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Die zerebrale Sinusthrombose kann eine vielfaltige Symptomatik mit entsprechend schwieriger Diagnosestellung aufweisen. Es existieren nur wenige evidenzbasierte Daten bezuglich Therapie und Prognose, insbesondere bezuglich tiefer Hirnvenen. Bei der Thrombose der Vena Galeni wird eine schlechtere Prognose angenommen. Unser Fallbericht beschreibt die lokale kombinierte neurointerventionelle Therapie als individueller Heilversuch bei fulminantem Verlauf.

We present the first copper iridium binary metal oxide with the chemical formula Cu

Direct ink writing enables the layer-by-layer manufacture of ordered, porous structures whose mechanical behavior is driven by architecture and material properties. Here, we incorporate two different gas filled microsphere pore formers to evaluate the effect of shell stiffness and Tg on compressive behavior and compression set in siloxane matrix printed structures. The lower Tg microsphere structures exhibit substantial compression set when heated near and above Tg, with full structural recovery upon reheating without constraint. By contrast, the higher Tg microsphere structures exhibit reduced compression set with no recovery upon reheating. Aside from their role in tuning the mechanical behavior of direct ink write structures, polymer microspheres are good candidates for shape memory elastomers requiring structural complexity, with potential applications toward tandem shape memory polymers.

A representative spiro[benzopyran-isoxazole], 3′-(3,4-dimethoxyphenyl)-N,N-diethyl-4-methyl-4′H-spiro[2H-1-benzopyran-2,5′-isoxazol]-7-amine 3a, was submitted for single crystal X-ray analysis. It has been prepared by the condensation–cyclization of dilithiated C(α),O-3′,4′-dimethoxyacetophenone oxime with a substituted coumarin, 7-(diethylamino)-4-methyl-2H-1-benzopyran-2-one. This results from the 1,2-carbonyl addition, Claisen type, of the dilithiated oxime with this coumarin ester carbonyl to afford C-acylated intermediates that were not isolated, but were acid cyclized to the spiro[benzopyran-isoxazoles], a new spiro heterocyclic system. There was no evidence for Michael-type 1,4-addition found during this initial investigation. An indication that the experimental multiple anion procedure is general, has been the preparation of two additional spiro(benzopyran-isoxazoles) 3b and 3c. Crystals of C24H28N2O4 3a are triclinic, $$p\bar{1}$$ , a = 9.161(2) A, b = 9.716(2) A, c = 12.869(3) A, α = 75.84(3)°, β = 81.03(3)°, γ = 73.96(3)°, Z = 2, V = 1062.5(4) A3, R 1 = 0.0539 and wR 2 = 0.1366 for reflections with I > 2σ(I). X-ray crystal analysis confirmed the structure of 3′-(3,4-dimethoxyphenyl)-N,N-diethyl-4-methyl-4′H-spiro(2H-1-benzopyran-2,5′-isoxazol)-7-amine prepared by the condensation–cyclization of dilithiated C(α),O-3′,4′-dimethoxyacetophenone oxime with a substituted coumarin, 7-(diethylamino)-4-methyl-2H-1-benzopyran-2-one.

Three-dimensional printing of viscoelastic inks to create porous, elastomeric architectures with mechanical properties governed by the ordered arrangement of their sub-millimeter struts is reported. Two layouts are patterned, one resembling a “simple cubic” (SC)-like structure and another akin to a “face-centered tetragonal” (FCT) configuration. These structures exhibit markedly distinct load response with directionally dependent behavior, including negative stiffness. More broadly, these findings suggest the ability to independently tailor mechanical response in cellular solids via micro-architected design. Such ordered materials may one day replace random foams in mechanical energy absorption applications.

The 2008 wildfires in the Big Sur region of California’s central coast—the first to occur in forests impacted by Phytophthora ramorum, the non-native, invasive pathogen that causes sudden oak death—provided the rare opportunity to study the response of scolytid and other subcortical beetles to this novel disturbance interaction. We used sticky card traps attached to the main stem of tanoak, Notholithocarpus densiflorus, the tree species most susceptible to P. ramorum, to determine which subcortical beetle species may be using tanoak as a host and to compare insect landing rates on these trees in forest plots impacted by neither disturbance, either wildfire or P. ramorum disturbance alone, or both disturbances combined. Xyleborinus saxesenii and Gnathotrichus pilosus, two species of ambrosia beetles (Coleoptera: Scolytidae), composed the majority (48% and 40%, respectively) of subcortical beetles landing on tanoaks during both years of the study. Adults of two species of a small, branch-feeding flatheaded borer (Anthaxia sp.; Coleoptera: Buprestidae) were also captured in relative abundance landing on tanoaks in the combined disturbance plots during the second year of the study. All but two of the 2779 scolytid beetles collected in this study were trapped on tanoaks in forest plots disturbed by P. ramorum and/or fire, and 75% of these scolytids were trapped during the fall 2009 season. The majority of scolytids were trapped on tanoaks in plots containing both disturbances (81% in 2009 and 79% in 2010), and, of the two disturbances, more scolytids were trapped on tanoaks in burned plots than in P. ramorum-infested plots (92% more in 2009 and 476% more in 2010). Semiochemicals emanating from the tanoaks upon which the sticky cards were attached—either in the form of host volatile compounds or scolytid aggregation pheromones—presumably affected ambrosia beetle landing rates, and greater quantities of moribund and recently-killed trees in the plots disturbed both by P. ramorum and fire may have led to greater population densities of ambrosia beetles in these areas. Our findings of elevated ambrosia beetle landing rates in Big Sur forests with mixed disturbances suggest a heightened threat to tanoak in these areas, but additional research is needed to determine the actual frequency of ambrosia beetle gallery initiation in living tanoaks and whether colonization hastens or leads to tree mortality.

1-Benzoylacetone 1 was dilithiated with lithium diisopropylamide or lithium hexamethyl-disilazide, and the resulting dianion type intermediate 1a was condensed with (lithium) 4-hydroxybenzaldehyde, 4-dimethylaminobenzaldehyde, or 4-chlorobenzaldehyde to afford hydroxyl-β-diketones that were not isolated but underwent linear dehydration to afford products, (2Z,4E)-5-(4-hydroxyphenyl)-3-hydroxy-1-phenylpenta-2,4-dien-1-one 2 C17H14O3; (2Z,4E)-5-(4-(dimethylamino)phenyl)-3-hydroxy-1-phenylpenta-2,4-dien-1-one 3 C19H19NO2; and (2Z,4E)-5-(4-chlorophenyl)-3-hydroxy-1-phenylpenta-2,4-dien-1-one 4 C17H13ClO2. Crystals of C17H14O3 2 are orthorhombic, Pna21, a = 20.937(4) A, b = 11.683(3) A, c = 5.490(1) A, Z = 4, V = 1343.1(5) A3, R 1 = 0.0478 and wR 2 = 0.1143 for reflections with I > 2σ(I); crystals of C19H19NO2 3 are monoclinic, P21/c, a = 16.637(3) A, b = 10.736(2) A, c = 9.197(1) A, β = 105.670(5)°, Z = 4, V = 1581.7(5) A3, R 1 = 0.0609 and wR 2 = 0.1491 for reflections with I > 2σ(I); crystals of C17H13 ClO2 4 are monoclinic, P21/c, a = 31.574(6) A, b = 5.780(1) A, c = 7.423(2) A, β = 94.47(3)°, Z = 4, V = 1350.5(5) A3, R 1 = 0.0696 and wR 2 = 0.2423 for reflections with I > 2σ(I). X-ray crystal analysis was essential for identifying which tautomer resulted from the condensation-elimination of dilithiated 1-benzoylacetone with select substituted benzaldehydes to form curcumin analogs, (2Z,4E)-5-(4-substituted phenyl)-3-hydroxy-1-phenylpenta-2,4-dien-1-ones. Each crystalline compound showed the same curcumin-enol bonding structural features.

BACKGROUND Many tropical forest tree species delay greening their leaves until full expansion. This strategy is thought to provide newly flushing leaves with protection against damage by herbivores by keeping young leaves devoid of nutritive value. Because young leaves suffer the greatest predation from invertebrate herbivores, delayed greening could prevent costly tissue loss. Many species that delay greening also produce anthocyanin pigments in their new leaves, giving them a reddish tint. These anthocyanins may be fungicidal, protect leaves against UV damage or make leaves cryptic to herbivores blind to the red part of the spectrum. METHODS A comprehensive survey was undertaken of seedlings, saplings and mature trees in two diverse tropical forests: a rain forest in western Amazonia (Yasuni National Park, Ecuador) and a deciduous forest in Central America (Barro Colorado Island, Panama). A test was made of whether individuals and species with delayed greening or red-coloured young leaves showed lower mortality or higher relative growth rates than species that did not. KEY RESULTS At both Yasuni and Barro Colorado Island, species with delayed greening or red young leaves comprised significant proportions of the seedling and tree communities. At both sites, significantly lower mortality was found in seedlings and trees with delayed greening and red-coloured young leaves. While there was little effect of leaf colour on the production of new leaves of seedlings, diameter relative growth rates of small trees were lower in species with delayed greening and red-coloured young leaves than in species with regular green leaves, and this effect remained when the trade-off between mortality and growth was accounted for. CONCLUSIONS Herbivores exert strong selection pressure on seedlings for the expression of defence traits. A delayed greening or red-coloured young leaf strategy in seedlings appears to be associated with higher survival for a given growth rate, and may thus influence the species composition of later life stages.

The geographic range of tanoak, Notholithocarpus densiflorus (Hook. & Arn.) Manos, Cannon & S. H. Oh (Fagaceae), encompasses tremendous physiographic variability, diverse plant communities, and complex disturbance regimes (e.g., development, timber harvest, and wildfire) that now also include serious threats posed by the invasive forest pathogen Phytophthora ramorum S. Werres, A.W.A.M. de Cock. Knowing where these disturbance factors interact is critical for developing comprehensive strategies for conserving the abundance, structure, and function of at-risk tanoak communities. In this study, we present a rule-based spatial model of the range-wide threat to tanoak populations from four disturbance factors that were parameterized to encode their additive effects and two-way interactions. Within a GIS, we mapped threats posed by silvicultural activities; disease caused by P. ramorum; human development; and altered fire regimes across the geographic range of tanoak, and we integrated spatially coinciding disturbances to quantify and map the additive and interacting threats to tanoak. We classified the majority of tanoak's range at low risk (3.7 million ha) from disturbance interactions, with smaller areas at intermediate (222,795 ha), and high (10,905 ha) risk. Elevated risk levels resulted from the interaction of disease and silviculture factors over small extents in northern California and southwest Oregon that included parts of Hoopa and Yurok tribal lands. Our results illustrate tanoak populations at risk from these interacting disturbances based on one set of hypothesized relationships. The model can be extended to other species affected by these factors, used as a guide for future research, and is a point of departure for developing a comprehensive understanding of threats to tanoak populations. Identifying the geographic location of disturbance interactions and risks to foundation species such as tanoak is critical for prioritizing and targeting conservation treatments with limited resources.

Human activities and climate change have altered historical disturbance regimes, introduced disturbances, and encouraged novel interactions between multiple disturbances. Ecosystems and the species that comprise them may be poorly equipped to withstand or recover from these altered disturbance regimes. In the fire-prone coastal forests of California and Oregon, sudden oak death (SOD), caused by the pathogen Phytophthora ramorum, is an emerging, non-native plant disease that causes widespread tree mortality and associated implications for fire regimes. Disease-related tree mortality alters fuel loads, with patterns of fuel accumulation varying depending on stand composition, disease severity, and time since pathogen invasion. Simulations and observational studies suggest these altered fuel profiles can impact subsequent fire behavior, and the extent of this interaction may depend on the severity and timing of disease impacts. Initial tree death can elevate the risk of crown ignition, while latter stages can increase surface fuel loading and have been linked to increased fire severity in wildfires. Further, disease history can also influence fire severity with cascading effects leading to unexpected increases in mortality of non-susceptible tree species and changes in nutrient cycling. The longer-term impacts of SOD-fire interactions on system resilience and recovery remain to be seen, but increased fire severity, changed stand structure, and altered biogeochemical cycling may have important consequences for post-fire regeneration and future ecosystem function. Fuels management strategies that diminish crown fire hazards at early stages and mitigate surface fuel hazards at later stages offer some promise, but have yet to be tested in large landscapes. Given SOD-wildfire interactions, further integration of disease- and fire-related management plans will be essential to minimizing impacts of these compounded disturbances.

In the Peruvian Amazon, white-sand forests are patchily distributed and restricted to a few localities in the North. Although recent studies have documented patterns of habitat specialization by plants in these unique forests, very few studies of the fauna of these habitats have been conducted. The species composition of the avifauna of the white-sand forests at six localities in the region was sampled by conducting transects and point counts. Surrounding habitats were also sampled to compare avifaunal communities and to determine the degree of restriction of bird species to white-sand habitats. Non-metric multidimensional scaling analysis showed that bird communities of white-sand forests were more similar to each other than they were to terra firme or flooded forest communities. Sites on either side of the Amazon-Mara~� barrier were the most similar within habitat type consistent with the hypothesis that these rivers represent a major biogeographic barrier. Twenty-six species, belonging to 13 families, were to some degree specialized to white-sand forests. This is the first comprehensive ornithological assessment carried out on these habitats in Peru. The high degree of habitat specialization found in these 26 bird species highlights the need for conservation and management measures that will protect white-sand forests.

Dow Corning SE 1700 (reinforced polydimethylsiloxane) porous structures were made by direct ink writing (DIW) in a simple cubic (SC) configuration. The filament diameter was 250 μm. Structures consisting of 4, 8, or 12 layers were fabricated with center-to-center filament spacing (“road width” (RW)) of 475, 500, 525, 550, or 575 μm. Three compressive load-unload cycles to 2000 kPa were performed on four separate areas of each sample; three samples of each thickness and filament spacing were tested. Geometry-dependent buckling of the SC structure was evident. At a given strain during the third loading phase, stress varied inversely with porosity. At strains of 25% and higher, the stress varied inversely with the number of layers (i.e., thickness); however, the relationship between stress and number of layers was more complex at lower strains. Intra-and inter-sample variability of the load deflection response was higher for thinner and less porous structures.

Dow Corning SE 1700 (reinforced polydimethylsiloxane) porous structures were made by direct ink writing (DIW) in a face centered tetragonal (FCT) configuration. The filament diameter was 250 μm. Structures consisting of 4, 8, or 12 layers were fabricated with center-to-center filament spacing (“road width” (RW)) of 475, 500, 525, 550, or 575 μm. Three compressive load-unload cycles to 2000 kPa were performed on four separate areas of each sample; three samples of each thickness and filament spacing were tested. At a given strain during the third loading phase, stress varied inversely with porosity. At 10% strain, the stress was nearly independent of the number of layers (i.e., thickness). At higher strains (20- 40%), the stress was highest for the 4-layer structure; the 8- and 12-layer structures were nearly equivalent suggesting that the load deflection is independent of number of layers above 8 layers. Intra-and inter-sample variability of the load deflection response was higher for thinner and less porous structures.

Summary The first wildfires in sudden oak death-impacted forests occurred in 2008 in the Big Sur region of California, creating the rare opportunity to study the interaction between an invasive forest pathogen and a historically recurring disturbance. To determine whether and how the sudden oak death pathogen, Phytophthora ramorum, survived the wildfires, we completed intensive vegetation-based surveys in forest plots that were known to be infested before the wildfires. We then used 24 plot-based variables as predictors of P. ramorum recovery following the wildfires. The likelihood of recovering P. ramorum from burned plots was lower than in unburned plots both 1 and 2 yr following the fires. Post-fire recovery of P. ramorum in burned plots was positively correlated with the number of pre-fire symptomatic California bay laurel (Umbellularia californica), the key sporulating host for this pathogen, and negatively correlated with post-fire bay laurel mortality levels. Patchy burn patterns that left green, P. ramorum-infected bay laurel amidst the charred landscape may have allowed these trees to serve as inoculum reservoirs that could lead to the infection of newly sprouting vegetation, further highlighting the importance of bay laurel in the sudden oak death disease cycle.

2-Methylbenzoic acid phenylhydrazide was polylithiated with excess lithium diisopropylamide, and the resulting polylithiated intermediate was condensed with methyl 4-dimethylaminobenzoate or methyl 4-methoxybenzoate to afford C-acylated intermediates that were immediately acid cyclized to afford 3-(4-(dimethylamino)-phenyl)-2-(phenylamino)isoquinolin-1(2H)-one C23H21N3O or 3-(4-methoxyphenyl)-2-(phenylamino)isoquinolin-1(2H)-one C22H18N2O2. The polylithiated intermediate underwent N-acylation when it was condensed with methyl 4-methylbenzoate to give 2-methyl-N′-(4-methylbenzoyl)-N′-phenylbenzohydrazide C22H20N2O2. Crystals of C23H21N3O 4a are triclinic, P $$ \overline{1} $$ , a = 9.138(2) A, b = 10.519(2) A, c = 11.082(2) A, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) A3, R 1 = 0.0711 and wR 2 = 0.1828 for reflections with I > 2σ(I); crystals of C22H18N2O2 4b are monoclinic, P21/c, a = 8.821(1) A, b = 13.276(2) A, c = 15.482(3) A, β = 105.271(4)°, Z = 4, V = 1748.9(5) A3, R 1 = 0.0416 and wR 2 = 0.1030 for reflections with I > 2σ(I); crystals of C22H20N2O2 3 are orthorhombic, Pbca, a = 13.505(3) A, b = 9.733(2) A, c = 28.601(6) A, Z = 8, V = 3759.4(13) A3, R 1 = 0.1683 and wR 2 = 0.3526 for reflections with I > 2σ(I). X-ray crystal analysis was important for the confirmation of the structure of 3-(4-(dimethylamino)phenyl)-2-(phenylamino)isoquinolin-1(2H)-one C23H21N3O 4a, 3-(4-methoxyphenyl)-2-(phenylamino)isoquinolin-1(2H)-one C22H18N2O2 4b, and 2-methyl-N′-(4-methylbenzoyl)-N′-phenylbenzohydrazide C22H20N2O2 3 prepared from polylithiated 2-methylbenzoicacid phenylhydrazide and methyl 4-dimethylaminobenzoate, methyl 4-methoxybenzoate, or methyl 4-methylbenzoate. Crystals of C23H21N3O 4a are triclinic, P $$ \overline{1} $$ , a = 9.138(2) A, b = 10.519(2) A, c = 11.082(2) A, α = 91.55(3)°, β = 108.92(3)°, γ = 111.16(3)°, Z = 2, V = 927.1(3) A3, R 1 = 0.0711 and wR 2 = 0.1828 for reflections with I > 2σ(I); crystals of C22H18N2O2 4b are monoclinic, P21/c, a = 8.821(1) A, b = 13.276(2) A, c = 15.482(3) A, β = 105.271(4)°, Z = 4, V = 1748.9(5) A3, R 1 = 0.0416 and wR 2 = 0.1030 for reflections with I > 2σ(I); crystals of C22H20N2O2 3 are orthorhombic, Pbca, a = 13.505(3) A, b = 9.733(2) A, c = 28.601(6) A, Z = 8, V = 3759.4(13) A3, R 1 = 0.1683 and wR 2 = 0.3526 for reflections with I > 2σ(I).

Summary With growing incidence of bone disorders (such as osteoporosis), the demand for fast and reliable alternatives to existing screens based on mammalian bone is increasing. Cell culture-based models that currently are being used, have limited value in the study of cell-cell and cell-matrix interactions. The dermal bone of fish scales offers an unprecedented and attractive model to study bone physiology, both in vivo and in vitro. The elasmoid scale of teleost fishes is of particular interest as it could stand as a model for direct bone formation as found in mammals and it has many advantageous traits: scales carry both bone-forming and bone-degrading cell populations, attached on their natural substrate, such that interactions between cell populations remain intact. The scale contains a collagen type-I matrix impregnated with apatites. Scales come in the hundreds per fish, are easily harvested and can be exposed in vitro for direct study of bone regulatory compounds. Scales are transparent allowing real-time visualization of cellular activities on either side of the scale. Removed scales are replaced quickly and the regeneration process strongly resembles osteogenesis as seen in early bone development. These advantages warrant more fundamental research on scales as models in biomedical bone research. We here address the state-of-the-art on development, structure and physiology of fish scales.

Summary Collagen matrices, mineralized with calcium phosphates in a hydroxyapatite phase, are generally found in skeletal tissues. However, mechanisms of biomineral formation and regulation are still poorly understood. Elasmoid scales are part of the dermal skeleton and regenerate quickly when damaged or lost. This makes the scale a convenient target to study mineral compostion and formation. The X-ray diffractogram of the mineral layer of carp scales only show speaks corresponding with hydroxyapatite. Energy-dispersive X-ray spectroscopy (EDX) during scanning electron microscopy identifies the elements calcium and phosphorus, which are restricted to the external layer of the scale. In contrast with various other species, calcium phosphate crystals are not present in the elasmodine layer. The clean boundary between calcified and uncalcified matrix suggests that subsequental mineralization of the elasmodine layer is inhibited. Quantification of the calcium and phosphorus content allows definition of a calcium/phosphorus ratio, which is indicative ofthe crystalline phase of the minerals. Through accurate measurements of total calcium and phosphorus (by ICP-MS) in zebrafish scales, different ratios were found for newly formed (regenerating) scales compared to ontogenetic or completely regenerated scales. This shows that the mineral is not at first deposited as hydroxyapatite, but in a precursor phase. Although the nature of the phase remains to be established, this first analysis shows that cyprinids scales can easily be used to gain insights in the dynamics of biomineralization.

Summary 1. One of the earliest hypotheses to explain high tropical forest diversity proposes that species are differentially specialized in their germination or growth and survival to particular habitats. 2. I examined evidence for habitat associations in seedling density and demography in 9 years of seedling dynamics data from Yasuni National Park, Ecuador, a lowland rain forest where previous studies have demonstrated habitat preferences among adult trees. I included 136 species or morphospecies from multiple annual seedling cohorts with known age of recruitment. 3. Approximately 90% of the species examined demonstrated negative or positive associations with one or more topographic habitats in their recruitment, growth and/or mortality at some point in the study, and approximately 60% of species had significant associations in at least half of the census periods studied. The survival of newly recruited seedlings varied among seedlings in response to topographic gradients, indicating the potential for species to partition habitat niches at a young stage. 4. There was significant inter-annual variation in seedling habitat associations, indicating the characteristics of the topographic niche important to seedling performance change through time. This variability alone can contribute to the maintenance of species diversity through storage effects. While associations may also be weak or ephemeral, the seedling dynamics for many species supported the possibility that associations seen in adult populations develop through differential mortality across habitats as seedlings. 5. Synthesis. That species’ seedlings perform differently among topographic habitats and that these differences are detectable very early on in a plant’s life indicate the potential for the abiotic environment to mediate or exaggerate the roles of other mechanisms in influencing the composition of the understorey seedling assemblage.

In this paper we describe an ongoing project where the goal is to develop competence and confidence among chemistry faculty so they are able to utilize computational chemistry as an effective teaching tool. Advances in hardware and software have made research-grade tools readily available to the academic community. Training is required so that faculty can take full advantage of this technology, begin to transform the educational landscape, and attract more students to the study of science.

Magnetic van der Waals (vdW) materials are the centerpiece of atomically thin devices with spintronic and optoelectronic functions. Exploring new chemistry paths to tune their magnetic and optical properties enables significant progress in fabricating heterostructures and ultracompact devices by mechanical exfoliation. The key parameter to sustain ferromagnetism in 2D is magnetic anisotropy-a tendency of spins to align in a certain crystallographic direction known as easy-axis. In layered materials, two limits of easy-axis are in-plane (XY) and out-of-plane (Ising). Light polarization and the helicity of topological states can couple to magnetic anisotropy with promising photoluminescence or spin-orbitronic functions. Here, a unique experiment is designed to control the easy-axis, the magnetic transition temperature, and the optical gap simultaneously in a series of CrCl3-x Brx crystals between CrCl3 with XY and CrBr3 with Ising anisotropy. The easy-axis is controlled between the two limits by varying spin-orbit coupling with the Br content in CrCl3-x Brx . The optical gap, magnetic transition temperature, and interlayer spacing are all tuned linearly with x. This is the first report of controlling exchange anisotropy in a layered crystal and the first unveiling of mixed halide chemistry as a powerful technique to produce functional materials for spintronic devices.

(E)-Phenyl 2-(3,4-dihydro-1(2H)-naphthalenylidine)hydrazinecarboxylate and (E)-phenyl (2,4-dichlorophenylmethylene)hydrazinecarboxylate were prepared by the condensation of 1-tetralone or 2,4-dichlorobenzaldehyde with phenyl hydrazinecarboxylate. Crystals of C17H16N2O2 3 are monoclinic, C2/c, a = 17.763(4) A, b = 8.353(2) A, c = 40.233(8) A, Z = 16, V = 5,839(2) A3, R 1 = 0.0448 and wR 2 = 0.1104 for reflections with I > 2σ(I). Crystals of C14H10N2O2Cl2 5 are orthorhombic, P212121, a = 8.288(3) A, b = 14.082(2) A, c = 23.788(5) A, Z = 8, V = 2,777(1) A3, R 1 = 0.0815 and wR 2 = 0.2006 for reflections with I > 2σ(I). The molecular packing in the crystal for both compounds is the result of N–H···O hydrogen bonding. X-ray crystal analysis was important for the confirmation of the structure of phenyl 2-(3,4-dihydro-1(2H)-naphthalenylidine)hydrazinecarboxylate and phenyl (2,4-dichlorophenylmethylene)hydrazinecarboxylate that have been prepared by the 1:1 condensation of 1-tetralone or 2,4-dichlorobenzaldehyde with phenyl hydrazinecarboxylate.

A new type of substituted benzothiopyranone, 3-phenyl-2-(2-phenylhydrazino)-4H-1-benzothiopyran-4-one, has been prepared by the condensation-acid cyclization of polylithiated phenylacetic acid phenylhydrazide with lithiated methyl thiosalicylate. Absorption spectra, especially 13C NMR, provided good indication of its structure, which was conclusively established with X-ray crystal structure analysis. In comparison to the few benzothiopyran X-ray reports documented, the benzothiopyranone ring of the molecule was found to be essentially planar, with the 3-phenyl ring nearly perpendicular to the benzothiopyranone fused-ring system. Crystals of C21H16N2OS are orthorhombic, P212121, a = 10.140(4) A, b = 10.432(4) A, c = 16.228(7) A, Z = 4, V = 1717(1) A3, R 1 = 0.0267 and wR 2 = 0.0725 for reflections with I > 2σ(I). The molecular packing in the crystal is the result of N–H···O hydrogen bonding. X-ray crystal analysis confirmed the structure of 3-phenyl-2-(2-phenylhydrazino)-4H-1-benzothiopyran-4-one prepared by the condensation–cyclization of polylithiated phenylacetic acid phenylhydrazide with lithiated methyl thiosalicylate.

Dilithiated C(α), N-carbomethoxyhydrazones were condensed with lithiated methyl 2-(aminosulfonyl)benzoate to afford intermediates that were isolated and not characterized but cyclized with acetic anhydride, which also resulted in N-acetylation. The X-ray crystal structure determinations of methyl 2-acetyl-5′-phenyl-2H-spiro[benzo[d]isothiazole-3,3′-pyrazole]-1,1-dioxide-2′(4′H)-carboxylate and methyl 2-acetyl-5′-(2-thienyl)-2H-spiro[benzo[d]isothiazole-3,3′-pyrazole]-1,1-dioxide-2′(4′H)-carboxylate products were a follow up for absorption spectra, and they confirmed their structures. Mechanistic intermediates to describe the reaction may include C-acylated intermediates that cyclize to spiro(N-benzoisothiazole dioxide-pyrazole) instead of N-carbomethoxypyrazole-ortho-benzenesulfonamides. Crystals of C19H17N3O5S 7 are monoclinic, P21/c, a = 11.899(2) A, b = 17.562(4) A, c = 9.484(2) A, β = 111.03(3)°, Z = 4, V = 1849.9(6) A3, R 1 = 0.0857 and wR 2 = 0.2216 for reflections with I > 2σ(I); crystals of C17H15N3O5S2 8 are orthorhombic, Pbca, a = 16.045(3) A, b = 10.746(2) A, c = 20.389(4) A, Z = 8, V = 3516(1) A3, R 1 = 0.0841 and wR 2 = 0.2179 for all reflections with I > 2σ(I). X-ray crystal analysis was important for determining the conformation of the structure of N-acetyl-N′-carbomethoxy-spiro(benzoisothiazole–pyrazole)dioxides prepared by the condensation and twofold cyclization of dilithiated C(α), N-carbomethoxyhydrazones and methyl 2-(aminosulfonyl)benzoate.

A variety of substituted spiro(benzoisothiazole-pyrazoles) have been prepared by the condensation of dilithiated C(α),N-carboalkoxyhydrazones with lithiated methyl 2-(aminosulfonyl)benzoate followed by the cyclization of intermediates with acetic anhydride, which also resulted in spiro N-acetylated products when carbomethoxyhydrazones or carboethoxyhydrazones were used, and spiro NH products when carbo-tert-butoxyhydrazones were used. J. Heterocyclic Chem., 46, 231 (2009).

Lithium hexamethyldisilazide (LiHMDS) was used to condense substituted benzoate esters with acetone to afford symmetrical 1,5-diaryl-1,3,5-pentanetriones that were isolated, characterized (including a representative X-ray crystallographic analysis), and acid cyclized to the respective 2,6-diaryl-4H-pyran-4-ones.

We present a fully automated DNA purification module comprised of a micro-fabricated chip and sequential injection analysis system that is designed for use within autonomous instruments that continuously monitor the environment for the presence of biological threat agents. The chip has an elliptical flow channel containing a bed (3.5 x 3.5 mm) of silica-coated pillars with height, width and center-to-center spacing of 200, 15, and 30 microm, respectively, which provides a relatively large surface area (ca. 3 cm(2)) for DNA capture in the presence of chaotropic agents. We have characterized the effect of various fluidic parameters on extraction performance, including sample input volume, capture flow rate, and elution volume. The flow-through design made the pillar chip completely reusable; carryover was eliminated by flushing lines with sodium hypochlorite and deionized water between assays. A mass balance was conducted to determine the fate of input DNA not recovered in the eluent. The device was capable of purifying and recovering Bacillus anthracis genomic DNA (input masses from 0.32 to 320 pg) from spiked environmental aerosol samples, for subsequent analysis using polymerase chain reaction-based assays.

Spatial and temporal variation in seedling dynamics was assessed using records of community-wide seedling demography collected with identical monitoring methods at four tropical lowland forests in Panama, Malaysia, Ecuador and French Guiana for periods of between 3 and 10 y. At each site, the fates of between 8617 and 391 777 seedlings were followed through annual censuses of the 370–1008 1-m2 seedling plots. Within-site spatial and inter-annual variation in density, recruitment, growth and mortality was compared with among-site variability using Bayesian hierarchical modelling to determine the generality of each site's patterns and potential for meaningful comparisons among sites. The Malaysian forest, which experiences community-wide masting, was the most variable in both seedling density and recruitment. However, density varied year-to-year at all sites (CVamong years at site = 8–43%), driven largely by high variability in recruitment rates (CV = 40–117%). At all sites, recruitment was more variable than mortality (CV = 5–64%) or growth (CV = 12–51%). Increases in mortality rates lagged 1 y behind large recruitment events. Within-site spatial variation and inter-annual differences were greater than differences among site averages in all rates, emphasizing the value of long-term comparative studies when generalizing how spatial and temporal variation drive patterns of recruitment in tropical forests.

The carbomethoxhydrazones of 1-tetralone, 6-methoxy-1-tetralone, and 5,7-dimethyl-1-tetralone were converted to dilithiated intermediates with excess lithium diisopropylamide and condensed with aromatic esters to give C-acylated intermediates that were not usually isolated but cyclized directly with acid to afford the N-carbomethoxydihydrobenzindazoles. These compounds could be separately saponified followed by decarboxylation to the targeted NH-dihydrobenzindazoles. Single-crystal X-ray analysis for several compounds indicated that a single tautomer was present, with the NH-hydrogen atom bonded exclusively to the N-2 of the products. Theoretical calculations indicated this product to be the more stable of the two tautomers.

Several dilithiated C(α), O-oximes were prepared in excess lithium diisopropylamide-tetramethyl-ethylenediamine (LDA/TMEDA) and condensed with methyl 2-(aminosulfonyl)benzoate followed by acid cyclization of intermediates to spiro(benzoisothiazole-isoxazole) dioxides, a new spiro and fused-ring system. Distortionless enhancement by polarization transfer (DEPT) and liquid chromatography mass spectrometry (LCMS) for all products, as well as X-ray single crystal analysis on a representative product, were especially relevant for structure confirmation in this synthesis.

Dow Corning SE 1700 (reinforced polydimethylsiloxane) porous structures were made by direct ink writing (DIW). The specimens (~50% porosity) were subjected to various compressive strains (15, 30, 45%) and temperatures (room temperature, 35, 50, 70°C) in a nitrogen atmosphere (active purge) for 1 year. Compression set and load retention of the aged specimens were measured periodically during the study. Compression set increased with strain and temperature. After 1 year, specimens aged at room temperature, 35, and 50°C showed ~10% compression set (relative to the applied compressive deflection), while those aged at 70°C showed 20-40%. Due to the increasing compression set, load retention decreased with temperature, ranging from ~90% at room temperature to ~60-80% at 70°C. Long-term compression set and load retention at room temperature were predicted by applying time-temperature superposition (TTS). The predictions show compression set relative to the compressive deflection will be ~10-15% with ~70-90% load retention after 50 years at 15-45% strain, suggesting the material will continue to be mechanically functional. Comparison of the results to previously acquired data for cellular (M97*, M9760, M9763) and RTV (S5370) silicone foams suggests that the SE 1700 DIW porous specimens are on par with, or outperform, the legacy foams.

Dow Corning SE 1700 (reinforced polydimethylsiloxane) porous structures were made by direct ink writing (DIW). The specimens (~50% porosity) were subjected to a compressive strain of ~25% while exposed to a gamma radiation dose of 1, 5, or 10 Mrad under vacuum. Compression set and load retention of the aged specimens were measured after a ~24 h relaxation period. Compression set (relative to deflection) increased with radiation dose: 11, 35, and 51% after 1, 5, and 10 Mrad, respectively. Load retention was 96-97% for the doses tested. The SE 1700 compared favorably to M9763 cellular silicone tested under the same conditions.

Importance The risk of bleeding and recurrent venous thromboembolism (VTE) among patients receiving long-term warfarin sodium therapy for secondary VTE prevention who require temporary interruption of anticoagulant therapy for surgery or invasive diagnostic procedures has not been adequately described. Objective To describe the rates of clinically relevant bleeding and recurrent VTE among patients in whom warfarin therapy is interrupted for invasive procedures and compare these rates among patients who did and did not receive bridge therapy. Design, Setting, and Participants A retrospective cohort study was conducted at Kaiser Permanente Colorado, an integrated health care delivery system. Patients in whom warfarin therapy was interrupted for invasive diagnostic or surgical procedures between January 1, 2006, and March 31, 2012, were identified via queries of administrative data sets. A total of 1812 procedures in 1178 patients met inclusion criteria. Data on outcomes and exposures were collected between June 1, 2005, and April 30, 2012. Exposures Use of bridge therapy vs no bridge therapy during warfarin interruption. Main Outcomes and Measures Thirty-day clinically relevant bleeding, recurrent VTE, and all-cause mortality. Outcomes were verified via manual review of medical records. Results Among the 1178 patients, the mean (SD) age was 66.1 (12.7) years, 830 procedures (45.8%) were in men, and the most common indication for warfarin therapy was deep vein thrombosis (56.3%). Most patients were considered to be at low risk for VTE recurrence at the time of warfarin interruption (1431 procedures [79.0%]) according to the consensus guidelines of the American College of Chest Physicians. Clinically relevant bleeding within 30 days after the procedure in the bridge therapy and non–bridge therapy groups occurred in 15 patients (2.7%) and 2 patients (0.2%), respectively (hazard ratio, 17.2; 95% CI, 3.9-75.1). There was no significant difference in the rate of recurrent VTE between the bridge and non–bridge therapy groups (0 vs 3; P = .56). No deaths occurred in either group. Conclusions and Relevance Bridge therapy was associated with an increased risk of bleeding during warfarin therapy interruption for invasive procedures in patients receiving treatment for a history of VTE and is likely unnecessary for most of these patients. Further research is needed to identify patient- and procedure-related characteristics associated with a high risk of perioperative VTE recurrence during warfarin therapy interruption.

Several β-ketoesters were dilithiated with an excess of lithium diisopropylamide, followed by condensation with methyl 2-(aminosulfonyl)benzoate to give intermediates that were not isolated but cyclized to 3-substituted 1,2-benzisothiazole-1,1-dioxides. In most instances involving the ester-sulfonamide, a single β-ketoester tautomer is usually formed after recrystallization from ethanol. The same dilithiated β-ketoesters generally condense less well with 1,2-benzisothiazol-3(2H)-one-1,1-dioxide (saccharin) under the same conditions to afford the same products usually in the same or lower yields. The use of N,N,N',N'-tetramethylethylenediamine during these syntheses has sometimes resulted in improved yields of products.

Dilithiated 1-tetralone oxime was condensed with several electron enriched aromatic aldehydes, such as 4-methoxybenzaldehyde or lithiated 4-hydroxybenzaldehyde, followed by acid cyclization to new tetrahydronaphthisoxazoles, 3,3a,4,5-tetrahydronaphth[1,2-c]isoxazoles, with a trans geometry of the C3-H and C3a-H protons that was confirmed by X-ray single crystal analysis.

The regulation of skin darkness in vertebrates is mediated by alpha-melanophore-stimulating-hormone (alphaMSH). For this action, alphaMSH binds to the melanocortin (MC)-1 receptor, a 7-transmembrane receptor located in melanophore cell membranes. The Mozambique tilapia, Oreochromis mossambicus, can change the hue of its body in response to a change in background, a process that may involve alphaMSH and the MC1R. Scale melanophores were isolated from tilapia that were acclimatised for 25 days to a black, control grey or white background and then tested for their sensitivity to des-, mono-, and di-acetylated alphaMSH. On all backgrounds, mono-acetylated alphaMSH was the dominant isoform present in pituitary homogenates. Mono-acetylated alphaMSH also had the highest potency to disperse melanosomes. Black background adapted fish showed the highest dispersing response to alphaMSH, independent of the isoform applied. We elucidated the nucleotide and amino acid sequence of the tilapia MC1R. We show that its expression in skin does not change when tilapia are acclimatised for 25 days to a black, grey or white background, while a clear change in hue is visible. This finding, combined with the absence of differential MC1R gene expression following background acclimation indicates that the increased sensitivity to alphaMSH is most likely a result of changes in the intracellular signalling system in melanophores of black background adapted fish, rather than up-regulation of the MC1R.

Contains fulltext : 33308.pdf (Publisher’s version ) (Closed access) Cortisol release from fish head kidney during the acute phase of the stress response is controlled by the adrenocorticotropic hormone (ACTH) from the pituitary pars distalis (PD). Alpha-melanocyte-stimulating hormone (alpha-MSH) and beta-endorphin, from the pars intermedia (PI), have been implicated in cortisol release during the chronic phase. The present study addresses the regulation of cortisol release by ACTH and alpha-MSH in common carp (Cyprinus carpio) and includes characterization of their receptors, namely, the melanocortin-2 and melanocortin-5 receptors (MC2R and MC5R). We could not demonstrate corticotropic activity of alpha-MSH, beta-endorphin, and combinations of these. We do show a corticotrope in the PI, but its identity is as yet uncertain. Carp restrained for 1 and 7 days showed elevated plasma cortisol and alpha-MSH levels; cortisol is still elevated but lower at day 7 than day 1 of restraint. Interrenal response capacity is unaffected, as estimated by stimulation with a maximum dose ACTH in a superfusion setup. MC2R and MC5R appear phylogenetically well conserved. MC2R is predominantly expressed in head kidney; a low abundance was found in spleen and kidney. MC5R is expressed in brain, pituitary PD, kidney, and skin. Quantitative PCR analysis of MC2R and MC5R expression in the head kidney of restrained fish reveals MC2R mRNA downregulation after 7 days restraint, in line with lower plasma cortisol levels seen. We discuss regulation of corticosteroid production from a phylogenetic perspective. We propose that increased levels of alpha-MSH exert a positive feedback on hypothalamic corticotropin-releasing hormone release to sustain a mild stress axis activity.

Select C(α), N-phenylhydrazones were dilithiated in excess lithium diisopropylamide followed by condensation with methyl 2-(aminosulfonyl)benzoate and acid cyclization to afford new pyrazol-benzenesul-fonamides, 2-(1-phenyl-1H-pyrazol-5-yl)benzenesulfonamides.

Fatigue crack nucleation at grain boundaries near the endurance limit was examined combining the results of fatigue tests with local orientation measurements and with finite element calculations. Coarse-grained thin sheets were examined in which the orientation and inclination of each boundary could be measured directly. These results were used as input for FEM calculation in which the stress concentrations near the grain boundaries were calculated. In the fatigue tests, the boundaries, at which the first cracks nucleate, were measured by a replica technique. A comparison between the experimental results and the FE calculation showed that the cracks nucleated and propagated along the boundaries with the largest stress concentration. When a crack hits a boundary with a lower stress concentration, it either stops or propagates transgranularly depending on the local stress concentration given by the microstructure. From these results, it can be concluded that elastic strain incompatibility combined with the microstructure (grain size and orientation) can be used to predict the crack nucleation sites and the scatter in life time for fatigue near the endurance limit.

Select dilithiated ortho-toluic acids were prepared in excess lithium diisopropylamide and condensed with methyl 2-(aminosulfonyl)benzoate followed by a twofold cyclization of intermediates to afford benzoisothiazolo[1,2-b][1,2]isoquinolin-11-one-1,1-dioxides, a new fused-ring heterocyclic system.

An analysis of claims data from a managed care health plan was performed to evaluate whether patients use chiropractic care as a substitution for medical care or in addition to medical care. Rates of neuromusculoskeletal complaints in 9e diagnostic categories were compared between groups with and without chiropractic coverage. For the 4-year study period, there were 3,129,752 insured member years in the groups with chiropractic coverage and 5,197,686 insured member years in the groups without chiropractic coverage. Expressed in terms of unique patients with neuromusculoskeletal complaints, the cohort with chiropractic coverage experienced a rate of 162.0 complaints per 1000 member years compared with 171.3 complaints in the cohort without chiropractic coverage. These results indicate that patients use chiropractic care as a direct substitution for medical care.

Adrenocorticotropic hormone (ACTH) takes a central role in the hypothalamo-pituitary-interrenal axis (HPI axis), which is activated during stress. ACTH is produced by the corticotrope cells of the pituitary pars distalis (PD) and is under control of factors from the nucleus preopticus (NPO). The distribution of ACTH in the hypothalamo-pituitary system in common carp (Cyprinus carpio L.) was assessed by immunohistochemistry. ACTH and beta-endorphin immunoreactivity was observed in the ACTH cells in the PD and in the NPO. Nerve fibers, originating from the NPO and projecting to the pituitary gland, contain beta-endorphin, but not ACTH, and these fibers either control the pituitary pars intermedia (PI) through beta-endorphin or release it to the blood. The release of pituitary ACTH (studied in a superfusion setup) must in vivo be under predominant inhibitory control of dopamine. Release of ACTH is stimulated by corticotropin-releasing hormone, but only when ACTH cells experience dopaminergic inhibition. The expression of the precursor pro-opiomelanocortin in (POMC) NPO, PD and PI was studied in an acute restraint stress paradigm by real-time quantitative polymerase chain reaction (RQ-PCR). POMC gene expression is upregulated in these three key tissues of the hypothalamo-pituitary complex, revealing a hitherto unforeseen complex role for POMC-derived peptides in the regulation of responses to stress.

Contains fulltext : 58054.pdf (Publisher’s version ) (Closed access) We elucidated the structure of the principle factors regulating the initiation of the acute stress response in common carp: corticotrophin-releasing hormone (CRH), CRH-receptor 1 (CRH-R1) and CRH-binding protein (CRH-BP). Phylogenetic analyses reveal that these proteins are evolutionarily well conserved in vertebrates. CRH and CRH-BP expression are not co-localised in the same hypothalamic perikarya. On the contrary, CRH-BP expression is limited to the perimeter of the nucleus preopticus (NPO), but is abundant in other regions, including an area directly rostral from, and in close proximity to, the NPO. Despite the lack of co-expression, the nerve fibres projecting onto both the rostral pars distalis (rPD) as well as the large fibre bundles projecting onto the pars intermedia (PI) contain CRH as well as CRH-BP, suggesting that both ACTH release from the rPD as well as the release of PI melanotrope content is regulated via CRH and CRH-BP. Finally, we show via real-time quantitative PCR that expression of hypothalamic CRH and CRH-BP following a 24 h restraint significantly increases, whereas PD CRH-R1 expression decreases; this reflects desensitisation of the PD for hypothalamic CRH output. We conclude that these factors are actively involved in the regulation of acute stress responses in the teleost fish.

Acetoacetanilide and 4′-chloroacetoacetanilide were trilithiated with excess lithium diisopropylamide and condensed with several aromatic esters, followed by neutralization, separate acid cyclization, and rearrangements. After C-acylation of trilithiated acetoacetanilides and cyclization to 4H-pyran-4-ones, these compounds underwent multistep rearrangements to 4-anilino-6-aryl-2H-pyran-2-ones.Key words: pyranones, trianions, Claisen-type condensations, rearrangements.

An automated sample preparation module, based upon sequential injection analysis (SIA), has been developed for use within an autonomous pathogen detection system. The SIA system interfaced aerosol sampling with multiplexed microsphere immunoassay-flow cytometric detection. Metering and sequestering of microspheres using SIA was found to be reproducible and reliable, over 24-h periods of autonomous operation. Four inbuilt immunoassay controls showed excellent immunoassay and system stability over five days of unattended continuous operation. Titration curves for two biological warfare agents, Bacillus anthracis and Yersinia pestis, obtained using the automated SIA procedure were shown to be similar to those generated using a manual microtiter plate procedure.

We have developed and tested a fully autonomous pathogen detection system (APDS) capable of continuously monitoring the environment for airborne biological threat agents. The system is designed to provide early warning to civilians in the event of a terrorist attack. The final APDS will be completely automated, offering aerosol sampling, in-line sample preparation fluidics, multiplexed detection and identification immunoassays, and orthogonal, multiplexed PCR (nucleic acid) amplification and detection. The system performance (current capabilities include aerosol collection, multiplexed immunoassays, sample archiving, data reporting, and alarming) was evaluated in a field test conducted in a Biosafety Level 3 facility, where the system was challenged with, and detected, a series of aerosolized releases containing two live, virulent biological threat agents (Bacillus anthracis and Yersinia pestis). Results presented here represent the first autonomous, simultaneous measurement of these agents.

Isogenic carp Cyprinus carpio L. were acclimated to water temperatures of 15, 22 and 29 degrees C for at least 8 weeks. The acclimations consistently resulted in slightly, but significantly, different plasma osmolality, sodium, potassium and chloride concentrations between the groups studied. Plasma total and ionic calcium levels were unaffected, indicating successful adaptation. The apparent changes in set point for plasma ion levels are explained by altered sodium pump activity and hormonal control of branchial permeability to water and ions. It appears that in 15 degrees C-acclimated fish, a lower apparent Na(+)/K(+)-ATPase activity is compensated by strongly enhanced Na(+)/K(+)-ATPase expression (determined biochemically and immunohistochemically). In 29 degrees C-acclimated fish, the higher ambient temperature activates the enzyme. Arrhenius plots for branchial Na(+)/K(+)-ATPase preparations of the three groups of fish suggest the occurrence of different enzyme isoforms or protein (in)stability as explanations for differences in apparent enzyme activities, rather than temperature-dependent changes in membrane fluidity. As for hormonal control over permeability, prolactin mRNA expression (and anticipated production and release) is lower in fish kept at 29 degrees C, suggesting that control over branchial permeability to water and ions needs to be downregulated at higher temperatures. In so doing, enhanced sodium pump activity is balanced by a controlled passive ion loss to fine-tune plasma sodium levels. Basal plasma cortisol levels did not correlate positively with Na(+)/K(+)-ATPase expression, but doubling plasma cortisol levels in control fish by administering exogenous cortisol (for 7 days, using implanted minipumps and thus stress-free) enhanced Na(+)/K(+)-ATPase expression. This effect must be the result of a glucocorticoid action of the steroid: in fish, mineralocorticoid receptors have higher affinity for cortisol than glucocorticoid receptors. At a lower ambient temperature, branchial Na(+)/K(+)-ATPase expression is upregulated to counteract the temperature-inhibited activity of the sodium pump, perhaps via a mineralocorticoid receptor.

Cerebral venous thrombosis may present with multifaceted symptoms and therefore be difficult to diagnose. Only few evidence-based data exist with respect to therapy and prognosis, especially concerning the deep cerebral venous system. A thrombosis of the vein of Galen is deemed to have a poorer prognosis. Our case report describes the local combined neuro-interventional therapy as an individual attempt to cure a patient with a fulminant disease course.

Tight interactions among different cell types contributing to bone formation are of key importance in the maintenance of bone homeostasis. Based on the high similarity in responses to (anti)osteogenic signals between zebrafish scales and mammalian bone, we developed and validated a model to screen large numbers of compounds using ex-vivo cultured scales of a sp7:luciferase transgenic zebrafish. This model combines the high predictive value of explant cultures with quick, sensitive, and quantifiable readout converging the effects via various pathways including WNT-signaling, to SP7/osterix promoter activity. Sp7 is pivotal in osteoblast differentiation and activity and its promoter activity provides an excellent surrogate for sp7 expression. Bmp-2a was shown to dose-dependently increase sp7-driven luciferase activity ex vivo. Next, we identified novel effects on bone for 51.7% of the compounds from a small library of WNT-signaling modulators, including a strong osteogenic effect for niclosamide. From all previously characterized compounds, the effect on bone was correctly predicted for 70% of compounds, resulting in a 7% false positive- and 21% false negative rate. The proposed sp7:luciferase zebrafish scale model is unique, powerful and efficient new tool to assess compounds with osteogenic effects, prior to further testing in rodents.