Atom interferometers covering macroscopic domains of space-time are a spectacular manifestation of the wave nature of matter. Because of their unique coherence properties, Bose-Einstein condensates are ideal sources for an atom interferometer in extended free fall. In this Letter we report on the realization of an asymmetric Mach-Zehnder interferometer operated with a Bose-Einstein condensate in microgravity. The resulting interference pattern is similar to the one in the far field of a double slit and shows a linear scaling with the time the wave packets expand. We employ delta-kick cooling in order to enhance the signal and extend our atom interferometer. Our experiments demonstrate the high potential of interferometers operated with quantum gases for probing the fundamental concepts of quantum mechanics and general relativity.
The in vivo role of the nuclear receptor SHP in feedback regulation of bile acid synthesis was examined. Loss of SHP in mice caused abnormal accumulation and increased synthesis of bile acids due to derepression of rate-limiting CYP7A1 and CYP8B1 hydroxylase enzymes in the biosynthetic pathway. Dietary bile acids induced liver damage and restored feedback regulation. A synthetic agonist of the nuclear receptor FXR was not hepatotoxic and had no regulatory effects. Reduction of the bile acid pool with cholestyramine enhanced CYP7A1 and CYP8B1 expression. We conclude that input from three negative regulatory pathways controls bile acid synthesis. One is mediated by SHP, and two are SHP independent and invoked by liver damage and changes in bile acid pool size.
It is estimated that, at present, approximately 50% of all lubricants sold worldwide end up in the environment via total loss applications, volatility, spills or accidents. More than 95% of these materials are currently mineral oil based. In view of their high ecotoxicity and low biodegradability, mineral oil-based lubricants constitute a considerable threat to the environment. In contrast, most lubricants and hydraulic fluids based on plant oils are rapidly and completely biodegradable and are of low ecotoxicity; moreover, lubricants based on plant oils display excellent tribological properties and generally have very high viscosity indices and flashpoints. However, in order to compete with mineral-oil-based products, some of their inherent disadvantages must be corrected, such as their sensitivity to hydrolysis and oxidative attack, and their behaviour at low temperatures. Various methods to improve the undesirable properties of native plant oils will be discussed. In parallel, government regulations that encourage or enforce the use of bio-based fluids, at least in ecologically sensitive areas, will help to increase their market share. Using the numerous possibilities for selective breeding and/or chemical improvement of the double bond systems of natural fatty acids by increased R&D, the major obstacles regarding the use of plant-based raw materials for the production of lubricant base fluids can be overcome and bio-based fluids should expect a future with increasing market shares.
Tumors use tryptophan-catabolizing enzymes such as indoleamine 2,3-dioxygenase (IDO-1) to induce an immunosuppressive environment. IDO-1 is induced in response to inflammatory stimuli and promotes immune tolerance through effector T-cell anergy and enhanced Treg function. As such, IDO-1 is a nexus for the induction of a key immunosuppressive mechanism and represents an important immunotherapeutic target in oncology. Starting from HTS hit 5, IDO-1 inhibitor 6 (EOS200271/PF-06840003) has been developed. The structure-activity relationship around 6 is described and rationalized using the X-ray crystal structure of 6 bound to human IDO-1, which shows that 6, differently from most of the IDO-1 inhibitors described so far, does not bind to the heme iron atom and has a novel binding mode. Clinical candidate 6 shows good potency in an IDO-1 human whole blood assay and also shows a very favorable ADME profile leading to favorable predicted human pharmacokinetic properties, including a predicted half-life of 16-19 h.
Regioisomerically pure 1,3‐sn‐diacylglycerols are conveniently prepared in high yields (>80%) and in large quantities by enzymatic esterification of glycerol in the presence of various 1,3‐selective lipases(Chromobacterium viscosum, Rhizopus delemar, Rhizomucor miehei) and a variety of different acyl donors like free fatty acids, fatty acid alkyl esters and vinyl esters. All reactions are carried out in aprotic organic solvents of low water content, namelyn‐hexane, diethyl ether or tBuOMe. The creation of an artificial interphase between the solvent‐immiscible hydrophilic glycerol and the hydrophobic reaction media by the adsorption of glycerol onto a solid support prior to use was essential for the success of these transformations. The effects of reaction conditions and the regioselectivities of the lipases on the product yields are described in detail.
Sorptive stabilization of organic matter by amorphous Al hydroxideSchneider, M.P.W.; Scheel, Th.; Mikutta, R.; van Hees, P.; Kaiser, K.; Kalbitz, K. General rightsIt is not permitted to download or to forward/distribute the text or part of it without the consent of the author(s) and/or copyright holder(s), other than for strictly personal, individual use, unless the work is under an open content license (like Creative Commons). Disclaimer/Complaints regulationsIf you believe that digital publication of certain material infringes any of your rights or (privacy) interests, please let the Library know, stating your reasons. In case of a legitimate complaint, the Library will make the material inaccessible and/or remove it from the website. Please Ask the Library: http://uba.uva.nl/en/contact, or a letter to: Library of the University of Amsterdam, Secretariat, Singel 425, 1012 WP Amsterdam, The Netherlands. You will be contacted as soon as possible. ) with OM extracted from organic horizons under a Norway spruce and a European beech forest. The stabilization of OM by sorption was analyzed by comparing the CO 2 mineralized during the incubation of sorbed and non-sorbed OM. The mineralization of OM was evaluated based in terms of (i) the availability of the am-Al(OH) 3 , thus surface OM loadings, (ii) spectral properties of OM, and (iii) the presence of phosphate as a competitor for OM. This was done by varying the solid-to-solution ratio (SSR = 0.02-1.2 g L À1 ) during sorption. At low SSRs, hence limited am-Al(OH) 3 availability, only small portions of dissolved OM were sorbed; for OM from Oa horizons, the mineralization of the sorbed fraction exceeded that of the original dissolved OM. The likely reason is competition with phosphate for sorption sites favouring the formation of weak mineral-organic bindings and the surface accumulation of N-rich, less aromatic and less complex OM. This small fraction controlled the mineralization of sorbed OM even at higher SSRs. At higher SSRs, i.e., with am-Al(OH) 3 more available, competition of phosphate decreased and aromatic compounds were sorbed selectively, which resulted in pronounced resistance of sorbed OM against decay. The combined OC mineralization of sorbed and non-sorbed OM was 12-65% less than that of the original DOM. Sorbed OM contributed only little to the overall OC mineralization. Stabilization of OC increased in direct proportion to am-Al(OH) 3 availability, despite constant aromatic C ($30%). The strong stabilization at higher mineral availability is primarily governed by strong Al-OM bonds formed under less competitive conditions. Due to these strong bonds and the resulting strong stabilization, the surface loading, a proxy for the mineral's occupation by OM, was not a factor in the mineralization of sorbed OM over a wide range of C sorption (0.2-1.1 mg C m À2). This study demonstrates that sorption to am-Al(OH) 3 results in stabilization of OM. The mineral availability as well as the inorganic solution chemistry control sorptive interactions, thereby th...
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