafer technology. The ferromagnetic platelets have been applied with varying geometry (rectangles, ellipses and squares), lateral dimension (in the range of several micrometers) and orientation to the magnetic field pulse to study the magnetization behaviour in dependence of these magnitudes. The observation of magnetic switching processes in the gigahertz range became only possible due to the joined effort of producing ultra-short X-ray pulses at the synchrotron source BESSY II (operated in the so-called low-alpha mode) and optimizing the wave guide design of the samples for high frequency electromagnetic excitation (FWHM typically several 100 ps). Space and time resolution of the experiment could be reduced to d = 100 nm and deltat = 15 ps, respectively.rnIn conclusion, it could be shown that the magnetization dynamics of the free layer of a synthetic GMR spin valve stack deviates significantly from a simple phase coherent rotation. In fact, the dynamic response of the free layer is a superposition of an averaged critically damped precessional motion and localized higher order spin wave modes. In a square platelet a standing spin wave with a period of 600 ps (1.7 GHz) was observed. At a first glance, the damping coefficient was found to be independent of the shape of the spin-valve element, thus favouring the model of homogeneous rotation and damping. Only by building the difference in the magnetic rotation between the central region and the outer rim of the platelet, the spin wave becomes visible. As they provide an additional efficient channel for energy dissipation, spin waves contribute to a higher effective damping coefficient (alpha = 0.01). Damping and magnetic switching behaviour in spin valves thus depend on the geometry of the element. Micromagnetic simulations reproduce the observed higher-order spin wave mode.rnBesides the short-run behaviour of the magnetization of spin valves Permalloy single layers with thicknesses ranging from 3 to 40 nm have been studied. The phase velocity of a spin wave in a 3 nm thick ellipse could be determined to 8.100 m/s. In a rectangular structure exhibiting a Landau-Lifschitz like domain pattern, the speed of the field pulse induced displacement of a 90°-Néel wall has been determined to 15.000 m/s.rn

Early steps in ventral nerve cord development in chelicerates and myriapods and formation of brain compartments in spiders

The central point of this work is the investigation of neurogenesis in chelicerates and myriapods. By comparing decisive mechanisms in neurogenesis in the four arthropod groups (Chelicerata, Crustacea, Insecta, Myriapoda) I was able to show which of these mechanisms are conserved and which developmental modules have diverged. Thereby two processes of embryonic development of the central nervous system were brought into focus. On the one hand I studied early neurogenesis in the ventral nerve cord of the spiders Cupiennius salei and Achaearanea tepidariorum and the millipede Glomeris marginata and on the other hand the development of the brain in Cupiennius salei.rnWhile the nervous system of insects and crustaceans is formed by the progeny of single neural stem cells (neuroblasts), in chelicerates and myriapods whole groups of cells adopt the neural cell fate and give rise to the ventral nerve cord after their invagination. The detailed comparison of the positions and the number of the neural precursor groups within the neuromeres in chelicerates and myriapods showed that the pattern is almost identical which suggests that the neural precursors groups in these arthropod groups are homologous. This pattern is also very similar to the neuroblast pattern in insects. This raises the question if the mechanisms that confer regional identity to the neural precursors is conserved in arthropods although the mode of neural precursor formation is different. The analysis of the functions and expression patterns of genes which are known to be involved in this mechanism in Drosophila melanogaster showed that neural patterning is highly conserved in arthropods. But I also discovered differences in early neurogenesis which reflect modifications and adaptations in the development of the nervous systems in the different arthropod groups.rnThe embryonic development of the brain in chelicerates which was investigated for the first time in this work shows similarities but also some modifications to insects. In vertebrates and arthropods the adult brain is composed of distinct centres with different functions. Investigating how these centres, which are organised in smaller compartments, develop during embryogenesis was part of this work. By tracing the morphogenetic movements and analysing marker gene expressions I could show the formation of the visual brain centres from the single-layered precheliceral neuroectoderm. The optic ganglia, the mushroom bodies and the arcuate body (central body) are formed by large invaginations in the peripheral precheliceral neuroectoderm. This epithelium itself contains neural precursor groups which are assigned to the respective centres and thereby build the three-dimensional optical centres. The single neural precursor groups are distinguishable during this process leading to the assumption that they carry positional information which might subdivide the individual brain centres into smaller functional compartments.rn

Magnetization exchange with water and T(1) relaxation of the downfield resonances in human brain spectra at 3.0 T

The use of water suppression for in vivo proton MR spectroscopy diminishes the signal intensities from resonances that undergo magnetization exchange with water, particularly those downfield of water. To investigate these exchangeable resonances, an inversion transfer experiment was performed using the metabolite cycling technique for non-water-suppressed MR spectroscopy from a large brain voxel in 11 healthy volunteers at 3.0 T. The exchange rates of the most prominent peaks downfield of water were found to range from 0.5 to 8.9 s(-1), while the T(1) relaxation times in absence of exchange were found to range from 175 to 525 ms. These findings may help toward the assignments of the downfield resonances and a better understanding of the sources of contrast in chemical exchange saturation transfer imaging.