Data2Dynamics: a modeling environment tailored to parameter estimation in dynamical systems.

UNLABELLED: Modeling of dynamical systems using ordinary differential equations is a popular approach in the field of systems biology. Two of the most critical steps in this approach are to construct dynamical models of biochemical reaction networks for large datasets and complex experimental conditions and to perform efficient and reliable parameter estimation for model fitting. We present a modeling environment for MATLAB that pioneers these challenges. The numerically expensive parts of the calculations such as the solving of the differential equations and of the associated sensitivity system are parallelized and automatically compiled into efficient C code. A variety of parameter estimation algorithms as well as frequentist and Bayesian methods for uncertainty analysis have been implemented and used on a range of applications that lead to publications. AVAILABILITY AND IMPLEMENTATION: The Data2Dynamics modeling environment is MATLAB based, open source and freely available at http://www.data2dynamics.org. CONTACT: andreas.raue@fdm.uni-freiburg.de SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Defect structures in ZnO studied by high-resolution structural and spectroscopic imaging.

The formation of characteristic inversion domain structures in zinc oxide (ZnO) is triggered by the addition of trivalent Fe(3+) or In(3+) dopants. As-grown and inverted ZnO domains are separated by two types of inversion domain boundaries (IDBs): basal b-IDBs parallel to {0001}, and pyramidal p-IDBs parallel to {21¯1¯5} lattice planes in three equivalent variants. Cs-corrected analytical TEM/STEM is the method of choice for a comprehensive structural and compositional characterization of these materials. It is shown by electron and X-ray spectroscopic imaging in STEM that dopant species are essentially localized within both types of IDBs, whereas solid solubility of trivalent dopants within ZnO domains is rather low (<0.5at%). Under the assumption of one monolayer per IDB the relation between inversion domain structure and integral dopant concentration correlates well with integral EDS and EELS measurements in STEM over well defined sample regions. The presence of one close-packed monolayer of trivalent dopant ions within a b-IDB is unambiguously confirmed by atomic resolution STEM imaging. Columns of cations are clearly imaged in high-angle annular dark-field (HAADF) STEM imaging, whereas annular bright-field (ABF) STEM is capable of imaging both light and heavy atom columns simultaneously. It is shown that structural details in ABF images are directly interpretable even in specimen regions with thickness >50nm. The structural inversion associated with a stacking fault as a consequence of the presence of octahedrally coordinated In(3+) in the b-IDB is directly revealed by atomic resolution imaging. Column positions in atomic resolution ABF imaging in In2O3-ZnO nanorods show that the oxygen sub-lattice continues across the b-IDB with only marginal distortions, whereas the cation sub-lattice suffers a rigid shift relative to the oxygen lattice as a result of the coordination geometry of ZnO4 tetrahedrons sharing common oxygen ions with the InO6 coordination octahedrons.

Structural and elemental analysis of iron and indium doped zinc oxide by spectroscopic imaging in Cs-corrected STEM.

ZnO with additions of Fe2O3 or In2O3 shows characteristic inversion domain structures. ZnO domains are separated by two types of inversion domain boundaries (IDBs): basal b-IDBs parallel to (0001) planes, and complementary pairs of three possible variants of pyramidal p-IDBs parallel to {2115} lattice planes. The structure and composition of IDBs were investigated in a sophisticated aberration-corrected scanning transmission electron microscope (probe-corrected TEM/STEM). It is shown that Fe and In additions are essentially located in monolayers within the IDBs, and EELS electron spectroscopic imaging (ESI) as well as EDS spectroscopic imaging by X-rays (SIX) are capable of rapidly mapping the element distribution. With solid solubility of trivalent dopant species well below 1at.% within ZnO domains, the lateral spacings of b-IDBs are inversely proportional to the dopant concentration. Quantification of data acquired by ESI and SIX from well defined sample regions in STEM both confirm the assumption of one full monolayer of dopants per IDB. Atom columns of cations are well resolved in HAADF STEM imaging; experimental contrast intensities are approximately proportional to Z¹·6. Furthermore, annular bright-field (ABF)-STEM imaging is capable of resolving oxygen columns even in thick sample regions, thus providing highly localized information on atom positions and lattice distortions, and enables the construction of more reliable structure models of IDBs in doped ZnO.

Direct visualization of damage cascades in lithium niobate crystals caused by high-energy ions.

Congruently melting undoped lithium niobate crystals are irradiated with 20 MeV (3)He ions which penetrate the entire crystal volume. Radiation damage effects are directly visualized by transmission electron microscopy (TEM) where damage zones with diameters of 4 nm give rise to circular Fresnel fringe contrasts. These regions of modified material, appearing circular in cross-section, are interpreted as damage cascades inflicted by fast Nb and O atoms displaced in knock-on collisions with primary (3)He ions. This two-step displacement process results in local density changes manifested by the contrast behaviour of Fresnel fringes observed in TEM images.

Crystallinity of plant epicuticular waxes: electron and X-ray diffraction studies.

The crystal structure of the epicuticular waxes of 35 plant species has been examined by electron diffraction and X-ray powder diffraction. The waxes include the most common morphological wax types such as platelets, tubules, films and rodlets. Most of them were prepared with a special mechanical isolation method, which preserves the original crystal structure. Solvent-extracted recrystallized plant waxes were compared with mechanically isolated samples. The waxes were found to occur in three different crystal structures. Most of the waxes exhibited an orthorhombic structure which is the most common for aliphatic compounds. Tubules containing mainly secondary alcohols showed diffraction reflections of a triclinic phase; broad reflection peaks indicated a significant disorder. Ketones, in particular beta-diketone tubules, displayed the reflections of a hexagonal structure. Mixtures of different phases could be identified. For most of the waxes, the 'long spacing' diffraction reflections indicated a layer structure with the characteristics of the major component. Others showed no 'long spacing' reflections indicating a strong disorder of the molecular layers.

Oxidation states of Mn and Fe in various compound oxide systems.

Energy-loss near-edge structure (ELNES) data of Mn-L(2,3) and Fe-L(2,3) ionization edges have been measured by means of quantitative electron energy-loss spectroscopy (EELS) for two series of Mn and Fe oxides with known formal cation oxidation states. In both series the absolute energy positions of Mn-L(2,3) and Fe-L(2,3) white-lines, as well as the white-line intensity ratio (L3/L2) vary with cation oxidation states. Additionally, spin-orbit spitting, i.e. the energy difference deltaE(L2-L3) between Mn-L(2,3) white-lines decreases with increasing Mn oxidation state. With these data from known standards calibration curves on white-line intensity ratio Mn(L3/L2) vs. Mn oxidation state, and Fe(L3/L2) vs. Fe oxidation state were established. EELS measurements on Mn and Fe doped ZnO thin films showed that the valence states of the dopants can unambiguously be determined by calibrating the Mn-L(2,3) and Fe-L(2,3) ELNES data against the measured standards. It is revealed that Mn in ZnO adopt a divalent state, thus Mn2+ ions substitute for Zn2+, whereas Fe dopants retain a trivalent oxidation state in the ZnO host lattice. Measurements on (Ba, Fe, Mn)-oxides revealed that both Fe and Mn cations are in a trivalent state. Thus, it is assumed that Mn3+ can partially be substituted for Fe3+ in barium hexaferrites.

Critical assessment of the speckle statistics in fluctuation electron microscopy and comparison to electron diffraction.

The technique of fluctuation electron microscopy (FEM) is applied to thin films of amorphous germanium and of polycrystalline gold in a transmission electron microscope. Even though the method was introduced as a tool for quantitative analysis of structural fluctuations in amorphous materials, the basic principles are applicable to any disordered specimen independent of the dimension of disorder. Hence, we extended the technique of FEM to a well-known specimen, gold, whereby it was possible to reinterpret the results of the measurements on amorphous germanium. The hollow-cone dark field images, the statistical analysis of which is the basis of FEM, are examined with respect to the effects of frequency filtering, and are compared to electron diffraction. We find that the angular dependence of the normalised variance, as measured by FEM, yields information similar to the average intensity of hollow-cone dark field image series. Both plots are basically identical to a scan through a selected-area diffraction pattern convoluted by the corresponding angular resolution function. Hence, it appears questionable whether standard FEM analysis provides more information than the classical pair distribution function, which is experimentally limited to short-range order. Frequency selective analysis of the normalised variance, however, gives supplementary information on preferred inter-atomic distances related to the medium-range order of the specimen.

Biochemical properties of the fibrinogen component of a fibrin glue before and after severe dry heat treatment.

Functional biochemical properties of 5 batches of the fibrinogen component of a fibrin glue produced by the ZLB Central Laboratory, Bern, each consisting of 4 different in-process samples (taken after the first and second precipitation step, lyophilization, and dry-heat treatment) were studied in vitro. We focused our attention on the effect of the anti-viral treatment of the lyophilized product by dry heat for 1 h at 100 degrees C. A slight reduction in maximal turbidity of all heat-treated samples was observed during the clotting assay compared to nontreated samples. Treatment with dry heat did not result in generation of fibrinogen fragments that might accelerate tissue-plasminogen-activator (t-PA)-enhanced plasminogen to plasmin conversion. The time course of fibrin cross-linking by factor XIII showed no differences between heated and unheated samples. This result indicates that exposure of the fibrinogen component to severe heat neither reduced activity of factor XIIIa nor affected the correct alignment of cross-linking sites in polymerized fibrin. Incubation of fibrinogen with thrombin, plasminogen, and t-PA resulted in a slightly enhanced degradation of fibrin derived from the heat-treated samples. The amount of residual moisture, determined to be within the range of 0.6-2.1% before heat treatment, did not influence clotting, cross-linking, and fibrinolysis parameters. In conclusion, the virus inactivation treatment by dry heat for 1 h at 100 degrees C induces no significant alterations of the in vitro biochemical properties of the fibrinogen component of this fibrin glue.

Measurement of lens aberrations by means of image displacements in beam-tilt series

Electron microscope image aberrations are determined by means of the beam tilt/image displacement method with respect to the precision required to obtain a resolution of 1 A. The method simultaneously yields all image aberrations to the fourth order and it is independent of the material used for the procedure. The experimental procedure using amorphous carbon is described and errors in measuring beam-tilt angles, magnifications and image displacements can be kept sufficiently small to achieve the required accuracy. The method is applied to determine aberration constants of a CM300 FEG/UT microscope with correction of the three-fold astigmatism. The coefficient of spherical aberration and the modulus of the three-fold astigmatism were measured to 0.60 (+/- 0.02) mm and 150 (+/- 50) nm, respectively. The beam tilt/image displacement procedure is also computer simulated using an amorphous model structure yielding the same values for the lens aberrations which are used for imaging. However, a coefficient of spherical aberration of 0.67 mm is obtained by applying the focus variation/diffractogram analysis on the same model.

Element specific imaging with high lateral resolution: an experimental study on layer structures.

Planar defects and individual layers in ceramic material are chemically imaged by high resolution energy-filtering TEM using a post-column imaging electron energy filter. Objects are barium layers in the cuprate superconductor NdBa2Cu3O7-delta (isostructual to YBa2Cu3O7-delta) as well as planar defects and precipitates of beta-WB in tungsten- and chromium-doped TiB2. The barium layers with a spacing of 0.42 nm in the cuprate are resolved in jump-ratio images using the Ba_N edge. In the boride system the beta-WB precipitates with thickness of 0.8 nm can be chemically imaged in elemental maps of B_K, Ti_L,Cr_L and W_M. The B as well as the Ti map show a decrease in intensity at the precipitates, whereas in the W map an increase in intensity is observed. The boron-deficient layers with a spacing of 0.38 nm in the beta-WB precipitate can be resolved in boron jump-ratio images. Additionally, defects containing single boron-deficient layers are chemically imaged. Hence structures in the dimension of interatomic distances can be imaged with respect to their elemental constituents. Although high resolution electron spectroscopic images contain strong interference contrast from elastic scattering, after normalization or background subtraction the element specific images are dominated by chemical contrast.

Physiological and anatomical identification of the nucleus of the optic tract and dorsal terminal nucleus of the accessory optic tract in monkeys.

Physiological and anatomical criteria were used to clearly establish the existence of a pretectal relay of visual information to the ipsilateral inferior olive in the macaque monkey. After injection of horseradish peroxidase into the inferior olivary nucleus, retrogradely labelled neurons were found in the nucleus of the optic tract (NOT) and the dorsal terminal nucleus of the accessory optic tract (DTN). The labelled cells were distributed in a sparse band arching below the margin of the brachium of the superior colliculus between the dorsal and lateral borders of the brainstem at the caudal edge of the pulvinar. Various types of cells could be distinguished. More superficially the cells were extremely spindle shaped, cells deeper within the midbrain had more compact somata. NOT-DTN neurons in the same region were also found to respond with short latencies to electrical stimulation of both the inferior olive and the optic chiasm. All neurons in the NOT-DTN which were antidromically activated from the inferior olive were also found to have direction specific binocular visual responses. Such neurons were excited by ipsiversive motion and suppressed by contraversive motion, regardless of whether large area random dot stimuli moved across the visual field or small single dots moved across the fovea. Direct retinal input to these neurons was via slowly conducting fibers (3-9 m/s) from the monkey's optic tract conduction velocity spectrum. As shown previously for non-primates, NOT-DTN cells may also in the monkey carry a signal representing the velocity error between stimulus and retina (retinal slip), and relay this signal into the circuitry mediating the optokinetic reflex.

[Prospective study on the effect of various preparations of 1% mepivacaine solutions without preservatives]. / Prospektive Studie über den Einfluss verschiedener Zubereitungen von 1%igen Mepivacainlösungen ohne Konservierungsmittel.

On 30 volunteers the pain sensitivity and macroscopic changes at the area of intracutaneous injection of 1% mepivacain solutions without adrenalin (and a sodium chloride reference solution) were investigated. It was found that the injection of solutions with only sodium chloride as ingredient were relatively pain sensitive, whereas the injection of preparations which contained also calcium chloride or this alone were much more comfortable. Clinically relevant side effects at the site of injection were not seen for any of the used solutions.