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The multimodal antidepressant vortioxetine is thought to mediate its pharmacological effects via 5-HT 1A receptor agonism, 5-HT 1B receptor partial agonism, 5-HT 1D , 5-HT 3 , 5-HT 7 receptor antagonism and 5-HT transporter inhibition. Here we studied vortioxetine's functional effects across species (canine, mouse, rat, guinea pig and human) in cellular assays with heterologous expression of 5-HT 3A receptors (in Xenopus oocytes and HEK-293 cells) and in mouse neuroblastoma N1E-115 cells with endogenous expression of 5-HT 3A receptors. Furthermore, we studied the effects of vortioxetine on activity of CA1 Stratum Radiatum interneurons in rat hippocampus slices using current- and voltage-clamping methods. The patched neurons were subsequently filled with biocytin for confirmation of 5-HT 3 receptor mRNA expression by in situ hybridization. Whereas, both vortioxetine and the 5-HT 3 receptor antagonist ondansetron potently antagonized 5-HT-induced currents in the cellular assays, vortioxetine had a slower off-rate than ondansetron in oocytes expressing 5-HT 3A receptors. Furthermore, vortioxetine's but not ondansetron's 5-HT 3 receptor antagonistic potency varied considerably across species. Vortioxetine had the highest potency at rat and the lowest potency at guinea pig 5-HT 3A receptors. Finally, in 5-HT 3 receptor-expressing GABAergic interneurons from the CA1 stratum radiatum, vortioxetine and ondansetron blocked depolarizations induced by superfusion of either 5-HT or the 5-HT 3 receptor agonist mCPBG. Taken together, these data add to a growing literature supporting the idea that vortioxetine may inhibit GABAergic neurotransmission in some brain regions via a 5-HT 3 receptor antagonism-dependent mechanism and thereby disinhibit pyramidal neurons and enhance glutamatergic signaling.

The correlation between surface structure, stoichiometry and atomic occupancy of the polar MgAl2O4(100) surface has been studied with an interplay of noncontact atomic force microscopy, x-ray photoelectron spectroscopy and surface x-ray diffraction under ultrahigh vacuum conditions. The Al/Mg ratio is found to significantly increase as the surface is sputtered and annealed in oxygen at intermediate temperatures ranging from 800-1000 [degree]C. The Al excess is explained by the observed surface structure, where the formation of nanometer sized pits and elongated patches with Al terminated step edges contribute to stabilizing the structure by compensating surface polarity. Surface x-ray diffraction reveals a reduced occupancy in the top two surface layers for both Mg, Al, and O and, moreover, vacancies are preferably located in octahedral sites, indicating that Al and Mg ions interchange sites. The excess of Al and high concentration of octahedral vacancies, very interestingly means, that the top few surface layers of the MgAl2O4(100) adopts a surface structure similar to that of a spinel-like transition Al2O3 film. However, after annealing at a high temperature of 1200 [degree]C, the Al/Mg ratio restores to its initial value, the occupancy of all elements increases, and the surface transforms into a well-defined structure with large flat terraces and straight step edges, indicating a restoration of the surface stoichiometry. It is proposed, that the tetrahedral vacancies at these high temperatures are filled by Mg from the bulk, due to the increased mobility at high annealing temperatures.

The multimodal antidepressant vortioxetine is thought to mediate its pharmacological effects via 5-HT

To improve the understanding of sintering in diesel and lean-burn engine exhaust after-treatment catalysts, we examined oxygen-induced sintering in a model catalyst consisting of Pt nanoparticles supported on a planar, amorphous Al2O3 substrate. After aging at increasing temperatures, a transmission electron microscopy analysis reveals that a highly monodispersed ensemble of nanoparticles transformed into an ensemble with bimodal and subsequently Lifshitz–Slyozov–Wagner particle size distribution. Moreover, scanning transmission electron microscopy and atomic force microscopy analyses suggest that the Pt nanoparticle had size-dependent morphologies after sintering in the oxidizing environment. The evolution of the particle sizes is described by a simple kinetic model for ripening, and the size-dependent particle morphology is proposed as an explanation for the observed bimodal particle size distribution shape.

A simple protocol for the practical, scalable, catalytic asymmetric synthesis of γ-quaternary acylcyclopentenes in up to 91% overall yield and 92% ee has been developed. The reaction sequence employs a palladium-catalyzed enantioselective alkylation reaction and exploits the unusual stability of β-hydroxy cycloheptanones to achieve a general and robust method for performing two-carbon ring contractions. The resulting enantioenriched, highly-functionalized acylcyclopentenes provide a variable substituent and four additional functional group handles for chemoselective manipulation and potential application to the total synthesis of a wide array of natural products.

We study a crystalline epitaxial alumina thin film with the characteristics of a spinel-type transition Al2O3(100) surface by using atom-resolved noncontact atomic force microscopy and density functional theory. It is shown that the films are terminated by an Al-O layer rich in Al vacancies, exhibiting a strong preference for surface hydroxyl group formation in two configurations. The transition alumina films are crystalline and perfectly stable in ambient atmospheres, a quality which is expected to open the door to new fundamental studies of the surfaces of transition aluminas.

We study a crystalline epitaxial alumina thin film with the characteristics of a spinel-type transition Al2O3(100) surface by using atom-resolved noncontact atomic force microscopy and density functional theory. It is shown that the films are terminated by an Al-O layer rich in Al vacancies, exhibiting a strong preference for surface hydroxyl group formation in two configurations. The transition alumina films are crystalline and perfectly stable in ambient atmospheres, a quality which is expected to open the door to new fundamental studies of the surfaces of transition aluminas.

Carbon nanotube terminated atomic force microscopy (AFM) probes have been used for the imaging of 5 nm wide surface supported Pt nanoclusters by non-contact (dynamic mode) AFM in an ultra-high vacuum. The results are compared to AFM measurements done with conventional Si-tips, as well as with transmission electron microscopy images, which give accurate measures for cluster widths. Despite their ideal aspect ratio, tip-broadening is concluded to be a severe problem even when imaging with carbon nanotube tips, which overestimates the cluster width by several times the nominal width of the nanotube tip. This broadening is attributed to a bending of the carbon nanotubes, and not to pure geometrical factors, which coincidentally results in a significant improvement for relative height measurements of tightly spaced high aspect ratio structures, as compared to what can be achieved with geometrically limited conventional probes. Superior durability also stands out as a defining feature of carbon nanotube terminated probes, allowing them to give results with a greatly enhanced reproducibility.

Nanostructuring of materials is an effective way to lower the thermal conductivity. A novel supercritical/near-critical water approach was developed for the fabrication of Bi 2 Te 3 nanoparticles. The method provides a rapid, “green” and large scale synthesis of nanoparticles with uniform particle sizes, and the production can be scaled up for commercial production. The synthesis temperature and the pH condition were studied for the synthesis of Bi 2 Te 3 . It is found the formation mechanisms are different when the NaOH concentration is changed in the solution. The method may be applied for preparing nanoparticles of other metals and intermetallic compounds.

The key transformation is the palladium-catalyzed asymmetric decarboxylative alkylation of seven-membered β-ketoesters (I) to form quaternary vinylogous esters (II).

General catalytic asymmetric routes toward cyclopentanoid and cycloheptanoid core structures embedded in numerous natural products have been developed. The central stereoselective transformation in our divergent strategies is the enantioselective decarboxylative alkylation of seven-membered β-ketoesters to form α-quaternary vinylogous esters. Recognition of the unusual reactivity of β-hydroxyketones resulting from the addition of hydride or organometallic reagents enabled divergent access to γ-quaternary acylcyclopentenes through a ring contraction pathway or γ-quaternary cycloheptenones through a carbonyl transposition pathway. Synthetic applications of these compounds were explored through the preparation of mono-, bi-, and tricyclic derivatives that can serve as valuable intermediates for the total synthesis of complex natural products. This work complements our previous work with cyclohexanoid systems.

The morphology and thermal stability of Ni and Co nanoclusters grown by physical vapour deposition on a reconstructed (1120) surface of α-Al(2)O(3) is investigated using non-contact atomic force microscopy (NC-AFM). NC-AFM images reveal that the clean α-Al(2)O(3)(1120) substrate adopts a characteristic (12 × 4) reconstruction when prepared in vacuum at high temperature. Subsequent deposition of Ni and Co onto this substrate at room temperature facilitates the growth of well-ordered metal nanocluster arrays with a preferred inter-cluster distance determined by the (12 × 4) periodicity of the substrate surface. The order in the cluster arrangement remains intact even upon annealing the system to temperatures up to 500 °C indicating a high resistance against sintering. The reconstructed α-Al(2)O(3)(1120) surface can, therefore, serve as an appropriate insulating template for studies of size-dependent magnetic or catalytic effects in a well-defined ensemble of metallic nanoclusters.

Enantioselective decarboxylative internal allylation of esters (I) followed by hydride reduction and base-promoted ring contraction of the intermediate cyclic β-hydroxy ketones affords densely functionalized chiral acylcyclopentenes.

Formation and growth of the title nanocrystals in high-temperature, high-pressure aqueous KOH solutions of Fe(NO3)3 and Bi(NO3)3 is monitored by in situ synchrotron powder XRD.

In situ synchrotron radiation powder X-ray diffraction (SR-PXRD) was applied to study the formation and growth of BiFeO3 nanocrystals, revealing that phase pure BiFeO3 can be obtained in high-temperature, high-pressure aqueous solution using Bi(NO3)3 and Fe(NO3)3·9H2O as precursors and KOH as mineralizer. The method gives a rapid way for preparation of nanomaterials, and the formation of BiFeO3 can be finished within seconds after its initial nucleation in near-critical aqueous solution. As proof of concept BiFeO3 nanocrystals were subsequently synthesized in a continuous flow supercritical system and for reference also in autoclaves. High resolution multitemperature SR-PXRD data were measured between 100 and 1000 K with a step size of 100 K. The magnetic properties of both the autoclave and the continuous flow samples are studied.

In order to establish if the canine 5-hydroxytryptamine type 3A (5-HT(3A)) receptors share the pharmacological profile with human 5-HT(3A) receptors, we cloned and performed a molecular pharmacological characterization of the canine 5-HT(3A) receptor. The 5-HT(3A) cDNA was cloned from canine brain by polymerase chain reaction amplification. It encodes a 483 amino acid peptide that exhibits from 80% (mice) to 90% (ferrets) identity to other sequenced mammalian 5-HT(3A) receptors. The receptor agonists 5-hydroxytryptamine (5-HT) and meta-chlorophenylbiguanide (mCPBG) showed little differences between the two species, whereas 2-methyl-5-hydroxytryptamine (2-Me-5-HT) was ten times weaker at canine receptors than at human receptors. The potencies at the canine 5-HT(3) receptors were 9.9 microM (5-HT), 79 microM (2-Me-5-HT) and 0.8 microM (mCPBG). The selective, competitive receptor antagonist ondansetron was ten times more potent at human receptors compared to canine receptors (K(b)=0.9 nM), while (+)-tubocurarine was 1000-fold more potent at canine receptors (K(b)=3.0 nM) than at human receptors. Examination of the presumed ligand binding extracellular domain revealed one residue, where the canine receptor differs from all previously characterized 5-HT(3A) receptors, i.e. other species contain a conserved Trp(195), whereas the canine orthologue contains a Leu(195). To address the differences in potencies at the human and canine 5-HT(3A) receptors seen in this study, we introduced a L195W point mutation in the canine orthologue. Data showed that the 195 residue can affect receptor agonist potency and efficacy as well as antagonist potency, but did produce a pharmacological profile identical to the human orthologue. We therefore conclude that position 195 is strongly involved in the receptor-ligand interaction, but additional residues must contribute to the overall pharmacological profile.