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排序方式: 共有355条查询结果,搜索用时 31 毫秒
101.
Dr. Sascha Häseli Marion Holy Dr. Markus Joksch Dr. Carina Bergner Dr. Andreas Wree Dr. Jens Kurth Aylin Cankaya Dr. Markus Piel Dr. Bernd J. Krause Dr. Harald H. Sitte Dr. Frank Rösch 《ChemMedChem》2021,16(5):804-808
The development of radiometal-labelled pharmaceuticals for neuroimaging could offer great potential due to easier handling during labelling and availability through radionuclide generator systems. Nonetheless, to date, no such tracers are available for positron emission tomography, primarily owing to the challenge of crossing the blood–brain barrier (BBB) and loss of affinity through chelator attachment. We have prepared a variety of 68Ga-labelled phenyltropanes showing that, through a simple hydrocarbon-linker, it is possible to introduce a chelator onto the lead structure while maintaining its high affinity for hDAT (human dopamine transporter) and simultaneously achieving adequate lipophilicity. One of the candidates, [68Ga]Ga-HBED-hexadiyne-tropane, showed an IC50 value of 66 nM, together with a log D7.4 of 0.96. A μPET study in a hemi-parkinsonian rat model showed a fast wash-out of the tracer, and no specific uptake in the brain, thus implying an inability to penetrate the BBB. 相似文献
102.
Karin N. Westlund Marena A. Montera Aleyah E. Goins Sascha R. A. Alles Nikita Suri Sabrina L. McIlwrath Robyn Bartel Ravi V. Durvasula Adinarayana Kunamneni 《International journal of molecular sciences》2021,22(24)
Non-opioid single-chain variable fragment (scFv) small antibodies were generated as pain-reducing block of P2X4R receptor (P2X4R). A panel of scFvs targeting an extracellular peptide sequence of P2X4R was generated followed by cell-free ribosome display for recombinant antibody selection. After three rounds of bio-panning, a panel of recombinant antibodies was isolated and characterized by ELISA, cross-reactivity analysis, and immunoblotting/immunostaining. Generated scFv antibodies feature binding activity similar to monoclonal antibodies but with stronger affinity and increased tissue penetrability due to their ~30% smaller size. Two anti-P2X4R scFv clones (95, 12) with high specificity and affinity binding were selected for in vivo testing in male and female mice with trigeminal nerve chronic neuropathic pain (FRICT-ION model) persisting for several months in untreated BALBc mice. A single dose of P2X4R scFv (4 mg/kg, i.p.) successfully, completely, and permanently reversed chronic neuropathic pain-like measures in male mice only, providing retention of baseline behaviors indefinitely. Untreated mice retained hypersensitivity, and developed anxiety- and depression-like behaviors within 5 weeks. In vitro P2X4R scFv 95 treatment significantly increased the rheobase of larger-diameter (>25 µm) trigeminal ganglia (TG) neurons from FRICT-ION mice compared to controls. The data support use of engineered scFv antibodies as non-opioid biotherapeutic interventions for chronic pain. 相似文献
103.
Volker Weiser Norbert Eisenreich Sascha Poller Stefan Kelzenberg Roger Lo Harry Adirim 《Propellants, Explosives, Pyrotechnics》2002,27(3):150-155
Cryogenic Solid Propellant (CSP)‐technology is a new approach to develop more powerful rocket motors. CSPs include the advantages of classical solid propellants to save weight as well as those of a high energy content and safety of modern liquid propellants. The charges consist of liquid and/or gaseous fuels and oxidizers, both frozen. Two main versions of CSP‐technology can be realised: 1. Mono‐CSPs show the burning behavior of solid propellants. Experiments with mono‐CSPs have been carried out under inert pressure conditions in a window bomb. Mono‐CSPs have a stable burning behavior with a constant regression rate which follows the Vieille's law under varying pressure conditions. 2. The advantage of high safety is obtained by assembling oxidizer and fuel in sandwich configurations. The grain geometry governs the burning behavior. Such systems can be externally controlled, e.g. by the heat from a gas generator or they can work self‐sustained. A Rod‐in‐Matrix burner shows self‐sustained combustion in an inert pressure atmosphere with overall burning rates in a similar range as solid rocket propellants which obey also a Vieille‐like pressure law. Disc stack burners have also been investigated, the combustion of which is strongly dependent on the disc thickness. For a short time Mach's nodes have been observed in the exhaust plume of a disc stack burner. Currently, the temperature ranges are limited to the boiling temperature of liquid nitrogen. Therefore, liquid oxidizers like H2O2 have been used. However, for the first time a propellant strand of polymer rods embedded in solid oxygen was prepared and burnt. The experiments with CSPs end in the combustion of a small rocket motor showing no serious technical obstacles. Simplified models based on the heat flow equation can simulate the burning characteristics of the frozen energetic materials including phase transitions. 相似文献
104.
Curcumin‐Derived Pyrazoles and Isoxazoles: Swiss Army Knives or Blunt Tools for Alzheimer's Disease?
Narlawar R Pickhardt M Leuchtenberger S Baumann K Krause S Dyrks T Weggen S Mandelkow E Schmidt B 《ChemMedChem》2008,3(1):165-172
Curcumin binds to the amyloid beta peptide (Abeta) and inhibits or modulates amyloid precursor protein (APP) metabolism. Therefore, curcumin-derived isoxazoles and pyrazoles were synthesized to minimize the metal chelation properties of curcumin. The decreased rotational freedom and absence of stereoisomers was predicted to enhance affinity toward Abeta(42) aggregates. Accordingly, replacement of the 1,3-dicarbonyl moiety with isosteric heterocycles turned curcumin analogue isoxazoles and pyrazoles into potent ligands of fibrillar Abeta(42) aggregates. Additionally, several compounds are potent inhibitors of tau protein aggregation and depolymerized tau protein aggregates at low micromolar concentrations. 相似文献
105.
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107.
This paper introduces a temporal logic framework to reason about the coordination mechanisms and data flow of exogenous coordination models. We take a CTL-like branching time logic, augmented with regular expressions that specify the observable I/O-operations, as a starting point. The paper provides the syntax and semantics of our logic and introduces the corresponding model checking algorithm. The second part of the paper reports an implementation that relies on a symbolic representation of the coordination network and the connected components by means of binary decision diagrams. A couple of examples are given to illustrate the efficiency of the model checking techniques and their implementation. 相似文献
108.
The paper reports on the foundations and experimental results with a model checker for component connectors modelled by networks of channels in the calculus Reo. The specification formalisms is a branching time logic that allows to reason about the coordination principles of and the data flow in the network. The underlying model checking algorithm relies on variants of standard automata-based approaches and model checking for CTL-like logics. The implementation uses a symbolic representation of the network and the enabled I/O-operations by means of binary decision diagrams. It has been applied to a couple examples that illustrate the efficiency of our model checker. 相似文献
109.
Usenko S Hageman KJ Schmedding DW Wilson GR Simonich SL 《Environmental science & technology》2005,39(16):6006-6015
An analytical method was developed for the trace analysis of a wide range of semivolatile organic compounds (SOCs) in 50-L high-elevation snow and lake water samples. The method was validated for 75 SOCs from seven different chemical classes (polycyclic aromatic hydrocarbons, organochlorine pesticides, amides, triazines, polychlorinated biphenyls, thiocarbamates, and phosphorothioates) that covered a wide range of physical-chemical properties including 7 orders of magnitude of octanol-water partition coefficient (log K(ow) = 1.4-8.3). The SOCs were extracted using a hydrophobically and hydrophilically modified divinylbenzene solid-phase extraction device (modified Speedisk). The average analyte recovery from 50 L of reverse osmosis water, using the modified Speedisk, was 99% with an average relative standard deviation of 4.8%. Snow samples were collected from the field, melted, and extracted using the modified Speedisk and a poly(tetrafluoroethylene) remote sample adapter in the laboratory. Lake water was sampled, filtered, and extracted in situ using an Infiltrex 100 fitted with a 1-microm glass fiber filter to trap particulate matter and the modified Speedisk to trap dissolved SOCs. The extracts were analyzed by gas chromatographic mass spectrometry with electron impact ionization and electron capture negative ionization using isotope dilution and selective ion monitoring. Estimated method detection limits for snow and lake water ranged from 0.2 to 125 pg/L and 0.5-400 pg/L, respectively. U.S. historic and current-use pesticides were identified and quantified in snow and lake water samples collected from Rocky Mountain National Park, CO. The application of the analytical method to the analysis of SOCs in large-volume groundwater samples is also shown. 相似文献
110.
Xanthohumol (XN), a component of hops, is lost in significant quantities in the conventional brewing process. In commercial beers less than 0.2 mg XN/L are found. In order to increase the yield of XN in the brewing process, the parameters of XN recovery were studied. During wort boiling, XN is largely isomerised to isoxanthohumol. Further losses are owing to the precipitation and absorption of XN to yeast cells and haze particles and by filtration. The use of XN-enriched hop products combined with a late hop dosage during wort boiling proved to be effective in increasing the XN content in beer. The yield was further raised by a low-pitching rate and the abnegation of beer stabilisation. The use of dark malts had a positive effect on the XN recovery. Investigations of roasted malt extracts revealed several high-molecular substances that are able to form complexes with XN. These complexes proved to be stable in the brewing process. Depending on the addition of roasted malt or special XN-enriched roasted malt extracts, dark beers with more than 10 mg XN/L were achieved. Results obtained led to a brewing technology that produced on an industrial scale pale wheat beer with more than 1 mg XN/L. 相似文献