One-pot heterogeneous synthesis of Δ(3)-tetrahydrocannabinol analogues and xanthenes showing differential binding to CB(1) and CB(2) receptors

Δ(9)-tetrahydrocannabinol (Δ(9)-THC) is the major psychoactive cannabinoid in hemp (Cannabis sativa L.) and responsible for many of the pharmacological effects mediated via cannabinoid receptors. Despite being the major cannabinoid scaffold in nature, Δ(9)-THC double bond isomers remain poorly studied. The chemical scaffold of tetrahydrocannabinol can be assembled from the condensation of distinctly substituted phenols and monoterpenes. Here we explored a microwave-assisted one pot heterogeneous synthesis of Δ(3)-THC from orcinol (1a) and pulegone (2). Four Δ(3)-THC analogues and corresponding Δ(4a)-tetrahydroxanthenes (Δ(4a)-THXs) were synthesized regioselectively and showed differential binding affinities for CB1 and CB2 cannabinoid receptors. Here we report for the first time the CB1 receptor binding of Δ(3)-THC, revealing a more potent receptor binding affinity for the (S)-(-) isomer (hCB1Ki = 5 nM) compared to the (R)-(+) isomer (hCB1Ki = 29 nM). Like Δ(9)-THC, also Δ(3)-THC analogues are partial agonists at CB receptors as indicated by [(35)S]GTPγS binding assays. Interestingly, the THC structural isomers Δ(4a)-THXs showed selective binding and partial agonism at CB2 receptors, revealing a simple non-natural natural product-derived scaffold for novel CB2 ligands.

Na 50 Nachlass Arthur Schopenhauer - 'Schopenhauer-Archiv', 955 - Mitteilung über die Beendigung des Streites mit Jules Lunteschütz über das Gemälde Schopenhauer

u.a. Anfertigung eines weiteren Gemäldes Schopenhauers;

Miocene to Pliocene planktonic foraminifers in ODP Hole 134-832B

One hundred and sixty core samples were analyzed from Hole 832B to evaluate planktonic foraminiferal datum levels, and to zone and correlate the borehole succession. A total of 32 biostratigraphic events were recognized in the interval from Core 134-832B-59R through 134-832B-73R (702.49 through 846.4 meters below seafloor [mbsf]). These include 17 first appearance datum levels (FAD), 10 last appearance datum levels (LAD), and 5 coiling-change events in trochospiral species. The studied succession has been subdivided into nine planktonic foraminiferal zones (viz. downsequence N.22, N.21, N.20, N.19, N.18, N.17B, N.17A-N.16, N.15, N.8). The zonal index species occur in the expected stratigraphic order for zonal correlation, but some of the zonal boundaries may be diachronous compared to other localities in the western Pacific region. The FAD of Globorotalia (Truncorotalia) truncatulinoides (d' Orbigny) at 714.10 mbsf defines the boundary between the Zone N.22 and N.21; the boundary between Zones N.21 and N.20 at 741.73 mbsf is marked by the FAD of Globorotalia (Truncorotalia) tosaensis Takayanagi and Saito. The lower boundary of Zone N.20 is placed at 747.65 mbsf, based on the FAD of Globorotalia (Truncorotalia) crassaformis s.s. (Galloway and Wissler); the FAD of Sphaeroidinella dehiscens (Parker and Jones) at 756.61 mbsf defines the boundary between Zones N.18 and N.19. The FAD of Globorotalia (Globorotalia) tumida tumida (Brady) at 811.15 mbsf marks the boundary between Zones N.18 and N.17B. The boundary between Zones N.17B and N.17Ais placed at 843.52 mbsf, based on the FAD of Pulleniatina primalis Banner and Blow. A change in depositional conditions occurs at 846.4 mbsf just below the Zone N.17B lower boundary and is marked by the first appearance of abundant planktonic foraminifers in the region. The interval between 849.13 and 856.1 mbsf is placed in undifferentiated Zones N.17A and N.16, based on the rare occurrence of Neogloboquadrina acostaensis (Blow). The sparsely fossiliferous volcanic sandstone unit between 934.19 and 955.67 mbsf is positioned within Zone N.15 based on the presence of Globigerina (Zeaglobigerina) nepenthes Todd and Globigerinoides (Zeaglobigerina) druryi Arkers, and absence of N. acostaensis and Globorotalia (Jenkinsella) siakensis LeRoy. An unconformity between 955.67 and 971.80 mbsf may explain the absence of Zones N.14 through N.9. Basal Zone N.8 is recognized at 971.80 to 1008.60 mbsf by the presence of Globigerinoides sicanus De Stefani and the absence of Praeorbulina and Orbulina spp. The age of the succession between 702.49 and 1008.6 mbsf extends from the latest Pliocene or earliest Pleistocene (Zone N.22) to the earliest middle Miocene (Zone N.8). Among the datum levels evaluated here, the following events are considered to be the most reliable for time correlation in the studied region: the FADs of G. (T.) truncatulinoides, G. (T.) tosaensis, G. (T.) crassaformis, S. dehiscens, G. conglobatus (Brady), G. (G.) tumida tumida, and P. primalis; and the LADs of Globorotalia (Menardella) multicamerata Cushman and Jarvis, and Dentoglobigerina altispira altispira (Cushman and Jarvis). Application of a chronometric scale to part of the succession, suggests that the interval of calcareous sediment between 702.49 and 846.4 mbsf accumulated at about 30 m/m.y.

(Table 2) Comparison of annual mass fluxes measured with shallower and deeper sediment traps off Cape Blanc (CB)

The ocean off NW Africa is the second most important coastal upwelling system with a total annual primary production of 0.33 Gt of carbon per year (Carr in Deep Sea Res II 49:59-80, 2002). Deep ocean organic carbon fluxes measured by sediment traps are also fairly high despite low biogenic opal fluxes. Due to a low supply of dissolved silicate from subsurface waters, the ocean off NW Africa is characterized by predominantly carbonate-secreting primary producers, i.e. coccolithophorids. These algae which are key primary producers since millions of years are found in organic- and chlorophyll-rich zooplankton fecal pellets, which sink rapidly through the water column within a few days. Particle flux studies in the Mauretanian upwelling area (Cape Blanc) confirm the hypothesis of Armstrong et al. (Deep Sea Res II 49:219-236, 2002) who proposed that ballast availability, e.g. of carbonate particles, is essential to predict deep ocean organic carbon fluxes. The role of dust as ballast mineral for organic carbon, however, must be also taken into consideration in the coastal settings off NW Africa. There, high settling rates of larger particles approach 400 m day**-1, which may be due to a particular composition of mineral ballast. An assessment of particle settling rates from opal-production systems in the Southern Ocean of the Atlantic Sector, in contrast, provides lower values, consistent with the assumptions of Francois et al. (Global Biogeochem Cycles 16(4):1087, 2002). Satellite chlorophyll distributions, particle distributions and fluxes in the water column off NW Africa as well as modelling studies suggest a significant lateral flux component and export of particles from coastal shelf waters into the open ocean. These transport processes have implications for paleo-reconstructions from sediment cores retrieved at continental margin settings.

Raw grain-size distributions of the sediment trap time series CB 14 upper, CB 15 lower, CB 16 lower, CBi 1 upper, CBi 2 upper and CBi 3 upper

in preparation

Aplicaciones basadas en las propiedades eléctricas y térmicas de recubrimientos de sílice-cb obtenidos por el método sol-gel

En los últimos años el interés en los recubrimientos obtenidos por sol-gel ha aumentado mucho en aplicaciones de protección y refuerzo de superficies contra la corrosión. Asimismo, el uso de polimorfos de carbono (nanofibras de carbono, grafeno, grafito...) para mejorar las propiedades mecánicas y conferirle propiedades conductoras a algunos materiales, también se ha desarrollado mucho en los últimos años. En trabajos previos se prepararon y estudiaron recubrimientos híbridos de sílice-CB obtenidos por el método sol-gel. Mediante el estudio de la microestructura y composición de estos recubrimientos (SEM, Raman, ATD-TG, y FT-IR) y de las propiedades eléctricas se obtuvo que en función la temperatura de sinterización de los recubrimientos, se podía controlar la respuesta eléctrica de los composites. Esto permite abrir enormemente el campo de aplicaciones, ya que para temperaturas de sinterización por debajo de 400ºC se consiguen resistividades del orden de 10-4Ωm, apropiadas para aplicaciones en dispositivos electrónicos, electrodos, apantallamiento de interferencias electromagnéticas y radiofreciencia, etc; mientras que para temperaturas de sinterización por encima de 400ºC, obtenemos recubrimientos más resistivos que pueden aplicarse como dispositivos calefactores, anticongelantes. Por tanto, el objetivo de este trabajo es desarrollar más profundamente estas aplicaciones, así como diseñar experimentos que demuestren las múltiples posibilidades que estos recubrimientos conductores obtenidos por sol-gel pueden aportar.

Replication-dependent Histone Gene Expression Is Related to Cajal Body (CB) Association but Does Not Require Sustained CB Contact

Interactions between Cajal bodies (CBs) and replication-dependent histone loci occur more frequently than for other mRNA-encoding genes, but such interactions are not seen with all alleles at a given time. Because CBs contain factors required for transcriptional regulation and 3′ end processing of nonpolyadenylated replication-dependent histone transcripts, we investigated whether interaction with CBs is related to metabolism of these transcripts, known to vary during the cell cycle. Our experiments revealed that a locus containing a cell cycle-independent, replacement histone gene that produces polyadenylated transcripts does not preferentially associate with CBs. Furthermore, modest but significant changes in association levels of CBs with replication-dependent histone loci mimic their cell cycle modulations in transcription and 3′ end processing rates. By simultaneously visualizing replication-dependent histone genes and their nuclear transcripts for the first time, we surprisingly find that the vast majority of loci producing detectable RNA foci do not contact CBs. These studies suggest some link between CB association and unusual features of replication-dependent histone gene expression. However, sustained CB contact is not a requirement for their expression, consistent with our observations of U7 snRNP distributions. The modest correlation to gene expression instead may reflect transient gene signaling or the nucleation of small CBs at gene loci.

CB-norm estimates for maps between noncommutative Lp-spaces and quantum channel theory.

In the first part of this work, we show how certain techniques from quantum information theory can be used in order to obtain very sharp embeddings between noncommutative Lp-spaces. Then, we use these estimates to study the classical capacity with restricted assisted entanglement of the quantum erasure channel and the quantum depolarizing channel. In particular, we exactly compute the capacity of the first one and we show that certain nonmultiplicative results hold for the second one.